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In JoVE (2)
- Use of Human Perivascular Stem Cells for Bone Regeneration
- Repair of a Critical-sized Calvarial Defect Model Using Adipose-derived Stromal Cells Harvested from Lipoaspirate
Other Publications (203)
- Orthodontics : the Art and Practice of Dentofacial Enhancement
- International Journal of Cardiology
- Applied Optics
- Immune Network
- Korean Circulation Journal
- Journal of Korean Neurosurgical Society
- Diabetes & Metabolism Journal
- Korean Circulation Journal
- Dermatitis : Contact, Atopic, Occupational, Drug : Official Journal of the American Contact Dermatitis Society, North American Contact Dermatitis Group
- Biological & Pharmaceutical Bulletin
- Journal of Natural Products
- Journal of the Korean Surgical Society
- Stem Cells (Dayton, Ohio)
- Plastic and Reconstructive Surgery
- Molecular & Cellular Proteomics : MCP
- Colloids and Surfaces. B, Biointerfaces
- Stem Cell Research
- Human Molecular Genetics
- Advanced Materials (Deerfield Beach, Fla.)
- Natural Product Research
- Life Sciences
- Stem Cells (Dayton, Ohio)
- Biosensors & Bioelectronics
- The Korean Journal of Internal Medicine
- Korean Circulation Journal
- Die Pharmazie
- Yonsei Medical Journal
- Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics
- Nature Structural & Molecular Biology
- The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi
- Optics Express
- Circulation Journal : Official Journal of the Japanese Circulation Society
- The Journal of Biological Chemistry
- Korean Circulation Journal
- Dalton Transactions (Cambridge, England : 2003)
- International Journal of Nanomedicine
- Journal of the American Chemical Society
- Biochemical and Biophysical Research Communications
- Journal of Separation Science
- Liver International : Official Journal of the International Association for the Study of the Liver
- AJR. American Journal of Roentgenology
- AJR. American Journal of Roentgenology
- Chonnam Medical Journal
- Immune Network
- The Korean Journal of Parasitology
- Organic Letters
- Journal of Agricultural and Food Chemistry
- Molecular Pain
- International Journal of Cardiology
- Journal of Cellular Physiology
- Biochemical and Biophysical Research Communications
- Breast Cancer Research and Treatment
- PLoS Genetics
- Psychiatry Investigation
- Metabolism: Clinical and Experimental
- Lung Cancer (Amsterdam, Netherlands)
- Chemical Communications (Cambridge, England)
- Investigative Ophthalmology & Visual Science
- Journal of the Korean Society of Coloproctology
- Water Research
- Macromolecular Rapid Communications
- Breast Cancer Research and Treatment
- Journal of Biomedical Materials Research. Part A
- AJR. American Journal of Roentgenology
- Breast Cancer Research : BCR
- Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
- European Journal of Pharmacology
- Biological & Pharmaceutical Bulletin
- Abdominal Imaging
- Journal of Korean Medical Science
- Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
- Annals of Diagnostic Pathology
- Archives of Pharmacal Research
- World Journal of Surgical Oncology
- International Journal of Cardiology
- Journal of Proteomics
- Journal of the Korean Surgical Society
- Antimicrobial Agents and Chemotherapy
- Luminescence : the Journal of Biological and Chemical Luminescence
- Investigational New Drugs
- European Journal of Endocrinology / European Federation of Endocrine Societies
- Acta Radiologica (Stockholm, Sweden : 1987)
- Fish & Shellfish Immunology
- Molecular Pharmacology
- Cancer Biology & Therapy
- Journal of Orofacial Pain
- Korean Circulation Journal
- Korean Circulation Journal
- Journal of the Korean Surgical Society
- Dalton Transactions (Cambridge, England : 2003)
- Stem Cell Research
- International Journal of Cardiology
- Colloids and Surfaces. B, Biointerfaces
- The Journal of Clinical Psychiatry
- Plastic and Reconstructive Surgery
- Lung Cancer (Amsterdam, Netherlands)
- Breast Cancer Research and Treatment
- The Journal of Physiology
- BMC Infectious Diseases
- Magnetic Resonance Imaging
- Journal of Cardiology
- AJR. American Journal of Roentgenology
- Journal of Neuroinflammation
- Acta Radiologica (Stockholm, Sweden : 1987)
- Epidemiology and Health
- Acta Biomaterialia
- Investigative Radiology
- Journal of Cardiology
- Journal of Cardiology
- The Journal of Asthma : Official Journal of the Association for the Care of Asthma
- Journal of the American Chemical Society
- The American Journal of Cardiology
- Skeletal Radiology
- Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
- The Journal of Surgical Research
- World Journal of Gastroenterology : WJG
- Journal of Korean Medical Science
- Methods in Molecular Biology (Clifton, N.J.)
- Nano Letters
- Korean Circulation Journal
- Korean Circulation Journal
- Korean Circulation Journal
- Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie
- Clinical Nutrition (Edinburgh, Scotland)
- Clinics and Research in Hepatology and Gastroenterology
- BJU International
- Fish & Shellfish Immunology
- Langmuir : the ACS Journal of Surfaces and Colloids
- Journal of Biomedical Materials Research. Part A
- Journal of Clinical Pharmacology
- Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery
- International Journal of Cardiology
- Journal of Biomedical Materials Research. Part B, Applied Biomaterials
- Diabetes Research and Clinical Practice
- Journal of Microbiology and Biotechnology
- Physiological Reviews
- Biochimica Et Biophysica Acta
- Cellular Signalling
- Journal of Food Protection
- European Journal of Obstetrics, Gynecology, and Reproductive Biology
- Circulation Journal : Official Journal of the Japanese Circulation Society
- International Journal of Cardiology
- Chonnam Medical Journal
- Chonnam Medical Journal
- Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)
- The Journal of Biological Chemistry
- Journal of Pediatric Orthopedics
- Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
- Lung Cancer (Amsterdam, Netherlands)
- Food Microbiology
- International Journal of Pharmaceutics
- PloS One
- AJR. American Journal of Roentgenology
- Cellular Signalling
- Journal of Pharmaceutical Sciences
- International Journal of Cardiology
- Molecular Pain
- Journal of the American Chemical Society
- Archives of Pharmacal Research
- Korean Journal of Urology
- Clinical Endoscopy
- The Analyst
- Antimicrobial Agents and Chemotherapy
- Archives of Plastic Surgery
- International Journal of Pharmaceutics
- Developmental Cell
- Acta Biomaterialia
- Journal of Applied Physiology (Bethesda, Md. : 1985)
- International Journal of Clinical Pharmacology and Therapeutics
- Biotechnology for Biofuels
- PloS One
- Journal of Nanoscience and Nanotechnology
- Journal of Agricultural and Food Chemistry
- Molecular Plant
- International Journal of Dermatology
- Angewandte Chemie (International Ed. in English)
- IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
- The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi
- BMB Reports
- Journal of the American Chemical Society
- Molecules (Basel, Switzerland)
- Journal of Hepatology
- Cold Spring Harbor Perspectives in Medicine
- Surgical Laparoscopy, Endoscopy & Percutaneous Techniques
- Diabetes Technology & Therapeutics
- International Journal of Dermatology
- The Korean Journal of Hematology
- European Journal of Radiology
- European Radiology
- Genomics & Informatics
- Korean Journal of Pathology
- Molecular Immunology
Articles by Min Lee in JoVE
Use of Human Perivascular Stem Cells for Bone Regeneration
Aaron W. James*1, Janette N. Zara*2, Mirko Corselli2, Michael Chiang1, Wei Yuan2, Virginia Nguyen1, Asal Askarinam1, Raghav Goyal1, Ronald K. Siu3, Victoria Scott1, Min Lee3, Kang Ting1, Bruno Péault2,4, Chia Soo2
1Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA, 2UCLA and Orthopaedic Hospital, Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, UCLA, 3Department of Bioengineering, UCLA, 4Center for Cardiovascular Science, University of Edinburgh
Human perivascular stem cells (PSCs) are a novel stem cell class for skeletal tissue regeneration similar to mesenchymal stem cells (MSCs). PSCs can be isolated by FACS (fluorescence activated cell sorting) from adipose tissue procured during standard liposuction procedures, then combined with an osteoinductive scaffold to achieve bone formation in vivo.
Repair of a Critical-sized Calvarial Defect Model Using Adipose-derived Stromal Cells Harvested from Lipoaspirate
David D. Lo*1,2, Jeong S. Hyun*1,3, Michael T. Chung1, Daniel T. Montoro1, Andrew Zimmermann1, Monica M. Grova1,4, Min Lee5, Derrick C. Wan1, Michael T. Longaker1
1Department of Surgery, Stanford University, 2Department of Surgery, Duke University, 3Department of Surgery, Saint Joseph Mercy Hospital, 4School of Medicine, University of California, San Francisco, 5School of Dentistry, University of California, Los Angeles
This protocol describes the isolation of adipose-derived stromal cells from lipoaspirate and the creation of a 4 mm critical-sized calvarial defect to evaluate skeletal regeneration.
Other articles by Min Lee on PubMed
Association Between Study Design and Citation Counts of Articles Published in the American Journal of Orthodontics and Dentofacial Orthopedics and Angle Orthodontist
Orthodontics : the Art and Practice of Dentofacial Enhancement. | Pubmed ID: 22567631
Objective: The scientific community views meta-analyses and systematic reviews, in addition to well-designed randomized controlled clinical trials, as the highest echelon in the continuum of hierarchy of evidence. The objective of this study was to examine the association between different study designs and citation counts of articles published in the American Journal of Orthodontics and Dentofacial Orthopedics and Angle Orthodontist. Methods: All articles, excluding editorial comments, letters to the editor, commentaries, and special articles, that were published in the American Journal of Orthodontics and Dentofacial Orthopedics and Angle Orthodontist during the years 2004 and 2005 were examined in this study. The number of times an article was cited in the first 24 months after its publication was computed. The PubMed database was used to index the study design of the articles. The association between study design and citation counts was examined using the Kruskal-Wallis test. A multivariable negative binomial regression model was used to examine the association between citation count and study design along with several other confounding variables. Results: A total of 624 articles were selected for analysis. Of these, there were 25 meta-analyses or review articles, 42 randomized clinical trials, 59 clinical trials, 48 animal studies, 64 case reports, and 386 quasiexperimental/miscellaneous study designs. The mean ± SD citation count was 1.04 ± 1.46. Nearly half of the articles (n = 311) were not cited even once during the observation period. Case reports were cited less frequently than meta-analyses or reviews (incident risk ratio, 0.37; 95% confidence interval, 0.19 to 0.72; P = .003), even after adjusting for other independent variables. Conclusion: Among various study designs, meta-analyses and review articles are more likely to be cited in the first 24 months after publication. This study demonstrates the importance of publishing more meta-analyses and review articles for quicker dissemination of research findings.
Impact of Tissue Prolapse After Stent Implantation on Short- and Long-term Clinical Outcomes in Patients with Acute Myocardial Infarction: An Intravascular Ultrasound Analysis
International Journal of Cardiology. Dec, 2011 | Pubmed ID: 22177591
BACKGROUND: We used intravascular ultrasound (IVUS) to evaluate the association of tissue prolapse (TP) with short- and long-term outcomes after stent implantation in 418 acute myocardial infarction (AMI) patients. METHODS: We evaluated the incidences of stent thrombosis, no-reflow, and long-term outcomes between patients with TP (n=142) and those without TP (n=276). RESULTS: twb.42w?>Acute and subacute stent thromboses occurred more frequently in patients with TP compared with those without TP (3.5% vs. 0.7%, p=0.035, and 4.2% vs. 0.7%, p=0.013, respectively). TP volumes in 14 patients with stent thrombosis were significantly greater than those in 128 patients without stent thrombosis (3.3±1.6mm(3) vs. 2.6±1.9mm(3), p=0.012). No-reflow was developed more frequently in patients with TP compared with those without TP (25.4% vs. 9.8%, p<0.001). Creatine kinase-MB and cardiac-specific troponin I were elevated more significantly after stenting in patients with TP compared with those without TP (Δ=+9.0±25.2U/l vs. -4.2±41.6U/l, p=0.001 and Δ=+10.0±43.5ng/ml vs. -1.2±35.6ng/ml, p=0.005, respectively). There were no significant differences in the incidences of cardiac death, MI, and target vessel revascularization at 1-year. Multivariate analysis showed that TP was the independent predictor of composite of acute and subacute stent thromboses [odds ratio (OR)=4.211; 95% CI 1.198-14.805, p=0.025] and composite of acute stent thrombosis and no-reflow (OR=2.551; 95% CI 1.315-4.952, p=0.006). CONCLUSIONS: TP was associated with poor short-term outcomes (more acute and subacute thromboses and no-reflow phenomenon), however it was not associated with worse long-term outcomes after stent implantation for infarct-related arteries in patients with AMI.
Applied Optics. Dec, 2011 | Pubmed ID: 22193134
High-frequency guided acoustic Brillouin modes have recently been observed in small-core silica photonic crystal fibers. In this paper, we investigate the temperature dependence of the optical sideband frequency generated by one of these guided acoustic waves. The experimental results show a temperature coefficient of 100 kHz/°C at an acoustic resonance frequency of 1.15 GHz and are in very good agreement with the theoretical predictions. This coefficient demonstrates a temperature sensitivity 10 times larger than that previously reported in conventional single-mode fibers, which is promising in view of potential applications to optical fiber sensors.
Gene Expression Profile of T-cell Receptors in the Synovium, Peripheral Blood, and Thymus During the Initial Phase of Collagen-induced Arthritis
Immune Network. Oct, 2011 | Pubmed ID: 22194709
Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium.
Korean Circulation Journal. Nov, 2011 | Pubmed ID: 22194765
A 51-year-old man was admitted due to an acute anterior ST-segment elevation myocardial infarction. After thrombolytic therapy using recombinant tissue plasminogen activator, stent implantation was performed from the proximal left anterior descending artery (LAD) to the mid LAD using a bare-metal stent (BMS). Since then, the patient suffered five repeated episodes of in-stent restenosis (ISR). At the first ISR, he was treated with plain old balloon angioplasty (POBA). At the second ISR, he was treated with brachytherapy, and at the third ISR, he was treated with POBA and one more BMS distal to the previously implanted stent. At the forth, only POBA was performed, and finally, at the fifth ISR, a sirolimus-eluting stent was implanted. Following that, the patient remained asymptomatic and follow-up coronary angiography showed no ISR.
Journal of Korean Neurosurgical Society. Oct, 2011 | Pubmed ID: 22200024
Leptomeningeal metastasis is a devastating complication of advanced stage cancer. It is frequently accompanied by hydrocephalus and intracranial hypertension that must be treated by ventriculoperitoneal shunts. However, there are actual risks of peritoneal seeding or accumulation of malignant ascites after the cerebrospinal fluid diversion procedure, though it has not been reported. Here, we present the case of a patient with non-small cell lung cancer with leptomeningeal metastasis in whom malignant ascites developed after a subduroperitoneal shunt.
The Relationship Between Diabetes Mellitus and Health-Related Quality of Life in Korean Adults: The Fourth Korea National Health and Nutrition Examination Survey (2007-2009)
Diabetes & Metabolism Journal. Dec, 2011 | Pubmed ID: 22247901
Diabetes is a major health problem in Korea. However, interest in the quality of life in patients with diabetes is low. We examined the effects of diabetes on health-related quality of life (HRQoL) and compared it with HRQoL in the general Korean population using the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV) (2007-2009).
Korean Circulation Journal. Dec, 2011 | Pubmed ID: 22259608
We report our experience of very late stent thrombosis (VLST) in a young male patient who underwent implantation of two paclitaxel-eluting stents (PES) six years ago. The patient was compliant with standard dual antiplatelet therapy, but he presented with acute myocardial infarction which was associated with VLST. Intravascular ultrasound showed neointimal rupture with thrombus within the PES implanted in the right coronary artery. The lesion was successfully treated with balloon angioplasty without complications, however he was found to be hyporesponsive to clopidogrel when tested for adenosine diphosphate-induced platelet aggregation. The patient was discharged after uneventful recovery with triple anti-platelet therapy using aspirin, clopidogrel and cilostazol. To the best of our knowledge, a time interval of 2,223 days is the longest reported time interval between PES deployment and VLST occurrence. VLST may indeed occur in clinically stable patients, as multiple factors can influence the pathological mechanisms of VLST.
Dermatitis : Contact, Atopic, Occupational, Drug : Official Journal of the American Contact Dermatitis Society, North American Contact Dermatitis Group. Nov-Dec, 2011 | Pubmed ID: 22653012
Biological & Pharmaceutical Bulletin. 2011 | Pubmed ID: 22130236
The aim of the present study was to investigate whether hirsutenone affects the human ether-a-go-go related gene (hERG) K(+) channels. Many drugs promote formation of the acquired form of long QT syndrome (LQTS) by blocking the hERG K(+) channels. Hirsutenone, a new candidate for the treatment inflammatory skin lesions, induced a concentration-dependent decrease in hERG K(+) current amplitudes. Hirsutenone significantly decreased the time constants at the onset of inactivation. However, the reductions in the time constants of steady-state inactivation and the recovery from inactivation after hirsutenone treatment were not significant. In addition, the drug had no effect on the voltage-dependent activation curve or the steady-state inactivation curve. In summary, hirsutenone potentially acts as a blocker of hERG K(+) channels functioning by modifying the channel inactivation kinetics.
Cyclic Ether-containing Macrolactins, Antimicrobial 24-membered Isomeric Macrolactones from a Marine Bacillus Sp
Journal of Natural Products. Dec, 2011 | Pubmed ID: 22133265
Bioassay-guided isolation of bioactive metabolites from the ethyl acetate extract of a marine Bacillus sp. fermentation broth has led to the discovery of three new 24-membered macrolactones, macrolactins 1-3, which contain an oxetane, an epoxide, and a tetrahydropyran ring, respectively. The configurations of 1-3 were assigned by a combination of coupling constants, ROESY data analysis, and application of the modified Mosher's method. Compounds 1-3 showed in vitro antimicrobial activity.
Journal of the Korean Surgical Society. Dec, 2011 | Pubmed ID: 22319738
Torsion of a mucocele of the vermiform appendix is an extremely rare condition and also a rare cause of an acute abdomen with a clinical presentation that is indistinguishable from acute appendicitis, and thus, the condition is diagnosed during operation. Here, the authors describe the case of a 78-year-old female, who presented with intermittent abdominal pain. The appendix had a pelvic position and the torsion was counterclockwise. In addition, the torsion was associated with mucocele of the appendix, which was considered a secondary factor of torsion. Appendectomy and drainage were performed.
Antihyperlipidemic Effect of Dietary Lentinus Edodes on Plasma, Feces and Hepatic Tissues in Hypercholesterolemic Rats
Mycobiology. Jun, 2011 | Pubmed ID: 22783084
We investigated diet supplementation with shiitake mushroom fruiting bodies on biochemical and histological changes in hypercholesterolemic rats. Six-wk old female Sprague-Dawley albino rats were divided into three groups of 10 rats each. A diet containing 5% Lentinus edodes fruiting bodies given to hypercholesterolemic rats reduced plasma total cholesterol, triglyceride, low-density lipoprotein (LDL), total lipid, phospholipids, and the LDL/high-density lipoprotein ratio by 34.33, 53.21, 75.00, 34.66, 25.73, and 71.43%, respectively. Feeding mushroom also significantly reduced body weight in hypercholesterolemic rats. However, it had no detrimental effects on plasma albumin, total bilirubin, direct bilirubin, creatinine, blood urea nitrogen, uric acid, glucose, total protein, calcium, sodium, potassium, chloride, inorganic phosphate, magnesium, or enzyme profiles. Feeding mushroom increased total lipid and cholesterol excretion in feces. The plasma lipoprotein fraction, separated by agarose gel electrophoresis, indicated that L. edodes significantly reduced plasma β and pre-β-lipoprotein but increased α-lipoprotein. A histological study of hepatic cells by conventional hematoxylin-eosin and oil red-O staining showed normal findings for mushroom-fed hypercholesterolemic rats. These results suggest that shiitake mushrooms could be recommended as a natural cholesterol lowering substance in the diet.
Dura Mater Stimulates Human Adipose-derived Stromal Cells to Undergo Bone Formation in Mouse Calvarial Defects
Stem Cells (Dayton, Ohio). Aug, 2011 | Pubmed ID: 21656608
Human adipose-derived stromal cells (hASCs) have a proven capacity to aid in osseous repair of calvarial defects. However, the bone defect microenvironment necessary for osseous healing is not fully understood. In this study, we postulated that the cell-cell interaction between engrafted ASCs and host dura mater (DM) cells is critical for the healing of calvarial defects. hASCs were engrafted into critical sized calvarial mouse defects. The DM-hASC interaction was manipulated surgically by DM removal or by insertion of a semipermeable or nonpermeable membrane between DM and hASCs. Radiographic, histologic, and gene expression analyses were performed. Next, the hASC-DM interaction is assessed by conditioned media (CM) and coculture assays. Finally, bone morphogenetic protein (BMP) signaling from DM was investigated in vivo using novel BMP-2 and anti-BMP-2/4 slow releasing scaffolds. With intact DM, osseous healing occurs both from host DM and engrafted hASCs. Interference with the DM-hASC interaction dramatically reduced calvarial healing with abrogated BMP-2-Smad-1/5 signaling. Using CM and coculture assays, mouse DM cells stimulated hASC osteogenesis via BMP signaling. Through in vivo manipulation of the BMP-2 pathway, we found that BMP-2 plays an important role in DM stimulation of hASC osteogenesis in the context of calvarial bone healing. BMP-2 supplementation to a defect with disrupted DM allowed for bone formation in a nonhealing defect. DM is an osteogenic cell type that both participates in and stimulates osseous healing in a hASC-engrafted calvarial defect. Furthermore, DM-derived BMP-2 paracrine stimulation appears to play a key role for hASC mediated repair.
Differences in Osteogenic Differentiation of Adipose-derived Stromal Cells from Murine, Canine, and Human Sources in Vitro and in Vivo
Plastic and Reconstructive Surgery. Aug, 2011 | Pubmed ID: 21788829
Given the diversity of species from which adipose-derived stromal cells are derived and studied, the authors set out to delineate the differences in the basic cell biology that may exist across species. Briefly, the authors found that significant differences exist with regard to proliferation and osteogenic potentials of adipose-derived stromal cells across species.
A Serum Protein Profile Predictive of the Resistance to Neoadjuvant Chemotherapy in Advanced Breast Cancers
Molecular & Cellular Proteomics : MCP. Oct, 2011 | Pubmed ID: 21799047
Prediction of the responses to neoadjuvant chemotherapy (NACT) can improve the treatment of patients with advanced breast cancer. Genes and proteins predictive of chemoresistance have been extensively studied in breast cancer tissues. However, noninvasive serum biomarkers capable of such prediction have been rarely exploited. Here, we performed profiling of N-glycosylated proteins in serum from fifteen advanced breast cancer patients (ten patients sensitive to and five patients resistant to NACT) to discover serum biomarkers of chemoresistance using a label-free liquid chromatography-tandem MS method. By performing a series of statistical analyses of the proteomic data, we selected thirteen biomarker candidates and tested their differential serum levels by Western blotting in 13 independent samples (eight patients sensitive to and five patients resistant to NACT). Among the candidates, we then selected the final set of six potential serum biomarkers (AHSG, APOB, C3, C9, CP, and ORM1) whose differential expression was confirmed in the independent samples. Finally, we demonstrated that a multivariate classification model using the six proteins could predict responses to NACT and further predict relapse-free survival of patients. In summary, global N-glycoproteome profile in serum revealed a protein pattern predictive of the responses to NACT, which can be further validated in large clinical studies.
Fabrication of Highly Porous Poly (ɛ-caprolactone) Fibers for Novel Tissue Scaffold Via Water-bath Electrospinning
Colloids and Surfaces. B, Biointerfaces. Dec, 2011 | Pubmed ID: 21856134
Highly porous fibers were prepared by water-bath electrospinning from pure poly(ɛ-caprolactone) (PCL), and its blends with methoxy poly(ethylene glycol) (MPEG). These fibers were further analyzed by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and gravimetric as well as contact angle measurement. SEM images showed that the fibers diameters as well as pores diameter on the fibers were affected by the weight ratio of MPEG/PCL. DSC and XRD not only revealed suppression of crystallinity of PCL but also indicated the presence of trace amount of MPEG in PCL water-bath collected fibers. The potential use of these hydrophilic porous electrospun fibrous mats as scaffolding materials was evaluated in vitro using mouse osteoblasts (MC3T3-E1) as reference cell lines. Cytotoxicity assessment of the fiber mats indicated that the porous electrospun mat containing trace amount of MPEG was nontoxic to the cell. Cell culture results showed that porous fibrous mats were good in promoting the cell attachment and proliferation. This novel electrospun matrix could be used as potential tissue scaffold material.
Enhancement of Differentiation Efficiency of HESCs into Vascular Lineage Cells in Hypoxia Via a Paracrine Mechanism
Stem Cell Research. Nov, 2011 | Pubmed ID: 21907161
Hypoxia is one way of inducing differentiation due to the activation of the key regulatory factor, Hypoxia-inducible factor 1 alpha (HIF-1α). However, the action of HIF-1α on the differentiation of hESCs was unclear until now. To investigate the effect of hypoxia on the differentiation of hESCs, we compared the differentiation efficacy into vascular lineage cells under normoxic and hypoxic conditions. We observed HIF-1α expression and the related expression of pro-angiogenic factors VEGF, bFGF, Ang-1 and PDGF in hEBs cultured under hypoxic conditions. Along with this, differentiation efficacy into vascular lineage cells was improved under hypoxic conditions. When HIF-1α was blocked by echinomycin, both angiogenic factors and the differentiation efficacy were down-regulated, suggesting that the enhancement of differentiation efficacy was caused by intrinsic up-regulation of HIF-1α and these pro-angiogenic factors under hypoxic condition. This response might be primarily regulated by the HIF-1α signal pathway, and hypoxia might be the key to improving the differentiation of hESCs into vascular lineage cells. Therefore, this study demonstrated that microenvironmental changes (i.e., hypoxia) can improve differentiation efficacy of hESCs into a vascular lineage without exogenous factors via cell-intrinsic up-regulation of angiogenic factors. These facts will contribute to the regulation of stem cell fate.
Genome-wide Association Study Identifies Breast Cancer Risk Variant at 10q21.2: Results from the Asia Breast Cancer Consortium
Human Molecular Genetics. Dec, 2011 | Pubmed ID: 21908515
Although approximately 20 common genetic susceptibility loci have been identified for breast cancer risk through genome-wide association studies (GWASs), genetic risk variants reported to date explain only a small fraction of heritability for this common cancer. We conducted a four-stage GWAS including 17 153 cases and 16 943 controls among East-Asian women to search for new genetic risk factors for breast cancer. After analyzing 684 457 SNPs in 2062 cases and 2066 controls (Stage I), we selected for replication among 5969 Chinese women (4146 cases and 1823 controls) the top 49 SNPs that had neither been reported previously nor were in strong linkage disequilibrium with reported SNPs (Stage II). Three SNPs were further evaluated in up to 13 152 Chinese and Japanese women (6436 cases and 6716 controls) (Stage III). Finally, two SNPs were evaluated in 10 847 Korean women (4509 cases and 6338 controls) (Stage IV). SNP rs10822013 on chromosome 10q21.2, located in the zinc finger protein 365 (ZNF365) gene, showed a consistent association with breast cancer risk in all four stages with a combined per-risk allele odds ratio of 1.10 (95% CI: 1.07-1.14) (P-value for trend = 5.87 × 10(-9)). In vitro electrophoretic mobility shift assays demonstrated the potential functional significance of rs10822013. Our results strongly implicate rs10822013 at 10q21.2 as a genetic risk variant for breast cancer among East-Asian women.
Binder-free and Full Electrical-addressing Free-standing Nanosheets with Carbon Nanotube Fabrics for Electrochemical Applications
Advanced Materials (Deerfield Beach, Fla.). Oct, 2011 | Pubmed ID: 21913236
Anti-oxidative, Anti-inflammatory and Whitening Effects of Phenolic Compounds from Bambusae Caulis in Liquamen
Natural Product Research. Oct, 2011 | Pubmed ID: 21985061
Bambusae Caulis in Liquamen (BCL) is the distilled product of the condensation from the burning of Phyllostachys nigra var. henosis (Gramineae). The activity-guided isolation of BCL yielded four phenolic compounds: 2,6-dimethoxyphenol (1), 1,2-dihydroxybenzene (2), 1,3-dihydroxybenzene (3) and 1,2-dibenzenecarboxylic acid (4). We evaluated the anti-oxidative, anti-inflammatory and whitening effects of these compounds, via assays, of 1,1-diphenyl-2-picrylhydazyl (DPPH) radical scavenging activity and inhibition of nitric oxide (NO) production in lipopolysaccharide-stimulated RAW 264.7 macrophage cells as well as inhibition of tyrosinase activity and melanin production in B16F10 melanoma cells. The results showed that 2 and 3 exhibited significant DPPH radical scavenging activity as well as inhibitory effects on NO production, tyrosinase activity and melanin production. These results suggested that BCL and compounds 2 and 3 can be developed as anti-oxidative, anti-inflammatory and whitening ingredients.
Anti-inflammatory Effect of Transduced PEP-1-cyclophilin A in Raw264.7 Cells and 12-O-tetradecanoylphorbol-13-acetate-induced Mice
Life Sciences. Dec, 2011 | Pubmed ID: 21989206
Cyclophilin A (CypA) is an immunophilin that acts as a receptor for the immunosuppressant drug cyclosporine A (CsA). CypA has emerged as a potential drug target for several inflammatory diseases, although the details of its mechanism are unclear. We examined the protective effects of CypA on inflammation in Raw 264.7 cells and animal models.
Nonintegrating Knockdown and Customized Scaffold Design Enhances Human Adipose-derived Stem Cells in Skeletal Repair
Stem Cells (Dayton, Ohio). Dec, 2011 | Pubmed ID: 21997852
An urgent need exists in clinical medicine for suitable alternatives to available techniques for bone tissue repair. Human adipose-derived stem cells (hASCs) represent a readily available, autogenous cell source with well-documented in vivo osteogenic potential. In this article, we manipulated Noggin expression levels in hASCs using lentiviral and nonintegrating minicircle short hairpin ribonucleic acid (shRNA) methodologies in vitro and in vivo to enhance hASC osteogenesis. Human ASCs with Noggin knockdown showed significantly increased bone morphogenetic protein (BMP) signaling and osteogenic differentiation both in vitro and in vivo, and when placed onto a BMP-releasing scaffold embedded with lentiviral Noggin shRNA particles, hASCs more rapidly healed mouse calvarial defects. This study therefore suggests that genetic targeting of hASCs combined with custom scaffold design can optimize hASCs for skeletal regenerative medicine.
Biosensors & Bioelectronics. Dec, 2011 | Pubmed ID: 22000759
We reported that peptide could be utilized as receptor molecule in the gas phase for application in micro/nano sensors by using a specific peptide that recognizes 2,4-dinitrotoluene at room temperature and in an atmospheric environment and measuring changes in the resonant frequency of the peptide immobilized microcantilevers. By using these peptides as receptors on a microcantilever sensor, we were able to experimentally detect 2,4-dinitrotoluene (DNT) vapor at concentrations as low as parts per billion (ppb) in the gas phase. While resonant frequency changes after binding between 2,4-DNT and the specific peptide receptor that was immobilized on microcantilevers were observed, the resonant frequency of DNT nonspecific peptide immobilized microcantilever did not change when exposed to 2,4-DNT vapor. The limit of detection (LOD) was calculated to be 431 ppt of limit of detection is numerically expected by experimental based on an equation that describes the relationship between the noise-equivalent analyte concentration. These results indicate that the peptide receptors hold great promise for use in the development of an artificial olfactory system and electronic nose based on micro/nanotechnology for monitoring various chemical vapors in the gas phase such as explosive mixtures of chemicals and/or volatile organic compounds.
Comparison of Clinical Outcomes of Hydrophilic and Lipophilic Statins in Patients with Acute Myocardial Infarction
The Korean Journal of Internal Medicine. Sep, 2011 | Pubmed ID: 22016590
A controversy exists about which statin is preferable for patients with acute myocardial infarction (AMI), and clinical impacts of different statins according to lipophilicity have not been established.
Effects of Ramiprilat-coated Stents on Neointimal Hyperplasia, Inflammation, and Arterial Healing in a Porcine Coronary Restenosis Model
Korean Circulation Journal. Sep, 2011 | Pubmed ID: 22022329
The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of neointimal hyperplasia, and a role for angiotensin II in the migration and proliferation of vascular smooth muscle cells in restenotic lesions has been proposed. The aim of this study was to determine the anti-proliferative and anti-inflammatory effects of ramiprilat-coated stents in a porcine coronary overstretch restenosis model.
Die Pharmazie. Oct, 2011 | Pubmed ID: 22026158
Crystallization is an essential step in pharmaceutical processing. The discovery of a non-classical crystallization pathway would be a promising strategy to engineer the properties of drug crystalline particles for specific delivery conditions. Herein, polymer-directed crystallization was successfully employed to modify the characteristics of a model drug, adefovir dipivoxil (AD). Polyacrylic acid (PAA), ethyl cellulose (EC), and hydroxypropyl cellulose were added as active polymers to control the crystallization pathway of AD. Changes in crystal habit were observed in all cases. A novel polymorph was found after the addition of PAA and EC, and was confirmed by XRD and DSC results. In FTIR investigations, the crystals derived from PAA-directed crystallization showed strong interactions between PAA and AD. The polymer content in polymer-directed crystallization-derived powders varied from 7 to 24 wt%, and the presence of polymers lead to sustained release of AD. These results make polymer-directed crystallization a simple and efficient technique to engineer the physical and chemical properties of drug crystals.
Parameters Measuring Beta-cell Function Are Only Valuable in Diabetic Subjects with Low Body Mass Index, High Blood Glucose Level, or Long-standing Diabetes
Yonsei Medical Journal. Nov, 2011 | Pubmed ID: 22028157
The aim of this study was to identify the most precise and clinically practicable parameters that predict future oral hypoglycemic agent (OHA) failure in patients with type 2 diabetes, and to determine whether these parameters are valuable in various subgroups.
Prevalence and Impact of Complications on Outcomes in Patients Hospitalized for Oral and Oropharyngeal Cancer Treatment
Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. Nov, 2011 | Pubmed ID: 22035652
We studied the association between presence of complications and hospitalization outcomes, including hospital charges, length of stay in hospital, and in-hospital mortality.
Nature Structural & Molecular Biology. Nov, 2011 | Pubmed ID: 22037170
The Saccharomyces cerevisiae proteasome comprises a 19-subunit regulatory particle and a 28-subunit core particle. To be degraded, substrates must cross the core particle-regulatory particle interface, a site for complex conformational changes and regulatory events. This interface includes two aligned heteromeric rings, one formed by the six ATPase (Rpt) subunits of the regulatory particle and the other by the seven α subunits of the core particle. The Rpt C termini bind to intersubunit cavities in the α-ring, thus directing core particle gating and proteasome assembly. We mapped the Rpt C termini to the α subunit pockets, using a cross-linking approach that revealed an unexpected asymmetry: one side of the ring shows 1:1 contacts of Rpt2-α4, Rpt6-α3 and Rpt3-α2, whereas on the opposite side, the Rpt1, Rpt4 and Rpt5 tails each cross-link to multiple α pockets. Rpt-core particle cross-links are all sensitive to nucleotides, implying that ATP hydrolysis drives dynamic alterations at the core particle-regulatory particle interface.
Retroperitoneal Hemorrhage After Endoscopic Removal of a Fish Bone Stuck in the Duodenum of a Patient Receiving Hemodialysis
The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi. Oct, 2011 | Pubmed ID: 22042422
Fish bones are often ingested accidently. Most of them passes out through the gastrointestinal tract safely, but serious complications, such as perforation, abscess, obstruction, and bleeding in the gastrointestinal tract, can occur. An ingested fish bone can be easily removed by endoscopy, and surgery is rarely required. However, there may be complications related to the endoscopic procedure including mucosal laceration, bleeding, fever, and perforation. Here, we report a case of retroperitoneal hemorrhage developed after endoscopic removal of a fish bone stuck in the duodenal wall, and then resolved spontaneously by conservative care.
Experimental and Numerical Analysis on Temporal Dynamics of Polarization Switching in an Injection-locked 1.55-μm Wavelength VCSEL
Optics Express. Aug, 2011 | Pubmed ID: 21935054
We present experimental and numerical study of temporal characteristics of injection-locked polarization switching of a conventional-type 1.55-μm wavelength single-mode vertical cavity surface-emitting laser (VCSEL). Delayed recovery response of the main-mode of the VCSEL was observed when short and strong optical injection pulses of an orthogonal polarization to the VCSEL's main polarization-mode were applied. Numerical analysis based on a spin-flip model describes that the relatively long upper level lifetimes compared to a short injection-pulse width and long cavity photon lifetimes cause delayed recovery response of the main-mode of the VCSEL. An optimum bias current of the VCSEL was also observed for the shortest recovery time of its free-running polarization mode after the orthogonal polarization beam pulse injection.
Relationship Between Microalbuminuria and Vulnerable Plaque Components in Patients with Acute Coronary Syndrome and with Diabetes Mellitus. Virtual Histology-intravascular Ultrasound
Circulation Journal : Official Journal of the Japanese Circulation Society. 2011 | Pubmed ID: 21946357
The purpose of the present study was to use virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relationship between microalbuminuria and plaque components in 920 patients.
CD105 Protein Depletion Enhances Human Adipose-derived Stromal Cell Osteogenesis Through Reduction of Transforming Growth Factor β1 (TGF-β1) Signaling
The Journal of Biological Chemistry. Nov, 2011 | Pubmed ID: 21949130
Clinically available sources of bone for repair and reconstruction are limited by the accessibility of autologous grafts, infectious risks of cadaveric materials, and durability of synthetic substitutes. Cell-based approaches for skeletal regeneration can potentially fill this need, and adipose tissue represents a promising source for development of such therapies. Here, we enriched for an osteogenic subpopulation of cells derived from human subcutaneous adipose tissue utilizing microfluidic-based single cell transcriptional analysis and fluorescence-activated cell sorting (FACS). Statistical analysis of single cell transcriptional profiles demonstrated that low expression of endoglin (CD105) correlated with a subgroup of adipose-derived cells with increased osteogenic gene expression. FACS-sorted CD105(low) cells demonstrated significantly enhanced in vitro osteogenic differentiation and in vivo bone regeneration when compared with either CD105(high) or unsorted cells. Evaluation of the endoglin pathway suggested that enhanced osteogenesis among CD105(low) adipose-derived cells is likely due to identification of a subpopulation with lower TGF-β1/Smad2 signaling. These findings thus highlight a potential avenue to promote osteogenesis in adipose-derived mesenchymal cells for skeletal regeneration.
Relation Between High-sensitivity C-reactive Protein and Coronary Plaque Components in Patients with Acute Coronary Syndrome: Virtual Histology-intravascular Ultrasound Analysis
Korean Circulation Journal. Aug, 2011 | Pubmed ID: 21949527
We used virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relationship between high-sensitivity C-reactive protein (hs-CRP) levels and plaque components in 279 acute coronary syndrome (ACS) patients.
Dalton Transactions (Cambridge, England : 2003). Nov, 2011 | Pubmed ID: 21968798
A triarylborane (2) bearing three o-carborane cages at peripheral positions on the aryl groups was prepared and its crystal structure was determined from X-ray diffraction study. Treatment of 2 with KF in the presence of 18-crown-6 led to the potassium salt, [2F](-). A UV-vis titration experiment carried out in THF/H(2)O (9/1 v/v) showed that 2 binds fluoride ions with a binding constant (K) of 4.8 × 10(4) M(-1), which is an order-of-magnitude greater than K for the mono-carborane substituted triarylborane. The enhanced fluoride ion affinity of 2 indicates an apparent additive effect of multiple carborane substitutions on the Lewis acidity enhancement of the triarylborane. The highly Lewis acidic nature of 2 was further utilized in evaluating the fluoride ion affinity of tris(pentafluorophenyl)borane (B(C(6)F(5))(3)). A fluoride exchange reaction between [2F](-) and B(C(6)F(5))(3) resulted in 15 times higher fluorophilicity for B(C(6)F(5))(3) than for 2. The lower Lewis acidity of 2 compared with B(C(6)F(5))(3) was confirmed from its greater cathodic reduction potential.
Tat Peptide-admixed Elastic Liposomal Formulation of Hirsutenone for the Treatment of Atopic Dermatitis in NC/Nga Mice
International Journal of Nanomedicine. 2011 | Pubmed ID: 22072881
The aim of the present study was to enhance a topical delivery of hirsutenone (HST), a naturally occuring immunomodulator, employing Tat peptide-admixed elastic liposomes (EL/T).
A Small Molecule That Binds to an ATPase Domain of Hsc70 Promotes Membrane Trafficking of Mutant Cystic Fibrosis Transmembrane Conductance Regulator
Journal of the American Chemical Society. Dec, 2011 | Pubmed ID: 22074182
Cystic fibrosis transmembrane conductance regulator (CFTR) is a cell-surface anion channel that permeates chloride and bicarbonate ions. The most frequent mutation of CFTR that causes cystic fibrosis is the deletion of phenylalanine at position 508 (ΔF508), which leads to defects in protein folding and cellular trafficking to the plasma membrane. The lack of the cell-surface CFTR results in a reduction in the lifespan due to chronic lung infection with progressive deterioration of lung function. Hsc70 plays a crucial role in degradation of mutant CFTR by the ubiquitin-proteasome system. To date, various Hsc70 inhibitors and transcription regulators have been tested to determine whether they correct the defective activity of mutant CFTR. However, they exhibited limited or questionable effects on restoring the chloride channel activity in cystic fibrosis cells. Herein, we show that a small molecule apoptozole (Az) has high cellular potency to promote membrane trafficking of mutant CFTR and its chloride channel activity in cystic fibrosis cells. Results from affinity chromatography and ATPase activity assay indicate that Az inhibits the ATPase activity of Hsc70 by binding to its ATPase domain. In addition, a ligand-directed protein labeling and molecular modeling studies also suggest the binding of Az to an ATPase domain, in particular, an ATP-binding pocket. It is proposed that Az suppresses ubiquitination of ΔF508-CFTR maybe by blocking interaction of the mutant with Hsc70 and CHIP, and, as a consequence, it enhances membrane trafficking of the mutant.
High Density Cultures of Embryoid Bodies Enhanced Cardiac Differentiation of Murine Embryonic Stem Cells
Biochemical and Biophysical Research Communications. Dec, 2011 | Pubmed ID: 22079290
Murine embryonic stem cell (mESC)-derived cardiomyocytes represent a promising source of cells for use in the development of models for studying early cardiac development as well as cell-based therapies in postnatal pathologies. Here, we report a highly efficient cardiac differentiation system in which high density embryoid body (EB) cultures leads to a marked increase of cardiomyocytes production from multiple mESC lines without the addition of any cardiogenic growth factors. Our results show that high density EB cultures significantly increase the yield of functional cardiomyocytes, which express typical cardiac markers, exhibit normal rhythmic Ca(2+) transients, and respond to both β-adrenergic and electric stimulations. During the differentiation period, the inhibition of bone morphogenetic protein (BMP) signaling significantly attenuates the increase of cardiac differentiation as well as the increased expression of cardiac-specific genes, NK2 transcription factor related 5 (Nkx2.5) and myosin light chain 2v (Mlc2v) by high density EB cultures. Therefore, we believe that we offer a novel and efficient means of cardiomyocyte production for practical use of mESCs in cardiac regenerative medicine.
Preparative Isolation and Purification of Antioxidative Diarylheptanoid Derivatives from Alnus Japonica by High-speed Counter-current Chromatography
Journal of Separation Science. Dec, 2011 | Pubmed ID: 22083971
This study employed the online HPLC-2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS)(+) bioassay to rapidly determine the antioxidant compounds occurring in the crude extract of Alnus japonica. The negative peaks of the ABTS(+) radical scavenging detection system, which indicated the presence of antioxidant activity, were monitored by measuring the decrease in absorbance at 734 nm. The ABTS(+)-based antioxidant activity profile showed that three negative peaks exhibited antioxidant activity. High-speed counter-current chromatography (HSCCC) was used for preparative scale separation of the three active peaks from the extract. The purity of the isolated compounds was analyzed by HPLC and their structures were identified by (1)H- and (13)C-nuclear magnetic resonance spectrometry (NMR), heteronuclear multiple bond correlation (HMBC), and heteronuclear single quantum correlation (HSQC). Two solvent systems composed of n-hexane/ethylacetate/methanol/water (4:6:4:6, v/v) and of ethyl acetate/methanol/water (1:0.1:1, v/v) were performed in high-speed counter-current chromatography. Consequently, a total of 527 mg of hirsutanonol 5-O-β-D-glucopyranoside, 80.04 mg of 3-deoxohirsutenonol 5-O-β-D-glucopyranoside, and 91.0 mg of hirsutenone were obtained with purity of 94.7, 90.5, and 98.6%, respectively.
Prevention of Free Fatty Acid-induced Hepatic Lipotoxicity by Carnitine Via Reversal of Mitochondrial Dysfunction
Liver International : Official Journal of the International Association for the Study of the Liver. Oct, 2011 | Pubmed ID: 22093454
Mitochondria are the main sites for fatty acid oxidation and play a central role in lipotoxicity and nonalcoholic steatohepatitis.
Gastroduodenal Glomus Tumors: Differentiation from Other Subepithelial Lesions Based on Dynamic Contrast-enhanced CT Findings
AJR. American Journal of Roentgenology. Dec, 2011 | Pubmed ID: 22109289
The purpose of this study was to describe the CT features of gastroduodenal glomus tumors and determine the CT features differentiating glomus tumors from other subepithelial lesions.
AJR. American Journal of Roentgenology. Dec, 2011 | Pubmed ID: 22109305
This study was designed to evaluate the frequency, morphological patterns, sequential changes, and clinical significance of venous thrombosis after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC).
Chonnam Medical Journal. Apr, 2011 | Pubmed ID: 22111057
A 76-year-old female present to the emergency department with dysarthria, dizziness, dyspnea. The patient had hypertension and atrial fibrillation. Brain MRI revealed right cerebellar infarction. Transthoracic echocardiography showed a large round mass in the left atrium. Transesophageal echocardiography showed large complex echogenic round mass lesion attached on left atrial side of interatrial septum. Coronary angiogram revealed round movable mass lesion in left atrium with feeding arteries originated from right coronary artery. She underwent removal of mass and Maze operation, and pathologic finding was compatible with myxoma.
Immune Network. Dec, 2011 | Pubmed ID: 22346784
Dextran sodium sulfate (DSS) is a widely used chemical model for inflammatory bowel disease (IBD). It is thought that imbalances in the T helper (Th) cell subsets contribute to IBD. Recent studies suggest that the acute DSS-colitis model is polarized toward a Th1/Th17 profile based on RT-PCR analysis of colonic tissues. In the current study we determined whether colonic Th cells from DSS-colitis mice were skewed toward the Th17 profile. Mice were treated with 5% DSS for 7 days and colonic T cells isolated and examined for production of IFN-γ (Th1 cell), IL-4 (Th2 cell) and IL-17 (Th17 cell) by intracellular flow cytometry. We found that the percentage of colonic Th17 cells were similar to non-treated controls but the percentage of Th1 cells were elevated in DSS-colitis mice. These results suggest that in the acute DSS-colitis model the colonic Th cells exhibit a Th1 profile and not a Th17 profile.
A 24 KDa Excretory-secretory Protein of Anisakis Simplex Larvae Could Elicit Allergic Airway Inflammation in Mice
The Korean Journal of Parasitology. Dec, 2011 | Pubmed ID: 22355204
We have reported that a 24 kDa protein (22U homologous; As22U) of Anisakis simplex larvae could elicit several Th2-related chemokine gene expressions in the intestinal epithelial cell line which means that As22U may play a role as an allergen. In order to determine the contribution of As22U to allergic reactions, we treated mice with 6 times intra-nasal application of recombinant As22U (rAs22U). In the group challenged with rAs22U and ovalbumin (OVA), the number of eosinophils in the bronchial alveolar lavage fluid (BALF) was significantly increased, as compared to the group receiving only OVA. In addition, mice treated with rAs22U and OVA showed significantly increased airway hyperresponsiveness. Thus, severe inflammation around the airway and immune cell recruitment was observed in mice treated with rAs22U plus OVA. The levels of IL-4, IL-5, and IL-13 cytokines in the BALF increased significantly after treatment with rAs22U and OVA. Similarly, the levels of anti-OVA specific IgE and IgG1 increased in mice treated with rAs22U and OVA, compared to those treated only with OVA. The Gro-α (CXCL1) gene expression in mouse lung epithelial cells increased instantly after treatment with rAs22U, and allergy-specific chemokines eotaxin (CCL11) and thymus-and-activation-regulated-chemokine (CCL17) gene expressions significantly increased at 6 hr after treatment. In conclusion, rAs22U may induce airway allergic inflammation, as the result of enhanced Th2 and Th17 responses.
Organic Letters. Mar, 2012 | Pubmed ID: 22360451
Ieodoglucomides A (1) and B (2), unique glycolipopeptides consisting of an amino acid, a new fatty acid, a succinic acid, and a sugar, were isolated from a Marine-derived bacterium Bacillus licheniformis. The absolute stereochemistry of 1 and 2 was determined by deploying coupling constants, Marfey's and Mosher's methods, and literature reviews. Compounds 1 and 2 displayed moderate in vitro antimicrobial activity. Furthermore, ieodoglucomide B (2) exhibited cytotoxic activity against lung cancer and stomach cancer cell lines with GI(50) values of 25.18 and 17.78 μg/mL, respectively.
Hypoglycemic Activity of Gymnema Sylvestre Extracts on Oxidative Stress and Antioxidant Status in Diabetic Rats
Journal of Agricultural and Food Chemistry. Mar, 2012 | Pubmed ID: 22360666
Diabetes mellitus, which is associated with oxidative damage, has a significant impact on health, quality of life, and life expectancy. An ethanol extract of Gymnema sylvestre leaf was examined in vitro and in vivo to investigate the role of antioxidants in diabetic rats. The extract exhibited strong antioxidant activity in the assays, including TBA (56%), SOD-like (92%), and ABTS (54%). Blood glucose levels in the diabetic rats fed G. sylvestre extract decreased to normal levels. The presence of the antihyperglycemic compounds gymnemagenin and gymnemic acids in G. sylvestre extract was detected by LC/MS analysis. Lipid peroxidation levels were decreased by 31.7% in serum, 9.9% in liver, and 9.1% in kidney in the diabetic rats fed the extract. Feeding G. sylvestre extract to the diabetic rats decreased the activity of glutathione peroxidase in cytosolic liver and glutamate pyruvate transaminase in serum to normal levels.
Molecular Pain. 2012 | Pubmed ID: 22364340
Minocycline prevents the development of neuropathic and inflammatory pain by inhibiting microglial activation and postsynaptic currents. But, how minocycline obviates acute visceral pain is unclear. The present study investigated whether minocycline had an any antinociceptive effect on acetic acid-induced acute abdominal pain after intraperitoneal (i.p.) administration of saline or minocycline 1 hour before acetic acid injection (1.0%, 250 μl, i.p.).
Positive Remodeling is Associated with Vulnerable Coronary Plaque Components Regardless of Clinical Presentation: Virtual Histology-intravascular Ultrasound Analysis
International Journal of Cardiology. Feb, 2012 | Pubmed ID: 22370367
OBJECTIVE: We used virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relation between coronary artery remodeling pattern and plaque components in 1133 patients. METHODS: We divided the patients into two groups according to the remodeling pattern as positive remodeling (PR, remodeling index>1.05) (n=192) and intermediate remodeling (IR, remodeling index≤1.05 and ≥0.95)/negative remodeling (NR, remodeling index<0.95) (n=941). VH-IVUS analysis classified the color-coded tissue into four major components: green (fibrotic, FT); yellow-green (fibro-fatty); white (dense calcium); and red (necrotic core, NC). Thin-cap fibroatheroma (TCFA) was defined as focal, NC-rich (≥10% of the cross-sectional area) plaques being in contact with the lumen in a plaque burden≥40%. RESULTS: At the minimum lumen site, PR group had greater plaque plus media area (12.8±4.9 vs. 9.9±3.8mm(2), p<0.001) and greater %NC area (21.7±12.3 vs. 18.2±11.6%, p<0.001) and smaller %FT area (57.0±14.5 vs. 59.4±14.6%, p=0.037) compared with IR/NR group. PR group had greater plaque volume (188±150 vs. 135±130mm(3), p<0.001) and greater %NC volume (19.1±9.6 vs. 16.6±9.2%, p=0.001) and smaller %FT volume (58.3±11.7 vs. 60.6±11.0%, p=0.009) compared with IR/NR group. PR group had more TCFA compared with IR/NR group (21% vs. 13%, p=0.006). Similar findings about plaque components were observed in terms of greater %NC volume and smaller %FT volume in PR group compared with IR/NR group in patients with both acute coronary syndrome and stable angina. CONCLUSIONS: VH-IVUS analysis demonstrates that PR was associated with more vulnerable plaque components compared with IR/NR regardless of their clinical presentation.
Journal of Cellular Physiology. Feb, 2012 | Pubmed ID: 22378347
Dogmatic views of how proteins and other cellular components may traffic within and between eukaryotic cells have been challenged in the past few years. Beyond the classical secretory/exocytic pathway and its established players, other pathways of cell surface membrane transport, generally termed "unconventional secretion," are now better understood. More insights have also been gleaned on the roles of secreted or shedding microvesicles, either exosomal or ectosomal in origin, in unconventional secretion. Recent works have also revealed key molecular components, particularly the Golgi reassembly stacking protein (GRASP), and the importance of stress-induced autophagy, in unconventional exocytic transport. This GRASP and autophagy-dependent (GAD) mode appears to underlie the unconventional exocytosis of many soluble and membrane cargoes. Likewise, recent findings have revealed transport processes that contrast the classically known mitochondria import, namely vesicular transport from the mitochondria to peroxisomes and lysosomes. Mitochondria-peroxisomal targeting of mitochondria-derived vesicles appears to involve the retromer complex, which was classically associated with endosome-Golgi membrane traffic. The routes of intracellular membrane transport and communications between eukaryotic organelles now appear far more complex that one would have imagined 10 years ago.
Requirement of Protein L-isoaspartyl O-methyltransferase for Transcriptional Activation of Trefoil Factor 1 (TFF1) Gene by Estrogen Receptor Alpha
Biochemical and Biophysical Research Communications. Apr, 2012 | Pubmed ID: 22382029
Lysine- and arginine-specific methyltransferases have been shown to act as either direct or secondary transcriptional co-activator of the estrogen receptor (ERα). However, little is known about the role of protein l-isoaspartyl O-methyltransferase (PIMT) on transcriptional regulation. Here, we show that PIMT acts as a co-activator for ERα-mediated transcription. Activation of the estrogen response element (ERE) promoter by β-estradiol (E(2)) was suppressed by knockdown of PIMT, and enhanced by overexpression of wild-type PIMT. However, the ERE promoter activity was resistant to E(2) stimulation in cells overexpressing a catalytically inactive PIMT mutant, G88A. Consistent with these results, the expression of the endogenous ERα response gene trefoil factor 1 (TFF1) by E(2) was completely abrogated by PIMT depletion and decreased to approximately 50% when PIMT mutant G88A was expressed. In addition, over-expression of PIMT significantly increased the levels of TFF1 mRNA in the presence or absence of E(2). Interestingly, PIMT interacted with ERα and was distributed to the cytosol and the nucleus. The chromatin immunoprecipitation analysis revealed that PIMT was recruited to the promoter of TFF1 gene together with ERα in an E(2)-dependent manner, which was accompanied by uploading of RNA polymerase II on the promoter. Taken together, the results suggest that PIMT may act as a co-activator in ERα-mediated transcription through its recruitment to the promoter via interacting with ERα.
Prevalence of BRCA1 and BRCA2 Mutations in Non-familial Breast Cancer Patients with High Risks in Korea: the Korean Hereditary Breast Cancer (KOHBRA) Study
Breast Cancer Research and Treatment. Mar, 2012 | Pubmed ID: 22382806
Prevalence and phenotype of BRCA mutation can vary by race. The purpose of this study is to evaluate the prevalence of BRCA1/2 mutations in non-familial breast cancer patients with high risks in Korea. A subset of 758 patients was selected for this study from the KOHBRA nationwide multicenter prospective cohort study. Mutations in BRCA1/2 genes were tested using fluorescent-conformation sensitive gel electrophoresis, denaturing high performance liquid chromatography or direct sequencing. Mutation of BRCA1/2 genes were identified in 65 (8.6%) patients among total 758 patients [BRCA1 mutation: 25 (3.3%), BRCA2 mutation: 40 (5.3%)]. According to risk groups, mutation of BRCA1/2 genes were identified in 53 (8.5%) of 625 early onset patients (age ≤ 40), in 22 (17.7%) of 124 bilateral breast cancer patients, in 3 (50.0%) of 6 breast and ovarian cancer patients, in one (5.9%) of 17 male breast cancer patients, in 5 cases (7.6%) of 66 multiple organ cancer patients. The most common mutation was 509C>A for BRCA1 and 7708C>T for BRCA2. The prevalence of BRCA1/2 mutations by age in early onset patients was significantly different (age <35 vs age ≥35; 10.0 vs 2.9%, p = 0.0007). BRCA1/2 mutations for non-familial Korean breast cancer patients were detected at a high rate, particularly, in patients with early onset of less than 35 years of age, bilateral breast cancer, and breast and ovarian cancer. Individualized genetic counseling should be offered for non-familial breast cancer patients with these risk factors.
PLoS Genetics. Feb, 2012 | Pubmed ID: 22383897
Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8×10(-12) in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85-0.94) and 0.80 (0.75-0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9×10(-6) from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6×10(-7)), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively.
Development and Validation of a Screening Scale for Depression in Korea: the Lee and Rhee Depression Scale
Psychiatry Investigation. Mar, 2012 | Pubmed ID: 22396683
The aim of this study was to develop a culturally sensitive instrument that addressed how individuals express and experience depression to detect this disorder in Koreans. We also assessed the validity, reliability, and diagnostic utility of this scale (Lee and Rhee Depression Scale; LRDS).
Fibroblast Growth Factor-21 Protects Human Skeletal Muscle Myotubes from Palmitate-induced Insulin Resistance by Inhibiting Stress Kinase and NF-κB
Metabolism: Clinical and Experimental. Mar, 2012 | Pubmed ID: 22398021
We investigated the effects of fibroblast growth factor-21 (FGF-21) on palmitate-induced insulin resistance in skeletal muscle myotubes. First, to determine the effect of FGF-21 on palmitate-induced insulin resistance, we measured 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose uptake and levels of proteins involved in insulin signaling pathways (IRS-1 and Akt) in human skeletal muscle myotubes (HSMMs) exposed to palmitate for 24h, and compared HSMMs exposed to palmitate and different doses of recombinant FGF-21. Second, to determine the mechanisms underlying the contribution of FGF-21 to palmitate-induced insulin resistance, we compared levels of proteins linked to palmitate-induced insulin resistance (PKC-θ, IKKα/β, JNK, p38, IκBα, and NF-κB) in HSMMs exposed to palmitate and different doses of recombinant FGF-21 for 24h. Palmitate-reduced glucose uptake was restored by FGF-21. Palmitate inhibited phosphorylation of Akt and thereby impaired insulin signaling in HSMMs. FGF-21 prevented palmitate from inhibiting the phosphorylation of Akt. These results indicate that FGF-21 prevented palmitate-induced insulin resistance in HSMMs. Palmitate activated NF-κB in HSMMs, thereby impairing the action of insulin and initiating chronic inflammation. FGF-21 inhibited palmitate-induced NF-κB activation in HSMMs. The results of the present study suggest that FGF-21 prevents palmitate-induced insulin resistance in HSMMs by inhibiting the activation of stress kinase and NF-κB.
Lung Cancer (Amsterdam, Netherlands). May, 2012 | Pubmed ID: 22398139
Chordomas are rare, low-grade, primary malignant bone tumors that are locally invasive and frequently recur. Despite the provision of radical excision as a primary treatment, local recurrences ultimately develop in most patients with chordoma. For these reasons, postoperative therapy such as radiation therapy is often required. However, the chemotherapy, as the treatment of chordoma relapse, has not only limited experiences but also considerable controversy on its effectiveness. In addition, in the case of pulmonary nodules, it is difficult to diagnose or suspect pulmonary metastatic chordoma initially due to its rarity and similar histologic features to other malignancies. Herein, we present an interesting case of metastatic chordoma in a 52-year old woman, which has been well controlled by platinum-based chemotherapy.
Chemical Communications (Cambridge, England). Apr, 2012 | Pubmed ID: 22399017
A new diarylethene-derived photochromic compound, with little cytotoxicity, plasma membrane-permeability, and efficient photoswitchability in cells upon alternative UV and visible light irradiation, was synthesized and applied to live cell imaging.
Multigene Methylation Analysis of Ocular Adnexal MALT Lymphoma and Their Relationship to Chlamydophila Psittaci Infection and Clinical Characteristics in South Korea
Investigative Ophthalmology & Visual Science. 2012 | Pubmed ID: 22410569
We investigated the aberrant promoter methylation status of known or suspected tumor suppressor genes in ocular adnexal lymphoma (OAL) and the possible association with clinical characteristics and Chlamydophila psittaci infection.
Multivariate Analysis of the Survival Rate for Treatment Modalities in Incurable Stage IV Colorectal Cancer
Journal of the Korean Society of Coloproctology. Feb, 2012 | Pubmed ID: 22413080
The aim of this study was to compare survival in patients that underwent palliative resection treatment versus non-resection for incurable colorectal cancer (ICRC).
Hyperbranched Double Hydrophilic Block Copolymer Micelles of Poly(ethylene Oxide) and Polyglycerol for PH-responsive Drug Delivery
Biomacromolecules. Apr, 2012 | Pubmed ID: 22414172
We report the synthesis of a well-defined hyperbranched double hydrophilic block copolymer of poly(ethylene oxide)-hyperbranched-polyglycerol (PEO-hb-PG) to develop an efficient drug delivery system. In specific, we demonstrate the hyperbranched PEO-hb-PG can form a self-assembled micellar structure on conjugation with the hydrophobic anticancer agent doxorubicin, which is linked to the polymer by pH-sensitive hydrazone bonds, resulting in a pH-responsive controlled release of doxorubicin. Dynamic light scattering, atomic force microscopy, and transmission electron microscopy demonstrated successful formation of the spherical core-shell type micelles with an average size of about 200 nm. Moreover, the pH-responsive release of doxorubicin and in vitro cytotoxicity studies revealed the controlled stimuli-responsive drug delivery system desirable for enhanced efficiency. Benefiting from many desirable features of hyperbranched double hydrophilic block copolymers such as enhanced biocompatibility, increased water solubility, and drug loading efficiency as well as improved clearance of the polymer after drug release, we believe that double hydrophilic block copolymer will provide a versatile platform to develop excellent drug delivery systems for effective treatment of cancer.
Sequential Treatment of PTA Wastewater in a Two-stage UASB Process: Focusing on P-toluate Degradation and Microbial Distribution
Water Research. May, 2012 | Pubmed ID: 22417741
Two-stage upflow anaerobic sludge blanket (UASB) process was investigated as an efficient process configuration option for the treatment of purified terephthalic acid (PTA) wastewater. To study its feasibility in a defined condition, synthetic wastewater containing only the major pollutants (i.e., acetate, benzoate, terephthalate and p-toluate) was used. By focusing the role of the second stage on the p-toluate degradation, improved overall COD and p-toluate removal capacities of 4.18 and 1.35 g-thCOD/L·day could be achieved together with a complete COD removal efficiency. In this situation, all the pollutants except p-toluate were completely degraded in the first stage while 38 and 62% of p-toluate originally present in the wastewater were consecutively degraded in the individual stages. The concomitant methane production rate in each stage was 0.91 and 0.35 L/L·day respectively, and the methane yield on p-toluate was determined to be 0.12 L/g-thCOD. Batch tests using the granules obtained from each stage revealed that the acidogenic microorganisms enriched in both stages had a universal ability to degrade all aromatic pollutants present in the PTA wastewater. Moreover, image analysis using scanning electron microscope and confocal laser scanning microscopy combined with fluorescence in situ hybridization technique elucidated that the distribution of acidogens and methanogens within the granule was varied in each stage, which influenced the mass transfer regime resulting in the different pollutant degradation rates during the batch tests.
Macromolecular Rapid Communications. Mar, 2012 | Pubmed ID: 22434580
Vinyl addition homo- and copolymerization of norbornene monomer (M1) functionalized with a PCBM moiety using a Pd(II) catalyst in combination with a 1-octene chain transfer agent efficiently produces polynorbornenes with side-chain PCBM groups. Characterization by NMR spectroscopy and elemental analysis reveals that the copolymers constitute a well-defined polymer structure with controlled incorporation of M1. Although the homopolymer is insoluble in organic solvents, the copolymers containing 62 mol% (P2) and 50 mol% (P3) of the PCBM moiety are soluble in chlorinated solvents such as o-dichlorobenzene. The bulk-heterojunction organic photovoltaic devices fabricated based on the P3HT:P3 blends show that P3 can adequately function as an electron acceptor, leading to a cell with a power conversion efficiency of 1.5%, which is outstanding among the polymeric rivals.
Comparison of Four Immunohistochemical Tests and FISH for Measuring HER2 Expression in Gastric Carcinomas
Pathology. Apr, 2012 | Pubmed ID: 22437741
: Accurate testing for HER2 is essential to identify patients who are likely to benefit from trastuzumab therapy. Although comparative studies on the performance of commercially available immunohistochemistry (IHC) antibodies for HER2 have been performed in breast cancer, similar studies have not been done in gastric carcinoma (GC) thus far.
Breast Cancer Research and Treatment. Mar, 2012 | Pubmed ID: 22438049
BRCAPRO and Myriad II are widely used models for predicting BRCA1/2 mutation probability before genetic testing. However, the accuracy of these models in Koreans is not known. This study was performed to evaluate the accuracy of the BRCAPRO and Myriad II models. Two hundred thirty-six women with breast cancer who underwent comprehensive BRCA1/2 genetic testing at our hospital between 2003 and 2010 were included in this study. We evaluated the performance of each model by comparing the numbers of observed versus predicted mutation carriers. We calculated sensitivity, specificity, and predictive values at 10 % estimated probability. Forty-six individuals were identified to carry a deleterious BRCA mutation. The prevalence of BRCA mutation (19.5 %) was significantly higher than that predicted by BRCAPRO (9.0 %, p = 0.001) and Myriad (5.6 %, p < 0.001). In familial breast cancer patients, BRCA mutation rate (observed 22.7 %) was underestimated by both BRCAPRO (expected 11.4 %, p = 0.006) and Myriad II (expected 6.4 %, p < 0.001). Subgroup analyses showed that both models underestimated the risk of BRCA mutation in patients with a family history of breast cancer (probands' age at breast cancer diagnosis >50 years), with only one relative with breast cancer, and with non-familial early-onset breast cancer or bilateral breast cancer. Using a 10 % cut-off, the sensitivities were 47.8 % (BRCAPRO) and 50.0 % (Myriad), and positive predictive values were 44.9 % (BRCAPRO) and 43.4 % (Myriad). Both BRCAPRO and Myriad II underestimated the risk of BRCA1/2 mutation in Koreans. Our findings suggest that these models are less sensitive in Korean women, and therefore a new BRCA mutation prediction model based on Korean data is needed for proper genetic counseling.
Beta-tricalcium Phosphate Particles As a Controlled Release Carrier of Osteogenic Proteins for Bone Tissue Engineering
Journal of Biomedical Materials Research. Part A. Jul, 2012 | Pubmed ID: 22447727
Beta-tricalcium phosphate (β-TCP) has been widely used as bone substitutes and delivery carriers of osteogenic proteins. However, low protein carrying capacity and agent burst release profiles of β-TCP limit their usage. This study investigates strategies to enhance protein carrying capacity of β-TCP particles with reduced initial burst by surface etching in citric acid solution or by creating apatite coatings with the simulate body fluid immersion approach. The release kinetics of protein from the modified β-TCP particles was investigated using Nel-like molecule-1 (Nell-1), a novel osteogenic protein, as a model protein. Although chemical etching treatments reduced the initial burst release of protein from the particles, a rapid burst release was observed with high protein dose. In contrast, the burst release of protein was significantly reduced by the apatite coating and a high protein dose was successfully delivered over a prolonged period from the apatite-coated particles. Protein release was further modulated by simultaneously delivering proteins from two different substrates: acid-etched and apatite-coated particles. The bioactivity of the protein was preserved during the loading procedure onto the particles. In addition, protein-loaded particles maintained biological activity in the lyophilized state over 4 weeks. These findings suggest that the protein carrying capacity of β-TCP can be modulated by surface modification, which has a potential for use as a protein carrier with controlled release.
AJR. American Journal of Roentgenology. Apr, 2012 | Pubmed ID: 22451556
The purpose of this article is to determine whether bright rim lesions on MRI are a marker for anterior talofibular ligament injury.
A Genome-wide Association Study Identifies a Breast Cancer Risk Variant in ERBB4 at 2q34: Results from the Seoul Breast Cancer Study
Breast Cancer Research : BCR. Mar, 2012 | Pubmed ID: 22452962
Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent.
Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. Mar, 2012 | Pubmed ID: 22453629
Hypoglycemia-induced cerebral neuropathy can occur in patients with diabetes who attempt tight control of blood glucose and may lead to cognitive dysfunction. Accumulating evidence from animal models suggests that hypoglycemia-induced neuronal death is not a simple result of glucose deprivation, but is instead the end result of a multifactorial process. In particular, the excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) consumes cytosolic nicotinamide adenine dinucleotide (NAD(+)), resulting in energy failure. In this study, we investigate whether lactate administration in the absence of cytosolic NAD(+) affords neuroprotection against hypoglycemia-induced neuronal death. Intraperitoneal injection of sodium L-lactate corrected arterial blood pH and blood lactate concentration after hypoglycemia. Lactate administered without glucose was not sufficient to promote electroencephalogram recovery from an isoelectric state during hypoglycemia. However, supplementation of glucose with lactate reduced neuronal death by ∼80% in the hippocampus. Hypoglycemia-induced superoxide production and microglia activation was also substantially reduced by administration of lactate. Taken together, these results suggest an intriguing possibility: that increasing brain lactate following hypoglycemia offsets the decrease in NAD(+) due to overactivation of PARP-1 by acting as an alternative energy substrate that can effectively bypass glycolysis and be fed directly to the citric acid cycle to maintain cellular ATP levels.
Guanylate Cyclase Activator YC-1 Potentiates Apoptotic Effect of Licochalcone A on Human Epithelial Ovarian Carcinoma Cells Via Activation of Death Receptor and Mitochondrial Pathways
European Journal of Pharmacology. May, 2012 | Pubmed ID: 22465181
Natural phenol licorice compounds have been shown to induce apoptosis in cancer cells. 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) may enhance the sensitivity of cancer cells to anticancer drugs. However, the combined effect of licochalcone A and YC-1 on cell death in ovarian cancer cells has not been studied. We assessed the combined effect of licochalcone A and YC-1 on apoptosis in human epithelial ovarian carcinoma cell lines in relation to the cell death process. In the OVCAR-3 and SK-OV-3 cell lines, licochalocone A induced a decrease in Bid, Bcl-2, Bcl-xL and survivin protein levels; an increase in Bax levels; loss of the mitochondrial transmembrane potential; cytochrome c release; activation of caspases (-8, -9 and -3); cleavage of PARP-1; and an increase in the tumor suppressor p53 levels. YC-1 enhanced licochalcone A-induced apoptosis-related protein activation, nuclear damage and cell death. These results suggest that YC-1 may potentiate the apoptotic effect of licochalcone A on ovarian carcinoma cell lines by increasing the activation of the caspase-8- and Bid-dependent pathway and the mitochondria-mediated apoptotic pathway, leading to caspase activation. The combination of licochalcone A and YC-1 may confer a benefit in the treatment of human epithelial ovarian adenocarcinoma.
Preparative Isolation and Purification of Neuroprotective Compounds from Rhus Verniciflua by High Speed Counter-current Chromatography
Biological & Pharmaceutical Bulletin. 2012 | Pubmed ID: 22466561
In the present study, extracts from Rhus verniciflua were demonstrated to significantly attenuate the negative effects of hydrogen peroxide (H(2)O(2)) on transformed retinal ganglion cell line (RGC-5 cells), indicating that they may be protective against oxidative stress-induced retinal degeneration. The inclusion of R. verniciflua in the culture was found to both reduce the levels of reactive oxygen species (ROS) present and lessen the up-regulation of apoptotic proteins such as cleaved poly(ADP-ribose) polymerase, cleaved caspase-3, and cleaved caspase-9. Active compounds were also successfully isolated from R. verniciflua using high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (3.5:5:3.5:5, v/v). Using this method, we successfully separated 252.1 mg of fustin at a purity of over 93.09%, 51.2 mg of fisetin at a purity of over 95.45%, 39.7 mg of sulfuretin at a purity of over 95.17%, and 10.7 mg of butein at a purity of over 95.01% from 1.5 g of R. verniciflua extract. The chemical structures of these compounds were elucidated by chemical and spectral analyses. There isolated compounds also significantly attenuated the negative effects of H(2)O(2) on RGC-5 cells. Results therefore suggest that, due to its anti-oxidative and anti-apoptotic effects, R. verniciflua could be used as a lead substance for the treatment of retinal diseases such as glaucoma.
Abdominal Imaging. Apr, 2012 | Pubmed ID: 22467060
Current guidelines advocate percutaneous radiofrequency (RF) ablation as a standard treatment of early stage hepatocellular carcinoma (HCC) for up to three tumors ≤3 cm in diameter. The local efficacy evaluated with short-term radiological examination may be overrated, whereas that assessed by histopathological measure might be underestimated. Long-term clinical follow-up studies guarantee the effectiveness of RF ablation for small HCC, which is now almost comparable in benefits to surgical resection. US is the most common guiding modality for percutaneous RF ablation for small HCC. However, the technical feasibility is often limited due to poor conspicuity of the index tumor on US. Implementation of artificial ascites, contrast-enhanced harmonic US, and fusion imaging of US with CT/MR can be helpful to enhance the technical feasibility of US-guided RF ablation of small HCC.
Relation Between Anemia and Vulnerable Coronary Plaque Components in Patients with Acute Coronary Syndrome: Virtual Histology-intravascular Ultrasound Analysis
Journal of Korean Medical Science. Apr, 2012 | Pubmed ID: 22468099
The aim of the present study was to evaluate the plaque components and the predictors of thin-cap fibroatheroma (TCFA) in anemic patients with acute coronary syndrome using virtual histology-intravascular ultrasound (VH-IVUS). Anemia was defined according to criteria of the World Health Organization, (i.e. , hemoglobin levels < 13 g/dL in men and < 12 g/dL in women) and we compared VH-IVUS findings between anemia group (171 patients, 260 lesions) and non-anemia group (569 patients, 881 lesions). Anemia group had greater % necrotic core (NC) volume (21% ± 9% vs 19% ± 9%, P = 0.001) compared with non-anemia group. Hemoglobin level correlated negatively with absolute NC volume (r = -0.235, P < 0.001) and %NC volume (r = -0.209, P < 0.001). Independent predictors of TCFA by multivariate analysis were diabetes mellitus (odds ratio [OR], 2.213; 95% confidence interval [CI], 1.403-3.612, P = 0.006), high-sensitivity C-reactive protein (OR, 1.143; 95% CI, 1.058-1.304, P = 0.012), microalbuminuria (albumin levels of 30 to 300 mg/g of creatinine) (OR, 2.124; 95% CI, 1.041-3.214, P = 0.018), and anemia (OR: 2.112; 95% CI 1.022-3.208, P = 0.028). VH-IVUS analysis demonstrates that anemia at the time of clinical presentation is associated with vulnerable plaque component in patients with acute coronary syndrome.
Aberrant L1 Cell Adhesion Molecule Affects Tumor Behavior and Chemosensitivity in Anaplastic Thyroid Carcinoma
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. May, 2012 | Pubmed ID: 22472175
Anaplastic thyroid carcinoma (ATC) is one of the most invasive human cancers and has a poor prognosis. Molecular targets of ATC that determine its highly aggressive nature remain unidentified. This study investigated L1 cell adhesion molecule (L1CAM) expression and its role in tumorigenesis of ATCs.
Myoid Angioendothelioma of the Spleen Mimicking Metastatic Disease in a Patient with Rectal Cancer: a Radiologic-pathologic Correlation
Annals of Diagnostic Pathology. Apr, 2012 | Pubmed ID: 22476050
Myoid angioendothelioma of the spleen is an uncommon, benign vascular tumor that is morphologically characterized by a composite of vascular spaces and stromal cells with myoid feature. Herein, we report a case of the myoid angioendothelioma of the spleen, concurrent with rectal adenocarcinoma. A 41-year-old woman presented with hematochezia for several weeks. Grossly, the rectal mass was a 2.5 × 2-cm ulcerative fungating lesion. The splenic mass was a 2.2 × 2-cm well-circumscribed lesion. Microscopically, the rectal mass was a well-differentiated adenocarcinoma that invaded into the pericolic adipose tissue. The splenic mass was composed of slit-like vascular spaces and fascicles of elongated stromal cells. Vascular endothelial cells were immunopositive for CD31, factor VIII-related antigen, and CD34 but negative for CD8. Stromal cells were immunopositive for smooth muscle actin but negative for desmin.
Archives of Pharmacal Research. Mar, 2012 | Pubmed ID: 22477185
The ubiquitin-proteasome system (UPS) harbors elaborated protein quality control systems in eukaryotic cells. Recently, the UPS is emerging as an important regulator in controlling the magnitude and the duration of the steroid hormone responses. Upon steroid hormone stimuli, their cognate steroid receptors, including androgen receptor (AR) and estrogen receptor (ER), not only mediate transcriptional activation, but also undergo ubiquitination and consequent proteasomal degradation. Many reports have strongly suggested that UPS machinery, particularly the E3 ubiquitin ligases, are closely involved in the receptor-mediated gene expression regulation. Both ligand-dependent and -independent recruitment of E3 ubiquitin ligases often prompt the degradation of target steroid receptors and correct transcription activation. Here, we review that the deep mechanistic connections between AR and ER-dependent transcription and the UPS for the correct expression of target genes. We also emphasize that this regulatory system has a significant potential for future clinical application, including the treatment of breast and prostate cancers by facilitating the degradation of related hormone receptors.
World Journal of Surgical Oncology. 2012 | Pubmed ID: 22482828
The tumor-associated calcium signal transducer (TACSTD) genes, originally designated epithelial cell adhesion molecule (EpCAM) and TROP2, represent true oncogenes. Little is known about EpCAM and TROP2 gene expression in non-small cell lung carcinoma (NSCLC). This study evaluated EpCAM and TROP2 protein expression and clinicopathologic significance in cases of NSCLC.
Additive Impact of Diabetes Mellitus on Patients with Metabolic Syndrome and Acute ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
International Journal of Cardiology. May, 2012 | Pubmed ID: 22483421
Journal of Proteomics. Mar, 2012 | Pubmed ID: 22484055
Bovine pregnancy is commonly diagnosed by rectal palpation or ultrasonography and changes in progesterone concentration. To determine a simpler and less expensive diagnostic method, we sought to identify early pregnancy-specific proteins in bovine milk by comparing samples collected from pregnant and non-pregnant Holstein cattle. Of the 600-700 protein spots visible on 2-DE gel images, 39 were differentially expressed in milk from pregnant and non-pregnant cattle. Antibodies generated against synthetic peptides of milk whey proteins expressed specifically during pregnancy were used to confirm protein expression patterns. Western blot analysis showed that the levels of expression of lactoferrin (lactotransferrin) and alpha1G T-type calcium channel subunit (alpha-1G) were higher in samples from pregnant than non-pregnant cattle. These findings suggest that assays for pregnancy-specific milk proteins may be used to diagnose pregnancy in cattle.
Journal of the Korean Surgical Society. Apr, 2012 | Pubmed ID: 22493763
The aim of this study was to determine the incidence and duration of postoperative pneumoperitoneum on plain radiographs and to identify the radiologic findings associated with anastomotic leakage.
Antimicrobial Agents and Chemotherapy. Apr, 2012 | Pubmed ID: 22508297
Asunaprevir (BMS-650032) is a potent hepatitis C virus (HCV) NS3 protease inhibitor demonstrating efficacy in alfa interferon-sparing, direct-acting antiviral dual-combination regimens (together with the NS5A replication complex inhibitor daclatasvir) in patients chronically infected with HCV genotype 1b. Here, we describe a comprehensive in vitro genotypic and phenotypic analysis of asunaprevir-associated resistance against genotypes 1a and 1b using HCV replicons and patient samples obtained from clinical studies of short-term asunaprevir monotherapy. During genotype 1a resistance selection using HCV replicons, the primary NS3 protease substitutions identified were R155K, D168G, and I170T, which conferred low- to moderate-level asunaprevir resistance (5- to 21-fold) in transient-transfection susceptibility assays. For genotype 1b, a higher level of asunaprevir-associated resistance was observed at the same selection pressures, ranging from 170- to 400-fold relative to the wild-type control. The primary NS3 protease substitutions identified occurred predominantly at amino acid residue D168 (D168A/G/H/V/Y) and were associated with high-level asunaprevir resistance (16- to 280-fold) and impaired replication capacity. In asunaprevir single-ascending-dose and 3-day multiple-ascending-dose studies in HCV genotype 1a- or 1b-infected patients, the predominant pre-existing NS3 baseline polymorphism was NS3-Q80K. This substitution impacted initial virologic response rates in a single-ascending-dose study, but its effects after multiple doses were more ambiguous. Interestingly, for patient NS3 protease sequences containing Q80 and those containing K80, susceptibilities to asunaprevir were comparable when tested in an enzyme assay. No resistance-associated variants emerged in these clinical studies that significantly impacted susceptibility to asunaprevir. Importantly, asunaprevir-resistant replicons remained susceptible to an NS5A replication complex inhibitor, consistent with a role for asunaprevir in combination therapies.
Luminescence : the Journal of Biological and Chemical Luminescence. Apr, 2012 | Pubmed ID: 22511620
We prepared an aminothiourea-derived Schiff base (DA) as a fluorescent chemosensor for Hg(2+) ions. Addition of 1 equiv of Hg(2+) ions to the aqueous solution of DA gave rise to an obvious fluorescence enhancement and the subsequent addition of more Hg(2+) induced gradual fluorescence quenching. Other competing ions, including Pb(2+) , Cd(2+) , Cr(3+) , Zn(2+) , Fe(2+) , Co(3+) , Ni(2+) , Ca(2+) , Mg(2+) , K(+) and Na(+) , did not induce any distinct fluorescence changes, indicating that DA can selectively detect Hg(2+) ions in aqueous solution. Copyright © 2012 John Wiley & Sons, Ltd.
Nanotechnology. May, 2012 | Pubmed ID: 22516621
A tri-stable memristive switching was demonstrated on a Pt/TiO₂/Pt device and its underlying mechanism was suggested through a series of electrical measurements. Tri-stable switching could be initiated from a device in unipolar reset status. The unipolar reset status was obtained by performing an electroforming step on a pristine cell which was then followed by unipolar reset switching. It was postulated that tri-stable switching occurred at the location where the conductive filament (initially formed by the electroforming step) was ruptured by a subsequent unipolar reset process. The mechanism of the tri-stable memristive switching presented in this article was attributed to the migration of oxygen ions through the ruptured filament region and the resulting modulation of the Schottky-like interfaces. The assertion was further supported by a comparison study performed on a Pt/TiO₂/TiO(2-x)/Pt cell.
Investigational New Drugs. Apr, 2012 | Pubmed ID: 22526834
Substituted 2-pyrones are important structural sub-units present in a number of natural products having broad range of biological activity. However, little is known about the anti-cancer effect of 2-pyrone derivatives including leukemia. Therefore, this present study was undertaken to investigate the effect of 2-pyrone derivatives in human acute myeloid leukemia (AML). Among 23 synthesized derivatives, 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (code name; pyrone 9) showed the most potent antileukemic activity with 5 × 10(-6) M to 5 × 10(-5) M of IC(50) in various AML cell lines as well as primary leukemic blasts from AML patients, while normal peripheral blood mononuclear cells was not affected by pyrone 9. Flow cytometric analysis indicated that pyrone 9 induced the G1 and G2 phase dual arrest of the cell cycle in HL-60 cells. To address the mechanism of the antileukemic effect of pyrone 9, we examined the effect of pyrone 9 on cell cycle-related proteins in HL-60 cell. The levels of CDK2, CDK4, CDK6, CDK1, cyclin B1 and cyclin E were decreased; in contrast, cyclin A was not altered. In addition, pyrone 9 not only increased the p27 level but also enhanced its binding to with CDK2, CDK4 and CDK6 which resulted in the reduction of CDK2-, CDK4- and CDK6-associated kinase activities. Pyrone 9 also induced the apoptosis in HL-60 cells. The apoptotic process of HL-60 cells was associated with increased Bax, decreased Bcl-2 and activation of caspase-8, -9, -3 and PARP. Antileukemic effect of pyrone 9 was associated with activation of mitogen-activated protein kinase (MAPK) pathway, as evidenced by activation of p-ERK and p38 MAPK. In addition, pyrone 9 was influenced PI3 kinase pathway. Expressions of p-Akt (ser473), p-Raf, and p-PDK were down-regulated; in contrast, those of PTEN and p-PTEN were up-regulated. Furthermore, pyrone 9 suppressed NF-κB pathway signaling. To gain insights into the antileukemic activity of pyrone 9 in vivo, BALB/c mouse leukemic model was established using intraperitoneal inoculation of syngeneic WEHI-3BD(+) mouse leukemic cells. Pyrone 9 inhibited in vitro and in vivo the growth of WEHI-3BD(+) cells, and ultimately, prolonged the survival of pyrone 9-treated mice. These findings suggest that the pyrone 9 inhibits the cell proliferation of human AML cell line, HL-60, through MAPK and PI3 kinase pathway as well as induction of cell cycle arrest. In particular, pyrone 9 prolonged the survival of pyrone 9-treated leukemic mice.
European Journal of Endocrinology / European Federation of Endocrine Societies. Apr, 2012 | Pubmed ID: 22535643
The genetic mutations causing the constitutive activation of MEK/ERK have been regarded as an initiating factor in papillary thyroid carcinoma (PTC). The ERK-specific dual specificity phosphatase 6 (DUSP6) is part of the ERK-dependent transcriptional output. Therefore, the coordinated regulation of the activities of ERK kinases and DUSP6 may need to be reestablished to make new balances in PTC.
Detection and Characterization of Small Focal Hepatic Lesions (≤2.5 Cm in Diameter): a Comparison of Diffusion-weighted Images Before and After Administration of Gadoxetic Acid Disodium at 3.0T
Acta Radiologica (Stockholm, Sweden : 1987). Apr, 2012 | Pubmed ID: 22535883
As diffusion-weighted imaging (DWI) is routinely incorporated into the standard clinical protocol, it is clinically relevant to determine whether DWI after gadoxetic acid is comparable to pre-contrast DWI, with regard to the detection and characterization of focal liver lesions.
Purification and Characterization of an Antimicrobial Histone H1-like Protein and Its Gene from the Testes of Olive Flounder, Paralichthys Olivaceus
Fish & Shellfish Immunology. Apr, 2012 | Pubmed ID: 22538352
An approximately 21 kDa antimicrobial protein was purified from an acidified testis extract of olive flounder, Paralichthys olivaceus, by ion-exchange and C(18) reversed-phase HPLC. A comparison of the N-terminal amino acid sequence with those of other known antimicrobial polypeptides revealed high homology between this antimicrobial protein and other histone H1 molecules; thus, it was designated flounder histone H1-like protein (fH1LP). fH1LP showed potent antimicrobial activity against Gram-positive bacteria, including Bacillus subtilis, Staphylococcus aureus, and Streptococcus iniae (minimal effective concentrations [MECs], 2.8-30.0 μg/ml), Gram-negative bacteria, including Aeromonas hydrophila, Escherichia coli D31, Vibrio parahaemolyticus (MECs, 1.4-12.0 μg/ml), and Candida albicans (MEC, 2.0 μg/ml). cDNA cloning and tissue distribution studies of fH1LP indicated that it is constitutively expressed in testis and ovary. The fH1LP expression level was significantly dependent on developmental stage, and decreased dramatically after hatching. However, lipopolysaccharide stimulation did not induce fH1LP mRNA in other immune organs, including the kidney and spleen. These results suggest that fH1LP plays an important role in innate immunity in fish during reproduction, including mating, fertilization, and hatching.
Molecular Pharmacology. May, 2012 | Pubmed ID: 22550094
Abnormal activation of the canonical Wnt/β-catenin pathway and up-regulation of the β-catenin/T-cell factor (TCF) response to transcriptional signaling play a critical role early in colorectal carcinogenesis. Therefore, Wnt/β-catenin signaling is considered an attractive target for cancer chemotherapeutic or chemopreventive agents. Small molecules derived from the natural products were used in our cell-based reporter gene assay to identify potential inhibitors of Wnt/β-catenin signaling. Magnolol, a neolignan from the cortex of Magnolia obovata, was identified as a promising candidate because it effectively inhibited β-catenin/TCF reporter gene (TOPflash) activity. Magnolol also suppressed Wnt3a-induced β-catenin translocation and subsequent target gene expression in human embryonic kidney 293 cells. To further investigate the precise mechanisms of action in the regulation of Wnt/β-catenin signaling by magnolol, we performed Western blot analysis, real-time reverse transcriptase-polymerase chain reactions, and an electrophoretic mobility shift assay in human colon cancer cells with aberrantly activated Wnt/β-catenin signaling. Magnolol inhibited the nuclear translocation of β-catenin and significantly suppressed the binding of β-catenin/TCF complexes onto their specific DNA-binding sites in the nucleus. These events led to the down-regulation of β-catenin/TCF-targeted downstream genes such as c-myc, matrix metalloproteinase-7, and urokinase-type plasminogen activator in SW480 and HCT116 human colon cancer cells. In addition, magnolol inhibited the invasion and motility of tumor cells and exhibited antitumor activity in a xenograft nude mouse model bearing HCT116 cells. These findings suggest that the growth inhibition of magnolol against human colon cancer cells can be partly attributed to the regulation of the Wnt/β-catenin signaling pathway.
TRPM8 Ion Channel is Aberrantly Expressed and Required for Preventing Replicative Senescence in Pancreatic Adenocarcinoma: Potential Role of TRPM8 As a Biomarker and Target
Cancer Biology & Therapy. Jun, 2012 | Pubmed ID: 22555807
Pancreatic adenocarcinoma is mostly fatal and generally resistant to conventional treatments, such that effective therapies with tolerable side effects are desperately needed. Ion channels including the transient receptor potential (TRP) channels have been implicated in human malignancies, but their roles in pancreatic cancer were mostly unknown. Recent identification of the melastatin-subfamily members of the TRP family of ion channels, and their functions in pancreatic epithelia and adenocarcinoma, is expected to provide a new perspective to understanding the mechanism underlying pancreatic tumorigenesis. In this report, we present the clinical and pathological features of a mini-series of patients with pancreatic adenocarcinoma, which aberrantly exhibits immunoreactivity against the TRPM8 channel. We have recently demonstrated the proliferative role of TRPM8 channel in pancreatic cancer cells. Here, we present evidence that RNA interference-mediated silencing of TRPM8 induces replicative senescence in pancreatic adenocarcinoma cells. This suggests that the aberrantly expressed TRPM8 channel may contribute to pancreatic tumorigenesis by preventing oncogene-induced senescence, and targeted inhibition of TRPM8 may enhance tumor sensitivity to therapeutics. Based on these observations, we hypothesize that the TRPM8 ion channel plays a crucial role in the growth and progression of pancreatic neoplasia during tumorigenesis. We propose that TRPM8 can be exploited as a clinical biomarker and as a therapeutic target for developing personalized therapy in pancreatic adenocarcinoma.
Participation of Microglial P38 MAPK in Formalin-induced Temporomandibular Joint Nociception in Rats
Journal of Orofacial Pain. 2012 | Pubmed ID: 22558613
To investigate nociceptive behavior and the immunoreactivity of microglia and phosphorylated-p38 (p-p38) mitogen-activated protein kinase (MAPK) following intracisternal administration of SB203580, a p38 MAPK inhibitor, or minocycline, a microglia inhibitor, in rats with temporomandibular joint (TMJ) inflammation.
Low Density Lipoprotein-cholesterol/high Density Lipoprotein-cholesterol Ratio Predicts Plaque Vulnerability in Patients with Stable Angina
Korean Circulation Journal. Apr, 2012 | Pubmed ID: 22563337
The relationship between lipid profile and coronary plaque tissue characteristics in patients with stable angina pectoris (SAP) is unclear. The aim of this study was to evaluate the relationship between tissue characteristics and lipid profile and predictors of unstable plaques (UPs) in patients with SAP by virtual histology intravascular ultrasonography (VH-IVUS).
Successful Primary Percutaneous Coronary Intervention in a Patient with Acute Myocardial Infarction and Single Coronary Artery Ostium
Korean Circulation Journal. Apr, 2012 | Pubmed ID: 22563344
One of the single anomalous origins of coronary artery that has rarely been reported is a congenital anomaly of coronary circulation that occurs in the left coronary artery originating from the right coronary sinus of valsalva. We report a 49-year-old male patient with non-ST segment elevated myocardial infarction that was identified to have an anomalous origin of the left coronary artery from the right coronary artery (RCA) with thrombotic total occlusion of RCA by coronary angiography and cardiac computed tomography. The patient underwent successful percutaneous coronary intervention in total occlusion of the RCA and was discharged after uneventful recovery.
Journal of the Korean Surgical Society. May, 2012 | Pubmed ID: 22563543
Interdigitating dendritic cell sarcoma (IDCS) is a very rare disease around the world and its prognosis is known to be aggressive. This reports a case diagnosed as IDCS of the axillary region treated in Soonchunhyang University Hospital. A 57-year-old female visited Soonchunhyang University Hospital with a left axillary mass. The mass was hard and fixed. Computed tomography observed a 7 cm lymph node at the left axilla, and core biopsy suspected sarcoma. In another study, there was no specific finding except the axillary lesion. Left axillary lymph node dissection (level I, II) was conducted and the pathologic report finally showed IDCS. The patient was treated with only radiotherapy and followed up without recurrence for 13 months up to now. IDCS is a very rare sarcoma that is hard to diagnose and progresses fast. Thus, treatment is very difficult. Proper treatment can be better established after more experiences.
Dalton Transactions (Cambridge, England : 2003). Jan, 2012 | Pubmed ID: 22116403
Two new tetranuclear cationic metalla-bowls 4 and 5 were self-assembled from a bis-pyridine amide ligand (H(2)L) (1) and arene-ruthenium acceptors, [(Ru(2)(μ-η(4)-C(2)O(4))(η(6)-p-cymene)(2)](O(3)SCF(3))(2) (2) and [Ru(2)(dhnd)(η(6)-p-cymene)(2)](O(3)SCF(3))(2) (dhnd = 6,11-dihydroxy-5,12-naphthacenedionato) (3), respectively. The metalla-bowls were characterized by multinuclear NMR, ESI-MS, UV-Vis spectroscopy, and single crystal X-ray diffraction study of 4. The crystal structure of 4 reveals unambiguous proof for the molecular shape of the metalla-bowl and the encapsulation of one triflate anion in the cavity through hydrogen bonding. The metalla-bowl 5 has been evaluated for anion binding studies by use of amide ligand as a hydrogen bond donor and arene-Ru acceptor as a signalling unit. UV-Vis titration studies showed that 5 selectively binds with multi-carboxylate anions such as oxalate, tartrate and citrate in a 1 : 1 fashion with high binding constants of 4.0-5.5 × 10(4) M(-1). Furthermore, the addition of multi-carboxylate anions into a solution of 5 gave rise to a large enhancement of fluorescence intensity attributable to the blocking of a photo-induced electron transfer process from the arene-ruthenium moiety to the amidic donor in 5. However, the fluorescence intensity almost remains unchanged upon addition of other anions including F(-), Cl(-), PF(6)(-), MeCOO(-), NO(3)(-) and PhCOO(-), as identically seen in the UV-Vis titration experiments, pointing to the high selectivity of 5 for the sensing of multi-carboxylate anions.
Derivation of Functional Ventricular Cardiomyocytes Using Endogenous Promoter Sequence from Murine Embryonic Stem Cells
Stem Cell Research. Jan, 2012 | Pubmed ID: 22099020
The purpose of this study is to establish a murine embryonic stem cell (mESC) line for isolation of functional ventricular cardiomyocytes (VCMs) and then to characterize the derived VCMs. By crossing the myosin light chain 2v (Mlc2v)-Cre mouse line with the reporter strain Rosa26-yellow fluorescent protein (YFP), we generated mESC lines from these double transgenic mice, in which Cre-mediated removal of a stop sequence results in the expression of YFP under the control of the ubiquitously active Rosa26 promoter specifically in the VCM. After induction of differentiation via embryoid body (EB) formation, contracting YFP(+) cells were detected within EBs and isolated by fluorescence-activated cell sorting. N-cadherin, the cadherin expressed in cardiomyocytes, and the major cardiac connexin (Cx) isoform, Cx43, were detected in the respective adherens and gap junctions in these VCMs. Using current clamp recordings we demonstrated that mESC-derived VCMs exhibited action potential characteristics comparable to those of neonatal mouse VCMs. Real-time intracellular calcium [Ca(2+)](i) imaging showed rhythmic intracellular calcium transients in these VCMs. The amplitude and frequency of calcium transients were increased by isoproterenol stimulation, suggesting the existence of functional β-adrenergic signaling. Moreover, [Ca(2+)](i) oscillations responded to increasing frequencies of external electrical stimulation, indicating that VCMs have functional excitation-contraction coupling, a key factor for the ultimate cardiac contractile performance. The present study makes possible the production of homogeneous and functional VCMs for basic research as well as for cardiac repair and regeneration.
Impact of Diabetes Mellitus on Plaque Vulnerability and Clinical Outcome in Patients with Acute Myocardial Infarction with Plaque Rupture
International Journal of Cardiology. Jan, 2012 | Pubmed ID: 22075418
Ophthalmology. Feb, 2012 | Pubmed ID: 21978591
To investigate the prevalence and clinical features of acquired lower eyelid epiblepharon in Korean patients with thyroid-associated ophthalmopathy (TAO) and compare the pathogenic features of acquired and congenital epiblepharon.
Chest. Apr, 2012 | Pubmed ID: 21980060
Interferon-γ release assays (IGRAs) have been incorporated into several national guidelines for latent TB infection (LTBI) diagnosis. However, their optimal application is still controversial and evolving. The aim of this study is to evaluate the performance of confirmatory IGRAs in addition to tuberculin skin tests (TSTs) in high school students with TST-positive (TST+) results who have had contact with another student who had TB (referred to in this article as "contacts") in TB outbreaks in a high BCG-vaccinated population.
Colloids and Surfaces. B, Biointerfaces. Jan, 2012 | Pubmed ID: 21958539
The dispersing power of surfactant-modified multiwalled carbon nanotubes (MWCNTs) and their effect on the antibacterial activity were examined. The MWCNTs were modified using a dioctyl sodium sulfosuccinate (AOT) surfactant. UV-vis spectroscopy and transmission electron microscopy (TEM) were used to characterize the dispersion of MWCNTs in the aqueous phase. Fourier transform infrared spectroscopy confirmed the results of UV-vis spectroscopy and TEM, indicating that the AOT molecules had been adsorbed successfully onto the MWCNT surface. The highly dispersed AOT-modified MWCNTs showed strong antibacterial activity to Streptococcus mutans. The fluorescence images showed that the AOT-modified MWCNTs were capable of capturing bacteria and forming cell aggregates as well as killing them. The optical density growth curves and colony-forming units assays confirmed that the antibacterial activity of the AOT-modified MWCNTs was concentration-dependent and treatment time-dependent. This finding might be useful for applications of AOT-modified MWCNTs as an antibacterial agent to eliminate pathogens from a biocontaminated water phase.
The Relation of Serotonin-related Gene and COMT Gene Polymorphisms with Criminal Behavior in Schizophrenic Disorder
The Journal of Clinical Psychiatry. Feb, 2012 | Pubmed ID: 22053918
It has been suggested that patients with schizophrenia might be involved in criminal behavior, such as homicidal and violent behavior. However, the relationship between criminal behavior and genes in patients with schizophrenia has not been clearly elucidated. The objective of this study was to examine the relation between criminal behavior and serotonin-related gene or catechol-O-methyltransferase (COMT) gene polymorphisms in patients with schizophrenia.
Enhancement of Human Adipose-derived Stromal Cell Angiogenesis Through Knockdown of a BMP-2 Inhibitor
Plastic and Reconstructive Surgery. Jan, 2012 | Pubmed ID: 21915082
Previous studies have demonstrated the role of noggin, a bone morphogenetic protein-2 inhibitor, in vascular development and angiogenesis. The authors hypothesized that noggin suppression in human adipose-derived stromal cells would enhance vascular endothelial growth factor secretion and angiogenesis in vitro and in vivo to a greater extent than bone morphogenetic protein-2 alone.
Detection and Comparison of Peptide Nucleic Acid-mediated Real-time Polymerase Chain Reaction Clamping and Direct Gene Sequencing for Epidermal Growth Factor Receptor Mutations in Patients with Non-small Cell Lung Cancer
Lung Cancer (Amsterdam, Netherlands). Mar, 2012 | Pubmed ID: 21930325
EGFR tyrosine kinase inhibitors (EGFR-TKIs) are recommended as first-line therapy in patients with advanced, recurrent, or metastatic non-squamous non-small cell lung cancer (NSCLC) that have active EGFR mutations. The importance of rapid and sensitive methods for the detection of EGFR mutations is emphasized. The aim of this study is to examine the EGFR mutational status by both direct DNA sequencing and peptide nucleic acid (PNA)-mediated real-time PCR clamping and to evaluate the correlation between the EGFR mutational status and the clinical response to EGFR-tyrosine kinase inhibitors. Clinical specimens from 240 NSCLC patients were analyzed for EGFR mutations in exons 18, 19, 20 and 21. All clinical data and tumor specimens were obtained from 8 centers of the Korean Molecular Lung Cancer Group (KMLCG). After genomic DNA was extracted from paraffin-embedded tissue specimens, we performed PNA-mediated real-time PCR clamping and direct DNA sequencing for the detection of EGFR mutations. Of 240 tumor samples, PNA-mediated PCR clamping was used to detect genomic alterations in 83 (34.6%) samples, including 61 identified by sequencing and 22 additional samples (10 in exon 19, 9 in exon 21, and 3 in both exons); direct DNA sequencing was used to identify a total of 63 (26.3%) mutations that contained 40 deletion mutations in exon 19 (63.5%) and 18 substitution mutations (28.6%) in exon 21. PNA-mediated PCR clamping was used to identify more mutations than clinical direct sequencing, whereas clinical outcomes were not significantly different between the groups harboring activating mutations detected by each method. These data suggest that PNA-mediated real-time PCR clamping exhibits high sensitivity and is a simple procedure relative to direct DNA sequencing that is a useful screening tool for the detection of EGFR mutations in clinical settings.
Characteristics and Spectrum of BRCA1 and BRCA2 Mutations in 3,922 Korean Patients with Breast and Ovarian Cancer
Breast Cancer Research and Treatment. Aug, 2012 | Pubmed ID: 22798144
This investigation is aimed at evaluating the epidemiologic characteristics of BRCA1/2 germline mutations in Korean patients with breast and ovarian cancer (BOC). We analyzed the entire mutational data of BRCA1/2 genes in BOC patients who were tested in Korea since the first Korean report of BRCA1 mutation in 1995 with the exception of the data covered in the Korean Hereditary Breast Cancer (KOHBRA) study, the project launched in 2007 for establishing BRCA1/2 carrier cohorts in Korea. In total, BRCA1/2 gene mutations of 3,922 Korean BOC patients were evaluated, including the unpublished data of 2,139 breast cancer patients examined by four Korean institutions and the data of 1,783 BOC patients covered in ten previous reports. Overall, 420 (150 distinct) pathogenic mutations were identified, 211 (73 distinct) in BRCA1 and 209 (77 distinct) in BRCA2. The majority (134 of 150) of the distinct mutations resulted in premature termination codon of the BRCA1/2 translation. BRCA1 c.4186-1593_4676-1465del was the only large genomic rearrangements mutation. Out of 150 distinct BRCA1/2 mutations, 84 (56 %) mutations were considered specific to Korean BOC. Eighty-five BRCA1/2 mutations were detected in at least two unrelated patients. These recurrent mutations account for 84.5 % (355 of 420) of mutations detected in the Korean population. In the pooled mutational data of BRCA1/2 genes, this study discovered the prevalence of BRCA1/2 mutations in the Korean BOC patients is similar to those found in other ethnic groups. Large genomic rearrangements in BRCA1/2 genes were infrequently detected among the Korean patients with BOC. There were several BRCA1/2 mutation candidates for founder mutations. To further establish a Korean cohort for BRCA1/2 mutations, the nationwide KOHBRA study is in progress.
Cystic Fibrosis Transmembrane Conductance Regulator Mutant F508del Membrane Expression Rescues Epithelial HCO3- Secretion in Murine Intestine
The Journal of Physiology. Sep, 2012 | Pubmed ID: 22802588
This study investigated whether expression of the common cystic fibrosis transmembrane conductance regulator (CFTR) mutant F508del in the apical membrane of enterocytes confers increased bicarbonate secretory capacity on the intestinal epithelium of F508del mutant mice compared to that of CFTR knockout (KO) mice. CFTR KO, F508del mutant mice (F508del) and wild-type (WT) littermates were bred on the FVB/N background. F508del isolated brush border membrane (BBM) contained approximately 5-10% fully glycosylated band C protein compared to WT BBM. Similarly, the forskolin (FSK)- induced, CFTR-dependent short-circuit current (ΔI(sc)) of F508del mucosa was approximately 5-10% of WT, whereas the HCO(3)(-) secretory response (ΔJ(HCO3)(-)) was almost half that of WT in both duodenum and mid colon studied in vitro and in vivo. While WT intestine retained full FSK-induced Δ(JHCO3)(-) in the absence of luminal Cl(-), the markedly higher ΔJ(HCO3)(-) than ΔI(sc) in F508del intestine was depend-ent on the presence of luminal Cl(-), and was blocked by CFTR inhibitors. The Ste20-related proline-alanine-rich kinases (SPAK/OSR1), which are downstream of the with no lysine (K) protein kinases (WNK), were rapidly phosphorylated by FSK in WT and F508del, but significantly more slowly in CFTR KO intestine. In conclusion, the data demonstrate that low levels of F508del membrane expression in the intestine of F508del mice significantly increased FSK-induced HCO(3)(-) secretion mediated by Cl(-)/HCO(3)(-) exchange. However, in WT mucosa FSK elicited strong SPAK/OSR1 phosphorylation and Cl(-)-independent HCO(3)(-) efflux. This suggests that therapeutic strategies, which deliver F508del to the apical membrane have the potential to significantly enhance epithelial HCO(3)(-) secretion.
Osteomyelitis of a Long Bone Due to Fusobacterium Nucleatum and Actinomyces Meyeri in an Immunocompetent Adult: A Case Report and Literature Review
BMC Infectious Diseases. 2012 | Pubmed ID: 22817336
Magnetic Resonance Imaging. Jul, 2012 | Pubmed ID: 22817957
Although some therapeutics provide an opportunity for cure, recurrence is a major obstacle to achieve a complete remission for lung cancers. Therefore, precise assessment of lung cancers has been a task with challenge. In recent years, integration of positron emission tomography and computed tomography (PET-CT) and whole-body magnetic resonance imaging (WB-MRI) have been introduced as an alternative to standard multimodality imaging strategies and are now increasingly applied to various malignancies. However, there is little information on the surveillance capability of WB-MRI in patients with lung cancers. We aimed to investigate the clinical potential of WB-MRI as a novel surveillance modality after curative treatments for lung cancers, comparing it with PET-CT. Sixty two consecutive patients with lung malignancy who underwent both WB-MRI and PET-CT were selected to assess the recurrent malignant lesions. The clinical data including radiologic and pathologic findings were collected and analyzed retrospectively. On each lymph node station, the ability of WB-MRI to detect malignant lesions significantly correlated with that of PET-CT (γ=0.86; P<.01). The correlation coefficient ranged from 0.999 to 1 for assessing distant metastases from lung cancers by two modalities (P<.01). Based on the pathologic confirmation, both modalities showed an equivalent diagnostic accuracy (PET-CT: sensitivity 85.71%, specificity 47.27% versus WB-MRI: sensitivity 85.71%, specificity 56.25%). This study demonstrates the clinical potential of WB-MRI, together with PET-CT, as a novel surveillance modality for lung cancers after curative treatments.
Prognostic Impact of Diabetes Mellitus and Hypertension for Mid-term Outcome of Patients with Acute Myocardial Infarction Who Underwent Percutaneous Coronary Intervention
Journal of Cardiology. Oct, 2012 | Pubmed ID: 22819036
The synergistic effect of diabetes mellitus (DM) and hypertension on mid-term outcome among acute myocardial infarction (MI) patients undergoing percutaneous coronary intervention (PCI) is still controversial.
Aborted Myocardial Infarction: Evaluation of Changes in Area at Risk, Late Gadolinium Enhancement, and Perfusion over Time and Comparison with Overt Myocardial Infarction
AJR. American Journal of Roentgenology. Aug, 2012 | Pubmed ID: 22826393
The objective of our study was to analyze comprehensive MRI findings of aborted myocardial infarction (MI) in terms of the area at risk, late enhancement, and perfusion on initial and follow-up studies compared with overt MI.
Recurrent/moderate Hypoglycemia Induces Hippocampal Dendritic Injury, Microglial Activation, and Cognitive Impairment in Diabetic Rats
Journal of Neuroinflammation. 2012 | Pubmed ID: 22830525
Small Hepatocellular Carcinomas: Improved Sensitivity by Combining Gadoxetic Acid-enhanced and Diffusion-weighted MR Imaging Patterns
Radiology. Sep, 2012 | Pubmed ID: 22843769
To determine if the combination of gadoxetic acid-enhanced magnetic resonance (MR) imaging and diffusion-weighted (DW) imaging helps to increase accuracy and sensitivity in the diagnosis of small hepatocellular carcinomas (HCCs) compared with those achieved by using each MR imaging technique alone.
Detection of Hepatocellular Carcinoma in Gadoxetic Acid-enhanced MRI and Diffusion-weighted MRI with Respect to the Severity of Liver Cirrhosis
Acta Radiologica (Stockholm, Sweden : 1987). Oct, 2012 | Pubmed ID: 22847903
Background As gadoxetic acid-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) have been widely used for the evaluation of hepatocellular carcinoma (HCC), it is clinically relevant to determine the diagnostic efficacy of gadoxetic acid-enhanced MRI and DWI for detection of HCCs with respect to the severity of liver cirrhosis. Purpose To compare the diagnostic accuracy and sensitivity of gadoxetic acid-enhanced MRI and DWI for detection of HCCs with respect to the severity of liver cirrhosis. Material and Methods A total of 189 patients with 240 HCCs (≤3.0 cm) (Child-Pugh A, 81 patients with 90 HCCs; Child-Pugh B, 65 patients with 85 HCCs; Child-Pugh C, 43 patients with 65 HCCs) underwent DWI and gadoxetic acid-enhanced MRI at 3.0 T. A gadoxetic acid set (dynamic and hepatobiliary phase plus T2-weighted image) and DWI set (DWI plus unenhanced MRIs) for each Child-Pugh class were analyzed independently by two observers for detecting HCCs using receiver-operating characteristic analysis. The diagnostic accuracy and sensitivity were calculated. Results There was a trend toward decreased diagnostic accuracy for gadoxetic acid and DWI set with respect to the severity of cirrhosis (Child-Pugh A [mean 0.974, 0.961], B [mean 0.904, 0.863], C [mean 0.779, 0.760]). For both observers, the sensitivities of both image sets were highest in Child-Pugh class A (mean 95.6%, 93.9%), followed by class B (mean 83.0%, 77.1%), and class C (mean 60.6%, 60.0%) (P < 0.05). Conclusion In HCC detection, the diagnostic accuracy and sensitivity for gadoxetic acid-enhanced MRI and DWI were highest in Child-Pugh class A, followed by Child-Pugh class B, and Child-Pugh class C, indicating a tendency toward decreased diagnostic capability with the severity of cirrhosis.
Case Series of Mycobacterium Abscessus Infections Associated with a Trigger Point Injection and Epidural Block at a Rural Clinic
Epidemiology and Health. 2012 | Pubmed ID: 22323979
The aim of this report is to investigate Mycobacterium abscessus infections at a rural clinic and carry out a surveillance program to determine the extent and source of these infections.
Acta Biomaterialia. May, 2012 | Pubmed ID: 22330279
In situ gelling constructs, which form a hydrogel at the site of injection, offer the advantage of delivering cells and growth factors to the complex structure of the defect area for tissue engineering. In the present study, visible light crosslinkable hydrogel systems were presented using methacrylated glycol chitosan (MeGC) and three blue light initiators: camphorquinone (CQ), fluorescein (FR) and riboflavin (RF). A minimal irradiation time of 120 s was required to produce MeGC gels able to encapsulate cells with CQ or FR. Although prolonged irradiation up to 600 s improved the mechanical strength of CQ- or FR-initiated gels (compressive modulus 2.8 or 4.4 kPa, respectively), these conditions drastically reduced encapsulated chondrocyte viability to 5% and 25% for CQ and FR, respectively. Stable gels with 80-90% cell viability could be constructed using radiofrequency (RF) with only 40s irradiation time. Increasing irradiation time up to 300s significantly improved the compressive modulus of the RF-initiated MeGC gels up to 8.5 kPa without reducing cell viability. The swelling ratio and degradation rate were smaller at higher irradiation time. RF-photoinitiated hydrogels supported proliferation of encapsulated chondrocytes and extracellular matrix deposition. The feasibility of this photoinitiating system as in situ gelling hydrogels was further demonstrated in osteochondral and chondral defect models for potential cartilage tissue engineering. The MeGC hydrogels using RF offer a promising photoinitiating system in tissue engineering applications.
Diagnostic Accuracy and Sensitivity of Diffusion-weighted and of Gadoxetic Acid-enhanced 3-T MR Imaging Alone or in Combination in the Detection of Small Liver Metastasis (≤ 1.5 Cm in Diameter)
Investigative Radiology. Mar, 2012 | Pubmed ID: 22330426
To compare the diagnostic accuracy and sensitivity of combined gadoxetic acid-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) with each imaging approach alone for detecting small hepatic metastases (≤ 1.5 cm).
Can Metabolic Syndrome Predict the Vulnerable Plaque in Patients with Stable Angina Pectoris? Virtual Histology-intravascular Ultrasound Analysis
Journal of Cardiology. May, 2012 | Pubmed ID: 22341056
Vulnerable plaque in coronary artery can progress to plaque rupture and thrombosis, and have a strong potential to induce acute coronary syndrome. Many studies have demonstrated that metabolic syndrome (MetS) is associated with increased risk for cardiovascular diseases and related mortalities.
Clinical Impact of Thrombus Aspiration During Primary Percutaneous Coronary Intervention: Results from Korea Acute Myocardial Infarction Registry
Journal of Cardiology. May, 2012 | Pubmed ID: 22341434
The role of thrombus aspiration (TA) as an adjunct to primary percutaneous coronary intervention (PPCI) remains a matter of controversy.
Macrophage Migration Inhibitory Factor Isolated from a Parasite Inhibited Th2 Cytokine Production in PBMCs of Atopic Asthma Patients
The Journal of Asthma : Official Journal of the Association for the Care of Asthma. Feb, 2012 | Pubmed ID: 22149098
In a previous study, we demonstrated that the human macrophage migration inhibitory factor (MIF)-like protein (As-MIF) isolated from helminths could inhibit allergic airway inflammation via the recruitment of CD4(+)CD25(+)Foxp3(+) T cells.
Hepatocyte-targeting Single Galactose-appended Naphthalimide: a Tool for Intracellular Thiol Imaging in Vivo
Journal of the American Chemical Society. Jan, 2012 | Pubmed ID: 22171762
We present the design, synthesis, spectroscopic properties, and biological evaluation of a single galactose-appended naphthalimide (1). Probe 1 is a multifunctional molecule that incorporates a thiol-specific cleavable disulfide bond, a masked phthalamide fluorophore, and a single galactose moiety as a hepatocyte-targeting unit. It constitutes a new type of targetable ligand for hepatic thiol imaging in living cells and animals. Confocal microscopic imaging experiments reveal that 1, but not the galactose-free control system 2, is preferentially taken up by HepG2 cells through galactose-targeted, ASGP-R-mediated endocytosis. Probe 1 displays a fluorescence emission feature at 540 nm that is induced by exposure to free endogenous thiols, most notably GSH. The liver-specificity of 1 was confirmed in vivo via use of a rat model. The potential utility of this probe in indicating pathogenic states and as a possible screening tool for agents that can manipulate oxidative stress was demonstrated in experiments wherein palmitate was used to induce lipotoxicity in HepG2 cells.
Comparison of Chronic Kidney Disease and Risk for Presenting with Painless Versus Nonpainless Acute Myocardial Infarction
The American Journal of Cardiology. Sep, 2012 | Pubmed ID: 22657394
Chronic kidney disease increases the risk for developing ischemic heart disease, but it has not been well known whether it also affects the manifestation of painless acute myocardial infarction (AMI), which has important clinical implications. The aim of this study was to identify whether chronic kidney disease is associated with the presentation of painless AMI. A total of 2,656 consecutively hospitalized patients with AMI from January 2008 to February 2012 were enrolled. Estimated glomerular filtration rate (eGFR) was calculated using calibrated serum creatinine and the abbreviated Modification of Diet in Renal Disease (MDRD) equation. Patient clinical characteristics, angiographic findings, and the use of medications were reviewed. Multivariate logistic regression analysis was used to examine the association of reduced eGFR and presentation with painless AMI. A total of 2,176 adults with painful AMI and 480 adults with painless AMI were studied, and baseline eGFR was calculated. Mean eGFR was lower in subjects with painless AMI compared to those with painful AMI. Compared to an eGFR >90 ml/min/1.73 m(2), a strong, graded, independent association was observed between reduced eGFR and presentation with painless AMI, with adjusted odds ratios of 1.65 (95% confidence interval 1.16 to 2.36) for an eGFR of 60 to 89 ml/min/1.73 m(2), 2.92 (95% confidence interval 1.89 to 4.52) for an eGFR of 45 to 59 ml/min/1.73 m(2), and 3.44 (95% confidence interval 2.20 to 5.38) for an eGFR <45 ml/min/1.73 m(2). In conclusion, lower eGFR was a strong, independent predictor of presentation with painless AMI versus painful AMI.
Usefulness of IDEAL T2-weighted FSE and SPGR Imaging in Reducing Metallic Artifacts in the Postoperative Ankles with Metallic Hardware
Skeletal Radiology. Jun, 2012 | Pubmed ID: 22669731
PURPOSE: The aim of this work is to prospectively compare the effectiveness of iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL), T2-weighted fast spin-echo (FSE), and spoiled gradient-echo (SPGR) MR imaging to frequency selective fat suppression (FSFS) protocols for minimizing metallic artifacts in postoperative ankles with metallic hardware. MATERIALS AND METHODS: The T2-weighted and SPGR imaging with IDEAL and FSFS were performed on 21 ankles of 21 patients with metallic hardware. Two musculoskeletal radiologists independently analyzed techniques for visualization of ankle ligaments and articular cartilage, uniformity of fat saturation, and relative size of the metallic artifacts. A paired t test was used for statistical comparisons of MR images between IDEAL and FSFS groups. RESULTS: IDEAL T2-weighted FSE and SPGR images enabled significantly improved visualization of articular cartilage (p < 0.05), the size of metallic artifact (p < 0.05), and the uniformity of fat saturation (p < 0.05). However, no significant improvement was found in the visibility of ligaments. CONCLUSIONS: IDEAL T2-weighted FSE and SPGR imaging effectively reduces the degree of tissue-obscuring artifacts produced by fixation hardware in ankle joints and improves image quality compared to FSFS T2-weighted FSE and SPGR imaging. However, visibility of ligaments was not improved using IDEAL imaging.
Factors Associated with Length of Stay and Hospital Charges for Patients Hospitalized with Mouth Cellulitis
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. Jan, 2012 | Pubmed ID: 22677688
Dental conditions that are neglected could progress to infectious lesions that are severe enough to require hospital admission for treatment. The objective of this study was to examine outcomes in patients hospitalized for cellulitis and abscesses of mouth in the USA in year 2008.
Therapeutic Hypothermia Attenuates Liver Injury in Polymicrobial Sepsis Model of Rats Via Akt Survival Pathway
The Journal of Surgical Research. Jun, 2012 | Pubmed ID: 22683079
BACKGROUND: Therapeutic hypothermia has been proposed to protect organs in some diseases. However, the effect of therapeutic hypothermia on liver injury in sepsis is unknown. The aim of this study was to evaluate the effects of therapeutic hypothermia on liver injury in sepsis. METHODS: Male Sprague-Dawley rats underwent cecal ligation and incision (CLI). We randomly allocated rats into one of two groups 1 h after CLI: hypothermia (HT) and normothermia (NT). In the HT group, body temperature decreased to 32°C ± 0.5°C and was maintained 4 h, followed by rewarming to 37°C for 2 h. In the NT group, body temperature was maintained at 37°C ± 0.5°C throughout the experimental periods. At 7 h after CLI, we harvested blood and liver tissues and measured serum alanine aminotransferase and the histological liver injury score. We performed immunohistochemistry for cleaved caspase-3 and evaluated phosphorylation of Akt, GSK-3β and Bad with the Western blot assay. RESULTS: Serum alanine aminotransferase was significantly lower in the HT group than in the NT group (57.0 ± 6.0 IU/L versus 192.5 ± 92.5 IU/L; P = 0.028). The histological liver injury score was also significantly lower in the HT group than in the NT group (2.9 ± 0.5 versus 5.4 ± 0.6; P = 0.016). Phosphorylation of Akt, GSK-3β, and Bad was significantly increased in the HT group compared with the NT group (P < 0.001, P = 0.007, and P = 0.001, respectively). Hypothermia significantly mitigated expression of cleaved caspase-3 compared with the NT group (P = 0.032). CONCLUSIONS: Therapeutic hypothermia attenuated liver injury in a polymicrobial sepsis model of rats by enhancing the Akt signaling pathway and decreasing apoptosis.
Clinical Course of Sub-centimeter-sized Nodules Detected During Surveillance for Hepatocellular Carcinoma
World Journal of Gastroenterology : WJG. Jun, 2012 | Pubmed ID: 22690074
To evaluate the outcome of sub-centimeter-sized nodules (SCSNs) detected during surveillance for hepatocellular carcinoma (HCC) in patients at risk.
Endothelial Dysfunction and Increased Carotid Intima-media Thickness in the Patients with Slow Coronary Flow
Journal of Korean Medical Science. Jun, 2012 | Pubmed ID: 22690091
Flow mediated brachial dilatation (FMD) and carotid intima-media thickness (IMT) have been a surrogate for early atherosclerosis. Slow coronary flow in a normal coronary angiogram is not a rare condition, but its pathogenesis remains unclear. A total of 85 patients with angina were evaluated of their brachial artery FMD, carotid IMT and conventional coronary angiography. Coronary flow was quantified using the corrected thrombosis in myocardial infarction (TIMI) frame count method. Group I was a control with normal coronary angiography (n = 41, 56.1 ± 8.0 yr) and group II was no significant coronary stenosis with slow flow (n = 44, 56.3 ± 10.0 yr). Diabetes was rare but dyslipidemia and family history were frequent in group II. Heart rate was higher in group II than in group I. White blood cells, especially monocytes and homocysteine were higher in group II. The FMD was significantly lower in group II than in group I. Elevated heart rate, dyslipidemia and low FMD were independently related with slow coronary flow in regression analysis. Therefore, endothelial dysfunction may be an earlier vascular phenomenon than increased carotid IMT in the patients with slow coronary flow.
Methods in Molecular Biology (Clifton, N.J.). 2012 | Pubmed ID: 22692615
Computer-aided tissue engineering enables the fabrication of multifunctional scaffolds that meet the structural, mechanical, and nutritional requirements based on optimized models. In this chapter, three-dimensional printing technology is described, and several limitations in the current direct printing approach are discussed. This chapter also describes indirect three-dimensional printing protocol to overcome convergent demands with a traditional method, without sacrificing the key advantage of material versatility.
Nano Letters. Jul, 2012 | Pubmed ID: 22694195
One of the major challenges in further advancement of III-V electronics is to integrate high mobility complementary transistors on the same substrate. The difficulty is due to the large lattice mismatch of the optimal p- and n-type III-V semiconductors. In this work, we employ a two-step epitaxial layer transfer process for the heterogeneous assembly of ultrathin membranes of III-V compound semiconductors on Si/SiO(2) substrates. In this III-V-on-insulator (XOI) concept, ultrathin-body InAs (thickness, 13 nm) and InGaSb (thickness, 7 nm) layers are used for enhancement-mode n- and p- MOSFETs, respectively. The peak effective mobilities of the complementary devices are ∼1190 and ∼370 cm(2)/(V s) for electrons and holes, respectively, both of which are higher than the state-of-the-art Si MOSFETs. We demonstrate the first proof-of-concept III-V CMOS logic operation by fabricating NOT and NAND gates, highlighting the utility of the XOI platform.
Nature. Jun, 2012 | Pubmed ID: 22699620
Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.
Clinical Impact of Non-high Density Lipoprotein-cholesterol and Apolipoprotein B on Clinical Outcomes in Metabolic Syndrome Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention
Korean Circulation Journal. May, 2012 | Pubmed ID: 22701134
Non-high density lipoprotein-cholesterol (non-HDL-C) and apolipoprotein B (ApoB) are markers of atherosclerotic risk and predictors of cardiovascular events. The aim of this study was to evaluate clinical impact of non-HDL-C and ApoB on clinical outcomes in metabolic syndrome (MS) patients with acute myocardial infarction (AMI) undergoing percuatneous coronary intervetion.
Successful Percutaneous Coronary Intervention in a Centenarian Patient with Acute Myocardial Infarction
Korean Circulation Journal. May, 2012 | Pubmed ID: 22701138
Despite an increasing prevalence and burden of disease in the elderly, little is known about the management and outcomes of acute coronary syndromes in this group. We report the case of a 101-year-old female patient with a non-ST segment elevation myocardial infarction. Coronary angiography showed a total occlusion of the proximal right coronary artery (RCA), and a significant stenosis in the proximal to mid left anterior descending artery (LAD). Despite a very poor initial clinical status, a percutaneous coronary intervention was successfully performed for the total occlusion in the RCA. The LAD lesion was treated with medical therapy only, on account of the age and general condition of the patient. She was discharged after recovering to a good health status, free of chest pain or dyspnea.
Korean Circulation Journal. May, 2012 | Pubmed ID: 22701500
Traumatic thoracic aortic injury is typically fatal. However, recent improvements in pre-hospital care and diagnostic modalities have resulted in an increased number of patients with traumatic aortic injury arriving alive at the hospital. Also, the morbidity and mortality associated with endovascular repair are significantly lower than with conventional open surgery in traumatic thoracic aorta injury. We experienced two cases of successful management of traumatic thoracic aortic dissection with endovascular stents caused by traffic accidents.
Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie. Oct, 2012 | Pubmed ID: 22706405
The aim of this work is to investigate the prevalence and clinical characteristics of congenital lacrimal fistula in Down syndrome patients.
Catch-up Growth After Long-term Implementation and Weaning from Ketogenic Diet in Pediatric Epileptic Patients
Clinical Nutrition (Edinburgh, Scotland). Jun, 2012 | Pubmed ID: 22749312
BACKGROUND & AIMS: To assess the presence of growth retardation during long-term implementation of ketogenic diet (KD) among children with epilepsy, and verify the presence of catch-up growth in same patients 1 year after diet discontinuation. METHODS: Retrospective chart review of 20 males and 20 females was performed and z scores of height, weight and body mass index was obtained at baseline, 2 years into KD, and 1 year after discontinuation of KD. RESULTS: Our analysis revealed significant reduction in both height and weight gain among children with epilepsy after prolonged KD. After a year of diet discontinuation, significant catch-up growth was evident in both height and weight. In regard to specific subsets, ambulation had favorable influence on growth during KD and after diet discontinuation. Uncontrolled epilepsy, and younger age at the start of KD contributed a negative impact on a child's growth. CONCLUSIONS: This preliminary observation into long-term growth pattern among recipients of KD will aid both health care providers and patients alike in planning for long-term care extending beyond the duration of dietary treatment.
Clinicoradiologic Characteristics and Outcomes of Metastatic Cancer to the Pancreas and Double Primary Pancreatic Cancer
Clinics and Research in Hepatology and Gastroenterology. Jun, 2012 | Pubmed ID: 22749698
OBJECTIVES: The goal of this study was to identify clinicoradiologic characteristics to distinguish metastatic cancer to the pancreas (MCP) from double primary pancreatic cancer (DPPC). METHODS: From 2000 to 2011, we retrospectively identified MCP and DPPC patients among patients with histories of other primary malignancies. RESULTS: A total of 94 patients with histories of other primary malignancies were histologically confirmed to have pancreatic cancer. Among them, 34 patients had MCP and 60 patients had DPPC, which were ductal adenocarcinomas. The kidney was the most common primary cancer site that metastasized to the pancreas (12, 35.3%). In the DPPC group, the stomach was the most common primary cancer site (11, 18.3%). There were 21 patients (61.8%) with metachronous pancreatic cancer in the MCP group and 29 (48.3%) in the DPPC group (P=0.210). Among the metachronous pancreatic cancer patients, the disease-free interval was 88.3months in the MCP group, and 49.6months in the DPPC group (P=0.062). The number of the patients who showed elevated CA 19-9 levels was higher in the DPPC group than in the MCP group (39 (65%) vs. 9 (26.5%); P=0.001). Total bilirubin (P=0.006) and fasting plasma glucose (P=0.050) were also higher in the DPPC group. The numbers of patients who showed pancreatic duct dilatation (P=0.002) and pancreatic atrophy (P=0.008) on radiographs were meaningfully higher in the DPPC group than in the MCP group. On the other hand, the numbers of patients who showed well demarcated tumor margin (P<0.000), tumor necrosis (P=0.002), enhancement (P=0.005) and distant metastasis (P=0.028) were significantly higher in the MCP group than in the DPPC group. We evaluated differences in survival between the two groups. The median survival time in the MCP group (55months) was significantly longer than that in the DPPC group (20months). CONCLUSIONS: Other than elevated levels of CA 19-9, total bilirubin and fasting glucose, radiologic findings were the most reliable factors for distinguishing the MCP from the DPPC.
Dutasteride, Who is It More Effective For? Second to Fourth Digit Ratio and the Relationship with Prostate Volume Reduction by Dutasteride Treatment
BJU International. Jul, 2012 | Pubmed ID: 22755506
Study Type - Prognosis (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The second to fourth digit ratio (hereafter the digit ratio) of the right hand is related to the activity of the androgen receptor. Five α-reductase inhibitor (5ARI) reduces the prostate volume of patients with BPH. In terms of prostate volume reduction, large-scale placebo-controlled studies show that patients with BPH do not always respond well to 5ARI treatment. Patients with a higher digit ratio respond well to dutasteride treatment compared to those with a lower digit ratio. These results suggest that the digit ratio might be a predictor of the response to dutasteride treatment. OBJECTIVE: • To investigate the relationship between second to fourth digit ratio (hereafter the digit ratio) and prostate volume reduction by dutasteride treatment. PATIENTS AND METHODS: • A total of 142 men aged ≥40 years with a clinical diagnosis of benign prostatic hyperplasia and an enlarged prostate (prostate volume ≥30 mL) were prospectively enrolled. • Before prostate-specific antigen (PSA) level determination and transrectal ultrasonography (TRUS), the lengths of the second and fourth digits of the right hand were measured by an investigator using a digital vernier calliper. • Using TRUS, pre- and post-treatment prostate volume (PV1 and PV2) were measured by an uroradiologist who was unaware of finger lengths. We investigated the change in prostate volume and PSA level at least 6 months after the initiation of dutasteride therapy. RESULTS: • When the patients were divided into two groups according to digit ratio (A: digit ratio <0.95, n= 71; B: digit ratio ≥0.95, n= 71), there was a greater reduction in prostate volume in group B compared to group A (PV2-PV1: -9.4 mL vs -13.2 mL, P= 0.042; [PV2-PV1]/PV1: -17.5% vs -24.5%, P= 0.027; [PV2-PV1]/duration: -1.1 mL/month vs -1.6 mL/month, P= 0.041; [PV2-PV1]/PV1/duration: -2.0%/month vs -3.0%/month, P= 0.016). • Significant negative correlations were found between the digit ratio and reduction rate ([PV2-PV1]/duration: r=-0.165, P= 0.049; [PV2-PV1]/PV1/duration: r=-0.191, P= 0.023). CONCLUSIONS: • Patients with higher digit ratios respond well to dutasteride treatment. • The results obtained in the present study suggest that the digit ratio is a predictor of the response to dutasteride treatment.
Purification and Characterization of YFGAP, a GAPDH-related Novel Antimicrobial Peptide, from the Skin of Yellowfin Tuna, Thunnus Albacares
Fish & Shellfish Immunology. Oct, 2012 | Pubmed ID: 22771964
A 3.4 kDa of antimicrobial peptide was purified from an acidified skin extract of the yellowfin tuna, Thunnus albacares, by preparative acid-urea-polyacrylamide gel electrophoresis and C(18) reversed-phase HPLC. A comparison of the N-terminal amino acid sequence of the purified peptide with that of other known polypeptides revealed high homology with the N-terminus of glyceraldehyde-3-phosphate dehydrogenase (GAPDH); thus, this peptide was designated as the yellowfin tuna GAPDH-related antimicrobial peptide (YFGAP). YFGAP showed potent antimicrobial activity against Gram-positive bacteria, such as Bacillus subtilis, Micrococcus luteus, and Streptococcus iniae (minimal effective concentrations [MECs], 1.2-17.0 μg/mL), and Gram-negative bacteria, such as Aeromonas hydrophila, Escherichia coli D31, and Vibrio parahaemolyticus (MECs, 3.1-12.0 μg/mL) without significant hemolytic activity. According to the secondary structural prediction and the homology modeling, this peptide forms an amphipathic structure and consists of three secondary structural motifs including one α-helix and two parallel β-strands. This peptide did not show membrane permeabilization ability and its activity was bacteriostatic rather than bactericidal. This is the first report of the isolation of an antimicrobial peptide from a tuna species and the first description of the antimicrobial function of the N-terminus of GAPDH of an animal species.
Langmuir : the ACS Journal of Surfaces and Colloids. Feb, 2012 | Pubmed ID: 22272821
The present work contains the results of the experiments with two tiny drops on partially wettable substrates with contact angles of 10°, 24°, 27°, and 56°, which coalesce in the regime entirely dominated by viscous forces. Both side and bottom views are examined. The results for these three-dimensional coalescence flows are compared with scaling laws and the numerical two-dimensional model developed in the present work.
Chitosan-based Nanoparticles As a Sustained Protein Release Carrier for Tissue Engineering Applications
Journal of Biomedical Materials Research. Part A. Apr, 2012 | Pubmed ID: 22275184
Chitosan/tripolyphosphate/chondroitin sulfate (Chi/TPP/CS) nanoparticles were prepared by an ionic gelation method to obtain a controlled release of proteins. Using Nel-like molecule-1 (Nell-1), a novel osteogenic protein, as a model protein, it was demonstrated that adjusting the composition of the particles modulated the protein association and release kinetics of incorporated proteins. Increasing the amounts of Chi crosslinking agents, TPP and CS, in the particles achieved sustained protein release. An increase in crosslinking density decreased degradation rates of the particles. Furthermore, the bioactivity of the protein was preserved during the encapsulating procedure into the particles. To demonstrate the feasibility of Chi/TPP/CS nanoparticles as sustained release carriers for tissue engineering scaffold applications, protein-loaded nanoparticles were successfully incorporated into collagen hydrogels or prefabricated porous poly(lactide-co-glycolide) (PLGA) scaffolds without obstructing the integrity of the hydrogels or porous structure of the scaffolds. Thus, we expect that these particles have a potential for efficient protein carriers in tissue engineering applications, and will be further evaluated in vivo.
Increased Systemic Exposure of Fimasartan, an Angiotensin II Receptor Antagonist, by Ketoconazole and Rifampicin
Journal of Clinical Pharmacology. Jan, 2012 | Pubmed ID: 22282527
The authors studied the effects of ketoconazole and rifampicin on the pharmacokinetics of a single dose of fimasartan (BR-A-657), a newly developed angiotensin II receptor antagonist for the treatment of hypertension, in 22 healthy participants. Ketoconazole increased the maximum plasma concentration (C(max)) and area under the plasma concentration vs time curve to infinity (AUC(∞)) of fimasartan by 2.47-fold (90% confidence interval [CI], 1.61-3.79) and 2.03-fold (1.56-2.64), respectively. Concomitant administration of rifampicin increased the C(max) and AUC(∞) of fimasartan by 10.33-fold (90% CI, 6.74-15.81) and 4.60-fold (3.54-5.97). In vitro studies indicated that ketoconazole inhibited the uptake of fimasartan into cells expressing OATP1B1 with a K(i) of 107.7 µM, and rifampicin inhibited OAT1- and OATP1B1-mediated fimasartan transport with a K(i) of 212 µM and 12.2 µM, respectively. The systemic exposure of fimasartan was significantly increased by coadministration of ketoconazole or rifampicin in healthy volunteers. This is consistent with the in vitro results, in which fimasartan is a substrate of CYP3A and OATP1B1.
Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery. Jan, 2012 | Pubmed ID: 22282867
Segmental mandibular defects can result after the treatment of various pathologic processes, including osteoradionecrosis, tumor resection, or fracture nonunion with sequestration. The variety of etiologies and the frequency of occurrence make the reconstruction of segmental mandibular defects a topic of significant interest. Despite these incentives, a well-established small-animal model of the segmental mandibulectomy, including composite resection, does not exist. The objective of this study is the creation of a reliable animal model that can be used to study the reconstruction of en bloc mandibular defects. Surgical techniques and an array of reconstructive options are described.
Predictive Value of Glycosylated Hemoglobin for Mortality of Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention
International Journal of Cardiology. Jan, 2012 | Pubmed ID: 22284970
Corrosion Behavior and Cytotoxicity of Mg-35Zn-3Ca Alloy for Surface Modified Biodegradable Implant Material
Journal of Biomedical Materials Research. Part B, Applied Biomaterials. May, 2012 | Pubmed ID: 22287336
This study was conducted to investigate the biocompatibility of Mg-Zn-Ca ternary alloy as a biodegradable material. The casting alloy underwent anodization in an alkaline electrolyte at current density 300 mA/cm(2) and frequency 50 Hz to obtain porous oxide layer. Plasma anodization film using pulse was shown to form irregular porous oxide film. As a result of corrosion test, the corrosion current was shown to decrease and the corrosion voltage was shown to increase in the anodized group, which showed the improvement of corrosion resistance after surface treatment. Sodium silicate (0.1 M) was directly oxidized due to high charges caused by spark and then formed SiO(2), and the compounds produced inside the film were shown MgO, Mg(2) SiO(4), and SiO(2.) In the histological examination in rats, all samples of the untreated group were shown to be absorbed 3 weeks later into the body. After the magnesium alloy was implanted, blood vessel expansion and tissue change were shown in the adjacent tissues. However, the changed tissues were shown to return to normal muscle tissues 4 weeks later when the alloy was completely absorbed. These results suggest that anodized Mg-35Zn-3Ca alloy has good biocompatibility in vivo and controls the absorption rate of biomaterials.
Serum Fibroblast Growth Factor 21 Was Elevated in Subjects with Type 2 Diabetes Mellitus and Was Associated with the Presence of Carotid Artery Plaques
Diabetes Research and Clinical Practice. May, 2012 | Pubmed ID: 22293928
Fibroblast growth factor 21 (FGF21) is an important regulator of glucose/lipid metabolism. Although there are studies examining the relationship between serum FGF21 levels and glucose homeostasis, the role of FGF21 remains unclear. The objective of this study was to examine whether serum FGF21 levels are associated with metabolic parameters in subjects with varying degrees of obesity and glucose tolerance and with complications in subjects with type2 diabetes mellitus (T2DM).
Cells Transformed by PLC-gamma 1 Overexpression Are Highly Sensitive to Clostridium Difficile Toxin A-induced Apoptosis and Mitotic Inhibition
Journal of Microbiology and Biotechnology. Jan, 2012 | Pubmed ID: 22297219
Phospholipase C-γl (PLC-γl) expression is associated with cellular transformation. Notably, PLC-gamma is up-regulated in colorectal cancer tissue and breast carcinoma. Because exotoxins released by Clostridium botulinum have been shown to induce apoptosis and promote growth arrest in various cancer cell lines, we examined here the potential of Clostridium difficile toxin A to selectively induce apoptosis in cells transformed by PLC-γl overexpression. We found that PLC-γl-transformed cells, but not vectortransformed (control) cells, were highly sensitive to C. difficile toxin A-induced apoptosis and mitotic inhibition. Moreover, expression of the proapoptotic Bcl2 family member, Bim, and activation of caspase-3 were significantly up-regulated by toxin A in PLC-γl-transformed cells. Toxin A-induced cell rounding and paxillin dephosphorylation were also significantly higher in PLC-γl-transformed cells than in control cells. These findings suggest that C. difficile toxin A may have potential as an anticancer agent against colorectal cancers and breast carcinomas in which PLC-γl is highly up-regulated.
Physiological Reviews. Jan, 2012 | Pubmed ID: 22298651
Fluid and HCO(3)(-) secretion is a vital function of all epithelia and is required for the survival of the tissue. Aberrant fluid and HCO(3)(-) secretion is associated with many epithelial diseases, such as cystic fibrosis, pancreatitis, Sjögren's syndrome, and other epithelial inflammatory and autoimmune diseases. Significant progress has been made over the last 20 years in our understanding of epithelial fluid and HCO(3)(-) secretion, in particular by secretory glands. Fluid and HCO(3)(-) secretion by secretory glands is a two-step process. Acinar cells secrete isotonic fluid in which the major salt is NaCl. Subsequently, the duct modifies the volume and electrolyte composition of the fluid to absorb the Cl(-) and secrete HCO(3)(-). The relative volume secreted by acinar and duct cells and modification of electrolyte composition of the secreted fluids varies among secretory glands to meet their physiological functions. In the pancreas, acinar cells secrete a small amount of NaCl-rich fluid, while the duct absorbs the Cl(-) and secretes HCO(3)(-) and the bulk of the fluid in the pancreatic juice. Fluid secretion appears to be driven by active HCO(3)(-) secretion. In the salivary glands, acinar cells secrete the bulk of the fluid in the saliva that is driven by active Cl(-) secretion and contains high concentrations of Na(+) and Cl(-). The salivary glands duct absorbs both the Na(+) and Cl(-) and secretes K(+) and HCO(3)(-). In this review, we focus on the molecular mechanism of fluid and HCO(3)(-) secretion by the pancreas and salivary glands, to highlight the similarities of the fundamental mechanisms of acinar and duct cell functions, and to point out the differences to meet gland-specific secretions.
Biochimica Et Biophysica Acta. Apr, 2012 | Pubmed ID: 22310479
Using a proteomic approach, a study was conducted for determination of the effects of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PCDF) on proteins secreted by HepG2 cells. Briefly, HepG2 cells were exposed to various concentrations of 2,3,4,7,8-PCDF for 24 or 48h. MTT and comet assays were then conducted for determination of cytotoxicity and genotoxicity, respectively. Results of an MTT assay showed that 1nM of 2,3,4,7,8-PCDF was the maximum concentration that did not cause cell death. In addition, a dose- and time dependent increase of DNA damage was observed in HepG2 cells exposed to 2,3,4,7,8-PCDF. Therefore, two different concentrations of 2,3,4,7,8-PCDF, 1 and 5nM, were selected for further analysis of proteomic biomarkers using two different pI ranges (4-7 and 6-9) and large two dimensional gel electrophoresis. Results showed identification of 32 proteins ( 29 up- and 3 down-regulated) by nano-LC-ESI-MS/MS and nano-ESI on a Q-TOF2 MS. Among these, the identities of pyridoxine-5'-phosphate oxidase, UDP-glucose 6-dehydrogenase, plasminogen activator inhibitor I precursor, plasminogen activator inhibitor-3, proteasome activator complex subunit 1, isoform 1 of 14-3-3 protein sigma, peptidyl-prolyl cis-trans isomerase A, 14-3-3 protein gamma, protein DJ-1, and nucleoside diphosphate kinase A were confirmed by western blot analysis. The differential expression of protein DJ-1, proteasome activator complex subunit 1 and plasminogen activator inhibitor-3 was further validated in plasma proteins from rats exposed to 2,3,4,7,8-PCDF. These proteins could be used as potential toxicological biomarkers of 2,3,4,7,8-PCDF.
Cellular Signalling. Apr, 2012 | Pubmed ID: 22201561
The transient receptor potential (TRPC) family of Ca²⁺ permeable, non-selective cation channels is abundantly expressed in the brain, and can function as store-operated (SOC) and store-independent channels depending on their interaction with the ER Ca²⁺ sensor STIM1. TRPC1 and TRPC5 have critical roles in neurite outgrowth, however which of their functions regulate neurite outgrowth is unknown. In this study, we investigated the effects of TRPC channels and their STIM1-induced SOC activity on neurite outgrowth of PC12 cells. We report that PC12 cell differentiation down-regulates TRPC5 expression, whereas TRPC1 expression is retained. TRPC1 and TRPC5 interact with STIM1 through the STIM1 ERM domain. Transfection of TRPC1 and TRPC5 increased the receptor-activated Ca²⁺ influx that was markedly augmented by the co-expression of STIM1. Topical expression of TRPC1 in PC12 cells markedly increased neurite outgrowth while that of TRPC5 suppressed neurite outgrowth. Suppression of neurite outgrowth by TRPC5 requires the channel function of TRPC5. However, strikingly, multiple lines of evidence show that the TRPC1-induced neurite outgrowth was independent of TRPC1-mediated Ca²⁺ influx. Thus, a) TRPC1 and TRPC5 similarly increased Ca²⁺ influx but only TRPC1 induced neurite outgrowth, b) the constitutively STIM1(D76A) mutant that activates Ca²⁺ influx by TRPC and Orai channels did not increase neurite outgrowth, c) co-expression of TRPC5 with TRPC1 suppressed the effect of TRPC1 on neurite outgrowth, d) and most notable, channel-dead pore mutant of TRPC1 increased neurite outgrowth to the same extent as TRPC1(WT). Suppression of TRPC1-induced neurite outgrowth by TRPC5 was due to a marked reduction in the surface expression of TRPC1. We conclude that the regulation of neurite outgrowth by TRPC1 is independent of Ca²⁺ influx and TRPC1-promoted neurite outgrowth depends on the surface expression of TRPC1. It is likely that TRPC1 acts as a scaffold at the cell surface to assemble a signaling complex to stimulate neurite outgrowth.
Journal of Food Protection. Jan, 2012 | Pubmed ID: 22221376
This study was conducted to determine the concentration and optimal treatment time of chlorine for reducing feline calicivirus (FCV) and murine norovirus (MNV) as surrogates of norovirus (NoV) on stainless steel surfaces and to develop a predictive inactivation method using a response surface methodology. The reduction levels of FCV VR-782 and MNV on stainless steel surfaces after treatment with various concentrations of chlorine (0 to 5,000 ppm) for various times (0 to 5 min) were measured. The reduction values of both FCV and MNV on stainless steel surfaces after 5,000 ppm of chlorine treatment for 5 min were 5.20 TCID(50) per coupon. The predictive results obtained by central composite design were analyzed by standard analysis of variance. The application of multiple regression analysis was related to the following polynomial equations: (i) FCV (log TCID(50) per coupon) = -0.3714 + 0.8362x(1) + 0.0011x(2) + 0.0001x(1)x(2) - 0.1143x(2)(1) -0.0001x(2)(2) (x(1), time; x(2), concentration) and (ii) MNV (log TCID(50) per coupon) = + 0.0471 + 0.0807x(1) + 0.0011x(2) + 0.0001x(1)x(2) -0.0910x(2)(1) -0.0001x(2)(2) (x(1), time; x(2), concentration). It was concluded that these polynomial equation models of reduction of FCV and MNV could be used to determine the minimum concentration of chlorine and exposure times to control human NoV on food contact surfaces.
Association of IL-18 Genotype with Impaired Glucose Regulation in Korean Women with Polycystic Ovary Syndrome
European Journal of Obstetrics, Gynecology, and Reproductive Biology. Mar, 2012 | Pubmed ID: 22226490
Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age. The pro-inflammatory cytokine, interleukin (IL)-18, is associated with metabolic syndrome, and elevated serum IL-18 levels are related to obesity and insulin resistance in PCOS patients. However, the role of IL-18 in the PCOS remains unclear. So we examined whether or not two functional polymorphisms in the IL-18 gene, -137G>C and +183A>G, are associated with PCOS itself or glucose intolerance in Korean women with PCOS.
Percutaneous Coronary Intervention With Drug-Eluting Stent Implantation Vs. Coronary Artery Bypass Grafting for Multivessel Coronary Artery Disease in Metabolic Syndrome Patients With Acute Myocardial Infarction
Circulation Journal : Official Journal of the Japanese Circulation Society. Jan, 2012 | Pubmed ID: 22240598
Background: Coronary artery bypass grafting (CABG) has been the treatment of choice for management of multivessel coronary artery disease, but percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is increasingly being preferred. The aim of the present study was to compare outcomes of PCI with DES implantation (PCI-DES) and CABG for treating multivessel disease in metabolic syndrome patients with acute myocardial infarction (AMI). Methods and Results: A total of 1,839 consecutive metabolic syndrome patients with AMI who underwent PCI-DES (n=1,715) and CABG (n=124) for treatment of multivessel disease were selected from Korea Acute Myocardial Infarction Registry from November 2005 through December 2006. Primary endpoint was 12-month all-cause mortality. The mortality rate at 12 months was significantly lower in the PCI-DES group (4.8% vs. 12.2% in CABG, P=0.014) on univariate analysis. According to a Cox model, 12-month mortality was similar between the 2 groups (P=0.603), which remained the same despite propensity score adjustment (P=0.485). Rate of repeat revascularization was significantly higher in the PCI-DES group compared to the CABG group (P<0.001). At 12 months, major adverse cardiovascular and cerebrovascular event (MACCE)-free survival was higher in ST-elevation MI (STEMI) patients in the CABG group. Conclusions: PCI-DES had an equivalent 12-month mortality risk to CABG for the treatment of multivessel disease in metabolic syndrome patients with AMI. CABG is more favorable for STEMI patients in terms of MACCE.
Differential Effects of Trimetazidine on Vascular Smooth Muscle Cell and Endothelial Cell in Response to Carotid Artery Balloon Injury in Diabetic Rats
International Journal of Cardiology. Jan, 2012 | Pubmed ID: 22240760
BACKGROUND: Treatment with trimetazidine (TMZ), 1-[2,3,4-trimethoxybenzyl] piperazine, dihydrochloride, improves cardiac function and ameliorates endothelial dysfunction. However, its potential efficacy against restenosis after balloon injury has not been addressed. We investigated the effect of TMZ on reducing the occurrence of restenosis in the carotid artery in response to balloon injury and explored potential mechanisms for the effects. MATERIAL AND METHODS: Streptozotocin (40mg/kg)-injected Sprague-Dawley rats and Otsuka Long-Evans Tokushima Fatty rats were used for type 1 and type 2 diabetes models, respectively. Both types of rats were divided into three groups: control and TMZ treatment 10 and 20mg/kg per day (n=10 per group). TMZ or normal saline was given orally from 2weeks before to 2weeks after carotid injury. RESULTS: Four weeks of TMZ treatment resulted in a significant and dose-dependent reduction in the intima-media ratio in diabetic rats. This effect was accompanied by decreased proliferation of vascular smooth muscle cells (VSMCs) and accelerated re-endothelialization after carotid balloon injury. In vitro study with VSMCs decreased proliferation and migration, while human umbilical vein endothelial cells (HUVECs) increased proliferation and decreased apoptosis after TMZ treatment. Antioxidative effects of TMZ were observed in both VSMCs and HUVECs. CONCLUSIONS: Reduction of restenosis by TMZ treatment involved changes in antioxidative and anti-inflammatory properties, which are cell-specific effects on either survival or apoptosis. The specific actions and physiological effects of TMZ may contribute to better understanding of the pathogenesis of atherosclerosis, which is a major complication of diabetes mellitus.
Is Myocardial Infarction in Patients Without Significant Stenosis on a Coronary Angiogram As Benign As Believed?
Chonnam Medical Journal. Apr, 2012 | Pubmed ID: 22570814
The present study aimed to investigate the clinical characteristics and 1-year outcomes of acute myocardial infarction (AMI) patients without significant stenosis on a coronary angiogram comparison with the clinical characteristics and outcomes of patients with significant coronary artery stenosis. A total of 1,220 patients with AMI were retrospectively classified into Group I (≥50% diameter stenosis, n=1,120) and Group II (<50%, n=100). Group II was further divided into two subgroups according to the underlying etiology: cryptogenic (Group II-a, n=54) and those with possible causative factors (Group II-b, n=46). Patients in Group II were younger, were more likely to be women, and were less likely to smoke and to have diabetes mellitus than were patients in Group I. The levels of cardiac enzymes, LDL-cholesterol levels, and the apo-B/A1 ratio were lower in Group II. However, 1-month and 12-month rates of major adverse cardiac events (MACE) were not significantly different between the two groups. The Group II-b subgroup comprised 29 patients with vasospasm, 11 with myocardial bridge, and 6 with spontaneous thrombolysis. Left ventricular ejection fraction and creatinine clearance were lower and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) were higher in Group II-a than in Group II-b. However, outcomes including MACE and mortality at 12 months were not significantly different between the two subgroups. The 1-year outcomes of patients in Group II were similar to those of patients in Group I. The clinical outcomes in Group II-a were also similar to those of Group II-b, although the former group showed higher levels of NT-proBNP and hs-CRP.
Chonnam Medical Journal. Apr, 2012 | Pubmed ID: 22570816
The aim of this study was to evaluate the clinical effect of a continuous infusion of urokinase in cerebral stoke patients who were late admitted over 6 hours after onset. From January to December in 2008, acute cerebral stroke patients (n=143) treated with intravenous urokinase infusion (Group I, n=93) or not (Group II, n=50) after 6 hours and within 72 hours of stroke onset were reviewed. Continuous intravenous infusion of urokinase was done for 5 days. The clinical outcome for each patient was evaluated by using the modified National Institutes of Health Stroke Scale (NIHSS) on admission and on the day of discharge. The NIHSS score was decreased at discharge compared with admission in the urokinase treatment group (Group I; from 4.8±2.2 to 3.8±1.9; p=0.002). There was an improvement in the patients who initiated urokinase treatment within 24 hours from stroke onset in Group I (from 5.1±1.9 to 3.9±1.5; p=0.04). In patients with initiated urokinase treatment within 24 hours from stroke onset, intravenous urokinase infusion could be an effective modality in acute ischemic stroke patients admitted later than 6 hours after onset.
EAAC1 Gene Deletion Alters Zinc Homeostasis and Enhances Cortical Neuronal Injury After Transient Cerebral Ischemia in Mice
Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS). May, 2012 | Pubmed ID: 22575539
The excitatory amino acids glutamate and cysteine are actively transported into neurons from the extracellular space by the high affinity glutamate transporter EAAC1. The astrocyte glutamate transporters, GLT1 and GLAST, are the primary mediators of glutamate clearance. EAAC1 has a limited role in this function. However, uptake of cysteine into neurons via EAAC1 contributes to neuronal antioxidant function by providing cysteine substrate for glutathione synthesis. Mice in which the EAAC1 gene has been deleted were seen to have enhanced susceptibility to neuronal oxidative stress and developed brain atrophy and cognitive function decline with aging. The aim of the current study was to evaluate if EAAC1 confers protection against ischemic events. Young adult CD-1 wild-type or EAAC1(-/-) mice were subjected to 30 min of bilateral common carotid artery occlusion and evaluated for neuronal death and zinc translocation. The intensity of TSQ fluorescence in the cytoplasm of cortical neurons in the EAAC1(-/-) mice was significantly higher than wild-type mice, indicating that the cortical neurons of EAAC1(-/-) mice contain higher cytoplasmic concentrations of labile (or free) zinc. Zinc translocation into cortical neurons was also enhanced in EAAC1(-/-) mice. Three days after ischemia, Fluoro-Jade B staining revealed that EAAC1(-/-) mice had more than twice as many degenerating neurons as wild-type mice. N-acetylcysteine, a membrane-permeant cysteine pro-drug, normalized basal zinc levels, reduced TSQ (+) neurons and reduced ischemic neuronal death in the EAAC1(-/-) mice when delivered in a pre-treatment fashion. Taken together, this study implicates EAAC1-dependent cysteine uptake as an endogenous source of enhancing antioxidant function and zinc homeostasis in neurons in the ischemic brain.
Characterization of Arginylation Branch of N-end Rule Pathway in G-protein-mediated Proliferation and Signaling of Cardiomyocytes
The Journal of Biological Chemistry. May, 2012 | Pubmed ID: 22577142
The N-end rule pathway is a proteolytic system in which destabilizing N-terminal amino acids of short lived proteins are recognized by recognition components (N-recognins) as an essential element of degrons, called N-degrons. In eukaryotes, the major way to generate N-degrons is through arginylation by ATE1 arginyl-tRNA-protein transferases, which transfer Arg from aminoacyl-tRNA to N-terminal Asp and Glu (and Cys as well in mammals). We have shown previously that ATE1-deficient mice die during embryogenesis with defects in cardiac and vascular development. Here, we characterized the arginylation-dependent N-end rule pathway in cardiomyocytes. Our results suggest that the cardiac and vascular defects in ATE1-deficient embryos are independent from each other and cell-autonomous. ATE1-deficient myocardium and cardiomyocytes therein, but not non-cardiomyocytes, showed reduced DNA synthesis and mitotic activity ~24 h before the onset of cardiac and vascular defects at embryonic day 12.5 associated with the impairment in the phospholipase C/PKC-MEK1-ERK axis of Gα(q)-mediated cardiac signaling pathways. Cardiac overexpression of Gα(q) rescued ATE1-deficient embryos from thin myocardium and ventricular septal defect but not from vascular defects, genetically dissecting vascular defects from cardiac defects. The misregulation in cardiovascular signaling can be attributed in part to the failure in hypoxia-sensitive degradation of RGS4, a GTPase-activating protein for Gα(q). This study is the first to characterize the N-end rule pathway in cardiomyocytes and reveals the role of its arginylation branch in Gα(q)-mediated signaling of cardiomyocytes in part through N-degron-based, oxygen-sensitive proteolysis of G-protein regulators.
Rasch Analysis of the Pediatric Outcomes Data Collection Instrument in 720 Patients with Cerebral Palsy
Journal of Pediatric Orthopedics. Jun, 2012 | Pubmed ID: 22584846
The pediatric outcomes data collection instrument (PODCI) was originally developed to carry out a functional assessment of children and adolescents (including patients with cerebral palsy), focusing on musculoskeletal health. Validated questionnaires are important for assessing the functional outcome of cerebral palsy, and are meant to have unidimensionality, proper item gap, no ceiling and floor effects, and no item redundancy. The advances in health measurements have led to the application of Rasch analysis to assess questionnaires. This study evaluated PODCI in patients with cerebral palsy using Rasch analyses.
Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. May, 2012 | Pubmed ID: 22595354
Recent studies suggest that subtotal resection (STR) followed by adjuvant radiation therapy is an appealing alternative to gross total resection (GTR) for craniopharyngioma, as STR provides similar tumor control without the associated endocrinological and behavioral morbidity. We have examined the impact of maximal safe resection on the clinical outcome of patients with craniopharyngioma. A total of 90 patients underwent surgical resection of craniopharyngioma at a single institution between January 1995 and April 2009. Sixty-one patients underwent GTR alone, four underwent GTR followed by adjuvant radiotherapy, 15 underwent STR alone, and 10 underwent partial removal followed by adjuvant radiotherapy. We analyzed and compared the clinical and endocrinological outcomes and radiological follow-up data of these patients. During the follow-up period, tumor recurrence following the initial resection occurred in 36 of 90 patients (40%). The repeat resection rate was higher in the STR group than the GTR group. Recurrence occurred in 20 of 61 patients (32.8%) from the GTR alone group, in 11 of 15 patients (73.3%) from the STR alone group, and in five of 10 (50%) patients from the STR with adjuvant radiation, such as radiotherapy or stereotactic radiosurgery, group (p=0.030). Maximal safe resection of craniopharyngioma leads to excellent local control. STR with adjuvant radiation therapy does not assure preservation of endocrine function, although it provides better local control than STR alone.
Clinical Significance of ERCC2 Haplotype-tagging Single Nucleotide Polymorphisms in Patients with Unresectable Non-small Cell Lung Cancer Treated with First-line Platinum-based Chemotherapy
Lung Cancer (Amsterdam, Netherlands). May, 2012 | Pubmed ID: 22608006
First-line platinum-based chemotherapy is currently considered the standard treatment for unresectable non-small cell lung cancer (NSCLC). However, resistance to platinum-based chemotherapy results in poor prognoses. The DNA repair pathway is a crucial molecular mechanism potentially involved in resistance to platinum-based chemotherapy. ERCC2 plays an integral role in the nucleotide excision repair pathway. Furthermore, single nucleotide polymorphisms (SNPs) and haplotypes in the ERCC2 gene are thought to be associated with the risk of developing lung cancer and clinical outcomes. Therefore, we evaluated the impact of ERCC2 haplotype-tagging SNPs (htSNPs) on the clinical parameters of first-line platinum-based chemotherapy in unresectable NSCLC.
Food Microbiology. Sep, 2012 | Pubmed ID: 22608225
Among the traditional fermented vegetables in Korea, Dongchimi is a type of kimchi with a large water base. We aimed to investigate the survival of norovirus surrogates during Dongchimi fermentation. Dongchimi spiked with feline calicivirus (FCV) or murine norovirus (MNV) was prepared following a traditional recipe. Dongchimi was initially fermented at room temperature overnight and then kept at 4 °C. The number of lactic acid bacteria, pH, acidity, and virus titer were measured 0, 1, 2, 3, 5, 7, 10, 15, 20 days after fermentation. During the fermentation process, lactic acid bacteria and acidity increased. At the end of the fermentation, population of FCV and MNV decreased about 4.12 and 1.47 log units, respectively. Based on the significant reduction of norovirus surrogate during Dongchimi fermentation, we conclude that the risk of norovirus in Dongchimi may be low.
Cell-penetrating Peptide Mimicking Polymer-based Combined Delivery of Paclitaxel and SiRNA for Enhanced Tumor Growth Suppression
International Journal of Pharmaceutics. May, 2012 | Pubmed ID: 22613208
Cancer chemotherapy is often limited, since more than one molecule is usually involved with the cancer pathogenesis. A combination of therapeutic drugs would be a promising approach to overcome the complexity of tumors. In this study, a conjugate (DA3) of deoxycholic acid and low molecular weight polyethylenimine (PEI 1.8 kDa), which has a property that mimics that of cell penetrating peptides (CPPs), was used for simultaneous delivery of an anticancer drug and siRNA. When complexed with siRNA, DA3 showed significantly higher target gene silencing efficiency than PEI 25 kDa. The gene silencing efficiency of DA3 was maintained even in the presence of endocytosis inhibitors, suggesting that the polymeric carrier can mediate an endocytosis-independent macromolecular transduction similar to CPPs. The capability of forming a micelle-like core-shell structure enables the conjugates to encapsulate and dissolve paclitaxel (PTX), a water-insoluble drug. The drug-loaded cationic micelles can then interact with siRNA to form stable complexes (PTX/DA3/siRNA). The PTX/DA3/siRNA showed significantly enhanced inhibition of cancer cell growth. When administered into tumor-bearing animals, the PTX/DA3/siRNA demonstrated significant suppression of tumor growth, providing potential usefulness in clinical settings.
UBR2 of the N-end Rule Pathway is Required for Chromosome Stability Via Histone Ubiquitylation in Spermatocytes and Somatic Cells
PloS One. 2012 | Pubmed ID: 22616001
The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells.
Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma: Fusion Imaging Guidance for Management of Lesions with Poor Conspicuity at Conventional Sonography
AJR. American Journal of Roentgenology. Jun, 2012 | Pubmed ID: 22623560
The purpose of this study was to determine whether fusion imaging-guided percutaneous radiofrequency ablation (RFA) is effective in the management of hepatocellular carcinoma (HCC) that has poor conspicuity at conventional sonography.
Cellular Signalling. Sep, 2012 | Pubmed ID: 22627094
SLC26A3 functions as a chloride/bicarbonate anion exchanger expressed in the secretory epithelial cells in the intestine, pancreas, and salivary glands. SLC26A3 has a C-terminal class I PDZ binding motif that assembles regulatory factors or other transporters by anchoring to various PDZ scaffold proteins. NHERF4 is an epithelial-enriched PDZ domain scaffold protein that has attracted attention because of its enriched tissue expression in the intestine and kidney. In this study, we identified SLC26A3 as a novel binding transporter of NHERF4. We investigated the functional role of NHERF4 in the regulation of SLC26A3 by using integrated biochemical and physiological approaches. A direct protein-protein interaction was identified between the PDZ-binding motif of SLC26A3 and the third PDZ domain of NHERF4. Interaction with NHERF4 decreased the level of SLC26A3 expression on the plasma membrane, which led to reduced SLC26A3 anion exchange activity. Notably, interaction with NHERF4 induced rapid internalisation of SLC26A3 from the plasma membrane. The SLC26A3-NHERF4 interaction was modulated by phosphorylation; serine 329 of NHERF4-PDZ3 played a critical role in modulating binding selectivity. Our findings suggest that NHERF4 is a novel modulator of luminal fluidity in the intestine by adjusting SLC26A3 expression and activity through a phosphorylation-dependent mechanism.
Journal of Pharmaceutical Sciences. Aug, 2012 | Pubmed ID: 22628192
Living organisms secrete minerals composed of peptides and proteins, resulting in "mesocrystals" of three-dimensional-assembled composite structures. Recently, this biomimetic polymer-directed crystallization technique has been widely applied to inorganic materials, although it has seldom been used with drugs. In this study, the technique was applied to the drowning-out crystallization of atorvastatin using various polymers. Nucleation and growth at optimized conditions successfully produced composite crystals with significant polymer contents and unusual characteristics. Atorvastatin composite crystals containing polyethylene glycol, polyacrylic acid, polyethylene imine, and chitosan showed a markedly decreased melting point and heat of fusion, improved stability, and sustained-release patterns. The use of hydroxypropyl cellulose yielded a unique combination of enhanced in vitro release and improved drug stability under a forced degradation condition. The formation hypothesis of unique mesocrystal structures was strongly supported by an X-ray diffraction pattern and substantial melting point reduction. This polymer-directed crystallization technique offers a novel and effective way, different from the solid dispersion approach, to engineer the release, stability, and processability of drug crystals.
Relation Between Poststenting Peristent Plaque Components and Late Stent Malapposition After Drug-eluting Stent Implantation: Virtual Histology-intravascular Ultrasound Analysis
International Journal of Cardiology. May, 2012 | Pubmed ID: 22633434
BACKGROUND: Impact of plaque composition on late stent malapposition (LSM) after drug-eluting stent (DES) implantation has not been evaluated. METHODS: We evaluated the relation between plaque components at poststenting peristent area (between external elastic membrane and stent areas) and LSM after DES implantation in 266 patients (314 native lesions; paclitaxel-eluting stent in 205 lesions, sirolimus-eluting stent in 66 lesions, zotarolimus-eluting stent in 32 lesions and everolimus-eluting stent in 11 lesions) in whom virtual-histology intravascular ultrasound was performed at index (poststenting) and follow-up (mean: 11.7±4.8months). RESULTS: LSM occurred in 24 patients with 30 lesions (9.6%) and there were no significant differences in the incidences of LSM among 4 DES groups [21/205 (10.2%) in paclitaxel-eluting stent, 6/66 (9.1%) in sirolimus-eluting stent, 2/32 (6.3%) in zotarolimus-eluting stent and 1/11 (9.1%) in everolimus-eluting stent, p=0.5)]. Patients with LSM were presented with more acute myocardial infarction (50% vs. 28%, p=0.026) and were more diabetics (50% vs. 30%, p=0.030) compared with those without LSM. Lesions with LSM had more poststenting peristent %necrotic core (NC) volume compared with those without LSM (25.8±11.1% vs. 21.0±5.7%, p<0.001). Independent predictors of LSM were poststenting peristent %NC volume [odds ratio (OR); 1.216, 95% CI; 1.053-1.405, p=0.008], acute myocardial infarction (OR; 2.897, 95% CI; 1.675-4.118, p=0.029), and diabetes mellitus (OR; 2.413, 95% CI; 1.543-3.996, p=0.038). CONCLUSIONS: Poststenting peristent NC component especially in patients with acute myocardial infarction and in those with diabetes mellitus is associated with the development of LSM after DES implantation.
Ethyl Pyruvate Attenuates Formalin-induced Inflammatory Nociception by Inhibiting Neuronal ERK Phosphorylation
Molecular Pain. 2012 | Pubmed ID: 22640699
Direct Fluorescence Monitoring of the Delivery and Cellular Uptake of a Cancer-targeted RGD Peptide-appended Naphthalimide Theragnostic Prodrug
Journal of the American Chemical Society. Aug, 2012 | Pubmed ID: 22642558
Presented here is a multicomponent synthetic strategy that allows for the direct, fluorescence-based monitoring of the targeted cellular uptake and release of a conjugated therapeutic agent. Specifically, we report here the design, synthesis, spectroscopic characterization, and preliminary in vitro biological evaluation of a RGD peptide-appended naphthalimide pro-CPT (compound 1). Compound 1 is a multifunctional molecule composed of a disulfide bond as a cleavable linker, a naphthalimide moiety as a fluorescent reporter, an RGD cyclic peptide as a cancer-targeting unit, and camptothecin (CPT) as a model active agent. Upon reaction with free thiols in aqueous media at pH 7.4, disulfide cleavage occurs. This leads to release of the free CPT active agent, as well as the production of a red-shifted fluorescence emission (λ(max) = 535 nm). Confocal microscopic experiments reveal that 1 is preferentially taken up by U87 cells over C6 cells. On the basis of competition experiments involving okadaic acid, an inhibitor of endocytosis, it is concluded that uptake takes place via RGD-dependent endocytosis mechanisms. In U87 cells, the active CPT payload is released within the endoplasmic reticulum, as inferred from fluorescence-based colocalization studies using a known endoplasmic reticulum-selective dye. The present drug delivery system (DDS) could represent a new approach to so-called theragnostic agent development, wherein both a therapeutic effect and drug uptake-related imaging information are produced and can be readily monitored at the subcellular level. In due course, the strategy embodied in conjugate 1 could allow for more precise monitoring of dosage levels, as well as an improved understanding of cellular uptake and release mechanisms.
Inhibitory Effect of Dibutyryl Chitin Ester on Nitric Oxide and Prostaglandin E₂ Production in LPS-stimulated RAW 264.7 Cells
Archives of Pharmacal Research. Jul, 2012 | Pubmed ID: 22864752
Inflammation is a highly complex process that protects against foreign challenge or tissue injury. The ester derivative dibutyryl chitin (DBC) reportedly accelerates wound healing and exerts an anti-inflammatory effect. However, little is known regarding the inhibitory effect of DBC in anti-inflammation. In this study, we investigated the effect of DBC on the inducible nitric oxide synthetase (iNOS) and cyclooxygenage-2 (COX-2) pathways and pro-inflammatory cytokine production in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Our results demonstrate that DBC (MW 3,772) significantly inhibits overproduction of NO and PGE(2) as well as pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β, in LPS-stimulated RAW 264.7 macrophages. Inhibition of NO and PGE(2) overproduction in LPSstimulated RAW 264.7 macrophages by DBC was mediated through the down-regulation of iNOS and COX-2 expression. These results demonstrate that DBC efficiently inhibits inflammation and has potential as an effective anti-inflammatory and wound healing agent.
Korean Journal of Urology. Jul, 2012 | Pubmed ID: 22866225
Anterior urethral valve is a rare congenital anomaly that can cause obstructive uropathy. Herein, we report a case of an anterior urethral valve that led to the development of febrile urinary tract infection in a neonate.
Clinical Endoscopy. Jun, 2012 | Pubmed ID: 22866255
Benign colon (18)F-fluorodeoxyglucose (FDG) uptake is frequently observed in asymptomatic individuals. Aims of this study were to investigate the benign colon uptake by whole body FDG-positron emission tomography (PET) in asymptomatic adults and to correlate those results with colonoscopic and histologic findings.
The Analyst. Oct, 2012 | Pubmed ID: 22866327
A novel ferrocene-based anion receptor bearing amide and triazolium donor groups and its anion complexation have been reported. We found that it shows marked electrochemical selectivity to F(-), followed by AcO(-) > Cl(-) > Br(-) > I(-), which is in accordance with (1)H NMR titration results.
Preclinical Profile and Characterization of the Hepatitis C Virus NS3 Protease Inhibitor Asunaprevir (BMS-650032)
Antimicrobial Agents and Chemotherapy. Oct, 2012 | Pubmed ID: 22869577
Asunaprevir (ASV; BMS-650032) is a hepatitis C virus (HCV) NS3 protease inhibitor that has demonstrated efficacy in patients chronically infected with HCV genotype 1 when combined with alfa interferon and/or the NS5A replication complex inhibitor daclatasvir. ASV competitively binds to the NS3/4A protease complex, with K(i) values of 0.4 and 0.24 nM against recombinant enzymes representing genotypes 1a (H77) and 1b (J4L6S), respectively. Selectivity was demonstrated by the absence of any significant activity against the closely related GB virus-B NS3 protease and a panel of human serine or cysteine proteases. In cell culture, ASV inhibited replication of HCV replicons representing genotypes 1 and 4, with 50% effective concentrations (EC(50)s) ranging from 1 to 4 nM, and had weaker activity against genotypes 2 and 3 (EC(50), 67 to 1,162 nM). Selectivity was again demonstrated by the absence of activity (EC(50), >12 μM) against a panel of other RNA viruses. ASV exhibited additive or synergistic activity in combination studies with alfa interferon, ribavirin, and/or inhibitors specifically targeting NS5A or NS5B. Plasma and tissue exposures in vivo in several animal species indicated that ASV displayed a hepatotropic disposition (liver-to-plasma ratios ranging from 40- to 359-fold across species). Twenty-four hours postdose, liver exposures across all species tested were ≥110-fold above the inhibitor EC(50)s observed with HCV genotype-1 replicons. Based on these virologic and exposure properties, ASV holds promise for future utility in a combination with other anti-HCV agents in the treatment of HCV-infected patients.
Lower Extremity Reconstruction Using Vastus Lateralis Myocutaneous Flap Versus Anterolateral Thigh Fasciocutaneous Flap
Archives of Plastic Surgery. Jul, 2012 | Pubmed ID: 22872841
The anterolateral thigh (ALT) perforator flap has become a popular option for treating soft tissue defects of lower extremity reconstruction and can be combined with a segment of the vastus lateralis muscle. We present a comparison of the use of the ALT fasciocutaneous (ALT-FC) and myocutaneous flaps.
International Journal of Pharmaceutics. Nov, 2012 | Pubmed ID: 22877696
Drug nanoparticles prepared in a liquid medium are commonly freeze-dried for the preparation of an oral dosage in solid dosage form. The freezing rate is known to be a critical parameter for redispersible nanoformulations. However, there has been controversy as to whether a fast or slow freezing rate prevents irreversible aggregation. A systematic investigation is presented herein regarding the effect of both the molecular weight of the cryoprotectant and the freezing rate in order to elucidate the mechanism underlying irreversible aggregation. It was found that irreversible aggregation occurred during drying rather than freezing, although a proper freezing rate is critical. A more homogeneous distribution of the cryoprotectant and drug nanoparticles led to more redispersible powders. Thus, keeping the local concentration distribution of the nanoparticles and cryoprotectant fixed during the freezing step plays a critical role in how the freezing rate affects the redispersibility. The kinetic approach of excluding the tendency of ice crystal growth permitted an explanation of the controversial results. This study will facilitate an in-depth understanding of the aggregation process of nanoparticles or proteins during freeze-drying.
Context-dependent Proangiogenic Function of Bone Morphogenetic Protein Signaling is Mediated by Disabled Homolog 2
Developmental Cell. Aug, 2012 | Pubmed ID: 22898784
Bone morphogenetic proteins (BMPs) have diverse functions during development in vertebrates. We have recently shown that BMP2 signaling promotes venous-specific angiogenesis in zebrafish embryos. However, factors that confer a context-dependent proangiogenic function of BMP2 signaling within endothelial cells need to be identified. Here, we report that Disabled homolog 2 (Dab2), a cargo-specific adaptor protein for Clathrin, is essential to mediate the proangiogenic function of BMP2 signaling. We find that inhibition of Dab2 attenuates internalization of BMP receptors and abrogates the proangiogenic effects of BMP signaling in endothelial cells. Moreover, inhibition of Dab2 decreases phosphorylation of SMAD-1, 5, and 8, indicating that Dab2 plays an essential role in determining the outcome of BMP signaling within endothelial cells and may provide a molecular basis for a context-dependent proangiogenic function of BMP2 signaling.
Circulation. Oct, 2012 | Pubmed ID: 22914687
Supravalvular aortic stenosis (SVAS) is caused by mutations in the elastin (ELN) gene and is characterized by abnormal proliferation of vascular smooth muscle cells (SMCs) that can lead to narrowing or blockage of the ascending aorta and other arterial vessels. Having patient-specific SMCs available may facilitate the study of disease mechanisms and development of novel therapeutic interventions.
Acta Biomaterialia. Aug, 2012 | Pubmed ID: 22935326
Injectable cartilaginous constructs that can form gels in tissue defects have many advantages in tissue engineering applications. In this study we created an injectable hydrogel consisting of methacrylated glycol chitosan (MeGC) and hyaluronic acid (HA) by photocrosslinking with a riboflavin photoinitiator under visible light. A minimum irradiation time of 40s was required to produce stable gels for cell encapsulation with 87-90% encapsulated chondrocyte viability. Although increasing the irradiation time from 40 to 600s significantly enhanced the compressive modulus of the hydrogels up to 11 or 17kPa for MeGC or MeGC/HA, respectively, these conditions reduced the encapsulated cell viability to 60-65%. The majority of chondrocytes encapsulated in MeGC hydrogels after 300s irradiation maintained a rounded shape with a high cell viability of ∼80-87% over a 21day culture period. The incorporation of HA in MeGC hydrogels increased the proliferation and deposition of cartilaginous extracellular matrix by encapsulated chondrocytes. These findings demonstrate that MeGC/HA composite hydrogels have the potential for cartilage repair.
Voluntary Resistance Running with Short Distance Enhances Spatial Memory Related to Hippocampal BDNF Signaling
Journal of Applied Physiology (Bethesda, Md. : 1985). Oct, 2012 | Pubmed ID: 22936723
Although voluntary running has beneficial effects on hippocampal cognitive functions if done abundantly, it is still uncertain whether resistance running would be the same. For this purpose, voluntary resistance wheel running (RWR) with a load is a suitable model, since it allows increased work levels and resultant muscular adaptation in fast-twitch muscle. Here, we examined whether RWR would have potential effects on hippocampal cognitive functions with enhanced hippocampal brain-derived neurotrophic factor (BDNF), as does wheel running without a load (WR). Ten-week-old male Wistar rats were assigned randomly to sedentary (Sed), WR, and RWR (to a maximum load of 30% of body weight) groups for 4 wk. We found that in RWR, work levels increased with load, but running distance decreased by about half, which elicited muscular adaptation for fast-twitch plantaris muscle without causing any negative stress effects. Both RWR and WR led to improved spatial learning and memory as well as gene expressions of hippocampal BDNF signaling-related molecules. RWR increased hippocampal BDNF, tyrosine-related kinase B (TrkB), and cAMP response element-binding (CREB) protein levels, whereas WR increased only BDNF. With both exercise groups, there were correlations between spatial memory and BDNF protein (r = 0.41), p-CREB protein (r = 0.44), and work levels (r = 0.77). These results suggest that RWR plays a beneficial role in hippocampus-related cognitive functions associated with hippocampal BDNF signaling, even with short distances, and that work levels rather than running distance are more determinant of exercise-induced beneficial effects in wheel running with and without a load.
Efficacy and Tolerability of Diphenyl-dimethyldicarboxylate Plus Garlic Oil in Patients with Chronic Hepatitis
International Journal of Clinical Pharmacology and Therapeutics. Nov, 2012 | Pubmed ID: 22943930
Objective: To investigate the hepatoprotective effect, safety and tolerability of oral preparation comprising dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) plus garlic oil (GO) in chronic hepatitis patients. Methods: In this double-blind, placebo-controlled clinical trial conducted for 6 weeks with 1-week follow-up, a total of 88 patients with histologically confirmed chronic hepatitis and persistently elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were enrolled and randomly assigned to one of 4 treatment groups: placebo (Group A) and 3 escalating dose groups (2, 3, or 6 study drug capsules a day) (Groups B - D). Each study drug capsule contains 25 mg DDB plus 50 mg GO. Efficacy was assessed by monitoring changes in the circulating activities of ALT and AST as surrogate markers for liver injury. Safety and tolerability were assessed based on the evaluation of clinically adverse events and laboratory test results. Results: Of 88 patients, 83 took at least one dose of study drug and 79 completed the study without any protocol violation. The majority of patients (81/83, 98%) had been infected with HBV. The proportions of patients whose ALT levels returned to normal ranges at Week 6, a primary outcome, were significantly different among 4 groups: 16% (3/19), 41% (9/22), 52% (11/21), and 88% (15/17) in Groups A, B, C, and D, respectively (p < 0.001). The proportions were significantly higher in Groups C (p = 0.022) and D (p < 0.001) but not in Group B compared to Group A. Interestingly, the proportion of Group D was higher than that of Group C (p = 0.034), suggesting a dose-response effect of DDB plus GO on the decrease of ALT levels. The mean ALT levels started to decrease from Week 1 in patients treated with DDB plus GO, whereas no decrease was seen in placebo group. The mean AST levels had a decreasing trend in all doses of DDB plus GO groups. Notably, patients treated with 6 capsules of DDB plus GO daily exhibited the statistically significant decrease in AST levels from Week 3. However, there was no difference in the proportions of patients with the AST decrease to normal ranges after 6-week therapy among 4 groups. The effects of DDB plus GO on decreases in ALT and AST levels lasted until 1 week after completion of treamment. Additionally, the ratios of ALT to AST gradually decreased in patients treated with DDB plus GO over time, suggesting higher degrees of reduction in ALT than in AST in those groups. No clinically meaningful adverse events and laboratory abnormalities were observed during the study period. Conclusions: The 6-week treatment of DDB plus GO lowered serum aminotransferase activities in patients with chronic hepatitis induced by HBV and/or HCV and was well tolerated. For the treatment of viral hepatitis patients, the optimal dose of this preparation was 3 to 6 capsules per day.
3,4,5-tricaffeoylquinic Acid Inhibits the Lipopolysaccharide-stimulated Production of Inflammatory Mediators in Keratinocytes
Pharmacology. 2012 | Pubmed ID: 22947851
Background and Purpose: Microbial product lipopolysaccharide (LPS) has been shown to be involved in the pathogenesis of inflammatory skin diseases. Caffeoyl derivatives have demonstrated anti-inflammatory and antioxidant effects. However, the effect of 3,4,5-tricaffeoylquinic acid (3,4,5-triCQA) on the production of microbial product-induced inflammatory mediators in keratinocytes has not yet been studied. Experimental Approach: Using human keratinocytes, we investigated the effect of 3,4,5-triCQA on the LPS-stimulated production of inflammatory mediators in relation to the nuclear factor (NF)-ĸB, Akt and ERK pathways. Results: 3,4,5-triCQA inhibited the LPS-induced expression of Toll-like receptor 4, and the production of cytokines and chemokines in keratinocytes. 3,4,5-triCQA, Bay 11-7085, Aĸt inhibitor and ERK inhibitor each attenuated the LPS-induced production of inflammatory mediators by inhibiting the NF-ĸB, Akt and ERK pathways. Conclusions and Implications: 3,4,5-triCQA may attenuate the LPS-stimulated production of inflammatory mediators in keratinocytes by suppressing the Toll-like receptor 4 expression-mediated activation of the Akt, ERK and NF-ĸB pathways. 3,4,5-triCQA may exert a preventive effect against microbial product-induced inflammatory skin diseases.
Biotechnology for Biofuels. Sep, 2012 | Pubmed ID: 22958710
ABSTRACT: BACKGROUND: In the present study, three ionic liquids, namely 1-butyl-3-methylimidazolium chloride ([BMIM]Cl), 1-ethyl-3-methylimidazolium acetate ([EMIM]OAc), and 1-ethyl-3-methylimidazolium diethyl phosphate ([EMIM]DEP), were used to partially dissolve rice husk, after which the cellulose were regenerated by the addition of water. The aim of the investigation is to examine the implications of the ionic liquid pretreatments on rice husk composition and structure. RESULTS: From the attenuated total reflectance Fourier transform-infrared (ATR FT-IR) spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM) results, the regenerated cellulose were more amorphous, less crystalline, and possessed higher structural disruption compared with untreated rice husk. The major component of regenerated cellulose from [BMIM]Cl and [EMIM]DEP pretreatments was cellulose-rich material, while cellulose regenerated from [EMIM]OAc was a matrix of cellulose and lignin. Cellulose regenerated from ionic pretreatments could be saccharified via enzymatic hydrolysis, and resulted in relatively high reducing sugars yields, whereas enzymatic hydrolysis of untreated rice husk did not yield reducing sugars. Rice husk residues generated from the ionic liquid pretreatments had similar chemical composition and amorphousity to that of untreated rice husk, but with varying extent of surface disruption and swelling. CONCLUSIONS: The structural architecture of the regenerated cellulose and rice husk residues showed that they could be used for subsequent fermentation or derivation of cellulosic compounds. Therefore, ionic liquid pretreatment is an alternative in the pretreatment of lignocellulosic biomass in addition to the conventional chemical pretreatments.
Interleukin-6 Induces S100A9 Expression in Colonic Epithelial Cells Through STAT3 Activation in Experimental Ulcerative Colitis
PloS One. 2012 | Pubmed ID: 22962574
Intestinal epithelium is essential for maintaining normal intestinal homeostasis; its breakdown leads to chronic inflammatory pathologies, such as inflammatory bowel diseases (IBDs). Although high concentrations of S100A9 protein and interleukin-6 (IL-6) are found in patients with IBD, the expression mechanism of S100A9 in colonic epithelial cells (CECs) remains elusive. We investigated the role of IL-6 in S100A9 expression in CECs using a colitis model.
Journal of Nanoscience and Nanotechnology. Jul, 2012 | Pubmed ID: 22966631
The reliability of sensor characteristics for a nano-bismuth (Bi)/silver (Ag) paste electrode has been investigated by comparison with Hg/Bi film electrodes in terms of accuracy and precision. Using Ag paste instead of carbon paste as a conducting layer, the sensitivity and detection limit of the sensor electrode were more enhanced due to a lower electrical conductivity of Ag. For the evaluation of detecting ability, the Zn, Cd, and Pb ion concentrations of the prepared standard solutions were experimentally measured on Hg film, Bi film, and nano-Bi electrodes using anodic stripping voltammetry. A nano-Bi electrode can detect Zn, Cd, and Pb ions at 0.1 ppb with higher precision and accuracy compared with Hg film and Bi film electrodes. From the trace analyses of Zn, Cd, and Pb ions in commercial drinking water and river water using a nano-Bi electrode and inductively coupled plasma (ICP) technique, it was concluded that the nano-Bi electrode exhibited excellent sensing characteristics with high reliability, and could detect even traces of Zn, Cd, and Pb ions that were not detected by the ICP method.
Brazilin Induces Apoptosis and G2/M Arrest Via Inactivation of Histone Deacetylase in Multiple Myeloma U266 Cells
Journal of Agricultural and Food Chemistry. Oct, 2012 | Pubmed ID: 22967175
Although brazilin [7,11b-dihydrobenz(b)indeno[1,2-d]pyran-3,6a,9,10(6H)-tetrol] isolated from Caesalpinia sappan was known to have various biological activities, including anti-inflammation, antibacteria, and antiplatelet aggregation, there is no report yet on its anticancer activity. In the present study, the anticancer mechanism of brazilin was elucidated in human multiple myeloma U266 cells. We found that brazilin significantly inhibited the activity of histone deacetylases (HDACs), transcription factors involved in the regulation of apoptosis and cell cycle arrest in U266 cells. Consistently, brazilin enhanced acetylation of histone H3 at Lys 23, indicating activation of histone acetyltransferase (HAT), and also suppressed the expressions of HDAC1 and HDAC2 at both protein and mRNA levels. Additionally, brazilin significantly increased the number of sub-G1 cell population and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells undergoing apoptosis and also activated caspase-3 and regulated the expression of Bcl-2 family proteins, including Bax, Bcl-x(L), and Bcl-2 in U266 cells, indicating that brazilin induces apoptosis through the mitochondria-dependent pathway. Interestingly, cell cycle analysis revealed that brazilin induced G2/M phase arrest along with apoptosis induction. Consistently, brazilin attenuated the expression of cyclin-dependent kinases (CDKs), such as cyclin D1, cyclin B1, and cyclin E, and also activated p21 and p27 in U266 cells. Furthermore, HAT inhibitor anacardic acid reversed activation of acetyl-histone H3 and cleavage of PARP induced by brazilin, while pan-caspase inhibitor Z-VAD-FMK001 did not affect the expression of HDAC induced by brazilin that brazilin mediates apoptosis via inactivation of HDAC in U266 cells. Notably, brazilin significantly potentiated the cytotoxic effect of standard chemotherapeutic agents, such as bortezomib or doxorubicin, in U266 cells. When our findings are taken together, they suggest that brazilin has potential as a chemotherapeutic agent alone or in combination with an anticancer agent for multiple myeloma treatment.
Cytokine. Dec, 2012 | Pubmed ID: 22980485
The effects of therapeutic hypothermia (HT) during experimental sepsis may be influenced by disease severity. We experimentally investigated the effect of therapeutic HT on varying disease severity in a septic rat model.
Overexpression of Arabidopsis YUCCA6 in Potato Results in High-auxin Developmental Phenotypes and Enhanced Resistance to Water Deficit
Molecular Plant. Sep, 2012 | Pubmed ID: 22986790
Indole-3-acetic acid (IAA), a major plant auxin, is produced in both tryptophan-dependent and tryptophan-independent pathways. A major pathway in Arabidopsis thaliana generates IAA in two reactions from tryptophan. Step one converts tryptophan to indole-3-pyruvic acid (IPA) by tryptophan aminotransferases followed by a rate-limiting step converting IPA to IAA catalyzed by YUCCA proteins. We identified eight putative StYUC (Solanum tuberosum YUCCA) genes whose deduced amino acid sequences share 50 % to 70 % identity with those of Arabidopsis YUCCA proteins. All include canonical, conserved YUCCA sequences: FATGY motif, FMO signature sequence, and FAD-binding and NADP-binding sequences. In addition, five genes were found with ~50% amino acid sequence identity to Arabidopsis tryptophan aminotransferases. Transgenic potato (Solanum tuberosum cv Jowon) constitutively overexpressing Arabidopsis AtYUC6 displayed high auxin phenotypes such as narrow downward curled leaves, increased height, erect stature and longevity. Transgenic potato plants overexpressing AtYUC6 showed enhanced drought tolerance based on reduced water loss. The phenotype was correlated with reduced levels of reactive oxygen species in leaves. The results suggest a functional YUCCA pathway of auxin biosynthesis in potato that may be exploited to alter plant responses to the environment.
Distinct Variant of Sweet's Syndrome: Bortezomib-induced Histiocytoid Sweet's Syndrome in a Patient with Multiple Myeloma
International Journal of Dermatology. Sep, 2012 | Pubmed ID: 22998496
Angewandte Chemie (International Ed. in English). Oct, 2012 | Pubmed ID: 23001825
Perfect texture: The roles of surface nanotexturing, TiO(2) passivation, and a ruthenium cocatalyst on the photoelectrochemical evolution of hydrogen by using p-InP photocathodes are investigated. Higher current densities and more favorable onset potentials are observed after surface nanotexturing. NHE=normal hydrogen electrode.
IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control. Sep, 2012 | Pubmed ID: 23007757
Chemical-solution-derived thin film synthesis and dielectric characterizations of (1 - x)BaTiO(3-x)Bi(Mg,Ti) O(3) complex perovskites with compositions x <0.15 have been explored for temperature-stable high-energy-density capacitor applications. Solution chemistry has been optimized to synthesize and stabilize the precursor solution. Solution-derived (1 - x)BaTiO(3-x)Bi(Mg,Ti)O(3) thin film samples in thicknesses ranging from 250 to 500 nm were fabricated by repeated spinning and subsequent crystallization processes. These thin films showed nearly linear polarization response with high relative dielectric permittivity exceeding 900, which is beneficial for high-capacitance-density and high-energy-density capacitors. Average dielectric breakdown strengths of the dense films were as high as 2.08 MV/cm. The BaTiO(3)-Bi(Mg,Ti) O3 samples showed very low leakage current densities of the order of 10-8 A/cm(2) even at temperatures of 200°C. Based on the structural stability at high temperatures of the pseudocubic perovskite, the high dielectric permittivity and the typical P-E behaviors of the BaTiO(3)-Bi(Mg,Ti)O(3) thin films were also maintained at such high temperatures. Resulting energy density of the 500-nm-thick 0.88BaTiO(3)-0.12Bi(Mg,Ti) O(3) thin film was as high as 37 J/cm(3) at 1.9 MV/cm. The high energy density and excellent temperature stability of the Ba- TiO(3)-Bi(Mg,Ti)O(3) complex perovskite show promise for use in high-temperature pulse power capacitor applications.
The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi. Jul, 2012 | Pubmed ID: 23008851
BMB Reports. Sep, 2012 | Pubmed ID: 23010174
Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-α)-induced cell death during carcinogenesis. In the present study, we examined whether parkin acts as a tumor suppressor in HeLa cells, a human cervical cancer cell line resistant to TNF-α-induced cell death. TNF-α-treatment alone did not affect HeLa cell viability. However, expression of parkin restored TNF-α-induced apoptosis in HeLa cells. Increased cell death was due to the activation of the apoptotic pathway. Expression of parkin in TNF-α-treated HeLa cells stimulated cleavage of the pro-apoptotic proteins caspase-8, -9, -3, -7 and poly ADP ribose polymerase (PARP). In addition, parkin expression resulted in decreased expression of the caspase inhibitory protein, survivin. These results suggest that parkin acts as a tumor suppressor in human cervical cancer cells by modulating survivin expression and caspase activity. We propose that this pathway is a novel molecular mechanism by which parkin functions as a tumor suppressor. [BMB Reports 2012; 45(9): 526-531].
Journal of the American Chemical Society. Oct, 2012 | Pubmed ID: 23017013
We synthesized a new probe, Mito-Naph, to visualize mitochondrial thioredoxin (Trx) activity in cells. A fluorescence off-on change is induced by disulfide cleavage of the probe, resulting from a reaction with Trx and subsequent intramolecular cyclization by the released thiolate to give a fluorescent product. By measuring the fluorescence at 540 nm, Trx activity can be detected at nanomolar concentrations (down to 50 nM) well below its physiological levels. The in vitro and in vivo Trx preference of Mito-Naph was demonstrated by fluorometric and confocal microscopic experiments. In vitro kinetic analysis of the disulfide bond cleavage revealed that the second-order rate constant for Trx is (4.04 ± 0.26) × 10(3) (M s)(-1), approximately 5000 times faster than that for GSH. The inhibition experiments involving PX-12, a selective inhibitor of Trx, also revealed that the emission from Mito-Naph significantly decreased in PX-12 dose-dependent manners, both in living cells and in cellular protein extracts. The Trx preference was further supported by an observation that the fluorescence intensity of rat liver extract was decreased according to the Trx depletion by immunoprecipitation. On the basis of these results, it is concluded that Mito-Naph preferentially reacts with Trx, compared with other biological thiols containing amino acids in vitro and in vivo.
The Antioxidant and Anti-inflammatory Effects of Phenolic Compounds Isolated from the Root of Rhodiola Sachalinensis A. BOR
Molecules (Basel, Switzerland). 2012 | Pubmed ID: 23018923
Isolation of compounds from the root of Rhodiola sachalinensis (RRS) yielded tyrosol (1), salidroside (2), multiflorin B (3), kaempferol-3,4'-di-O-β-D-glucopyranoside (4), afzelin (5), kaempferol (6), rhodionin (7), and rhodiosin (8). Quantification of these compounds was performed by high-performance liquid chromatography (HPLC). To investigate the antioxidant and anti-inflammatory effects of the compounds, DPPH radical scavenging, NBT superoxide scavenging and nitric oxide production inhibitory activities were examined in LPS-stimulated Raw 264.7 cells. We suggest that the major active components of RRS are herbacetin glycosides, exhibiting antioxidant activity, and kaempferol, exhibiting anti-inflammatory activity.
Ten-year Outcomes of Percutaneous Radiofrequency Ablation As First-line Therapy of Early Hepatocellular Carcinoma: Analysis of Prognostic Factors
Journal of Hepatology. Sep, 2012 | Pubmed ID: 23023009
BACKGROUND AND AIMS: The aim was to assess ten-year outcomes of radiofrequency ablation as a first-line therapy of early-stage hepatocellular carcinoma with an analysis of prognostic factors. METHODS: From April 1999 to April 2011, 1305 patients (male:female=993:312; mean age, 58.4 years) with 1502 early-stage hepatocellular carcinomas (mean size, 2.2cm) were treated with percutaneous radiofrequency ablation as a first-line option. Follow-up period ranged 0.4-146.6 months (median, 33.4 months). We assessed the ten-year follow-up results of recurrences and survival with the analyses of prognostic factors. RESULTS: Recurrences occurred in 795 patients (1-17 times), which were managed with various therapeutic modalities. The cumulative local tumor progression rates were 27.0% and 36.9% at five and ten years, respectively, for which the only significant risk factor was large tumor size (B=0.584, p=0.001). Cumulative intrahepatic distant and extrahepatic recurrence rates were 73.1% and 88.5%, and 19.1% and 38.2% at five and ten years, respectively. Corresponding overall survival rates were 59.7% and 32.3%, respectively. Poor survival was associated with old age (B=0.043, p=0.010), Child-Pugh class B (B=-1.054, p<0.001), absence of antiviral therapy during follow-up (B=-0.699, p=0.034), and presence of extrahepatic recurrence (B=0.971, p=0.007). CONCLUSIONS: Ten-year survival outcomes after percutaneous radiofrequency ablation as a first-line therapy of hepatocellular carcinoma were excellent despite frequent tumor recurrences. Overall survival was influenced by age, Child-Pugh class, antiviral therapy, or extrahepatic recurrence.
Cold Spring Harbor Perspectives in Medicine. 2012 | Pubmed ID: 23028131
Many cystic fibrosis transmembrane conductance regulator (CFTR)-expressing epithelia secrete bicarbonate (HCO(3)(-))-containing fluids. Recent evidence suggests that defects in epithelial bicarbonate secretion are directly involved in the pathogenesis of cystic fibrosis, in particular by building up hyperviscous mucus in the ductal structures of the lung and pancreas. Pancreatic juice is one of the representative fluids that contain a very high concentration of bicarbonate among bodily fluids that are secreted from CFTR-expressing epithelia. We introduce up-to-date knowledge on the basic principles of transepithelial bicarbonate transport by showing the mechanisms involved in pancreatic bicarbonate secretion. The model of pancreatic bicarbonate secretion described herein may also apply to other exocrine epithelia. As a central regulator of bicarbonate transport at the apical membrane, CFTR plays an essential role in both direct and indirect bicarbonate secretion. The major role of CFTR in bicarbonate secretion would be variable depending on the tissue and cell type. For example, in epithelial cells that produce a low concentration of bicarbonate-containing fluid (up to 80 mm), either CFTR-dependent Cl(-)/HCO(3)(-) exchange or CFTR anion channel with low bicarbonate permeability would be sufficient to generate such fluid. However, in cells that secrete high-bicarbonate-containing fluids, a highly selective CFTR bicarbonate channel activity is required. Therefore, understanding the molecular mechanism of transepithelial bicarbonate transport and the role of CFTR in each specific epithelium will provide therapeutic strategies to recover from epithelial defects induced by hyposecretion of bicarbonate in cystic fibrosis.
Surgical Laparoscopy, Endoscopy & Percutaneous Techniques. Oct, 2012 | Pubmed ID: 23047399
: Several techniques of laparoscopic feeding jejunostomy have been described. Most of them require costly commercial kits. Here we present a novel, simple, low-cost method for laparoscopic jejunostomy tube placement.
Association Between Serum Ceruloplasmin Levels and Arterial Stiffness in Korean Men with Type 2 Diabetes Mellitus
Diabetes Technology & Therapeutics. Oct, 2012 | Pubmed ID: 23050733
Abstract Background: Increased oxidative stress contributes to the development of arterial stiffness. Arterial stiffness, as measured by brachial-ankle pulse wave velocity (baPWV), has been known to be correlated with oxidative stress. Serum ceruloplasmin (CP), a copper-carrying protein, may indicate the overall level of oxidative stress in the body. The present study investigated whether serum CP levels are associated with baPWV in Korean men with type 2 diabetes mellitus (DM). Subjects and Methods: Serum CP levels and conventional risk factors were measured in 760 Korean men with type 2 DM. Arterial stiffness was assessed by baPWV obtained with an automatic device (model VP-1000; Colin, Komaki, Japan). Results: Correlation analysis indicated a significant positive association between serum CP and baPWV (r=0.109, P=0.003). Age-adjusted baPWV increased gradually according to serum CP quartiles (Q1, 1,500.3±18.4 cm/s; Q2, 1,511.6±17.8 cm/s; Q3, 1,551.8±17.9 cm/s; Q4, 1,622.1±17.8 cm/s; P for trend<0.001). Multivariate linear regression analysis showed that serum CP was independently associated with baPWV in various models. Conclusions: A positive relationship was identified between CP and baPWV in adult male subjects with type 2 DM, which was independent of conventional cardiovascular risk factors. Further studies are needed to confirm whether CP contributes to the pathogenesis of increased arterial stiffness in subjects with type 2 DM.
International Journal of Dermatology. Nov, 2012 | Pubmed ID: 23067092
The Korean Journal of Hematology. Sep, 2012 | Pubmed ID: 23071477
This study evaluates the effectiveness of immunochemotherapy and radiation therapy in the treatment of patients with primary bone lymphoma (PBL).
Changes in the Signal- and Contrast-to-noise Ratios of Hepatocellular Carcinomas on Gadoxetic Acid-enhanced Dynamic MR Imaging
European Journal of Radiology. Oct, 2012 | Pubmed ID: 23079045
OBJECTIVE: Our objective was to evaluate whether the enhancement pattern, measured by changes in the signal- (SNRs) and contrast-to-noise ratios (CNRs), of hepatocellular carcinomas (HCCs) on gadoxetic acid-enhanced MRI reflects tumor differentiation. SUBJECTS AND METHODS: Two hundred eighty-five patients with 286 surgically-confirmed HCCs who underwent gadoxetic acid-enhanced MRI were included (11 grade I, 267 grade II, 7 grade III, and 1 grade IV tumor). Unenhanced and dynamic images with a T1-weighted 3D turbo-field-echo sequence were obtained. Relative signal intensities of the tumors with respect to surrounding liver were evaluated and the SNRs and CNRs were calculated. RESULTS: SNR measurements demonstrated a fluctuating pattern (an increase in the SNR, followed by a decrease and a subsequent increase [or a decrease in the SNR followed by an increase and a subsequent decrease]) in 282 of 286 (98.6%) tumors. The SNR measurements also showed a single-peak SNR in the arterial phase (1.0% [3/286]) and 3min delayed images (0.3% [1/286]) followed by a decrease in 4 (1.4% [4/286]) grade II tumors. Nearly all tumors (88.1% [252/286]), 9 (81.8% [9/11]) grade I, 236 (88.4% [236/267]) grade II, 6 (85.7% [6/7]) grade III, and 1 (100% [1/1]) grade IV tumor showed maximum absolute CNRs with negative values, which were most commonly found in 20min delayed images (67.5% [170/252]). The remaining 34 of 286 (11.9%) tumors showed maximum absolute CNRs with positive values. CONCLUSION: Regardless of the tumor grades, the most common manifestation was a SNR with a fluctuating pattern with time and maximum absolute CNRs with negative values, which were most commonly noted in the hepatobiliary phase.
Early Diffuse Recurrence of Hepatocellular Carcinoma After Percutaneous Radiofrequency Ablation: Analysis of Risk Factors
European Radiology. Oct, 2012 | Pubmed ID: 23085860
OBJECTIVE: To evaluate the risk factors affecting early diffuse recurrence within 1 year of percutaneous ultrasound-guided radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: Out of 146 patients who received transcatheter arterial chemoembolisation (TACE) for treatment of recurrent HCC after percutaneous ultrasound-guided RFA, we selected 23 patients with early diffuse recurrence. Early diffuse recurrence was defined as three or more new recurrent HCCs within 1 year of initial RFA. As a control group, we selected 23 patients, matched exactly for age and sex, in which there was no local tumour progression or new recurrence after RFA. To analyse the risk factors, we examined patient factors and tumour factors. RESULTS: Recurrent tumours occurred from 30 to 365 days after RFA (median time, 203 days). Univariate analysis indicated that larger tumour size and poorly defined margin were significant risk factors (P < 0.05). Multivariate analysis indicated that poorly defined margin was a significant risk factor (P < 0.05). CONCLUSION: Larger tumour size and poorly defined margin may be risk factors for early diffuse recurrence of HCC within 1 year of RFA. Tumours with such risk factors should be treated with a combination of TACE to minimise the potential for therapeutic failure. KEY POINTS: • Ultrasound-guided radiofrequency ablation (RFA) is widely used for hepatocellular carcinoma (HCC). • Early diffuse recurrence after RFA is an important prognostic factor • The risk factors for recurrence are larger tumour size and poorly defined margins • Tumours with such risk factors should be treated with transarterial chemoembolisation.
Genomics & Informatics. Mar, 2012 | Pubmed ID: 23105924
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by formation of multiple fluid-filled cysts that expand over time and destroy renal architecture. The proteins encoded by the PKD1 and PKD2 genes, mutations in which account for nearly all cases of ADPKD, may help guard against cystogenesis. Previously developed mouse models of PKD1 and PKD2 demonstrated an embryonic lethal phenotype and massive cyst formation in the kidney, indicating that PKD1 and PKD2 probably play important roles during normal renal tubular development. However, their precise role in development and the cellular mechanisms of cyst formation induced by PKD1 and PKD2 mutations are not fully understood. To address this question, we presently created Pkd2 knockout and PKD2 transgenic mouse embryo fibroblasts. We used a mouse oligonucleotide microarray to identify messenger RNAs whose expression was altered by the overexpression of the PKD2 or knockout of the Pkd2. The majority of identified mutations was involved in critical biological processes, such as metabolism, transcription, cell adhesion, cell cycle, and signal transduction. Herein, we confirmed differential expressions of several genes including aquaporin-1, according to different PKD2 expression levels in ADPKD mouse models, through microarray analysis. These data may be helpful in PKD2-related mechanisms of ADPKD pathogenesis.
Plexiform Angiomyxoid Myofibroblastic Tumor of the Stomach: Report of Two Cases and Review of the Literature
Korean Journal of Pathology. Jun, 2012 | Pubmed ID: 23110018
Plexiform angiomyxoid myofibroblastic tumor (PAMT) of the stomach is a recently recognized entity. Because of its rarity, only 22 cases have been reported in the English-language literature and most of these are single case reports. We report two cases of gastric PAMT. The tumor cells were bland and plexiform arranged in a myxoid stroma, which was positive for alcian blue. Immunohistochemically, the tumor cells were positive for smooth muscle actin, but negative for c-kit, CD34, desmin, S-100 protein, epithelial membrane antigen, neurofilament, and protein kinase C-theta. Mutation analyses for exon 9, 11, 13, and 17 of KIT genes and 12, 14, and 18 of the platelet-derived growth factor receptor alpha (PDGFRA) genes were performed and the tumors were wild-type for mutation.
Purification and Antimicrobial Function of Ubiquitin Isolated from the Gill of Pacific Oyster, Crassostrea Gigas
Molecular Immunology. Jan, 2013 | Pubmed ID: 22858580
An antimicrobial polypeptide was purified from an acidified gill extract of Pacific oyster (Crassostrea gigas) by C(18) reversed-phase HPLC. The purified polypeptide had a molecular weight of 8471Da containing 74 amino acid residues. Comparison of the obtained N-terminal sequences with those of others revealed that it was identical to ubiquitin reported from other species and named cgUbiquitin. cgUbiquitin showed broad potent antimicrobial activity against Gram-positive and -negative bacteria including Streptococcus iniae and Vibrio parahemolyticus (minimal effective concentrations, 7.8 and 9.8μg/mL), respectively, without hemolytic activity. The cgUbiquitin cDNA was identified from an expressed sequence tag (EST) library of oyster gill as a precursor form, encoding ubiquitin consisting of 76 amino acids fused to ribosomal protein of S27. Although the cgUbiquitin precursor mRNA was expressed at the intermediate level in the gill, the mRNA was significantly up-regulated at 48h post injection with Vibrio sp. Analysis of the cgUbiquitin C-terminus by carboxypeptidase B treatment and comparison of the retention times revealed that cgUbiquitin lacks the terminal Gly-Gly doublet and ends in an C-terminal Arg residue which might be related to antimicrobial activity. Study of the kinetics of killing and membrane permeabilization showed that this peptide was not membrane permeable and acted through a bacteriostatic process. According to the homology modeling, this peptide is composed of three secondary structural motifs including three α-helices and four β-strands separated by 7 loops regions. Our results indicate that cgUbiquitin might be related to the innate immune defenses in the Pacific oyster and this is the first report for antimicrobial function of ubiquitin isolated from any oyster species.