In JoVE (1)

Other Publications (100)

Articles by Yong Hoon Kim in JoVE

Other articles by Yong Hoon Kim on PubMed

Synthesis of Chiral C(2)-Symmetric Bisferrocenyldiamines. X-ray Crystal Structure of Ru(2)Cl(2).2CHCl(3) (2 = N1,N2-Bis{(R)-1-[(S)-2-(diphenylphosphino)]ferrocenylethyl}- N1,N2-dimethyl-1,2-ethanediamine)

Inorganic Chemistry. Mar, 1999  |  Pubmed ID: 11670860

A new class of chiral C(2)-symmetrical bisferrocenyl diamines, N1,N2-bis[(R)-1-ferrocenylethyl]-N1,N2-dimethyl-1,2-ethanediamine (1) and N1,N2-bis{(R)-1-[(S)-2-(diphenylphosphino)]ferrocenylethyl}-N1,N2-dimethyl-1,2-ethanediamine (2), were prepared from the chiral template (R)-N,N-(dimethylamino)-1-ferrocenylethylamine ((R)-FA). Compound 1 was prepared from the reaction of (R)-FA with MeI followed by nucleophilic substitution with N,N'-dimethylethylenediamine, while 2 was formed from 1 via ortho lithiation followed by electrophilic substitution with chlorodiphenylphosphine. Compound 2 reacts with Ru(DMSO)(4)Cl(2) to give trans-Ru(2)Cl(2) (3) in which the ligand is tetradentate. This complex crystallizes in the orthorhombic system: P2(1)2(1)2(1) (No. 19); a = 11.7230(4) Ã…, b = 16.5951(6) Ã…, c = 27.853(1) Ã…; Z = 4; R = 0.046; R(w) = 0.104. The geometry around the central metal is an octahedron with a pair of chlorine atoms trans to each other. This complex exhibits catalytic activity toward asymmetric cyclopropanation of some olefins and alkyl diazoacetates, giving enantioselectivity up to 95%.

Excitonic Optical Spectrum of Semiconductors Obtained by Time-dependent Density-functional Theory with the Exact-exchange Kernel

Physical Review Letters. Aug, 2002  |  Pubmed ID: 12190423

Applying a novel exact-exchange (EXX) approach within time-dependent density-functional theory, we obtained the optical absorption spectrum of bulk silicon in good agreement with experiments including excitonic features. Analysis of the EXX kernel shows that inclusion of the Coulomb coupling of electron-hole pairs and the correct long-wavelength behavior in the kernel is crucial for the proper description of excitonic effects in semiconductors.

Clinical Features of Eosinophilic Bronchitis

The Korean Journal of Internal Medicine. Mar, 2002  |  Pubmed ID: 12014210

Eosinophilic inflammation of the airway is usually associated with airway hyper-responsiveness in bronchial asthma. However, there is a small group of patients which has the eosinophilic inflammation in the bronchial tree with normal spirometry and no evidence of airway hyper-responsiveness, which was named eosinophilic bronchitis. The objectives of this study are 1) to investigate the incidence of eosinophilic bronchitis in the chronic cough syndrome and 2) to evaluate the clinical features and course of eosinophilic bronchitis.

Evaluation of Emphysema in Patients with Asthma Using High-resolution CT

The Korean Journal of Internal Medicine. Mar, 2002  |  Pubmed ID: 12014209

Bronchial asthma is a clinical syndrome characterized by reversibility of airway obstruction. However, many asthmatics have evidence of residual airway obstruction. It has become evident that the repair of the chronic inflammatory process can lead to various irreversible changes. It is generally accepted that the most common cause for the change is cigarette smoking but it is controversial whether asthma progresses to emphysema. High resolution computed tomography (HRCT) is more sensitive and more accurate than chest plain films in determining the type and extent of emphysema. This study was carried out to determine whether asthma can be a cause of emphysema without the effect of cigarette smoking and to evaluate clinical characteristics in asthmatics with emphysema.

Association of Thromboxane A2 Receptor (TBXA2R) with Atopy and Asthma

The Journal of Allergy and Clinical Immunology. Aug, 2003  |  Pubmed ID: 12897758

Association of Eotaxin Gene Family with Asthma and Serum Total IgE

Human Molecular Genetics. Jun, 2003  |  Pubmed ID: 12761043

The Eotaxin gene family (Eotaxin1, Eotaxin2 and Eotaxin3) recruits and activates CCR3-bearing cells such as eosinophils, mast cells and Th2 lymphocytes that play a major role in allergic disorders. To date, the effect of polymorphisms of Eotaxin genes on asthma phenotypes has not been thoroughly examined. In our research, we sequenced whole regions of the Eotaxin gene family to identify polymorphisms, which may be involved in the development of asthma and total serum IgE. We have identified 37 SNPs in the Exotaxin gene family (Exotaxin1, 2 and 3), and 17 common polymorphic sites were selected for genotyping in our asthma cohort (n=721). Statistical analysis revealed that the EOT2+1265A>G G* allele showed significantly lower frequency in asthmatics than in normal healthy controls (0.14 versus 0.23, P=0.002), and that distribution of the EOT2+1265A>G G* allele-containing genotypes was also much lower in asthmatics (26.3 versus 40.8%, P=0.003). In addition, a non-synonymous SNP in Eotaxin1, EOT1+123Ala>Thr showed significant association with total serum IgE levels (P=0.002-0.02). The effect of EOT1+123Ala>Thr on total serum IgE appeared in a gene-dose-dependent manner. Our findings suggest that the development of asthma may be associated with EOT2+1265A>G polymorphisms, and the susceptibility to high IgE production may be attributed to the EOT1+123Ala>Thr polymorphism. Eotaxin variation/haplotype information identified in this study might provide valuable insights into strategies for the control of asthma.

Bilateral Pedicle Stress Fracture After Instrumented Posterolateral Lumbar Fusion: a Case Report

Spine. Apr, 2003  |  Pubmed ID: 12698135

A case of bilateral pedicle stress fracture is reported, and the literature is reviewed.

High-resolution CT Findings in Patients with Near-fatal Asthma: Comparison of Patients with Mild-to-severe Asthma and Normal Control Subjects and Changes in Airway Abnormalities Following Steroid Treatment

Chest. Dec, 2004  |  Pubmed ID: 15596682

Extensive airway inflammation and excessive mucus production are implicated in deaths from asthma. High-resolution CT (HRCT) can be used to image both large and small airway abnormalities in asthmatics. The aims of this study were to clarify the distinction of HRCT features between near-fatal asthma (NFA) and non-NFA, and to evaluate serial follow-up HRCT scans of patients with NFA.

Density Functional Theory Studies of the [2]rotaxane Component of the Stoddart-heath Molecular Switch

Journal of the American Chemical Society. Oct, 2004  |  Pubmed ID: 15453797

The central component of the programmable molecular switch recently demonstrated by Stoddart and Heath is [2]rotaxane, which consists of a cyclobis(paraquat-p-phenylene) shuttle (CBPQT(4+))(PF(6)(-))(4) (the ring) encircling a finger and moving between two stations, tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP). As a step toward understanding the mechanism of this switch, we report here its electronic structure using two flavors of density functional theory (DFT): B3LYP/6-31G and PBE/6-31G. We find that the electronic structure of composite [2]rotaxane can be constructed reasonably well from its parts by combining the states of separate stations (TTF and DNP) with or without the (CBPQT)(PF(6))(4) shuttle around them. That is, the "CBPQT@TTF" state, (TTF)(CBPQT)(PF(6))(4)-(DNP), is described well as a combination of the (TTF)(CBPQT)(PF(6))(4) complex and free DNP, and the "CBPQT@DNP" state, (TTF)-(DNP)(CBPQT)(PF(6))(4), is described well as a combination of free TTF and the (DNP)(CBPQT)(PF(6))(4) complex. This allows an aufbau or a "bottom-up" approach to predict the complicated [n]rotaxanes in terms of their components. This should be useful in designing new components to lead to improved properties of the switches. A critical function of the (CBPQT(4+))(PF(6)(-))(4) shuttle in switching is that it induces a downshift of the frontier orbital energy levels of the station it is on (TTF or DNP). This occurs because of the net positive electrostatic potential exerted by the CBPQT(4+) ring, which is located closer to the active station than the four PF(6)(-)'s. This downshift alters the relative position of energy levels between TTF and DNP, which in turn alters the electron tunneling rate between them, even when the shuttle is not involved directly in the actual tunneling process. Based on this switching mechanism, the "CBPQT@TTF" state is expected to be a better conductor since it has better aligned levels between the two stations. A second potential role of the (CBPQT(4+))(PF(6)(-))(4) shuttle in switching is to provide low-lying LUMO levels. If the shuttle is involved in the actual tunneling process, the reduced HOMO-LUMO gap (from 3.6 eV for the isolated finger to 1.1 eV for "CBPQT@TTF" or to 0.6 eV for "CBPQT@DNP" using B3LYP) would significantly facilitate the electron tunneling through the system. This might occur in a folded conformation where a direct contact between free station and the shuttle on the other station is possible. When this becomes the main switching mechanism, we expect the "CBPQT@DNP" state to become a better conductor because its HOMO-LUMO gap is smaller and because its HOMO and LUMO are localized at different stations (HOMO exclusively at TTF and LUMO at CBPQT encircling DNP) so that the HOMO-to-LUMO tunneling would be through the entire molecule of [2]rotaxane. Thus an essential element in designing these switches is to determine the configuration of the molecules (e.g., through self-assembled monolayers or incorporation of conformation stabilizing units).

Protective Effect of Ginseng Extract Against Apoptotic Cell Death Induced by 2,2',5,5'-tetrachlorobiphenyl in Neuronal SK-N-MC Cells

Life Sciences. Aug, 2004  |  Pubmed ID: 15261766

Oxidative stress plays an important role in the pathological processes of neurodegenerative diseases. Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants, some of which may be neurotoxic. 2,2',5,5'-Tetrachlorobiphenyl (PCB 52) induces apoptotic death in human neuronal SK-N-MC cells, as demonstrated by gel electrophoresis, which demonstrates the proteolytic cleavage of beta-catenin and poly(ADP-ribose) polymerase (PARP) and the characteristic ladder patterns of DNA fragmentation. In the present study, we investigated whether Panax ginseng extract protect human neuronal SK-N-MC cells from PCB 52-induced apoptosis. The addition of 500 microg/ml of ginseng extract to a culture medium significantly protected neuronal cell from the apoptosis mediated by PCB 52 and remarkably attenuated lipid peroxidation, the generation of reactive oxygen species, and DNA fragmentation, and markedly reduced the PCB 52 induced proteolytic cleavage of beta-catenin and PARP. These results show that Panax ginseng extract protects human neuronal SK-N-MC cells from the apoptosis induced by PCB 52. We suggest that Panax ginseng extracts may protect neuronal cells from oxidative injury.

The Effect of Passive Smoking on Asthma Symptoms,atopy,and Airway Hyperresponsiveness in Schoolchildren

Journal of Korean Medical Science. Apr, 2004  |  Pubmed ID: 15082893

Passive smoking is a major cause of respiratory morbidity, and is associated with increased bronchial responsiveness in children. To evaluate the effect of smoking by a parent on asthma symptoms, atopy, and airway hyperresponsiveness (AHR), we conducted a cross-sectional survey of 503 schoolchildren that involved questionnaires, spirometry, allergy testing, and a bronchial challenge test. If the PC20 methacholine was less than 16 mg/mL, the subject was considered to have AHR. The prevalence of a parent who smoked was 68.7%. The prevalence of AHR was 45.0%. The sensitization rate to common inhalant allergens was 32.6%. Nasal symptoms such as rhinorrhea, sneezing, nasal itching, and nasal obstruction were present in 42.7%. Asthma symptoms such as cough and wheezing were present in 55.4%. The asthma symptoms were significantly more prevalent in children who had a parent who smoked than in those whose parents did not. The nasal symptoms, atopy, and AHR did not differ according to whether a parent smoked. In a multiple logistic regression model, the asthma symptoms and atopy were independently associated with AHR, when adjusted for confounding variables. Passive smoking contributed to asthma symptoms in schoolchildren and was not an independent risk factor of airway hyperresponsiveness in an epidemiological survey.

Density Functional Theory Study of the Geometry, Energetics, and Reconstruction Process of Si111 Surfaces

Langmuir : the ACS Journal of Surfaces and Colloids. Dec, 2005  |  Pubmed ID: 16343021

We report the structures and energies from first principles density functional calculations of 12 different reconstructed (111) surfaces of silicon, including the 3x3 to 9x9 dimer-adatom-stacking fault (DAS) structures. These calculations used the Perdew-Burke-Ernzerhof generalized gradient approximation of density functional theory and Gaussian basis functions. We considered fully periodic slabs of various thicknesses. We find that the most stable surface is the DAS 7x7 structure, with a surface energy of 1.044 eV/1x1 cell (1310 dyn/cm). To analyze the origins of the stability of these systems and to predict energetics for more complex, less-ordered systems, we develop a model in which the surface energy is partitioned into contributions from seven different types of atom environments. This analysis is used to predict the surface energy of larger DAS structures (including their asymptotic behavior for very large unit cells) and to study the energetics of the sequential size change (SSC) model proposed by Shimada and Tochihara for the observed dynamical reconstruction of the Si(111) 1x1 structure. We obtain an energy barrier at the 2x2 cell size and confirm that the 7x7 regular stage of the SSC model (corresponding to the DAS 7x7 reconstruction) provides the highest energy reduction per unit cell with respect to the unreconstructed Si111 1x1 surface.

Low-grade Fibromyxoid Sarcoma: CT, Sonography, and MR Findings in 3 Cases

Journal of Thoracic Imaging. Nov, 2005  |  Pubmed ID: 16282909

Low-grade fibromyxoid sarcoma (LGFMS) is a distinctive variant of fibrosarcoma characterized by deceptively bland histologic features and a paradoxically aggressive clinical course. The radiologic finding of this uncommon tumor has not been described to date. In this report, 3 cases of LGFMS occurring in axilla, chest wall, and pleura are presented with CT, MRI, and sonographic findings.

Molecular Dynamics Simulation of Amphiphilic Bistable [2]rotaxane Langmuir Monolayers at the Air/water Interface

Journal of the American Chemical Society. Oct, 2005  |  Pubmed ID: 16231934

Bistable [2]rotaxanes display controllable switching properties in solution, on surfaces, and in devices. These phenomena are based on the electrochemically and electrically driven mechanical shuttling motion of the ring-shaped component, cyclobis(paraquat-p-phenylene) (CBPQT(4+)), between a monopyrrolotetrathiafulvalene (mpTTF) unit and a 1,5-dioxynaphthalene (DNP) unit located along a dumbbell component. The most stable state of the rotaxane (CBPQT(4+)@mpTTF) is that in which the CBPQT(4+) ring encircles the mpTTF unit, but a second less favored metastable co-conformation with the CBPQT(4+) ring surrounding the DNP (CBPQT(4+)@DNP) can be formed experimentally. For both co-conformations of an amphiphilic bistable [2]rotaxane, we report here the structure and surface pressure-area isotherm of a Langmuir monolayer (LM) on a water subphase as a function of the area per molecule. These results from atomistic molecular dynamics (MD) studies are validated by comparing with experiments based on similar amphiphilic rotaxanes. For both co-conformations, we found that as the area per molecule increases the thickness of the LM decreases while the molecular tilt increases. Both co-conformations led to similar LM thicknesses at the same packing area. From the simulated LM systems, we calculated the electron density profiles of the monolayer as a function of area per molecule, which show good agreement with experimental analyses from synchrotron X-ray reflectivity measurements of related systems. Decomposing the overall electron density profiles into component contributions, we found distinct differences in molecular packing in the film depending upon the co-conformation. Thus we find that the necessity of allowing the tetracationic ring to become solvated by water leads to differences in the structures for the two co-conformations in the LM. At the same packing area, the value of the overall tilt angle does not seem to be sensitive to whether the CBPQT(4+) ring is encircling the mpTTF or the DNP unit. However, the conformation of the dumbbell does depend on the location of the CBPQT(4+) ring, which is reflected in the segmental tilt angles of the mpTTF and DNP units. Using the Kirkwood-Buff formula in conjunction with MD calculations, we find the surface pressure-area isotherms for each co-conformation in which the CBPQT(4+)@mpTTF form has smaller surface tension and therefore larger surface pressure than the CBPQT(4+)@DNP at the same packing area, differences that decreases with increasing area per molecule, which is verified experimentally.

Clinical Implications of the Ethane in Exhaled Breath in Patients with Acute Paraquat Intoxication

Chest. Sep, 2005  |  Pubmed ID: 16162750

Pulmonary fibrosis due to lipid peroxidation is a major symptom of paraquat intoxication. Ethane in the expired breath (exEth) reflects lipid peroxidation and may be a measure of the damage effected by oxygen radicals in acute lung injury. The purpose of this study was to evaluate the clinical efficacy of exEth as a measure of exposure to paraquat and as an indicator of lung damage.

Factors Influencing the Responsiveness to Inhaled Glucocorticoids of Patients with Moderate-to-severe Asthma

Chest. Sep, 2005  |  Pubmed ID: 16162699

Inhaled glucocorticoids (GCs) are the most effective control therapy for asthma. Although the clinical effects of inhaled GCs vary, there are few data on the differences in the responsiveness of individuals to inhaled GCs. The purpose of this study was to identify those factors that are associated with responsiveness to high-dose inhaled GCs in patients with moderate-to-severe asthma.

Conformations and Charge Transport Characteristics of Biphenyldithiol Self-assembled-monolayer Molecular Electronic Devices: a Multiscale Computational Study

The Journal of Chemical Physics. Jun, 2005  |  Pubmed ID: 16035789

We report a computational study of conformations and charge transport characteristics of biphenyldithiol (BPDT) monolayers in the (sqrt.3 x sqrt.3)R30 degrees packing ratio sandwiched between Au(111) electrodes. From force-field molecular-dynamics and annealing simulations of BPDT self-assembled monolayers (SAMs) with up to 100 molecules on a Au(111) substrate, we identify an energetically favorable herringbone-type SAM packing configuration and a less-stable parallel packing configuration. Both SAMs are described by the (2sqrt.3 x sqrt.3)R30 degrees unit cell including two molecules. With subsequent density-functional theory calculations of one unit cell of the (i) herringbone SAM with the molecular tilt angle theta approximately 15 degrees , (ii) herringbone SAM with theta approximately 30 degrees , and (iii) parallel SAM with theta approximately 30 degrees, we confirm that the herringbone packing configuration is more stable than the parallel one but find that the energy variation with respect to the molecule tilting within the herringbone packing is very small. Next, by capping these SAMs with the top Au(111) electrode, we prepare three molecular electronic device models and calculate their coherent charge transport properties within the matrix Green's function approach. Current-voltage (I-V) curves are then obtained via the Landauer-Buttiker formula. We find that at low-bias voltages (|V| < or = 0.2 V) the I-V characteristics of models (ii) and (iii) are similar and the current in model (i) is smaller than that in (ii) and (iii). On the other hand, at higher-bias voltages (|V| > or 0.5 V), the I-V characteristics of the three models show noticeable differences due to different phenyl band structures. We thus conclude that the BPDT SAM I-V characteristics in the low-bias voltage region are mainly determined by the -Au [corrected] interaction within the individual molecule-electrode contact, while both intramolecular conformation and intermolecular interaction can affect the BPDT SAM I-V characteristics in the high-bias voltage region.

[Four Cases of Hepatic Fascioliasis Mimicking Cholangiocarcinoma]

The Korean Journal of Hepatology. Jun, 2005  |  Pubmed ID: 15980676

Human fascioliasis is a zoonosis caused by Fasciola hepatica, and this is a trematode that infests cattle and sheep. Humans are accidental hosts in the life cycle of this parasite. People are infected by ingestion of the water or the raw aquatic vegetables that are contaminated with the metacercaria. This fluke's worldwide distribution occurs in areas where sheep, cattle and goats are raised, and there is a life-cycle niche for this fluke in lymnaeid snails. However, it is a rare disease in Korea. We experienced four human fascioliasis which were difficult to differentiate from hepatic malignancy in three patients, and this was misdiagnosed as common hepatic duct tumor in one patient. The patients manifested only vague abdominal symptoms. Intrahepatic fascioliasis showed multiple ill-defined hypoattenuating lesions and filling defects of the lesion lumens on radiologic study. A striking eosinophilia from the patients' blood was identified and a positive finding of a serum enzyme linked immunosorbent assay for the Fasciola hepatica was also noted in three of four patients. The therapeutic trial with triclabendazole and praziquantel was not successful.

[Effect of Transjugular Intrahepatic Portosystemic Shunt for Variceal Bleeding in Hepatocellular Carcinoma Patients with Portal Vein Thrombosis]

The Korean Journal of Hepatology. Jun, 2005  |  Pubmed ID: 15980674

Transjugular Intrahepatic Portosystemic Shunt (TIPS) is commonly used in patients with variceal bleeding. However, this procedure is contraindicated in hepatocellular carcinoma patients with portal vein thrombosis. This study was done to evaluate the effect of TIPS in those patients with variceal bleeding.

Correlation Between Levels of N-terminal Pro-B-type Natriuretic Peptide and Degrees of Heart Failure

The Korean Journal of Internal Medicine. Mar, 2005  |  Pubmed ID: 15906950

The N-terminal fragment of pro Brain Natriuretic Peptide (NT-pro BNP) is a neuro-hormone synthesized in the cardiac ventricles in response to increased wall tension. The purpose of this study was to assess the correlation between the NT-pro BNP levels and the New York Heart Association function class (NYHA Fc) of dyspnea and echocardiographic findings for the patients who visited our cardiology departments.

First-principles Study of the Switching Mechanism of [2]catenane Molecular Electronic Devices

Physical Review Letters. Apr, 2005  |  Pubmed ID: 15904172

We present a first-principles study of the coherent charge transport properties of bistable [2]catenane molecular monolayers sandwiched between Au(111) electrodes. We find that conduction channels around the Fermi level are dominated by the two highest occupied molecular orbital levels from tetrathiafulvalene (TTF) and dioxynaphthalene (DNP) and the two lowest unoccupied molecular orbital levels from tetracationic cyclophane (CBPQT4+), and the OFF to ON switching results from the energetic shifts of these orbitals as CBPQT4+ moves from TTF to DNP. We show that the superposition principle can be adopted for predicting the function of the composite device.

Structures and Properties of Self-assembled Monolayers of Bistable [2]rotaxanes on Au (111) Surfaces from Molecular Dynamics Simulations Validated with Experiment

Journal of the American Chemical Society. Feb, 2005  |  Pubmed ID: 15686390

Bistable [2]rotaxanes display controllable switching properties in solution, on surfaces, and in devices. These phenomena are based on the electrochemically and electrically driven mechanical shuttling motion of the ring-shaped component, cyclobis(paraquat-p-phenylene) (CBPQT(4+)) (denoted as the ring), between a tetrathiafulvalene (TTF) unit and a 1,5-dioxynaphthalene (DNP) ring system located along a dumbbell component. When the ring is encircling the TTF unit, this co-conformation of the rotaxane is the most stable and thus designated the ground-state co-conformer (GSCC), whereas the other co-conformation with the ring surrounding the DNP ring system is less favored and so designated the metastable-state co-conformer (MSCC). We report here the structure and properties of self-assembled monolayers (SAMs) of a bistable [2]rotaxane on Au (111) surfaces as a function of surface coverage based on atomistic molecular dynamics (MD) studies with a force field optimized from DFT calculations and we report several experiments that validate the predictions. On the basis of both the total energy per rotaxane and the calculated stress that is parallel to the surface, we find that the optimal packing density of the SAM corresponds to a surface coverage of 115 A(2)/molecule (one molecule per 4 x 4 grid of surface Au atoms) for both the GSCC and MSCC, and that the former is more stable than the latter by 14 kcal/mol at the optimum packing density. We find that the SAM retains hexagonal packing, except for the case at twice the optimum packing density (65 A(2)/molecule, the 3 x 3 grid). For the GSCC and MSCC, investigated at the optimum coverage, the tilt of the ring with respect to the normal is theta = 39 degrees and 61 degrees, respectively, while the tilt angle of the entire rotaxane is psi = 41 degrees and 46 degrees , respectively. Although the tilt angle of the ring decreases with decreasing surface coverage, the tilt angle of the rotaxane has a maximum at 144 A(2)/molecule (the 4 x 5 grid/molecule) of 50 degrees and 51 degrees for the GSCC and MSCC, respectively. The hexafluorophosphate counterions (PF(6)(-)) stay localized around the ring during the 2 ns MD simulation. On the basis of the calculated density profile, we find that the thickness of the SAM is 40.5 A at the optimum coverage for the GSCC and 40.0 A for MSCC, and that the thicknesses become less with decreasing surface coverage. The calculated surface tension at the optimal packing density is 45 and 65 dyn/cm for the GSCC and MSCC, respectively. This difference suggests that the water contact angle for the GSCC is larger than for the MSCC, a prediction that is verified by experiments on Langmuir-Blodgett monolayers of amphiphilic [2]rotaxanes.

Tumoral Calcinosis of the Hand: Three Unusual Cases with Painful Swelling of Small Joints

Archives of Pathology & Laboratory Medicine. Apr, 2006  |  Pubmed ID: 16594750

Tumoral calcinosis is a rare ectopic calcification syndrome characterized by irregular soft tissue masses originally described as being found mainly in large joints. We report 3 cases of tumoral calcinosis that occurred in unusual locations, the metacarpophalageal and proximal interphalangeal joints of the hand. The patients were women who ranged in age from 26 to 44; all presented with complaints of painful swelling of the joints. Laboratory tests demonstrated normal serum phosphate and calcium levels. Radiologic examination disclosed para-articular calcified masses. On surgical excision, the deep-seated calcified masses were attached to collateral ligaments of the joints. Milky and chalklike fluid was released during surgery. The masses measured 1.5, 0.9, and 0.8 cm in length and had irregular surfaces. Microscopically, the masses had fibrous capsule and the inner small cystic spaces that contained granular, calcified material. These cysts contained proliferating capillaries, mononuclear lymph plasma cells, and giant cells. No recurrences were found in any of the patients during the follow-up periods.

CT of Nasal-type T/NK Cell Lymphoma in the Lung

Journal of Thoracic Imaging. Mar, 2006  |  Pubmed ID: 16538154

Nasal-type T-cell/natural killer cell lymphoma is a new distinctive clinicopathologic entity with a characteristic immunophenotypic expression of CD56. Most cases show a predilection for the nasopharyngeal region and are referred to as nasal T/NK-cell lymphoma. Few cases occur in areas other than the nose. To the best of our knowledge, nasal type T/NK cell lymphoma with isolated lung involvement has not been reported. We illustrate here the CT findings of this rare tumor occurring primarily in the lung.

Primary Extraskeletal Mesenchymal Chondrosarcoma Arising from the Pancreas

Korean Journal of Radiology : Official Journal of the Korean Radiological Society. Nov-Dec, 2007  |  Pubmed ID: 18071285

We report here on a case of primary extraskeletal mesenchymal chondrosarcoma that arose from the pancreas. A 41-year-old man was evaluated by CT to find the cause of his abdominal pain. The CT scans showed a heterogeneously enhancing necrotic mass with numerous areas of coarse calcification, and this was located in the left side of the retroperitoneal space and involved the body and tail of the pancreas. Portal venography via the celiac axis also showed invasion of the splenic vein. Following excision of the mass, it was pathologically confirmed to be primary extraskeletal mesenchymal chondrosarcoma that arose from the pancreas.

Genetic Effect of CCR3 and IL5RA Gene Polymorphisms on Eosinophilia in Asthmatic Patients

The Journal of Allergy and Clinical Immunology. Nov, 2007  |  Pubmed ID: 17983872

Eosinophilic infiltration and peripheral blood eosinophilia in asthma require the cooperation of eosinophil-specific cytokines and chemokines and their receptors.

Anti-tumor Activity of Gastrodia Elata Blume is Closely Associated with a GTP-Ras-dependent Pathway

Oncology Reports. Oct, 2007  |  Pubmed ID: 17786345

Gastrodia elata Blume (GEB) is an important medicinal plant in Korea. In order to confirm the anti-tumor activities of GEB extracts, we carried out various in vitro anti-tumor assays, including a wound assay and an invasion assay using an ethyl ether extract of GEB. The results showed that the GEB extract exhibits potent anti-tumor activity in vitro in a dose-dependent manner. The expression of CD44, cdc42, Timp-2 or RhoA mRNA did not change by GEB treatment, compared to that of the control. GTP-Ras, an active form of a G-coupled protein family, however, is associated with the anti-tumor activity of GEB extracts. We examined various molecular markers related to metastasis by reverse transcriptase-polymerase chain reaction with the extract of GEB-treated B16 cells. There was an increase in GTP-Ras expression by the Gastrodia elata Blume extract. Together, these results suggest that the Gastrodia elata Blume extract could have potential in alleviating tumorigenesis, by a GTP-Ras-dependent pathway; although the precise molecular mechanisms are still being examined.

Preoperative Left Atrial Volume Index is a Predictor of Successful Sinus Rhythm Restoration and Maintenance After the Maze Operation

The Journal of Thoracic and Cardiovascular Surgery. Aug, 2007  |  Pubmed ID: 17662788

The purpose of this study was to identify the relationship of preoperative and postoperative left atrial volume indices and dimensions with successful restoration of sinus rhythm after the maze operation.

Uniform Image Quality Achieved by Tube Current Modulation Using SD of Attenuation in Coronary CT Angiography

AJR. American Journal of Roentgenology. Jul, 2007  |  Pubmed ID: 17579170

The objective of our study was to evaluate whether the SD of CT attenuation values obtained from unenhanced scans of the left atrium is a reliable parameter for the individual modulation of tube current to achieve uniform image quality in coronary CT angiography (CTA).

Primary Mucinous Adenocarcinoma of a Seminal Vesicle Cyst Associated with Ectopic Ureter and Ipsilateral Renal Agenesis: a Case Report

Korean Journal of Radiology : Official Journal of the Korean Radiological Society. May-Jun, 2007  |  Pubmed ID: 17554197

Primary adenocarcinoma of the seminal vesicles is a rare neoplasm. Congenital seminal vesicle cysts are commonly associated with unilateral renal agenesis or dysgenesis. To the best of our knowledge, mucinous adenocarcinoma of the seminal vesicle cyst that's associated with an ectopic ureter opening into the seminal vesicle and ipsilateral renal agenesis has not been described in the radiological literature. We report here on the radiological findings of a primary adenocarcinoma of a seminal vesicle cyst in this condition.

Association Analysis of CD40 Polymorphisms with Asthma and the Level of Serum Total IgE

American Journal of Respiratory and Critical Care Medicine. Apr, 2007  |  Pubmed ID: 17255560

The CD40 protein plays important roles in cell-mediated and humoral immune responses, especially in immunoglobulin class-switching to IgE.

An ROC Study of Chest Radiographs: 2K Versus 4K High-resolution Soft-copy Images

Journal of Digital Imaging : the Official Journal of the Society for Computer Applications in Radiology. Dec, 2007  |  Pubmed ID: 17191100

Computed radiography of chest with a 4K image array was recently introduced. We performed a multiobserver study to compare the diagnostic accuracy of 2K (standard) and 4K (high quality) chest radiographs displayed on a 5-mega-pixel monitor (2K monitor). One hundred cases of posteroanterior chest radiographs (a total of 200 images) were selected by two chest radiologists. Those radiographs included pneumothorax (n = 14), nodules (n = 15), interstitial disease (n = 10), or neither abnormality (n = 61). These were interpreted by four radiologists in two separate sessions. They recorded their confidence scale for the presence or absence of abnormality. Diagnostic accuracy was determined by receiver operating characteristic (ROC) analysis for each observer. ROC analysis showed no statistically significant difference between the 2K and 4K modes for the detection of any of the different abnormalities by individual readers. Our preliminary study suggests that 2K mode would be sufficient for the detection of abnormality on chest radiograph and there is no considerable validity to incline toward the 4K mode in current picture archiving and communication system environment using 2K monitor. However, we think that additional investigation using more subtle parenchymal or rib lesion should be followed.

Electrical and Mechanical Switching in a Realistic [2]rotaxane Device Model

Journal of Nanoscience and Nanotechnology. Sep, 2008  |  Pubmed ID: 19049065

Improving the efficiency of our first-principles calculation approach to the charge transport properties of nanoscale junctions, we consider an electronic device model based on the full rotaxane molecular structure including stoppers. We demonstrate that the conformational switching of molecules from the ground-state to the metastable-state conformation can be activated and the corresponding electrical switching from the OFF to the ON state can be observed in the rotaxane-based solid-state tunnel junctions.

Coronary Stent Fracture: Detection with 64-section Multidetector CT Angiography in Patients and in Vitro

Radiology. Dec, 2008  |  Pubmed ID: 19011182

To evaluate 64-section multidetector coronary computed tomographic (CT) angiography for the depiction of coronary stent fracture in patients and in vitro.

Charge Transport Through Polyene Self-assembled Monolayers from Multiscale Computer Simulations

The Journal of Physical Chemistry. B. Nov, 2008  |  Pubmed ID: 18947250

We combine first-principles density-functional theory with matrix Green's function calculations to predict the structures and charge transport characteristics of self-assembled monolayers (SAMs) of four classes of systems in contact with Au(111) electrodes: conjugated polyene chains (n = 4, 8, 12, 16, and 30) thiolated at one or both ends and saturated alkane chains (n = 4, 8, 12, and 16) thiolated at one or both ends. For the polyene SAMs, we find no decay in the current as a function of chain length and conclude that these 1-3 nm long polyene SAMs act as metallic wires. We also find that the polyene-monothiolate leads to a contact resistance only 2.8 times higher than that for the polyene-dithiolate chains, indicating that the device conductance is dominated by the properties of the molecular connector with less importance in having a second molecule-electrode contact. For the alkane SAMs, we observe the normal exponential decay in the current as a function of the chain length with a decay constant of beta(n) = 0.82 for the alkane-monothiolate and 0.88 for the alkane-dithiolate. We find that the contact resistance for the alkane-monothiolate is 12.5 times higher than that for the alkane-dithiolate chains, reflecting the extra resistance due to the weak contact on the nonthiolated end. These contrasting charge transport characteristics of alkane and polyene SAMs and their contact dependence are explained in terms of the atomic projected density of states.

Effects of Light Treatment on Isoflavone Content of Germinated Soybean Seeds

Journal of Agricultural and Food Chemistry. Nov, 2008  |  Pubmed ID: 18841981

Our research objective was to increase isoflavone content in the germinated soybean seeds of four different varieties (Pungsannamulkong, Cheongjakong, Aga4, and Aga3) by optimizing light treatments (dark, greenhouse, fluorescent, incandescent, and ultraviolet lamps). The results demonstrated that the highest isoflavone content was produced from the Aga3 variety, which was developed by an interspecific cross between Eunhakong (Glycine max) and KLG10084 (G. soja) at the Plant Genetic Laboratory, Kyunpook National University. Aga3 is known to have one of the highest isoflavone content in the world at present. Our results recommend exposure of 7-day-old Aga3 sprouts to a combined light treatment of greenhouse lamps (12 h per day) and ultraviolet light (40 min per day) for maximum isoflavone production. Aga3 produced high levels of isoflavone because, in part, it contained very high isoflavone levels within the seed as compared with the other varieties. Under stress conditions, Aga3 could produce over 1.90 times more isoflavone than its seed content and 1.53 times more isoflavone than when grown under dark conditions.

[Risk Factors for Early Recurrence After Surgical Resection for Hepatocellular Carcinoma]

The Korean Journal of Hepatology. Sep, 2008  |  Pubmed ID: 18815460

Early recurrence (ER) after liver resection is one of the most important factors impacting the prognosis and survival of patients with hepatocellular carcinoma (HCC). This study aimed to identify the factors associated with ER after curative hepatic resection for HCC.

Genetic Interactions Model Among Eotaxin Gene Polymorphisms in Asthma

Journal of Human Genetics. 2008  |  Pubmed ID: 18712274

Eotaxin family (Eotaxin 1,2 and 3) recruits and activates CCR3-bearing cells such as eosinophil, mast cells, and Th2 lymphocytes that play a major role in allergic disorders. We examined the polygenetic effects of the Eotaxin gene family in a Korean population. Gene-gene interactions were tested using a multistep approach with multifactor dimensionality reduction (MDR) method between asthmatics and normal controls. The overall best MDR model of the main effect single nucleotide polymorphisms (SNPs) included EOT2 + 1272A > G and EOT3 + 77C > T (model 1) [testing accuracy 0.597, cross-validation consistency (CVC) 10/10, P < 0.001]. The overall best MDR model of the SNPs with no main effects included EOT2 + 304C > A, EOT3 + 716A > G, and EOT3 + 1579G > A (model 2) (testing accuracy 0.616, CVC 10/10, P < 0.001). Model 3 was obtained by including the MDR variables for models 1 and 2. This new composite model predicted asthma with better accuracy than either model 1 or model 2 (testing accuracy 0.643, CVC 10/10, P < 0.001). The detection of statistical interaction models is one evidence of gene-gene interactions among Eotaxin genes, and this interaction is thought to influence the development of asthma. Although the models are limited to determining statistical interactions within a population, they may be useful for identifying groups at high risk of developing asthma.

Obesity in Aspirin-tolerant and Aspirin-intolerant Asthmatics

Respirology (Carlton, Vic.). Nov, 2008  |  Pubmed ID: 18699807

Obesity is an important factor in the development of asthma. Aspirin hypersensitivity affects 5-10% of asthmatics. The association between obesity and aspirin hypersensitivity in asthma is unclear. This study evaluated the association of BMI and asthma in patients with aspirin-tolerant asthma (ATA) and aspirin-intolerant asthma (AIA).

Isoflavone Attenuates Vascular Contraction Through Inhibition of the RhoA/Rho-kinase Signaling Pathway

The Journal of Pharmacology and Experimental Therapeutics. Sep, 2008  |  Pubmed ID: 18577703

Isoflavones decrease blood pressure, improve lipid profiles, and restore vascular function. We hypothesized that isoflavone attenuates vascular contraction by inhibiting RhoA/Rho-kinase signaling pathway. Rat aortic rings were denuded of endothelium, mounted in organ baths, and contracted with 11,9 epoxymethano-prostaglandin F(2alpha) (U46619), a thromboxane A2 analog, or KCl 30 min after the pretreatment with genistein (4',5,7-trihydroxyisoflavone), daidzein (4',7-dihydroxyisoflavone), or vehicle. We determined the phosphorylation level of the myosin light chain (MLC(20)), myosin phosphatase-targeting subunit 1 (MYPT1), and protein kinase C-potentiated inhibitory protein for heterotrimeric myosin light-chain phosphatase of 17 kDa (CPI17) by means of the Western blot. We also measured the amount of GTP RhoA as a marker regarding RhoA activation. The cumulative additions of U46619 or KCl increased vascular tension in a concentration-dependent manner, which were inhibited by pretreatment with genistein or daidzein. Both U46619 (30 nM) and KCl (50 mM) increased MLC(20) phosphorylation levels, which were inhibited by genistein and daidzein. Furthermore, both genistein and daidzein decreased the amount of GTP RhoA activated by either U46619 or KCl. U46619 (30 nM) increased phosphorylation of the MYPT1(Thr855) and CPI17(Thr38), which were also inhibited by genistein or daidzein. However, neither genistein nor daidzein inhibited phorbol 12,13-dibutyrate-induced vascular contraction and CPI17 phosphorylation. In conclusion, isoflavone attenuates vascular contraction, at least in part, through inhibition of the RhoA/Rho-kinase signaling pathway.

Coronary-to-bronchial Artery Fistula: Demonstration by 64-multidetector Computed Tomography with Retrospective Electrocardiogram-gated Reconstructions

Journal of Computer Assisted Tomography. May-Jun, 2008  |  Pubmed ID: 18520554

The aim of this study was to evaluate the incidence of coronary-to-bronchial artery fistula (CBF) and clinical significance in 1300 patients examined with 64-multidetector computed tomography (MDCT) coronary angiography.

[A Case of Stump Appendicitis After Appendectomy]

The Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi. Jan, 2008  |  Pubmed ID: 18349562

Stump appendicitis is an acute inflammation of the residual appendix and a rare complication after an appendectomy. Although the signs and symptoms do not differ from acute appendicitis, the diagnosis is often not considered because of the past surgical history. Only a small number of stump appendicitis cases have been reported, but there has been no report of stump appendicitis in Korea. Herein, we report a case of stump appendicitis. A 28-year-old female was admitted to our hospital due to right lower quadrant abdominal pain. Fifteen months ago, the patient had a laparoscopic appendectomy under the diagnosis of an acute appendicitis, but she subsequently suffered from intermittent abdominal pain and fever. Abdominal ultrasonography and CT scan showed an inflamed appendiceal stump. Laparoscopic stump appendectomy was done and the biopsy revealed stump appendicitis.

Pathological Features of Bone Marrow Transplantation-related Toxicity in a Mouse

Journal of Veterinary Science. Dec, 2009  |  Pubmed ID: 19934605

In this case report, we present a mock-transduced bone marrow (BM) transplantation in a mouse, which was found moribund and autopsied to evaluate pathogenesis. Macroscopically, red discoloration of systemic organs was observed. Hematological values revealed a decrease in white blood cells, red blood cells, hematocrit, hemoglobin, and platelets, but an increase in reticulocytes. In BM cytology, hematopoietic cell lines were severely depleted. Histopathologically, hemorrhage in the cerebellar parenchyma, hemosiderin deposition and hemorrhage in the heart, necrosis and telangiectasia in liver, pulmonary parenchymal cysts, spermatogenic germ cells necrosis, atrophy and hemorrhage in testis, oligospermia and hemorrhage in the epididymis, and atrophy of BM, thymus and spleen were observed. In conclusion, autoimmune-like complications such as hematological value change, BM dysplasia and systemic hemorrhage appear to be the lethal cause of the mouse transplanted with mock-transduced BM.

Acute Lower Gastrointestinal Bleeding Due to Appendiceal Mucosal Erosion

Surgical Laparoscopy, Endoscopy & Percutaneous Techniques. Oct, 2009  |  Pubmed ID: 19851256

Acute lower gastrointestinal hemorrhage associated with the appendix is rare. We report on a 42-year-old male patient who presented with hematochezia from solitary appendiceal bleeding. The patient was admitted to our hospital with rectal bleeding, and abdominal computed tomography identified active contrast leakage in the distal portion of the appendix. During a subsequent urgent colonoscopy, active bleeding in the appendiceal orifice was identified. The patient was successfully treated with a laparoscopic appendectomy and hematochezia did not recur postoperatively. Microscopic examination revealed an eroded appendiceal mucosa, focal inflammatory infiltrates, and a normal submucosal vessel without evidence of vascular malformation.

Hepatocyte Growth Factor Family Negatively Regulates Hepatic Gluconeogenesis Via Induction of Orphan Nuclear Receptor Small Heterodimer Partner in Primary Hepatocytes

The Journal of Biological Chemistry. Oct, 2009  |  Pubmed ID: 19720831

Hepatic gluconeogenesis is tightly balanced by opposing stimulatory (glucagon) and inhibitory (insulin) signaling pathways. Hepatocyte growth factor (HGF) is a pleiotropic growth factor that mediates diverse biological processes. In this study, we investigated the effect of HGF and its family member, macrophage-stimulating factor (MSP), on hepatic gluconeogenesis in primary hepatocytes. HGF and MSP significantly repressed expression of the key hepatic gluconeogenic enzyme genes, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (Glc-6-Pase) and reduced glucose production. HGF and MSP activated small heterodimer partner (SHP) gene promoter and induced SHP mRNA and protein levels, and the effect of HGF and MSP on SHP gene expression was demonstrated to be mediated via activation of the AMP-activated protein kinase (AMPK) signaling pathway. We demonstrated that upstream stimulatory factor-1 (USF-1) specifically mediated HGF effect on SHP gene expression, and inhibition of USF-1 by dominant negative USF-1 significantly abrogated HGF-mediated activation of the SHP promoter. Elucidation of the mechanism showed that USF-1 bound to E-box-1 in the SHP promoter, and HGF increased USF-1 DNA binding on the SHP promoter via AMPK and DNA-dependent protein kinase-mediated pathways. Adenoviral overexpression of USF-1 significantly repressed PEPCK and Glc-6-Pase gene expression and reduced glucose production. Knockdown of endogenous SHP expression significantly reversed this effect. Finally, knockdown of SHP or inhibition of AMPK signaling reversed the ability of HGF to suppress hepatocyte nuclear factor 4alpha-mediated up-regulation of PEPCK and Glc-6-Pase gene expression along with the HGF- and MSP-mediated suppression of gluconeogenesis. Overall, our results suggest a novel signaling pathway through HGF/AMPK/USF-1/SHP to inhibit hepatic gluconeogenesis.

Interleukin-13 and Its Receptors in Idiopathic Interstitial Pneumonia: Clinical Implications for Lung Function

Journal of Korean Medical Science. Aug, 2009  |  Pubmed ID: 19654941

Idiopathic interstitial pneumonia (IIP) is characterized by varying degrees of interstitial fibrosis. IL-13 and IL-4 are strong inducers of tissue fibrosis, whereas IFN-gamma has antifibrotic potential. However, the roles of these substances in IIP remain unknown. IL-13, IL-4, and IFN-gamma were measured in the BAL fluid of 16 idiopathic pulmonary fibrosis (IPF) patients, 10 nonspecific interstitial pneumonia (NSIP) patients, and 8 normal controls. The expression of IL-13 and IL-13Ralpha1/alpha2 in lung tissues was analyzed using ELISA and immunohistochemistry. IL-13 levels were significantly higher in IPF patients than the others (P<0.05). IL-4 levels were higher in both IPF and NSIP patients than in normal controls (P<0.05), and IFN-gamma levels were lower in NSIP patients than in normal controls (P=0.047). IL-13 levels correlated inversely with FVC% (r=-0.47, P=0.043) and DLCO% (r=-0.58, P=0.014) in IPF and NSIP patients. IL-13 was strongly expressed in the smooth muscle, bronchial epithelium, alveolar macrophages and endothelium of IPF patients. IL-13Ralpha1, rather than IL-13Ralpha2, was strongly expressed in the smooth muscle, bronchial epithelium, and endothelium of IPF patients. IL-13 and its receptors may contribute to the pathogenesis of fibrosis in IIP and appear to be related to the severity of the disease.

DAX-1 Acts As a Novel Corepressor of Orphan Nuclear Receptor HNF4alpha and Negatively Regulates Gluconeogenic Enzyme Gene Expression

The Journal of Biological Chemistry. Oct, 2009  |  Pubmed ID: 19651776

DAX-1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is an atypical member of the nuclear receptor family and acts as a corepressor of a number of nuclear receptors. HNF4alpha (hepatocyte nuclear factor 4alpha) is a liver-enriched transcription factor that controls the expression of a variety of genes involved in cholesterol, fatty acid, and glucose metabolism. Here we show that DAX-1 inhibits transcriptional activity of HNF4alpha and modulates hepatic gluconeogenic gene expression. Hepatic DAX-1 expression is increased by insulin and SIK1 (salt-inducible kinase 1), whereas it is decreased in high fat diet-fed and diabetic mice. Coimmunoprecipitation assay from mouse liver samples depicts that endogenous DAX-1 interacts with HNF4alpha in vivo. In vivo chromatin immunoprecipitation assay affirms that the recruitment of DAX-1 on the phosphoenolpyruvate carboxykinase (PEPCK) gene promoter is inversely correlated with the recruitment of PGC-1alpha and HNF4alpha under fasting and refeeding, showing that DAX-1 could compete with the coactivator PGC-1alpha for binding to HNF4alpha. Adenovirus-mediated expression of DAX-1 decreased both HNF4alpha- and forskolin-mediated gluconeogenic gene expressions. In addition, knockdown of DAX-1 partially reverses the insulin-mediated inhibition of gluconeogenic gene expression in primary hepatocytes. Finally, DAX-1 inhibits PEPCK and glucose-6-phosphatase gene expression and significantly lowers fasting blood glucose level in high fat diet-fed mice, suggesting that DAX-1 can modulate hepatic gluconeogenesis in vivo. Overall, this study demonstrates that DAX-1 acts as a corepressor of HNF4alpha to negatively regulate hepatic gluconeogenic gene expression in liver.

Fenofibrate Differentially Regulates Plasminogen Activator Inhibitor-1 Gene Expression Via Adenosine Monophosphate-activated Protein Kinase-dependent Induction of Orphan Nuclear Receptor Small Heterodimer Partner

Hepatology (Baltimore, Md.). Sep, 2009  |  Pubmed ID: 19593819

Plasminogen activator inhibitor type I (PAI-1) is a marker of the fibrinolytic system and serves as a possible predictor for hepatic metabolic syndromes. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARalpha) agonist, is a drug used for treatment of hyperlipidemia. Orphan nuclear receptor small heterodimer partner (SHP) plays a key role in transcriptional repression of crucial genes involved in various metabolic pathways. In this study, we show that fenofibrate increased SHP gene expression in cultured liver cells and in the normal and diabetic mouse liver by activating the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in a PPARalpha-independent manner. Administration of transforming growth factor beta (TGF-beta) or a methionine-deficient and choline-deficient (MCD) diet to induce the progressive fibrosing steatohepatitis model in C57BL/6 mice was significantly reversed by fenofibrate via AMPK-mediated induction of SHP gene expression with a dramatic decrease in PAI-1 messenger RNA (mRNA) and protein expression along with other fibrotic marker genes. No reversal was observed in SHP null mice treated with fenofibrate. Treatment with another PPARalpha agonist, WY14643, showed contrasting effects on these marker gene expressions in wild-type and SHP null mice, demonstrating the specificity of fenofibrate in activating AMPK signaling. Fenofibrate exhibited a differential inhibitory pattern on PAI-1 gene expression depending on the transcription factors inhibited by SHP. Conclusion: By demonstrating that a PPARalpha-independent fenofibrate-AMPK-SHP regulatory cascade can play a key role in PAI-1 gene down-regulation and reversal of fibrosis, our study suggests that various AMPK activators regulating SHP might provide a novel pharmacologic option in ameliorating hepatic metabolic syndromes.

Synthesis and Base Pairing Properties of DNA-RNA Heteroduplex Containing 5-hydroxyuridine

BMB Reports. Jun, 2009  |  Pubmed ID: 19558797

5-Hydroxyuridine (5-OHU) is a major lesion of uridine and cytosine produced in RNA by various chemical oxidants. To elucidate its biochemical and biophysical effects on RNA replication, the site-specifically modified oligoribonucleotides containing 5-OHU were synthesized with C5-hydroxy-5'-O-DMTr-2'-TBDMS-uridine phosphoramidite using automated solid phase synthesis. The base-pairing properties of nucleotides opposite 5-OHU in 24 mer oligoribonulcleotides with dNTP were studied using three reverse transcriptases (Super-Script(TM)II-, AMV-, MMLV-RT) in cDNA synthesis. Adenine as well as guanine was incorporated preferentially by all reverse transcriptases. In the UV-melting temperature experiment, the results from the relative stabilities of the base pairs were A : 5-OHU > G : 5-OHU > T : 5-OHU approximately C : 5-OHU. Circular Dichroism (CD) studies showed that DNA-RNA containing 5-OHU heteroduplexes exhibit a similar conformation between the A-type RNA and B-type DNA. These results suggest that 5-OHU from oxidative damage was mainly influenced by adenine mismatch.

Frequency of Myocardial Bridges and Dynamic Compression of Epicardial Coronary Arteries: a Comparison Between Computed Tomography and Invasive Coronary Angiography

Circulation. Mar, 2009  |  Pubmed ID: 19255347

The objective of the present study was to describe the relative frequency of myocardial bridging and dynamic compression of the coronary arteries as assessed by CT angiography and conventional angiography.

Association of IL-17RB Gene Polymorphism with Asthma

Chest. May, 2009  |  Pubmed ID: 19118269

Interleukin (IL)-17E is a member of the IL-17 family, which induces IL-4, IL-5, IL-13, and eotaxin in experimental animals via IL-17 receptor B (IL-17RB). The activation of IL-17RB amplifies allergic-type inflammatory responses by inducing Jun kinase (or JNK), p38 mitogen-activated protein kinase (or MAPK), and nuclear factor-kappaB.

Genome-wide and Follow-up Studies Identify CEP68 Gene Variants Associated with Risk of Aspirin-intolerant Asthma

PloS One. 2010  |  Pubmed ID: 21072201

Aspirin-intolerant asthma (AIA) is a rare condition that is characterized by the development of bronchoconstriction in asthmatic patients after ingestion of non-steroidal anti-inflammatory drugs including aspirin. However, the underlying mechanisms of AIA occurrence are still not fully understood. To identify the genetic variations associated with aspirin intolerance in asthmatics, the first stage of genome-wide association study with 109,365 single nucleotide polymorphisms (SNPs) was undertaken in a Korean AIA (n = 80) cohort and aspirin-tolerant asthma (ATA, n = 100) subjects as controls. For the second stage of follow-up study, 150 common SNPs from 11 candidate genes were genotyped in 163 AIA patients including intermediate AIA (AIA-I) subjects and 429 ATA controls. Among 11 candidate genes, multivariate logistic analyses showed that SNPs of CEP68 gene showed the most significant association with aspirin intolerance (P values of co-dominant for CEP68, 6.0×10(-5) to 4.0×10(-5)). All seven SNPs of the CEP68 gene showed linkage disequilibrium (LD), and the haplotype of CEP68_ht4 (T-G-A-A-A-C-G) showed a highly significant association with aspirin intolerance (OR= 2.63; 95% CI= 1.64-4.21; P = 6.0×10(-5)). Moreover, the nonsynonymous CEP68 rs7572857G>A variant that replaces glycine with serine showed a higher decline of forced expiratory volume in 1s (FEV(1)) by aspirin provocation than other variants (P = 3.0×10(-5)). Our findings imply that CEP68 could be a susceptible gene for aspirin intolerance in asthmatics, suggesting that the nonsynonymous Gly74Ser could affect the polarity of the protein structure.

Putative Association of SMAPIL Polymorphisms with Risk of Aspirin Intolerance in Asthmatics

The Journal of Asthma : Official Journal of the Association for the Care of Asthma. Nov, 2010  |  Pubmed ID: 20831471

Aspirin-intolerant asthma (AIA), as a clinical syndrome caused by aspirin, is characterized by lung inflammation and reversible bronchoconstriction. Recently, the altered trafficking and diminished airway reactivity have been implicated in allergic airway remodeling. The stromal membrane-associated protein 1-like (SMAP1L) exerts common and distinct functions in vesicle trafficking including endocytosis. The disturbance of pulmonary surfactant synthesis has been elucidated to be associated with asthma experimentally. Moreover, in alveolar type II (ATII) cells that synthesize pulmonary surfactant, alterations of clathrin-dependent endocytosis cause disturbance at the surfactant function, suggesting that SMAP1L, which directly interacts with clathrin, could be associated with asthma and related phenotypes.

Antioxidant Effects of the Chestnut (Castanea Crenata) Inner Shell Extract in T-BHP-treated HepG2 Cells, and CCl4- and High-fat Diet-treated Mice

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. Nov, 2010  |  Pubmed ID: 20732376

The antioxidant effects of chestnut inner shell extract (CISE) were investigated in a tert-butylhydroperoxide (t-BHP)-treated HepG2 cells, and in mice that were administered carbon tetrachloride (CCl(4)) and fed a high-fat diet (HFD). Pre-incubation with CISE significantly blocked the oxidative stress induced by t-BHP treatment in HepG2 cells (P<0.05) and preserved the activities of catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase compared to group treated with t-BHP only. Similarly, the CCl(4)- and HFD-induced reduction of antioxidant enzymes activities in liver was prevented by CISE treatment compared to control groups. Furthermore, hepatic lipid peroxidation were remarkably lower (P<0.05) in the CISE-treated groups with t-BHP or HFD. To determine the active compound of CISE, the fractionation of CISE has been conducted and scoparone and scopoletin were identified as main compounds. These compounds were also shown to inhibit the t-BHP-induced ROS generation and reduction in antioxidant enzyme activity in an in vitro model system. From these results, it was demonstrated that CISE has the ability to protect against damage from oxidative stressors such as t-BHP, CCl(4) and HFD in in vitro and in vivo models. The CISE might be useful for the prevention of oxidative damage in liver cells and tissues.

Differential Modulatory Effects of Rosiglitazone and Pioglitazone on White Adipose Tissue in Db/db Mice

Life Sciences. Sep, 2010  |  Pubmed ID: 20723549

this study was performed to clarify the different action mechanisms through which rosiglitazone and pioglitazone regulate lipogenesis in white adipose tissues of db/db mice, an animal model of diabetes.

AMPK-dependent Repression of Hepatic Gluconeogenesis Via Disruption of CREB.CRTC2 Complex by Orphan Nuclear Receptor Small Heterodimer Partner

The Journal of Biological Chemistry. Oct, 2010  |  Pubmed ID: 20688914

Orphan nuclear receptor small heterodimer partner (SHP) plays a key role in transcriptional repression of gluconeogenic enzyme gene expression. Here, we show that SHP inhibited protein kinase A-mediated transcriptional activity of cAMP-response element-binding protein (CREB), a major regulator of glucose metabolism, to modulate hepatic gluconeogenic gene expression. Deletion analysis of phosphoenolpyruvate carboxykinase (PEPCK) promoter demonstrated that SHP inhibited forskolin-mediated induction of PEPCK gene transcription via inhibition of CREB transcriptional activity. In vivo imaging demonstrated that SHP inhibited CREB-regulated transcription coactivator 2 (CRTC2)-mediated cAMP-response element-driven promoter activity. Furthermore, overexpression of SHP using adenovirus SHP decreased CRTC2-dependent elevations in blood glucose levels and PEPCK or glucose-6-phosphatase (G6Pase) expression in mice. SHP and CREB physically interacted and were co-localized in vivo. Importantly, SHP inhibited both wild type CRTC2 and S171A (constitutively active form of CRTC2) coactivator activity and disrupted CRTC2 recruitment on the PEPCK gene promoter. In addition, metformin or overexpression of a constitutively active form of AMPK (Ad-CA-AMPK) inhibited S171A-mediated PEPCK and G6Pase gene expression, and hepatic glucose production and knockdown of SHP partially relieved the metformin- and Ad-CA-AMPK-mediated repression of hepatic gluconeogenic enzyme gene expression in primary rat hepatocytes. In conclusion, our results suggest that a delayed effect of metformin-mediated induction of SHP gene expression inhibits CREB-dependent hepatic gluconeogenesis.

Association of IKBA Gene Polymorphisms with the Development of Asthma

Human Immunology. Nov, 2010  |  Pubmed ID: 20674643

Nuclear factor-κB (NF-κB) orchestrates the expression of genes responsible for airway inflammation and remodeling in asthma. The activity of NF-κB is tightly regulated by IKBA, which may be modulated by genetic polymorphisms of the IKBA gene. We investigated the association between asthma susceptibility and IKBA gene polymorphisms in a Korean population. Genotyping was performed in BA (bronchial asthma) and NC (normal control). We measured reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, and luciferase reporter assays, respectively. A -673A>T (rs2233407) was associated with asthma development in subjects with atopic asthma (odds ratio = 0.56, p = 0.004). The IKBA mRNA level was higher in B-cell lines with the rs2233407 TT genotype compared with those with the AA genotype (p = 0.024). The luciferase activity of the rs2233407 T genotype was higher than that of the A (p = 0.002). The cytoplasmic levels of total IKBA and IKBA [p-S32] were higher in B cell lines of the rs2233407 TT genotype than those of the AA (p = 0.016 and p = 0.036, respectively), whereas nuclear NF-κB activity in cells with the IKBA rs2233407 AA genotype was higher than in cells with the AA (p = 0.038). The IKBA rs2233407 A>T polymorphism may predispose individuals to the development of atopic asthma via regulation of IKBA gene expression at the transcriptional level.

Inhibitory Effect of Glyceollin Isolated from Soybean Against Melanogenesis in B16 Melanoma Cells

BMB Reports. Jul, 2010  |  Pubmed ID: 20663406

Natural products with non-toxic and environmentally friendly properties are good resources for skin-whitening cosmetic agents when compared to artificial synthetic chemicals. Here, we investigated the effect of glyceollin produced to induce disease resistance responses of soybean to specific races of an incompatible pathogen, phytophthora sojae, on melanogenesis and discussed their mechanisms in melanin biosynthesis. We found that glyceollin inhibits melanin synthesis and tyrosinase activity in B16 melanoma cells without cytotoxicity. To elucidate the mechanism of the effect of glyceollin on melanogenesis, we conducted western blot analysis for melanogenic enzymes such as tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2. Glyceollin inhibited tyrosinase and TRP-1 protein expression. Additionally, glyceollin effectively inhibited intracellular cAMP levels in B16 melanoma cells stimulated by alpha-melanocyte stimulating hormone (alpha-MSH). These results suggest that the whitening activity of glyceollin may be due to the inhibition of cAMP involved in the signal pathway of alpha-MSH in B16 melanoma cells.

Association Analysis of N-acetyl Transferase-2 Polymorphisms with Aspirin Intolerance Among Asthmatics

Pharmacogenomics. Jul, 2010  |  Pubmed ID: 20602614

Cysteinyl leukotrienes are inactivated by acetyl coenzyme A-dependent N-acetyltransferase (NAT). Thus, functional alterations of the NAT gene may contribute to the risk of aspirin-intolerant asthma.

Association of SLC6A12 Variants with Aspirin-intolerant Asthma in a Korean Population

Annals of Human Genetics. Jul, 2010  |  Pubmed ID: 20597903

Aspirin-intolerant asthma (AIA) occurs from asthma exacerbation after exposure to aspirin. However, the underlying mechanisms of AIA occurrence are still unclear. The critical role of the solute carrier family 6 (neurotransmitter transporter, betaine/GABA) member 12 (SLC6A12) gene in GABAergic transmission, which is associated with mucus production in asthma, makes it a candidate gene for AIA association study. Eight single nucleotide polymorphisms (SNPs) in SLC6A12 were genotyped in 163 aspirin-intolerant asthma (AIA) and 429 aspirin-tolerant asthma (ATA) patients of Korean ethnicity. Associations between polymorphisms of SLC6A12 and AIA were analysed using multivariate logistic analysis. Results showed that two polymorphisms and a haplotype in SLC6A12, rs499368 (P= 0.005; P(corr)= 0.03), rs557881 (non-synonymous C10R, P= 0.007; P(corr)= 0.04), and SLC6A12_BL1_ht1 (P= 0.009; P(corr)= 0.05) respectively, were significantly associated with AIA after multiple testing corrections. In addition, SNPs of SLC6A12 were significantly associated with the fall rate of FEV(1) by aspirin provocation suggesting that SLC6A12 could affect reversibility of lung function abnormalities in AIA patients. Although these results are preliminary and future replications are needed to confirm these findings, this study showed evidence of association between variants in SLC6A12 and AIA occurrence among asthmatics in a Korean population.

Association of PTGER Gene Family Polymorphisms with Aspirin Intolerant Asthma in Korean Asthmatics

BMB Reports. Jun, 2010  |  Pubmed ID: 20587336

Aspirin-intolerant asthma (AIA) is characterized by severe asthmatic attack after ingestion of aspirin and/or non-steroidal anti-inflammatory drugs. In this study, we investigated the relationship between Prostaglandin E2 receptor (PTGER) gene family polymorphisms and AIA in 243 AIA patients and 919 aspirin-tolerant asthma (ATA) controls of Korean ethnicity in two separate study cohorts. After genotyping 120 SNPs of the PTGER gene family for the 1(st) cohort study, four SNPs in PTGER1, ten in PTGER3, six in PTGER3, and a haplotype of PTGER2 showed association signals with decreased or increased risk of AIA. Among the positively associated SNPs, one in PTGER1 and four in PTGER3 were analyzed in the 2(nd) cohort study. The results show that rs7543182 and rs959 in PTGER3 retained their effect, although no statistical significance was retained in the 2(nd) cohort study. Our findings provide further evidence that polymorphisms in PTGER3 might play a significant role in aspirin hypersensitivity among Korean asthmatics.

Association Between Colony-stimulating Factor 1 Receptor Gene Polymorphisms and Asthma Risk

Human Genetics. Sep, 2010  |  Pubmed ID: 20574656

Colony-stimulating factor 1 receptor (CSF1R) is expressed in monocytes/macrophages and dendritic cells. These cells play important roles in the innate immune response, which is regarded as an important aspect of asthma development. Genetic alterations in the CSF1R gene may contribute to the development of asthma. We investigated whether CSF1R gene polymorphisms were associated with the risk of asthma. Through direct DNA sequencing of the CSF1R gene, we identified 28 single nucleotide polymorphisms (SNPs) and genotyped them in 303 normal controls and 498 asthmatic patients. Expression of CSF1R protein and mRNA were measured on CD14-positive monocytes and neutrophils in peripheral blood of asthmatic patients using flow cytometry and real-time PCR. Among the 28 polymorphisms, two intronic polymorphism (+20511C>T and +22693T>C) were associated with the risk of asthma by logistic regression analysis. The frequencies of the minor allele at CSF1R +20511C>T and +22693T>C were higher in asthmatic subjects than in normal controls (4.6 vs. 7.7%, p = 0.001 in co-dominant and dominant models; 16.4 vs. 25.8%, p = 0.0006 in a recessive model). CSF1R mRNA levels in neutrophils of the asthmatic patients having the +22693CC allele were higher than in those having the +22693TT allele (p = 0.026). Asthmatic patients with the +22693CC allele also showed significantly higher CSF1R expression on CD14-positive monocytes and neutrophils than did those with the +22693TT allele (p = 0.045 and p = 0.044). The +20511C>T SNP had no association with CSF1R mRNA or protein expression. In conclusion, the minor allele at CSF1R +22693T>C may have a susceptibility effect in the development of asthma, via increased CSF1R protein and mRNA expression in inflammatory cells.

Acute Lower Gastrointestinal Bleeding Due to Appendiceal Mucosal Erosion

Surgical Laparoscopy, Endoscopy & Percutaneous Techniques. Jun, 2010  |  Pubmed ID: 20568343

Acute lower gastrointestinal hemorrhage associated with the appendix is rare. We report on a 42-year-old male patient who presented with hematochezia from solitary appendiceal bleeding. The patient was admitted to our hospital with rectal bleeding, and abdominal computed tomography identified active contrast leakage in the distal portion of the appendix. During a subsequent urgent colonoscopy, active bleeding in the appendiceal orifice was identified. The patient was successfully treated with a laparoscopic appendectomy and hematochezia did not recur postoperatively. Microscopic examination revealed an eroded appendiceal mucosa, focal inflammatory infiltrates, and a normal submucosal vessel without evidence of vascular malformation.

Atypical Appearance of a Neural Foraminal Elastofibroma of the Lumbar Spine Mimicking a Schwannoma on Computed Tomography and Magnetic Resonance Imaging

Japanese Journal of Radiology. May, 2010  |  Pubmed ID: 20512551

Elastofibromas are rare benign lesions that are most commonly found in the periscapular region. We describe a rare case of a 40-year-old woman presenting with right buttock radiating pain. Computed tomography and magnetic resonance imaging revealed a homogeneously enhanced mass occupying the right neural foramen at the L4/5 level. The clinical and radiological presentation suggested a schwannoma. Pathology examination of the tissue indicated elastofibroma.

Mesothelial Cyst of the Round Ligament Mimicking a Metastasis: a Case Report

Korean Journal of Radiology : Official Journal of the Korean Radiological Society. May-Jun, 2010  |  Pubmed ID: 20461192

A mesothelial cyst of the round ligament is a rare cause of an inguinal mass. Clinically, it is frequently misdiagnosed as one of commoner diseases such as an inguinal hernia, femoral hernia, lipoma, and lymphadenopathy upon physical examination. Some previous reports elaborated the sonographic features of a mesothelial cyst of the round ligament. However, to our knowledge, few reports have described the CT features of a mesothelial cyst. We illustrated here the sonographic and multidetector CT features of a case of a mesothelial cyst of the round ligament that presented as an inguinal palpable mass and mimicked a metastasis in a patient with a Sertoli-Leydig cell tumor of the ovary.

A New Association Between Polymorphisms of the SLC6A7 Gene in the Chromosome 5q31-32 Region and Asthma

Journal of Human Genetics. Jun, 2010  |  Pubmed ID: 20431603

The human chromosomal 5q31-33 region has been implicated as a susceptibility locus for several immune-mediated diseases including asthma in several populations. Recently, the extraneuronal GABAergic system has been implicated as a new link to airway obstruction in asthma. In addition, the SLC6A7 gene, which is positioned at 5q31-32 and encodes the transporter for an excitatory neurotransmitter of L-proline, has never been studied for its association with asthma. In this study, resequencing of all exon, promoter region (2 kb), and exon-intron boundary regions in the SLC6A7 gene found a total of 33 single nucleotide polymorphisms (SNPs) in 24 Korean asthmatic patients. After the initial SNP survey, a total of 17 common SNPs with minor allele frequency (MAF) over 10% were genotyped in 498 asthmatic patients and 303 normal controls. Logistic analyses revealed significant associations between genetic variants of the SLC6A7 gene and asthma (P-value up to 6.0 x 10(-4); P(corr) value up to 0.009). In further regression analyses, minor alleles of intronic +11431T>C, +12213C>T and +12927A>G in linkage disequilibrium block 2 and +20113T>C in 3'UTR significantly increased the bronchodilator response in asthmatics (P-value of recessive model up to 0.008; which are not significant after multiple correction). Therefore, our findings suggest that SLC6A7 could be a susceptible gene for asthma.

Effects of Glyceollin I on Vascular Contraction in Rat Aorta

Naunyn-Schmiedeberg's Archives of Pharmacology. Jun, 2010  |  Pubmed ID: 20354679

The present study was undertaken to investigate the molecular mechanisms by which glyceollin I inhibits vascular contraction in rat aorta. Rat aortic rings were treated with either glyceollin I or vehicle when vascular contraction reached plateaus. We measured the activity of GTP-RhoA and Rho GTPase-activating protein (RhoGAP) and the phosphorylation level of the myosin light chain (MLC(20)), myosin phosphatase targeting subunit 1 (MYPT1), and PKC-potentiated inhibitory protein for heterotrimeric MLCP of 17 kDa (CPI17). Glyceollin I reduced vascular contraction whether endothelium is present or denuded. Glyceollin I reduced vascular contraction induced by NaF, U46619, phenylephrine, or PDBu. Blockers of K(+) channels did not affect the vasorelaxation induced by glyceollin I. Glyceollin I reduced activation of RhoA as well as phosphorylation level of MLC(20). Glyceollin I also reduced phosphorylation of MYPT1 and CPI17 induced by NaF but not PDBu. However, glyceollin I had no direct effect on RhoGAP activation in vitro. Glyceollin I reduced vascular contraction, at least in part, through inhibition of the RhoA/Rho-kinase signaling pathway.

Protection of Leukotriene Receptor Antagonist Against Aspirin-induced Bronchospasm in Asthmatics

Allergy, Asthma & Immunology Research. Jan, 2010  |  Pubmed ID: 20224678

Leukotriene receptor antagonists (LTRAs) are used to treat aspirin-intolerant asthma (AIA); however, the protective effects of long-term LTRA administration against aspirin-induced bronchospasm have not been evaluated.

Desalinated Underground Seawater of Jeju Island (Korea) Improves Lipid Metabolism in Mice Fed Diets Containing High Fat and Increases Antioxidant Potential in T-BHP Treated HepG2 Cells

Nutrition Research and Practice. Feb, 2010  |  Pubmed ID: 20198202

This study was performed to investigate the effect of desalinated underground seawater (named as 'magma seawater', MSW) of Jeju Island in Korea on lipid metabolism and antioxidant activity. MSW was collected from underground of Han-Dong in Jeju Island, and freely given to high fat diet (HFD)-fed C57BL/6 mice for 10 weeks. Although there were no significant differences in the body weight changes and plasma lipid levels, hepatic triglyceride levels were significantly lower in the MSW group than in the normal tap water (TW)-drunken control group. Furthermore, the activity of fatty acid synthase (FAS) was significantly decreased and carnitine palmitoyltransferase (CPT) activity was increased in MSW group compared to TW group. Similarly, real-time PCR analysis revealed that mRNA expressions of lipogenic genes were lowered in MSW groups compared to the control group. In a morphometric observation on the liver tissue, accumulation of fats was remarkably reduced in MSW group. Meanwhile, in vitro assay, free radical scavenging activity measured by using diphenylpicrylhydrazyl (DPPH) was increased in MSW group. The 2'-7'-dichlorofluorescein diacetate (DCF-DA) staining followed with fluorescent microscopy showed a low intensity of fluorescence in MSW-treated HepG2 cells, compared to TW-treated HepG2 cells, which indicated that the production of reactive oxygen species by tert-butyl hydroperoxide (t-BHP) in HepG2 cells was decreased by MSW treatment. The antioxidant effect of MSW on t-BHP-induced oxidative stress in HepG2 cells was supported by the increased activities of intracellular antioxidant enzymes such as catalase and glutathione reductase. From these results, we speculate that MSW has an inhibitory effect on lipogenesis in liver and might play a protective role against cell damage by t-BHP-induced oxidative stress.

Preventative Effects of Platycodon Grandiflorum Treatment on Hepatic Steatosis in High Fat Diet-fed C57BL/6 Mice

Biological & Pharmaceutical Bulletin. 2010  |  Pubmed ID: 20190408

Platycodon grandiflorum (PG) (Korean name, Doraji; Chinese name, Jiegeng; and Japanese name, Kikyo) is a perennial plant in the Campanulaceae family that contains triterpenoid saponins, carbohydrates, and fibers. This study was carried out to investigate effects of root of PG on fatty liver inhibition in high fat diet (HFD)-fed C57BL/6 mice. C57BL/6 mice were divided into control, total extract of PG (T-PG, 500 mg/kg) and saponin fraction (S-PG, 50 mg/kg)-treated groups. Significant decreases in body weight, associated with fat mass reduction, were observed in PG-treated groups (p<0.05). Hepatic lipid content and score index calculated from morphometric observations on fatty liver were significantly decreased in the PG-treated groups (p<0.05). Moreover, activities of fatty acid synthase (FAS) and carnitine palmitoyl-transferase (CPT) were significantly suppressed and increased as compared with the control group, respectively (p<0.05). mRNA expressions of the sterol regulatory element binding protein (SREBP1c) and stearoyl-CoA desaturase (SCD1) gene were suppressed in the T-PG and S-PG groups (p<0.05). From these findings, we speculate that fatty liver inhibition effects of PG extract and its saponins appear to be conferred by hepatic lipogenesis and acceleration of energy expenditure, along with modulation of liver FAS and CPT activities in HFD-fed C57BL/6 mice.

Modulation of Cytokine and Nitric Oxide by Mesenchymal Stem Cell Transfer in Lung Injury/fibrosis

Respiratory Research. 2010  |  Pubmed ID: 20137099

No effective treatment for acute lung injury and fibrosis currently exists. Aim of this study was to investigate the time-dependent effect of bone marrow-derived mesenchymal stem cells (BMDMSCs) on bleomycin (BLM)-induced acute lung injury and fibrosis and nitric oxide metabolites and inflammatory cytokine production.

Findings from CT, MRI, and PET/CT of a Primary Malignant Melanoma Arising in a Spinal Nerve Root

European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. Jul, 2010  |  Pubmed ID: 20127497

Primary spinal malignant melanoma is an extremely rare condition. We here describe a case of a 71-year-old Asian female presenting with left upper extremity tingling sensation. Computed tomography (CT) showed a homogeneously enhanced mass occupying the left neural foramen at the C6-7 level. Magnetic resonance imaging revealed enhanced mass in intra- and extradural space compressing the spinal cord at this level. It also widened the neural foramen mimicking neurofibroma or schwannoma. Partial resection of the mass was performed. Pathologic diagnosis of the mass was malignant melanoma. Postoperative whole body positron emission tomography/CT scan demonstrated an intense (18)F-FDG uptake at the residual mass site without abnormal uptake at other sites in the body.

Orphan Nuclear Receptor DAX-1 Acts As a Novel Corepressor of Liver X Receptor Alpha and Inhibits Hepatic Lipogenesis

The Journal of Biological Chemistry. Mar, 2010  |  Pubmed ID: 20080977

DAX-1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is a member of the nuclear receptor superfamily that can repress diverse nuclear receptors and has a key role in adreno-gonadal development. Our previous report has demonstrated that DAX-1 can inhibit hepatocyte nuclear factor 4alpha transactivity and negatively regulate gluconeogenic gene expression (Nedumaran, B., Hong, S., Xie, Y. B., Kim, Y. H., Seo, W. Y., Lee, M. W., Lee, C. H., Koo, S. H., and Choi, H. S. (2009) J. Biol. Chem. 284, 27511-27523). Here, we further expand the role of DAX-1 in hepatic energy metabolism. Transfection assays have demonstrated that DAX-1 can inhibit the transcriptional activity of nuclear receptor liver X receptor alpha (LXRalpha). Physical interaction between DAX-1 and LXRalpha was confirmed Immunofluorescent staining in mouse liver shows that LXRalpha and DAX-1 are colocalized in the nucleus. Domain mapping analysis shows that the entire region of DAX-1 is involved in the interaction with the ligand binding domain region of LXRalpha. Competition analyses demonstrate that DAX-1 competes with the coactivator SRC-1 for repressing LXRalpha transactivity. Chromatin immunoprecipitation assay showed that endogenous DAX-1 recruitment on the SREBP-1c gene promoter was decreased in the presence of LXRalpha agonist. Overexpression of DAX-1 inhibits T7-induced LXRalpha target gene expression, whereas knockdown of endogenous DAX-1 significantly increases T7-induced LXRalpha target gene expression in HepG2 cells. Finally, overexpression of DAX-1 in mouse liver decreases T7-induced LXRalpha target gene expression, liver triglyceride level, and lipid accumulation. Overall, this study suggests that DAX-1, a novel corepressor of LXRalpha, functions as a negative regulator of lipogenic enzyme gene expression in liver.

Antiatherogenic Effect of Antioxidant Polyphenols from Phellinus Baumii in Apolipoprotein E-deficient Mice

Annals of Nutrition & Metabolism. 2011  |  Pubmed ID: 22142871

The present study was carried out to investigate the antiatherosclerotic effect of antioxidant polyphenols from Phellinus baumii (PBE) in apolipoprotein E-deficient (apoE-/-) mice.

Genes Associated with Recurrence of Hepatocellular Carcinoma: Integrated Analysis by Gene Expression and Methylation Profiling

Journal of Korean Medical Science. Nov, 2011  |  Pubmed ID: 22065898

Gene expression is suppressed by DNA methylation. The goal of this study was to identify genes whose CpG site methylation and mRNA expression are associated with recurrence after surgical resection for hepatocellular carcinoma (HCC). Sixty-two HCCs were examined by both whole genome DNA methylation and transcriptome analysis. The Cox model was used to select genes associated with recurrence. A validation was performed in an independent cohort of 66 HCC patients. Among fifty-nine common genes, increased CpG site methylation and decreased mRNA expression were associated with recurrence for 12 genes (Group A), whereas decreased CpG site methylation and increased mRNA expression were associated with recurrence for 25 genes (Group B). The remaining 22 genes were defined as Group C. Complement factor H (CFH) and myosin VIIA and Rab interacting protein (MYRIP) in Group A; proline/serine-rich coiled-coil 1 (PSRC1), meiotic recombination 11 homolog A (MRE11A), and myosin IE (MYO1E) in Group B; and autophagy-related protein LC3 A (MAP1LC3A), and NADH dehydrogenase 1 alpha subcomplex assembly factor 1 (NDUFAF1) in Group C were validated. In conclusion, potential tumor suppressor (CFH, MYRIP) and oncogenes (PSRC1, MRE11A, MYO1E) in HCC are reported. The regulation of individual genes by methylation in hepatocarcinogenesis needs to be validated.

Generation of Human Induced Pluripotent Stem Cells from Osteoarthritis Patient-derived Synovial Cells

Arthritis and Rheumatism. Oct, 2011  |  Pubmed ID: 21953087

This study was undertaken to generate and characterize human induced pluripotent stem cells (PSCs) from patients with osteoarthritis (OA) and to examine whether these cells can be developed into disease-relevant cell types for use in disease modeling and drug discovery.

Inflammatory Pseudotumors Mimicking Intrahepatic Cholangiocarcinoma of the Liver; IgG4-positivity and Its Clinical Significance

Journal of Hepato-biliary-pancreatic Sciences. Sep, 2011  |  Pubmed ID: 21894477

BACKGROUND: Inflammatory pseudotumor (IPT) of the liver is a benign condition with a good prognosis. However, it is difficult to distinguish clinical and radiological findings of IPT from those of malignancies. The aims of this study are to determine the clinical, radiological, and pathological characteristics, particularly relating to the role of the autoimmune mechanism in the development of inflammatory pseudotumours (IPTs) of the liver, and to suggest appropriate diagnostic and therapeutic strategy. STUDY DESIGN: The clinical, diagnostic, and pathological characteristics including IgG4 immunohistochemical stain and follow-up data of 22 IPT patients were retrospectively analyzed. RESULTS: The patients were 16 men and 6 women with a mean age of 59 years. Fifteen patients (68.2%) had associated biliary diseases. Of the 16 patients treated conservatively, the masses completely resolved in 10 patients, and reduced in size in 5 patients within the first 6 months. The remaining 6 patients were treated by surgical resection. IgG4 staining of 17 tissue samples from 22 patients were negative, most of the infiltrate being of fibrohistiocytic type, whereas 4 of 5 lymphoplasmacytic cells of dominant tumors show positive staining of IgG4. Although IgG4-related sclerosing cholangitis was mostly of lymphoplasmacytic type, other histological and clinical characteristics were similar in both types of IPTs. CONCLUSIONS: IPTs of the liver can be diagnosed based on radiological and pathological findings by needle biopsy. Although the lymphoplasmacytic type of IPTs seems to correspond to IgG4-related disease, as assessed by IgG4 immunohistochemical stain, its clinical significance is unknown. Although most IPTs can be resolved with conservative therapy, surgical resection should be considered in cases of uncertain biopsy result, presumed malignant lesion, combination with other pathology, or lack of response to conservative management.

Hepatoprotective Effect of Platycodon Grandiflorum Against Chronic Ethanol-induced Oxidative Stress in C57BL/6 Mice

Annals of Nutrition & Metabolism. 2011  |  Pubmed ID: 21811061

This study was carried out to evaluate the hepatoprotective effect of Platycodon grandiflorum (PG) in ethanol (EtOH)-induced liver damage.

Cannabinoid Receptor Type 1 (CB1R) Signaling Regulates Hepatic Gluconeogenesis Via Induction of Endoplasmic Reticulum-bound Transcription Factor CAMP-responsive Element-binding Protein H (CREBH) in Primary Hepatocytes

The Journal of Biological Chemistry. Aug, 2011  |  Pubmed ID: 21693703

Activated cannabinoid 1 receptor (CB1R) signaling has been implicated in the development of phenotypes associated with fatty liver, insulin resistance, and impaired suppression of hepatic glucose output. Endoplasmic reticulum stress-associated liver-specific transcription factor CREBH is emerging as a critical player in various hepatic metabolic pathways and regulates hepatic gluconeogenesis in diet-induced obese settings. In this study, we elucidated the critical role of CREBH in mediating CB1R signaling to regulate glucose homeostasis in primary rat and human hepatocytes. mRNA and protein levels and glucose production were analyzed in primary rat and human hepatocytes. ChIP assays were performed together with various transcriptional analyses using standard techniques. CB1R activation by 2-arachidonoylglycerol (2-AG) specifically induced CREBH gene expression via phosphorylation of the JNK signaling pathway and c-Jun binding to the AP-1 binding site in the CREBH gene promoter. 2-AG treatment significantly induced hepatic gluconeogenic gene expression and glucose production in primary hepatocytes, and we demonstrated that the CREBH binding site mutant significantly attenuated 2-AG-mediated activation of the gluconeogenic gene promoter. Endogenous knockdown of CREBH led to ablation of 2-AG-induced gluconeogenic gene expression and glucose production, and the CB1R antagonist AM251 or insulin exhibited repression of CREBH gene induction and subsequently inhibited gluconeogenesis in both rat and human primary hepatocytes. These results demonstrate a novel mechanism of action of activated CB1R signaling to induce hepatic gluconeogenesis via direct activation of CREBH, thereby contributing to a better understanding of the endocannabinoid signaling mechanism involved in regulating the hepatic glucose metabolism.

Multidetector Computed Tomography (MDCT) Images with Soft Tissue and Bone Algorithm Reconstruction in Head and Facial Trauma

Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. Jul, 2011  |  Pubmed ID: 21561774

We aimed to evaluate the usefulness of multidetector CT (MDCT) scan images with soft tissue and bone algorithm reconstruction in nine patients for investigation of head and facial trauma. We compared these MDCT scans with the conventional brain CT scans and facial bone CT scans of eight patients with head and facial trauma. The overall radiation dose did not differ significantly between the two groups (Mann-Whitney test, p=0.370) but the MDCT scans with soft tissue and bone algorithm reconstruction avoided overlapping scan range radiation exposure, especially to the eye and lower half of the brain.

Activation of NAD(P)H:quinone Oxidoreductase Ameliorates Spontaneous Hypertension in an Animal Model Via Modulation of ENOS Activity

Cardiovascular Research. Aug, 2011  |  Pubmed ID: 21502369

Hypertension is one of the most common human diseases worldwide, and extensive research efforts are focused upon the identification and utilizing of novel therapeutic drug targets. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is an important regulator of blood pressure (BP). β-Lapachone (βL), a well-known substrate of NAD(P)H:quinone oxidoreductase (NQO1), increases the cellular NAD(+)/NADH ratio via the activation of NQO1. In this study, we evaluated whether βL-induced activation of NQO1 modulates BP in an animal model of hypertension.

Hepatoprotective Effects of Chestnut (Castanea Crenata) Inner Shell Extract Against Chronic Ethanol-induced Oxidative Stress in C57BL/6 Mice

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. Jul, 2011  |  Pubmed ID: 21457746

This study was carried out to evaluate the protective effects of chestnut inner shell extract (CISE) on chronic ethanol-induced oxidative stress in liver. Mice were fed a control liquid diet (Normal-control), liquid diet containing ethanol alone (EtOH+Vehicle), or were administered CISE and ethanol (EtOH+CISE) for 6 weeks. Administration of ethanol induced liver damage with significant increase of plasma GOT, GPT, hepatic triglyceride (TG) and thiobarbituric acid reactive substance (TBARS) levels. By contrast, co-treatment of CISE with ethanol significantly decreased the activities of GOT and GPT in the plasma, and hepatic TG and TBARS levels. Histological observations were consistent with the result obtained from hepatic lipid quantification. Moreover, CISE treatment with ethanol decreased CYP2E1 expression and increased activities of catalase and superoxide dismutase, which were significantly inhibited by treatment with ethanol alone. To determine the active compound of CISE, fractionation of CISE was conducted and scoparone and scopoletin were identified as main compounds. These compounds were also shown to inhibit the ethanol-induced reduction in antioxidant enzyme activity in an in vitro model system. These results suggest that CISE has protective effects against ethanol-induced oxidative damage, possibly by inhibition of lipid accumulation, peroxidation and increase of antioxidant defense system in the liver.

Association Analysis of Thromboxane A Synthase 1 Gene Polymorphisms with Aspirin Intolerance in Asthmatic Patients

Pharmacogenomics. Mar, 2011  |  Pubmed ID: 21449675

Thromboxane A synthase (TBXAS1) converts prostaglandin H to thromboxane A, a potent constrictor of smooth respiratory muscle. Thus, functional alterations of the TBXAS1 gene may contribute to aspirin-intolerant asthma (AIA).

Prevalence of Electrocardiographic Findings Suggestive of Sudden Cardiac Death Risk in 10,867 Apparently Healthy Young Korean Men

Pacing and Clinical Electrophysiology : PACE. Jun, 2011  |  Pubmed ID: 21332562

The objective of this study was to determine the prevalence of electrocardiographic (ECG) findings suggestive of sudden cardiac death risk in apparently healthy young Korean men.

A Phellinus Baumii Extract Reduces Obesity in High-fat Diet-fed Mice and Absorption of Triglyceride in Lipid-loaded Mice

Journal of Medicinal Food. Mar, 2011  |  Pubmed ID: 21332399

This study evaluated the anti-obesity effects of Phellinus baumii extract (PBE) in high-fat diet (HFD)-fed mice. Male 8-week-old C57BL/6 mice were randomly divided into four groups: control, normal chow diet plus vehicle; HFD-control, high-fat plus vehicle; HFD plus orlistat (Xenical(®), Roche, Basel, Switzerland) (50 mg/kg); and HFD plus PBE (500 mg/kg). PBE was administered daily by oral gavage for 12 weeks. Oral administration of PBE (500 mg/kg) significantly reduced body weight gain, hepatic lipid concentrations, and fat accumulation in epididymal adipocytes compared with mice fed HFD alone (P < .05). mRNA expression of genes related to triglyceride (TG) synthesis was suppressed in the PBE groups, and fatty acid synthase activity was also significantly inhibited (P < .05). Furthermore, we evaluated the effect of PBE on TG absorption and detected marked reduction in TG absorption in Xenical- and PBE-treated mice compared with the control group (P < .05). To determine the active compound of PBE, fractionation was conducted, and interfungin A, davallialactone, and hypholomine B were identified as the main compounds. Among the three identified compounds, as a representative compound, davallialactone was also shown to suppress fat accumulation in an in vitro model system. These anti-obesity and hypolipidemic effects appear to be partly mediated by suppressing plasma and hepatic fat accumulation through the inhibition of enzymes associated with hepatic and intestinal lipid absorption and synthesis.

The Association of a Single-nucleotide Polymorphism of the IL-2 Inducible T-cell Kinase Gene with Asthma

Annals of Human Genetics. May, 2011  |  Pubmed ID: 21323647

Asthma manifests as TH2-dominant airway inflammation regulated by inducible T-cell kinase (ITK). To investigate associations between genetic variants of the ITK gene and asthma, 31 single-nucleotide polymorphisms (SNPs) were genotyped in 303 normal controls and 498 asthmatics and the two groups were compared using logistic regression models. The functional effects of the ITK promoter SNP were assessed using pGL3 luciferase reporter systems and gel-shift assays. The minor allele-196C>T in the promoter region of the ITK gene was significantly more frequent in asthmatics than in controls. The luciferase activity of the PGL3-ITK-196T allele construct was higher than that of the -196C allele. In the gel-shift assay, -196T double-stranded oligonucleotides bound more strongly to Jurkat cell nuclear protein compared to the -196C double-stranded oligonucleotides. People with the -rare allele 196C>T may be more susceptible to asthma via transcriptional regulation of the ITK gene.

Relationship Between Group-specific Component Protein and the Development of Asthma

American Journal of Respiratory and Critical Care Medicine. Sep, 2011  |  Pubmed ID: 21169467

Airway inflammation and remodeling during asthma are attributed to the altered expression of biologically relevant proteins.

Air Trapping is a Major Determinant of Persistent Airway Obstruction in Asthmatics

Respiratory Medicine. Jun, 2012  |  Pubmed ID: 22445772

Chronic persistent airway obstruction has been observed in moderate-to-severe asthmatics despite treatment with inhaled corticosteroids. We investigated which airway changes were associated with this obstruction. High-resolution computed tomography (HRCT) was performed at study entry and reexamined at the time of follow-up when the FEV1 reached a maximally constant level after treatment for 1 year or more with inhaled corticosteroids. Bronchial wall area and air trapping extent were compared in the recovered group (n = 18) and the persistent airway obstruction group (n = 14). Bronchial wall area and air trapping of the initial HRCT were similar between the two groups. On follow-up HRCT, air trapping was markedly decreased in the recovered group compared with that on initial HRCT (P = 0.017), whereas bronchial wall area did not change. In the persistent-airway-obstruction group, these two parameters did not change during follow-up. When follow-up HRCT was compared, air trapping was significantly greater in the persistent-airway-obstruction group than in the recovered group (P = 0.003). Difference post-bronchodilator FEV1 value between at initial and 2nd HRCT exam was correlated with difference air trapping value between at initial and 2nd HRCT exam(%) on the follow-up HRCT (P = 0.017). The presence of persistent airflow obstruction were significantly associated with the air trapping % difference between initial and 2nd time (RR = 1.70, P = 0.018). Persistence of AT could be a main contributing factor to chronic persistent airflow obstruction in asthma.

HLA-DRA Polymorphisms Associated with Risk of Nasal Polyposis in Asthmatic Patients

American Journal of Rhinology & Allergy. Jan-Feb, 2012  |  Pubmed ID: 22391069

Nasal polyps, part of the aspirin triad symptoms, are edematous protrusions arising from the mucosa of the nasal sinuses. Although the causative factors and pathogenesis of the polyps are unknown, the significant effect of human leukocyte antigen-DR (HLA-DR) expression in nasal polyps and genetic associations of the major histocompatibility complex class II, DR alpha (HLA-DRA) with immune-mediated diseases have been revealed.

Potential Association of DDR1 Genetic Variant with FEV1 Decline by Aspirin Provocation in Asthmatics

The Journal of Asthma : Official Journal of the Association for the Care of Asthma. Apr, 2012  |  Pubmed ID: 22380734

The discoidin domain receptor tyrosine kinase 1 (DDR1) is positioned within the major histocompatibility complex (MHC) region which plays an important role in the immune system. In addition, DDR1 has been elucidated to be downregulated during the epithelial-mesenchymal transition of bronchial epithelium.

Association Analysis of Formyl Peptide Receptor 2 (FPR2) Polymorphisms and Aspirin Exacerbated Respiratory Diseases

Journal of Human Genetics. Mar, 2012  |  Pubmed ID: 22377711

Aspirin-exacerbated respiratory diseases (AERD) are associated with the metabolism of arachidonic acid. FPR2 (formyl peptide receptor2) is a high-affinity ligand receptor for potent anti-inflammatory lipid metabolites: lipoxins. Thus, functional alterations of the FPR2 may contribute to AERD. We investigated the relationship between single-nucleotide polymorphisms (SNPs) in the FPR2 and AERD. Asthmatics were categorized into AERD <15% decreases in forced expiratory volume in one second (FEV(1)), and/or naso-ocular reactions after oral aspirin challenge (n=170) and aspirin-tolerant asthma (ATA, n=268). In all, 11 SNPs were genotyped. FPR2 protein expressions on CD14-positive monocytes in peripheral blood were measured using flow cytometric analysis. We performed RT-PCR of the FPR2 mRNA expressed by peripheral blood mononuclear cells. Logistic regression analysis showed that the minor allele frequency of FPR2 -4209T>G (rs1769490) in intron 2 was significantly lower in the AERD group (n=170) than in the ATA group (n=268) (P=0.006, P(corr)=0.04, recessive model). The decline of FEV(1) after aspirin challenge was significantly lower in the subjects with GG homozygotes of FPR2 -4209T>G than those with the other genotypes (P=0.0002). Asthmatic homozygotes for FPR2 -4209T>G minor allele exhibited significantly higher FPR2 protein expression in CD14-positive monocytes than did those with the common allele of FPR2 -4209T>G allele (P=0.01). There was no difference in the expression of the wild form and the exon 2 deleted variant form of FPR2 gene according to the genotypes of FPR2 -4209T>G. The minor allele at FPR2 -4209T>G may have a protective role against the development of AERD, via increase of FPR2 protein expression in inflammatory cells.Journal of Human Genetics advance online publication, 1 March 2012; doi:10.1038/jhg.2012.12.

Susceptibility to Gold Nanoparticle-induced Hepatotoxicity is Enhanced in a Mouse Model of Nonalcoholic Steatohepatitis

Toxicology. Jan, 2012  |  Pubmed ID: 22330258

Although the safety of gold nanoparticle (AuNP) use is of growing concern, most toxicity studies of AuNPs had focused on their chemical characteristics, including their physical dimensions, surface chemistry, and shape. The present study examined the susceptibility of rodents with healthy or damaged livers to AuNP-induced hepatotoxicity. To induce a model of liver injury, mice were fed a methionine- and choline-deficient (MCD) diet for 4 weeks. Sizes and biodistribution of 15-nm PEGylated AuNPs were analyzed by transmission electron microscopy. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were estimated with an automatic chemical analyzer, and liver sections were subjected to pathological examination. Activities of antioxidant enzymes were determined by biochemical assay. Lateral tail vein injection of MCD diet-fed mice with 5 mg kg(-1) AuNPs significantly elevated the serum ALT and AST levels compared to MCD diet-fed mice injected with mPEG (methylpolyethylene glycol). Similarly, severe hepatic cell damage, acute inflammation, and increased apoptosis and reactive oxygen species (ROS) production were observed in the livers of AuNP-injected mice on the MCD diet; these liver injuries were attenuated in mice fed a normal chow diet. The results suggest that AuNPs display toxicity in a stressed liver environment by stimulating the inflammatory response and accelerating stress-induced apoptosis. These conclusions may point to the importance of considering health conditions, including liver damage, in medical applications of AuNPs.

Papillary Fibroelastoma of the Aortic Valve with Atypical Chest Pain: Late Presentation with Acute Myocardial Infarction and Cardiac Arrest

Journal of Cardiac Surgery. Feb, 2012  |  Pubmed ID: 22321193

Abstract  We report a case of a 54-year-old female with papillary fibroelastoma of the aortic valve who presented with ST-elevation myocardial infarction and cardiac arrest. Though her initial symptom was only atypical chest pain, life-threatening complications such as acute myocardial infarction and cardiac arrest developed. After cardiopulmonary resuscitation, we promptly resected the fibroelastoma on cardiopulmonary bypass, and the patient was discharged without any other complications. (J Card Surg 2012;**:1-3).

Contribution of the OBSCN Nonsynonymous Variants to Aspirin Exacerbated Respiratory Disease Susceptibility in Korean Population

DNA and Cell Biology. Jan, 2012  |  Pubmed ID: 22251166

Airway remodeling and exacerbated airway narrowing in asthma have been attributed to the regulation of intracellular Ca(2+) by sarcoplasmic reticulum (SR) of the airway smooth muscle cells. The protein encoded by obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF (OBSCN) is a crucial factor in determining the SR architecture in Obscn(-/-) mice. This study genotyped a total of 55 common single-nucleotide polymorphisms (SNPs) in 592 Korean asthmatics including 163 aspirin exacerbated respiratory disease (AERD) cases and 429 aspirin-tolerant asthma (ATA) controls. Eight SNPs, including two nonsynonymous polymorphisms rs1188722C>T (Leu2116Phe) and rs1188729G>C (Cys4642Ser), and one haplotype BL2_ht1 showed statistically significant associations with AERD development (p=0.003-0.03). Two variants, rs1188722C>T (Leu2116Phe) and rs369252C>A, also revealed nominal association with FEV1 decline by aspirin provocation in asthmatics (p=0.03-0.04). Intriguingly, rs1188722C>T (Leu2116Phe) is a highly conserved amino acid residue among species, suggesting its functional relevance to AERD. In addition, the A allele of rs369252C>A, which was more prevalent in AERD than in ATA, was predicted as a potential branch point (BP) site for alternative splicing (BP score=4.29). Although further functional evaluation is required, our findings suggest that OBSCN polymorphisms, in particular, highly conserved nonsynonymous Leu2116Phe variant, might contribute to aspirin hypersensitivity in asthmatics.

Soybean Glyceollins Mitigate Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Expression Levels Via Suppression of the NF-κB Signaling Pathway in RAW 264.7 Cells

International Journal of Molecular Medicine. Apr, 2012  |  Pubmed ID: 22246209

Glyceollins, produced to induce disease resistance responses against specific species, such as an incompatible pathogen Phytophthora sojae in soybeans, have the potential to exhibit anti-inflammatory activity in RAW 264.7 cells. To investigate the anti-inflammatory effects of elicited glyceollins via a signaling pathway, we studied the glyceollin signaling pathway using several assays including RNA and protein expression levels. We found that soybean glyceollins significantly reduced LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production, as well as the expression of inducible ΝΟ synthase (iNOS) and cyclooxygenase-2 (COX-2) via the suppression of NF-κB activation. Glyceollins also inhibited the phosphorylation of IκBα kinase (IKK), the degradation of IκBα, and the formation of NF-κB-DNA binding complex in a dose-dependent manner. Furthermore, they inhibited pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-18, but increased the generation of the anti-inflammatory cytokine IL-10. Collectively, the present data show that glyceollins elicit potential anti-inflammatory effects by suppressing the NF-κB signaling pathway in RAW 264.7 cells.

Prevention of Salt-induced Renal Injury by Activation of NAD(P)H:quinone Oxidoreductase 1, Associated with NADPH Oxidase

Free Radical Biology & Medicine. Mar, 2012  |  Pubmed ID: 22227174

NADPH oxidase (NOX) is a predominant source of reactive oxygen species (ROS), and the activity of NOX, which uses NADPH as a common rate-limiting substrate, is upregulated by prolonged dietary salt intake. β-Lapachone (βL), a well-known substrate of NAD(P)H:quinone oxidoreductase 1 (NQO1), decreases the cellular NAD(P)H/NAD(P)(+) ratio via activation of NQO1. In this study, we evaluated whether NQO1 activation by βL modulates salt-induced renal injury associated with NOX-derived ROS regulation in an animal model. Dahl salt-sensitive (DS) rats fed a high-salt (HS) diet were used to investigate the renoprotective effect of NQO1 activation. βL treatment significantly lowered the cellular NAD(P)H:NAD(P)(+) ratio and dramatically reduced NOX activity in the kidneys of HS diet-fed DS rats. In accordance with this, total ROS production and expression of oxidative adducts also decreased in the βL-treated group. Furthermore, HS diet-induced proteinuria and glomerular damage were markedly suppressed, and inflammation, fibrosis, and apoptotic cell death were significantly diminished by βL treatment. This study is the first to demonstrate that activation of NQO1 has a renoprotective effect that is mediated by NOX activity via modulation of the cellular NAD(P)H:NAD(P)(+) ratio. These results provide strong evidence that NQO1 might be a new therapeutic target for the prevention of salt-induced renal injury.

Controlled Deposition of a High-performance Small-molecule Organic Single-crystal Transistor Array by Direct Ink-jet Printing

Advanced Materials (Deerfield Beach, Fla.). Jan, 2012  |  Pubmed ID: 22213548

Ink-jet printed small-molecule organic single-crystal transistors are realized by using selective surface energy modification, precise control of volume density of ink droplets on spatially patterned areas, and a co-solvent system to control solvent evaporation properties. The single-crystal formation in bottom-contact-structured transistors via direct printing is expected to permit high-density array fabrication in large-area electronics.

Diet-induced Obesity Dramatically Reduces the Efficacy of a 2009 Pandemic H1N1 Vaccine in a Mouse Model

The Journal of Infectious Diseases. Jan, 2012  |  Pubmed ID: 22147801

Obesity, a risk factor for increased severity of diverse diseases, is believed to have negative impact on vaccine efficacy. Recently, mortality has emerged as an outcome of pandemic influenza A virus subtype H1N1, necessitating development of effective vaccine strategies. Here we investigated effects of diet-induced obesity on vaccine-induced immune responses and protective efficacy against pandemic H1N1 influenza virus.

Role of Neutrophils in Persistent Airway Obstruction Due to Refractory Asthma

Respirology (Carlton, Vic.). Feb, 2012  |  Pubmed ID: 22040093

One of the clinical manifestations of refractory asthma (RA) in a certain group of patients is persistent airway obstruction (PAO), despite treatment with high doses of inhaled and/or systemic corticosteroids. Airway neutrophilic inflammation is frequently observed in RA; however, the relationship between neutrophilic inflammation and PAO has not been evaluated in this group of patients. The aim of this study was to compare the clinical parameters and patterns of inflammatory cells between patients with or without PAO due to RA, and to identify the factors associated with PAO.

Association of FANCC Polymorphisms with FEV1 Decline in Aspirin Exacerbated Respiratory Disease

Molecular Biology Reports. Mar, 2012  |  Pubmed ID: 21670957

Aspirin exacerbated respiratory disease (AERD) is a clinical condition characterized by severe decline in forced expiratory volume in one second (FEV1) following the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin. The exacerbated inflammatory response in Fancc-deficient mice has been reported to be associated with hemopoietic responses that are also related to AERD pathogenesis. To investigate associations of FANCC polymorphisms with AERD and related phenotypes, this study genotyped 25 common single nucleotide polymorphisms (SNPs) in a total of 592 Korean asthmatics including 163 AERD and 429 aspirin-tolerant asthma (ATA) subjects. Logistic analysis revealed that genetic polymorphisms of the FANCC gene might not be directly related to AERD development and nasal polyposis (P > 0.05). However, the FEV1 decline by aspirin provocation showed significant associations with FANCC polymorphisms (P = 0.006-0.04) and a haplotype (unique to rs4647416G > A, P = 0.01 under co-dominant, P = 0.006 under recessive model). In silico analysis showed that the "A" allele of rs4647376C > A, which was more prevalent in AERD than in ATA, could act as a potential branch point (BP) site for alternative splicing (BP score = 4.16). Although replications in independent cohorts and further functional evaluations are still needed, our preliminary findings suggest that FANCC polymorphisms might be associated with the obstructive symptoms in allergic diseases.

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