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Find video protocols related to scientific articles indexed in Pubmed.
Comparison of thoracoscopic segmentectomy and thoracoscopic lobectomy on the patients with non-small cell lung cancer: a propensity score matching study†
Eur J Cardiothorac Surg
PUBLISHED: 11-20-2014
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Thoracoscopic lobectomy has been widely performed on patients with early-stage lung cancer; meanwhile indications of thoracoscopic segmentectomy have not been clearly defined due to technical difficulties and unclear oncological outcomes. The aim of this study was to compare early and late outcomes between thoracoscopic segmentectomy and thoracoscopic lobectomy.
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Apolipoprotein E4 Affects Topographical Changes in Hippocampal and Cortical Atrophy in Alzheimer's Disease Dementia: A Five-Year Longitudinal Study.
J. Alzheimers Dis.
PUBLISHED: 11-14-2014
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Apolipoprotein E4 (APOE4) is a genetic risk factor for developing Alzheimer's disease (AD). Once AD manifests clinically, however, the effects of APOE4 are less clear. Therefore, we investigated the longitudinal effects of APOE4 on topographical changes in AD patient brain atrophy. We prospectively recruited 35 patients with AD (19 APOE4 carriers and 16 non-carriers), and 14 normal controls, then followed them for five years. We measured hippocampal deformities and cortical thickness. Hippocampal comparison between APOE4 carriers and non-carriers with AD showed carriers had rapid changes in the head and body, while non-carriers had rapid changes in a small portion of the body. Cortical thickness comparison between APOE4 carriers and non-carriers with AD dementia showed carriers had rapid thinning in the lateral frontal, temporal, and parietal regions, while no region showed more rapid cortical thinning in non-carriers than in carriers. These findings underlined the importance of the APOE4 allele for designing and interpreting future treatment trials in patients with AD dementia.
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Effects of Amyloid and Small Vessel Disease on White Matter Network Disruption.
J. Alzheimers Dis.
PUBLISHED: 11-07-2014
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There is growing evidence that the human brain is a large scale complex network. The structural network is reported to be disrupted in cognitively impaired patients. However, there have been few studies evaluating the effects of amyloid and small vessel disease (SVD) markers, the common causes of cognitive impairment, on structural networks. Thus, we evaluated the association between amyloid and SVD burdens and structural networks using diffusion tensor imaging (DTI). Furthermore, we determined if network parameters predict cognitive impairments. Graph theoretical analysis was applied to DTI data from 232 cognitively impaired patients with varying degrees of amyloid and SVD burdens. All patients underwent Pittsburgh compound-B (PiB) PET to detect amyloid burden, MRI to detect markers of SVD, including the volume of white matter hyperintensities and the number of lacunes, and detailed neuropsychological testing. The whole-brain network was assessed by network parameters of integration (shortest path length, global efficiency) and segregation (clustering coefficient, transitivity, modularity). A greater PiB retention ratio was not associated with any white matter network parameters. Greater white matter hyperintensity volumes or lacunae numbers were significantly associated with decreased network integration (increased shortest path length, decreased global efficiency) and increased network segregation (increased clustering coefficient, increased transitivity, increased modularity). Decreased network integration or increased network segregation were associated with poor performances in attention, language, visuospatial, memory, and frontal-executive functions. Our results suggest that amyloid burden disrupts white matter network integration, while SVD alters white matter network integration and segregation, which further predicts cognitive dysfunction.
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A Comparison of Receptive-Expressive Language Profiles between Toddlers with Autism Spectrum Disorder and Developmental Language Delay.
Yonsei Med. J.
PUBLISHED: 10-18-2014
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It is well known that expressive language impairment is commonly less severe than receptive language impairment in children with autism spectrum disorder (ASD). However, this result is based on experiments in Western countries with Western language scales. This study tries to find whether the result above is applicable for toddlers in a non-Western country; more specifically, in Korea with non-Western language scales.
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ATP-Based Chemotherapy Response Assay in Primary or Recurrent Ovarian and Peritoneal Cancer.
Yonsei Med. J.
PUBLISHED: 10-18-2014
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To investigate chemosensitivity with an adenosine triphosphate-based chemotherapy response assay in patients with epithelial ovarian or peritoneal cancer according to tumor histology, grade, and disease status.
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Higher education affects accelerated cortical thinning in Alzheimer's disease: a 5-year preliminary longitudinal study.
Int Psychogeriatr
PUBLISHED: 09-17-2014
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ABSTRACT Background: Epidemiological studies have reported that higher education (HE) is associated with a reduced risk of incident Alzheimer's disease (AD). However, after the clinical onset of AD, patients with HE levels show more rapid cognitive decline than patients with lower education (LE) levels. Although education level and cognition have been linked, there have been few longitudinal studies investigating the relationship between education level and cortical decline in patients with AD. The aim of this study was to compare the topography of cortical atrophy longitudinally between AD patients with HE (HE-AD) and AD patients with LE (LE-AD). Methods: We prospectively recruited 36 patients with early-stage AD and 14 normal controls. The patients were classified into two groups according to educational level, 23 HE-AD (>9 years) and 13 LE-AD (?9 years). Results: As AD progressed over the 5-year longitudinal follow-ups, the HE-AD showed a significant group-by-time interaction in the right dorsolateral frontal and precuneus, and the left parahippocampal regions compared to the LE-AD. Conclusion: Our study reveals that the preliminary longitudinal effect of HE accelerates cortical atrophy in AD patients over time, which underlines the importance of education level for predicting prognosis.
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Long non-coding RNA HOTAIR is associated with human cervical cancer progression.
Int. J. Oncol.
PUBLISHED: 08-20-2014
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The functions of many long non-coding RNAs (lncRNAs) in human cancers remain to be clarified. The lncRNA Hox transcript antisense intergenic RNA (HOTAIR) has been reported to reprogram chromatin organization and promote breast and colorectal cancer metastasis, the involvement of lncRNAs in cervical cancer is just beginning to be studied. In the present study, we examined the expression and the functional role of HOTAIR in cervical cancer. HOTAIR expression was determined in cervical cancer tissues (n=111) and corresponding normal tissues (n=40) by using real-time polymerase chain reaction, and its correlation with clinical parameters and prognosis were analyzed. To determine the effect of HOTAIR knockdown and overexpression in cervical cancer cell lines, we used the CCK-8 assay, wound healing migration and matrigel invasion assay. The expression level of HOTAIR in cervical cancer tissues was higher than that in corresponding non-cancerous tissues. High HOTAIR expression correlated with lymph node metastasis, and reduced overall survival. A multivariate analysis showed that HOTAIR was a prognostic factor for predicting cervical cancer recurrence. Knockdown of HOTAIR reduced cell proliferation, migration, and invasion in cervical cancer cell lines. Moreover, HOTAIR regulated the expression of vascular endothelial growth factor, matrix metalloproteinase-9 and epithelial-to-mesenchymal transition (EMT)-related genes, which are important for cell motility and metastasis. Therefore, HOTAIR may promote tumor aggressiveness through the upregulation of VEGF and MMP-9 and EMT-related genes. These findings indicate that HOTAIR may represent a novel biomarker for predicting recurrence and prognosis and serve as a promising therapeutic target in cervical cancer.
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A Functional Polymorphism in CSF1R Gene Is a Novel Susceptibility Marker for Lung Cancer among Never-Smoking Females.
J Thorac Oncol
PUBLISHED: 08-20-2014
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It has been estimated that the proportion of never-smokers among females with lung cancer is 53% worldwide and 75% in Korea. We conducted a two-stage study to identify genetic factors responsible for lung cancer susceptibility in female never-smokers.
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Characteristics of benign solitary pulmonary nodules confirmed by diagnostic video-assisted thoracoscopic surgery.
Clin Respir J
PUBLISHED: 08-08-2014
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The solitary pulmonary nodule (SPN) is a common clinical problem usually detected incidentally during screening tests for lung cancer. Video-assisted thoracoscopic surgery (VATS) is performed for diagnosing SPNs when there are technical difficulties with transthoracic needle aspiration biopsy or bronchoscopic biopsy, inconclusive biopsy results, or when there is a high suspicion of malignancy. This study aimed to identify factors that can reduce unnecessary VATS for the diagnosis of SPNs.
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Surgical treatment of mediastinal aspergilloma in a immunocompetent patient.
Korean J Thorac Cardiovasc Surg
PUBLISHED: 08-05-2014
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Aspergillus is a common saprophytic fungi of the human airways and causes a broad spectrum of diseases, ranging from aspergilloma to invasive aspergillosis. There are few reports on mediastinal aspergilloma without any underlying pulmonary disease or immunocompromise. Herein, we report a case of mediastinal aspergilloma that we experienced and treated by thoracoscopic resection and oral antifungal medication.
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Surgical resection of thoracic duct lymphangioma.
Korean J Thorac Cardiovasc Surg
PUBLISHED: 08-05-2014
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A 67-year-old male patient came to the hospital due to lung cancer and mediastinal cystic mass which was suspected to be esophageal duplication cyst. Video-assisted thoracoscopic surgery (VATS) was performed and intra-operative finding suggested it as a cystic mass along the thoracic duct. Thoracic duct was ligated and the cyst was completely resected. A 48-year-old female patient visited the hospital for dysphagia. Mediastinal cystic mass was suspected to be an esophageal duplication cyst. Intraoperative finding suggest a thoracic duct lymphangioma. After thoracic duct ligation, the mass was completely resected with VATS. Postoperative chylothorax did not develop in both cases.
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A successful bilateral lung transplantation in a patient with high panel reactive antibody and positive cross matching.
Korean J Thorac Cardiovasc Surg
PUBLISHED: 08-05-2014
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A 44-year-old pregnant female patient gave stillbirth while being treated for pneumonia. She developed acute respiratory failure, which resulted in mechanical ventilator support. Diagnostic lung biopsy revealed a cryptogenic organizing pneumonia. The patient's condition deteriorated and a venous-venous extracorporeal membrane oxygenation was placed. She was listed for lung transplantation. Because of her worsening condition lung transplantation was performed despite positive cross matching result. She was treated with rituximab, intravenous immunoglobulin, and plasmapheresis and recovered without event. There is no sign of rejection at the time of last follow-up.
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Insulin-Based Regulation of Glucose-functionalized Nanoparticle Uptake in Muscle Cells.
J Mater Chem B Mater Biol Med
PUBLISHED: 08-05-2014
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Effective regulation of nanoparticle (NP) uptake facilitates the NP-based therapeutics and diagnostics. Here, we report the use of insulin and 2-deoxyglucose (2-DG) to modulate the cellular uptake of glucose-functionalized quantum dots (Glc-QDs) in C2C12 muscle cells. The cellular uptake of Glc-QDs can be modulated up to almost two-fold under insulin stimulation while be down-regulated in the presence of 2-DG. These results demonstrate the use of secondary regulators to control the cellular uptake of NPs through membrane protein recognition in a specific and fine-tunable fashion.
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Predicting the Performance of Motor Imagery in Stroke Patients: Multivariate Pattern Analysis of Functional MRI Data.
Neurorehabil Neural Repair
PUBLISHED: 07-25-2014
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Background. In a brain-computer interface for stroke rehabilitation, motor imagery is a preferred means for providing a gateway to an effector action or behavior. However, stroke patients often exhibit failure to comply with motor imagery, and therefore their motor imagery performance is highly variable. Objective. We sought to identify motor cortical areas responsible for motor imagery performance in stroke patients, specifically by using a multivariate pattern analysis of functional magnetic resonance imaging data. Methods. We adopted an imaginary finger tapping task in which motor imagery performance could be monitored for 12 chronic stroke patients with subcortical infarcts and 12 age- and sex-matched healthy controls. We identified the typical activation pattern elicited for motor imagery in healthy controls, as computed over the voxels within each searchlight in the motor cortex. Then we measured the similarity of each individual's activation pattern to the typical activation pattern. Results. In terms of activation levels, the stroke patients showed no activation in the ipsilesional primary motor cortex (M1); in terms of activation patterns, they showed lower similarity to the typical activation pattern in the area than the healthy controls. Furthermore, the stroke patients were better able to perform motor imagery if their activation patterns in the bilateral supplementary motor areas and ipsilesional M1 were close to the typical activation pattern. Conclusions. These findings suggest functional roles of the motor cortical areas for compliance with motor imagery in stroke, which can be applied to the implementation of motor imagery-based brain-computer interface for stroke rehabilitation.
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Surgical outcomes of robotic radical hysterectomy using three robotic arms versus conventional multiport laparoscopy in patients with cervical cancer.
Yonsei Med. J.
PUBLISHED: 07-23-2014
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To compare surgical outcomes of robotic radical hysterectomy (RRH) using 3 robotic arms with those of conventional laparoscopy in patients with early cervical cancer.
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Ultrasonographic features of vascular closure devices: initial and 6-month follow-up results.
Ultrasonography
PUBLISHED: 07-16-2014
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This study aimed to evaluate the ultrasonographic findings for various types of vascular closure devices (VCDs) immediately after the angiographic procedure and at 6-month follow-up.
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A New Isolated Mediastinal Lymph Node or Small Pulmonary Nodule Arising during Breast Cancer Surveillance Following Curative Surgery: Clinical Factors That Differentiate Malignant from Benign Lesions.
Cancer Res Treat
PUBLISHED: 07-15-2014
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A newly isolated mediastinal lymph node (LN) or a small pulmonary nodule, which appears during breast cancer surveillance, may pose a diagnostic dilemma with regard to malignancy. We conducted this study to determine which clinical factors were useful for the differentiation of malignant lesions from benign lesions under these circumstances.
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.
Zhaoming Wang, Bin Zhu, Mingfeng Zhang, Hemang Parikh, Jinping Jia, Charles C Chung, Joshua N Sampson, Jason W Hoskins, Amy Hutchinson, Laurie Burdette, Abdisamad Ibrahim, Christopher Hautman, Preethi S Raj, Christian C Abnet, Andrew A Adjei, Anders Ahlbom, Demetrius Albanes, Naomi E Allen, Christine B Ambrosone, Melinda Aldrich, Pilar Amiano, Christopher Amos, Ulrika Andersson, Gerald Andriole, Irene L Andrulis, Cecilia Arici, Alan A Arslan, Melissa A Austin, Dalsu Baris, Donald A Barkauskas, Bryan A Bassig, Laura E Beane Freeman, Christine D Berg, Sonja I Berndt, Pier Alberto Bertazzi, Richard B Biritwum, Amanda Black, William Blot, Heiner Boeing, Paolo Boffetta, Kelly Bolton, Marie-Christine Boutron-Ruault, Paige M Bracci, Paul Brennan, Louise A Brinton, Michelle Brotzman, H Bas Bueno-de-Mesquita, Julie E Buring, Mary Ann Butler, Qiuyin Cai, Géraldine Cancel-Tassin, Federico Canzian, Guangwen Cao, Neil E Caporaso, Alfredo Carrato, Tania Carreon, Angela Carta, Gee-Chen Chang, I-Shou Chang, Jenny Chang-Claude, Xu Che, Chien-Jen Chen, Chih-Yi Chen, Chung-Hsing Chen, Constance Chen, Kuan-Yu Chen, Yuh-Min Chen, Anand P Chokkalingam, Lisa W Chu, Francoise Clavel-Chapelon, Graham A Colditz, Joanne S Colt, David Conti, Michael B Cook, Victoria K Cortessis, E David Crawford, Olivier Cussenot, Faith G Davis, Immaculata De Vivo, Xiang Deng, Ti Ding, Colin P Dinney, Anna Luisa Di Stefano, W Ryan Diver, Eric J Duell, Joanne W Elena, Jin-Hu Fan, Heather Spencer Feigelson, Maria Feychting, Jonine D Figueroa, Adrienne M Flanagan, Joseph F Fraumeni, Neal D Freedman, Brooke L Fridley, Charles S Fuchs, Manuela Gago-Dominguez, Steven Gallinger, Yu-Tang Gao, Susan M Gapstur, Montserrat Garcia-Closas, Reina Garcia-Closas, Julie M Gastier-Foster, J Michael Gaziano, Daniela S Gerhard, Carol A Giffen, Graham G Giles, Elizabeth M Gillanders, Edward L Giovannucci, Michael Goggins, Nalan Gokgoz, Alisa M Goldstein, Carlos González, Richard Gorlick, Mark H Greene, Myron Gross, H Barton Grossman, Robert Grubb, Jian Gu, Peng Guan, Christopher A Haiman, Göran Hallmans, Susan E Hankinson, Curtis C Harris, Patricia Hartge, Claudia Hattinger, Richard B Hayes, Qincheng He, Lee Helman, Brian E Henderson, Roger Henriksson, Judith Hoffman-Bolton, Chancellor Hohensee, Elizabeth A Holly, Yun-Chul Hong, Robert N Hoover, H Dean Hosgood, Chin-Fu Hsiao, Ann W Hsing, Chao Agnes Hsiung, Nan Hu, Wei Hu, Zhibin Hu, Ming-Shyan Huang, David J Hunter, Peter D Inskip, Hidemi Ito, Eric J Jacobs, Kevin B Jacobs, Mazda Jenab, Bu-Tian Ji, Christoffer Johansen, Mattias Johansson, Alison Johnson, Rudolf Kaaks, Ashish M Kamat, Aruna Kamineni, Margaret Karagas, Chand Khanna, Kay-Tee Khaw, Christopher Kim, In-Sam Kim, Jin Hee Kim, Yeul Hong Kim, Young-Chul Kim, Young Tae Kim, Chang Hyun Kang, Yoo Jin Jung, Cari M Kitahara, Alison P Klein, Robert Klein, Manolis Kogevinas, Woon-Puay Koh, Takashi Kohno, Laurence N Kolonel, Charles Kooperberg, Christian P Kratz, Vittorio Krogh, Hideo Kunitoh, Robert C Kurtz, Nilgun Kurucu, Qing Lan, Mark Lathrop, Ching C Lau, Fernando Lecanda, Kyoung-Mu Lee, Maxwell P Lee, Loic Le Marchand, Seth P Lerner, Donghui Li, Linda M Liao, Wei-Yen Lim, Dongxin Lin, Jie Lin, Sara Lindstrom, Martha S Linet, Jolanta Lissowska, Jianjun Liu, Börje Ljungberg, Josep Lloreta, Daru Lu, Jing Ma, Nuria Malats, Satu Mannisto, Neyssa Marina, Giuseppe Mastrangelo, Keitaro Matsuo, Katherine A McGlynn, Roberta Mckean-Cowdin, Lorna H McNeill, Robert R McWilliams, Beatrice S Melin, Paul S Meltzer, James E Mensah, Xiaoping Miao, Dominique S Michaud, Alison M Mondul, Lee E Moore, Kenneth Muir, Shelley Niwa, Sara H Olson, Nick Orr, Salvatore Panico, Jae Yong Park, Alpa V Patel, Ana Patiño-García, Sofia Pavanello, Petra H M Peeters, Beata Peplonska, Ulrike Peters, Gloria M Petersen, Piero Picci, Malcolm C Pike, Stefano Porru, Jennifer Prescott, Xia Pu, Mark P Purdue, You-Lin Qiao, Preetha Rajaraman, Elio Riboli, Harvey A Risch, Rebecca J Rodabough, Nathaniel Rothman, Avima M Ruder, Jeong-Seon Ryu, Marc Sanson, Alan Schned, Fredrick R Schumacher, Ann G Schwartz, Kendra L Schwartz, Molly Schwenn, Katia Scotlandi, Adeline Seow, Consol Serra, Massimo Serra, Howard D Sesso, Gianluca Severi, Hongbing Shen, Min Shen, Sanjay Shete, Kouya Shiraishi, Xiao-Ou Shu, Afshan Siddiq, Luis Sierrasesúmaga, Sabina Sierri, Alan Dart Loon Sihoe, Debra T Silverman, Matthias Simon, Melissa C Southey, Logan Spector, Margaret Spitz, Meir Stampfer, Pär Stattin, Mariana C Stern, Victoria L Stevens, Rachael Z Stolzenberg-Solomon, Daniel O Stram, Sara S Strom, Wu-Chou Su, Malin Sund, Sook Whan Sung, Anthony Swerdlow, Wen Tan, Hideo Tanaka, Wei Tang, Ze-Zhang Tang, Adonina Tardón, Evelyn Tay, Philip R Taylor, Yao Tettey, David M Thomas, Roberto Tirabosco, Anne Tjonneland, Geoffrey S Tobias, Jorge R Toro, Ruth C Travis, Dimitrios Trichopoulos, Rebecca Troisi, Ann Truelove, Ying-Huang Tsai, Margaret A Tucker, Rosario Tumino, David Van Den Berg, Stephen K Van Den Eeden, Roel Vermeulen, Paolo Vineis, Kala Visvanathan, Ulla Vogel, Chaoyu Wang, Chengfeng Wang, Junwen Wang, Sophia S Wang, Elisabete Weiderpass, Stephanie J Weinstein, Nicolas Wentzensen, William Wheeler, Emily White, John K Wiencke, Alicja Wolk, Brian M Wolpin, Maria Pik Wong, Margaret Wrensch, Chen Wu, Tangchun Wu, Xifeng Wu, Yi-Long Wu, Jay S Wunder, Yong-Bing Xiang, Jun Xu, Hannah P Yang, Pan-Chyr Yang, Yasushi Yatabe, Yuanqing Ye, Edward D Yeboah, Zhihua Yin, Chen Ying, Chong-Jen Yu, Kai Yu, Jian-Min Yuan, Krista A Zanetti, Anne Zeleniuch-Jacquotte, Wei Zheng, Baosen Zhou, Lisa Mirabello, Sharon A Savage, Peter Kraft, Stephen J Chanock, Meredith Yeager, Maria Terese Landi, Jianxin Shi, Nilanjan Chatterjee, Laufey T Amundadottir.
Hum. Mol. Genet.
PUBLISHED: 07-15-2014
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Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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Inhibition of the Calcineurin Pathway by Two Tannins, Chebulagic Acid and Chebulanin, Isolated from Harrisonia abyssinica Oliv.
J. Microbiol. Biotechnol.
PUBLISHED: 07-09-2014
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In order to discover and develop novel signaling inhibitors from plants, a screening system was established targeting the two-component system of Cryptococcus neoformans by using the wild type and a calcineurin mutant of C. neoformans, based on the counter-regulatory action of high-osmolarity glycerol (Hog1) mitogen-activated protein kinase and the calcineurin pathways in C. neoformans. Among 10,000 plant extracts, that from Harrisonia abyssinica Oliv. exhibited the most potent inhibitory activity against C. neoformans var. grubii H99 with fludioxonil. Bioassay-guided fractionation was used to isolate two bioactive compounds from H. abyssinica, and these compounds were identified as chebulagic acid and chebulanin using spectroscopic methods. These compounds specifically inhibited the calcineurin pathway in C. neoformans. Moreover, they exhibited potent antifungal activities against various human pathogenic fungi with minimum inhibitory concentrations ranging from 0.25 to over 64 µg/ml.
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Procarbazine, CCNU, and Vincristine Chemotherapy in Gliomatosis Cerebri.
Brain Tumor Res Treat
PUBLISHED: 07-02-2014
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A 49-year-old female patient was admitted due to memory disturbances. Magnetic resonance (MR) imaging suggested gliomatosis cerebri (GC), which had spread to both insular lobes, both frontal and basal ganglia and the brain stem. A stereotactic biopsy was performed at the high signal intensity area of the T2-weighted MR image, and the revealed a diffuse astrocytoma. Radiation therapy was judged not to be an appropriate treatment for the patient because of her cognitive impairment. A combinatorial chemotherapy regiment consisting of Procarbazine, CCNU, and Vincristine (PCV) was agreed upon after discussion. The patient underwent six cycles of PCV chemotherapy (a full dose was applied until the 3rd cycle, and dose then was reduced to 75% for the remaining cycles). Although the patient exhibited side effects such as bone marrow suppression and gastrointestinal symptoms, these were managed by medication. Over the 28 months following initiation of treatment, the high signal area in the right frontal and temporal lobes in the T2-weighted MR image decreased, and the patient's cognitive function [global deterioration scale (GDS) 4 points, mini-mental state examination (MMSE) 25 point] also improved (GDS 1 points, MMSE 29 points). PCV chemotherapy can therefore be an alternative therapeutic option for patients with GC who cannot be treated with radiation therapy or other chemotherapies.
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Enhanced oral bioavailability and antiasthmatic efficacy of curcumin using redispersible dry emulsion.
Biomed Mater Eng
PUBLISHED: 06-24-2014
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Dry emulsion containing curcumin (DE-CUR) was prepared for oral delivery of poorly water-soluble curcumin, and its oral bioavailability and antiasthmatic efficacy was evaluated. After comparison of the solubility of curcumin in various oils, Plurol® Oleique CC497 was selected to be the oil phase due to its higher solubility of CUR than other oils. A dry emulsion prepared by spray-drying of a homogenized oil-in-water emulsion was well-reconstituted in water, fabricating similar particle distribution and in vitro release to that of a dispersed homogeneous emulsion before spraying. The release of DE-CUR was much higher than that of curcumin (85.3 vs. 1.7% release at 60 min). Consequently, DE-CUR resulted in 12.0- and 7.1-fold higher Cmax and AUC0-24h than curcumin. In a murine asthma model, DE-CUR effectively suppressed airway hyperresponsiveness and levels of T-helper cytokines such as interleukin-4, inteleukin-5, and interleukin-13. These findings demonstrate that the DE-CUR shows a potential for the development of functional foods or medicines including CUR.
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Enhanced oral bioavailability and controlled release of dutasteride by a novel dry elixir.
Biomed Mater Eng
PUBLISHED: 06-24-2014
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To develop a solid dosage form of dutasteride for improving its oral bioavailability, a novel dry elixir (DE) system was fabricated. DEs incorporating dextrin and/or xanthan gum were prepared using spray-drying and evaluated by morphology, ethanol content, crystallinity, dissolution and oral bioavailability. DEs were spherical with a smooth surface and had an average particle size of 20-25 ?m. The ethanol content could be easily varied by controlling the spray-drying temperature. The dissolution profiles of dutasteride from each DE proved to be much faster than that of dutasteride powder due to the amorphous state and a high amount of incorporated ethanol. In particular, the pharmacokinetic profiles of dutasteride were significantly altered depending on the proportions of dextrin and xanthan gum. Blood concentrations of dutasteride from DE formulations were similar to those of market products and much greater than those of native dutasteride. Interestingly, the dissolution and pharmacokinetic profiles were easily controlled by changing the ratio of dextrin to xanthan gum. The data suggests that a DE using dextrin and/or xanthan gum could provide an applicable solid dosage form to improve the dissolution and bio-availability of dutasteride as well as to modulate its pharmacokinetics.
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Improved bioavailability and antiasthmatic efficacy of poorly soluble curcumin-solid dispersion granules obtained using fluid bed granulation.
Biomed Mater Eng
PUBLISHED: 06-24-2014
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The intestinal absorption and antiasthmatic efficacy of poorly water-soluble curcumin (CUR), which has low solubility and permeability, was increased by fabricating solid dispersion granules (SDGs). The SDG containing CUR (SDG-CUR) was prepared by dispersing CUR in excess Cremophor RH40 as a solubilizer and Ryoto sugar ester L-1695 as an absorption enhancer using fluid bed granulation. We evaluated the physicochemical properties such as crystallinity and dissolution, pharmacokinetics, and antiasthmatic efficacy of SDG-CUR. Our results showed that CUR was molecularly dispersed, and the dissolution of SDG-CUR was significantly higher than that of native CUR. In addition, the blood concentration of SDG-CUR in rats was much higher than that of native CUR. Compared to CUR, SDG-CUR showed a 9.1- and 13.1-fold increase in area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax), respectively. Further, SDG-CUR effectively alleviated airway hyperresponsiveness and levels of T-helper 2 cytokines (interleukin-4, interleukin-5, and interleukin-13) in a murine model of asthma. In conclusion, our results suggest that the SDGs could be considered as a potential oral formulation to enhance the absorption and efficacy of CUR.
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A recurrent cellular schwannoma.
Korean J Thorac Cardiovasc Surg
PUBLISHED: 06-10-2014
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Cellular schwannoma is an uncommon variant of schwannomas that can occur in a peripheral nerve. Although cellular schwannomas typically do not differ in prognosis from regular schwannomas, they are known to cause local recurrence when not completely resected. Here, we report the case of a patient with cellular schwannoma of the posterior mediastinum, which recurred after 13 years.
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The Role of (18)?F-FDG PET/CT in Assessing Therapy Response in Cervix Cancer after Concurrent Chemoradiation Therapy.
Nucl Med Mol Imaging
PUBLISHED: 06-06-2014
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To determine whether persisting cervical fluorodeoxyglucose (FDG) uptake after concurrent chemoradiotherapy (CCRT) for cervical cancer can reflect residual malignancy.
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Renal function is associated with bone mineral density and arterial stiffness in healthy postmenopausal women.
Gynecol. Obstet. Invest.
PUBLISHED: 05-18-2014
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This study aimed to investigate the effect of renal function on bone mineral density (BMD) and arterial stiffness in postmenopausal women.
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Pulmonary adenocarcinomas appearing as part-solid ground-glass nodules: Is measuring solid component size a better prognostic indicator?
Eur Radiol
PUBLISHED: 05-15-2014
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To assess whether measuring the solid portion of adenocarcinomas appearing as part-solid ground-glass nodules (GGNs) can predict a patient's prognosis accurately and how the prognosis corresponds to that of solid nodules.
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Significance of longitudinal changes in the default-mode network for cognitive recovery after stroke.
Eur. J. Neurosci.
PUBLISHED: 04-24-2014
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Although a considerable number of patients suffer from cognitive impairments after stroke, the neural mechanism of cognitive recovery has not yet been clarified. Repeated resting-state functional magnetic resonance imaging (fMRI) was used in this study to examine longitudinal changes in the default-mode network (DMN) during the 6 months after stroke, and to investigate the relationship between DMN changes and cognitive recovery. Out of 24 initially recruited right-hemispheric stroke patients, 11 (eight males, mean age 55.7 years) successfully completed the repeated fMRI protocol. Patients underwent three fMRI sessions at 1, 3 and 6 months after stroke. Their DMNs were analysed and compared with those of 11 age-matched healthy subjects (nine males, mean age 56.2 years). Correlations between DMN connectivity and improvement of the cognitive performance scores were also assessed. The stroke patients were found to demonstrate markedly decreased DMN connectivity of the posterior cingulate cortex, precuneus, medial frontal gyrus and inferior parietal lobes at 1 month after stroke. At 3 months after stroke, the DMN connectivity of these brain areas was almost restored, suggesting that the period is critical for neural reorganization. The DMN connectivity of the dorsolateral prefrontal cortex in the contralesional hemisphere showed a significant correlation with cognitive function recovery in stroke patients, and should be considered a compensatory process for overcoming cognitive impairment due to brain lesion. This is the first longitudinal study to demonstrate the changes in DMN during recovery after stroke and the key regions influencing cognitive recovery.
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Brain topological correlates of motor performance changes after repetitive transcranial magnetic stimulation.
Brain Connect
PUBLISHED: 04-07-2014
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Repetitive transcranial magnetic stimulation (rTMS) influences the brain temporally beyond the stimulation period and spatially beyond the stimulation site. Application of rTMS over the primary motor cortex (M1) has been shown to lead to plastic changes in interregional connectivity over the motor system as well as alterations in motor performance. With a sequential combination of rTMS over the M1 and functional magnetic resonance imaging (fMRI), we sought changes in the topology of brain networks and specifically the association of brain topological changes with motor performance changes. In a sham-controlled parallel group experimental design, real or sham rTMS was administered to each of the 15 healthy subjects without prior motor-related dysfunctions, over the right M1 at a high frequency of 10 Hz. Before and after the intervention, fMRI data were acquired during a sequential finger motor task using the left, nondominant hand. Changes in the topology of brain networks were assessed in terms of global and local efficiency, which measures the efficiency in transporting information at global and local scales, respectively, provided by graph-theoretical analysis. Greater motor performance changes toward improvements after real rTMS were shown in individuals who exhibited more increases in global efficiency and more decreases in local efficiency. The enhancement of motor performance after rTMS is supposed to be associated with brain topological changes, such that global information exchange is facilitated, while local information exchange is restricted.
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The presence of extrathoracic metastasis is more prognostic of survival than Masaoka stage (IVa/IVb) in metastatic thymic epithelial tumor: a retrospective cohort study.
Lung Cancer
PUBLISHED: 04-05-2014
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Our aim in this study was to identify independent prognostic factors for overall survival (OS) in order to explain the heterogeneity of OS in patients with metastatic thymic epithelial tumor (TET).
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Seoul criteria for PiB(-) subcortical vascular dementia based on clinical and MRI variables.
Neurology
PUBLISHED: 03-28-2014
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The purpose of this study was to propose new criteria for differentiating Pittsburgh compound B (PiB)-negative from PiB-positive subcortical vascular dementia (SVaD) using clinical and MRI variables.
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Role of postoperative radiotherapy after curative resection and adjuvant chemotherapy for patients with pathological stage N2 non-small-cell lung cancer: a propensity score matching analysis.
Clin Lung Cancer
PUBLISHED: 03-16-2014
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The objective of this study was to evaluate the role of postoperative radiotherapy (PORT) in the setting of adjuvant chemotherapy for pathological stage N2 (pN2) non-small-cell lung cancer (NSCLC).
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The role of phosphatidylcholine and deoxycholic acid in inflammation.
Life Sci.
PUBLISHED: 03-04-2014
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Phosphatidylcholine with deoxycholic acid (PC/DA) is widely used to reduce localized fat deposits with mild adverse effects. We previously demonstrated that PC induces lipolysis with mild PMN infiltration, while DA induces adipose tissue damage. Therefore, the aim of this study was to extend our understanding of the pro-inflammatory responses of PC, DA, and PC/DA.
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White matter hyperintensities are associated with amyloid burden in APOE4 non-carriers.
J. Alzheimers Dis.
PUBLISHED: 03-01-2014
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Previous preclinical studies have suggested a close relationship between cerebrovascular disease (CVD) and Alzheimer's disease. However, a direct correlation between CVD and amyloid burden has not yet been shown in humans. If there is a relationship between CVD and amyloid burden, it is possible that the apolipoprotein E4 (APOE4) genotype may have an effect on this relationship because APOE4 is a risk factor for the development of AD. We therefore evaluated the effects of APOE4 on the relationship between white matter hyperintensities (WMH), a marker of CVD, and amyloid burden, measured by 11C-Pittsburgh compound B (PiB) PET. We recruited 53 patients with subcortical vascular cognitive impairments, who had both WMH on MRI and amyloid deposition assessed by PiB PET. Twenty-two of these patients were APOE4 carriers (41.5%). In the APOE4 non-carriers, a significant positive correlation was shown between the volume of WMH and PiB retention (? = 7.0 × 10-3, p = 0.034) while no significant correlation was found in APOE4 carriers (? = -9.0 × 10-3, p = 0.085). Statistical parametric mapping analyses in APOE4 non-carriers showed that WMH were associated with PiB retention in the bilateral medial occipitotemporal gyrus, cuneus, and superior cerebellum. Our results suggested that WMH are correlated with amyloid burden especially in the posterior brain regions in APOE4 non-carriers. However, this correlation was not observed in APOE4 carriers, perhaps because in these subjects the influence of APOE4 overrides the effect of CVD.
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Preoperative embolization of cerebellar hemangioblastoma with onyx: report of three cases.
Neurointervention
PUBLISHED: 02-28-2014
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Hemangioblastoma is a benign and highly vascular tumor. Complete surgical resection of highly vascular tumor such as hemangioblastoma may be challenging due to excessive bleeding. Preoperative embolization of these lesions may decrease the intraoperative blood loss and facilitate excision. We report three cases of cerebellar hemangioblastomas that were embolized using Onyx.
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Gold nanoparticles for nucleic acid delivery.
Mol. Ther.
PUBLISHED: 02-21-2014
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Gold nanoparticles provide an attractive and applicable scaffold for delivery of nucleic acids. In this review, we focus on the use of covalent and noncovalent gold nanoparticle conjugates for applications in gene delivery and RNA-interference technologies. We also discuss challenges in nucleic acid delivery, including endosomal entrapment/escape and active delivery/presentation of nucleic acids in the cell.
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Synergistic effects of ischemia and ?-amyloid burden on cognitive decline in patients with subcortical vascular mild cognitive impairment.
JAMA Psychiatry
PUBLISHED: 02-21-2014
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Cerebrovascular disease (CVD) and Alzheimer disease are significant causes of cognitive impairment in the elderly. However, few studies have evaluated the relationship between CVD and ?-amyloid burden in living humans or their synergistic effects on cognition. Thus, there is a need for better understanding of mild cognitive impairment (MCI) before clinical deterioration begins.
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The role of metabolic tumor volume and total lesion glycolysis on ¹?F-FDG PET/CT in the prognosis of epithelial ovarian cancer.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 02-06-2014
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This study assessed the prognostic value of pre-operative 2-[(18)F] fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) volumetric parameters, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), in patients with epithelial ovarian cancer.
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A comparison of clinical and surgical outcomes between laparo-endoscopic single-site surgery and traditional multiport laparoscopic surgery for adnexal tumors.
Obstet Gynecol Sci
PUBLISHED: 01-22-2014
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The purpose of this study was to compare clinical and surgical outcomes between laparo-endoscopic single-site (LESS) surgery and traditional multiport laparoscopic (TML) surgery for treatment of adnexal tumors.
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DLG1 influences distal ureter maturation via a non-epithelial cell autonomous mechanism involving reduced retinoic acid signaling, Ret expression, and apoptosis.
Dev. Biol.
PUBLISHED: 01-17-2014
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The absence of Discs-large 1 (DLG1), the mouse ortholog of the Drosophila discs-large tumor suppressor, results in congenital hydronephrosis characterized by urinary tract abnormalities, reduced ureteric bud branching, and delayed disconnection of the ureter from the common nephric duct (CND). To define the specific cellular requirements for Dlg1 expression during urogenital development, we used a floxed Dlg1 allele and Pax2-Cre, Pax3-Cre, Six2-Cre, and HoxB7-Cre transgenes to generate cell type-restricted Dlg1 mutants. In addition, we used Ret(GFP) knockin and retinoic acid response element-lacZ transgenic mice to determine the effects of Dlg1 mutation on the respective morphogenetic signaling pathways. Mutation of Dlg1 in urothelium and collecting ducts (via HoxB7-Cre or Pax2-Cre) and in nephron precursors (via Pax2-Cre and Six2-Cre) resulted in no apparent abnormalities in ureteric bud branching or in distal ureter maturation, and no hydronephrosis. Mutation in nephrons, ureteric smooth muscle, and mesenchyme surrounding the lower urinary tract (via the Pax3-Cre transgene) resulted in congenital hydronephrosis accompanied by reduced branching, abnormal distal ureter maturation and insertion, and smooth muscle orientation defects, phenotypes very similar to those in Dlg1 null mice. Dlg1 null mice showed reduced Ret expression and apoptosis during ureter maturation and evidence of reduced retinoic acid signaling in the kidney. Taken together, these results suggest that Dlg1 expression in ureter and CND-associated mesenchymal cells is essential for ensuring distal ureter maturation by facilitating retinoic acid signaling, Ret expression, and apoptosis of the urothelium.
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Shape changes of the basal ganglia and thalamus in Alzheimer's disease: a three-year longitudinal study.
J. Alzheimers Dis.
PUBLISHED: 01-14-2014
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A large number of Alzheimer's disease (AD) studies have focused on medial temporal and cortical atrophy, while changes in the basal ganglia or thalamus have received less attention.
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Reverse v-shape kinking of the left lower lobar bronchus after a left upper lobectomy and its surgical correction.
Korean J Thorac Cardiovasc Surg
PUBLISHED: 01-03-2014
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A 76-year-old male underwent a left upper lobectomy with wedge resection of the superior segment of the left lower lobe using video-assisted thoracoscopic surgery (VATS) for non-small-cell lung cancer of the left upper lobe. He presented with shortness of breath, fever, and leukocytosis. Chest radiography showed atelectasis at the remaining left lower lobe. Bronchoscopy revealed narrowing of the left lower bronchus with purulent secretion, and computed tomography showed downward kinking of the left lower lobar bronchus. He underwent exploratory VATS, and intraoperative findings showed an inferiorly kinked left lower lobar bronchus with upward displacement of the left lower lobe. After adhesiolysis, the kinked bronchus was straightened, and bronchopexy was performed to the pericardium to prevent the recurrence of bronchial kinking. Also, the inferior pulmonary ligament was reattached to prevent upward displacement. Postoperative follow-up bronchoscopy revealed no evidence of residual bronchial obstruction, and chest radiography showed no atelectasis thereafter.
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Association of pancreatic adenocarcinoma up-regulated factor expression in ovarian mucinous adenocarcinoma with poor prognosis.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Pancreatic adenocarcinoma up-regulated factor (PAUF) expression is elevated in both ovarian tumors and pancreatic adenocarcinoma. However, PAUF expression in ovarian tumors according to histologic subtype and grade has not been investigated. In this study, we examined various clinicopathologic features of 24 patients with mucinous cystadenoma (MCA), 36 with mucinous borderline tumors (MBTs), and 46 with mucinous adenocarcinomas (MACs) according to PAUF expression status assessed using immunohistochemistry. We found that MACs more frequently stained positive for PAUF than did MCAs and MBTs (P < 0.0001). Although there was no significant differences with respect to other clinicopathologic characteristics of MACs according to PAUF expression status, patients with PAUF-weakly positive and PAUF-strongly positive MACs tended to have a shorter overall survival (OS) than those with PAUF-negative MAC, determined using a Kaplan-Meier analysis (P = 0.1885). After adjusting for various clinicopathologic parameters, PAUF positivity of MACs was a significant predictive factor for disease-free survival (DFS) (negative vs. weakly positive: P = 0.045, hazard ratio [HR] = 57.406, 95% confidence interval [CI]: 1.090-3022.596; and negative vs. strongly positive: P = 0.034, HR = 97.890, 95% CI: 1.412-6785.925). In conclusion, PAUF was more frequently expressed in MAC than in its benign and borderline counterparts, and was associated with a poor OS and DFS in MAC patients. Therefore, we suggest that PAUF may be a practical biomarker for histopathological categorization and a prognostic marker for patients with an ovarian mucinous tumor.
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Early clinical outcomes of robot-assisted surgery for anterior mediastinal mass: its superiority over a conventional sternotomy approach evaluated by propensity score matching.
Eur J Cardiothorac Surg
PUBLISHED: 12-08-2013
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We performed this study to assess early clinical outcomes of robot-assisted surgery for anterior mediastinal mass by comparing results of the robot group with those of the sternotomy group after propensity score matching.
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Lipoma arborescens associated with osseous/chondroid differentiation in subdeltoid bursa.
Int J Shoulder Surg
PUBLISHED: 10-30-2013
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Lipoma arborescens (LA) is a rare benign lesion of unknown etiology. It is characterized histologically by villous proliferation of the synovial membrane and diffuse replacement of the subsynovial tissue by mature fat cells. This condition affects the knee joint most commonly. Cases involving other locations including glenohumeral joint,[1] hip,[2] elbow,[3] hand[4] and ankle[5] have been rarely described. Involvement of the subdeltoid bursa has also been reported, but to date no case has described LA with osseous/chondroid differentiation of this bursa. Another significant finding in our case was the coexistence of LA with intermuscular lipoma, SLAP lesion and labral cyst.
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Video-assisted thoracoscopic lobectomy in non-small-cell lung cancer patients with chronic obstructive pulmonary disease is associated with lower pulmonary complications than open lobectomy: a propensity score-matched analysis.
Eur J Cardiothorac Surg
PUBLISHED: 09-19-2013
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Non-small-cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD) are at an increased risk of pulmonary complications after pulmonary resection. This study aimed to identify whether video-assisted thoracoscopic (VATS) lobectomy can reduce postoperative pulmonary complications compared with lobectomy by thoracotomy in NSCLC patients with COPD.
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Multiplexed imaging of nanoparticles in tissues using laser desorption/ionization mass spectrometry.
J. Am. Chem. Soc.
PUBLISHED: 08-15-2013
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Imaging of nanomaterials in biological tissues provides vital information for the development of nanotherapeutics and diagnostics. Multiplexed imaging of different nanoparticles (NPs) greatly reduces costs, the need to use multiple animals, and increases the biodistribution information that can enhance diagnostic applications and accelerate the screening of potential therapeutics. Various approaches have been developed for imaging NPs; however, the readout of existing imaging techniques relies on specific properties of the core material or surface ligands, and these techniques are limited because of the relatively small number of NPs that can be simultaneously measured in a single experiment. Here, we demonstrate the use of laser desorption/ionization mass spectrometry (LDI-MS) in an imaging format to investigate surface chemistry dictated intraorgan distribution of NPs. This new LDI-MS imaging method enables multiplexed imaging of NPs with potentially unlimited readouts and without additional labeling of the NPs. It provides the capability to detect and image attomole levels of NPs with almost no interferences from biomolecules. Using this new imaging approach, we find that the intraorgan distributions of same-sized NPs are directly linked to their surface chemistry.
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Localized cortical thinning in patients with obstructive sleep apnea syndrome.
Sleep
PUBLISHED: 08-02-2013
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To investigate differences in cortical thickness in patients with obstructive sleep apnea (OSA) syndrome and healthy controls.
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Replenishable dendrimer-nanoparticle hybrid membranes for sustained release of therapeutics.
Nanoscale
PUBLISHED: 07-16-2013
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We report a versatile hybrid membrane for sustained release therapeutic delivery systems. Chemically-directed assembly of a hybrid membrane of nanoparticles and dendrimers was integrated with a fluidic delivery device and a refillable drug reservoir, providing continuous sustained release.
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Learning curve analysis of robot-assisted radical hysterectomy for cervical cancer: initial experience at a single institution.
J Gynecol Oncol
PUBLISHED: 07-14-2013
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The aim of this study was to evaluate the learning curve and perioperative outcomes of robot-assisted laparoscopic procedure for cervical cancer.
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Brain Gray Matter Deficits in Patients with Chronic Primary Insomnia.
Sleep
PUBLISHED: 07-02-2013
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To investigate the structural changes in patients with chronic primary insomnia and the relationships with clinical features of insomnia.
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Comparative study of voiding and male sexual function following open and laparoscopic total mesorectal excision in patients with rectal cancer.
J Surg Oncol
PUBLISHED: 07-01-2013
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This study aimed to compare voiding and male sexual dysfunction between open and laparoscopic rectal cancer surgery.
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Invasion of the great vessels or atrium predicts worse prognosis in thymic carcinoma.
Radiat Oncol J
PUBLISHED: 05-20-2013
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We evaluated treatment outcomes of thymic carcinomas to determine prognostic factors for survival.
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Scaffolding proteins DLG1 and CASK cooperate to maintain the nephron progenitor population during kidney development.
J. Am. Soc. Nephrol.
PUBLISHED: 05-09-2013
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DLG1 (discs-large homolog 1) and CASK (calcium/calmodulin-dependent serine protein kinase) interact at membrane-cytoskeleton interfaces and function as scaffolding proteins that link signaling molecules, receptors, and other scaffolding proteins at intercellular and synaptic junctions. Dlg1-null mice exhibit hydronephrosis, hydroureter, and occasionally hypoplastic kidneys, whereas Cask-null mice do not. To investigate whether DLG1 and CASK cooperate in the developing urogenital system, we generated mice deficient in both DLG1 and CASK either 1) globally, 2) in metanephric mesenchyme, or 3) in nephron progenitors. With each approach, Dlg1;Cask double-knockout (DKO) kidneys were severely hypoplastic and dysplastic and demonstrated rapid, premature depletion of nephron progenitors/stem cells. Several cellular and molecular defects were observed in the DKO kidneys, including reduced proliferation and increased apoptosis of cells in the nephrogenic zone and a progressive decrease in the number of cells expressing SIX2, a transcription factor essential for maintaining nephron progenitors. Fgf8 expression was reduced in early-stage DKO metanephric mesenchyme, accompanied by reduced levels of components of the Ras pathway, which is activated by fibroblast growth factor (FGF) signaling. Moreover, Dlg1(+/-);Cask(-/-) (het/null) kidneys were moderately hypoplastic and demonstrated impaired aggregation of SIX2-positive cells around the ureteric bud tips. Nephron progenitor-specific het/null mice survived with small kidneys but developed glomerulocystic kidney disease and renal failure. Taken together, these results suggest that DLG1 and CASK play critical cooperative roles in maintaining the nephron progenitor population, potentially via a mechanism involving effects on FGF signaling.
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Effects of APOE ?4 on brain amyloid, lacunar infarcts, and white matter lesions: a study among patients with subcortical vascular cognitive impairment.
Neurobiol. Aging
PUBLISHED: 04-22-2013
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The relationship between the apolipoprotein E ?4 allele (APOE4) and factors associated with vascular cognitive impairment (VCI) is unclear. We aimed to examine the effects of APOE4 on brain amyloid beta using Pittsburg compound B (PiB) and subcortical cerebrovascular disease, as assessed by lacunes and white matter hyperintensities (WMH) in subcortical VCI (SVCI) patients. We recruited 230 subjects with normal cognition, 111 subjects with cognitive impairment due to clinically defined Alzheimers disease (ADCI), and 134 subjects with clinically defined SVCI. A PiB retention ratio greater than 1.5 was considered to be PiB positive. Logistic regression analysis was performed to investigate whether APOE4 increased the risk for each cognitive impairment group. Multiple linear regression analysis was performed to investigate whether APOE4 was associated with brain amyloid beta, lacunes, and WMH. APOE4 did not increase the risk of PiB(-) SVCI (odds ratio [OR], 1.50; 95% confidence interval [CI], 0.79-2.84), whereas APOE4 increased the risk of PiB(+) SVCI (OR, 4.52; 95% CI, 1.70-11.97) and PiB(+) ADCI (odds ratio, 4.84; 95% CI, 2.54-7.91). In SVCI patients, APOE4 was positively associated with PiB retention ratio, whereas APOE4 was not associated with the number of lacunes or with WMH volume. Our results suggest that amyloid beta burden can occur in patients with and without subcortical cerebrovascular disease, and that it is associated with APOE4. However APOE4 might be independent of subcortical cerebrovascular disease.
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Onyx Embolization of Dural Arteriovenous Fistula, using Scepter C Balloon Catheter: a Case Report.
Neurointervention
PUBLISHED: 04-20-2013
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We report our experience using Onyx for embolization of dural arteriovenous fistula (DAVF) under dual lumen balloon catheter flow arrest. Transfemoral cerebral angiography revealed a superior sagittal sinus (SSS) DAVF that was supplied via multiple branches of the external carotid arteries, the right anterior cerebral arteries, and the meningeal branches of the internal carotid artery. There was no anterograde venous drainage through the SSS, and venous drainage was almost retrograde through the medullary and cortical veins. Under general anesthesia, a transvenous approach was utilized to place the microcatheter close to the fistula site. After intravenous embolization with various coils, DAVF was partially occluded; Balloon catheter gained access to the DAVF via the right middle meningeal artery. We injected Onyx through the Scepter C catheter, after which DAVF was nearly completely occluded. Balloon-assisted Onyx embolization is a feasible and effective approach for the management of DAVF.
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The N-end rule proteolytic system in autophagy.
Autophagy
PUBLISHED: 04-15-2013
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The N-end rule pathway is a cellular proteolytic system that utilizes specific N-terminal residues as degradation determinants, called N-degrons. N-degrons are recognized and bound by specific recognition components (N-recognins) that mediate polyubiquitination of low-abundance regulators and selective proteolysis through the proteasome. Our earlier work identified UBR4/p600 as one of the N-recognins that promotes N-degron-dependent proteasomal degradation. In this study, we show that UBR4 is associated with cellular cargoes destined to autophagic vacuoles and is degraded by the lysosome. UBR4 loss causes multiple misregulations in autophagic pathways, including an increased formation of LC3 puncta. UBR4-deficient mice die during embryogenesis primarily due to defective vascular development in the yolk sac (YS), wherein UBR4 is associated with a bulk lysosomal degradation system that absorbs maternal proteins from the YS cavity and digests them into amino acids. Our results suggest that UBR4 plays a role not only in selective proteolysis of short-lived regulators through the proteasome, but also bulk degradation through the lysosome. Here, we discuss a possible mechanism of UBR4 as a regulatory component in the delivery of cargoes destined to interact with the autophagic core machinery.
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Role of postoperative radiotherapy for microscopic margin involvement in the squamous cell carcinoma of esophagus.
Cancer Res Treat
PUBLISHED: 04-07-2013
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The objective of this study was to assess the effect of postoperative radiotherapy on the outcome of esophageal cancer with microscopically positive resection margin by comparing the results with those of patients with negative resection margin.
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The Effectiveness of Early Tracheostomy (within at least 10 Days) in Cervical Spinal Cord Injury Patients.
J Korean Neurosurg Soc
PUBLISHED: 04-01-2013
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This study aimed to determine the optimal time for tracheostomy by evaluating the benefits and safety of early versus late tracheostomy in spinal cord injury (SCI) patients.
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Effects of cerebrovascular disease and amyloid beta burden on cognition in subjects with subcortical vascular cognitive impairment.
Neurobiol. Aging
PUBLISHED: 03-22-2013
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Cerebrovascular disease (CVD) and amyloid burden are the most frequent pathologies in subjects with cognitive impairment. However, the relationship between CVD, amyloid burden, and cognition are largely unknown. We aimed to evaluate whether CVD (lacunes, white matter hyperintensities, and microbleeds) and amyloid burden (Pittsburgh compound B [PiB] retention ratio) contribute to cognitive impairment independently or interactively. We recruited 136 patients with subcortical vascular cognitive impairment who underwent magnetic resonance imaging, PiB-positron emission tomography, and neuropsychological testing. The number of lacunes was associated with memory, frontal dysfunctions, and disease severity. The volume of white matter hyperintensities and the PiB retention ratio were associated only with memory dysfunction. There was no direct correlation between CVD markers and PiB retention ratio except that the number of lacunes was negatively correlated with the PiB retention ratio. In addition, there were no interactive effects of CVD and PiB retention ratio on cognition. Our findings suggest that CVD and amyloid burden contribute independently and not interactively to specific patterns of cognitive dysfunction in patients with subcortical vascular cognitive impairment.
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The ON-Q pain management system in elective gynecology oncologic surgery: Management of postoperative surgical site pain compared to intravenous patient-controlled analgesia.
Obstet Gynecol Sci
PUBLISHED: 03-12-2013
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The goal of this study was to compare postoperative surgical site pain in gynecologic cancer patients who underwent elective extended lower midline laparotomy and managed their pain with either the ON-Q pain management system (surgical incision site pain relief system, ON-Q pump) or an intravenous patient-controlled analgesia pump (IV PCA).
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Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment.
Ann. Neurol.
PUBLISHED: 03-12-2013
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Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment.
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Topographic distribution of cortical thinning in subtypes of multiple system atrophy.
Parkinsonism Relat. Disord.
PUBLISHED: 02-25-2013
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Despite the predominant degeneration of subcortical structures, recent studies have suggested the evidence of cortical involvement in multiple system atrophy (MSA). This study aimed to identify the different topographic pattern of cortical thinning in MSA according to clinical subtypes, and the association of cortical thinning with cerebellar atrophy and other disease related metrics.
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UBR box N-recognin-4 (UBR4), an N-recognin of the N-end rule pathway, and its role in yolk sac vascular development and autophagy.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 02-19-2013
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The N-end rule pathway is a proteolytic system in which destabilizing N-terminal residues of short-lived proteins act as degradation determinants (N-degrons). Substrates carrying N-degrons are recognized by N-recognins that mediate ubiquitylation-dependent selective proteolysis through the proteasome. Our previous studies identified the mammalian N-recognin family consisting of UBR1/E3?, UBR2, UBR4/p600, and UBR5, which recognize destabilizing N-terminal residues through the UBR box. In the current study, we addressed the physiological function of a poorly characterized N-recognin, 570-kDa UBR4, in mammalian development. UBR4-deficient mice die during embryogenesis and exhibit pleiotropic abnormalities, including impaired vascular development in the yolk sac (YS). Vascular development in UBR4-deficient YS normally advances through vasculogenesis but is arrested during angiogenic remodeling of primary capillary plexus associated with accumulation of autophagic vacuoles. In the YS, UBR4 marks endoderm-derived, autophagy-enriched cells that coordinate differentiation of mesoderm-derived vascular cells and supply autophagy-generated amino acids during early embryogenesis. UBR4 of the YS endoderm is associated with a tissue-specific autophagic pathway that mediates bulk lysosomal proteolysis of endocytosed maternal proteins into amino acids. In cultured cells, UBR4 subpopulation is degraded by autophagy through its starvation-induced association with cellular cargoes destined to autophagic double membrane structures. UBR4 loss results in multiple misregulations in autophagic induction and flux, including synthesis and lipidation/activation of the ubiquitin-like protein LC3 and formation of autophagic double membrane structures. Our results suggest that UBR4 plays an important role in mammalian development, such as angiogenesis in the YS, in part through regulation of bulk degradation by lysosomal hydrolases.
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Coiling as Retreatment in Intracranial Aneurysm of de novo Formation or Regrowth: Case Report.
Neurointervention
PUBLISHED: 02-05-2013
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Development of de novo aneurysm or aneurysm regrowth after complete clipping of an intracranial aneurysm is rare. We report coiled cases of de novo aneurysm and aneurysm regrowth. We retrospectively reviewed 107 cases of intracranial aneurysm coiling performed in our hospital, identifying five cases of coiled aneurysm that were de novo aneurysm or aneurysm regrowth. In all the cases, total or near total occlusion was seen. There were no complications related to the procedure. In two of the three patients with ruptured aneurysms, consciousness level on admission was stupor. When the patient was discharged after the treatment, one of them had 4 of the modified Rankin Scale. The other one had 5 on discharge. The rest three patients had 0. As for a de novo aneurysm or a regrowth of aneurysm, coiling may be considered when clipping is difficult.
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Natural history of ground-glass nodules detected on the chest computed tomography scan after major lung resection.
Ann. Thorac. Surg.
PUBLISHED: 01-29-2013
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Detection of ground-glass nodules (GGNs) on computed tomography (CT) is increasing due to advances in CT technology and the findings of the National Lung Screening Trial. Ground-glass nodules are detected on screening chest CTs and CT scans after lung resection surgery. It is important to investigate the natural history of GGNs as it is not yet well known, and a standardized approach to manage them has not been established.
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Cervicofacial tissue infarction in patients with acute invasive fungal sinusitis: prevalence and characteristic MR imaging findings.
Neuroradiology
PUBLISHED: 01-22-2013
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Tissue infarction is known as one of the characteristic features of invasive fungal sinusitis (IFS). The purpose of this study was to investigate the prevalence and characteristic MR imaging findings of cervicofacial tissue infarction (CFTI) associated with acute IFS.
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Transcranial direct current stimulation increases resting state interhemispheric connectivity.
Neurosci. Lett.
PUBLISHED: 01-13-2013
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Transcranial direct current stimulation (tDCS) has been increasingly used to investigate human brain functions. Especially, tDCS on the dorsolateral prefrontal cortex (DLPFC) enhances cognitive functions in both healthy subjects and patients with neuropsychiatric disorders. In spite of its effects on behavioral improvement, neural correlates of tDCS on the DLPFC have not been fully described. In this study, we acquired resting state functional magnetic resonance imaging data before and after real or sham stimulation on the left DLPFC. Resting state functional connectivity of the stimulated brain region was compared between the two groups. Compared to the sham stimulation group, the tDCS group showed increased DLPFC connectivity to the right hemisphere and decreased DLPFC connectivity to the brain regions around the stimulation site in the left hemisphere. Application of tDCS on the DLPFC may induce increased interhemispheric connectivity even at rest, possibly associated with the behavioral effects of tDCS.
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The role of surface functionality in determining nanoparticle cytotoxicity.
Acc. Chem. Res.
PUBLISHED: 01-07-2013
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Surface properties dictate the behavior of nanomaterials in vitro, in vivo, and in the environment. Such properties include surface charge and hydrophobicity. Also key are more complex supramolecular interactions such as aromatic stacking and hydrogen bonding, and even surface topology from the structural to the atomic level. Surface functionalization of nanoparticles (NPs) provides an effective way to control the interface between nanomaterials and the biological systems they are designed to interact with. In medicine, for instance, proper control of surface properties can maximize therapeutic or imaging efficacy while minimizing unfavorable side effects. Meanwhile, in environmental science, thoughtful choice of particle coating can minimize the impact of manufactured nanomaterials on the environment. A thorough knowledge of how NP surfaces with various properties affect biological systems is essential for creating NPs with such useful therapeutic and imaging properties as low toxicity, stability, biocompatibility, favorable distribution throughout cells or tissues, and favorable pharmacokinetic profiles--and for reducing the potential environmental impact of manufactured nanomaterials, which are becoming increasingly prominent in the marketplace. In this Account, we discuss our research and that of others into how NP surface properties control interactions with biomolecules and cells at many scales, including the role the particle surface plays in determining in vivo behavior of nanomaterials. These interactions can be benign, beneficial, or lead to dysfunction in proteins, genes and cells, resulting in cytotoxic and genotoxic responses. Understanding these interactions and their consequences helps us to design minimally invasive imaging and delivery agents. We also highlight in this Account how we have fabricated nanoparticles to act as therapeutic agents via tailored interactions with biomacromolecules. These particles offer new therapeutic directions from traditional small molecule therapies, and with potentially greater versatility than is possible with proteins and nucleic acids.
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