tbuckley/cabot-search huggingface dataset:
Comparison of Primary Neuroblastoma Tumors and Derivative Early-Passage Cell Lines Using Genome-Wide Single Nucleotide Polymorphism Array Analysis
Authors: Samuel L. Volchenboum, Cheng Li, Shuli Li, Edward F. Attiyeh, C. Patrick Reynolds, John M. Maris, A. Thomas Look, Rani E. George
Journal: Cancer Research (2009)

Stromal contamination is one of the major confounding factors in the analysis of solid tumor samples by single nucleotide polymorphism (SNP) arrays. As we propose to use genome-wide SNP microarray analysis as a diagnostic platform for neuroblastoma, the sensitivity, specificity, and accuracy of these studies must be optimized. To investigate the effects of stromal contamination, we derived early-passage cell lines from nine primary tumors and compared their genomic signature with that of the primary tumors using 100K SNP arrays. The average concordance between tumor and cell line for raw loss of heterozygosity (LOH) calls was 96% (range, 91-99%) and for raw copy number alterations, 71% (range, 43-87%). In general, there were a larger number of LOH events identified in the cell lines compared with the matched tumor samples (mean increase, 3.2% +/- 1.9%). We have developed an algorithm that shows that the presence of stroma contributes to under-reporting of LOH and copy number loss. Notable findings in this sample set were uniparental disomy of chromosome arms 11p, 1q, 14q, and 15q and a novel area of amplification on chromosome band 11p15. Our analysis shows that LOH was identified significantly more often in derived cell lines compared with the original tumor samples. Although these may in part be due to clonal selection during adaptation to tissue culture, our study indicates that stromal contamination may be a major contributing factor in underestimation of LOH and copy number loss events.
Nonclostridial gas gangrene due to Streptococcus anginosus in a diabetic patient
Authors: Takahiro Shimizu, Mikihiko Harada, Nobuya Zempo, Daikai Sadamitsu, Hiroko Furumoto, Hiroshi Uchida, Hiro Yasui, Reiko Ofuji, Masahiko Muto
Journal: Journal of the American Academy of Dermatology (1999)
Type V collagen induced pulmonary fibrosis in C57Bl/6mice
Authors: Walcy Rosolia Teodoro, Ana Paula Pereira Velosa, Antonio dos Santos Filho, Priscila Cristina Andrade, Vanessa Martins, Sandra Morais Fernezlian, Sérgio Catanozi, Vera Luisa Capelozzi
Journal: European Respiratory Journal (2014)

Background : Fibrosing lung diseases are a serious problem to health and are ranked high among chronic degenerative diseases due to its morbidity. Type V collagen [col (V)] is a minor collagen normally sequestered within the lung interstitium and therefore, hidden from the immune system. This collagen regulates heterotypic fiber diameter, and the maintenance of its properties is important for maintaining normal tissue architecture and function. Previously, we discovered an experimental model of systemic sclerosis by immunizing healthy New Zealand rabbits with human col (V). This resulted in intense inflammation of the lung and progressive ECM remodeling of the septal and bronchovascular axis. Objective: To evaluate the pulmonary parenchyma after immunization healthy C57Bl/6 mice. Methods: For induction of pulmonary fibrosis, groups of male mice C57Bl/6 (n=6), aged 4 to 6 weeks-old with 20-25g, were immunized with 150µg/200µl of Col(V) in complete Freund's adjuvant, followed by more two boosters in incomplete Freund's adjuvant. Sterile saline was used as control. For analysis, mice were sacrificed 75 days after induction. Lungs were removed for routine histology, immunohistochemistry and histomorphometry. Results: The immunized group presented intense inflammation of the lung and progressive ECM remodeling with significant higher amount of CD4 (p=0.002). The higher amounts of type I collagen, TGF and CTGF expression were observed in immunized groups respectively, (p<0.005, p<0.0025 and p<0.0001) when compared with control group. Conclusions: We concluded that human col (V)induced pulmonary fibrosis in healthy C57Bl/6 mice, suggesting a new pulmonary fibrosis model important for pulmonary fibrosis pathogenesis.
Acute renal failure in membranous glomerulonephropathy
Authors: S H James, Y H Lien, S J Ruffenach, G E Wilcox
Journal: Journal of the American Society of Nephrology (1995)

A patient who presented with acute renal failure and anasarca secondary to crescentic glomerulonephritis superimposed on existing membranous glomerulonephropathy of 15 years' duration is described. The patient responded to an initial course of prednisone but failed to respond to a second course after relapse. The differential diagnosis of acute renal failure in the setting of nephrotic syndrome is discussed. Eighteen cases of crescentic glomerulonephritis superimposed on membranous glomerulonephropathy are reviewed. The clinical setting is heterogeneous with variable presentation and outcome. It appears that patients without antiglomerular basement membrane antibodies have a better prognosis than those who have antibodies. Patients with membranous glomerulonephropathy who develop unexplained acute renal failure should undergo early renal biopsy in order to rule out unexpected pathologic complications.
Placebo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury
Authors: Joseph T. Giacino, John Whyte, Emilia Bagiella, Kathleen Kalmar, Nancy Childs, Allen Khademi, Bernd Eifert, David Long, Douglas I. Katz, Sooja Cho, Stuart A. Yablon, Marianne Luther, Flora M. Hammond, Annette Nordenbo, Paul Novak, Walt Mercer, Petra Maurer-Karattup, Mark Sherer
Journal: New England Journal of Medicine (2012)

Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery.We enrolled 184 patients who were in a vegetative or minimally conscious state 4 to 16 weeks after traumatic brain injury and who were receiving inpatient rehabilitation. Patients were randomly assigned to receive amantadine or placebo for 4 weeks and were followed for 2 weeks after the treatment was discontinued. The rate of functional recovery on the Disability Rating Scale (DRS; range, 0 to 29, with higher scores indicating greater disability) was compared over the 4 weeks of treatment (primary outcome) and during the 2-week washout period with the use of mixed-effects regression models.During the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit with respect to the primary outcome measure. In a prespecified subgroup analysis, the treatment effect was similar for patients in a vegetative state and those in a minimally conscious state. The rate of improvement in the amantadine group slowed during the 2 weeks after treatment (weeks 5 and 6) and was significantly slower than the rate in the placebo group (difference in slope, 0.30 points per week; P=0.02). The overall improvement in DRS scores between baseline and week 6 (2 weeks after treatment was discontinued) was similar in the two groups. There were no significant differences in the incidence of serious adverse events.Amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness. (Funded by the National Institute on Disability and Rehabilitation Research; ClinicalTrials.gov number, NCT00970944.).
A polymorphism in the gene encoding the Fc IIIA receptor is a possible genetic marker to predict the primary response to infliximab in Japanese patients with rheumatoid arthritis
Authors: S Tsukahara, K Ikari, E Sato, H Yamanaka, M Hara, T Tomatsu, S Momohara, N Kamatani
Journal: Annals of the Rheumatic Diseases (2008)

The prediction of treatment outcome of patients with rheumatoid arthritis (RA) may avoid wasting time and cost of treatment, and allow better targeting of aggressive treatment. Recently, an amino acid-changing polymorphism in the gene encoding the Fcγ IIIA receptor (FcγRIIIA), valine (V)/phenylalanine (F) (rs396991), was found to be associated with increased likelihood of response to tumour necrosis factor (TNF)-α inhibitors in the treatment of RA.1 The aim of the present study was to determine whether this FcγRIIIA V/F polymorphism is associated with treatment outcome of infliximab (the first TNF-α inhibitor approved in Japan) in Japanese patients with RA.

The study was approved by the Tokyo Women’s Medical University Genome Ethics Committee. The …
Overexpression of ELAV-like Protein HuR is Associated with Increased COX-2 Expression in Atrophy, High-grade Prostatic Intraepithelial Neoplasia, and Incidental Prostate Cancer in Cystoprostatectomies
Authors: Francesca Barbisan, Roberta Mazzucchelli, Alfredo Santinelli, Antonio Lopez-Beltran, Liang Cheng, Marina Scarpelli, Francesco Montorsi, Rodolfo Montironi
Journal: European Urology (2008)
Reliability of N-terminal pro-brain natriuretic peptide assay in diagnosis of heart failure: cohort study in representative and high risk community populations
Authors: F D R Hobbs
Journal: BMJ (2002)

<b>Introduction - Objective:</b> Migraine is a diseases characterized with severe headaches,with neurological and systemic findings.It is known that atopic disorders may be related with migraine.The purpose of this study is to investigate the prevalence of migraine and to examine whether there is a relationship between atopic disorders,parental history and migraine in asthma patients. <b>Method:</b> A total of 288 asthma outpatients were included. The presence of headache, atopic symptoms and parental history about asthma, atopic disorders and migraine were asked. The patients with headache were consultated by neurology department.The diagnosis of migraine was confirmed by International Headache Society(IHS) criteria. <b>Results:</b> 60.4% of patients described a headache.There were 94 patients (32.6%) with migraine. Atopic symptoms were present in 86.8% of patients.There were asthma in 47.9%,atopic symptoms in %39.6 and migraine in 22.2% of parents. Patients with atopic symptoms were found to have significantly high rate of headache (p=0.007). There was a significant relationship between headache in asthmatic patients and the parental history of asthma(p=0.01), atopic symptoms (p=0.015) and migraine( p=0.038).The prevalence of migraine was significantly high in patients with parental atopic symptoms (p=0.002). <b>Conclusions:</b> There is a high prevalence of migraine headaches in patients with asthma.The coexistence of asthma and headaches may be related with a similar pathophysiological mechanism, in which parental history and common genetic compounds may play role.The headaches,atopic symptoms and family history should be questioned,and clinicians should be careful about the presence of migraine in asthma patients.
The complex relationship between weight and sleep apnoea
Authors: S. R. Patel
Journal: Thorax (2014)

Obesity has long been recognised as the most important reversible risk factor for obstructive sleep apnoea (OSA). Analyses from the Wisconsin Sleep Cohort Study suggest that 41% of adult OSA cases, including 58% of moderate-to-severe cases, are attributable to overweight or obesity.1 As such, weight loss has long been recommended as an ancillary treatment for OSA. Longitudinal analyses from the Sleep Heart Health Study support the notion that weight loss is associated with improvements in OSA severity.2 However, the beneficial impact of weight loss was much less than the adverse effect of the same amount of weight gain in that study suggesting that the relationship between obesity and OSA is more complex than can be explained by an acute (and reversible) unidirectional causal model.

Given evidence that short sleep durations and poor quality sleep predict an increased rate of weight gain,3 ,4 many have postulated that OSA may itself predispose to obesity. Retrospective data indicate that those with recently diagnosed OSA are more likely to have had recent weight gain.5 These findings have been used to support the contention that OSA causes weight gain but of course, this may simply reflect the impact of weight gain on OSA risk. An association between OSA and elevated leptin levels, which fall with CPAP therapy, suggests that an effect of OSA on weight gain may be mediated by leptin resistance whereby improvements in leptin resistance with OSA treatment would produce weight loss.6 Uncontrolled studies have reported that initiation of CPAP therapy is associated with induction of mild weight loss.7 However, given that most patients are educated on the association between obesity and OSA at …
Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial
Authors: Andrew J Davidson, Nicola Disma, Jurgen C de Graaff, Davinia E Withington, Liam Dorris, Graham Bell, Robyn Stargatt, David C Bellinger, Tibor Schuster, Sarah J Arnup, Pollyanna Hardy, Rodney W Hunt, Michael J Takagi, Gaia Giribaldi, Penelope L Hartmann, Ida Salvo, Neil S Morton, Britta S von Ungern Sternberg, Bruno Guido Locatelli, Niall Wilton, Anne Lynn, Joss J Thomas, David Polaner, Oliver Bagshaw, Peter Szmuk, Anthony R Absalom, Geoff Frawley, Charles Berde, Gillian D Ormond, Jacki Marmor, Mary Ellen McCann
Journal: The Lancet (2015)
Induced sputum genes associated with spirometric and radiological disease severity in COPD ex-smokers
Authors: D. Singh, S. M. Fox, R. Tal-Singer, J. Plumb, S. Bates, P. Broad, J. H. Riley, B. Celli
Journal: Thorax (2011)

Background Induced sputum is used to sample inflammatory cells, predominantly neutrophils and macrophages, from the airways of COPD patients. The author's aim was to identify candidate genes associated with the degree of airflow obstruction and the extent of emphysema by expression profiling, and then to confirm these findings for selected candidates using PCR and protein analysis. Methods Two sputum studies were performed in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2–4 COPD ex-smokers from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort. First, gene array profiling at baseline in samples from 148 patients. The findings were replicated in a separate population of 176 patients using real-time PCR. The findings for one selected gene IL-18R were further analysed using immunohistochemistry in lung tissue and induced sputum from patients outside the ECLIPSE cohort. Results Gene expression profiling revealed changes in 277 genes associated with GOLD stage 2 versus 3 and 4, and 198 genes with changes associated with the degree of emphysema (p<0.01 for each gene). Twelve of these candidate genes were analysed by PCR in the replication cohort, with significant changes (p<0.05) observed for 11 genes. IL-18R protein expression was higher on alveolar macrophages in lung tissue of COPD patients (mean 23.2%) compared to controls (mean ex-smokers 2% and non-smokers 2.5%). Conclusion Gene expression profiling in sputum cells identified candidate genes that may play roles in molecular mechanisms associated with COPD. The replication by PCR and protein in different studies confirms these findings, and highlights a potential role for IL-18R upregulation in severe COPD.
JMJD2B Promotes Epithelial–Mesenchymal Transition by Cooperating with β-Catenin and Enhances Gastric Cancer Metastasis
Authors: Li Zhao, Wenjuan Li, Wen Zang, Zhifang Liu, Xia Xu, Han Yu, Qing Yang, Jihui Jia
Journal: Clinical Cancer Research (2013)

This study investigated the role of histone demethylase Jumonji domain-containing protein 2B (JMJD2B) in promoting epithelial-mesenchymal transition (EMT) and underlying molecular mechanisms in the progression of gastric cancer.The induction of EMT by JMJD2B in gastric cancer cells and its underlying mechanisms were examined by a series of assays. In vivo and in vitro assays were performed to clarify invasive potential of JMJD2B in gastric cancer cells. The expression dynamics of JMJD2B were detected using immunohistochemistry in 101 cases of primary gastric cancer tissues.Inhibition of JMJD2B by specific siRNA suppresses EMT of gastric cancer cells, whereas ectopic expression of JMJD2B induces EMT. Importantly, JMJD2B is physically associated with β-catenin and enhances its nuclear localization and transcriptional activity. JMJD2B, together with β-catenin, binds to the promoter of the β-catenin target gene vimentin to increase its transcription by inducing H3K9 demethylation locally. JMJD2B inhibition attenuates migration and invasion of gastric cancer cells in vitro and metastasis in vivo. The expression of JMJD2B was positively correlated with tumor size (P = 0.017), differentiation status (P = 0.002), tumor invasion (P = 0.045), lymph node metastasis (P = 0.000), distant metastasis (P = 0.024), and tumor-node-metastasis (TNM) stage (P = 0.002) in patients with gastric cancer.The data reveal a novel function of JMJD2B in promoting EMT and gastric cancer invasion and metastasis, implicating JMJD2B as a potential target for reversing EMT and intervention of the progression of gastric cancer.
JX06 Selectively Inhibits Pyruvate Dehydrogenase Kinase PDK1 by a Covalent Cysteine Modification
Authors: Wenyi Sun, Zuoquan Xie, Yifu Liu, Dan Zhao, Zhixiang Wu, Dadong Zhang, Hao Lv, Shuai Tang, Nan Jin, Hualiang Jiang, Minjia Tan, Jian Ding, Cheng Luo, Jian Li, Min Huang, Meiyu Geng
Journal: Cancer Research (2015)

Abstract Pyruvate dehydrogenase kinase PDK1 is a metabolic enzyme responsible for switching glucose metabolism from mitochondrial oxidation to aerobic glycolysis in cancer cells, a general hallmark of malignancy termed the Warburg effect. Herein we report the identification of JX06 as a selective covalent inhibitor of PDK1 in cells. JX06 forms a disulfide bond with the thiol group of a conserved cysteine residue (C240) based on recognition of a hydrophobic pocket adjacent to the ATP pocket of the PDK1 enzyme. Our investigations of JX06 mechanism suggested that covalent modification at C240 induced conformational changes at Arginine 286 through Van der Waals forces, thereby hindering access of ATP to its binding pocket and in turn impairing PDK1 enzymatic activity. Notably, cells with a higher dependency on glycolysis were more sensitive to PDK1 inhibition, reflecting a metabolic shift that promoted cellular oxidative stress and apoptosis. Our findings offer new mechanistic insights including how to therapeutically target PDK1 by covalently modifying the C240 residue. Cancer Res; 75(22); 4923–36. ©2015 AACR.
Parathyroid hormone gene expression in hypophosphatemic rats.
Authors: R Kilav, J Silver, T Naveh-Many
Journal: Journal of Clinical Investigation (1995)

Phosphate is central to bone metabolism and we have therefore studied whether parathyroid hormone (PTH) is regulated by dietary phosphate in vivo. Weanling rats were fed diets with different phosphate contents for 3 wk: low phosphate (0.02%), normal calcium (0.6%), normal phosphate (0.3%), and calcium (0.6%); high phosphate (1.2%), high calcium (1.2%). The low phosphate diet led to hypophosphatemia, hypercalcemia, and increased serum 1,25(OH)2D3 together with decreased PTH mRNA levels (25 +/- 8% of controls, P < 0.01) and serum immunoreactive PTH (4.7 +/- 0.8: 22.1 +/- 3.7 pg/ml; low phosphate: control, P < 0.05). A high phosphate diet led to increased PTH mRNA levels. In situ hybridization showed that hypophosphatemia decreased PTH mRNA in all the parathyroid cells. To separate the effect of low phosphate from changes in calcium and vitamin D rats were fed diets to maintain them as vitamin D-deficient and normocalcemic despite the hypophosphatemia. Hypophosphatemic, normocalemic rats with normal serum 1,25(OH)2D3 levels still had decreased PTH mRNAs. Nuclear transcript run-ons showed that the effect of low phosphate was posttranscriptional. Calcium and 1,25(OH)2D3 regulate the parathyroid and we now show that dietary phosphate also regulates the parathyroid by a mechanism which remains to be defined.
Testosterone replacement therapy: current trends and future directions
Authors: E. Nieschlag, H.M. Behre, P. Bouchard, J.J. Corrales, T.H. Jones, G.K. Stalla, S.M. Webb, F.C.W. Wu
Journal: Human Reproduction Update (2004)

Male hypogonadism is characterized by abnormally low serum testosterone levels associated with typical symptoms, including mood disturbance, sexual dysfunction, decreased muscle mass and strength, and decreased bone mineral density. By restoring serum testosterone levels to the normal range using testosterone replacement therapy, many of these symptoms can be relieved. For many years, injectable testosterone esters or surgically implanted testosterone pellets have been the preferred treatment for male hypogonadism. Recently, newer treatment modalities have been introduced, including transdermal patches and gels. The development of a mucoadhesive sustained-release buccal tablet is the latest innovation, which will provide patients with an additional option. The availability of new treatment modalities has helped to renew interest in the management of male hypogonadism, highlighting the need to address a number of important but previously neglected questions in testosterone replacement therapy. These include the risks and benefits of treatment in different patient populations (e.g. the elderly) and the need for evidence-based diagnosis and treatment monitoring guidelines. While some recommendations have been developed in individual countries, up-to-date, internationally accepted evidence-based guidelines that take into account national differences in clinical practice and healthcare delivery would optimize patient care universally.
Prevalence of COPD and emphysema at the time of diagnosis of primary lung cancer
Authors: Monica Linea Vold, Per Christian Moe, Ellinor Ytterstad, Audhild Hjalmarsen
Journal: European Respiratory Journal (2014)

Aims  Chronic obstructive pulmonary disease (COPD) is an independent risk factor for developing lung cancer. The aim of this study was to examine the prevalence of COPD and emphysema as well as impacts on survival.  Methods  We retrospectively reviewed patients with diagnosed primary lung cancer from 2008 to 2010. History, pulmonary function tests and CT scans of the lungs were studied. We used comparisons between groups and Cox regression analysis.  Results  Of the 174 patients, 67 (38.5 %) had COPD and 102 (58.6 %) had emphysema. The male : female ratios were 101 (58.0 %) : 73 (42.0 %), 40 (59.7 %) : 27 (40.3 %) and 65 (63.7 %) : 37 (36.3 %), respectively. When adjusted for age, smoking status, obstructive lung disease and stage of lung cancer, we found a significantly poorer survival in women above 75 years of age (p = 0.0006). Survival was also significantly poorer in patients with undiagnosed COPD without coexisting emphysema (p = 0.008). Among never smokers, survival of women was significantly increased (p = 009).  Conclusion  Emphysema was more common than COPD among our lung cancer patients. Patients with undiagnosed COPD without coexisting emphysema showed the poorest survival.
A new short-term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis
Authors: Emma L. Beckett, Richard L. Stevens, Andrew G. Jarnicki, Richard Y. Kim, Irwan Hanish, Nicole G. Hansbro, Andrew Deane, Simon Keely, Jay C. Horvat, Ming Yang, Brian G. Oliver, Nico van Rooijen, Mark D. Inman, Roberto Adachi, Roy J. Soberman, Sahar Hamadi, Peter A. Wark, Paul S. Foster, Philip M. Hansbro
Journal: Journal of Allergy and Clinical Immunology (2013)