tbuckley/cabot-search huggingface dataset:
A Novel Somatic Mouse Model to Survey Tumorigenic Potential Applied to the Hedgehog Pathway
Authors: Junhao Mao, Keith L. Ligon, Elena Y. Rakhlin, Sarah P. Thayer, Roderick T. Bronson, David Rowitch, Andrew P. McMahon
Journal: Cancer Research (2006)

Abstract We report a novel mouse model for the generation of sporadic tumors and show the efficiency of this approach by surveying Hedgehog (Hh)–related tumors. Up-regulation of the Hh pathway is achieved by conditionally regulated expression of an activated allele of Smoothened (R26-SmoM2) using either sporadic leakage or global postnatal induction of a ubiquitously expressed inducible Cre transgene (CAGGS-CreER). Following postnatal tamoxifen induction, CAGGS-CreER; R26-SmoM2 mice developed tumors with short latency and high penetrance. All mice exhibited rhabdomyosarcoma and basal cell carcinoma; 40% also developed medulloblastoma. In addition, mice showed a novel pancreatic lesion resembling low-grade mucinous cystic neoplasms in humans. In contrast, widespread activation of SmoM2 in the postnatal prostate epithelium results in no detectable morphologic outcome in 12-month-old mice. Comparison of gene expression profiles among diverse tumors identified several signature genes, including components of platelet-derived growth factor and insulin-like growth factor pathways, which may provide a common mechanistic link to the Hh-related malignancies. This experimental model provides a robust tool for exploring the process of Hh-dependent tumorigenesis and the treatment of such tumors. More generally, this approach provides a genetic platform for identifying tumorigenic potential in putative oncogenes and tumor suppressors and for more effective modeling of sporadic cancers in mice. (Cancer Res 2006; 66(20): 10171-7)
Catalase, myeloperoxidase and hydrogen peroxide in cystic fibrosis
Authors: D Worlitzsch, G Herberth, M Ulrich, G Doring
Journal: European Respiratory Journal (1998)

An oxidant-antioxidant imbalance with damaging consequences for the bronchial epithelium has been hypothesized in the airways of patients with cystic fibrosis (CF). It is based on the assumption that neutrophils entering the lumen of the infected airways undergo activation and release toxic oxygen metabolites and myeloperoxidase (MPO), an enzyme which transforms hydrogen peroxide (H2O2) into highly toxic oxygen metabolites. Our aims were to substantiate this hypothesis. H2O2 levels were measured in breath condensates of 63 CF patients and 51 normal subjects. In CF sputum samples, activities and concentrations of MPO and catalase (CAT) were determined. MPO/H2O2-mediated cytotoxicity of CF sputum was measured in cell culture assays. H2O2 levels were similar in CF patients and normal subjects (mean +/-SD) 0.97 +/- 0.69 versus 1.11+/-0.78 microM; p=0.427). Concentrations and activities of CAT (0.31+/-0.18 microM; 105+/-69 units) and MPO (5.93+/-4.8 microM; 87.8+/-75 units) were detectable in 38 CF sputa. Addition of H2O2 to in vitro cells preincubated with CF sputum did not induce cytotoxicity even when CAT was removed from sputum. Sputum MPO together with H2O2 did not inactivate alpha-proteinase inhibitor. Preincubation of MPO with sulphated glycoconjugates or deoxyribonucleic acid (DNA) totally inhibited its cytotoxic effect. In conclusion, catalase, sulphated glycoconjugates and deoxyribonucleic acid may prevent myeolperoxidase-mediated oxygen radical generation in cystic fibrosis sputum.
Effect of prefeeding lipid on food intake and satiety in man.
Authors: C P Sepple, N W Read
Journal: Gut (1990)

Experiments were carried out in normal volunteers to investigate whether preingestion of lipid reduces food intake. In the first set of experiments, 300 ml beef consomme soup with or without 60 g margarine was fed to each of six volunteers, followed 20 minutes later by either a low fat solid meal or a preselected appetising meal. Subjects were allowed to eat as much of the meal as they wished. Preingestion of the high fat soup had no significant effect on the consumption of either of the solid meals and did not influence sensations of hunger or fullness. As we have previously shown that prefeeding a fatty soup delays gastric emptying of a subsequent meal, this suggests that gastric distension may play a relatively minor role in regulating food intake. In the second set of experiments, we studied the effect of ingesting either a high fat breakfast (65 g fat, 927 kcal) or a similar low fat breakfast (8-1 g fat, 418 kcal) on the consumption of a preselected appetising lunch in six healthy volunteers. The high fat breakfast significantly reduced the amount of the meal eaten at lunchtime (p less than 0.02), the total energy intake from the meal (p less than 0.05) and the rate of eating (p less than 0.05) compared with the low fat breakfast. When the subjects were presented with their lunchtime meal they felt significantly less hungry after the high fat breakfast (p less than 0.05). Only a small proportion of either meal (15% of the high fat meal v 12% of the low fat meal) remained in the stomach and plasma glucose concentrations had returned to fasting levels. Plasma triglyceride concentrations were much higher at lunchtime after ingestion of the high fat breakfast (p<0.001). The energy intake from the breakfast and lunch combined was not significantly different on the high fat breakfast day, indicating that the energy consumption at lunch compensates for the amount eaten at breakfast. These results are compatible with the concept that the interaction of nutrients with small intestinal receptors may play a part in limiting food intake.
Relationship between serum IgE and airway responsiveness in adults with asthma☆☆☆★★★
Authors: Jordi Sunyer, Josep M. Antó, Josefina Sabrià, Josep Roca, Ferran Morell, Roberto Rodríguez-Roisin, María J. Rodrigo
Journal: Journal of Allergy and Clinical Immunology (1995)
Pancytopenia associated with clonazepam
Authors: Marnelli A Bautista-Quach, Yu-Min Liao, Chung-Tsen Hsueh
Journal: Journal of Hematology & Oncology (2010)

Abstract We report a case of a 48-year-old Chinese female with end-stage renal disease and chronic anemia on hemodialysis. Clonazepam was prescribed for myoclonus disorder two weeks prior to her hospitalization. Subsequently, she was hospitalized for neutropenic fever with thrombocytopenia and worsening anemia. Bone marrow examination demonstrated a markedly hypocellular marrow (10-20% total cellularity). Clonazepam was discontinued, with gradual improvement of thrombocytopenia, and neutropenia in 1-2 weeks. To our knowledge, this is the first reported case of pancytopenia associated with clonazepam. We recommend patients taking clonazepam to be monitored with regular complete blood count to check for clinically significant pancytopenia or thrombocytopenia.
Comparison of gel contraction mediated by airway smooth muscle cells from patients with and without asthma
Authors: H. Matsumoto, L. M Moir, B. G G Oliver, J. K Burgess, M. Roth, J. L Black, B. E McParland
Journal: Thorax (2007)

<b>Backgrounds:</b> Exaggerated bronchial constriction is the most significant and life threatening response of patients with asthma to inhaled stimuli. However, few studies have investigated the contractility of airway smooth muscle (ASM) from these patients. The purpose of this study was to establish a method to measure contraction of ASM cells by embedding them into a collagen gel, and to compare the contraction between subjects with and without asthma. <b>Methods:</b> Gel contraction to histamine was examined in floating gels containing cultured ASM cells from subjects with and without asthma following overnight incubation while unattached (method 1) or attached (method 2) to casting plates. Smooth muscle myosin light chain kinase protein levels were also examined. <b>Results:</b> Collagen gels containing ASM cells reduced in size when stimulated with histamine in a concentration-dependent manner and reached a maximum at a mean (SE) of 15.7 (1.2) min. This gel contraction was decreased by inhibitors for phospholipase C (U73122), myosin light chain kinase (ML-7) and Rho kinase (Y27632). When comparing the two patient groups, the maximal decreased area of gels containing ASM cells from patients with asthma was 19 (2)% (n = 8) using method 1 and 22 (3)% (n = 6) using method 2, both of which were greater than that of cells from patients without asthma: 13 (2)% (n = 9, p = 0.05) and 10 (4)% (n = 5, p = 0.024), respectively. Smooth muscle myosin light chain kinase levels were not different between the two groups. <b>Conclusion:</b> The increased contraction of asthmatic ASM cells may be responsible for exaggerated bronchial constriction in asthma.
Cardiological Problems in Younger Women: Including Those of Pregnancy and the Puerperium
Authors: A. R. Gilchrist
Journal: BMJ (1963)

Women are endowed with certain advantages.They face fewer hazards than the male, whom they tend to outlive.In infancy and childhood mortality among boys is greater than in girls, and in middle life ischaemic heart disease takes a much greater toll among men.The Registrar-General's figures tell us, for instance, that in the five-year period 1953-7 the mortality from coronary artery disease in the age-group 55-59 years was four and a half times higher for men than for women.Age and sex may thus influence the development and progression of vascular disease.Life expectancy for the female now exceeds that of the male by a greater number of years than ever before.Hence a closer study of the "feminine" response to long-term cardiovascular damage ought to increase our understanding of the basic processes involved. CORONARY ARTERY DISEASE
Responses to the Seasonal Pattern Assessment Questionnaire in Different Seasons
Authors: Eiliv Lund, Vidje Hansen
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The study investigated whether results on the Seasonal Pattern Assessment Questionnaire, which is used for diagnosis of seasonal affective disorder, differed by the season in which the questionnaire was completed. METHOD: Every third month from March 1997 to February 1998, a population-based panel of 200 men and women age 27–72 years in Gamvik, northern Norway, completed a standardized questionnaire that included all items from the Seasonal Pattern Assessment Questionnaire. RESULTS: The average score for seasonal affective disorder changed over the year. The difference between the highest score, in March, and the lowest, in September, was 8.8%. CONCLUSIONS: Results on the Seasonal Pattern Assessment Questionnaire varied by season, but did not vary by seasonal differences in the amount of daylight.
Diabetes Medication Satisfaction Tool
Authors: Roger T. Anderson, Cynthia J. Girman, Manjiri D. Pawaskar, Fabian T. Camacho, Jorge Calles, William S. Kelly, Carla DeMuro, Rajesh Balkrishnan
Journal: Diabetes Care (2008)

To develop and test a patient questionnaire on treatment satisfaction with diabetes regimens.Survey items were developed from community clinic focus groups, pretested in patients with diabetes, and examined in two samples of treated patients.Sixteen items performed well in assessing treatment experiences: ease and convenience, lifestyle burdens, well-being, and medical control. Construct validity was supported by associations (P < 0.05) with treatment complexity, self-rated glucose control, health worries, and A1C. Internal consistency ranged from 0.89 to 0.95.The Diabetes Medication Satisfaction Tool offers a comprehensive assessment of patient acceptability, with diabetes therapy useful for individualizing therapeutic decision making.
Incidence of small-intestinal mucosal abnormalities and of clinical coeliac disease in the relatives of children with coeliac disease
Authors: D. C. Robinson, A. J. Watson, E. H. Wyatt, J. M. Marks, D. F. Roberts
Journal: Gut (1971)

Evidence is presented of a higher than normal incidence both of clinical coeliac disease and of small-intestinal mucosal abnormalities in relatives of children with coeliac disease. In such relatives the incidence of mucosal abnormality may differ from the incidence of clinical coeliac disease. The data show an absence of any simple Mendelian pattern of inheritance: in place of the hypothesis that inheritance is through a dominant gene of reduced penetrance, it is argued that the pathogenesis of coeliac disease is multifactorial, the genetic basis of susceptibility being polygenic and interacting with environmental factors. On this hypothesis the relative contributions of inheritance and environment to liability to the clinical condition are estimated, the genetic component being 45% +/- 9. Environmental factors appear more important in the development of mucosal abnormality.
Imatinib Is Effective in Children With Previously Untreated Chronic Myelogenous Leukemia in Early Chronic Phase: Results of the French National Phase IV Trial
Authors: Frédéric Millot, André Baruchel, Joelle Guilhot, Arnaud Petit, Thierry Leblanc, Yves Bertrand, Françoise Mazingue, Patrick Lutz, Cécile Vérité, Christian Berthou, Claire Galambrun, Frédéric Bernard, Karima Yacouben, Pierre Bordigoni, Christine Edan, Yves Reguerre, Gérard Couillault, Françoise Méchinaud, Jean-Michel Cayuela, François Guilhot
Journal: Journal of Clinical Oncology (2011)

Purpose Imatinib is the standard of care in adults with chronic myeloid leukemia (CML) in chronic phase (CP). Only a few studies to assess efficacy in children have been performed. We report on the results of the French prospective trial (ClinicalTrials.gov identifier NCT00845221) conducted in children and adolescents with newly diagnosed CML in CP. Patients and Methods A total of 44 patients from age 10 months to 17 years with newly diagnosed CML in CP received daily imatinib 260 mg/m 2 . Progression-free survival, responses, and tolerance were evaluated. Results With a median follow-up times of 31 months (range, 11 to 64 months), the estimated progression-free survival rate at 36 months was 98% (95% CI, 85% to 100%). A complete hematologic response was achieved in 98% of the patients. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were 61% and 31% at 12 months, respectively. During follow-up, CCyR and MMR were achieved in 36 children (77%) and 25 children (57%), respectively. Overall, 30% of the patients discontinued imatinib, mainly because of unsatisfactory response. The most common adverse events were neutropenia and musculoskeletal events. Conclusion Imatinib is effective in children with CML in CP with response rates similar to rates reported in adults. The adverse effects are acceptable, but longer follow-up studies are required to fully assess the long-term impact.
Disease Control Rate at 8 Weeks Predicts Clinical Benefit in Advanced Non–Small-Cell Lung Cancer: Results From Southwest Oncology Group Randomized Trials
Authors: Primo N. Lara, Mary W. Redman, Karen Kelly, Martin J. Edelman, Stephen K. Williamson, John J. Crowley, David R. Gandara
Journal: Journal of Clinical Oncology (2008)

Tumor shrinkage categorized as complete response (CR) or partial response (PR) is a fundamental efficacy measure for new cancer treatments and often considered a surrogate for overall survival. However, for any given treatment, many more patients typically achieve stable disease (SD) or have progressive disease (PD) than achieve response. We hypothesized that PD (or its converse, disease control rate [DCR], consisting of CR, PR, SD) is a stronger predictor of survival than response alone in advanced non-small-cell lung cancer (NSCLC), and that this determination might be assessable early on during therapy.Data from 984 NSCLC patients entered onto three randomized Southwest Oncology Group trials of platinum-based chemotherapy were pooled and subjected to Landmark survival analysis. Patients were categorized according to proportions alive at weeks 8, 14, and 20 after registration, as well as response status. Elements were fitted into a Cox proportional hazards model.Tumor response (CR, PR) was seen in 260 patients (27%). Median time to response, time to progression, and survival time were 2.0, 4.3 and 8.9 months, respectively. Median survival times among patients with CR/PR, SD, or PD were 13.5, 8.4, and 3.1 months, respectively. Of 892 patients alive at week 8, DCR was 62%. Although CR/PR at week 8 was associated with longer survival (hazard ratio [HR] = 0.61; P < .001), DCR was superior in predicting survival (HR = 0.45; P < .0001).DCR at week 8 is a more powerful predictor of subsequent survival than is the traditional tumor response rate in advanced NSCLC and provides an early assessment of subsequent outcome.
Methionine-induced positive inotropic effect in rat heart: possible role of phospholipid N-methylation.
Authors: V Panagia, M P Gupta, P K Ganguly, N S Dhalla
Journal: Circulation Research (1988)

Perfusion of isolated rat heart with L-methionine produced a positive inotropic effect that was temporally preceded, as well as accompanied, by an increase of methyl group incorporation into N-methylated phospholipids of the myocardium. Maximal increase in contractile force development was associated with maximal methyl group incorporation. Both parameters showed a dose-related dependence on methionine and correlated positively (r = 0.965) upon regression analysis of the data. The presence of adenosine, L-homocysteine thiolactone and erythro-9-(2-hydroxy-3-nonyl) adenine in the perfusion medium inhibited the positive inotropic effect as well as the incorporation of methyl groups into phospholipids. Cycloleucine, an inhibitor of S-adenosylmethionine synthetase, also reduced the increase in contractility by methionine. Methionine-induced positive inotropic effect could be modulated by varying Ca2+ concentration in the perfusate and was inhibited by ryanodine, a blocker of sarcoplasmic reticular Ca2+ release. These observations indicate that L-methionine may serve as a powerful positive inotropic agent and suggest that phospholipid N-methylation plays an important role in functional activity of rat heart.
Positive and negative signals transduced through surface immunoglobulins in human B cells
Authors: Mitsufumi Mayumi, Tsuyoshi Ishigami, Shu-Ichi Kanazashi, Koji Yamaoka, Shin-Ichi Sumimoto, Toshio Heike, Kenji Katamura, Daisuke Hata, Kwang-Myong Kim
Journal: Journal of Allergy and Clinical Immunology (1994)
The Relative Contribution of Prepregnancy Overweight and Obesity, Gestational Weight Gain, and IADPSG-Defined Gestational Diabetes Mellitus to Fetal Overgrowth
Authors: Mary Helen Black, David A. Sacks, Anny H. Xiang, Jean M. Lawrence
Journal: Diabetes Care (2012)

OBJECTIVE The International Association of Diabetes in Pregnancy Study Groups (IADPSG) criteria for diagnosis of gestational diabetes mellitus (GDM) identifies women and infants at risk for adverse outcomes, which are also strongly associated with maternal overweight, obesity, and excess gestational weight gain. RESEARCH DESIGN AND METHODS We conducted a retrospective study of 9,835 women who delivered at ≥20 weeks’ gestation; had a prenatal, 2-h, 75-g oral glucose tolerance test; and were not treated with diet, exercise, or antidiabetic medications during pregnancy. Women were classified as having GDM based on IADPSG criteria and were categorized into six mutually exclusive prepregnancy BMI/GDM groups: normal weight ± GDM, overweight ± GDM, and obese ± GDM. RESULTS Overall, 5,851 (59.5%) women were overweight or obese and 1,892 (19.2%) had GDM. Of those with GDM, 1,443 (76.3%) were overweight or obese. The prevalence of large-for-gestational-age (LGA) infants was significantly higher for overweight and obese women without GDM compared with their normal-weight counterparts. Among women without GDM, 21.6% of LGA infants were attributable to maternal overweight and obesity, and the combination of being overweight or obese and having GDM accounted for 23.3% of LGA infants. Increasing gestational weight gain was associated with a higher prevalence of LGA in all groups. CONCLUSIONS Prepregnancy overweight and obesity account for a high proportion of LGA, even in the absence of GDM. Interventions that focus on maternal overweight/obesity and gestational weight gain, regardless of GDM status, have the potential to reach far more women at risk for having an LGA infant.
Molecular Adaptation during a Rapid Adaptive Radiation
Authors: Maxim V. Kapralov, Antonina A. Votintseva, Dmitry A. Filatov
Journal: Molecular Biology and Evolution (2013)

"Explosive" adaptive radiations on islands remain one of the most puzzling evolutionary phenomena and the evolutionary genetic processes behind such radiations remain unclear. Rapid morphological and ecological evolution during island radiations suggests that many genes may be under fairly strong selection, although this remains untested. Here, we report that during a rapid recent diversification in the Hawaiian endemic plant genus Schiedea (Caryophyllaceae), 5 in 36 studied genes evolved under positive selection. Positively selected genes are involved in defence mechanisms, photosynthesis, and reproduction. Comparison with eight mainland plant groups demonstrates both the relaxation of purifying selection and more widespread positive selection in Hawaiian Schiedea. This provides compelling evidence that adaptive evolution of protein-coding genes may play a significant role during island adaptive radiations.
Dutch patients, retail chicken meat and poultry share the same ESBL genes, plasmids and strains
Authors: M.A. Leverstein-van Hall, C.M. Dierikx, J. Cohen Stuart, G.M. Voets, M.P. van den Munckhof, A. van Essen-Zandbergen, T. Platteel, A.C. Fluit, N. van de Sande-Bruinsma, J. Scharinga, M.J.M. Bonten, D.J. Mevius
Journal: Clinical Microbiology and Infection (2011)
Cicatricial pemphigoid with circulating IgA and IgG autoantibodies to the central portion of the BP180 ectodomain: Beneficial effect of adjuvant therapy with high-dose intravenous immunoglobulin
Authors: Martin Leverkus a, Matthias Georgi a, Zhuxiang Nie b, Takashi Hashimoto b, Eva-Bettina Bröcker a, Detlef Zillikens a
Journal: Journal of the American Academy of Dermatology (2002)
Identification of Circulating miR-101, miR-375 and miR-802 as Biomarkers for Type 2 Diabetes
Authors: Chigusa Higuchi, Atsuko Nakatsuka, Jun Eguchi, Sanae Teshigawara, Motoko Kanzaki, Akihiro Katayama, Satoshi Yamaguchi, Naoto Takahashi, Kazutoshi Murakami, Daisuke Ogawa, Sakiko Sasaki, Hirofumi Makino, Jun Wada
Journal: Metabolism (2014)
Immunotherapy generates selective pressure for acquisition of immunogenic neoantigens in escape tumors
Authors: Jenny H Pan, Suman Vodnala, Robert L Eil, Zhiya Yu, Jared J Gartner, David Clever, Rahul Roychoudhuri, Shashank J Patel, Christopher A Klebanoff, Madhusudhanan Sukumar, Tori Yamamoto, Nicholas P Restifo
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Host immunosurveillance as a mechanism to promote tumor growth or to suppress tumor development is well studied. It is less known how immuno-selective pressure in the form of immunotherapies can instruct the immune system during this process. We hypothesized that the application