tbuckley/cabot-search huggingface dataset:
Virulence Factors of <i>Helicobacter pylori</i> Responsible for Gastric Diseases in Mongolian Gerbil
Authors: Keiji Ogura, Shin Maeda, Masafumi Nakao, Takeshi Watanabe, Mayumi Tada, Toshimasa Kyutoku, Haruhiko Yoshida, Yasushi Shiratori, Masao Omata
Journal: The Journal of Experimental Medicine (2000)

Helicobacter pylori infection induces various gastroduodenal diseases. We examined the role of two genes, vacA and cagE, in the gastric pathogenesis induced by H. pylori using a long-term (62 wk) animal model. Reportedly, both genes are associated with the virulence of H. pylori: vacA encodes vacuolating cytotoxin, and cagE, with other genes in the cag pathogenicity islands, encodes a type IV secretion system. Mongolian gerbils were challenged in this study by a wild-type TN2 strain and its isogenic mutants of cagE or vacA. The wild-type and vacA mutants induced severe gastritis, whereas cagE mutants induced far milder changes. Gastric ulcer was induced at the highest rate (22/23) by the wild-type TN2, followed by the vacA mutant (19/28). No ulcer was found in the gerbils infected with the cagE mutant (0/27) or in controls (0/27). Intestinal metaplasia was also found in the gerbils infected with the wild-type (14/23) or vacA mutant (15/28). Gastric cancer developed in one gerbil with wild-type infection and in one with vacA mutant infection. In conclusion, the knocking out of the cagE gene deprived wild-type H. pylori of the pathogenicity for gastritis and gastric ulcer, suggesting that the secretion system encoded by cag pathogenicity island genes plays an essential role.
Pre-illness dietary factors in inflammatory bowel disease.
Authors: S Reif, I Klein, F Lubin, M Farbstein, A Hallak, T Gilat
Journal: Gut (1997)

The effect of environmental factors has been demonstrated in the pathogenesis of inflammatory bowel disease (IBD). Nutrition may be one of them.To investigate the pre-illness diet in patients with recent IBD in comparison with matched population and clinic controls.Quantified dietary histories were obtained from 87 patients with recent IBD (54 ulcerative colitis (UC) and 33 Crohn's disease (CD)) and 144 controls. Odds ratios (OR) for IBD were derived for intake levels of various foods.A high sucrose consumption was associated with an increased risk for IBD (OR 2.85 (p = 0.03) against population controls and 5.3 (p = 0.00) against clinic controls). Lactose consumption showed no effect while fructose intake was negatively associated with risk for IBD (NS). Similar trends were noted in UC and CD. A high fat intake was associated with an increased risk for UC; this was particularly marked for animal fat (OR 4.09, p = 0.02) and cholesterol (OR 4.57, p = 0.02). A high intake of fluids (p = 0.04), magnesium (p = 0.04), vitamin C, and fruits (NS) was negatively associated with the risk for IBD, while a positive association was found for retinol (p = 0.01). Most of the findings were similar in UC and CD except for potassium and vegetable consumption which showed a negative association only with risk for CD.An association was found between pre-illness diet and subsequent development of UC and CD. The effect of dietary components may be primary or modulatory.
Superiority of Allogeneic Hematopoietic Stem-Cell Transplantation Compared With Chemotherapy Alone in High-Risk Childhood T-Cell Acute Lymphoblastic Leukemia: Results From ALL-BFM 90 and 95
Authors: André Schrauder, Alfred Reiter, Helmut Gadner, Dietrich Niethammer, Thomas Klingebiel, Bernhard Kremens, Christina Peters, Wolfram Ebell, Martin Zimmermann, Felix Niggli, Wolf-Dieter Ludwig, Hansjörg Riehm, Karl Welte, Martin Schrappe
Journal: Journal of Clinical Oncology (2006)

The role of hematopoietic stem-cell transplantation (SCT) in first complete remission (CR1) for children with very high-risk (VHR) acute lymphoblastic leukemia (ALL) is still under critical discussion.In the ALL-Berlin-Frankfurt-Münster (BFM) 90 and ALL-BFM 95 trials, 387 patients were eligible for SCT if there was a matched sibling donor (MSD). T-cell ALL (T-ALL) patients with poor in vivo response to initial treatment represented the largest homogeneous subgroup within VHR patients.Of 191 high-risk (HR) T-ALL patients, 179 patients (94%) achieved CR1. Twenty-three patients received an MSD-SCT. Furthermore, in trial ALL-BFM 95, eight matched unrelated donors (MUDs) and five mismatched family donors (MMFDs) were used. The median time to SCT was 5 months (range, 2.4 to 10.8 months) from diagnosis. The 5-year disease-free survival (DFS) was 67% +/- 8% for 36 patients who received an SCT in CR1 and 42% +/- 5% for the 120 patients treated with chemotherapy alone having an event-free survival time of at least the median time to transplantation (Mantel-Byar, P = .01). Overall survival (OS) rate for the SCT group was 67% +/- 8% at 5 years, whereas patients treated with chemotherapy alone had an OS rate of 47% +/- 5% at 5 years (Mantel-Byar, P = .01). Outcome of patients who received MSD-SCT versus MUD-/MMFD-SCT was comparable (DFS, 65% +/- 10% v 69% +/- 13%, respectively). However, relapses only occurred after MSD-SCT (eight of 23 patients), whereas treatment-related mortality only occurred after MUD-/MMFD-SCT (four of 13 patients).SCT in CR1 is superior to treatment with chemotherapy alone for childhood HR-T-ALL.
Endogenous Steroid Hormone Concentrations and Risk of Breast Cancer: Does the Association Vary by a Woman's Predicted Breast Cancer Risk?
Authors: A. Heather Eliassen, Stacey A. Missmer, Shelley S. Tworoger, Susan E. Hankinson
Journal: Journal of Clinical Oncology (2006)

To examine whether the associations of endogenous estrogens and testosterone with breast cancer risk differ between high- and low-risk women, as determined by the Gail model and the Rosner and Colditz model, and by family history of breast cancer.We conducted a prospective nested case-control study within the Nurses' Health Study. From 1989 or 1990 until June 2000, blood samples were collected, 418 breast cancer patient cases were identified, and two controls (total n = 817) were matched to each case. We classified women as high or low risk based on their family history of breast cancer, their 5-year Gail risk score, and their 5-year Rosner and Colditz risk score. Multivariate relative risks (RR) and 95% CI were calculated by unconditional logistic regression, adjusting for matching and breast cancer risk factors.Estrone sulfate was statistically significantly associated with breast cancer risk among women with low (< 1.66%) and high (> or = 2.52%; 75th percentile) Gail predicted risk (fourth v first quartile RR = 3.6; 95% CI, 1.9 to 7.0; RR = 2.5; 95% CI, 1.2 to 5.1, respectively). Testosterone results were similar across strata of predicted risk, with two times the risk in the fourth (v first) quartile. Estradiol appeared more strongly associated with breast cancer in women with higher predicted risk (RR = 4.5; 95% CI, 2.1 to 9.5) compared with women with lower risk (RR = 2.1; 95% CI, 1.2 to 3.6), but differences were not statistically significant. Results were similar across predicted Rosner and Colditz risk scores.These data suggest that higher levels of endogenous estrogens and testosterone are associated with increased breast cancer risk, regardless of predicted risk or family history of breast cancer.
Treatment With Dimethylthiourea Prevents Left Ventricular Remodeling and Failure After Experimental Myocardial Infarction in Mice
Authors: Shintaro Kinugawa, Hiroyuki Tsutsui, Shunji Hayashidani, Tomomi Ide, Nobuhiro Suematsu, Shinji Satoh, Hideo Utsumi, Akira Takeshita
Journal: Circulation Research (2000)

Oxidative stress might play an important role in the progression of left ventricular (LV) remodeling and failure that occur after myocardial infarction (MI). We determined whether reactive oxygen species (ROS) are increased in the LV remodeling and failure in experimental MI with the use of electron spin resonance spectroscopy and whether the long-term administration of dimethylthiourea (DMTU), hydroxyl radical (.OH) scavenger, could attenuate these changes. We studied 3 groups of mice: sham-operated (sham), MI, and MI animals that received DMTU (MI+DMTU). Drugs were administered to the animals daily via intraperitoneal injection for 4 weeks.OH was increased in the noninfarcted myocardium from MI animals, which was abolished in MI+DMTU. Fractional shortening was depressed by 65%, LV chamber diameter was increased by 53%, and the thickness of noninfarcted myocardium was increased by 37% in MI. MI+DMTU animals had significantly better LV contractile function and smaller increases in LV chamber size and hypertrophy than MI animals. Changes in myocyte cross-sectional area determined with LV mid-free wall specimens were concordant with the wall thickness data. Collagen volume fraction of the noninfarcted myocardium showed significant increases in the MI, which were also attenuated with DMTU. Myocardial matrix metalloproteinase-2 activity, measured with gelatin zymography, was increased with MI after 7 and 28 days, which was attenuated in MI+DMTU. Thus, the attenuation of increased myocardial ROS and metalloproteinase activity with DMTU may contribute, at least in part, to its beneficial effects on LV remodeling and failure. Therapies designed to interfere with oxidative stress might be beneficial to prevent myocardial failure.
Making, Baking, and Breaking: the Synthesis, Storage, and Hydrolysis of Neutral Lipids
Authors: Kelly V. Ruggles, Aaron Turkish, Stephen L. Sturley
Journal: Annual Review of Nutrition (2013)

The esterification of amphiphilic alcohols with fatty acids is a ubiquitous strategy implemented by eukaryotes and some prokaryotes to conserve energy and membrane progenitors and simultaneously detoxify fatty acids and other lipids. This key reaction is performed by at least four evolutionarily unrelated multigene families. The synthesis of this "neutral lipid" leads to the formation of a lipid droplet, which despite the clear selective advantage it confers is also a harbinger of cellular and organismal malaise. Neutral lipid deposition as a cytoplasmic lipid droplet may be thermodynamically favored but nevertheless is elaborately regulated. Optimal utilization of these resources by lipolysis is similarly multigenic in determination and regulation. We present here a perspective on these processes that originates from studies in model organisms, and we include our thoughts on interventions that target reductions in neutral lipids as therapeutics for human diseases such as obesity and diabetes.
Contribution of respiratory acidosis to diaphragmatic fatigue at exercise
Authors: S. Jonville, N. Delpech, A. Denjean
Journal: European Respiratory Journal (2002)

The factors that may modulate ventilatory muscle fatigue during exercise are controversial. In this study the contribution of acidosis to exercise-induced diaphragmatic fatigue was investigated, using measurements of the twitch mouth pressure response (tw,<i>P</i><sub>mo</sub>) to cervical magnetic stimulation. After learning sessions, 14 healthy subjects performed two cycling tests (at 60% of maximal aerobic power for 16 min), one while breathing spontaneously (mean minute ventilation (<i>V</i>′e) 67.9 L·min<sup>−1</sup>) and the other while hypoventilating voluntarily (mean<i>V</i>′<sub>E</sub> 53.8 L·min<sup>−1</sup>). Exercise was voluntarily set at a moderate power to avoid a fatiguing effect of exercise <i>per se</i>. As compared with spontaneous breathing (SB), voluntary hypoventilation (VHV) significantly increased mean carbon dioxide tension in arterial blood (<i>P</i><sub>a,CO<sub>2</sub></sub>) (51 mmHg <i>versus</i> 41 mmHg) and significantly decreased arterial pH (7.28 <i>versus</i> 7.34). After 10 min of SB test, tw,<i>P</i><sub>mo</sub> was unchanged compared to the baseline value (19.1 <i>versus</i> 18.5 cmH<sub>2</sub>O) whereas tw,<i>P</i><sub>mo</sub> fell significantly as compared to baseline (17.1 <i>versus</i> 18.5 cmH<sub>2</sub>O) and to SB (17.1 <i>versus</i> 19.1 cmH<sub>2</sub>O) after the VHV test. The results of this study suggest that exposure to hypercapnia may impair respiratory muscle function. This impairment could be more clinically relevant in patients with chronic obstructive lung disease.
Targeting Metabolic Scavenging in Pancreatic Cancer
Authors: Costas A. Lyssiotis, Lewis C. Cantley
Journal: Clinical Cancer Research (2013)

Abstract Pancreatic tumor metabolism is rewired to facilitate survival and growth in a nutrient-depleted environment. This leads to a unique dependence on metabolic recycling and scavenging pathways, including NAD salvage. Targeting this pathway in pancreatic cancer disrupts metabolic homeostasis and impairs tumor growth. Clin Cancer Res; 20(1); 6–8. ©2013 AACR.
Abnormal Lung Aging in Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis
Authors: Rosa Faner, Mauricio Rojas, William MacNee, Alvar Agustí
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Aging is a natural process characterized by progressive functional impairment and reduced capacity to respond appropriately to environmental stimuli and injury. The incidence of two common chronic respiratory diseases (chronic obstructive pulmonary disease [COPD] and idiopathic pulmonary fibrosis [IPF]) increases with advanced age. It is plausible, therefore, that abnormal regulation of the mechanisms of normal aging may contribute to the pathobiology of both COPD and IPF. This review discusses the available evidence supporting a number of aging mechanisms, including oxidative stress, telomere length regulation, cellular and immunosenescence, as well as changes in a number of antiaging molecules and the extracellular matrix, which are abnormal in COPD and/or IPF. A better understanding of these abnormalities may help in the design of novel and better therapeutic interventions for these patients.
Phosphorylation of EZH2 Activates STAT3 Signaling via STAT3 Methylation and Promotes Tumorigenicity of Glioblastoma Stem-like Cells
Authors: Eunhee Kim, Misuk Kim, Dong-Hun Woo, Yongjae Shin, Jihye Shin, Nakho Chang, Young Taek Oh, Hong Kim, Jingeun Rheey, Ichiro Nakano, Cheolju Lee, Kyeung Min Joo, Jeremy N. Rich, Do-Hyun Nam, Jeongwu Lee
Journal: Cancer Cell (2013)
Effect of Niacin on Lipid and Lipoprotein Levels and Glycemic Control in Patients With Diabetes and Peripheral Arterial Disease
Authors: Marshall B. Elam, Donald B. Hunninghake, Kathryn B. Davis, Rekha Garg, Craig Johnson, Debra Egan, John B. Kostis, David S. Sheps, Eliot A. Brinton, None for the ADMIT Investigators
Journal: JAMA (2000)

ContextAlthough niacin increases low levels of high-density lipoprotein cholesterol (HDL-C), which frequently accompany diabetes, current guidelines do not recommend use of niacin in patients with diabetes because of concerns about adverse effects on glycemic control; however, this is based on limited clinical data.ObjectiveTo determine the efficacy and safety of lipid-modifying dosages of niacin in patients with diabetes.Design and SettingProspective, randomized placebo-controlled clinical trial conducted in 6 clinical centers from August 1993 to December 1995.ParticipantsA total of 468 participants, including 125 with diabetes, who had diagnosed peripheral arterial disease.InterventionsAfter an active run-in period, participants were randomly assigned to receive niacin (crystalline nicotinic acid), 3000 mg/d or maximum tolerated dosage (n = 64 with diabetes; n = 173 without diabetes), or placebo (n = 61 with diabetes; n = 170 without diabetes) for up to 60 weeks (12-week active run-in and 48-week double-blind).Main Outcome MeasuresPlasma lipoprotein, glucose, hemoglobin A1c (HbA1c), alanine aminotransferase, and uric acid levels; hypoglycemic drug use; compliance; and adverse events, in patients with diabetes vs without who were receiving niacin vs placebo.ResultsNiacin use significantly increased HDL-C by 29% and 29% and decreased triglycerides by 23% and 28% and low-density lipoprotein cholesterol (LDL-C) by 8% and 9%, respectively, in participants with and without diabetes (P<.001 for niacin vs placebo for all). Corresponding changes in participants receiving placebo were increases of 0% and 2% in HDL-C and increases of 7% and 0% in triglycerides, and increases of 1% and 1% in LDL-C. Glucose levels were modestly increased by niacin (8.7 and 6.3 mg/dL [0.4 and 0.3 mmol/L]; P = .04 and P<.001) in participants with and without diabetes, respectively. Levels of HbA1c were unchanged from baseline to follow-up in participants with diabetes treated with niacin. In participants with diabetes treated with placebo, HbA1c decreased by 0.3% (P = .04 for difference). There were no significant differences in niacin discontinuation, niacin dosage, or hypoglycemic therapy in participants with diabetes assigned to niacin vs placebo.ConclusionsOur study suggests that lipid-modifying dosages of niacin can be safely used in patients with diabetes and that niacin therapy may be considered as an alternative to statin drugs or fibrates for patients with diabetes in whom these agents are not tolerated or fail to sufficiently correct hypertriglyceridemia or low HDL-C levels.
The non-peptide thrombopoietin receptor agonist eltrombopag stimulates megakaryopoiesis in bone marrow cells from patients with relapsed multiple myeloma
Authors: Jee-Yeong Jeong, Michelle S Levine, Nirmalee Abayasekara, Nancy Berliner, Jacob Laubach, Gary J Vanasse
Journal: Journal of Hematology & Oncology (2015)

Thrombocytopenia is a significant problem in patients with relapsed or refractory multiple myeloma, precipitating a need for supportive platelet transfusions and necessitating decreases in delivered doses of chemotherapy. Eltrombopag is a non-peptide, small molecule thrombopoietin (TPO) receptor agonist that promotes megakaryopoiesis similar to endogenous human TPO and may be an effective agent for thrombocytopenia in this patient population. We examined the effects of eltrombopag on megakaryocyte colony-forming capacity in CD34+ cells in patients with multiple myeloma and investigated its impact on proliferation, viability, and apoptosis in primary CD138+ human myeloma cells and myeloma cell lines. Eltrombopag at doses of 0.1 to 100 μM did not enhance proliferation of primary human CD138+ multiple myeloma cells from patients with relapsed disease or myeloma cell lines when used alone or in combination with erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) and did not alter cell viability nor apoptosis of human myeloma cells exposed to bortezomib and lenalidomide. Eltrombopag stimulated megakaryopoiesis in human CD34+ cells from normal individuals and from patients with relapsed multiple myeloma via activation of Akt signaling pathways. These results provide proof-of-principle supporting the design of future clinical studies examining eltrombopag for the treatment of thrombocytopenia in patients with advanced multiple myeloma.
Sports-related concussion increases the risk of subsequent injury by about 50% in elite male football players
Authors: Anna Nordström, Peter Nordström, Jan Ekstrand
Journal: British Journal of Sports Medicine (2014)

Background Little is known about the short-term and long-term sequelae of concussion, and about when athletes who have sustained such injuries can safely return to play. Purpose To examine whether sports-related concussion increases the risk of subsequent injury in elite male football players. Study design Prospective cohort study. Methods Injuries were registered for 46 male elite football teams in 10 European countries in the 2001/2002–2011/2102 seasons. Two survival models were used to analyse whether concussion increased the subsequent risk of an injury in the first year. Results During the follow-up period, 66 players sustained concussions and 1599 players sustained other injuries. Compared with the risk following other injuries, concussion was associated with a progressively increased risk of a subsequent injury in the first year (0 to &lt;3 months, HR=1.56, 95% CI 1.09 to 2.23; 3 to &lt;6 months, HR=2.78, 95% CI 1.58 to 4.89; 6–12 months, HR=4.07, 95% CI 2.14 to 7.76). In the second model, after adjustment for the number of injuries in the year preceding the concussion, this injury remained significantly associated with the risk of subsequent injury in the first year (HR=1.47, 95% CI 1.05 to 2.05). Conclusions Concussion was a risk factor for sustaining subsequent injury within the following year. In-depth medical evaluation, which includes neurological and cognitive assessment, is warranted within the concussion management and return-to- play process.
Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock
Authors: Emanuel Rivers, Bryant Nguyen, Suzanne Havstad, Julie Ressler, Alexandria Muzzin, Bernhard Knoblich, Edward Peterson, Michael Tomlanovich
Journal: New England Journal of Medicine (2001)

Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit.
A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy
Authors: Michal F Kaminski, Marcin Polkowski, Ewa Kraszewska, Maciej Rupinski, Eugeniusz Butruk, Jaroslaw Regula
Journal: Gut (2014)

<h3>Abstract</h3> G protein-coupled receptors (GPCRs) and other membrane proteins are valuable drug targets, and their dynamic nature makes them attractive systems for study with molecular dynamics simulations and free energy approaches. Here, we report the development, implementation, and validation of OPLS-AA/M force field parameters to enable simulations of these systems. These efforts include the introduction of post-translational modifications including lipidations and phosphorylation. We also modify previously reported parameters for lipids to be more consistent with the OPLS-AA force field standard and extend their coverage. These new parameters are validated on a variety of test systems, with the results compared to high-level quantum mechanics calculations, experimental data, and simulations with CHARMM36m where relevant. The results demonstrate that the new parameters reliably reproduce the behavior of membrane protein systems.
Neutrophils in antiretroviral therapy–controlled HIV demonstrate hyperactivation associated with a specific IL-17/IL-22 environment
Authors: Laure Campillo-Gimenez, Sarah Casulli, Yasmine Dudoit, Sophie Seang, Guislaine Carcelain, Sidonie Lambert-Niclot, Victor Appay, Brigitte Autran, Roland Tubiana, Carole Elbim
Journal: Journal of Allergy and Clinical Immunology (2014)
Defective PTEN regulation contributes to B cell hyperresponsiveness in systemic lupus erythematosus
Authors: Xiang-ni Wu, Yan-xia Ye, Jing-wen Niu, Yang Li, Xin Li, Xin You, Hua Chen, Li-dan Zhao, Xiao-feng Zeng, Feng-chun Zhang, Fu-lin Tang, Wei He, Xue-tao Cao, Xuan Zhang, Peter E. Lipsky
Journal: Science Translational Medicine (2014)

Decreased expression of PTEN regulated by miR-7 contributes to B cell hyperresponsiveness and disturbed B cell homeostasis in SLE.