tbuckley/cabot-search huggingface dataset:
Physiological Insights Gained from Gene Expression Analysis in Obesity and Diabetes
Authors: Mark P. Keller, Alan D. Attie
Journal: Annual Review of Nutrition (2010)

Microarray technology permits the interrogation of nearly all expressed genes under a wide range of conditions. Patterns of gene expression in response to obesity and diabetes have yielded important insights into the pathogenesis of diabetes and its relationship to obesity. In muscle, microarray studies have motivated research into mitochondrial function. In adipose tissue, clues have pointed to the importance of inflammation in obesity. New adipocyte-derived hormones involved in insulin resistance have been found; a notable example is retinol binding protein 4. In liver, genes responsive to master regulators of lipid metabolism have been identified. In β-cells, genes involved in cell survival, cell proliferation, and insulin secretion have been identified. These studies have greatly expanded our understanding of mechanisms underlying the pathogenesis of obesity-induced diabetes. When combined with genetic information, microarray data can be used to construct causal network models linking gene expression with disease.
NEURONAL INJURY ASSOCIATED WITH HIV-1: Approaches to Treatment
Authors: Stuart A. Lipton
Journal: The Annual Review of Pharmacology and Toxicology (1998)

▪ Abstract Mounting evidence suggests that cognitive dysfunction developing as a result of HIV-1 infection is mediated at least in part by generation of excitotoxins and free radicals in the brain. This syndrome is currently designated HIV-1-associated cognitive/motor complex, was originally termed the AIDS Dementia Complex, and for simplicity, is called AIDS dementia in this review. Recently, brains of patients with AIDS have been shown to manifest neuronal injury and apoptotic-like cell death. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the virus? Experiments from several different laboratories have lent support to the existence of HIV- and immune-related toxins in a variety of in vitro and in vivo paradigms. In one recently defined pathway to neuronal injury, HIV-infected macrophages and microglia, or immune-activated macrophages and astrocytes (activated by the shed HIV-1 envelope protein, gp120, or other viral proteins and cytokines), appear to secrete excitants and neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO • and O 2 •− ), glutamate, quinolinate, cysteine, amines, and as yet unidentified factors emanating from stimulated macrophages and reactive astrocytes. A final common pathway for neuronal susceptibility is operative, similar to that observed in stroke and several neurodegenerative diseases. This mechanism involves excessive activation of N-methyl-d-aspartate (NMDA) receptor–operated channels, with resultant excessive influx of Ca 2+ and the generation of free radicals, leading to neuronal damage. With the very recent development of clinically tolerated NMDA antagonists, there is hope for future pharmacological intervention.
A frameshift polymorphism in P2X5 elicits an allogeneic cytotoxic T lymphocyte response associated with remission of chronic myeloid leukemia
Authors: B. d. Rijke
Journal: Journal of Clinical Investigation (2005)

Minor histocompatibility antigens (mHAgs) constitute the targets of the graft-versus-leukemia response after HLA-identical allogeneic stem cell transplantation. Here, we have used genetic linkage analysis to identify a novel mHAg, designated lymphoid-restricted histocompatibility antigen–1 (LRH-1), which is encoded by the P2X5 gene and elicited an allogeneic CTL response in a patient with chronic myeloid leukemia after donor lymphocyte infusion. We demonstrate that immunogenicity for LRH-1 is due to differential protein expression in recipient and donor cells as a consequence of a homozygous frameshift polymorphism in the donor. Tetramer analysis showed that emergence of LRH-1–specific CD8+ cytotoxic T cells in peripheral blood and bone marrow correlated with complete remission of chronic myeloid leukemia. Furthermore, the restricted expression of LRH-1 in hematopoietic cells including leukemic CD34+ progenitor cells provides evidence of a role for LRH-1–specific CD8+ cytotoxic T cells in selective graft-versus-leukemia reactivity in the absence of severe graft-versus-host disease. These findings illustrate that the P2X5-encoded mHAg LRH-1 could be an attractive target for specific immunotherapy to treat hematological malignancies recurring after allogeneic stem cell transplantation.
Chest Wall Pain
Authors: J. Lee Sedwitz
Journal: JAMA (1979)

<h3>To the Editor.—</h3> The timely contribution on chest wall syndrome (241:2793, 1979) failed to mention Tietze's disease, which in early stages can be characterized by painful parasternal rib cartilages without notable swelling. This entity, which is found as a cause of unexplained chest wall pain, frequently responds to regional injection of repository steroid injections.
Involvement of Fas-Mediated Apoptosis in the Inhibitory Effects of Interferon-α in Chronic Myelogenous Leukemia
Authors: Carmine Selleri, Tadatsugu Sato, Luigi Del Vecchio, Luigia Luciano, A. John Barrett, Bruno Rotoli, Neal S. Young, Jaroslaw P. Maciejewski
Journal: Blood (1997)
The Diabeo Software Enabling Individualized Insulin Dose Adjustments Combined With Telemedicine Support Improves HbA1c in Poorly Controlled Type 1 Diabetic Patients
Authors: Guillaume Charpentier, Pierre-Yves Benhamou, Dured Dardari, Annie Clergeot, Sylvia Franc, Pauline Schaepelynck-Belicar, Bogdan Catargi, Vincent Melki, Lucy Chaillous, Anne Farret, Jean-Luc Bosson, Alfred Penfornis
Journal: Diabetes Care (2011)

To demonstrate that Diabeo software enabling individualized insulin dose adjustments combined with telemedicine support significantly improves HbA(1c) in poorly controlled type 1 diabetic patients.In a six-month open-label parallel-group, multicenter study, adult patients (n = 180) with type 1 diabetes (>1 year), on a basal-bolus insulin regimen (>6 months), with HbA(1c) ≥ 8%, were randomized to usual quarterly follow-up (G1), home use of a smartphone recommending insulin doses with quarterly visits (G2), or use of the smartphone with short teleconsultations every 2 weeks but no visit until point end (G3).Six-month mean HbA(1c) in G3 (8.41 ± 1.04%) was lower than in G1 (9.10 ± 1.16%; P = 0.0019). G2 displayed intermediate results (8.63 ± 1.07%). The Diabeo system gave a 0.91% (0.60; 1.21) improvement in HbA(1c) over controls and a 0.67% (0.35; 0.99) reduction when used without teleconsultation. There was no difference in the frequency of hypoglycemic episodes or in medical time spent for hospital or telephone consultations. However, patients in G1 and G2 spent nearly 5 h more than G3 patients attending hospital visits.The Diabeo system gives a substantial improvement to metabolic control in chronic, poorly controlled type 1 diabetic patients without requiring more medical time and at a lower overall cost for the patient than usual care.
Participant skepticism: If you can't beat it, model it
Authors: Craig R. M. McKenzie, John T. Wixted
Journal: Behavioral and Brain Sciences (2001)

For a variety of reasons, including the common use of deception in psychology experiments, participants often disbelieve experimenters' assertions about important task parameters. This can lead researchers to conclude incorrectly that participants are behaving non- normatively. The problem can be overcome by deriving and testing normative models that do not assume full belief in key task parameters. A real experimental example is discussed.
EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases
Authors: J N Hoes, J W G Jacobs, M Boers, D Boumpas, F Buttgereit, N Caeyers, E H Choy, M Cutolo, J A P Da Silva, G Esselens, L Guillevin, I Hafstrom, J R Kirwan, J Rovensky, A Russell, K G Saag, B Svensson, R Westhovens, H Zeidler, J W J Bijlsma
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To develop evidence-based recommendations for the management of systemic glucocorticoid (GC) therapy in rheumatic diseases. <h3>Methods:</h3> The multidisciplinary guideline development group from 11 European countries, Canada and the USA consisted of 15 rheumatologists, 1 internist, 1 rheumatologist–epidemiologist, 1 health professional, 1 patient and 1 research fellow. The Delphi method was used to agree on 10 key propositions related to the safe use of GCs. A systematic literature search of PUBMED, EMBASE, CINAHL, and Cochrane Library was then used to identify the best available research evidence to support each of the 10 propositions. The strength of recommendation was given according to research evidence, clinical expertise and perceived patient preference. <h3>Results:</h3> The 10 propositions were generated through three Delphi rounds and included patient education, risk factors, adverse effects, concomitant therapy (ie, non-steroidal anti-inflammatory drugs, gastroprotection and cyclo-oxygenase-2 selective inhibitors, calcium and vitamin D, bisphosphonates) and special safety advice (ie, adrenal insufficiency, pregnancy, growth impairment). <h3>Conclusion:</h3> Ten key recommendations for the management of systemic GC-therapy were formulated using a combination of systematically retrieved research evidence and expert consensus. There are areas of importance that have little evidence (ie, dosing and tapering strategies, timing, risk factors and monitoring for adverse effects, perioperative GC-replacement) and need further research; therefore also a research agenda was composed.
The effect of changes in the fluid state of rat liver plasma membrane on the transport of taurocholate
Authors: Peter R. Mills, Peter J. Meier, Daniel J. Smith, Nazzareno Ballatori, James L. Boyer, Ellen R. Gordon
Journal: Hepatology (1987)

The fluidity of basolateral and canalicular rat liver plasma membranes was compared with respect to their response to the membrane perturbants ethanol and calcium. The relation between membrane fluidity and taurocholate transport, a liver plasma membrane function mediated by carrier proteins, was also examined. Membrane fluidity was measured by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene as a probe. Uptake of [3H]taurocholate into basolateral rat liver plasma membrane and canalicular rat liver plasma membrane vesicles was measured by a rapid Millipore filtration technique. Anisotropy values were found to be significantly lower for the basolateral rat liver plasma membrane (0.2287 +/- 0.0014) than for the canalicular rat liver plasma membrane (0.2612 +/- 0.0012), indicating that basolateral rat liver plasma membranes are more fluid than canalicular rat liver plasma membranes. Ethanol produced a concentration-dependent effect on lipid fluidity and inhibition of taurocholate uptake, in both membrane preparations. Pretreatment of the membrane with calcium increased the rigidity of both membrane preparations. However, the change in the anisotropy with calcium was only slight in the more rigid canalicular rat liver plasma membrane, while the change in anisotropy was greater and associated with a decrease in taurocholate uptake in the basolateral rat liver plasma membrane. Both the effects of ethanol and calcium were more pronounced in basolateral rat liver plasma membrane than in canalicular rat liver plasma membrane. These results indicate that the fluid state of the hydrophobic bilayer of liver plasma membrane lipids play an important role in regulating bile acid transport in both sinusoidal and canalicular domains.
Conversion of CD4+ CD25− cells into CD4+ CD25+ regulatory T cells in vivo requires B7 costimulation, but not the thymus
Authors: Shuang Liang, Pascale Alard, Yuan Zhao, Sarah Parnell, Sherry L. Clark, Michele M. Kosiewicz
Journal: The Journal of Experimental Medicine (2005)

The CD4+ CD25+ regulatory T cells play a critical role in controlling autoimmunity, but little is known about their development and maintenance. In this study, we investigated whether CD4+ CD25− cells can convert to CD4+ CD25+ regulatory T cells in vivo under natural conditions. CD4+ CD25− cells from CD45.1+ mice were sorted and transferred into congenic CD45.2+ mice. Converted CD4+ CD25+ cells could be detected in lymphoid organs as early as 1 wk after transfer and by 6 wk after transfer, 5–12% of transferred CD4+ cells expressed CD25. Converted CD4+ CD25+ cells themselves failed to proliferate after stimulation, but could suppress proliferation of responder cells in vitro, and also expressed high levels of Foxp3 mRNA. In addition, CD4+ CD25− cells transferred into thymectomized congenic mice converted to CD4+ CD25+ cells that also suppressed responder cell proliferation in vitro, and expressed high levels of Foxp3 mRNA. Finally, CD4+ CD25− cells transferred into B7−/− mice failed to convert into CD4+ CD25+ cells that exhibit the regulatory phenotype. These data indicate that CD4+ CD25− cells convert into CD4+ CD25+ regulatory T cells spontaneously in vivo and suggest that this conversion process could contribute significantly to the maintenance of the peripheral CD4+ CD25+ regulatory T cell population.
Experimental arthritis in C57black/6 normal and beige (Chediak-Higashi) mice: in vivo and in vitro observations on cartilage degradation.
Authors: J Schalkwijk, L.A Joosten, W.B van den Berg, L.B van de Putte
Journal: Annals of the Rheumatic Diseases (1988)

Mice with the beige mutation are known to be deficient for polymorphonuclear leucocyte (PMN) elastase and cathepsin G and can therefore be used as a model for protease dependence of tissue destruction in inflammatory conditions. The in vitro and in vivo effect of PMN activation on cartilage damage in C57black/6 normal and beige mice was measured. In vitro it was found that stimulation of normal PMNs with chemotactic peptide caused degradation of articular cartilage matrix owing to an elastase dependent mechanism; PMNs of beige mice did not induce degradation of cartilage. In vivo, using zymosan induced arthritis, which is a model characterised by a PMN-rich infiltrate and exudate, no significant differences were found between the two strains with respect to (a) joint oedema formation as measured by technetium-99m uptake; (b) matrix degradation as measured quantitatively and with histology; (c) chondrocyte proteoglycan synthesis as measured by radiosulphate uptake. At day 28 after induction of arthritis, when inflammation is waning, no differences in end stage irreversible damage to joint tissues were found. The relevance of these observations to the supposed role of PMN derived neutral proteases in joint inflammation is discussed.
Hypoxia and hypoxia-inducible factor-1α provoke toll-like receptor signalling-induced inflammation in rheumatoid arthritis
Authors: Fanlei Hu, Rong Mu, Jiaxin Zhu, Lianjie Shi, Yingni Li, Xu Liu, Wenwei Shao, Guiye Li, Minghui Li, Yin Su, Philip L Cohen, Xiaoyan Qiu, Zhanguo Li
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Hyperplasia of synovial fibroblasts, infiltration with lymphocytes and tissue hypoxia are major characteristics of rheumatoid arthritis (RA). Extensive data support a key role for toll-like receptors (TLRs) in RA. Little is known regarding the impact of hypoxia on TLR-induced inflammation in RA. The aim of this study was to reveal the effects of hypoxia and its regulator, hypoxia-inducible factor-1α (HIF-1α), on the inflammatory response of RA synovial fibroblasts (RASF) to TLR ligands. <h3>Methods</h3> Hypoxia was induced in RASF by incubation with Na<sub>2</sub>S<sub>2</sub>O<sub>4</sub>. TLR3 ligand polyIC, TLR2 ligand peptidoglycan, TLR4 ligand LPS and TLR9 ligand CpG were used to stimulate the cells. Effects of hypoxia on TLR-induced inflammatory mediators were determined by RT-PCR, qPCR and ELISA. Overexpression of HIF-1α as well as knocking-down its expression was used to reveal its fundamental role. RASF-induced inflammatory T cell expansion was determined by flow cytometry analysis of T helper (Th)1/Th17 cells, and IFN-γ/IL-17 production by ELISA after RASF/T cell coculture. <h3>Results</h3> Hypoxia potentiated the expression of inflammatory cytokines, metalloproteinases and VEGF in RASF stimulated by different TLR ligands, especially polyIC, a synthetic mimic of dsRNA from viruses or apoptotic cells. HIF-1α played a fundamental role in this synergy. Moreover, HIF-1α overexpression enhanced RASF-mediated expansion of inflammatory Th1 and Th17 cells, leading to proinflammatory IFN-γ and IL-17 production. <h3>Conclusions</h3> Our findings suggest that hypoxia and HIF-1α may function in conjunction with TLR-stimulated innate immune responses to drive inflammation in RA. This pathway may serve as a therapeutic target for the disease.
Disease-Free Survival as a Surrogate for Overall Survival in Adjuvant Trials of Gastric Cancer: A Meta-Analysis
Authors: Koji Oba, Xavier Paoletti, Steven Alberts, Yung-Jue Bang, Jacqueline Benedetti, Harry Bleiberg, Paul Catalano, Florian Lordick, Stefan Michiels, Satoshi Morita, Yasuo Ohashi, Jean-pierre Pignon, Philippe Rougier, Mitsuru Sasako, Junichi Sakamoto, Daniel Sargent, Kohei Shitara, Eric Van Cutsem, Marc Buyse, Tomasz Burzykowski
Journal: JNCI Journal of the National Cancer Institute (2013)

In investigations of the effectiveness of surgery and adjuvant chemotherapy for gastric cancers, overall survival (OS) is considered the gold standard endpoint. However, the disadvantage of using OS as the endpoint is that it requires an extended follow-up period. We sought to investigate whether disease-free survival (DFS) is a valid surrogate for OS in trials of adjuvant chemotherapy for gastric cancer. The GASTRIC group initiated a meta-analysis of individual patient data collected in randomized clinical trials comparing adjuvant chemotherapy vs surgery alone for patients with curatively resected gastric cancer. Surrogacy of DFS was assessed through the correlation between the endpoints as well as through the correlation between the treatment effects on the endpoints. External validation of the prediction based on DFS was also evaluated. Individual patient data from 14 randomized clinical trials that included a total of 3288 patients were analyzed. The rank correlation coefficient between DFS and OS was 0.974 (95% confidence interval [CI] = 0.971 to 0.976). The coefficient of determination between the treatment effects on DFS and on OS was as high as 0.964 (95% CI = 0.926 to 1.000), and the surrogate threshold effect based on adjusted regression analysis was 0.92. In external validation, the six hazard ratios for OS predicted according to DFS were in very good agreement with those actually observed for OS. DFS is an acceptable surrogate for OS in trials of cytotoxic agents for gastric cancer in the adjuvant setting.
Apolipoprotein E genotype and sex influence C-reactive protein levels regardless of exercise training status
Authors: Theodore J. Angelopoulos, Mary P. Miles, Joshua Lowndes, Stephen A. Sivo, Richard L. Seip, Linda S. Pescatello, Robert F. Zoeller, Paul S. Visich, Paul M. Gordon, Niall M. Moyna, Paul D. Thompson
Journal: Metabolism (2008)
Quality of Life Among Long-Term Survivors of Non-Hodgkin Lymphoma: A Follow-Up Study
Authors: Sophia K. Smith, Deborah K. Mayer, Sheryl Zimmerman, Christianna S. Williams, Habtamu Benecha, Patricia A. Ganz, Lloyd J. Edwards, Amy P. Abernethy
Journal: Journal of Clinical Oncology (2012)

Little is known about change in quality of life (QOL) among long-term cancer survivors. We examined change over time in QOL among long-term survivors of non-Hodgkin lymphoma and identified demographic, clinical, and psychosocial risk factors for poor outcomes.
Cerebral Blood Flow and Glucose Metabolism in Appetite-Related Brain Regions in Type 1 Diabetic Patients After Treatment With Insulin Detemir and NPH Insulin
Authors: Larissa W. van Golen, Richard G. IJzerman, Marc C. Huisman, Jolanda F. Hensbergen, Roel P. Hoogma, Madeleine L. Drent, Adriaan A. Lammertsma, Michaela Diamant
Journal: Diabetes Care (2013)

OBJECTIVE To test the hypothesis that insulin detemir, which is associated with less weight gain than other basal insulin formulations, exerts its weight-modulating effects by acting on brain regions involved in appetite regulation, as represented by altered cerebral blood flow (CBF) or cerebral glucose metabolism (CMRglu). RESEARCH DESIGN AND METHODS Twenty-eight male type 1 diabetic patients (age 36.9 ± 9.7 years, BMI 24.9 ± 2.7 kg/m2, A1C 7.5 ± 0.6%) successfully completed a randomized crossover study, consisting of two periods of 12-week treatment with either insulin detemir or NPH insulin, both in combination with prandial insulin aspart. After each treatment period, patients underwent positron emission tomography scans to measure regional CBF and CMRglu. RESULTS After 12 weeks, A1C, daily insulin doses, fasting insulin, and blood glucose levels were similar between treatments. Insulin detemir resulted in body weight loss, whereas NPH insulin induced weight gain (between-treatment difference 1.3 kg; P = 0.02). After treatment with insulin detemir relative to NPH insulin, CBF was higher in brain regions involved in appetite regulation, whereas no significant difference in CMRglu was observed. CONCLUSIONS Treatment with insulin detemir versus NPH insulin resulted in weight loss, paralleled by increased CBF in appetite-related brain regions in the resting state, in men with well-controlled type 1 diabetes. These findings lend support to the hypothesis that a differential effect on the brain may contribute to the consistently observed weight-sparing effect of insulin detemir.
Economic man – or straw man?
Authors: Ken Binmore
Journal: Behavioral and Brain Sciences (2005)

The target article by Henrich et al. describes some economic experiments carried out in fifteen small-scale societies. The results are broadly supportive of an approach to understanding social norms that is commonplace among game theorists. It is therefore perverse that the rhetorical part of the paper should be devoted largely to claiming that “economic man” is an experimental failure that needs to be replaced by an alternative paradigm. This brief commentary contests the paper's caricature of economic theory, and offers a small sample of the enormous volume of experimental data that would need to be overturned before “economic man” could be junked.
Fate of the rectum and distal colon after subtotal colectomy for ulcerative colitis.
Authors: B I Korelitz, W P Dyck, F M Klion
Journal: Gut (1969)

Once the gastroenterologist and surgeon have agreed that there is an indication for definitive surgery in the patient with ulcerative colitis, they usually intend that the entire colon and rectum be resected.The