tbuckley/cabot-search huggingface dataset:
A Role for Fibroblast Growth Factor 19 and Bile Acids in Diabetes Remission After Roux-en-Y Gastric Bypass
Authors: Glenn S. Gerhard, Amanda M. Styer, G. Craig Wood, Stephen L. Roesch, Anthony T. Petrick, Jon Gabrielsen, William E. Strodel, Christopher D. Still, George Argyropoulos
Journal: Diabetes Care (2013)

OBJECTIVE Roux-en-Y gastric bypass (RYGB) in humans can remit type 2 diabetes, but the operative mechanism is not completely understood. In mice, fibroblast growth factor (FGF) 15 (FGF19 in humans) regulates hepatic bile acid (BA) production and can also resolve diabetes. In this study, we tested the hypothesis that the FGF19–BA pathway plays a role in the remission of human diabetes after RYGB surgery. RESEARCH DESIGN AND METHODS Cohorts of diabetic and nondiabetic individuals of various body weights were used. In addition, RYGB patients without diabetes (No-Diabetes), RYGB patients with diabetes who experienced remission for at least 12 months after surgery (Diabetes-R), and RYGB patients with diabetes who did not go into remission after surgery (Diabetes-NoR) were studied. Circulating FGF19 and BA levels, hepatic glycogen content, and expression levels of genes regulating the FGF19–BA pathway were compared among these groups of patients using pre- and postoperative serum samples and intraoperative liver biopsies. RESULTS Preoperatively, patients with diabetes had lower FGF19 and higher BA levels than nondiabetic patients, irrespective of body weight. In diabetic patients undergoing RYGB, lower FGF19 levels were significantly correlated with increased hepatic expression of the cholesterol 7alpha-hydroxylase 1 (CYP7A1) gene, which modulates BA production. Following RYGB surgery, however, FGF19 and BA levels (particularly cholic and deoxycholic acids) exhibited larger increases in Diabetic-R patients compared with nondiabetic and Diabetic-NoR patients. CONCLUSIONS Taken together, the baseline and postoperative data implicate the FGF19–CYP7A1–BA pathway in the etiology and remission of type 2 diabetes following RYGB surgery.
Extracellular pH and P-31 Magnetic Resonance Spectroscopic Variables are Related to Outcome in Canine Soft Tissue Sarcomas Treated with Thermoradiotherapy
Authors: Michaël Lora-Michiels, Daohai Yu, Linda Sanders, Jean M. Poulson, Chieko Azuma, Beth Case, Zeljko Vujaskovic, Donald E. Thrall, H. Cecil Charles, Mark W. Dewhirst
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The objective was to test whether tumor pH and 31P magnetic resonance spectroscopic end points were related to treatment outcome in pet canine patients with spontaneous soft tissue sarcomas treated with thermoradiotherapy. Experimental Design: Forty-two dogs with evaluable 31P magnetic resonance spectroscopic end points and pH data were included in this study. Tumor variables (grade and volume), extracellular pH (pHe), T2 relaxation times, intracellular pH, and selected phosphometabolite ratios were examined for correlation with clinical outcome. Results: From 39 dogs, pHe was a predictor of metastasis-free survival (MFS), with hazard ratio (HR, 0.29; P = 0.005) and overall survival (OS) with (HR, 0.36; P = 0.013). Tumor volume (&amp;gt;19 cm3) was related to MFS (HR, 2.14; P = 0.04), time to local failure (HR, 3.4; P = 0.025), and OS (HR, 2.27; P = 0.03). There was no association between T2 or intracellular pH and clinical outcome. Tumor grade (high versus low/intermediate) and phosphodiester/βATP ratio were identified as significant predictors for MFS, with (HR, 2.66; P = 0.009) and (HR, 0.75; P = 0.027), respectively, and as predictors of OS with (HR, 2.66; P = 0.009) and (HR, 0.76; P = 0.03), respectively. The phosphodiester/phosphocreatinine ratio predicted time to local failure (HR, 1.24; P = 0.017). Conclusions: pHe was predictive of metastasis and OS in canine spontaneous sarcomas. To our knowledge, this is the first time that pHe has been shown to be predictive of clinical outcome. The results suggest that additional studies should be considered evaluating the prognostic significance of this variable. Phospholipid resonances, related to membrane metabolism, were related to clinical outcome, confirming recent results reported in human patients with soft tissue sarcomas treated with thermoradiotherapy.
Size-dependent intracellular immunotargeting of therapeutic cargoes into endothelial cells
Authors: Rainer Wiewrodt, Anu P. Thomas, Luca Cipelletti, Melpo Christofidou-Solomidou, David A. Weitz, Sheldon I. Feinstein, David Schaffer, Steven M. Albelda, Michael Koval, Vladimir R. Muzykantov
Journal: Blood (2002)
Smooth Skyride through a Rough Skyline: Bayesian Coalescent-Based Inference of Population Dynamics
Authors: V. N. Minin, E. W. Bloomquist, M. A. Suchard
Journal: Molecular Biology and Evolution (2008)

Kingman's coalescent process opens the door for estimation of population genetics model parameters from molecular sequences. One paramount parameter of interest is the effective population size. Temporal variation of this quantity characterizes the demographic history of a population. Because researchers are rarely able to choose a priori a deterministic model describing effective population size dynamics for data at hand, nonparametric curve-fitting methods based on multiple change-point (MCP) models have been developed. We propose an alternative to change-point modeling that exploits Gaussian Markov random fields to achieve temporal smoothing of the effective population size in a Bayesian framework. The main advantage of our approach is that, in contrast to MCP models, the explicit temporal smoothing does not require strong prior decisions. To approximate the posterior distribution of the population dynamics, we use efficient, fast mixing Markov chain Monte Carlo algorithms designed for highly structured Gaussian models. In a simulation study, we demonstrate that the proposed temporal smoothing method, named Bayesian skyride, successfully recovers "true" population size trajectories in all simulation scenarios and competes well with the MCP approaches without evoking strong prior assumptions. We apply our Bayesian skyride method to 2 real data sets. We analyze sequences of hepatitis C virus contemporaneously sampled in Egypt, reproducing all key known aspects of the viral population dynamics. Next, we estimate the demographic histories of human influenza A hemagglutinin sequences, serially sampled throughout 3 flu seasons.
Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL
Authors: April Chiu, Weifeng Xu, Bing He, Stacey R. Dillon, Jane A. Gross, Eric Sievers, Xugang Qiao, Paul Santini, Elizabeth Hyjek, Joong-won Lee, Ethel Cesarman, Amy Chadburn, Daniel M. Knowles, Andrea Cerutti
Journal: Blood (2006)
Characterization of Insulin-Like Growth Factor-1–Induced Activation of the JAK/STAT Pathway in Rat Cardiomyocytes
Authors: Toshiyuki Takahashi, Keiichi Fukuda, Jing Pan, Hiroaki Kodama, Motoaki Sano, Shinji Makino, Takahiro Kato, Tomohiro Manabe, Satoshi Ogawa
Journal: Circulation Research (1999)

Abstract —This study was designed to investigate whether insulin-like growth factor-1 (IGF-1) transduces signaling through the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway in cardiomyocytes and to assess the upstream signals of serine and tyrosine phosphorylation of STAT family proteins. Primary cultured neonatal rat cardiomyocytes were stimulated with IGF-1 (10 −8 mol/L). JAK1, but not JAK2 or Tyk2, was phosphorylated by IGF-1 as early as 2 minutes and peaked at 5 minutes. IGF-1 induced both tyrosine and serine phosphorylation of STAT1 and STAT3. Tyrosine phosphorylation of STAT1 peaked at 15 minutes and correlated with that of JAK1, whereas that of STAT3 was sustained up to 120 minutes and was dissociated from the activation of JAK1. Tyrosine phosphorylation of STAT3 was unaffected by the preincubation with CV11974 (AT 1 blocker), TAK044 (endothelin-1 receptor blocker), RX435 (anti-gp130 blocking antibody), PD98058, wortmannin, EDTA, or KN62 but was significantly attenuated by BAPTA-AM and chelerythrine. The time course of a gel mobility shift of SIE ( sis -inducing element) coincided with the phosphorylation of STAT3. Serine phosphorylation of STAT1 peaked at 30 minutes and that of STAT3 was observed from 5 to 60 minutes. These results indicated that (1) IGF-1 activated JAK1 but not JAK2 or Tyk2 in rat cardiomyocytes; (2) IGF-1 induced both tyrosine and serine phosphorylation of STAT1 and STAT3; and (3) the tyrosine phosphorylation of STAT3 was not caused by JAK1 alone, and protein kinase C and intracellular Ca 2+ were required for phosphorylation.
Receptor-dependent mechanisms of glucocorticoid and dioxin-induced cleft palate.
Authors: R M Pratt
Journal: Environmental Health Perspectives (1985)

Glucocorticoids (triamcinolone) and dioxins (TCDD) are highly specific teratogens in the mouse, in that cleft palate is the major malformation observed. Glucocorticoids and TCDD both readily cross the yolk sac and placenta and appear in the developing secondary palate. Structure-activity relationships for glucocorticoid- and TCDD-induced cleft palate suggest a receptor involvement. Receptors for glucocorticoids and TCDD are present in the palate and their levels in various mouse strains are highly correlated with their sensitivity to cleft palate induction. Receptors for glucocorticoids appear to be more prevalent in the palatal mesenchymal cells whereas those for TCDD are probably located in the palatal epithelial cells. Glucocorticoids exert their teratogenic effect on the palate by inhibiting the growth of the palatal mesenchymal cells whereas TCDD alters the terminal cell differentiation of the medial palatal epithelial cells.
Blood Pressure Trajectories Prior to Death in Patients With Diabetes
Authors: Mary A.M. Rogers, Kathleen Ward, Tanya R. Gure, Hae M. Choe, Pearl G. Lee, Steven J. Bernstein, Caroline S. Blaum
Journal: Diabetes Care (2011)

The goals of this study were to examine trajectories of blood pressure (BP) in adults with diabetes and investigate the association of trajectory patterns with mortality.A nonconcurrent longitudinal design was used to monitor 3,766 Medicare patients with diabetes from 2005 through 2008. Data were extracted from a registry of Medicare beneficiaries, which was developed by a large academic practice that participated in the Physician Group Practice Medicare Demonstration. The relationship between BP trajectories and all-cause mortality was modeled using multilevel mixed-effects linear regression.During the 4-year study period, 10.7% of the patients died, half of whom were aged≥75 years. The crude and adjusted models both showed a greater decline in systolic and diastolic BP in patients who died than in those who did not die. In a model adjusted for age, sex, race, medications, and comorbidities, the mean systolic BP decreased by 3.2 mmHg/year (P<0.001) in the years before death and by 0.7 mmHg/year (P<0.001) in those who did not die (P<0.001 for the difference in slopes). Similarly, diastolic BP declined by 1.3 mmHg/year for those who died (P<0.001) and by 0.6 mmHg/year for those who did not die (P<0.001); the difference in slopes was significant (P=0.021).Systolic and diastolic BP both declined more rapidly in the 4 years before death than in patients who remained alive.
The origin of DNA associated with mucus glycoproteins in cystic fibrosis sputum
Authors: MI Lethem, SL James, C Marriott, JF Burke
Journal: European Respiratory Journal (1990)

The relative importance of host and bacteria-derived deoxyribonucleic acid (DNA) in the increased viscoelasticity of purulent sputum in cystic fibrosis (CF) and other airway diseases is unclear. We report the identification of the DNA associated with mucus glycoproteins purified from the purulent sputum of 9 patients with CF. Mucus glycoproteins were purified from CF sputum by gel exclusion chromatography and the co-purifying DNA isolated by phenol extraction. Electrophoresis indicated that the DNA preparations had a size of approximately 300 to greater than 50,000 bases. The origin of the DNA was determined by slot blotting and subsequent hybridization with 32P-labelled DNA probes specific for human DNA sequences and those from bacterial species commonly isolated from CF sputum. The results indicated that in all cases the DNA was almost entirely human in origin. This implies that it is the patient's own DNA which may contribute to the rheological abnormalities of CF sputum.
Changes in central catecholaminergic neurons in the spontaneously (genetic) hypertensive rat.
Authors: J M Saavedra, H Grobecker, J Axelrod
Journal: Circulation Research (1978)

Catecholamines and catecholamine-synthesizing enzymes have been examined in specific brain areas during the development of spontaneously (genetic) hypertensive (SH) rats. Changes in catecholamine metabolism were localized to regions of the brain implicated in the regulation of blood pressure. Norepinephrine levels and dopamine-beta-hydroxylase (DBH) activities were decreased in specific nuclei of the hypothalamus and in the nucleus interstitialis striae terminalis ventralis, in both young and adult rats. The decrease in the formation of norepinephrine can result in a reduced activation of central alpha-adrenergic receptors which may be related causally to the onset of hypertension. The activity of the epinephrine-forming enzyme, phenylethanolamine-N-methyltransferase (PNMT), was increased in the A1 and A2 areas of the brainstem in young SH rats, but it was normal in adult hypertensive animals. These results implicate adrenergic neurons in the brainstem and noradrenergic neurons in the hypothalamus in the development of spontaneous (genetic) hypertension in rats.
Effect of atrial natriuretic peptide on renal and vascular permeability in diabetes mellitus.
Authors: R Zietse, F H Derkx, W Weimar, M A Schalekamp
Journal: Journal of the American Society of Nephrology (1995)

Synthetic human atrial natriuretic peptide (ANP) (102-126) 0.01 microgram/kg per minute or vehicle was intravenously infused for 2 h in 10 patients with insulin-dependent diabetes mellitus and microalbuminuria (albumin excretion, 20 to 200 micrograms/min) and in 10 healthy subjects. In the diabetic group, the immunoglobulin G clearance was higher, but both size index and charge index as calculated from albumin and immunoglobulin clearances were equal compared with normal values. The fractional clearances of small dextrans (< 3.6 nm) were lower in diabetics, which was compatible with a depressed hydraulic permeability (Kf). During ANP infusion, the excretion of albumin and immunoglobulin G increased in the diabetic subjects (189 +/- 12 to 521 +/- 84 and 7.1 +/- 3.5 to 21 +/- 8.1 micrograms/min, respectively; both P < 0.05) only. In the diabetics, the clearance of dextrans > 54 A increased and our calculations indicated an increase in "shut-flow" (omega o). The transcapillary escape rate of albumin, which was elevated in the diabetics at baseline, increased in the diabetic group only. Thus, ANP uncovers altered size selectivity of the filtration barrier in a phase that is otherwise characterized by charge-selective changes only. Moreover, the increased susceptibility of the glomerular capillaries in diabetics to ANP seems to be part of a more generalized capillary abnormality, because ANP also increases the transcapillary escape of albumin.
Photodynamic Therapy and Antitumor Immunity
Authors: Sandra O. Gollnick
Journal: Journal of the National Comprehensive Cancer Network (2012)

Preclinical studies have shown that local photodynamic therapy (PDT) enhances systemic antitumor immunity. In addition, it has long been known that the long-term efficacy of PDT depends on the presence of an intact adaptive immune system. Years of research in the laboratory have attempted to shed light on the mechanisms of the PDT-enhanced antitumor immune response, suggesting that increased expression of proinflammatory cytokines may play a key role. This overview on the immunologic potential of PDT briefly explores these proposed mechanisms and addresses preliminary results with PDT vaccines in combination with surgery as perhaps a new clinical strategy for cancer treatment outside the laboratory.
TCT-559 Incidence, Predictors, and Three-Year Outcome of Tissue Prolapse After Stent Implantation in ST-Segment Elevation Myocardial Infarction Patients
Authors: Hyuck-Jun Yoon, In-Cheol Kim, Jeong-Eun Lee, Yun-Kyeong Cho, Hyoung-Seob Park, Hyungseop Kim, Chang-Wook Nam, Yoon-Nyun Kim, Kwon-Bae Kim
Journal: Journal of the American College of Cardiology (2013)
Longitudinal decline in FEV1 in United States coalminers.
Authors: M D Attfield
Journal: Thorax (1985)

Changes in ventilatory function measurements of United States miners who had participated in two surveys held nine years apart were analysed in relation to smoking habits, dust exposure, and other factors. The results showed trends similar to those reported among British miners. Loss of FEV1 over time and found to be related to smoking (0.1 litre excess decline in current smokers compared with those who had never smoked over 11 years) and to occupational exposure (0.036-0.084 litres over 11 years, depending on the index used). The results offer confirmation of the relationship between work in coal mines and loss in ventilatory function observed in British miners, and also seen in cross sectional studies.
C-reactive protein in schoolchildren and its relation to adiposity, physical activity, aerobic fitness and habitual diet
Authors: N-E Thomas, J S Baker, M R Graham, S-M Cooper, B Davies
Journal: British Journal of Sports Medicine (2008)

Objective: To investigate the relation between C-reactive protein (CRP), adiposity, physical activity, aerobic fitness and habitual diet in a cohort of schoolchildren. Methods: A cross-sectional study of 164 schoolchildren aged 12–13 years was conducted in two schools. Adiposity was estimated using body mass index and waist circumference. Blood samples were taken after an overnight fast and measured for CRP. Aerobic fitness and habitual physical activity were assessed using the 20 metres multistage fitness test, and a seven-day recall, respectively. A seven-day food diary provided measures of dietary intake. Results: To improve the distribution of this variable, CRP levels were logarithmically transformed in all analyses. There was no significant difference in mean CRP concentration between boys (1.07 (1.33) mg/l) and girls (1.24 (1.87) mg/l) (p⩾0.05). Compared to girls, boys reported significantly higher (i) aerobic fitness 59.2 (20.3) shuttles vs 42.9 (15.3) shuttles, (ii) vigorous activity levels per week 92 (123) minutes vs 11.2 (34.6) minutes and (iii) waist circumference 69.8 (1.1) cm vs 65.2 (0.9) cm (p⩽0.05). Among boys and girls, adiposity was significantly associated with log transformed CRP (p⩽0.05). CRP was not significantly related to any other variable. Conclusion: Elevated CRP was evident in this cohort; however, whether high CRP levels during childhood and adolescence leads to an increased risk of CVD in later life has not been determined. Adiposity was related to CRP concentration, suggesting that reducing adiposity may be effective in lowering CRP and preventing future cardiovascular events.
A common structure for concepts of individuals, stuffs, and real kinds: More Mama, more milk, and more mouse
Authors: Ruth Garrett Millikan
Journal: Behavioral and Brain Sciences (1998)

Concepts are highly theoretical entities. One cannot study them empirically without committing oneself to substantial preliminary assumptions. Among the competing theories of concepts and categorization developed by psychologists in the last thirty years, the implicit theoretical assumption that what falls under a concept is determined by description (“descriptionism”) has never been seriously challenged. I present a nondescriptionist theory of our most basic concepts, “substances,” which include (1) stuffs (gold, milk), (2) real kinds (cat, chair), and (3) individuals (Mama, Bill Clinton, the Empire State Building). On the basis of something important that all three have in common, our earliest and most basic concepts of substances are identical in structure. The membership of the category “cat,” like that of “Mama,” is a natural unit in nature, to which the concept “cat” does something like pointing, and continues to point despite large changes in the properties the thinker represents the unit as having. For example, large changes can occur in the way a child identifies cats and the things it is willing to call “cat” without affecting the extension of its word “cat.” The difficulty is to cash in the metaphor of “pointing” in this context. Having substance concepts need not depend on knowing words, but language interacts with substance concepts, completely transforming the conceptual repertoire. I will discuss how public language plays a crucial role in both the acquisition of substance concepts and their completed structure.
The role of heat shock protein 60, vascular endothelial growth factor and antiphospholipid antibodies in Behçet disease
Authors: O. Shaker, M.A. Ay El-Deen, H. El Hadidi, B.D. Grace, H. El Sherif, A. Abdel Halim
Journal: British Journal of Dermatology (2006)

Behçet disease is a systemic inflammatory disease of unknown aetiology. T cells in this disease proliferate vigorously in response to a specific peptide of heat shock protein (HSP) 60 in an antigen-specific fashion. Vascular endothelial cell growth factor (VEGF) is a cytokine participating in the inflammatory process. One of the prominent features of Behçet disease is vasculitis as a result of endothelial dysfunction. Antiphospholipid antibodies (APA) may play a role in the development of thrombosis by inhibiting production of prostacyclin by endothelial cells.To investigate the role of HSP60, VEGF and APA in Behçet disease and their relation to clinical manifestations and disease activity.Thirty patients with Behçet disease were included; 17 were in the active stage and 13 were in the inactive. Fifteen age- and sex-matched healthy subjects served as controls. Complete clinical examination and Doppler examination were done. Serum levels of HSP60, VEGF and APA were performed.Serum levels of HSP60, VEGF and APA were significantly higher in patients than in controls; however, their level did not correlate with disease activity. The serum level of VEGF correlated significantly with the presence of vascular manifestations and ocular involvement. The serum level of APA was greater in patients with thrombosis. HSP60 has an important role in aetiopathogenesis of Behçet disease, which sheds new light on its autoimmune nature.An elevated serum level of VEGF may be a risk factor for the development of ocular disease contributing to poor visual outcome.