tbuckley/cabot-search huggingface dataset:
Microarchitecture of the dyad
Authors: David R.L. Scriven, Parisa Asghari, Edwin D.W. Moore
Journal: Cardiovascular Research (2013)

This review highlights recent and ongoing discoveries that are transforming the previously held view of dyad structure and function. New data show that dyads vary greatly in both structure and in their associated molecules. Dyads can contain varying numbers of type 2 ryanodine receptor (RYR2) clusters that range in size from one to hundreds of tetramers and they can adopt numerous orientations other than the expected checkerboard. The association of Cav1.2 with RYR2, which defines the couplon, is not absolute, leading to a number of scenarios such as dyads without couplons and those in which only a fraction of the clusters are in couplons. Different dyads also vary in the transporters and exchangers with which they are associated producing functional differences that amplify their structural diversity. The essential role of proteins, such as junctophilin-2, calsequestrin, triadin, and junctin that maintain both the functional and structural integrity of the dyad have recently been elucidated giving a new mechanistic understanding of heart diseases, such as arrhythmias, hypertension, failure, and sudden cardiac death.
Acute Pancreatitis in Type 2 Diabetes Treated With Exenatide or Sitagliptin
Authors: Rajesh Garg, William Chen, Merri Pendergrass
Journal: Diabetes Care (2010)

Cases of acute pancreatitis have been reported in association with exenatide, sitagliptin, and type 2 diabetes without use of these medications. It remains unknown whether exenatide or sitagliptin increase the risk of acute pancreatitis.A retrospective cohort study of a large medical and pharmacy claims database was performed. Data for 786,656 patients were analyzed. Cox proportional hazard models were built to compare the risk of acute pancreatitis between diabetic and nondiabetic subjects and between exenatide, sitagliptin, and control diabetes medication use.Incidence of acute pancreatitis in the nondiabetic control group, diabetic control group, exenatide group, and sitagliptin group was 1.9, 5.6, 5.7, and 5.6 cases per 1,000 patient years, respectively. The risk of acute pancreatitis was significantly higher in the combined diabetic groups than in the nondiabetic control group (adjusted hazard ratio 2.1 [95% CI 1.7-2.5]). Risk of acute pancreatitis was similar in the exenatide versus diabetic control group (0.9 [0.6-1.5]) and sitagliptin versus diabetic control group (1.0 [0.7-1.3]).Our study demonstrated increased incidence of acute pancreatitis in diabetic versus nondiabetic patients but did not find an association between the use of exenatide or sitagliptin and acute pancreatitis. The limitations of this observational claims-based analysis cannot exclude the possibility of an increased risk.
Discoordinate Modulation of Natriuretic Peptides During Acute Cardiac Allograft Rejection in Humans
Authors: Roy G. Masters, Ross A. Davies, John P. Veinot, Paul J. Hendry, Stuart J. Smith, Adolfo J. de Bold
Journal: Circulation (1999)

Increased circulating levels of the cardiac polypeptide hormones atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) may be observed after orthotopic cardiac transplantation. Both the hypertrophic and inflammatory processes in the allograft may contribute to this increase, but no mechanistic explanation has been suggested for this observation.Plasma immunoreactive ANF and BNP determinations were performed in 10 consecutive transplant patients. These were correlated with degree of rejection as reflected by histopathological findings at serial endomyocardial biopsies. Three patients had associated hemodynamic measurements and blood samples 24 hours before and after transplantation. All rejection episodes that received treatment were accompanied by a marked increase in BNP plasma levels to > approximately 400 pg/mL. Steadily increasing BNP levels preceded overt rejection as assessed by histopathological criteria. The increase in plasma BNP was not always accompanied by an increase in ANF, which suggests the specific upregulation of BNP gene expression during acute rejection episodes. Treatment of the acute rejection episodes led to a substantial decrease of BNP plasma levels.The significant selective increase in plasma BNP levels found in the present study has not been previously described. This finding provides a new insight into the mechanism of allograft rejection and the modulation of natriuretic peptide synthesis and release. Furthermore, although preliminary, the data suggest that BNP plasma levels could form the basis for a new, noninvasive screening test to predict acute cardiac allograft rejection. Because treatment with the antilymphocyte monoclonal antibody OKT3 (murine monoclonal antibody to the CD3 antigen of the human T-cell) decreased BNP plasma levels, cytokine production by T-cells may mediate the selective increase in circulating BNP.
A<i>Plasmodium falciparum</i>Homologue of<i>Plasmodium vivax</i>Reticulocyte Binding Protein (PvRBP1) Defines a Trypsin-resistant Erythrocyte Invasion Pathway
Authors: Julian C. Rayner, Esmeralda Vargas-Serrato, Curtis S. Huber, Mary R. Galinski, John W. Barnwell
Journal: The Journal of Experimental Medicine (2001)

Invasion of erythrocytes by Plasmodium merozoites is an intricate process involving multiple receptor-ligand interactions. The glycophorins and an unknown trypsin sensitive factor are all erythrocyte receptors used during invasion by the major human pathogen Plasmodium falciparum. However, only one erythrocyte receptor, Glycophorin A, has a well-established cognate parasite ligand, the merozoite protein erythrocyte binding antigen-175 (EBA-175). The involvement of several other parasite proteins during invasion have been proposed, but no direct evidence links them with a specific invasion pathway. Here we report the identification and characterization of P. falciparum normocyte binding protein 1 (PfNBP1), an ortholog of Plasmodium vivax reticulocyte binding protein-1. PfNBP1 binds to a sialic acid dependent trypsin-resistant receptor on the erythrocyte surface that appears to be distinct from known invasion receptors. Antibodies against PfNBP1 can inhibit invasion of trypsinized erythrocytes and two P. falciparum strains that express truncated PfNBP1 are unable to invade trypsinized erythrocytes. One of these strain, 7G8, also does not invade Glycophorin B-negative erythrocytes. PfNBP1 therefore defines a novel trypsin-resistant invasion pathway and adds a level of complexity to current models for P. falciparum erythrocyte invasion.
Cancer and the gut microbiota: An unexpected link
Authors: Laurence Zitvogel, Lorenzo Galluzzi, Sophie Viaud, Marie Vétizou, Romain Daillère, Miriam Merad, Guido Kroemer
Journal: Science Translational Medicine (2015)

Gut microbiota and its interactions with the host immune system play a role in oncogenesis and can alter the effectiveness of anticancer agents.
Genome-Wide Study of Hypomethylated and Induced Genes in Patients with Liver Cancer Unravels Novel Anticancer Targets
Authors: Barbara Stefanska, David Cheishvili, Matthew Suderman, Ani Arakelian, Jian Huang, Michael Hallett, Ze-Guang Han, Mamun Al-Mahtab, Sheikh Mohammad Fazle Akbar, Wasif Ali Khan, Rubhana Raqib, Imrana Tanvir, Haseeb Ahmed Khan, Shafaat A. Rabbani, Moshe Szyf
Journal: Clinical Cancer Research (2014)

We utilized whole-genome mapping of promoters that are activated by DNA hypomethylation in hepatocellular carcinoma (HCC) clinical samples to shortlist novel targets for anticancer therapeutics. We provide a proof of principle of this approach by testing six genes short-listed in our screen for their essential role in cancer growth and invasiveness.We used siRNA- or shRNA-mediated depletion to determine whether inhibition of these genes would reduce human tumor xenograft growth in mice as well as cell viability, anchorage-independent growth, invasive capacities, and state of activity of nodal signaling pathways in liver, breast, and bladder cancer cell lines.Depletion of EXOSC4, RNMT, SENP6, WBSCR22, RASAL2, and NENF effectively and specifically inhibits cancer cell growth and cell invasive capacities in different types of cancer, but, remarkably, there is no effect on normal cell growth, suggesting a ubiquitous causal role for these genes in driving cancer growth and metastasis. Depletion of RASAL2 and NENF in vitro reduces their growth as explants in vivo in mice. RASAL2 and NENF depletion interferes with AKT, WNT, and MAPK signaling pathways as well as regulation of epigenetic proteins that were previously demonstrated to drive cancer growth and metastasis.Our results prove that genes that are hypomethylated and induced in tumors are candidate targets for anticancer therapeutics in multiple cancer cell types. Because these genes are particularly activated in cancer, they constitute a group of targets for specific pharmacologic inhibitors of cancer and cancer metastasis. Clin Cancer Res; 20(12); 3118-32. ©2014 AACR.
Multiple duodenal polyps in uraemia: a little known clinical entity.
Authors: H Paimela, L G Tallgren, S Stenman, H von Numers, T M Scheinin
Journal: Gut (1984)

Multiple duodenal polyps were found by endoscopy in five out of 33 patients with chronic renal failure and in one of 300 controls. In the uraemic cases the polyps were caused by circumscribed nodular hyperplasia of Brunner9s glands. One of these five patients later underwent surgery for duodenal obstruction caused by the polyps; the other patients were asymptomatic. One of the controls had multiple duodenal polyps. The recorded incidence of multiple duodenal polyps was significantly higher among patients with chronic renal failure than in patients without renal disease. Patients with chronic renal failure and polyps did not differ significantly from the other renal patients in the comparison of variables such as gastric acid secretion, serum concentrations of gastrin and group I pepsinogens or mean length of dialysis treatment. The mean pH of gastric resting juice was significantly higher, however, in uraemic patients with polyps than in those without. Uraemic patients displayed a gastric acid secretion capacity within normal range, and significantly raised serum gastrin and group I pepsinogen concentrations.
The stimulus-secretion coupling of glucose-induced insulin release. Metabolic and functional effects of NH4+ in rat islets.
Authors: A Sener, J C Hutton, S Kawazu, A C Boschero, G Somers, G Devis, A Herchuelz, W J Malaisse
Journal: Journal of Clinical Investigation (1978)

NH4+ caused a dose-related, rapid, and reversible inhibition of glucose-stimulated insulin release by isolated rat islets. It also inhibited glyceraldehyde-, Ba2+-, and sulfonylurea-stimulated insulun secretion. NH4+ failed to affect glucose utilization and oxidation, glucose-stimulated proinsulin biosynthesis, the concentration of ATP, AD, and AMP, and the intracellular pH. NH4+ also failed to affect the ability of theophylline and cytochalasin B to augment glucose-induced insulin release. However, in the presence and absence of glucose, accumulation of NH4+ in islet cells was associated with a fall in the concentration of NADH and HADPH and a concomitant alteration of 86Rb+ and 45Ca2+ (or 133Ba2+) handling. These findings suggest that reduced pyridine nucleotides, generated by the metabolism of endogenous of exogenous nutrients, may modulate ionophoretic processes in the islet cells and by doing so, affect the net uptake of Ca2+ and subsequent release of insulin.
Involvement of the TCR Cβ FG Loop in Thymic Selection and T Cell Function
Authors: Tetsuro Sasada, Maki Touma, Hsiu-Ching Chang, Linda K. Clayton, Jia-huai Wang, Ellis L. Reinherz
Journal: The Journal of Experimental Medicine (2002)

The asymmetric disposition of T cell receptor (TCR) Cβ and Cα ectodomains creates a cavity with a side-wall formed by the rigid Cβ FG loop. To investigate the significance of this conserved structure, we generated loop deletion (βΔFG) and βwt transgenic (tg) mice using the TCR β subunit of the N15 CTL. N15βwt and N15βΔFG H-2b animals have comparable numbers of thymocytes in S phase and manifest developmental progression through the CD4−CD8− double-negative (DN) compartment. N15βΔFG facilitates transition from DN to CD4+8+ double-positive (DP) thymocytes in recombinase activating gene (RAG)-2−/− mice, showing that pre-TCR function remains. N15βΔFG animals possess ∼twofold more CD8+ single-positive (SP) thymocytes and lymph node T cells, consistent with enhanced positive selection. As an altered Vα repertoire observed in N15βΔFG mice may confound the deletion's effect, we crossed N15αβ TCR tg RAG-2−/− with N15βΔFG tg RAG-2−/− H-2b mice to generate N15αβ RAG-2−/− and N15αβ.βΔFG RAG-2−/− littermates. N15αβ.βΔFG RAG-2−/− mice show an 8–10-fold increase in DP thymocytes due to reduced negative selection, as evidenced by diminished constitutive and cognate peptide-induced apoptosis. Compared with N15αβ, N15αβ.βΔFG T cells respond poorly to cognate antigens and weak agonists. Thus, the Cβ FG loop facilitates negative selection of thymocytes and activation of T cells.
The strength of the Fas ligand signal determines whether hepatocytes act as type 1 or type 2 cells in murine livers
Authors: Sven Schüngel, Laura Elisa Buitrago-Molina, Padmavathi devi Nalapareddy, Margitta Lebofsky, Michael P. Manns, Hartmut Jaeschke, Atan Gross, Arndt Vogel
Journal: Hepatology (2009)

Abstract The BH3-interacting domain death agonist Bid has been shown to be critical for Fas-induced hepatocellular apoptosis. Furthermore, some studies have suggested that phosphorylation of Bid may determine its apoptotic function and may act as a switch to nonapoptotic functions. The aim of this study was to evaluate the role of Bid and phosphorylated Bid for Fas ligand (FasL)-induced apoptosis in murine livers. The monoclonal antibody Jo2 and a hexameric form of sFasL (MegaFasL) were used to induce apoptosis in wild-type, Bid-deficient ( Bid −/− ), Bid transgenic mice expressing a nonphosphorable form of Bid and Fas receptor-deficient lpr mice. Apoptosis sensitivity was determined in healthy mice and in mice following bile duct ligation, partial hepatectomy, or suramin pretreatment. As previously reported, loss of Bid protects mice against Jo2-induced liver failure. Remarkably however, Bid −/− mice are highly sensitive to MegaFasL-induced apoptosis. MegaFasL-treated Bid −/− mice showed a typical type I cell signaling behavior with activation of caspase-3 without Bax translocation to the mitochondria and no cytochrome C/Smac release into the cytosol. In contrast to previous in vitro findings, phosphorylation of Bid does not affect the sensitivity of hepatocytes to Fas receptor-mediated apoptosis in vivo. Conclusion: Our data suggest that Bid mainly amplifies a weak death receptor signal in quiescent and nonquiescent hepatocytes rendering the liver more sensitive to FasL-induced apoptosis. Thus, depending on the efficacy of Fas receptor activation, hepatocytes and nonparenchymal cells can either behave as type I or type II cells. (Hepatology 2009.)
THE DISTRIBUTION OF FAT IN THE LIVER
Authors: John McCrae, Oskar Klotz
Journal: The Journal of Experimental Medicine (1910)

1. Nearly all livers at autopsy contain fat which is histologically demonstrable. 2. Fatty substances in the liver appear chiefly in two forms, as small granules and as globules of various sizes. 3. We suppose that granules indicate the (protoplasmic) change commonly spoken of as fatty degeneration, and that globules of small size are excess of fat, stored up by reason of some pathological change which may be merely temporary. 4. Fat is oftenest central, least often in the mid-zone. 5. A heavy deposit of fat is compatible with a competent liver. 6. Intense fattiness, generally globular, occurs with intoxications of bacterial and chemical nature, as well as in cases where a complex toxin is manufactured by the body-cells. 7. Granular fat occurs oftener than globular: it affects most often the central zone; globular affects most often the peripheral. 8. " Accidental " masses of globular fat are found at times, and appear to follow no rule of position: these are comparable to lipomata, which are evidently the result of a pathological process. 9. We found no deposit of fat characteristic of uremia. 10 We know of no analysis of the liver fats in the granular and globular states respectively: it seems to have been taken for granted that the deposits were one and the same. To determine the relationship, if any, between these two forms should be the basis of investigation.
Thymoma: a clinicopathological comparative study of 25 cases
Authors: F Offner, J Vallaeys, H Roels, M Van der Straeten
Journal: European Respiratory Journal (1991)

We reviewed 25 patients with thymoma for clinical symptoms at presentation, X-ray findings and outcome. The tumours of all patients were classified using 3 different pathologic classification systems and each system was evaluated for its predictive power with respect to survival. The recent classification system by Müller-Hermelink allowed to distinguish thymomas with associated systemic syndromes from those without. However, no good prediction with respect to outcome could be made by any of the 3 systems.
Mental Disorders and Use of Cardiovascular Procedures After Myocardial Infarction
Authors: B G Druss, D W Bradford, R A Rosenheck, M J Radford, H M Krumholz
Journal: JAMA (2000)

ContextA number of studies have found race- and sex-based differences in rates of cardiovascular procedures in the United States. Similarly, mental disorders might be expected to be associated with lower rates of such procedures on the basis of clinical, socioeconomic, patient, and provider factors.ObjectiveTo assess whether having a comorbid mental disorder is associated with a lower likelihood of cardiac catheterization and/or revascularization after acute myocardial infarction.DesignRetrospective cohort study using data from medical charts and administrative files as part of the Cooperative Cardiovascular Project.SettingAcute care nongovernmental hospitals in the United States.PatientsNational cohort of 113,653 eligible patients 65 years or older who were hospitalized for confirmed acute myocardial infarction between February 1994 and July 1995.Main Outcome MeasuresLikelihood of cardiac catheterization, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass graft (CABG) surgery during the index hospitalization, comparing patients with and without mental disorders (classified as schizophrenia, major affective disorder, substance abuse/dependence disorder, or other mental disorder).ResultsCompared with the remainder of the sample, patients with any comorbid mental disorder (n = 5365; 4.7%) were significantly less likely to undergo PTCA (11.8% vs 16.8%; P&lt;.001) or CABG (8.2% vs 12.6%; P&lt;.001). After adjusting for demographic, clinical, hospital, and regional factors, individuals with mental disorders were 41% (for schizophrenia) to 78% (for substance use) as likely to undergo cardiac catheterization as those without mental disorders (P&lt;.001 for all). Among those undergoing catheterization, rates of PTCA or CABG for patients with mental disorders were not significantly different from rates for patients without mental disorders (for those with any mental disorder, P = .12 for PTCA and P = .06 for CABG). In multivariate models, the 30-day mortality did not differ between patients with and without mental disorders.ConclusionsIn this study, individuals with comorbid mental disorders were substantially less likely to undergo coronary revascularization procedures than those without mental disorders. Further research is needed to understand the degree to which patient and provider factors contribute to this difference and its implications for quality and long-term outcomes of care.
Effects of Mild Chronic Hypoxia on the Pulmonary Circulation in Calves with Reactive Pulmonary Hypertension
Authors: JOHN H. K. VOGEL, DAN G. McNAMARA, GRADY HALLMAN, HARVEY ROSENBERG, GAIL JAMIESON, J. D. McCRADY
Journal: Circulation Research (1967)

The effects of the mild hypoxia at an altitude of 5280 ft on the pulmonary circulation were examined in normal calves and calves with a preexisting stimulus to maintain a reactive pulmonary vascular bed. In a serial study, 9 calves born at 5280 ft and 9 calves born at sea level underwent left pulmonary artery (LPA) ligation; 3 calves born at 5280 ft and 8 calves born at sea level underwent right pulmonary artery (RPA) ligation within 24 to 48 hours after birth. Progressive pulmonary hypertension and right ventricular heart failure developed in all calves operated on at 5280 ft but not in those with LPA ligation performed at sea level until they were transferred to 5280 ft. In contrast, in some animals with RPA ligation at sea level, progressive pulmonary hypertension was noted. The increased pulmonary blood flow consequent to LPA ligation does not result in progressive pulmonary hypertension at sea level but the addition of the mild hypoxia at 5280 ft appears to provide additional sufficient stimulus to result in progressive pulmonary hypertension. However, the slightly higher pulmonary blood flow subsequent to RPA ligation is capable of producing progressive pulmonary hypertension at sea level. Correlation was found between these results and human patients with congenital unilateral absence of a pulmonary artery, indicating that, in subjects with some stimulus to maintain a reactive pulmonary vascular bed, the mild hypoxia of 5280 ft may exert a significant effect on the pulmonary circulation.
Experience in the treatment of Crohn's disease of the large intestine.
Authors: J H Jones, J E Lennard-Jones, H E Lockhart-Mummery
Journal: Gut (1966)

EDITORIAL COMMENT Limited resection for localized disease with total colectomy for diffuse disease have given good results.Medical treatment has given symptomatic relief but in this series rarely gave permanent benefit.It is possible that with earlier recognition of the disease it will become appreciated that corticosteroids have a greater role to play than is apparent in this series.on July 12,
Effects of cold-water immersion of legs after training session on serum creatine kinase concentrations in rugby players: Table 1
Authors: Giuseppe Banfi, Gianluca Melegati, Pascal Valentini
Journal: British Journal of Sports Medicine (2007)

The use of methods other than passive recovery for improving recovery after intense training and competitions in sports is growing. In particular, in rugby, the use of cold water, possibly associated with active recovery (cycling), and the use of cold and hot water immersion are quite popular. In our experience, the perception of muscle soreness after heavy exercise in top-level rugby players decreases when cold-water immersion of legs is performed during recovery period, as also quantified by a semiquantitative scale.1

Gill and coworkers described the effectiveness of contrast water therapy (CWT) for improving the post-match recovery in elite rugby players.2

CWT was performed by immersion of the body to …