tbuckley/cabot-search huggingface dataset:
Post-feeding hyperammonaemia in patients with transjugular intrahepatic portosystemic shunt and liver cirrhosis: role of small intestinal ammonia release and route of nutrient administration
Authors: M Plauth
Journal: Gut (2000)

Hyperammonaemia is a pathogenetic factor for hepatic encephalopathy that may be augmented after a transjugular intrahepatic portosystemic shunt (TIPS). Experimental data suggest that hyperammonaemia may be caused to a large extent by metabolism of small intestinal enterocytes rather than colonic bacteria.To evaluate if ammonia release and glutamine metabolism by small intestinal mucosa contribute to hyperammonaemia in vivo in patients with liver cirrhosis.Using TIPS to examine mesenteric venous blood, we measured mesenteric venous-arterial concentration differences in ammonia and glutamine in patients with liver cirrhosis before, during, and after enteral (n = 8) or parenteral (n = 8) isonitrogenous infusion of a glutamine containing amino acid solution.During enteral nutrient infusion, ammonia release increased rapidly compared with the post-absorptive state (65 (58-73) v. 107 (95-119) micromol/l after 15 min; mean (95% confidence interval)) in contrast with parenteral infusion (50 (41-59) v. 62 (47-77) micromol/l). This resulted in a higher portal ammonia load (29 (21-36) v. 14 (8-21) mmol/l/240 minutes) and a higher degree of systemic hyperammonaemia (14 (11-17) v. 9 (6-12) mmol/l/240 minutes) during enteral than parenteral infusion. The mesenteric venous-arterial concentration difference in glutamine changed from net uptake to release at the end of the enteral infusion period (-100 (-58 to -141) v. 31 (-47-110) micromol/l) with no change during parenteral nutrition.These data suggest that small intestinal metabolism contributes to post-feeding hyperammonaemia in patients with cirrhosis. When artificial nutrition is required, parenteral nutrition may be superior to enteral nutrition in patients with portosystemic shunting because of the lower degree of systemic hyperammonaemia.
Noninvasive Diagnosis of Actionable Mutations by Deep Sequencing of Circulating Free DNA in Lung Cancer from Never-Smokers: A Proof-of-Concept Study from BioCAST/IFCT-1002
Authors: Sébastien Couraud, Felipe Vaca-Paniagua, Stéphanie Villar, Javier Oliver, Tibor Schuster, Hélène Blanché, Nicolas Girard, Jean Trédaniel, Laurent Guilleminault, Radj Gervais, Nathalie Prim, Michel Vincent, Jacques Margery, Sébastien Larivé, Pascal Foucher, Bernard Duvert, Maxime Vallee, Florence Le Calvez-Kelm, James McKay, Pascale Missy, Franck Morin, Gérard Zalcman, Magali Olivier, Pierre-Jean Souquet
Journal: Clinical Cancer Research (2014)

Tumor somatic mutation analysis is part of the standard management of metastatic lung cancer. However, physicians often have to deal with small biopsies and consequently with challenging mutation testing. Circulating free DNA (cfDNA) is a promising tool for accessing the tumor genome as a liquid biopsy. Here, we evaluated next-generation sequencing (NGS) on cfDNA samples obtained from a consecutive series of patients for the screening of a range of clinically relevant mutations.
Enhancement of clonogenicity of human multiple myeloma by dendritic cells
Authors: Anjli Kukreja, Aisha Hutchinson, Kavita Dhodapkar, Amitabha Mazumder, David Vesole, Revathi Angitapalli, Sundar Jagannath, Madhav V. Dhodapkar
Journal: The Journal of Experimental Medicine (2006)

Infiltration by dendritic cells (DCs) is a common feature of most human tumors. Prior studies evaluating the interaction of DCs with tumors have focused largely on their immunologic properties (for review see Banchereau, J., and R.M. Steinman. 1998. Nature. 392:245–252). In this study, we show that the clonogenicity of several human tumor cell lines and primary tumor cells from myeloma patients is enhanced by their interactions with DCs. Myeloma cells cultured in the presence of DCs have an altered phenotype with an increased proportion of cells lacking terminal plasma cell differentiation marker CD138. DC–tumor interaction also leads to the up-regulation of B cell lymphoma 6 expression in myeloma cells. Effects of DCs on myeloma cells are inhibited by blockade of the receptor activator of NF-kB (RANK)–RANK ligand and B cell–activating factor–APRIL (a proliferation-inducing ligand)-mediated interactions. Together, these data suggest that tumor–DC interactions may directly impact the biology of human tumors, particularly multiple myeloma, and may be a target for therapeutic intervention.
The Effect of Dihydrocholesterol on the Absorption of Cholesterol by the Rat
Authors: RAY H. ROSENMAN, SANFORD O. BYERS, MEYER FRIEDMAN
Journal: Circulation Research (1954)

Simultaneous feeding of dihydrocholesterol and cholesterol to rats significantly reduced the amount of cholesterol absorbed into the thoracic lymph. Hypercholesteremia and hyperphospholipemia developed in rats simultaneously fed cholesterol and cholic acid for 8 weeks. The addition of dihydrocholesterol to this diet also decreased the rate of development and magnitude of the hypercholesteremia, but had no apparent effect upon the rise of plasma phospholipids.
B Cell Signaling and Fate Decision
Authors: Tomohiro Kurosaki, Hisaaki Shinohara, Yoshihiro Baba
Journal: Annual Review of Immunology (2009)

Antigen receptors on the surface of B lymphocytes trigger adaptive immune responses after encountering their cognate antigens but also control a series of antigen-independent checkpoints during B cell development. These physiological processes are regulated by the expression and function of cell surface receptors, intracellular signaling molecules, and transcription factors. The function of these proteins can be altered by a dynamic array of post-translational modifications, using two interconnected mechanisms. These modifications can directly induce an altered conformational state in the protein target of the modification itself. In addition, they can create new binding sites for other protein partners, thereby contributing to where and when such multiple protein assemblies are activated within cells. As a new type of post-transcriptional regulator, microRNAs have emerged to influence the development and function of B cells by affecting the expression of target mRNAs.
Obesity and the Development of Insulin Resistance and Impaired Fasting Glucose in Black and White Adolescent Girls
Authors: David J. Klein, Lisa Aronson Friedman, William R. Harlan, Bruce A. Barton, George B. Schreiber, Robert M. Cohen, Linda C. Harlan, John A. Morrison
Journal: Diabetes Care (2004)

OBJECTIVE—Age at onset of type 2 diabetes has decreased during the past 20 years, especially in black women. Studies of factors associated with insulin resistance and hyperglycemia in preadolescent and adolescent populations are essential to understanding diabetes development. RESEARCH DESIGN AND METHODS—The National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study (NGHS) is a 10-year cohort study of the development of obesity in black and white girls. Two NGHS centers examined the associations of obesity, puberty, and race with fasting insulin, glucose, and homeostasis model assessment of insulin resistance (HOMA-IR; a calculated index of insulin resistance) measures at 9–10 years of age (baseline) and 10 years later. RESULTS—Black girls had greater baseline and year-10 BMI than white girls, with a greater 10-year incidence of obesity. BMI-insulin correlations were positive in both black and white girls at both visits, but insulin remained higher in black girls after controlling for BMI. In black girls, insulin and HOMA-IR were higher in the prepubertal period (before the emergence of racial differences in BMI), increased more during puberty, and decreased less with its completion. Baseline BMI predicted year-10 glucose and the development of impaired fasting glucose (IFG) in black girls. In white girls, the rate of BMI increase during follow-up predicted these outcomes. The 10-year incidence of diabetes in black girls was 1.4%. CONCLUSIONS—Black-white differences in insulin resistance are not just a consequence of obesity, but precede the pubertal divergence in BMI. The development of IFG appears to be a function of the rate of increase of BMI in white girls and early obesity in black girls.
Analytical Performance Characteristics, Quality Assurance and Clinical Utility of Immunological Assays for Human IgE Antibodies of Defined Allergen Specificities. (CLSI-ILA20-A3)
Authors: Robert G. Hamilton, Per N. Matsson, Debra L. Hovanec-Burns, Mark Van Cleve, Sic Chan, Anita Kober, Joerg R. Kleine-Tebbe, Harald Renz, Carina Magnusson, Ron Quicho, N. Franklin Adkinson
Journal: Journal of Allergy and Clinical Immunology (2015)
Drug Disposition in Obesity: Toward Evidence-Based Dosing
Authors: Catherijne A.J. Knibbe, Margreke J.E. Brill, Anne van Rongen, Jeroen Diepstraten, Piet Hein van der Graaf, Meindert Danhof
Journal: The Annual Review of Pharmacology and Toxicology (2014)

Obesity and morbid obesity are associated with many physiological changes affecting pharmacokinetics, such as increased blood volume, cardiac output, splanchnic blood flow, and hepatic blood flow. In obesity, drug absorption appears unaltered, although recent evidence suggests that this conclusion may be premature. Volume of distribution may vary largely, but the magnitude and direction of changes seem difficult to predict, with extrapolation on the basis of total body weight being the best approach to date. Changes in clearance may be smaller than in distribution, whereas there is growing evidence that the influence of obesity on clearance can be predicted on the basis of reported changes in the metabolic or elimination pathways involved. For obese children, we propose two methods to distinguish between developmental and obesity-related changes. Future research should focus on the characterization of physiological concepts to predict the optimal dose for each drug in the obese population.
A Dose-Ranging Study of Cabozantinib in Men with Castration-Resistant Prostate Cancer and Bone Metastases
Authors: Richard J. Lee, Philip J. Saylor, M. Dror Michaelson, S. Michael Rothenberg, Malgorzata E. Smas, David T. Miyamoto, Carol A. Gurski, Wanling Xie, Shyamala Maheswaran, Daniel A. Haber, Jonathan G. Goldin, Matthew R. Smith
Journal: Clinical Cancer Research (2013)

Cabozantinib is an oral MET/VEGFR2 inhibitor. A recent phase II study of cabozantinib (100 mg daily) showed improved bone scans in subjects with metastatic castration-resistant prostate cancer (mCRPC), but adverse events (AE) caused frequent dose reductions. This study was designed to determine the efficacy and tolerability of cabozantinib at lower starting doses.An adaptive design was used to determine the lowest active daily dose among 60, 40, and 20 mg. The primary endpoint was week 6 bone scan response, defined as ≥30% decrease in bone scan lesion area. The secondary endpoint was change in circulating tumor cells (CTC).Among 11 evaluable subjects enrolled at 40 mg, there were 9 partial responses (PR), 1 complete response, and 1 stable disease (SD). Of 10 subjects subsequently enrolled at 20 mg, there were 1 PR, 5 SDs, and 4 with progressive disease. Among 13 subjects enrolled on the 40 mg expansion cohort, there were 6 PRs and 7 SDs. No subjects required dose reduction or treatment interruption at 6 or 12 weeks; 3 subjects at dose level 0 discontinued due to AEs by 12 weeks. At 40 mg, median treatment duration was 27 weeks. 58% of subjects with ≥5 CTCs/7.5 mL at baseline converted to <5.Cabozantinib 40 mg daily was associated with a high rate of bone scan response. Cabozantinib 40 mg daily was associated with better tolerability than previously reported for cabozantinib 100 mg daily. These observations informed the design of phase III studies of cabozantinib in mCRPC.
Retrovirus-Induced Ovine Pulmonary Adenocarcinoma, an Animal Model for Lung Cancer
Authors: M. Palmarini, H. Fan
Journal: JNCI Journal of the National Cancer Institute (2001)

Studies on the molecular mechanisms of transformation of retrovirus-induced neoplasms in domestic and laboratory animal species have provided insights into the genetic basis of cancer. Ovine pulmonary adenocarcinoma (OPA) is a retrovirus-induced spontaneous lung tumor of sheep that has striking analogies to some forms of human adenocarcinoma. The etiologic agent of OPA, jaagsiekte sheep retrovirus (JSRV), is unique among retroviruses for having a specific tropism for the differentiated epithelial cells of the lung, and it is the only virus known to cause a naturally occurring lung adenocarcinoma. Expression of the JSRV envelope protein is sufficient to induce cell transformation in vitro, possibly via the activation of the phosphatidylinositol 3-kinase/Akt-signaling pathway mediated by the cytoplasmic tail of the transmembrane protein. The aim of this review is to draw the attention of basic and clinical scientists engaged in lung cancer research to this unique animal model, to explore the possible use of OPA as a tool to investigate the mechanisms of pulmonary carcinogenesis, and to underline the similarities between OPA and some forms of human lung adenocarcinoma. The possibility of a viral etiology for the latter will be evaluated in this review.
Usual Source of Care as a Health Insurance Substitute for U.S. Adults With Diabetes?
Authors: Jennifer E. DeVoe, Carrie J. Tillotson, Lorraine S. Wallace
Journal: Diabetes Care (2009)

OBJECTIVE The purpose of this study was to examine the effects of health insurance and/or a usual source of care (USC) on receipt of diabetic-specific services and health care barriers for U.S. adults with diabetes. RESEARCH DESIGN AND METHODS Secondary analyses of data from 6,562 diabetic individuals aged ≥18 years from the nationally representative Medical Expenditure Panel Survey from 2002 to 2005 were performed. Outcome measures included receipt of seven diabetic services plus five barriers to care. RESULTS More than 84% of diabetic individuals in the U.S. had full-year coverage and a USC; 2.3% had neither one. In multivariate analyses, the uninsured with no USC had one-fifth the odds of receiving A1C screening (odds ratio 0.23 [95% CI 0.14–0.38]) and one-tenth the odds of a blood pressure check (0.08 [0.05–0.15]), compared with insured diabetic individuals with a USC. Similarly, being uninsured without a USC was associated with 5.5 times the likelihood of unmet medical needs (5.51 [3.49–8.70]) and three times more delayed urgent care (3.13 [1.53–6.38]) compared with being insured with a USC. Among the two groups with either insurance or a USC, diabetic individuals with only a USC had rates of diabetes-specific care more similar to those of insured individuals with a USC. In contrast, those with only insurance were closer to the reference group with fewer barriers to care. CONCLUSIONS Insured diabetic individuals with a USC were better off than those with only a USC, only insurance, or neither one. Policy reforms must target both the financing and the delivery systems to achieve increased receipt of diabetes services and decreased barriers to care.
T cell lines characterize events in the pathogenesis of the Wiskott-Aldrich syndrome.
Authors: I J Molina, D M Kenney, F S Rosen, E Remold-O'Donnell
Journal: The Journal of Experimental Medicine (1992)

The Wiskott-Aldrich syndrome (WAS) is a severe immunodeficiency and platelet deficiency disease arising from an X-linked defect. The disease is correctable by transplantation of hematopoietic stem cells, but the product of the defective gene is unidentified and the number of defects in patient blood cells is large. The current hurdle is the need to identify the early pathogenic event(s) that are the cause of other defects. As a step toward this goal, we have generated and examined a panel of interleukin 2-dependent allospecific T cell lines from peripheral lymphocytes of seven WAS patients and five normal individuals. WAS cell lines, like normal lines, undergo vigorous proliferation when challenged with specific allostimulant or with phorbol myristate acetate and ionomycin. Both normal and WAS T cell lines express cell surface molecules CD2, CD3, T cell receptor-alpha/beta, human histocompatibility leukocyte antigen class I, CD45 and CD11a, and varying ratios of CD4 and CD8, and are negative for natural killer cell and monocyte surface molecules. WAS T cell lines express CD43 (sialophorin/leukosialin) with molecular weight and in an amount comparable with normal T cell lines. WAS T cell lines thus do not express defects in CD43 (decreased amount, abnormal molecular weight), previously documented in WAS circulating lymphocytes. On the other hand, as detected by scanning electron microscopy, WAS cell lines exhibit severe morphological abnormalities, including decreased size and density of the microvillus surface projections. The morphological abnormalities of WAS T cell lines are similar to, or more extensive than, those previously reported for WAS peripheral lymphocytes, indicating that the generation of morphological (cytoarchitectural) defects is an early pathogenic event in this disease. The findings suggest that the gene that is defective in the WAS encodes a protein that normally functions to maintain or regulate the cytoskeletal structure of blood cells.
Substantial Differences in Specificity of HIV-Specific Cytotoxic T Cells in Acute and Chronic HIV Infection
Authors: Philip J.R. Goulder, Marcus A. Altfeld, Eric S. Rosenberg, Thi Nguyen, Yanhua Tang, Robert L. Eldridge, Marylyn M. Addo, Suqin He, Joia S. Muckerjee, Mary N. Phillips, Michael Bunce, Spyros A. Kalams, Rafick P. Sekaly, Bruce D. Walker, Christian Brander
Journal: The Journal of Experimental Medicine (2001)

Cytotoxic T lymphocytes (CTLs) play a vital part in controlling viral replication during human viral infections. Most studies in human infections have focused on CTL specificities in chronic infection and few data exist regarding the specificity of the initial CTL response induced in acute infection. In this study, HIV-1 infection in persons expressing human histocompatibility leukocyte antigen (HLA)-A*0201 was used as a means of addressing this issue. In chronic infection, the dominant HLA-A*0201-restricted CTL response is directed towards the epitope SLYNTVATL ("SL9") in p17 Gag (residues 77-85). This epitope is targeted by 75% of HLA-A*0201-positive adults, and the magnitude of this A*0201-SL9 response shows a strong negative association with viral load in progressive infection. Despite using the highly sensitive peptide-major histocompatibility complex tetramer and intracellular cytokine assays, responses to the SL9 epitope were not detectable in any of 11 HLA-A*0201-positive subjects with acute HIV-1 infection (P = 2 x 10(-6)), even when assays were repeated using the SL9 peptide variant that was encoded by their autologous virus. In contrast, multiple responses (median 3) to other epitopes were evident in 7 of the 11 A*0201-positive subjects. Longitudinal study of two subjects confirmed that the A*0201-SL9 response emerged later than other CTL responses, and after viral set point had been reached. Together, these data show that the CTL responses that are present and that even may dominate in chronic infection may differ substantially from those that constitute the initial antiviral CTL response. This finding is an important consideration in vaccine design and in the evaluation of vaccine candidates.
Lymphoid follicles in (very) severe COPD: beneficial or harmful?
Authors: G. G. Brusselle, T. Demoor, K. R. Bracke, C-A. Brandsma, W. Timens
Journal: European Respiratory Journal (2009)

Inflammation is a main pathogenetic factor in the development and progression of chronic obstructive pulmonary disease (COPD). Recently, it has become clear that not only the innate, but also the specific immune response plays a role. A striking finding, in particular in lungs of patients with severe COPD, often with a predominant emphysema phenotype, is the presence of B-cell follicles. As seen in other tissues, these follicles are the result of lymphoid neogenesis. The finding of oligoclonality in B-cell follicles in COPD suggests that they play a role in local antigen specific immune responses. To date, it is not known which antigens may be involved; microbial antigens, cigarette smoke-derived antigens and antigens from extracellular matrix breakdown products have been suggested. Consequently, the pathogenetic role of this follicular B-cell response is not yet clear. It might be protective against microbial colonisation and infection of the lower respiratory tract and, therefore, beneficial, or it could be of a more harmful (autoimmune) nature, directed against lung tissue components. It is necessary to determine the specific antigen(s) and to explore the exact role of the COPD related B-cell response in order to include modulation of this response and develop therapeutic options.
Patients' responses to barium x-ray studies.
Authors: J Wilson-Barnett
Journal: BMJ (1978)

the obvious aggregation with 0-1 mmol/l seen before treatment.This effect lasted for 12 hours, during which she was free of symptoms.The patient was treated with flurbiprofen for three months, during which time her symptoms did not recur.Within a few days of discontinuing this treatment she complained of the same symptoms.Since then it has been decided to start long-term flurbiprofen treatment again and subsequently she has remained asymptomatic.Her gastrointestinal symptoms also dis- appeared.This suggests the possibility that the spontaneous platelet aggre- gation was also causing gut ischaemia.
The characteristics of a low resistance breathing valve designed for the measurement of high aerobic capacity.
Authors: P. Jakeman, B. Davies
Journal: British Journal of Sports Medicine (1979)

The study of physical performance capacity has been of particular interest to the exercise physiologist and many accurate techniques have been designed for the measurement of human performance. The use of maximal oxygen uptake has, since its development by Hill et al in 1924, been regarded as a valuable measure of cardiorespiratory function and used extensively as a criterion of performance capacity of endurance athletes (e.g. Taylor et al, 1955; Saltin and Astrand, 1967; Hanson, 1973).
Protective effect of androgens against inflammation induced cartilage degradation in male rodents.
Authors: J A Da Silva, J P Larbre, T D Spector, L A Perry, D L Scott, D A Willoughby
Journal: Annals of the Rheumatic Diseases (1993)

Rheumatoid arthritis (RA) is a disease which predominantly affects women. Interestingly, low serum androgen levels and clinical improvement with androgen replacement have been reported in male patients. The aetiopathogenic role of sex hormones in arthritis and their potential long term effects on joint destruction and disability remains unclear, however. This study was designed to investigate the potential influence of sex hormones on inflammation induced cartilage degradation in male rodents.An in vivo model of cotton wrapped cartilage implants was used to assess the effects of androgen, oestradiol, and progesterone on inflammation induced cartilage degradation, and in vitro techniques were used to investigate the direct actions on cartilage metabolism and cytokine production in male animals.Orchidectomy resulted in accelerated cartilage damage which was reversed by replacement of physiological levels of androgens. Granulomatous tissue from castrated male rodents produced higher amounts of interleukin 1. Sex hormones reduced spontaneous proteoglycan loss in vitro but did not interfere with the effects of interleukin 1 on cultured cartilage.Androgens appear to protect cartilage from inflammation induced breakdown in male animals. These results support a pathogenic role for hypoandrogenism in rheumatoid arthritis and suggest that long term androgen replacement may help prevent joint damage and disability.