tbuckley/cabot-search huggingface dataset:
Peritoneal Transport Properties and Dialysis Dose Affect Growth and Nutritional Status in Children on Chronic Peritoneal Dialysis
Authors: FRANZ SCHAEFER, GÜNTER KLAUS, OTTO MEHLS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. To evaluate a possible effect of peritoneal transport properties and dialysis dose on the physical development of children on chronic peritoneal dialysis, a cohort of 51 children was prospectively followed for 18 mo. Peritoneal transport characteristics were assessed by serial peritoneal equilibration tests (PET), dialysis efficacy by dialysate and residual renal clearance measurements, and growth and nutritional status by the longitudinal changes (Δ) of height SD score (SDS), body mass index (BMI) SDS, and serum albumin. Δ height SDS was negatively correlated with the creatinine equilibration rate observed in the initial PET ( r = -0.31, P &lt; 0.05). Multiple regression analysis confirmed the negative effect of the high transporter state (partial r 2 = 0.07), and disclosed an additional positive effect of dialytic C Cr (partial r 2 = 0.11) and a weak negative effect of daily dialysate volume (partial r 2 = 0.04) on Δ height SDS. Δ BMI SDS was strongly age-dependent ( r = -0.48, P &lt; 0.001); while relative body mass gradually increased below 4 yr of age, it remained stable in older children. Positive changes in BMI SDS were associated with rapid PET creatinine equilibration rates (univariate r = 0.35, P &lt; 0.05) and/or large dialysate volumes (multivariate partial r 2 = 0.11), suggesting a role of dialytic glucose uptake in the development of obesity. The change in serum albumin concentrations was positively correlated with dialysate volume (partial r 2 = 0.14), and negatively affected by dialytic protein losses (partial r 2 = 0.06). In conclusion, the peritoneal transporter state is a weak but significant determinant of growth and body mass gain in children on chronic peritoneal dialysis. Rapid small solute equilibration contributes to impaired growth but enhanced acquisition of body mass. Dialytic small solute clearance has a weak positive effect on statural growth independent of the transporter state, but does not affect body mass gain.
Renal Dysfunction Associated with Intra-abdominal Hypertension and the Abdominal Compartment Syndrome
Authors: Hashim Mohmand, Stanley Goldfarb
Journal: Journal of the American Society of Nephrology (2011)

Once considered mostly a postsurgical condition, intra-abdominal hypertension (IAH) and the abdominal compartment syndrome (ACS) are now thought to increase morbidity and mortality in many patients receiving medical or surgical intensive care. Animal data and human observational studies indicate that oliguria and acute kidney injury are early and frequent consequences of IAH/ACS and can be present at relatively low levels of intra-abdominal pressure (IAP). Among medical patients at particular risk are those with septic shock and severe acute pancreatitis, but the adverse effects of IAH may also be seen in cardiorenal and hepatorenal syndromes. Factors predisposing to IAH/ACS include sepsis, large volume fluid resuscitation, polytransfusion, mechanical ventilation with high intrathoracic pressure, and acidosis, among others. Transduction of bladder pressure is the gold standard for measuring intra-abdominal pressure, and several nonsurgical methods can help reduce IAP. The role of renal replacement therapy for volume management is not well defined but may be beneficial in some cases. IAH/ACS is an important possible cause of acute renal failure in critically ill patients and screening may benefit those at increased risk.
Pharmacogenomics of adverse drug reactions
Authors: Ann K Daly
Journal: Genome Medicine (2013)

Considerable progress has been made in identifying genetic risk factors for idiosyncratic adverse drug reactions in the past 30 years. These reactions can affect various tissues and organs, including liver, skin, muscle and heart, in a drug-dependent manner. Using both candidate gene and genome-wide association studies, various genes that make contributions of varying extents to each of these forms of reactions have been identified. Many of the associations identified for reactions affecting the liver and skin involve human leukocyte antigen (HLA) genes and for reactions relating to the drugs abacavir and carbamazepine, HLA genotyping is now in routine use prior to drug prescription. Other HLA associations are not sufficiently specific for translation but are still of interest in relation to underlying mechanisms for the reactions. Progress on non-HLA genes affecting adverse drug reactions has been less, but some important associations, such as those of SLCO1B1 and statin myopathy, KCNE1 and drug-induced QT prolongation and NAT2 and isoniazid-induced liver injury, are considered. Future prospects for identification of additional genetic risk factors for the various adverse drug reactions are discussed.
Inhibition of Hedgehog signaling sensitizes NSCLC cells to standard therapies through modulation of EMT-regulating miRNAs
Authors: Aamir Ahmad, Ma’in Y Maitah, Kevin R Ginnebaugh, Yiwei Li, Bin Bao, Shirish M Gadgeel, Fazlul H Sarkar
Journal: Journal of Hematology & Oncology (2013)

Abstract Background Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKIs) benefit Non-small cell lung cancer (NSCLC) patients, and an EGFR-TKIi erlotinib, is approved for patients with recurrent NSCLC. However, resistance to erlotinib is a major clinical problem. Earlier we have demonstrated the role of Hedgehog (Hh) signaling in Epithelial-to-Mesenchymal transition (EMT) of NSCLC cells, leading to increased proliferation and invasion. Here, we investigated the role of Hh signaling in erlotinib resistance of TGF-β1-induced NSCLC cells that are reminiscent of EMT cells. Methods Hh signaling was inhibited by specific siRNA and by GDC-0449, a small molecule antagonist of G protein coupled receptor smoothened in the Hh pathway. Not all NSCLC patients are likely to benefit from EGFR-TKIs and, therefore, cisplatin was used to further demonstrate a role of inhibition of Hh signaling in sensitization of resistant EMT cells. Specific pre- and anti-miRNA preparations were used to study the mechanistic involvement of miRNAs in drug resistance mechanism. Results siRNA-mediated inhibition as well as pharmacological inhibition of Hh signaling abrogated resistance of NSCLC cells to erlotinib and cisplatin. It also resulted in re-sensitization of TGF-β1-induced A549 (A549M) cells as well the mesenchymal phenotypic H1299 cells to erlotinib and cisplatin treatment with concomitant up-regulation of cancer stem cell (CSC) markers (Sox2, Nanog and EpCAM) and down-regulation of miR-200 and let-7 family miRNAs. Ectopic up-regulation of miRNAs, especially miR-200b and let-7c, significantly diminished the erlotinib resistance of A549M cells. Inhibition of Hh signaling by GDC-0449 in EMT cells resulted in the attenuation of CSC markers and up-regulation of miR-200b and let-7c, leading to sensitization of EMT cells to drug treatment, thus, confirming a connection between Hh signaling, miRNAs and drug resistance. Conclusions We demonstrate that Hh pathway, through EMT-induction, leads to reduced sensitivity to EGFR-TKIs in NSCLCs. Therefore, targeting Hh pathway may lead to the reversal of EMT phenotype and improve the therapeutic efficacy of EGFR-TKIs in NSCLC patients.
Overexpression of Hyaluronan Synthase 2 Alters Hyaluronan Distribution and Function in Proximal Tubular Epithelial Cells
Authors: Wisam Selbi, Anthony J. Day, Marilyn S. Rugg, Csaba Fülöp, Carol A. de la Motte, Timothy Bowen, Vincent C. Hascall, Aled O. Phillips
Journal: Journal of the American Society of Nephrology (2006)

The functional consequences of increased renal cortical hyaluronan that is associated with both acute injury and progressive scarring are unclear. The aim of this study was to characterize hyaluronan synthase-2 (HAS2)-driven HA synthesis and determine its effect on renal proximal tubular epithelial cell (PTC) function, because this is known to be the inducible form of HA synthase in this cell type. Overexpression of HAS2 mRNA increased HA generation, which in the supernatant predominantly was HA of large molecular weight, whereas there was an increase in low molecular weight HA in cell-associated fractions. This was associated with increased expression of hyaluronidases, inhibition of HA cable formation concurrent with reduction in HA-dependent monocyte binding, and increased pericellular HA matrix. Overexpression of HAS2 led to enhanced cell migration. HA can be modified by the covalent attachment of heavy chains that are derived from the serum protein inter-alpha-inhibitor (IalphaI), a process that is known to be catalyzed by TNF-alpha-stimulated gene 6 (TSG-6; an inflammation-associated protein). Enhanced migration was abrogated by blocking antibodies to either IalphaI or TSG-6. Addition of recombinant full-length TSG-6 (TSG-6Q) or TSG-6Q_Y94F, a mutant variant with impaired HA binding, increased cell migration. Both of these proteins were able to mediate the covalent transfer of heavy chains, from IalphaI and pre-alpha-inhibitor, onto HA. Addition of the isolated TSG-6-Link module (Link_TSG-6), which binds HA but is unable to form covalent complexes with IalphaI/pre-alpha-inhibitor, had no effect on migration, suggesting that TSG-6-mediated formation of heavy chain-HA complexes is critical in the formation of a pericellular HA matrix.
THE FORMATION OF CHELOIDS IN RELATION TO THE TREATMENT OF LUPUS VULGARIS
Authors: F. F. HELLIER
Journal: British Journal of Dermatology (1936)

Journal Article THE FORMATION OF CHELOIDS IN RELATION TO THE TREATMENT OF LUPUS VULGARIS Get access F. F. HELLIER F. F. HELLIER Department of Dermatology, Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 48, Issue 2, 1 February 1936, Pages 91–96, https://doi.org/10.1111/j.1365-2133.1936.tb10305.x Published: 01 February 1936
Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial
Authors: Yohann Loriot, Kurt Miller, Cora N Sternberg, Karim Fizazi, Johann S De Bono, Simon Chowdhury, Celestia S Higano, Sarah Noonberg, Stefan Holmstrom, Harry Mansbach, Frank G Perabo, De Phung, Cristina Ivanescu, Konstantina Skaltsa, Tomasz M Beer, Bertrand Tombal
Journal: The Lancet Oncology (2015)
Ultrasound guided fine needle biopsy of early hepatocellular carcinoma complicating liver cirrhosis: a multicentre study
Authors: E Caturelli
Journal: Gut (2004)

Because hepatic cirrhosis is a major risk factor for hepatocellular carcinoma, recent guidelines by the European Association for the Study of the Liver (EASL) on clinical management of hepatocellular carcinoma recommend periodic ultrasound surveillance of cirrhotic patients with immediate workup for nodules >1 cm; an increase in the frequency of screening is considered sufficient for smaller lesions.To determine the actual risk of hepatocellular carcinoma associated with the latter lesions and to assess the role of ultrasound guided-fine needle biopsy in their diagnosis.Data were analysed for 294 new nodular lesions <20 mm, including 48 that were <10 mm, detected during a prospective multicentre study involving ultrasound surveillance of 4375 patients with hepatic cirrhosis. In the absence of alpha fetoprotein (AFP) levels diagnostic of hepatocellular carcinoma, ultrasound guided-fine needle biopsy was performed (n = 274). AFP and fine needle biopsy diagnoses of malignancies (hepatocellular carcinoma and lymphoma) were considered definitive. Non-malignant fine needle biopsy diagnoses (dysplastic or regenerative nodule) were verified by a second imaging study. Diagnoses of hepatocellular carcinoma based on this study were considered definitive; non-malignant imaging diagnoses were considered definitive after at least one year of clinical and ultrasound follow up.Overall, 258/294 (87.6%) nodules proved to be hepatocellular carcinoma, including 33/48 (68.7%) of those < or =10 mm. Overall typing accuracy of ultrasound guided-fine needle biopsy was 89.4%, and 88.6% for lesions < or =10 mm.In a screening population, well over half of very small nodules arising in cirrhotic livers may prove to be hepatocellular carcinoma, and approximately 90% of these malignancies can be reliably identified with ultrasound guided-fine needle biopsy.
Standing out in a crowd: knockout of ApoE increases the potency of endothelium-dependent vasodilators in mesenteric arteries
Authors: W. F. Jackson
Journal: Cardiovascular Research (2011)

This editorial refers to ‘Enhanced K+-channel-mediated endothelium-dependent local and conducted dilation of small mesenteric arteries from ApoE −/− mice’ by T. Beleznai et al. , pp. 199–208, this issue. 

Hypercholesterolaemia is a risk factor for cardiovascular disease, and a number of prior studies have shown that endothelium-dependent vasodilation is compromised in animal models of this condition1–4 as well as in humans.5–7 The study by Beleznai et al .8 goes against this trend and demonstrates that small mesenteric arteries from apolipoprotein E -knockout ( ApoE−/− ) mice are actually more sensitive to endothelium-dependent vasodilators than are vessels from wild-type mice. Increased vasodilator potency has been previously reported in other models of dyslipidaemia, but only after inhibition of NO and prostaglandin synthesis.9–11 These studies clearly demonstrate that there is significant regional heterogeneity in the vascular adaptation to loss of ApoE, which has implications for the design and application of drugs and therapies directed at combating the vascular consequences of hypercholesterolaemia. What remains to be established are the mechanisms responsible for the increased potency of endothelium-dependent vasodilators in small mesenteric …
Proteomics-Based Approach Identifying Autoantibody against Peroxiredoxin VI as a Novel Serum Marker in Esophageal Squamous Cell Carcinoma
Authors: Yoshihisa Fujita, Toyofumi Nakanishi, Masako Hiramatsu, Hideaki Mabuchi, Yoshiharu Miyamoto, Akiko Miyamoto, Akira Shimizu, Nobuhiko Tanigawa
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Detection of novel tumor-related antigens and autoantibodies will aid in diagnosis of early-stage cancer and in development of more effective immunotherapies. The purpose of this study was to identify novel tumor antigens in an esophageal squamous cell carcinoma (ESCC) cell line (TE-2) and related autoantibodies in sera from patients with ESCC using a proteomics-based approach. Experimental Design: TE-2 proteins were separated by two-dimensional PAGE, followed by Western blot analysis in which sera of patients with ESCC, healthy controls, and patients with other cancers were tested for primary antibodies. Positive spots were excised from silver-stained gels and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS). Results: Sera from patients with ESCC yielded multiple spots, one of which was identified as peroxiredoxin (Prx) VI by MALDI-TOF/TOF MS. Western blot analysis against recombinant Prx VI showed reactivity in sera from 15 of 30 (50%) patients with ESCC and 2 of 30 (6.6%) healthy individuals. Autoantibody against Prx VI was found in sera from 1 of 30 (3.3%) patients with other types of cancer (colon cancer). Conclusion: We have identified for the first time an autoantibody against Prx VI in ESCC patients. The proteomic approach implemented here offers a powerful tool for identifying novel serum markers that may display clinical usefulness against cancer.
Contribution of endogenous endothelin to the extension of myocardial infarct size in rats.
Authors: T Watanabe, N Suzuki, N Shimamoto, M Fujino, A Imada
Journal: Circulation Research (1991)

Pathophysiological roles of endogenous endothelin have been studied from the viewpoint of its contribution to the extension of myocardial infarct size. A monoclonal antibody against endothelin 1 (AwETN40) suppressed changes induced by endothelin 1 and endothelin 2 but did not modify those by endothelin 3 in vivo or in vitro. Effects of AwETN40 on myocardial infarct size were investigated. Coronary ligation (1 hour) and reperfusion (24 hours) in rats caused infarction in 35% of the left ventricle. Repetitive or single administration of AwETN40 reduced the infarct size; an intravenous injection of 22.5 mg/kg of the antibody 5 minutes after coronary occlusion or 5 minutes before reperfusion reduced the size by 38% or 31% of the control, respectively. Plasma and tissue endothelin 1 and plasma big endothelin 1 in rats were measured at various stages after occlusion. Plasma endothelin 1 showed a fourfold increase 10 minutes after reperfusion (from 1.02 to 3.96 pg/ml) and had returned to the control value after 8 hours. Plasma big endothelin 1 showed changes similar to those of plasma endothelin 1. No significant changes in plasma endothelin 2 and endothelin 3 were observed. Cardiac tissue contained seven times as much endothelin 1 as the control value 1 hour after reperfusion (4.59 versus 33.1 pg/g tissue), and a high concentration (13.2 pg/g tissue) was maintained even after 48 hours. We concluded that an increase in endogenous endothelin 1 plays an important role in the extension of myocardial infarct size.
Mobilisation of enterocyte fat stores by oral glucose in humans
Authors: M D Robertson
Journal: Gut (2003)

<b>Background and aims:</b> When a high fat oral load is followed several hours later by further ingestion of nutrients, there is an early postprandial peak in plasma triacylglycerol (TG). The aim of this study was to investigate the location and release of lipid from within the gastrointestinal tract. <b>Methods:</b> Ten healthy patients undergoing oesopho-gastro-duodenoscopy (OGD) were recruited. At t=0, all patients consumed a 50 g fat emulsion and at t=5 hours they consumed either water or a 38 g glucose solution. OGD was performed at t=6 hours and jejunal biopsy samples were evaluated for fat storage. A subgroup of five subjects then underwent a parallel metabolic study in which postprandial lipid and hormone measurements were taken during an identical two meal protocol. <b>Results:</b> Following oral fat at t=0, samples from patients that had subsequently ingested glucose exhibited significantly less staining for lipid within the mucosa and submucosa of the jejunum than was evident in patients that had consumed only water (p=0.028). There was also less lipid storage within the cytoplasm of enterocytes (p=0.005) following oral glucose. During the metabolic study, oral glucose consumed five hours after oral fat resulted in a postprandial peak in plasma TG, chylomicron-TG, and apolipoprotein B48 concentration compared with oral water. <b>Conclusion:</b> After a fat load, fat is retained within the jejunal tissue and released into plasma following glucose ingestion, resulting in a peak in chylomicron-TG which has been implicated in the pathogenesis of atherosclerosis.
Clinical, neurological, and electrophysiological features of nodding syndrome in Kitgum, Uganda: an observational case series
Authors: James J Sejvar, Angelina M Kakooza, Jennifer L Foltz, Issa Makumbi, Anne Deborah Atai-Omoruto, Mugagga Malimbo, Richard Ndyomugyenyi, Lorraine N Alexander, Betty Abang, Robert G Downing, Andrew Ehrenberg, Kristin Guilliams, Sandra Helmers, Paul Melstrom, Dennis Olara, Seth Perlman, Jeffrey Ratto, Edwin Trevathan, Andrea S Winkler, Scott F Dowell, DKW Lwamafa
Journal: The Lancet Neurology (2013)
PPARγ Ligand Inhibits Osteopontin Gene Expression Through Interference With Binding of Nuclear Factors to A/T-Rich Sequence in THP-1 Cells
Authors: Yuko Oyama, Nobuhiro Akuzawa, Ryozo Nagai, Masahiko Kurabayashi
Journal: Circulation Research (2002)

Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily that acts as a key player in adipocyte differentiation, glucose metabolism, and macrophage differentiation. Osteopontin (OPN), a component of extracellular matrix, is elevated during neointimal formation in the vessel wall and is synthesized by macrophages in atherosclerotic plaques. In the present study, we investigated the molecular mechanisms regulating OPN gene expression by PPARγ in THP-1 cells, a cell line derived from human monocytic leukemia cells. Northern and Western blot analyses showed that exposure of THP-1 cells to PMA (phorbol 12-myristate 13-acetate) increases OPN mRNA and protein levels in a time-dependent manner. PMA-induced OPN expression was significantly decreased by troglitazone (Tro) and other PPARγ ligands. Transient transfection assays of the human OPN promoter/luciferase construct showed that PPARγ represses OPN promoter activity, and the PPARγ-responsive region within the OPN promoter lies between −1000 and −970 relative to the transcription start site. Site-specific mutation analysis and electrophoretic mobility shift assays indicated that a homeobox-like A/T-rich sequence between −990 and −981, which functions as a binding site for PMA-induced nuclear factors other than PPARγ, mediates the repression of OPN expression by Tro. Furthermore, concatenated A/T-rich sequences conferred the PPARγ responsiveness on the heterologous promoter. Taken together, these data suggest that PPARγ ligand inhibits OPN gene expression through the interference with the binding of nuclear factors to A/T-rich sequence in THP-1 cells.
Episodic Positive Selection in Ape Cytochrome c Oxidase Subunit IV
Authors: Derek E. Wildman, Wei Wu, Morris Goodman, Lawrence I. Grossman
Journal: Molecular Biology and Evolution (2002)

Periods of elevated rates of nonsynonymous nucleotide substitutions for electron transport chain (ETC) genes have occurred during the evolution of anthropoid primates (New World monkeys, Old World monkeys, apes, and humans) (Grossman et al. 2001).Given the vital role the ETC genes play in energy metabolism, and the coadaptive evolution apparently undergone by the holoenzymes of cytochrome bc 1 (Complex III) and cytochrome c oxidase (Complex IV) in anthropoid primates (Andrews and Easteal 2000;Grossman et al. 2001;Schmidt et al. 2001), it is likely that positive selection rather than reduction of functional constraints is the cause of the elevated nonsynonymous substitution rates.ETC genes that have been identified as having undergone periods of positive selection in anthropoid primates are cytochromes b and c (CYB, CYC) and the Complex IV genes COX1, COX2, cytochrome c oxidase subunit IV ubiquitous isoform (COX4-1), 1 and COX7AH (reviewed in Grossman et al. 2001).Lomax et al. (1992) first showed that the human COX4-1 gene had accumulated many more nonsynonymous substitutions than had its orthologues in mouse and cow, but they could not localize the specific ancestral primate lineage on which the rate increase occurred.In a phylogenetic study conducted after sequencing COX4-1 from a range of primates, Wu et al. (1997) provided evidence that positive selection for adaptive evolution of COX4-1 occurred in certain haplorhine primate lineages.Positive selection was especially pronounced in the descent of the stem catarrhines (the internode connecting anthropoids to catarrhines) and the stem hominids (the internode connecting Old World monkeys to apes and humans).In this lineage the nonsynonymous rate (Ka [nonsynonymous substitutions/nonsynonymous site]) was faster than the synonymous rate (Ks [synonymous substitutions/synonymous site]) but later, in the descent of the gorilla, chimpanzee, and human lineages, it was much