tbuckley/cabot-search huggingface dataset:
Rapid Angiogenesis Onset after Discontinuation of Sunitinib Treatment of Renal Cell Carcinoma Patients
Authors: Arjan W. Griffioen, Laurie A. Mans, Annemarie M.A. de Graaf, Patrycja Nowak-Sliwinska, Céline L.M.M. de Hoog, Trees A.M. de Jong, Florry A. Vyth-Dreese, Judy R. van Beijnum, Axel Bex, Eric Jonasch
Journal: Clinical Cancer Research (2012)

To investigate the angiogenic changes in primary tumor tissue of renal cell carcinoma (RCC) patients treated with VEGF-targeted therapy.Phase II trials of VEGF pathway-targeted therapy given before cytoreductive surgery were carried out with metastatic RCC patients with the primary tumor in situ to investigate the necessity of nephrectomy. Primary tumor tissues were obtained and assessed for angiogenesis parameters. Results were compared with similar analyses on untreated tumors.Sunitinib or bevacizumab pretreatment resulted in a significant reduction of microvessel density in the primary tumor. Also, an increase in vascular pericyte coverage was found in sunitinib-pretreated tumors, consistent with efficient angiogenesis inhibition. Expression of several key regulators of angiogenesis was found to be suppressed in pretreated tissues, among which VEGFR-1 and VEGFR-2, angiopoietin-1 and angiopoietin-2 and platelet-derived growth factor-B. In addition, apoptosis in tumor and endothelial cells was induced. Interestingly, in sunitinib-pretreated tissues a dramatic increase of the number of proliferating endothelial cells was observed, which was not the case in bevacizumab-pretreated tumors. A positive correlation with the interval between halting the therapy and surgery was found, suggesting a compensatory angiogenic response caused by the discontinuation of sunitinib treatment.This study describes, for the first time, the angiostatic response in human primary renal cancers at the tissue level upon treatment with VEGF-targeted therapy. Discontinuation of treatment with tyrosine kinase inhibitors leads to accelerated endothelial cell proliferation. The results of this study contribute important data to the ongoing discussion on the discontinuation of treatment with kinase inhibitors.
Mechanisms for defects in muscle protein metabolism in rats with chronic uremia. Influence of metabolic acidosis.
Authors: R C May, R A Kelly, W E Mitch
Journal: Journal of Clinical Investigation (1987)

Chronic renal failure (CRF) is associated with metabolic acidosis and abnormal muscle protein metabolism. As we have shown that acidosis by itself stimulates muscle protein degradation by a glucocorticoid-dependent mechanism, we assessed the contribution of acidosis to changes in muscle protein turnover in CRF. A stable model of uremia was achieved in partially nephrectomized rats (plasma urea nitrogen, 100-120 mg/dl, blood bicarbonate less than 21 meq/liter). CRF rats excreted 22% more nitrogen than pair-fed controls (P less than 0.005), so muscle protein synthesis and degradation were measured in perfused hindquarters. CRF rats had a 90% increase in net protein degradation (P less than 0.001); this was corrected by dietary bicarbonate. Correction of acidosis did not reduce the elevated corticosterone excretion rate of CRF rats, nor did it improve a second defect in muscle protein turnover, a 34% lower rate of insulin-stimulated protein synthesis. Thus, abnormal nitrogen production in CRF is due to accelerated muscle proteolysis caused by acidosis and an acidosis-independent inhibition of insulin-stimulated muscle protein synthesis.
Management of Anemia in Children Receiving Chronic Peritoneal Dialysis
Authors: Dagmara Borzych-Duzalka, Yelda Bilginer, Il Soo Ha, Mustafa Bak, Lesley Rees, Francisco Cano, Reyner Loza Munarriz, Annabelle Chua, Silvia Pesle, Sevinc Emre, Agnieszka Urzykowska, Lily Quiroz, Javier Darío Ruscasso, Colin White, Lars Pape, Virginia Ramela, Nikoleta Printza, Andrea Vogel, Dafina Kuzmanovska, Eva Simkova, Dirk E. Müller-Wiefel, Anja Sander, Bradley A. Warady, Franz Schaefer
Journal: Journal of the American Society of Nephrology (2013)

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (<10 g/dl or <9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.
Independent regulation of DNA recombination and immunoglobulin (Ig) secretion during isotype switching to IgG1 and IgE.
Authors: J M Purkerson, P C Isakson
Journal: The Journal of Experimental Medicine (1994)

Induction of switch recombination to the gamma 1 and epsilon immunoglobulin (Ig) heavy chain loci was examined in B cells preactivated with anti-Ig (B lymphoblasts). In B lymphoblasts cultured with interleukin 4 (IL-4), IL-5 induced the accumulation of S micro-S gamma 1 rearrangements, but not epsilon recombination. Thus, IL-5 facilitates switch recombination directed to the gamma 1 heavy chain locus by IL-4, but additional signals are required to drive rearrangements to epsilon. Lipopolysaccharide (LPS), in the presence of IL-4, induced the accumulation of both S micro-S gamma 1 and S micro-S epsilon rearrangements, and cells treated with LPS exhibited 40-50-fold more S micro-S gamma 1 rearrangements than cells cultured with IL-5. Induction of switch recombination was not always associated with secretion of the respective Ig isotype, since concentrations of IL-4 that were sufficient to direct switch recombination to gamma 1 and epsilon in blasts treated with LPS failed to elicit secretion of IgG1 and IgE. These results demonstrate differential requirements for switch recombination to the gamma 1 and epsilon loci, as well as independent regulation of Ig gene rearrangement and secretion of each isotype.
Short QT Syndrome or Andersen Syndrome
Authors: Eric Schulze-Bahr
Journal: Circulation Research (2005)

n 1994, the complete human cDNA of an inwardly rectifying Kϩ channel gene, KCNJ2 or Kir2.1, was isolated.Kir2.1 channels are important regulators of resting membrane potential of the cardiac (and also skeletal) muscle and cellular excitability, 1 since they cause an outflow of Kϩ in the hyperpolarized membrane state during the terminal phase of cardiac action potential repolarization.The cDNA encodes a small protein of 427 amino acids with 2 putative transmembrane domains (M1, M2) and a pore region (H5) and regulates the inward rectifier Kϩ current I K1 .Northern blot analysis demonstrated a 5.5-kb transcript with high levels in the heart, brain, placenta, lung, and skeletal muscle and lower levels in the kidney; in the heart, Kir2.1 channels are abundant in the atria, ventricle (with a high I K1 conductance) and Purkinje fibers, but less frequent in nodal cells.On current knowledge, 4 subunits form a functional (ie, tetrameric) channel, but they also may co-assemble with other subunits of the Kir2.xfamily as heteromultimers 2 which indicates functional complexity and diversity.In 2001, Plaster et al performed a genome-wide linkage analysis to identify the disease locus for Andersen (also Andersen-Tawil) syndrome. 3This rare syndrome can be found as a sporadic or autosomal dominant genetic trait and is characterized by a skeletal muscle phenotype (potassiumsensitive periodic paralysis caused by abnormal muscle relaxation, and histologically tubular aggregates), a cardiac phenotype (borderline or mildly prolonged QT interval, adrenergically mediated multifocal ventricular ectopy or tachycardia) and a distinct developmental dysmorphology that may include short stature, scoliosis, clinodactyly, hypertelorism (wide-set eyes), low-set small ears, micrognathia, and a broad forehead. 34][5] Because significant genetic linkage of the disease locus for Andersen syndrome was found on the long arm of chromosome 17 (lod score, 3.23 at ϭ0) and overlapped the KCNJ2 gene locus (region
Biased Gene Conversion Affects Patterns of Codon Usage and Amino Acid Usage in the Saccharomyces sensu stricto Group of Yeasts
Authors: R. J. Harrison, B. Charlesworth
Journal: Molecular Biology and Evolution (2010)

Patterns of synonymous codon usage vary between organisms and are controlled by neutral processes (such as drift and mutation) as well as by selection. Here we show that an additional neutral process, GC-biased gene conversion (gBGC), plays a part in shaping patterns of both synonymous codon usage and amino acid composition in a manner dependent upon the local recombination rate. We obtain estimates of the strength of gBGC acting on synonymous sites in five species of yeast, which we find to be a much weaker force than selection. We use this to correct estimates of the strength of selection on codon usage bias, which are normally confounded by the action of gBGC. Our estimate of the rate of gBGC agrees well with an experimentally determined value obtained from Saccharomyces cerevisiae. We also find that, contrary to expectation, codon usage bias is highest in areas of intermediate levels of recombination for GC-ending optimal codons. Possible reasons for this are discussed.
Cross-striated banded structures in cutaneous Leishmaniasis
Authors: MIRIAM SANDBANK
Journal: British Journal of Dermatology (1977)

Banded structures were observed in 4 cases of cutaneous leishmaniasis. These structures were found in proximity to macrophages containing leishmania and were intermingled with native collagen, elastic fibres and ground substance fibrils. The possibility that banded structures are an indication of active, accelerated collagen production is discussed.
Annual Report to the Nation on the Status of Cancer, 1975-2007, Featuring Tumors of the Brain and Other Nervous System
Authors: B. A. Kohler, E. Ward, B. J. McCarthy, M. J. Schymura, L. A. G. Ries, C. Eheman, A. Jemal, R. N. Anderson, U. A. Ajani, B. K. Edwards
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundThe American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute, and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information on cancer occurrence and trends in the United States. This year's report highlights brain and other nervous system (ONS) tumors, including nonmalignant brain tumors, which became reportable on a national level in 2004.
<b> <i>In vivo</i> </b> Models for Experimental Therapeutics Relevant to Human Cancer
Authors: Miriam S. Gitler, Edward A. Sausville, Melinda Hollingshead, Robert Shoemaker
Journal: Cancer Research (2004)

The Developmental Therapeutics Program (DTP) of the National Cancer Institute (NCI) sponsored a symposium on In vivo Models for Experimental Therapeutics Relevant to Human Cancer on April 1, 2004, in Frederick, Maryland. About 50 scientists attended, with 8 invited speakers coming from Germany, the
Ovarian Aging: Mechanisms and Clinical Consequences
Authors: F. J. Broekmans, M. R. Soules, B. C. Fauser
Journal: Endocrine Reviews (2009)

Menopause is the final step in the process referred to as ovarian ageing. The age related decrease in follicle numbers dictates the onset of cycle irregularity and the final cessation of menses. The parallel decay in oocyte quality contributes to the gradual decline in fertility and the final occurrence of natural sterility.
Saltatory remodeling of Hox chromatin in response to rostrocaudal patterning signals
Authors: Esteban O Mazzoni, Shaun Mahony, Mirza Peljto, Tulsi Patel, Seraphim R Thornton, Scott McCuine, Christopher Reeder, Laurie A Boyer, Richard A Young, David K Gifford, Hynek Wichterle
Journal: Nature Neuroscience (2013)
miR-21: An Androgen Receptor–Regulated MicroRNA that Promotes Hormone-Dependent and Hormone-Independent Prostate Cancer Growth
Authors: Judit Ribas, Xiaohua Ni, Michael Haffner, Erik A. Wentzel, Amirali Hassanzadeh Salmasi, Wasim H. Chowdhury, Tarana A. Kudrolli, Srinivasan Yegnasubramanian, Jun Luo, Ron Rodriguez, Joshua T. Mendell, Shawn E. Lupold
Journal: Cancer Research (2009)

Androgen receptor (AR)-mediated oncogenic pathways have not been fully elucidated. In this study, we used high-throughput microarray analysis on two AR-positive prostate cancer (CaP) cell lines to identify 16 AR-responsive microRNAs (miRNA). We focused on miR-21 because of its previously reported oncogenic activity in other cancers. We show androgen-induced AR binding to the defined miR-21 promoter, miPPR-21, suggesting direct transcriptional regulation. Inhibition of miR-21 diminished androgen-induced CaP cell proliferation, providing new evidence that miRNAs can contribute to androgen-driven cell growth. Elevated expression of miR-21 enhanced CaP tumor growth in vivo and, surprisingly, was sufficient for androgen-dependent tumors to overcome castration-mediated growth arrest. Thus, elevated miR-21 expression alone is sufficient to impart castration resistance. Moreover, quantitative reverse transcription-PCR analysis revealed elevated miR-21 expression in CaP when compared with adjacent normal tissue. These results suggest that miR-21 may contribute to CaP pathogenesis.
Electrical potential difference and absorption of water, sodium, and potassium by the terminal ileum of ileostomy patients
Authors: J. P. P. De Moraes-Filho, C. Salas-Coll, L. Blendis, C. J. Edmonds
Journal: Gut (1974)

Measurements of electrical potential difference (pd) and of absorption by a dialysis method were carried out in the terminal ileum of patients with an ileostomy. The pd measured with saline in the lumen and at a few centimetres within the stoma averaged 9.2 mV, lumen negatively charged. The pd values were similar whether the ileostomy had been recently or long established. The pd rose considerably when glucose was added to the luminal solution, the maximum effect being attained with a concentration of 40 mmol/1. With a saline bicarbonate solution (Na 145 or 140 m-equiv/1, K 5, or 10 m-equiv/1) in the dialysis tube, considerable absorption of fluid and sodium was demonstrable with little change in sodium concentration. Potassium secretion occurred with the lower, and absorption with the higher, concentration. The final luminal potassium concentration reached was consistent with a passive distribution between blood and lumen.
High-Throughput RNAi Screening Reveals Novel Regulators of Telomerase
Authors: Maria Antonietta Cerone, Darren J Burgess, Cristina Naceur-Lombardelli, Christopher J. Lord, Alan Ashworth
Journal: Cancer Research (2011)

Abstract Telomerase is considered an attractive anticancer target on the basis of its common and specific activation in most human cancers. While direct telomerase inhibition is being explored as a therapeutic strategy, alternative strategies to target regulators of telomerase that could disrupt telomere maintenance and cancer cell proliferation are not yet available. Here, we report the findings of a high-throughput functional RNA interference screen to globally profile the contribution of kinases to telomerase activity (TA). This analysis identified a number of novel telomerase modulators, including ERK8 kinase, whose inhibition reduces TA and elicited characteristics of telomere dysfunction. Given that kinases represent attractive drug targets, we addressed the therapeutic implications of our findings, such as demonstrating how limiting TA via kinase blockade could sensitize cells to inhibition of the telomere-associated protein tankyrase. Taken together, our findings suggest novel combinatorial approaches to targeting telomere maintenance as a strategy for cancer therapy. Cancer Res; 71(9); 3328–40. ©2011 AACR.
The Effect of Race and Income on Living Kidney Donation in the United States
Authors: Jagbir Gill, James Dong, Caren Rose, Olwyn Johnston, David Landsberg, John Gill
Journal: Journal of the American Society of Nephrology (2013)

Studies of racial disparities in access to living donor kidney transplantation focus mainly on patient factors, whereas donor factors remain largely unexamined. Here, data from the US Census Bureau were combined with data on all African-American and white living kidney donors in the United States who were registered in the United Network for Organ Sharing (UNOS) between 1998 and 2010 (N=57,896) to examine the associations between living kidney donation (LKD) and donor median household income and race. The relative incidence of LKD was determined in zip code quintiles ranked by median household income after adjustment for age, sex, ESRD rate, and geography. The incidence of LKD was greater in higher-income quintiles in both African-American and white populations. Notably, the total incidence of LKD was higher in the African-American population than in the white population (incidence rate ratio [IRR], 1.20; 95% confidence interval [95% CI], 1.17 to 1.24]), but ratios varied by income. The incidence of LKD was lower in the African-American population than in the white population in the lowest income quintile (IRR, 0.84; 95% CI, 0.78 to 0.90), but higher in the African-American population in the three highest income quintiles, with IRRs of 1.31 (95% CI, 1.22 to 1.41) in Q3, 1.50 (95% CI, 1.39 to 1.62) in Q4, and 1.87 (95% CI, 1.73 to 2.02) in Q5. Thus, these data suggest that racial disparities in access to living donor transplantation are likely due to socioeconomic factors rather than cultural differences in the acceptance of LKD.
Cystic Fibrosis and Bone Disease: Defective Osteoblast Maturation with the F508del Mutation in Cystic Fibrosis Transmembrane Conductance Regulator
Authors: Frédéric Velard, Martial Delion, Carole Le Henaff, Christine Guillaume, Sophie Gangloff, Jacky Jacquot, Olivier Tabary, Lhousseine Touqui, Françoise Barthes, Isabelle Sermet-Gaudelus
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
Screening, Monitoring, and Treatment of Albuminuria
Authors: Paul E. de Jong, Gary C. Curhan
Journal: Journal of the American Society of Nephrology (2006)

Microalbuminuria is an early sign of progressive cardiovascular and renal disease in individuals with and without diabetes. Despite compelling data, at present only a minority of patients with diabetes and rarely individuals without diabetes are screened for albuminuria in a systematic way. All of the criteria to implement systematic albuminuria screening are fulfilled in diabetes, and most are nearly fulfilled for microalbuminuria screening in individuals without diabetes. Because of the growing evidence that treatment of microalbuminuria in individuals without diabetes may offer a cost-effective benefit to prevent cardiovascular disease, nephrologists and other health care providers should pay more attention to the early detection and subsequent treatment of individuals with microalbuminuria.
Evidence for a Vasopressin System in the Rat Heart
Authors: Harald Hupf, Daniela Grimm, Günter A. J. Riegger, Heribert Schunkert
Journal: Circulation Research (1999)

Abstract —Traditionally, a hypothalamo-neurohypophysial system is thought to be the exclusive source of arginine vasopressin (AVP), a potent antidiuretic, vasoconstricting, and growth-stimulating neuropeptide. We have identified de novo synthesis of AVP in the heart as well as release of the hormone into the cardiac effluents. Specifically, molecular cloning of sequence tags amplified from isolated, buffer-perfused, and pressure-overloaded rat hearts allowed the detection of cardiac AVP mRNA. Subsequent experiments revealed a prominent induction of AVP mRNA (peak at 120 minutes, 59-fold, P &lt;0.01 versus baseline) and peptide (peak at 120 minutes, 11-fold, P &lt;0.01 versus baseline) in these isolated hearts. Newly induced vasopressin peptide was localized most prominently to endothelial cells and vascular smooth muscle cells of arterioles and perivascular tissue using immunohistochemistry. In addition to pressure overload, nitric oxide (NO) participated in these alterations, because inhibition of NO synthase by N ω -nitro- l -arginine methyl ester markedly depressed cardiac AVP mRNA and peptide induction. Immediate cardiac effects related to cardiac AVP induction in isolated, perfused, pressure-overloaded hearts appeared to be coronary vasoconstriction and impaired relaxation. These functional changes were observed in parallel with AVP induction and largely prevented by addition of a V 1 receptor blocker (10 −8 mol/L [deamino-Pen 1 , O-Me-Tyr 2 , Arg 8 ]-vasopressin) to the perfusion buffer. Even more interesting, pressure-overloaded, isolated hearts released the peptide into the coronary effluents, offering the potential for systemic actions of AVP from cardiac origin. We conclude that the heart, stressed by acute pressure overload or NO, expresses vasopressin in concentrations sufficient to cause local and potentially systemic effects.
Platelet Dysfunction in Type 2 Diabetes
Authors: Aaron I. Vinik, Tomris Erbas, Tae Sun Park, Roger Nolan, Gary L. Pittenger
Journal: Diabetes Care (2001)

Insulin resistance is a uniform finding in type 2 diabetes, as are abnormalities in the microvascular and macrovascular circulations. These complications are associated with dysfunction of platelets and the neurovascular unit. Platelets are essential for hemostasis, and knowledge of their function is basic to understanding the pathophysiology of vascular disease in diabetes. Intact healthy vascular endothelium is central to the normal functioning of smooth muscle contractility as well as its normal interaction with platelets. What is not clear is the role of hyperglycemia in the functional and organic microvascular deficiencies and platelet hyperactivity in individuals with diabetes. The entire coagulation cascade is dysfunctional in diabetes. Increased levels of fibrinogen and plasminogen activator inhibitor 1 favor both thrombosis and defective dissolution of clots once formed. Platelets in type 2 diabetic individuals adhere to vascular endothelium and aggregate more readily than those in healthy people. Loss of sensitivity to the normal restraints exercised by prostacyclin (PGI2) and nitric oxide (NO) generated by the vascular endothelium presents as the major defect in platelet function. Insulin is a natural antagonist of platelet hyperactivity. It sensitizes the platelet to PGI2 and enhances endothelial generation of PGI2 and NO. Thus, the defects in insulin action in diabetes create a milieu of disordered platelet activity conducive to macrovascular and microvascular events.