tbuckley/cabot-search huggingface dataset:
Role for Amplification and Expression of <i>Glypican-5</i> in Rhabdomyosarcoma
Authors: Daniel Williamson, Joanna Selfe, Tony Gordon, Yong-Jie Lu, Kathy Pritchard-Jones, Kasumi Murai, Phil Jones, Paul Workman, Janet Shipley
Journal: Cancer Research (2007)

Overexpression of genes, through genomic amplification and other mechanisms, can critically affect the behavior of tumor cells. Genomic amplification of the 13q31-32 region is reported in many tumors, including rhabdomyosarcomas that are primarily pediatric sarcomas resembling developing skeletal muscle. The minimum overlapping region of amplification at 13q31-32 in rhabdomyosarcomas was defined as containing two genes: Glypican-5 (GPC5) encoding a cell surface proteoglycan and C13orf25 encompassing the miR-17-92 micro-RNA cluster. Genomic copy number and gene expression analyses of rhabdomyosarcomas indicated that GPC5 was the only gene consistently expressed and up-regulated in all cases with amplification. Constitutive overexpression and knockdown of GPC5 expression in rhabdomyosarcoma cell lines increased and decreased cell proliferation, respectively. A correlation between expression levels of nascent pre-rRNA and GPC5 (P = 0.001), but not a C13orf25 transcript containing miR-17-92, in primary samples supports an association of GPC5 with proliferative capacity in vivo. We show that GPC5 increases proliferation through potentiating the action of the growth factors fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), and Wnt1A. GPC5 enhanced the intracellular signaling of FGF2 and HGF and altered the cellular distribution of FGF2. The mesoderm-inducing effect of FGF2 and FGF4 in Xenopus blastocysts was also enhanced. Our data are consistent with a role of GPC5, in the context of sarcomagenesis, in enhancing FGF signaling that leads to mesodermal cell proliferation without induction of myogenic differentiation. Furthermore, the properties of GPC5 make it an attractive target for therapeutic intervention in rhabdomyosarcomas and other tumors that amplify and/or overexpress the gene.
Time course of resolution of pulmonary hypertension and right ventricular remodeling after orthotopic cardiac transplantation.
Authors: S J Bhatia, J M Kirshenbaum, R J Shemin, L H Cohn, J J Collins, V J Di Sesa, P J Young, G H Mudge, M G Sutton
Journal: Circulation (1987)

Most patients with severe congestive heart failure have secondary pulmonary hypertension (PHT). Elevation of pulmonary vascular resistance (PVR) to greater than 480 dynes.sec.cm-5 (6 Wood units) is currently the principle hemodynamic contraindication to orthotopic cardiac transplantation. We performed serial two-dimensional Doppler echocardiographic examinations and right heart catheterizations in 24 recipients (21 men, 14-58 years old) of orthotopic cardiac transplants to determine the time course of resolution of PHT and the concomitant remodeling of the donor right ventricle. Right and left heart filling pressures declined in parallel and reached the upper normal range at 2 weeks after the transplant procedure and remained unchanged at 1 year follow-up. Mean pulmonary arterial pressure (mm Hg) decreased from 38 +/- 9 preoperatively to 22 +/- 5 at 2 weeks and was 19 +/- 5 at 1 year after the transplantation procedure. At 1 year after surgery, PVR had decreased from 202 +/- 89 dynes.sec.cm-5 preoperatively to 99 +/- 36 dynes.sec.cm-5 (p less than .001), while cardiac output increased from 3.7 +/- 1.2 to 6.3 +/- 1.5 liters/min (p less than .001). Echocardiographic analysis showed that transplant recipients had an enlarged right ventricle on day 1 after surgery, and a volume overload contraction pattern and tricuspid regurgitation was present in the majority. This increase in right ventricular size was maintained at 1 year follow-up while the incidence of tricuspid regurgitation decreased. We conclude that there is rapid resolution of moderately elevated pulmonary arterial pressures after cardiac transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical Dilemmas in Inflammatory Bowel Disease
Authors: D P Jewell
Journal: Gut (2007)

Edited by P M Irving, D S Rampton, Fergus Shanahan. Published by Blackwell Publishing, Oxford, 2006, $59.95, pp 248. ISBN 978-1-4051-3377-7

Ulcerative colitis and Crohn’s disease never cease to fascinate those of us whose professional life is continually marked by their heterogeneity, their complex aetiology and pathogenesis, and the management issues that frequently stretch clinical skills to the limit. For all of us, but especially perhaps for those in training, …
Health and fitness of young people: what is the role of sport?
Authors: Margo Mountjoy
Journal: British Journal of Sports Medicine (2011)

President Rogge in his opening address at the Olympic Movement in Society Congress in Copenhagen, 2009, expressed his concern over the health of young people globally and the importance of the role of sport in society in addressing the issue: In the late 1800s, de Coubertin worried that youth in his native France were turning away from physical activity. Today, we see the same problem in the growing rate of youth obesity throughout the world… We are here to make sure that the Olympic Movement will continue to serve athletes, the world's youth and society at large for decades to come.1 

One of the themes during the Olympic Movement in Society Congress was ‘Olympism and Youth’. Following the presentations and discussions in Copenhagen on this theme, Recommendation #51 was proposed as guidance for members of the Olympic Family:   Everyone involved in the Olympic Movement must become more aware of the fundamental importance of physical activity and sport for a healthy life style, not least in the growing battle against obesity, and must reach out to parents and schools as part of a strategy to counter the rising inactivity …
The Cation/Ca2+ Exchanger Superfamily: Phylogenetic Analysis and Structural Implications
Authors: Xinjiang Cai, Jonathan Lytton
Journal: Molecular Biology and Evolution (2004)

Cation/Ca(2+) exchangers are an essential component of Ca(2+) signaling pathways and function to transport cytosolic Ca(2+) across membranes against its electrochemical gradient by utilizing the downhill gradients of other cation species such as H(+), Na(+), or K(+). The cation/Ca(2+) exchanger superfamily is composed of H(+)/Ca(2+) exchangers and Na(+)/Ca(2+) exchangers, which have been investigated extensively in both plant cells and animal cells. Recently, information from completely sequenced genomes of bacteria, archaea, and eukaryotes has revealed the presence of genes that encode homologues of cation/Ca(2+) exchangers in many organisms in which the role of these exchangers has not been clearly demonstrated. In this study, we report a comprehensive sequence alignment and the first phylogenetic analysis of the cation/Ca(2+) exchanger superfamily of 147 sequences. The results present a framework for structure-function relationships of cation/Ca(2+) exchangers, suggesting unique signature motifs of conserved residues that may underlie divergent functional properties. Construction of a phylogenetic tree with inclusion of cation/Ca(2+) exchangers with known functional properties defines five protein families and the evolutionary relationships between the members. Based on this analysis, the cation/Ca(2+) exchanger superfamily is classified into the YRBG, CAX, NCX, and NCKX families and a newly recognized family, designated CCX. These findings will provide guides for future studies concerning structures, functions, and evolutionary origins of the cation/Ca(2+) exchangers.
Transfer in L2 grammars
Authors: Rakesh M. Bhatt, Barbara Hancin-Bhatt
Journal: Behavioral and Brain Sciences (1996)

Abstract Although the Full-access hypothesis accounts for a range of empirical generalizations of L2A, it underrepresents the role of language transfer in the construction of the L2 grammar. We suggest the possibility that linguistic principles which constrain the L2 grammar are available both directly from UG and via the L1, a logical hypothesis which Epstein et al. do not consider.
Control of Immunity by the TNFR-Related Molecule OX40 (CD134)
Authors: Michael Croft
Journal: Annual Review of Immunology (2010)

TNFR/TNF superfamily members can control diverse aspects of immune function. Research over the past 10 years has shown that one of the most important and prominent interactions in this family is that between OX40 (CD134) and its partner OX40L (CD252). These molecules strongly regulate conventional CD4 and CD8 T cells, and more recent data are highlighting their ability to modulate NKT cell and NK cell function as well as to mediate cross-talk with professional antigen-presenting cells and diverse cell types such as mast cells, smooth muscle cells, and endothelial cells. Additionally, OX40-OX40L interactions alter the differentiation and activity of regulatory T cells. Blocking OX40L has produced strong therapeutic effects in multiple animal models of autoimmune and inflammatory disease, and, in line with a prospective clinical future, reagents that stimulate OX40 signaling are showing promise as adjuvants for vaccination as well as for treatment of cancer.
Loss-of-Function Mutations in<i>APOC3,</i>Triglycerides, and Coronary Disease
Journal: New England Journal of Medicine (2014)

Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype.We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons.An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G→A and IVS3+1G→T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P=8×10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P=4×10(-6)).Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.).
Receptor Binding Properties of Human Insulin (recombinant DNA) and Human Proinsulin and Their Interaction at the Receptor Site
Authors: Rudolf Prager, Guntram Schernthaner
Journal: Diabetes Care (1982)

The binding properties of human insulin (recombinant DNA) and human proinsulin were compared in seven healthy volunteers. Specific cell binding of human proinsulin was significantly lower compared with the human insulin receptor binding with an approximately 100-fold lower average affinity (3.71 mol-1 X 10(8) for human insulin versus 0.042 mol-1 X 10(8) for human proinsulin). Native human proinsulin at low concentrations had no significant effect on specific human insulin receptor binding. Only at high hormone concentrations human proinsulin could displace human insulin from the insulin receptor. We conclude that in vivo proinsulin-insulin interactions at the receptor do not possess major clinical relevance.
SNPs in BRAP associated with risk of myocardial infarction in Asian populations
Authors: Kouichi Ozaki, Hiroshi Sato, Katsumi Inoue, Tatsuhiko Tsunoda, Yasuhiko Sakata, Hiroya Mizuno, Tsung-Hsien Lin, Yoshinari Miyamoto, Asako Aoki, Yoshihiro Onouchi, Sheng-Hsiung Sheu, Shiro Ikegawa, Keita Odashiro, Masakiyo Nobuyoshi, Suh-Hang H Juo, Masatsugu Hori, Yusuke Nakamura, Toshihiro Tanaka
Journal: Nature Genetics (2009)
Intestinal mucus affinity and biological activity of an orally administered antibacterial and anti-inflammatory peptide
Authors: Aline Dupont, Yani Kaconis, Ines Yang, Thorben Albers, Sabrina Woltemate, Lena Heinbockel, Mats Andersson, Sebastian Suerbaum, Klaus Brandenburg, Mathias W Hornef
Journal: Gut (2014)

<h3>Objective</h3> Antimicrobial peptides (AMP) provide protection from infection by pathogenic microorganisms and restrict bacterial growth at epithelial surfaces to maintain mucosal homeostasis. In addition, they exert a significant anti-inflammatory activity. Here we analysed the anatomical distribution and biological activity of an orally administered AMP in the context of bacterial infection and host–microbial homeostasis. <h3>Design</h3> The anatomical distribution as well as antibacterial and anti-inflammatory activity of the endogenous AMP cryptdin 2 and the synthetic peptide Pep19-2.5 at the enteric mucosal surface were analysed by immunostaining, functional viability and stimulation assays, an oral <i>Salmonella enterica</i> subsp. <i>enterica</i> sv. Typhimurium (S. Typhimurium) model and comparative microbiota analysis. <h3>Results</h3> Endogenous cryptdin 2 was found attached to bacteria of the enteric microbiota within the intestinal mucus layer. Similarly, the synthetic peptide Pep19-2.5 attached rapidly to bacterial cells, exhibited a marked affinity for the intestinal mucus layer in vivo, altered the structural organisation of endotoxin in a mucus matrix and demonstrated potent anti-inflammatory and antibacterial activity. Oral Pep19-2.5 administration induced significant changes in the composition of the enteric microbiota as determined by high-throughput 16S rDNA sequencing. This may have contributed to the only transient improvement of the clinical symptoms after oral infection with S. Typhimurium. <h3>Conclusions</h3> Our findings demonstrate the anti-inflammatory activity and mucus affinity of the synthetic AMP Pep19-2.5 and characterise the influence on microbiota composition and enteropathogen infection after oral administration.
Prevention of CNS disease in intermediate-risk acute lymphoblastic leukemia: comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: a Childrens Cancer Group report.
Authors: D G Tubergen, G S Gilchrist, R T O'Brien, P F Coccia, H N Sather, M J Waskerwitz, G D Hammond
Journal: Journal of Clinical Oncology (1993)

PURPOSE This study (Childrens Cancer Group [CCG]-105) was designed in part to determine in a prospective randomized trial whether intrathecal methotrexate (IT MTX) administered during induction, consolidation, and maintenance could provide protection from CNS relapse equivalent to that provided by cranial radiation (CXRT) in children with acute lymphoblastic leukemia (ALL) and intermediate-risk features. PATIENTS AND METHODS We randomized 1,388 children with intermediate-risk ALL to the two CNS regimens. They received either IT MTX at intervals throughout their course of therapy or CXRT (18 Gy) during consolidation with IT MTX during induction, consolidation, and delayed intensification. Systemic therapy was randomized to one of four treatment regimens derived from a regimen used by CCG in recent studies for this patient population and three more intensive regimens based on the Berlin-Frankfurt-Munster trials. RESULTS Life-table estimates at 7 years show a 93% and 91% CNS relapse-free survival rate for the CXRT and IT MTX groups, respectively. The corresponding event-free survival (EFS) rates are 68% and 64%. The differences are not significant. Patients who received more intensive systemic therapy had a 94% CNS relapse-free survival rate on either CXRT or IT MTX, while patients who received standard systemic therapy had 90% and 80% rates for CXRT and IT MTX, respectively (P &lt; .0001). Patients less than 10 years of age who received CXRT or IT MTX had 72% and 71% EFS rates if they received more intensive systemic therapy. Patients 10 years or older who received CXRT had an improved EFS (61% v 53%) with a more intensive systemic program. This was primarily due to fewer bone marrow relapses (P = .04). CONCLUSIONS IT MTX during induction, consolidation, and maintenance provides protection from CNS relapse in patients with intermediate-risk ALL equivalent to that provided by CXRT if more intensive systemic therapy is given. The CNS relapse rate with either CXRT or IT MTX is in part dependent on the associated systemic therapy. For intermediate-risk patients less than 10 years of age, IT MTX with an intensified systemic regimen provided CNS prophylaxis comparable to that provided by CXRT, whereas older patients had fewer systemic relapses if they received CXRT.
A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance: Part 47
Authors: N A Burd, S J Stear, L M Burke, L M Castell
Journal: British Journal of Sports Medicine (2013)

Not surprisingly, we originally intended that the last word on our A–Z supplement series should come under ‘Z’. However, we did not anticipate the attention provided to a topic that we had overlooked under ‘P’, namely peptides. Some peptides—technically defined as chains of amino acids of lengths ranging from 2 to 50—can be considered nutrients. Indeed, there is now increased recognition that some proteins in our diet (eg, milk proteins) are broken down and absorbed in such fragments, exerting biological effects of their own in addition to their contribution to the body's amino acid pool. However, it is synthetic peptides that have become a major talking point in sport, due to publicity in 2013 regarding their alleged use in some professional football codes in Australia as part of a ‘supplement scheme’. These products include chemicals that have been registered in clinical trials as potential secretagogues of growth hormone. Whether some of these products are unapproved medicines or supplements found on websites targeting body builders has become blurred. Because of the apparent confusion and controversy over such products, we have invited a special editorial on the topic.

### Peptides Editorial

#### NA Burd

The production of sport nutrition foods (or parts of foods) and supplements to improve athletic performance, image or health for the consumer is a multibillion dollar industry. Within the broad supplement spectrum are the protein and/or free-form amino acid-based supplements. Research substantiating the efficacy of these supplements …
Interrelationship Between Cardiac Hypertrophy, Heart Failure, and Chronic Kidney Disease
Authors: Jeffrey G. Dickhout, Rachel E. Carlisle, Richard C. Austin
Journal: Circulation Research (2011)

Synthesis of transmembrane and secretory proteins occurs within the endoplasmic reticulum (ER) and is extremely important in the normal functioning of both the heart and kidney. The dysregulation of protein synthesis/processing within the ER causes the accumulation of unfolded proteins, thereby leading to ER stress and the activation of the unfolded protein response. Sarcoplasmic reticulum/ER Ca 2+ disequilibrium can lead to cardiac hypertrophy via cytosolic Ca 2+ elevation and stimulation of the Ca 2+ /calmodulin, calcineurin, NF-AT3 pathway. Although cardiac hypertrophy may be initially adaptive, prolonged or severe ER stress resulting from the increased protein synthesis associated with cardiac hypertrophy can lead to apoptosis of cardiac myocytes and result in reduced cardiac output and chronic heart failure. The failing heart has a dramatic effect on renal function because of inadequate perfusion and stimulates the release of many neurohumoral factors that may lead to further ER stress within the heart, including angiotensin II and arginine–vasopressin. Renal failure attributable to proteinuria and uremia also induces ER stress within the kidney, which contributes to the transformation of tubular epithelial cells to a fibroblast-like phenotype, fibrosis, and tubular cell apoptosis, further diminishing renal function. As a consequence, cardiorenal syndrome may develop into a vicious circle with poor prognosis. New therapeutic modalities to alleviate ER stress through stimulation of the cytoprotective components of the unfolded protein response, including GRP78 upregulation and eukaryotic initiation factor 2α phosphorylation, may hold promise to reduce the high morbidity and mortality associated with cardiorenal syndrome.
A CONTROLLED STUDY OF HALOPERIDOL: THE EFFECTS OF SMALL DOSAGES
Authors: ARTHUR S. SAMUELS
Journal: American Journal of Psychiatry (1961)

The clinical effects of Haloperidol in dosages small enough to avoid troublesome side effects were observed in a small, carefully controlled study. The overall beneficial effects noted were inconclusive statistically as compared with placebo, although there was a significant reduction of anxiety on the drug. More extensive evaluation of this compound is indicated.
An evaluation of the psychological impact of operational rest and recuperation in United Kingdom Armed Forces personnel: a post-intervention survey
Authors: Norman Jones, Mohammed Fertout, Laura Parsloe, Neil Greenberg
Journal: Journal of the Royal Society of Medicine (2013)

Rest and Recuperation (R&R) is a period of home leave taken during an operational deployment; we sought to examine the relationship between taking R&R and mental health.A survey-based post-intervention evaluation.UK PARTICIPANTS: 232 members of the UK Armed Forces; 42 of which completed pre and post R&R surveys.Alcohol use, Post Traumatic Stress Disorder, Common Mental Disorder Symptoms and R&R experiences.12.1% of respondents (n=27) reported symptoms of common mental disorder and 3.7% (n=8) reported probable PTSD. 50.0% (n=110) reported hazardous use of alcohol during R&R. In the pre- and post-assessed sample, mental health status and alcohol use levels were similar at both survey points. Using principal component analysis, five components of R&R were identified; mentally switching off from deployment, travel experience, physical recovery, relaxation, rest and social support. R&R was extremely popular and although it did not improve mental health overall, the ability to engage with or derive satisfaction from aspects of the five components was significantly associated with better mental health and less alcohol use at the end of R&R.Operational commanders should advise personnel about the best way to actively engage with R&R before they leave theatre and be aware of the significant detrimental impact of disrupted travel arrangements upon the ability to benefit from R&R.