tbuckley/cabot-search huggingface dataset:
P<scp>EROXISOMAL</scp>β-O<scp>XIDATION AND</scp>P<scp>EROXISOME</scp>P<scp>ROLIFERATOR</scp>–A<scp>CTIVATED</scp>R<scp>ECEPTOR</scp>α: An Adaptive Metabolic System
Authors: Janardan K Reddy, Takashi Hashimoto
Journal: Annual Review of Nutrition (2001)

▪ Abstract β-Oxidation occurs in both mitochondria and peroxisomes. Mitochondria catalyze the β-oxidation of the bulk of short-, medium-, and long-chain fatty acids derived from diet, and this pathway constitutes the major process by which fatty acids are oxidized to generate energy. Peroxisomes are involved in the β-oxidation chain shortening of long-chain and very-long-chain fatty acyl-coenzyme (CoAs), long-chain dicarboxylyl-CoAs, the CoA esters of eicosanoids, 2-methyl-branched fatty acyl-CoAs, and the CoA esters of the bile acid intermediates di- and trihydroxycoprostanoic acids, and in the process they generate H 2 O 2 . Long-chain and very-long-chain fatty acids (VLCFAs) are also metabolized by the cytochrome P450 CYP4A ω-oxidation system to dicarboxylic acids that serve as substrates for peroxisomal β-oxidation. The peroxisomal β-oxidation system consists of (a) a classical peroxisome proliferator–inducible pathway capable of catalyzing straight-chain acyl-CoAs by fatty acyl-CoA oxidase, L-bifunctional protein, and thiolase, and (b) a second noninducible pathway catalyzing the oxidation of 2-methyl-branched fatty acyl-CoAs by branched-chain acyl-CoA oxidase (pristanoyl-CoA oxidase/trihydroxycoprostanoyl-CoA oxidase), D-bifunctional protein, and sterol carrier protein (SCP)x. The genes encoding the classical β-oxidation pathway in liver are transcriptionally regulated by peroxisome proliferator–activated receptor α (PPARα). Evidence derived from mice deficient in PPARα, peroxisomal fatty acyl-CoA oxidase, and some of the other enzymes of the two peroxisomal β-oxidation pathways points to the critical importance of PPARα and of the classical peroxisomal fatty acyl-CoA oxidase in energy metabolism, and in the development of hepatic steatosis, steatohepatitis, and liver cancer.
Dysfunctional T regulatory cells in multiple myeloma
Authors: Rao H. Prabhala, Paola Neri, Jooeun E. Bae, Pierfrancesco Tassone, Masood A. Shammas, Charles K. Allam, John F. Daley, Dharminder Chauhan, Elizabeth Blanchard, Hemant S. Thatte, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2005)
Fibrinolysis in Congenital Heart Disease: Preoperative Treatment with Epsilon Aminocaproic Acid.
Authors: Isadore Brodsky
Journal: Annals of Internal Medicine (1968)

s1 May 1968Fibrinolysis in Congenital Heart Disease: Preoperative Treatment with Epsilon Aminocaproic Acid.Isadore Brodsky, M.D., F.A.C.P., Donald N. Gill, M.D., Charles J. Lusch, M.D.Isadore Brodsky, M.D., F.A.C.P.Search for more papers by this author, Donald N. Gill, M.D.Search for more papers by this author, Charles J. Lusch, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1165_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe existence of preoperative fibrinolysis and the response to treatment with epsilon aminocaproic acid (EACA) were studied in six patients with cyanotic or acyanotic congenital heart disease. The fibrinolytic mechanism and the third stage of coagulation were evaluated with [1] euglobulin clot lysis time, [2] serial thrombin time, [3] platelet count, [4] plasma fibrinogen, and [5] presence of split products of fibrinogen. The first and second stages of coagulation were studied with prothrombin time, partial thromboplastin time, and factor V assay. All six patients had primary fibrinolysis of varying degrees of severity and were treated preoperatively with EACA. This resulted... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByFibrinogen half-life in children with cyanotic congenital heart diseaseReference 1 May 1968Volume 68, Issue 5Page: 1165-1165KeywordsBlood plasmaCongenital heart diseaseFibrinogenFibrinolysisPartial thromboplastin timePlateletsProthrombin timeThrombin Issue Published: 1 May 1968 PDF DownloadLoading ...
Management of bone disease in patients on long term glucocorticoid therapy
Authors: J E COMPSTON
Journal: Gut (1999)

Osteoporosis is a well documented complication of gastrointestinal disease. Its pathogenesis is multifactorial but glucocorticoid therapy is likely be an important contributory factor, particularly in patients with inflammatory bowel disease.1A widely recognised condition, glucocorticoid induced osteoporosis is under diagnosed and often inadequately treated. Two recent surveys, one from a large teaching hospital2 and one community based,3 reported that only a small minority of patients receiving long term glucocorticoid therapy were offered prophylaxis against bone loss. However, recent evidence shows that intervention can prevent bone loss and reduce the significant morbidity associated with glucocorticoid induced osteoporosis.4 5 This emphasises the need to adopt a more aggressive approach towards prevention of osteoporosis, and to define management strategies for patients who are treated with glucocorticoids.

The time course of glucocorticoid induced bone loss has not been well documented but there is evidence that the rate of loss is most rapid in the first six to 12 months of treatment and decreases thereafter.6 7 If these findings are confirmed, there are clear implications for the timing of intervention. Although not all studies are in agreement, most data indicate that the spine and proximal femur are affected similarly8 and observational studies suggest that the risk both of hip and vertebral fractures is higher in patients treated with glucocorticoids.9 10 Data from placebo controlled primary prevention trials indicate rates of bone loss in untreated patients in the region of 2–4% each year, both in the spine and proximal femur.4 11 This is considerably in excess of rates of bone loss expected in a healthy population of similar age and sex distribution.

Attempts to show a correlation between the dose and duration of glucocorticoid therapy, and bone loss, have produced conflicting results. This may partly reflect the confounding …
URINARY EXCRETION OF FOREIGN ANTIGENS AND RNA FOLLOWING PRIMARY AND SECONDARY INJECTIONS OF ANTIGENS
Authors: Justine S. Garvey, Dan H. Campbell, Manik L. Das
Journal: The Journal of Experimental Medicine (1967)

Two soluble antigens, BSA and KLH labeled with sulfanilate-35S, when injected intravenously into normal animals, were excreted in the urine to over 70% in 24 hr. Over the next 6 days, 25% more was excreted after which time only a trace could be detected. Much of the antigen remaining from the primary injection appeared in the urine following a secondary injection of the unlabeled protein carrier at 7 days after primary injection. The antigen material found in the urine was quite heterogeneous with respect to physical properties and much of it was associated with RNA material as shown by chromatographic analyses. The main difference between the labeled material released following the primary and secondary injection was the higher degree of association of antigen material with nucleotide material after secondary injection as compared with primary injection. Further study is needed to distinguish qualitative from quantitative changes of the components, antigen and nucleic acid, and also the nature of their association. Possible similarities were found for the RNA-antigen material released from tissue after secondary injection of unlabeled antigen, and the material that was isolated previously from liver.
Polysialic acid/neural cell adhesion molecule modulates the formation of ductular reactions in liver injury
Authors: Atsunori Tsuchiya, Wei-Yu Lu, Birgit Weinhold, Luke Boulter, Benjamin M. Stutchfield, Michael J. Williams, Rachel V. Guest, Sarah E. Minnis-Lyons, Alison C. MacKinnon, David Schwarzer, Takafumi Ichida, Minoru Nomoto, Yutaka Aoyagi, Rita Gerardy-Schahn, Stuart J. Forbes
Journal: Hepatology (2014)

In severe liver injury, ductular reactions (DRs) containing bipotential hepatic progenitor cells (HPCs) branch from the portal tract. Neural cell adhesion molecule (NCAM) marks bile ducts and DRs, but not mature hepatocytes. NCAM mediates interactions between cells and surrounding matrix; however, its role in liver development and regeneration is undefined. Polysialic acid (polySia), a unique posttranslational modifier of NCAM, is produced by the enzymes, ST8SiaII and ST8SiaIV, and weakens NCAM interactions. The role of polySia with NCAM synthesizing enzymes ST8SiaII and ST8SiaIV were examined in HPCs in vivo using the choline-deficient ethionine-supplemented and 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet models of liver injury and regeneration, in vitro using models of proliferation, differentiation, and migration, and by use of mouse models with gene defects in the polysialyltransferases ( St8sia 2+/ −4+/ − , and St8sia2− / −4− / − ). We show that, during liver development, polySia is required for the correct formation of bile ducts because gene defects in both the polysialyltransferases ( St8sia2+/ −4+/ − and St8sia2− / −4− / − mice) caused abnormal bile duct development. In normal liver, there is minimal polySia production and few ductular NCAM+ cells. Subsequent to injury, NCAM+ cells expand and polySia is produced by DRs/HPCs through ST8SiaIV. PolySia weakens cell-cell and cell-matrix interactions, facilitating HGF-induced migration. Differentiation of HPCs to hepatocytes in vitro results in both transcriptional down-regulation of polySia and cleavage of polySia-NCAM. Cleavage of polySia by endosialidase (endoN) during liver regeneration reduces migration of DRs into parenchyma. Conclusion : PolySia modification of NCAM+ ductules weakens cell-cell and cell-matrix interactions, allowing DRs/HPCs to migrate for normal development and regeneration. Modulation of polySia levels may provide a therapeutic option in liver regeneration. (Hepatology 2014;60:1727–1740)
[704] MITOCHONDRIAL DNA HAPLOGROUPS ASSOCIATED WITH HISTOLOGICAL SEVERITY IN NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
Authors: N.M. De Alwis, C. Mowbray, A. Pyle, E. Henderson, J. Leathart, G.P. Aithal, P.F. Chinnery, C.P. Day
Journal: Journal of Hepatology (2007)
Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity
Authors: Joseph Tam, V. Kiran Vemuri, Jie Liu, Sándor Bátkai, Bani Mukhopadhyay, Grzegorz Godlewski, Douglas Osei-Hyiaman, Shinobu Ohnuma, Suresh V. Ambudkar, James Pickel, Alexandros Makriyannis, George Kunos
Journal: Journal of Clinical Investigation (2010)

Obesity and its metabolic consequences are a major public health concern worldwide. Obesity is associated with overactivity of the endocannabinoid system, which is involved in the regulation of appetite, lipogenesis, and insulin resistance. Cannabinoid-1 receptor (CB1R) antagonists reduce body weight and improve cardiometabolic abnormalities in experimental and human obesity, but their therapeutic potential is limited by neuropsychiatric side effects. Here we have demonstrated that a CB1R neutral antagonist largely restricted to the periphery does not affect behavioral responses mediated by CB1R in the brains of mice with genetic or diet-induced obesity, but it does cause weight-independent improvements in glucose homeostasis, fatty liver, and plasma lipid profile. These effects were due to blockade of CB1R in peripheral tissues, including the liver, as verified through the use of CB1R-deficient mice with or without transgenic expression of CB1R in the liver. These results suggest that targeting peripheral CB1R has therapeutic potential for alleviating cardiometabolic risk in obese patients.
Psychotherapy for Depression With Executive Dysfunction
Authors: Julie Loebach Wetherell
Journal: American Journal of Psychiatry (2010)

A second assumption called into question by the article, termed the "Dodo bird verdict," is that all psychotherapy approaches are equivalent (Rosenzweig [7] quoted this character from Alice's Adventures in Wonderland [8], who declares after a race that "everybody has won, and all must have prizes").
Identification of a human T lymphocyte surface protein associated with the E-rosette receptor.
Authors: M Kamoun, P J Martin, J A Hansen, M A Brown, A W Siadak, R C Nowinski
Journal: The Journal of Experimental Medicine (1981)

We describe a new monoclonal murine antibody that reacts with a 50,000-mol wt polypeptide that appears to be present on all E-rosetting cells. We conclude that this antigen is either identical to or closely associated with the E receptor because of (a) the high degree of concordance between E-rosette formation and 9.6 antigen expression, (b) the inhibition of rosette formation by preincubation of cells with 9.6 antibody, and (c) the observed failure of cells lysostripped of 9.6 antigen to form E-rosettes. This last finding suggests cocapping of 9.6 antigen and the E receptor.
Effects of Exercise on Glycemic Control and Body Mass in Type 2 Diabetes Mellitus
Authors: Normand G. Boulé, Elizabeth Haddad, Glen P. Kenny, George A. Wells, Ronald J. Sigal
Journal: JAMA (2001)

Exercise is widely perceived to be beneficial for glycemic control and weight loss in patients with type 2 diabetes. However, clinical trials on the effects of exercise in patients with type 2 diabetes have had small sample sizes and conflicting results.To systematically review and quantify the effect of exercise on glycosylated hemoglobin (HbA(1c)) and body mass in patients with type 2 diabetes.Database searches of MEDLINE, EMBASE, Sport Discuss, Health Star, Dissertation Abstracts, and the Cochrane Controlled Trials Register for the period up to and including December 2000. Additional data sources included bibliographies of textbooks and articles identified by the database searches.We selected studies that evaluated the effects of exercise interventions (duration >/=8 weeks) in adults with type 2 diabetes. Fourteen (11 randomized and 3 nonrandomized) controlled trials were included. Studies that included drug cointerventions were excluded.Two reviewers independently extracted baseline and postintervention means and SDs for the intervention and control groups. The characteristics of the exercise interventions and the methodological quality of the trials were also extracted.Twelve aerobic training studies (mean [SD], 3.4 [0.9] times/week for 18 [15] weeks) and 2 resistance training studies (mean [SD], 10 [0.7] exercises, 2.5 [0.7] sets, 13 [0.7] repetitions, 2.5 [0.4] times/week for 15 [10] weeks) were included in the analyses. The weighted mean postintervention HbA(1c) was lower in the exercise groups compared with the control groups (7.65% vs 8.31%; weighted mean difference, -0.66%; P<.001). The difference in postintervention body mass between exercise groups and control groups was not significant (83.02 kg vs 82.48 kg; weighted mean difference, 0.54; P =.76).Exercise training reduces HbA(1c) by an amount that should decrease the risk of diabetic complications, but no significantly greater change in body mass was found when exercise groups were compared with control groups.
Is there a gold standard test for diagnosing exercise induced asthma in elite athletes?
Authors: A Khan
Journal: Thorax (2006)

▴ Dickinson JW, Whyte GP, McConnell AK, Harries MG. Screening elite winter athletes for exercise induced asthma: a comparison of three challenge methods. Br J Sports Med2006;40:179–82 [OpenUrl][1][Abstract/FREE Full Text][2] Exercise induced asthma (EIA) is a common yet often unrecognised condition that occurs in both known asthmatics and otherwise healthy individuals. Misdiagnosis—both over- and under-diagnosis—frequently occurs. In order to diagnose EIA accurately, a bronchoprovocation challenge test must be performed. The provocation tests used to identify subjects with EIA include exercise (laboratory or field), eucapnic voluntary hyperventilation (EVH), and pharmacological … [1]: {openurl}?query=rft.jtitle%253DBritish%2BJournal%2Bof%2BSports%2BMedicine%26rft.stitle%253DBr.%2BJ.%2BSports.%2BMed.%26rft.issn%253D0306-3674%26rft.aulast%253DDickinson%26rft.auinit1%253DJ%2BW%26rft.volume%253D40%26rft.issue%253D2%26rft.spage%253D179%26rft.epage%253D182%26rft.atitle%253DScreening%2Belite%2Bwinter%2Bathletes%2Bfor%2Bexercise%2Binduced%2Basthma%253A%2Ba%2Bcomparison%2Bof%2Bthree%2Bchallenge%2Bmethods%2B%2A%2BCommentary%26rft_id%253Dinfo%253Apmid%252F16432008%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=bjsports&resid=40/2/179&atom=%2Fthoraxjnl%2F61%2F5%2F439.atom
Reduced LIMK2 expression in colorectal cancer reflects its role in limiting stem cell proliferation
Authors: Filipe C Lourenço, June Munro, Jennifer Brown, Julia Cordero, Rhoda Stefanatos, Karen Strathdee, Clare Orange, Stephan M Feller, Owen J Sansom, Marcos Vidal, Graeme I Murray, Michael F Olson
Journal: Gut (2013)

<h3>Objective</h3> Colorectal cancer (CRC) is a major contributor to cancer mortality and morbidity. LIM kinase 2 (LIMK2) promotes tumour cell invasion and metastasis. The objectives of this study were to determine how LIMK2 expression is associated with CRC progression and patient outcome, and to use genetically modified <i>Drosophila</i> and mice to determine how LIMK2 deletion affects gastrointestinal stem cell regulation and tumour development. <h3>Design</h3> LIMK2 expression and activity were measured by immunostaining tumours from CRC-prone mice, human CRC cell lines and 650 human tumours. <i>LIMK</i> knockdown in <i>Drosophila</i> or <i>Limk2</i> deletion in mice allowed for assessment of their contributions to gastrointestinal stem cell homeostasis and tumour development. <h3>Results</h3> LIMK2 expression was reduced in intestinal tumours of cancer-prone mice, as well as in human CRC cell lines and tumours. Reduced LIMK2 expression and substrate phosphorylation were associated with shorter patient survival. Genetic analysis in <i>Drosophila</i> midgut and intestinal epithelial cells isolated from genetically modified mice revealed a conserved role for LIMK2 in constraining gastrointestinal stem cell proliferation. <i>Limk2</i> deletion increased colon tumour size in a colitis-associated colorectal mouse cancer model. <h3>Conclusions</h3> This study revealed that LIMK2 expression and activity progressively decrease with advancing stage, and supports the hypothesis that there is selective pressure for reduced LIMK2 expression in CRC to relieve negative constraints imposed upon gastrointestinal stem cells.
Effect of late preterm birth on longitudinal lung spirometry in school age children and adolescents
Authors: Sarah J Kotecha, W John Watkins, Shantini Paranjothy, Frank D Dunstan, A John Henderson, Sailesh Kotecha
Journal: Thorax (2011)

<h3>Background</h3> Rates of preterm birth have increased in most industrialised countries but data on later lung function of late preterm births are limited. A study was undertaken to compare lung function at 8–9 and 14–17 years in children born late preterm (33–34 and 35–36 weeks gestation) with children of similar age born at term (≥37 weeks gestation). Children born at 25–32 weeks gestation were also compared with children born at term. <h3>Methods</h3> All births from the Avon Longitudinal Study of Parents and Children (n=14 049) who had lung spirometry at 8–9 years of age (n=6705) and/or 14–17 years of age (n=4508) were divided into four gestation groups. <h3>Results</h3> At 8–9 years of age, all spirometry measures were lower in the 33–34-week gestation group than in controls born at term but were similar to the spirometry decrements observed in the 25–32-week gestation group. The 35–36-week gestation group and term group had similar values. In the late preterm group, at 14–17 years of age forced expiratory volume in 1 s (FEV<sub>1</sub>) and forced vital capacity (FVC) were not significantly different from the term group but FEV<sub>1</sub>/FVC and forced expiratory flow at 25–75% FVC (FEF<sub>25–75%</sub>) remained significantly lower than term controls. Children requiring mechanical ventilation in infancy at 25–32 and 33–34 weeks gestation had in general lower airway function (FEV<sub>1</sub> and FEF<sub>25–75</sub>) at both ages than those not ventilated in infancy. <h3>Conclusions</h3> Children born at 33–34 weeks gestation have significantly lower lung function values at 8–9 years of age, similar to decrements observed in the 25–32-week group, although some improvements were noted by 14–17 years of age.
Telomerase-Dependent Virotherapy Overcomes Resistance of Hepatocellular Carcinomas against Chemotherapy and Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand by Elimination of Mcl-1
Authors: Thomas Wirth, Florian Kühnel, Bettina Fleischmann-Mundt, Norman Woller, Meta Djojosubroto, Karl Lenhard Rudolph, Michael Manns, Lars Zender, Stefan Kubicka
Journal: Cancer Research (2005)

Abstract Hepatocellular carcinomas (HCC) are drug-resistant tumors that frequently possess high telomerase activity. It was therefore the aim of our study to investigate the potential of telomerase-dependent virotherapy in multimodal treatment of HCC. In contrast to normal liver, HCC xenografts showed high telomerase activity, resulting in tumor-restricted expression of E1A by a telomerase-dependent replicating adenovirus (hTERT-Ad). Neither tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) or chemotherapy alone nor the combined treatment with both agents resulted in significant destruction of HCC cells. Application of hTERT-Ad at low titers was also not capable to destroy HCC cells, but telomerase-dependent virotherapy overcame the resistance of HCC against TRAIL and chemotherapy. The synergistic effects are explained by a strong down-regulation of Mcl-1 expression through hTERT-Ad that sensitizes HCC for TRAIL- and chemotherapy-mediated apoptosis. To investigate whether down-regulation of Mcl-1 alone is sufficient to explain synergistic effects observed with virotherapy, Mcl-1 expression was inhibited by RNA interference. Treatment with Mcl-1-siRNA significantly enhanced caspase-3 activity after chemotherapy and TRAIL application, confirming that elimination of Mcl-1 is responsible for the drug sensitization by hTERT-Ad. Consistent with these results, heterologous overexpression of Mcl-1 significantly reduced the sensitization of hTERT-Ad transduced cells against apoptosis-inducing agents. Chemotherapy did not interfere with quantitative hTERT-Ad production in HCC cells. Whereas hTERT-Ad virotherapy alone was only capable to inhibit the growth of Hep3B xenografts, virochemotherapy resulted in vast destruction of the drug-resistant HCC. In conclusion our data indicate that telomerase-dependent virotherapy is an attractive strategy to overcome the natural resistance of HCC against anticancer drugs by elimination of Mcl-1.