tbuckley/cabot-search huggingface dataset:
Transnasal bile duct catheterisation after endoscopic sphincterotomy: method for biliary drainage, perfusion, and sequential cholangiography.
Authors: P B Cotton, P G Burney, R R Mason
Journal: Gut (1979)

We describe a method for leaving a catheter in the common bile duct for several days, even weeks, after endoscopic sphincterotomy. This provides reliable biliary drainage, and permits perfusion of the duct with simple fluids or solvents. It reduces the need for instrumental stone extraction and for repeated endoscopy and cholangiography to check whether stones have passed, since transnasal cholangiograms can be performed simply and repeatedly without discomfort.
Chondroitin sulphation patterns in synovial fluid in osteoarthritis subsets
Authors: S. Lewis, M. Crossman, J. Flannelly, C. Belcher, M. Doherty, M. T Bayliss, R. M Mason
Journal: Annals of the Rheumatic Diseases (1999)

To determine concentrations of chondroitin sulphate (CS) disaccharides in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables differ between different diseases and subsets of OA.OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA), with 25, 9, and 11 people in each subset respectively. The SF of 13 normal subjects was also volunteered for analysis along with 15 RA patients. Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Concentrations of unsaturated CS disaccharides Deltadi6S and Deltadi4S were measured by capillary zone electrophoresis.Concentrations of Deltadi6S were lower in RA (5.90 ng/ml) and OA (13.24 ng/ml) fluids compared with normal (21.0 ng/ml) but no significant differences were seen between disease and normal fluids for Deltadi4S (about 4-6 ng/ml). The ratio of Deltadi6S:Deltadi4S were RA<OA<normal subjects (p<0.001 for all comparisons). The disaccharide concentration values along with the ratios are below. Higher Deltadi6S:Deltadi4S ratios were obtained for LJOA and CPA compared with NGOA. Uninflamed knees had lower concentrations of Deltadi6S than inflamed knees (p<0.01). In patients with bilateral samples, there were strong correlations between right and left knees for all SF variables.Altered ratios of CS sulphation patterns occur in OA and within OA subsets. These further justify considering NGOA as a subset with a different aetiopathogenesis.
Deacetylation of FoxO by Sirt1 Plays an Essential Role in Mediating Starvation-Induced Autophagy in Cardiac Myocytes
Authors: Nirmala Hariharan, Yasuhiro Maejima, Jun Nakae, Jihye Paik, Ronald A. DePinho, Junichi Sadoshima
Journal: Circulation Research (2010)

Rationale: Autophagy, a bulk degradation process of cytosolic proteins and organelles, is protective during nutrient starvation in cardiomyocytes (CMs). However, the underlying signaling mechanism mediating autophagy is not well understood. Objective: We investigated the role of FoxOs and its posttranslational modification in mediating starvation-induced autophagy. Methods and Results: Glucose deprivation (GD) increased autophagic flux in cultured CMs, as evidenced by increased mRFP-GFP-LC3 puncta and decreases in p62, which was accompanied by upregulation of Sirt1 and FoxO1. Overexpression of either Sirt1 or FoxO1 was sufficient for inducing autophagic flux, whereas both Sirt1 and FoxO1 were required for GD-induced autophagy. GD increased deacetylation of FoxO1, and Sirt1 was required for GD-induced deacetylation of FoxO1. Overexpression of FoxO1(3A/LXXAA), which cannot interact with Sirt1, or p300, a histone acetylase, increased acetylation of FoxO1 and inhibited GD-induced autophagy. FoxO1 increased expression of Rab7, a small GTP-binding protein that mediates late autophagosome–lysosome fusion, which was both necessary and sufficient for mediating FoxO1-induced increases in autophagic flux. Although cardiac function was maintained in control mice after 48 hours of food starvation, it was significantly deteriorated in mice with cardiac-specific overexpression of FoxO1(3A/LXXAA), those with cardiac-specific homozygous deletion of FoxO1 (c-FoxO1 −/− ), and beclin1 +/− mice, in which autophagy is significantly inhibited. Conclusions: These results suggest that Sirt1-mediated deacetylation of FoxO1 and upregulation of Rab7 play an important role in mediating starvation-induced increases in autophagic flux, which in turn plays an essential role in maintaining left ventricular function during starvation.
Plasma Phytoestrogens and Subsequent Breast Cancer Risk
Authors: Martijn Verheus, Carla H. van Gils, Lital Keinan-Boker, Philip B. Grace, Sheila A. Bingham, Petra H.M. Peeters
Journal: Journal of Clinical Oncology (2007)

Phytoestrogens are plant compounds that are structurally and functionally similar to mammalian estrogens. By competing for estrogen receptors, phytoestrogens possibly inhibit binding of the more potent endogenous estrogens and decrease their potential effects on breast cancer risk. We investigated the association between plasma phytoestrogen levels and breast cancer risk in a prospective manner.We performed a nested case-control study within the Prospect cohort, one of the two Dutch cohorts participating in the European Prospective Investigation into Cancer and Nutrition. A total of 383 women (87 pre- or perimenopausal women [mean age, 52 years] and 296 postmenopausal women [mean age, 59 years]) who developed breast cancer were selected as case subjects and were matched to 383 controls, on date of blood sampling. Plasma levels of isoflavones (daidzein, genistein, glycitein, O-desmethylangolensin, and equol) and lignans (enterodiol and enterolactone) were measured. The isotope dilution liquid chromatography/tandem mass-spectrometry method incorporating triply 13C-labeled standards was used for all analyses. Breast cancer odds ratios were calculated for tertiles of phytoestrogen plasma levels using conditional logistic regression analysis.For genistein, the risk estimate for the highest versus the lowest tertile was 0.68 (95% CI, 0.47 to 0.98). Similar protective effects, although not statistically significant, were seen for the other isoflavones. Lignan levels did not appear to be related to breast cancer risk. Results were the same in pre- or perimenopausal women, and in postmenopausal women.High genistein circulation levels are associated with reduced breast cancer risk in the Dutch population. No effects of lignans on breast cancer risk were observed.
Rhinitis alone or rhinitis plus asthma: what makes the difference?
Authors: A Magnan, C Fourre-Jullian, H Jullian, M Badier, A Lanteaume, D Vervloet, D Charpin
Journal: European Respiratory Journal (1998)

This paper examines the clinical expression of asthma in a group of patients displaying rhinitis according to age, sex, associated symptoms, smoking, familial history of asthma, atopy, type of sensitization to aeroallergens (pollens and/or indoor allergens), total serum immunoglobulin E (IgE), and blood eosinophils. A total of 117 adults with rhinitis were analysed on the basis of symptoms. Among them, 51 also displayed asthma, defined as a history of recurrent episodes of dyspnoea with a reversible airflow obstruction or a positive methacholine challenge. The logistic regression analysis carried out in a stepwise approach, combining several factors, showed that various parameters affected the risk of having asthma associated with rhinitis. A further analysis was made in 74 rhinitis patients comparing 42 subjects without nonallergic airway hyperresponsiveness (NAAH) to 32 patients with asthma and NAAH. Atopy, high total serum IgE levels, elevated blood eosinophil count and maternal asthma were associated with asthma. Furthermore, in atopic patients, pollen sensitization was more closely related to rhinitis alone, whereas sensitization to indoor allergens was a major determinant for the association of asthma with the symptoms of rhinitis. The same risk factors as those found in the clinical part of the study discriminated the patients with rhinitis without NAAH from those with rhinitis, asthma and NAAH. In conclusion, this study gives new insights into the relationships between asthma and rhinitis.
Clinical Outcome and Phenotypic Expression in &lt;emph type="ital"&gt;LAMP2&lt;/emph&gt; Cardiomyopathy
Authors: Barry J. Maron
Journal: JAMA (2009)

ETABOLIC MYOCARDIAL2][3][4][5][6][7] The morphologic expression and the clinical course experienced by patients with this newly identified cardiomyopathy 2-7 are incompletely resolved.Therefore, it is informative to report our experience with an assessment of the natural history associated with LAMP2 cardiomyopathy. METHODSThe most current clinical status of 7 previously identified patients with LAMP2 mutations 1 was reexamined as of October 2008.Two-dimensional and Doppler echocardiographic studies were performed according to standard methodology with commercially available instruments.As previously described in detail, 1,8 sequence analyses of genes that encode 8 sarcomere proteins (␤ cardiac myosin heavy chain, cardiac myosin-binding protein C, cardiac troponin T, cardiac troponin I, cardiac actin, essential myosin
Controlled trial of psychotherapy for bulimia nervosa
Authors: C P L Freeman, F Barry, J Dunkeld-Turnbull, A Henderson
Journal: BMJ (1988)

In a randomised controlled trial of different types of psychotherapy for bulimia 92 women were assigned to receive cognitive-behaviour therapy (n=32), behaviour therapy (30), or group therapy (30) for 15 weeks and a further 20 (controls) assigned to remain on a waiting list for 15 weeks. Eating behaviour and psychopathology were assessed by standard methods. At the end of the trial the controls had significantly higher scores than the treated groups on all measures of bulimic behaviour. In terms of behavioural change all three treatments were effective, 71 (77%) of the 92 women having stopped bingeing. In addition, scores on eating and depression questionnaires were reduced and self esteem improved. Follow up was continuing, but of 24 women available at one year, 21 were not bingeing and had maintained their improved scores on psychometric scales. Bulimia nervosa is amenable to treatment by once weekly structured psychotherapy in either individual or group form.
<i>FGFR1</i> Emerges as a Potential Therapeutic Target for Lobular Breast Carcinomas
Authors: Jorge Sergio Reis-Filho, Pete T. Simpson, Nicholas C. Turner, Maryou Ballo Lambros, Chris Jones, Alan Mackay, Anita Grigoriadis, David Sarrio, Kay Savage, Tim Dexter, Marjan Iravani, Kerry Fenwick, Barbara Weber, David Hardisson, Fernando Carlos Schmitt, Jose Palacios, Sunil R. Lakhani, Alan Ashworth
Journal: Clinical Cancer Research (2006)

Classic lobular carcinomas (CLC) account for 10% to 15% of all breast cancers. At the genetic level, CLCs show recurrent physical loss of chromosome16q coupled with the lack of E-cadherin (CDH1 gene) expression. However, little is known about the putative therapeutic targets for these tumors. The aim of this study was to characterize CLCs at the molecular genetic level and identify putative therapeutic targets.We subjected 13 cases of CLC to a comprehensive molecular analysis including immunohistochemistry for E-cadherin, estrogen and progesterone receptors, HER2/neu and p53; high-resolution comparative genomic hybridization (HR-CGH); microarray-based CGH (aCGH); and fluorescent and chromogenic in situ hybridization for CCND1 and FGFR1.All cases lacked the expression of E-cadherin, p53, and HER2, and all but one case was positive for estrogen receptors. HR-CGH revealed recurrent gains on 1q and losses on 16q (both, 85%). aCGH showed a good agreement with but higher resolution and sensitivity than HR-CGH. Recurrent, high level gains at 11q13 (CCND1) and 8p12-p11.2 were identified in seven and six cases, respectively, and were validated with in situ hybridization. Examination of aCGH and the gene expression profile data of the cell lines, MDA-MB-134 and ZR-75-1, which harbor distinct gains of 8p12-p11.2, identified FGFR1 as a putative amplicon driver of 8p12-p11.2 amplification in MDA-MB-134. Inhibition of FGFR1 expression using small interfering RNA or a small-molecule chemical inhibitor showed that FGFR1 signaling contributes to the survival of MDA-MB-134 cells.Our findings suggest that receptor FGFR1 inhibitors may be useful as therapeutics in a subset of CLCs.
883 EPIDEMIOLOGY AND THE INITIAL PRESENTATION OF AUTOIMMUNE HEPATITIS TYPE 1 IN SWEDEN, A NATIONWIDE STUDY
Authors: M. Werner, H. Prytz, B. Ohlsson, S. Almer, E. Bjornsson, A. Bergquist, S. Wallerstedt, H. Sandberg-Gertzen, R. Hultcrantz, P. Sangfelt, O. Weiland, A. Danielsson
Journal: Journal of Hepatology (2008)
Serum Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Levels Are Elevated in Acute Coronary Syndrome
Authors: Kazutaka Hayashida, Noriaki Kume, Takatoshi Murase, Manabu Minami, Daisuke Nakagawa, Tsukasa Inada, Masaru Tanaka, Akira Ueda, Goro Kominami, Hirofumi Kambara, Takeshi Kimura, Toru Kita
Journal: Circulation (2005)

Markers of cardiac injury, including troponin-T (TnT), are used to diagnose acute coronary syndrome (ACS); however, markers for plaque instability may be more useful for diagnosing ACS at the earliest stage. Lectin-like oxidized LDL receptor-1 (LOX-1) appears to play crucial roles in the pathogenesis of atherosclerotic plaque rupture and ACS onset. LOX-1 is released in part as soluble LOX-1 (sLOX-1) by proteolytic cleavage.We examined serum sLOX-1 levels in 521 patients, consisting of 427 consecutive patients undergoing coronary angiography, including 80 ACS patients, 173 symptomatic coronary heart disease patients, 122 patients with significant coronary stenosis without ischemia, and 52 patients without apparent coronary atherosclerosis plus 34 patients with noncardiac acute illness and 60 patients with noncardiac chronic illness. Time-dependent changes in sLOX-1 and TnT levels were analyzed in an additional 40 ACS patients. Serum sLOX-1 levels were significantly higher in ACS than the other groups and were associated with ACS as shown by multivariable logistic regression analyses. Given a cutoff value of 1.0 ng/mL, sLOX-1 can discriminate ACS from other groups with 81% and 75% of sensitivity and specificity, respectively. sLOX-1 can also discriminate ACS without ST elevation or abnormal Q waves and ACS without TnT elevation from non-ACS with 91% and 83% of sensitivity, respectively. Peak values of sLOX-1 in ACS were observed earlier than those of TnT.sLOX-1 appears to be a useful marker for early diagnosis of ACS.
Antiinflammatory and Antiarteriosclerotic Actions of HMG-CoA Reductase Inhibitors in a Rat Model of Chronic Inhibition of Nitric Oxide Synthesis
Authors: Weihua Ni, Kensuke Egashira, Chu Kataoka, Shiro Kitamoto, Masamichi Koyanagi, Shujiro Inoue, Akira Takeshita
Journal: Circulation Research (2001)

Recent studies suggest that some of the beneficial effects of 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may be due to their cholesterol-lowering independent effects on the blood vessels. Chronic inhibition of endothelial nitric oxide (NO) synthesis by oral administration of N ω -nitro- l -arginine methyl ester (L-NAME) to rats induces early vascular inflammation as well as subsequent arteriosclerosis. The aim of the study is to test whether treatment with statins attenuates such arteriosclerotic changes through their cholesterol-lowering independent effects. We investigated the effect of statins (pravastatin and cerivastatin) on the arteriosclerotic changes in the rat model. We found that treatment with statins did not affect serum lipid levels but markedly inhibited the L-NAME–induced vascular inflammation and arteriosclerosis. Treatment with statins augmented endothelial NO synthase activity in L-NAME–treated rats. We also found the L-NAME induced increase in Rho membrane translocation in hearts and its prevention by statins. Such vasculoprotective effects of statins were suppressed by the higher dose of L-NAME. In summary, in this study, we found that statins such as pravastatin and cerivastatin inhibited vascular inflammation and arteriosclerosis through their lipid-lowering independent actions in this model. Such antiarteriosclerotic effects may involve the increase in endothelial NO synthase activity and the inhibition of Rho activity.
Chronic Activation of Glomerular Mitogen-Activated Protein Kinases in Dahl Salt-Sensitive Rats
Authors: AKINORI HAMAGUCHI, SHOKEI KIM, YASUKATSU IZUMI, HIROSHI IWAO
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The in vivo role of mitogen-activated protein kinases (MAPK) in the development of glomerular injury is poorly understood. In the present study, glomerular MAPK activities, including extracellular signal-regulated kinases (ERK), c-Jun NH 2 -terminal kinases (JNK), and transcriptional factor, activator protein-1 (AP-1) were examined in glomerular injury of salt-induced hypertensive rats. Six-week-old Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were maintained on a high-salt (8.0% NaCl) diet for 1, 5, and 10 wk. In Dahl-S rats, as shown by in-gel kinase assay, an increase in BP by a high-salt diet was followed by chronic activation of glomerular ERK and JNK, which continued until 10 wk after a high-salt diet. Western blot analysis demonstrated a significant increase in the protein expression of glomerular ERK and JNK in Dahl-S rats fed a high-salt diet. As determined by gel-mobility shift assay, ERK and JNK activations were associated with an increase in glomerular AP-1 DNA binding activity. On the other hand, in Dahl-R rats fed a high-salt diet, BP remained normal throughout the experiments. However, glomerular ERK and JNK activities and AP-1 DNA binding activity in Dahl-R rats were not affected by 1 or 5 wk of a high-salt diet, but significantly increased by 10 wk of treatment with a high-salt diet, indicating that chronic sodium overload itself stimulated glomerular ERK and JNK and AP-1 activities. These kinase activations in both Dahl-S and Dahl-R rats were accompanied by an increase in urinary protein excretion and renal growth. These observations provide the first evidence that salt-sensitive hypertension causes chronic activation of glomerular ERK and JNK, probably leading to the activation of AP-1. Thus, glomerular MAPK may be responsible for the development of salt-induced glomerular injury.
An Inhibitor of Exported <i>Mycobacterium tuberculosis</i> Glutamine Synthetase Selectively Blocks the Growth of Pathogenic Mycobacteria in Axenic Culture and in Human Monocytes: Extracellular Proteins as Potential Novel Drug Targets
Authors: Günter Harth, Marcus A. Horwitz
Journal: The Journal of Experimental Medicine (1999)

Mycobacterium tuberculosis and other pathogenic mycobacteria export abundant quantities of proteins into their extracellular milieu when growing either axenically or within phagosomes of host cells. One major extracellular protein, the enzyme glutamine synthetase, is of particular interest because of its link to pathogenicity. Pathogenic mycobacteria, but not nonpathogenic mycobacteria, export large amounts of this protein. Interestingly, export of the enzyme is associated with the presence of a poly-l-glutamate/glutamine structure in the mycobacterial cell wall. In this study, we investigated the influence of glutamine synthetase inhibitors on the growth of pathogenic and nonpathogenic mycobacteria and on the poly-l-glutamate/glutamine cell wall structure. The inhibitor l-methionine-S-sulfoximine rapidly inactivated purified M. tuberculosis glutamine synthetase, which was 100-fold more sensitive to this inhibitor than a representative mammalian glutamine synthetase. Added to cultures of pathogenic mycobacteria, l-methionine- S-sulfoximine rapidly inhibited extracellular glutamine synthetase in a concentration-dependent manner but had only a minimal effect on cellular glutamine synthetase, a finding consistent with failure of the drug to cross the mycobacterial cell wall. Remarkably, the inhibitor selectively blocked the growth of pathogenic mycobacteria, all of which release glutamine synthetase extracellularly, but had no effect on nonpathogenic mycobacteria or nonmycobacterial microorganisms, none of which release glutamine synthetase extracellularly. The inhibitor was also bacteriostatic for M. tuberculosis in human mononuclear phagocytes (THP-1 cells), the pathogen's primary host cells. Paralleling and perhaps underlying its bacteriostatic effect, the inhibitor markedly reduced the amount of poly-l-glutamate/glutamine cell wall structure in M. tuberculosis. Although it is possible that glutamine synthetase inhibitors interact with additional extracellular proteins or structures, our findings support the concept that extracellular proteins of M. tuberculosis and other pathogenic mycobacteria are worthy targets for new antibiotics. Such proteins constitute readily accessible targets of these relatively impermeable organisms, which are rapidly developing resistance to conventional antibiotics.
Paracrine regulation of fat cell formation in bone marrow cultures via adiponectin and prostaglandins
Authors: Takafumi Yokota, C.S. Reddy Meka, Kay L. Medina, Hideya Igarashi, Phillip C. Comp, Masahiko Takahashi, Makoto Nishida, Kenji Oritani, Jun-ichiro Miyagawa, Tohru Funahashi, Yoshiaki Tomiyama, Yuji Matsuzawa, Paul W. Kincade
Journal: Journal of Clinical Investigation (2002)

Adiponectin, an adipocyte-derived hormone, was recently shown to have potential therapeutic applications in diabetes and obesity because of its influence on glucose and lipid metabolism. We found that brown fat in normal human bone marrow contains this protein and used marrow-derived preadipocyte lines and long-term cultures to explore potential roles in hematopoiesis. Recombinant adiponectin blocked fat cell formation in long-term bone marrow cultures and inhibited the differentiation of cloned stromal preadipocytes. Adiponectin also caused elevated expression of cyclooxygenase-2 (COX-2) by these stromal cells and induced release of prostaglandin E2 (PGE2). The COX-2 inhibitor Dup-697 prevented the inhibitory action of adiponectin on preadipocyte differentiation, suggesting involvement of stromal cell–derived prostanoids. Furthermore, adiponectin failed to block fat cell generation when bone marrow cells were derived from B6,129SPtgs2tm1Jed (COX-2+/–) mice. These observations show that preadipocytes represent direct targets for adiponectin action, establishing a paracrine negative feedback loop for fat regulation. They also link adiponectin to the COX-2–dependent PGs that are critical in this process.
Molecular Imaging with Activatable Reporter Systems
Authors: Gang Niu, Xiaoyuan Chen
Journal: Theranostics (2012)

Molecular imaging is a newly emerged multiple disciplinary field that aims to visualize, characterize and quantitatively measure biological processes at cellular and molecular levels in humans and other living systems. A reporter gene is a piece of DNA encoding reporter protein, which presents as a readily measurable phenotype that can be distinguished easily from the background of endogenous protein. After being transferred into cells of organ systems (transgenes), the reporter gene can be utilized to visualize transcriptional and posttranscriptional regulation of gene expression, protein-protein interactions, or trafficking of proteins or cells in living subjects. Herein, we review previous classification of reporter genes and regroup the reporter gene based imaging as basic, inducible and activatable, based on the regulation of reporter gene transcription and post-translational modification of reporter proteins. We then focus on activatable reporters, in which the signal can be activated at the posttranslational level for visualizing protein-protein interactions, protein phosphorylation or tertiary structure changes. The applications of several types of activatable reporters will also be summarized. We conclude that activatable reporter imaging can benefit both basic biomedical research and drug development.