tbuckley/cabot-search huggingface dataset:
Role of C-kitreceptor tyrosine kinase in development of oval cells in the rat 2-acetylaminofluorene/partial hepatectomy model
Authors: Satoshi Matsusaka, Tohru Tsujimura, Akihiro Toyosaka, Keiji Nakasho, Ayako Sugihara, Eizo Okamoto, Kunio Uematsu, Nobuyuki Terada
Journal: Hepatology (1999)

Oval cells that develop in the rat 2–acetylaminofluorene/partial hepatectomy (AAF/PH) model express the c– kit receptor tyrosine kinase (KIT) and its ligand, stem cell factor (SCF). We investigated the role of the SCF/KIT system in the development of oval cells using Ws/Ws rats, whose c– kit kinase activity was severely impaired owing to a small deletion in the kinase domain. On days 7, 9, and 13 after PH in the AAF/PH model, the development of oval cells was remarkably suppressed in Ws/Ws rats when compared with that of the control normal (+/+) rats. However, oval cells that developed in Ws/Ws rats expressed marker proteins of oval cells, such as α–fetoprotein (AFP), cytokeratin–19 (CK–19), and flt –3 receptor tyrosine kinase, similar to those of +/+ rats. Furthermore, labeling with [ 3 H]–thymidine and immunostaining of Ki–67 showed that the proliferative activity of oval cells that developed in Ws/Ws rats was comparable with that of +/+ rats. The present results indicate that the signal transduction of the SCF/KIT system plays a crucial role in the development of oval cells, at least, in the rat AAF/PH model, and suggest that KIT–mediated signal transduction plays only a small role in determining the phenotype and in the proliferative activity of oval cells.
ECCENTRIC HAMSTRING STRENGTH DURING THE NORDIC HAMSTRING EXERCISES IS A RISK FACTOR FOR HAMSTRING STRAIN INJURY IN ELITE AUSTRALIAN FOOTBALL: A PROSPECTIVE COHORT STUDY
Authors: D Opar, M Williams, R Timmins, J Hickey, S Duhig, A Shield
Journal: British Journal of Sports Medicine (2014)

Background The Nordic hamstring exercise (NHE) reduces the risk of hamstring strain injury (HSI). It is unknown if measuring eccentric hamstring strength during the NHE can predict risk of future HSI in elite Australian footballers. Objective To determine if measures of eccentric hamstring strength during the NHE identify athletes at risk of future HSI. Design Prospective cohort study. Setting Single competitive season in elite Australian football. Participants Elite Australian footballers able to perform the NHE maximally at the time of testing. 210 athletes from 5 teams had their eccentric hamstring strength assessed. Risk factor assessment Eccentric hamstring strength was determined using a custom made device at the start and end of pre-season training. Reports of previous history of hamstring, quadriceps, groin and calf injury in the prior 12 months and any history of anterior cruciate ligament injury for all athletes were ascertained. Main Outcome Measurements Prospective occurrence of HSI. The hypotheses ( a priori ), were that athletes with lower levels of eccentric hamstring strength and greater between limb imbalances in strength would be at greater risk of HSI. Results Low levels of eccentric hamstring strength at the start and end of preseason training increased the risk of future HSI by 3.3 (P=.002) and 2.8 fold (P=.027) respectively. Prior HSI increased the risk of future HSI by 3.1 fold (P=.018). No measure of between limb imbalance or any other prior injury data increased the risk of future HSI. Multivariate logistic regression revealed an interaction between increasing age and eccentric hamstring weakness leading to an increased risk of HSI. Conclusions Low levels of eccentric hamstring strength during the NHE increases the risk of future HSI in elite Australian footballers and this effect is magnified in older athletes.
Clinical evaluation of hsPR3-ANCA ELISA for detection of antineutrophil cytoplasmatic antibodies directed against proteinase 3
Authors: J U Holle, E Csernok, G Fredenhagen, M Backes, J P Bremer, W L Gross
Journal: Annals of the Rheumatic Diseases (2010)

Antineutrophil cytoplasmatic antibodies (ANCA) are used as a diagnostic marker for Wegener’s granulomatosis (WG), microscopic polyangiitis (MPA) and Churg-Strauss syndrome (CSS), as high levels of ANCA are found in these conditions. Consensus guidelines currently recommend performing an immunofluorescence test (IFT) together with an ELISA to detect the ANCA pattern and the target antigen.1 Conventional ELISAs using proteinase 3 (PR3) immobilised to the surface of the ELISA plate show great variations in performance and often lack sensitivity.2 Capture ELISA is superior in overall diagnostic performance to direct ELISA,2 but the sensitivity of capture ELISA may be reduced by the capturing antibodies hiding relevant epitopes. hsPR3-ANCA ELISA immobilises PR3 …
IFNL3 expression and response to treatment: Behind the HCV tricks
Authors: Solana Alculumbre, Emilie Estrabaud, Vassili Soumelis, Tarik Asselah
Journal: Journal of Hepatology (2014)

IFNL3, which encodes interferon-k3 (IFN-k3), has received considerable attention in the hepatitis C virus (HCV) field, as many independent genome-wide association studies have identified a strong association between polymorphisms near IFNL3 and clearance of HCV. However, the mechanism underlying this association has remained elusive. In this study, we report the identification of a functional polymorphism (rs4803217) in the 30 untranslated region (UTR) of IFNL3 mRNA that dictated transcript stability. We found that this polymorphism influenced AU-rich element (ARE)-mediated decay (AMD) of IFNL3 mRNA, as well as the binding of HCV-induced microRNAs during infection. Together these pathways mediated robust repression of the unfavorable IFNL3 polymorphism. Our data reveal a previously unknown mechanism by which HCV attenuates the antiviral response and indicate new potential therapeutic targets for HCV treatment. Open access under CC BY-NC-ND license. 2014 European Association for the Study of the Liver. Published by Elsevier B.V. While direct acting antivirals for hepatitis C virus (HCV) infection become available in some countries, interferon (IFN)-based regimen remains an option for many patients worldwide [1]. A strong association has been observed between polymorphisms located within the IFNL3 locus (IL28B) and the response to IFNbased therapy [2–4]. Nevertheless, until now no mechanism Open access under CC BY-NC-ND license. Journal of Hepatology 20
False negative results of anticardiolipin antibody test.
Authors: S Kobayashi, M Tanaka, H Tsuda, H Hashimoto, S Hirose, T Saikawa, K Yoshida
Journal: Annals of the Rheumatic Diseases (1993)

Comparison of the distribution of T cell subsets in the peripheral blood (PB) and synovial fluid (SF).Values are given as means (SD) 7 cell subsets (% or ratio) (A) HTLV-I seropositive RA (B) H1LV-I seronegative RA 1-26 (0-76) 0-17 (0-11) Differences were statistically significant between peripheral blood and synovial fluid.kp<0-01.No significant differences were observed between groups A and B. arthritis which does not fulfil the RA criteria.If some subtle changes are present in HTLV-I infected arthritic patients, further analysis using functional assays of lymphocytes may be useful for detecting these changes.
Common variants in mismatch repair genes and risk of colorectal cancer
Authors: T Koessler, M Z Oestergaard, H Song, J Tyrer, B Perkins, A M Dunning, D F Easton, P D P Pharoah
Journal: Gut (2008)

The mismatch repair (MMR) genes are in charge of maintaining genomic integrity. Mutations in the MMR genes are at the origin of a familial form of colorectal cancer (CRC). This syndrome accounts for only a small proportion of the excess familial risk of CRC. The characteristics of the alleles that account for the remainder of cases are unknown. To assess the putative associations between common variants in MMR genes and CRC, we performed a genetic case-control study using a single-nucleotide polymorphism (SNP) tagging approach.A total of 2299 cases and 2284 unrelated controls were genotyped for 68 tagging SNPs in seven MMR genes (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2). Genotype frequencies were measured in cases and controls and analysed using univariate analysis. Haplotypes were constructed and analysed using logistic regression. We also carried out a two-locus interaction analysis and a global test analysis.Genotype frequencies were found to be marginally different in cases and controls for MSH3 rs26279 with a rare homozygote OR = 1.31 [95% confidence interval (CI) 1.05 to 1.62], p(trend) = 0.04. We found a rare MLH1 (frequency <5%) haplotype, increasing the risk of colorectal cancer: (OR = 9.76; 95% CI, 1.25 to 76.29; p = 0.03). The two-locus interaction analysis has exhibited signs of interaction between SNPs located in genes MSH6 and MSH2. Global testing has showed no evidence of interaction.It is unlikely that common variants in MMR genes contribute significantly to colorectal cancer.
The clinical relevance of heart rate increase in the interpretation of six-minute walk test in pulmonary hypertension
Authors: Gabor Kovacs, Christina Stöckl, Alexander Avian, Xhylsime Kqiku, Vasile Foris, Maria Tscherner, Horst Olschewski
Journal: European Respiratory Journal (2012)

Background: Six-minute walk test (6MWT) is an important prognostic marker in pulmonary hypertension (PH). We hypothesized that clinical improvement might not only be characterized by an increased walk distance but also by changes in Borg dyspnea score (BDS) and heart rate.

Patients and Methods: Patients with PH and subjects without PH but with abnormal exercise-induced pulmonary arterial pressure (PAP) increase were included. Each patient performed a 6MWT with “normal”, “less than normal” and “more than normal” effort.

Results: 23 patients with PH (n=11pulmonary arterial hypertension, n=10 chronic thromboembolic PH, n=2 other; mean PAP: 40±12mmHg) and 6 subjects with abnormal exercise-induced PAP increase (resting mean PAP: 16±4mmHg) participated. 6MWT were 482±98, 447±80 and 402±82m in the walks with “more than normal”, “normal” and “less than normal” effort (472±104 vs 437±84 vs 392±84m in PH patients). The respective BDS and heart rate increase was 3.2±1.5, 2.0±1.2 and 0.7±0.9, and 38±16, 31±14 and 23±14 min-1 (3.0±1.4, 2.0±1.3 and 0.8±0.9, and 40±16 vs 34±13 vs 23±15 min-1 in PH patients). The difference in walk distance between “less than normal” and “more than normal” tests was associated with the difference in heart rate increase during the test (p=0.001, r=0.61 in all subjects; p<0.001, r=0.76 in PH patients). On average, an 80m increase in 6MWT was associated with an additional 15 min-1 heart rate increase. Between the BDS and 6MWT there was no significant correlation.

Conclusion: Based on our pilot study, heart rate may be suitable to assess the effort level of subjects and may be incorporated to refine 6MWT in the follow-up of PH patients.
Transverse stiffness: a method for estimation of myocardial wall stress.
Authors: H R Halperin, P H Chew, M L Weisfeldt, K Sagawa, J D Humphrey, F C Yin
Journal: Circulation Research (1987)

Determination of regional ventricular wall stress would allow quantification of both regional contractile state and its interplay with global function. Current methods for quantifying regional stress include mathematical modelling and measurements with strain gauges. Both methods are difficult to validate. We hypothesized that transverse stiffness (i.e., the ratio of indentation stress to strain as the ventricular wall is indented in the direction perpendicular to the wall) would be proportional to the stresses in the plane of the wall and could be used to estimate the latter. To test this hypothesis, 6 arterially perfused canine ventricular septa were mounted in an apparatus that could exert biaxial load in the plane of the wall. A servo system maintained the central third of the septa isometric during active contractions while the septa were paced at 30-60 pulses/min. In the center of the isometric region, a probe of 7 mm diameter indented the septa while the transverse indentation stress and strain were measured. For values of peak systolic in-plane stress from 0.56 to 2.6 g/mm2, the transverse stiffness varied from 1.2 to 11.7 g/mm2 and was linearly related to the in-plane wall stress in each septum (p less than 0.001, ANOVA). After cardioplegia, the transverse stiffness also correlated with passively applied wall stress for each dog (p less than 0.001). The slopes of the individual relations between transverse stiffness and wall stress from active contractions were similar to those from passively applied stress (mean +/- SEM; 1.82 +/- 0.36 versus 1.45 +/- 0.31, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
1005-65 Percutaneous left atrial appendage transcatheter occlusion (PLAATO™) to prevent stroke in patients with atrial fibrillation: Interim results of the multicenter feasibility trial
Authors: Yves L Bayard, Franziska Buscheck, Stefan Ostermayer, Mark Reisman, Michael D Lesh, Toshiko Nakai, William Gray, Heyder Omran, Paul Kramer, Antonio Bartorelli, Paolo Della Bella, Peter Block, Carlo DiMario, Ray Matthews, Jeffrey Moses, Athena Poppas, David Williams, Allan Skanes, Bernhard Meier, Paul Teirstein, Kai Billinger, Thomas Trepels, Dirk Fleschenberg, Horst Sievert
Journal: Journal of the American College of Cardiology (2004)
Acetylcholine antagonism of the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers.
Authors: J C Bailey, A M Watanabe, H R Besch, D A Lathrop
Journal: Circulation Research (1979)

The purpose of these experiments was to determine whether or not acetylcholine modulated the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers. Conventional microelectrode techniques were used. Predictably, isoproterenol produced shortening of action potential duration; acetylcholine significantly blunted this effect of isoproterenol. Isoproterenol restored excitability to fibers exposed to 22 mM potassium solutions, and acetylcholine abolished this isoproterenol-restored excitability. Both of these antagonistic effects of acetylcholine were blocked by atropine. Acetylcholine alone did not affect action potential duration in polarized fibers or excitability in potassium-depolarized fibers. Furthermore, acetylcholine had no effect on the decrease in action potential duration induced by premature electrical stimulation or by acetylstrophanthidin administration, or on excitability of fibers exposed to a zero sodium, high calcium superfusant. These data demonstrate a direct cellular basis for cholinergic antagonism of the electrophysiological effects of beta-adrenergic stimulation of canine cardiac specialized intraventricular conducting tissue.
Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia
Authors: Mark J. Kiel, Thirunavukkarasu Velusamy, Delphine Rolland, Anagh A. Sahasrabuddhe, Fuzon Chung, Nathanael G. Bailey, Alexandra Schrader, Bo Li, Jun Z. Li, Ayse B. Ozel, Bryan L. Betz, Roberto N. Miranda, L. Jeffrey Medeiros, Lili Zhao, Marco Herling, Megan S. Lim, Kojo S. J. Elenitoba-Johnson
Journal: Blood (2014)
Personalized Epigenomic Signatures That Are Stable Over Time and Covary with Body Mass Index
Authors: Andrew P. Feinberg, Rafael A. Irizarry, Delphine Fradin, Martin J. Aryee, Peter Murakami, Thor Aspelund, Gudny Eiriksdottir, Tamara B. Harris, Lenore Launer, Vilmundur Gudnason, M. Daniele Fallin
Journal: Science Translational Medicine (2010)

A genome-scale, gene-specific analysis of DNA methylation in the same individuals over a decade apart identifies a personalized epigenomic signature that may correlate with a common genetic trait.
Roles of saturated vs. polyunsaturated fat in heart failure survival: not all fats are created equal
Authors: G. V. Halade, Y.-F. Jin, M. L. Lindsey
Journal: Cardiovascular Research (2011)

This editorial refers to ‘High intake of saturated fat, but not polyunsaturated fat, improves survival in heart failure despite persistent mitochondrial defects’ by T.F. Galvao et al. , doi:10.1093/cvr/cvr258. 

Galvao et al. 1 compare the effects of two high-fat diets, both 45% kcal but sourced from either polyunsaturated fatty acids (PUFA; linoleic and α-linolenic acids) or saturated fat (palmitate and stearate) in a male δ-sarcoglycan null Bio TO2 hamster model of heart failure. Surprisingly, the heart failure hamsters fed the diet high in saturated fat showed increased survival compared with hamsters fed a diet high in PUFA or the control standard diet (12% kcal from fat). Importantly, in all three diet groups, the hamsters developed dysfunction at both the left ventricle and cardiac mitochondria levels. Despite the lack of a cardiac function phenotype, the PUFA-fed hamsters showed elevated Ca2+-induced mitochondrial permeability transition pore opening rates compared with both the saturated fat and standard fed hamsters. The clear distinction in obesity effects differentially driven by high-fat diets from different lipid sources, in the context of heart failure, has not been previously studied. The present study is important because it reveals the strong impact of fat source on cardiovascular events and survival rates in the setting of existing heart failure.

A diet high in saturated fat promotes obesity by stimulating an inflammatory response that can induce cardiac concentric hypertrophy and alter the stress response.2 Obesity resulting either from saturated or PUFA …
Effect of polyamine antimetabolites on cultured human keratinocytes from normal and uninvolved psoriatic skin
Authors: K. KAPYAHO, A.-L. KARINIEMI, I. VIRTANEN, J. JANNE
Journal: British Journal of Dermatology (1984)

We describe the effect of two polyamine antimetabolites on polyamine and macromolecule synthesis of cultured human keratinocytes obtained by suction blisters from normal skin and the uninvolved skin of psoriatic patients. The concentrations of spermidine and spermine steadily increased during the culture of normal keratinocytes in vitro, whereas the putrescine concentration showed only a transient rise at the beginning of the active growth phase. Treatment with difluoromethylornithine decreased the concentrations of putrescine and spermidine in both normal and uninvolved psoriatic keratinocytes, but had no effect on either DNA or protein synthesis. Methylglyoxal bis(guanylhydrazone) marginally decreased the levels of spermidine and spermine and significantly inhibited the DNA and protein synthetic activities. Pretreatment of uninvolved psoriatic keratinocytes with difluoromethylornithine enhanced the accumulation of methylglyoxal bis(guanylhydrazone), resulting in a profound inhibition of cellular macromolecule synthesis. This synergistic effect was not seen in normal keratinocytes. Thus, although no statistically significant difference was observed between the cells derived from normal and uninvolved psoriatic epidermis, the psoriatic keratinocytes appeared to be more sensitive to the action of polyamine antimetabolites. The inhibition of DNA and protein synthesis by methylglyoxal bis(guanylhydrazone) was prevented by concomitant treatment with spermidine.
Nursing euologies ignored ethos of control and punishment
Authors: C. Essex
Journal: BMJ (1995)

<h3>Abstract</h3> Oil is frequently used as a solvent to inject lipophilic substances into the peritoneum of laboratory animals. Although mineral oil causes chronic peritoneal inflammation, little is known whether other oils are better suited. Here we show that olive, peanut, corn or mineral oil causes xanthogranulomatous inflammation with depletion of resident peritoneal macrophages. However, there were striking differences in the severity of the inflammatory response. Peanut and mineral oil caused severe chronic inflammation with persistent neutrophil and monocyte recruitment, expansion of the vasculature and fibrosis. Corn and olive oil provoked no or only mild signs of chronic inflammation. Mechanistically, the vegetal oils were taken up by macrophages leading to foam cell formation and induction of cell death. Olive oil triggered caspase-3 cleavage and apoptosis, which facilitates the resolution of inflammation. Peanut oil and, to a lesser degree, corn oil triggered caspase-1 activation and macrophage pyroptosis, which impairs the resolution of inflammation. As such, intraperitoneal oil administration can interfere with the outcome of subsequent experiments. As a proof-of-principle, intraperitoneal peanut oil injection was compared to its oral delivery in a thioglycolate-induced peritonitis model. The chronic peritoneal inflammation due to peanut oil injection impeded the proper recruitment of macrophages and the resolution of inflammation in this peritonitis model. In summary, the data indicate that it is advisable to deliver lipophilic substances like tamoxifen by oral gavage instead of intraperitoneal injection.
Serrated Polyps and Colorectal Cancer: New Pathway to Malignancy
Authors: Amy E. Noffsinger
Journal: Annual Review of Pathology Mechanisms of Disease (2009)

Until recently, two major forms of colorectal epithelial polyp were recognized: the adenoma and the hyperplastic polyp. Adenomas were perceived to represent the precursor to colorectal cancer, whereas hyperplastic polyps were viewed as innocuous lesions with no potential for progression to malignancy. We now recognize, however, that the lesions formerly classified as hyperplastic actually represent a heterogeneous group of polyps, some of which have a significant risk for neoplastic transformation. These serrated polyps include not only hyperplastic polyps but also traditional serrated adenomas and sessile serrated adenomas. These polyps demonstrate characteristic molecular alterations not commonly seen in colorectal adenomas, and they probably progress to colorectal cancer by means of a new pathway: the serrated neoplasia pathway. The morphologic features of serrated colorectal lesions, the molecular alterations that characterize them, and their role in colorectal cancer development are discussed herein.
(41) Darier's disease
Authors: E.A. Bingham, D. Burrows
Journal: British Journal of Dermatology (1984)

Journal Article (41) Darier's disease Get access E.A. Bingham, E.A. Bingham Royal Victoria Hospital, Belfast Search for other works by this author on: Oxford Academic Google Scholar D. Burrows D. Burrows Royal Victoria Hospital, Belfast Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s26, 1 July 1984, Pages 88–89, https://doi.org/10.1111/j.1365-2133.1984.tb05311.x Published: 01 July 1984
Investigation of chromosome 2q in osteoarthritis of the hand: no significant linkage in a Tasmanian population
Authors: J Stankovich
Journal: Annals of the Rheumatic Diseases (2002)

<b>Background:</b> Previous studies have suggested a strong genetic component to osteoarthritis (OA), especially that of the hand, and three linkage studies have suggested the existence of susceptibility loci in disparate regions of chromosome 2q. <b>Objective:</b> To examine for linkage to 2q in a Tasmanian population of women and men with familial hand OA. <b>Methods:</b> Hand OA (distal interphalangeal, carpometacarpal, and Heberden9s nodes) was assessed by a combination of hand photographs and radiographs. A non-parametric linkage (NPL) analysis was performed on chromosome 2q of 69 members in 22 families with severe distal interphalangeal joint OA using Genehunter. A quantitative trait linkage analysis of a larger group of 456 members in 68 families was also performed using SOLAR. <b>Results:</b> The maximum non-parametric linkage score was 1.05 (p=0.15) at marker IL1R1, close to the centromere. All components of hand OA scores had significant heritability in this dataset (28%–35%, all p&lt;0.001). Despite this, the quantitative trait analysis (after adjustment for age and, where appropriate, sex) yielded maximum LOD scores of 0.90 for Heberden9s nodes (both sexes combined), and 1.19 for carpometacarpal OA score (women only). <b>Conclusions:</b> These results do not provide confirmation of linkage on chromosome 2q in the larger white population with hand OA. They suggest that there are regional variations in the genetic cause of hand OA and that other loci not on 2q may be important in this disease.