tbuckley/cabot-search huggingface dataset:
Return to play after thigh muscle injury in elite football players: implementation and validation of the Munich muscle injury classification
Authors: Jan Ekstrand, Carl Askling, Henrik Magnusson, Kai Mithoefer
Journal: British Journal of Sports Medicine (2013)

Background Owing to the complexity and heterogeneity of muscle injuries, a generally accepted classification system is still lacking. Aims To prospectively implement and validate a novel muscle injury classification and to evaluate its predictive value for return to professional football. Methods The recently described Munich muscle injury classification was prospectively evaluated in 31 European professional male football teams during the 2011/2012 season. Thigh muscle injury types were recorded by team medical staff and correlated to individual player exposure and resultant time-loss. Results In total, 393 thigh muscle injuries occurred. The muscle classification system was well received with a 100% response rate. Two-thirds of thigh muscle injuries were classified as structural and were associated with longer lay-off times compared to functional muscle disorders (p&lt;0.001). Significant differences were observed between structural injury subgroups (minor partial, moderate partial and complete injuries) with increasing lay-off time associated with more severe structural injury. Median lay-off time of functional disorders was 5–8 days without significant differences between subgroups. There was no significant difference in the absence time between anterior and posterior thigh injuries. Conclusions The Munich muscle classification demonstrates a positive prognostic validity for return to play after thigh muscle injury in professional male football players. Structural injuries are associated with longer average lay-off times than functional muscle disorders. Subclassification of structural injuries correlates with return to play, while subgrouping of functional disorders shows less prognostic relevance. Functional disorders are often underestimated clinically and require further systematic study.
Tumour necrosis factor signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice
Authors: Kengo Tomita, Gen Tamiya, Satoshi Ando, Kayoko Ohsumi, Tomoko Chiyo, Akiko Mizutani, Naoto Kitamura, Kyoko Toda, Takehiko Kaneko, Yoshinori Horie, Jing-Yan Han, Shinzo Kato, Masayuki Shimoda, Yuichi Oike, Maiko Tomizawa, Satoshi Makino, Tamiko Ohkura, Hidetsugu Saito, Naoki Kumagai, Hiroshi Nagata, Hiromasa Ishii, Toshifumi Hibi
Journal: Gut (2005)

While tumour necrosis factor alpha (TNF-alpha) appears to be associated with the development of non-alcoholic steatohepatitis (NASH), its precise role in the pathogenesis of NASH is not well understood.Male mice deficient in both TNF receptors 1 (TNFR1) and 2 (TNFR2) (TNFRDKO mice) and wild-type mice were fed a methionine and choline deficient (MCD) diet or a control diet for eight weeks, maintaining isoenergetic intake.MCD dietary feeding of TNFRDKO mice for eight weeks resulted in attenuated liver steatosis and fibrosis compared with control wild-type mice. In the liver, the number of activated hepatic Kupffer cells recruited was significantly decreased in TNFRDKO mice after MCD dietary feeding. In addition, hepatic induction of TNF-alpha, vascular cell adhesion molecule 1, and intracellular adhesion molecule 1 was significantly suppressed in TNFRDKO mice. While in control animals MCD dietary feeding dramatically increased mRNA expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) in both whole liver and hepatic stellate cells, concomitant with enhanced activation of hepatic stellate cells, both factors were significantly lower in TNFRDKO mice. In primary cultures, TNF-alpha administration enhanced TIMP-1 mRNA expression in activated hepatic stellate cells and suppressed apoptotic induction in activated hepatic stellate cells. Inhibition of TNF induced TIMP-1 upregulation by TIMP-1 specific siRNA reversed the apoptotic suppression seen in hepatic stellate cells.Enhancement of the TNF-alpha/TNFR mediated signalling pathway via activation of Kupffer cells in an autocrine or paracrine manner may be critically involved in the pathogenesis of liver fibrosis in this NASH animal model.
Mutations in INF2 Are a Major Cause of Autosomal Dominant Focal Segmental Glomerulosclerosis
Authors: Olivia Boyer, Geneviève Benoit, Olivier Gribouval, Fabien Nevo, Marie-Josèphe Tête, Jacques Dantal, Brigitte Gilbert-Dussardier, Guy Touchard, Alexandre Karras, Claire Presne, Jean-Pierre Grunfeld, Christophe Legendre, Dominique Joly, Philippe Rieu, Nabil Mohsin, Thierry Hannedouche, Valérie Moal, Marie-Claire Gubler, Isabelle Broutin, Géraldine Mollet, Corinne Antignac
Journal: Journal of the American Society of Nephrology (2011)

The recent identification of mutations in the INF2 gene, which encodes a member of the formin family of actin-regulating proteins, in cases of familial FSGS supports the importance of an intact actin cytoskeleton in podocyte function. To determine better the prevalence of INF2 mutations in autosomal dominant FSGS, we screened 54 families (78 patients) and detected mutations in 17% of them. All mutations were missense variants localized to the N-terminal diaphanous inhibitory domain of the protein, a region that interacts with the C-terminal diaphanous autoregulatory domain, thereby competing for actin monomer binding and inhibiting depolymerization. Six of the seven distinct altered residues localized to an INF2 region that corresponded to a subdomain of the mDia1 diaphanous inhibitory domain reported to co-immunoprecipitate with IQ motif-containing GTPase-activating protein 1 (IQGAP1). In addition, we evaluated 84 sporadic cases but detected a mutation in only one patient. In conclusion, mutations in INF2 are a major cause of autosomal dominant FSGS. Because IQGAP1 interacts with crucial podocyte proteins such as nephrin and PLCε1, the identification of mutations that may alter the putative INF2-IQGAP1 interaction provides additional insight into the pathophysiologic mechanisms linking formin proteins to podocyte dysfunction and FSGS.
Retention and Distribution Patterns of Lithium, a Pharmacological Tool in Studying the Pathophysiology of Manic-Depressive Psychosis
Authors: KENNETH GREENSPAN, RICHARD GREEN, JACK DURELL
Journal: American Journal of Psychiatry (1968)

The authors review the evidence for their conclusion that acutely manic patients retain more lithium ion and distribute it differently in the total body water than do normothymic patients. The pattern of lithium ion retention and distribution was studied in depressed patients and found to more closely approximate that of the normothymic patients than that of the manic patients. There was suggestive evidence of a redistribution pattern upon recovery from depression which resembled but was smaller in magnitude than the redistribution pattern previously observed in manic patients.
Lateral wedge insoles for medial knee osteoarthritis: 12 month randomised controlled trial
Authors: K. L. Bennell, K.-A. Bowles, C. Payne, F. Cicuttini, E. Williamson, A. Forbes, F. Hanna, M. Davies-Tuck, A. Harris, R. S. Hinman
Journal: BMJ (2011)

<b>Objective</b> To assess the effect of lateral wedge insoles compared with flat control insoles on improving symptoms and slowing structural disease progression in medial knee osteoarthritis. <b>Design</b> Randomised controlled trial. <b>Setting</b> Community in Melbourne, Australia. <b>Participants</b> 200 people aged 50 or more with clinical and radiographic diagnosis of mild to moderately severe medial knee osteoarthritis. <b>Interventions</b> Full length 5 degree lateral wedged insoles or flat control insoles worn inside the shoes daily for 12 months. <b>Main outcome measures</b> Primary symptomatic outcome was change in overall knee pain (past week) measured on an 11 point numerical rating scale. Primary structural outcome was change in volume of medial tibial cartilage from magnetic resonance imaging scans. Secondary clinical outcomes included changes in measures of pain, function, stiffness, and health related quality of life. Secondary structural outcomes included progression of medial cartilage defects and bone marrow lesions. <b>Results</b> Between group differences did not differ significantly for the primary outcomes of change in overall pain (−0.3 points, 95% confidence intervals −1.0 to 0.3) and change in medial tibial cartilage volume (−0.4 mm<sup>3</sup>, 95% confidence interval −15.4 to 14.6), and confidence intervals did not include minimal clinically important differences. None of the changes in secondary outcomes showed differences between groups. <b>Conclusion</b> Lateral wedge insoles worn for 12 months provided no symptomatic or structural benefits compared with flat control insoles. <b>Trial registration</b> Australian New Zealand Clinical Trials Registry ACTR12605000503628 and ClinicalTrials.gov NCT00415259.
Evaluation of lung lesions in LATY136F mutant mice ∼Are they recognized as the models of IgG4 related lung disease?∼
Authors: Yuko Waseda, Shoko Matsui, Kazunori Yamada, Satoshi Watanabe, Ryo Matsunuma, Hazuki Takato, Mitsuhiro Kawano, Masahide Yasui, Kazuo Kasahara
Journal: European Respiratory Journal (2014)

[Background] The transmembrane protein LAT, linker for activation of T cells, couples the T cell receptor to downstream signaling effectors. LAT Y136F Knock-in mice (Lat mice) harbor a point mutation in Tyr136 of the linker for activation of T cells and show Th2 predominant immunoreactions with elevated serum IgG1 levels, corresponding to human IgG4.  IgG4 related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4 positive plasma cells. A pathological change is famous for the pancreas, lacrimal gland and salivary glands, and lung pathological change also exists.  [Objective] The aim of this study is to estimate lung lesion of Lat mice and evaluate whether Lat mice would constitute an appropriate model of lung lesion for human IgG4-RD.  [Methods]Lat mice (Homo) and wild-type mice (WT) were included in this study. Lung tissue samples were obtained for pathological evaluation, and cell fractions of broncho-alveolar lavage fleud (BALF) were analyzed.  [Results] Marked inflammation and fibrosis of lung were observed in Homo group, but not in WT group. Lymphocytic infiltration and IgG1 positive plasma cells were seen around broncho-vascular bundles. In analysis of BALF, total cell count and percentage of lymphocyte increased significantly in Homo group than in WT group. (4.4±8.4*10 5 /μl (p l 0.005), 62.0±30.7% (p l 0.005))  [Conclusion] The features of lung lesion of Lat mice have a similar with those of human IgG4-RD. We considered that Lat mice are useful as a model for IgG4-RD.
Effect of Mechanical Forces on Growth and Matrix Protein Synthesis in the In Vitro Pulmonary Artery
Authors: Valeri Kolpakov, Mark D. Rekhter, David Gordon, Wei Hua Wang, Thomas J. Kulik
Journal: Circulation Research (1995)

Abstract The effect of mechanical stimuli on pulmonary artery growth and matrix tissue synthesis (and how individual cell types in the vessel wall respond to such stimuli) is incompletely characterized. Rabbit pulmonary arteries were placed in tissue culture medium and subjected to varying magnitudes of stretch or hydrostatic pressure (separately) for 4 days. The rate of protein synthesis in smooth muscle cells (by quantitative autoradiography) was positively related to the magnitude of stretch, as were the percentage of procollagen type I–positive cells and the rate of cell replication. In adventitial fibroblasts, stretch increased the rate of replication but not of protein synthesis. Hydrostatic pressure had little or no effect on the variables measured in either smooth muscle cells or fibroblasts. Stretch also increased the rate of elastin and collagen synthesis in the whole pulmonary artery segment, and after 4 days of stretch, the contents of actin and elastin were increased. Removal of the endothelium did not affect stretch-induced protein, collagen, or elastin synthesis but augmented stretch-induced smooth muscle replication. These data suggest that in the intact pulmonary artery, stretch, but not pressure, can stimulate hypertrophy and hyperplasia in smooth muscle cells and hyperplasia in fibroblasts. Matrix protein synthesis and accumulation are also increased by stretch. Neither stretch-mediated growth nor matrix protein synthesis required endothelium in this model.
Systematic review of topical treatments for fungal infections of the skin and nails of the feet
Authors: R. Hart, S. E M Bell-Syer, F. Crawford, D. J Torgerson, P. Young, I. Russell
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To identify and synthesise the evidence for efficacy and cost effectiveness of topical treatments for superficial fungal infections of the skin and nails of the feet. <b>Design:</b> Systematic review. <b>Interventions:</b> Topical treatments for superficial fungal infections. <b>Main outcome measures:</b> Cure confirmed by culture and microscopy for skin and by culture for nails in patients with clinically diagnosed fungal infections. <b>Results:</b> Of 126 trials identified in 121 papers, 72 (57.1%) met the inclusion criteria. Placebo controlled trials yielded pooled relative risks of failure to cureskin infections: allylamines (0.30, 95% confidence interval 0.24 to 0.38); azoles (0.54, 0.42 to 0.68); undecenoic acid (0.28, 0.11 to 0.74); and tolnaftate (0.46, 0.17 to 1.22). Although meta-analysis of 11 trials comparing allylamines and azoles showed a relative risk of failure to cure of 0.88 (0.78 to 0.99) in favour of allylamines, there was evidenceof language bias. Seven reports in English favoured allylamines (0.79, 0.69 to 0.91), butfour reports in foreign languages showed no difference between the two drugs (1.01, 0.90 to 1.13). Neither trial of nail infections showed significant differences between alternative topical treatments. <b>Conclusions:</b> Allylamines, azoles, and undecenoic acid were efficacious in placebo controlled trials. There are sufficient comparative trials to judge relative efficacy only between allylamines and azoles. Allylamines cure slightly more infections than azoles but are much more expensive than azoles. The most cost effective strategy is first to treat with azoles or undecenoic acid and to use allylamines only if that fails. <h3>Key messages</h3> About 15% of the population have fungal infections of the skin or nails of the foot Topical allylamines—available only on prescription—cure slightly more infections of the skin of the foot than topical azoles or undecenoic acid, both of which are available over the counter No significant differences in efficacy between individual allylamines or individual azoles were found Allylamines cost more than over the counter preparations and their few extra cures are expensive, with a marginal cost per cure that is more than five times as high as that of azoles Topical allylamines are therefore best reserved for athlete9s foot that does not respond to initial treatment with azoles or undecenoic acid
A Parting Shot at Tobacco
Authors: C. Everett Koop
Journal: JAMA (1989)

ON SEPTEMBER 13, 1989, I made my last appearance as Surgeon General before the US Congress. I used the occasion to address the one issue with which previous Surgeons General and I have become most closely associated: tobacco and health. In testimony before the Subcommittee on Transportation and Hazardous Substances, Committee on Energy and Commerce, US House of Representatives, I focused my remarks on two topics that this subcommittee had considered in previous hearings: tobacco advertising and children's access to tobacco products. The purpose of this article is to share with a wider audience the comments I made at that hearing. <h3>Tobacco Advertising</h3> The bill introduced by Subcommittee Chairman Thomas A. Luken (D, Ohio), HR 1250, would eliminate all image-based tobacco advertising (allowing only so-called tombstone advertising). On several occasions during my tenure as Surgeon General, I endorsed proposals that would ban all tobacco advertising and promotion. I certainly support
International Union of Pharmacology. LXI. Peroxisome Proliferator-Activated Receptors
Authors: Liliane Michalik, Johan Auwerx, Joel P. Berger, V. Krishna Chatterjee, Christopher K. Glass, Frank J. Gonzalez, Paul A. Grimaldi, Takashi Kadowaki, Mitchell A. Lazar, Stephen O'Rahilly, Colin N. A. Palmer, Jorge Plutzky, Janardan K. Reddy, Bruce M. Spiegelman, Bart Staels, Walter Wahli
Journal: Pharmacological Reviews (2006)

The three peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear hormone receptor superfamily. They share a high degree of structural homology with all members of the superfamily, particularly in the DNA-binding domain and ligand- and cofactor-binding domain. Many cellular and systemic roles have been attributed to these receptors, reaching far beyond the stimulation of peroxisome proliferation in rodents after which they were initially named. PPARs exhibit broad, isotype-specific tissue expression patterns. PPARα is expressed at high levels in organs with significant catabolism of fatty acids. PPARβ/δ has the broadest expression pattern, and the levels of expression in certain tissues depend on the extent of cell proliferation and differentiation. PPARγ is expressed as two isoforms, of which PPARγ2 is found at high levels in the adipose tissues, whereas PPARγ1 has a broader expression pattern. Transcriptional regulation by PPARs requires heterodimerization with the retinoid X receptor (RXR). When activated by a ligand, the dimer modulates transcription via binding to a specific DNA sequence element called a peroxisome proliferator response element (PPRE) in the promoter region of target genes. A wide variety of natural or synthetic compounds was identified as PPAR ligands. Among the synthetic ligands, the lipid-lowering drugs, fibrates, and the insulin sensitizers, thiazolidinediones, are PPARα and PPARγ agonists, respectively, which underscores the important role of PPARs as therapeutic targets. Transcriptional control by PPAR/RXR heterodimers also requires interaction with coregulator complexes. Thus, selective action of PPARs in vivo results from the interplay at a given time point between expression levels of each of the three PPAR and RXR isotypes, affinity for a specific promoter PPRE, and ligand and cofactor availabilities.
Snow sports injuries in Scotland: a case-control study
Authors: M Langran, S Selvaraj
Journal: British Journal of Sports Medicine (2002)

Objectives: To examine the incidence and patterns of snow sports injuries at the three largest commercial ski areas in Scotland and to identify factors associated with injury risk. Methods: A prospective case-control study of all injured people at Cairngorm, Glenshee, and Nevis Range ski areas during the 1999–2000 winter season. Personal details, snow sports related variables, diagnosis, and treatment were recorded. Control data were collected at random from uninjured people at all three areas. Random counts were performed to analyse the composition of the on slope population. Results: A total of 732 injuries were recorded in 674 people. Control data were collected from 336 people. The injury rate for the study was 3.7 injuries per 1000 skier days. Alpine skiers comprised 67% of the on slope population, snowboarders 26%, skiboarders 4%, and telemark skiers 2%. Lower limb injuries and sprains were the commonest injuries in alpine skiers and skiboarders. Snowboarders sustained more injuries to the upper limb and axial areas. Skiboarders and snowboarders had a higher incidence of fractures. After adjustment for other variables, three factors were all independently associated with injury: snowboarding (odds ratio (OR) 4.07, 95% confidence interval (CI) 1.65 to 10.08), alpine skiing (OR 3.82, CI 1.6 to 9.13), and age &lt;16 years (OR 1.9, CI 1.14 to 3.17). More than five days of experience in the current season and at least one week of experience in total had a protective effect against injury. Conclusions: Despite a change in the composition of the alpine population at Scottish ski areas, the overall rate and pattern of injury are similar to those reported previously in comparable studies. Several factors are associated with an increased risk of injury and should be targeted in future injury prevention campaigns.
The MLL partial tandem duplication: evidence for recessive gain-of-function in acute myeloid leukemia identifies a novel patient subgroup for molecular-targeted therapy
Authors: Susan P. Whitman, Shujun Liu, Tamara Vukosavljevic, Laura J. Rush, Li Yu, Chunhui Liu, Marko I. Klisovic, Kati Maharry, Martin Guimond, Matthew P. Strout, Brian Becknell, Adrienne Dorrance, Rebecca B. Klisovic, Christoph Plass, Clara D. Bloomfield, Guido Marcucci, Michael A. Caligiuri
Journal: Blood (2005)
Public and private V beta T cell receptor repertoires against hen egg white lysozyme (HEL) in nontransgenic versus HEL transgenic mice.
Authors: R Cibotti, J P Cabaniols, C Pannetier, C Delarbre, I Vergnon, J M Kanellopoulos, P Kourilsky
Journal: The Journal of Experimental Medicine (1994)

We have previously produced a transgenic mouse line for hen egg lysozyme (HEL), an experimental model for analyzing tolerance to self-antigens at the peptide level. We have now characterized transgenic mice with HEL blood levels below 2 ng/ml, where significant T cell proliferative responses to HEL and its immunodominant peptide were observed. This HEL-low transgenic model was chosen because it mimics physiological conditions in which autoreactive T lymphocytes, recognizing self-components expressed at very low levels, persist without inducing a break in tolerance. Furthermore, in H-2d mice, HEL-specific T lymphocytes are triggered by a single immunodominant region, allowing us to compare the HEL-specific T cell V beta repertoires of transgenic and nontransgenic animals against a single peptide presented as self or foreign, respectively. We found that a V beta 8.2-D beta 1-J beta 1.5 rearrangement is found in response to HEL in all nontransgenic mice, whereas this V beta-restricted response is absent in HEL-low transgenic animals. At the nucleotide level, this rearrangement results from the trimming of the genomic segments during VDJ or DJ joining, without N additions, suggesting that the dominant rearrangement is selected early during fetal or neonatal life, before the expression of terminal deoxynucleotidyl transferase. In HEL-low transgenic mice, no dominant rearrangements are found as alternatives to the one observed in normal mice. Instead, each transgenic animal uses a different set of V beta-J beta combinations in its response to the immunodominant HEL peptide. In nontransgenic mice, besides the dominant V beta 8.2-D beta 1-J beta 1.5 combination, minor V beta repertoires were found which differed in each animal and were distinct from the rearrangements used by individual transgenic mice. These findings suggest that the T cell response to an immunodominant peptide involves a "public" V beta repertoire found in all animals and a "private" one which is specific to each individual.