tbuckley/cabot-search huggingface dataset:
TGF- 1 causes airway fibrosis and increased collagen I and III mRNA in mice
Authors: N J Kenyon
Journal: Thorax (2003)

<b>Background:</b> Subepithelial collagen and extracellular matrix protein deposition are important pathophysiological components of airway remodelling in chronic asthma. Animal models based on the local reaction to antigens show structural alterations in the airway submucosal region and provide important information regarding disease pathophysiology. We describe a murine model of peribronchial fibrosis using intratracheally instilled transforming growth factor (TGF)-β<sub>1</sub> in BALB/C mice that facilitates a mechanistic approach to understanding the cellular and molecular pathways leading to airway fibrosis. <b>Methods:</b> BALB/C mice were intratracheally instilled with either TGF-β<sub>1</sub> or buffered saline. Airway fibrosis was assessed by light microscopy, hydroxyproline content, and polymerase chain reaction (PCR) for collagen I and III on microdissected airway samples. The lysyl oxidase inhibitor β-aminoproprionitrile (BAPN) was administered to TGF-β<sub>1</sub> treated mice to block airway collagen deposition. Airway hyperresponsiveness was also measured after treatment with TGF-β<sub>1</sub>. <b>Results:</b> During the 7 days after administration of TGF-β<sub>1</sub> the mice developed increased subepithelial collagen which could be blocked by BAPN. Increased mRNAs for collagen types I and III were seen in microdissected airways 1 week after TGF-β<sub>1</sub>, and significantly increased total collagen was found in the airways 4 weeks after TGF-β<sub>1</sub>. A detectable increase in airway hyperreactivity occurred. <b>Conclusions:</b> This new model should facilitate detailed study of airway remodelling that occurs in the absence of detectable cellular inflammation, and allow examination of the functional consequences of a major structural alteration in the conducting airways uncomplicated by inflammatory cell influx.
High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas
Authors: S Le Gouvello, S Bastuji-Garin, N Aloulou, H Mansour, M-T Chaumette, F Berrehar, A Seikour, A Charachon, M Karoui, K Leroy, J-P Farcet, I Sobhani
Journal: Gut (2007)

Colorectal cancer (CRC) harbours different types of DNA alterations, including microsatellite instability (MSI). Cancers with high levels of MSI (MSI-H) are considered to have a good prognosis, probably related to lymphocyte infiltration within tumours. The aim of the present study was to characterise the intratumoural expression of markers associated with the antitumour immune response in mismatch repair (MMR)-proficient (MSS) colon cancers. Ninety human colon cancers (T) and autologous normal colon mucosa (NT) were quantified for the expression of 15 markers of the immune response with quantitiative reverse transcription-PCR (qRT-PCR). mRNA expression levels were correlated with MMR status. Immunohistochemistry (IHC) was performed using both interleukin 17 (IL17) and CD3 antibodies. Expression of cytotoxic markers (FasL, granzyme B and perforin), inflammatory cytokines (IL1beta, IL6, IL8, IL17 and transforming growth factor beta (TGFbeta)) and a marker of regulatory T cells (forkhead box P3 (Foxp3)) was significantly higher in tumours than in autologous normal tissues. Adjusting for MMR status, higher tumoural expression of both granzyme B and perforin was associated with the MSI-H phenotype, and the perforin T/NT ratio was higher in MSI-H tissues than in MSS tissues. Higher tumoural expression of Foxp3, IL17, IL1beta, IL6 and TGFbeta was associated with the MSS phenotype, and the IL17 T/NT ratio was higher in MSS tissues than in MSI-H tissues as assessed by both qRT-PCR and IHC. Immune gene expression profiling in CRC displayed different patterns according to MMR status. Higher Foxp3, IL6, TGFbeta and IL17 expression is a particular determinant in MMR-proficient CRC. These may be potential biomarkers for a new prognostic "test set" in sporadic CRCs.
A unique elastase in human blood platelets.
Authors: H L James, Y T Wachtfogel, P L James, M Zimmerman, R W Colman, A B Cohen
Journal: Journal of Clinical Investigation (1985)

Previous investigations suggested that elastolytic activity found in platelets could be due to contamination by neutrophil elastase. In the present study, the lysate of blood platelets free of detectable neutrophils was examined for elastase-like activity using tertiary-butyloxycarbonyl (tBOC)-ala-ala-pro-ala-aminomethyl coumarin (I), tBOC-ala-ala-pro-val-aminomethyl coumarin (II), and succinyl-tri-ala-rho-nitroanilide (SAPNA), and for elastolytic activity using 3H-labeled dog and human lung elastins. The platelet lysate degraded I at a higher rate than II, while the reverse was true of neutrophil elastase. The rate of degradation of I, II, and SAPNA by the lysate increased with reaction time up to 20 min. The rate of I, II, and SAPNA degradation by the lysate was decreased by the presence of 0.5 M NaCl, whereas NaCl greatly potentiated their degradation by neutrophil elastase. Plasma alpha 2-macroglobulin inhibited elastolysis by the platelet lysate, whereas plasma alpha 1-antitrypsin did not. The lysate activity was inhibited by diisopropyl fluorophosphate, phenylmethylsulfonyl fluoride, elastatinal, Trasylol, and furoyl-saccharin. The optimum pH for platelet lysate activity was 8.5-9.0, as in other studies using elastin as substrate. The pH 4.5 eluate obtained after incubation of the lysate with dog lung elastin at neutral pH exhibited the same catalytic properties as the activity in the lysate. The different substrate and inhibitor specificities and the failure of IgG specific for neutrophil elastase to remove elastase-like and elastolytic activities from the lysate indicate that a unique elastase occurs in platelets.
ANTIMONY TARTRATE IN BILHARZIOSIS AND TACHYCARDIA
Authors: J. B. Christopherson
Journal: BMJ (1919)

ANTI51ONY TARTRATh' "IN BILrA6JL OSIL.rAPRIL 19, 1919 negative, but owing to the facts that leishmanial bodies had been found before, and that clinicallv the con(lition was characteristic and active, the injections were proceeded wvith.Besides the finding of the leishmanial bodies, the diagnosis was supported by the fact that the case originated in Central America, and assumed the form characteristic of the disease in those regions (oreja de los chicleros).See descriptions by
Influence of vibration on delayed onset of muscle soreness following eccentric exercise
Authors: Amir H Bakhtiary, Ziaeddin Safavi-Farokhi, Atefeh Aminian-Far
Journal: British Journal of Sports Medicine (2006)

Delayed onset muscle soreness (DOMS), which may occur after eccentric exercise, may cause some reduction in ability in sport activities. For this reason, several studies have been designed on preventing and controlling DOMS. As vibration training (VT) may improve muscle performance, we designed this study to investigate the effect of VT on controlling and preventing DOMS after eccentric exercise. Methods: Fifty healthy non-athletic volunteers were assigned randomly into two experimental, VT (n = 25) and non-VT (n = 25) groups. A vibrator was used to apply 50 Hz vibration on the left and right quadriceps, hamstring and calf muscles for 1 min in the VT group, while no vibration was applied in the non-VT group. Then, both groups walked downhill on a 10° declined treadmill at a speed of 4 km/hour. The measurements included the isometric maximum voluntary contraction force (IMVC) of left and right quadriceps muscles, pressure pain threshold (PPT) 5, 10 and 15 cm above the patella and mid-line of the calf muscles of both lower limbs before and the day after treadmill walking. After 24 hours, the serum levels of creatine-kinase (CK), and DOMS level by visual analogue scale were measured. Results: The results showed decreased IMVC force (P = 0.006), reduced PPT (P = 0.0001) and significantly increased mean of DOMS and CK levels in the non-VT group, compared to the VT group (P = 0.001). Conclusion: A comparison by experimental groups indicates that VT before eccentric exercise may prevent and control DOMS. Further studies should be undertaken to ascertain the stability and effectiveness of VT in athletics.
Regular physical activity reduces hospital admission and mortality in chronic obstructive pulmonary disease: a population based cohort study
Authors: J Garcia-Aymerich, P Lange, M Benet, P Schnohr, J M Anto
Journal: Thorax (2006)

<b>Background:</b> Information about the influence of regular physical activity on the course of chronic obstructive pulmonary disease (COPD) is scarce. A study was undertaken to examine the association between regular physical activity and both hospital admissions for COPD and all-cause and specific mortality in COPD subjects. <b>Methods:</b> From a population-based sample recruited in Copenhagen in 1981–3 and 1991–4, 2386 individuals with COPD (according to lung function tests) were identified and followed until 2000. Self-reported regular physical activity at baseline was classified into four categories (very low, low, moderate, and high). Dates and causes of hospital admissions and mortality were obtained from Danish registers. Adjusted associations between physical activity and hospital admissions for COPD and mortality were obtained using negative binomial and Cox regression models, respectively. <b>Results:</b> After adjustment for relevant confounders, subjects reporting low, moderate or high physical activity had a lower risk of hospital admission for COPD during the follow up period than those who reported very low physical activity (incidence rate ratio 0.72, 95% confidence interval (CI) 0.53 to 0.97). Low, moderate and high levels of regular physical activity were associated with an adjusted lower risk of all-cause mortality (hazard ratio (HR) 0.76, 95% CI 0.65 to 0.90) and respiratory mortality (HR 0.70, 95% CI 0.48 to 1.02). No effect modification was found for sex, age group, COPD severity, or a background of ischaemic heart disease. <b>Conclusions:</b> Subjects with COPD who perform some level of regular physical activity have a lower risk of both COPD admissions and mortality. The recommendation that COPD patients be encouraged to maintain or increase their levels of regular physical activity should be considered in future COPD guidelines, since it is likely to result in a relevant public health benefit.
Experimental Genomic Evolution: Extensive Compensation for Loss of DNA Ligase Activity in a Virus
Authors: D. Rokyta, M. R. Badgett, I. J. Molineux, J. J. Bull
Journal: Molecular Biology and Evolution (2002)

Deletion of the viral ligase gene drastically reduced the fitness of bacteriophage T7 on a ligase-deficient host. Viral evolution recovered much of this fitness during long-term passage, but the final fitness remained below that of the intact virus. Compensatory changes occurred chiefly in genes involved in DNA metabolism: the viral endonuclease, helicase, and DNA polymerase. Two other compensatory changes of unknown function also occurred. Using a method to distinguish compensatory mutations from other beneficial mutations, five additional substitutions from the recovery were shown to enhance adaptation to culture conditions and were not compensatory for the deletion. In contrast to the few previous studies of viral recovery from deletions, the compensatory changes in T7 did not restore the deletion or duplicate major regions of the genome. The ability of this deleted genome to recover much of the lost fitness via mutations in its remaining genes reveals a considerable evolutionary potential to modify the interactions of its elements in maintaining an essential set of functions.
Assessment of the flexibility of elite athletes using the modified Thomas test.
Authors: D Harvey
Journal: British Journal of Sports Medicine (1998)

To analyse the modified Thomas test and obtain measures of flexibility for the iliopsoas, quadriceps and tensor fascia lata/iliotibial band.The modified Thomas test was used to determine the range of flexibility of 117 elite athletes in tennis, basketball, rowing, and running.The study has provided objective data for a clinical test measuring flexibility of the iliopsoas, quadriceps, and tensor fascia lata/iliotibial band. It is recommended that sufficient flexibility is obtained to perform a specific sport and that asymmetries between limbs are addressed.
Reversing Resistance to Vascular-Disrupting Agents by Blocking Late Mobilization of Circulating Endothelial Progenitor Cells
Authors: Melissa Taylor, Fanny Billiot, Virginie Marty, Valérie Rouffiac, Patrick Cohen, Elodie Tournay, Paule Opolon, Fawzia Louache, Gilles Vassal, Corinne Laplace-Builhé, Philippe Vielh, Jean-Charles Soria, Françoise Farace
Journal: Cancer Discovery (2012)

Abstract The prevailing concept is that immediate mobilization of bone marrow–derived circulating endothelial progenitor cells (CEP) is a key mechanism mediating tumor resistance to vascular-disrupting agents (VDA). Here, we show that administration of VDA to tumor-bearing mice induces 2 distinct peaks in CEPs: an early, unspecific CEP efflux followed by a late yet more dramatic tumor-specific CEP burst that infiltrates tumors and is recruited to vessels. Combination with antiangiogenic drugs could not disrupt the early peak but completely abrogated the late VDA-induced CEP burst, blunted bone marrow–derived cell recruitment to tumors, and resulted in striking antitumor efficacy, indicating that the late CEP burst might be crucial to tumor recovery after VDA therapy. CEP and circulating endothelial cell kinetics in VDA-treated patients with cancer were remarkably consistent with our preclinical data. These findings expand the current understanding of vasculogenic “rebounds” that may be targeted to improve VDA-based strategies. Significance: Our findings suggest that resistance to VDA therapy may be strongly mediated by late, rather than early, tumor-specific recruitment of CEPs, the suppression of which resulted in increased VDA-mediated antitumor efficacy. VDA-based therapy might thus be significantly enhanced by combination strategies targeting late CEP mobilization. Cancer Discov; 2(5); 434–49. ©2012 AACR. Read the Commentary on this article by De Palma and Nucera, p. 395. This article is highlighted in the In This Issue feature, p. 377.
Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking.
Authors: C Tysk, E Lindberg, G Jarnerot, B Floderus-Myrhed
Journal: Gut (1988)

By running the Swedish twin registry containing about 25,000 pairs of twins of the same sex together with the central national diagnosis register of hospital inpatients, 80 twin pairs suffering from inflammatory bowel disease were found. In the ulcerative colitis group one of 16 monozygotic pairs was concordant for the disease, but all the other 20 pairs (dizygotic or unknown zygosity) were discordant. In the Crohn's disease group eight of 18 monozygotic pairs and one of 26 dizygotic pairs were concordant. The proband concordance rate among monozygotic twins was 6.3% for ulcerative colitis and 58.3% for Crohn's disease. The calculated heritability of liability based on monozygotic pairs was 0.53 and 1.0 respectively. Thus heredity as an aetiological factor is stronger in Crohn's disease than in ulcerative colitis. Monozygotic twins with Crohn's disease were more likely to be smokers than monozygotic twins with ulcerative colitis. Smoking did not explain the discordance of twin pairs with either ulcerative colitis, or Crohn's disease. The combination of identical heredity and similar smoking habit is not sufficient to cause disease.
Structure-Driven Design of Radionuclide Tracers for Non-Invasive Imaging of uPAR and Targeted Radiotherapy. The Tale of a Synthetic Peptide Antagonist
Authors: Michael Ploug
Journal: Theranostics (2013)

Research performed during the last two decades has provided a wealth of information to highlight the role of the urokinase-type plasminogen activator receptor (uPAR) in the progression and dissemination of invasive and metastatic cancer.In parallel, our perception of the structure-function relationships in uPAR has been refined to such a level that a rational design of uPAR function as well as compounds specifically targeting defined functions of uPAR are now realistic options.This knowledge opens new avenues for developing therapeutic intervention regimens targeting uPAR as well as for monitoring the effects of such treatments by non-invasive imaging using e.g.positron emission tomography.This mini-review will focus on recent advancements in translational research devoted to non-invasive targeting of uPAR, with a view to molecular imaging of its expression in live individuals as well as specific eradication of these cells by targeted radiotherapy.
Incidence and clinical presentation of groin injuries in sub-elite male soccer
Authors: Per Hölmich, Kristian Thorborg, Christian Dehlendorff, Kim Krogsgaard, Christian Gluud
Journal: British Journal of Sports Medicine (2013)

Groin injuries cause major problems in the football codes, as they are prevalent and lead to prolonged symptoms and high recurrence. The aim of the present study was to describe the occurrence and clinical presentation of groin injuries in a large cohort of sub-elite soccer players during a season.Physiotherapists allocated to each of the participating 44 soccer clubs recorded baseline characteristics and groin injuries sustained by a cohort of 998 sub-elite male soccer players during a full 10-month season. All players with groin injuries were examined using the clinical entity approach, which utilises standardised reproducible examination techniques to identify the injured anatomical structures. The exposure time and the injury time were also recorded. Injury time was analysed using multiple regression on the log of the injury times as the data were highly skewed. Effects are thus reported at relative injury time (RIT).Adductor-related groin injury was the most common entity found followed by iliopsoas-related and abdominal-related injuries. The dominant leg was significantly more often injured. Age and previous groin injury were significant risk factors for sustaining a groin injury. Groin injuries were generally located on the same side as previously reported groin injuries. Adductor-related injuries with no abdominal pain had significantly longer injury times compared to injuries with no adductor and no abdominal pain (RIT 2.28, 95% CI 1.22 to 4.25, p=0.0096). Having both adductor and abdominal pain also increased the injury time significantly when compared to injuries with no adductor and no abdominal pain (RIT=4.56, 95% CI 1.91 to 10.91, p=0.001).Adductor-related groin injury was the most common clinical presentation of groin injuries in male soccer players and the cause of long injury time, especially when combined with abdominal-related injury.
Mast Cells in Rapidly Progressive Glomerulonephritis
Authors: TIBOR TÓTH, RIA TÓTH-JAKATICS, SHIRO JIMI, MAKOTO IHARA, HIDENORI URATA, SHIGEO TAKEBAYASHI
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The role of mast cells (MC) in tubulointerstitial damage in glomerulonephritis (GN) is not fully understood. The distribution of MC was compared in renal biopsies from 50 patients with different stages of rapidly progressive GN (RPGN) and in 20 control samples. The immunoreactivity of renal MC with anti-tryptase and anti-chymase antibodies was studied. Interstitial myofibroblasts were stained with anti-α-smooth muscle actin (α-SMA) antibody, and inflammatory cells were identified by anti-CD3, -CD20, and -CD68 monoclonal antibodies. Positively stained cells were counted, and the relative interstitial and fractional areas of anti-α-SMA-stained cells were measured. MC were rarely found in control samples. In contrast, samples showing crescentic GN contained numerous tryptase-positive MC (MC T ) (43.7 ± 4.65 versus 7.14 ± 1.3/mm 2 ) and fewer tryptase- and chymase-positive MC (MC TC ) (13.8 ± 1.86 versus 1.89 ± 0.86/mm 2 ) in the renal interstitium but never in the glomerulus. Double immunostaining demonstrated the presence of both phenotypes of MC. Accumulation of MC was significantly correlated with the numbers of T lymphocytes (MC T , r = 0.67) and interstitial macrophages (MC T , r = 0.455). There was also a significant correlation between the number of MC T and the relative interstitial area. The number of MC TC was well correlated with the fractional area of α-SMA-positive interstitium ( r = 0.749) and the percentage of the interstitial fibrotic area ( r = 0.598). There was also a significant negative correlation between interstitial MC TC accumulation and creatinine clearance ( r = 0.661). The density of MC TC was higher (1.4-fold) in advanced forms of GN associated with fibrocellular crescents and interstitial fibrosis. These results show the potential involvement of MC in the fibroproliferative process in the renal interstitium of patients with RPGN. The results indicate that these cells constitute part of the overall inflammatory cell accumulation in RPGN.
BRD7, a Subunit of SWI/SNF Complexes, Binds Directly to BRCA1 and Regulates BRCA1-Dependent Transcription
Authors: Mary T. Harte, Garrett J. O'Brien, Niamh M. Ryan, Julia J. Gorski, Kienan I. Savage, Nyree T. Crawford, Paul B. Mullan, D. Paul Harkin
Journal: Cancer Research (2010)

We carried out a yeast two-hybrid screen using a BRCA1 bait composed of amino acids 1 to 1142 and identified BRD7 as a novel binding partner of BRCA1. This interaction was confirmed by coimmunoprecipitation of endogenous BRCA1 and BRD7 in T47D and HEK-293 cells. BRD7 is a bromodomain containing protein, which is a subunit of PBAF-specific Swi/Snf chromatin remodeling complexes. To determine the functional consequences of the BRCA1-BRD7 interaction, we investigated the role of BRD7 in BRCA1-dependent transcription using microarray-based expression profiling. We found that a variety of targets were coordinately regulated by BRCA1 and BRD7, such as estrogen receptor alpha (ERalpha). Depletion of BRD7 or BRCA1 in either T47D or MCF7 cells resulted in loss of expression of ERalpha at both the mRNA and protein level, and this loss of ERalpha was reflected in resistance to the antiestrogen drug fulvestrant. We show that BRD7 is present, along with BRCA1 and Oct-1, on the ESR1 promoter (the gene which encodes ERalpha). Depletion of BRD7 prevented the recruitment of BRCA1 and Oct-1 to the ESR1 promoter; however, it had no effect on the recruitment of the other Swi/Snf subunits BRG1, BAF155, and BAF57 or on RNA polymerase II recruitment. These results support a model whereby the regulation of ERalpha transcription by BRD7 is mediated by its recruitment of BRCA1 and Oct-1 to the ESR1 promoter.