tbuckley/cabot-search huggingface dataset:
Tuberculin testing in two Liverpool social clubs: the effects of a tuberculosis outbreak on background positivity.
Authors: Q Syed, M A Bellis, N J Beeching, K Tocque, C S Williams, S Jamieson, A Steele, P D Davies
Journal: Thorax (1996)

BACKGROUND: Tuberculin testing remains the standard method for assessing infection due to tuberculosis in the UK. However, there are no data on the incidence of tuberculin positivity among the general adult population in the UK and consequently interpretation of Heaf test results is often difficult. METHODS: During the investigation of an outbreak of tuberculosis in a Liverpool social club 198 members were interviewed and Heaf tested and 171 members of a second social club in Liverpool were similarly screened as a control group. Comparisons between the results from the two populations provided both an estimate of baseline Heaf test positivity in indigenous white adults from a British inner city population, and a measure of the effect on this baseline of recent exposure to tuberculosis. RESULTS: In both club populations the proportion of positive Heaf tests increased with age. Independent of age, the tuberculosis exposed population had a higher proportion of positive Heaf grade results (40.9%) than those in the control group (26.9%). Multivariate analysis confirmed both the differences in Heaf results between clubs and between age groups but identified no other behavioural or medical factors which affected Heaf test results. CONCLUSIONS: Heaf test positivity increases with age at least up to 54 years, and recent exposure to tuberculosis increases the proportion of positive Heaf tests in each age group. Interpretation of positive Heaf tests when assessing the effects of a tuberculosis outbreak should take account of background levels of Heaf positivity.
In vitro evaluation of c7E3-Fab (ReoPro™) eluting polymer-coated coronary stents
Authors: J Baron
Journal: Cardiovascular Research (2000)

Stent thrombosis and in-stent restenosis remain problematic in certain patient sub-groups. c7E3-Fab (ReoPro, abciximab) inhibits the platelet glycoprotein IIb/IIIa receptor as well as the smooth muscle cell alpha(v)beta3 receptor, and thus may influence both processes, especially if high local concentrations could be achieved. We have studied the adsorption and elution characteristics of c7E3-Fab on commercially available polymer-coated stents. We have also investigated the effect of such antibody binding on platelet deposition in vitro, and on antibody deposition into ex vivo human saphenous vein wall to assess whether such stents may influence stent thrombosis and restenosis.Adsorption was measured using a radioisotope technique after immersing segments of polymer-coated stents in c7E3-Fab solutions. Uptake was dependent on antibody concentration and duration of immersion of wire in the solution. After 22 h (at 5 mg ml(-1)), 1146+/-101 ng cm(-1) wire was adsorbed. In an in vitro perfusion circuit, the antibody eluted slowly, with 53% remaining after 12 days washing. To determine the value that such stents might have in clinical practise, adsorption to balloon-mounted stents was assessed at room temperature, using commercially available c7E3-Fab (2 mg ml(-1)). Efficacy of eluting c7E3-Fab was determined by measuring deposition of 111-Indium platelets. Immersing stents in c7E3-Fab for 20 min inhibited platelet deposition by 82.3% compared to controls (P=0.018). Deployment of treated stents in ex vivo saphenous vein resulted in the deposition of c7E3-Fab in the intima and media.c7E3-Fab can be passively adsorbed onto polymer-coated stents. It elutes slowly and in a predictable manner, significantly inhibiting platelet deposition in vitro. These studies pave the way to developing stent-based delivery of a potent anti-platelet agent that may additionally affect smooth muscle cell activity.
METHODS FOR FOLLOWING THE FATE OF INFECTIOUS AGENTS FED TO SINGLE FLIES
Authors: Lawrence R. Penner, Joseph L. Melnick
Journal: The Journal of Experimental Medicine (1952)

Methods have been devised which facilitate the handling, feeding, and collection of excreta from individual flies bred in the laboratory. Using these methods, quantitative studies can be carried out in which known amounts of infectious material are fed to flies and the fate of these agents determined. It has been possible to determine the persistence of excretion of viruses, and the amount of the ingested virus recovered in the excreta and in the bodies of the flies as well.
Oxidative Stress and Respiratory Muscle Dysfunction in Severe Chronic Obstructive Pulmonary Disease
Authors: Esther Barreiro, Beatriz de la Puente, Joan Minguella, Josep M. Corominas, Sergi Serrano, Sabah N. A. Hussain, Joaquim Gea
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Oxidative stress is involved in the skeletal muscle dysfunction observed in patients with severe chronic obstructive pulmonary disease (COPD). We hypothesized that the diaphragms of such patients might generate greater levels of oxidants than those neutralized by antioxidants.To assess the levels of both oxidative and nitrosative stress and different antioxidants in the diaphragms of those patients, and to analyze potential relationships with lung and respiratory muscle dysfunctions.We conducted a case-control study in which reactive carbonyl groups, hydroxynonenal-protein adducts, antioxidant enzyme levels, nitric oxide synthases, and 3-nitrotyrosine formation were detected using immunoblotting and immunhistochemistry in diaphragm specimens (thoracotomy) obtained from six patients with severe COPD, six patients with moderate COPD, and seven control subjects.Diaphragms of patients with severe COPD showed both higher protein carbonyl groups and hydroxynonenal-protein adducts than control subjects. When only considering patients with COPD, negative correlations were found between carbonyl groups and airway obstruction, and between hydroxynonenal-protein adducts and respiratory muscle strength. Although diaphragmatic neuronal nitric oxide synthase did not differ among the three groups and no inducible nitric oxide synthase was detected in any muscle, muscle endothelial nitric oxide synthase was lower in patients with severe COPD than in control subjects. Muscle nitrotyrosine levels were similar in both patients with severe COPD and control subjects.This study shows that oxidative stress rather than nitric oxide is likely to be involved in the respiratory muscle dysfunction in severe COPD.
Comparison of the Atkins, Ornish, Weight Watchers, and Zone Diets for Weight Loss and Heart Disease Risk Reduction
Authors: Michael L. Dansinger, Joi Augustin Gleason, John L. Griffith, Harry P. Selker, Ernst J. Schaefer
Journal: JAMA (2005)

ContextThe scarcity of data addressing the health effects of popular diets is an important public health concern, especially since patients and physicians are interested in using popular diets as individualized eating strategies for disease prevention.ObjectiveTo assess adherence rates and the effectiveness of 4 popular diets (Atkins, Zone, Weight Watchers, and Ornish) for weight loss and cardiac risk factor reduction.Design, Setting, and ParticipantsA single-center randomized trial at an academic medical center in Boston, Mass, of overweight or obese (body mass index: mean, 35; range, 27-42) adults aged 22 to 72 years with known hypertension, dyslipidemia, or fasting hyperglycemia. Participants were enrolled starting July 18, 2000, and randomized to 4 popular diet groups until January 24, 2002.InterventionA total of 160 participants were randomly assigned to either Atkins (carbohydrate restriction, n=40), Zone (macronutrient balance, n=40), Weight Watchers (calorie restriction, n=40), or Ornish (fat restriction, n=40) diet groups. After 2 months of maximum effort, participants selected their own levels of dietary adherence.Main Outcome MeasuresOne-year changes in baseline weight and cardiac risk factors, and self-selected dietary adherence rates per self-report.ResultsAssuming no change from baseline for participants who discontinued the study, mean (SD) weight loss at 1 year was 2.1 (4.8) kg for Atkins (21 [53%] of 40 participants completed, P = .009), 3.2 (6.0) kg for Zone (26 [65%] of 40 completed, P = .002), 3.0 (4.9) kg for Weight Watchers (26 [65%] of 40 completed, P &lt; .001), and 3.3 (7.3) kg for Ornish (20 [50%] of 40 completed, P = .007). Greater effects were observed in study completers. Each diet significantly reduced the low-density lipoprotein/high-density lipoprotein (HDL) cholesterol ratio by approximately 10% (all P&lt;.05), with no significant effects on blood pressure or glucose at 1 year. Amount of weight loss was associated with self-reported dietary adherence level (r = 0.60; P&lt;.001) but not with diet type (r = 0.07; P = .40). For each diet, decreasing levels of total/HDL cholesterol, C-reactive protein, and insulin were significantly associated with weight loss (mean r = 0.36, 0.37, and 0.39, respectively) with no significant difference between diets (P = .48, P = .57, P = .31, respectively).ConclusionsEach popular diet modestly reduced body weight and several cardiac risk factors at 1 year. Overall dietary adherence rates were low, although increased adherence was associated with greater weight loss and cardiac risk factor reductions for each diet group.
An unusual case of bilateral pyoderma gangrenosum with Achilles tendon rupture
Authors: G.A. Fremlin, C. Rawlings, J.A. Livingstone, A.P.J.J. Bray
Journal: British Journal of Dermatology (2014)

Pyoderma gangrenosum (PG) is a rare, noninfectious, inflammatory disease characterized by neutrophilic infiltration of the dermis and destruction of tissue. PG is a diagnostic challenge, which can lead to late diagnosis, delayed treatment and detrimental surgical interventions. We describe a presentation not previously reported, affecting deep muscle and tendon leading to tendon rupture. Furthermore, we show the multidisciplinary team approach to management of a patient with PG and the reconstructive surgical element. A 31-year-old woman presented with a rapid onset painful, tender, left calf and ankle, which was associated with a mild flare of ulcerative colitis. Investigations revealed a white cell count of 26 × 109 cells L−1, a C-reactive protein count of 226 mg L−1, no deep vein thrombosis on ultrasound, no bone or joint involvement on X-ray and no organisms on joint aspirate. Debridement was undertaken after the left ankle developed a foul-smelling discharging wound. Repeat debridement led to worsening of the condition (pathergy). Intraoperative tissue cultures and microscopy showed no evidence of fungi, bacteria or mycobacteria. Histology showed granulation, inflammatory infiltrate, abscess formation and focal necrotizing vasculitis. Dermatology opinion confirmed PG. Awareness of the diagnosis of PG, and early involvement of dermatology, in a rapidly progressing wound is essential to avoid delayed treatment and prevent worsening through pathergy.
Blockade of the hedgehog pathway inhibits osteophyte formation in arthritis
Authors: Gisela Ruiz-Heiland, Angelika Horn, Pawel Zerr, Willy Hofstetter, Wolfgang Baum, Michael Stock, Jörg H Distler, Falk Nimmerjahn, Georg Schett, Jochen Zwerina
Journal: Annals of the Rheumatic Diseases (2012)

Background Osteophyte formation is a common phenomenon in arthritis. Bone formation by endochondral ossification is considered a key pathophysiological process in the formation of osteophytes. Objective To examine the hypothesis that inhibition of smoothened (Smo), a key component of the hedgehog pathway inhibits osteophyte formation as the hedgehog pathway mediates endochondral ossification. Methods Arthritis was induced in 8-week-old C57/BL6 mice by serum transfer (K/BxN model). Mice were then treated by daily administration of either vehicle or LDE223, a specific small molecule inhibitor for Smo, over 2 weeks starting at the onset of disease. Clinical course of arthritis, histological and molecular changes of bone in the affected joints as well as systemic bone changes were assessed. Results Serum transfer-induced arthritis led to severe osteophyte formation within 2 weeks of onset. Blockade of Smo inhibited hedgehog signalling in vivo and also significantly inhibited osteophyte formation, whereas the clinical and histopathological signs of arthritis were not affected. Also, systemic bone mass did not change. Smo inhibitor particularly blocked the formation of hypertrophic chondrocytes and collagen type X expression. Conclusions The data indicate that blockade of hedgehog signalling by targeting Smo specifically inhibits osteophyte formation in arthritis without affecting inflammation and without eliciting bone destruction at the local and systemic level. Blockade of Smo may thus be considered as a strategy to specifically influence the periosteal bone response in arthritis associated with bone apposition.
A trial of clenbuterol in bronchial asthma.
Authors: G Anderson, E Wilkins
Journal: Thorax (1977)

Clenbuterol is a beta 2-sympathomimetic bronchodilator. In a double-blind cross-over trial in 19 asthmatic patients with reversible airways obstruction, oral administration of both clenbuterol (40 microgram) and salbutamol (4 mg) caused significantly greater increased in peak expiratory flow rate (PEFR) than placebo, that of clenbuterol lasting longer. The patients9 subjective assessment also suggested the relief of their symptoms by the active drugs. Side-effects were minimal.
Sequence Variation and Haplotype Structure at the Putative Flowering-Time Locus COL1 of Brassica nigra
Authors: Ulf Lagercrantz, Marita Kruskopf Osterberg, Martin Lascoux
Journal: Molecular Biology and Evolution (2002)

Motivated by a previous study indicating that polymorphism at an indel, Ind2, within the Brassica nigraCOL1 gene is significantly associated with flowering time, we searched for evidence of selection in a sample of 41 complete sequences of B. nigraCOL1. The within–gene population recombination rate is moderate, and all neutrality tests used in the present study failed to detect departure from the standard neutral model or evidence of selection. The haplotype structure of the 5′-half of the gene is primarily associated with the demographic history of the species and more specifically with the split between European and Ethiopian populations, whereas the structure of the 3′-half reflects the polymorphism at Ind2. This could be the result of selection or a combination of recombination and migration during the history of the sample of sequences. Without additional information on polymorphism in flanking areas, these two alternatives are difficult to tell apart. If selection acted on the gene, we suggest that if the indel itself is not the target of selection, among the polymorphic sites cosegregating with the polymorphism at Ind2, replacement polymorphisms around sites 890 and 1260 are the most likely quantitative trait nucleotides within the gene.
Induction of Early B Cell Factor (EBF) and Multiple B Lineage Genes by the Basic Helix-Loop-Helix Transcription Factor E12
Authors: Barbara L. Kee, Cornelis Murre
Journal: The Journal of Experimental Medicine (1998)

The transcription factors encoded by the E2A and early B cell factor (EBF) genes are required for the proper development of B lymphocytes. However, the absence of B lineage cells in E2A- and EBF-deficient mice has made it difficult to determine the function or relationship between these proteins. We report the identification of a novel model system in which the role of E2A and EBF in the regulation of multiple B lineage traits can be studied. We found that the conversion of 70Z/3 pre-B lymphocytes to cells with a macrophage-like phenotype is associated with the loss of E2A and EBF. Moreover, we show that ectopic expression of the E2A protein E12 in this macrophage line results in the induction of many B lineage genes, including EBF, IL7Rα, λ5, and Rag-1, and the ability to induce κ light chain in response to mitogen. Activation of EBF may be one of the critical functions of E12 in regulating the B lineage phenotype since expression of EBF alone leads to the activation of a subset of E12-inducible traits. Our data demonstrate that, in the context of this macrophage line, E12 induces expression of EBF and together these transcription factors coordinately regulate numerous B lineage–associated genes.
Association of Erectile Dysfunction With Cardiovascular Risk Factors and Increasing Existing Vascular Disease in Male Chinese Type 2 Diabetic Patients
Authors: G. Neil Thomas, Brian Tomlinson, Abu S.M. Abdullah, Vincent T.F. Yeung, Juliana C.N. Chan, Ka Sing Wong
Journal: Diabetes Care (2005)

Erectile dysfunction (ED) is a prevalent health problem and impacts considerably on the quality of life of middle-aged men (1). Previous studies have reported an association between ED, vascular disease (2,3), and cardiovascular risk factors (2–5), with ED being reported as both a symptom and marker of vascular disease progression (6,7). In Hong Kong, there is a high prevalence of diabetes and other risk factors, with 22.6% of older males (65–74 years) having diabetes, 37.2% having dyslipidemia, and 51.7% having hypertension (8). The Massachusetts Male Aging Study emphasized the close relationship between diabetes and ED, which was three times more prevalent in diabetic subjects than their nondiabetic counterparts (28 vs. 10%) (2). The high prevalence of diabetes and other risk factors may therefore have a significant impact on the prevalence of ED in Hong Kong.

Patients were diagnosed as having type 2 diabetes using World Health Organization criteria (9) and underwent structured assessments using the EuroDiab Protocol (10). They were seen in a teaching hospital and tertiary referral center, but the government-funded health care system is such that many patients use the facility as their only source of subsidised medical care. Therefore, the study represents patients of low- and middle-income socioeconomic status.

All patients gave written, informed consent. Assessments for micro- and macrovascular disease, including retinopathy, peripheral vascular disease, and middle cerebral artery (MCA) stenosis …
Regulation of pancreatic cancer cell migration and invasion by RhoC GTPase and Caveolin-1
Authors: Min Lin, Melinda M DiVito, Sofia D Merajver, Madanamohan Boyanapalli, Kenneth L van Golen
Journal: Molecular Cancer (2005)

Abstract Background In the current study we investigated the role of caveolin-1 (cav-1) in pancreatic adenocarcinoma (PC) cell migration and invasion; initial steps in metastasis. Cav-1 is the major structural protein in caveolae; small Ω-shaped invaginations within the plasma membrane. Caveolae are involved in signal transduction, wherein cav-1 acts as a scaffolding protein to organize multiple molecular complexes regulating a variety of cellular events. Recent evidence suggests a role for cav-1 in promoting cancer cell migration, invasion and metastasis; however, the molecular mechanisms have not been described. The small monomeric GTPases are among several molecules which associate with cav-1. Classically, the Rho GTPases control actin cytoskeletal reorganization during cell migration and invasion. RhoC GTPase is overexpressed in aggressive cancers that metastasize and is the predominant GTPase in PC. Like several GTPases, RhoC contains a putative cav-1 binding motif. Results Analysis of 10 PC cell lines revealed high levels of cav-1 expression in lines derived from primary tumors and low expression in those derived from metastases. Comparison of the BxPC-3 (derived from a primary tumor) and HPAF-II (derived from a metastasis) demonstrates a reciprocal relationship between cav-1 expression and p42/p44 Erk activation with PC cell migration, invasion, RhoC GTPase and p38 MAPK activation. Furthermore, inhibition of RhoC or p38 activity in HPAF-II cells leads to partial restoration of cav-1 expression. Conclusion Cav-1 expression inhibits RhoC GTPase activation and subsequent activation of the p38 MAPK pathway in primary PC cells thus restricting migration and invasion. In contrast, loss of cav-1 expression leads to RhoC-mediated migration and invasion in metastatic PC cells.
Receptor protein tyrosine phosphatase beta/zeta is a functional binding partner for vascular endothelial growth factor
Authors: Marina Koutsioumpa, Evangelia Poimenidi, Evangelia Pantazaka, Christina Theodoropoulou, Angeliki Skoura, Vasileios Megalooikonomou, Nelly Kieffer, Jose Courty, Shuji Mizumoto, Kazuyuki Sugahara, Evangelia Papadimitriou
Journal: Molecular Cancer (2015)

Receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) is a chondroitin sulphate (CS) transmembrane protein tyrosine phosphatase and is a receptor for pleiotrophin (PTN). RPTPβ/ζ interacts with ανβ₃ on the cell surface and upon binding of PTN leads to c-Src dephosphorylation at Tyr530, β₃ Tyr773 phosphorylation, cell surface nucleolin (NCL) localization and stimulation of cell migration. c-Src-mediated β₃ Tyr773 phosphorylation is also observed after vascular endothelial growth factor 165 (VEGF₁₆₅) stimulation of endothelial cells and is essential for VEGF receptor type 2 (VEGFR2) - ανβ₃ integrin association and subsequent signaling. In the present work, we studied whether RPTPβ/ζ mediates angiogenic actions of VEGF.Human umbilical vein endothelial, human glioma U87MG and stably transfected Chinese hamster ovary cells expressing different β₃ subunits were used. Protein-protein interactions were studied by a combination of immunoprecipitation/Western blot, immunofluorescence and proximity ligation assays, properly quantified as needed. RPTPβ/ζ expression was down-regulated using small interference RNA technology. Migration assays were performed in 24-well microchemotaxis chambers, using uncoated polycarbonate membranes with 8 μm pores.RPTPβ/ζ mediates VEGF₁₆₅-induced c-Src-dependent β₃ Tyr773 phosphorylation, which is required for VEGFR2-ανβ₃ interaction and the downstream activation of phosphatidylinositol 3-kinase (PI3K) and cell surface NCL localization. RPTPβ/ζ directly interacts with VEGF165, and this interaction is not affected by bevacizumab, while it is interrupted by both CS-E and PTN. Down-regulation of RPTPβ/ζ by siRNA or administration of exogenous CS-E abolishes VEGF₁₆₅-induced endothelial cell migration, while PTN inhibits the migratory effect of VEGF₁₆₅ to the levels of its own effect.These data identify RPTPβ/ζ as a cell membrane binding partner for VEGF that regulates angiogenic functions of endothelial cells and suggest that it warrants further validation as a potential target for development of additive or alternative anti-VEGF therapies.