tbuckley/cabot-search huggingface dataset:
Effect of a platelet-activating factor (PAF) antagonist, SR 27417A, on PAF-induced gas exchange abnormalities in mild asthma
Authors: FP Gomez, J Roca, JA Barbera, KF Chung, VI Peinado, R Rodriguez-Roisin
Journal: European Respiratory Journal (1998)

Inhaled platelet-activating factor (PAF), both in normals and in asthmatic patients, provokes transient systemic effects, neutropenia, bronchoconstriction and arterial oxygenation abnormalities similar to those shown in spontaneous exacerbations of asthma. To investigate the efficacy of a new PAF-receptor antagonist, SR 27417A, on all these changes after PAF challenge, 12 nonsmoking patients (four females and eight males) (mean+/-SEM) age 24+/-1 yrs with mild asthma (forced expiratory volume in one second (FEV1) 93+/-3% predicted) were studied in a double-blind, placebo-controlled, cross-over fashion 2 weeks apart. PAF aerosol challenge (18 microg) was carried out 3 h after oral administration of either SR 27417A (20 mg) or placebo. Respiratory system resistance (Rrs) and arterial blood gases and neutrophil cell counts were measured at baseline, before compound/placebo administration, and at 5, 15 and 45 min after PAF. Compared to vehicle, SR 27417A brought about moderate attenuation of PAF-induced neutropenia at 5 min (by 140%; p<0.025), and rebound neutrophilia at 15 and 45 min (p<0.025), increases of Rrs (by 90-65%) (p<0.01) and of alveolar-arterial pressure difference for oxygen (PA-a,O2) at 5 min (by 68%) and 15 min (by 63%), and decreases of arterial oxygen tension (Pa,O2) at 5 min (by 57%; p<0.025, each). Furthermore, systemic effects and platelet aggregation tests (p<0.001) were abolished after the administration of the compound. We conclude that SR 27417A is effective in inhibiting systemic, cellular and pulmonary effects after platelet-activating factor challenge in patients with mild bronchial asthma.
Improved isovolumetric relaxation in canine reperfused myocardium after 1 adrenergic stimulation
Authors: M. Bohm
Journal: Cardiovascular Research (1992)

Journal Article Improved isovolumetric relaxation in canine reperfused myocardium after β1 adrenergic stimulation Get access Malte Böhm Malte Böhm Abt für Pathophysiologic Zentrum für Innere Medizin, Universität Essen, Hufelandstraβe 55, D-4300 Essen 1, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 26, Issue 3, March 1992, Pages 273–278, https://doi.org/10.1093/cvr/26.3.273 Published: 01 March 1992 Article history Received: 08 July 1991 Accepted: 11 September 1991 Published: 01 March 1992
<i>N</i>-acetylcysteine attenuates PKCβ<sub>2</sub>overexpression and myocardial hypertrophy in streptozotocin-induced diabetic rats
Authors: Zhengyuan Xia, Kuo-Hsing Kuo, Prabhakara R. Nagareddy, Fang Wang, Zhixin Guo, Tianhai Guo, Jihong Jiang, John H. McNeill
Journal: Cardiovascular Research (2006)

Oxidative stress-mediated activation of protein kinase C (PKC) beta(2) in the myocardium has been implicated in the development of cardiomyopathy. Overexpression of PKCbeta(2) is associated with increased expression of connective tissue growth factor (CTGF) in myocardium, resulting in myocardial hypertrophy. We hypothesized that chronic treatment with the antioxidant N-acetylcysteine (NAC) would normalize oxidative stress-mediated overexpression of myocardial PKCbeta(2) and CTGF and attenuate the development of myocardial hypertrophy.Control and streptozotocin-induced diabetic rats were treated with NAC in drinking water for 8 weeks. At termination rats were surgically prepared for hemodynamic measurement, subsequent to which their hearts were removed to evaluate cardiac performance and histological and biochemical changes. Further, the role of PKCbeta(2) in hyperglycemia-induced cardiomyocyte hypertrophy was tested in cultured neonatal cardiomyocytes.Myocardial hypertrophy, characterized by an increased ratio of ventricle weight to body weight and cardiomyocyte cross-sectional area was found to be higher in untreated diabetic rats. Further, in myocardium, increased levels of 15-F(2t)-isoprostane were accompanied by an increased expression of membrane-bound PKCbeta(2) and CTGF. N-acetylcysteine treatment not only attenuated these changes but also prevented hyperglycemia-induced hypertrophy in cultured neonatal rat cardiomyocytes.The results suggest that PKCbeta(2) overexpression represents a mechanism causing hyperglycemia-mediated myocardial hypertrophy, which can be prevented by the antioxidant N-acetylcysteine.
Blood flow-dependent arterial remodelling is facilitated by inflammation but directed by vascular tone
Authors: E. N.T.P. Bakker, H. L. Matlung, P. Bonta, C. J. de Vries, N. van Rooijen, E. VanBavel
Journal: Cardiovascular Research (2008)

AimsAltered blood flow affects vascular tone, attracts inflammatory cells, and leads to microvascular remodelling. We tested the hypothesis that inflammation facilitates the remodelling response, but that vascular tone determines its direction (inward or outward).
Prognostic significance of UBE2C mRNA expression in high-risk early breast cancer. A Hellenic Cooperative Oncology Group (HeCOG) Study
Authors: A. Psyrri, K.T. Kalogeras, R. Kronenwett, R.M. Wirtz, A. Batistatou, E. Bournakis, E. Timotheadou, H. Gogas, G. Aravantinos, C. Christodoulou, T. Makatsoris, H. Linardou, D. Pectasides, N. Pavlidis, T. Economopoulos, G. Fountzilas
Journal: Annals of Oncology (2011)

The ubiquitin-proteasome system (UPS) plays a pivotal role in tumorigenesis. Components of the UPS have recently been implicated in breast cancer progression. In the present study, we sought to explore the prognostic and/or predictive significance of UBE2C messenger RNA (mRNA) expression on disease-free survival (DFS) and overall survival (OS) in high-risk operable breast cancer patients.Five hundred and ninety-five high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative, dose-dense sequential chemotherapy with epirubicin followed by CMF (cyclophosphamide, methotrexate and 5-fluorouracil) with or without paclitaxel (Taxol). RNA was extracted from 313 formalin-fixed primary tumor tissue samples followed by one-step quantitative RT-PCR for assessment of mRNA expression of UBE2C.High UBE2C mRNA expression was associated with poor DFS (Wald's P = 0.003) and OS (Wald's P = 0.005). High tumor grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of UBE2C. Results of the Cox multivariate regression analysis revealed that high UBE2C mRNA expression remained an independent adverse prognostic factor for relapse (P = 0.037) and death (P = 0.05).High UBE2C mRNA expression was found to be of adverse prognostic significance in high-risk breast cancer patients. These findings need to be validated in larger cohorts.
Application of a standard test to the in vitro performance of mouthguards
Authors: A Greasley, G Imlach, B Karet
Journal: British Journal of Sports Medicine (1998)

To use a simulated upper jaw made from a rubber arch containing replaceable ceramic teeth and a renewable composite ceramic jawbone to compare the effectiveness of seven custom made mouthguard designs and a "boil and bite" mouthguard.Following an earlier development of a standard impact test using a selection of projectile shapes and energies, the most sensitive conditions were selected. These were then applied to a series of six guards constructed in ethylene vinyl acetate and styrene butadiene. The guards were constructed to reflect possible variations in both design and materials.Significant differences between the mouthguard performances were observed in response to the impact conditions selected. All the custom made designs gave better performance than the "boil and bite" mouthguard.The differences observed indicated that the standard test should be sensitive enough to be used as an assessment procedure for the approval of the manufacture of these safety devices. A sequence of tests on eight identical mouthguards selected from a batch of 12, based on the best design, gave remarkably consistent results, indicating that both the manufacturing technique and the test method are reliable. The features of the best design should be incorporated into the current "best practice" for the construction of these devices.
Myeloid-Derived Suppressor Cell Inhibition of the IFN Response in Tumor-Bearing Mice
Authors: Bethany L. Mundy-Bosse, Gregory B. Lesinski, Alena C. Jaime-Ramirez, Kristen Benninger, Mahmood Khan, Periannan Kuppusamy, Kristan Guenterberg, Sri Vidya Kondadasula, Abhik Ray Chaudhury, Krista M. La Perle, Melanie Kreiner, Gregory Young, Denis C. Guttridge, William E. Carson
Journal: Cancer Research (2011)

Abstract Our group and others have determined that immune effector cells from patients with advanced cancers exhibit reduced activation of IFN signaling pathways. We hypothesized that increases in immune regulatory cells termed myeloid-derived suppressor cells (MDSC) could interfere with the host immune response to tumors by inhibiting immune cell responsiveness to IFNs. The C26 murine adenocarcinoma model was employed to study immune function in advanced malignancy. C26-bearing mice had significantly elevated levels of GR1+CD11b+ MDSC as compared with control mice, and splenocytes from tumor-bearing mice exhibited reduced phosphorylation of STAT1 (P-STAT1) on Tyr701 in response to IFN-α or IFN-γ. This inhibition was seen in splenic CD4+ and CD8+ T cells as well as natural killer cells. In vitro coculture experiments revealed that MDSC inhibited the IFN responsiveness of splenocytes from normal mice. Treatment of C26-bearing mice with gemcitabine or an anti-GR1 antibody led to depletion of MDSC and restored splenocyte IFN responsiveness. Spleens from C26-bearing animals displayed elevated levels of iNOS protein and nitric oxide. In vitro treatment of splenocytes with a nitric oxide donor led to a decreased STAT1 IFN response. The elevation in nitric oxide in C26-bearing mice was associated with increased levels of nitration on STAT1. Finally, splenocytes from iNOS knockout mice bearing C26 tumors exhibited a significantly elevated IFN response as compared with control C26 tumor-bearing mice. These data suggest that nitric oxide produced by MDSC can lead to reduced IFN responsiveness in immune cells. Cancer Res; 71(15); 5101–10. ©2011 AACR.
ADAM-17 Expression in Breast Cancer Correlates with Variables of Tumor Progression
Authors: Patricia M. McGowan, Bríd M. Ryan, Arnold D.K. Hill, Enda McDermott, Niall O'Higgins, Michael J. Duffy
Journal: Clinical Cancer Research (2007)

Abstract The ADAMs are a family of membrane proteins possessing a disintegrin and metalloprotease domain. One of their main functions is shedding of membrane proteins. The aim of this study was to test the hypothesis that ADAM-17 (also known as tumor necrosis factor-α converting enzyme) is involved in breast cancer progression. Overexpression of ADAM-17 in MCF-7 breast cancer cells increased in vitro invasion and proliferation, whereas down-regulation of ADAM-17 expression in MDA-MB-435 cells decreased invasion and proliferation. At both mRNA and protein levels, ADAM-17 expression was significantly up-regulated in breast cancer compared with normal breast tissue. Using Western blotting, ADAM-17 protein in breast cancer was shown to exist in two forms migrating with approximate molecular masses of 100 and 120 kDa. Based on their known molecular mass, these bands were taken to represent the active and precursor forms of ADAM-17, respectively. The proportion of active to total ADAM-17 increased progressively from normal breast tissue to primary breast cancer to lymph node metastases (P = 0.017, Kruskal-Wallis test). In primary cancers, the active form was expressed more frequently in node-positive compared with node-negative tumors (P = 0.034, χ2 test). Furthermore, in primary carcinomas, both forms of ADAM-17 correlated significantly (Spearman correlation analysis) with levels of urokinase plasminogen activator (precursor form: r = 0.246, P = 0.032, n = 83 and active form: r = 0.428, P = 0.0001, n = 83) and proliferating cell nuclear antigen (precursor form: r = 0.524, P &amp;lt; 0.0001, n = 73 and active form: r = 0.365, P = 0.002, n = 73). Our results support the hypothesis that ADAM-17 is involved in breast cancer progression.
Differences in the response of inbred mouse strains to the factor increasing monocytopoiesis.
Authors: W Sluiter, I Elzenga-Claasen, A van der Voort van der Kley-van Andel, R van Furth
Journal: The Journal of Experimental Medicine (1984)

Previous studies have shown that monocyte production during an inflammatory response is controlled by the factor increasing monocytopoiesis (FIM), secreted by macrophages at the site of inflammation. The inflammatory reaction to latex particles and a saline-soluble extract of Listeria monocytogenes (SEL), expressed as the number of monocytes in the circulation and of macrophages at the site of inflammation, was about twice as strong in C57BL/10 mice compared with CBA mice. This raised the question as to the mechanism underlying these differences. One possibility might be that these mouse strains differ with respect to the production of FIM, but this cannot be the case because the maximum levels of FIM activity in the serum of both C57BL/10 and CBA mice given latex or SEL intraperitoneally were almost the same; however, the courses of FIM activity in the two strains after intraperitoneal latex were not exactly synchronous. Another possibility is that the sensitivity of monocyte precursor cells for FIM differs. Evidence for the latter was provided by the finding that the intravenous injection of sera with FIM activity obtained from C57BL/10 and from CBA mice into the C57BL/10 mice evoked monocytosis, whereas CBA mice did not respond to these sera. Earlier studies showed that an increase of monocytes after the injection of serum containing FIM reflects increased monocyte production. Taken together, the results of the present study demonstrate that one of the mechanisms underlying the genetic control of the inflammatory response is, rather than enhanced FIM synthesis, the ability of monocyte precursors in the bone marrow to respond to FIM by increased monocyte production.
Response to: ‘Risk of vascular disease with gout: overadjustment of the statistical analyses?’ by van Durme <i>et al</i>
Authors: Lorna Clarson, Samantha L Hider, John Belcher, Carl Heneghan, Edward Roddy, Christian D Mallen
Journal: Annals of the Rheumatic Diseases (2014)

We thank van Durme et al for their interest in our paper and for the opportunity to discuss these important methodological issues regarding possible overadjustment for chronic renal disease.1 However, there are a number of reasons that we would refute the suggestion of overadjustment in our analyses.

First, the definition of renal disease used as part of the Charlson comorbidity index (CCI), and thus the codes used to identify these conditions, was different to those used in our analysis. We were interested specifically in chronic kidney disease (CKD), defined as “kidney damage or glomerular filtration …
Prevalence and pattern of radiographic hand osteoarthritis and association with pain and disability (the Rotterdam study)
Authors: S Dahaghin
Journal: Annals of the Rheumatic Diseases (2004)

To investigate the prevalence and pattern of radiographic osteoarthritis (ROA) of the hand joints and its association with self reported hand pain and disability.Baseline data on a population based study (age >/=55 years) were used (n = 3906). Hand ROA was defined as the presence of Kellgren-Lawrence grade >/=2 radiological changes in two of three groups of hand joints in each hand. The presence of hand pain during the previous month was defined as hand pain. The health assessment questionnaire was used to measure hand disability.67% of the women and 54.8% of the men had ROA in at least one hand joint. DIP joints were affected in 47.3% of participants, thumb base in 35.8%, PIP joints in 18.2%, and MCP joints in 8.2% (right or left hand). ROA of other joint groups (right hand) co-occurred in 56% of DIP involvement, 88% of PIP involvement, 86% of MCP involvement, and 65% of thumb base involvement. Hand pain showed an odds ratio of 1.9 (1.5 to 2.4) with the ROA of the hand (right). Hand disability showed an odds ratio of 1.5 (1.1 to 2.1) with ROA of the hand (right or left).Hand ROA is common in the elderly, especially in women. Co-occurrence of ROA in different joint groups of the hand is more common than single joint disease. There is a modest to weak association between ROA of the hand and hand pain/disability, varying with the site of involvement.
Meta-analysis of glioblastoma multiforme versus anaplastic astrocytoma identifies robust gene markers
Authors: Jonathan M Dreyfuss, Mark D Johnson, Peter J Park
Journal: Molecular Cancer (2009)

Abstract Background Anaplastic astrocytoma (AA) and its more aggressive counterpart, glioblastoma multiforme (GBM), are the most common intrinsic brain tumors in adults and are almost universally fatal. A deeper understanding of the molecular relationship of these tumor types is necessary to derive insights into the diagnosis, prognosis, and treatment of gliomas. Although genomewide profiling of expression levels with microarrays can be used to identify differentially expressed genes between these tumor types, comparative studies so far have resulted in gene lists that show little overlap. Results To achieve a more accurate and stable list of the differentially expressed genes and pathways between primary GBM and AA, we performed a meta-analysis using publicly available genome-scale mRNA data sets. There were four data sets with sufficiently large sample sizes of both GBMs and AAs, all of which coincidentally used human U133 platforms from Affymetrix, allowing for easier and more precise integration of data. After scoring genes and pathways within each data set, we combined the statistics across studies using the nonparametric rank sum method to identify the features that differentiate GBMs and AAs. We found &gt;900 statistically significant probe sets after correction for multiple testing from the &gt;22,000 tested. We also used the rank sum approach to select &gt;20 significant Biocarta pathways after correction for multiple testing out of &gt;175 pathways examined. The most significant pathway was the hypoxia-inducible factor (HIF) pathway. Our analysis suggests that many of the most statistically significant genes work together in a HIF1A / VEGF -regulated network to increase angiogenesis and invasion in GBM when compared to AA. Conclusion We have performed a meta-analysis of genome-scale mRNA expression data for 289 human malignant gliomas and have identified a list of &gt;900 probe sets and &gt;20 pathways that are significantly different between GBM and AA. These feature lists could be utilized to aid in diagnosis, prognosis, and grade reduction of high-grade gliomas and to identify genes that were not previously suspected of playing an important role in glioma biology. More generally, this approach suggests that combined analysis of existing data sets can reveal new insights and that the large amount of publicly available cancer data sets should be further utilized in a similar manner.
Clinical Lecture on Excision of the Head and Neck of the Femur in Cases of Hip-Joint Disease
Authors: J. Morton
Journal: BMJ (1872)

Ja. 63 tranquil sleep in maniacal delirium, and to remove or relieve many other distressing symptoms without in any way impairing the patient's constitution, or thwarting the natural tendency to recovery.From what I have stated, you cannot fail to perceive that to carry out successfully the medical treatment of disease, a scientific knowledge of diseases in all their bearings, and an intimate acquaintance with the patient's constitution, are absolutely necessary.ational medicine, the principles of which I shall endeavour in these lectures to teach to you, differs from quackery in not professing to have an antidote for every disease in the nosology, and in its basis being, not physic, lut anatomy, physiology, chemistry, pathology, and therapeutics.It ought also to differ from it in affecting no mystery, and-in perfect honesty of purpose.
Ontogenesis of taurocholate transport by rat ileal brush border membrane vesicles.
Authors: J A Barnard, F K Ghishan, F A Wilson
Journal: Journal of Clinical Investigation (1985)

Developmental aspects of taurocholate transport into ileal brush border membrane vesicles were studied in 2-wk-old (suckling), 3-wk-old (weanling), and 6-wk-old (adolescent) rats. Taurocholate uptake (picomoles per milligram protein) into brush border membrane vesicles prepared from 2-wk-old rats was similar under Na+ and K+ gradient conditions (outside greater than inside). By contrast, uptake in 3- and 6-wk-old rats was significantly enhanced at 20 s, and at 1, 2, and 5 min of incubation in the presence of a Na+ gradient when compared with a K+ gradient incubation (P less than 0.05). Under isotope exchange conditions, a plot of active uptake velocity versus taurocholate concentration (0.10-1.0 mM) in 2-wk-old rat membrane vesicles was linear and approached the horizontal axis, suggesting the absence of active transport. However, similar plots in 3- and 6-wk-old rats described a rectangular hyperbola, indicating a Na+-dependent, saturable cotransport system. Woolf-Augustinsson-Hofstee plots of the uptake velocity versus concentration data from 3- and 6-wk-old rat brush border membrane vesicles yielded Vmax values that were not significantly different, 844 and 884 pmol uptake/mg protein per 120 s, respectively. The respective Km values were 0.59 and 0.66 mM taurocholate. The induction of an electrochemical diffusion potential by incubating K+-loaded vesicles with valinomycin did not significantly enhance taurocholate uptake in 2-, 3-, or 6-wk-old rat vesicle preparations. These data indicate that taurocholate transport into rat ileal brush border membrane vesicles is mediated by an electroneutral, sodium-coupled, cotransport system that is incompletely developed in the 2-wk-old suckling rat but fully developed by the time of weaning at 3 wk of age.