tbuckley/cabot-search huggingface dataset:
Macrophage inflammatory protein 1 alpha expression by synovial fluid neutrophils in rheumatoid arthritis
Authors: Y. Hatano, T. Kasama, H. Iwabuchi, R. Hanaoka, H. T Takeuchi, L. Jing, Y. Mori, K. Kobayashi, M. Negishi, H. Ide, M. Adachi
Journal: Annals of the Rheumatic Diseases (1999)

To determine the contribution made by synovial fluid (SF) neutrophils to the augmented expression of macrophage inflammatory protein 1 alpha (MIP-1alpha) in rheumatoid arthritis (RA).Neutrophils were isolated from samples of SF from RA patients and peripheral blood (PB) samples from RA patients and healthy controls. Cell associated MIP-1alpha was visualised immunohistochemically, and cell associated MIP-1alpha as well as MIP-1alpha secreted into the SF was assayed by ELISA. Steady state expression of MIP-1alpha mRNA was assessed by reverse transcription polymerase chain reaction (RT-PCR).Freshly isolated SF neutrophils contained significantly higher concentrations of both MIP-1alpha protein and its transcript than PB neutrophils from either RA patients or healthy controls; incubation in the absence or presence of tumour necrosis factor alpha for 24 hours resulted in a significant increase in MIP-1alpha secretion by RA SF neutrophils compared with neutrophils obtained from either normal PB or RA PB; and expression of MIP-1alpha by SF neutrophils was well correlated with both RA disease activity and SF mononuclear cell (MNC) counts.Expression and secretion of MIP-1alpha by SF neutrophils may be indicative of local and systemic inflammation in RA. Moreover, this C-C chemokine may contribute to the recruitment of MNCs from the bloodstream into synovial joints and tissues.
Clinical Value of Erythrocyte Sedimentation Rate
Authors: J. R. Sinton
Journal: BMJ (1948)

RETROPERITONEAL HAEMORRHAGE IN PREGNANCYMEDBIRALt 391 ahe haemorrhage had a pelvic origin, the shock was less profound, and the patient recovered. .My case naturally falls into the same category as the first five cases.The site of the haemorrhage is of interest because the tear in the peritoneum of the floor of the lesser sac lay directly over the course of the splenic artery, just distal to the bifurcation of the coeliac artery.The actual ,origin of the haemorrhage could not be determined because of the friability of the various tissues of the area, but, judging from the speed with which the patient bled to death, the vessel concerned must certainly have been of fairly large calibre, and the pressure behind the blood must have been sufficient to rupture the peritoneal floor of the lesser sac.This catastrophe's occurrence in close proximity to the coeliac plexus no doubt further aggravated the shock.The retroperitoneal haemorrhage which caused the death of the ,patient occurred on the fourth day after caesarean section for accidental haemorrhage, and it would be of interest to correlate, if possible, the condition of retroperitoneal haemorrhage with toxaemia of pregnancy.One of the out- standing features of the pathology of eclampsia is capillary thrombosis followed by extravasation of red blood cells, and 1 wonder whether or not a similar occurrence might happen in vessels of larger calibre in isolated instances.Certainly i two of the previously reported cases a condition of toxaemia of pregnancy was present. SummaryA case of eclampsia complicated by an accidental haemor- fhage is described.Conservative management of the haemorrhage had to be libandoned in favour of classical caesarean section owing to the fact that the uterus remained obstinately tense, and a sudden increase in the retroplacental haemorrhage made immediate operative intervention imperative.The patient made a smooth recovery until the fourth post- operative day, when she developed a massive retroperitoneal haemorrhage which seemed to originate in the region of the p,nction of the body and neck of the pancreas.The haemor- rhage burst through the peritoneum of the lesser sac, and from 4 to 5 pints (2.27 to 2.84 litres) of blood passed through the aditus of the lesser sac into the general peritoneal cavity, causing death from internal haemorrhage.A review of the literature to date is given, and an attempt is made to correlate a possible connexion between the toxaemias of pregnancy and retroperitoneal haemorrhage occurring during ,pregnancy.My thanks are due to, Dr. J. Seed, Medical Superintendent, ;4riffield County Hospital, East Yorks, for permission to publish the case, and to Dr. Barnard, County
Evaluating Left Ventricular Functions in Primary Mitral Regurgitation by Two Dimensional Strain Echocardiography
Authors: Burcu Zihni, Mustafa Beyazıt Alkan, Murat Bilgin, Ahmet Sayın, Hatice Soner Kemal, Cahide Soydaş Çınar
Journal: Journal of the American College of Cardiology (2013)
Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease
Authors: Angharad M. Roberts, James S. Ware, Daniel S. Herman, Sebastian Schafer, John Baksi, Alexander G. Bick, Rachel J. Buchan, Roddy Walsh, Shibu John, Samuel Wilkinson, Francesco Mazzarotto, Leanne E. Felkin, Sungsam Gong, Jacqueline A. L. MacArthur, Fiona Cunningham, Jason Flannick, Stacey B. Gabriel, David M. Altshuler, Peter S. Macdonald, Matthias Heinig, Anne M. Keogh, Christopher S. Hayward, Nicholas R. Banner, Dudley J. Pennell, Declan P. O’Regan, Tan Ru San, Antonio de Marvao, Timothy J. W. Dawes, Ankur Gulati, Emma J. Birks, Magdi H. Yacoub, Michael Radke, Michael Gotthardt, James G. Wilson, Christopher J. O’Donnell, Sanjay K. Prasad, Paul J. R. Barton, Diane Fatkin, Norbert Hubner, Jonathan G. Seidman, Christine E. Seidman, Stuart A. Cook
Journal: Science Translational Medicine (2015)

The recent discovery of heterozygous human mutations that truncate full-length titin (TTN, an abundant structural, sensory, and signaling filament in muscle) as a common cause of end-stage dilated cardiomyopathy (DCM) promises new prospects for improving heart failure management. However, realization of this opportunity has been hindered by the burden of TTN-truncating variants (TTNtv) in the general population and uncertainty about their consequences in health or disease. To elucidate the effects of TTNtv, we coupled TTN gene sequencing with cardiac phenotyping in 5267 individuals across the spectrum of cardiac physiology and integrated these data with RNA and protein analyses of human heart tissues. We report diversity of TTN isoform expression in the heart, define the relative inclusion of TTN exons in different isoforms (using the TTN transcript annotations available at http://cardiodb.org/titin), and demonstrate that these data, coupled with the position of the TTNtv, provide a robust strategy to discriminate pathogenic from benign TTNtv. We show that TTNtv is the most common genetic cause of DCM in ambulant patients in the community, identify clinically important manifestations of TTNtv-positive DCM, and define the penetrance and outcomes of TTNtv in the general population. By integrating genetic, transcriptome, and protein analyses, we provide evidence for a length-dependent mechanism of disease. These data inform diagnostic criteria and management strategies for TTNtv-positive DCM patients and for TTNtv that are identified as incidental findings.
Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study
Authors: F. B Hu, M. J Stampfer, J. E Manson, E. B Rimm, G. A Colditz, B. A Rosner, F. E Speizer, C. H Hennekens, W. C Willett
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To examine the relation between nut consumption and risk of coronary heart disease in a cohort of women from the Nurses9 Health Study. <b>Design:</b> Prospective cohort study. <b>Setting:</b> Nurses9 Health Study. <b>Subjects:</b> 86&nbsp;016 women from 34&nbsp;to 59&nbsp;years of age without previously diagnosed coronary heart disease, stroke, or cancer at baseline in 1980. <b>Main outcome measures:</b> Major coronary heart disease including non-fatal myocardial infarction and fatal coronary heart disease. <b>Results:</b> 1255 major coronary disease events (861&nbsp;cases of non-fatal myocardial infarction and 394&nbsp;cases of fatal coronary heart disease) occurred during 14&nbsp;years of follow up. After adjusting for age, smoking, and other known risk factors for coronary heart disease, women who ate more than five units of nuts (one unit equivalent to 1&nbsp;oz of nuts) a week (frequent consumption) had a significantly lower risk of total coronary heart disease (relative risk 0.65,&nbsp;95% confidence interval 0.47&nbsp;to 0.89,&nbsp;P for trend=0.0009) than women who never ate nuts or who ate less than one unit a month (rare consumption). The magnitude of risk reduction was similar for both fatal coronary heart disease (0.61,&nbsp;0.35&nbsp;to 1.05, P for trend=0.007) and non-fatal myocardial infarction (0.68, 0.47&nbsp;to 1.00,&nbsp;P for trend=0.04). Further adjustment for intakes of dietary fats, fibre, vegetables, and fruits did not alter these results. The inverse association persisted in subgroups stratified by levels of smoking, use of alcohol, use of multivitamin and vitamin E supplements, body mass index, exercise, and intake of vegetables or fruits. <b>Conclusions:</b> Frequent nut consumption was associated with a reduced risk of both fatal coronary heart disease and non-fatal myocardial infarction. These data, and those from other epidemiological and clinical studies, support a role for nuts in reducing the risk of coronary heart disease.
Air Pollution, Smoking, and Plasma Homocysteine
Authors: Andrea Baccarelli, Antonella Zanobetti, Ida Martinelli, Paolo Grillo, Lifang Hou, Guido Lanzani, Pier Mannuccio Mannucci, Pier Alberto Bertazzi, Joel Schwartz
Journal: Environmental Health Perspectives (2006)

BackgroundMild hyperhomocysteinemia is independently associated with an increased risk of cardiovascular disease. Air pollution exposure induces short-term inflammatory changes that may determine hyperhomocysteinemia, particularly in the presence of a preexisting proinflammatory status such as that found in cigarette smokers.ObjectiveWe examined the relation of air pollution levels with fasting and postmethionine-load total homocysteine (tHcy) in 1,213 normal subjects from Lombardia, Italy.MethodsWe obtained hourly concentrations of particulate matter < 10 μm in aerodynamic diameter (PM10) and gaseous pollutants (carbon monoxide, nitrogen dioxide, sulfur dioxide, ozone) from 53 monitoring sites covering the study area. We applied generalized additive models to compute standardized regression coefficients controlled for age, sex, body mass index, smoking, alcohol, hormone use, temperature, day of the year, and long-term trends.ResultsThe estimated difference in tHcy associated with an interquartile increase in average PM10 concentrations in the 24 hr before the study was nonsignificant [0.4%; 95% confidence interval (CI), −2.4 to 3.3 for fasting; and 1.1%, 95% CI, −1.5 to 3.7 for postmethionine-load tHcy]. In smokers, 24-hr PM10 levels were associated with 6.3% (95% CI, 1.3 to 11.6; p < 0.05) and 4.9% (95% CI, 0.5 to 9.6; p < 0.05) increases in fasting and postmethionine-load tHcy, respectively, but no association was seen in nonsmokers (p-interaction = 0.005 for fasting and 0.039 for postmethionine-load tHcy). Average 24-hr O3 concentrations were associated with significant differences in fasting tHcy (6.7%; 95% CI, 0.9 to 12.8; p < 0.05), but no consistent associations were found when postmethionine-load tHcy and/or 7-day average O3 concentrations were considered.ConclusionsAir particles may interact with cigarette smoking and increase plasma homocysteine in healthy subjects.
Proposal of a prognostically relevant grading scheme for pulmonary squamous cell carcinoma
Authors: Wilko Weichert, Claudia Kossakowski, Alexander Harms, Peter Schirmacher, Thomas Muley, Hendrik Dienemann, Arne Warth
Journal: European Respiratory Journal (2015)

Recent studies in lung adenocarcinoma established a clinically relevant histomorphology-based classification. In contrast, no morphological classifiers have yet been implemented into routine diagnostics for lung squamous cell carcinoma (SQCC). However, morphology-based characteristics putatively impacting on survival have been proposed.We analysed a cohort of 541 SQCC patients with complete clinical follow-up data for morphological characteristics (keratinisation, tumour cell budding, size of tumour cell nests, nuclear size and stromal content). Morphological characteristics were correlated with clinical data and patient outcome.Keratinisation, budding, stromal content and tumour cell nest size, but not nuclear size, were associated with distinct clinicopathological characteristics and survival. SQCC patients with keratinisation, small cell nest size, high stromal content and extensive budding had shorter overall survival. A combined grading scheme composed of the two most reliable validated prognostic markers, i.e. budding and nest size, resulted in an age-, stage- and sex-independent prognosticator for overall survival with a hazard ratio of 1.6 for grade 2 tumours and a hazard ratio of 3.7 for grade 3 tumours when compared with grade 1 neoplasms (p<0.001).Morphological characteristics of SQCC have significant prognostic impact and could constitute the basis for a diagnostically relevant future SQCC grading scheme.
Cardiovascular Aging Is Associated With Vitamin E Increase
Authors: Bernd van der Loo, Ralf Labugger, Claude P. Aebischer, Jeremy N. Skepper, Markus Bachschmid, Volker Spitzer, Juliane Kilo, Lukas Altwegg, Volker Ullrich, Thomas F. Lüscher
Journal: Circulation (2002)

Background — Aging is an independent risk factor for the development of cardiovascular disease. Therefore, therapies to delay vascular aging may have enormous medical consequences. In this context, vitamin E is of particular interest, mainly because of its antioxidative properties. Methods and Results — In 3-year-old rats, which are not susceptible to atherosclerosis, vitamin E levels, as measured by reversed-phase high-performance liquid chromatography, were markedly increased both in plasma and in major organs ( P &lt;0.01 to P &lt;0.0001). The highest increase (at least 70-fold) was found in the aortic wall. Conclusions — This unexpected accumulation of vitamin E appears to be a compensatory mechanism that attempts to counterbalance age-associated oxidative stress and that may represent a self-regulatory protective adaptation.
Long-term safety aspects of systemic therapy with fumaric acid esters in severe psoriasis
Authors: J.J. Hoefnagel, H.B. Thio, R. Willemze, J.N. Bouwes Bavinck
Journal: British Journal of Dermatology (2003)

Therapy with fumaric acid esters (FAE) has been shown to be safe and effective in patients with severe psoriasis in several clinical studies with limited follow-up periods. In view of the chronic character of psoriasis, long-term safety aspects are of major importance in determining the suitability of a drug during prolonged periods of treatment.To investigate adverse events of therapy with systemic FAE with follow-up periods of up to 14 years, in order to determine safety aspects of their long-term use in patients with severe psoriasis.Current and/or past therapeutic use of FAE was reviewed in 66 patients with severe psoriasis.Forty-one of 66 patients had received FAE for at least 1 year, and 12 of these 41 patients had received FAE for between 10 and 14 years. Adverse events were reported in 73% of the patients. These were usually mild and mainly consisting of flushing (55%), diarrhoea (42%), nausea (14%), tiredness (14%) and stomach complaints (12%). A relative lymphocytopenia was observed in 76% of patients during therapy with FAE, resulting in a permanent discontinuation of therapy with FAE in four patients. A transient eosinophilia and moderate liver enzyme elevations were observed in 14% and 25% of patients, respectively.The present study indicates that FAE can be considered as a safe long-term treatment in patients with severe psoriasis.
Durable Remissions of Myelodysplastic Syndrome and Acute Myeloid Leukemia After Reduced-Intensity Allografting
Authors: D.C. Taussig, A.J. Davies, J.D. Cavenagh, H. Oakervee, D. Syndercombe-Court, S. Kelsey, J.A.L. Amess, A.Z.S. Rohatiner, T.A. Lister, M.J. Barnett
Journal: Journal of Clinical Oncology (2003)

To evaluate the use of reduced-intensity (RI) conditioning with allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-identical family donors in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).Sixteen patients (median age, 54 years; range, 37 to 66 years) underwent RI-HSCT using a conditioning regimen of fludarabine 25 mg/m2 daily for 5 days and either cyclophosphamide 1 g/m2 daily for 2 days (14 patients) or melphalan 140 mg/m2 for 1 day (two patients). The median number of CD34+ cells and CD3+ cells infused per kilogram of recipient weight was 4.5 x 106 (range, 1.8 to 7.3 x 106 cells) and 2.9 x 108 (range, 0.1 to 9.6 x 108 cells), respectively.There was no transplant-related mortality (TRM) within 100 days of HSCT. Grade 1 to 2 acute graft-versus-host disease (GVHD) occurred in three patients, but neither grade 3 nor grade 4 disease was observed. Chronic GVHD occurred in 10 patients. One patient had cytomegalovirus (CMV) reactivation but did not develop CMV disease. With a median follow-up of 26 months (range, 15 to 45 months), 11 patients are alive (nine in continuous complete remission and one in complete remission after a second transplantation), and five have died (four from disease progression and one from bone-marrow aplasia induced by cyclosporine withdrawal). The 2-year actuarial overall and event-free survival rates were 69% (95% confidence interval [CI], 40% to 86%) and 56% (95% CI, 30% to 68%), respectively.This strategy of RI-HSCT resulted in reliable engraftment with low incidence of acute GVHD and TRM. Durable remissions were observed in patients with MDS and AML consistent with a graft-versus-leukemia effect.
HLA C and D antigens associated with psoriasis
Authors: A.J. McMICHAEL, V. MORHENN, R. PAYNE, T. SASAZUKI, E.M. FARBER
Journal: British Journal of Dermatology (1978)

The frequency of two newly defined HLA antigens, HLA CT7 and DMA, was found to be greatly increased in patients with psoriasis. These two antigens and those previously found to be associated with the disease, B13, BW16 and BW17, frequently occurred together. The disease may be primarily associated with HLA DMA, or with the HLA haplotypes CT7--B13/W16/W17--DMA.
Pulmonary vasodilator response to vagal stimulation is blocked by N omega-nitro-L-arginine methyl ester in the cat.
Authors: T J McMahon, J S Hood, P J Kadowitz
Journal: Circulation Research (1992)

The effect of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor production, on the vasodilator response to efferent vagal stimulation was investigated in the pulmonary vascular bed of the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. When pulmonary vascular tone was increased with U46619, efferent vagal stimulation decreased lobar arterial pressure in a stimulus-frequency-dependent manner. The decreases in lobar arterial pressure were enhanced by pretreatment with reserpine, were blocked by atropine, and were not altered by propranolol, indicating that the neurogenic vasodilator response was cholinergic in nature. The decreases in lobar arterial pressure in response to vagal stimulation and to exogenously administered acetylcholine were reduced after administration of L-NAME (100 mg/kg i.v.). Although L-NAME decreased pulmonary vasodilator responses to vagal stimulation and to acetylcholine, responses to adenosine, nicorandil, lemakalim, isoproterenol, prostaglandin E1, sodium nitroprusside, and 8-bromo-cGMP, agents that act by a variety of mechanisms, were not decreased. These results are consistent with the hypothesis that efferent vagal stimulation releases acetylcholine, which dilates the pulmonary vascular bed by stimulating the production of nitric oxide or a labile nitroso compound from L-arginine.
CLONAL MEMORY
Authors: A. J. McMichael, A. R. Williamson
Journal: The Journal of Experimental Medicine (1974)

A single clone of B cells producing anti-DNP antibody recognizable by the isoelectric-focusing spectrum has been used, in a double transfer system, to study clonal memory. Trasnsferable B memory develops between 4 and 7 days after the first transfer with antigen. B-memory cells thus proliferate before or concomitantly with antibody-forming cells.
Inhibition of platelet prostaglandin synthetase by oral aspirin.
Authors: J W Burch, N Stanford, P W Majerus
Journal: Journal of Clinical Investigation (1978)

Aspirin inhibits platelet function by permanently acetylating the cyclooxygenase that forms prostaglandins. We determined the sensitivity of platelets to aspirin in normal subjects by measuring [3H-acetyl]aspirin-susceptible cyclooxygenase in washed platelets obtained at various times after aspirin ingestion. A single 325-mg aspirin dose inactivated 89% of platelet cyclooxygenase. The inhibition persisted for 2 days suggesting that oral aspirin also inactivated megakaryocyte cyclooxygenase. Thereafter, active enzyme returned with a time-course reflecting platelet turnover (life-span 8.2+/-2 days). Single doses of 20-650 mg aspirin resulted in 34- greater than 95% inhibition after 24 h. Daily doses of 20-325 mg aspirin for brief periods produced 61- greater than 95% inactivation when measured 24 h after cessation of the drug. Platelet cyclooxygenase is more sensitive to inactivation by aspirin than enzyme in sheep seminal vesicles.
Gefitinib in Pretreated Non–Small-Cell Lung Cancer (NSCLC): Analysis of Efficacy and Correlation With HER2 and Epidermal Growth Factor Receptor Expression in Locally Advanced or Metastatic NSCLC
Authors: Federico Cappuzzo, Vanesa Gregorc, Elisa Rossi, Alessandra Cancellieri, Elisabetta Magrini, Carlo Terenzio Paties, Giovanni Ceresoli, Laura Lombardo, Stefania Bartolini, Cesare Calandri, Marisa De Rosa, Eugenio Villa, Lucio Crinò
Journal: Journal of Clinical Oncology (2003)

To evaluate the correlation between HER2 expression and gefitinib (ZD 1839, Iressa; AstraZeneca, London, United Kingdom) efficacy in terms of response rate, time to progression (TTP), and overall survival (OS) time.Patients with pretreated advanced non-small-cell lung cancer (NSCLC) received gefitinib at a daily dose of 250 mg until disease progression. Tumor tissue specimens obtained at the time of primary diagnosis were collected to determine HER2/epidermal growth factor receptor (EGFR) status by immunohistochemistry.From February 2001 to June 2002, 63 consecutive patients were enrolled onto the study. The overall disease control rate was 58.7% (partial response [PR], 15.9%; stable disease [SD], 42.8%), median TTP was 3.3 months, and median OS was 4.1 months. Among the 43 patients in whom EGFR/HER2 status was determined, we observed six PRs (14%) and 18 SDs (42%). Disease control, including PR and SD, was 40% in the 15 patients overexpressing HER2 and 64.3% in the 28 patients not overexpressing HER2 (P =.126). No difference was found between the two groups in terms of TTP (3.5 v 3.7 months, respectively) and OS (5.7 v 6.8 months, respectively). In addition, we did not find any difference in TTP, OS, toxicity, and symptom outcome in the group of patients overexpressing both HER2 and EGFR compared with patients who had no overexpression of HER2According to these data, efficacy, toxicity, and symptom outcome in patients with NSCLC treated with gefitinib do not seem to be related to HER2 expression.