tbuckley/cabot-search huggingface dataset:
Deficiencies of Cardiovascular Risk Prediction Models for Type 1 Diabetes
Authors: Janice C. Zgibor, Gretchen A. Piatt, Kristine Ruppert, Trevor J. Orchard, Mark S. Roberts
Journal: Diabetes Care (2006)

OBJECTIVE—Cardiovascular risk prediction models are available for the general population (Framingham) and for type 2 diabetes (U.K. Prospective Diabetes Study [UKPDS] Risk Engine) but may not be appropriate in type 1 diabetes, as risk factors including younger age at diabetes onset and presence of diabetes complications are not considered. Therefore, our objective was to examine the accuracy of Framingham and UKPDS models for predicting coronary heart disease (CHD) in a type 1 diabetic cohort. RESEARCH DESIGN AND METHODS—Ten-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a prospective cohort study of 658 subjects with childhood-onset type 1 diabetes diagnosed between 1950 and 1980 first seen in 1986–1988, were analyzed. EDC study data were used to calculate the 10-year probability of CHD (fatal CHD, nonfatal myocardial infarction, or Q-waves) applying to the Framingham and UKPDS equations. RESULTS—Mean age at CHD onset was 39 years. When fatal/nonfatal myocardial infarction and CHD death were modeled, both the UKPDS and Framingham models showed significant lack of calibration (P &amp;lt; 0.0001) but moderate discrimination (0.76 UKPDS, 0.77 Framingham men, and 0.88 Framingham women). Both the UKPDS and Framingham models underestimated probability of events in highest risk deciles. CONCLUSIONS—Currently available CHD models poorly predict events in type 1 diabetes. Future research should focus on determining the risk factors accounting for the lack of fit and developing prediction models specific to this high-risk group.
Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis
Authors: Marc I. Chimowitz, Michael J. Lynn, Colin P. Derdeyn, Tanya N. Turan, David Fiorella, Bethany F. Lane, L. Scott Janis, Helmi L. Lutsep, Stanley L. Barnwell, Michael F. Waters, Brian L. Hoh, J. Maurice Hourihane, Elad I. Levy, Andrei V. Alexandrov, Mark R. Harrigan, David Chiu, Richard Paul Klucznik, Joni M. Clark, Cameron G. McDougall, Mark D. Johnson, G. Lee Pride, Michel T. Torbey, Osama O. Zaidat, Zoran Rumboldt, Harry J. Cloft
Journal: New England Journal of Medicine (2011)

Atherosclerotic intracranial arterial stenosis is an important cause of stroke that is increasingly being treated with percutaneous transluminal angioplasty and stenting (PTAS) to prevent recurrent stroke. However, PTAS has not been compared with medical management in a randomized trial.
Tyrosine phosphorylation of an interleukin 2 receptor-like protein in cells transformed by human T cell leukemia virus type I.
Authors: R Ogawa, K Sugamura, Y Watanabe
Journal: The Journal of Experimental Medicine (1987)

Three interleukin 2 (IL-2)-independent human T cell lines transformed with human T cell leukemia virus type I were analyzed for o-phosphotyrosine-containing proteins (Ptyr proteins). Membrane and intracellular immunofluorescence was positive with antibody to Ptyr (Ptyr antibody). 10 size classes of Ptyr proteins with molecular masses of 81-28 kD were isolated with Ptyr antibodies. Among these, proteins of 64 kD (pI 4.5 and 4.8-5.3) and 45 kD (pI 4.3) were found on the outer cell surface. The Ptyr protein of 64 kD (pI 4.5) had the characteristics of the IL-2 receptor (IL-2-R) in that it was recognized by two monoclonal antibodies directed against different epitopes on the IL-2-R.
Interleukin 7 stimulates tumour necrosis factor alpha and Th1 cytokine production in joints of patients with rheumatoid arthritis
Authors: J A G van Roon
Journal: Annals of the Rheumatic Diseases (2003)

<b>Background:</b> A large number of activated T cells are found in the joints of patients with rheumatoid arthritis (RA). Interleukin 7 (IL7), a T cell growth factor and a regulator of Th1 and Th2 cytokine production, is produced by synoviocytes from patients with RA. <b>Objective:</b> To investigate the effect on proinflammatory cytokine production of synovial fluid mononuclear cells (SFMC) and the mechanism by which IL7 influences CD4+ T cell activity in patients with RA. <b>Methods:</b> In a cross sectional group of patients with RA, IL7 levels were compared with those of healthy controls and related to disease activity. The effect of IL7 on cytokine production was tested by RA SFMC and on SF CD4+ T cells in the presence of mononuclear cells (MC). Production of tumour necrosis factor α (TNFα), IL1β, interferon γ (IFNγ), and IL4 was measured by enzyme linked immunosorbent assay (ELISA) and by single cell FACS analysis. Expression of the IL7 receptor α chain on CD4+ T cells (essential for IL7 signalling) was assessed. Direct effects of IL7 on isolated synovial fluid (SF) CD4+ T cells were studied by cytokine analysis. By neutralisation of IL12 in MC cultures, indirect effects of IL7 on T cells through accessory cells were studied. <b>Results:</b> IL7 serum levels were higher in patients with RA than in healthy controls and correlated positively with C reactive protein levels. IL7 stimulated TNFα production by SFMC and very potently stimulated IFNγ and TNFα production by SF CD4+ T cells. These effects were probably mediated through the IL7 receptor α chain, which was abundantly expressed on SF CD4+ T cells. Besides the direct stimulation of T cell cytokine production by IL7, its action was partly dependent on IL12, indicating that IL7 also stimulates accessory cell function, leading to T cell activation. <b>Conclusion:</b> IL7 stimulates proinflammatory cytokine production of intra-articular CD4+ T cells and accessory cells from patients with RA. The correlation with measures of disease activity indicates that IL7 might substantially contribute to the perpetuation of Th1 and TNFα mediated proinflammatory responses in patients with RA.
Treatment of Hyperglycemia in a 7-Year-Old Child Diagnosed With Neonatal Diabetes
Authors: Eba Hathout, John Mace, Graeme I. Bell, Pål R. Njølstad
Journal: Diabetes Care (2006)

Permanent neonatal diabetes is persistent, insulin-requiring hyperglycemia occurring before 1 month of life. Recent studies have identified activating mutations in KCNJ11 encoding the Kir6.2 subunit of the ATP-sensitive K+ channel as a common cause of neonatal diabetes (1,2,3,4,5). These patients can be successfully managed with oral sulfonylureas rather than insulin (2 …
Replication of a Genetic Association between Polymorphisms in KCNMA1 and Asthma in Six Populations of African Ancestry
Authors: V.J. Mantese, N. Rafaels, T. Murray, C. Vergara, L. Gao, M.I. Araujo, L. Caraballo, J.M. Knight-Madden, J. Ford, G. Dunston
Journal: Journal of Allergy and Clinical Immunology (2011)
KATP activation prevents progression of cardiac hypertrophy to failure induced by pressure overload via protecting endothelial function
Authors: S. Gao, C.-L. Long, R.-H. Wang, H. Wang
Journal: Cardiovascular Research (2009)

We investigated the effects of iptakalim, a new ATP-sensitive potassium channel (KATP) opener providing endothelial protection, on the progression of cardiac hypertrophy to failure in a rat model of pressure overloading caused by abdominal aortic banding (AAB). Endothelial dysfunction is central to cardiac hypertrophy and failure induced by pressure overload. It would be useful to clarify whether iptakalim could prevent this. The effects of pressure overload were assessed in male Sprague–Dawley rats 6 weeks after AAB using progression of cardiac hypertrophy to heart failure as the endpoint. The AAB-treated rats had significantly elevated blood pressure, systolic and diastolic cardiac dysfunction, evidence of left ventricular hypertrophy (LVH), and transition to heart failure. LVH was characterized by increases in the ratios of heart and left ventricular weights to body weight, increased myocyte cross-sectional areas, myocardial and perivascular fibrosis, and elevated cardiac hydroxyproline. These could be prevented by treatment with iptakalim at daily oral doses of 1, 3, and 9 mg/kg for 6 weeks. Progression to cardiac failure, demonstrated by increases in relative lung and right ventricular weights, cardiac function disorders and overexpression of atrial and B-type natriuretic peptide mRNA, could also be prevented. The downregulated nitric oxide signalling system was enhanced, whereas the upregulated endothelin signalling system was inhibited, resulting in normalization of the balance between these two systems. Iptakalim protected the endothelium and prevented progression of cardiac hypertrophy to failure induced by a pressure overload.
Occupational asthma caused by iroko wood
Authors: J. Azofra, J. M. Olaguibel
Journal: Allergy (1989)

We report on a patient with occupational asthma caused by iroko. BPT induced an early and late response with a long recovery period, and absence of inhibition on pretreatment with cromoglycate and beclomethasone. Three months after leaving his job, the patient was symptom‐free, but non‐specific bronchial hyperreactivity was still demonstrated.
Selective BCG vaccination in a country with low incidence of tuberculosis
Authors: V Romanus
Journal: Eurosurveillance (2006)

In 1975 the BCG vaccination policy in Sweden changed from routine vaccination of all newborn infants to selective vaccination of groups at higher risk. This report aims to evaluate the present BCG policy, with focus on the tuberculosis situation in Sweden during the period from 1989 to 2005. The population structure in Sweden has changed, with increasing numbers and proportions of people who were born outside Sweden, especially in countries with high prevalence of tuberculosis. BCG vaccination coverage fell from more than 95% before 1975 to less than 2% in 1976 to 1980, and then again increased to around 16% (corresponding to about 88% of the risk group recommended for vaccination). The increasing proportion of foreign born tuberculosis patients among all tuberculosis cases of illness in Sweden, and the high age-specific incidence of tuberculosis in the childbearing age groups in the foreign-born population, indicate the need to continue selective vaccination of children in families originating from countries with high tuberculosis incidence. The cumulative incidence of tuberculosis in the 30 cohorts born in Sweden after 1974 and observed to the end of 2004 was estimated at 0.5 cases per 100 000 person-years. Sweden still has one of the lowest incidences of tuberculosis in the world, which means a minimal average risk of infection for the majority of children born to Swedish parents. The observed increase of tuberculosis in 2005, partly attributed to an outbreak at a day nursery, is a reminder of the serious consequences of delayed diagnosis. Intensified active case finding is the most important action to prevent childhood tuberculosis, by means of eliminating the sources of infection to prevent transmission to the child population. Early detection and treatment of infected children is necessary to prevent development of serious disseminated tuberculosis.
Systematic Review of Microsatellite Instability and Colorectal Cancer Prognosis
Authors: S. Popat, R. Hubner, R.S. Houlston
Journal: Journal of Clinical Oncology (2005)

A number of studies have investigated the relationship between microsatellite instability (MSI) and colorectal cancer (CRC) prognosis. Although many have reported a better survival with MSI, estimates of the hazard ratio (HR) among studies differ. To derive a more precise estimate of the prognostic significance of MSI, we have reviewed and pooled data from published studies.Studies stratifying survival in CRC patients by MSI status were eligible for analysis. The principal outcome measure was the HR. Data from eligible studies were pooled using standard techniques.Thirty-two eligible studies reported survival in a total of 7,642 cases, including 1,277 with MSI. There was no evidence of publication bias. The combined HR estimate for overall survival associated with MSI was 0.65 (95% CI, 0.59 to 0.71; heterogeneity P = .16; I(2) = 20%). This benefit was maintained restricting analyses to clinical trial patients (HR = 0.69; 95% CI, 0.56 to 0.85) and patients with locally advanced CRC (HR = 0.67; 95% CI, 0.58 to 0.78). In patients treated with adjuvant fluorouracil (FU) CRCs with MSI had a better prognosis (HR = 0.72; 95% CI, 0.61 to 0.84). However, while data are limited, tumors with MSI derived no benefit from adjuvant FU (HR = 1.24; 95% CI, 0.72 to 2.14).CRCs with MSI have a significantly better prognosis compared to those with intact mismatch repair. Additional studies are needed to further define the benefit of adjuvant chemotherapy in locally advanced tumors with MSI.
Exposure to Dogs and Cats in the First Year of Life and Risk of Allergic Sensitization at 6 to 7 Years of Age
Authors: Dennis R. Ownby, Christine Cole Johnson, Edward L. Peterson
Journal: JAMA (2002)

OF asthma in the United States and other developed countries over the last few decades has been a cause for concern. 1,24][5][6] Many studies have attempted to elucidate relationships between environmental exposures, especially during infancy, and the risk of allergic sensitization in later life. 7,8These studies are based on the theory that an individual's genetic predisposition to allergic disease is activated or enhanced by early allergen exposure. 4,7,9The outcome of interactions between genetic influences and allergen exposures may be influenced by other environmental exposures, such as passive exposure to environmental tobacco smoke. 7,9If these relationships were better understood it might become possible to reduce the prevalence of allergic sensitization and perhaps asthma in children.Exposure to dogs and cats during infancy has been thought to increase the
Insulin Resistance Is Associated With a Poor Response to Intravenous Thrombolysis in Acute Ischemic Stroke
Authors: Ana I. Calleja, Pablo García-Bermejo, Elisa Cortijo, Rosa Bustamante, Esther Rojo Martínez, Enrique González Sarmiento, Rosa Fernández-Herranz, Juan F. Arenillas
Journal: Diabetes Care (2011)

OBJECTIVE Insulin resistance (IR) may not only increase stroke risk, but could also contribute to aggravate stroke prognosis. Mainly through a derangement in endogenous fibrinolysis, IR could affect the response to intravenous thrombolysis, currently the only therapy proved to be efficacious for acute ischemic stroke. We hypothesized that high IR is associated with more persistent arterial occlusions and poorer long-term outcome after stroke thrombolysis. RESEARCH DESIGN AND METHODS We performed a prospective, observational, longitudinal study in consecutive acute ischemic stroke patients presenting with middle cerebral artery (MCA) occlusion who received intravenous thrombolysis. Patients with acute hyperglycemia (≥155 mg/dL) receiving insulin were excluded. IR was determined during admission by the homeostatic model assessment index (HOMA-IR). Poor long-term outcome, as defined by a day 90 modified Rankin scale score ≥3, was considered the primary outcome variable. Transcranial Duplex-assessed resistance to MCA recanalization and symptomatic hemorrhagic transformation were considered secondary end points. RESULTS A total of 109 thrombolysed MCA ischemic stroke patients were included (43.1% women, mean age 71 years). The HOMA-IR was higher in the group of patients with poor outcome (P = 0.02). The probability of good outcome decreased gradually with increasing HOMA-IR tertiles (80.6%, 1st tertile; 71.4%, 2nd tertile; and 55.3%, upper tertile). A HOMA-IR in the upper tertile was independently associated with poor outcome when compared with the lower tertile (odds ratio [OR] 8.54 [95% CI 1.67–43.55]; P = 0.01) and was associated with more persistent MCA occlusions (OR 8.2 [1.23–54.44]; P = 0.029). CONCLUSIONS High IR may be associated with more persistent arterial occlusions and worse long-term outcome after acute ischemic stroke thrombolysis.
Medical complications and deaths in 21 and 56 km road race runners: a 4-year prospective study in 65 865 runners—SAFER study I
Authors: Karen Schwabe, Martin Schwellnus, Wayne Derman, Sonja Swanevelder, Esme Jordaan
Journal: British Journal of Sports Medicine (2014)

Background Cardiac arrest and sudden death during distance-running events have been reported but other medical complications, including serious life-threatening complications have not been well described. Objective To document the incidence and nature of medical complications during 21 and 56 km running races. Design Prospective study. Setting Two Oceans Marathon races (21 and 56 km races). Participants 65 865 race starters (39 511—21 km runners, 26 354—56 km runners). Methods Medical complications (defined as any runner requiring assessment by a doctor at the race medical facility or a local hospital on race day) were recorded in each of the 4 years of the study period. Complications were further subdivided into serious (potentially life-threatening) complications and deaths and were also analysed by system and final diagnosis. Results In the 4 years, 545 medical complications were recorded, resulting in an overall incidence (per 1000 race starters) of 8.27. The incidence of serious (potentially life-threatening) medical complications was 0.56 (37 serious complications). Two deaths occurred in 21 km runners (incidence of 0.05). The most common specific medical complications were exercise-associated collapse (postural hypotension), dermatological conditions, musculoskeletal injuries and serious exercise-associated muscle cramping. Conclusions The incidence of medical complications was higher in 56 km runners but sudden cardiac deaths only occurred in 21 km runners. Serious medical complications were as common in 21 km as in 56 km runners. Risk factors for medical complications need to be determined in 21 and 56 km runners to plan strategies to reduce the risk of adverse medical events in endurance runners.
A HIGH SPEED VACUUM CENTRIFUGE SUITABLE FOR THE STUDY OF FILTERABLE VIRUSES
Authors: Johannes H. Bauer, Edward G. Pickels
Journal: The Journal of Experimental Medicine (1936)

1. A high speed centrifuge is described in which the speed is limited only by the strength of the material of which the rotor is made. It carries sixteen tubes, each of which conveniently accommodates 7 cc. of fluid. 2. The centrifuge operates in a very high vacuum and therefore requires only a small amount of driving energy. The arrangement has been found to eliminate the possibility of producing injurious frictional heat. 3. The rotating parts are supported by anair-bearing and are driven by compressed air. 4. The centrifuge has been successfully operated at a speed of 30,000 revolutions per minute, representing a maximum centrifugal force in the fluid of 95,000 times gravity. 5 Celluloid tubes used for centrifugation of fluid at high speeds are described. 6. Experiments are described in which good sedimentation of the yellow fever virus was obtained.
Mitral Stenosis with Exertional Cyanosis and Pulmonary Hemosiderosis
Authors: JAMES A. WIER, AMO J. PICCOLI, DAVID G. GREENE, CLAYTON W. GREENE
Journal: Circulation (1952)

A patient with mitral stenosis is reported who suffered from exertional cyanosis for the last eight years of his life. Radiologic examination of his chest demonstrated a diffuse pulmonary hemosiderosis, which was confirmed at autopsy. Physiologic studies in the last few weeks of life showed that the cyanosis was not due to impairment of oxygenation of the blood in the lungs but rather to slowed circulation, possibly augmented by local changes in the anatomy of the vessels of the skin.
The Evolution of Human Cells in Terms of Protein Innovation
Authors: Adam J. Sardar, Matt E. Oates, Hai Fang, Alistair R.R. Forrest, Hideya Kawaji, Julian Gough, Owen J.L. Rackham
Journal: Molecular Biology and Evolution (2014)

Humans are composed of hundreds of cell types. As the genomic DNA of each somatic cell is identical, cell type is determined by what is expressed and when. Until recently, little has been reported about the determinants of human cell identity, particularly from the joint perspective of gene evolution and expression. Here, we chart the evolutionary past of all documented human cell types via the collective histories of proteins, the principal product of gene expression. FANTOM5 data provide cell-type–specific digital expression of human protein-coding genes and the SUPERFAMILY resource is used to provide protein domain annotation. The evolutionary epoch in which each protein was created is inferred by comparison with domain annotation of all other completely sequenced genomes. Studying the distribution across epochs of genes expressed in each cell type reveals insights into human cellular evolution in terms of protein innovation. For each cell type, its history of protein innovation is charted based on the genes it expresses. Combining the histories of all cell types enables us to create a timeline of cell evolution. This timeline identifies the possibility that our common ancestor Coelomata (cavity-forming animals) provided the innovation required for the innate immune system, whereas cells which now form the brain of human have followed a trajectory of continually accumulating novel proteins since Opisthokonta (boundary of animals and fungi). We conclude that exaptation of existing domain architectures into new contexts is the dominant source of cell-type–specific domain architectures.
A Key Role for Matrix Metalloproteinases and Neutral Sphingomyelinase-2 in Transplant Vasculopathy Triggered by Anti-HLA Antibody
Authors: Sylvain Galvani, Magali Trayssac, Nathalie Augé, Jean-Claude Thiers, Denis Calise, Hans-Willi Krell, Federico Sallusto, Nassim Kamar, Lionel Rostaing, Mogens Thomsen, Anne Nègre-Salvayre, Robert Salvayre
Journal: Circulation (2011)

Outcomes for organ transplantation are constantly improving because of advances in organ preservation, surgical techniques, immune clinical monitoring, and immunosuppressive treatment preventing acute transplant rejection. However, chronic rejection including transplant vasculopathy still limits long-term patient survival. Transplant vasculopathy is characterized by progressive neointimal hyperplasia leading to arterial stenosis and ischemic failure of the allograft. This work sought to decipher the manner in which the humoral immune response, mimicked by W6/32 anti-HLA antibody, contributes to transplant vasculopathy.Studies were performed in vitro on cultured human smooth muscle cells, ex vivo on human arterial segments, and in vivo in a model consisting of human arterial segments grafted into severe combined immunodeficiency/beige mice injected weekly with anti-HLA antibodies. We report that anti-HLA antibodies are mitogenic for smooth muscle cells through a signaling mechanism implicating matrix metalloproteinases (MMPs) (membrane type 1 MMP and MMP2) and neutral sphingomyelinase-2. This mitogenic signaling and subsequent DNA synthesis are blocked in smooth muscle cells silenced for MMP2 or for neutral sphingomyelinase-2 by small interfering RNAs, in smooth muscle cells transfected with a vector coding for a dominant-negative form of membrane type 1 MMP, and after treatment by pharmacological inhibitors of MMPs (Ro28-2653) or neutral sphingomyelinase-2 (GW4869). In vivo, Ro28-2653 and GW4869 reduced the intimal thickening induced by anti-HLA antibodies in human mesenteric arteries grafted into severe combined immunodeficiency/beige mice.These data highlight a crucial role for MMP2 and neutral sphingomyelinase-2 in vasculopathy triggered by a humoral immune response and open new perspectives for preventing transplant vasculopathy with the use of MMP and neutral sphingomyelinase inhibitors, in addition to conventional immunosuppression.