tbuckley/cabot-search huggingface dataset:
Role of Genetic Polymorphism Peroxisome Proliferator–Activated Receptor-γ2 Pro12Ala on Ethnic Susceptibility to Diabetes in South-Asian and Caucasian Subjects
Authors: Venkatesan Radha, Karani S. Vimaleswaran, Hunsur Narayan S. Babu, Nicola Abate, Manisha Chandalia, Pankaj Satija, Scott M. Grundy, Saurabh Ghosh, Partha P. Majumder, Raj Deepa, Sathyanarayana M.R. Rao, Viswanathan Mohan
Journal: Diabetes Care (2006)

OBJECTIVE—To determine whether the peroxisome proliferator–activated receptor (PPAR)-γ Pro12ala polymorphism modulates susceptibility to diabetes in South Asians. RESEARCH DESIGN AND METHODS—South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-γ Pro12Ala was determined using restriction fragment–length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects. RESULTS—The Caucasian diabetic subjects had significantly lower prevalence of PPAR-γ 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR-γ Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 ± 68 and 54 ± 33 μU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-γ Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas. CONCLUSIONS—Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-γ Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.
Evidence for time-dependent activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina.
Authors: B Jude, B Agraou, E P McFadden, S Susen, C Bauters, P Lepelley, C Vanhaesbroucke, P Devos, A Cosson, P Asseman
Journal: Circulation (1994)

BACKGROUND Platelet activation plays a pivotal role in the pathogenesis of acute coronary disease. Monocytes are involved in the progression of atherosclerosis and are potent activators of blood coagulation through their ability to synthesize tissue factor (TF). The aim of this study was to compare markers of monocyte and coagulation activation in the systemic blood of patients with unstable angina, acute myocardial infarction, or stable angina. METHODS AND RESULTS We studied 26 patients with unstable angina (10 +/- 5 hours after the onset of the last episode of pain), 18 patients with acute myocardial infarction (5 +/- 4 hours after the onset of pain), and 34 patients with stable angina. We measured levels of TF expression in peripheral blood mononuclear cells (isolated by gradient centrifugation and incubated for 16 hours, with or without endotoxin stimulation), levels of plasma prothrombin fragment 1 + 2 (F1 + 2), and levels of fibrinogen in peripheral blood. In patients with unstable angina, both stimulated and unstimulated cells exhibited higher levels of TF expression than in patients with stable angina (P = .0001). In patients with acute myocardial infarction, monocyte TF activity did not differ from that in patients with stable angina. Mean levels of F1 + 2 and of fibrinogen did not differ significantly between groups. Only in the unstable angina group, a modest correlation was found between fibrinogen (r = .72, P = .005) and F1 + 2 levels (r = .54, P = .001) levels and the degree of monocyte TF expression. In patients with unstable angina, monocyte TF expression (both stimulated and unstimulated, assessed by biological activity and by antigen techniques) and fibrinogen levels were correlated with the time elapsed from the beginning of the most recent episode of pain (.61 &lt; r &lt; .72, .02 &lt; P &lt; .0001). By contrast, there was no correlation between these variables and the time from onset of pain in patients with acute myocardial infarction. CONCLUSIONS A time-dependent activation of systemic monocytes and a time-dependent increase in fibrinogen levels occurs in unstable angina but not in myocardial infarction. These findings provide further evidence that a specific inflammatory process occurs in unstable angina. Further studies are required to determine whether monocyte activation is a cause or a consequence of plaque instability in patients with unstable angina and to clarify the interrelations between platelet and monocyte activation in these circumstances.
IDENTIFICATION OF MARROW-DERIVED AND THYMUS-DERIVED SMALL LYMPHOCYTES IN THE LYMPHOID TISSUE AND THORACIC DUCT LYMPH OF NORMAL RATS
Authors: Jonathan C. Howard, S. V. Hunt, J. L. Gowans
Journal: The Journal of Experimental Medicine (1972)

These experiments show that small lymphocytes from the thoracic duct of rats are normally a mixture of thymus-derived and marrow-derived cells, and define the traffic areas in lymphoid tissues through which the two populations recirculate. Thoracic duct lymphocytes were labeled in vitro with uridine-3H and their histological distribution in the lymphoid tissues of normal recipients was demonstrated by radioautography. Labeled lymphocytes occupied two adjacent areas distinguished by a marked difference in the intensity of labeling; heavily labeled cells were found in thymus-dependent traffic areas of lymphocyte recirculation, while lightly labeled cells localized in the thymus-independent follicular areas around germinal centers. A corresponding heterogeneity of uridine uptake among small lymphocytes from normal donors was demonstrated by sedimentation at 1 g; slowly sedimenting cells incorporated little uridine and localized in follicular areas after transfusion while rapidly sedimenting cells incorporated more uridine and localized in thymus-dependent areas after transfusion. Experimentally prepared marrow-derived small lymphocytes behaved in sedimentation studies and after transfusion like a pure population of the lightly labeled small lymphocytes in normal lymph. Artificially reconstituted mixtures of marrow-derived and thymus-derived lymphocytes were qualitatively indistinguishable from normal lymphocyte populations.
Outcome of Critically Ill Allogeneic Hematopoietic Stem-Cell Transplantation Recipients: A Reappraisal of Indications for Organ Failure Supports
Authors: Frédéric Pène, Cécile Aubron, Elie Azoulay, François Blot, Guillaume Thiéry, Bruno Raynard, Benoît Schlemmer, Gérard Nitenberg, Agnès Buzyn, Philippe Arnaud, Gérard Socié, Jean-Paul Mira
Journal: Journal of Clinical Oncology (2005)

Because the overall outcome of critically ill hematologic patients has improved, we evaluated the short-term and long-term outcomes of the poor risk subgroup of allogeneic hematopoietic stem-cell transplantation (HSCT) recipients requiring admission to the intensive care unit (ICU).This was a retrospective multicenter study of allogeneic HSCT recipients admitted to the ICU between 1997 and 2003.Two hundred nine critically ill allogeneic HSCT recipients were included in the study. Admission in the ICU occurred during the engraftment period (< or = 30 days after transplantation) for 70 of the patients and after the engraftment period for 139 patients. The overall in-ICU, in-hospital, 6-month, and 1-year survival rates were 48.3%, 32.5%, 27.2%, and 21%, respectively. Mechanical ventilation was required in 122 patients and led to a dramatic decrease in survival rates, resulting in in-ICU, in-hospital, 6-month, and 1-year survival rates of 18%, 15.6%, 14%, and 10.6%, respectively. Mechanical ventilation, elevated bilirubin level, and corticosteroid treatment for the indication of active graft-versus-host disease (GVHD) were independent predictors of death in the whole cohort. In the subgroup of patients requiring mechanical ventilation, associated organ failures, such as shock and liver dysfunction, were independent predictors of death. ICU admission during engraftment period was associated with acceptable outcome in mechanically ventilated patients, whereas patients with late complications of HSCT in the setting of active GVHD had a poor outcome.Extensive unlimited intensive care support is justified for allogeneic HSCT recipients with complications occurring during the engraftment period. Conversely, initiation or maintenance of mechanical ventilation is questionable in the setting of active GVHD.
Rescue of retinal degeneration by intravitreally injected adult bone marrow–derived lineage-negative hematopoietic stem cells
Authors: Atsushi Otani, Michael Ian Dorrell, Karen Kinder, Stacey K. Moreno, Steven Nusinowitz, Eyal Banin, John Heckenlively, Martin Friedlander
Journal: Journal of Clinical Investigation (2004)

Inherited retinal degenerations afflict 1 in 3,500 individuals and are a heterogeneous group of diseases that result in profound vision loss, usually the result of retinal neuronal apoptosis. Atrophic changes in the retinal vasculature are also observed in many of these degenerations. While it is thought that this atrophy is secondary to diminished metabolic demand in the face of retinal degeneration, the precise relationship between the retinal neuronal and vascular degeneration is not clear. In this study we demonstrate that whenever a fraction of mouse or human adult bone marrow–derived stem cells (lineage-negative hematopoietic stem cells [Lin– HSCs]) containing endothelial precursors stabilizes and rescues retinal blood vessels that would ordinarily completely degenerate, a dramatic neurotrophic rescue effect is also observed. Retinal nuclear layers are preserved in 2 mouse models of retinal degeneration, rd1 and rd10, and detectable, albeit severely abnormal, electroretinogram recordings are observed in rescued mice at times when they are never observed in control-treated or untreated eyes. The normal mouse retina consists predominantly of rods, but the rescued cells after treatment with Lin– HSCs are nearly all cones. Microarray analysis of rescued retinas demonstrates significant upregulation of many antiapoptotic genes, including small heat shock proteins and transcription factors. These results suggest a new paradigm for thinking about the relationship between vasculature and associated retinal neuronal tissue as well as a potential treatment for delaying the progression of vision loss associated with retinal degeneration regardless of the underlying genetic defect.
Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial
Authors: P Verschueren, D De Cock, L Corluy, R Joos, C Langenaken, V Taelman, F Raeman, I Ravelingien, K Vandevyvere, J Lenaerts, E Geens, P Geusens, J Vanhoof, A Durnez, J Remans, B Vander Cruyssen, E Van Essche, A Sileghem, G De Brabanter, J Joly, S Meyfroidt, K Van der Elst, R Westhovens
Journal: Annals of the Rheumatic Diseases (2014)

To compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial.400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified into high risk or low risk according to classical prognostic markers. High-risk patients (n=290) were randomised to 1/3 treatment strategies: combination therapy for early rheumatoid arthritis (COBRA) Classic (methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7.5 mg daily from W7), COBRA Slim (MTX+30 mg prednisone tapered to 5 mg from W6) and COBRA Avant-Garde (MTX+leflunomide+30 mg prednisone tapered to 5 mg from W6). Treatment modifications to target low-disease activity were mandatory from W8, if desirable and feasible according to the rheumatologist. The primary outcome was remission (28 joint disease activity score calculated with C-reactive protein <2.6) at W16 (intention-to-treat analysis). Secondary endpoints were good European League Against Rheumatism response, clinically meaningful health assessment questionnaire (HAQ) response and HAQ equal to zero. Adverse events (AEs) were registered.Data from 98 Classic, 98 Slim and 94 Avant-Garde patients were analysed. At W16, remission was reached in 70.4% Classic, 73.6% Slim and 68.1% Avant-Garde patients (p=0.713). Likewise, no significant differences were shown in other secondary endpoints. However, therapy-related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006).For high-risk eRA, MTX associated with a moderate step-down dose of GCs was as effective in inducing remission at W16 as DMARD combination therapies with moderate or high step-down GC doses and it showed a more favourable short-term safety profile.2008-007225-39.
Transglutaminase 4 as a prostate autoantigen in male subfertility
Authors: Nils Landegren, Donald Sharon, Anthony K. Shum, Imran S. Khan, Kayla J. Fasano, Åsa Hallgren, Caroline Kampf, Eva Freyhult, Brita Ardesjö-Lundgren, Mohammad Alimohammadi, Sandra Rathsman, Jonas F. Ludvigsson, Dan Lundh, Ruben Motrich, Virginia Rivero, Lawrence Fong, Aleksander Giwercman, Jan Gustafsson, Jaakko Perheentupa, Eystein S. Husebye, Mark S. Anderson, Michael Snyder, Olle Kämpe
Journal: Science Translational Medicine (2015)

TGM4 is a male-specific autoantigen for prostatitis associated with autoimmune polyendocrine syndrome type 1.
Value of Myoglobin, Troponin T, and CK-MB <sub>mass</sub> in Ruling Out an Acute Myocardial Infarction in the Emergency Room
Authors: Robbert J. de Winter, Rudolph W. Koster, Augueste Sturk, Gerard T. Sanders
Journal: Circulation (1995)

Background Ruling out acute myocardial infarction (AMI) on the basis of rapid assays for cardiac markers will allow early triage of patients and cost-effective use of available coronary care facilities. Methods and Results We studied the value of myoglobin, creatine kinase (CK)–MB mass , and troponin T in ruling out an AMI in the emergency room in 309 consecutive patients presenting with chest pain. The gold standard for AMI was the combination of history, ECG, and a typical curve of the CK-MB activity (CK-MB act ). Myoglobin was the earliest marker, and its negative predictive value (NPV) was significantly higher than for CK-MB mass and troponin T from 3 to 6 hours after the onset of symptoms (myoglobin versus CK-MB mass , P &lt;.03; myoglobin versus troponin T, P &lt;.01). The NPV of myoglobin reached 89% 4 hours after the onset of symptoms. The NPV of CK-MB mass reached 95% 7 hours after the onset of symptoms. Troponin T was not an early marker for ruling out AMI, and NPV changed over time, together with CK-MB act . The early NPV was higher in a subgroup of patients with a low probability of the presence of AMI for the three markers. Cardiac markers rise earlier in patients with large infarcts than in patients with small infarcts as indicated by the cumulative proportion of the marker above the upper reference limit at each time point (myoglobin, P =.04; CK-MB mass , P =.013; troponin T, P =.016). Conclusions For ruling out AMI in the emergency room, myoglobin is a better marker than CK-MB mass or troponin T from 3 until 6 hours after the onset of symptoms, but the maximal NPV reaches only 89%. At 7 hours, the NPV of CK-MB mass is 95%. The test characteristics are influenced by the probability of the presence of AMI in the patients studied and by the size of their AMI. Infarct size of AMI patients should be reported in studies evaluating cardiac markers.
A Randomized, Controlled Trial of Foscarnet in the Treatment of Cytomegalovirus Retinitis in Patients with AIDS
Authors: A G Palestine, M A Polis, M D De Smet, B F Baird, J Falloon, J A Kovacs, R T Davey, J J Zurlo, K M Zunich, M Davis
Journal: Annals of Internal Medicine (1991)

Objective: To evaluate foscarnet sodium in treating cytomegalovirus retinitis in patients with AIDS. Patients: Twenty-four previously untreated persons with AIDS and cytomegalovirus retinitis who were at low risk for loss of their visual acuity. Intervention: Patients were randomly assigned to receive either no therapy (delayed treatment, control group) or immediate treatment with intravenous foscarnet at a dose of 60 mg/kg body weight three times a day for 3 weeks (induction regimen) followed by a maintenance regimen of 90 mg/kg once a day. Measurements: Patients were examined weekly until they reached the primary clinical end point, defined as progression of their retinitis border by 750 µm or the development of a new retinal lesion due to cytomegalovirus. Progression was evaluated using retinal photographs by masked readers. Secondary evaluations included changes in visual acuity, cytomegalovirus shedding in the blood and urine, serum levels of human immunodeficiency virus type 1 (HIV-1) p24 antigen, and total CD4 T lymphocyte counts. Results: The mean time to progression of retinitis was 3.2 weeks in the control group (n = 11) compared with 13.3 weeks in the treatment group (n = 13) (P < 0.001). Nine of 13 patients in the treatment group had positive blood cultures for cytomegalovirus at entry and all nine cleared their blood of cytomegalovirus by the end of the induction period (P = 0.004) compared with one of six patients in the control group. No reductions in p24 levels were seen in the control patients compared with a reduction of more than 50% in p24 levels for all four patients on treatment for whom follow-up levels were available. The main adverse effects of foscarnet treatment were seizures (2 of 13 patients), hypomagnesemia (9 of 13), hypocalcemia (11 of 13), and elevations in serum creatinine above 176.8 µmol/L (2.0 mg/dL) (3 of 13). The control patients received an average of 0.2 units of blood per week compared with an average of 0.6 units of blood per week for the patients on treatment. Conclusions: The administration of foscarnet decreases the rate of progression of cytomegalovirus retinitis in persons with AIDS. Its judicious use is likely to prevent loss of vision in these patients. In this study, however, there was little change in visual acuity in patients in either the immediate or delayed treatment group because only patients with non-sight-threatening disease were selected.
Poly(ADP-ribose) polymerase inhibition reduces tumor necrosis factor-induced inflammatory response in rheumatoid synovial fibroblasts
Authors: S Garcia, A Bodano, J L Pablos, J J Gomez-Reino, C Conde
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> To investigate the effect of poly(ADP-ribose) polymerase (PARP) inhibition on the production of inflammatory mediators and proliferation in tumour necrosis factor (TNF)-stimulated fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). <h3>Methods:</h3> Cultured FLS from patients with RA were treated with two PARP inhibitors, 3,4-dihydro-5-[4-1(1-piperidinyl)buthoxy]-1(2H)-isoquinolinona (DPQ) or 4-amino-1,8-naphthalimida (ANI) before TNF stimulation. PARP-1 expression was also suppressed in RA FLS by small interfering RNA (siRNA) transfection. Expression and secretion of inflammatory mediators were analysed by quantitative polymerase chain reaction and by enzyme-linked immunosorbent assay, respectively. Proliferation of RA FLS was also determined. Mitogen-activated protein kinase (MAPK) activity was analysed by western blot assay and activator protein (AP)-1 and nuclear factor (NF)κB binding by electrophoretic mobility shift assay. <h3>Results:</h3> We show, for the first time, that PARP inhibition either with specific inhibitors or by siRNA transfection significantly reduced TNF-induced cytokine and chemokine expression in FLS from patients with RA. PARP inhibitors also decreased TNF-induced RA FLS proliferation. PARP inhibition reduced TNF-induced JNK phosphorylation and AP-1 and NFκB binding activities were partially impaired by treatment with PARP inhibitors or by PARP-1 knockdown. <h3>Conclusion:</h3> PARP inhibition reduces the production of inflammatory mediators and the proliferation of RA FLS (in response to TNF), suggesting that PARP inhibitors could have therapeutic benefits in RA.
Selected Characteristics of Black Physicians in the United States, 1972
Authors: Theodis Thompson
Journal: JAMA (1974)

The profile of black physicians in the United States has not changed appreciably since 1967. A sample of 3,405 black physicians (91% male, 9% female) who responded to a mailed questionnaire survey shows that black physicians are more likely to concentrate in the fields of general practice, medical and surgical specialties, and solo practice as opposed to group practice than the universe of US physicians. Black male physicians are twice as likely to be in solo practice or self-employed than are black female physicians. Fee-for-service is reported as the primary source of income. (<i>JAMA</i>229:1758-1761, 1974)
Computed Tomography Coronary Angiography in Patients With Acute Myocardial Infarction Without Significant Coronary Stenosis
Authors: Annachiara Aldrovandi, Filippo Cademartiri, Daniele Arduini, Daniela Lina, Fabrizio Ugo, Erica Maffei, Alberto Menozzi, Chiara Martini, Alessandro Palumbo, Federico Bontardelli, Tiziano Gherli, Livia Ruffini, Diego Ardissino
Journal: Circulation (2012)

It is known that a significant number of patients experiencing an acute myocardial infarction have normal coronary arteries or nonsignificant coronary disease at coronary angiography (CA). Computed tomography coronary angiography (CTCA) can identify the presence of plaques, even in the absence of significant coronary stenosis. This study evaluated the role of 64-slice CTCA in detecting and characterizing coronary atherosclerosis in these patients.Consecutive patients with documented acute myocardial infarction but without significant coronary stenosis at CA underwent late gadolinium-enhanced magnetic resonance and CTCA. Only the 50 patients with an area of myocardial infarction identified by late gadolinium-enhanced magnetic resonance were included in the study. All of the coronary segments were assessed for the presence of plaques. CTCA identified 101 plaques against the 41 identified by CA: 61 (60.4%) located in infarct-related arteries (IRAs) and 40 (39.6%) in non-IRAs. In the IRAs, 22 plaques were noncalcified, 17 mixed, and 22 calcified; in the non-IRAs, 5 plaques were noncalcified, 8 mixed, and 27 calcified (P=0.005). Mean plaque area was greater in the IRAs than in the non-IRAs (6.1±5.4 mm(2) versus 4.2±2.1 mm(2); P=0.03); there was no significant difference in mean percentage stenosis (33.5%±14.6 versus 31.7%±12.2; P=0.59), but the mean remodeling index was significantly different (1.25±0.41 versus 1.08±0.21; P=0.01).CTCA detects coronary plaques in nonstenotic coronary arteries that are underestimated by CA, and identifies a different distribution of plaque types in IRAs and non-IRAs. It may therefore be valuable for diagnosing coronary atherosclerosis in acute myocardial infarction patients without significant coronary stenosis.