tbuckley/cabot-search huggingface dataset:
Platelet-Derived Growth Factor–Producing CD4<sup>+</sup> Foxp3<sup>+</sup> Regulatory T Lymphocytes Promote Lung Fibrosis
Authors: Sandra Lo Re, Marylène Lecocq, Francine Uwambayinema, Yousof Yakoub, Monique Delos, Jean-Baptiste Demoulin, Sophie Lucas, Tim Sparwasser, Jean-Christophe Renauld, Dominique Lison, François Huaux
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: There is evidence that CD4+ effector T lymphocytes (T eff) participate in the development of lung fibrosis, but the role of their CD4+ regulatory T-cell (T reg) counterparts remains to be determined.Objectives: To elucidate the contribution of T reg cells in a mouse model of lung fibrosis induced by silica (SiO2) particles.Methods: Lung T reg and T eff cells purified from SiO2–treated Foxp3-GFP transgenic mice were cocultured with naive lung fibroblasts or transferred to the lungs of healthy mice. DEREG mice, which express the diphtheria toxin receptor under the control of the foxp3 gene, were used to deplete T reg cells during fibrogenesis.Measurements and Main Results: CD4+ Foxp3+ T reg cells were persistently recruited in the lungs in response to SiO2. T reg accumulation paralleled the establishment of pulmonary immunosuppression and fibrosis. T reg cells highly expressed platelet-derived growth factor (PDGF)-B via a TGF-β autocrine signaling pathway, directly stimulated fibroblast proliferation in vitro, and increased lung collagen deposition upon transfer in the lung of naive mice. The direct profibrotic effects of T reg cells were abolished by the inhibitor of the PDGF-B/TGF-β signaling pathway, imatinib mesylate. Neutralization of T reg–immunosuppressive activity resulted in enhanced accumulation of T eff cells and IL-4–driven pulmonary fibrogenesis, further demonstrating that T reg cells control T eff cell functions during inflammatory fibrosis.Conclusions: Our study indicates that T reg cells contribute to lung fibrosis by stimulating fibroblasts through the secretion of PDGF-B in noninflammatory conditions and regulate detrimental T eff cell activities during inflammation-related fibrosis.
EAU Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent—Update 2013
Authors: Axel Heidenreich, Patrick J. Bastian, Joaquim Bellmunt, Michel Bolla, Steven Joniau, Theodor van der Kwast, Malcolm Mason, Vsevolod Matveev, Thomas Wiegel, F. Zattoni, Nicolas Mottet
Journal: European Urology (2013)
Nodular Fasciitis on F-18 FDG PET
Authors: Martin Gotthardt, Anne Arens, Erik van der Heijden, Lioe-Fee de Geus-Oei, Wim J. G. Oyen
Journal: Clinical Nuclear Medicine (2010)

A 36-year-old woman underwent positron emission tomography imaging with F-18-fluorodeoxyglucose (FDG) for evaluation of pulmonary nodules detected in the work-up for persisting dyspnea following respiratory tract infection. The lesions were visible on computed tomography while having only low uptake on the PET images, rendering malignancy less probable. However, increased uptake of FDG was noted in the left groin, where the patient was known to have intramuscular nodular fasciitis. Nodular fasciitis is a benign disorder caused by proliferating fibroblasts and myofibroblasts, which may mimic soft-tissue malignancy clinically, histopathologically, and on imaging procedures.
Muscle carnitine deficiency in patients with severe peripheral vascular disease.
Authors: G Brevetti, C Angelini, M Rosa, R Carrozzo, S Perna, M Corsi, A Matarazzo, A Marcialis
Journal: Circulation (1991)

This study was designed to evaluate the effect of severe peripheral arterial insufficiency on carnitine concentrations and carnitine acetyltransferase and palmitoyltransferase activities in the ischemic skeletal muscles of patients with severe peripheral vascular disease.Nine biopsy specimens of ischemic muscles were obtained from five patients undergoing reconstructive vascular surgery. Biopsies from 35 normal subjects served as controls. Ischemic muscles showed a significant reduction in total carnitine from the control value of 20.9 +/- 5.2 to 11.6 +/- 6.2 nmol/mg noncollagen protein (p less than 0.01). A significantly lower free carnitine and acylcarnitine content contributed to this reduction. Similarly, carnitine acetyltransferase activity was reduced in the ischemic muscles from the control value of 102.1 +/- 41.2 to 52.9 +/- 22.1 nmol/min/mg noncollagen protein (p less than 0.01). On the contrary, carnitine palmitoyltransferase activity did not show any change (0.29 +/- 0.05 nmol/min/mg noncollagen protein in the ischemic muscles and 0.28 +/- 0.07 nmol/min/mg noncollagen protein in controls). Carnitine, acylcarnitines, and enzyme activities were also measured in the ischemic muscles in four additional patients 2 days after intravenous administration of L-propionylcarnitine (1.5 g as a single bolus followed by an infusion of 1 mg/kg/min for 30 minutes). Treatment restored normal levels of carnitine and its esters in the ischemic muscles but did not affect enzyme activities.Demonstration of carnitine deficiency in severe peripheral vascular disease substantiates previous findings showing the efficacy of carnitine supplementation to ischemic muscles. Furthermore, the feasibility of restoring carnitine homeostasis with L-propionylcarnitine provides the basis for clinical trials aimed at assessing the efficacy of this carnitine ester in the treatment of peripheral vascular disease.
Indian endocrinologists set guidance to combat vitamin D deficiency
Authors: Ganapati Mudur
Journal: BMJ (2015)

The Endocrine Society of India has recommended vitamin D supplementation for Indian people in a set of guidelines intended to combat the country’s high prevalence of vitamin D deficiency.

The guidelines, which were written by a group of 22 experts convened by the society, recommended 400 international units (IU) of vitamin D a day for infants, 600-1000 IU for children, 1000 IU for adolescents and pregnant women after 12 weeks’ gestation, and 1000-2000 IU for adults.

They recommended testing for vitamin D only in patients who have signs of osteomalacia, osteoporosis, musculoskeletal disorders, chronic liver or kidney disease, inflammatory bowel …
PSGL-1–mediated activation of EphB4 increases the proangiogenic potential of endothelial progenitor cells
Authors: Philippe Foubert, Jean-Sébastien Silvestre, Boussad Souttou, Véronique Barateau, Coralie Martin, Téni G. Ebrahimian, Carole Leré-Déan, Jean Olivier Contreres, Eric Sulpice, Bernard I. Levy, Jean Plouët, Gérard Tobelem, Sophie Le Ricousse-Roussanne
Journal: Journal of Clinical Investigation (2007)

Endothelial progenitor cell (EPC) transplantation has beneficial effects for therapeutic neovascularization; however, only a small proportion of injected cells home to the lesion and incorporate into the neocapillaries. Consequently, this type of cell therapy requires substantial improvement to be of clinical value. Erythropoietin-producing human hepatocellular carcinoma (Eph) receptors and their ephrin ligands are key regulators of vascular development. We postulated that activation of the EphB4/ephrin-B2 system may enhance EPC proangiogenic potential. In this report, we demonstrate in a nude mouse model of hind limb ischemia that EphB4 activation with an ephrin-B2–Fc chimeric protein increases the angiogenic potential of human EPCs. This effect was abolished by EphB4 siRNA, confirming that it is mediated by EphB4. EphB4 activation enhanced P selectin glycoprotein ligand-1 (PSGL-1) expression and EPC adhesion. Inhibition of PSGL-1 by siRNA reversed the proangiogenic and adhesive effects of EphB4 activation. Moreover, neutralizing antibodies to E selectin and P selectin blocked ephrin-B2–Fc–stimulated EPC adhesion properties. Thus, activation of EphB4 enhances EPC proangiogenic capacity through induction of PSGL-1 expression and adhesion to E selectin and P selectin. Therefore, activation of EphB4 is an innovative and potentially valuable therapeutic strategy for improving the recruitment of EPCs to sites of neovascularization and thereby the efficiency of cell-based proangiogenic therapy.
Delta-like 4/Notch Signaling and Its Therapeutic Implications
Authors: Minhong Yan, Greg D. Plowman
Journal: Clinical Cancer Research (2007)

Abstract Intense research efforts have been focused toward the identification of regulators of angiogenesis and the development of antiangiogenesis-based cancer therapies. The approval of anti–vascular endothelial growth factor (VEGF) monoclonal antibody (bevacizumab) for use in colorectal and lung cancer provides clinical validation for targeting angiogenesis for the treatment of cancer. Delta-like 4 (Dll4)–mediated Notch signaling represents another key pathway essential for vascular development. Recent studies yield substantial insights into the role of Dll4 in angiogenesis. Dll4 is downstream of VEGF signaling and its activation triggers a negative feedback that restrains the effects of VEGF. Attenuation of Dll4/Notch signaling results in chaotic vascular network with excessive branching and sprouting. In preclinical studies, blocking of Dll4/Notch signaling is associated with a paradoxical increase in tumor vessel density, yet causes marked growth inhibition due to functionally defective vasculature. Dll4 blockade holds promise as an additional strategy for angiogenesis-based cancer therapy, especially when resistance to and/or escape from existing therapies evolve.
Education, income inequality, and mortality: a multiple regression analysis
Authors: A. Muller
Journal: BMJ (2002)

To test whether the relation between income inequality and mortality found in US states is because of different levels of formal education.Cross sectional, multiple regression analysis.All US states and the District of Columbia (n=51).US census statistics and vital statistics for the years 1989 and 1990.Multiple regression analysis with age adjusted mortality from all causes as the dependent variable and 3 independent variables-the Gini coefficient, per capita income, and percentage of people aged >/=18 years without a high school diploma.The income inequality effect disappeared when percentage of people without a high school diploma was added to the regression models. The fit of the regression significantly improved when education was added to the model.Lack of high school education accounts for the income inequality effect and is a powerful predictor of mortality variation among US states.
Adenosine deaminase deficiency: disappearance of adenine deoxynucleotides from a patient's erythrocytes after successful marrow transplantation.
Authors: S H Chen, H D Ochs, C R Scott, E R Giblett, A J Tingle
Journal: Journal of Clinical Investigation (1978)

Accumulation of adenine deoxynucleotides (dATP and dADP) in the erythrocytes of a patient with adenosine deaminase (ADA) deficiency was confirmed. The patient, now 18 mo old, was treated with a bone marrow transplantation from his HLA identical sister at 7 mo of age. Before and after the transplant, his erythrocyte and lymphocyte ADA activities, as well as his erythrocyte nucleotide profiles, were measured. 10 wk after the marrow transplant, no ADA activity could be detected in his erythrocytes, whereas there was a mixture of donor and patient lymphocytes as measured by ADA assays and karyotyping. At the same time, both dATP and dADP had disappeared from his erythrocytes, which were entirely of patient origin. These findings indicate that partial engraftment of donor lymphocytes into an ADA-deficient patient is capable of "correcting" alterations of deoxynucleotide concentrations in the patient's ADA-deficient erythrocytes.
Validation of microscopic observation drug susceptibility testing for rapid, direct rifampicin and isoniazid drug susceptibility testing in patients receiving tuberculosis treatment
Authors: J. Coronel, M.H. Roper, C. Herrera, C. Bonilla, O. Jave, C. Gianella, I. Sabogal, V. Huancaré, E. Leo, A. Tyas, A. Mendoza-Ticona, L. Caviedes, D.A.J. Moore
Journal: Clinical Microbiology and Infection (2013)

Drug susceptibility testing (DST) is often needed in patients clinically failing tuberculosis (TB) therapy. Most studies of phenotypic direct drug susceptibility tests, such as microscopic observation drug susceptibility (MODS) tests, have been performed in patients not receiving TB treatment. The effect of ongoing TB treatment on the performance of MODS direct DST has not been previously explored, but patients failing such therapy constitute an important target group. The aim of this study was to determine the performance of MODS direct rifampicin and isoniazid DST in patients clinically failing first-line TB treatment, and to compare MODS direct DST with indirect proportion method DST. Sputa from 264 TB patients were cultured in parallel in Lowenstein-Jensen (LJ) and MODS assays; strains were tested for rifampicin and isoniazid susceptibility by the proportion method at the national reference laboratory. Ninety-three samples were culture-positive by LJ and MODS (concordance of 96%; kappa 0.92). With conventional MODS plate DST reading (performed on the same day as the sample is classified as culture-positive), the isoniazid DST concordance was 96.8% (kappa 0.89), and the concordance for rifampicin susceptibility testing was 92.6% (kappa 0.80). Reading of MODS DST plates 1 week after cultures had been determined to be culture-positive improved overall performance marginally-the isoniazid DST concordance was 95.7% (kappa 0.85); and the rifampicin DST concordance was 96.8% (kappa 0.91). Sensitivity for detection of multidrug-resistant TB was 95.8%. MODS testing provided reliable rifampicin and isoniazid DST results for samples obtained from patients receiving TB therapy. A modified DST reading schedule for such samples, with a final reading 1 week after a MODS culture turns positive, marginally improves the concordance with reference DST.
Effects of Myocardial Strains on Coronary Blood Flow
Authors: JAMES M. DOWNEY, H. FRED DOWNEY, EDWARD S. KIRK
Journal: Circulation Research (1974)

Systole causes a redistribution of coronary blood flow away from the subendocardium. In the present study the relative contribution of shortening of the myocardial fibers (wall strains) and of pressure development in the ventricular lumen to redistribution were determined. The distribution of coronary blood flow during systole in hearts ejecting into a severed aorta (large wall strains and near-zero afterload) was compared with that in isovolumetrically contracting hearts (reduced wall strains and significant afterload). A quantitative index of the distribution of coronary blood flow during systole was provided by the myocardial uptake of a bolus of 86 Rb or 42 K injected when constant-pressure perfusion of the left coronary artery was restricted with a solenoid-controlled pump to the period of systole. The coronary blood flow during systole in the subendocardium of the ejecting heart was 62% of that in the subepicardium. A similar gradient in the systolic flow with the endocardium receiving 37% of the blood flow to the epicardium was observed in the hearts contracting isovolumetrically. Removing the afterload by severing the aorta abolished the transmural differences in coronary blood flow. In the present experiment cardiac strains per se did not redistribute coronary blood flow through shear or traction forces on the coronary vasculature, but rather, coronary blood flow was affected only by compressive stresses in the myocardium. Contraction in the absence of afterload influenced overall coronary resistance, however; 18% of the resting coronary resistance was associated with shortening alone. An additional 11% of the resting coronary resistance appeared when pressure development accompanied shortening. Coronary blood flow patterns indicated two separate compressive stresses in the left ventricle. The first stress was associated with pressure development and increased with myocardial depth. The second stress was smaller; it was associated with shortening and uniformly distributed.
Mycotic aortic aneurysm with protective coarctation
Authors: I. M Loftus, K. J Molloy, P. R F Bell, A R. Naylor
Journal: Journal of the Royal Society of Medicine (2003)

Mycotic aneurysms of the aorta have a high mortality, even with surgical treatment. We report a case in which the patient's life was probably saved by an accompanying anomaly.
Combined Endoscopy, Aspiration, and Biopsy Analysis for Identifying Infectious Colitis in Patients With Ileocecal Ulcers
Authors: Naoyoshi Nagata, Takuro Shimbo, Katsunori Sekine, Shouhei Tanaka, Ryota Niikura, Kazuhisa Mezaki, Eriko Morino, Hirohisa Yazaki, Toru Igari, Norio Ohmagari, Junichi Akiyama, Shinichi Oka, Naomi Uemura
Journal: Clinical Gastroenterology and Hepatology (2013)
Ablation of Neutral Cholesterol Ester Hydrolase 1 Accelerates Atherosclerosis
Authors: Motohiro Sekiya, Jun-ichi Osuga, Shuichi Nagashima, Taichi Ohshiro, Masaki Igarashi, Hiroaki Okazaki, Manabu Takahashi, Fumiko Tazoe, Taeko Wada, Keisuke Ohta, Mikio Takanashi, Masayoshi Kumagai, Makiko Nishi, Satoru Takase, Naoya Yahagi, Hiroaki Yagyu, Ken Ohashi, Ryozo Nagai, Takashi Kadowaki, Yusuke Furukawa, Shun Ishibashi
Journal: Cell Metabolism (2009)
Neutrophil Adhesion Molecule Surface Expression and Responsiveness in Cystic Fibrosis
Authors: KENNETH J. RUSSELL, JAMES McREDMOND, NINA MUKHERJI, CHRISTINE COSTELLO, VERA KEATINGS, SEAMUS LINNANE, MICHAEL HENRY, MUIRIS X. FITZGERALD, CLARE M. O'CONNOR
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The neutrophil-dominated inflammation of the lung in cystic fibrosis (CF) has traditionally been seen as a physiological response to continuous opportunistic infection. Recent studies suggest, however, that regulation of the inflammatory response itself may be altered in CF. Neutrophil migration from the bloodstream involves alterations in surface expression of the adhesion molecules L-selectin and Mac-1 (CD11b/CD18). The aim of this study was to assess neutrophil adhesion molecule expression and responsiveness in CF. Neutrophils from chronic (n = 16) and acutely infected (n = 13) CF patients and 15 normal control subjects were directly assessed by Fluorescence-activated cell sorter (FACS) analysis for surface expression of L-selectin and CD11b before and after stimulation with interleukin 8 (IL-8) or f-Met-Leu-Phe (fMLP). Neutrophils from stable (n = 5) and acutely infected (n = 5) non-CF bronchiectasis patients were also assessed. Surface upregulation of CD11b was similar in all groups. Basal levels of L-selectin were also comparable among all groups, however, when stimulated, neutrophils from both stable and acutely infected CF patients shed significantly less L-selectin than those from control subjects (p < 0.05 and p < 0.01, respectively). This decreased responsiveness was not observed in either stable or acutely infected non-CF bronchiectasis patients. These results add to the accumulating evidence suggestive of a defective inflammatory response in CF.
A mobile telephone-based interactive self-care system improves asthma control
Authors: W-T. Liu, C-D. Huang, C-H. Wang, K-Y. Lee, S-M. Lin, H-P. Kuo
Journal: European Respiratory Journal (2010)

The self-management of asthma can improve clinical outcomes. Recently, mobile telephones have been widely used as an efficient, instant personal communication tool. This study investigated whether a self-care system will achieve better asthma control through a mobile telephone-based interactive programme. This was a prospective, controlled study in outpatient clinics. From 120 consecutive patients with moderate-to-severe persistent asthma, 89 were eventually recruited for the study, with 43 in the mobile telephone group (with a mobile telephone-based interactive asthma self-care system). In the mobile telephone group, mean± sem peak expiratory flow rate significantly increased at 4 (378.2±9.3 L·min −1 ; n = 43; p = 0.020), 5 (378.2±9.2 L·min −1 ; n = 43; p = 0.008) and 6 months (382.7±8.6 L·min −1 ; n = 43; p = 0.001) compared to the control group. Mean± sem forced expiratory volume in 1 s significantly increased at 6 months (65.2±3.2% predicted; n = 43; p&lt;0.05). Patients in the mobile telephone group had better quality of life after 3 months, as determined using the Short Form-12® physical component score, and fewer episodes of exacerbation and unscheduled visits than the control group. Patients in the mobile telephone group significantly increased their mean daily dose of either systemic or inhaled corticosteroids compared with the control group. The mobile telephone-based interactive self-care system provides a convenient and practical self-monitoring and -management of asthma, and improves asthma control.
Inhibition of inducible nitric oxide synthase in macrophages by oxidized low-density lipoproteins.
Authors: X Yang, B Cai, R R Sciacca, P J Cannon
Journal: Circulation Research (1994)

Uptake of oxidized low-density lipoprotein (LDL) by monocyte/macrophages to form "foam" cells has been implicated in atherogenesis. Activated monocyte/macrophages synthesize nitric oxide (NO) from L-arginine. NO is cytotoxic, antiproliferative, and a vasodilator that inhibits platelet and monocyte adhesion. NO synthase mRNA, protein, and enzyme activity were induced in J774.A1 macrophages activated with lipopolysaccharide and gamma interferon. When macrophages were incubated with oxidized LDL for 24 hours and activated, there was a dose- and time-dependent inhibition of NO synthesis, assessed as nitrite accumulation in the media. When activated cells were incubated with nontoxic doses of lipoprotein (25 micrograms/mL), neither native LDL nor acetyl LDL inhibited NO production, whereas oxidized LDL produced 50% inhibition. Levels of enzyme protein were unchanged by Western blot. Inhibition was a function of the degree of oxidation of LDL but was independent of cholesteryl esterification by the cells. Incubations of oxidized LDL with cells that had been pretreated with dextran sulfate or cytochalasin B yielded no evidence that inhibition was dependent on the scavenger receptor or directed endocytosis. Kinetic studies of inducible NO synthase from J774.A1 cells that were incubated with increasing doses of oxidized LDL indicated a pattern of noncompetitive inhibition. Inhibition of the enzyme was produced by lipids extracted from oxidized LDL but not by lipids extracted from native LDL. Because phosphatidylcholine (PC) is converted to lysophosphatidylcholine (LPC) during the oxidation of LDL, the effects of LPC were investigated. PC vesicles containing LPC did not inhibit enzyme activity but produced modest reductions in nitrite accumulation from cells. In contrast, PC vesicles had no significant effect. The data indicate that oxidized LDL lipid inhibits the activity of inducible NO synthase in activated macrophages. NO production by this enzyme and its inhibition by oxidized LDL lipid may influence cell-to-cell interactions and vasomotor tone in atherosclerotic blood vessels.