tbuckley/cabot-search huggingface dataset:
Endothelial renin-angiotensin pathway: evidence for intracellular synthesis and secretion of angiotensins.
Authors: I Kifor, V J Dzau
Journal: Circulation Research (1987)

Cultured bovine aortic endothelial cells (BAEC) contain renin and angiotensinogen. To examine whether angiotensins are synthesized intracellularly and secreted by these cells, we assayed cell extracts as well as serum-free media of intact confluent BAEC. Angiotensins were identified by their retention time on reverse phase high performance liquid chromatography and direct radioimmunoassay. BAEC and their media contain angiotensin II and angiotensin III. The rate of angiotensin accumulation in the media was a nonlinear function of time; the highest rate occurred in the first 15 minutes. The amount of angiotensin II accumulated in 30 minutes exceeded 200% of the intracellular concentration and that of angiotensin III exceeded 500% of the initial intracellular content. Neither renin nor angiotensinogen could be detected in the media. The viability of these cells was supported by low lactic dehydrogenase activity in the media (less than 0.5% of cellular level). These data suggest that BAEC is capable of synthesizing and secreting angiotensins. We postulate that this endothelial-derived angiotensin system may play an important paracrine or autocrine role in influencing local vascular tone.
The Differential Effect of Prenatal Care on the Incidence of Low Birth Weight among Blacks and Whites in a Prepaid Health Care Plan
Authors: Jann L. Murray, Merton Bernfield
Journal: New England Journal of Medicine (1988)

Abstract Black infants are born with low birth weights (<2500 g) and very low birth weights (<1500 g) at twice the rate of white infants. We investigated the effect of prenatal care delivered in a health maintenance organization on the birth weights of black and white infants at normal risk for low birth weight. Using birth certificates for all children born in 1978 in the California Kaiser–Permanente hospitals, we studied data on more than 31,000 black and white newborns whose mothers' ages and levels of education were comparable. The data show that black mothers used prenatal care less extensively and had a higher incidence of infants with low birth weights (8.4 vs. 3.6 percent) and very low birth weights (2.0 vs. 0.7 percent) than white mothers. The difference in the use of prenatal care, however, accounted for less than 15 percent of the difference in the incidence of low birth weight. The rates of low birth weight, very low birth weight, and preterm birth (<260 days' gestation) decreased with increasing levels of prenatal care for both blacks and whites. However, increasing levels of care were associated with a greater reduction among black infants than among white infants in low birth weight, very low birth weight, and low birth weight at term (≥260 days' gestation). When we compared mothers who received adequate care with those who received inadequate care, the relative risk of giving birth to a very-low-birth-weight infant was reduced 3.6-fold (95 percent confidence interval, 2.0 to 6.6) for black mothers and 2.1-fold (confidence interval, 1.3 to 3.4) for white mothers; the relative risk of giving birth to a low-birth-weight infant at term was reduced 3.4-fold (95 percent confidence interval, 2.2 to 5.4) for black mothers and 1.6-fold (confidence interval, 1.1 to 2.3) for white mothers. We conclude that even in a population of women at low risk for giving birth to low-birth-weight infants, prenatal care is more beneficial for blacks than for whites. (N Engl J Med 1988;319:1385–91.)
Donor CD8 cells prevent allogeneic marrow graft rejection in mice: potential implications for marrow transplantation in humans.
Authors: P J Martin
Journal: The Journal of Experimental Medicine (1993)

Numerous experimental models have demonstrated that graft-vs.-host disease (GVHD) does not occur in irradiation chimeras when the graft does not contain mature, immunocompetent T lymphocytes, but clinical studies have shown that T cell depletion of donor marrow can be associated with a greatly increased risk of graft failure. We have developed a model where engraftment of (C57BL/6J x C3H/HeJ)F1 (B6C3) marrow in 800-cGy-irradiated (BALB/cJ x C57BL/6J)F1 (CB6) recipients depends on the presence of donor T cells in the graft. Recipients transplanted with 5.0 x 10(6) marrow cells depleted of T lymphocytes showed host lymphoid and myeloid reconstitution, whereas recipients transplanted with the same marrow plus 2.5 x 10(5) purified donor T cells showed donor reconstitution. Adding as few as 0.5 x 10(5) CD8-enriched donor T cells to marrow grafts containing 5.0 x 10(6) T cell-depleted donor cells was sufficient to enable donor reconstitution, while surviving recipients transplanted with the same marrow and 0.5-2.5 x 10(5) CD4-enriched donor cells showed only host reconstitution. To address the question of whether donor CD4 cells could facilitate engraftment under conditions where GVHD would not represent a limiting factor, engraftment of bm1 marrow was tested in major histocompatibility complex (MHC) class I-disparate B6.Ly5a recipients. Results indicated that the donor CD8-enriched population was at least fivefold more active than the CD4-enriched population for facilitating allogeneic marrow engraftment in this strain combination. Thus, the lymphokines and MHC class II-specific cytotoxic T cells generated by CD4 cells were relatively ineffective for enhancing engraftment, possibly reflecting the fact that the host T cells that contain effectors responsible for causing rejection do not express MHC class II antigens. The ability of donor CD8 cells to facilitate engraftment could reflect the activity of a cytokine uniquely elaborated after recognition of an MHC class I disparity. More likely, the graft-enhancing effect of donor CD8 cells may result from the generation of MHC class I-specific or class I-restricted cytotoxic T cells that recognize the host CD4 and CD8 cells responsible for causing rejection. The possibility remains that other mechanisms such as veto inactivation of host T cells by donor CD8 cells may also contribute to the graft-enhancing effect.
Glucagon-like peptide-1 can reverse the age-related decline in glucose tolerance in rats.
Authors: Y Wang, R Perfetti, N H Greig, H W Holloway, K A DeOre, C Montrose-Rafizadeh, D Elahi, J M Egan
Journal: Journal of Clinical Investigation (1997)

Wistar rats develop glucose intolerance and have a diminished insulin response to glucose with age. The aim of this study was to investigate if these changes were reversible with glucagon-like peptide-1 (GLP-1), a peptide that we have previously shown could increase insulin mRNA and total insulin content in insulinoma cells. We infused 1.5 pmol/ kg-1.min-1 GLP-1 subcutaneously using ALZET microosmotic pumps into 22-mo-old Wistar rats for 48 h. Rat infused with either GLP-1 or saline were then subjected to an intraperitoneal glucose (1 g/kg body weight) tolerance test, 2 h after removing the pump. 15 min after the intraperitoneal glucose, GLP-1-treated animals had lower plasma glucose levels (9.04+/-0.92 mmol/liter, P < 0.01) than saline-treated animals (11.61+/-0.23 mmol/liter). At 30 min the plasma glucose was still lower in the GLP-1-treated animals (8.61+/-0.39 mmol/liter, P < 0.05) than saline-treated animals (10.36+/-0.43 mmol/liter). This decrease in glucose levels was reflected in the higher insulin levels attained in the GLP-1-treated animals (936+/-163 pmol/liter vs. 395+/-51 pmol/liter, GLP-1 vs. saline, respectively, P < 0.01), detected 15 min after glucose injection. GLP-1 treatment also increased pancreatic insulin, GLUT2, and glucokinase mRNA in the old rats. The effects of GLP-1 were abolished by simultaneous infusion of exendin [9-39], a specific antagonist of GLP-1. GLP-1 is therefore able to reverse some of the known defects that arise in the beta cell of the pancreas of Wistar rats, not only by increasing insulin secretion but also by inducing significant changes at the molecular level.
Reconstructing the nasal tip
Authors: L. Stigall, J. Zitelli
Journal: British Journal of Dermatology (2014)

Given the intricate contours of adjacent concavities and convexities, the limited area from which to recruit similar skin, and variable areas of skin thickness, elasticity and adnexal density, reconstruction of the nasal tip is a challenging process. When approaching nasal reconstruction we have often found it helpful to partition defects into two subgroups: those that fall within the upper two-thirds of the nose and those that fall within the lower third. Within this framework of the lower third, we present our reconstructive approach to surgical defects of the nasal tip.
Exosomes Mediate the Cytoprotective Action of Mesenchymal Stromal Cells on Hypoxia-Induced Pulmonary Hypertension
Authors: Changjin Lee, S. Alex Mitsialis, Muhammad Aslam, Sally H. Vitali, Eleni Vergadi, Georgios Konstantinou, Konstantinos Sdrimas, Angeles Fernandez-Gonzalez, Stella Kourembanas
Journal: Circulation (2012)

Hypoxia induces an inflammatory response in the lung manifested by alternative activation of macrophages with elevation of proinflammatory mediators that are critical for the later development of hypoxic pulmonary hypertension. Mesenchymal stromal cell transplantation inhibits lung inflammation, vascular remodeling, and right heart failure and reverses hypoxic pulmonary hypertension in experimental models of disease. In this study, we aimed to investigate the paracrine mechanisms by which mesenchymal stromal cells are protective in hypoxic pulmonary hypertension.We fractionated mouse mesenchymal stromal cell-conditioned media to identify the biologically active component affecting in vivo hypoxic signaling and determined that exosomes, secreted membrane microvesicles, suppressed the hypoxic pulmonary influx of macrophages and the induction of proinflammatory and proproliferative mediators, including monocyte chemoattractant protein-1 and hypoxia-inducible mitogenic factor, in the murine model of hypoxic pulmonary hypertension. Intravenous delivery of mesenchymal stromal cell-derived exosomes (MEX) inhibited vascular remodeling and hypoxic pulmonary hypertension, whereas MEX-depleted media or fibroblast-derived exosomes had no effect. MEX suppressed the hypoxic activation of signal transducer and activator of transcription 3 (STAT3) and the upregulation of the miR-17 superfamily of microRNA clusters, whereas it increased lung levels of miR-204, a key microRNA, the expression of which is decreased in human pulmonary hypertension. MEX produced by human umbilical cord mesenchymal stromal cells inhibited STAT3 signaling in isolated human pulmonary artery endothelial cells, demonstrating a direct effect of MEX on hypoxic vascular cells.This study indicates that MEX exert a pleiotropic protective effect on the lung and inhibit pulmonary hypertension through suppression of hyperproliferative pathways, including STAT3-mediated signaling induced by hypoxia.
HLA-DR histocompatibility leukocyte antigens permit cultured human melanoma cells from early but not advanced disease to stimulate autologous lymphocytes.
Authors: D Guerry, M A Alexander, M F Herlyn, L M Zehngebot, K F Mitchell, C M Zmijewski, E J Lusk
Journal: Journal of Clinical Investigation (1984)

HLA-DR histocompatibility antigens are commonly expressed by the melanocytes of melanoma and its precursors, but not by the melanocyte of normal skin. Further, the primary lesion of biologically early melanoma is commonly infiltrated with host T cells. Advanced disease is characterized by a paucity of such cells. To investigate the interaction of melanoma cells and autologous lymphocytes and its dependence on HLA-DR expression, we have established cell lines from biologically early (4 lines) and advanced disease (11 lines) and examined their capacity to stimulate blastogenesis of autologous T cells in vitro. Melanocytes from early disease expressed HLA-DR antigens and stimulated autologous T cells. Those from advanced disease, irrespective of DR expression, were nonstimulatory. To determine whether expression of DR was required for melanoma cells to be stimulatory, we first treated a stimulating cell line of DR3 allospecificity with anti-DR3-specific serum and demonstrated marked inhibition of its capacity to provoke blastogenesis. Next we used fluorescence-activated flow cytometry to sort a stimulating line heterogeneous for DR expression into DR-enriched and -depleted populations. When such cells were examined in the lymphocyte proliferation assay, their stimulatory capacity was proportional to their quantitative expression of HLA-DR. These studies indicate that cell lines may reflect important biological differences between early and advanced melanoma. HLA-DR expression may be an early event in neoplasia of melanocytes. These antigens are able to interact directly with autologous T cells; and their expression is necessary, but not sufficient, for melanoma cells to induce lymphocyte proliferation.
Gene-Expression Profiling in Acute Myeloid Leukemia
Authors: David Grimwade, Torsten Haferlach
Journal: New England Journal of Medicine (2004)

The past three decades have seen considerable advances in our understanding of the underlying mechanisms of acute myeloid leukemia (AML) and dramatic improvements in treatment. At present, decisions about therapy are largely based on prognostic factors identified at the time of diagnosis or shortly thereafter. These features include age, the karyotype of the leukemic clone, the initial leukocyte count, and the response to induction chemotherapy. Karyotypic analysis is particularly important, because it not only provides a key prognostic indicator but also serves to identify biologically distinct subgroups of AML, which in some instances require specific types of treatment.1 All-trans . . .
A combined analysis of the short-term effects of photochemical air pollutants on mortality within the EMECAM project.
Authors: Marc Saez, Ferran Ballester, Maria Antònia Barceló, Santiago Pérez-Hoyos, Juan Bellido, José María Tenías, Ricardo Ocaña, Adolfo Figueiras, Federico Arribas, Nuria Aragonés, Aurelio Tobías, Lluís Cirera, Alvaro Cañada
Journal: Environmental Health Perspectives (2002)

In recent years, some epidemiologic studies have attributed adverse effects of air pollutants on health not only to particles and sulfur dioxide but also to photochemical air pollutants (nitrogen dioxide and ozone). The effects are usually small, leading to some inconsistencies in the results of the studies. Furthermore, the different methodologic approaches of the studies used has made it difficult to derive generic conclusions. We provide here a quantitative summary of the short-term effects of photochemical air pollutants on mortality in seven Spanish cities involved in the EMECAM project, using generalized additive models from analyses of single and multiple pollutants. Nitrogen dioxide and ozone data were provided by seven EMECAM cities (Barcelona, Gijón, Huelva, Madrid, Oviedo, Seville, and Valencia). Mortality indicators included daily total mortality from all causes excluding external causes, daily cardiovascular mortality, and daily respiratory mortality. Individual estimates, obtained from city-specific generalized additive Poisson autoregressive models, were combined by means of fixed effects models and, if significant heterogeneity among local estimates was found, also by random effects models. Significant positive associations were found between daily mortality (all causes and cardiovascular) and NO(2), once the rest of air pollutants were taken into account. A 10 microg/m(3) increase in the 24-hr average 1-day NO(2)level was associated with an increase in the daily number of deaths of 0.43% [95% confidence interval (CI), -0.003-0.86%] for all causes excluding external. In the case of significant relationships, relative risks for cause-specific mortality were nearly twice as much as that for total mortality for all the photochemical pollutants. Ozone was independently related only to cardiovascular daily mortality. No independent statistically significant relationship between photochemical air pollutants and respiratory mortality was found. The results in this study suggest that, given the present levels of photochemical pollutants, people living in Spanish cities are exposed to health risks derived from air pollution.
Immune interferon inhibits proliferation and induces 2'-5'-oligoadenylate synthetase gene expression in human vascular smooth muscle cells.
Authors: S J Warner, G B Friedman, P Libby
Journal: Journal of Clinical Investigation (1989)

Proliferation of vascular smooth muscle cells (SMC) contributes to formation of the complicated human atherosclerotic plaque. These lesions also contain macrophages, known to secrete SMC mitogens, and T lymphocytes. Many of the SMC in the lesions express class II major histocompatibility antigens, an indication that activated T cells secrete immune IFN-gamma locally in the plaque. We therefore studied the effect of IFN-gamma on the proliferation of cultured SMC derived from adult human blood vessels. IFN-gamma (1,000 U/ml) reduced [3H]thymidine (TdR) incorporation into DNA by SMC stimulated with the well-defined mitogens IL 1 (from 15.3 +/- 0.7 to 6.2 +/- 0.7 dpm X 10(-3)/24 h) or platelet-derived growth factor (PDGF) (from 18.5 +/- 1.0 to 7.3 +/- 0.7 dpm X 10(-3)/24 h). Kinetic and nuclear labeling studies indicated that this effect of IFN-gamma was not due to altered thymidine transport or specific radioactivity of TdR in the cell. In longer term experiments (4-16 d) IFN-gamma prevented net DNA accumulation by SMC cultures stimulated by PDGF. IFN-gamma also delayed (from 30 to 60 min) the time to peak level of c-fos RNA in IL 1-treated SMC. It is unlikely that cytotoxicity caused these effects of IFN-gamma, as the inhibition of growth was reversible and we detected no cell death in SMC cultures exposed to this cytokine. Activation of 2'-5' oligoadenylate synthetase gene expression may mediate certain antiproliferative and antiviral effects of interferons. Both IFN-gamma and type I IFNs (IFN-alpha or IFN-beta) induced 2'-5' oligoadenylate synthetase mRNA and enzyme activity in SMC cultures, but with concentration dependence and time course that may not account for all of IFN-gamma's cytostatic effect on SMC. The accumulation of SMC in human atherosclerotic lesions is a long-term process that must involve altered balance between growth stimulatory and inhibitory factors. The cytostatic effect of IFN-gamma on human SMC demonstrated here may influence this balance during human atherogenesis, because T cells present in the complicated atherosclerotic plaque likely produce this cytokine.
Vanadium distribution in rats and DNA cleavage by vanadyl complex: implication for vanadium toxicity and biological effects.
Authors: H Sakurai
Journal: Environmental Health Perspectives (1994)

Vanadium ion is toxic to animals. However, vanadium is also an agent used for chemoprotection against cancers in animals. To understand both the toxic and beneficial effects we studied vanadium distribution in rats. Accumulation of vanadium in the liver nuclei of rats given low doses of compounds in the +4 or +5 oxidation state was greater than in the liver nuclei of rats given high doses of vanadium compounds or the vanadate (+5 oxidation state) compound. Vanadium was incorporated exclusively in the vanadyl (+4 oxidation state) form. We also investigated the reactions of vanadyl ion and found that incubation of DNA with vanadyl ion and hydrogen peroxide (H2O2) led to intense DNA cleavage. ESR spin trapping demonstrated that hydroxyl radicals are generated during the reactions of vanadyl ion and H2O2. Thus, we propose that the mechanism for vanadium-dependent toxicity and antineoplastic action is due to DNA cleavage by hydroxyl radicals generated in living systems.
Randomised trial of personalised computer based information for patients with schizophrenia
Authors: R. B Jones
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objectives:</b> To compare use, effect, and cost of personalised computer education with community psychiatric nurse education for patients with schizophrenia. <b>Design:</b> Randomised trial of three interventions. Modelling of costs of alternatives. <b>Participants:</b> 112 patients with schizophrenia in contact with community services; 67 completed the intervention. <b>Interventions:</b> Three interventions of five educational sessions: (<i>a</i>) computer intervention combining information from patient9s medical record with general information about schizophrenia; (<i>b</i>) sessions with a community psychiatric nurse; (<i>c</i>) "combination" (first and last sessions with nurse and remainder with computer). <b>Main outcome measures:</b> Patients9 attendance, opinions, change in knowledge, and psychological state; costs of interventions and patients9 use of NHS community services; modelling of costs for these three, and alternative, interventions. <b>Results:</b> Rates of completion of intervention did not differ significantly (71% for combination intervention, 61% for computer only, 46% for nurse only). Computer sessions were shorter than sessions with nurse (14 minutes <i>v</i> 60 minutes). More patients given nurse based education thought the information relevant. Of 20 patients in combination group, 13 preferred the sessions with the nurse and seven preferred the computer. There were no significant differences between groups in psychological outcomes. Because of the need to transport patients to the computer for their sessions, there was no difference between interventions in costs, but computer sessions combined with other patient contacts would be substantially cheaper. <b>Conclusions:</b> The computer based patient education offered no advantage over sessions with a community psychiatric nurse. Investigation of computer use combined with other health service contacts would be worth while. <h3>What is already known on this topic</h3> Education of patients with schizophrenia has limited but positive outcomes Computer based approaches have not been thoroughly evaluated <h3>What this study adds</h3> A computer based method of education for patients with schizophrenia, which personalised the information with details from each patient9s medical record, was acceptable and as effective as educational sessions given by a community psychiatric nurse However, because of the need to provide transport for patients to attend their sessions, the computer based intervention was as costly as the nurse based one Investigating the addition of computer based education to other routine patient contacts would be worthwhile
Deception in Research Is Morally Problematic … and so too Is Not Using It Morally: Reply to Open Peer Commentaries on “The Use of Deception in Public Health Behavioral Intervention Trials: A Case Study of Three Online Alcohol Trials”
Authors: Jim McCambridge, Kypros Kypri, Preben Bendtsen, John Porter
Journal: The American Journal of Bioethics (2014)

We are very pleased that the explorationsoftheethical issues raised by our research practice (McCambridge et al. 2013a) have stimulated such thoughtful and diverse responses. Almost all indicate concern that it may be wrong to accept the moral hazards we are prepared to face, and we agree there are many reasons to take very seriously these issues, hence our attempts to do so. Most appear to accept that our research practices are of low risk and not likely to cause harm to participants, and the key issues center on informed consent. It is interesting that there are such differences in the particular concerns identified by the commentators, and we are struck by the breadth of their concerns.