HIV risk assessment: physician and patient communication.
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Communication↗
Biomedical subjects
K Mayer
Publications and source records attributed to K Mayer.
Impact of arachidonic versus eicosapentaenoic acid on exotonin-induced lung vascular leakage: relation to 4-series versus 5-series leukotriene generation.
Escherichia coli hemolysin (HlyA) is a proteinaceous pore-forming exotoxin that is implicated as a significant pathogenicity factor in extraintestinal E. coli infections including sepsis. In perfused rabbit lungs, subcytolytic concentrations of the toxin evoke thromboxane-mediated vasoconstriction and prostanoid-independent protracted vascular permeability increase (11). In the present study, the influence of submicromolar concentrations of free arachidonic acid (AA) and eicosapentaenoic acid (EPA) on the HlyA-induced leakage response was investigated. HlyA at concentration from 0.02 to 0.06 hemolytic units/ml provoked a dose-dependent, severalfold increase in the capillary filtration coefficient (Kfc), accompanied by the release of leukotriene(LT)B4, LTC4, and LTE4 into the recirculating buffer fluid. Simultaneous application of 100 nmol/L AA markedly augmented the HlyA-elicited leakage response, concomitant with an amplification of LTB4 release and a change in the kinetics of cysteinyl-LT generation. In contrast, 50 to 200 nmol/L EPA suppressed in a dose-dependent manner the HlyA-induced increase in Kfc values. This was accompanied by a blockage of 4-series LT generation and a dose-dependent appearance of LTB5, LTC5, and LTE5. In addition, EPA fully antagonized the AA-induced amplification of the HlyA-provoked Kfc increase, again accompanied by a shift from 4-series to 5-series LT generation. We conclude that the vascular leakage provoked by HlyA in rabbit lungs is differentially influenced by free AA versus free EPA, related to the generation of 4- versus 5-series leukotrienes. The composition of lipid emulsions used for parenteral nutrition may thus influence inflammatory capillary leakage.
Animals↗
Synthesis of 4- and 5-series leukotrienes in the lung microvasculature challenged with Escherichia coli hemolysin: critical dependence on exogenous free fatty acid supply.
Escherichia coli hemolysin (HlyA) has been identified as a potent inductor of phosphoinositide hydrolysis and related metabolic responses in neutrophils (Grimminger and colleagues, 1991, J. Clin. Invest. 88:1531-1539). In isolated perfused rabbit lungs, which harbor a large number of entrapped microvascular leukocytes, we investigated the effect of a low dose of HlyA on lipoxygenase product formation in the presence of exogenous free arachidonic acid (AA), eicosapentaenoic acid (EPA), or both precursor fatty acids. Leukotrienes (LT) and hydroxyeicosatetra(penta)enoic acids (HET[P]E) in the recirculating perfusate were quantified using high-performance liquid chromatography techniques. In the absence of exogenous precursor fatty acid supply, 0.02 hemolytic units/ml HlyA elicited only minor amounts of LTs and 5-HETE. AA, 10 microM, provoked the generation of limited quantities of LTB4, LTE4, and 5-HETE. Combined application of HlyA and AA caused a manifold amplification of 4-series LT and 5-HETE generation, with predominance of cysteinyl-LTs. EPA, 10 microM, elicited the synthesis of 5-series LTs accompanied by marked quantities of 5-HEPE. Dual stimulation with HlyA and EPA provoked exclusive generation of excessive quantities of all 5-series 5-lipoxygenase products. When HlyA was administered in the presence of both AA (10 microM) and EPA (10 microM), the n-3 fatty acid clearly turned out to be the preferred substrate, with ratios of the various 5-series to 4-series products ranging between 1.8 and 14.5. Moreover, the absolute quantities of AA-derived metabolites and the total sum of all 5-lipoxygenase products was markedly reduced under these conditions. We conclude that the HlyA-evoked 5-lipoxygenase product formation in the pulmonary vasculature of the rabbit is critically dependent on the presence of free precursor fatty acids. The profile of LTs suggests neutrophil (PMN)-related transcellular eicosanoid synthesis as a major underlying metabolic pathway. EPA represents the preferred substrate as compared with AA, resulting in a marked suppression of AA metabolite formation. Therapeutic attempts to provide n-3 fatty acids via the intravenous route may have a major impact on lipid mediator profiles in PMN-related inflammatory events.
Animals↗
A tale of two health care delivery systems.
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Acquired Immunodeficiency Syndrome↗
HIV and syphilis prevalence in chittagong, Bangladesh.
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Adolescent↗
Efficiency of aerosolized nitric oxide donor drugs to achieve sustained pulmonary vasodilation.
Inhalation of nitric oxide (NO) causes selective pulmonary vasodilation, but demands continuous supply of the gaseous agent. We investigated the suitability of aerosolization of NO-donor drugs for achieving sustained reduction of pulmonary vascular tone. In buffer-perfused rabbit lungs, stable pulmonary hypertension was achieved by continuous infusion of the thromboxane-analogue U46619. The NO-donor drugs molsidomine, 3-morpholinosydnone-imine (SIN-1), sodium nitroprusside (SNP) and glyceryl-trinitrate reduced the pulmonary hypertension in a dose-dependent fashion, whether admixed to the perfusate or inhaled as alveolar-accessible aerosol particles (aerosolization time 3-6 min), with an efficiency ranking of SNP > SIN-1 >> molsidomine and glyceryl-trinitrate. Notably, nearly identical dose-response curves were obtained when corresponding molar quantities of the most potent agents, SNP and SIN-1, were applied either via transbronchial or via intravascular routes, with respect to rapidity of onset, extent (pressure reduction to near baseline) and duration (>90 min) of vasorelaxation. Appearance of sydnonimines in the perfusate after aerosolization and reduction of SIN-1 efficacy when nebulized in nonrecirculatingly perfused lungs demonstrated substantial entry of this prodrug into the vascular space after alveolar deposition. In contrast, undiminished vasodilatory efficacy of aerosolized SNP under conditions of non-recirculating perfusion suggested predominant efficacy via local NO release for this agent. We conclude that short aerosolization maneuvers of NO-donor drugs are suitable to achieve dose-dependent, extensive and sustained vasodilation in the pulmonary circulation, thus offering a new therapeutic approach in pulmonary hypertension.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
An essential regulatory role for macrophage migration inhibitory factor in T-cell activation.
The protein known as macrophage migration inhibitory factor (MIF) was one of the first cytokines to be discovered and was described 30 years ago to be a T-cell-derived factor that inhibited the random migration of macrophages in vitro. A much broader role for MIF has emerged recently as a result of studies that have demonstrated it to be released from the anterior pituitary gland in vivo. MIF also is the first protein that has been identified to be secreted from monocytes/macrophages upon glucocorticoid stimulation. Once released, MIF acts to "override" or counter-regulate the suppressive effects of glucocorticoids on macrophage cytokine production. We report herein that MIF plays an important regulatory role in the activation of T cells induced by mitogenic or antigenic stimuli. Activated T cells produce MIF and neutralizing anti-MIF antibodies inhibit T-cell proliferation and interleukin 2 production in vitro, and suppress antigen-driven T-cell activation and antibody production in vivo. T cells also release MIF in response to glucocorticoid stimulation and MIF acts to override glucocorticoid inhibition of T-cell proliferation and interleukin 2 and interferon gamma production. These studies indicate that MIF acts in concert with glucocorticoids to control T-cell activation and assign a previously unsuspected but critical role for MIF in antigen-specific immune responses.
Animals↗
HIV-1 Langerhans' cell tropism associated with heterosexual transmission of HIV.
Heterosexual transmission by vaginal intercourse accounts for most transmission of human immunodeficiency virus-type 1 (HIV-1) in Africa and Asia but is less important in the HIV-1 epidemics of the United States and Western Europe. Epithelial Langerhans' cells (LCs) represent a possible source of initial cell contact for vaginal infection. Fifteen primary isolates of HIV-1 from U.S. homosexuals and 18 HIV-1 isolates from Thailand heterosexuals were evaluated for growth in LCs of U.S. origin. All the viruses from the Thai heterosexuals, which were subtype E, grew more efficiently in the LCs than any of the viruses from the U.S. homosexuals, which are subtype B. These results suggest that LC tropism is associated with the efficiency of heterosexual transmission of HIV.
Cell Line↗
Omega-3 lipid infusion in a heart allotransplant model. Shift in fatty acid and lipid mediator profiles and prolongation of transplant survival.
BACKGROUND: omega-3 Fatty acids may have a major impact on immune responses involved in heart transplant rejection. We compared the effects of posttransplant intravenous supplementation with omega-3-rich versus omega-6-rich lipid emulsions on graft survival, plasma fatty acid profiles, and levels of arachidonic acid versus eicosapentaenoic acid-derived lipid mediators. METHODS AND RESULTS: Inbred PVG and Wistar-Kyoto rats were used as donors and recipients, respectively, in a model of heterotopic heart transplantation. Animals received 9 g/kg body wt per day of either fish oil-derived (n = 8) or soybean oil-derived fat (n = 7) in the form of a continuously infused lipid emulsion; controls were sham-infused with saline (n = 8). Graft rejection was assessed by loss of activity of the transplant. The fish oil-derived preparation but not that originating from soybean oil caused an increase in total and free plasma fatty acids. Substantial quantities of eicosapentaenoic acid and docosahexaenoic acid appeared in the free fatty acid fraction, surpassing those of arachidonic acid. Ex vivo stimulation of neutrophils with the Ca2+ ionophore A23187 demonstrated an increase in 5-series leukotriene (LT) generation in animals undergoing omega-3 lipid infusion (LTB5, omega-oxidation products of LTB5, LTA5 secretion), with 5-series/4-series LT ratios ranging between 0.08 and 0.36. Ratios of TX B3/B2 liberated from ex vivo stimulated platelets even approached 1:1 in omega-3 supplemented rats. Graft survival was 7.6 +/- 0.3 (mean +/- SEM) days in saline-infused, 10.4 +/- 0.7 in omega-6 lipid-infused, and 12.9 +/- 0.4 in omega-3 lipid-infused animals. CONCLUSIONS: Posttransplant intravenous alimentation with fish oil-derived lipid emulsions prolongs heart transplant survival in excess to omega-6 lipids. Profound changes in fatty acid profiles and lipid mediator generation may underlie this finding.
Animals↗
Cocaine use and HIV disease progression among heterosexuals.
Evidence derived fromin vitro experiments would suggest that cocaine exposure may hasten the progression of HIV disease among infected individuals. Epidemiologic support for this association is equivocal at best. We examined the relationship between cocaine use and decline in CD4 cell counts over a 6-month period in a cohort of 81 heterosexually active men and women who were infected with HIV. Overall, cocaine users were 1.4 times (90% CI=1.0-2.1) more likely to experience a decline in CD4 count than were non-cocaine users. Cocaine users with a baseline CD4 count of greater than 500 cells/mm(3) were at 1.6 times (90% CI=1.2-2.3) greater risk for a CD4 decline than non-cocaine users at this baseline CD4 level. Concurrent treatment with an antiretroviral agent [AZT] modified the strength of this association, as evidenced by a cumulative incidence ratio (CIR) of 0.4 (90% CI=0.1-1.3) among AZT users and a CIR=2.2 (90% CI=1.5-3.2) among those not undergoing AZT treatment. The results of this study raise concerns about the negative effects of cocaine on people living with HIV infection, particularly those not receiving antiretroviral therapy who entered our study with a relatively intact immune system.
Journal Article↗
[Golden chloride: concerning some chemical and histochemical studies of Sigmund Freud].
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Austria↗
The human high mobility group (HMG)-box transcription factor TCF-1: novel isoforms due to alternative splicing and usage of a new exon IXA.
The C-terminal peptide sequences of the human lymphocyte-specific high mobility group (HMG)-box transcription factor TCF-1 are determined by alternative splice mechanisms affecting the exons VIII to X. Here we report, in addition to four splice forms described previously (TCF-1A, B, C, D), the identification of three novel transcripts designated TCF-1E, F, G. Cloning and sequencing of the novel cDNAs revealed (i) joining of the exons VIII and IX to an internal exon X splice acceptor site resulting in a new open reading frame (ORF) of 99 amino acids derived from exon X sequences, (ii) the identification of an additional functional splice acceptor site within exon X, and (iii) a new 81-nucleotide insertion between exon VIII and exon X sequences in a novel transcript form. Genomic cloning and sequence analysis of this transcribed segment of 81 basepairs revealed that it was bordered by canonical splice consensus sites and located in a distance of some 400 bp from both the exons IX and X. It was therefore termed exon IXA. Novel ORFs were generated as a consequence of these alternative splice mechanisms resulting in TCF-1 gene products with significantly different C-terminal peptide sequences, which are prone to selective protein-protein interactions or transactivating functions.
Alternative Splicing↗
Dietary intake of female collegiate heavyweight rowers.
The purpose of this study was to evaluate the adequacy of dietary intake in 16 female heavyweight rowers during the sprint racing phase of the season. Caloric intake for the rowers was 2,633 kcal/day, lower than expected given the training regimen of these athletes. On average, rowers consumed below-optimal levels of carbohydrate. Protein intake was satisfactory but fat intake was higher than recommended. For the majority of rowers, micronutrient intake met the RDA. However, calcium, zinc, B6, and B12 fell short of meeting two-thirds of the RDA for a significant percentage of rowers. The preevent meal consumed both 15 hr and 2 hr before the event provided less carbohydrate and fluid but more fat than desirable. Female heavyweight rowers would benefit from nutritional counseling that provides strategies for increasing complex carbohydrates, calcium, zinc, B6, and B12 while reducing dietary fat. Adequate fluid intake is also essential.
Adult↗
Differential influence of arachidonic vs. eicosapentaenoic acid on experimental pulmonary hypertension.
The impact of the 2- and 3-series prostanoid precursors arachidonic acid (AA) and eicosapentaenoic acid (EPA) on experimental pulmonary hypertension was investigated. The model of buffer-perfused rabbit lungs was stimulated by infusion of Escherichia coli hemolysin (HlyA), which is known to provoke sustained thromboxane (Tx)-mediated pulmonary hypertension. Release of di- and trienoic Tx into the recirculating perfusate was quantified by a post-high-performance liquid chromatography enzyme-linked immunosorbent assay technique. HlyA at 0.08 hemolytic unit/ml caused a sustained rise in pulmonary arterial pressure (PAP; maximum increase 14 +/- 2 mmHg) accompanied by progressive TxB2 liberation (maximum perfusate concn 33 +/- 4 pg/ml, baseline < 2 pg/ml). Between 5 and 30 nM, AA provoked a transient monophasic rise in PAP (maximum pressor response 1.5-15 mmHg) and concomitant TxB2 release (peak concn 2-30 pg/ml). Simultaneous administration of HlyA and AA exhibited additive effects with regard to mediator release and pressor responses. EPA at 200-2,000 nM caused a transient rise in PAP similar to that provoked by 5-30 nM AA (maximum pressor response 3-18 mmHg). This was accompanied by liberation of TxB2 (peak concn 16 +/- 5 and 28 +/- 4 pg/ml after 1,000 and 2,000 nM EPA) and TxB3 (peak concn 9 +/- 4 and 30 +/- 3 pg/ml). Combined application of HlyA and EPA resulted in approximate addition of the TxB2 release reaction to each single compound, and TxB3 liberation more than doubled (maximum concn 59 +/- 12 pg/ml). The pressor responses to HlyA-EPA (200-2,000 nM) did not, however, surpass those to HlyA-AA (5-30 nM).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The impact of age on the quality of life in persons with HIV infection.
The authors administered the Medical Outcomes Study (MOS 20) Short Form Health Survey to 369 persons with HIV disease. The MOS survey measures six domains of health: physical function, role function, social function, mental health, health perception, and pain. Additional data included sociodemographics, HIV risk group, time since HIV diagnosis, symptoms (dyspnea, diarrhea, fever, chills, sweats, weight loss, weakness, numbness, memory trouble, seizures), and CD4 lymphocyte count within 3 months of the MOS survey. Bivariate analyses revealed worse MOS scores associated with older age in five health domains: physical function (p less than .01), health perception (p <.10), role function (n.s.), social function (n.s.), and mental health (n.s.). Older subjects reported less pain. When controlling for CD4 count and for sociodemographic and clinical variables, older age was significantly (p less than .05) associated with worse MOS scores in physical function, social function, and health perception, nonsignificantly associated with worse MOS scores in role function and mental health, and nonsignificantly associated with less reporting of pain.
Adolescent↗
[Immunosuppressive effect of parenteral fat emulsions in defined immunostimulation].
BACKGROUND: In the heterotopic rat heart allotransplant model we have previously shown that intravenous fat emulsions are to a various extent immunosuppressive or immunoneutral, dependent on their n-3/n-6 fatty acid ratio. Safflower oil (n-3: n-6 = 1:370), fish oil (7.6:1) and soybean oil (1:6.5) prolonged the transplant survival time to 13.3, 12.3 and 10.4 days compared to 6.7 days (oil control group; 1.2.1) and 7.8 days (saline control group) (p < 0.01), respectively. This study presents a correlation of graft survival to immunohistological, cell biological and biochemical parameters. MATERIALS AND METHODS: 20% emulsions of safflower oil, fish oil, soybean oil and a 1:1 mixture of safflower and fish oil (oil control group) were continuously infused (9 g fat/kg body weight/day; n = 10 each group) after transplantation. Subpopulations of infiltrating and circulating immunocompetent cells and leukotriene B4 and B5 release of circulating mononuclear cells were analyzed (on the 4th postoperative day). RESULTS: In the 2 groups with the highest prolongation of graft survival the number of infiltrating cells was reduced by up to 40% and the peripheral blood mononuclear cell interleukin-6 release by up to 45%. Beyond that, circulating T cells were reduced in the fish oil group. Leukotriene B4 was released in all groups to the same extent, leukotriene B5 exclusively in the fish oil group. CONCLUSIONS: Intravenous fat emulsions show a varying immunomodulatory effect in dependence of the n-3/n-6 fatty acid ratio. Both n-6 and n-3 fatty acids, if applied as main fatty acid source, exert immunosuppressive effects by a diminished infiltration and mobilisation of immunocompetent cells. Soybean oil with a more balanced n-3/n-6 fatty acid ratio than safflower oil is significantly less immunosuppressive than safflower oil, and fat emulsions with a n-3/n-6 fatty acid ratio of 1:2 are immunologically neutral.
Animals↗
Association of perioperative transfusions with poor outcome in resection of gastric adenocarcinoma.
The clinical records of patients identified by a prospective database as having undergone curative gastric resections for adenocarcinoma not involving the gastroesophageal junction were reviewed in order to examine transfusional practices and to determine if perioperative transfusion had an adverse effect on outcome. Between January 1985 and January 1992, 232 patients received such curative resections. The median follow-up for these patients was 19.0 months, whereas median survival for nonsurvivors was 12.3 months. Fifty-eight percent of the patients received transfusion of blood products. Fifty-four percent of these transfusions amounted to less than 2 units of blood products. By chi 2 analysis, advanced stage of disease (p = .03), advanced T-stage of primary tumor (p = .004), and total gastrectomy (p = .04) were associated with greater likelihood of transfusion. By univariate analysis, male sex (p = .004), total gastrectomy (p = .01), advanced stage of disease (p = .000006), high histologic grade of tumor (p = .03), and blood transfusion (p = .006) were predictors of poor outcome. By multivariate analysis using the proportional hazards model with stage, tumor grade, gender, extent of resection, and transfusion as covariates, blood transfusion was an independent predictor of poor outcome (p = .029, hazard 1.74). These results encourage prospective studies of transfusion on cancer recurrence and studies of alternatives to allogeneic blood transfusions in restoration of oxygen-carrying capacity during surgery in patients with gastric cancer.
Adenocarcinoma↗
Cocaine use and heterosexual exposure to human immunodeficiency virus.
We examined the relation between recent cocaine use and heterosexual exposure to human immunodeficiency virus (HIV). Five hundred nineteen heterosexually active participants in the New England Behavioral Health Study, an HIV testing and counseling program, provided information for this study. The outcome measure included behaviors that increased the risk for exposure to HIV via contact with infected genital secretions. Nearly one-third (31.8%) of participants reported use of cocaine during the year before study entry. These individuals were 1.3 times [90% confidence interval (CI) = 1.1-1.7] more likely to risk HIV exposure than people not using cocaine during this period, with evidence of a dose-dependent relation among HIV-positive cocaine users. HIV-positive crack users were at 1.9 times greater risk (90% CI = 1.2-2.9) for HIV risk-taking behavior than those who did not use crack. The effect of cocaine was present even among those individuals without other injection drug use.
Adult↗