Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD4-targeted therapy with a nondepleting RIB-5/2 mAb abrogates accelerated (< 36 h) rejection in presensitized LEW rats and results in permanent acceptance of LBNF1 cardiac allografts in conjunction with the features of infectious tolerance. This study examined the role and functional significance of the Th1 and Th2 cytokine network and systemic host allospecific Ab (allo-Ab) responses in the development of the infectious tolerance pathway in this model. Long term survival of cardiac transplants in rats treated with the tolerizing RIB-5/2 mAb regimen was accompanied by profound depression of Th1 (IL-2 and IFN-gamma) and Th2 (IL-4, IL-10) cytokines at the graft site, as shown by competitive template reverse transcription-PCR and immunohistochemistry. In contrast, the expression of Th2-type cytokines was selectively up-regulated after transfer of infectious tolerance by spleen cells into new generations of primary and secondary test recipients. Donor-specific circulating IgM allo-Ab responses were diminished throughout, and the switch from IgM to IgG allo-Ab was completely prevented in tolerant hosts, as shown by flow cytometry. The demonstration that treatment with cytolytic anti-CD4, but not anti-CD8, mAb recreated rejection of test cardiac allografts with simultaneous down-regulation of IL-4 mRNA/protein expression underlines the importance of this cytokine in the development of infectious tolerance. Hence, this report documents distinct cytokine elaboration patterns in animals tolerized by CD4-targeted therapy compared with those rendered tolerant by putative regulatory Th2-like cells. The mechanism of tolerance in anti-CD4 mAb-treated hosts appears distinct from that operating in the absence of mAb, when the tolerant state is being transferred in an infectious manner to new cohorts of test recipients.
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PMID:Type 2 helper T cell-type cytokines and the development of "infectious" tolerance in rat cardiac allograft recipients. 902 92

The hematologic consequences of infection with the noncytopathic lymphocytic choriomeningitis virus (LCMV) were studied in wild-type mice with inherent variations in their interferon (IFN)-alpha/beta responder ability and in mutant mice lacking alpha/beta (IFN-alpha/beta R0/0) or gamma IFN (IFN-gamma R0/0) receptors. During the first week of infection, wild type mice demonstrated a transient pancytopenia. Within a given genetic background, the extent of the blood cell abnormalities did not correlate with the virulence of the LCMV isolate but variations were detected between different mouse strains: they were found to depend on their IFN-alpha/beta responder phenotype. Whereas IFN-gamma R0/0 mice were comparable to wild-type mice, IFN-alpha/beta R0/0 mice exhibited unchanged peripheral blood values during acute LCMV infection. In parallel, the bone marrow (BM) cellularity, the pluripotential and committed progenitor compartments were up to 30-fold reduced in wild type and IFN-gamma R0/0, but remained unchanged in IFN-alpha/beta R0/0 mice. Viral titers in BM 3 d after LCMV infection were similar in these mice, but antigen localization was different. Viral antigen was predominantly confined to stromal BM in normal mice and IFN-gamma R0/0 knockouts, whereas, in IFN-alpha/beta R0/0 mice, LCMV was detected in > 90% of megakaryocytes and 10-15% of myeloid precursors, but not in erythroblasts Although IFN-alpha/beta efficiently prevented viral replication in potentially susceptible hematopoietic cells, even in overwhelming LCMV infection, unlimited virus multiplication in platelet and myeloid precursors in IFN-alpha/beta R0/0 mice did not interfere with the number of circulating blood cells. Natural killer (NK) cell expansion and activity in the BM was comparable on day 3 after infection in mutant and control mice. Adaptive immune responses did not play a major role because comparable kinetics of LCMV-induced pancytopenia and transient depletion of the pluripotential and committed progenitor compartments were observed in CD8(0/0) and CD4(0/0) mice, in mice depleted of NK cells, in lpr mice, and in perforin-deficient (P0/0) mice lacking lytic NK cells. Thus, the reversible depression of hematopoiesis during early LCMV infection was not mediated by LCMV-WE-specific cytotoxic T lymphocyte, cytolysis, or secreted IFN-gamma from virally induced NK cells but was a direct effect of IFN-alpha/beta.
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PMID:Virus-induced transient bone marrow aplasia: major role of interferon-alpha/beta during acute infection with the noncytopathic lymphocytic choriomeningitis virus. 905 52

Interferon-gamma (IFN-gamma) has the most potent immunomodulatory activity of all the interferons. This phase II-B study was performed to define time- and dose-dependent immunomodulatory effects mediated by IFN-gamma in a subset of patients with melanoma treated in the dose-seeking therapeutic trial conducted by the Eastern Cooperative Oncology Group E4687 (13). The effects of IFN-gamma (Genentech, San Francisco, CA) were evaluated for phenotype and function of peripheral blood lymphocytes obtained twice prestudy, and on days 2, 9, and 29 of IFN-gamma therapy for 50 patients. Early significant increases in CD4/CD8 ratio (p = 0.001) were noted, largely due to a rise in CD4+ and fall in CD8+ T-cell populations sustained through day 29 at only the lowest dosage. Increased natural killer cell (NK) activity (p = 0.001 on day 9; p = 0.01 on day 29) was accompanied by durable increases in circulating activated NK cells (CD56+DR+% p = 0.001, day 9; p = 0.001, day 29). After initial depression of CD56+ and CD16+ cells on day 2, the total percent of CD56+ and CD16+ cells increased significantly by day 29. Increases in NK cell activity were maximal at doses > or =0.1 mg. Monocyte CD14+ expression of DQ+ rose early (p = 0.011 and 0.001 on days 2 and 9), accompanied by elevation in CD14+DR+ cells that was less significant. Immunomodulatory effects of IFN-gamma reported in this trial have major implications for interpretation of past and current clinical trials, and the design of future trials. This is the first trial in which IFN-gamma has been shown to have significant effects on the T-cell compartment of the immune system.
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PMID:Immunomodulatory function of interferon-gamma in patients with metastatic melanoma: results of a phase II-B trial in subjects with metastatic melanoma, ECOG study E 4987. Eastern Cooperative Oncology Group. 908 87

The present study investigates whether there is a relationship between subjective well-being and the change of immune markers in HIV-infected subjects. Twenty-one HIV-infected persons completed questionnaires. Immune markers (CD4-percentage and CD4/CD8-ratio) were measured at the beginning of the study, after 8 months and after 15 months. In a hierarchical multiple regression model, baseline values of immune markers explained most of the variance of the immune markers, both after 8 and 15 months. After including several control variables in the model, depression values and the values on the symptom checklist explained an additional increment of variance of both immune markers after eight months. Therefore, data of the present study suggest that predominantly depressive feelings co-determine immune status in HIV-infected persons.
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PMID:[Depressive affect and surrogate markers in HIV infected patients]. 913 25

We evaluated 85 human immunodeficiency virus (HIV)-negative patients with tuberculosis for clinical features and CD4 cell counts. Thirty-seven patients had low CD4 cell counts (mean +/- SD, 341 +/- 116 cells/microL), and 48 patients had normal CD4 cell counts (mean +/- SD, 830 +/- 254 cells/microL). CD4 cell counts were most strongly correlated with total lymphocyte counts (r = 0.84). If total lymphocyte count was excluded, depressed CD4 cell counts were significantly associated with low serum albumin levels, extensive pulmonary disease, low body-mass index, and low hematocrit. Of these four variables, multivariate linear discriminant analysis revealed that the serum albumin level was the best single predictor of low CD4 cell counts and that the other three variables did not improve predictive value. Because these four variables are markers of severe tuberculosis, these findings suggest that disease severity is associated with greater depression of the total lymphocyte and CD4 cell counts. The CD4 cell counts returned to normal levels in most patients after 1 month of therapy.
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PMID:CD4 cell counts in human immunodeficiency virus-negative patients with tuberculosis. 914 8

The primary purpose of this study was to assess the prevalence of major psychiatric disorders in human immunodeficiency virus-positive (HIV+) men with acquired immune deficiency syndrome (AIDS)-defining conditions. Secondary goals were to identify correlates of distress and psychopathology, and to determine whether there is a gradient of distress associated with progressive HIV illness. One hundred twelve men with AIDS-defining conditions, 61 HIV+ men without AIDS, and 84 HIV-seronegative gay men were assessed. Measures included the Structured Clinical Interview for DSM-IV (SCID), Hamilton Rating Scale for Depression (HAM-D), and other dimensional measures of distress and outlook, as well as laboratory markers of HIV stage, including HIV RNA viral load assays. Rates of major depression, consistent with other findings, were in the 5% to 10% range. Mean scores on dimensional measures of distress and outlook were within the "not depressed" range and did not increase despite increasing HIV illness severity. However, rates of dysthymia were elevated among men with CD4 cell counts less than 500, and the cumulative rates of any current axis I depressive disorder for three of the four study groups were in the range of 15% to 20%. The strongest correlates of dimensional measures of distress were current HIV symptoms and social support, and to a lesser extent, a lifetime history of major depression and current use of antidepressants and/or anxiolytics. Overall, most men displayed effective adaptation to illness, but a significant minority experienced moderate psychological distress, which warrants consideration by health providers who serve this population.
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PMID:Prevalence of axis I disorders in an AIDS cohort: a cross-sectional, controlled study. 915 70

This report documents findings from an open trial of dextroamphetamine in the treatment of depression and low energy in AIDS patients. Dextroamphetamine offers the potential for rapid onset of effect and activation properties, both of which are important to persons with late stage HIV illness. Primary inclusion criteria included having a DSM-III-R depressive disorder, debilitating low energy, CD4 cell count below 200 cells/mm3, and no history of drug dependence. The trial consisted of open treatment in a 6-week protocol, with indefinite follow-up. Twenty-four men entered the study, 18 of 19 (95%) patients who completed at least 6 weeks of treatment reported substantial improvement with regard to both mood and energy at a median dosage of 10 mg/day. These results suggest that dextroamphetamine is a potentially effective, fast acting antidepressant treatment for this population and call for a larger, controlled trial.
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PMID:Dextroamphetamine as a treatment for depression and low energy in AIDS patients: a pilot study. 916 Feb 80

The effects of orally administered sodium nitrite (20 mg NaNO2/kg b. w) on the responses of T and B lymphocytes collected from the mesenteric lymph nodes were studied in resistant AKR/J, H-2(k) haplotype mice infected with Trichinella spiralis nematode. On days 6, 9, and 12 postinfection, the mesenteric lymph node cells (MLNC) were collected from the mice and assayed for lymphocyte subsets (CD4(+), CD8(+), B220(+)), cytokines (IL-2, IL-5), and INF-gamma. At the same time, the number of adult worms in the small intestine were counted. Infection of the nitrite-treated mice with T. spiralis L1 larvae caused a marked increase in the number of adult worms in the small intestine. However, preincubation of T. spiralis L1 larvae with nitrite before infecting the mice resulted in a significant reduction in the number of adult worms (p < 0.05). Preincubation of T. spiralis L1 larvae with nitrite also caused an increase in the number of CD4(+) and CD8(+) cells as well as IL-2, IL-5, and INF-gamma levels. An increased level of CD8(+) subsets and a depression of IL-2 and IL-5 production by MLNC were observed in mice infected with larvae without nitrite pretreatment. Since supplementary rIL-1alpha was found to alter INF-gamma secretion by MLNC in vitro, the pattern of MLNC proliferation was examined further with the nitrite-treated mice. Sodium nitrite increased thymidine incorporation into the MLNC. However, INF-gamma production was not enhanced when rIL-1alpha was added to the MLNC culture obtained from nitrite-treated mice.
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PMID:Nitrite mediated T lymphocyte responses in the intestinal immune system of mice infected with Trichinella spiralis nematode. 917 17

The progression of HIV infection is accompanied by severe immunodepression and cachexia, particularly during advanced stages. The immune depression is due largely to a dramatic drop in the number of CD4 cells. The loss of body weight is mainly due to a reduced fat-free mass with no change in adipose tissue. We determined the serum concentrations of cortisol and DHEA and their correlations with absolute CD4 cell counts and changes in body weight of HIV-positive men. The results of five retrospective and prospective studies indicate that the serum concentrations of cortisol and DHEA in HIV-infected patients were different from those of HIV-negative controls. Serum cortisol was elevated at all stages of infection (+20 to +50%, p < .05 to p < .001) particularly in AIDS patients (stage IV C). In contrast, the serum DHEA concentrations were closely correlated with the stage of HIV-infection, being higher in the early stages (stages II and III or > 500 CD4) than in advanced stages (IV C or < 500 CD4)-in the latter being below those of HIV-negative men-or in controls (+40 to 100%, p < .01 to p < .001). There was a negative linear correlation between the CD4 cell counts and cortisol (r = -0.4, p < .02) and a positive linear correlation with DHEA (r = +0.36, p < .01). There was no significant correlation between delta body weight and serum cortisol. In contrast, there was a negative correlation between serum DHEA and delta body weight (%) (r = -0.69, p < .0001) and a positive correlation with the cortisol/DHEA ratio (r = +0.61, p < .0001). There is thus a link between the circulating concentrations of adrenal steroids and the progression of immunosuppression and cachexia during HIV-infection. This raises the question of whether there is a cause-and-effect relationship between clinical progression and circulating steroid concentrations. Further investigations into the relationship between the ratio cortisol/DHEA and the immune response and cachexia should indicate the contributions of these steroids to the etiology of HIV infection and lead to the development of new therapeutic strategies.
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PMID:Serum cortisol and DHEA concentrations during HIV infection. 926 42

To review the natural history of HIV infection in older women, a retrospective review of women enrolled in the HIV Outpatient Program based at the Medical Center of Louisiana in New Orleans was performed. Eighty-four of the women were at least 40 years of age. Older women were more likely to be diagnosed with selected psychosocial illnesses (e.g., injection drug use, alcohol abuse, anxiety, depression, psychosis, dementia) compared with women <40 years of age. There was no association with age and other opportunistic processes or HIV-related symptoms, but cervical dysplasia and chlamydia cervicitis were less common in older women. In a multivariate proportional hazards model, characteristics predictive for death among older women included a CD4 cell count <200 cells/mm3 (relative risk [RR], 2.86; 95% confidence interval [CI], 1.18, 6.86; p < .02), a diagnosis of an opportunistic process (RR, 3.25; 95% CI, 1.24, 8.55; p < .02), antiretroviral combination therapy (RR, 0.36; 95% CI, 0.12, 1.13: p < .08), and hormone replacement therapy (HRT) (RR, 0.28; 95% CI, 0.07, 1.10; p < .06). HRT should be considered in the management of postmenopausal HIV-infected women for its known documented benefits shown in populations of persons not infected with HIV. Prospective studies to better evaluate risks and benefits of HRT in HIV-infected women are warranted.
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PMID:Clinical manifestations and predictors of survival in older women infected with HIV. 934 53


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