Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Examination of 374 patients with acute viral hepatitis B made it possible to unravel certain mechanisms of the development of secondary immunodeficiency in the T immunity system: hypoxia and hypoxemia, activation of lipid peroxidation, suppression of antioxidant activity of blood serum, derangement of the synthesis of free radical forms of oxygen by mono- and polynuclear cells and ATR deficiency in them, disturbance of the interferonogenesis and synthesis of cyclic nucleotides, suppression of metabolic activity of immunocompetent cells. The character and intensity of immunodeficiency states underlie the formation of different clinical forms of viral hepatitis B.
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PMID:[The clinical significance of immunodeficiency states in patients with viral hepatitis B]. 150 74

Candida albicans and Cryptococcus neoformans are major causes of systemic fungal infections, particularly in patients with acquired immunodeficiency syndrome. Metabolic labeling studies revealed that these organisms synthesize a small number of N-myristoylproteins, the most prominent being 20-kDa ADP-ribosylation factors (Arfs). C. albicans Arf has approximately 80% identity with the essential Arf1 and Arf2 proteins of Saccharomyces cerevisiae. [3H]Myristic acid analogs with oxygen for -CH2- substitutions at C4, C6, C11, and C13 are incorporated into cellular N-myristoylproteins, phospholipids, and neutral lipids produced by these three yeasts during exponential growth at 30 degrees C in complex media. Analog- and organism-specific differences in the efficiency of labeling of proteins and lipid classes were observed. The effects of oxatetradecanoic acids with oxygen for -CH2- substitutions at C3-C13 on C. neoformans, C. albicans, and S. cerevisiae were assessed during mid-log phase growth at 30 degrees C. A single dose of 3-oxa-, 4-oxa-, 5-oxa- or 6-oxatetradecanoic acid (O3-O6, final concentration = 300 microM) was able to inhibit growth of C. neoformans in the order O4 greater than O5 greater than O3 approximately O6. The other compounds were inactive. 4-Oxatetradecanoic acid was fungicidal, producing a 10,000-fold reduction in viable cell number 1 h after administration and continued suppression of cell growth for 7 h. A clear dose response was observed over a concentration range of 100-300 microM. 4-Oxatridecanoic acid was 100-fold less potent in reducing cell viability than 4-oxatetradecanoic acid but more potent than 5-oxatridecanoic acid. O4 produced approximately 10-100-fold reductions in the viability of C. albicans and S. cerevisiae at 300-500 microM, respectively, whereas O5 and O6 were less active. Since N-myristoylation of the Pr55gag polyprotein precursor produced by human immunodeficiency virus I (HIV-I) is essential for its assembly, we also assessed the antiviral effects of 4-oxatetradecanoic acid. O4 is able to produce a 50% reduction in the replication of HIV-I in acutely infected human T-lymphocyte cell lines at a concentration of 18 microM. Together, these data suggest that (i) the position of the oxygen for methylene substitution is a critical determinant of the fungicidal activity of O4 and (ii) NMT may be an attractive therapeutic target for treating opportunistic fungal infections in patients infected with HIV-I.
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PMID:4-oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus I. 151 54

Several investigators have implicated depletion of glutathione (GSH) and production of reactive oxygen intermediates (ROIs) in the regulation of the human immunodeficiency virus (HIV). We have shown directly that N-acetylcysteine (NAC) blocks HIV expression in chronic and acute infection models, and HIV replication in normal peripheral blood mononuclear cells. NAC is a cysteine prodrug which maintains intracellular thiol levels during oxidative stress and replenishes depleted GSH. The observed antiviral effect of NAC is due to inhibition of viral stimulation by ROIs, which are produced in response to inflammatory cytokines. We have also shown that HIV-infected individuals have decreased intracellular GSH levels in their circulating T cells. Since GSH is the major protection against the production of ROIs, we hypothesize that the observed decrease is due to a chronic oxidative stress induced by continual exposure to elevated levels of inflammatory cytokines. Together, these results provide a rationale for clinical trials testing the efficacy of GSH-replenishing drugs such as NAC in the treatment of AIDS. NAC is different than many other antiviral drugs in that it inhibits host-mediated stimulation of viral replication arising in normal immune responses, and may thereby extend latency. In addition, it inhibits the action of inflammatory cytokines which may mediate cachexia, thereby raising the possibility that it may alleviate the deleterious wasting that accompanies late stage AIDS.
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PMID:N-acetylcysteine: a new approach to anti-HIV therapy. 154 Apr 8

Aerosolized pentamidine has been recommended as an alternative mode of antipneumocystis prophylaxis in human immunodeficiency virus-infected children with trimethoprim-sulfamethoxazole intolerance. However, there have been no definitive data concerning the most appropriate dose and the tolerance of aerosolized pentamidine in children. In the present study, we assessed the tolerance of aerosolized pentamidine in older children using a regimen similar to the one recommended in adults. A 300-mg dose of pentamidine was administered to our human immunodeficiency virus-infected patients monthly using the Respirgard II nebulizer. Patients were assessed for their heart rate, respiratory rate, breath sounds and oxygen saturations during and after pentamidine aerosolization. During a 21-month period (August, 1989, to May, 1991), 22 patients (mean age, 9.8 +/- 0.6 years; range, 3 to 15 years) received a total of 185 treatments. Patients complained of either a bitter taste (16 of 22) or developed short periods of coughing (15 of 22) during the aerosol. Five patients developed reversible bronchospasm requiring bronchodilators; no patients developed oxygen desaturation. None of the patients developed Pneumocystis carinii pneumonia during the limited protocol follow-up (mean, 9.8 months). Thus aerosolized pentamidine for antipneumocystis prophylaxis is well-tolerated in older children. However, more comprehensive investigations of efficacy are indicated.
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PMID:Aerosolized pentamidine: a well-tolerated mode of prophylaxis against Pneumocystis carinii pneumonia in older children with human immunodeficiency virus infection. 156 53

Seven patients with necrotizing soft tissue infections of the perineum are described. Predisposing factors related to infection were present in four patients (diabetes mellitus, multiple myeloma, HIV, and a poorly defined immunodeficiency syndrome). Anaerobic and facultative anaerobic bacteria were cultured in each case. Two patients required skin graft closure of the debrided wounds, with the remaining wounds closed by contracture and epithelialization. A diverting sigmoid colostomy to facilitate wound care was performed on one patient who had complete dissolution of all anal sphincters. The role of hyperbaric oxygen therapy in four patients was of uncertain value.
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PMID:Synergistic soft tissue infections of the perineum. 161 51

A wide range of enveloped viruses, including human herpes simplex virus type 1, human cytomegalovirus, human T cell leukemia/lymphoma virus type I, human immunodeficiency virus type 1, Sindbis virus, and Friend erythroleukemia virus, are highly susceptible to merocyanine 540 (MC 540)-sensitized photoinactivation. By contrast, human pluripotent hematopoietic stem cells, red cells, factor VIII, and von Willebrand factor are much less sensitive. This suggests that MC 540 may be useful for the inactivation of enveloped viruses in blood and blood products. The dye has a low acute systemic toxicity, is rapidly eliminated from the blood stream, and has little or no mutagenic potential. The currently available data support the view that MC 540-sensitized photo-inactivation interferes with early events in the infectious process, notably the ability of the virus to adhere to and penetrate its host cell. The viral envelope is a major target of photodynamic damages which appear to be mediated at least in part by singlet molecular oxygen.
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PMID:Merocyanine-sensitized photoinactivation of enveloped viruses. 161 87

The results of the study of the phagocytic element of immunity in cases of primary immunodeficiency, made with the use of a complex of functional tests, are presented. As shown in this study, in patients with definitely characterized phagocytic defect (chronic granulomatous disease) a decrease in all parameters under study, with the exception of phagocyte index, is observed. In patients with immunodeficient states of nonphagocytic nature moderate mosaic deviations of phagocytosis characteristics are noted. For further and more profound study of phagocytosis disturbances in such patients, it is expedient, in particular, to carry out studies in the activity of myeloperoxidaze and the intensity of oxygen-dependent metabolism. The use of the complex of methods used in this investigation has shown their high diagnostic value. It may be recommended for clinical practice under the condition of strict standardization of experimental techniques.
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PMID:[A comprehensive study of the phagocytic link in immunity in primary immunodeficiency states]. 165 74

To examine the mechanism of mitochondrial myocytotoxicity caused by long-term administration of zidovudine (AZT) in human immunodeficiency virus-positive patients, we examined the effect of AZT in vitro on human muscle in tissue culture and in vivo in rats treated with daily intraperitoneal injections of AZT at doses equivalent to the total daily dose used in acquired immunodeficiency syndrome patients. After 19 days, the AZT-treated myotubes in tissue culture exhibited abnormal mitochondria characterized by proliferation (mean +/- SD, 27.5 +/- 8 mitochondria/16 microns2 surface area, compared with 12.8 +/- 4 in the control cultures (p less than 0.001], enlarged size, abnormal cristae and electron-dense deposits in their matrix. The changes were partially reversible after AZT withdrawal. Rats treated with AZT developed weight loss, 100-fold elevation of creatine kinase, and increased serum lactate and glucose. In tissues, AZT had its highest concentration in the skeletal muscle and the heart. Skeletal and heart muscles from the treated animals, but not the controls, showed enlarged mitochondria with disorganized or absent cristae and electron-dense deposits in their matrix. Study of the mitochondrial functions assessed by evaluating stimulated oxygen consumption rate, enzymatic activities of electron transport chain and coupling state of oxidative phosphorylation (respiratory control ratio) revealed a decrease in rotenone-sensitive NADH cytochrome C reductase (complex I + III) and an uncoupling effect demonstrated by decreased respiratory control ratio. We conclude that AZT, a DNA chain terminator, is a muscle mitochondrial toxin that affects the oxidation-phosphorylation coupling and the activity of complex I and III of the mitochondrial respiratory chain.
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PMID:Abnormal skeletal and cardiac muscle mitochondria induced by zidovudine (AZT) in human muscle in vitro and in an animal model. 175 16

To confirm the presence of cardiac dysfunction in a group of patients seropositive for the human immunodeficiency virus with either dyspnea on exertion or a reduced anaerobic threshold, 9 patients with no history of opportunistic infection underwent exercise right-sided heart catheterization. When compared with 13 control patients previously exercised in the same manner, the patients showed elevated exercise pulmonary capillary wedge pressure (14.6 +/- 3.3 mm of mercury versus 9.9 +/- 3.3 mm of mercury; P less than .005) and right atrial pressure (10.1 +/- 2.1 mm of mercury versus 4.7 +/- 3.2 mm of mercury; P less than .001) at a similar exercise oxygen consumption and cardiac index. Of the 9 patients, 8 had at least 1 catheterization value outside the 95% confidence limits for the control group and 4 patients had multiple abnormalities. Values for blood CD4 lymphocytes were 0.2 x 10(9) per liter or more for 7 of the 9. One patient underwent endomyocardial biopsy with findings consistent with a cardiomyopathy. We conclude that cardiac disease may occur at any immunologic stage of human immunodeficiency virus infection. These observations suggest an effect of this disease on the heart.
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PMID:Cardiac dysfunction in patients seropositive for the human immunodeficiency virus. 177 74

The effects of oxygen deprivation, or anoxia, on human immunodeficiency virus (HIV-1) expression in chronically (ACH.2) and acutely (H9/HIV-1-IIIB) infected cell lines was investigated. Temporary cellular anoxia has previously been shown to activate transcription of endogenous type C leukemia virus sequences, resulting in a significant increase in retroviral RNA within the cell (1). Here we report a 15-fold increase in HIV-1-specific RNA in unstimulated ACH.2 T cells within 24 h of anoxia. This induction of RNA is accompanied by an accumulation of intracellular p24 gag protein as well as an increase in envelope protein. Anoxia induces a further increase in total HIV-1 RNA in ACH.2 cells prestimulated to produce virus by phorbol 12-myristate 13-acetate and in H9 T cells acutely infected with HIV-1-IIIB. The induction of RNA in ACH.2 cells appears to be reversible. Anoxic culture for 24 h followed by a 24-h re-oxygenation period results in a return to "resting state" levels of HIV-1 RNA. These data indicate that oxygen tension within the cellular environment modulates HIV-1 expression, providing a model system in which to study the reversible regulation of HIV-1 RNA and viral gene products within the cell.
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PMID:Anoxia induces human immunodeficiency virus expression in infected T cell lines. 190 63


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