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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functional activity of peripheral phagocytes were comparatively studied in 14 HIV-infected patients and 28 patients with chronic Herpes simplex viral infection. The two groups exhibited lowered adhesive capacity of phagocytes, impaired production and excretion of active oxygen metabolites. In addition, the patients with chronic Herpes simplex infection showed much elevated levels of myeloperoxidase and acid phosphatase, which indicated its compensatory pattern. The HIV infected had no enhanced enzymatic activity. One cannot rule out that these differences in the functional activity of phagocytes are associated with different effects of viral peptides on the cellular wall of phagocytes.
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PMID:[Comparative analysis of functional activity of peripheral blood phagocytes in HIV-infected patients and in those with recurrent herpes simplex]. 128 17

Through interaction with antibody, IgG Fc receptors provide an interface between specific humoral immunity and Fc gamma R-bearing host cells. Fc gamma R trigger such diverse functions as immune complex clearance, phagocytosis of opsonized pathogens, reactive oxygen intermediate and enzyme secretion, and antibody-dependent cellular cytotoxicity (ADCC). Moreover, Fc gamma R are the exclusive trigger molecules for tumor cell killing by human myeloid cells. Studies of Fc gamma R function have been aided by the use of bispecific antibodies to link cells or pathogens to specific host cell molecules, including Fc gamma R. These reagents have permitted determination of the role of Fc gamma R in ADCC of the protozoan, Toxoplasma gondii, by human effector cells. This approach has also indicated that Fc gamma R do not serve as entry points for viruses such as dengue virus and HIV. Taken together, these results provide insight into the utility of manipulating Fc gamma R function in the therapy of cancer and infectious disease.
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PMID:Fc gamma receptors in cancer and infectious disease. 128 16

Dithiocarbamates and iron chelators were recently considered for the treatment of AIDS and neurodegenerative diseases. In this study, we show that dithiocarbamates and metal chelators can potently block the activation of nuclear factor kappa B (NF-kappa B), a transcription factor involved in human immunodeficiency virus type 1 (HIV-1) expression, signaling, and immediate early gene activation during inflammatory processes. Using cell cultures, the pyrrolidine derivative of dithiocarbamate (PDTC) was investigated in detail. Micromolar amounts of PDTC reversibly suppressed the release of the inhibitory subunit I kappa B from the latent cytoplasmic form of NF-kappa B in cells treated with phorbol ester, interleukin 1, and tumor necrosis factor alpha. Other DNA binding activities and the induction of AP-1 by phorbol ester were not affected. The antioxidant PDTC also blocked the activation of NF-kappa B by bacterial lipopolysaccharide (LPS), suggesting a role of oxygen radicals in the intracellular signaling of LPS. This idea was supported by demonstrating that treatment of pre-B and B cells with LPS induced the production of O2- and H2O2. PDTC prevented specifically the kappa B-dependent transactivation of reporter genes under the control of the HIV-1 long terminal repeat and simian virus 40 enhancer. The results from this study lend further support to the idea that oxygen radicals play an important role in the activation of NF-kappa B and HIV-1.
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PMID:Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells. 131 83

Several novel imidotriphosphate analogues of thymidine have been synthesized and have been shown to be effective inhibitors of human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT). When the alpha,beta-bridging oxygens of thymidine triphosphate (TTP) and 3'-azido-3'-deoxythymidine 5'-triphosphate (AZTTP) were replaced by a nitrogen, the resulting analogues were no longer substrates but instead became competitive inhibitors of HIV-1 RT. The most potent of the alpha,beta-imidotriphosphate derivatives tested was thymidine 5'-[alpha,beta-imido]triphosphate (TMPNPP, 1a). This analogue has a Ki value of 2.4 microM, inhibiting HIV-1 RT 400-fold more potently than it inhibits DNA polymerase I large fragment (Klenow). 3'-Azido-3'-deoxythymidine 5'-[alpha,beta-imido]triphosphate (AZTMPNPP, 1b) gave a Ki value about 10-fold greater than that for TMPNPP, indicating that a 3'-azido substituent decreases the affinity of AZTTP to HIV-1 RT relative to the normal 3'-OH substituent. Dideoxythymidine 5'-[alpha,beta-imido]triphosphate (ddTMPNPP, 1c) was intermediate in potency, giving a Ki value of 15 microM. In contrast, substitution at the beta,gamma-bridging oxygen by nitrogen did not block the enzymatic cleavage of the adjacent alpha,beta-phosphate linkage, and 3'-azidothymidine 5'-[beta,gamma-imido]triphosphate (AZTMPPNP, 1e), the 5'-[beta,gamma-imido]triphosphate analogue of AZTTP, is therefore both a substrate for and a potent inhibitor of HIV-1 RT with an observed Ki value of 87 nM. Further nitrogen substitution of the bridging oxygens in the phosphate chain decreases the inhibitory potency by approximately 10-fold, as in the case of thymidine 5'-[alpha,beta:beta,gamma-diimido]triphosphate (TMPNPNP, 1d).
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PMID:New thymidine triphosphate analogue inhibitors of human immunodeficiency virus-1 reverse transcriptase. 137 62

3'-Azido-3'-deoxythymidine-5'-phosphonate was synthesized by a five-step reaction sequence. The 5'-phosphonate was inactive against HIV-1 in MT4 cells. The absence of activity against HIV-1 was at least partially explained by demonstrating that the Km value for the 5'-deoxy-5'-methylphosphonic acid diphosphate analog with HIV-1 reverse transcriptase (RT) was 320-fold greater than the Km value for 3'-azido-3'- deoxythymidine-5'-triphosphate (AZTTP), and the kcat value for the 5'-deoxy-5'-methylphosphonic acid diphosphate analog was one-seventh the value for AZTTP. These differences in kinetic constants were due to a change in the rate-determining step from dissociation of the RT chain-terminated template-primer complex to the catalytic step. Thus, substitution of a methylene group for the 5'-oxygen atom of AZTTP resulted in an 1800-fold reduction in the rate constant for RT-catalyzed phosphodiester bond formation.
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PMID:3'-Azido-3',5'-dideoxythymidine-5'-methylphosphonic acid diphosphate: synthesis and HIV-1 reverse transcriptase inhibition. 138 May 61

In the coming decade, it is likely that oxygen-carrying alternatives to red blood cells will become available for clinical use. The driving force behind their development is the risk of transfusion of homologous blood, which includes transmission of viral disease (HIV and hepatitis) and transfusion reactions as well as the expense of collecting and storing human blood. A number of clinical applications for these products can be anticipated now, but when available, it is likely that the list will grow. How widely these products will be used depends on their safety. In addition to these clinical applications, blood substitutes will be useful in furthering our understanding of basic oxygen transport physiology.
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PMID:Potential clinical applications for blood substitutes. 139 35

Lyophilized PHP as an oxygen carrier is prepared from outdated red cell and dicarboxymethylated polyoxyethylene. In order to apply PHP for a clinical use, a large scale production of high quality PHP has been studied. We have set up a 20 L scale production flow of PHP88. The product was tested to confirm the quality and lot-to-lot consistency. The blood group specific materials were weakly positive in stroma-free hemoglobin (SFH), however, were found negative in the PHP of this scale. The amount of phosphatidylethanolamine (PE) in purified SFH and PHP88 reconstituted solution was 0.19 +/- 0.04 and 0.03 +/- 0.01 ppm, respectively. Contamination of viruses such as HBV and Non A non B hepatitis virus could not be observed in the final product. Elimination and inactivation of HIV was validated through a spike test. The characterizations of the final products in 20 L scale were done through MW, P50, Hill coefficient, viscosity, and molecular weight distribution by SDS-PAGE and batch to batch consistency was also confirmed. The results show that production process is appropriate to eliminate the blood group materials, PE and virus, and produce PHP of high quality. Lyophilized PHP88 can be produced by addition of maltose and can be stored over 1 year.
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PMID:Large scale production and characterization of lyophilized pyridoxalated hemoglobin-polyoxyethylene (PHP). 139 59

Serum lactate dehydrogenase levels, alveolar-arterial oxygen gradient, and percentage of neutrophils in bronchoalveolar lavage correlate most strongly with early mortality in Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. However, the individual outcome can not be predicted by these parameters due to a considerable overlap between survivors and nonsurvivors. We prospectively investigated a PCP severity score, which has been developed earlier based on a retrospective analysis. Seven of 94 consecutively examined HIV-infected patients died within 14 days after diagnosis of PCP. A PCP severity score greater than 7 had a positive predictive value for early fatal outcome of 66.7 percent (6/9) and a negative predictive value of 98.8 percent (84/85). The overall diagnostic accuracy was 95.7 percent (90/94). The positive predictive value for early fatal outcome of a P(A-a)O2 > 35 mm Hg was 24 percent (6/25); the negative predictive value was 98.6 percent (68/69). However, the overall diagnostic accuracy was only 78.7 percent (74/94). The PCP severity score is a valuable tool for clinical decision making, for the early identification of patients with a prognostic unfavorable course, and for the comparison of patient populations in future studies of HIV-associated PCP.
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PMID:Prospective evaluation of a prognostic score for Pneumocystis carinii pneumonia in HIV-infected patients. 139 41

To determine if the use of aerosolized pentamidine prophylaxis decreases the clinical severity or the sensitivity of diagnostic tests for Pneumocystis carinii pneumonia (PCP), we conducted a retrospective matched cohort comparison study of patients admitted to San Francisco General Hospital with PCP from August 1, 1989, to June 30, 1990. Patients who had received pentamidine prophylaxis during at least the 2 months prior to the diagnosis of PCP were matched with patients who had not received the drug. Matching was based on the number of prior episodes of PCP, sex, age, and risk factors for human immunodeficiency virus infection. As markers of clinical severity, we chose alveolar-arterial oxygen difference, serum lactate dehydrogenase levels, outpatient versus inpatient treatment, length of hospitalization, length of intravenous anti-pneumocystis treatment, development of respiratory failure, in-hospital mortality, and chest radiographic appearance. Although, of the 27 matched pairs identified, significantly fewer of the pentamidine cohort were treated as inpatients, and significantly more of this cohort had upper lobe dominant disease on chest radiograph, we found no other significant differences between markers of clinical severity for the two cohorts. In addition, we found no significant differences in the rate of sputum or bronchoalveolar lavage positivity for P. carinii between the two cohorts. We conclude that, although hospitalization is less common in patients with a history of prophylactic pentamidine use, aerosolized pentamidine prophylaxis does not decrease the clinical severity or the sensitivities of sputum induction or bronchoalveolar lavage as diagnostic tests for PCP.
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PMID:Effect of aerosolized pentamidine prophylaxis on the clinical severity and diagnosis of Pneumocystis carinii pneumonia. 141 8

HIV infection affects various parts of the immune system, including the CD4+ lymphocytes and mononuclear phagocytes, and causes a progressive immunodeficiency. This renders the patient susceptible to various opportunistic infections and neoplasms. Reactive oxygen intermediates (ROI) are important for the intracellular killing of microorganisms by mononuclear phagocytes and neutrophils. Although data are discrepant, several studies suggest that the generation of ROI is impaired in mononuclear phagocytes, and possibly also in neutrophils, from HIV-infected individuals. This may lead to deficient killing of intracellular microorganisms predisposing the HIV-infected patient to certain opportunistic infections. Recently, in vitro studies have shown that ROI activate the intracellular transcription factor nuclear factor kappa B (NF-kappa B) which stimulates HIV replication. Intracellular antioxidant systems, such as the glutathione system, seem to be of importance for the regulation of ROI levels and thus probably for HIV replication in vitro. However, the role of ROI in regulation of HIV replication in vivo is unknown at present. The role of ROI in HIV infection is thus difficult to assess, both at the cellular and clinical level. Reduced intracellular concentrations of ROI may lead to impaired phagocyte microbicidal functions, thus predisposing HIV-infected patients to various opportunistic infections. On the other hand, increased ROI levels may be associated with a stimulation of HIV replication leading to clinical deterioration.
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PMID:Reactive oxygen intermediates and human immunodeficiency virus (HIV) infection. 145 84


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