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

To find out whether Pneumocystis carinii pneumonia (PCP) can be detected while still in an early phase by the degree of exercise-induced oxygen desaturation, arterial oxygen saturation was measured by continuous pulse oximetry in patients positive for antibody to the human immunodeficiency virus and clinically suspected of having PCP, in patients with other chest diseases, and in controls. Among patients with proven PCP 94% of those with low arterial oxygen pressures (PaO2) showed desaturation on exercise oximetry, as did 80% of those with a normal oxygen pressure at rest, whereas only 10% of patients with other chest disorders and HIV disease showed significant desaturation.
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PMID:Severe exercise hypoxaemia with normal or near normal X-rays: a feature of Pneumocystis carinii infection. 290 79

We report two cases of human immunodeficiency virus (HIV) seropositivity and pulmonary hypertension seen at our institution and present a comprehensive literature review and available histopathologic findings of the association between HIV seropositivity and pulmonary hypertension. Studies and reviews pertaining to HIV seropositivity and pulmonary hypertension were identified through a MEDLINE search and reference citations. All studies and series found in the MEDLINE search were reviewed and are discussed in this article. Where data were available, comparisons and analyses were made between groups of reported cases of HIV seropositivity and pulmonary hypertension with regard to the following parameters: sex distribution, mode of acquiring HIV infection, presence or absence of the acquired immunodeficiency syndrome, CD4 cell counts, PO2 or oxygen saturation by pulse oximetry, concurrent lower respiratory tract infection, and histopathologic features. We conclude that there is strong evidence for pulmonary hypertension associated with HIV infection that is histologically indistinguishable from primary pulmonary hypertension. Consequently, HIV-seropositive patients with unexplained dyspnea should be evaluated for primary pulmonary hypertension. Prospective studies in HIV-positive patients are indicated.
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PMID:Primary pulmonary hypertension and the human immunodeficiency virus. Report of two cases and a review of the literature. 748 62

When the single-stranded RNA genome of HIV-1 is copied into double-stranded DNA, the viral enzyme reverse transcriptase (RT) catalyzes the addition of approximately 20,000 nucleotides; however, the precise mechanism of nucleotide addition is unknown. In this study, we attempt to integrate the genetic data and biochemical mechanism of DNA polymerization with the structure of HIV-1 RT complexed with a dsDNA template-primer. The first step of polymerization involves the physical association of a polymerase with its nucleic acid substrate. A comparison of the structures of HIV-1 RT in the presence and absence of DNA indicates that the tip of the p66 thumb moves approximately 30 A upon DNA binding. This conformational change permits numerous interactions between residues of alpha-helices H and I in the thumb subdomain and the DNA. Measurements of DNA binding affinity for nucleic acids with double-stranded DNAs that have an increasing number of bases in the template overhang and molecular modeling suggest that portions of beta 3 and beta 4 within the fingers subdomain bind single-stranded regions of the template. Measurements of nucleotide incorporation efficiency (kcat/Km) show that the binding and incorporation of the next complementary nucleotide are not dependent on the length of the template overhang. Molecular modeling of an incoming nucleotide triphosphate (dTTP), based in part on the position of mercury atoms in a RT/DNA/Hg-UTP/Fab structure, suggests that portions of secondary structural elements alpha C-beta 6, alpha E, beta 11b, and beta 9-beta 10 determine the topology of the dNTP-binding site. These results also suggest that nucleotide incorporation is accompanied by a protein conformational change that positions the dNTP for nucleophilic attack. Nucleophilic attack by the oxygen atom of the 3'-OH group of the primer strand could be metal-mediated, and Asp185 may be directly involved in stabilizing the transition state. The translocation step may be characterized by rotational as well as translational motions of HIV-1 RT relative to the DNA double helix. Some of the energy required for translocation could be provided by dNTP hydrolysis and could be coupled with conformational changes within the nucleic acid. A structural comparison of HIV-1 RT, Klenow fragment, and T7 RNA polymerase identified regions within T7 RNA polymerase which are not present in the other two polymerases that might help this polymerase to remain bound with nucleic acids and contribute to the ability of the T7 RNA polymerase to polymerize processively.
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PMID:Insights into DNA polymerization mechanisms from structure and function analysis of HIV-1 reverse transcriptase. 753 90

Reference neutralizing antibody (NA) reagents are needed for laboratories to be able to compare results of neutralization assays that will be used to monitor HIV-1 vaccine recipients. In an effort to establish such reference reagents two asymptomatic, seropositive patients were identified with medium to high amounts of cross-reactive NA activity against a number of HIV-1 strains. Sera obtained from each individual at three or four sequential phlebotomies were pooled, and the two pools were each distributed in > 3000 aliquots into glass ampoules and lyophilized, and the ampoules were flame sealed. An HIV-1 antibody-negative reference serum was prepared in a similar fashion after pooling serum from four individuals. Ampoules were tested for uniformity of fill, sterility, moisture content, residual oxygen, stability, infectivity, and presence of antibody. An international collaborative study was conducted to determine the potency of the samples in six laboratories, each using their own neutralization assays and reagents. The results indicated reasonable consistency between laboratories and that both sera have sufficient titers against a variety of strains for use as reference reagents. These reference sera have been included in the World Health Organization (WHO) AIDS Reagent Project and are available through the three AIDS reagent repositories.
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PMID:Preparation and characterization of human HIV type 1 neutralizing reference sera. 754 4

Microglia form a regularly spaced network of resident glial cells throughout the central nervous system (CNS). They are morphologically, immunophenotypically and functionally related to cells of the monocyte/macrophage lineage. In the ultimate vicinity of the blood-brain barrier two specialized subsets of macrophages/microglia can be distinguished: firstly, perivascular cells which are enclosed within the basal lamina and secondly juxtavascular microglia which make direct contact with the parenchymal side of the CNS vascular basal lamina but represent true intraparenchymal resident microglia. Bone marrow chimera experiments indicates that a high percentage of the perivascular cells undergoes replacement with bone marrow-derived cells. In contrast, juxtavascular microglia like other resident microglia form a highly stable pool of CNS cells with extremely little turnover with the bone marrow compartment. Both the perivascular cells and the juxtavascular microglia play an important role in initiating and maintaining CNS autoimmune injury due to their strategic localization at a site close to the blood-brain barrier, their rapid inducibility for MHC class II antigens and their potential scavenger role as phagocytic cells. The constantly replaced pool of perivascular cells probably represents an entry route by which HIV gets access to the brain. Microglia are the first cell type to respond to several types of CNS injury. Microglial activation involves a stereotypic pattern of cellular responses, such as proliferation, increased or de-novo expression of immunomolecules, recruitment to the site of injury and functional changes, e.g., the release of cytotoxic and/or inflammatory mediators. In addition, microglia have a strong antigen presenting function and a pronounced cytotoxic function. Microglial activation is a graded response, i.e., microglia only transform into intrinsic brain phagocytes under conditions of neuronal and or synaptic/terminal degeneration. In T-cell-mediated autoimmune injury of the nervous system, microglial activation follows these lines and occurs at an early stage of disease development. In experimental autoimmune encephalomyelitis (EAE), microglia proliferate vigorously, show a strong expression of MHC class I and II antigens, cell adhesion molecules, release of reactive oxygen intermediates and inflammatory cytokines and transform into phagocytic cells. Due to their pronounced antigen presenting function in vitro, activated microglia rather than astrocytes or endothelial cells are the candidates as intrinsic antigen presenting cel of the brain. In contrast to microglia, astrocytes react with a delay, appear to encase morphologically the inflammatory lesion and may be instrumental in downregulating the T-cell-mediated immune injury by inducing T-cell apoptosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Microglia: intrinsic immuneffector cell of the brain. 755 Mar 61

The promoter of the Escherichia coli gene nirB is induced by both the presence of nitrite in the environment and by low oxygen tensions. It has been used to direct the high-level expression of heterologous proteins by E. coli strains in fermentors, and attenuated Salmonella strains expressing foreign proteins under nirB promoter (pnir) control have efficiently induced an immune response against these proteins. The genes encoding two different E. coli envelope proteins, the outer membrane protein LamB and the periplasmic protein MalE, were placed under pnir control on pBR322 derivatives, and both proteins were expressed at high levels during anaerobic growth. Our results showed that the expression level of MalE was influenced by the distance between the pnir promoter and the Shine-Dalgarno sequence: the highest levels were obtained by the longest constructs made; pnir directed a 4-fold increase in the level of MalE expression relative to the level reached by the previously described ptac-MalE expression vector. The best pnir construct produced 25 mg of MalE protein per 5 x 10(11) bacteria, which represents over 20% of total cell protein. Overexpression of MalE was well tolerated by E. coli, even under strict anaerobic conditions; for LamB, optimal induction was achieved under partial anaerobiosis. A MalE-HIV1 hybrid protein (33 residues from the V3 loop of HIV1 gp160 inserted into site 133 of MalE) was also overexpressed at a similar yield under pnir control, without apparent degradation of the hybrid protein. Moreover, when expressed in attenuated aroA S. typhimurium strain SL3261, the plasmids carrying malE and malE-HIV genes were stable in vitro and in vivo.
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PMID:Studies of the anaerobically induced promoter pnirB and the improved expression of bacterial antigens. 756 14

We have studied the effect of several environmental chemicals on the transient expression of a chloramphenicol acetyltransferase (cat) reporter gene linked to the promoter sequences in the long terminal repeat (LTR) of the human immunodeficiency virus type 1 (HIV-1). Aflatoxin B1, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) and benzo[a]pyrene cause a significant increases in CAT expression in mouse hepatoma Hepa-1 cells. The induction of CAT after TCDD treatment is abolished by administration of N-acetyl-L-cysteine or 2-mercaptoethanol and does not take place in a mutant cell line that lacks CYP1A1 enzymatic activity. Linker-scanning mutational analysis of transcription factor binding sites in the promoter revealed that both the NF kappa B and an adjacent aromatic hydrocarbon response element (AhRE) are required for TCDD-dependent CAT expression. In addition, mutation of the NFAT/AP-1 binding sites in the negative regulatory region of the promoter increases the magnitude of the TCDD effect. We conclude that induction of a functional CYP1A1 monooxygenase by TCDD stimulates a pathway that generates thiol-sensitive reactive oxygen intermediates which, in turn, are responsible for the TCDD-dependent activation of genes linked to the LTR. These data might provide an explanation for findings that TCDD increases infectious HIV-1 titers in experimental systems and for epidemiologic reports suggesting that exposure to aromatic hydrocarbons, such as found in cigarette smoke, is associated with an acceleration in AIDS progression.
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PMID:Dioxin activates HIV-1 gene expression by an oxidative stress pathway requiring a functional cytochrome P450 CYP1A1 enzyme. 760 37

A redox imbalance caused by an over-production of prooxidants or a decrease in antioxidants seems to play a role in the programmed cell death that occurs in various developmental programs. Such a physiological function for oxidative stress is particularly applicable to the immune system, wherein individual lymphocytes undergo continuous scrutiny to determine if they should be preserved or programmed to die. Following activation, lymphocytes produced increased levels of reactive oxygen species (ROS) which may serve as intracellular signaling molecules. The ultimate outcome of this increased ROS formation, i.e., lymphocyte proliferation versus programmed cell death, may be dictated by macrophage-derived costimulatory molecules that bolster or diminish lymphocyte antioxidant defenses. HIV-1-infected individuals display multiple symptoms of redox imbalance consistent with their being in oxidative stress, and lymphocytes from such individuals are more prone to undergo apoptosis in vitro. It is suggested that oxidative stress, and lymphocytes from such individuals are more prone to undergo apoptosis in vitro. It is suggested that oxidative stress is a physiological mediator of programmed cell death in lymphoid cells, and that HIV disease represents an extreme case of what can happen when regulatory safeguards are compromised.
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PMID:Redox regulation of programmed cell death in lymphocytes. 763 68

Reactive oxygen species like hydrogen peroxide (H2O2) have been shown to serve as messengers in the induction of NF-kappa B and, hence, in the activation and replication of human immunodeficiency virus type 1 (HIV-1) in human cells. Several antioxidant compounds and iron chelators have been shown to interfere with both NF-kappa B and HIV-1 activation under oxidative stress. Because 2,3-dihydroxybenzoic acid (DHB) and its ethyl ester derivative (DHB-EE) are potent oral iron chelators, we started to investigate their effects on monocytes treated with increasing H2O2 concentrations. These two compounds exert important protective effects against the cytotoxic effect of H2O2 as 300 microM DHB or DHB-EE increased cell survival from 30 to 85%. The treatment of monocytes with increasing amounts of H2O2 (from 0 to 3 mM) leads to the nuclear induction of NF-kappa B which is dose dependently inhibited by both DHB and DHB-EE. Addition of ferric ions to DHB only partially restores the NF-kappa B induction by H2O2, while this effect is almost completely restored by ferric ion addition to DHB-EE. Using spin trapping coupled to electron spin resonance, we have demonstrated that DHB and, to a lesser extent, DHB-EE trapped hydroxyl radicals produced by H2O2 photolysis. These data demonstrate that small aromatic molecules harboring both iron-chelating and antioxidant properties like DHB and DHB-EE can effectively interfere with the deleterious effects of H2O2 in monocytes where iron overload can be observed in HIV-1-infected patients.
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PMID:NF-kappa B transcription factor activation by hydrogen peroxide can be decreased by 2,3-dihydroxybenzoic acid and its ethyl ester derivative. 763 30

alpha-Lipoic acid, which plays an essential role in mitochondrial dehydrogenase reactions, has recently gained considerable attention as an antioxidant. Lipoate, or its reduced form, dihydrolipoate, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, hypochlorous acid, peroxyl radicals, and singlet oxygen. It also protects membranes by interacting with vitamin C and glutathione, which may in turn recycle vitamin E. In addition to its antioxidant activities, dihydrolipoate may exert prooxidant actions through reduction of iron. alpha-Lipoic acid administration has been shown to be beneficial in a number of oxidative stress models such as ischemia-reperfusion injury, diabetes (both alpha-lipoic acid and dihydrolipoic acid exhibit hydrophobic binding to proteins such as albumin, which can prevent glycation reactions), cataract formation, HIV activation, neurodegeneration, and radiation injury. Furthermore, lipoate can function as a redox regulator of proteins such as myoglobin, prolactin, thioredoxin and NF-kappa B transcription factor. We review the properties of lipoate in terms of (1) reactions with reactive oxygen species; (2) interactions with other antioxidants; (3) beneficial effects in oxidative stress models or clinical conditions.
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PMID:alpha-Lipoic acid as a biological antioxidant. 764 94


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