Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase (NOS) type II are induced in macrophages by interferon (IFN)-gamma and lipopolysaccharide (LPS). Nitric oxide has been previously shown to inhibit IDO activity. We studied whether metabolites of tryptophan via the IDO pathway could alter NOS II activity. In RAW 264.7 cells, the phenolic antioxidant 3-hydroxyanthranilic acid (OH-AA), but not anthranilic acid, inhibited citrulline synthesis by NOS II at sub-millimolar concentrations, when added 1 h before IFN-gamma and LPS. OH-AA inhibited NOS II activity in cytosolic extracts, suggesting a direct action of OH-AA on NOS II protein. Moreover, expression of NOS II mRNA and activation of the nuclear factor kappa B (NF-kappa B) in RAW 264.7 cells were decreased by a pretreatment with OH-AA, but not anthranilic acid, before addition of IFN-gamma and LPS. This pretreatment also inhibited activation of NF-kappa B in response to TNF-alpha in lymphoblastoid J.Jhan5-1 cells. Finally, expression of a long terminal repeat of the human immunodeficiency virus (HIV-LTR)-driven luciferase reporter gene, controlled by NF-kappa B activation, was severely decreased by OH-AA or 3-hydroxykynurenine in J.Jhan5-1 cells. Other tryptophan derivatives were inactive. These data identify OH-AA as an aminophenolic tryptophan derivative inhibiting NF-kappa B activation and impairing both NOS II expression and activity in a millimolar concentration range.
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PMID:Inhibition of nitric oxide synthase expression and activity in macrophages by 3-hydroxyanthranilic acid, a tryptophan metabolite. 912 84

The life span of HIV-infected patients has increased because of anti-retroviral therapy and improved means for treating opportunistic infections. However, HIV infection and subsequent immunosuppression result in an increased risk of high-grade B-cell lymphomas. The purpose of this study was to determine the incidence, localization, clinical features, therapy and survival time of patients with HIV-related lymphomas of the head and neck. Between 1988 and 1995, 280 HIV-infected patients presented with otolaryngologic symptoms. Seventy-two (25.7%) were found to have a neoplastic disease. Fifty-six of these patients (20%) were diagnosed as having Kaposi's sarcoma and 12 (4.3%) had lymphomas. According to the Kiel classification, lymphomas were subdivided into Hodgkin's disease (2 cases) and B-cell lymphomas of high-grade malignancy (10 cases). These latter cases were centroblastic (n = 4), Burkitt's type (n = 4), anaplastic large cell (n = 1) and not classifiable (n = 1). All patients with HIV-related non-Hodgkin's lymphomas (NHL) were men and 8 were homosexuals. The mean age was 36.1 years. In addition to 7 nodal locations, high-grade B-cell lymphomas were found in the oropharynx (n = 2) and palate (n = 1). Four patients underwent chemotherapy, 1 patient underwent radiation therapy and 2 were treated with both methods. Two patients did not receive any treatment and 1 patient underwent laser therapy. The survival time depended on the previous diagnosis of AIDS, the patients' immune status and the karnofsky index. In 2 patients the lymphoma led to the diagnosis of HIV infection. Our findings show that any solitary or enlarging tumors or ulcerating lesions in the head and neck region of HIV patients must be examined histologically to exclude HIV-NHL. We also recommend that young patients with high-grade B-cell lymphomas should undergo HIV screening.
HNO 1997 Jan
PMID:[HIV-associated non-Hodgkin's lymphomas (HIV-NHL) in the area of the head-neck]. 913 94

Endogenous opioid peptides play a variety of roles in the central nervous system (CNS) from development to immune modulation. These functions are mediated mostly via specific opioid receptors uniquely localized in different brain regions and cells. Exogenous opioids can influence and modulate neuronal and glial cell function via an opioid receptor mediated mechanism, leading to either protection or damage of the brain. Mechanisms underlying CNS opioid effects may be mediated via immune mediators, such as cytokines, beta-chemokines, and free radicals (i.e. reactive oxygen intermediates (ROI) and nitric oxide (NO)) produced by activated glial cells (microglia and astrocytes). In the pathogenesis of HIV-1 infection in drug addicts, opiates such as morphine have been postulated to promote the progression of this virus and the development of secondary opportunistic infections. Kappa opioid receptor (KOR) ligands, on the other hand, may play a neuroprotective role. Differences in species, age, sex, cell culture system, stimuli, opioid administration route, concentrations used, strain of infectious agents, and treatment regimes have contributed to many conflicting results in the field of opioid research. More studies are needed to delineate how opioids exert their effects on glial cells as well as neurons with the goal of finding new therapeutic approaches for neurodegenerative diseases, such as AIDS dementia.
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PMID:Immunomodulatory role of opioids in the central nervous system. 943 91

As nitric oxide (.NO) is hypothesised to play a role in the immunopathogenesis of neurological complications associated with inflammation, we compared levels of cerebrospinal fluid (CSF) and serum .NO metabolites in 24 patients with HIV-1 infection, to those in 58 non-HIV infected patients with neurological disorders. Levels of .NO metabolites were correlated with blood-brain-barrier dysfunction. CSF and serum nitrate and nitrite levels were measured by the nitrate reductase and Griess reaction methods. The .NO metabolites, nitrate and nitrite, were raised in the CSF and serum of patients with AIDS and central nervous system complications, when compared to non-HIV infected patients with inflammatory and non-inflammatory neurological disorders (median nitrate and nitrite: CSF=18.3 microM vs. 11.1 microM vs. 7.0 microM, P<0.001, and serum=53.8 microM vs. 50.3 microM vs. 41.4 microM, P=0.04, respectively). CSF nitrate and nitrite levels correlated with the albumin quotient. This study supports the evidence that .NO is a potential mediator of blood-brain-barrier breakdown in inflammatory diseases of the central nervous system.
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PMID:Elevated cerebrospinal fluid and serum nitrate and nitrite levels in patients with central nervous system complications of HIV-1 infection: a correlation with blood-brain-barrier dysfunction. 955 87

Macrophages recognize and are activated by unmethylated CpG motifs in bacterial DNA. Here we demonstrate that production of nitric oxide (NO) from murine RAW 264 macrophages and bone marrow-derived macrophages (BMM) in response to bacterial DNA is absolutely dependent on interferon-gamma (IFN-gamma) priming. Similarly, arginine uptake and expression of the inducible nitric oxide synthase (iNOS) gene in response to bacterial DNA in BMM occurred only after IFN-gamma priming. In contrast, mRNA for the cationic amino acid transporter, CAT2, was induced by plasmid DNA alone, and priming with IFN-gamma had no effect on this response. Tumor necrosis factor-alpha (TNF-alpha) release from RAW 264 and BMM in response to bacterial DNA was augmented by IFN-gamma pretreatment. In a stably transfected HIV-1 long terminal repeat (LTR) luciferase RAW 264 cell line, IFN-gamma and bacterial DNA synergized in activation of the HIV-1 LTR. Bacterial DNA has been shown to induce IFN-gamma production in vivo as an indirect consequence of interleukin-12 (IL-12) and TNF-alpha production from macrophages. The results herein suggest the existence of a self-amplifying loop that may have implications for therapeutic applications of bacterial DNA.
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PMID:IFN-gamma primes macrophage responses to bacterial DNA. 956 29

During HIV1 infection, nitric oxide (NO) could significantly contribute to immune dysregulation by its multiple effects on the modulation of the host immune response. The in vivo regulation of NO production is attributable to several nitric oxide synthases, one of which is a cytokine-inducible enzyme (iNOS). In vitro experiments suggest that iNOS expression in macrophages may be directly modulated by HIV infection. Acute infection of macaques with a pathogenic strain of the simian immunodeficiency virus (SIV) represents a relevant animal model for the in vivo study of the relationships between iNOS expression and lentiviral replication. Indeed, acute infection in this model is characterized by high rates of viral replication associated with early cytokine dysregulations, in the absence of opportunistic infection. In our experiment, two cynomolgus macaques were inoculated intravenously with a pathogenic isolate of SIVmac251, and iNOS gene expression was investigated ex vivo during acute infection in mononuclear cells obtained from bronchoalveolar lavage (BALMCs). An enhancement of this gene expression was observed as early as the second week of infection, at the time of peak of systemic viraemia, and increased until day 31 p.i. This overexpression was concomitant with a marked linear increase in IFN gamma expression in BALMCs. At the time of systemic viral load peak, the production of NO in plasma of these two monkeys was evidenced by the detection of large amounts of nitrate.
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PMID:Nitric oxide synthesis during acute SIV mac251 infection of macaques. 960 2

Activation of brain glial cells with the bacterial endotoxin lipopolysaccharide (LPS), the HIV-1 coat protein gp120, or beta-amyloid-derived peptides, stimulates the expression of several cytokines, including tumor necrosis factor-alpha (TNFalpha), interleukin-1 (IL-1) and IL-6. and nitric oxide (NO) which have been proposed as causes of neurodegeneration in the brain. In the present study, the neurotoxic effects of several cytokines, alone or in various combinations, and the correlations of the release of lactate dehydrogenase, the loss of neurons, and the secretion of NO in brain neuronal cell injury were investigated in murine primary mixed neuronal/glial cell cultures. A specific combination of cytokines, i.e., IL-1 (1 ng/ml)+ TNFalpha (10 ng/ml)/interferon-gamma (IFNgamma) (200 u/ml), induced a dramatic neuronal cell injury in the neuron/glia cultures, and its cytotoxic profile was very similar to that seen with the LPS/IFNgamma-induced neuron injury. This indicates that among the many toxic immune mediators secreted in response to LPS, IL-1 and TNFalpha can mimic LPS as the triggering signals and primary mediators for glia-mediated neuron injury in the presence of IFNgamma. This study provides new insights about the cytotoxic mechanism(s) for cytokine-mediated neuron injury.
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PMID:Synergistic neurotoxic effects of combined treatments with cytokines in murine primary mixed neuron/glia cultures. 962 92

Acyclic nucleotide analogues exhibit strong activity against a broad range of viruses, including HIV-1 and -2. We have investigated their effects on in vitro secretion of cytokines and production of nitric oxide (NO) by murine peritoneal macrophages, factors known to play a role in virus replication. Included in the study were the most prominent compounds of the series: 9-(2-phosphonomethoxyethyl)adenine, 9-(2-phosphonomethoxyethyl)-2,6-diaminopurine, the (R)- and (S)-enantiomers of 9-(2-phosphonomethoxypropyl) adenine [(R)- or (S)-PMPA], (R)- and (S)-enantiomers of 9-(2-phosphonomethoxypropyl)-2,6-diaminopurine [(R)- or (S)-PMPDAP], 9-(2-phosphonomethoxyethyl)guanine (PMEG), and (S)-enantiomer of 1-(3-hydroxy-2-phosphonomethoxypropyl)cytosine [(S)-HPMPC]. PMEG, (R)-PMPA, and (S)-PMPA greatly enhanced the secretion of both tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10), (R)-PMPDAP stimulated only TNF-alpha, other test compounds were ineffective. None of them influenced the secretion of IL-2 or interferon-gamma (IFN-gamma). Both TNF-alpha and IL-10 have been found to be major factors determining enhancing effects of PMEG, (R)-PMPA, and (S)-PMPA on production of NO generated by exogenous IFN-gamma. The study points to a possible implication of immunomodulatory properties in the antiviral effects of some acyclic nucleotide analogues. In addition, our data support the view that endogenous IL-10 can stimulate certain macrophage functions.
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PMID:Immunomodulatory properties of antiviral acyclic nucleotide analogues: cytokine stimulatory and nitric oxide costimulatory effects. 963 59

HIV type-1 (HIV-1) coat glycoprotein gp120 causes necrotic death in human neuroblastoma CHP100 cells. Here, we investigated the possible role of the arachidonate cascade and membrane peroxidation in gp120-induced cell necrosis. It is shown that gp120 increases the intracellular concentrations of prostaglandin E2 and leukotriene B4 by up-regulating the activity and expression of the arachidonate-metabolizing enzymes prostaglandin H synthase and 5-lipoxygenase respectively. Consistent with this observation, selective inhibitors of prostaglandin H synthase (i.e. indomethacin) and 5-lipoxygenase (i.e. MK886 and caffeic acid) protected CHP100 cells against gp120-induced necrosis. Treatment with gp120 also enhanced membrane lipid peroxidation and this may be implicated in the execution of cell damage. Interestingly, incubation with exogenous nitric oxide (NO) mimicked the effects of gp120 on necrotic death of CHP100 cells and activation of prostaglandin H synthase and 5-lipoxygenase. This suggests that NO might participate in the mechanism by which gp120 activates the arachidonate cascade.
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PMID:Cytotoxic effect of HIV-1 coat glycoprotein gp120 on human neuroblastoma CHP100 cells involves activation of the arachidonate cascade. 963 60

The cytokines are a large and diverse family of polypeptide regulators with multiple regulatory functions that have been comprehensively evaluated in the immune system under strictly controlled experimental conditions. These peptide signals exhibit often unpredictable interactions when evaluated for their pathophysiological involvement in specific inflammatory conditions in vivo. In our joint efforts to understand the basis for early pathophysiological changes in the brains of HIV-infected subjects, we have developed animal models for lentivirus infections, and assessed the actions of various cytokines acutely on transmitter release properties in vitro, and in an in vivo transgenic mouse model. IL1beta, IL2, IL6, and IFNalpha will each enhance the release of AVP in slices of rat hypothalamus and amygdala. TGFbeta selectively blocks the ability of ACh to release AVP from hypothalamus or amygdala, but has no effects on the release stimulated by other cytokines. IFNalpha, but not TGFbeta will also activate CRH release; as with AVP, TGF selectively blocks the ACh-stimulated CRH release in both amygdala and hypothalamus. The IFNalpha-stimulated release of AVP and CRH appears to be mediated by cyclic GMP production, and this release by IFNalpha and IL-2 may be mediated in part by activation of constitutive nitric oxide synthase. These combined in vitro actions would suggest that cns cytokine actions should upregulate the hypothalamic pituitary adrenal axis. In a transgenic mouse model with increased astrocytic expression and release of the cytokine IL6, the HPA axis is upregulated, but the effect seems attributable to adrenocortical hypersensitization to ACTH. Lastly, in studies of cytokine mediated effects on astrocytic uptake of the excitatory transmitter glutamate, the reactive oxygen species hydrogen peroxide and peroxynitrite, but not nitric oxide, inhibited glutamate uptake in a concentration-dependent manner. Although superoxide and nitric oxide had no effect by themselves on the rate of glutamate uptake by astrocytes, the same cultures did respond to nitric oxide with a sustained increase in cytoplasmic free calcium. Thus while reactive oxygen species do provide a potential path to neurotoxicity but one apparently not involving nitric oxide. These various data provide important opportunities for early therapeutic interventions in neuro-inflammatory states such as Neuro-AIDS.
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PMID:Inflammatory cytokines: putative regulators of neuronal and neuro-endocrine function. 965 48


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