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

The development of graft-versus-host disease (GVHD) is associated with long-lasting and profound deficits in immune function that lead to increased morbidity and mortality after bone marrow transplantation (BMT). We investigated a mechanism of T-cell immunodeficiency in response to mitogen or alloantigen in an experimental model of acute GVHD by analyzing the roles of two immunosuppressive moieties: interferon gamma (IFN-gamma) and nitric oxide (NO). Splenocytes from mice with GVHD did not proliferate either to the T-cell mitogen, concanavalin A (Con A), or to host alloantigens, but only mitogen-activated cultures produced increased levels of NO. The abrogation of NO synthesis with LG-mono-methyl-arginine (NMMA) restored mitogen-induced proliferation but not the response to host antigens. The mechanism of impared proliferation to mitogen was dependent on IFN-gamma because blockade of this cytokine in culture inhibited NO production and restored proliferation to Con A to levels similar to those in transplanted control mice without GVHD. NMMA did not substantially reduce IFN-gamma levels, demonstrating that NO acted distally to IFN-gamma in the pathway of immunosuppression in response to mitogen. Furthermore, the prevention of IFN-gamma production in vivo after allogeneic BMT, by transplantation of polarized type 2 donor T cells (secreting interleukin-4 but not IFN-gamma), also prevented NO production and restored splenocyte responses to mitogen. Our data demonstrate the existence of NO-dependent and NO-independent pathways involved in suppression of T-cell proliferation during acute GVHD. Excess NO synthesis appears to be one mechanism by which IFN-gamma induces immunodeficiency after allogeneic BMT.
 ...
PMID:Interferon-gamma suppresses T-cell proliferation to mitogen via the nitric oxide pathway during experimental acute graft-versus-host disease. 870 22

Nitric oxide (NO) is a newly discovered gas that plays an important role in cell communication and host resistance to infection. The production of NO was examined in the sera of seven children infected with human immunodeficiency virus type 1 (HIV-1) and in the sera of 14 children who became seronegative for HIV-1 during the first year of life. In addition, we determined serum levels of various cytokines, such as interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and gamma interferon (IFN-gamma), inasmuch as these cytokines are potent inducers of NO production. Production of NO, detected as circulating serum levels of nitrite, was measured with use of the Griess reagent. Serum levels of cytokines were determined by enzyme immunoassay. Increased serum levels of nitrite were observed in children with HIV-1 infection (0.4 +/- 0.2 mumol/L; P = .013), and in those who became seronegative for HIV-1 during the first year of life (0.5 +/- 0.3 mumol/L; P = .04). Furthermore, serum levels of IL-1 beta and TNF-alpha were significantly elevated in children with HIV-1 infection (37.5 +/- 23.6 pg/mL and 91.2 +/- 45.1 pg/mL, respectively). Prophylactic administration of intravenous immune globulin provoked a significant decrease of circulating levels of nitrite in children with HIV-1 infection. In conclusion, NO may play a role as a cytostatic or cytotoxic factor for invading microorganisms, and thus it is probably involved in limiting and/or eradicating infection.
 ...
PMID:Increased levels of nitrite in the sera of children infected with human immunodeficiency virus type 1. 872 4

To examine the role of nitric oxide (NO) in murine AIDS (MAIDS) pathogenesis, we determined NO production and inducible NOS (iNOS) mRNA expression in the macrophages of LP-BM5-infected mice, together with the in vivo effects of L-NAME, a competitive inhibitor of NO synthase. LP-BM5 infection induced neither spontaneous nitrite production nor iNOS mRNA expression. No differences in IFN gamma + LPS-induced nitrite production or iNOS mRNA expression were observed in macrophages, from non-infected or infected mice. Spleen weight, ecotropic MuLV replication, the blood lymphocyte phenotype and proliferative response of splenocytes were not modified by L-NAME. LP-BM5 infection did not increase macrophage NO production and NO production did not appear to protect against LP-BM5-induced immunodeficiency.
 ...
PMID:Absence of involvement of nitric oxide in LP-BM5-induced immunodeficiency syndrome. 888 Jan 43

The purpose of this review is to analyze the role of reactive oxygen species (ROS) in the pathogenesis of viral infections, an area of research that has recently gained momentum given the accumulation of evidence regarding the role of ROS in the pathogenesis of infection with the human immunodeficiency virus (HIV). Attention will be focussed on three classes of viruses: (1) RNA viruses, (2) DNA viruses, and (3) retroviruses, with particular attention to influenza viruses, hepatitis B virus, and HIV as representative examples of these three classes, respectively. For each type of virus, evidence for the following will be analyzed: (1) the effect of the virus on activation of phagocytic cells to release ROS and pro-oxidant cytokines such as tumor necrosis factor; (2) the effect of the virus on the pro-/antioxidant balance in host cells, including virally induced inhibition of antioxidant enzymes such as superoxide dismutase and virally induced increases in pro-oxidants such as nitric oxide; (3) effects of the redox state of the cell on the genetic composition of the virus as well as ROS-mediated release of host cell nuclear transcription factor-kappa-B, resulting in increased viral replication; and (4) efficacy of antioxidants as therapeutic agents in viral diseases of both animal models and patients.
 ...
PMID:Oxidative stress during viral infection: a review. 889 67

The objective of our study was to determine the production of nitric oxide (NO) in patients infected with human immunodeficiency virus (HIV) and its relation to cellular immunity, activation of mononuclear phagocytes and the amount of circulating virus. Therefore, serum nitrate, the stable metabolite of NO, the number of peripheral CD4+ T-lmphocytes, serum neopterin, plasma HIV-RNA and HIV-DNA in peripheral blood mononuclear cells of afebrile HIV-infected patients were determined. Serum nitrate levels were significantly (p = 0.002) increased in HIV-infected patients (median 37 microM, range 13-137 microM, n = 77) in comparison to healthy subjects (median 28 microM, range 21-40 microM, n = 17). Serum nitrate levels did not correlate with the number of CD4+ T-lymphocytes (r = 0.05, p > 0.05). Serum nitrate levels were positively correlated with neopterin (r = 0.36, p = 0.05, n = 30), the amount of HIV-DNA in peripheral blood mononuclear cells (r = 0.63, p < 0.001, n =27) and plasma HIV-RNA levels (r = 0.35, p = 0.08, n = 27). A possible explanation of our findings is that HIV induces the production of NO by means of activated mononuclear phagocytes.
 ...
PMID:Increased production of nitric oxide correlates with viral load and activation of mononuclear phagocytes in HIV-infected patients. 889 95

To induce peptide-specific antibodies in mice, as a model for vaccination against human immunodeficiency virus (HIV), lipopeptide analogs conjugated with three repeating units (KAB-112; designated as gp120-peptide) of a part (Gly-Pro-Gly-Arg-Ala-Phe) of the amino acid sequences of the V3 loop region in gp120 of HIV were synthesized. The mitogenicity, production of nitric oxide (NO) and induction of peptide-specific antibodies in mice by synthetic lipopeptides were examined. Compounds, KAB-8 (diacylglycerol-tetrapeptide having a part of the amino acid sequence in Escherichia coli), KAB-116 (diacylglycerol-cysteine), KAB-117 (diacylglycerol with gp120-peptide) and KAB-121 (KAB-8 with gp120-peptide) were capable of increasing significantly the incorporation of [3H]thymidine into splenocytes of C3H/He mice at concentrations ranging from 12.5 to 100 microM, but KAB-112 (gp120-peptide) and KAB-115 (monoacylglycerol with gp120-peptide) did not show such activity. The compounds, KAB-8, KAB-117 and 121, exhibited NO production in murine macrophages. When 50 nmol of these compounds was administered intraperitoneally into BALB/c mice on days 0, 16 and 46, the peptide-specific antibody titers in their sera produced by each compound were determined with ELISA. The sera of KAB-117 and KAB-121, which were obtained on days 14, 30, 42, 57 and 70, had a higher titer than that of KAB-112 and KAB-115, suggesting that the diacylglycerol derivative enhance the production of the peptide-specific antibodies.
 ...
PMID:Antibody-producing effects in mice by synthetic immunoactive lipopeptides with the conjugated amino acid sequence of gp120 in human immunodeficiency virus. 891 95

Indirect mechanisms are implicated in the pathogenesis of the dementia associated with human immunodeficiency virus-type 1 (HIV-1) infection. Proinflammatory molecules such as tumor necrosis factor alpha and eicosanoids are elevated in the central nervous system of patients with HIV-1-related dementia. Nitric oxide (NO) is a potential mediator of neuronal injury, because cytokines may activate the immunologic (type II) isoform of NO synthase (iNOS). The levels of iNOS in severe HIV-1-associated dementia coincided with increased expression of the HIV-1 coat protein gp41. Furthermore, gp41 induced iNOS in primary cultures of mixed rat neuronal and glial cells and killed neurons through a NO-dependent mechanism. Thus, gp41-induced NO formation may contribute to the severe cognitive dysfunction associated with HIV-1 infection.
 ...
PMID:Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41. 894 6

Ataxia-telangiectasia (A-T) is a human autosomal recessive disease characterised by immunodeficiency, extreme sensitivity to ionising radiation and progressive cerebellar ataxia. The defective gene has recently been cloned and is a member of the phosphatidylinositol 3-kinase family. We have investigated the possibility that the neurodegeneration in A-T might be induced by an endogenously formed mutagen causing radiation-like damage. Nitric oxide is known to be formed in the cerebellum and we present evidence that A-T fibroblasts are hypersensitive to killing by the nitric oxide donor S-nitrosoglutathione (GSNO), as are fibroblasts from a radiosensitive individual without ataxia. Killing was determined as loss of colony forming ability. GSNO induces dose-dependent DNA strand breakage, but to no greater extent in A-T fibroblasts. Breakdown of GSNO to nitrite and nitrate appears to occur to the same extent in both normal and A-T fibroblasts. Cell killing by GSNO appears to be associated in both types of cell with formation of nitrite, rather than nitrate, as the ultimate oxidation product of nitric oxide.
 ...
PMID:Hypersensitivity of ataxia-telangiectasia fibroblasts to a nitric oxide donor. 895 60

Infectious diseases and malnutrition represent major burdens afflicting millions of people in developing countries. Both conditions affect individuals in industrialized nations, particularly the aged, the HIV-infected, and people with chronic diseases. While malnutrition is known to induce a state of immunodeficiency, the mechanisms responsible for compromised antimicrobial resistance in malnourished hosts remain obscure. In the present study, mice fed a 2% protein diet and developing protein calorie malnutrition, in contrast to well-nourished controls receiving a 20% protein diet, rapidly succumbed to infection with Mycobacterium tuberculosis. Malnourished mice exhibited a tissue-specific diminution in the expression of interferon gamma, tumor necrosis factor alpha, and the inducible form of nitric oxide synthase in the lungs, but not the liver. The expression of these molecules critical to the production of mycobactericidal nitrogen oxides was depressed in malnourished animals in the lungs specifically at early times (< 14 days) after infection. At later times, levels of expression became comparable to those in well-nourished controls, although the bacillary burden in the malnourished animals continued to rise. Nevertheless, urinary and serum nitrate contents, an index of total nitric oxide (NO) production in vivo, were not detectably diminished in malnourished, mycobacteria-infected mice. In contrast to the selective and early reduction of lymphokines and the inducible form of nitric oxide synthase in the lung, a marked diminution of the granulomatous reaction was observed in malnourished mice throughout the entire course of infection in all tissues examined (lungs, liver, and spleen). Remarkably, the progressively fatal course of tuberculosis observed in the malnourished mice could be reversed by restoring a full protein (20%) diet. The results indicate that protein calorie malnutrition selectively compromises several components of the cellular immune response that are important for containing and restricting tuberculous infection, and suggest that malnutrition-induced susceptibility to some infectious diseases can be reversed or ameliorated by nutritional intervention.
 ...
PMID:Effects of protein calorie malnutrition on tuberculosis in mice. 896 45

A majority of human immunodeficiency virus type I (HIV-1)-infected-individuals manifest a plethora of central nervous system (CNS) diseases unrelated to opportunistic infections, including acquired immune deficiency syndrome (AIDS)-dementia complex (ADC), encephalitis, and various other disorders of the CNS. A series of devastating clinical conditions in the CNS of certain HIV-1-infected-individuals may be caused by infection of cells in the brain parenchyma. ADC is characterized by cognitive dysfunction, motor difficulties, coordination abnormalities and other neurological signs and symptoms, which develop in many HIV-1-infected-individuals. The precise molecular mechanisms leading to AIDS dementia remain incompletely explained. Various mechanisms including cytokine dysregulation, toxic effects of viral proteins and release of certain toxic substances from macrophages, especially nitric oxide, have been implicated as pathogenic mediators in the development of ADC. We have examined post mortem CNS tissues collected from 22 patients, previously diagnosed with AIDS, to explore if nitric oxide is responsible for the observed pathology in ADC. As controls, we utilized tissues collected from the brains of patients who expired without AIDS or other CNS pathologies. In addition, we also utilized post-mortem brain tissues from eight patients who were diagnosed with multiple sclerosis (MS) and were found to express inducible nitric oxide synthase (iNOS) in our previous studies, as positive controls. Highly sensitive in situ reverse transcriptase-initiated polymerase chain reaction (RT-IS-PCR) studies demonstrated that iNOS mRNA was present in the CNS tissues from all the positive MS controls, but were absent in all 22 specimens from AIDS patients, as well as in the brain tissues from normal controls. We have also analyzed the tissues for the presence of the NO reaction product, nitrotyrosine, to evaluate the presence of a protein nitrosalation adduct. Nitrotyrosine was not demonstrable in any of the AIDS brains. These findings indicate that iNOS may not play a significant role in the neuropathogenesis of most cases of ADC.
 ...
PMID:Absence of the inducible form of nitric oxide synthase in the brains of patients with the acquired immunodeficiency syndrome. 911 Nov 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>