Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Virus-associated hemophagocytic syndrome (VAHS) is a disorder characterized by benign generalized histiocytic proliferation and marked hemophagocytosis associated with systemic viral infection. An immunodeficiency which includes an extremely decreased leukocyte and platelet count together with abnormalities in the CD4/CD8 ratio are the most common features of VAHS. Here we report an early-onset periodontitis (EOP) patient with VAHS from the standpoint of host-parasite interaction to understand the effect of this systemic disorder which might possibly influence susceptibility to periodontal disease. The patient is a 16-year-old Japanese male clinically diagnosed as having generalized EOP with slight gingival inflammation and moderate bone loss. This patient manifested VAHS at 3 years of age, and then had an unusual 4 recurrences (at 5, 7, 11, and 14 years old). Laboratory tests conducted include: 1) complete blood analyses: 2) peripheral neutrophil functions (chemotaxis, phagocytosis, superoxide production, and adherence); 3) peripheral lymphocyte subpopulations and functions, T-cell proliferative activity and productivity of cytokines (interleukin-2 [IL-2], interferon gamma [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]); 4) serum cytokine levels (IL-1 beta, IL-2, soluble IL-2 receptor [sIL-2R], IL-4, IL-6, IFN-gamma, and TNF-alpha; 5) serum immunoglobulin G (IgG) antibody titers against periodontopathic bacteria; 6) serological human leukocyte antigen (HLA) typing; and 7) determination of bacterial flora of the periodontal pockets. The results indicated that the patient's neutrophil chemotaxis and random migration were below the normal range. In lymphocyte examinations, T-cell proliferative activity, IL-2, and IFN-gamma productivity were elevated. Serum IFN-gamma level was also significantly higher than normal range. No specific periodontopathic bacteria were predominant in the periodontal pockets, however, the serum IgG titer against Porphyromonas gingivalis was elevated throughout the examination period. It is suggested that VAHS might be a possible risk factor for periodontal disease, and hence may serve as a model in understanding the role of host defense mechanisms in the establishment of inflammatory periodontal disease.
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PMID:Host defensive, immunological, and microbiological observations of an early-onset periodontitis patient with virus-associated hemophagocytic syndrome. 944 99

Because malaria-stimulated cytokine production may have deleterious effects on human immunodeficiency virus type 1 (HIV-1) replication, the effects of Plasmodium falciparum antigens on HIV-1 replication were studied. Stimulation with malarial antigens significantly enhanced HIV-1 replication of HIV-1LAV and primary HIV-1 isolates (subtype A) in CD8-depleted peripheral blood mononuclear cells from naive donors. The malarial antigen-induced activation of HIV-1 was due to cellular activation as judged by the expression of cell activation markers and proliferative responses. While malarial antigen stimulation increased expression of tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6), only monoclonal antibodies (MAbs) to TNF-alpha inhibited malarial antigen-induced HIV-1 replication, whereas MAb to IL-6 had no effect. Malarial antigen increased HIV-1 replication by increasing viral mRNA expression and by activating long terminal repeat-directed viral transcription. These data suggest that P. falciparum infection can modulate HIV-1 pathogenesis by activating lymphocytes and stimulating viral replication through the production of cytokines.
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PMID:Plasmodium falciparum antigen-induced human immunodeficiency virus type 1 replication is mediated through induction of tumor necrosis factor-alpha. 946 33

We have characterized the mechanism for human immunodeficiency virus type 1 (HIV-1) latent infection in a human T cell line MOLT-4 subclone no. 8 (MOLT-#8). The inocula used were HIV-1 recovered from MT-4 during the acute (NL-A) and persistent (NL-P) phases after HIV-1 infection. On infection of MOLT-#8 with NL-A, viral antigens first appeared in almost 100% of the cells whereafter the numbers of viable antigen-positive cells declined. In contrast, following infection with NL-P the expression of viral antigens was maintained in almost 100% of the cells. In fact, limiting dilution of NL-P-infected cells allowed us to isolate 43 subclones, all of which were positive for viral antigen expression in almost 100% of the cells (type I). In sharp contrast, only two of 41 subclones from NL-A-infected cells were of type I. Seven subclones were latently infected with HIV-1; latent HIV-1 in six subclones (type II), but not in one type III subclone, was activated by tumour necrosis factor (TNF)-alpha or phorbol 12-myristate 13-acetate. The remaining subclones were negative for the viral genome. Of particular note is the effect of endogenous TNF-alpha generated during the acute phase of virus replication which shifted the virus phenotype. Thus, the presence of TNF-alpha during the acute phase of virus replication seems to play a key role in the selective destruction of cells expressing higher levels of viral antigens and in subsequent establishment of latent infection in host T cells.
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PMID:Generation of endogenous tumour necrosis factor-alpha in MOLT-4 cells during the acute replication phase of human immunodeficiency virus type 1 determines the subsequent latent infection. 947 6

Replication of human immunodeficiency virus type 1 (HIV-1) is regulated by a host transcription factor, nuclear factor kappaB (NF-kappaB). NF-kappaB belongs to a group of inducible transcription factors and its activity is regulated by multiple cellular signal transduction pathways, including kinases. These kinases are known to be involved in signal-induced NF-kappaB activation and in the induction of HIV-1 gene expression from latently infected cells. In this study we have examined the effect of a newly developed serine/threonine kinase inhibitor, fasudil hydrochloride (FH), on the replication of HIV-1. Although FH was initially developed as a compound that inhibited a myosin light chain kinase (MLCK) and had been approved for clinical use in the treatment of vasospasm after subarachnoid hemorrhage, this study shows its efficacy in blocking HIV-1 replication in latently infected patients. When FH was added to monocytic cell lines latently infected with HIV-1, U1 and OM10.1, the induction of HIV-1 replication by TNF-alpha was blocked at noncytotoxic doses. The IC50 values of HIV-1 induction by FH were 9.3 and 24 microM for U1 and OM10.1, respectively. Because FH could block TNF-alpha-induced, NF-kappaB-dependent gene expression, as examined by the transient luciferase expression assay, the effect of FH was considered to be due to the blocking of the signal transduction pathway of NF-kappaB activation. Although the in vivo effect of FH in blocking HIV-1 induction is not yet known, these findings indicate the feasibility of clinical use of FH and its derivatives in decreasing viral load to prevent clinical development of acquired immunodeficiency syndrome (AIDS) among HIV-1-infected individuals.
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PMID:Inhibition of human immunodeficiency virus type 1 replication by a bioavailable serine/threonine kinase inhibitor, fasudil hydrochloride. 951 89

X-irradiation has been used in the treatment of several human diseases, including AIDS-related-malignancies. X-irradiation might induce the transcription and the replication of human immunodeficiency virus type 1 (HIV-1) and enhance nuclear factor kappa B (NF-kappaB). In the present article we show that the activation of the HIV-1 long terminal repeat (LTR) by direct X-irradiation can be mimicked by coculture of transfected cells with X-irradiated nontransfected (HIV-1-negative) cells. In the human colonic carcinoma cell line HT29, the activation seems to depend on an extracellular factor(s) released by a cell line treated with X-rays. The HIV-1 LTR cis-acting element conferring X-indirect responsiveness was identified as the kappaB tandem motif. The two main nuclear HIV-1 kappaB-binding complexes activated by X-direct and -indirect irradiation were the NF-kappaB p50/p65 and c-Rel/p65 heterodimers. Nuclear NF-kappaB activation was dependent on protein neosynthesis. It was partially inhibited by 100 microM pyrrolidine dithiocarbamate, a potent antioxidant drug, but was not correlated with a significant decrease in cellular IkappaBalpha. Furthermore, X-irradiation induces the expression of several cytokine genes generally associated with stress response and antibodies against interleukin 6 and TNF-alpha partially inhibited the X-indirect activation of the HIV-1 LTR. The use of protein kinase C (PKC)-specific inhibitor and of forskolin, an adenylate cyclase activator, suggests that a PKC-dependent pathway and the cAMP intracellular concentration could play a role in the X-indirect enhancement of HIV-1 LTR transcription in the HT29 cell line. In addition, supernatants of an X-irradiated HT29 cell culture activated the HIV-1 stimulation in infected peripheral blood monocytes.
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PMID:Secretion of extracellular factor(s) induced by X-irradiation activates the HIV type 1 long terminal repeat through its kappaB motif. 951 97

The relationship between Mycobacterium avium complex (MAC) bacteremia and proinflammatory cytokine and human immunodeficiency virus type 1 (HIV-1) RNA levels in AIDS was investigated. During a prospective study, blood samples were drawn monthly for mycobacterial cultures. Sera were available at baseline and onset of MAC bacteremia from 20 cases and at corresponding times from 19 controls. Mean interleukin-6 (IL-6) levels were 154% greater at the time of MAC bacteremia in cases than in controls. The IL-6 levels correlated with body temperature, serum tumor necrosis factor (TNF-alpha) levels, and alkaline phosphatase levels (P < or = .004 for each). Although TNF-alpha levels tended to rise more in MAC patients than in controls, the difference was not significant. However, among both cases and controls, serum TNF-alpha levels rose significantly from baseline to the time of last sample, irrespective of MAC infection (P = .015). Bacteremia was not associated with increased serum HIV-1 RNA levels. Thus, early MAC bacteremia is associated with increases in serum IL-6 levels, while TNF-alpha levels rise over time during advanced AIDS.
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PMID:Proinflammatory cytokine and human immunodeficiency virus RNA levels during early Mycobacterium avium complex bacteremia in advanced AIDS. 960 63

Tuberculosis has emerged as an epidemic, extended by the large number of individuals infected with human immunodeficiency virus type 1 (HIV-1). The major goal of this study was to determine whether the mycobacterial cell wall component mannose-capped lipoarabinomannan (ManLAM) of Mycobacterium tuberculosis (M. tuberculosis) could activate transcription of HIV-1 in T cells with the use of an in vitro cell culture system. These experiments are of prime importance considering that CD4-expressing T lymphocytes represent the major virus reservoir in the peripheral blood of infected individuals. Using the 1G5 cell line harbouring the luciferase reporter gene under the control of the HIV-1 LTR, it was first found that culture protein filtrates (CFP) from M. tuberculosis or purified ManLAM could activate HIV-1 LTR-dependent gene expression unlike similarly prepared CFP extracts devoid of ManLAM. The implication of protein tyrosine kinase(s), protein kinase A and/or protein kinase C was highlighted by the abrogation of the ManLAM-mediated activation of HIV-1 LTR-driven gene expression using herbimycin A and H7. It was also determined, using electrophoresis mobility shift assays, that M. tuberculosis ManLAM led to the nuclear translocation of the transcription factor NF-kappaB. M. tuberculosis ManLAM resulted in clear induction of the luciferase gene placed under the control of the wild-type, but not the kappaB-mutated, HIV-1 LTR region. Finally, the ManLAM-mediated activation of HIV-1 LTR transcription was found to be independent of the autocrine or paracrine action of endogenous TNF-alpha. The results suggest that M. tuberculosis can upregulate HIV-1 expression in T cells and could thus have the potential to influence the pathogenesis of HIV-1 infection.
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PMID:Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-kappaB-dependent activation of human immunodeficiency virus type 1 long terminal repeat in T cells. 963 75

The simian immunodeficiency virus (SIV) isolate, SIVsmmPBj14, contains an immunoreceptor tyrosine-based activation motif (ITAM) within its nef gene product and triggers efficient lymphoproliferation in vitro. In experimentally inoculated macaque monkeys, this virus causes acutely lethal enteropathy, which is accompanied by high levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha. Since TNF-alpha has been shown to possess weak comitogenic activity for antigen- or mitogen-induced human T-cell proliferation, experiments were conducted to examine whether TNF-alpha might also contribute to SIVsmmPBj14-induced lymphoproliferation. Addition of a dimeric soluble human TNF receptor (sTNFR):Fc fusion protein to SIVsmmPBj14-infected simian peripheral blood mononuclear cells (PBMC) resulted in a partial (> 50%) inhibition of virally-induced lymphoproliferation, but had no effect on the strong T-cell activation signal provided by phytohemagglutinin and interleukin-2. Finally, the addition of exogenous human TNF-alpha to simian PBMC infected with a non-mitogenic variant of SIVsmmPBj14 failed to result in detectable lymphoproliferation, suggesting that TNF-alpha alone is not sufficient to cause the proliferation of SIV infected T-cells. Taken together, the data suggest that endogenous TNF-alpha enhances SIVsmmPBj14-induced lymphoproliferation in simian PBMC cultures.
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PMID:Endogenous tumor necrosis factor-alpha contributes to lymphoproliferation induced by simian immunodeficiency virus variant, SIVsmmPBj14. 971 38

Lymphokine activated killer (LAK) cells are capable of killing not only malignant cells but also hyphal form of Candida albicans in vitro. When peripheral blood mononuclear cells (PBMC) from normal healthy donors were cultured for 72-96 hrs with 1,500 international unit (IU)/ml interleukin-2 (IL-2), marked LAK activity was induced. However, even prior to IL-2 activation, PBMC isolated from some normal subjects and those from almost all individuals who are infected by human immunodeficiency virus type 1 (HIV-1) exhibited significant levels of anti-fungal activity. Such pre-activation ("in situ") antifungal activity of PBMC decreased during the initial 48 hrs of IL-2 activation. PBMC from HIV-1 seropositive subjects showed higher levels of "in situ" anti-fungal activity than normal PBMC did. After a decline of "in situ" activity during the initial 48 hours, LAK activity gradually increased and reached near maximal levels by day 4 and remained more or less constant until day 6. No significant difference was observed between the LAK activity of normal and HIV-1(+) PBMCs on days 4-6. In IL-2 activated normal and HIV-1(+) PBMC cultures, both CD4 and CD8 T cells produced IL-2, INF-gamma as well as TNF-alpha. Production of IL-2 by both CD4 and CD8 T cells was suppressed in HIV-1(+) PBMC cultures, but no significant suppression of INF-gamma production was noted. Meanwhile, TNF-alpha production by CD4 was very much suppressed but no significant changes in TNF-alpha production by CD8 T cells was noted in HIV-1(+) PBMC cultures.
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PMID:Anti-fungal and cytokine producing activities of CD8 + T lymphocytes from HIV-1 infected individuals. 973 53

Proinflammatory cytokines, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-6, have multiple effects in the central nervous system (CNS) not strictly cytotoxic being involved in controlling neuronal and glial activation, proliferation, differentiation and survival, thus influencing neuronal and glial plasticity, degeneration as well as development and regeneration of the nervous system. Moreover, they can contribute to CNS disorders, including multiple sclerosis. Alzheimer's disease and human immunodeficiency virus-associated dementia complex. Recent results with deficient mice in the expression of those cytokines indicate that they are in general more sensible to insults resulting in neural damage. Some of the actions induced by TNF-alpha, and IFN-gamma, including both beneficial and detrimental, are mediated by inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) production. NO produced by iNOS may be beneficial by promoting the differentiation and survival of neurons. IL-6 does not induce iNOS, explaining why this cytokine is less often involved in this dual role protection pathology. Some of the proinflammatory as well as the neurotrophic effects of those cytokines also involve upregulation of cell adhesion molecules (CAM). Those apparently conflicting results may be reconciled considering that proinflammatory cytokines are involved in promoting the disease, mostly by inducing expression of CAM leading to alteration of the blood-brain barrier integrity, whereas they have a protective role once disease is established due to its immunosuppressive or neurotrophic role. Understanding the dichotomy pathogenesis/neuroprotection of those cytokines may provide a rationale for better therapeutic strategies.
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PMID:The role of tumour necrosis factor, interleukin 6, interferon-gamma and inducible nitric oxide synthase in the development and pathology of the nervous system. 977 Feb 42


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