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)

Acemannan, a complex carbohydrate shown to stimulate interleukin-1, tumor necrosis factor alpha and prostaglandin E2 production by macrophages, has also demonstrated antiviral activity in vitro against human immunodeficiency virus, Newcastle disease virus and influenza virus. A pilot study was undertaken to determine acemannan's effect in 49 feline immunodeficiency virus (FIV) infected cats with clinical signs of disease (Stage 3, 4 or 5), 23 of which had severe lymphopenia. Cats received acemannan either by intravenous (Group 1) or subcutaneous (Group 2) injection once weekly for 12 weeks, or by daily oral (Group 3) administration for 12 weeks. Upon entry into the study, cats were randomly assigned to one of the three groups. Laboratory analyses were performed at the beginning of the study and at Weeks 6 and 12. Cats were allowed to continue with a predetermined maintenance regimen of acemannan after completing the 12-week study. Thirteen cats died during the course of treatment. Upon necropsy, the most frequent histopathologic findings were neoplastic, kidney and pancreatic disease. Friedman's two-way ANOVA test showed no significant differences in efficacy among groups administered acemannan by the different routes. Therefore, groups were combined and a signed-ranks test was used to determine changes over time. A significant increase was seen in lymphocyte counts (P < 0.001). Neutrophil counts decreased significantly (P = 0.007), as did incidence of sepsis (P = 0.008). When cats entering with lymphopenia were analyzed separately, a much greater increase in lymphocyte counts was noted (235%) compared with non-lymphopenic cats (42%). A survival rate of 75% was found for all three groups. Thirty-six of 49 animals are alive 5-19 months post-entry. These results suggest that acemannan therapy may be of significant benefit in FIV-infected cats exhibiting clinical signs of disease.
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PMID:Pilot study of the effect of acemannan in cats infected with feline immunodeficiency virus. 133 96

The immunomodulatory capacities of N,N-dimethylglycine (DMG) were examined in random-source cats. Blood mononuclear leukocytes of healthy adult cats that had negative results to tests for FeLV and feline immunodeficiency virus were exposed in vitro to various concentrations of DMG (10 to 1,000 micrograms/ml) and were evaluated for proliferative responses to T- or B-cell phytomitogens. Although increased, mean lymphocyte blastogenic responses to phytolectins in DMG-treated cultures did not differ significantly from responses of untreated cultures. For in vivo studies, cats were given a solution containing either 100 mg of DMG or a control solution without DMG orally at 8 AM and 6 PM for 40 consecutive days. On post-treatment day 24 and 25, mean blastogenic responses to phytolectins in DMG-treated and control cats inoculated 10 days earlier with an inactivated feline virus vaccine were similar. Cats given DMG and inoculated twice in a 3-week interval with a commercial vaccine containing inactivated feline herpesvirus-1 and feline calicivirus had significantly (P = 0.045) lower virus neutralizing serum antibody titers against feline herpesvirus-1, compared with titers of control cats, whereas feline calicivirus titers were similar in both groups. On day 25, mean serum interferon activity, induced after IV inoculation of Newcastle disease virus, was significantly (P = 0.021) lower in the DMG-treated cats. Results of this study of DMG in healthy cats failed to demonstrate enhancement of either specific or nonspecific immunity.
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PMID:Immunologic responses in healthy random-source cats fed N,N-dimethylglycine-supplemented diets. 138 80

Monocytes treated with interferon-alpha (IFN-alpha) at virus challenge show no evidence of human immunodeficiency virus (HIV) infection: no p24 antigen or reverse transcriptase (RT) activity, no viral mRNA and no proviral DNA. Levels of p24 antigen and RT activity in monocytes infected with HIV 1-3 weeks before IFN-alpha treatment gradually decrease to baseline. HIV-induced cytopathic changes are markedly reduced, as are levels of HIV mRNA: the frequency of productively infected cells is less than or equal to 1%. But, levels of proviral DNA in the IFN-alpha-treated and control HIV-infected cells are indistinguishable, and remain so through 3 weeks. Large quantities of proviral DNA in IFN-alpha-treated cells with little active transcription suggest true microbiological latency. The major potential source for IFN-alpha in HIV-infected patients is the macrophage. With any of 15 virus isolates, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, IFN-omega or IFN-beta are not detected nor the mRNA expressed in HIV-infected or uninfected monocytes. Both uninfected and HIV-infected monocytes produce high levels of these cytokines after treatment with synthetic double-stranded RNA (poly-I:C). Uninfected monocytes also produce high levels of IFN-alpha after treatment with Poly-I:C, Newcastle disease virus or herpes simplex virus. In marked contrast, HIV-infected monocytes express no IFN-alpha activity or mRNA before or after treatment with any of these agents. The markedly diminished capacity of HIV-infected monocyte to produce IFN-alpha reflects a specific transcriptional block and may be an adaptive mechanism of virus to alter basic microbicidal functions of this cell.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of cytokine and viral gene expression in monocytes infected with the human immunodeficiency virus. 188 15

Interferon alpha (IFN-alpha) induces significant antiretroviral activities that affect the ability of human immunodeficiency virus (HIV) to infect and replicate in its principal target cells, CD4+ T cells and macrophages. A major endogenous source of IFN-alpha during any infection is the macrophage. Thus, macrophages have the potential to produce both IFN-alpha and HIV. In this study, we examined the production of IFN-alpha and other cytokines by macrophage colony-stimulating factor (M-CSF)-treated cultured monocytes during HIV infection. Tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), IL-6, IFN-omega, or IFN-beta were not detected nor was the mRNA expressed in either uninfected or HIV-infected monocytes. However, both uninfected and HIV-infected monocytes produced high levels of each of these cytokines after treatment with synthetic double-stranded RNA [poly(I).poly(C)]. Uninfected monocytes also produced high levels of IFN-alpha after treatment with poly(I).poly(C), Newcastle disease virus, or herpes simplex virus. In marked contrast to the preceding observations, HIV-infected monocytes produced little or no IFN-alpha before or after treatment with any of these agents. The absence of detectable IFN-alpha activity and mRNA in poly(I).poly(C)-treated HIV-infected monocytes was coincident with high levels of 2',5' oligoadenylate synthetase and complete ablation of HIV gene expression. The antiviral activity induced by poly(I).poly(C) may be a direct effect of this synthetic double-stranded RNA or secondary to the low levels of IFN-beta and IFN-omega produced by infected cells. The markedly diminished capacity of HIV-infected monocytes to produce IFN-alpha may reflect a specific adaptive mechanism of virus to alter basic microbicidal functions of this cell. The inevitable result of this HIV-induced cytokine dysregulation is virus replication and persistence in mononuclear phagocytes.
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PMID:A selective defect of interferon alpha production in human immunodeficiency virus-infected monocytes. 198 24

Virus inducible elements (IE) in promoters of mouse alpha-interferon and human beta 1-interferon genes contain multiple copies of the hexanucleotide sequence AGT-GAA or its variants which are also found in the interferon-stimulated response element of genes transcriptionally induced by interferon. We have examined the similarities between virus and interferon induction of gene expression and the role of AGTGAA and AAT-GAA hexamers in these responses. Hybrid plasmids were constructed by inserting the IE region, the alpha 4 promoter, or the multiple copies of AGTGAA or AAT-GAA 5' to the inactive-45 human immunodeficiency-chloramphenicol acetyltransferase hybrid gene, and their inducible expression was studied in a transient expression assay. In L-cells, multiple hexamers were efficiently induced both by infection with Newcastle disease virus and by interferon treatment; while the alpha 4 promoter and the IE inducible region were induced predominantly by virus rather than by interferon. In order to dissociate the effect of virus and endogenous interferon on the induction process, we examined the gene expression in Vero cells, which have undergone homozygous deletion of type 1 interferon genes, and in VNPT-159 cells, which were derived from Vero cells by insertion of an inducible human interferon beta 1 gene. The results show that while the alpha 4 promoter was efficiently induced only by virus in both cell types, the constructs containing shorter segments of the IE were induced by both virus and interferon in Vero cells. However, the inducibility by interferon was not detected in VNPT-159 cells, suggesting that the presence of endogenous interferon suppresses interferon-induced expression of hexanucleotide repeats and the short inducible region. In contrast, virus inducibility of endogenous interferon-stimulated genes, ISG-15 and ISG-54, was about 100-fold more efficient in VNPT-159 cells than in Vero cells, suggesting that this induction is largely mediated through synthesis of endogenous interferon. Hence, endogenous interferon may play a role in the autoregulation of both interferon genes and interferon-stimulated genes.
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PMID:Virus infection and interferon can activate gene expression through a single synthetic element, but endogenous genes show distinct regulation. 255 Apr 51

We have identified and functionally characterized DNA sequences that are required for the inducible and cell-restricted expression of the murine alpha 4-interferon gene. Hybrid plasmids in which the alpha 4 promoter region or its 5' deletions were inserted upstream of the CAT gene were constructed, and the expression of these hybrid genes was studied in mouse L-cells both in permanent and transient assays with comparable results. Inducible expression was not affected by deletions up to -109; however, when the deletion was extended to -96, inducibility by Newcastle disease virus was abolished; however, this hybrid plasmid was expressed constitutively. Further deletion to -88 did not permit either constitutive or inducible expression. Insertion of the 35-base pair-long sequence (-109 to -75 base pairs) from the alpha 4 promoter region 5' of the minimal alpha 4 or human immunodeficiency virus promoter region, conferred inducibility to these two inactive promoters. The 5' deleted hybrids or plasmids containing the inducible element were induced only at low levels in transfected NIH/3T3 cells that do not express endogenous alpha 4 gene efficiently, indicating that the inducible region also determines the cell-specific expression. A tandem repeat of AGTGAA, which is present in the -109 to -88 region of alpha 4 in two copies, showed both basal levels of expression and inducibility in L-cells, while its analogue AATGAA was highly inducible but was not expressed constitutively. The inducibility of the synthetic hexamer repeats did not show cell type-restricted expression, suggesting that their response does not fully reflect the range of expression observed for the inducible region and the endogenous alpha genes.
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PMID:Upstream regulatory elements of murine alpha 4-interferon gene confer inducibility and cell type-restricted expression. 273 62

Tests for lymphoproliferation and interferon induction in normal blood donors and patients with rheumatoid arthritis (RA) were performed in a whole-blood assay. Patients with high inflammatory RA showed significantly reduced lymphoproliferation and interferon gamma production after stimulation with phytohemagglutinin (PHA) and concanavalin A (Con A) when compared with patients with low inflammatory activity, or with normal control individuals. Similarly, patients with high and low inflammatory RA exhibited a significantly reduced interferon alpha production after stimulation with Newcastle Disease Virus (NDV) when compared with normal blood donors. Our findings may point to an important immunodeficiency of the circulating lymphocytes of RA patients and may explain some of the in vitro immunoregulatory abnormalities reported in this disease.
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PMID:Reduced production of interferon alpha and interferon gamma in leukocyte cultures from patients with active rheumatoid arthritis. 311 75

Alpha- and gamma-interferon (IFN) production by peripheral blood mononuclear cells (PBMC) from 18 patients affected by primary immunodeficiency syndromes was examined and compared with that of 20 normal donors. Patients included 8 with common variable immunodeficiency (CVI), 2 with congenital agammaglobulinemia, 4 with ataxia-telangiectasia, 2 with hyper-IgE syndrome, 1 with chronic EBV infection, 1 with combined immunodeficiency, and 1 with immunodeficiency with hyper-IgM. No spontaneous IFN production was observed in either patients and controls. Newcastle disease virus-induced alpha-IFN production was found to be normal in all patients. Gamma-IFN was induced by both galactose oxidase and staphylococcal enterotoxin (B). Gamma-interferon production was low or undetectable in patients with ataxia-telangiectasia, in immunodeficiency with hyper-IgM, and in hyper-IgE syndrome. No major defect of gamma-IFN was found in other types of immunodeficiency, despite the presence of occasional low producers (1 of 8 CVI patients and 1 case of congenital agammaglobulinemia). No correlation was found between IFN production and natural killer activity in individual patients. The analysis of lymphocyte subsets by monoclonal antibodies revealed gross imbalances of helper/inducer and suppressor/cytotoxic subpopulations, but no overall correlation could be established with gamma-IFN production. The observation of major defects in gamma-IFN yield only in diseases with depression of T cell-mediated immunity might contribute to a better understanding of the pathogenetical mechanisms in these diseases. Moreover, future studies should monitor these in vitro functions and their modifications by in vitro or in vivo manipulations.
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PMID:Interferon production in primary immunodeficiencies. 609 14

The human peripheral blood mononuclear cells responsible for IFN-alpha production in response to viral stimuli have been most often described as either monocytes (as typified by the response to Sendai virus) or as a light density, HLA-DR+ population which is negative for most cell surface markers characteristic of mature T cells, B cells, monocytes, or natural killer cells (as typified by the response to Herpes simplex virus (HSV)). The frequency of IFN-alpha-producing cells (IPC) responding to Sendai virus is typically 10-fold or more higher than those responding to HSV. In the current study, we have used ELISpot assays to determine the frequency of IPC responding to DNA and RNA viruses including HSV, Sendai, vesicular stomatitis virus, cytomegalovirus, adenovirus, SV40, influenza, measles, mumps, Newcastle disease virus (NDV) and human immunodeficiency virus (HIV). The enveloped viruses but not the nonenveloped viruses (adenovirus and SV40) elicited an IFN-alpha response. The frequency of IPC for each of the other viruses was more similar to the low frequency HSV-responding population than to the higher frequency Sendai virus response. These included several viruses in the same family as Sendai virus, namely the paramyxo viruses measles, mumps, and NDV. IPC were also tested for sensitivity to the lysosomotropic drug chloroquine, which diminishes IFN-alpha produced in response to HSV but not Sendai virus. With the exception of Sendai virus, chloroquine treatment abrogated the majority of IFN-alpha produced and IPC against each of the viruses. We conclude that low frequency, nonmonocytic NIPC account for the majority of IFN-alpha production in response to different viruses.
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PMID:Viral induction of low frequency interferon-alpha producing cells. 809 44

Furin, a subtilisin-like mammalian endoprotease, is thought to be responsible for the processing of many proprotein precursors of cellular and viral origin, including gp160 of human immunodeficiency virus type 1, which share the consensus processing site motif, Arg-X-Lys/Arg-Arg, for protease recognition (for reviews, see P. J. Barr, Cell 66:1-3, 1991, and Y. Nagai, Trends Microbiol. 1:81-87, 1993). To confirm and extend the concept that gp160 is processed by furin, we used here a cell line, LoVo, which was recently demonstrated to be furin defective. Unexpectedly, LoVo cells were found to process gp160 as efficiently as normal cell lines do, hence being able to fuse with CD4-expressing HeLa cells and to produce fully infectious virions. On the other hand, the same cell line was almost totally incapable of processing Newcastle disease virus fusion glycoprotein with a similar oligobasic cleavage recognition motif, providing a strong case for furin-mediated processing. Our present study thus raises a further need to search for and identify the proteinases involved in human immunodeficiency virus type 1 gp160 processing rather than supporting the notion that furin is responsible.
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PMID:A furin-defective cell line is able to process correctly the gp160 of human immunodeficiency virus type 1. 818 47


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