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)

An in vitro system has been developed to elucidate the nature of the cellular defect in primary immunodeficiency diseases. Incubation, on human thymic epithelial monolayer cultures, of peripheral blood lymphocytes and bone-marrow cells from a child with documented severe combined immunodeficiency disease resulted in the appearance of a population of cells that formed rosettes with sheep erythrocytes. The same cell preparation permitted the synthesis of antigen-specific, complement-dependent antibodies after in vitro education, as demonstrated in a plaque assay system. In addition, thymic tissue from the same child gave morphologic and functional evidence of maturation when cultured in vitro. The experimental results suggest that in this case, lymphoid precursor cells were present in the bone marrow but failed to differentiate to functional maturity due to a defect in maturation of thymic tissue.
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PMID:Demonstration of an intrathymic defect in a case of severe combined immunodeficiency disease. 109 26

In vitro infectivity of the MT4 lymphoid cell line with human immunodeficiency virus (HIV) has been studied in correlation with the degree of expression of the CD4 molecule at the cell surface. To modulate this CD4 expression in vitro, pre-incubation with phorbol myristate acetate (PMA) was used. The lowest CD4 expression was obtained after 1 to 5 hours. Thereafter, a partial re-expression of OKT4 was observed, e.g., when the incubation time with PMA was extended to 20 hours. Reverse transcriptase (RT) activity decreased and was delayed proportionally to the length of incubation of cells with PMA. This observation was confirmed by the comparable variation of cytopathic effects and of p24 antigen release in culture supernatants. The decrease in HIV infectivity hence correlated with that of OKT4 expression when PMA treatment did not exceed a few hours. By contrast, after extended treatment, infectivity remained decreased although OKT4 expression reappeared.
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PMID:Phorbol ester induces down-regulation of CD4 molecule expression and resistance to in vitro infection by HIV1. 128 70

The long terminal repeat (LTR) of a retrovirus contains sequence elements that constitute a promoter for controlling viral gene expression in infected cells. We have examined regulation of LTR-directed gene expression in feline immunodeficiency virus (FIV), a T-lymphocytopathic lentivirus associated with a fatal AIDS-like disease in domestic cats. Two independent virus isolates, designated FIV-Petaluma and FIV-PPR, have been molecularly cloned and show greater than 85% sequence homology. Both clones (termed pF34 and pPPR) produce infectious virus after transfection of permissive feline cells. Basal promoter activity of the LTRs was measured in various cell lines in transient expression assays using plasmids containing the viral LTR linked to the bacterial chloramphenicol acetyltransferase gene. Both LTRs were strong promoters in several cell lines, although in some cell lines the pF34 LTR had four- to fivefold higher basal activity than the pPPR LTR. FIV LTR mutations affecting the first AP4 site, AP1 site, ATF site, or NF-kappa B site resulted in decreased basal activity of the FIV promoter. Mutational analysis also revealed a negative regulatory element. In cotransfection experiments, both pF34 proviral DNA and pPPR proviral DNA appeared to transactivate either the pF34 LTR or the pPPR LTR; however, levels of transactivation were very low. Cotransfection of both LTRs with FIV subgenomic clones containing various viral open reading frames resulted in low level or no transactivation. The LTRs of both FIV clones responded to cell activation signals in human T-lymphoid cells (Jurkat) treated with phytohemagglutinin and phorbol-12-myristate-13-acetate. Promoter function of both FIV LTRs was also enhanced in cells treated with either forskolin, an inducer of intracellular cyclic-AMP (c-AMP), or dibutyryl c-AMP. Analysis of site-specific mutants showed that a potential AP1 site in the U3 domain of the LTR was required for T-cell activation responses mediated by protein kinase C, whereas a putative ATF site was the target for c-AMP-induced responses mediated by protein kinase A. These studies revealed that cellular transcription factors play a significant role in regulation of FIV gene expression.
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PMID:Regulation of gene expression directed by the long terminal repeat of the feline immunodeficiency virus. 131 May 54

Murine acquired immunodeficiency syndrome (MAIDS) develops when C57B1/6 mice are inoculated with LP-BM5 murine leukemia viruses. Disease progression in these animals is characterized by lymphadenopathy, polyclonal B-cell activation, severe immunodeficiency, and death. Mice with MAIDS have been used to examine the efficacy of antiretroviral therapies for possible use in AIDS patients. In the present work, MAIDS mice were employed to test the hypothesis that established retroviral infection might be cured by the combined use of a cytotoxic agent (cyclophosphamide) and total body irradiation--a regimen reported to have successfully cured HIV-1 infection in one AIDS patient. Results indicate that the ablation of retrovirus-infected lymphoid cells reduced but did not eliminate LP-BM5 infection. Moreover, this regimen was no more effective at controlling virus proliferation or preventing the polyclonal IgG activation characteristic of murine AIDS than was AZT alone.
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PMID:Effect of cyclophosphamide, total body irradiation, and zidovudine on retrovirus proliferation and disease progression in murine AIDS. 131 Jun 3

To develop the polymerase chain reaction (PCR) for the detection of simian T-lymphotropic virus type I (STLV-I) infection, cell lines or peripheral-blood mononuclear cells (PBMC) from 2 non-human primate species [African green monkeys (AGM), Cercopithecus aethiops; baboon, Papio cynocephalus] were evaluated for their STLV-I status using oligonucleotide primer pairs and probes specific for the tax and pol gene regions of the closely related human T-lymphotropic virus type I (HTLV-I). These PCR results were compared with serologic (Western blot assay) and viral culture (p24-antigen capture assay) data. PCR products for both gene regions were detected in established baboon, Japanese macaque and rhesus macaque STLV-I-producing cell lines. STLV-I tax and pol products were also detected in PBMC from 4 of 4 infected AGM and 4 of 4 infected baboons, each of which were also Western-blot-positive and p24-antigen-capture-positive. Of the remaining AGM (n = 7) and baboon (n = 1) which were PCR-negative, each was also Western-blot-negative and p24-antigen-capture-negative. Two seronegative and virus-culture-negative AGM were classified as PCR indeterminate with weak reactivity using tax primers. These primer pairs failed to amplify DNA from uninfected human PBMC, an uninfected human lymphoid cell line, a simian immunodeficiency virus macaque (SIVmac251)-infected cell line and a simian-retrovirus-type-D(SRV-D)-infected cell line. HTLV-II-pol-specific primer pairs failed to amplify DNA from STLV-I-infected cell lines and PBMC from STLV-I-infected monkeys. Further, HTLV-I pol and tax primer pairs successfully amplified RNA from HTLV-I- and STLV-I-infected cell lines by reverse transcriptase (RT)-PCR. We have demonstrated excellent specificity in the detection of STLV-I by PCR using these HTLV-I-derived primers and probes. Additionally, our data suggest that the tax and pol gene regions are conserved between HTLV-I and STLV-I strains found among these diverse species of non-human primates.
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PMID:Detection of simian T-lymphotropic virus type I using the polymerase chain reaction. 131 66

Taking advantage of the abundant expression of the small Epstein-Barr virus (EBV)-encoded RNAs (EBERs) in latently infected cells, we have analyzed 72 normal and hyperplastic lymph nodes and three tonsils of acute infectious mononucleosis (IM) for the presence and distribution of EBV+ cells using EBER-specific in situ hybridization, in some cases combined with immunohistologic demonstration of cell type-characteristic antigens. In IM, large numbers of EBV+ lymphoid B blasts were detectable in extrafollicular areas, whereas germinal centers were generally free of EBV+ cells. In reactive lymph nodes, the frequency of EBV+ cells varied with the degree of lymphoid hyperplasia and underlying immune status. The lowest numbers of EBV+ cells were detected in nonactivated lymph nodes and highest in human immunodeficiency virus-associated lymphadenopathy. If present in these lymph nodes, EBV+ cells were almost exclusively localized to extrafollicular areas, as also observed in IM. However, in contrast to IM, these cells were mainly small lymphocytes. Furthermore, in some instances, occasional scattered EBV+ cells were seen within germinal centers, and in two cases diffuse expansions of EBV+ cells occurred within a single germinal center each, indicating that under certain circumstances EBV+ B lymphocytes may participate in physiologic germinal center reactions. These findings reflect the interference of EBV with physiologic lymphoid differentiation pathways and provide a link to EBV-associated malignant lymphomas with a postulated origin from germinal center cells.
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PMID:Patterns of Epstein-Barr virus infection in non-neoplastic lymphoid tissue. 131 83

An infectious molecular clone of the TM1 strain of feline immunodeficiency virus (FIV) was transfected into each of one feline (CRFK), two simian (COS and Vero) and two human (SW480 and HeLa) non-lymphoid cell lines, and virus production was assayed on feline T lymphoblastoid MYA-1 cells by monitoring reverse transcriptase activity. Infectious virus was produced in CRFK, Vero and HeLa cells, but not in COS and SW480 cells. When the basal promoter activity of the FIV long terminal repeat (LTR) was examined in these cell lines by using a chloramphenicol acetyltransferase assay, the activity correlated with the virus production in each cell line. Furthermore, when the activity of the FIV LTR was compared with those of three primate lentivirus LTRs, the highest activity in all the cell lines examined was produced by the LTR of simian immunodeficiency virus from African green monkey (SIVAGM), suggesting that it has a wide expression range. In COS and SW480 cells, the activity of the FIV LTR was much lower than that of the SIVAGM LTR. These results indicate that, whereas the primary block to FIV infection of certain cells may occur at the cell surface, the FIV LTR may also participate in controlling virus replication, as an intracellular mechanism.
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PMID:Production of feline immunodeficiency virus in feline and non-feline non-lymphoid cell lines by transfection of an infectious molecular clone. 131 47

The prevalence of Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) in acquired immunodeficiency syndrome (AIDS)-related primary central nervous system (CNS) lymphoma was examined. Deoxyribonucleic acid (DNA) extracted from 12 formalin-fixed, paraffin-embedded tumors was used as substrate for the polymerase chain reaction (PCR). Targets for amplification were the EBNA-1 region of EBV, the gag region of HIV, and a single copy cellular sequence as a control. The cases studied were autopsy and surgical specimens collected between the years 1985 and 1989. By the working formulation for non-Hodgkin's lymphomas, five had large cell, four had mixed large and small cleaved cell, two had small cleaved cell, and one had an unclassified histology. Epstein-Barr virus was detected in 6 of 12 tumors studied. Human immunodeficiency virus was not detected in any of the tumors. The presence of EBV was not correlated with any particular histologic tumor type. It is concluded that EBV, not HIV, can be detected in a large percentage (50%) of AIDS-related primary central nervous system (CNS) lymphomas. This viral association may be significant in light of the demonstrated ability of EBV to induce lymphoid tumors in experimental mammalian systems.
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PMID:Epstein-Barr and human immunodeficiency viruses in acquired immunodeficiency syndrome-related primary central nervous system lymphoma. 132 21

2',3'-Dideoxyguanosine (ddGuo) is a selective inhibitor of the replication of human immunodeficiency virus in vitro and the most active antihepadnavirus nucleoside analog known in vitro and in vivo, in a Peking duck model. However, the exact route by which this and related guanosine analogs are anabolized to their putative active metabolites in target cells is controversial. The anabolic pathway for the activation of ddGuo was investigated with the use of mutant human lymphoid CCRF-CEM and WI-L2 cell lines deficient in known nucleoside kinases. Uptake of ddGuo by human lymphoid cells and subsequent conversion to mono-, di-, and triphosphorylated metabolites is dose dependent and occurs proportionately to the exogenous concentration of drug. Studies with kinase-deficient CCRF-CEM and WI-L2 mutants revealed that at least two different routes of metabolism are operating in these cells to initiate the phosphorylation of ddGuo to its active dideoxynucleotides, one being deoxycytidine (dCyd) kinase and the other a cytosolic-5'-nucleotidase acting in the anabolic direction as a phosphotransferase. The evidence for this included 1) a lower but significant accumulation of drug anabolites in dCyd kinase-deficient mutants, 2) a lack of cross-resistance of the kinase-deficient mutants to growth inhibition by ddGuo, compared with that by the related analogs dideoxycytidine and arabinosylcytosine, known substrates for dCyd kinase, and 3) identification of different phosphorylation activities for ddGuo in extracts of wild-type cells and kinase-deficient mutants. Knowledge of the enzyme systems involved in anabolism of ddGuo analogs should be important for both new drug design and optimal therapeutic application.
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PMID:Metabolic pathways for the activation of the antiviral agent 2',3'-dideoxyguanosine in human lymphoid cells. 132 48

We reviewed our experience with 30 nodal and extranodal lymphoid lesions from 17 patients with common variable immunodeficiency (CVID). Immunohistochemical studies were performed on biopsies from 15 patients, in situ hybridization for Epstein-Barr virus in nine cases, and gene rearrangement analysis on seven lesions. The biopsies were classified into four groups: malignant lymphoma (two cases); atypical lymphoid hyperplasia (eight cases); reactive lymphoid hyperplasia (14 cases); and chronic granulomatous inflammation (six cases). The two malignant lymphomas were diagnosed using histologic criteria; tissue was not available for the assessment of clonality. In one neoplasm, Epstein-Barr virus was identified in the tumor cells by in situ hybridization. The cases of reactive lymphoid hyperplasia and chronic granulomatous inflammation had no atypical architectural, cytologic, or immunohistochemical features. The cases of atypical lymphoid hyperplasia were of particular interest, as these patients had either widespread involvement or massive disease. The diagnosis of lymphoma was considered likely by the clinicians and, in three cases, the histologic slides were originally interpreted as malignant lymphoma by the referring pathologists. Although the architecture of these lesions appeared to be effaced on hematoxylin and eosin-stained sections, immunohistochemical analysis demonstrated preserved architecture with florid expansion of B-cell and T-cell compartments. In addition, clinical follow-up of these patients was benign, and gene rearrangement analysis in three lesions revealed no evidence of clonality. We conclude that the majority of lymphoid lesions in patients with CVID are benign. Immunohistochemical and gene rearrangement studies are particularly helpful in the assessment of cases of atypical lymphoid hyperplasia.
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PMID:Lymphoproliferative lesions in patients with common variable immunodeficiency syndrome. 133 78


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