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)

For the sake of clarity and in agreement with the World Health Organization immunodeficiency classification, it is important to distinguish the congenital, inherited malformative lesions called generically 'thymic dysplasia' from the secondary, acquired changes, designated under the broad term of 'severe thymic atrophy'. Thymic dysplasia represents the archetype of thymic changes in cellular immunodeficiency, since there is no example of a thymic dysplasia associated with a normal T-cell function. Thymic dysplasia is observed in several inherited diseases, the most frequent of them being severe combined immunodeficiency. More than the depletion of lymphoid cells, the lack of differentiation of the thymic epithelium, responsible for the absence of Hassal's corpuscles, is the main and constant feature of this condition. Thymic dysplasia underscores the crucial role of the thymic epithelium in the normal differentiation of the T-cell population. Severe thymic atrophy is secondary to various causes, including prolonged protein malnutrition and immunosuppressive or cytotoxic drugs, graft versus host reaction and, chiefly today, chronic viral infection, especially with HIV-1. The morphological changes are similar and are characterized by a partial lymphoid depletion, involving mainly the CD1+ population, necrosis and calcification of epithelial cells, the frequent presence of plasma cells and, more significantly, fibrohyaline changes of the basement membrane of the vessels and thymic epithelium. The severity of the atrophic changes and the immunodeficiency-related manifestations depend on the duration of the aetiological factors and, more significantly, with their early occurrence, within the first months of life. The mechanisms underlying thymic atrophy are poorly understood. A primary impairment of lymphoid cells seems at present to be the most likely hypothesis.
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PMID:Thymic pathology in primary and secondary immunodeficiencies. 146 48

The processing of the human immunodeficiency virus (HIV) gag and gag-pol precursor proteins by the virus-encoded protease is an essential step in maturation of infectious virus particles. Like most retroviral proteases, the HIV protease belongs to the aspartyl-protease family and can be inhibited by specific inhibitors. Twenty-four synthetic peptides known to be inhibitors of human renin were tested for inhibition of HIV replication in tissue cultures. One of them, a synthetic peptide analogue, SR41476, which has been shown to be a specific inhibitor of purified recombinant HIV1 protease in vitro, totally blocked infection with different isolates including the HIV1 LAV prototype, the highly cytopathic Zairian isolate HIV1 NDK, and HIV2 ROD, both in primary blood lymphocytes (PBL) and in the lymphoid cell lines MT4 and CEM, for at least 3 weeks. It also significantly reduced virus replication in chronically infected CEM cells, without any effect on cell proliferation. Radioimmunoprecipitation assay revealed that the inhibitor blocked processing of polyprotein precursors p55 gag and p40 gag into a mature form of gag proteins, p25 and p18. Synthetic peptide analogue SR 41476, when added before infection, efficiently inhibited formation of HIV DNA provirus and successfully suppressed synthesis of HIV-specific proteins. These results imply that the HIV protease inhibitor not only inhibited virus maturation in the late phase of the HIV replication cycle, but also interfered in the early phase, before the provirus was formed. This mechanism of antiviral activity provides new possibilities and strategies for AIDS chemotherapy.
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PMID:Inhibition of HIV by an anti-HIV protease synthetic peptide blocks an early step of viral replication. 148 Aug 23

A 16 year old boy underwent allogeneic bone marrow transplantation (BMT) from an human leukocyte antigen (HLA)-identical sibling for severe aplastic anaemia. He was symptomatic for 7 years before transplantation and had received multiple red blood cell and platelet transfusions. Conditioning for BMT consisted of cyclophosphamide, antilymphocyte globulin and total lymphoid irradiation. Engraftment was rapid, there was no evidence of rejection despite the history of multiple blood product transfusions and he did not develop acute or chronic graft versus host disease. He was well for the first 8 months after transplantation but then developed fevers, interstitial pneumonia, herpes simplex infections and cytomegalovirus enteritis. Serological studies revealed antibodies to human immunodeficiency virus (HIV) and he was considered to have acquired immune deficiency syndrome (AIDS). Retrospective analysis of the serum samples showed that he was seronegative for HIV until approximately 10 months before transplantation when his serum became HIV positive. Lymphocyte function studies done after transplantation suggested immunologic recovery at 3 months post-transplant with a brisk though subnormal response to phytohaemagglutinin stimulation. T cell subset analysis performed subsequently showed complete absence of CD4 positive cells indicating immune incompetence which was associated with clinical features of AIDS. Bone marrow transplantation had failed to produce sustained immunologic reconstitution and prevent the progression of HIV to which he ultimately succumbed.
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PMID:Failure of allogeneic bone marrow transplantation to benefit HIV infection. 149 64

Rectal mucosal biopsy specimens from 75 human immunodeficiency virus (HIV)-seropositive and 16 HIV-seronegative subjects were examined. The histopathologic changes were correlated with immunoperoxidase staining for UCHL-1 and HIV core protein p24, quantitative p24 enzyme-linked immunosorbent assay (ELISA) assay in homogenized rectal tissue and serum, and a modified Walter Reed clinical stage. Four phases were seen in the HIV-infected subjects: (1) early phase, in Walter Reed stage 1-2 subjects, with nearly normal histology and low p24; (2) inflammatory phase, typically in Walter Reed stage 3-4 subjects, with a superficial lamina propria infiltrate of lymphocytes, plasma cells, and eosinophils with degranulation, abundant UCHL-1 staining, and maximal p24 by both immunoperoxidase staining and ELISA; (3) transitional phase, in many Walter Reed 5 and some Walter Reed 6 subjects, with normal lymphocyte population density but with subtle inflammatory changes; and (4) lymphoid depletion phase, mainly in Walter Reed stage 6 subjects, with decreased lymphocytes but often with endothelial cell activation and apoptosis. These phases presumably result from effective HIV suppression by a relatively intact immune system, followed by maximal HIV infection and lymphocyte activation, then progressive lymphocyte depletion. The inflammation correlated with the presence and amount of HIV in rectal tissue determined by immunohistochemistry and ELISA and was maximal before overt immunodeficiency developed. Intestinal mucosa could be a preferred site of HIV proliferation and T-cell destruction.
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PMID:Rectal mucosal pathology varies with human immunodeficiency virus antigen content and disease stage. 149 43

Replication of human immunodeficiency virus type 1 (HIV-1) was inhibited by stable intracellular expression of antisense RNA in the human T-lymphoid cell line Jurkat. When the viral subregion encoding the HIV-1 activator proteins was targeted, the extent of antisense RNA-mediated inhibition was greater than 97% during the first 2 weeks postinfection. Later in the time course, productive HIV-1 infection broke through at high initial infective doses. However, at initial multiplicities of infection equal to or smaller than 0.1, HIV-1 production was not detectable during the 5 weeks of observation. The results underline the effectiveness of stable intracellular antisense RNA expression in inhibiting HIV-1 replication.
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PMID:Tat- and Rev-directed antisense RNA expression inhibits and abolishes replication of human immunodeficiency virus type 1: a temporal analysis. 150 Dec 92

The Tat protein of human immunodeficiency virus type 1 (HIV-1) is essential for productive infection and is a potential target for antiviral therapy. Tat, a potent activator of HIV-1 gene expression, serves to greatly increase the rate of transcription directed by the viral promoter. This induction, which seems to be an important component in the progression of acquired immune deficiency syndrome (AIDS), may be due to increased transcriptional initiation, increased transcriptional elongation, or a combination of these processes. Much attention has been focused on the interaction of Tat with a specific RNA target termed TAR (transactivation responsive) which is present in the leader sequence of all HIV-1 mRNAs. This interaction is believed to be an important component of the mechanism of transactivation. In this report we demonstrate that in certain CNS-derived cells Tat is capable of activating HIV-1 through a TAR-independent pathway. A Tat-responsive element is found upstream within the viral promoter that in glial-derived cell lines allows transactivation in the absence of TAR. Deletion mapping and hybrid promoter constructs demonstrate that the newly identified Tat-responsive element corresponds to a sequence within the viral long terminal repeat (LTR) previously identified as the HIV-1 enhancer, or NF-kappa B domain. DNA band-shift analysis reveals NF-kappa B binding activity in glial cells that differs from that present in T lymphoid cells. Further, we observe that TAR-deleted mutants of HIV-1 demonstrate normal late gene expression in glial cells as evidenced by syncytia formation and production of viral p24 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation. 150 23

In order to further characterize the interaction of human immunodeficiency viruses (HIV) with the CD4 receptor at the molecular level, a binding test was performed using iodine-labeled glycoproteins, 125I-gp160 from HIV-1 and 125I-gp140 from HIV-2, to bind to lymphoid cells expressing the CD4 receptor. The inhibition of binding of the radiolabeled glycoproteins to CD4+ cells by increasing concentrations of nonradiolabeled gp160 or gp140 was used to determine the affinity of the interaction between the glycoproteins and CD4. The gp-CD4 association occurs with a high affinity: K0.5 gpHIV-1 = 9 x 10(-9) M and K0.5 gpHIV-2 = 7 x 10(-8) M, indicating that the affinity of the interaction between HIV-2 gp140 and CD4 is 10 times lower than that observed with HIV-1 gp160. The N-linked glycans of the HIV-1 and HIV-2 glycoproteins account for a high proportion of their molecular mass (about 50%). Total deglycosylation of gp160 and gp140 by enzymatic treatment with Endo F-N glycanase occurred under nondenaturing conditions, indicating the high accessibility of the N-linked glycan chains in the three-dimensional structure of the molecule. Moreover, the deglycosylated proteins retained a significant binding capacity to CD4. These results show that the carbohydrate chains of HIV-2 gp140, as those of HIV-1 gp160, do not play a major role in the gp-CD4 interaction.
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PMID:Study of the interaction of HIV-1 and HIV-2 envelope glycoproteins with the CD4 receptor and role of N-glycans. 151 10

Human immunodeficiency virus type 1 (HIV-1) infection causes progressive depletion of CD4/HIV-receptor-positive T helper lymphocytes, ultimately leading to AIDS. The major HIV reservoir and site of T-helper cell infection in lymphoid tissues, however, has remained poorly defined. The authors used in situ hybridization in combination with immunohistologic labeling techniques to identify the phenotype of HIV-infected cells in lymph nodes from patients at different stages of HIV-infection. The number of HIV-infected macrophages, widely considered the major site of HIV replication, was extremely low. There was no evidence for HIV-infection of endothelial and interdigitating reticulum cells. However, HIV RNA was found in small but consistent proportions of CD45RO-positive T cells and in the vast majority of follicular dendritic cells (FDC) in a pattern suggestive of active infection in addition to HIV-immunocomplex trapping on cell membranes. FDC may therefore be a major HIV reservoir and since T-helper cells travel through the FDC meshwork during their migration within lymphoreticular tissues, it appears likely that HIV-replicating T cells may infect FDC, which then infect new T cells, thus causing a gradual dissemination of the virus to all FDC and thereby a steadily increasing infection of T-helper/memory cells within germinal centers. This results in CD4+ T cell depletion, and ultimately, in immunodeficiency.
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PMID:Follicular dendritic cells are a major reservoir for human immunodeficiency virus type 1 in lymphoid tissues facilitating infection of CD4+ T-helper cells. 153 Sep 97

Human interleukin 1 receptor antagonist protein (IRAP) is a specific antagonist of interleukin 1 (IL-1) action in both in vitro and in vivo experimental models. Presently, the significance of this protein in human pathophysiology is unknown. In the present study, monoclonal antibodies against IRAP were prepared and used to demonstrate IRAP expression in human tissues, immunohistochemically. Specifically, this study focused on lymphoid tissues and granulomatous inflammatory reactions since IL-1 is believed to play roles in lymphocyte development and inflammation. In addition, these tissues were also stained for IL-1 beta to compare the expression of agonist and antagonist. These findings indicate that IRAP expression is largely limited to macrophages and their derivatives. Strong IRAP expression was observed in germinal center macrophages of lymph nodes, spleen, and tonsil. In contrast, IL-1 was marginally expressed in these organs. Granulomas associated with active M. tuberculosis infection, sarcoidosis and foreign bodies all contained strongly IRAP positive cells, which included macrophages, epithelioid cells and multinucleate giant cells. Unlike reactive lymphoid tissue, tuberculous and sarcoid granulomas also contained IL-1 positive cells which included macrophages and their derivatives, as well as some stromal cells. Foreign body lesions showed minimal IL-1 expression. Interestingly, granulomas in patients with acquired immunodeficiency disease (AIDS) associated with M. avium-intracellulare contained IRAP positive cells but were negative for IL-1 expression. Taken together, these findings suggest that IRAP takes part in both physiologic and pathologic reactions. Moreover, they provide a basis to design future studies to determine the precise contribution of IRAP to these reactions.
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PMID:Immunohistochemical demonstration of interleukin-1 receptor antagonist protein and interleukin-1 in human lymphoid tissue and granulomas. 153 98

Increased proportions of the small lymphoid subset expressing T cell receptor (TCR) gamma delta occur in different infectious diseases, particularly in mycobacterial infections. In this study the two main subsets of TCR gamma delta+ cells in peripheral blood mononuclear cells (PBMC) of 54 patients with human immunodeficiency virus type 1 infection were analyzed. These subsets were defined by indirect immunofluorescence techniques and FACS analysis using BB3 and A13 monoclonal antibodies, which specifically react with V delta 2- and V delta 1-encoded forms of TCR gamma delta. The proportion of BB3+(V delta 2+) and A13+(V delta 1+) cells was analyzed in purified PBMC populations. Patients were stratified according to Walter Reed (WR) clinical stage. A sharp increase in percentage of A13+(V delta 1+) cells was observed in all stages of the disease. In addition, a strict correlation was found with stage of the disease and percentage of CD8+ PBMC. An inverse correlation was found with the proportion of CD4+ PBMC. An early (WR2) inversion of the V delta 2-to-V delta 1 ratio was consistently detected even before the inversion of the CD4-to-CD8 ratio.
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PMID:Selective increase of a subset of T cell receptor gamma delta T lymphocytes in the peripheral blood of patients with human immunodeficiency virus type 1 infection. 153 37


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