Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1396851 (Epstein)
 24,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hairy leukoplakia (HL) is an Epstein-Barr (EB) virus related lesion of oral mucosa that is principally associated with human immunodeficiency virus-induced immunosuppression. To understand the nature of EB virus involvement in these lesions, this study compares the distribution of EB virus DNA and EB viral gene products with the pattern of keratinocyte differentiation in 12 lateral tongue biopsies of HL. Evidence of replicating EB viral infection and abundant virus production was demonstrated in the superficial epithelium of most (92%) samples by means of in situ hybridization and immunocytochemical techniques. Epstein-Barr virus latent membrane protein also was identified in 45% of samples, suggesting that this viral gene product, which is usually associated with EB virus latent infection, may be transiently expressed during viral replication in HL epithelium. The absence of detectable EB virus involvement in basal keratinocytes, however, fails to support the theory that latent infection occurs in basal epithelium. From this study, EB viral gene expression in HL appears to be linked with epithelial maturation. Conversely, the normal patterns of keratinocyte differentiation in these lesions do not appear to be appreciably altered by association with EB virus.
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PMID:Epstein-Barr virus gene expression and epithelial cell differentiation in oral hairy leukoplakia. 166 Oct 74

The association of malignant lymphoma with the acquired immunodeficiency syndrome (AIDS) has been recognized since early in the human immunodeficiency virus epidemic. Important clues regarding the etiology of AIDS-related non-Hodgkin's lymphoma (AIDS-NHL) and estimates of the future incidence of AIDS-NHL have been derived from epidemiologic studies. Recent epidemiologic and cohort studies reviewed in this article have confirmed that the incidence of non-Hodgkin's lymphoma is high in patients with human immunodeficiency virus infection, and increase with the duration of severe immunodeficiency in patients receiving antiretroviral therapies. A recent retrospective analysis of clinical features associated with AIDS-NHL described two groups of patients possessing distinct prognostic features. Finally, a number of new observations relating to the molecular and pathogenic mechanism underlying the development of AIDS-NHL have recently been described. The role of Epstein-Barr virus in the pathogenesis of AIDS-NHL continues to be enigmatic, and there may be multiple mechanisms contributing to the development of lymphoma, even in an individual patient.
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PMID:Clinical aspects of AIDS-related non-Hodgkin's lymphoma. 166 Nov 69

A simian type D retrovirus designated SRV induces a fatal immunosuppressive disease in rhesus macaques. This syndrome shows many clinical similarities to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus-infected individuals. To investigate the mechanisms of immune dysfunction in SRV infection, we have focused on the interactions of SRV serotype 1 (SRV-1) with macaque B-lymphoblastoid cell lines (B-LCL). Procedures were optimized for establishing B-LCL by immortalization of macaque B lymphocytes with rhesus Epstein-Barr virus (EBV). These cell lines express B-cell surface markers, secrete immunoglobulins of the IgG or IgM isotypes, and release EBV which transforms monkey B cells. In vitro cultures of B-LCL supported replication of SRV-1. Several B-LCL infected with SRV-1 showed downregulation of major histocompatibility complex (MHC) class II antigen expression whereas levels of MHC class I antigen remained unchanged. Infection of B-LCL with SRV-1 did not alter the level of secreted immunoglobulin. Rhesus EBV was also used to obtain B-LCL from macaques infected with SRV-1; these cell lines were found to release infectious SRV-1. Investigations on the interactions of SRV-1 with B cells will be useful for elucidating mechanisms involved in the immunopathogenesis of primate retroviruses.
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PMID:Characterization of rhesus macaque B-lymphoblastoid cell lines infected with simian type D retrovirus. 166 56

The expression "immunocompromised host" refers to an individual who has one or more defects in the body's natural defense, which leads to severe, often life-threatening, infections. Alcoholism, diabetes mellitus, advanced age, the use of antacids, and viral infections have immune-modulating effects. The human immunodeficiency virus, cytomegalovirus, Epstein-Barr virus, and Non A, Non B hepatitis virus also contribute to immunosuppression. The lung has a special vulnerability to infection, and pneumonia accounts for more than 40% of deaths in the immunosuppressed population. Diagnostic methods include detection of microbial antigens by monoclonal antibodies, DNA sequences by the polymerase chain-reactions or DNA probes, and unique metabolites of pathogens by gas chromatography. Transtracheal aspiration was used to obtain uncontaminated respiratory secretions, but fiberoptic bronchoscopy with shielded brush and bronchoalveolar lavage (BAL) is a better means of diagnosis because of a 90% sensitivity in diagnosing pneumocystis infection. Percutaneous aspiration and open lung biopsy are reserved for more complicated cases. Empiric treatment is justified in far advanced AIDS or relapsed myelogenous leukemia with limited life expectancy, or when there is uncontrollable bleeding diathesis or impaired pulmonary function as invasion diagnostic procedures will not be tolerated. The most important antiinfective measure is careful hand washing, while prophylactic antibiotics, selective decontamination, and antifungal, antiviral, and antiparasitic agents can be used. Active and passive immunization against specific pathogens, immunological reconstitution with granulocyte-macrophage colony-stimulating factor (GM-CSF) and reducing the dosage of immunosuppression are the other strategies for prevention. In the last several decades there has been substantial progress in the management of chronic diseases which used to be fatal.
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PMID:Pulmonary infections in the immunocompromised host. 166 54

Our laboratory has undertaken an analysis of cellular and viral gene expression in CD4+ human lymphoid cell lines infected by the human and simian immunodeficiency viruses, HIV-1 and SIV/Mne, respectively. The purpose of the current study was to: (i) examine the effects of SIV/Mne infection on host macromolecular synthesis and compare the results to those in the HIV-1 system; and (ii) investigate the mechanisms responsible for the restriction of SIV/Mne infection in CD4 positive lymphoid cells which are readily infected by HIV-1. First we determined that SIV does not impose selective blocks on host macromolecular synthesis, unlike HIV-1, which induces both the selective inhibition of cellular protein synthesis and the degradation of cellular mRNAs (Agy, M., Wambach, M., Foy, K., and Katze, M. G., 1990, Virology 177, 251-258). No such selective reduction in cellular mRNA stability or protein synthesis was observed in cells infected by SIV/Mne. Additional differences between SIV and HIV-1 were observed using a panel of CD4+ human cell lines. While HIV-1-infected all cell lines. SIV/Mne efficiently infected only the MT-4, C8166, and 174 x CEM cell lines. Repeated efforts to infect CEM or Jurkat cells were unsuccessful as determined by PCR analysis of viral DNA. HUT 78 cells supported a limited infection detectable only by PCR analysis. These data suggest the block in viral replication in the nonsusceptible cell lines is at an early step. Interestingly, all the SIV susceptible cells were virally transformed, C8166 and MT-4 by HTLV-1, and 174 x CEM by Epstein-Barr virus. Furthermore FACS analysis revealed that all susceptible cells expressed two B cell associated markers, B7/BB1 and CD40. These observations taken together highlight differences between the HIV and SIV viruses, and suggest that for efficient replication, SIV/Mne may require an additional cell surface molecule, cofactors provided by transforming viruses, or a complex interplay between the two.
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PMID:Viral and cellular gene expression in CD4+ human lymphoid cell lines infected by the simian immunodeficiency virus, SIV/Mne. 167 22

We have studied four cases of fatal B-cell lymphoproliferative syndrome (LPS) developing among 333 patients (incidence 1.2%) treated with allogeneic bone marrow transplantation (BMT). All four patients had received a T-cell depleted graft. Onset of the first clinical symptoms (palpable lymph node enlargement in three and IgA-lambda paraproteinemia in two patients) occurred between 41 and 188 days post-BMT (median 76 days). The course of the LPS was rapidly progressive in all cases, leading to death in 2-5 weeks. The peripheral blood showed progressive pancytopenia with disproportionally high numbers of activated NK cells, apparently compensating for the T-cell deficiency. Post-mortem histological studies disclosed polymorphic B-cell proliferations, most pronounced in the lymph nodes, spleen, liver, lungs and kidneys. Lymphohemopoietic cells were of donor origin in three patients. In the fourth patient, graft failure suggested a host origin for the proliferating cells. Immunophenotyping and gene rearrangement analysis revealed polyclonal proliferation in one patient, monoclonal proliferation in another patient, and an oligoclonal pattern in the other two patients. The clinical behavior of the LPS was independent of clonality. Immunohistologically, the proliferating cells showed characteristics of relatively mature B-cells in three cases, and pre-B-cell features in one case. Epstein Barr virus (EBV) serology indicated seroconversion (primary infection) in one child, and chronic active EBV infection in both adults. EBV DNA as well as EBV nuclear antigen (EBNA) were detected in infiltrated tissues of all four patients. The labeling pattern on in situ hybridization suggested a replicative EBV infection comparable to that in lymphoblastoid cell lines. We conclude that EBV-associated LPS developing as a result of post-transplant immunodeficiency is a distinct clinicopathologic entity, differing from non-Hodgkin's lymphoma (including Burkitt's lymphoma) and infectious mononucleosis of the immunocompetent host.
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PMID:Fatal B-cell lymphoproliferative syndrome in allogeneic marrow graft recipients. A clinical, immunobiological and pathological study. 168 38

T-cell-mediated cytotoxicity may play an important role in control of infection by the human immunodeficiency virus (HIV). In this study, we have identified and characterized a relatively conserved epitope in the HIV-1 reverse transcriptase recognized by murine and human cytotoxic T cells. This epitope was identified using a murine antigen-specific CD8+ class I major histocompatibility complex-restricted cytotoxic T-cell (CTL) line, a transfected fibroblast cell line expressing the HIV-1 pol gene, recombinant vaccinia viruses containing different truncated versions of the pol gene, and overlapping synthetic peptides. The optimal antigenic site was identified as residues 203-219 by synthesizing extended or truncated peptide analogs of the antigenic fragment. The optimal peptide was then tested for sensitization of autologous Epstein-Barr virus-transformed B-cell targets for killing by fresh human peripheral blood mononuclear cells. It was recognized by CTLs from several HIV-seropositive patients but not from any seronegative donor. Therefore, this peptide is a good candidate for inclusion in an AIDS vaccine. This study demonstrates that the same CTL epitope can be seen by murine and human CD8+ CTLs, as previously demonstrated for epitopes recognized by CD4+ helper T cells, and suggests the utility of screening for immunodominant CTL epitopes in mice prior to carrying out studies in humans.
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PMID:An epitope in human immunodeficiency virus 1 reverse transcriptase recognized by both mouse and human cytotoxic T lymphocytes. 169 Apr 29

Eighteen tissue samples from lymphoproliferative lesions and lymphomas in immunodeficiency states were investigated for their content of Epstein-Barr virus (EBV) genome by dot blotting and for the distribution of EBV in tissue sections by in situ hybridization. Fourteen lymphomas from AIDS patients and four children with disorders of the immune system were available. For control reasons, six cases of infectious mononucleosis (IM) and eight Burkitt's lymphomas (BL) from malaria-free regions of Africa were included in the study. Two different patterns of EBV distribution are described: 1) heterogeneous scattered EBV-positive cells, as originally seen in IM and therefore called the IM-type pattern, 2) and a BL-type pattern seen in endemic Burkitt's lymphoma with homogeneous EBV-positive cells all over the tumor. In lymphomas in patients with inborn immunodeficiencies, an IM-type pattern was found. In lymphomas from AIDS patients, the two different patterns were found. There were lymphomas with the IM-type pattern as well as some with the BL-type pattern. In some AIDS-associated lymphomas, both patterns occurred in one tumor. The findings suggest that it is not the disease process that is the distinguishing feature between the two patterns of EBV infection but rather the patient's underlying disease and the extent of this disease.
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PMID:Different Epstein-Barr virus expression in lymphomas from immunocompromised and immunocompetent patients. 169 92

A human Epstein-Barr virus-transformed lymphoblastoid B-cell line was generated from peripheral blood mononuclear cells (PBMC) of an asymptomatic human immunodeficiency virus type I (HIV-1) seropositive donor, which produces a human monoclonal antibody K14 (IgG1), reactive with an epitope on the transmembrane part (gp41) of the envelope glycoprotein of HIV-1. This monoclonal antibody reacts with a lysate of HIV-1-infected H9 cells, gradient purified HIV-1, and a vaccinia recombinant HIV-1 gp160 protein, but not with HIV-2 antigens in an enzyme-linked immunosorbent assay (ELISA). When used as an immobilized ligand in an immune affinity column, K14 selectively purifies gp41 from a HIV-1-infected H9 cell lysate. Although no reactivity was observed in ELISA with a panel of partially overlapping synthetic nonapeptides spanning the whole length of HIV-1 gp41, it was shown to react with recombinant envelope proteins, provided that they did contain amino acids 643-692: deletion of this part resulted in the disappearance of the reactivity. Testing of an extensive panel of the sera from HIV-1 seropositive or seronegative donors from Europe and Africa, including a selected group of donors before and after HIV-1 seroconversion, in a competition ELISA with horseradish peroxidase-conjugated K14, showed that the epitope recognized on gp41 is immunodominant and conserved. K14 does not neutralize HIV-1 infectivity or virus-mediated cell fusion, and does not mediate antibody-dependent cellular cytotoxicity.
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PMID:Production and characterization of a human monoclonal antibody, reactive with a conserved epitope on gp41 of human immunodeficiency virus type I. 169 24

Our recent efforts have been directed at the development of selective inhibitors of different classes of viruses, including adeno, pox, and herpesviruses [herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV)], (+/-)RNA viruses (reo- and rotavirus), (-)RNA viruses (influenza, parainfluenza, measles, respiratory syncytial, vesicular stomatitis and rabies virus) and retroviruses [i.e. human immunodeficiency virus (HIV), the causative agent of AIDS]. In this search, the following molecular targets were envisaged: for DNA viruses in general, the viral DNA polymerase; for herpes simplex virus and varicella-zoster virus, the viral DNA polymerase via a specific phosphorylation by the viral 2'-deoxythymidine (dThd) kinase; for (+/-)RNA and (-)RNA viruses, S-adenosylhomocysteine (SAH) hydrolase, a key enzyme in transmethylation reactions required for the maturation of viral mRNA; for retroviruses, reverse transcriptase as initiator of virus replication and/or cell transformation; and for several enveloped viruses (i.e. retro-, herpes- and rhabdoviruses), virus adsorption to the outer cell membrane. Several new compounds have been developed that appear to act at these targets: i.e. (E)-5-(2-bromovinyl)-2'-deoxyuridine [bromovinyldeoxyuridine (BVDU)] and derivatives thereof [i.e. carbocyclic BVDU (C-BVDU)] as well as derivatives of acyclovir (i.e. 8-substituted acyclovir derivatives) as inhibitors of herpesviruses; (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and other phosphonylmethoxyalkylpurines and -pyrimidines as inhibitors of DNA viruses and retroviruses; acyclic and carbocyclic analogues of adenosine [such as (S)-9-(2,3-dihydroxypropyl)adenine [S)-DHPA), carbocyclic 3-deazaadenosine (C-c3Ado), (RS)-3-adenin-9-yl-2-hydroxypropanoic acid (AHPA) alkyl esters, neplanocin A, 3-deazaneplanocin A and the 5'-nor derivatives of neplanocin A and 3-deazaneplanocin A] as inhibitors of (+/-)RNA and (-)RNA viruses; 2',3'-dideoxynucleoside analogues as inhibitors of retroviruses; and sulfated polysaccharides (i.e. heparin, dextran sulfate, pentosan polysulfate, mannan sulfate), sulfated polyvinylalcohol and co-polymers of sulfated polyvinylalcohol with acrylic acid as inhibitors of retro-, herpes- and rhabdoviruses.
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PMID:Selective virus inhibitors. 169 49


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