Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the role of TFIIH in transcription by RNA polymerase II (pol II) in vivo by microinjection of antibodies against this factor into Xenopus oocytes. Five different antibodies directed against four subunits of TFIIH were tested for effects on transcription of coinjected human immunodeficiency virus type 2 and c-myc templates. Each of these antibodies severely reduced the efficiency of elongation through human immunodeficiency virus type 2 and c-myc terminator elements. In contrast, an anti-TFIIB antibody did not inhibit elongation. Anti-TFIIH antibodies also had a much smaller inhibitory effect on total transcription than did anti-TFIIB or anti-pol II large subunit. Three inhibitors of TFIIH kinase activity, H-7, H-8, and dichlororibofuranosylbenzimidazole (DRB), inhibited elongation similarly to anti-TFIIH antibodies. These results strongly suggest a role for TFIIH in the stimulation of transcriptional elongation in vivo.
 ...
PMID:TFIIH functions in regulating transcriptional elongation by RNA polymerase II in Xenopus oocytes. 866 44

AIDS-related non-Hodgkin's lymphomas (AIDS-NHLs) are almost invariably derived from B cells and are grouped into three distinct histologic categories, including small-non-cleaved-cell lymphoma (SNCCL), diffuse large-cell lymphoma (DLCL), and anaplastic large-cell lymphoma (ALCL). In addition, AIDS-NHLs presenting solely as a body cavity effusion are thought to be a peculiar clinicopathologic entity and are defined as body-cavity-based lymphoma (BCBL). At the biologic level, AIDS-related lymphomagenesis is characterized by activation of proto-oncogenes, inactivation of tumor suppressor genes, viral infection of the tumor clone, and deregulated cytokine production. Distinct AIDS-NHL types associate with specific molecular pathways. The first pathogenetic pathway clusters with AIDS-SNCCL, and is characterized by a relatively mild degree of host immunodeficiency. AIDS-SNCCL consistently associates with c-myc rearrangements and p53 inactivation in 100 and 60% of cases, respectively, whereas infection by Epstein-Barr virus (EBV) is restricted to 30% of the cases. Production of high levels of interleukin-10 is an additional peculiar feature of EBV-positive AIDS-SNCCL. The second pathogenetic pathway associates with AIDS-DLCL, which is usually accompanied by marked host immunodeficiency. AIDS-DLCL is characterized by EBV infection in the large majority of cases and by the mutually exclusive presence of bcl-6 rearrangements and c-myc translocations in 40% of the cases. A third pathway characterizes AIDS-BCBL, which associates in virtually all cases with infection by EBV and with the presence of DNA sequences of the recently identified Kaposi sarcoma herpesvirus in the apparent absence of other known genetic lesions. Finally, the pathogenetic features of AIDS-ALCL are still under investigation.
 ...
PMID:AIDS-related non-Hodgkin's lymphomas: molecular genetics, viral infection and cytokine deregulation. 867 42

Homeostasis of cell numbers in tissues is maintained by a critical balance between cell proliferation and programmed cell death or apoptosis. Many human viruses are able to develop suitable strategies for modifying apoptosis in virus-infected cells and in virus-primed T cells. Apoptosis is characterized by the fragmentation of nuclear DNA into 180-200 bp apoptotic bodies and can be analysed microscopically or by flow cytometry using staining with various dyes. Moreover DNA cleavage can be identified by electrophoresis and by specific labeling using in situ nucleotidyltransferase assay (ISNT), terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling technique (Tunel), or by Elisa. Adenovirus E1A induces expression of protooncogenes c-myc and c-fos which sensitize cells to apoptosis; EBV EBNA-5, and adenovirus E1A, HPV E7, and polyomavirus large T act in the same way by displacing pRB-bound E2F. EBV EBNA-5, HPV E6, Adenovirus E1B 55 kDa inactivate the tumor suppressor protein p53 and engage the cells in the transformation process. EBV LMP-1, HHV6, and HTLV1 tax induce the antiapoptotic bcl-2 protein. EBV BHRF1 encodes proteins with homology to bcl-2 and Adenovirus E1B 19 kDa encodes proteins that have protective functions similar to bcl-2. Activated lymphocytes responding to viral infections express high levels of fas and are susceptible to apoptosis. TNF alpha can down- or up-regulate fas and down-regulates TNF-R. Adenovirus E1B 19 kDa blocks the proapoptotic activity of TNF alpha. Inversly, Cytomegalovirus, hepatitis C virus and Myxoviruses up-regulate fas antigen prior to undergoing apoptosis. In HIV-infected patients, CD4+ T-cell apoptosis is mediated by the cytopathic effect of the virus and the cell surface expression of gp 120-env protein. Moreover, an accelerated T-cell apoptosis in HIV-infected individuals is characterized by (i) HIV gp120-CD4+ cross-linking and subsequent aberrant signaling of T-cells, (ii) involvement of TNF alpha-fas/Apo-1 (TNF-R) binding, (iii) involvement of accessory cells as an apoptosis inducer and as a result of defective antigen presentation, (iv) possible superantigen activity induced by HIV products and cofactors. Many viruses also encode proteins with protease activity which could induce apoptosis. The induction of apoptosis may result in virus clearance, in contrast the inhibition of apoptosis may result in virus cell transformation and viral persistence. Indirectly, the apoptosis of infected cells may be induced by CTLs, NK cells and cytokines. In addition, apoptosis-mediated physiological depletion of T lymphocytes in the course of viral infection can silence the immune response and can induce immunodeficiency.
 ...
PMID:[Apoptosis and human viral infections]. 886 58

The reasons why immunodeficiency leads to malignant disorders are multifactorial. The overall incidence of malignancies in persons infected with the human deficiency virus (HIV) is estimated to be 40%. Other infecting agents, especially herpesvirus species, play a pivotal role in HIV-associated non-Hodgkin's lymphoma (NHL) and Kaposi's sarcoma (KS). Mucosaassociated lymphatic tissue (MALT) lymphoma in the stomach may be a result of a chronic gastritis caused by Helicobacter pylori, a gram-negative bacterium. The Epstein-Barr virus (EBV) genome can be found in a high percentage of lymphoma cells of HIV-NHL (nearly 100% in the primary lymphoma of the CNS and about 50% in all other lymphoma entities). In body-cavity based NHL, characterized by the absence of EBV and c-myc oncogen, sequences of a herpesvirus were identified which corresponds to the gamma-herpes viremia found in KS. The Kaposi's sarcoma-associated herpesvirus (KSHV) was usually present in primary-effusion lymphoma (PEL). HIV-infection, which causes multiple dysfunctions within the immune system, triggers the cytokine dysregulation. An abnormal endogenous interferon (IFN)-alpha production is observed in HIV-infected patients with KS, especially in the later natural course of the disease. A monitoring of the IFN-system by MxA, a protein specifically induced by IFN's of type I, may be a necessary stratum of identifying patients who show superior effects and the greatest clinical benefit from treatment with IFN-alpha.
 ...
PMID:Immunodeficiency and its relation to lymphoid and other malignancies. 889 Jul 3

Efficient expression of the human immunodeficiency virus (HIV) genome requires the viral-encoded transactivator Tat. Tat interacts with the highly structured trans-activation-response (TAR) RNA that is found at the 5' end of all viral transcripts, and mediates the formation of transcription complexes that are capable of elongation through the entire length of the viral genome. By placing TAR immediately downstream from the P2 promoter of the mouse c-myc gene, we have previously shown that Tat can also direct transcriptional elongation through potential sites of premature termination within c-myc in transfected HeLa cells. We now demonstrate that Tat can activate c-myc transcription when TAR is positioned internally within the c-myc transcript at distances up to 353 nt downstream from the P2 promoter. We show that Tat can also activate transcription from the c-myc P1 promoter, which is located 165 nt upstream from P2 in these hybrid gene constructs. These novel findings show that Tat can activate transcription in vivo when TAR is positioned at distances up to 518 nt downstream from the site of transcriptional initiation. The ability of TAR to mediate Tat-activated transcription over distances greater than previously appreciated has important implications for the mechanism of action of Tat.
 ...
PMID:Effect of the position of TAR on transcriptional activation by HIV-1 Tat in vivo. 889 Sep 8

We tested the effect of three linear or two loop peptides derived from the V3 region of the HTLV-III BH10 clone or the SF2 strain of human immunodeficiency virus type 1 on IL-2-driven T cell proliferation. V3-BH10, which consists of 42 amino acids and has a loop structure, suppressed IL-2-driven proliferation of all IL-2-dependent cells [Kit225, ED-40515(+), KT-3, 7-day PHA-blasts, and fresh peripheral blood mononuclear cells] tested, whereas it did not suppress the cell growth of IL-2-independent cell lines (Hut102, Molt-4, and Jurkat). This suppressive effect was also seen in IL-2-driven cell growth of CD8-positive lymphocytes purified from 7-day PHA-blasts, indicating that CD4 molecules were not required for the suppression. The treatment with anti-V3 loop monoclonal antibody (902 antibody) completely abolished the suppressive effect of V3-BH10. In addition, V3-BH10 generated the arrest of Kit225 cells and also purified CD8-positive lymphocytes in G1 phase in the presence of IL-2. Neither chromatin condensation nor DNA fragmentation was detected in Kit225 cells cultured with V3-BH10 and IL-2. V3-BH10 neither blocked radiolabeled IL-2 binding to IL-2 receptors nor affected tyrosyl phosphorylation of several cellular proteins (p120, p98, p96, p54, and p38), which is immediately induced by IL-2 stimulation. However, V3-BH10 enhanced IL-2-induced mRNA expression of c-fos but not c-myc or junB. Thus, the binding of V3 loop of gp120 to the cell surface molecule(s) appears to affect intracellular IL-2 signaling, which leads to the suppression of IL-2-induced T cell growth.
 ...
PMID:V3 loop of human immunodeficiency virus type 1 suppresses interleukin 2-induced T cell growth. 900

Fifty-one cases of acquired immunodeficiency syndrome (AIDS)-related primary brain lymphomas (AR-PBL) were investigated for clinical characteristics; human immunodeficiency virus (HIV)-associated disorders; histopathologic features; immunophenotype; Epstein-Barr virus (EBV) infection; and, when frozen tissue was available, oncogene rearrangements. AR-PBL occurred late in the course of AIDS and were usually associated with other systemic or cerebral disorders and with a low level of CD4 lymphocytes. All cases were high grade lymphomas according to the Working Formulation or updated Kiel classification, and often displayed a multifocal pattern. Thirty cases were classified as immunoblastic with plasmacytic differentiation, 18 cases were large cell lymphomas with an immunoblastic component or centroblastic polymorphic lymphomas, and 2 were small noncleaved non-Burkitt lymphomas (Working Formulation). This latter category is classified as Burkitt's-like lymphoma in the REAL nomenclature. One case could not be classified because of necrosis. AR-PBL showed a high level expression of activation and adhesion molecules. The presence of EBV was detected in most cases, and, when PCR was used, this was a constant finding. bcl-2 oncoprotein and latent membrane protein-1 (LMP-1) were strongly expressed. None of the tested cases expressed p53, or were rearranged for bcl-2 or c-myc oncogenes. This study confirms the immunophenotypic specificity of AR-PBL, which may reflect the special immune status of the brain.
 ...
PMID:AIDS-related primary brain lymphomas: histopathologic and immunohistochemical study of 51 cases. The French Study Group for HIV-Associated Tumors. 904 3

The incidence of non-Hodgkin's lymphoma is greatly increased in human immunodeficiency virus (HIV)-infected individuals. Most are clinically aggressive B-cell lymphomas exhibiting Burkitt-type, immunoblastic or large-cell morphology. Approximately 80% arise systemically (nodal or extranodal), and the remaining 20% arise in the central nervous system. A small proportion are body cavity-based (primary effusion) lymphomas associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Possible factors contributing to lymphoma development include HIV-induced immunosuppression, chronic antigenic stimulation, and cytokine overproduction. These phenomena are associated with the development of oligoclonal B-cell expansions. The appearance of malignant lymphoma is characterized by the presence of a monoclonal B-cell population displaying a variety of genetic lesions including Epstein-Barr virus (EBV) infections, c-myc gene rearrangement, bcl-6 gene rearrangement, ras gene mutations, and p53 gene mutations/deletions. The number and type of genetic lesions varies according to anatomic site of origin and histopathology. In the case of Burkitt-type lymphoma, virtually 100% exhibit c-myc gene rearrangement, two thirds display p53 gene mutations, one third contain EBV, and none exhibit bcl-6 gene rearrangements. In contrast, in the case of immunoblastic lymphoma, virtually 100% contain EBV, 25% display c-myc gene rearrangements, 20% display bcl-6 gene rearrangements, and few exhibit p53 gene mutations. These findings suggest that more than one pathogenetic mechanism is operational in the development and progression of acquired immunodeficiency syndrome (AIDS)-related lymphoma. Further work is necessary to develop a thorough understanding of the origin and pathogenesis of malignant lymphoma in the setting of HIV infection. AIDS-related lymphoma remains an important biologic model for investigating the development and progression of high-grade non-Hodgkin lymphomas as well as malignant lymphomas that develop in immune-deficient hosts.
 ...
PMID:Molecular pathology of acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. 904 11

ZF5, which we have cloned as a repressor on the mouse c-myc promoter, is a zinc finger protein containing Kruppel-type zinc finger and ZiN/POZ domains. In a reverse transcriptase PCR assay using mouse skeletal muscle RNA, we identified a 827 bp PCR product including the zinc finger domain of ZF5 and the acidic domain of VP16. The presence of the VP16 acidic domain induced the reduction of DNA-binding activity of the zinc finger domain. In addition, the inhibitory effect of the VP16 acidic domain was demonstrated on the human immunodeficiency virus (HIV) promoter, but there was no effect on the thymidine kinase (TK) promoter.
 ...
PMID:Detection of mouse skeletal muscle-specific product, which includes ZF5 zinc fingers and a VP16 acidic domain, by reverse transcriptase PCR. 922 18

Human immunodeficiency virus (HIV)-related body cavity-based lymphomas (BCBLs) are known to exhibit unusual clinical, immunophenotypic, and genotypic features, and have recently been found to harbor DNA sequences of a new human herpesvirus, designated Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8). The authors have encountered eight cases of HHV-8-associated BCBL in HIV-infected patients. A literature search revealed an additional 50 reported cases of HIV-related BCBL, as well as reports of several other disorders associated with HHV-8 DNA. Comprehensive analysis of the clinical and pathobiological features of all 58 known cases of HIV-related BCBL shows it to be a unique B-cell neoplasm with a strong propensity for body-cavity involvement without mass lesions and with little or no dissemination, poor prognosis, high grade usually immunoblastic morphology, late B-cell phenotype and genotype, no associated c-myc gene rearrangement, frequent presence of Epstein-Barr virus (EBV) genome, and uniform association with HHV-8 DNA. Considering these features in the context of other disorders associated with HHV-8 DNA, HHV-8 appears to play a causal role in BCBL, possibly in concert with EBV, and may induce this lymphoma through dysregulation of cytokines, particularly interleukin-6, or infection of an unusual B-cell subset. The characteristics of HHV-8-associated BCBL suggest a possible role for antiherpes or anticytokine agents in the treatment of this lymphoma.
 ...
PMID:Human herpesvirus-8-associated body cavity-based lymphoma in human immunodeficiency virus-infected patients: a unique B-cell neoplasm. 922 48


<< Previous 1 2 3 4 5 6 7 8 Next >>