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)

Spontaneous lymphoblastoid cell lines (LCLs) were established from the peripheral blood of 10 human immunodeficiency virus (HIV)-seropositive patients in order to investigate whether or not progression of the cells towards a malignant state could be traced. The LCLs studied displayed no differences in their surface phenotype, karyotype, and tumorigenicity in nude mice as compared with a wide panel of control LCLs. Furthermore, no c-myc rearrangement could be detected in any of the LCLs. However, 4 of the 10 LCLs derived from HIV-seropositive patients formed colonies in agar with a cloning efficiency of 0.1-0.9%. This percentage was much lower than that of a control neoplastic B cell line (50%), but consistently higher than that observed for a battery of spontaneous LCLs. The cells of a number of sublines that were derived from the agar colonies expressed new activation markers (CD10 and Bac-1) but did not induce tumors in nude mice or display chromosomal abnormalities. These sublines might comprise cells that have progressed towards a more markedly transformed state.
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PMID:Studies on the oncogenic potential of Epstein-Barr-virus (EBV)-infected B cells in AIDS-related disorders. 255 27

This paper reviews the major information on lymphoproliferative diseases developing in primary and acquired immunodeficiencies, in organ allograft recipients, and in different diseases with immune impairment such as rheumatoid arthritis, angioimmunoblastic lymphadenopathy, and Hodgkin's disease (secondary lymphomas). The hypothetical role of Epstein-Barr virus (EBV) in the pathogenesis of lymphoproliferative diseases in immunocompromised hosts has come from the examination of lymphoma cells or tissues for Epstein-Barr nuclear antigen (EBNA), or carriage of the viral genome, and will be extensively reviewed. The characteristics and the prognosis of high-grade lymphomas developing in the acquired immunodeficiency disease (AIDS) will be analyzed, together with their pathogenetic mechanisms, with particular emphasis on the constant presence in the lymphoma cells (mostly of Burkitt-type) of the c-myc oncogene rearrangement and activation. The principal methods of study of secondary lymphomas and major attempts at therapy will reviewed as well.
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PMID:Secondary lymphomas: a review on lymphoproliferative diseases arising in immunocompromised hosts: prevalence, clinical features and pathogenetic mechanisms. 256 Jul 63

In two hemophilic brothers infected by the human immunodeficiency virus (HIV), Burkitt's leukemia developed within 1 year. Both patients were treated by aggressive chemotherapy, and both are still in complete remission for 23 and 14 months, respectively. Sera from both brothers contained anti-HIV antibodies. However, DNA extracted from the tumor cells, when analyzed by Southern blot using a cloned HIV probe, did not reveal HIV-related sequences. Hybridization experiments with an Epstein-Barr virus (EBV) probe revealed the presence of EBV-specific sequences in the tumors' DNA. In both patients' tumors rearranged c-myc genes were found. The rearrangements occurred in both genes 3' to the third exon of c-myc, thereby suggesting that a variant chromosomal translocation took place in both cases. Indeed, karyotype analysis of the malignant cells of one of the patients revealed the variant t(2:8) translocation. In contrast to the majority of Burkitt's tumors carrying this translocation, which are kappa light-chain producers, cells of our patient expressed lambda chains. Furthermore, in both cases the lymphoblasts carried IgG on the surface, again an unusual finding in Burkitt's tumors. Finally, because both patients had an identical HLA phenotype, the role of genetic factors in the development of such tumors should be considered.
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PMID:Molecular analysis of Burkitt's leukemia in two hemophilic brothers with AIDS. 282 33

The human promyelocytic leukemia cell line HL-60 overexpresses the c-myc protooncogene. A calculated secondary structure for c-myc mRNA placed the initiation codon in a bulge of a weakly base-paired region. Treatment of HL-60 cells with 5' d(AACGTTGAGGGGCAT) 3', complementary to the initiation codon and the next four codons of c-myc mRNA, inhibited c-myc protein expression in a dose-dependent manner. However, treatment of HL-60 cells with 5' d(TTGGGATAACACTTA) 3', complementary to nucleotides 17-31 of vesicular stomatitis virus matrix protein mRNA, displayed no such effects. These results agree with analogous studies of normal human T lymphocytes [Heikkila, R., Schwab, G., Wickstrom, E., Loke, S. L., Pluznik, D. H., Watt, R. & Neckers, L. M. (1987) Nature (London) 328, 445-449], except that only one-third as much oligomer was needed for a comparable effect. Proliferation of HL-60 cells in culture was inhibited in a sequence-specific, dose-dependent manner by the c-myc-complementary oligomer, but neither the oligomer complementary to vesicular stomatitis virus matrix protein mRNA nor 5' d(CATTTCTTGCTCTCC) 3', complementary to nucleotides 5399-5413 of human immunodeficiency virus tat gene mRNA, inhibited proliferation. It thus appears that antisense oligodeoxynucleotides added to myc-transformed cells via culture medium are capable of eliciting sequence-specific, dose-dependent inhibition of c-myc protein expression and cell proliferation.
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PMID:Human promyelocytic leukemia HL-60 cell proliferation and c-myc protein expression are inhibited by an antisense pentadecadeoxynucleotide targeted against c-myc mRNA. 327 86

We have previously shown by affinity chromatography that RAP30 and RAP74 are the mammalian proteins that have the highest affinity for RNA polymerase II. Here we show that RAP30 binds to RAP74 and that the RAP30-RAP74 complex (RAP30/74) is required for accurate initiation by RNA polymerase II. RAP30/74 is required for accurate transcription from the following promoters: the adenovirus major late promoter, the long terminal repeat of human immunodeficiency virus, P2 of the human c-myc gene, the mouse beta maj-globin promoter (all of which have TATA boxes), and the mouse dihydrofolate reductase promoter (which lacks a TATA box). RAP30/74 is not required for initiation by RNA polymerase III at the adenovirus virus-associated RNA promoters. Therefore, RAP30/74 is a general initiation factor that binds to RNA polymerase II.
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PMID:RAP30/74: a general initiation factor that binds to RNA polymerase II. 338 90

We have studied, at a molecular level, two small non-cleaved cell malignant lymphomas (Burkitt's type) that were separated by a disease-free interval of 3 years in a patient infected with the human immunodeficiency virus (HIV). The late occurrence of the apparent relapse suggested that the second lymphoma might be caused by a separate malignant transformation in a discrete clone of B cells. Although both tumors expressed the same immunologic surface markers (mu k) and carried the same t(8;14) translocation, Southern blot analysis of DNA from each tumor, using specific restriction endonucleases and probes to the c-myc and the immunoglobulin heavy chain loci, demonstrated that the chromosomal breakpoints relevant to the translocations differed between the tumors. This was corroborated by analysis of the immunoglobulin light-chain rearrangements in the two tumors. These observations indicate that the second tumor was not a recurrence of the first but represented the malignant transformation of a different clone of B cells. Thus late relapses of certain malignancies in individuals at high risk may be caused by the malignant transformation of discrete cell clones (i.e., induction of a new tumor).
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PMID:Development of a second clonally discrete Burkitt's lymphoma in a human immunodeficiency virus-positive homosexual patient. 340 98

AIDS (acquired immune deficiency syndrome) and ARC (AIDS-related complex) are associated with a spectrum of lymphoproliferative disorders ranging from lymphadenopathy syndrome (LAS), an apparently benign polyclonal lymphoid hyperplasia, to B cell non-Hodgkin's lymphoma (B-NHL), i.e., malignant, presumably monoclonal B cell proliferations. To gain insight into the process of lymphomagenesis in AIDS and to investigate a possible pathogenetic relationship between LAS and NHL, we investigated the clonality of the B or T lymphoid populations by Ig or T beta gene rearrangement analysis, the presence of rearrangements involving the c-myc oncogene locus, and the presence of human immunodeficiency virus (HIV) sequences in both LAS and B-NHL biopsies. Our data indicate that multiple clonal B cell expansions are present in a significant percentage of LAS (approximately 20%) and B-NHL (60%) biopsies. c-myc rearrangements/translocations are detectable in 9 of our 10 NHLs, but not in any of the LAS cases. However, only one of the B cell clones, identified by Ig gene rearrangements carries a c-myc gene rearrangement, suggesting that only one clone carries the genetic abnormality associated with malignant B cell lymphoma. Furthermore, the frequency of detection of c-myc rearrangements in AIDS-associated NHLs of both Burkitt and non-Burkitt type suggest that the biological alterations present in AIDS favor the development of lymphomas carrying activated c-myc oncogenes. Finally, our data show that HIV DNA sequences are not detectable in LAS nor in NHL B cell clones, suggesting that HIV does not play a direct role in NHL development. Taken together, these observations suggest a model of multistep lymphomagenesis in AIDS in which LAS would represent a predisposing condition to NHL. Immunosuppression and EBV infection present in LAS can favor the expansion of B cell clones, which in turn may increase the probability of occurrence of c-myc rearrangements leading to malignant transformation.
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PMID:Multiple monoclonal B cell expansions and c-myc oncogene rearrangements in acquired immune deficiency syndrome-related lymphoproliferative disorders. Implications for lymphomagenesis. 349 Nov 76

The regulation of transcriptional elongation plays a central role in the expression of a number of cellular and viral genes. For example, levels of c-myc RNA change during cellular proliferation and differentiation via alterations in transcriptional attenuation near the 5' end of the c-myc gene. The protein that regulates transcription through attenuation sites in c-myc has not been identified. However, a candidate protein of equivalent function exists in the human immunodeficiency virus (HIV) genome, where the transactivator Tat increases transcriptional elongation through the HIV LTR and coding sequences by interacting with the trans-acting-response (TAR) RNA stem-loop that is found at the 5' end of all viral transcripts. By placing TAR 3' to the P2 promoter of the mouse c-myc gene, we demonstrate that Tat can also direct read-through transcription in mouse c-myc in transfected HeLa cells. Thus we identified a viral transactivator whose cellular counterpart regulates transcriptional attenuation within c-myc and other proto-oncogenes.
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PMID:Human immunodeficiency virus type 1 tat directs transcription through attenuation sites within the mouse c-myc gene. 752 69

The relationship between clinical and molecular characteristics of 45 treated individuals with histologically-documented human immunodeficiency virus (HIV)-associated B-cell non-Hodgkin's lymphoma was examined to determine whether differences in molecular features of lymphoma were associated with differences in clinical outcome. Tissue specimens from these tumors were evaluated for evidence of Ig heavy-chain gene rearrangements using both Southern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Lymphomas were also evaluated for the presence of Epstein-Barr virus (EBV) DNA sequences and c-myc gene rearrangements. Twenty-five lymphomas were characterized as polyclonal and 20 as monoclonal. PCR amplification of expressed Ig variable (V)-region genes confirmed polyclonality in three extensively studied polyclonal lymphomas. The median CD4 count was significantly higher in the group with polyclonal disease (277/microL) than in the group with monoclonal disease (123/microL), P = .04. The complete response rate to therapy was significantly higher in patients with polyclonal disease (78%) and CD4 greater than 200/microL (81%) than in those with monoclonal disease (31%) and CD4 less than 200/microL (33%). CD4 count, clonality, and presence of EBV DNA sequences were the most important predictors of survival. Both Kaplan-Meier and Cox proportional hazards analyses showed a markedly prolonged survival in those patients with both CD4 > or = 200/microL and polyclonal disease. Histologically the polyclonal lymphomas were high grade in appearance and contained prominent macrophages. All seven surviving patients were in this group. Median survival for those individuals whose tumors contained EBV sequences was only 3.2 months (range, 0.4 to 19.5), whereas those with EBV- tumors survived for a median of 9.0 months (range, 0.7 to 65.2), P = .0007. These data indicate that molecular features of HIV-associated lymphomas may be important predictors of clinical outcome. These characteristics define a distinct subset of patients with polyclonal EBV- tumors and CD4 counts greater than 200/microL that appear to have a less aggressive clinical course.
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PMID:Influence of molecular characteristics on clinical outcome in human immunodeficiency virus-associated non-Hodgkin's lymphoma: identification of a subgroup with favorable clinical outcome. 753 86

Cartilage-hair hypoplasia (CHH) is an autosomal recessive disease of unknown etiology characterized by metaphyseal dysostosis, unpigmented hair, and defective cellular immunity. We studied peripheral blood mononuclear cells (PBMC) of a boy with CHH and combined immunodeficiency in an attempt to characterize further the immune defect in this disease. Stimulation of his PBMC with mitogens was associated with severely depressed IL-2 and interferon-gamma (IFN-gamma) synthesis and IL-2 receptor alpha-chain (IL-2R alpha) expression and resulted in poor lymphocyte proliferation that was only modestly upregulated by the addition of recombinant IL-2 (rIL-2). The defective proliferation and lymphokine synthesis were not corrected by the addition of phorbol myristate acetate (PMA) and ionomycin, agents that bypass receptor-mediated signalling, indicative of a distal abnormality. Importantly, the levels of mRNA encoding c-myc, IL-2R alpha, IL-2 and IFN-gamma were markedly decreased in patient lymphocytes stimulated with PMA+ionomycin as compared to control lymphocytes. The defect in the expression of these early activation genes was selective in that induction by mitogens of mRNA encoding other early activation gene products such as c-fos and c-jun was not impaired. These results suggest that the underlying defect in this patient and perhaps others with CHH may be an abnormality in a component of intracellular signalling pathways or in a trans-acting factor which regulates the expression of a selected number of early activation genes.
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PMID:Defective expression of early activation genes in cartilage-hair hypoplasia (CHH) with severe combined immunodeficiency (SCID). 755 1


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