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 have previously shown that expression of the adenovirus E1A 12S or 13S products in NIH 3T3 fibroblasts induces susceptibility to the cytotoxic actions of tumor necrosis factor alpha (TNF alpha). A large number of studies have mapped the multiple biological functions of the 12S and 13S products to three highly conserved regions (CR) within the E1A sequence. Here we used plasmids coding for E1A deletion and point mutants in these regions to generate target cell lines for TNF alpha cytotoxicity assays to determine which regions and functions are necessary for the induction of TNF alpha sensitivity. Expression of CR1 was required for the induction of TNF alpha sensitivity. This finding did not reflect a requirement for transforming or transcriptional repression activity, since some mutants that were defective in both of these properties were able to induce TNF alpha sensitivity. CR2 transformation-defective point mutants, but not a CR2/3 region deletion mutant, were also able to induce sensitivity. In addition, NIH 3T3 cells expressing the retroviral transcription activators tat from human immunodeficiency virus type 1 and tax from human T-lymphotropic virus type I were not sensitive to TNF alpha. However, the possibility that E1A-mediated transcriptional activation can augment the induction of TNF alpha sensitivity is not excluded. Comparison of data from previous biological studies with the TNF alpha cytotoxicity assays presented here suggested that the mechanism by which E1A induces sensitivity to TNF alpha in NIH 3T3 cells is independent of many of the known E1A biological functions, including transformation in cooperation with ras, immortalization, induction of DNA synthesis in quiescent cells, and transcriptional repression. A novel E1A-mediated effect may be involved, although our data do not exclude the possibility that sensitization to TNF alpha is mediated through E1A binding to cellular proteins.
 ...
PMID:Induction of sensitivity to the cytotoxic action of tumor necrosis factor alpha by adenovirus E1A is independent of transformation and transcriptional activation. 214 40

The amino acid L-tryptophan is known to be a modulator of many processes of cell metabolism. In this contribution we show that L-tryptophan interferes with some biological effects of the antileukemic and anti-human immunodeficiency virus agent avarol, possibly by different mechanisms. Avarol has been shown to be able to modulate posttranscriptional events of mRNA synthesis, resulting in an increase of the base-sequence complexities of the nonabundant and rare mRNA classes. Here it is demonstrated that this change in mRNA abundancy distribution is accompanied by an increase in the level of some specific, low abundant mRNAs (ras and c-myc). Addition of L-tryptophan was found to abolish avarol-caused gene relaxation in L1210 mouse leukemia cells. In addition, L-tryptophan suppressed the induction of gamma-interferon mRNA production in human peripheral blood lymphocytes. At the level of DNA, L-tryptophan inhibited the production of strand breaks by cytotoxic avarol concentrations in Friend erythroleukemia cells in vitro. Moreover, it competed with avarol for binding to the nuclear envelope binding site; this effect was not shown by other amino acids.
 ...
PMID:Suppression of the modulatory effects of the antileukemic and anti-human immunodeficiency virus compound avarol on gene expression by tryptophan. 249 75

Transient transfection of ras expression vectors into human fibroblasts and astrocytes has been used to test the hypothesis that p21 ras, a known membrane signal transductor, may participate in pathways linking cellular activation and human immunodeficiency virus (HIV) reactivation. Expression vectors carrying the chloramphenicol acetyl transferase coding sequence under the control of various fragments of the long terminal repeat (LTR) of HIV were co-transfected with expression vectors of the mutated (val 12) c-Ha-ras gene or of its normal counterpart. Both forms of the ras gene induced transactivation of the HIV-LTR via the two direct repeat sequences which constitute the HIV enhancer. This repeat sequence was shown to be sufficient for ras-induced LTR transactivation. Other LTR sequences tested were not found to be responsive to co-transfected ras expression vectors. Deletion of the TAR sequence impaired the response to tat, but not to ras co-transfection. The mutated ras gene was more efficient than the proto-oncogene in activating the HIV enhancer. Transfection of ras was shown to enhance transcription of a complete provirus DNA clone of HIV-1. Such findings may shed new light on the mechanisms through which cell membrane activation signals result in HIV reactivation.
 ...
PMID:c-Ha-ras transfection induces human immunodeficiency virus (HIV) transcription through the HIV-enhancer in human fibroblasts and astrocytes. 268 62

The clinical significance of the high prevalence of antibodies to hepatitis C virus (HCV) in dialysis patients remains undefined. In order to assess the relationship between seropositivity and potential infectivity, 63 patients undergoing maintenance hemodialysis were evaluated between April and May 1990. The mean duration of maintenance hemodialysis was 45 mo (range, 13 to 144). Eighty-two percent (52 of 63) had received blood transfusions, and 16% (10 of 63) had a history of iv drug abuse. Serum samples were analyzed by HCV-cDNA polymerase chain reaction; antibodies to HCV structural (core) and nonstructural regions NS3 and NS4 were determined by enzyme immunoassay. Specimens repeatedly reactive for anti-HCV and HCV-RNA-positive samples were tested by HCV MATRIX dot immunoblot assay and HBV-DNA PCR. Twenty-five percent (16 of 63) were anti-HCV-positive. Of the 16 anti-HCV-positive patients, HCV-RNA was detected in 5 (31%) with the NS3 primers and in 12 (75%) with 5'-noncoding primers. Among the anti-HCV-negative patients, HCV-RNA was detected in 2 (4.3%) of 47 patients. Eleven of the 18 patients with HCV infection (anti-HCV and/or HCV-RNA-positive) had evidence of additional present or past viral infections (human immunodeficiency virus and/or hepatitis B virus). In summary, HCV-RNA is present in at least 75% of anti-HCV-positive patients, suggesting that they may be infectious. The detection of HCV-RNA in anti-HCV-negative patients may indicate early or chronic HCV infection not detected by current antibody assays or the inability of these patients to mount or sustain a significant antibody response.
 ...
PMID:Detection of hepatitis C virus RNA in hemodialysis patients. 751 32

Cotransfection of NIH 3T3 cells with a mammalian expression vector containing a v-Ha-ras gene, together with a plasmid carrying the human immunodeficiency virus (HIV) long terminal repeat (LTR) linked to the chloramphenicol acetyl transferase (CAT) reporter gene, significantly stimulated CAT activity. High HIV LTR activation was also observed in cell lines carrying stably transfected ras oncogenes, activated by point mutation or amplification. By contrast an inactivated form of ras (Ha-ras Asn-17) did not stimulate the HIV-LTR but strongly inhibited its basal activity. Activation of the p21ras protein may thus be one of the signals that regulate LTR driven transcription during HIV infection.
 ...
PMID:Modulation of HIV-LTR activity by ras oncogenes. 760 37

Sera of 383 human immunodeficiency virus (HIV)-1-infected individuals from Frankfurt (Main)/Germany were assayed by two hepatitis C virus (HCV) screening tests (Abbott second generation, Ortho second generation). This population showed a prevalence for reactivity with both tests of 20.8% (80/383). Examination of all reactive sera (91/383) by a supplemental assay (Chiron RIBA 2) gave for 46 sera a positive, for 33 sera an indeterminate, and for 12 sera a negative result. Further analysis focussed on these RIBA 2-indeterminate and -negative samples. Analysis of the sera using an in-house Western blot with three different Escherichia coli-expressed HCV proteins revealed that none of the RIBA 2-negative, but 24 of the 33 RIBA 2-indeterminate sera, including 3 of 4 c33c (NS3)-reactive samples, were reactive with a recombinant core protein. Twenty-one of 22 c22-3 (core) indeterminates stained the core antigen in the in-house Western blot and 3 of them in addition a NS5 moiety. HCV-polymerase chain reaction (PCR) was positive for 14 of the 24 RIBA 2-indeterminate sera, but for none of the RIBA 2-negative or Western blot nonreactive samples. Discrepant results between the two screening tests could not be explained by differences in the antigen compositions (i.e., a NS3-NS4 moiety of 111 amino acids present in the Ortho enzyme-linked immunosorbent assay (ELISA), not present in the Abbott or RIBA 2 assays).
 ...
PMID:Hepatitis C virus antibody prevalence among human immunodeficiency virus-1-infected individuals: analysis with different test systems. 779 85

Lymphoma is one of the defining manifestations of AIDS. Most of these lymphoproliferations are high-grade B-cell non-Hodgkin's lymphoma. Unlike lymphoproliferations that arise in other settings of immunodeficiency, HIV-related lymphomas have a variable association with Epstein-Barr virus (EBV) and also contain alterations in c-myc and p53. EBV infection appears to precede clonal expansion, and its latent expression pattern (Epstein-Barr nuclear antigen1+/Epstein Barr nuclear antigen 2-/latent membrane protein+) is unique among non-Hodgkin's lymphomas. Both EBV types A and B are present in HIV-related lymphomas. Mutations in c-myc include translocations and point mutations. Other altered loci include ras and bcl-6. Although all of these somatic alterations can be detected in lymphomas arising in the general population, their accumulation in a relatively short period (6 to 8 years) after HIV infection suggests an acceleration of underlying mechanisms.
 ...
PMID:Biologic aspects of AIDS-related lymphoma. 782 54

Anaplastic large-cell lymphoma (ALCL) represents a morphologically distinct type of non-Hodgkin's lymphoma (NHL) characterized phenotypically by the expression of the CD30 antigen, a new member of the nerve growth factor gene family. The lymphoid origin of ALCL has been documented using immunohistochemical and molecular genetic analyses. However, very little is known so far regarding the precise pathogenetic mechanisms involved in its development and progression. Therefore, we investigated bcl-2, p53, and retinoblastoma gene (Rb) expression immunohistochemically; the occurrence of bcl-2, c-myc, and Rb gene rearrangements using Southern blotting; and the presence of ras and p53 gene somatic mutations by single-strand conformation polymorphism assay in a panel of 18 well-characterized ALCLs. In addition, the presence of Epstein-Barr (EBV) and human T-cell lymphotropic virus type I (HTLV-I) genomes were investigated using polymerase chain reaction. We identified abnormal c-myc gene products in 6 of 18 cases (33%) of ALCL. On the other hand, the bcl-2 and Rb genes were not rearranged and K-, N-, and H-ras gene somatic mutations were not found. Significant levels of p53 protein expression were found in more than 60% of ALCLs, but only a single ALCL carried a p53 gene mutation (exon 5). Only 3 ALCL cases, all occurring in human immunodeficiency virus-infected patients, were positive for EBV genomes. On the other hand, contrary to previous findings, no HTLV-I products could be identified. Despite the fact that the c-myc proto-oncogene appears to be frequently altered in ALCL, no pathognomonic abnormality could be identified and therefore additional studies and new strategies should be designed to identify the pathogenetic mechanisms involved in the development of ALCL.
 ...
PMID:Molecular characterization of CD30+ anaplastic large-cell lymphoma: high frequency of c-myc proto-oncogene activation. 820 84

We collected the nucleotide sequences of hepatitis C virus (HCV) from the international DNA data base DDBJ/EMBL/GenBank to carry out molecular evolutionary analysis of HCVs. Using these sequences, we constructed the phylogenetic trees for the 5' non-coding, Core, Env., E2/NS1, NS3, NS4 and NS5 regions of HCV. The number of nucleotide substitutions per site at all positions between all pairs of HCVs, for each region, were estimated by the 6-parameter method. Using these numbers, we constructed phylogenetic trees for each region of HCV by the neighbor-joining method. In these trees for the coding regions (Core, Env, E2/NS1, NS3, NS4 and NS5 regions), HCVs can be classified into two major and four minor genotypes, but into three major and six minor genotypes on the tree of the NS5 region. It appears that HCVs exist as at least two or three major and six minor types. The evolutionary rates of HCV was estimated to be about 10(-3) per site per year close to that of human immunodeficiency virus. The new genotypes of HCV may be therefore isolated elsewhere in the near future. Then, applying the distance between H77 and H90 strains to the phylogenetic trees, we estimated the divergence times of HCVs. The major genotypes diverged about 300-400 years ago from the ancestor virus and after then, each minor genotypes diversed about 200 years ago from their major genotypes. These data suggested that HCVs spread out all over the world during these hundred years.
 ...
PMID:[Molecular genotypes of hepatitis C virus and their divergence times]. 838 34

Two quantitative PCR methods with our nonisotopic enzyme-linked oligosorbent assay (ELOSA) in microtiter plate format were developed for quantitation of human immunodeficiency virus type 1 (HIV-1). Quantitative competitive PCR (QC-PCR) was based on the coamplification of the wild-type nef region with a mimic competitive nef gene template carrying mutations in the capture region. Correlation of wild-type HIV-1 nef DNA to mimic template copy number permitted quantitation of HIV-1 copy numbers in the range of 20 to 2,000 copies per micrograms of DNA. Internally controlled PCR (IC-PCR) was based on coamplification of the nef region and the ras gene as an internal endogenous standard. Correlation to known amounts of HIV-1 DNA permitted quantitation by IC-PCR of HIV-1 copy numbers in the range of 10 to 2,000 copies per microgram of DNA. QC- and IC-PCR-ELOSA were performed on a panel of 53 seropositive patients and 12 seronegative controls. The methods showed similar coefficients of variation below 24%. Quantitations by QC- and IC-PCR-ELOSA were identical for 77% of patient samples. The copy level ranged between 443 +/- 156 and 21,453 +/- 13,511 copies per 10(5) CD4 cells for asymptomatic and AIDS patients, respectively. The simplicity and reliability of QC- and IC-PCR-ELOSA methods make them appropriate for routine laboratory use in the quantitation of viral and bacterial DNAs.
 ...
PMID:Quantitation of human immunodeficiency virus type 1 DNA by two PCR procedures coupled with enzyme-linked oligosorbent assay. 858 3


1 2 3 4 5 6 7 8 Next >>