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)

There is indirect evidence that various viruses have aetiological roles in the idiopathic inflammatory myopathies. By means of a sensitive and specific method based on the polymerase chain reaction (PCR), we sought direct evidence for the presence in affected muscle of nucleic acid sequences from Coxsackie virus, mumps virus, encephalomyocarditis virus, adenovirus, human T-lymphotropic virus types I and II, and human immunodeficiency virus. RNA was extracted from muscle biopsy samples obtained from 44 patients with idiopathic inflammatory myopathies a mean of 45 (range 0-216) months after disease onset. All the subjects were older than 16 years at disease onset. The integrity of the mRNA extracted was confirmed by the successful PCR amplification of insulin receptor mRNA in all samples. The PCR method was able to detect between 1 and 20 molecules of added viral nucleic acid for the picornaviruses sought. No detectable virus sequences were found, however, in any of the patients' muscle samples or in samples from 13 controls. We tested for retroviral DNA in 22 samples (17 patients, 5 controls) that met our criterion for adequate DNA extraction (detectable beta-actin DNA by PCR); again no virus sequences were found. Persistence in muscle of these or closely related viruses is unlikely to be a continuing stimulus for disease in the idiopathic inflammatory myopathies.
 ...
PMID:Viruses in idiopathic inflammatory myopathies: absence of candidate viral genomes in muscle. 134 38

Ribozymes are RNAs that possess the dual properties of RNA sequence-specific recognition, analogous to conventional antisense molecules, and RNA substrate destruction via site-specific cleavage. The cleavage reaction is catalytic in that more than one substrate molecule is processed per ribozyme molecule. We have designed a hairpin ribozyme that cleaves human immunodeficiency virus type 1 (HIV-1) RNA in the leader sequence (at nucleotides +111/112 relative to the transcription initiation site). The ribozyme was tested in vitro and gave efficient and specific cleavage of RNA containing the leader sequence. To test the antiviral efficacy of this ribozyme, we have cotransfected into HeLa cells HIV-1 proviral DNA and a plasmid expressing the ribozyme from the human beta-actin promoter. HIV-1 expression was inhibited as measured by p24 antigen levels and reduced Tat activity. The antiviral effect of the ribozyme appears to be specific and results from directed RNA cleavage; activity requires both a target sequence and a functional RNA catalytic center. These results suggest that this HIV-1-directed hairpin ribozyme may be useful as a therapeutic agent.
 ...
PMID:Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme. 143 80

The bacterial neomycin phosphotransferase gene driven by the Moloney mouse leukemia virus long terminal repeat (LTR) or SV40 early region promoter was introduced into the human promonocyte-macrophage cell line, U937, and into the pluripotential human embryonic teratocarcinoma cell line, NT2/D1. Clonally derived cell lines capable of growing in 2-4 mg/ml of the aminoglycoside antibiotic, G418 (Geneticin), were established and transfected with pHIVCat, a plasmid expressing the bacterial chloramphenicol acetyl transferase (CAT) activity under the control of the human immunodeficiency virus (HIV-1) LTR. All of the G418 resistant (neo(r)) U937 cell lines and 10 of 14 neo(r) NT2/D1 cell lines exhibited reduced basal levels of CAT expression or impaired responses to activation of the HIV-1 LTR by phorbol 12-myristate 13-acetate (PMA) when compared to the parental lines. Other differences included inhibition of tat activation of the HIV-1 LTR and increased sensitivity of U937 cells to human tumor necrosis factor alpha. The expression of other eukaryotic promoters including the HTLV-1 LTR, SV40 ori sequences, and the human beta-actin gene promoter was similarly affected. However, differentiation of the neo(r) U937 cells into macrophages was neither delayed nor impaired. Because PMA is an activator of protein kinase C (PKC) and a potent inducer of HIV-1 directed gene expression, the amounts, sensitivity to G418, and cytosol to membrane translocation of this enzyme were determined in the wild type and neo(r) U937 cells. G418 at concentrations too low to affect cell growth (12-150 micrograms/ml) inhibited PMA-induced transactivation responses in wild type cells but did not inhibit PKC-dependent protein phosphorylation in vitro. PKC activities in the wild type and neo(r) cells were similar in absolute amounts and in the cytosol-membrane distribution of the enzyme. In contrast with wild type cells, however, all of the cytosolic Ca(2+)-phospholipid-dependent form of PKC disappeared from the neo(r) cells within 30 min after PMA induction. The results suggested that, depending upon the cell type, gene cotransfer using aminoglycoside resistance as a selectable marker may seriously perturb important cellular control mechanisms such as the PKC pathway leading to activation of gene expression.
 ...
PMID:Gene activation mediated by protein kinase C in human macrophage and teratocarcinoma cells expressing aminoglycoside phosphotransferase activity. 166 Apr 86

Tandem repeats of the transactivation response element (TAR) of the human immunodeficiency virus 1 (HIV-1) were generated using a specially constructed "tandemizing" plasmid, pGem-Tan. This plasmid exploits the rotational nonequivalence of Ava I restriction sites to generate multiple copies of an inserted sequence. Twelve tandem repeats of the TAR were then placed in sense and antisense orientations behind a strong human beta-actin gene promoter. The TAR constructs were transfected with an appropriate HIV-1-driven reporter and tat gene expression plasmids into NT2/D1 cells, a pluripotential human embryonic teratocarcinoma cell line. Twelve tandem TAR repeats in the sense orientation suppressed 85-90% of the transactivating function of the virus-encoded tat protein, whereas the antisense construct or constructs containing single copies of TAR in either sense or antisense orientations were relatively ineffective. The suppression was specific for reporter gene constructs containing an intact HIV-1 long terminal repeat: Reporter genes driven by other promoters or by an HIV-1 long terminal repeat lacking the TAR were not suppressed. Suppression of activation by tat required transcription into RNA: Similar constructs containing the TAR repeats but lacking a eukaryotic promoter failed to suppress tat activation. In the absence of tat, the TAR DNA stimulated 2- to 5-fold the expression of gene constructs driven not only by the HIV-1 long terminal repeat but also by the human beta-actin gene and the simian virus 40 promoters.
 ...
PMID:RNA transcripts of the human immunodeficiency virus transactivation response element can inhibit action of the viral transactivator. 169 12

Direct recognition of viral gene sequences can be used to detect human immunodeficiency virus (HIV-1) in clinical specimens. A modification of the polymerase chain reaction (PCR) for amplification of gene sequences was used for detection of HIV-1-specific RNA prepared from peripheral blood mononuclear cells (PBMC). The RNA served as a template for reverse transcriptase using primers derived from both the 3'ORF and the LTR regions of HIV-1, as well as from the control cellular sequences encoding beta-actin and T cell receptor. The resultant DNA was amplified with DNA polymerase. A transcriptional step using the bacteriophage T7 promoter recognition sequences, incorporated into the primers, was used to enhance the efficiency of the amplification process. This assay detects as few as 100 RNA copies of cloned HIV-1 genome. Starting with 1 microgram RNA isolated from PBMC, we were able to detect HIV-1 sequences in patients with symptomatic and asymptomatic HIV-1 infection. The inclusion of T cell-specific primers permitted simultaneous evaluation of an immunologic parameter. The PCR can be applied to RNA samples for detection of viral and cellular sequences and is a rapid and efficient means for detection of HIV-1 sequences as well as potentially informative cellular sequences.
 ...
PMID:Confirmation of HIV infection using gene amplification. 252 May 45

Avarol is a cytostatic and anti-human immunodeficiency virus (HIV) agent. In this study, the avarol caused induction of gamma-interferon (IFN-gamma) in buffy coat cells (human peripheral blood lymphocytes) is demonstrated by immunological and molecular biological techniques. IFN-gamma production was detected after a 24-hr incubation period with avarol; maximal production was obtained after 5 days in the presence of the optimal avarol concentration of 0.75 microgram/ml. Blotting experiments using human IFN-gamma cDNA and beta-actin cDNA containing plasmids showed that in the absence of avarol no IFN-gamma transcripts were present in lymphocytes. Already after a 24-hr incubation with avarol, IFN-gamma gene induction was detected, and maximal induction was found after a 5-day incubation period. The enhanced IFN-gamma production seems to be caused by a change at the transcriptional and/or post-transcriptional level, but not during subsequent nucleocytoplasmic transport of mRNA. This molecular event is specific, at least in relation to the expression of the beta-actin gene. Our studies demonstrate that avarol displays, besides its potential anti-tumor and anti-HIV activity, a potential immunomodulating effect.
 ...
PMID:Induction of gamma-interferon by avarol in human peripheral blood lymphocytes. 313 18

In order to study the function of human cytomegalovirus (HCMV) immediate early gene 2 (ie2) (UL122) gene products made at late times during infection, cDNA clones were isolated from an expression library made with 74 h post-infection mRNA. Based on screening of the library, 1% of transcripts in infected cells at this time were ie2 region-specific, and transcripts encoding gamma IE2(338aa), a 40K late gene product, were more abundant than those encoding IE2(579aa), an alpha gene product made throughout infection. As expected, the cDNA capable of directing the expression of gamma IE2(338aa) was derived from a contiguous genomic region within exon 5 of the ie1/ie2 region. The cDNA clones encoding gamma IE2(338aa) and IE2(579aa) were compared for their ability to trans-activate viral and cellular promoters and to repress expression from the ie1/ie2 promoter via the ie2 cis-repression signal. Unexpectedly, gamma IE2(338aa) trans-activated a variety of test promoters when cotransfected with the major alpha gene product, IE1(491aa). Promoters derived from the cellular beta-actin gene, the simian virus 40 early region and the human immunodeficiency virus were all responsive to gamma IE2(338aa) plus IE1(491aa), although several beta promoters derived from the HCMV genome were unresponsive. Thus, this abundant late product from the ie2 region may play a role in trans-activation in addition to its role as a repressor of alpha gene expression.
 ...
PMID:Human cytomegalovirus late protein encoded by ie2: a trans-activator as well as a repressor of gene expression. 807 32

From the sera of patients with advanced cancer, a novel factor called SDF (serum-derived factor) was partially purified. SDF was shown to stimulate transcription from the long terminal repeat (LTR) of human immunodeficiency virus type 1 (HIV-1) by transient CAT assay. It did not stimulate gene expression of various control promoters including Rous sarcoma virus, human c-fos, c-myc, c-H-ras and chicken beta-actin genes. The SDF preparation did not contain any detectable TNF-alpha or TNF-beta, and differed in its physicochemical properties from TNFs. We concluded that SDF might be a novel factor associated with the clinical features of advanced cancer. It is speculated that SDF might have some role in disease progression of AIDS as well as in the development of the cachectic conditions in AIDS associated with malignancies.
 ...
PMID:Identification in the sera from patients with advanced cancer of a factor which stimulates gene expression from human immunodeficiency virus type 1. 823 10

Ribozymes have enormous potential as antiviral agents. We have previously reported that a hairpin ribozyme expressed under the control of the beta-actin promoter that cleaves human immunodeficiency virus type 1 (HIV-1) RNA in the leader sequence can inhibit HIV-1 (pHXB2gpt) expression. For such a ribozyme in a retroviral vector delivery system to be useful in gene therapy for the treatment of HIV-1 infection, it must be able to inhibit the expression of multiple HIV-1 strains. We have now cloned this ribozyme into various regular expression vectors (including retroviral vectors) by using various gene expression control strategies. Here we show by transient transfection that inhibition of expression of diverse strains of HIV-1 can be achieved by this ribozyme expressed in the proper vectors. These data further support the potential of this hairpin ribozyme as a therapeutic agent for HIV-1.
 ...
PMID:A hairpin ribozyme inhibits expression of diverse strains of human immunodeficiency virus type 1. 832 16

The human immunodeficiency virus type 1 (HIV-1) transactivator Tat protein is essential for efficient viral gene expression and virus replication. The Tat core domain, a stretch of 12 amino acids between the cysteine-rich and the basic domain, is conserved in all HIV isolates and required for interaction with a number of cellular transcriptional regulatory proteins. Here we demonstrate that soluble peptide analogs of the Tat core domain (amino acid 36-50) are able to effectively block LTR transactivation. In transfection experiments, Tat core peptide analogs containing amino acid substitutions at position 41 and 44 inhibited Tat transactivation of an HIV-1 LTR-CAT reporter construct up to 80-fold. In contrast, inhibition of other promoters such as HTLV-I and CMV was approximately 2-fold. Tat peptide analog 36-50 (41/44) inhibited HIV virus replication by 85% in latently infected U1 cells induced with Tat. Furthermore, U1 cells treated with the Tat peptide 36-50 (41/44) analog showed markedly delayed virus transmission when cocultivated with parental U937 cells. Interestingly, while both short and long peptide analogs (amino acids 36-50 vs 36-72) inhibited Tat transactivation in transient assays, the short peptides were more effective inhibitors of virus replication in U1 cells. The Tat peptide analog did not decrease expression of cellular genes including beta-actin, GAPDH, and histone H2B.
 ...
PMID:Inhibition of HIV-1 transcription and virus replication using soluble Tat peptide analogs. 901 42


1 2 Next >>