Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine the occurrence and histologic correlates of viral infections in immunocompromised patients with pneumonia. Of the 44 immunocompromised patients studied, 37 had AIDS. Lung tissue from these patients, including 34 with pneumocystis pneumonia, was evaluated by in situ hybridization for the presence of cytomegalovirus (CMV), adenovirus, Epstein-Barr virus, and herpes simplex virus. Fifteen of the 44 patients were positive for at least one virus (34%); CMV (13 cases) was the most common. In an additional seven cases, CMV DNA was detected using the polymerase chain reaction (PCR), for an overall viral detection rate of 22 of 44 (50%). Histologic features were diagnostic of a viral infection in nine of 15 cases (60%) of the in situ positive cases and in nine of 22 (41%) of the tissues where viral DNA was detected by PCR. Mortality rate was significantly correlated with viral detection: 77% for the viral-positive cases and 27% for the viral-negative cases (p < 0.05). We concluded that in immunocompromised patients with pneumonitis, the detection of viral DNA is strongly correlated with survival and that histologic features of the inflamed lung tissue are a specific but insensitive means of diagnosing viral presence.
Diagn Mol Pathol 1993 Sep
PMID:Correlation of viral infection, histology, and mortality in immunocompromised patients with pneumonia. Analysis by in situ hybridization and the polymerase chain reaction. 828 33

We present a model for the three-dimensional structure of the HIV TAR stem-loop, based on a modeling algorithm which makes use of the known X-ray coordinates of tRNAs to generate a model structure, which has then been tested experimentally in solution by enzymatic and chemical structure probing of ribo-oligonucleotides encompassing the TAR sequence. The modeling suggested that the structure of TAR was similar to that of the anti-codon loop of tRNA(Asp), having a loop of just three single-stranded residues with a mismatched adenine excluded from the helical stem on the 3' side of the loop. The structural probing is consistent with such a structure for the loop, and reveals an unusual structure around the 5' uridine-rich bulge, which is the binding target for the transactivator protein Tat. These data may be useful in understanding the interaction of TAR with the Tat protein and may aid in the design of anti-AIDS drugs. The coordinates of the model are available on request.
J Mol Graph 1993 Jun
PMID:Modeling and solution structure probing of the HIV-1 TAR stem-loop. 834 68

The spatial structure model of peptide T (AIDS reproduction inhibitor, the amino acid sequence of which corresponds to the fragment into the binding site of the virus protein gp120 with T4 receptor) is proposed. Peptide structure modelling has been carried out by the previously developed method based on joint usage of the molecular mechanics algorithms and NMR spectroscopy data. To build the model, two-dimensional nuclear Overhauser effect spectroscopy data for RNase A homologous fragment 22-26 were taken from the literature. The result of the presented work was a set consisting of six types of low-energy structures with different spatial packing of the peptide main chain. All structural types have been shown to be characterized by the lack of strict determination of the side chain conformations of the amino acid residues that can be realized in a few states providing approximately equal (within the given type) stabilization of one main chain form. At the same time, despite the definite differences, all of the selected structures were characterized by the presence of two consecutive reverse polypeptide chain turns at the C-terminal pentapeptide fragment. This site is supposed to be responsible for the peptide binding with T4 receptor and the antiviral effect.
Mol Biol (Mosk)
PMID:[Model of the spatial structure of peptide T]. 836 99

A spectrum of pathogenicity has been observed for primate lentiviruses in their natural hosts. For example, human immunodeficiency virus type 1 (HIV-1) is a potent etiologic agent for AIDS in man, whereas there is no evidence to date which indicates that simian immunodeficiency virus from African green monkeys (SIVAGM) causes immunodeficiency in AGM. We measured the relative rates of amino acid change, as the ratio of the number of nonsynonymous to synonymous (silent) nucleotide substitutions, for six primate lentiviruses evolving in their respective hosts. These rates for the external envelope glycoprotein (gp120) and gag coding sequences are 2-3 times higher for pathogenic HIV-1 and SIVmac (macaque) than for minimally pathogenic SIVAGM and SIVsmm (sooty mangabey), and intermediate for HIV-2. We speculate that the increased rates of nonsynonymous changes in gp120 and gag coding sequences are due to viral escape from immune surveillance and are indicative of higher immunogenicity of these proteins in their hosts. Based on these results and available experimental data, we conclude that there is a positive correlation between lentiviral pathogenicity and immunogenicity of the Env and Gag proteins in a given host. This hypothesis is consistent with recent data suggesting that immune system activation or autoimmunity induced by viral antigens may be important in the pathogenesis of AIDS.
J Mol Evol 1993 Jul
PMID:Rates of amino acid change in the envelope protein correlate with pathogenicity of primate lentiviruses. 839 4

The Human Immunodeficiency Virus (HIV) integrates into host cellular DNA as a double strand DNA molecule. Here a previously studied HIV isolate was examined for binding and cleavage by topoisomerase II in vitro within the 5' LTR region and human flanking DNA. A cluster of strong binding and cleavage sites in the human sequences was located approximately 850 bp upstream from the integration site. This region maps to a locus consisting of a complex repeating element, and alternating purine/pyrimidine sequences. Topoisomerase II binding and cleavage sites were also located within the HIV 5' LTR, in particular a site overlying the DNA sequence coding for TAR, another inverted repeat element in the DNA.
J Mol Biol 1993 Aug 20
PMID:A cluster of strong topoisomerase II cleavage sites is located near an integrated human immunodeficiency virus. 839 47

We examined the mutagenicity of iso-butyl nitrite (IBN) vapor and aqueous IBN solution in the Ames test to help evaluate the hazard of sniffing this vapor, a habit which might play a role in the induction of Kaposi's sarcoma associated with acquired immune deficiency syndrome. Chemical analysis showed that the saturated vapor contained 190 micrograms IBN/ml at 25 degrees C, and saturated aqueous solution, 2.6 mg IBN/ml at 21-23 degrees C. When agar plates containing Salmonella typhimurium TA-1535 and rat liver S-9 were exposed to IBN vapor, the number of mutants reached a maximum after 40 min. A mean of 307 mutants/plate (22 x background) was observed when the plates were exposed to IBN vapor for 30 min. Addition of 0.2 ml saturated IBN solution in water to similar plates gave a mean of 179 mutants/plate (7.9 x background) in the absence of S-9, confirming published results. The S-9 did not affect the results. Based on the IBN level in medium exposed to IBN vapor, the vapor was apparently 11 times more mutagenic than IBN solution. This was attributed to continuous replenishment of unstable IBN in the medium by the vapor. The half-life of IBN at 21-23 degrees C was > 1 hr for solutions in water and < 3 min for solutions in the assay medium. This instability was traced to a reaction with phosphate, presumably hydrolysis to nitrite and iso-butanol. IBN in solution was 2.8 times more mutagenic than sodium nitrite, suggesting that IBN was not mutagenic because of its conversion to nitrite. Iso-butanol was not mutagenic. The results demonstrate the potential hazard of sniffing IBN vapor.
Environ Mol Mutagen 1993
PMID:Mutagenicity of iso-butyl nitrite vapor in the Ames test and some relevant chemical properties, including the reaction of iso-butyl nitrite with phosphate. 846 28

The antigenicity of Human Immunodeficiency Virus type 1 (HIV-1) matrix p18 protein was evaluated by analyzing the specificity of anti-p18 antibodies elicited either in HIV-1 infected humans, or in HIV-1 infected or immunized chimpanzees, against a panel of long and short overlapping synthetic peptides [from 12 to 46 amino acid (aa) residues] covering the entire sequence of p18. The relationship between peptide structure and antigenicity was further investigated by probing the secondary structures of the peptides by circular dichroism. The results obtained clearly showed the immunodominance of the N-terminal region mimicked by peptide P1 (aa 2-45), which reacted with 52 and 100% of human and chimpanzee anti-p18 sera, respectively. In contrast smaller 15 aa long peptides C1, C2, C3, C4 and P3 which cover the entire sequence of immunodominant peptide P1, showed only weak or no reactivity. In contrast to widely accepted hypotheses, circular dichroism analysis of both small and large peptides secondary structures did not show any obvious correlation between antigenicity and the ability of peptides to adopt an ordered conformation.
Mol Immunol 1993 Apr
PMID:Evaluation of structure-antigenicity relationship of peptides from human immunodeficiency virus type 1 (HIV-1) p18 protein by circular dichroism. 846 30

The efficiency of three different primer pairs, complementary to different Pneumocystis carinii DNA regions, was compared in the polymerase chain reaction (PCR) for the diagnosis of Pneumocystis carinii pneumonia (PCP) on bronchoalveolar fluid (BALF) from patients with AIDS. PCR coupled with dot-blot hybridization (BLOT) using primers and probe from the mitochondrial 23SrDNA region showed the highest sensitivity, with a lower detection limit of 0.5-1 organisms microliter-1. When testing 47 BALF, PCR plus BLOT of the mitochondrial 23SrDNA region showed also the best diagnostic efficiency (97% sensitivity, 100% specificity). Sensitivity was significantly higher than with PCR and BLOT of the 5SrDNA region (81.5% sensitivity; P = 0.025, McNemar test); and of the dehydrofolate reductase (DHFR) gene region (75.6% sensitivity; P = 0.019). Sensitivity was also significantly higher than indirect immunofluorescence (75.8% sensitivity; P = 0.008). Using DHFR primers and probe, specificity was also reduced. The diagnostic sensitivity in clinical specimens paralleled the detection limit in the standard dilutions. The use of repeated DNA sequences of proven specificity as target of PCR amplification favourably influences sensitivity and specificity. This comparative study demonstrates that primer selection plays a significant role in the diagnosis of PCP by PCR.
Mol Cell Probes 1995 Oct
PMID:Variable efficiency of three primer pairs for the diagnosis of Pneumocystis carinii pneumonia by the polymerase chain reaction. 856 74

The dideoxynucleoside analogue 2',3'-dideoxyinosine (ddI) has been used in the clinic as an alternative drug to zidovudine (AZT) in the treatment of patients with the acquired immunodeficiency syndrome (AIDS). However, it shows significant and variable toxicity in patients. It is known that various dideoxynucleoside analogues can cause the termination of the DNA chain following incorporation of the corresponding triphosphate metabolite by the polymerases. In the case of ddI, the presumed active metabolite is 2',3'-dideoxyadenosine 5'-triphosphate (ddATP). In order to understand the molecular basis for the toxicity of ddI, we evaluated the relationship between the intracellular formation of ddATP, its incorporation into cellular DNA and the effects on the growth of U937 cells, a human monocytoid cell line. Dideoxyinosine was not significantly toxic to U937 cells at concentrations as high as 500 microM in a 72 hrs. growth inhibition assay. The results of the uptake of 3HddI in this cell line showed a proportional increase in total metabolites with increasing concentrations of the drug (1-20 microM) after a 24 hrs. exposure. Incubation with 10 microM 3HddI resulted in the formation of low levels of ddATP within a period of 2 hrs. A significant amount of ddI-derived radioactivity was found in both DNA and RNA after exposure to 10 microM 3HddI for 24 to 72 hrs. However, no evidence of incorporation of ddATP into the cellular DNA fraction was obtained in these experimental conditions. Therefore, the lack of significant toxicity of ddI to U937 cells can be explained, at least in part, by its inability to incorporate ddATP into its cellular DNA at the doses studied.
Cell Mol Biol (Noisy-le-grand) 1995
PMID:Uptake and distribution of 2',3'-dideoxyinosine and its derivatives in a human monocytoid cell line. 857 39

We find that interleukin-2 (IL-2) production is severely depressed (80-90%) in AIDS T-cells (CD4+ or CD8+) stimulated with anti-CD3 or Con A together with phorbol ester (PMA) or anti-CD28 coactivation. Likewise, the proliferative response of CD4+ T-cells was suppressed, from a mean of 24.6% (HIV+) to 59.1% (AIDS) for PMA with activators OKT3 (anti-CD3), Con A, enterotoxin B or pokeweed mitogen, and 20.2% (HIV+) to 77.8% (AIDS) with anti-CD28 co-activation. Similar degrees of suppression were found with the CD8+ T-cells except for a much greater suppression at the HIV+ stage with anti-CD28 (57.7%), approximately 2.5 times higher than for PMA coactivation. However, when proliferation was induced by the two coactivators combined (PMA plus anti-CD28), much less suppression was observed: 8.5% (HIV+) to 19.0% (AIDS) for CD4+ cells and 8.2% to 26.5%, respectively, for CD8+ cells. The data suggest that during HIV infection the CD28 pathway becomes most defective, but can be bypassed to some extent by the less-impaired PMA pathway. The IL-2 (+PMA) signal in HIV+ and AIDS cells was also significantly less suppressed suggesting that the disregulation in HIV infection is more prominent prior to the IL-2 stage of the mitogenic pathway. It is remarkable that the CD4+ and CD8+ T-cells at both the HIV+ and AIDS stages generally show the same degree of suppression with all the various activators and coactivators used.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Mol Biol (Noisy-le-grand) 1995
PMID:Suppressed proliferative response and interleukin-2 production in hispanic HIV+ and AIDS T-cell subsets. 857 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>