Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Of the Edinburgh cohort of approximately 130 children born to HIV-infected women, 9 are infected and alive. This article describes results from the first 18 months of a natural history study of seven of these, and two adopted children, studying the CD8 T cell-mediated cytotoxicity against HIV proteins (Gag, Tat, Pol, and Env), over time, and relating it to clinical progression and viral activity. Autologous EBV cell lines infected with vaccinia-HIV constructs were used as target cells, and bulk-cultured peripheral blood mononuclear cells as effector cells. The children ranged in age from 0 to 93 months, with six of the nine showing CTL activity to one or more HIV proteins. The specificity of the response was directed against Tat in the younger children, switching to Pol, then Gag or Env. Preliminary analysis of virological data showed no association between CTL and virus activity. The children with CTLs tended to be well clinically, but the cohort needs to be studied longer before conclusions can be made about CTL activity and HIV disease progression. Cytotoxic T lymphocyte activity has also been observed in two children diagnosed as HIV uninfected. These results show the importance of looking at CTL specificity, and may have implications in vaccine design.
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PMID:Cytotoxic T lymphocyte activity in children infected with HIV. 786 39

Some of new derivatives of 4-acylquinoxalin-2-one obtained in the reaction of N,N'-bis(chloroacetyl)-4,5-dimethyl-o-phenylenediamine with primary amines are described. Compounds were tested for their anti-HIV activity and as ligands for 99mTc.
Acta Pol Pharm 1994
PMID:Synthesis of new derivatives of 4-acylquinoxalin-2-ones with potential pharmacological activity. 787 16

The structures of HIV-1 capsid protein (CA, p24) isolated from mature virions and CA protein autoprocessed from a recombinant Gag-Pol precursor expressed in Escherichia coli were compared using circular dichroic (CD) spectral analysis. The spectra obtained for the intact recombinant and viral proteins were indistinguishable, indicating that the backbone configurations directed by the primary amino acid sequences of the proteins were similar or identical. The structure predictions derived from CD were, in general, inconsistent with a model proposing the eight-stranded beta barrel motif found in several RNA viruses. However, aspects of the model were supported by experiments that identified surface-exposed regions. Biochemical analysis indicated that the recombinant CA protein formed nonrandom higher-ordered structures in vitro. Under physiological conditions, the protein assembled into oligomers containing subunits in two packing arrangements. In one arrangement, the central region near Arg100 was exposed and susceptible to tryptic digestion at low enzyme concentrations (enzyme:substrate ratios = 1:5000 to 1:100). Also, in this arrangement, the proteins were susceptible to crosslinking by the bifunctional agent DTSSP. Proteins in the other arrangement were resistant to proteolysis at low enzyme concentrations. The central region of these resistant molecules was inaccessible to monospecific antibodies that recognized antigenic sites between residues 94 and 107 and these proteins were not crosslinked by DTSSP or EGS. Following incubation with trypsin, both the resistant molecules and the fragments derived from the susceptible proteins in the oligomer migrated as smaller complexes, suggesting that the regions digested by trypsin stabilized the oligomer unit. The results indicate that the central region of the HIV-1 CA protein plays a role in formation of higher-ordered structures. Moreover, the relative stability of the N- and C-terminal partial digestion fragments arising from cleavage at Arg100/Gly101 suggests that this exposed central region separates two structural domains of the protein.
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PMID:Spectral analysis and tryptic susceptibility as probes of HIV-1 capsid protein structure. 794 18

An adherent human cell line (293) was made susceptible for HIV-1 infection by transfer of a CD4 expression plasmid. These cells could be infected with HIV-1 and produced infectious virus up to a titer of 10(6) TCID50/ml releasing p24 protein up to 1 micrograms/ml. Since they can be efficiently transfected with reporter genes, these cells are a suitable model system to monitor biochemical events during productive infection of HIV-1 and can be used for antiviral drugs. Translational frameshifting determines the balance of the structural Gag versus the catalytic Pol proteins which is probably crucial for correct virus assembly. We have genetically engineered CD4 expressing 293 cells with a sensitive in vivo reporter system to monitor the extent of frameshifting in HIV-1-infected versus uninfected cells. During the time course of productive HIV-1 infection the low efficiency of ribosomal frameshifting is not altered.
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PMID:CD4 expressing human 293 cells as a tool for studies in HIV-1 replication: the efficiency of translational frameshifting is not altered by HIV-1 infection. 797 34

Serum soluble interleukin 2 receptor (sIL-2R) concentration and the percentage of lymphocytes presenting this receptor (CD25+) were investigated in 28 asymptomatic HIV carriers or patients with lymphadenopathy only and in 15 AIDS patients. The levels of sIL-2R were found to be higher in AIDS patients (mean 1060 U/ml) than in persons during the initial stages of infection (mean 750 U/ml) or controls (mean 470 U/ml). No significant differences in the quantity of CD25+ lymphocytes between these groups were observed, with the means of 1.0; 1.3 and 1.1, respectively. However, a decrease in percentage of these cells were found in patients with advanced HIV infection. Since sIL-2R is regarded as a marker of immune system activation its detection could be helpful in the assessment of the immune status impairment in HIV infected patients.
Pol Arch Med Wewn 1994 Mar
PMID:[Occurrence of free receptor for interleukin 2 in serum and quantitative determinations of CD25+ in patients infected with HIV]. 802 27

Human immunodeficiency virus type 1 (HIV-1) Env-, Gag-, Pol-, Nef-, and Tat-specific cytotoxic T-lymphocyte (CTL) activities were quantitated temporally in five patients with symptomatic primary HIV-1 infection. A dominant CD8(+)-mediated, major histocompatibility complex class I-restricted CTL response to the HIV-1 envelope glycoprotein, gp160, was noted in four of the five patients studied. The level of HIV-1-specific CTL activity in the five patients paralleled the efficiency of control of primary viremia. Patients who mounted strong gp160-specific CTL responses showed rapid reduction of acute plasma viremia and antigenemia, while in contrast, primary viremia and antigenemia were poorly controlled in patients in whom virus-specific CTL activity was low or undetectable. These results suggest that HIV-1-specific CTL activity is a major component of the host immune response associated with the control of virus replication following primary HIV-1 infection and have important implications for the design of antiviral vaccines.
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PMID:Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. 805 91

Erythropoietin (EPO) is a glycoprotein produced primarily by the kidney in response to tissue hypoxia, and is the principal factor regulating red blood cell production. It stimulates erythroid precursors in the bone marrow to proliferate and mature into morphologically identifiable red blood cells. This hormone acts by binding to specific high-affinity receptor on erythroid precursors. Failure to produce adequate quantities of EPO leads to severe anemia, a situation most often encountered in patients with end stage renal disease. With the application of recombinant DNA technology, the gene for this hormone has been molecularly cloned, sequenced and expressed in a biologically active form in mammalian cells. The recombinant EPO has been demonstrated to correct anemia in patients with severe end stage renal disease and alleviate their transfusion requirements. It has also been studied for anemia associated with HIV infection/zidovudine therapy, in cancer, rheumatoid arthritis, and prematurity. In addition it has been studied as a facilitator of autologous blood predeposit in patients scheduled for elective surgery and as a perisurgical adjuvant to hasten hematologic recovery and possibly avoid the need for homologous transfusion after elective surgery. When administered with the current guidelines EPO appears to be safe drug with favorable risk/benefit ratio.
Acta Haematol Pol 1994
PMID:[Clinical applications of erythropoietin]. 806 96

The neuropathologic examination of symptomatic perinatal HIV infection was performed using a large group of cases from New York Medical Centers. Macroscopic evaluation demonstrated many cases with microencephaly and others with brain atrophy. Microscopically in a part of them, as far as in others without microencephaly/atrophy changes corresponding to HIV encephalitis were found, including multinucleated giant cells, microglial nodules and perivascular infiltrations. In other brains in which inflammatory changes were minimal, myelin lesions were also observed and the picture corresponded to the diagnosis of encephalopathy. In addition lesions of cortico-spinal tracts, mineralization within the basal ganglia and changes of vascular walls with secondary parenchymal lesions were found. Opportunistic infections and neoplastic changes were rare. The review demonstrated the picture of neuropathological changes in pediatric cases that died of AIDS.
Neurol Neurochir Pol
PMID:[Nervous system changes in infants with HIV virus. Neuropathological picture]. 808 64

Concentration of neopterin (NPT) was measured in 3-6 months intervals in the serum of HIV-infected drug users taking continuously intravenous drugs and those who stopped the habit (MONAR, ZOZ). After 6-12 months of observation the mean NPT concentration was higher in the active drug users what was statistically essential. The outcome of our study indicates that current state of the patient concerning taking of drugs must be taken under consideration when NPT concentration is assessed as marker of progression of HIV disease.
Pol Arch Med Wewn 1994 May
PMID:[Levels of neopterin in serum of narcotics abusers infected with human immunodeficiency virus (HIV)]. 808 13

Cytotoxic T lymphocytes may play a significant role in containing the spread of HIV in infected individuals. Although HIV-infection is associated with immune suppression, a vigorous T lymphocyte response has been detected in infected adults. HIV can be transmitted from mother to child, either during pregnancy, when differentiation of the T lymphoid compartment is ongoing, or at birth when the neonate immune system is partially competent. The shorter asymptomatic period of pediatric infection could be related to differences in the host immune control of viral replication. HIV-specific cell-mediated cytotoxicity (CMC) from fresh and in vitro stimulated PBMC of HIV-infected children was measured. CD8+CD3+ T lymphocytes were found to be the major effector population. The vast majority of children examined had detectable HIV-specific CMC. A cross-sectional analysis of CMC responses as a function of clinical status revealed that 71% of asymptomatic children (CDC stage P1) recognized the Env protein, 14% the Gag protein, but none of them recognized the Pol protein. Cytolytic activities directed against these three proteins were detected in two thirds of paucisymptomatic children (P2A). In contrast, symptomatic children (P2B-F) did not show cytolytic activities toward the Gag and Pol proteins, and only 20% recognized the Env protein. In contrast in vitro generated secondary CTL were consistently detected at all stages of disease, even in children with low CD4+ cells counts.
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PMID:Detection of HIV-specific cell-mediated cytotoxicity in the peripheral blood from infected children. 809 52


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