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

Viral genes capable of inducing vascular tumors in the skin of transgenic mice are the tat gene of HIV-1 and polyoma virus' middle T antigen gene. Instead of vascular tumors, the tat gene of HTLV-I causes thymic atrophy and mesenchymal tumors in transgenic mice. No proof exists that any of these genes contribute to the induction of KS but HIV-1 tat is a strong suspect. The gene product K-FGF of the oncogene K-fgf/hst (int) uses bFGF receptors, is homologous with bFGF and acts as a mitogen for fibroblasts, endothelial cells and melanocytes. The overexpression of the K-fgf gene in KS is not proven unequivocally; some doubts exist suggesting the activation of this gene during the laboratory procedure of transfection with KS cell heavy DNA. Growth factor(s) not well identified (IL-6?) are released from HTLV-I- or II, or HIV-1- or 2-infected T4 lymphocytes and in particular from HIV-1-infected macrophages. This growth factor(s) promote(s) the continuous proliferation of endothelial cells and KS cells. AIDS-KS cells release other growth factors identical with or closely related to basic FGF, a major inducer of angioneogenesis. In addition, acidic FGF, IL-1 alpha and -beta, GM-CSF, PDGF-B and TGF-beta are released from AIDS-KS cells. The release of GM-CSF is induced by IL-1. GM-CSF promotes granulocytic, monocytic and endothelial cell proliferation. TGF-beta is known to suppress lymphocyte-mediated cytotoxicity and may act as a local immunosuppressive factor together with interferon inactivators. We theorize that when TGF-beta production ceases, TNF-beta (lymphotoxin) production switches on leading to programmed cell death (apoptosis) of KS cells resulting in regression of these lesions. The newly discovered angiogenesis factors VEGF/VPF may emerge as protooncogene-oncogene products analogous to PDGF and c-sis activation. AIDS-KS heavy DNA transfects NIH3T3 cells. NIH3T3 cells carrying this gene induced angiosarcomas when implanted in mice. An as yet unidentified large virus (mycoplasma?) was derived from these cells during passages in culture. No causative relationship between this agent and Kaposi sarcoma has as yet been established. Even though IFN-alpha exerts antiretroviral effects in AIDS, we propose that the therapeutic effect of IFN-alpha in AIDS-KS is based on antiangiogenesis activity by suppressing protooncogenes-oncogenes of the FGF family.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Kaposi's sarcoma: its 'oncogenes' and growth factors. 165 29

Patients with advanced human immunodeficiency virus type 1 (HIV-1) infection who had p24 antigen despite treatment with zidovudine (AZT) for 4-28 months received 3 x 10(6) IU of native interferon-alpha (IFN-alpha) daily for 3 months. Infectious HIV was detected in the plasma of all patients, in most cases at high titers, before IFN-alpha treatment. There was no correlation between HIV titers and p24 antigen levels. Antiviral activity, as measured by significantly decreased levels of infectious virus or p24 antigen, was observed in six of eight completely treated but in only one of nine incompletely treated patients. After termination of IFN-alpha treatment, there was a significant rise of p24 antigen levels. During IFN treatment, absolute CD4 cell counts showed a tendency toward an increased rate of decline. The side effects were unexpectedly severe. Despite its anti-HIV effect in vivo, IFN-alpha in the dosages used does not seem to be a viable additional treatment for severely immunodeficient patients in ongoing AZT therapy.
 ...
PMID:Combined treatment of symptomatic human immunodeficiency virus type 1 infection with native interferon-alpha and zidovudine. 167 1

Hematopoietic disturbances are common in patients with HIV-1 infection. Recent studies on immune activation markers such as neopterin demonstrate that HIV-1 infection is associated with chronic immune activation. We investigated a possible association between serum neopterin concentrations and blood cell counts (CD4+ T cells, white blood cells, platelets, red blood cells) and hemoglobin and hematocrit in 94 HIV-1-seropositive individuals [52 Walter Reed (WR) stage 1, 31 WR2, one WR5, and 10 WR6]. There were significant negative correlations between neopterin concentrations and CD4+ T cells, hemoglobin, hematocrit and platelets. These correlations were also significant if either only WR1 and WR2 patients or the entire set of data were considered for calculations. Thus, hematological abnormalities are associated with chronic immune activation in patients with HIV-1 infection. Large amounts of neopterin are released by human macrophages on stimulation with interferon-gamma (IFN gamma), and tumor necrosis factor alpha (TNF alpha) further enhances the effect of IFN gamma. Therefore, our data suggest that activated immune cells and specific cytokines such as IFN gamma and TNF alpha are involved inhibiting hematopoiesis.
 ...
PMID:Negative correlation between blood cell counts and serum neopterin concentration in patients with HIV-1 infection. 167 19

1-[(2-Hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) has recently proved to be a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) in vitro. Combinations of HEPT and recombinant alpha interferon (IFN-alpha) synergistically inhibit the replication of HIV-1 in MT-4 cells at non-toxic concentrations. Synergistic inhibition of HIV-1 replication has also been observed in peripheral blood lymphocytes. These results indicate that the combination of HEPT with IFN-alpha should be further pursued in the treatment of retrovirus infections [i.e. acquired immune deficiency syndrome (AIDS)].
 ...
PMID:Synergistic inhibition of human immunodeficiency virus type 1 (HIV-1) replication in vitro by 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine (HEPT) and recombinant alpha interferon. 168 14

A number of in vivo and in vitro results suggest that interferons have an antiretroviral effect on HIV. To check this, 15 HIV-positive patients who had no full-blown AIDS, were treated with recombinant interferon alpha 2b (5 mill. IU s. c. three times a week) over a period of six months. Twelve to 16 weeks after the initiation of treatment, an increase in CD 4 lymphocytes (+16%), NK cells (+16%), lymphocytes stimulation by con A (+ 176%), neopterin (+66%), and beta-2-microglobulin (+19%) was observed. By the end of the study, all these parameters had slightly decreased again. In all patients with CD4 lymphocytes greater than 0.2 c/nl, we observed a decrease in p24 antigen levels, but in patients with CD4 lymphocytes less than 0.2 c/nl, an increase. It would thus seem that any antiretroviral effect of IFN (as shown by the p24 antigen parameter) is more pronounced in patients with superior immune parameters.
 ...
PMID:[Effect of alfa-2b interferon on prognostic parameters and clinical events in HIV positive patients in the LAS/ARC stage]. 168 13

HIV-1 infection of promonocytic U937 cells was used to examined induction of IFN-alpha/beta gene expression and to determine the inhibitory effects of IFN-alpha 2 and/or AZT on de novo HIV-1 infection, initiated either by coculture of virus-shedding U9-IIIB cells with uninfected cells or by incubation of U937 cells with virus-containing supernatants. Usually 21-28 days were required to transmit virus to greater than 90% of the cell culture. HIV-1 infection did not stimulate constitutive production of endogenous IFN-alpha 1/alpha 2 or IFN-beta genes, although induction of IFN RNA was observed following coinfection with the paramyxovirus Sendai. Exogenous rIFN-alpha 2 treatment decreased the intracellular accumulation of viral RNA 5- to 20-fold as determined by Northern blot analysis and the extracellular levels of HIV-1 as measured by p24 ELISA antigen capture. The effect was most dramatic at a time coincident with the rapid increase in virus spread through the cell culture (Days 10-18). During the fourth week of infection, HIV-1 multiplication was able to overcome the IFN-induced block in virus spread. AZT was not effective in limiting virus spread in the cocultivation experiments. When U937 cells were infected with virus-containing supernatants from U9-IIIB cells, IFN and AZT acted in combination to limit the number of infected cells and to inhibit intracellular accumulation of viral RNA. These experiments suggest that subtle differences in the mode of virus transmission in monocytic cells may alter the efficacy of combination antiretroviral therapy.
 ...
PMID:Inhibition of HIV-1 transmission by interferon and 3'-azido-3'-deoxythymidine during de novo infection of promonocytic cells. 169 54

The immunomodulatory drug isoprinosine has been found to delay the occurrence of opportunistic infections in HIV-infected individuals. To elucidate the mechanism of action, eight HIV-positive, healthy patients were treated with isoprinosine, 3 g/day for 28 days; six patients received no treatment but were examined in parallel, and two patients were withdrawn. All patients had blood collected just before the start as well as on days 14 and 28 of isoprinosine treatment. Isoprinosine significantly enhanced the lymphoproliferative response after stimulation with phytohaemagglutinin (PHA) and purified derivative of tuberculin (PPD), while isoprinosine had no effect on the following immune parameters: the expression of surface markers on blood mononuclear cells including CD2, CD3, CD4, CD8, CD14, CD19, CD20, CD25, leu-8, and HLA-DR. Furthermore isoprinosine did not influence the ability of interleukin 2 (IL-2) to stimulate the proliferation of lymphocytes or the natural killer (NK) cell activity either unstimulated or stimulated in vitro with alpha interferon (IFN-alpha), IL-2, or indomethacin. Neither did isoprinosine affect the in vitro production of (IL-1) alpha or beta, IL-2, IL-6, or tumour necrosis factor (TNF).
 ...
PMID:Effects of isoprinosine treatment of HIV-positive patients on blood mononuclear cell subsets, NK- and T-cell function, tumour necrosis factor, and interleukins 1, 2, and 6. 170 99

The role of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and LFA-1 in human immunodeficiency virus type 1 (HIV-1)-induced cell fusion was investigated in subclones of a T-cell leukemic cell line (CEM) with differing abilities to form syncytia. Addition of monoclonal antibodies 84H10 directed against ICAM-1 and MHM23 directed against the common beta subunit of LFA-1 (CD18) resulted in greater than 50% suppression of syncytia formation in cultures of these clones infected with cell-free virus. Two subclones, 2G5-144-84 and 2G5-1, were deficient in their ability to form syncytia and expressed reduced amounts of LFA-1 compared with the parental line. The expression of ICAM-1 but not LFA-1 was upregulated on the clones following treatment with interferon-gamma (IFN gamma); however, this did not overcome the delay in syncytia formation observed in these cells. The syncytia-positive subclones 1B11-39 and 17D-9 expressed high levels of LFA-1. Basal expression of ICAM-1 was upregulated on these cells by treatment with tumor necrosis factor-alpha (TNF alpha), which also accelerated and enhanced syncytia formation. However, anti-ICAM-1 and anti-LFA-1 (CD18) antibodies did not reverse the TNF alpha-induced enhancement of syncytia formation of HIV-1-infected clones 1B11-39 and 17D-9. Under conditions of low viral expression, adhesion molecules may contribute to syncytia formation if adequate levels of both receptor and ligand in the ICAM-1/LFA-1 complex are expressed.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Re-evaluation of the involvement of the adhesion molecules ICAM-1/LFA-1 in syncytia formation of HIV-1-infected subclones of a CEM T-cell leukemic line. 170 41

Interferon-alpha is an effective treatment for a subset of patients with AIDS-associated Kaposi's sarcoma. When given at high doses to patients who lack systemic signs, symptoms, and opportunistic infections associated with advanced HIV infection and who maintain some degree of cell-mediated immune function, tumor regression may be observed in a high proportion of patients. Although the addition of chemotherapy to IFN-alpha appears to confer no added benefits, the combination of IFN-alpha with zidovudine has induced high tumor response rates in preliminary studies, including responses in some patients considered unlikely to respond to IFN-alpha alone. IFN-alpha-induced tumor regression has also been associated with suppression of HIV, as measured by serum p24 antigen concentrations and peripheral blood virus cultures. Other biologic agents, including interferons beta and gamma, tumor necrosis factor, and IL-2, have also been tested, to a lesser extent, in patients with Kaposi's sarcoma. Although systemically administered IFN-beta and intralesional TNF injections have led to tumor regression in some cases, the role of these biologics has been incompletely defined. Additional studies of these agents in combination with nucleoside reverse transcriptase inhibitors such as zidovudine will be required to fully assess their role in the treatment of Kaposi's sarcoma and HIV infection. It can also be anticipated that newer biologic agents, which specifically inhibit the production or action of angiogenic factors believed to be involved in the genesis of Kaposi's sarcoma, will be studied in the near future.
 ...
PMID:Interferon and other biologic agents for the treatment of Kaposi's sarcoma. 170 60

To further document the role of interferons in the restriction of HIV1 replication in cells of the monocyte/macrophage lineage, the antiviral effects of alpha-interferon (IFN alpha) were studied in chronically HIV 1-infected promonocytic cells U937, in which IFN alpha was endogenously produced or to which recombinant IFN alpha was added. Protein analysis performed after immunoprecipitation of culture media revealed that the addition of anti-IFN alpha antibody led to an increase in the production of viral particles, whereas addition of IFN alpha caused its decrease in a dose-dependent manner, indicating that IFN alpha mainly affects viral assembly and virion release. However, the treatment of HIV 1-infected cells with IFN alpha did not cause an increase in the amount of intracellular viral proteins, suggesting that this cytokine might act on other steps in the viral life cycle. No decrease in the level of the 3 main types of viral RNA was observed by Northern blot analysis, indicating that proviral transcription was not restricted by IFN alpha. Furthermore, cotransfection experiments with TAR(trans-activation responsive)-element-containing expression plasmids demonstrated that viral replication appears to be restricted at either a post-transcriptional and/or a translational level. These experiments suggest that the double-stranded (ds) inverted repeat TAR sequence present in HIV1 leader RNA may inhibit viral protein synthesis by phosphorylating the dsRNA-activated protein kinase induced by IFN. These results provide an impetus for achieving antiretroviral therapy based on the constitutive expression of IFN in monocytes and macrophages.
 ...
PMID:Interferon-regulated viral replication in chronically HIV1-infected promonocytic U937 cells. 171 78


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