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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The accumulated knowledge about the organization and function of the human immune system contributes to a better understanding of the pathogenesis of most diverse disorders and is opening new avenues for therapeutic regimens. To gain further insight into the complex interactions within the components of the immune system, it has become increasingly necessary to develop rapid and simple methods to monitor the status of the immune system in patients. The determination of neopterin concentrations in human body fluids allows to investigate sensitively the cell-mediated immune status to be investigated with considerable sensitivity. In recent years it was shown that production and release of neopterin is inducible in human monocytes/macrophages by interferon gamma. Increased neopterin levels indicate endogenous formation of gamma interferon, and monitoring of neopterin levels therefore permits the activation status of the cell-mediated immune system to be examined. Neopterin concentrations in serum and in urine increase in parallel to the clinical course of infections with viruses, intracellular bacteria, and parasites. In patients with human immunodeficiency virus infection neopterin concentration in serum and urine is a significant predictor of disease progression, the statistical power being similar to CD4+ T-cell numbers. In patients with autoimmune disorders, neopterin levels correlate with the extent and the activity of the disease. Neopterin concentrations are also sensitive indicators of immunological complications in allograft recipients. In certain malignant diseases neopterin concentrations correlate with the stage of the disease and bear prognostic information. Results of neopterin measurements agree with the important role that the cellular immune system plays in these disorders.
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PMID:The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases. 148 21

We have employed a recombinant plasmid pBHIV-1 carrying the Long Terminal Repeat sequences (LTR) of the Human Immunodeficiency Virus (HIV-1) linked to the reporter chloramphenicol acetyl transferase (CAT) gene and to the aminoglycoside phosphotransferase (aph) gene as a selectable marker. We have introduced pBHIV-1 DNA in human breast cancer MCF-7 cells and obtained the MCF-7HIV-1 cell line, resistant to geneticin. We have studied the effect of hexamethylene-bisacetamide (HMBA), cis-platin, interferon-aB, dexamethasone and tamoxifen on the LTR regulated CAT activity in MCF-7HIV-1 cells. It was found that HMBA and cis-platin stimulated CAT activity, whereas interferon-aB, dexamethasone and tamoxifen had no significant effect.
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PMID:Hexamethylene bisacetamide and cis-platin stimulate the expression from the HIV-1 long terminal repeat sequence in human MCF-7 cells. 152 34

The effect on human immunodeficiency virus 1 (HIV-1) viral transcription and subsequent gene expression mediated by mixed purine-pyrimidine oligodeoxyribonucleotides (oligodeoxynucleotides) designed to form collinear DNA triplexes with purine-rich elements in the viral promoter was evaluated in intact mammalian cell lines (MT4 and U937). Oligonucleotides HIV31 (5'-GTTTTTGGGTGTTGTGGGTGTGTGTGGTTTG-3') and HIV38 (5'-TGGGTGGGGTGGGGTGGGGGGGTGTGGGGTGTGGGGTG-3') were designed to interact with the transcription initiation site (-16 to + 13) and nuclear factor Sp1 binding site (-81 to -44) of HIV-1, respectively. Oligonucleotides, synthesized with a 3' amine blocking group (5'-R-O-PO2-OCH (CHOH)-CH2-NH+3-3') to prevent degradation by cellular nucleases, were readily taken up by MT4 cells from the culture medium, achieving measured intranuclear concentrations higher than the medium in less than 2 h of incubation. The 3' amine modified oligonucleotides were recoverable from the cells after 24 h as greater than 90% intact material. Treatment of acutely infected MT4 cells with either HIV31 or HIV38 significantly inhibited viral-associated cytopathology and P24 antigen production (p less than 0.001). Additionally, inhibition of P24 antigen release, culture supernatant viral titer, and expression of the intact 9.2-kb HIV-1 mRNA was observed when the chronically infected promonocyte cell line, U937, was treated with 10 microM HIV38. Control oligonucleotides with similar base composition did not inhibit virus expression in either cell line. Furthermore, inhibition of viral expression was not due to alpha-interferon induction resulting from oligonucleotide treatment. Both HIV31 and HIV38 associate with their respective DNA target duplexes at micromolar concentrations, and a strong negative ellipticity near 210 nm, characteristic of DNA triplexes, was observed in the circular dichroism spectrum of either target-oligonucleotide complex. These observations suggest that oligonucleotides, designed to form nucleic acid triplexes with specific proviral target sequences, can selectively inhibit transcription of viral mRNA in intact cells and suppress accumulation of viral products.
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PMID:Inhibition of transcription of HIV-1 in infected human cells by oligodeoxynucleotides designed to form DNA triple helices. 154 43

We have developed a method for attenuating vaccinia virus recombinants by expressing a fusion protein of a lymphokine and an immunogen. Chimeric genes were constructed that coded for gamma interferon (IFN-gamma) and structural proteins of the human immunodeficiency virus type 1 (HIV-1). In this study, we describe the biological and immunological properties of vaccinia virus recombinants expressing chimeric genes of murine or human IFN-gamma with glycoprotein gp120, gag, and a fragment of gp41. All fusion proteins retained the antigenic characteristics of both IFN-gamma and HIV as shown by immunoblot analysis. However, the antiviral activity of IFN-gamma could be demonstrated only for the IFN-gamma-gag fusion protein. In contrast, the attenuating activity of IFN-gamma for nude mice was retained by all of the recombinants, albeit at various rates. Unlike the antiviral activity, the attenuating activity of IFN-gamma was not species specific. Implications for the development of attenuated live recombinant vaccines for AIDS are discussed.
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PMID:Vaccinia virus recombinants expressing chimeric proteins of human immunodeficiency virus and gamma interferon are attenuated for nude mice. 156 33

We have presented a case of HIV-associated thrombocytopenia successfully treated with low dose interferon alfa-2a. Increases in platelet levels were achieved within 1 week without hospitalization or surgery. Further, the patient had no systemic side effects from therapy. Zidovudine alone was ineffective in maintaining noncritical platelet counts. Interferon alfa-2a is a nonimmunosuppressive, nonsurgical therapy that can correct HIV-associated thrombocytopenia without requiring hospitalization.
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PMID:Correction of HIV-associated thrombocytopenia with low doses of interferon alfa. 158 12

As yet, the pathogenesis of Kaposi's sarcoma in the context of the acquired immunodeficiency syndrome (AIDS) is not completely understood; this is also true for the mechanisms of action of interferon-alpha against this tumour. The present review focuses on recent developments that may provide some further insight into these issues. These include the angiogenesis of the tumour and the possible role of growth factors, such as the HIV-transactivating (tat) gene product and interleukin-6, the possible meaning of immunomodulating activities of interferon-alpha, such as the rise in the number of CD4+ cells and the increase in beta 2-microglobulin serum concentrations in patients whose tumours respond to treatment, and the observed association between interferon's antiretroviral activity and tumour responses.
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PMID:AIDS-associated Kaposi's sarcoma and the mechanisms of interferon alpha's activity; a riddle within a puzzle. 158 54

Patients with classical European Kaposi's sarcoma were treated by intra- and peritumoral injections of human alpha leukocyte interferon (IFN) (12 cases) or, alternatively, with IFN and naturally synthesized IL-2 (8 cases). All the patients were HIV negative with tumors which had been present for at least six months. In each patient, one tumor received 1 ml (50,000 IU) IFN alone or alternatively associated with 1 ml IL-2 twice a week for 4-6 weeks; another nodule situated 10-12 cm away was considered as a control and remained uninjected. The clinical follow-up revealed that, in the same patient in the same anatomical area, the treated nodule was cured in all the investigated cases; the untreated one was not. These data strongly suggest that IFN is the factor responsible for the involution and final cure of these Kaposi tumors treated by perilesional inoculations. Association with IL-2 (and certainly also other interleukins) increases the beneficial clinical activation of the tumor involution. Histological examination showed that important histopathological changes occur in the treated nodules: complete disappearance of the Kaposi's aspect, fibrosclerous modifications progressively replacing the fibroblasts characteristic of Kaposi's sarcoma, abundant infiltrations of leukocytes, especially lymphocytes and necrotic patches, often with hemorrhagic centers. IL-2 association seems to especially induce this last type of histological phenomenon.
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PMID:Intralesional human leukocyte interferon treatment alone or associated with IL-2 in non-AIDS related Kaposi's sarcoma. 159 18

Several laboratories have shown that AZT-resistant variants of HIV-1 can be isolated from patients who have received prolonged therapy with this drug. Our laboratory has now been able to generate HIV-1 variants resistant to both AZT and ddI, in tissue culture, by using step-wise increases in the concentrations of each of these compounds over a 10-week period. This work has been performed by culturing wild-type clinical strains of HIV-1 as well as the HIV-3b laboratory strain of this virus under such conditions. The ID50 values obtained for the resistant viruses thus generated vary between 50-100 times above those of the parental wild-type strains in each case. Furthermore, we have identified several new mutation sites in the HIV-1 pol gene that are responsible for the observed resistance to AZT and ddI. We have not succeeded, however, in generating drug-resistant strains of HIV-1, under conditions in which several compounds or anti-viral agents were simultaneously present during the in vitro selection process. Combinations of drugs which failed to yield drug-resistant variants included AZT plus ddI, AZT plus alpha-interferon, and ddI plus alpha-interferon. These findings indicate that HIV drug resistance is less likely to occur in tissue culture when combinations of drugs are used, and provide rationale for the development of combination clinical trials for treatment of HIV-associated disease.
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PMID:Generation of nucleoside-resistant variants of HIV-1 by in vitro selection in the presence of AZT or DDI but no by combinations. 160 23

The underlying degree of immune suppression is an important consideration in the selection of treatment for AIDS-KS. In general, subjects with CD4+ T lymphocytes greater than 500/mm3 require only local therapy unless there is some specific disability caused by the AIDS-KS lesions. Subjects with CD4+ T lymphocytes between 200 and 500/mm3 may respond to recombinant interferon. This therapy is effective in controlling AIDS-KS, can be combined with zidovudine, and has anti-HIV properties. If interferon-alpha with zidovudine is clinically ineffective, systemic chemotherapy may then be required. Subjects with AIDS-KS and CD4+ T lymphocytes less than 200/mm3 should receive PCP prophylaxis, may require systemic chemotherapy, and should be maintained on antiretroviral therapy. Therapy of AIDS-KS is not curative, and a treatment plan of the underlying immune deficiency is essential for planning and implementing rational therapy. AIDS-KS is rarely life threatening but often cosmetically and functionally disabling. Treatment plans remain focused on palliative goals and include reduction of extremity or facial edema, elimination of painful lesions, relief of gastrointestinal disturbances induced by AIDS-KS lesions (including symptoms of outlet obstruction, diarrhea, and rarely blood loss), and reduction of the pulmonary burden of AIDS-KS to improve oxygenation and relieve obstructive pneumonias.
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PMID:AIDS-associated Kaposi's sarcoma. 160 60

The effect of AZT on serum HIV p24 antigen and endogenous serum alpha interferon levels was studied in AIDS and ARC patients. Following administration of AZT there was a rapid decline in the serum levels of both HIV p24 antigen and alpha interferon. When AZT treatment was interrupted, the levels of both HIV p24 antigen and of interferon rapidly increased. These findings suggest that HIV or some other AZT sensitive microorganism is the inducer of interferon which is characteristically found in the serum of AIDS and symptomatic HIV infected patients. They also suggest that the rapid decline in interferon levels may underlie some of the symptomatic benefit that follows administration of AZT.
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PMID:Modulation of alpha interferon levels by AZT treatment in HIV-seropositive patients. 162 38


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