Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Interferon alpha was one of the first drugs tested for the treatment of patients with AIDS-related Kaposi's sarcoma based on its known antiviral properties and its abilities to modulate immune function and inhibit neoplastic cell proliferation. In vitro studies demonstrated defective production of interferon by blood cells of HIV-infected individuals and suppression of HIV replication by interferons alpha and beta. Interferons have also been shown to inhibit angiogenesis induced by tumour cells or by allogeneic lymphocytes in mice. The efficacy of recombinant interferon alpha for the treatment of AIDS-related Kaposi's sarcoma has been well documented with antitumour responses seen in approximately 30% of all patients treated in single agent efficacy trials with doses of at least 20 MU/m2. In several uncontrolled studies, response of Kaposi's sarcoma to treatment with interferon alpha was associated with longer survival and few opportunistic infections. Tumour response appears to be correlated with an absence of opportunistic infection and with CD4 cell numbers. Several studies using high interferon alpha doses have demonstrated decreases in serum HIV P24 core antigens which appear to be confined to patients whose tumours also regressed. The use of interferon alpha in HIV-infected patients with or without Kaposi's sarcoma have demonstrated in vivo anti-HIV activity. Studies have recently evaluated the tolerance and therapeutic potential of interferon alpha in combination with the reverse transcriptase inhibitor, zidovudine (azidothymidine AZT). Synergistic suppression of HIV replication in vitro has been demonstrated with the combination of interferon alpha and zidovudine. The description of HIV isolates with reduced sensitivity to zidovudine following prolonged treatment, and the finding that interferon alpha, but not zidovudine, prevents HIV expression in chronically infected cell lines, suggests that this combination might be useful in long-term treatment of patients with HIV infection.
...
PMID:Interferon alpha in the treatment of AIDS-related Kaposi's sarcoma. 193 14

The results of HIV virus isolation from patient A. T., resident of Central Africa, are discussed, in whom Kaposi sarcoma was diagnosed clinically and histologically, and immunological examinations revealed the acquired immunodeficiency syndrome (AIDS). Cocultivation of the peripheral blood leukocytes of the patient with normal donor leukocytes yielded a leukocyte culture in which HIV virus expression was demonstrated. The HIV antigen was detected in the ultracentrifugate of the cultures by means of indirect enzyme-immunoassay using sera to the virus from the standard kits of Organon (Netherlands) and Abbot (USA). HIV antigen was also detected on the surface of lymphocytes in the culture by indirect immunofluorescence using the same sera. Besides, reverse transcriptase activity was demonstrated in ultracentrifugates of the culture fluid by exogenous reverse transcription test using poly(zA)-oligo(dT) matrix.
...
PMID:[Detection of the human immunodeficiency virus in a lymphocyte culture from a patient from Central Africa with acquired immunodeficiency syndrome and Kaposi's sarcoma]. 245 89

Published reports indicate that HIV is recovered from BAL fluid of patients with AIDS who have LIP but not with other AIDS-related pulmonary disease. Our experience has been different. Ten BAL specimens from nine patients with AIDS were cultured directly in peripheral blood mononuclear cells, and all ten cultures were positive for HIV as indicated by examination of the culture supernatant by reverse transcriptase assay and enzyme immunoassay for HIV antigen. Five of the specimens were also positive for Pneumocystis carinii, and other pulmonary diagnoses included histoplasmosis, lymphoma, Kaposi's sarcoma, and aspiration pneumonia. Five additional BAL specimens were cultured after freezing at -70 degrees C, but only two were culture-positive for HIV (p = 0.022; FET). This study indicates that HIV can be recovered from the BAL fluid in most patients with AIDS, unrelated to the type of pulmonary disease. In contrast to cultures, HIV antigen was detected in the BAL fluid of only one patient, and that patient had LIP with noncaseating granulomas. Therefore, HIV culture is not useful in the diagnosis of LIP, but HIV antigen detection should be studied further. All BAL fluids should be considered potentially infectious.
...
PMID:Recovery of human immunodeficiency virus and detection of p24 antigen in bronchoalveolar lavage fluid from adult patients with AIDS. 250 Mar 12

Zidovudine (Retrovir) is the only drug found to be useful for managing human immunodeficiency virus (HIV) infection in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. The drug is virostatic, ie, it prevents replication of HIV by inhibiting the enzyme reverse transcriptase. Zidovudine is well tolerated and provides short-term benefits by improving the quality of life and extending survival time. It is expensive and can be toxic, however, so its use requires close supervision. Zidovudine at present is approved only for patients with documented Pneumocystis carinii pneumonia or with a CD4 count below 200/mm3. Other probable indications include HIV wasting syndrome, HIV dementia complex, oral candidiasis, Kaposi's sarcoma, the presence of early markers of HIV infection, and HIV-related symptomatic thrombocytopenia. A stepwise approach to initiating zidovudine therapy should include detailed counseling and close surveillance.
...
PMID:Zidovudine for treating AIDS. What physicians need to know. 266 55

The human immunodeficiency virus is a member of the lentivirus subfamily of the retrovirus family. Retroviruses are RNA viruses which code for an RNA-dependent DNA polymerase (reverse transcriptase), which transcribes the RNA genome into a DNA provirus which, on integration with the host DNA, directs the synthesis of new virions. The RNA genome consists of a gag gene, which codes for the viral core proteins, a pol gene, which codes for the reverse transcriptase, an env gene, which codes for the glycoproteins of the viral envelope, and several genes (tat, rev, vif, vpr, and nef), that code for regulatory proteins. At each end of the genome are long terminal repeats, that contain regulatory elements for transcription. There are 3 subfamilies of Retroviridae (Oncovirinae, Spumavirinae, and Lentiverinae). The Lentiverinae ("slow viruses") include the bovine immunodeficiency virus (BIV), the feline immunodeficiency virus (FIV), the human immunodeficiency viruses (HIV), and the simian immunodeficiency viruses (SIV). SIV has been isolated from macaques (mac), African green monkeys (agm), sooty mangabeys (sm), and mandrills (mnd). Only SIVmac causes an AIDS-like disease in its natural host, but it is genetically closer to HIV-2 than to HIV-1. SIVsm causes an AIDS-like disease in macaques, but not in the sooty mangabey. Monkeys infected with SIV develop diarrhea, wasting, decrease in T4 lymphocytes, lymphadenopathy, development of giant cells, and encephalitis, as well as opportunistic infections. Kaposi's sarcoma, however, has not been found in SIV-infected primates. Virus is recovered from peripheral blood mononuclear cells and the brain. SIV models are useful for understanding the natural history of primate lentiviruses, for defining the pathogenesis of AIDS, and for developing vaccines. The ideal model would be one in which HIV causes AIDS, but so far only chimpanzees and gibbons have successfully been infected with HIV-1, and although virus, is recovered from peripheral blood mononuclear cells of chimpanzees within 2 weeks of infection, and 2 animals have lost antibodies to the p24 protein, none has so far developed clinical AIDS. Attempts to develop vaccines to immunize chimpanzees are continuing. Nonprimate lentiviruses include the visna virus, the feline immunodeficiency virus, and the bovine immunodeficiency virus. The visna virus infects fibroblasts by fusion of the viral envelope with the plasma membrane of the fibroblast; it infects macrophages by endocytosis. Infected macrophages regulate the production and dissemination of viral particles. The feline immunodeficiency virus infects T-lymphocytes of cats and produces oral, gastrointestinal and respiratory pathology as well as lymphadenopathy and opportunistic infections. Bovine immunodeficiency-like virus causes a generalized lymphadenopathy similar to that seen in AIDS-related complex.
...
PMID:Animal models for HIV infection and AIDS: memorandum from a WHO meeting. 285 Jan 18

Serological evidence for HTLV-I infection in the South African population has now been confirmed by the isolation of the virus from the peripheral blood lymphocytes of an adult Tsonga male. The subject was an indigenous black man from the south-eastern Transvaal who had suffered from Kaposi's sarcoma for a decade and in whom serum antibodies against HTLV-I were demonstrated. T-lymphocyte cell lines were established from his peripheral blood lymphocytes and shown to be productively infected with HTLV-I as evidenced by: the characteristic cell morphology; the typical viral morphogenesis on ultra-thin section electron microscopy; the viral genome in DNA extracted from the cell lines; characteristic reverse transcriptase activity and viral specific proteins in the cell culture supernatant fluids. Spread of infection occurs through sexual intercourse, from mother to child, and by blood transfusion. Donated blood should be screened to contain the spread of HTLV-I infection.
...
PMID:Isolation of human T-lymphotropic virus type I (HTLV-I) from a black South African with Kaposi's sarcoma. 289 64

Human retroviruses, or RNA viruses, including the 2 HIV agents associated with AIDS, and the 2 HTLV agents causing leukemia, are described from the viewpoint of history, detection, serology, transformation mechanism, disease pathophysiology, genetic function, associated disease, and related viruses. Both HTLV and HIV infect the human T-lymphocytes, also known as CD4 or helper cells. Both can now be grown in culture, and their genomes are well characterized. HTLV, an acronym for human T-lymphotropic leukemia virus, causes the fulminating adult T-cell leukemia-lymphoma (ATLL), 1st described in 1977. It is prevalent in population clusters, notably in the Caribbean and in southwestern Japan, and is spread by sexual, blood and perinatal routes, as is HIV. It is thought to promote transformation of target cells by release of growth promoting, soluble factor, perhaps a product of the viral "tat" gene. Besides leukemia, HTLV-1 causes a myelopathy sometimes called tropical spastic paraparesis. HIV, formerly known as HTLV-III, causes depletion of the T-cells, and also infects the brain and nervous system. IT has also been isolated from semen, cervical secretions, saliva, monocytes, milk, endothelial cells, tears and cornea. HIV has 5 more genes than HTLV, which regulate transcription, mRNA processing and virus maturation. Parts of the HIV genome are highly heterogeneous, and mutate rapidly, notable sections of the envelope protein. Thus, HIV has 2 main subtypes, but others are known and probably exist. Approaches toward developing AIDS therapeutic agents as of 1987 are outlined: an effective drug should cross the blood-brain barrier. Several anti-viral drugs that block the enzyme reverse transcriptase area being investigated. Possible mechanisms for growth of Kaposi's sarcoma, activation of herpes type viruses, and animal viruses related to HTLV and HIV are discussed.
...
PMID:Retroviruses: new viral infections in man. 289 67

Suramin sodium is a reverse transcriptase inhibitor with in vitro activity against the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). Ninety-eight patients with AIDS manifest as opportunistic infections (n = 38), AIDS with Kaposi's sarcoma (n = 38), AIDS-related complex (n = 20), or AIDS-associated non-Hodgkin's lymphoma (NHL) (n = 2) were treated with suramin sodium at 0.5, 1.0, or 1.5 g/wk for six weeks followed by maintenance therapy with 0.5 or 1.0 g/wk. Of 72 patients who were HIV culture positive before therapy and were assessable for subsequent HIV culture 40% became culture negative during treatment, with no apparent correlation between virus recovery and serum suramin concentration. No immunologic improvement was noted. One complete clinical remission was noted in a patient with Kaposi's sarcoma and stage IV NHL. Seven minor clinical responses were also noted. Toxic reactions were generally reversible, and included fever (78%), rash (48%), malaise (43%), nausea (34%), neurologic symptoms (33%), and vomiting (20%). Suramin-induced neutropenia was noted in 26%, thrombocytopenia in 12%, a serum creatinine level of 180 mumol/L or higher (greater than or equal to 2.1 mg/dL) in 12%, liver dysfunction in 14%, and clinical and/or laboratory evidence of adrenal insufficiency in 23%. Sixteen patients died while receiving suramin or within three weeks of discontinuation of drug therapy due to infection (n = 6), hepatic failure (n = 3), pulmonary Kaposi's sarcoma (n = 2), AIDS encephalitis (n = 2), AIDS-associated NHL (n = 1), iatrogenic hemo-pneumothorax (n = 1), or pulmonary disease of uncertain etiology. Suramin as currently administered cannot be recommended as effective therapy for AIDS.
...
PMID:Suramin therapy in AIDS and related disorders. Report of the US Suramin Working Group. 365 Mar 39

Mounting experimental evidence suggests that the TAT protein, released from human immunodeficiency virus-1 (HIV-1)-infected inflammatory cells, may genetically reprogram targeted cells within a localized environment to develop highly vascularized tumors of mesenchymal origin. The fibroblast growth factor (FGF) family of polypeptides has gained general acceptance as initiators of angiogenesis and functions as potent mitogens for mesoderm-derived cells. To evaluate a potential biological relationship between TAT and acidic FGF (FGF-1), primary murine embryonic fibroblasts either were transfected with the viral transactivator or were transduced (retrovirally mediated) with a secreted, chimeric form of the human polypeptide growth factor, human stomach tumor/Kaposi's sarcoma (hst/KS)FGF-1. Reverse transcriptase-polymerase chain reaction, Western blotting, in situ immunohistochemical, heparin affinity, DNA synthesis, and transient transfection techniques were used to confirm expression, localization, and functionality of the transgenes. Both transfected and transduced cells constitutively expressing either TAT or (hst/KS)FGF-1 adopted a transformed phenotype, maintained aggressive growth behavior, and demonstrated both induction of FGF-specific phosphotyrosyl proteins and nuclear association of FGF-1 and FGF-1 receptor. Increased levels of endogenous, murine FGF-1 mRNA (reverse transcriptase-polymerase chain reaction) and protein (immunoblot analysis) were apparent in both (hst/KS)FGF-1- and TAT-transformed cells. Medium conditioned by (hst/KS)FGF-1-transduced cells contained steady-state levels of biologically active FGF-1 which exhibited a representative molecular weight. Limited sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of the conditioned medium from TAT-transformed cells demonstrated the appearance of FGF-1 as latent, high molecular weight complexes requiring reducing agents to activate full biological activity. Collectively, these results suggest that TAT induces the expression and secretion of FGF-1, which may be potentially relevant to the pathophysiological development of AIDS-Kaposi's sarcoma.
...
PMID:The HIV-1 TAT protein induces the expression and extracellular appearance of acidic fibroblast growth factor. 754 39


1 2 3 4 5 Next >>

---