Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

3'-Azido-3'-deoxythymidine (AZT) is HIV-inhibitory in human macrophages, which is surprising in view of the low AZT phosphorylation reported in macrophage extracts. To elucidate the mechanism of AZT activation, we studied AZT anabolism as well as catabolism in human lymphocytes and macrophages, and compared it to that of thymidine. Thymidine kinase (TK)-specific activity in mitogen-stimulated lymphocytes was 15 times higher than in macrophages. However, the TK activity per cell was only 1.3 times higher, because of the large macrophage cell volume. Total cellular TK activity, but not specific activity, matched the level of intracellular AZT anabolism. The substrate specificity of TK in macrophages strongly suggests that mitochondrial TK2 was the enzyme phosphorylating thymidine and AZT in these cells, whereas it was cytosolic TK1 in stimulated lymphocytes. In vivo thymidine catabolism was extensive, forming thymine and dihydrothymine. In macrophages more than 95% of the added thymidine (0.5 microM) was degraded within 60 min. AZT, in contrast, was not catabolized, which explains the high AZT nucleotide accumulation, a process opposed only by AZTMP excretion. The lack of catabolism together with phosphorylation by TK2 clarifies how AZT can inhibit human immunodeficiency virus in macrophages. The fact that TK2 and not TK1 phosphorylates AZT in macrophages should have important implications for combination chemotherapy.
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PMID:Thymidine and 3'-azido-3'-deoxythymidine metabolism in human peripheral blood lymphocytes and monocyte-derived macrophages. A study of both anabolic and catabolic pathways. 159 39

WHO statistics indicated that as of October 1, 1991 there were 418,403 acquired immunodeficiency syndrome (AIDS) patients in the world, and an estimated 5-10 million persons infected with the human immunodeficiency virus (HIV) were at risk of developing AIDS. 50% of AIDS victims have died. It has been reported that after 1 year of clinical use HIV could develop resistance to AZT (azidothymidine), the only effective drug used worlwide and recommended for clinical use by the US government. AIDS has also been treated by acupuncture and moxibustion which recent experiments have associated with improving immune function and enhancing resistance to disease. The American scientists Smith and Naomi Rabinowitz used acupuncture and moxibustion in the clinical treatment of AIDS from 1982 to 1988 when they treated 350 patients with AIDS and AIDS related complex. 1 advanced case with Kaposi's sarcoma and signs of hemorrhage was significantly improved after treatment. Traditional Chinese medicine (TCM) has been used successfully in treating cholera, syphilis, epidemic encephalitis, influenza, and hepatitis with a great variety of clinical treatment measures and experiences. In recent years the treatment of AIDS by TCM using herbs and their extracts has been increasing. Dr. Yu of Santa Barbara, California, Hospital, in cooperation with Dr. Chen of China, successfully treated on AIDS patient with Chinese herbal medicine. The patient was still living and well more than 2 years later when another 24 cases which were not treated with TCM died during the same period. In China there are no special laboratories dealing with the prevention and treatment of AIDS, although scientific HIV research could benefit from such activities. On the other hand, foreign scientists and Chinese abroad have accomplished a significant amount of relevant research.
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PMID:Recent development of studies on traditional Chinese medicine in prophylaxis and treatment of AIDS. 159 94

A series of bicyclams have been shown to be potent and selective inhibitors of human immunodeficiency virus (HIV). The compounds are inhibitory to the replication of various HIV-1 and HIV-2 strains in various human T-cell systems, including peripheral blood lymphocytes, at 0.14-1.4 microM, without being toxic to the host cells at 2.2 mM. The bicyclam JM2763 is active against 3'-azido-3'-deoxythymidine (zidovudine; AZT)-resistant HIV-1 strains and acts additively with AZT. Mechanism of action studies revealed that the bicyclams (i.e., JM2763) interact with an early event of the retrovirus replicative cycle, which could be tentatively identified as a viral uncoating event.
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PMID:Potent and selective inhibition of human immunodeficiency virus (HIV)-1 and HIV-2 replication by a class of bicyclams interacting with a viral uncoating event. 160 36

Duration of the AIDS-free period after HIV-infection and survival time vary to a wide extent. About 50 percent of the patients develop AIDS within 10 years. The most important prognostic factor is the CD4-lymphocyte count. The risk of AIDS increases significantly after CD4-lymphocyte counts drop below 400/microliters. Another prognostic factor is age. In older patients disease progresses more rapidly. AIDS often is preceded by an AIDS-Related-Complex characterized for example by Oral Candidiasis, Hairy Leukoplakia or Zoster of more than one dermatome. AIDS mostly develops 1/2 to 1 year after AIDS-Related-Complex. After AIDS is diagnosed the median survival time is not longer than 1 1/2 years. Single patients live much longer. Prognosis is influenced by the disease defining AIDS. Kaposi's Sarcoma often occurs early in the course of immunodeficiency and median survival is longer than after other opportunistic diseases. Survival also is longer after Pneumocystis Carinii Pneumonia since it is well treatable. A very short survival has been noticed after Non-Hodgkin-Lymphoma. During the last few years survival after HIV-infection and AIDS has been prolonged a little by sufficient prophylaxis of Pneumocystis Carinii Pneumonia which is the most frequent opportunistic disease, by antiretroviral treatment with Zidovudine and by increase of knowledge which makes early diagnosis and treatment of opportunistic diseases possible.
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PMID:[Survival in HIV infection and AIDS]. 162 24

The Michigan Medicaid Program payment records generated in the period 1985-89 by 783 persons were analyzed for services related to human immunodeficiency virus (HIV) infection. Other data from death records and the Michigan AIDS Surveillance Registry were available for a subset of those persons. The average monthly payment in 1989 dollars for HIV-related services was $1,302.57. Services determined to be unrelated to HIV infection accounted for 12.5 percent of the total amount for health care received and another 2.5 percent was questionable. The average monthly expenditure for men was roughly twice that for women. The discrepancy did not exist among persons identified in the AIDS Surveillance Registry. Sex differences ceased to exist when Medicaid eligibility (disability versus Aid to Families with Dependent Children) was controlled for by analysis of variance. There were no significant differences between payments to those infected through male-to-male sexual contact and those infected through intravenous drug use. Payments for HIV treatments rose with age to about 40 years, and declined slightly among older adults. The sharpest rise was for those ages 19-25 years and 26-35 years. Large sex differences existed among those who received zidovudine (AZT), 61.4 percent of the men and 19.1 percent of the women. Controlling for Medicaid eligibility moderated those differences, but they remained statistically significant. Differences in zidovudine usage were not found between men and women in the subset identified in the AIDS Surveillance Registry nor among persons infected through male-to-male sexual contact and intravenous drug use.
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PMID:HIV infection treatment costs under Medicaid in Michigan. 164 44

We used a viral endpoint dilution assay to show changes in the proportion of zidovudine (azidothymidine; AZT)-resistant viruses within a heterogeneous mixture of human immunodeficiency virus type 1 (HIV-1) quasispecies isolated from patients on long-term AZT therapy. Several HIV-1 isolates, which could replicate in 10 microM AZT, were susceptible to both 2',3'-dideoxycytidine and a novel cytosine analog BCH-189, in which a sulfur atom replaces the 3' carbon of the pentose ring. In certain instances, cross-resistance was seen with 3'-didehydro-2',3'-dideoxythymidine. Although most strains of AZT-resistant HIV-1 displayed reduced susceptibility to 3'-azido-2',3'-dideoxyuridine, two strains were identified for which this was not the case.
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PMID:Biological comparison of wild-type and zidovudine-resistant isolates of human immunodeficiency virus type 1 from the same subjects: susceptibility and resistance to other drugs. 164 76

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.
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PMID:Combined treatment of symptomatic human immunodeficiency virus type 1 infection with native interferon-alpha and zidovudine. 167 1

We did a cost-effectiveness analysis of zidovudine therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection. The incremental direct medical costs of zidovudine therapy were determined, and data on the effects of therapy were derived from the report of the Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group Protocol 019. Zidovudine therapy has an annual incremental cost of $2653 per person. The cost per year of life saved ranges between $6553 and $70 526, depending on which epidemiologic model of potential long-term zidovudine effect is used (in sensitivity analyses, the cost per year of life saved ranges between $2649 and $250 546). Although expensive, zidovudine therapy has the potential to yield a substantial survival benefit to patients. The cost effectiveness of zidovudine therapy compares favorably with that of other common medical therapies.
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PMID:Cost effectiveness of low-dose zidovudine therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection. 190 49

The human immunodeficiency virus (HIV) may be responsible for several types of vasculitis: leucocytoclastic vasculitis, granulomatous angiitis, angiitis associated with lymphoproliferative syndromes or necrotizing vasculitis including periarteritis nodosa (PAN). We report a case of PAN in a 62-year old HIV1-positive woman. The patient had no co-occurrent hepatitis B virus infection and was negative for antinuclear antibodies. She presented with sicca syndrome, necrotic purpura, myalgias and polyneuropathy. Skin, muscle and nerve biopsies showed signs of necrotizing vasculitis. Multiple microaneurysms typical of PAN were present on branches of the abdominal aorta. The symptoms due to vasculitis regressed after treatment with corticosteroids in bolus injections and plasmapheresis. AZT was not given owing to intolerance. The literature on vasculitis associated with HIV infection is reviewed.
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PMID:[Periarteritis nodosa-type vasculitis and infection with human immunodeficiency virus]. 167 17

In the search for compounds active against human immunodeficiency virus (HIV), we have found that members of a novel series of tetrahydro-imidazo[4,5,1-jk][1,4]-benzodiazepine-2(1H)-one and -thione (TIBO) derivatives inhibit the replication of HIV-1, the main aetiological agent of AIDS, but not of HIV-2, or of any other DNA or RNA viruses. In five cell systems, HIV-1 is inhibited by TIBO derivatives in nanomolar amounts, which are 10(4)-10(5) times lower than the cytotoxic concentration. The unprecedented specificity of these compounds may be due to an interaction with a reverse transcriptase-associated process. By contrast, AZT (3'-azido-2',3'-dideoxythymidine), which is used for the treatment of AIDS, and DDC (2',3'-dideoxycytidine) and DDI (2',3'-dideoxyinosine), whose clinical application is being assessed, inhibit both HIV-1 and HIV-2 at concentrations that, depending on the cell systems, are 2 to 4 orders of magnitude below their cytotoxic concentration. TIBO-derivatives are new chemicals unrelated to any other antiviral agents. We believe that they are the most specific and potent inhibitors of HIV-1 replication studied so far.
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PMID:Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives. 168 15


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