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)

Both helper and cytotoxic T lymphocytes generally recognize protein antigens not in their intact form, as antibodies do, but on the surface of another cell, after "processing" by that cell to unfold or cleave the protein into fragments and after association of the processed antigen with major histocompatibility complex (MHC) molecules on that cell. This complex process leads to immunodominance of certain segments from the protein, which depends not only on structural features intrinsic to the antigenic segment itself, but also on antigen processing and on the structure of the MHC molecules of the responding individual. We have explored all three of these factors, including the enzymes involved in processing, the way peptides bind to MHC molecules, and structural features such as helical amphipathicity that seem to favour T cell recognition. We have used this information to locate and characterize antigenic sites of proteins of interest for vaccine development, including proteins from the malaria parasite and the AIDS virus, HIV. For HIV, we have identified both helper and cytotoxic T cell sites, coupled a helper site to a B cell site to produce a synthetic immunogen that elicits neutralizing antibodies, and studied the effect of viral sequence variation on cytotoxic T cell recognition and binding of the immunodominant peptide to MHC molecules. This information suggests strategies for the rational design of synthetic or recombinant vaccines.
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PMID:Mechanisms of T cell recognition with application to vaccine design. 170 2

A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radical reactions have been implicated in the pathology of more than 50 human diseases. Radicals and other reactive oxygen species are formed constantly in the human body, both by deliberate synthesis (e.g. by activated phagocytes) and by chemical side-reactions. They are removed by enzymic and nonenzymic antioxidant defence systems. Oxidative stress, occurring when antioxidant defences are inadequate, can damage lipids, proteins, carbohydrates and DNA. A few clinical conditions are caused by oxidative stress, but more often the stress results from the disease. Sometimes it then makes a significant contribution to the disease pathology, and sometimes it does not. Several antioxidants are available for therapeutic use. They include molecules naturally present in the body [superoxide dismutase (SOD), alpha-tocopherol, glutathione and its precursors, ascorbic acid, adenosine, lactoferrin and carotenoids] as well as synthetic antioxidants [such as thiols, ebselen (PZ51), xanthine oxidase inhibitors, inhibitors of phagocyte function, iron ion chelators and probucol]. The therapeutic efficacy of SOD, alpha-tocopherol and ascorbic acid in the treatment of human disease is generally unimpressive to date although dietary deficiencies of the last two molecules should certainly be avoided. Xanthine oxidase inhibitors may be of limited relevance as antioxidants for human use. Exciting preliminary results with probucol (antiatherosclerosis), ebselen (anti-inflammatory), and iron ion chelators (in thalassaemia, leukaemia, malaria, stroke, traumatic brain injury and haemorrhagic shock) need to be confirmed by controlled clinical trials. Clinical testing of N-acetylcysteine in HIV-1-positive subjects may also be merited. A few drugs already in clinical use may have some antioxidant properties, but this ability is not widespread and drug-derived radicals may occasionally cause significant damage.
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PMID:Drug antioxidant effects. A basis for drug selection? 172 62

Cases of induced malaria have been notified in S. Paulo State, Brazil, in recent years. At the same time the number of cases imported from endemic regions of Brazil has been increasing. One case of induced malaria by Plasmodium vivax was registered in Presidente Prudente, located in the west of the State, in 1988 and a further eleven cases in 1989. This city is considered to be one of the main transit ports for people who come into the State from the Amazonian region. The patients declared that they had not been to any possible transmission area of malaria. All of them had, however, taken cocaine, sharing the same contaminated needle and syringe. Previously, one person with imported malaria was detected, who had transmitted the disease to the first case in 1988 and also to a further group of 3 people in 1989. One of these three latter cases then transmitted the disease to two other people. As the group of people continued to use the drug among themselves, 2 new cases arose. Afterwards, they re-infected themselves again (one of the was re-infected twice). The test for Human Immunodeficiency Virus was positive for 5 individuals, of whom one had a negative result and 2 others did not undergo the test. This information is discussed within the present context.
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PMID:[Malaria in intravenous drug users associated with HIV seropositivity]. 178 55

A psychiatrist from Calcutta objects to the colonial culture which still dominates India. Specifically the call for prevention of AIDS and the spread of HIV made by developed countries, yet socioeconomic conditions in India hinder any prevention efforts. India faces other more common and preventable fatal diseases. The basic needs (food, shelter, health, and education) of most people cannot even be met. Thus an AIDS prevention program is an expensive luxury and probably would not reach those whose needs are already not met. 65% of AIDS cases are in Africa especially central Africa and almost 90% of AIDS cases in developing countries are in the most productive age group (20-49 years). The HIV/AIDS epidemic is indeed dealing countries an economic blow. For example, in 1988, AIDS related medical costs in the US stood at US$8.5 billion; lost wages US$55.6 billion; and research, education, and blood screening US$2.3 billion. Developing countries cannot absorb such an economic impact. The AIDS epidemic can strain a developing country's health system such as Zaire. For example, the cost of providing proper care for only 10 AIDS patients is higher than the entire budget of the largest hospital. Yet this hospital's physicians diagnose as many as 15 new cases daily. Economic loss/year due to AIDS deaths in Zaire will equal 8% of the gross national product by 1995. The poor often do not have access to health services. illiteracy (88%) in Brazil impedes AIDS prevention messages from reaching remote rural populations. Brazil already faces a high infant mortality rate and 33% of the population has malaria. Health and social problems in developing countries are so common that AIDS is just 1 more disease. Another obstacle to AIDS prevention in developing countries is that the poor cannot afford to buy condoms. The root cause of AIDS in developing countries is poverty.
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PMID:AIDS prevention: what are we talking about? 178 14

In Germany maternal mortality related to pregnancy, birth and child-bed is only about 11 women/100,000. In some African countries mortality is up to 100 times as high, UNICEF reported in 1991. The causes of high infant and maternal mortality are poverty, inadequate hygiene, and lack of preventive medical care and timely treatment of diseases for 60% of the population in the least developed countries. Countries in sub-Saharan Africa currently have the world's highest population growth rates of 3-4%/annum. Diarrheal and respiratory diseases are the most common causes of death, but recently tuberculosis has reappeared. Acute respiratory infection (ARI) causes at least 4 million deaths/year or 11,000/day. Each year about 800 million malaria infections occur worldwide. Although antimalarial drugs have reduced mortality, resistant Plasmodium strains have made therapy difficult. Schistosomiasis is endemic in 74 countries: about 200 million people are infected and more than 600 million people are at risk. Central and East Africa are the areas worst affected by the AIDS pandemic. In some cities more than 1/4 of men and women in the 20-40 age group are infected with HIV. Up to 90% seroprevalence rates have been found among female prostitutes. Perinatal transmission is becoming prevalent where 20% or more of the pregnant women are infected. In some regions of Africa prevalence rates can reach 505 and more for the adult population. By the early 1990s AIDS will be the leading cause of mortality in the 20-40 age group in some regions. A 1991 forecast for the Mbeya Region of Tanzania predicted that the 15-44 year age group would decline from 41% to 37% during 1988-94, while infant mortality may increase by 50-100/1000 live births. The only control measures of HIV transmission remain the avoidance of infected blood or infected medical equipment, and prevention is through education and information.
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PMID:Strategies to maintain health in the Third World. 179 44

After reminding the epidemiology of the HTLV1 infection the authors sum up the actually recommended diagnosis procedure. --Case finding by ELISA, confirmation by WESTERN-BLOT and/or RIPA (anti-gag and anti-env specificities), or even PCR which makes specific diagnosis of HTLV1/2. --Or if possible directly by PCR which has helped some authors to find provirus in seronegative people. Coinfections caused by HIV and by Strongyloides are the best documented. As a rule, HTLV1 seems to have rather a worsening effect on evolutiveness and on seriousness of the clinical picture caused by mixed infections, than the contrary (possibly for lack of experience and owing to slow evolution of HTLV1 pathology). Several mechanisms have been proposed concerning coinfections with HTLV1 and HIV (in vitro studies). --Immortalization of CD4 lymphocytes infected with HTLV1 by stimulating both IL2 and its receptor, and by activating lymphocytes with translocation of the replicating factor NF k B in the nucleus, on a promoting sequence of HIV-LTR by stimulating its replication. --The product of HTLV1 tax gene would also have a transactivating effect on the provirus HIV-LTR replication. And finally infection with HTLV1 may facilitate HIV by inducing CD4, molecule expression in non-expressing cells. In Strongyloides modulating effects of HTLV1 on the immune response would facilitate and predispose Strongyloides stercoralis multiplication. As far as other coinfections are concerned (caused by viruses, by parasites: such as malaria, filariasis, trypanosomiasis or by bacteria), epidemiological convergence (risk factors, and geographic distribution) on the one hand, and immunological dysregulation induced by the other, on the other hand, would be of varying importance. In conclusion, these data ask more questions than they answer. But it seems to be established that detection of HIV and Strongyloides should performed in every case HTLV1 carries and vice versa.
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PMID:[HTLV1 and coinfections]. 180 Aug 78

A fatal disease epidemic affected the Bentiu area in southern Sudan and led to a mass migration of the Nuer tribe searching for treatment. The initially available information revealed a high mortality rate due to a possible occurrence of tuberculosis, malaria, enteric fever or visceral leishmaniasis (VL). Serological screening of 53 of the most severely affected patients in an enzyme-linked immunosorbent assay (ELISA) or an improved direct agglutination test (DAT) revealed positivity for VL. In 39 of those patients, diagnosis was confirmed by identification of Leishmania donovani amastigotes in lymph node or bone-marrow aspirates. In a total of 2714 patients observed, 1195 (44.0%) had clinical symptoms suggesting VL: DAT positive titers (1:3200-greater than or equal to 1:12800) were obtained in 654 (24.1%), of whom 325 were confirmed parasitologically. Forty-two VL cases died before or during treatment, giving a mortality rate of 6.4%. Among the intercurrent infections diagnosed in the VL population (654), respiratory involvements (31.7%) and malaria (10.7%) were most prevalent. With the exception of four (0.6%), all other VL patients (509) responded readily to sodium stibogluconate. The factors initiating the outbreak are discussed. Malnutrition and nomadic movements to potential VL endemic areas appeared to be the most important. HIV infection as a possible predisposition seemed remote considering the clinical and epidemiological similarity to VL occurring in East Africa, adequate humoral response in DAT, and immediate positive response to specific anti-Leishmania chemotherapy.
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PMID:A killing disease epidemic among displaced Sudanese population identified as visceral leishmaniasis. 185 33

To evaluate the consequences of receiving human immunodeficiency virus type 1 (HIV-1)-seropositive blood, 90 HIV-1-seronegative recipients of HIV-1-seropositive blood (case patients) and 90 HIV-1-seronegative recipients of HIV-1-seronegative blood, matched for age, sex, number of transfusions, diagnosis, and severity of illness (controls), were followed for 12 months after transfusion at Mama Yemo Hospital in Kinshasa, Zaire. Of case patients and controls, 72% were children transfused for anemia caused by malaria. Of the 46 case patients case patients alive 6 months after transfusion and for whom HIV-1 serologic results were obtained, 44 (96%) had seroconverted. Significantly more case patients (47%) than controls (16%) died within 1 year after transfusion (P less than .001). In the first 3 months after transfusion, fatigue, diarrhea, fever, cough, pruritus, pallor, oral candidiasis, polyadenopathy, hepatosplenomegaly, and rhinorrhea were observed more often among seroconverters than controls (P less than .04). Six percent of case patients and no controls had developed clinical AIDS after 12 months of follow-up. These findings underscore the urgent need for appropriate HIV screening facilities in transfusion centers worldwide.
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PMID:Seroconversion rate, mortality, and clinical manifestations associated with the receipt of a human immunodeficiency virus-infected blood transfusion in Kinshasa, Zaire. 186 35

Both helper and cytotoxic T cells see primarily a limited number of immunodominant sites on a protein. The reasons for immunodominance are many. We have explored primarily the roles of antigen processing and binding to histocompatibility molecules, as well as the structural features of the antigenic peptide. This information has led to the identification and characterization of sites stimulating helper or cytotoxic T cells specific for antigens from malaria or HIV, and ways to couple and immunize with these, that may be useful for vaccine development. We also observed a striking concordance between helper and cytotoxic T cell sites.
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PMID:Antigenic peptide interaction with MHC molecules: implications for the design of artificial vaccines. 193 4

Eight cases of mother-to-child transmission of HIV-2 were documented by ELISA and Western blot in Gambia between January 1988-September 1989 from a hospital-based screening of 205 malnourished children, 864 subjects in a malaria study, 34 patients with probable immunodeficiency and 24 children of 17 HIV-2 seropositive mothers. AIDS was diagnosed by WHO clinical definition. Diagnosis of HIV-2 was made if sera were positive by ELISA and Western blot (LAV Blot2, Diagnostics Pasteur, Marnes-La-Coquette, France) and negative by Wellcozyme I competitive ELISA to HIV-a (Wellcome Diagnostics, Dartford, UK). The children ranged in age from 17 months-5 years, and in ponderal index from 50-90%. 6 had CD4 percentages or counts below the normal range. 7 of the 8 could only have been infected pre- or perinatally, while 1 had been transfused from her mother. The clinical features included 5 with diarrhea 1 month; 3 with Cryptosporidium, 3 with Candida, a pneumonia, an interstitial pneumonia by x-ray, a streptococcus abscess, a staphylococcus abscess, 1 infant with failure to thrive and 1 4-year old who was asymptomatic. This group of patients was more severely affected than a series reported from Guinea Bissau: their mothers also had advanced AIDS in comparison to asymptomatic mothers in the other series. While mother-to-child transmission of HIV-1 occurs in approximately 33% of children of HIV-1 seropositive mothers, these data cannot estimate the actual rate of transmission of HIV-2.
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PMID:AIDS following mother-to-child transmission of HIV-2. 197 26


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