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)

Between 1984-1991, physicians at Hospital del Mar in Barcelona, Spain and the area with the highest prevalence of tuberculosis (TB) diagnosed active pulmonary nondisseminated TB in 57 HIV infected patients. 3 of these patients consistently had normal chest radiographs. All 3 patients had fever and cough. Case 1 was a 26 year old female intravenous (IV) drug user. She had generalized lymphadenopathy. Hematologic tests revealed an HIV positive status. Her CD4+ lymphocyte count was 782 x 10 to the 6th power/1. Her tuberculin skin test was negative. Mycobacterium tuberculosis in her sputum grew in Lowenstein medium. Acid fast bacilli were detected in her sputum with Ziehl-Nielsen stain. Physicians began antiTB therapy (isoniazid, pyrazinamide, rifampin, and ethambutol). She improved within a few weeks. Case 2 was an HIV positive IV drug user and 33 years old. The CD4+ lymphocyte count was 645 x 10 to the 6th power/1. Acid fast bacilli were detected in his bronchoalveolar lavage with Ziehl-Nielsen stain. M. Tuberculosis in the lavage grew in Lowenstein medium. The physicians started him on the same antiTB therapy as Case 1. His condition improved with therapy. Case 3 was a 50 year old bisexual man. Hematologic tests showed HIV positivity. His CD4+ lymphocyte count was 790 x 10 to the 6th power/1. Further his tuberculin skin test was negative. Fibre optic bronchoscopic samples were negative for acid fast bacilli, but M. tuberculosis grew in Lowenstein culture. Blood, urine, bone marrow and gastric aspirates tested negative for M. tuberculosis. He began the same antiTB therapy as Cases 1 and 2. His condition improved. In conclusion, physicians should aggressively pursue a diagnosis to TB in HIV infected patients presenting with fever and cough. Their rate of hospitalization should fall with early diagnosis and treatment which will in turn prevent the spread of TB among the population.
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PMID:Pulmonary tuberculosis in HIV-infected patients with normal chest radiographs. 154 71

The N-terminal domain of human immunodeficiency virus (HIV-1) integrase (IN) contains the sequence motif His-Xaa3-His-Xaa23-Cys-Xaa2-Cys, which is strongly conserved in all retroviral and retrotransposon IN proteins. This structural motif constitutes a putative zinc finger in which a metal ion may be coordinately bound by the His and Cys residues. A recombinant peptide, IN(1-55), composed of the N-terminal 55 amino acids of HIV-1 IN was expressed in Escherichia coli and purified. Utilizing a combination of techniques including UV-visible absorption, circular dichroism, Fourier transform infrared, and fluorescence spectroscopies, we have demonstrated that metal ions (Zn2+, Co2+, and Cd2+) are bound with equimolar stoichiometry by IN(1-55). The liganded peptide assumes a highly ordered structure with increased alpha-helical content and exhibits remarkable thermal stability. UV-visible difference spectra of the peptide-Co2+ complexes directly implicate thiols in metal coordination, and Co2+ d-d transitions in the visible range indicate that Co2+ is tetrahedrally coordinated. Mutant peptides containing conservative substitutions of one of the conserved His or either of the Cys residues displayed no significant Zn(2+)-induced conformational changes as monitored by CD and fluorescence spectra. We conclude that the N terminus of HIV-1 IN contains a metal-binding domain whose structure is stabilized by tetrahedral coordination of metal by histidines 12 and 16 and cysteines 40 and 43. A preliminary structural model for this zinc finger is presented.
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PMID:Structural implications of spectroscopic characterization of a putative zinc finger peptide from HIV-1 integrase. 157 1

The retroviral gag nucleocapsid protein NCp7 (72 amino acids) of HIV-1 (LAV strain), which contains two successive zinc fingers of the Cys-X2-Cys-X4-His-X4-Cys form linked by a stretch of basic residues, promotes viral RNA dimerization and encapsidation and activates annealing of the primer tRNA to the initiation site of reverse transcription. The structure of NCp7 and other shorter fragments was studied by 600 MHz 1H nuclear magnetic resonance (NMR) in aqueous solution to account for its various biological properties. Complete sequence specific 1H NMR assignments of the 13-51 residues of NCp7 encompassing the two zinc fingers was achieved by two-dimensional NMR experiments and the three-dimensional structure of (13-51)NCp7 was deduced from DIANA calculations, using nuclear Overhauser effects as constraints. The structure of the zinc complexed form of NCp7 is characterized by a kink at the Pro31 level in the basic Arg29-Ala-Pro-Arg-Lys-Lys-Gly35 RNA binding linker leading to a proximity of the Lys14-Cys18 to the Gly35-Cys39 sequences, which belong to the folded proximal and distal zinc fingers, respectively. Accordingly, the aromatic residues Phe16 and Trp37 were found to be spatially close. The Lys33 and Lys34 side-chains involved in viral RNA dimerization were solvent exposed. The N- and C-terminal sequences of NCp7 behave as flexible independent domains. The proposed structure of NCp7 might be used to rationally design new anti-viral agents aimed at inhibiting its functions.
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PMID:Determination of the structure of the nucleocapsid protein NCp7 from the human immunodeficiency virus type 1 by 1H NMR. 163 74

A case is described of an HIV+ man who was successfully treated for Hodgkin's lymphoma, but who later developed non-Hodgkin's lymphoma 3 years later when his immune system became suppressed. The patient was 22 years old when he presented with fever, asthenia, weight loss, and cervical lymphadenopathy. With Hodgkin's lymphoma he also had positive serology for HIV and hepatitis B. He was treated with alternate courses of MOPP and ABVD chemotherapy. In 1990 he again appeared with high fever, progressive cervical, axillary and inguinal lymphadenopathy, with hilar and mediastinal lymph node enlargement on x-ray. CD4 lymphocytes were 577/cubic mm, and the CD4/CD8 ratio was 0.57 (normal 1.8). His cervical lymph node biopsy was classified as non-B non-T large-cell anaplastic lymphoma which was EBV-positive. A Western Blot was positive for small amounts of p24 and p18 antigens. The man was treated with MACOP-B chemotherapy, with some results, but died of sepsis 6 weeks later. The relationships between Hodgkins and non-Hodgkin's lymphoma, the timing of the neoplasm in the course of HIV infection, and the possible re-activation of hepatitis virus were discussed.
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PMID:Non-Hodgkin's lymphoma after prolonged remission of Hodgkin's disease in an HIV-infected patient. 166 42

A 25-year-old homosexual man with a childhood history of rheumatic heart disease presented with painful joints, fever and chest pain. He was diagnosed as having acute rheumatic fever and was found to be HIV antibody-positive. His illness responded to conventional treatment but he had a persistently low CD4 lymphocyte count and was started on zidovudine. Interpretation of the significance of a low CD4 lymphocyte count is problematic in a patient with coincident rheumatic fever and HIV infection as both conditions can cause CD4 lymphopenia.
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PMID:Acute rheumatic fever in human immunodeficiency virus infection. 167 90

We have modified an Escherichia coli vector expressing 66-kDa HIV-1 reverse transcriptase (p66) so that it simultaneously expresses this and the pol-coded protease. The twin expression cassette yields high quantities of both reverse transcriptase and protease; however, under these conditions, 50% of the over-expressed p66 reverse transcriptase is processed, resulting in accumulation of large quantities of p66/p51 enzyme. Furthermore, addition of a poly(histidine) affinity label at the amino terminus of the reverse-transcriptase-coding sequence (His-p66) permits a simple, rapid purification of milligram quantities of either p66 or p66/p51 enzyme from a crude lysate by metal chelate affinity chromatography. Purified His-p66 and His-p66/His-p51 reverse transcriptase exhibit both reverse transcriptase and RNase H activity. Purification by metal chelate chromatography of a p66/p51 enzyme wherein only the p66 component is labelled strengthens the argument for the existence of a heterodimer.
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PMID:Rapid purification of homodimer and heterodimer HIV-1 reverse transcriptase by metal chelate affinity chromatography. 168 98

The human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT) is a protein of 66 kDa, p66, which contains two domains, an amino-terminal DNA polymerase and an RNase H at the carboxy terminus of the molecule. In order to characterize the mode of action of the RNase H, two previously described mutant enzymes were used, with substitutions in the highly conserved histidine 539, which was mutated to the neutral amino acid asparagine and to the negatively charged aspartate. The purified wild-type (wt) and mutant (mt) enzyme activities are analyzed here using RNA-DNA hybrids consisting of in vitro transcribed RNA that harbors the polypurine tract (PPT) from HIV-1 and DNA oligonucleotides complementary to the PPT or to other regions of the RNA. Analysis of the radioactively labeled RNA of these model hybrids after RNase H treatment indicates that both, wt and mt enzymes, are capable of cleaving the RNA in an endonucleolytic manner. The mt enzymes exhibit a severely reduced exonuclease activity. They are more sensitive towards salt and competition with excess of unlabeled hybrid, suggesting a reduced substrate binding affinity. DNA elongation by the RT is coupled with RNA hydrolysis by the 3'-5' exonuclease of the wt RNase H. The RNase Hmt of the mt enzymes, however, does not exhibit such processive 3'-5' exonuclease activity during DNA synthesis but gives rise to sporadic endonucleolytic cuts, whereas the RT is not affected. The endonuclease activities of the RNase H mt enzymes exhibit cleavage preferences in the absence or presence of DNA synthesis different from those of the wt enzyme. They cannot recognize specific sequences required to generate a PPT-primer and therefore cannot initiate plus-strand DNA synthesis in vitro at the 3' end of the PPT, which is essential for viral replication.
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PMID:Mutations of a conserved residue within HIV-1 ribonuclease H affect its exo- and endonuclease activities. 171 5

A metal binding peptide, hexahistidine, preceding a renin cleavage sequence (Pro-Phe-His-Leu-Val-Ile-His-) was engineered on to the N-terminus of HIV-1 reverse transcriptase (RT). The chimeric protein was expressed in Escherichia coli and characterized after purification by DEAE chromatography and HPLC. Amino-terminal sequencing confirmed the presence of the first 15 amino acids of the chimeric protein. The chimeric exhibited RT activity like that of HIV-1 RT and was cleaved by human renin at the expected site. The potential of a hexa-histidine fusion in the purification of recombinant HIV-1 RT by immobilized metal affinity chromatography (IMAC) on the commonly used resin (IDA-Ni2+) was investigated. The chimeric gene product from a crude E. coli extract was strongly retarded on a immobilized nickel column, while most of the contaminating E. coli proteins were eliminated after elution with 20-35 mM imidazole. The bound chimeric protein was eluted with 300 mM imidazole and appeared predominantly as a single band on an SDS-polyacrylamide gel. The remarkable specificity of this affinity tail was further demonstrated by separating the chimeric protein from HIV-1 RT in a crude extract prepared by mixing extracts from cells expressing HIV-1 RT and the hexahistidine recombinant chimeric protein. The usefulness of a enzymatically cleavable metal binding peptide in the rapid purification and production of HIV-1 RT without proteolysis to a heterodimer is discussed.
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PMID:Metal affinity chromatography of recombinant HIV-1 reverse transcriptase containing a human renin cleavable metal binding domain. 171 13

The government of Uganda began its anti-AIDS campaign in 1986. A year later with AIDS Support Organization opened its doors as the situation worsened. Today it provides counseling and health care services for AIDS patients and trains counselors. It operates support centers in 8 districts. Staff make home visits to AIDS patients who reside within 20 km of a support center. Women and children comprise the majority of patients. Even though changes in behavior could restrict AIDS, social, economic, and cultural obstacles exist. For example, in some areas of Uganda, society expects the brother of a decreased man to have sexual intercourse with the widow and to be responsible for her and her children. His life and that of his wife or wives are in danger if the brother died of AIDS. Community workers encourage people to engage in practices that do not spread AIDS. This program provides training on AIDS awareness and community mobilization, counseling by community members, medical services, educational materials, and promotion of income generating efforts. Even though the most effective way of preventing the spread of HIV when having sexual intercourse is using a condom, cultural reasons and cost hinder its use. Counselors find it difficult to discuss sexual relations let alone condoms. Further promotion of condoms is often interpreted as promotion of immoral behavior. These obstacles have not stopped the AIDS Support Organization from providing information on condoms and it has targeted traditional healers and tribal and religious leaders to help in this effort. Women play a major role in AIDS education. They need to be informed of their rights and empowered to exercise them to improve their status and that of their children. Indeed their empowerment would improve the whole of society.
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PMID:Against a sea of troubles: AIDS control in Uganda. 177 19

The reasons for the rapid spread of AIDS in Thailand, and the impact of the unique non-governmental agency Population and Community Development Association (PDA) directed by the charismatic Dr. Mechai are described. The rapid spread of AIDS in Thailand is due to presence of all possible factors facilitating HIV transmission, a large population of injecting drug addicts, an extensive mobile domestic and tourist sex industry, and an active gay community. The number of HIV-positive persons rose from 179 in 1988 to 16,359 in 1989, and is now estimated at 100,000. 1% of the Thai population works in prostitution, and from 16% of the high-income to 72% of the low-income prostitutes are infected, with their infection rates rising 10% per month. 75% of Thai men use cheap prostitutes. While the government was ignoring the AIDS threat in the early '80s, Dr. Mechai, whose name translated as "condom," was organizing the grass-roots community-based condom distribution system PDA, said to be responsible for the fall in annual population growth from 3.4% in 1968 to 1.5% in 1990. His organization now distributes contraceptives to 16,000 villages by 12,000 volunteers. He uses booklets, cards, cassettes, slide shows, videos and appearances with condom-inflating contests and costumes to de-mystify condoms with humor. Now AIDS messages are heard in taxis, on military TV and radio, and in remote villages. Converting knowledge into practice is more difficult, requiring tactful convincing of brothel operators and finding some way to reach their clients, who exert economic control over young female prostitutes.
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PMID:AIDS in Thailand. 203 56


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