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)

Retroviral DNA integration requires the activity of at least one viral protein, the integrase (IN) protein. We cloned and expressed the integrase gene of feline immunodeficiency virus (FIV) in Escherichia coli as a fusion to the malE gene and purified the IN fusion protein by affinity chromatography. The protein is active in site-specific cleavage of the viral DNA ends, DNA strand transfer, and disintegration. FIV IN has a relaxed viral DNA substrate requirement: it cleaves and integrates FIV DNA termini, human immunodeficiency virus DNA ends, and Moloney murine leukemia virus DNA ends with high efficiencies. In the cleavage reaction, IN exposes a specific phosphodiester bond near the viral DNA end to nucleophilic attack. In vitro, either H2O, glycerol, or the 3' OH group of the viral DNA terminus can serve as nucleophile in this reaction. We found that FIV IN preferentially uses the 3' OH ends of the viral DNA as nucleophile, whereas HIV IN protein preferentially uses H2O and glycerol as nucleophiles.
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PMID:Activities of the feline immunodeficiency virus integrase protein produced in Escherichia coli. 810 10

Despite being a well-known pathogen for immunocompromised patients, Legionella pneumophila has infrequently been described in persons with infection due to human immunodeficiency virus (HIV). Since 1986, we have identified eight cases of legionella pneumonia among seven HIV-infected persons enrolled in the HIV Natural History Study of the U.S. Air Force. The median CD4+ T cell count for these patients was 83/mm3; 50% of the cases occurred in persons for whom AIDS was previously diagnosed, and five of the cases were nosocomial. Six of the patients had coexistent pulmonary infections. None of the cases occurred among persons receiving prophylactic therapy with trimethoprim-sulfamethoxazole. Therapeutically, all patients appeared to respond well to standard antilegionella therapy or high doses of trimethoprim-sulfamethoxazole. Overall, these seven patients represent 1.7% of the patients with late-stage HIV infection (Walter Reed stage 5 or 6) in this cohort. L. pneumophila, although remaining an uncommon pathogen for HIV-infected patients, may produce serious disease in this population. HIV-infected persons should be considered at risk for legionnaires' disease, particularly in institutions where potable water supplies have become contaminated.
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PMID:Legionnaires' disease in human immunodeficiency virus-infected patients: eight cases and review. 852 92

(-)-Carbovir (CBV) is a carbocyclic nucleoside analogue with in vitro activity against the human immunodeficiency virus. The sites and mechanism of absorption of (-)-CBV from the rat small intestine were studied in the anesthetized male Sprague-Dawley rat. (-)-CBV was perfused through either duodenal, jejunal, or ileal segments at three concentration levels ranging from 1 to 500 micrograms/mL. The fraction remaining to be absorbed at steady-state and the absorptive clearance were calculated for each experiment. The effect of solvent drag on the absorptive clearance was also investigated. Two-way ANOVA for the absorptive clearance per unit length was not significant for either (-)-CBV concentration or site of perfusion. The fraction remaining to be absorbed at steady-state was found to be 0.804 +/- 0.091 (n = 30). A strong correlation was found between the absorptive clearance and the net water absorptive flux. The mechanism of (-)-CBV absorption across the rat small intestine apparently consists of both passive diffusion and convection.
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PMID:Intestinal absorption of (-)-carbovir in the rat. 816 86

Proteolytic experiments in conjunction with 1H-NMR spectroscopy show that the Nef (negative factor) protein from human immunodeficiency virus type 1 probably consists of two main domains, the N-terminal anchor domain at amino acid positions 2-65 and the C-terminal core domain at positions 66-206. The N-terminal domain is likely to be located at the surface of the protein, while the C-terminal domain has a compactly folded core and is stable in the absence of the anchor domain. It is conceivable that the core domain represents a functional domain of the Nef protein, activated after the removal of the membrane anchor by the human-immunodeficiency-virus protease or cellular proteases. Nef is stable at pH 5-12 and denatures at 317-322 K. The Nef protein remains in its native conformation in dimethyl-sulfoxide/water mixtures up to 35% (by vol.), and in acetonitrile/water up to 14% (by vol.). Nef refolds spontaneously after denaturation with urea or guanidinium hydrochloride. The 1H-NMR parameters and pKa values of five of the nine histidine residues and one of the seven tyrosine residues were determined and were found in four cases to be typical for residues which are not located in the interior of the protein.
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PMID:Stability and proteolytic domains of Nef protein from human immunodeficiency virus (HIV) type 1. 817 61

The responses of a self-selected sample of Canadian college students draw attention to the salience of gender-based analysis in studies of sexual behavior and condom use. Respondents included 249 male and 237 female heterosexuals (mean age 22.6 and 21.9 years, respectively) who approached free condom distribution displays at 4 college campuses in Toronto and agreed to complete a brief questionnaire. Overall, 69% of students stated they were currently involved in a relationship; however, 65% of females compared to only 47% of males reported having just 1 sexual partner in the past year. 83% of students had used a condom at some point in their life and 69% reported condom use on at least 1 occasion in the past year. All respondents acknowledge at least 1 episode of sexual intercourse where a condom was not used. The most frequent reason for nonuse, among both males and females, was involvement in a steady relationship. However, males were significantly more likely than females to claim they did not use condoms for the following other reasons: did not have a condom, sex was so exciting, partner did not want to use a condom, and drugs or alcohol were involved. Males reported significantly higher rates of condom use than females during vaginal intercourse, oral sex, and anal intercourse. On the other hand, females had more positive attitudes toward condoms and were more conscientious in their proper use. There were significant gender differences on 6 of 10 attitude questions, with females disagreeing more strongly than males with the following statements: condoms are a turnoff, safe sex is boring, long-term lovers can have any type of sex without risk, drug or alcohol use makes it hard to practice safe sex, and it is hard to have safe sex with a very attractive partner. In terms of specific condom use guidelines intended to prevent human immunodeficiency virus (HIV) transmission, females were significantly more likely than males to be aware of or adhere to the following: never use vaseline, hold while withdrawing, withdraw just after ejaculation, use water-based lubricant, and always use spermicide. 87% of subjects considered themselves at low or no risk of HIV infection.
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PMID:Condom use and attitudes among heterosexual college students. 818 Sep 26

Glycerol has been used for a long time as a viral preservation medium in tissue samples at a 50 per cent concentration, however after a limited time span viruses could no longer be detected. This fact combined with the dehydrating action of glycerol, raised the suspicion that glycerol in a higher concentration could be virucidal. To test this hypothesis, experiments were done at various concentrations of glycerol at three different temperatures (4, 20 and 37 degrees C), using the following viruses: herpes simplex virus, a virus with an envelope, comparable to human immunodeficiency virus; and poliovirus as an example of small, hard to inactivate viruses without an envelope. Glycerol will dehydrate the skin, the extracted water being replaced by glycerol, preserving the original structure. The remaining water is optimally distributed throughout the tissue. However, the possibility exists that glycerol influences the enzymatic processes of nucleic acid breakdown. Plasmid DNA pBR322 was added to HeLa-cells in the presence and absence of glycerol. The outcome of the experiments showed that glycerol has a strong virucidal action. Preservation in 85 per cent glycerol was preferred, because using this concentration the glycerolized allograft skin retained its suppleness and was easy to manipulate during operations.
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PMID:Virucidal effect of glycerol as used in donor skin preservation. 799 86

Polyoxometalates are soluble mineral compounds formed principally of oxide anions and early transition metal cations. The polyoxometalates K12H2[P2W12O48].24H2O (JM 1591), K10[P2W18Zn4(H2O)2O68].20H2O (JM 1596), and [(CH3)3NH]8[Si2W18Nb6O77] (JM 2820) demonstrate potent antiviral activity against human immunodeficiency virus types 1 and 2, herpes simplex virus, and cytomegalovirus in vitro. The preclinical pharmacokinetics of these three compounds were characterized after single-dose intravenous administration of 50 mg/kg to rats. Plasma, urine, and feces were collected for 168 h, and polyoxometalate concentrations were determined by atomic emission. Serum protein binding was measured by equilibrium dialysis. All three compounds were highly bound to serum proteins in a concentration-dependent manner. Total and unbound concentrations of the three compounds in plasma declined in a triexponential manner with terminal half-lives of 246.0 +/- 127.0, 438.4 +/- 129.4, and 32.2 +/- 5.37 h (mean +/- standard deviation) for JM 1591, JM 1596, and JM 2820, respectively. Systemic clearances based on total concentrations in plasma were low, averaging 0.016 +/- 0.002, 0.015 +/- 0.002, and 0.018 +/- 0.003 liter/h/kg for JM 1591, JM 1596, and JM 2820, respectively. The clearances of unbound compounds from plasma averaged 0.966 +/- 0.136, 0.050 +/- 0.005, and 0.901 +/- 0.165 liter/h/kg for JM 1591, JM 1596, and JM 2820, respectively. For JM 1596, the clearance of unbound compound from the kidneys was lower than the glomerular filtration rate (0.086 liter/h/kg), suggesting this polyoxometalate underwent renal tubular reabsorption. However, JM 1591 and JM 2820 appeared to undergo tubular secretion. The fraction of the dose recovered in urine was 11.5, 46.8, and 10.6% for JM 1591, JM 1596, and JM 2820, respectively. Approximately 5% of the dose of each polyoxometalate was recovered in feces. The steady-state volume of distribution based on total concentrations averaged 1.44 liters/kg for JM 1591, 2.39 liters/kg for JM 1596, and 0.59 liter/kg for JM 2820, indicating moderate to wide distribution throughout the body. All three compounds were detected in various tissues 1 week after single-dose administrations, with the highest levels found in the kidneys and liver. The results of this study indicate that the disposition of polyoxometalates is highly dependent on their molecular structure.
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PMID:Pharmacokinetics of antiviral polyoxometalates in rats. 820 45

Bleach cleansing of injection equipment has been recommended to reduce the risk of human immunodeficiency virus (HIV) transmission associated with the reuse of injection equipment by injecting drug users (IDUs). We evaluated the recall and performance of the most commonly recommended bleach cleansing procedure of two complete fillings of the syringe with bleach, followed by two complete fillings with rinse water, and not putting used bleach and water back into source containers. IDUs were taught this procedure on enrollment in an HIV prevention demonstration project in Dade County, Florida. During follow-up session 6-12 months after initial training, the knowledge and ability of IDUs to perform bleach cleansing were assessed by trained observers using a standardized method. In 1988-90, we assessed the knowledge and ability of 450 IDUs to perform the bleach cleansing procedure taught at enrollment. More than 90% of IDUs assessed performed the basic steps. However, only 43.1% completely filled the syringe with bleach and only 35.8% completely filled the syringe with bleach at least twice. Substantial proportions of IDUs did not perform all the steps of the previously taught bleach cleansing procedure. Compliance decreased as the number of steps required was increased. This limited compliance may make bleach cleansing less effective and suggests that some IDUs may fail to adequately disinfect injection equipment and therefore sterile needles and syringes are safer than bleach-cleansed ones. Compliance testing can help assess the effectiveness of HIV prevention programs.
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PMID:Compliance to bleach disinfection protocols among injecting drug users in Miami. 820 62

The interrelationships between reproductive health, population growth, economic development, and changes in the environment are much debated. One school adheres to the Malthusian view that population growth outstrips the capacity of the earth to provide necessary sustenance until it is checked by crises. They see evidence in the fall in the human sperm count, the spread of human immunodeficiency virus (HIV) in Africa, recurring famines, and ethnic and religious conflicts in areas of high population. Another school argues that mankind has the ingenuity to provide technical solutions, but they fail to address the planet's capacity to absorb environmental destruction and the enormous inequality in resource consumption between the North and the South. Other predict that the inability to control advanced technology will eventually precipitate an irreversible global disaster (e.g., the 1986 Chernobyl disaster and the conflagration of the oil wells in Kuwait in 1991). World population will increase by 1000 million, or by 20%, within 10 years, with 95% of this increase in the South. In the 1990s, annually, 40-60 million pregnancies will be terminated and 5-10 million children will die within one year of birth. AIDS-related infections, notably tuberculosis, will undermine health care in Africa and probably kill 15-20% of the work force before 2000. 2-4 million people will have died from AIDS-related infections by 2000, and a father 100-120 million will have come infected with HIV. In Tanzania, agricultural production has already fallen by 10-20% because of AIDS-related morbidity within the work force. The key issues are migration, the spread of disease, the supply of water and the degradation of land, and fiscal policies with respect to family planning, pharmaceuticals and Third World debt. Full education of women, and more effective family planning in the South can alleviate the problem. Otherwise the developed countries will be engulfed by the health, economic and environmental problems of the South, with its projected population of 5400 million people for the year 2000.
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PMID:Reproductive health, population growth, economic development and environmental change. 822 91

We generated Chinese hamster ovary cell lines that stably express wild-type, secreted, and glycosylphosphatidylinositol (GPI)-anchored envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1). The cells expressing wild-type Env (WT cells) express both the precursor gp160 and the mature gp120/gp41 and readily form large syncytia when cocultivated with CD4+ human cells. The cells expressing secreted Env (SEC cells) release 140-kDa precursor and mature 120-kDa envelope glycoproteins into the supernatants. The cells expressing GPI-anchored Env (PI cells) express both 140-kDa precursor and mature gp120/gp41 envelope glycoproteins, which can be released from the cell surface by treatment with phosphatidylinositol-specific phospholipase C (PI-PLC). Both the secreted and PI-PLC-released envelope glycoproteins form oligomers that can be detected on nonreducing sodium dodecyl sulfate-polyacrylamide gels. In contrast to the WT cells, the SEC and PI cells do not form syncytia when cocultivated with CD4+ human cells. The availability of cells producing water-soluble oligomers of HIV-1 Env should facilitate studies of envelope glycoprotein structure and function. The WT cells, which readily induce syncytia with CD4+ cells, provide a convenient system for assessing potential fusion inhibitors and for studying the fusion mechanism of the HIV Env glycoprotein.
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PMID:Characterization of stable Chinese hamster ovary cells expressing wild-type, secreted, and glycosylphosphatidylinositol-anchored human immunodeficiency virus type 1 envelope glycoprotein. 823 Apr 30


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