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)

Molecular dynamics simulations have been carried out based on the GROMOS force field on the aspartyl protease (PR) of the human immunodeficiency virus HIV-1. The principal simulation treats the HIV-1 PR dimer and 6990 water molecules in a hexagonal prism cell under periodic boundary conditions and was carried out for a trajectory of 100 psec. Corresponding in vacuo simulations, i.e., treating the isolated protein without solvent, were carried out to study the influence of solvent on the simulation. The results indicate that including waters explicitly in the simulation results in a model considerably closer to the crystal structure than when solvent is neglected. Detailed conformational and helicoidal analysis was performed on the solvated form to determine the exact nature of the dynamical model and the exact points of agreement and disagreement with the crystal structure. The calculated dynamical model was further elucidated by means of studies of the time evolution of the cross-correlation coefficients for atomic displacements of the atoms comprising the protein backbone. The cross-correlation analysis revealed significant aspects of structure originating uniquely in the dynamical motions of the molecule. In particular, an unanticipated through-space, domain-domain correlation was found between the mobile flap region covering the active site and a remote regions of the structure, which collectively act somewhat like a molecular cantilever. The significance of these results is discussed with respect to the inactivation of the protease by site-specific mutagenesis, and in the design of inhibitors.
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PMID:Molecular dynamics of HIV-1 protease. 160 8

To reduce the risk of pathogenic virus transmission associated with the therapeutic administration of plasma-derived anti-hemophilic factor (FVIIIc), a process utilizing anti-FVIIIc immunoaffinity chromatography to isolate FVIIIc has been developed. In addition, the starting cryoprecipitate solution has been treated with an organic solvent/detergent mixture to inactivate lipid-enveloped viruses. A final ion exchange chromatography step is used to further remove contaminants, e.g., anti-FVIIIc antibody, potentially leached with FVIIIc during the immunoaffinity step. The purified FVIII is stabilized for lyophilization and storage by the addition of human albumin. The monoclonal anti-FVIIIc antibody used in the immunoaffinity step of the process is not detectable in the final preparation. Viral reduction studies performed at specific steps of the process demonstrate that 11 logs of human immunodeficiency virus (HIV) and greater than 4-5 logs of other lipid-enveloped viruses are inactivated within the first 30 s of exposure to the solvent/detergent mixture and 4-5 logs of various model viruses, e.g. Endomyocarditis virus (EMC), are physically removed during washing of the immunoaffinity column. The lyophilized product is reconstituted using sterile water in a matter of seconds. The pharmacokinetics of Hemofil M were compared to those obtained using a standard heat-treated concentrate (Hemofil CT) in five severe factor VIII deficient hemophiliacs in a randomized, cross-over study. No statistically significant differences were observed in mean half life (p greater than 0.6) or median recovery (p = 0.4) between the two preparations. No clinically significant adverse effects were observed in patients receiving either FVIII preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of hemophilia A with a highly purified factor VIII concentrate prepared by anti-FVIIIc immunoaffinity chromatography. 161 78

Two therapeutic modalities, zidovudine (targeting retroviral replication) and cyclosporin A (targeting immunopathologic consequences of retroviral expression) were evaluated in a murine model of AIDS. In previous studies, cyclosporin A treatment (40 or 60 mg/kg/day) before and after infection with LP-BM5 murine leukemia viruses protected against the development of immunodeficiency disease. The present study extends these findings. First, a low dose of cyclosporin A (20 mg/kg/day) was ineffective, and treatment initiated 5 days after infection did not protect against virus-induced lymphoproliferation and hypergammaglobulinemia. Second, zidovudine added to drinking water (0.1 mg initiated 5 days after infection and continued for 8 weeks) was more effective than 0.2 mg/mL given day 5-12 after infection. This treatment reduced lymph node size, disease severity as determined histologically, retrovirus-induced gp70 expression, and IgE (but not IgM and IgG) levels. Third, combined treatment had an additive, protective effect on lymphocyte proliferative capacity. This successful dual therapeutic strategy in a mouse model has potential applicability for similar approaches in treating human immunodeficiency virus infection.
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PMID:Effect of cyclosporin A and zidovudine on immune abnormalities observed in the murine acquired immunodeficiency syndrome. 163

Use of condoms has been advocated as an important method of reducing the risk of human immunodeficiency virus (HIV) transmission among high-risk groups such as homosexual and bisexual men, prostitutes, intravenous drug users, adolescents, and hemophiliacs. Despite risk-reduction education campaigns directed to gay men since the early 1980s, evidence shows continued deficits in condom-use skills and knowledge among gay men. Because most failures in the use of condoms are attributed to errors in use, increasing knowledge and skills in condom use is important in preventing HIV infection. Two groups of homosexual and bisexual men were sampled, those entering a risk-reduction education program and participants in a Gay Pride event. They were surveyed on their current sex practices and their efforts to reduce their risk of HIV infection. They were asked about their numbers of sex partners, specific sexual behaviors, use of condoms, types of condoms used, and lubricants used for genital-anal sex. The characteristics of those surveyed were similar to those of respondents in other studies of risk reduction among gay men. The use of an oil-based lubricant with condoms has been shown to weaken latex and to increase the likelihood of condom breakage, which use of water-based lubricants does not. Among respondents who reported having genital-anal sex, 60 percent reported use of an oil-based lubricant with a condom at least once during the year before the survey. Gay men in sexually exclusive relationships engaged in less consistent use of condoms for receptive genital-anal sex than did single gay men. The duration of their relationship with a partner was unrelated to the consistency of risk reducing behaviors practiced by men in sexually exclusive relationships. Gay Pride participants engaged in sexual behavior that was relatively more risky for HIV transmission than did the other group. Gay Pride participants used condoms less consistently for genital-anal sex than did the risk-reduction program entrants.The findings indicate the need for better risk reduction education efforts directed to gay men. Continued improvement in these efforts will require assessing the effectiveness and consistency of risk reduction efforts, determining the potential for gay men to relapse into more risky behavior, and identifying gaps in the knowledge of risk-reduction efforts among gay and bisexual men. Risk reduction programs need to emphasize motivational factors, provide basic information on how one determines the content of lubricants, explain why water-based lubricants only should be used, and teach how to use condoms properly. Active outreach is needed to gay and bisexual men who are unlikely to voluntarily enroll in risk-reduction programs.
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PMID:Inappropriate lubricant use with condoms by homosexual men. 164 45

Nosocomial pneumonias have various etiologies and their development depends mainly on the underlying condition of the patients. Intubated patients are prone to development of bacterial pneumonia from the oropharyngeal or gastric flora. Prevention relies on reducing exogenous as well as endogenous colonization of the bronchotracheal tree: avoidance of cross-contamination, maintenance of a physiological gastric pH and, possibly, selective digestive decontamination. Neutropenic patients may develop invasive aspergillus infection. Prevention depends on appropriate air filtration. Patients with cellular immunodeficiency are susceptible to various agents. Prevention of legionella depends on control of the water and ventilation systems. The prevention of cytomegalovirus infection includes the screening of blood products for certain patients and, in some cases, the administration of hyperimmune gammaglobulins and possibly ganciclovir. Even though Pneumocystis carinii pneumonia is thought to be due to reactivation, recent evidence suggests that transmission may occur between patients and therefore appropriate respiratory isolation is advisable. Finally, nosocomial tuberculosis is an increasing problem in which control depends on early diagnosis and treatment of patients as well as on appropriate air exchange in particular rooms of the hospital. In conclusion, the prevention of nosocomial pneumonia includes numerous measures which largely depend on the type of microorganisms.
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PMID:[Progress and problems in hospital infections: exemplified by pneumonia]. 165 22

Before integration of the human immunodeficiency virus (HIV) DNA, two nucleotides are removed from the 3' ends of the viral DNA by the integrase (IN) protein. We studied the chemistry of this reaction, and found that IN mediates site-specific hydrolysis of a phosphodiester bond, resulting in release of a dinucleotide. A class of alcohols (including glycerol, 1,2-propanediol, but not 1,3-propanediol) can also act as nucleophile in this reaction, and likewise the alcoholic amino acids L-serine and L-threonine can be covalently linked to the dinucleotide. No evidence was found for a covalent linkage between the IN protein and this dinucleotide, suggesting that IN directs a single nucleophilic attack of water at the specific phosphodiester bond.
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PMID:Site-specific hydrolysis and alcoholysis of human immunodeficiency virus DNA termini mediated by the viral integrase protein. 166 61

LP-BM5 MuLV infection of C57BL/6 mice induces a well characterized, lymphoproliferative, immunodeficiency disease (MAIDS), which is useful for evaluation of potential antiviral agents, because of the reproducibility of virological and clinical endpoints. This MAIDS retrovirus model was used to evaluate 3'azido-2,3'dideoxythymidine (AZT), using different doses, methods of administration and timing for initiation and continuation of therapy. AZT therapy 1 mg/ml in the drinking water given 30 days prior to virus challenge, and continued for 16 weeks, prevented LP-BM5 MuLV dissemination and disease in 13 of 15 treated mice. Efficacy was dose dependent for AZT concentrations of 1, 0.5, and 0.1 mg/ml in drinking water. One mg/ml AZT was most effective in preventing infection if therapy was begun within days prior to virus challenge or within the first four hours after virus inoculation. If treatment was initiated later, disease was delayed. Continuous infusion of AZT, 25 micrograms/h, was effective since virus was not detected in spleens of any mice during the 21 days of AZT treatment. However, after treatment was stopped treated mice became virus positive and disease progressed. Likewise, AZT administration at 1 mg/ml in the drinking water for only 21 days post virus inoculation (p.i.), was not sufficient to prevent virus dissemination or disease.
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PMID:Effect of 3'azidothymidine administered in drinking water or by continuous infusion on the development of MAIDS. 166 32

The risk of transmission of infection within the dental workplace is low, but recent data have indicated that human immunodeficiency virus transmission between dentist and patient can occur, and that while nosocomial transmission of hepatitis B virus is now less likely, a small but significant number of staff may be at risk of hepatitis C virus and varicella zoster virus infection during dental treatment. Despite these continued risks, shortcomings remain in cross-infection control in the dental workplace. Dental clinicians still fail to take adequate steps to minimize nosocomial infection, inconsistently using appropriate methods of sterilization and not providing ancillary staff with suitable protective clothing. Similarly, although vaccinated against hepatitis B virus, a substantial number of clinicians are reluctant to treat hepatitis B virus- or human immunodeficiency virus-infected patients. Cross-infection control procedures continue to be modified. Of importance, it has been confirmed that protective rubber gloves cannot be reused, as micropunctures develop during rewashing. Sharps injuries are common in dental practice, but there are still no effective measures to prevent postinjury human immunodeficiency virus or hepatitis C virus infection. Instrument sterilization is generally safe and effective, but the contamination of dental unit water supplies remains to be overcome, and while impressions can be placed in disinfectants for up to 1 hour without significant dimensional change, it is not known if infectious agents within the impression material are inactivated by this procedure.
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PMID:Infection control in dentistry. 166 10

We undertook an observational study of 1307 consecutive surgical procedures at San Francisco General Hospital to record descriptions of intraoperative exposures to blood and other body fluids, determine the factors predictive of these exposures, and identify interventions that might reduce their frequency. During a two-month period, circulating nurses took note of parenteral and cutaneous exposures to blood and recorded information about all procedures. In a follow-up validation study, 50 additional procedures were observed by the study investigators to determine the accuracy of the data collected by the nurses. A total of 960 gloves used by surgical personnel during the validation study were examined to determine the perforation rate. Accidental exposure to blood (parenteral or cutaneous) occurred during 84 procedures (6.4 percent; 95 percent confidence interval, 5.1 to 7.8 percent). Parenteral exposure occurred in 1.7 percent. The risk of exposure was highest when the procedures lasted more than three hours, when blood loss exceeded 300 ml, and when major vascular and intraabdominal gynecologic surgery was involved. Neither knowledge of diagnosed human immunodeficiency virus (HIV) infection nor awareness of a patient's high-risk status for such infection influenced the rate of exposure. Double gloving prevented perforations of the inner glove and cutaneous exposures of the hand. We conclude that all surgical personnel are at risk for intraoperative exposure to blood. Our data support the practice of double gloving and the increased use of water-proof garments and face shields to prevent mucocutaneous exposures to blood. No evidence was found to suggest that preoperative testing for HIV infection would reduce the frequency of accidental exposures to blood.
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PMID:Risk of exposure of surgical personnel to patients' blood during surgery at San Francisco General Hospital. 198 67

Human immunodeficiency virus 1 (HIV-1) reverse transcriptase has been found to conduct error-prone synthesis on DNA and RNA templates. We find here that tolerance of an A:G mispair with poly(rA) as template is particularly strong, such that extensive poly(dG) synthesis is conducted. This type of extensive misincorporation is not observed with several reference DNA polymerases. Surprisingly, HIV reverse transcriptase processivity and kcat for dGMP misincorporation and normal dTMP incorporation are about the same. However, the Km value for dGTP in poly(dG) synthesis is approximately 1000-fold higher than the Km for dTTP in poly(dT) synthesis. Comparison of thermodynamic parameters for dGMP misincorporation and normal dNMP incorporation indicates a lower energy of activation for dGMP misincorporation than for normal dNMP incorporation. Entropy of activation (delta S*) for normal dTMP incorporation is positive (approximately 10 cal/kmol), whereas delta S* for dGMP misincorporation is negative (-36 cal/kmol). Since differences in delta S* are usually considered to reflect differences in solvation for the transition state complex, these results are consistent with the interpretation that the active site of HIV reverse transcriptase is flexible enough to misincorporate dGMP without the usual dispersion of water molecules.
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PMID:Thermodynamics of A:G mismatch poly(dG) synthesis by human immunodeficiency virus 1 reverse transcriptase. 170 95


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