Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) may turn out to be the largest lethal epidemic of infection ever. The estimated global number of HIV-infected adults in 1993 was 13 million, with projections of up to 40 million by the year 2000. Human immunodeficiency virus infections and AIDS are relevant to surgeons with respect to the surgical management of AIDS patients in general, the treatment of the increasingly long list of surgical complications specific to AIDS patients in particular, and the risks of patient-to-surgeon and surgeon-to-patient HIV transmission. Because of migration of individuals and populations throughout the world, even surgeons practicing in relatively unaffected regions should be familiar with the potential surgical implications of AIDS. Ethical considerations arise, as well. Are surgeons obliged to operate on HIV-positive or AIDS patients? Some surgeons adhere strictly to the Hippocratic Oath, whereas others reserve the right to be selective on whom they operate, except in emergencies. Other common ethical considerations in the AIDS patient are similar to those arising in the terminal cancer case: whether to operate or not; whether to provide advanced support such as total parenteral nutrition or hemodialysis. Answers are not simple and require close collaboration between the surgeon, the AIDS specialist, and involved members of other specialties. Emergency operations become necessary to treat AIDS independent disease such as acute cholecystitis and appendicitis or AIDS-related life-threatening conditions such as gastrointestinal bleeding, obstruction, perforation, or ischemia complicating Kaposi's sarcoma, lymphoma, and cytomegalovirus or disseminated nontuberculous mycobacterial infections. Delays and errors in diagnosis are frequent. Poor nutritional state with weight loss, low serum albumin, and leukocyte count prevails in most patients requiring emergency operations and account for a high mortality. By applying solid judgment and selecting management appropriately, the surgeon has the ability to prolong life and to improve the quality of life for these unfortunate patients, and to do so with extremely minimal risk to himself and his team.
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PMID:AIDS, emergency operations, and infection control. 887 99

A chromatographic method for evaluation of the serum protein binding of a large number of non-peptide human immunodeficiency virus (HIV) protease inhibitors in short analysis time and automated fashion was developed. The method utilizes a size exclusion HPLC column. Bovine or human serum albumin is added to the mobile-phase running buffer. Qualitatively, a shift to shorter drug retention time in the presence of protein in the mobile phase is indicative of binding interaction of the drug and protein. The extent of binding of the drug to the protein is quantitated by comparison of the shift in retention time in the presence of protein to the retention time of the drug in the same buffer in the absence of protein (i.e., the drug's "intrinsic" retention time on the column). Binding measurements were carried out a 37 degrees C with a temperature-controlled autosampler and column oven. Results were compared with those obtained by ultrafiltration. The method yields thermodynamically valid binding measurements and is capable of directly detecting differences in the protein binding of individual stereoisomers present in mixtures (either enantiomers or diastereomers) without prior purification of the individual stereoisomers. The method measures overall binding to albumin and is not binding-site specific. Because of this, quantitative comparison of the extent of albumin binding of drugs which bind to the same site, different sites, or nonspecifically (i.e., not at discrete sites) is possible.
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PMID:Chromatographic measurement of drug-protein interaction: determination of HIV protease inhibitor-serum albumin association. 895 26

The binding characteristics of KNI-272, a potent and selective human immunodeficiency virus (HIV) protease inhibitor, were evaluated in rat and human plasma, and in solutions of human alpha 1-acid glycoprotein (AAG) and human serum albumin (HSA). The unbound fractions (Fu) of KNI-272 were 12.13 and 2.24% in rat and human plasma, respectively, at the drug concentration of 1.0 microgram mL-1. Although KNI-272 binds to both AAG and HSA, the Fu of KNI-272 in AAG solution was 1.83%, and only one-quarter of that in HSA solution (Fu = 6.78%). Binding displacing agents, such as disopyramide, warfarin, diazepam, and digitoxin, were used to determine the binding site of KNI-272 on these plasma proteins. The Fu of KNI-272 in AAG solution increased 14-fold when disopyramide was added to the AAG solution. In addition, warfarin, diazepam, and digitoxin were added to HSA solution as representative drugs bound to distinct binding sites on HSA, namely sites I, II, and III, respectively. The Fu values of KNI-272 in HSA solution significantly increased when warfarin and diazepam were added. In particular, with the addition of warfarin to HSA solution, the Fu of KNI-272 increased to 16%. The modified Scatchard plots of KNI-272 binding to AAG and HSA both showed biphasic curves, and the KNI-272 binding sites at low concentration range on AAG and HSA disappeared with the addition of disopyramide and warfarin, respectively. Therefore, it is considered that KNI-272 binds to the identical site as disopyramide on AAG and site I on HSA in the low KNI-272 concentration range. By comparing the KNI-272 binding parameters obtained in human plasma and these protein solutions, we can assume that KNI-272 binding at low concentration in human plasma is mainly concerned with the binding on AAG. As KNI-272 concentration in plasma increases, HSA becomes concerned with KNI-272 binding.
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PMID:Binding characteristics of KNI-272 to plasma proteins, a new potent tripeptide HIV protease inhibitor. 896 27

Negatively charged albumins (NCAs, with the prototypes succinylated human serum albumin (Suc-HSA) and aconitylated human serum albumin (Aco-HSA)), modified proteins with a potent anti-human immunodeficiency virus type 1 (anti-HIV-1) activity in vitro, were studied for their pharmacokinetic behaviour in mice and their in vivo anti-HIV-1 efficacy in an HIV-1 infection model in mice. In contrast to the saturation kinetics found in rats, intravenous injections of 10-300 mg/kg for both NCAs showed a linear correlation between the area under the curve (AUC) and the dose. The elimination t1/2 was 25 and 30 min for Suc-HSA and Aco-HSA, respectively. Preinjections of an excess of formaldehyde-treated albumin (Form-HSA) resulted in plasma levels that were 3- and 4-fold higher for Aco-HSA and Suc-HSA, respectively. These data indicate that elimination is at least partly (scavenger) receptor-mediated. Organ distribution studies 10 min after injection showed an accumulation in liver (Suc-HSA 17.3 +/- 6.6% of the dose; Aco-HSA 20.9 +/- 2.3%) and lungs (Suc-HSA 12.7 +/- 10.5%; Aco-HSA 16.0 +/- 13.6). Intraperitoneal injection of 300 mg/kg Suc-HSA resulted in a final bioavailability of about 0.45. Suc-HSA was also evaluated for its in vivo neutralizing capacity in a human-to-mouse chimeric model for HIV-1 infection. Intraperitoneal injections of 300 and 3 mg/kg Suc-HSA, given 15-30 min before the mice were challenged with the virus, sufficed to protect these mice against infection with the HIV-1 IIIB strain.
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PMID:Pharmacokinetics and anti-HIV-1 efficacy of negatively charged human serum albumins in mice. 902 Oct 51

We conducted a nonconcurrent prospective cohort study to examine associations between serum concentrations of vitamin B-6, vitamin B-12 and folate and the risk of progression to first acquired immunodeficiency syndrome (AIDS) diagnosis and CD4+ cell decline to < 2 x 10(8) cells/L. The study population was drawn from a cohort of homosexual and bisexual men in the Baltimore-Washington, DC, area. Eligible subjects were human immunodeficiency virus type 1 (HIV-1)-seropositive at study entry and had serum available in the serum repository from their 1984 baseline study visit. Serum micronutrient levels were assessed in 310 subjects. The follow-up period (April 1984 through December 1993) was approximately 9 y. In Kaplan-Meier analyses, participants with low serum vitamin B-12 concentrations (< 120 pmol/L) had significantly shorter AIDS-free time than those with adequate vitamin B-12 concentrations (median AIDS-free time = 4 vs. 8 y, respectively, P = 0.004). This effect persisted in Cox proportional hazards models after adjusting for HIV-1-related symptoms, CD4+ cell count, age, serum albumin, use of antiretroviral therapy before AIDS, frequency of alcohol consumption and serum folate concentration [relative hazard (RH) = 1.89, 95% confidence interval (CI) = 1.15-3.10). To further explore the temporal relation between low serum vitamin B-12 concentrations and disease progression, additional analyses were performed excluding subjects with more advanced disease at baseline. In these analyses, the increase in risk of progression to AIDS for those with low serum vitamin B-12 concentrations remained significant (RH = 2.21, 95% CI = 1.13-4.34), providing further evidence that low vitamin B-12 concentrations preceded disease progression. In contrast, low serum concentrations of vitamin B-6 and folate were not associated with either progression to AIDS or decline in CD4+ lymphocyte count. Intervention studies are needed to determine whether correction of low serum vitamin B-12 concentrations in early HIV-1 infection will influence the natural history of disease progression.
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PMID:Low serum vitamin B-12 concentrations are associated with faster human immunodeficiency virus type 1 (HIV-1) disease progression. 903 38

We conducted a cross-sectional survey to determine the relative course of patients with end-stage renal disease (ESRD) and human immunodeficiency virus (HIV) infection sustained on maintenance hemodialysis. All 34 patients with ESRD and HIV infection receiving hemodialysis in one hospital-based and three community-based outpatient hemodialysis facilities in Brooklyn, NY, were studied. We documented their known duration of HIV infection, duration of ESRD, and hemodialysis prescription, and noted the presence of clinical acquired immunodeficiency syndrome (AIDS). Total CD4 count, serum albumin concentration, and percent reduction of urea (predialysis blood urea nitrogen minus postdialysis blood urea nitrogen, divided by predialysis blood urea nitrogen x 100) were measured. The 34 study subjects (26 men and eight women) included 31 blacks (91%) and three Hispanics (9%) with a mean age of 42 +/- 7.5 years, 29 (85%) of whom had AIDS. Twenty subjects (59%) had a history of intravenous drug abuse. Only six subjects (18%) were receiving an antiretroviral drug (zidovudine = five, dideoxyinosine = one). In 23 subjects (68%), AIDS was diagnosed prior to ESRD and was presumed to be the cause of renal failure (HIV-associated nephropathy). The mean known duration of HIV infection was 50.5 +/- 34 months (median, 48 months); the mean duration of ESRD was 57 +/- 50 months, the mean total CD4 count was 140 +/- 150 cells/microL (median, 70 cells/microL), the mean hematocrit was 28% +/- 5%, and the mean serum albumin concentration was 3.5 +/- 0.37 g/dL. All subjects were receiving erythropoietin for anemia correction. The mean length of the prescribed thrice-weekly hemodialysis sessions was 3.5 +/- 0.4 hours. Our results suggest that the survival of many ESRD patients with HIV infection receiving hemodialysis has improved compared with the uniformly dismal survival rate reported in the 1980s. Decisions on whether to initiate renal replacement therapy in patients with AIDS and advanced renal failure should be individualized because the combination of ESRD and HIV infection does not necessarily signal near-term death.
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PMID:Uremia therapy in patients with end-stage renal disease and human immunodeficiency virus infection: has the outcome changed in the 1990s? 910 43

Kaposi's sarcoma (KS)-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV-8) may play an etiologic role in the pathogenesis of KS. In an attempt to assess KSHV/HHV-8 infection, an ELISA was developed using an 18-amino acid peptide from a putative minor capsid protein of KSHV/HHV-8 conjugated to bovine serum albumin. Overall, sera from human immunodeficiency virus type 1 (HIV-1)-positive patients with KS had a higher reactivity in the assay than did sera from HIV-1-positive patients without KS (P = .018). Of 35 HIV-1-positive patients with KS, 60% were antibody positive, compared with 27% of 33 HIV-1-positive patients without KS. Of 30 healthy blood donors, 20% were antibody positive. The ELISA responses did not correlate with antibody titers to Epstein-Barr virus. Given the homology and antigenic relatedness between KSHV/HHV-8 and Epstein-Barr virus, serologic assays involving unique KSHV/HHV-8 peptides may prove to be valuable in defining the epidemiology and clinical expression of this virus.
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PMID:Detection of serum antibodies to a Kaposi's sarcoma-associated herpesvirus-specific peptide. 912 68

We evaluated 85 human immunodeficiency virus (HIV)-negative patients with tuberculosis for clinical features and CD4 cell counts. Thirty-seven patients had low CD4 cell counts (mean +/- SD, 341 +/- 116 cells/microL), and 48 patients had normal CD4 cell counts (mean +/- SD, 830 +/- 254 cells/microL). CD4 cell counts were most strongly correlated with total lymphocyte counts (r = 0.84). If total lymphocyte count was excluded, depressed CD4 cell counts were significantly associated with low serum albumin levels, extensive pulmonary disease, low body-mass index, and low hematocrit. Of these four variables, multivariate linear discriminant analysis revealed that the serum albumin level was the best single predictor of low CD4 cell counts and that the other three variables did not improve predictive value. Because these four variables are markers of severe tuberculosis, these findings suggest that disease severity is associated with greater depression of the total lymphocyte and CD4 cell counts. The CD4 cell counts returned to normal levels in most patients after 1 month of therapy.
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PMID:CD4 cell counts in human immunodeficiency virus-negative patients with tuberculosis. 914 8

Succinylated human serum albumin (Suc-HSA) was synthesized by treating human serum albumin with succinic anhydride. Among similar proteins and neo(glyco)proteins tested, Suc-HSA exhibits a pronounced net negative charge, a feature that largely contributes to its efficacy against replication of human immunodeficiency virus type 1 (HIV-1). To assess further the antiviral effect of Suc-HSA, the effect on HIV-1 replication was studied in the presence of whole human plasma. Pretreatment of MT2 cells with Suc-HSA was more efficacious than direct Suc-HSA treatment of HIV prior to addition to the cells. No changes in the antiviral effect of Suc-HSA were observed in tissue culture medium, 30% plasma, or whole plasma when CPDA-1 (citrate-phosphate-dextrose-adenine 1) was used as the anticoagulant. However, a dramatic decrease (greater than 99%) in the antiviral activity was observed when these experiments were performed in plasma prepared from blood using heparin as anticoagulant. The antagonistic effect by heparin was observed both in the case that heparin was added prior to or after addition of Suc-HSA to the test system. In the present study we demonstrate that heparin largely reduces Suc-HSA activity on HIV replication in the same concentration in which if affects binding of Suc-HSA to the envelope protein gp120 and in particular its V3 domain. In the same concentration range, heparin reduced binding of Suc-HSA to MT4 cells, another HTLV-I-transformed cell line. It is concluded that heparin can displace Suc-HSA from its binding sites on hybrid lymphoid cells as well as on HIV-1 particles. Therefore, we conclude that both the binding to cells and to virus contribute to the potent anti-HIV-1 effect. The fact that heparin and heparin degradation products antagonize Suc-HSA without having a significant anti-HIV-1 effect indicates that the anticoagulant acts as a relatively weak partial inhibitor.
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PMID:The in vitro anti-HIV efficacy of negatively charged human serum albumin is antagonized by heparin. 916 36

Anionic charge-modified human serum albumin (HSA) has previously been shown to exert potent in vitro activity against human immunodeficiency virus type 1 (HIV-1). In these studies, introduction of the additional negative charges was performed by derivatizing the epsilon-amino groups of lysine residues with succinic (Suc-HSA) or cis-aconitic anhydride (Aco-HSA), by which primary amino groups are replaced with carboxylic acids. The anti-HIV-1 activity was related to inhibition of gp41-mediated membrane fusion. Here, we investigated the activity of aconitylated and succinylated proteins on influenza virus membrane fusion, which is mediated by the viral membrane glycoprotein hemagglutinin (HA). Aco-HSA and Suc-HSA markedly inhibited the rates and extents of fusion of fluorescently labeled virosomes bearing influenza HA, with target membranes derived from erythrocytes. The inhibitory activity was dependent on the overall negative-charge density; HSA modified with 36 or less extra negative charges failed to inhibit fusion. The inhibition of fusion showed a certain degree of specificity for the protein carrying the negative charges: polyanionic HSA and beta-lactoglobulin A derivatives had fusion-inhibitory activity, whereas succinylated BSA, lactalbumin, lactoferrin, lysozyme, and transferrin were inactive. Aco60-HSA and Aco-beta-lactoglobulin A inhibited influenza virus membrane fusion in a concentration-dependent manner, IC50 values being about 4 and 10 microg/mL, respectively. HA-mediated membrane fusion is pH dependent. Aco60-HSA did not induce a shift in the pH threshold or in the pH optimum. Fusion with liposomes of another low pH-dependent virus, Semliki Forest virus, was not specifically affected by any of the compounds reported here. In view of some structural and functional similarities between influenza HA and the HIV-1 gp120/gp41 complex, it is tempting to postulate that the current results might have some implications for the anti-HIV-1 mechanism of polyanionic proteins.
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PMID:Inhibition of influenza virus fusion by polyanionic proteins. 917 13


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