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)

Twenty-four patients with human immunodeficiency virus (HIV) infection were investigated for possible changes in certain indole amine constituents in blood and cerebrospinal fluid (CSF). Albumin in serum was determined and used as a rough nutritional marker. Six of the 24 patients had acquired immunodeficiency syndrome AIDS, four had other clinical symptoms of HIV infection, and 14 had no apparent symptoms. The HIV-seropositive patients had significantly decreased tryptophan values; their blood concentrations were 28% lower and their CSF concentrations 30% lower than corresponding values in 14 healthy controls. The blood concentrations of 5-hydroxytryptamine (5-HT) were 50% lower, and the platelet content of 5-HT was 36% lower in HIV-infected individuals than in the control group. The most pronounced changes were invariably seen in the six cases with AIDS and in patients with a low number of CD4+ cells. No significant difference between controls and HIV-seropositive patients was detected in the mean CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), although these levels were markedly reduced in four of the HIV patients. Neither was any significant difference seen between patients and controls in the serum concentrations of albumin.
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PMID:Indole amine deficiency in blood and cerebrospinal fluid from patients with human immunodeficiency virus infection. 247 44

The Wiskott-Aldrich syndrome is an immune deficiency disorder with an impairment of both humoral and cellular immune responses. Metabolic turnover studies of IgG, IgA, IgM, and albumin were conducted in seven patients with the Wiskott-Aldrich syndrome using purified radioiodinated proteins. The survival of each of the proteins studied was significantly shortened with a half-time of 7.5 days for IgG (normal 22.9 +/-4 SD), 3.0 days for IgA (normal 5.8 +/-1), 5.0 days for IgM (normal 10.1 +/-2.1), and 8.6 days for albumin (normal 17, range 13-20); the fractional catabolic rates were correspondingly elevated and the distribution of protein among the body compartments was normal. For three of the four proteins. IgG, IgA, and albumin, the steady-state synthetic rates were generally elevated leading to normal or even elevated serum proteins levels. Thus, in the case of IgA, the synthetic rate averaged five times normal while the fractional degradative rate was twice normal. The resulting serum concentration was, therefore, significantly elevated, IgM represented an exception to this pattern in that the increased rate of degradation was not counterbalanced by an increased synthetic rate and, therefore, the serum levels were low. Albumin clearance studies using albumin-(51)Cr showed gastrointestinal protein loss in these patients to be slightly greater than normal, but this could account for only a small fraction of the hypercatabolism observed. There was no proteinuria or abnormalities of thyroid, adrenal, renal, or liver function. Thus, none of the previously recognized causes of increased serum protein catabolism were present. Patients with the Wiskott-Aldrich syndrome, therefore, have a unique disorder of serum protein metabolism characterized by endogenous hypercatabolism of at least four major serum proteins. This phenomenon may be related to reticuloendothelial hyperfunction since the Wiskott-Aldrich syndrome is associated with reticuloendothelial hyperplasia and accelerated clearance of colloidal materials from the plasma.
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PMID:Hypercatabolism of IgG, IgA, IgM, and albumin in the Wiskott-Aldrich syndrome. A unique disorder of serum protein metabolism. 509 17

We prepared a series of modified proteins and peptides by derivatizing the positively charged epsilon-amino groups of the lysine amino acids through reaction with anhydrides of succinic acid (Suc) and aconitic acid (Aco). Human serum albumin (HSA) was modified by introduction of a single carboxylic group (Suc-HSA) or two carboxylic groups (Aco-HSA) per amine function, yielding strongly negatively charged compounds. The in vitro anti-human immunodeficiency virus (HIV)-1 IC50 of Suc-HSA was about 1 microgram/ml, and the most polyanionic modified albumin of the series (Aco-HSA) exhibited an IC50 as low as 0.02 microgram/ml. Similar derivatization of the plasma protein orosomucoid or the synthetic polypeptide polylysine did not produce compounds with significant anti-HIV-1 activity, indicating an HSA-specific effect. The mechanism of action of Suc-HSA was reported to be the inhibition of a post-binding virus-cell fusion event, probably due to interference with the gp41-mediated fusion process. In the present study we demonstrate that the more potent Aco-HSA also interferes with this fusion process but, additionally, this compound inhibits (i) the binding of soluble CD4 to HIV-infected cells, (ii) the binding of HIV particles to MT-4 cells, and (iii) the binding of anti-gp120 monoclonal antibody to the gp120 molecule. This indicates that Aco-HSA, apart from post-binding fusion, also inhibits virus-cell binding by shielding viral gp120. The simultaneous inhibition of binding and fusion may lead to a synergistic effect, explaining the extreme potency of Aco-HSA. The polyanionic HSAs are significantly less active against HIV-2 and do not interfere with the replication of feline immunodeficiency virus or 12 other DNA or RNA viruses, indicating a HIV-1-specific effect. In contrast, another polyanionic compound, the sulfated polysaccharide dextran sulfate, inhibits the replication of various viruses in a more nonspecific way, as a general polyanion. Dextran sulfate also exhibits strong anticoagulant activity, whereas Suc-HSA and Aco-HSA do not show this unwanted side effect.
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PMID:Novel, negatively charged, human serum albumins display potent and selective in vitro anti-human immunodeficiency virus type 1 activity. 790 28

This investigation retrospectively studied relationships between survival in human immunodeficiency virus-seropositive outpatients receiving recent therapies (n = 77) and two markers of nutritional status, serum albumin and percent of usual body weight. Subjects were observed for an average of 186 +/- 8 days; 19% died within the study period. Kaplan-Meier curves and Cox regressions showed that older subjects who had lower CD4 counts, lower albumin levels, or had lost more weight demonstrated poorer survival. Albumin levels and weight loss were related to CD4 counts. The relative risk of death for subjects with low albumin levels (< 3.5 g/dl) was 3.6 times greater (p < 0.021, with 95% confidence limits [95%CL] of 1.2-10.9) than that for subjects with normal albumin levels (> or = 3.5 g/dl), even after controlling for age and CD4 counts. Similarly, after controlling for CD4 counts and age, subjects whose baseline body weights were < 90% of their usual weight had a greater relative death risk (8.3 times greater, p < 0.002, 95% CL 2.3-34.1) than those who had lost less. Survivors and nonsurvivors who had similar CD4 counts differed significantly in albumin levels (p < 0.05). Thus, nutritional status influences survival independent of CD4 counts.
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PMID:Relationships among nutritional status, disease progression, and survival in HIV infection. 810 73

Human serum albumin (HSA) derivatized with cis-aconitic anhydride (Aco-HSA) that was earlier shown to inhibit replication of human immunodeficiency virus type 1 (HIV-1), was covalently coupled to conventional liposomes, consisting of phosphatidylcholine, cholesterol and maleimido-4-(p-phenylbutyryl)phosphatidylethanolamine, using the heterobifunctional reagent N-succinimidyl-S-acetylthioacetate (SATA). The amount of HSA that could be coupled to the liposomes depended on derivatization of the HSA and ranged from 64.2 +/- microgram HSA/micromol total lipid for native HSA to 29.5 +/- 2.7 microgram HSA/micromol total lipid for HSA in which 53 of the epsilon amino groups of lysine were derivatized with cis-aconitic anhydride (Aco53-HSA). Incorporation of 3.8 mol% of total lipid of a poly(ethylene glycol) derivative of phosphatidylethanolamine (PEG-PE) in the liposomes resulted in a lower coupling efficiency of Aco-HSA. The elimination and distribution of the liposomal conjugates in rats in vivo was largely dependent on the modification of the HSA coupled to the liposomes. With native HSA-liposomes, more than 70% of the conjugate was still found in the blood plasma 30 min after i.v. injection in rats, while at this time Aco-HSA-liposomes were completely cleared from the circulation. The rapid clearance of conventional Aco-HSA-liposomes was due to a rapid uptake into the liver and could be considerably decreased by incorporating PEG-PE in the liposomal bilayer. After 3 h 60% of Aco-HSA-PEG-liposome conjugates were found in the blood. In an in vitro anti-HIV-1 assay, the 50% inhibitory concentrations (IC50) for Aco39-HSA-liposomes and Aco53-HSA-liposomes expressed as protein weight, were 2.87 microgram/ml and 0.154 microgram/ml, respectively. When PEG-PE was incorporated, the Aco53-HSA-liposomes retained anti HIV-1 activity (IC50:3.13 microgram/ml). The possibility to modulate the residence time in the bloodstream of Aco-HSA-liposomes and the potent anti-HIV-1 activity of these conjugates, may allow the development of an intrinsically active drug carrier system. By incorporating anti HIV-1 drugs such as AZT into such liposomes a drug delivery system can be designed that might act simultaneously on the virus/cell binding by virtue of the coupled Aco-HSA and on the RNA/DNA transcription of the HIV-1 replication cycle through the nucleoside analogue.
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PMID:Preparation and characterization of conjugates of (modified) human serum albumin and liposomes: drug carriers with an intrinsic anti-HIV activity. 859 75

Loss of lean tissue often accompanies human immunodeficiency virus (HIV) infection. Exogenous human recombinant GH (hrGH) has been shown to be beneficial in reversing this wasting. However, catabolic effects of hrGH on muscle protein metabolism have also been reported. Therefore, the responsiveness of other GH-sensitive tissues, including bone formation and albumin synthesis, has been examined. Anabolic activity in bone, from serum levels of carboxy-terminal propeptide of type I collagen, was stimulated by 2 weeks of hrGH in controls (56 +/- 15%, P = 0.002), patients with asymptomatic HIV (24 +/- 10%, not significant), patients with AIDS (47 +/- 7%, P < 0.001), and patients with AIDS and > 10% weight loss (21 +/- 12%, P = 0.02). Albumin synthesis, determined from the incorporation of L-[2H5]phenylalanine, was increased in response to hrGH in controls (23 +/- 7%, P < 0.05), HIV+ subjects (39 +/- 16%, P < 0.05), and patients with AIDS (25 +/- 7%, P < 0.01). Patients with AIDS and weight loss, however, did not increase albumin synthesis (-0.6 +/- 12%) in response to hrGH. The results indicate variable anabolic responses to hrGH. Bone collagen synthesis remained sensitive to hrGH, whereas, the anabolic action of hrGH on the synthesis of albumin diminished with severity of disease. However unlike muscle protein synthesis, albumin synthesis was not depressed below basal levels by hrGH.
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PMID:Albumin synthesis and bone collagen formation in human immunodeficiency virus-positive subjects: differential effects of growth hormone administration. 974 2

The thymidine analog 3'-azido-3'-deoxythymidine (AZT) is still one of the effective drugs against human immunodeficiency (HIV) infection. AZT has been used as inhibitor of HIV-1 reverse transcriptase, the virus encoded enzyme which catalyzes transcription of viral RNA to DNA. The drug interaction with protein has been included in its mechanism of action. Human serum albumin (HSA) is a carrier of many drugs in vivo and thus AZT-HSA complexation can serve as a model for drug-protein interaction. This study was designed to examine the interaction of AZT with human serum albumin at physiological conditions using constant protein concentration (0.2% or 2%) and different drug contents (5 to 1000 microM). Capillary electrophoresis, FTIR and CD spectroscopic methods were used to determine the drug binding mode, the drug binding constant and the effects of drug-HSA complexation on the protein and AZT conformations in aqueous solution. Capillary electrophoresis and spectroscopic results showed two major bindings for the AZT-HSA complexes with K(1)=1.9 x 10(6) M(-1)and K(2)= 2.1 x 10(4) M(-1). Minor alterations of the protein secondary structure from that of the alpha-helix to beta-sheet were observed upon drug complexation, whereas the drug sugar pucker remained in the C2'-endo/anti conformation upon protein interaction.
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PMID:Interaction of AZT with human serum albumin studied by capillary electrophoresis, FTIR and CD spectroscopic methods. 1202 3

The aim of the present prospective study was to determine if malnutrition, measured using a simple validated score, is an independent risk factor for nosocomial infections (NI) in non-selected hospital in-patients. Between 29 and 31 May 2001, a survey on the prevalence of NI was conducted on all 1637 in-patients (61 (SD 25) years old) in a French university hospital as part of a national survey. Actual and usual body weights were recorded in all in-patients, and serum albumin levels were measured on all blood samples taken during the week before the study. Nutritional status was evaluated by using the nutritional risk index (NRI). Albumin values were obtained in 1084 patients, and complete weight information was obtained in 911. Therefore, NRI was calculated in 630 patients (61 (SD 20) years old): 427 (67.8 %) were malnourished. NI prevalence was 8.7 %: 4.4 % in non-malnourished patients, 7.6 % in moderately malnourished patients and 14.6 % in severely malnourished patients. In univariate analysis, the odds ratios for NI were 1.46 (95 % CI 1.2, 2.1) in moderately malnourished patients and 4.98 (95 % CI 4.6, 6.4) in severely malnourished patients. In multivariate analysis, age, immunodeficiency and NRI class influenced NI risk. Vascular and urinary catheters, and surgical intervention, were the extrinsic factors associated with NI, with odds ratios ranging from 2.0 (95 % CI 1.8, 2.6) for vascular catheters to 10.8 (95 % CI 8.8, 12.6) for association of the three factors. In conclusion, in non-selected hospitalized patients, malnutrition assessed with a simple and objective marker is an independent risk factor for NI. An early screening for malnutrition may therefore be helpful to reduce the high prevalence of NI.
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PMID:Malnutrition is an independent factor associated with nosocomial infections. 1523 Sep 93

Human serum albumin (HSA) has an extraordinary ligand-binding capacity, and transports Fe(III)heme and medium- and long-chain fatty acids. In human immunodeficiency virus-infected patients the administered drugs bind to HSA and act as allosteric effectors. Here, the binding of Fe(III)heme to HSA in the presence of three representative anti-HIV drugs and myristate is investigated. Values of the dissociation equilibrium constant K(d) for Fe(III)heme binding to HSA were determined at different myristate concentrations, in the absence and presence of anti-HIV drugs. Nuclear magnetic relaxation dispersion profiles of HSA-Fe(III)heme were measured, at different myristate concentrations, in the absence and presence of anti-HIV drugs. Structural bases for anti-HIV drug binding to HSA are provided by automatic docking simulation. Abacavir and nevirapine bind to HSA with K(d) values of 1 x 10(-6) and 2 x 10(-6) M, respectively. Therefore, at concentrations used in therapy (in the 1-5 x 10(-6) M range) abacavir and nevirapine bind to HSA and increase the affinity of heme for HSA. In the presence of abacavir or nevirapine, the affinity is not lowered by myristate. FA7 should therefore be intended as a secondary binding site for abacavir and nevirapine. Binding of atazanavir is limited by the large size of the drug, although preferential binding may be envisaged to a site positively coupled with FA1 and FA2, and negatively coupled to FA7. As a whole, these results provide a foundation for the comprehension of the complex network of links modulating HSA-binding properties.
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PMID:Modulation of heme and myristate binding to human serum albumin by anti-HIV drugs. An optical and NMR spectroscopic study. 1772 15

Acquired Immunodeficiency Syndrome (AIDS) is the final and most serious stage of the disease caused by human immunodeficiency virus. The Immune system is the target of AIDS. We investigate presently any possible involvement of thyroid hormone, the deficiency of which gives rise to oedema and susceptibility to nonspecific infections; with a view to finding the primary factor seeding the disease. It has been reported that circumcision reduced the incidence of HIV/AIDS infection. Beyond circumcision however there might be some constitutional factor that comprises HIV infection to clinical AIDS. It is against this background that our research team turned to possible dyshormonopoisis and to thyroid hormone as a prime suspect among other possible factors that cause clinical AIDS. Moreover the hormone has been reported to be crucial for optimum immune function. A population of 200 seropositive AIDS patients were investigated against a control of 50 subjects made up of 25 healthy circumcised males and 25 healthy females; all of who were seronegative for the disease. The parameters investigated include thyrotropin (TSH), Thyroxine (T4), Total protein (TP), Albumin (Alb), Globulin (Glob), Immune complex (IC3) and Bence Jones proteins (BJP) levels in serum or urine. All seropositive clinically HIV/AIDS patients were hypothyroid. Seronegatives had significantly higher T4, TP, and Alb levels at P < 0.001 and P < 0.05 for Glob than seropositives. Seropositive females exhibited significant (P < 0.001) higher levels of IC3 than seronegative males. The globulin levels of all HIV patients were significantly (P < 0.05) higher than control. BJP was also isolated in the urine of patients. The findings suggest that thyroid hormone deficiency is a primary culprit for the other inert or dormant factors to be activated.
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PMID:Thyroid hormone: a "prime suspect" in human immunodeficiency virus (HIV/AIDS) patients? 1943 16


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