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)

A new inhibitor of human immunodeficiency virus (HIV) has been isolated and purified to homogeneity from the seeds and fruits of the Momordica charantia. This compound, MAP 30 (Momordica Anti-HIV Protein), is a basic protein of about 30 kDa. It exhibits dose-dependent inhibition of cell-free HIV-1 infection and replication as measured by: (i) quantitative focal syncytium formation on CEM-ss monolayers; (ii) viral core protein p24 expression; and (iii) viral-associated reverse transcriptase (RT) activity in HIV-1 infected H9 cells. The doses required for 50% inhibition (ID50) in these assays were 0.83, 0.22 and 0.33 nM, respectively. No cytotoxic or cytostatic effects were found under the assay conditions. These data suggest that MAP 30 may be a useful therapeutic agent in the treatment of HIV-1 infections. The sequence of the N-terminal 44 amino acids of MAP 30 has been determined.
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PMID:MAP 30: a new inhibitor of HIV-1 infection and replication. 169 1

The use of the nonparametric expectation maximization (NPEM2) program to estimate pharmacokinetic parameters of ganciclovir in a group of patients with human immunodeficiency virus (HIV) and cytomegalovirus (CMV) infection was evaluated. A 10-point data set per patient obtained over 8 hours was analyzed. Mean pharmacokinetic parameters obtained included rate constant from the central to the peripheral compartment (KCP,3.1 hr-1), rate constant from the peripheral to the central compartment (KPC, 0.824 hr-1), slope of the volume of distribution to body weight (VS, 0.246 L/kg), and slope of clearance to creatinine clearance (Cl(cr)) and body weight (CLS,0.222L/hr/kg/100 mL/ min Cl(cr). Use of NPEM2 led to identification of a subset of patients with CMV retinitis who had a more rapid clearance of ganciclovir of 0.51 to 0.54 L/hr/kg/100 mL/min Cl(cr). Use of smaller, optimally timed samples of five, four, and three data points per patient produced mean pharmacokinetic parameter results consistent with the full ten-point data set. When Bayesian-derived parameter estimates using a five-point data set were compared with a traditional, nonlinear, least-square analysis of the entire ten-point data set, estimates of clearance were determined to be relatively unbiased and precise. The ability of NPEM2 to estimate pharmacokinetic parameters and to determine the population distribution of the parameters was demonstrated. By using points in the analysis chosen by D-optimal design theory, NPEM2 was able to give consistent parameter estimates with as few as three data points. Determination of the distribution appeared to have been dependent on the time points used, however. The approach of MAP-Bayesian analysis to derive patient-specific estimates using optimal samples and prior estimates from a previous population pharmacokinetic analysis for inclusion in subsequent pharmacodynamic analyses of drug exposure (area under the concentration-time curve) may enable development of exposure-response and exposure-toxicity relationships.
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PMID:Nonparametric expectation maximization population modeling of ganciclovir. 872 43

The third variable region (V3) of the feline immunodeficiency virus (FIV) surface glycoprotein is predicted to have similar physical properties to that of HIV and has been shown to contain immunodominant and neutralizing epitopes. Immunological characteristics of this region were investigated further using a peptide corresponding to the middle of the putative FIV V3 loop. The peptide was recognized in ELISA by sera from the majority of naturally FIV-infected cats, and absorbed a significant fraction of the virus neutralizing activity from a pool of sera of cats naturally infected with FIV, confirming the immunogenic nature of this region. A sheep immunized with an octameric form of the peptide (multiple antigenic peptide; MAP) in Freund's complete adjuvant generated neutralizing antibody to a higher titre than infected cats. However, immunization of cats with the same MAP in an acceptable adjuvant formulation (Quil A) induced antibody and cytotoxic T-cell responses to the immunizing peptides but only minimal neutralizing activity. These responses did not significantly alter the kinetics of infection or the proviral load after challenge with a homologous strain of FIV, compared with naive controls. While the potential efficacy of peptide vaccines to lentiviruses remains to be determined, this study shows that the immune response evoked may be highly dependent on the delivery and adjuvant regime used.
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PMID:Immunogenicity of a peptide from a major neutralising determinant of the feline immunodeficiency virus surface glycoprotein. 891 Oct 3

Nine pediatric symptomatic patients infected with human immunodeficiency virus with elevated pulmonary arterial pressure (MPA pressure) and ejection fraction (EF); and with fractional shortening, (FS) mean velocity of circumferential fiber shortening (MVCfc) and left ventricular peak systolic wall stress (PS) were prospectively evaluated using 2-dimensional and M-mode serial echocardiography and Doppler cardiography after administration of an ACE inhibitor (Inhibace 0.025 mg/kg/D orally) for 12 weeks. The MPA pressure was not decreased, however the MVCfc and PS improved significantly (p < 0.05). Further, long term evaluation is required to determine its effect in preventing dilated cardiomyopathy and elevated mean pulmonary pressure.
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PMID:Ventricular functions in children with human immunodeficiency virus infection after ACE-inhibitors. 944 24

The time course of intensive care for severe respiratory syncytial virus (RSV) lower respiratory tract illness may be predicted by the severity of gas exchange during the first 48 h of mechanical ventilation. To test this hypothesis, two studies were undertaken in RSV-positive mechanically ventilated patients who did not have chronic lung disease, congenital heart disease or immunodeficiency. First, a retrospective criteria-generating review of 45 infants was carried out. In these infants, more severe lower airway disease, as demonstrated by four-quadrant consolidation on chest X-ray, was associated with 'best' alveolar arterial oxygen gradients (AaDO2, torr) and mean airway pressure (MAP, cm H2O) values as follows: first 24h, AaDO2 > 400 and MAP > 10 (positive and negative predictive values 100% and 97%, respectively); second 24 h, AaDO2 > or = 300 and MAP > 10 (positive and negative predictive values 91% and 100%, respectively). The second study, a prospective, hypothesis-testing, analysis of length-of-stay in 44 infants stratified according to the above AaDO2 and MAP criteria demonstrated that the duration of intensive care was longer in the severe group: median (interquartile range in days) 17 (15-39) vs 7 (4-8) (p < 0.01). We suggest that, in mechanically ventilated infants with RSV, the time course of intensive care is predictable based on early clinical features and respiratory parameters. Therefore reports on the effectiveness of special therapies using intensive care stay as a measure of outcome should be interpreted with respect to these observations before drawing conclusions about efficacy.
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PMID:Time course of severe respiratory syncytial virus infection in mechanically ventilated infants. 1097 23

CXC chemokine receptor 4 (CXCR4) is a co-receptor for human immunodeficiency virus (HIV) infection and is believed to be involved in the pathogenesis of AIDS-associated neurologic disorders and brain tumors. The physiological roles of CXCR4 in developmental patterning of the nervous and hematopoietic system; gastrointestinal angiogenesis; and cardiac organogenesis were established by studies in gene-targeted mice. Studies on CXCR4 expression and regulation in neuroepithelial cells are fundamental for understanding its physiopathologic roles in the central nervous system (CNS). We show here that CXCR4 expression by primary mouse astrocytes is suppressed by exposure to tumor necrosis factor-alpha (TNF-alpha). TNF-alpha caused a pronounced down-regulation of CXCR4 mRNA in a dose- and time-dependent manner. TNF-alpha-mediated decrease of CXCR4 mRNA accumulation resulted in decreased CXCR4 protein expression. As a result, the ability of stromal cell-derived factor-1alpha (SDF-1alpha) to induce activation of MAP kinases, Erk1/2 was impaired. The half life of CXCR4 mRNA in the presence and absence of TNF-alpha stimulation was comparable, suggesting that TNF-alpha down-regulated CXCR4 mRNA at the transcriptional level. These results suggest that TNF-alpha could modulate HIV and brain tumor pathogenesis and immune-mediated inflammation in the central nervous system (CNS) by regulation of CXCR4 expression.
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PMID:TNF-alpha down-regulates CXCR4 expression in primary murine astrocytes. 1114 46

Several small studies conducted by the Centers for Disease Control and Prevention (CDC) have shown that although progesterone appears to increase the likelihood of simian immunodeficiency virus (SIV) transmission in exposed monkeys, women using hormone contraceptives do not appear to have the same increased risk for HIV. The results, published in the May issue of Science, show little, if any, increase in the rate of HIV infection in women on Depo-Provera, an injectable contraception containing progestin, compared to those who were not taking it. Another study, conducted in Thailand, found similar results. However, this contrasts sharply with the results of a monkey study that found that rhesus monkeys given progesterone experienced significant thinning of the vaginal wall. Researchers are examining the effects of progesterone on the lining of the vagina. Researchers are finding some thinning, but not to a significant degree. The CDC continues to stress that only abstinence or the use of latex condoms can prevent the spread of AIDS.
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PMID:Progesterone-HIV link questioned by new studies. 1136 49

After a recent study showing that monkeys given progesterone are more likely to acquire simian immunodeficiency virus (SIV), women's reproductive health experts are advising clinicians to stress the importance of condom use and calm worried women by pointing out that other studies are needed to understand the relationship between hormones and HIV risk. Researchers have learned that progestin causes a thinning of the vaginal wall--possibly an explanation for the increase in SIV infection in the monkey study. Because Depo-Provera and Norplant are long-acting progestin-based contraceptives, women using them to prevent pregnancy may be especially alarmed by reports of the monkey study. Women should be advised that using these contraceptives do protect them from pregnancy; women should assess the risk of contracting HIV or other sexually transmitted diseases; and women should modify their behavior to lower their risk.
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PMID:Advice for women seeking progesterone counseling. 1136 50

A cyclic closed-chain dodecapeptide (cDDR5) mimicking the conformation-specific domain of CCR5 was prepared in which Gly-Asp, as a dipeptide forming a spacer arm, links the amino and carboxyl termini of the decapeptidyl linear chain (Arg(168) to Thr(177)) derived from the undecapeptidyl arch (UPA; Arg(168) to Cys(178)) of extracellular loop 2 (ECL2) in CCR5. Novel monoclonal antibodies were raised against cDDR5 conjugated with a multiple-antigen peptide (cDDR5-MAP), and the purified antibody [KB8C12, immunoglobulin M(kappa)] reacted with cDDR5, but not with linear DDR5, in real-time biomolecular interaction analysis using surface plasmon resonance. The antibody also reacted with cells expressing CCR5, but not with cells expressing CXCR4, and the immunoreaction was competed by cDDR5-MAP. The antibody significantly interfered with chemotaxis induced by macrophage inflammatory protein, 1beta, and at a concentration of 1.67 nM it almost completely inhibited infection by human immunodeficiency virus type 1 (HIV-1) R5, but not by HIV-1 X4, as observed by use of a new phenotypic assay for drug susceptibility of HIV-1 using the CCR5-expressing HeLa CD4(+) cell clone 1-10 (MAGIC-5). Furthermore, cDDR5-MAP suppressed infection by HIV-1 R5 at relatively high concentrations (50 to 400 microM) in a dose-dependent manner but did not suppress infection by HIV-1 X4. Taken together, these results indicate that the antibody is conformation specific and recognizes the conformation-specific domain of the UPA of ECL2. Moreover, both the antibody and its immunogen, the cDDR5-MAP conjugate, may be useful in developing a new candidate vaccine for HIV therapy.
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PMID:A cyclic dodecapeptide-multiple-antigen peptide conjugate from the undecapeptidyl arch (from Arg(168) to Cys(178)) of extracellular loop 2 in CCR5 as a novel human immunodeficiency virus type 1 vaccine. 1168 43

Chemokines and chemokine receptors play a crucial role in the trafficking of leukocyte populations across the body, and are involved in the development of a large variety of human diseases. CCR5 is the main coreceptor used by macrophage (M)-tropic strains of human immunodeficiency virus type 1 (HIV-1) and HIV-2, which are responsible for viral transmission. CCR5 therefore plays an essential role in HIV pathogenesis. A number of inflammatory CC-chemokines, including MIP-1 alpha, MIP-1 beta, RANTES, MCP-2, and HCC-1[9-74] act as CCR5 agonists, while MCP-3 is a natural antagonist of the receptor. CCR5 is mainly expressed in memory T-cells, macrophages, and immature dendritic cells, and is upregulated by proinflammatory cytokines. It is coupled to the Gi class of heterotrimeric G-proteins, and inhibits cAMP production, stimulates Ca2+ release, and activates PI3-kinase and MAP kinases, as well as other tyrosine kinase cascades. A mutant allele of CCR5, CCR5 delta 32 is frequent in populations of European origin, and encodes a nonfunctional truncated protein that is not transported to the cell surface. Homozygotes for the delta 32 allele exhibit a strong, although incomplete, resistance to HIV infection, whereas heterozygotes display delayed progression to acquired immunodeficiency syndrome (AIDS). Many other alleles, affecting the primary structure of CCR5 or its promoter have been described, some of which lead to nonfunctional receptors or otherwise influence AIDS progression. CCR5 is considered as a drug target in the field of HIV, but also in a growing number of inflammatory diseases. Modified chemokines, monoclonal antibodies and small chemical antagonists, as well as a number of gene therapy approaches have been developed in this frame.
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PMID:CCR5 and HIV infection. 1240 6


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