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)

Inosine-pranobex (methisoprinol, isoprinosine; INPX) is the p-acetamidobenzoic salt of N,N-dimethylamino-2-propanol and inosine in a 3:1 molar ratio. In early studies, INPX was found to partially inhibit human immunodeficiency virus (HIV) and to increase the immunocompetence of HIV-infected subjects in vitro. We report the results of a randomised, multicentric clinical trial carried out on 553 HIV+ patients. 261 individuals were treated with INPX (two 500 mg tablets every 6 h for 3 months) and the remaining 292 constituted the untreated control group. INPX treatment was associated with a slightly improved clinical condition or with a trend in that direction, as compared to the untreated group. A preservation of the CD4/CD8 cell ratio values, a decrease in the CD8+ cells and an increase in the Leu 2-7+ cell number better than in the untreated individuals was also observed in the patients taking INPX. No serious or adverse effects of INPX have been observed.
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PMID:Clinical and immunological assessment in HIV+ subjects receiving inosine-pranobex. A randomised, multicentric study. 247 Oct 25

Estimation of neopterin in urine has become part of examination in phenylketonuria, malignities, immunodeficiency incl. AIDS and HIV infection. The authors describe a simple chromatographic method for estimation of neopterin which does not call for highly efficient liquid chromatography nor imported kits. The di- and tetrahydro- forms of neopterin are oxidized with MnO2 and stable neopterin is obtained. The specimen is purified on a Dowex 50WX4 (Fluka) column in a H+ cycle and on PRESEPC18 (TESSEK) columns. Then thin-layer chromatography on Merck Kieselgel 60F254 plates is used in a system of ethyl acetate--isopropanol--1 N NH4OH (35:45:25). Fluorescence is assessed on a densitometer (Shimadzu CS-920 at 367.5 nm). The RF of neopterin is 0.214. The fluorescence is linear within the range of 5-200 ng. The method is sufficiently sensitive also for the estimation of normal neopterin excretion. The authors submit the results of estimations in controls, immunopathies and AIDS.
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PMID:[Simple chromatographic determination of the neopterin marker in immunopathies]. 272 Jul 37

Simian immunodeficiency virus matrix protein has been crystallized from Tris-HCl buffer with polyethylene glycol and isopropanol as precipitants. The crystals belong to space group C2 with unit cell dimensions a = 69.9 A, b = 115.2 A, c = 32.5 A, beta = 108.1 degrees and diffract X rays to a minimum Bragg spacing of 2 A. These crystals appear suitable for a high resolution structure analysis.
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PMID:Crystallization and preliminary X-ray investigation of recombinant simian immunodeficiency virus matrix protein. 807 98

Hydrosoluble macromolecular fluorogenic substrates specific for the human immunodeficiency virus 1 (HIV-1) proteinase have been prepared. The fluoresceinyl peptide Ftc-epsilon-Ahx-Ser-Phe-Asn-Phe-Pro-Gln-Ile-Thr-(Gly)n, corresponding to the first cleavage site of HIV-1 gag-pol native precursor was linked to a water-soluble neutral (Lys)n derivative. The epsilon-aminohexanoyl residue (epsilon-Ahx) and the glycyl sequence were added in order to improve the stability of the substrate and the accessibility of the cleavage site to the HIV-1 proteinase respectively. This macro-molecular peptidic-substrate conjugate is significantly more water-soluble than the free peptide itself on a substrate molar concentration basis. The assay is based on the quantitative precipitation of the polymeric material by adding propan-2-ol whereas the fluorescent peptide moiety released upon proteolysis remains soluble in the supernatant. The proteinase activity is assessed by measuring the fluorescence of the supernatant. This assay allows the detection of a few fmol of HIV-1 proteinase, even in the presence of cell culture media, plasma or cell lysate and it gives accurate results within a large proteinase concentration range. The hydrosoluble macromolecular substrate is also suitable for determining the HIV-1 proteinase activity using 96-well microplates, allowing us to test accurately and rapidly numerous enzyme samples and/or the potency of new proteinase inhibitors.
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PMID:Sensitive, hydrosoluble, macromolecular fluorogenic substrates for human immunodeficiency virus 1 proteinase. 848 13

PIC 024-4 and PRO 2000 are naphthalene sulfonate polymers that bind to CD4 with nanomolar affinity and block binding of gp120. Both have activity against human immunodeficiency virus type 1 in H9 cells, peripheral blood mononuclear cells, and primary monocyte/macrophages, are synergistic with zidovudine, and do not inhibit tetanus toxoid-stimulated T-cell proliferation at anti-human immunodeficiency virus type 1 concentrations.
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PMID:Naphthalene sulfonate polymers with CD4-blocking and anti-human immunodeficiency virus type 1 activities. 878 13

A method for the determination of a metabolic of the human immunodeficiency virus protease inhibitor indinavir, in human plasma is described. Isolation of the analyte and the internal standard from plasma was achieved via liquid-liquid extraction with a mixture of isopropanol-chloroform (5:95, v/v). The analytes were chromatographed under reversed-phase conditions on a Waters Symmetry C, column. A Sciex API III+ tandem mass spectrometer equipped with a heated nebulizer was used as a detector and was operated in the positive ion mode. Multiple reaction monitoring using the precursor-->production combinations of m/z, 523.4-->273.4 and 512.4-->345.2 was used to quantify analyte and internal standard, respectively. The method was validated in the concentration range of 5-500 ng/ml plasma with adequate assay precision and accuracy. The assay was used to analyze samples collected during drug interaction studies of indinavir.
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PMID:Determination of an in vivo metabolite of a human immunodeficiency virus protease-inhibitor in human plasma by high-performance liquid chromatography with tandem mass spectrometry. 909 90

PRO 542 (CD4-IgG2) is a recombinant antibody-like fusion protein wherein the Fv portions of both the heavy and light chains of human IgG2 have been replaced with the D1D2 domains of human CD4. Unlike monovalent and divalent CD4-based proteins, tetravalent PRO 542 potently neutralizes diverse primary human immunodeficiency virus (HIV) type 1 isolates. In this phase 1 study, the first evaluation of this compound in humans, HIV-infected adults were treated with a single intravenous infusion of PRO 542 at doses of 0.2-10 mg/kg. PRO 542 was well tolerated, and no dose-limiting toxicities were identified. Area under the concentration-time curve, and peak serum concentrations increased linearly with dose, and a terminal serum half-life of 3-4 days was observed. No patient developed antibodies to PRO 542. Preliminary evidence of antiviral activity was observed as reductions in both plasma HIV RNA and plasma viremia. Sustained antiviral effects may be achieved with repeat dosing with PRO 542.
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PMID:Single-dose safety, pharmacology, and antiviral activity of the human immunodeficiency virus (HIV) type 1 entry inhibitor PRO 542 in HIV-infected adults. 1088 17

CCR5 serves as a requisite fusion coreceptor for clinically relevant strains of human immunodeficiency virus type 1 (HIV-1) and provides a promising target for antiviral therapy. However, no study to date has examined whether monoclonal antibodies, small molecules, or other nonchemokine agents possess broad-spectrum activity against the major genetic subtypes of HIV-1. PRO 140 (PA14) is an anti-CCR5 monoclonal antibody that potently inhibits HIV-1 entry at concentrations that do not affect CCR5's chemokine receptor activity. In this study, PRO 140 was tested against a panel of primary HIV-1 isolates selected for their genotypic and geographic diversity. In quantitative assays of viral infectivity, PRO 140 was compared with RANTES, a natural CCR5 ligand that can inhibit HIV-1 entry by receptor downregulation as well as receptor blockade. Despite their divergent mechanisms of action and binding epitopes on CCR5, low nanomolar concentrations of both PRO 140 and RANTES inhibited infection of primary peripheral blood mononuclear cells (PBMC) by all CCR5-using (R5) viruses tested. This is consistent with there being a highly restricted pattern of CCR5 usage by R5 viruses. In addition, a panel of 25 subtype C South African R5 viruses were broadly inhibited by PRO 140, RANTES, and TAK-779, although approximately 30-fold-higher concentrations of the last compound were required. Interestingly, significant inhibition of a dualtropic subtype C virus was also observed. Whereas PRO 140 potently inhibited HIV-1 replication in both PBMC and primary macrophages, RANTES exhibited limited antiviral activity in macrophage cultures. Thus CCR5-targeting agents such as PRO 140 can demonstrate potent and genetic-subtype-independent anti-HIV-1 activity.
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PMID:Potent, broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140. 1113 70

Progenics's rCD4-IgG2 (PRO-542) is a recombinant fusion protein, which has been developed using the company's Universal Antiviral Binding (UnAB) technology, and is in phase I/II clinical trials for the treatment of human immunodeficiency virus type I (HIV-1) infection [273391]. At the beginning of 1997, Progenics received a Phase II Small Business Innovation Research Program (SBIR) grant from the National Institute of Allergy and Infectious diseases (NIAID) to fund the development of PRO-542 [236048]. A further grant of $2.7 million was awarded in August 1998 for the clinical evaluation of PRO-542 and other anti-HIV therapies [294200]. Progenics is collaborating with the Aaron Diamond AIDS Research Center (ADARC) in New York and the Center for Disease Control and Prevention in Atlanta [178410]. In February 2000, Progenics and Genzyme Transgenics Corp signed an agreement to continue the development of a transgenic source of PRO-542. Genzyme will develop transgenic goats that produce PRO-542 in their milk in exchange for undisclosed fees and milestone payments. Genzyme will supply PRO-542 to Progenics for clinical trials with a possibility for eventual commercial supply [357291]. Following on from this, in October 2000, Progenics received an SBIR grant to fund a two-year project with Genzyme Transgenics into the development of cost-effective methods for the manufacture of PRO-542, by optimization of the production of the drug in the milk of transgenic dairy animals [385982]. In August 2000, Punk, Ziegel & Company predicted that Progenics Pharmaceuticals will become sustainably profitable in 2003 following the launch of PRO-542 and GMK (Progenics Pharmaceuticals) in 2002 [390063].
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PMID:Technology evaluation: PRO-542, Progenics Pharmaceuticals inc. 1124 48

The virucidal spectrum of a high concentration alcohol mixture (80% ethanol and 5% isopropanol) was determined for a broad series of lipid-enveloped (LE) and non-lipid-enveloped (NLE) viruses covering all relevant blood-borne viruses. LE viruses were represented by human immunodeficiency virus (HIV), bovine viral diarrhoea virus (BVDV), a specific model virus for hepatitis C virus (HCV), pseudorabies virus (PRV), and vaccinia virus. For the NLE viruses hepatitis A virus, canine parvovirus (a model for human parvovirus B19), and reovirus type 3 (Reo-3) were used. PRV, vaccinia, and Reo-3 served as general model viruses. The alcohol mixture was spiked with 5% (v/v) virus, mixed and tested for residual virus after 5 min treatment. Complete clearance (reduction by a factor of >10(6)) was observed for LE viruses, whereas incomplete to insignificant clearance (ranging from no reduction up to a maximum factor of 10(4)) was found for NLE viruses. In a second series of spiking experiments using the LE viruses BVDV, HIV, and PRV, complete clearance (reduction by a factor of >10(6)) was found after 20 s treatment. These data strongly suggest that treatment with a high concentration alcohol mixture has a high virucidal potential in particular for the blood-borne LE-viruses HIV, hepatitis B virus, and HCV. Such mixtures are well suited for rapid and frequent disinfection in dental practice being non-hazardous and non-toxic.
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PMID:The virucidal spectrum of a high concentration alcohol mixture. 1209 Jul 99


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