Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recently discovered locus for copper toxicosis (CT) in Bedlington terriers (BT) has a 13-kb deletion enveloping the 187-bp exon-2 of the MURR1 gene. This MURR1 gene is not only involved with biliary copper excretion but also associated with HIV-1 replication. The microsatellite C04107 lying in an intron of the MURR1 gene is highly associated with the disease but shows haplotype diversity. The only solid molecular test for the disease is by showing the deletion in exon-2 in cDNA in liver tissue; this test is not robust on RNA from peripheral leukocytes because of their low MURR1 expression level. Because of these drawbacks, we developed a new quantitative PCR (Q-PCR) protocol. Here we show that the MURR1 exon-2/exon-3 ratio measured by Q-PCR on genomic DNA correlates perfectly with the microsatellite marker and with RT-PCR data from blood samples, buccal swabs, and liver biopsies. In view of the important role of MURR1 in cells of many tissues, this new test has a wide range of applications in comparative biomedical research. Furthermore, Q-PCR on DNA may be a new tool in general to analyze mutations that cannot be approached by standard methods.
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PMID:Quantitative PCR method to detect a 13-kb deletion in the MURR1 gene associated with copper toxicosis and HIV-1 replication. 1607 72

On August 29-31, 2004, 84 academic and industry scientists from 16 countries gathered in Copper Mountain, Colorado USA to discuss certain issues at the forefront of the science of probiotics and prebiotics. The format for this invitation only meeting included six featured lectures: engineering human vaginal lactobacilli to express HIV-inhibitory molecules (Peter Lee, Stanford University), programming the gut for health (Thaddeus Stappenbeck, Washington University School of Medicine), immune modulation by intestinal helminthes (Joel Weinstock, University of Iowa Hospitals and Clinics), hygiene as a cause of autoimmune disorders (G. A. Rook, University College London), prebiotics and bone health (Connie Weaver, Purdue University) and prebiotics and colorectal cancer risk (Ian Rowland, Northern Ireland Centre for Food and Health). In addition, all participants were included in one of eight discussion groups on the topics of engineered probiotics, host-commensal bacteria communication, 'omics' technologies, hygiene and immune regulation, biomarkers for healthy people, prebiotic and probiotic applications to companion animals, development of a probiotic dossier, and physiological relevance of prebiotic activity. Brief conclusions from these discussion groups are summarized in this paper.
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PMID:Selected topics in probiotics and prebiotics: meeting report for the 2004 international scientific association for probiotics and prebiotics. 1610 38

Malnutrition is common in pulmonary tuberculosis (TB), and may impair survival. The objective of this study was to assess effects of multi-vitamin/mineral (MVM) and zinc (Zn) supplementation during TB treatment on mortality. Patients diagnosed with sputum-positive pulmonary TB in Mwanza, Tanzania, were randomised, using a two-by-two factorial design, to Zn (45 mg) or placebo, and MVM (vitamins A, B, C, D, E, and selenium and copper) or placebo. Survival status was ascertained at the end of the 8-month TB treatment and supplementation period. Of 499 TB patients, 213 (43 %) had HIV. The mean weight gain at 7 months was 6.88 kg (95 % CI 6.36, 7.41). Zn and MVM combined, but neither alone (interaction, P=0.03), increased weight gain by 2.37 kg (95 % CI 0.91, 3.83), irrespective of HIV status. Survival status at 8 months was determined for 422 patients (84.6 %), of which fifty-two (12.3 %) had died. Among fifty-two deaths, there were no effects of MVM (relative risk (RR) 0.73; 95 % CI 0.43, 1.23) and Zn (RR 0.76; 95 % CI 0.46, 1.28). However, among HIV co-infected patients, marginally significant effects of both MVM (RR 0.60; 95 % CI 0.34, 1.05) and Zn (RR 0.63, 95 % CI 0.37, 1.08) were seen, and MVM and Zn combined reduced mortality (RR 0.29; 95 % CI 0.10, 0.80; interaction ratio 0.52). In conclusion, supplementation with MVM, including Zn, during treatment of pulmonary TB may reduce mortality in those co-infected with HIV. A randomised trial of the effect of the combined intervention used in this study should be conducted in a different setting to confirm the finding.
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PMID:The effect of multi-vitamin/mineral supplementation on mortality during treatment of pulmonary tuberculosis: a randomised two-by-two factorial trial in Mwanza, Tanzania. 1657 Nov 56

Protein C (PC) is an essential blood factor in the human blood coagulation cascade. PC can help achieve blood hemostasis in many deadly disease conditions such as sepsis, cancer, HIV, etc.; reduced oxygen transport due to blood agglutination within the body can cause tissue death and organ failure as a result of low oxygen transport. Our goal is to produce large quantities of low cost zymogen PC for the treatment and prevention of blood clotting resulting from many disease states, as well as provide an effective therapy for PC deficiency. Current studies show that Immobilized Metal Affinity Chromatography (IMAC) has high specificity and can be used for difficult separations among homologous proteins at relatively low cost compared to current methods, such as Immunoaffinity Chromatography. Thus, we are investigating the optimization of IMAC for the separation and purification of PC from Cohn fraction IV-I. Molecular interactions within the chromatography column involve many parameters that include: the use and type of chromatographic gel and buffer solution, the pH, temperature, metal ion, chelator, and the sequence and structure of the protein itself. These parameters all influence the protein's interaction with the column. Experimental equilibrium isotherms show that PC has primary and secondary binding characteristics, demonstrating that the interaction is not just a simple process of one protein binding to one metal ion. Understanding the thermodynamics of interfacial interaction between proteins and surface-bound Cu2+ is essential to optimizing IMAC for PC purification, as well as for separation of other proteins in general. Hence we are undertaking theoretical and experimental studies of IDA-Cu/PC adsorption. The differences in structures of PC and other critical homologous blood factors are examined using the protein visualization program Cn3D. A better understanding of the interfacial phenomena will help determine the most effective conditions to achieve our goal.
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PMID:Protein C production: metal ion/protein interfacial interaction in immobilized metal affinity chromatography. 1659 76

Azurin, a member of a family of copper-containing proteins involved in electron transfer called cupredoxins, demonstrates structural features similar to the variable domains of the immunoglobulin superfamily members. An azurin-like protein called Laz with an additional N-terminal 39 amino acid peptide known as H.8 epitope is present on the surface of gonnococci and meningococci. We demonstrate that azurin, Laz and H.8-azurin can bind to the C-terminal cleavage product MSP1-19 of merozoite surface protein 1 (MSP1) of the malarial parasite Plasmodium falciparum and significantly reduce parasitemia. Azurin and Laz also bound strongly to HIV-1 gp120. Interestingly, azurin could not only bind to gp120 but also to the dendritic cell-specific adhesion receptor DC-SIGN, mimicking the functionality of the intercellular adhesion molecule ICAM-3 with which it also binds avidly. Furthermore, these three proteins significantly suppressed HIV-1 growth in peripheral blood mononuclear cells and such suppression appeared to be occurring at an entry stage in the infection process. The presence of both antimalarial and antiretroviral activity in azurin, H.8-azurin and Laz makes these proteins, or peptides derived from them, potential therapeutic agents in the treatment of malaria, HIV-1 infections or coinfections with both P. falciparum and HIV-1.
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PMID:Azurin, Plasmodium falciparum malaria and HIV/AIDS: inhibition of parasitic and viral growth by Azurin. 1686 97

Diethyldithiocarbamate (DDTC) is a member of the dithiocarbamate family and a potent copper-chelating agent. DDTC was used in a clinical trial for patients with HIV-1 infection and showed a significant delay in progression to AIDS. In this study, we investigated the effects of DDTC-copper complex in human prostate and breast cancer cells. We found that DDTC was capable of binding copper and forming a new complex that potently inhibited the proteasomal chemotrypsin-like activity, decreased expression of androgen receptor (AR), estrogen receptor (ER) alpha and ERbeta proteins, and induced apoptosis in both prostate and breast cancer cells. Our data support the concept of using accumulated copper in cancer cells and tissues as a novel target for chemotherapy. This study provides a mechanistic interpretation for utilization of copper chelators in cancer treatment.
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PMID:Sodium diethyldithiocarbamate, an AIDS progression inhibitor and a copper-binding compound, has proteasome-inhibitory and apoptosis-inducing activities in cancer cells. 1739 87

A new target in AIDS therapy development is HIV-1 integrase (IN). It was proven that HIV-1 IN required divalent metal cations to achieve phosphodiester bond cleavage of DNA. Accordingly, all newly investigated potent IN inhibitors contain chemical fragments possessing a high ability to chelate metal cations. One of the promising leads in the polyhydroxylated styrylquinolines (SQLs) series is (E)-8-hydroxy-2-[2-(4,5-dihydroxy-3-methoxyphenyl)-ethenyl]-7-quinoline carboxylic acid (1). The present study focuses on the quinoline-based progenitor (2), which is actually the most probable chelating part of SQLs. Conventional and synchrotron low-temperature X-ray crystallographic studies were used to investigate the chelating power of progenitor 2. Mg2+ and Cu2+ cations were selected for this purpose, and three types of metal complexes of 2 were obtained: Mg(II) complex (4), Cu(II) complex (5) and mixed Mg(II)-Cu(II) complexes (6 and 7). The analysis of the crystal structure of complex 4 indicates that two tridentate ligands coordinate two Mg2+ cations, both in octahedral geometry. The Mg-Mg distance was found equal to 3.221(1) A, in agreement with the metal-metal distance of 3.9 A encountered in the crystal structure of Escherichia coli DNA polymerase I. In 5, the complex is formed by two bidentate ligands coordinating one copper ion in tetrahedral geometry. Both mixed Mg(II)-Cu(II) complexes, 6 and 7 exhibit an original arrangement of four ligands linked to a central heterometallic cluster consisting of three octahedrally coordinated magnesium ions and one tetrahedrally coordinated copper ion. Quantum mechanics calculations were also carried out in order to display the electrostatic potential generated by the dianionic ligand 2 and complex 4 and to quantify the binding energy (BE) during the formation of the magnesium complex of progenitor 2. A comparison of the binding energies of two hypothetical monometallic Mg(II) complexes with that found in the bimetallic magnesium complex 4 was made.
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PMID:Crystal and electronic structures of magnesium(II), copper(II), and mixed magnesium(II)-copper(II) complexes of the quinoline half of styrylquinoline-type HIV-1 integrase inhibitors. 1748 11

The aim of this study was to evaluate the nutritional status of adults with HIV infection or with AIDS through the use of biochemical parameters. The study was performed on 43 patients (19 HIV+ and 24 AIDS patients), between 26 and 44 years of age, from low and medium socioeconomic status, with access to health care services; 35 patients were under highly active antiretroviral therapy (HAART) treatment. Body weight and height were determined, and the Body Mass Index calculated (kg/m2). Blood samples were collected from fasting patients. Plasma cholesterol (total, HDL and LDL), triacylglycerol, total protein, apolipoproteins A-I and B, albumin, transthyretin, retinol binding protein, and ceruloplasmin concentrations were determined. Plasma levels of zinc, copper, and selenium were determined in a haemolysis-free sample by flame atomic absorption spectrometry. Statistical analyses were performed with the Student's t-test. AIDS patients showed changes in biochemical parameters, particularly an increase in fibrinogen and a trend to decreased transthyretin levels. These findings stress the importance of the inclusion of functional biochemical parameters in the periodic evaluation of these patients. This would allow an early assessment of the need for appropriate nutritional support, implemented along with the specific retroviral treatment. This would aim at delaying the progression of the disease, and might improve the prospects of survival and quality of life.
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PMID:Nutritional status in patients with HIV infection and AIDS. 1792 52

The syntheses of configurationally restricted mono- and bis-macrocyclic copper(II) perchlorate complexes (copper(II) 5-benzyl-1,5,8,12-tetraazabicyclo[10.2.2]hexadecane and dicopper(II) 5,5'-[1,4-phenylenebis(methylene)]-bis(1,5,8,12-tetraazabicyclo[10.2.2]hexadecane)) are reported and the X-ray structure of the copper(II) mono-macrocyclic complex has been determined. EXAFS studies on the bis-macrocyclic species in aqueous solution show that the copper coordination spheres are essentially identical to the solid state structure, and do not vary in the presence of 20 equivalents of sodium acetate per metal centre. DFT calculations were carried out at the BP86/TZP level to determine the nature of potential binding interactions with CXCR4 aspartate residues. The alkylated single macrocyclic compound was modelled with an acetate included to represent the aspartate residue, demonstrating that the predicted macrocycle configuration has the lowest energy and the acetate interaction is effectively monodentate giving a distorted trigonal bipyramidal geometry at the copper centre. In vitro anti-HIV infection assays show that the configurationally restricted dicopper(II) complex is more active (average EC(50) = 0.026 microM against HIV-1) than the non-constrained dicopper(II) 1,1'-[1,4-phenylenebis(methylene)]-bis(1,4,8,11-tetraazacyclotetradecane) (average EC(50) = 0.047 microM against HIV-1) although it is an order of magnitude less active than the configurationally restricted dizinc(II) complex.
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PMID:Probing key coordination interactions: configurationally restricted metal activated CXCR4 antagonists. 1799 86

Human immunodeficiency virus type 1 (HIV-1) can be transmitted through breast-feeding and through contaminated blood donations. Copper has potent biocidal properties and has been found to inactivate HIV-1 infectivity. The objective of this study was to determine the capacity of copper-based filters to inactivate HIV-1 in culture media. Medium spiked with high titers of HIV-1 was exposed to copper oxide powder or copper oxide-impregnated fibers or passed through copper-based filters, and the infectious viral titers before and after treatment were determined. Cell-free and cell-associated HIV-1 infectivity was inhibited when exposed to copper oxide in a dose-dependent manner, without cytotoxicity at the active antiviral copper concentrations. Similar dose-dependent inhibition occurred when HIV-1 was exposed to copper-impregnated fibers. Filtration of HIV-1 through filters containing the copper powder or copper-impregnated fibers resulted in viral deactivation of all 12 wild-type or drug-resistant laboratory or clinical, macrophage-tropic and T-cell-tropic, clade A, B, or C, HIV-1 isolates tested. Viral inactivation was not strain specific. Thus, a novel means to inactivate HIV-1 in medium has been developed. This inexpensive methodology may significantly reduce HIV-1 transmission from "mother to child" and/or through blood donations if proven to be effective in breast milk or plasma and safe for use. The successful application of this technology may impact HIV-1 transmission, especially in developing countries where HIV-1 is rampant.
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PMID:Deactivation of human immunodeficiency virus type 1 in medium by copper oxide-containing filters. 1807 Sep 74


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