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)

Although human immunodeficiency virus-1 (HIV-1) infects quiescent and proliferating CD4+ lymphocytes, the virus replicates poorly in resting T cells. Factors that block viral replication in these cells might help to prolong the asymptomatic phase of HIV infection; however, the molecular mechanisms that control this process are not fully understood. Here we show that Murr1, a gene product known previously for its involvement in copper regulation, inhibits HIV-1 growth in unstimulated CD4+ T cells. This inhibition was mediated in part through its ability to inhibit basal and cytokine-stimulated nuclear factor (NF)-kappaB activity. Knockdown of Murr1 increased NF-kappaB activity and decreased IkappaB-alpha concentrations by facilitating phospho-IkappaB-alpha degradation by the proteasome. Murr1 was detected in CD4+ T cells, and RNA-mediated interference of Murr1 in primary resting CD4+ lymphocytes increased HIV-1 replication. Through its effects on the proteasome, Murr1 acts as a genetic restriction factor that inhibits HIV-1 replication in lymphocytes, which could contribute to the regulation of asymptomatic HIV infection and the progression of AIDS.
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PMID:The gene product Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes. 1468 42

Creutzfeldt-Jakob disease (CJD) is a presenile dementia characterized by rapidly progressive mental deterioration, myoclonic jerking, and other less common neurological signs. Few autoctonous cases have been described in Brazil. A 54-year-old white woman, was admitted in our service with a month history of progressive, bilateral cortical blindness. After admission, she developed right partial motor seizures( right facial, upper and lower limbs), she became progressively aphasic( mixed aphasia). Seizures were controlled with phenytoin, but she developed choreoathetotic movements on her right dimidium, with partial control after introduction of chlorpromazine 25 mg q/d. She could no longer stand up or walk due to severe ataxia. The first EEG (October, 2001) showed left hemisphere severe seizure activity (status epilepticus partialis). She was delivered home with enteral nutrition, phenytoin, chlorpromazine and mepacrine 100 mg qd. The following laboratorial tests were negative or normal: blood series, platelets, ESR, kidney and liver function, copper, ceruloplasmin, VDRL, HIV, HTLV-1, lactate, and cerebral DSA (performed in other service).A spinal tap with normal opening pressure was perform and CSF examination was normal. CSF 14-3-3 protein was positive, CSF specific neuronal enolase 7.5 ng/ml(normal). Genetic study of PRNP gene did not disclosed any known mutation. A MRI (October, 2001) showed areas of hyperintense signal (T2 and FLAIR) without Gd-enhancement on T1, in the left temporal lobe and in both occipital lobes; basal ganglia have a normal appearance. DWI imaging showed bright areas at the same sites. An EEG (March, 2002) disclosed a periodical sharp triphasic waves pattern, suggestive of CJD. A second MRI (April, 2002) showed mild generalized atrophy, no ventricular dilatation, and the hyperintense sites disappeared. She remained clinically stable and under use of chlorpromazine and mepacrine until she died due to pulmonary complications on April, 2003.
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PMID:[Creutzfeldt-Jakob disease, Heidenhain variant: case report with MRI (DWI) findings]. 1523 44

This country profile for Zambia was compiled between 1998 and 2002. The objectives of the exercise were to first of all avail policymakers, other key decision makers and leaders in Zambia, information about mental health in Zambia in order to assist policy and services development. Secondly, to facilitate comparative analyses of mental health services between countries. The work involved formation of a core group of experts who coordinated the collection of information from the various organizations in Zambia. The information was later shared to a broad spectrum of stakeholders for consensus. A series of focus group discussions (FGDs) supplemented the information collected. There are various factors that contribute to mental health in Zambia. It is clear from the Zambian perspective that social, demographic, economic, political, environmental, cultural and religious influences affect the mental health of the people. With a population of 10.3 million and annual growth rate of 2.9%, Zambia is one of the most urbanized countries in sub-Saharan Africa. Poverty levels stood at 72.9% in 1998. In terms of unemployment, the most urbanized provinces, Lusaka (the capital city), and the copper-belt are the most affected. The gross domestic product (GDP) is US$3.09 billion dollars while per capita income is US$300. The total budget allocation for health in the year 2002 was 15% while the proportion of the GDP per capita expenditure for health was 5.6%. The HIV/AIDS prevalence rates stand at 20% among the reproductive age group 15-49 years. Political instability and wars in neighbouring states has resulted in an influx of refugees. Environmental factors affecting the country include natural and man-made disasters such as floods and drought, mine accidents, and deforestation. To a large extent in Zambia, people who are mentally ill are stigmatized, feared, scorned at, humiliated and condemned. However, caring for mental ill health in old age is positively perceived. It is traditionally the duty and responsibility of the extended family to look after the aged. Gender based violence (GBV) is another issue. Women, who are totally dependent on their spouses economically, are forced by circumstances to continue living in abusive relationships to the detriment of their mental well-being. In Zambia, the family is considered sacrosanct and the affairs of the family members, private. It is within this context that GBV is regarded as a family affair and therefore a private affair, yet spouse beating has led to depression and in some cases death. In terms of psychiatric services, there are close to 560 beds for psychiatric patients across the country. Common mental disorders found in Zambia are acute psychotic episodes, schizophrenia, affective disorders, alcohol related problems and organic brain syndromes. About 70-80% of people with mental health problems consult traditional health practitioners before they seek help from conventional health practitioners. Over time the number of frontline mental health workers and professional staff has been declining. This is due to the 'brain drain', retirement, death and low output from training institutions. For practicing psychiatrists, only one is available for the whole country. Other key mental health workers such as psychologists, social workers and occupational therapists are also in short supply. All in all, the mental health services situation in Zambia could be described as critical, requiring urgent attention.
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PMID:Zambia mental health country profile. 1527 39

Copper ions, either alone or in copper complexes, have been used for centuries to disinfect liquids, solids, and human tissue. Today copper is used as a water purifier, algaecide, fungicide, nematocide, molluscicide, and antibacterial and antifouling agent. Copper also displays potent antiviral activity. We hypothesized that introducing copper into clothing, bedding, and other articles would provide them with biocidal properties. A durable platform technology has been developed that introduces copper into cotton fibers, latex, and other polymeric materials. This study demonstrates the broad-spectrum antimicrobial (antibacterial, antiviral, antifungal) and antimite activities of copper-impregnated fibers and polyester products. This technology enabled the production of antiviral gloves and filters (which deactivate HIV-1 and other viruses), antibacterial self-sterilizing fabrics (which kill antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci), antifungal socks (which alleviate symptoms of athlete's foot), and anti-dust mite mattress covers (which reduce mite-related allergies). These products did not have skin-sensitizing properties, as determined by guine pig maximization and rabbit skin irritation tests. Our study demonstrates the potential use of copper in new applications. These applications address medical issues of the greatest importance, such as viral transmissions; nosocomial, or healthcare-associated, infections; and the spread of antibiotic-resistant bacteria.
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PMID:Putting copper into action: copper-impregnated products with potent biocidal activities. 1534 89

The conformational space of the most biologically significant backbone folds of a suitable methionine peptide model was explored by density functional computational method. Using a medium [6-31G(d)] and a larger basis set [6-311++G(2d,2p)], the systematic exploration of low-energy backbone structures restricted for the "L-region" in the Ramachandran map of N-formyl-L-methioninamide results in conformers corresponding to the building units of an extended backbone structure (betaL), an inverse gamma-turn (gammaL), or a right-handed helical structure (alphaL). However, no poly-proline II type (epsilonL) fold was found, indicating that this conformer has no intrinsic stability, and highlighting the effect of molecular environment in stabilizing this backbone structure. This is in agreement with the abundance of the epsilonL-type backbone conformation of methionine found in proteins. Stability properties (DeltaE) and distinct backbone-side-chain interactions support the idea that specific intramolecular contacts are operative in the selection of the lowest energy conformers. Apart from the number of different folds, all stable conformers are within a 10 kcal x mol(-1) energy range, indicating the highly flexible behavior of methionine. This conformational feature can be important in supporting catalytic processes, facilitating protein folding and dimerization via metal ion binding. In both of the biological examples discussed (HIV-1 reverse transcriptase and PcoC copper-resistant protein), the conformational properties of Met residues were found to be of key importance. Spatial proximity to other types of residues or the same type of residue seems to be crucial for the structural integrity of a protein, whether Met is buried or exposed.
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PMID:Peptide models XLV: conformational properties of N-formyl-L-methioninamide and its relevance to methionine in proteins. 1561 85

L,L-Type and L,D-type (E)-alkene dipeptide isosteres (EADIs) that have unnatural side chains at the alpha-position were synthesized by the combination of stereoselective aziridinyl ring-opening reactions and organozinc-copper-mediated anti-S(N)2' reactions toward a single substrate of gamma,delta-cis-gamma,delta-epimino (E)-alpha,beta-enoate. The utility of this methodology was demonstrated by the stereoselective synthesis of a set of diastereomeric EADIs of L-Arg-L/D-3-(2-naphthyl)alanine (Nal) that is contained in a small CXCR4 antagonist FC131 [cyclo(-D-Tyr-Arg-Arg-Nal-Gly-)]. Furthermore, a (Nal-Gly)-type EADI was synthesized by samarium diiodide (SmI(2))-induced reduction of a gamma-acetoxy-alpha,beta-enoate. Several FC131 analogues, in which these EADIs were inserted for reduction of their peptide character, were synthesized with analogues containing reduced amide-type dipeptide isosteres to investigate the importance of these amide bonds for anti-HIV and CXCR4-antagonistic activity.
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PMID:Stereoselective synthesis of [L-Arg-L/D-3-(2-naphthyl)alanine]-type (E)-alkene dipeptide isosteres and its application to the synthesis and biological evaluation of pseudopeptide analogues of the CXCR4 antagonist FC131. 1565 52

The macrocyclic antiviral drug xylyl-bicyclam blocks entry of HIV into cells by targeting the CXCR4 coreceptor, a seven-helix transmembrane G-protein-coupled receptor. Its affinity for CXCR4 is enhanced by binding to Cu2+, Ni2+, or Zn2+. Metallocyclams have a rich configurational chemistry and proteins may bind selectively to specific metallocyclam configurations. Our studies of lysozyme reveal structural details of protein-metallocyclam interactions that are important for receptor recognition. Solution NMR studies show that Cu-cyclam interacts with specific tryptophan residues of lysozyme (Trp-62, Trp-63, and Trp-123). Two major binding sites for both Cu-cyclam and Cu2-xylyl-bicyclam were detected by x-ray crystallography. In the first site, Cu2+ in one cyclam ring of Cu2-xylyl-bicyclam adopts a trans configuration and is coordinated to a carboxylate oxygen of Asp-101, whereas for Cu-cyclam two ring NH groups form H bonds to the carboxylate oxygens of Asp-101, stabilizing an unusual cis (folded) cyclam configuration. For both complexes in this site, a cyclam ring is sandwiched between the indole side chains of two tryptophan residues (Trp-62 and Trp-63). In the second site, a trans cyclam ring is stacked on Trp-123 and H bonded to the backbone carbonyl of Gly-117. We show that there is a pocket in a model of the human CXCR4 coreceptor in which trans and cis configurations of metallobicyclam can bind by direct metal coordination to carboxylate side chains, cyclam-NH...carboxylate H bonding, together with hydrophobic interactions with tryptophan residues. These studies provide a structural basis for the design of macrocycles that bind stereospecifically to G-coupled and other protein receptors.
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PMID:Protein recognition of macrocycles: binding of anti-HIV metallocyclams to lysozyme. 1570 2

Sulfonated 5,10,15,20-tetra(1-naphthyl)porphyrin (T1NapS) and 5,10,15,20-tetra(2-naphthyl)porphyrin (T2NapS) and their copper and iron chelates show activity against the human immunodeficiency virus (HIV-1). The porphyrins were prepared by sulfonation of the parent structures with sulfuric acid. More highly sulfonated structures were prepared by sulfonation for longer times. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry showed species with as many as eight sulfonates. Some of the mass spectral peaks for the copper chelates were consistent with loss of water, apparently from intramolecular sulfone formation between two adjacent naphthalene rings that took place during copper insertion. The compounds could be separated using capillary electrophoresis; addition of beta- or gamma-cyclodextrin gave substantially better separation of the components. Activity against HIV was evaluated using an epithelial HeLa-CD4-CCR5 cell line; EC50 values for HIV-1 IIIB and HIV-1 JR-FL ranged from 1 to 15 microg/ml. The compounds exhibit low toxicity for human epithelial cells and have potential as microbicides which might be used to provide protection against sexual transmission of HIV.
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PMID:Sulfonated naphthyl porphyrins as agents against HIV-1. 1570 3

trans-Bis(resorcylaldoximato)copper(II) and trans-bis-(2,3,4-trihydroxybenzaldoximato)copper(II) (CuRES2 and CuTRI2, respectively) have been tested for antiviral properties against HIV, using an in vitro assay that measures the ability of the test compounds to prevent the killing of susceptible human cells by HIV. In the case of CuTRI2, T4 lymphocytes (CEM-V and CEM-Z cell lines) were exposed to HIV at a virus to cell ratio approx. 0.05 in microtiter plates. In the case of CuRES2, a human leukemia cell line (MT-2) was used instead. The tetrazolium salt XTT was added to all wells, and the cultures were incubated and analyzed spectrophotometrically to quantitate formazan production and viewed microscopically for detection of viable cells. In spite of their antiproliferative properties, neither agent had any detectable ability to prevent the cytopathic effects of HIV in cultures of the target cells used. Because the test system employed was constructed in such a way as to detect antiviral agents acting at any stage of the virus reproductive cycle, the results obtained strongly suggest that neither studied agent has any value as the direct prevention of the cell destruction caused by HIV is concerned.
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PMID:The antiproliferative agents trans-bis(resorcylaldoximato)copper(II) and trans-bis(2,3,4-trihydroxybenzaldoximato)copper(II) and cytopathic effects of HIV. 1581 88

A ribonuclease, with a molecular mass of 9 kDa and an N-terminal sequence resembling the sequence of a fragment of tRNA/rRNA cytosine-C5-methylase and a fragment of a alanyl-tRNA synthetase, was isolated from fresh fruiting bodies of the brown oyster mushroom Pleurotus ostreatus. The ribonuclease was purified using a very simple protocol that comprised ion-exchange chromatography on carboxymethyl (CM)-cellulose and affinity chromatography on Affi-gel blue gel. Subsequent gel filtration by fast protein liquid chromatography on Superdex 75 and sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis revealed that the ribonuclease was purified after the first two chromatographic steps. The ribonuclease was adsorbed on CM-cellulose and Affi-gel blue gel. The ribonuclease exhibited the highest activity toward poly A, lower activity toward poly C, slight activity toward poly G, and indiscernible activity toward poly U. The enzyme was stimulated upon exposure to 1 microm Mg2+ and 10 microm Zn2+, but was inhibited by the following ions at 10 mm: Ca2+, Mg2+, Zn2+, Cu2+, Fe2+, Mn2+, and Fe3+. The ribonuclease required a pH of 8.0 and a temperature of 50-70 degrees C to express maximal activity. It had a Km of 60 microm toward yeast tRNA. It lacked mitogenic and HIV-1 reverse transcriptase inhibiting activities, but exerted antiproliferative activity toward leukemia L1210 cells.
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PMID:A low-molecular mass ribonuclease from the brown oyster mushroom. 1594 90


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