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

Zinc is an important trace element in biology. An important pool of zinc in the brain is the one present in synaptic vesicles in a subgroup of glutamatergic neurons. In this form it can be released by electrical stimulation and may serve to modulate responses at receptors for a number of different neurotransmitters. These include both excitatory and inhibitory receptors, particularly the NMDA and GABA(A) receptors. This pool of zinc is the only form of zinc readily stained histochemically (the chelatable zinc pool), but constitutes only about 8% of the total zinc content in the brain. The remainder of the zinc is more or less tightly bound to proteins where it acts either as a component of the catalytic site of enzymes or in a structural capacity. The metabolism of zinc in the brain is regulated by a number of transport proteins, some of which have been recently characterized by gene cloning techniques. The intracellular concentration may be mediated both by efflux from the cell by the zinc transporter ZrT1 and by complexing with apothionein to form metallothlonein. Metallothionein may serve as the source of zinc for incorporation into proteins, including a number of DNA transcription factors. However, zinc is readily released from metallothionein by disulfides, increasing concentrations of which are formed under oxidative stress. Metallothionein is a very good scavenger of free radicals, and zinc itself can also reduce oxidative stress by binding to thiol groups, decreasing their oxidation. Zinc is also a very potent inhibitor of nitric oxide synthase. Increased levels of chelatable zinc have been shown to be present in cell cultures of immune cells undergoing apoptosis. This is very reminiscent of the zinc staining of neuronal perikarya dying after an episode of ischemia or seizure activity. Thus a possible role of zinc in causing neuronal death in the brain needs to be fully investigated. intraventricular injections of calcium EDTA have already been shown to reduce neuronal death after a period of ischemia. Pharmacological doses of zinc cause neuronal death, and some estimates indicate that extracellular concentrations of zinc could reach neurotoxic levels under pathological conditions. Zinc is released in high concentrations from the hippocampus during seizures. Unfortunately, there are contrasting observations as to whether this zinc serves to potentiate or decrease seizure activity. Zinc may have an additional role in causing death in at least some neurons damaged by seizure activity and be involved in the sprouting phenomenon which may give rise to recurrent seizure propagation in the hippocampus. In Alzheimer's disease, zinc has been shown to aggregate beta-amyloid, a form which is potentially neurotoxic. The zinc-dependent transcription factors NF-kappa B and Sp1 bind to the promoter region of the amyloid precursor protein (APP) gene. Zinc also inhibits enzymes which degrade APP to nonamyloidogenic peptides and which degrade the soluble form of beta-amyloid. The changes in zinc metabolism which occur during oxidative stress may be important in neurological diseases where oxidative stress is implicated, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Zinc is a structural component of superoxide dismutase 1, mutations in which give rise to one form of familiar ALS. After HIV infection, zinc deficiency is found which may be secondary to immune-induced cytokine synthesis. Zinc is involved in the replication of the HIV virus at a number of sites. These observations should stimulate further research into the role of zinc in neuropathology.
 ...
PMID:Zinc metabolism in the brain: relevance to human neurodegenerative disorders. 936 Dec 93

The usefulness of the direct virus detection by polymerase chain reaction (PCR) and reverse transcription/polymerase chain reaction (RT PCR) for blood donor screening was investigated, including the following viruses: cytomegalovirus (CMV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency type 1 virus (HIV1). Hepatitis C viraemia was detected by RT PCR in 97% of anti-HCV-positive haemophiliacs, in 48% of anti-HCV-positive hepatitis patients, in only 21% of anti-HCV-positive blood donors from North-West Germany, and not at all in 945 blood donors with elevated serum ALT. In order to compare HIV1 detection by PCR and by p24 antigen determination, we tested 34 anti-HIV1-positive AIDS patients for p24 antigen, HIV1 RNA and HIV1 provirus DNA. 97% had HIV1 provirus DNA, 35% had HIV RNA, but only 30% had p24 antigen. A multiplex PCR specific for HBV, HCV and HIV1 (RNA and DNA) was developed for the investigation of a blood donor population from Namibia, where HBV and HIV1 infections occur more frequently than in German blood donors. The prevalence of anti-HIV1 antibodies in this population was 0.6%. HIV1 RNA was never detected in the plasma of 2,569 anti-HIV1-negative donors. HIV1 provirus DNA was present in 75% of the 16 anti-HIV1-positive individuals. None of these anti-HIV1-positive blood donors was also positive for p24 antigen. CMV infections and reactivations in 130 immunocompromised heart transplant patients and in 420 healthy anti-CMV-positive blood donors were monitored using cytochemical detection of CMV early antigen, and PCR. CMV DNA was neither detected in the plasma nor in the leucocytes of any anti-CMV-positive blood donor. During the course of CMV reactivation in immunocompromised heart transplant patients, CMV DNA was always detectable first in granulocytes and afterwards in the plasma. The cytochemical demonstration of CMV early antigen was typically delayed by several days and was observed in only 11% of those blood samples which contained CMV DNA in leucocytes. The determination of CMV DNA in leucocytes proved to be the most sensitive method to detect viraemia. Thus, CMV detection in leucocytes is the method of choice for the monitoring of transplant patients. This method is also promising for blood donor screening. The sensitive routine monitoring of blood donations for virus infections by multiplex PCR is practicable. However, nucleic acid must be extracted both from the plasma and from the cellular compartments of blood in order to detect HIV and CMV provirus DNA. Lysate from EDTA blood is a suitable material for this purpose. The determination of the surrogate marker serum ALT activity is of no use in hepatitis C screening, and determination of p24 antigen is not required in HIV1 screening.
 ...
PMID:[Molecular biological screening of viruses important to transfusion medicine]. 948 64

Human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma are currently widely used clinically for prognostication and in monitoring antiretroviral therapy. Accurate and reproducible results are critical for patient management. To determine the effects of specimen collection and handling procedures on quantitative measurement of HIV-1 RNA, we compared anticoagulants and sample processing times. Whole blood was collected from 20 HIV-1-infected patients in EDTA, acid citrate dextrose (ACD), and heparin tubes, aliquoted, and stored at room temperature. Plasma was separated from whole-blood aliquots prepared at < or =1, 3, 6, 24, and 48 h postcollection and then stored at -70 degrees C until use. HIV-1 RNA levels were determined by the AMPLICOR HIV-1 MONITOR assay. Heparinized plasma samples, which were pretreated with heparinase prior to analysis, had the lowest baseline HIV-1 RNA levels. In the first 6 h, HIV-1 RNA levels decreased by 10, 20, and 31% in EDTA, ACD, and heparin tubes, respectively. From 6 to 48 h postcollection, HIV-1 RNA levels decreased in all anticoagulants, albeit at a slower, more consistent rate. Our results indicate that EDTA should be the anticoagulant of choice for plasma HIV-1 RNA measurement by reverse transcriptase PCR, but ACD tubes are acceptable if the plasma is separated within 6 h of blood collection. Caution must be applied in the interpretation of absolute HIV-1 RNA copy number values obtained with suboptimal specimen collection and processing procedures.
 ...
PMID:Optimization of specimen-handling procedures for accurate quantitation of levels of human immunodeficiency virus RNA in plasma by reverse transcriptase PCR. 954 39

Among the wall-less mycoplasmas only a few species have been identified with a capsule at their cell surface. Mycoplasma penetrans is a recently identified mycoplasma with unique morphology, isolated from HIV-infected patients. Using transmission electron microscopy, it was found that M. penetrans is surrounded by capsular material 11 nm (strain GTU-54-6A1) to 30 nm (strain HF-2) thick, which can be stained with ruthenium red and labelled with cationized ferritin. The polysaccharide composition of this capsule was indicated by its staining with periodic acid-thiocarbohydrazide silver proteinate and the abolition of ruthenium red staining of the cell surface by neuraminidase treatment. In addition, proteinase K treatment of the M. penetrans cells resulted in removal of the capsule, suggesting that polypeptides may contribute in anchoring it to the membrane or in its stability. Two different types of glycosylated material were detected in mycoplasma extracts by SDS-PAGE and periodic acid-Schiff staining. The first component was a high-molecular-mass material, which was heat- and proteinase-K-labile and which probably constitutes the capsular polymer. The other component was a low-molecular-mass glycolipid fraction, which was proteinase-K-, heat- and EDTA-resistant. The identification of a capsule at the M. penetrans cell surface is of particular interest for a mycoplasma which has been shown to adhere to various host cells and to penetrate into their intracellular compartments. The capsule may have significance in the pathogenesis of disease associated with infection by this organism.
 ...
PMID:Identification of two glycosylated components of Mycoplasma penetrans: a surface-exposed capsular polysaccharide and a glycolipid fraction. 961 99

Co-infections such as Mycobacterium tuberculosis (TB) and Pneumocystis pneumonia may affect the progress of HIV infection and speed the onset of death. As malaria and syphilis are both endemic in West Africa we examined their effects on HIV-2 infection, for these may also accelerate the progress of disease. A community-based case-control study was undertaken in a rural village in Guinea-Bissau, West Africa. One hundred and fifty asymptomatic subjects seropositive for HIV-2 and 154 age- and sex-matched controls were enrolled. Venous blood samples taken into EDTA were stained within six hours of collection with CD4 and CD8 monoclonal antibodies and processed by Q-Prep machine in the field. The stained cells were then transported on ice by road and analysed by FACS-can at the base laboratory in The Gambia within a week. The mean CD4% was significantly lower and geometric mean neopterin and beta 2-microglobulin levels were significantly higher in the HIV-2-infected subjects than in the controls (P < 0.01 for all cases versus all controls). The mean CD4% was lower and beta 2-microglobulin level was higher in both HIV-2 and control subjects with active or past syphilis when compared with subjects with no syphilis; however, syphilis did not have a marked effect on plasma neopterin level. Malaria infection raised neopterin levels, but had little effect on CD4%. Overall multiple regression analysis allowing for HIV-2 infection and other variables showed that syphilis lowered CD4% (P = 0.01) and raised beta 2-microglobulin levels (P = 0.05) and malaria raised neopterin levels (P = 0.05). The conclusions are that HIV-2 infection is associated with lower CD4% and higher neopterin and beta 2-microglobulin levels than controls, and co-infection with syphilis is associated with a further lowering of CD4%, suggesting a worse suppression of the immune system. Co-infection with malaria is associated with a modest immune disturbance.
 ...
PMID:Immune stimulation by syphilis and malaria in HIV-2-infected and uninfected villagers in West Africa. 962 34

Due to considerable technical progress during the last few years the diagnosis of HIV-infection has been substantially improved. Third generation antibody screening assays, which also detect antibodies of the IgM and IgA type, have considerably narrowed the immunological window. The determination of the viral load in peripheral blood employing nucleic acid amplification techniques is now generally available and used for diagnostic and prognostic purposes as well as for the monitoring of antiviral therapy. To detect a HIV-infection the antibody screening assay is primarily used and complemented by the HIV-1 p24 antigen assay provided an early primary infection is suspected. In the latter case the antibody screening assay is often negative or indeterminate, while the p24 antigen assay is positive. According to the 1998 guidelines of the Federal Office for Public Health, the physician will be informed of the screening assay result without the need to await a confirmatory test in case of a reactive screening assay in the first sample. Confirmation, e.g. by immunoblot, will be done in a second blood sample which should be sent to the laboratory as soon as possible. EDTA-blood is recommended for this purpose, because it is best suited for quantification of plasma viremia, which has become a prerequisite for the institution and follow-up of antiretroviral treatment. The second sample will also serve to exclude false positive results due to clerical errors, and to determine the type of HIV, i.e. HIV-1 or HIV-2. The concept outlined should accelerate the availability of reactive test results to the physician and should reduce the cost of the diagnostic procedure.
 ...
PMID:[HIV diagnosis 1998]. 964 24

Part of the neurodegenerative cascade in AIDS dementia may involve overexpression of matrix metalloproteinases (MMPs). Here, we examined the possible effect of HIV-1 gp41, which has been shown as a key determinant associated with pathogenesis of AIDS dementia, on the activity of MMPs using human neuronal and glial cell lines. Zymographic analysis revealed that treatment with the gp41 peptide (aa 583-599) for 24 h markedly elevated the activity of MMP with Mr 66 kDa in the cultured media of glioblastoma cell line T98G in a concentration-dependent manner as well as of neuroblastoma cell line SK-N-SH despite of lower magnitude of the activity. In contrast, the immediately adjacent gp41 peptide (aa 598-613) as well as the reverse peptide (aa 598-583) had a little effect. Recombinant gp41 protein containing extracellular domain also elicited a similar effect, although with a lesser extent. This 66 kDa MMP was confirmed as gelatinase A (MMP-2) based on the results of its activity dependent on Ca2+ and inhibited in the presence of 1,10-phenanthroline or EDTA, as well as its specific immunoreactivity on the Western blot. N-acetyl cysteine (NAC) downregulated this gp41 peptide-induced MMP-2 activity in T98G. The soluble form of amyloid precursor protein (sAPP), which is synthesized in the Escherichia coli system, also inhibited the MMP-2 activity in vitro. Taken together, these results implicate that high production of HIV-1 gp41 or its metabolites containing aa 583-599 within central nervous system (CNS) could result in the increased activity of MMP-2 and that the extracellular deficiency of reducing agent or decreased level of sAPP within CNS could exacerbate this gp41-induced MMP-2 activity.
 ...
PMID:Increased activity of matrix metalloproteinase-2 in human glial and neuronal cell lines treated with HIV-1 gp41 peptides. 969 54

False negativity in a commercial anti-HIV kit (IMx HIV-1/HIV-2 3rd Generation Plus (code 8B32) was investigated, and the kit that superseded it (IMx HIV-1/HIV-2 III Plus, code 8C98) was evaluated. In a comparison on 574 freshly collected anti-HIV-1-positive specimens, 97.2% were more reactive in 8C98 than in 8B32; 35.5% were more than twice as reactive and 8.5% were more than four times as reactive. In 8B32, the signal from 55 specimens selected because of weak reactivity was enhanced 1.5 to 8.8 times by preliminary heating at 56 degrees C for 30 min. The reactivity of the 55 heated sera was then similar to that of the same specimens tested without heat treatment in the 8C98 assay. Reactivity in 8B32 was also increased in 66 of 76 (at least twofold in 20) randomly chosen anti-HIV-positive serum specimens by the addition of EDTA (10 mM final concentration). One of these specimens was false negative (signal:cutoff (S:CO) ratio 0.76) in 8B32, though its reactivity was restored by addition of EDTA (S:CO ratio 9.54). These findings indicate that the inhibitory effect that originally led to false negative findings in 8B32 was probably due to complement activity, and that the same activity was present in the freshly collected specimens used here to evaluate the replacement IMx anti-HIV assay (8C98). The specimen panel employed to evaluate 8C98 included 1,892 anti-HIV-positive and 779 anti-HIV-negative specimens. There were no false negative reactions. The lowest S:CO ratio observed was 6.2 and only 17 (0.2%) anti-HIV-positive specimens gave ratios less than 10. Nine unreproducible false positive reactions arose, all possibly attributable to specimen carryover by the IMx instrument. The performance of 8C98 was also compared with that of 10 other current anti-HIV kits using 21 sets of seroconversion specimens (127 specimens in total), and five performance assessment panels (92 specimens in total) comprised mostly of single bleeds from recent seroconverters. IMx 8C98 was the second most sensitive assay. We found no evidence that the 8C98 kit was prone to the effect that had given rise to false negative results in its predecessor (8B32).
 ...
PMID:False negativity by an anti-HIV assay kit (IMx 8B32) and evaluation of its replacement (IMx 8C98). 974 70

The interferon-inducible, double-stranded (ds) RNA-dependent protein kinase (PKR) regulates protein synthesis initiation by phosphorylating the alpha-subunit of eukaryotic translation initiation factor 2 (eIF-2). The amino-terminal half of PKR contains two dsRNA binding domains, and the kinase domain resides in the carboxy-terminal half of the protein. PKR is a ribosomal-associated protein. In this report, we provide evidence that PKR contains three ribosome interaction sites, two that are localized in each of the dsRNA binding domains and one that is localized in the kinase domain. All three domains can associate with polysomes independently. The ribosome association of the dsRNA binding domains requires dsRNA binding activity. Ribosome interaction of either the individual or the combined dsRNA binding domains was disrupted by 0.1 M KCl. In contrast, the ribosome interaction of intact PKR and the isolated kinase domain was largely resistant to 0.5 M KCl. These results indicate that all three domains of PKR contribute to the high-affinity ribosomal association. After dissociation of polysomes with EDTA, both intact PKR and the isolated kinase domain were primarily associated with the 60S ribosomal subunit. Coexpression of the adenovirus VAI RNA, an RNA polymerase III gene product that binds and inactivates PKR, disrupted ribosomal association of intact PKR, but not of the isolated PKR kinase domain. The results support a model where VAI RNA induces a major conformational change in PKR to prohibit ribosome association of all interaction sites. In contrast, other inhibitors of PKR including vaccinia virus E3L and K3L gene products, and the HIV trans-activating response (TAR) element binding protein TRBP, did not disrupt ribosome association of PKR. The results suggest a novel mechanism by which viral RNAs may inactivate PKR through disrupting ribosome association.
 ...
PMID:Identification and requirement of three ribosome binding domains in dsRNA-dependent protein kinase (PKR). 975 71

A new immunochromatographic rapid test, Determine HIV-1/2, for the detection of antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2 in human whole blood, serum, and plasma was evaluated. Determine HIV-1/2 is a sandwich immunoassay and uses a nitrocellulose strip with a capture site for the patient's results and a procedural control site to confirm the validity of the assay. The results can be read visually, and a positive result is indicated by the formation of a red line within 15 min after sample application. The test showed 100% sensitivity for HIV-1 with 102 whole-blood, 152 serum, and 144 plasma samples obtained from Ramathibodi Hospital, Bangkok, Thailand. The sensitivity of the test for HIV-2 was 100% with 100 serum or plasma samples obtained from Ivory Coast. The sensitivity of the test with 4 anti-HIV-1 seroconversion panels from Boston Biomedica Inc. was equivalent to or better than those of another agglutination assay with serum or plasma and the enzyme immunoassay licensed by the U.S. Food and Drug Administration. The specificity was 100% with 367 sets of whole-blood, serum, and plasma samples from Ramathibodi Hospital. This method had an analytical sensitivity for the detection of HIV-1 equivalent to or better than that of another agglutination assay with serum or plasma. This test had an analytical sensitivity for the detection of HIV-1 better than that of another immunochromatographic test with whole blood. This evaluation demonstrated the excellent performance of this immunochromatographic test with EDTA-anticoagulated whole-blood, serum, and plasma samples. We conclude that this test is suitable for use in emerging countries and is an excellent alternative to HIV antibody testing at remote sites, as well as in traditional laboratories.
 ...
PMID:Evaluation of a rapid immunochromatographic test for detection of antibodies to human immunodeficiency virus. 988 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>