Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on the know epidemiology of the viruses that account for the bulk of the need for chimpanzees in biomedical research--hepatitis B virus (HBV), non-A, non-B (NANB) hepatitis virus, and human immunodeficiency virus (HIV)--as well as the psychosocial needs of this species, requirements for appropriate isolation conditions for these animals have been reviewed. We believe that animals should generally be housed in groups of at least two in the same cage, and that cages encased in solid-walled isolator boxes for housing of single chimpanzees are unnecessary for virologically adequate isolation for studies of HBV, NANB and HIV, and cause sensory and psychosocial deprivation, which contravenes their psychological well-being.
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PMID:Appropriate conditions for maintenance of chimpanzees in studies with blood-borne viruses: an epidemiologic and psychosocial perspective. 249 32

(2'R,5'S-)-cis-5-Fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine (524W91) is a nucleoside analog with potent anti-human immunodeficiency virus and anti-human hepatitis B virus activities in vitro. The pharmacokinetics and bioavailability of 524W91 after oral dosing were studied in mice dosed with 10, 100, and 600 mg of 524W91 per kg of body weight by the oral and intravenous routes. Cynomolgus monkeys were dosed with 10 and 80 mg of 524W91 per kg. In both species, the clearance of 524W91 was rapid, via the kidney, and was independent of dose. In monkeys, the total body clearance of 10 mg of 524W91 per kg was 0.7 +/- 0.1 liter/h/kg, and the volume of distribution at steady state was 0.8 +/- 0.02 liter/kg. The terminal elimination half-life was 1.0 +/- 0.2 h. The absolute bioavailability after oral dosing was 63% +/- 4% at 10 mg/kg. Concentrations of 524W91 in the cerebrospinal fluid were 4% +/- 0.7% of the corresponding levels in plasma. In mice, the total clearance of 10 mg of 524W91 per kg was 2.3 liters/kg/h, and the volume of distribution at steady state was 0.9 liter/kg. Absolute bioavailability in mice after oral dosing was 96% at a dose of 10 mg/kg. The metabolism of orally administered [6-3H]524W91 was studied in cynomolgus monkeys at a dose of 80 mg/kg and in mice at a dose of 120 mg/kg. Monkeys excreted 41% +/- 6% of the radioactive dose in the 0- to 72-h urine, 33% +/- 10% in the feces, and 10% +/- 7% in the cage wash. Unchanged 524W91 was 64% of the total radiolabeled drug recovered in the urine. The glucuronide was a minor urinary metabolite. 5-Fluorouracil was not detected (less than 0.02% of the dose). Mice dosed orally with 120 mg of [6-3H]524W91 per kg excreted 67% +/- 7% of the radiolable in the )- to 48-h urine. Small amounts of the 3' -sulfoxide and glucuronide metabolites were observed in the urine, but 5-fluorouracil was not detected. Good bioavailability after oral dosing and resistance to metabolism recommend 524W91 for further preclinical evaluation.
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PMID:Pharmacokinetics, oral bioavailability, and metabolism in mice and cynomolgus monkeys of (2'R,5'S-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] cytosine, an agent active against human immunodeficiency virus and human hepatitis B virus. 769 53

Our objective was to identify factors that might correlate with human immunodeficiency virus (HIV) disease stage in intravenous drug abusers (IVDA). Particular attention was given to alcohol abuse. We accordingly explored in a cross-sectional study the relation between stage of HIV disease and age, sex, needle sharing, ethnicity, self-reported history of alcohol consumption and CAGE scores. IVDA from a single municipal hospital were subdivided into three groups according to HIV disease status. Group 1 comprised 42 individuals with AIDS; group 2 comprised 114 who were HIV positive but without AIDS; and group 3 comprised 52 who were HIV negative. Information on alcohol consumption and CAGE responses were obtained by questionnaire and interview. Discriminant analysis indicated that alcohol abuse, assessed either by self-reported consumption or by CAGE scores, was significantly more common in the AIDS group than in either the HIV positive or the HIV negative groups, when controlled for age, sex, and needle sharing status. The relative risk of AIDS was 3.8 times higher in the heavy drinkers than in moderate drinkers. Needle sharing was also more common in the AIDS group than in the HIV positive or HIV negative groups when the other factors were controlled for. AIDS was more common in black than white IVDA, and this increased frequency did not appear related to alcohol consumption since the distribution of heavy drinkers within each category of HIV disease did not differ within the ethnic groups. These data indicate that a history of heavy alcohol consumption is more common in IVDA with AIDS than in IVDA at earlier stages of HIV disease.
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PMID:Alcohol abuse and stage of HIV disease in intravenous drug abusers. 877 37

Cancer-associated human papillomavirus (HPV) types are detected in genital warts removed from immunosuppressed individuals more commonly than from those occurring in otherwise healthy individuals. The prognosis of genital warts containing cancer-associated HPV types is not known. Because it is assumed that genital warts are benign lesions, they are usually treated by destructive therapies without prior knowledge of histopathology. The aim of the present study was to determine whether genital warts from individuals with or without human immunodeficiency virus (HIV) contain high-risk HPV types or areas of dysplasia. The study design was a nonrandomized analysis of genital warts removed by excision biopsy from 15 HIV-infected patients and 15 HIV-negative patients. The tissue was analyzed for HPV DNA by hybrid capture, and microscopic sections of each biopsy were examined for areas of dysplasia. Genital warts from HIV-infected patients contained cancer-associated ("high risk") HPV types in 9 of 15 cases, including 1 that contained only a high-risk type. High-grade dysplastic abnormalities were present in 2 of the 15 lesions from this group, both of which contained high-risk HPV types. Four genital warts removed from HIV-negative patients contained high-risk HPV types, but none contained dysplastic abnormalities. It is concluded that genital warts from HIV-infected patients often contain high-risk HPV types. Such lesions may exhibit dysplastic changes. The frequency of dysplastic changes in genital warts from HIV-infected patients is not known. Biopsy of genital warts may be indicated prior to additional therapy in HIV-infected patients, and surgical removal should be considered as a preferred treatment option in these patients.
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PMID:High-grade dysplasia in genital warts from two patients infected with the human immunodeficiency virus. 944 11

In an in vitro system that mimics the assembly of immature human immunodeficiency virus (HIV) particles, ordered arrays of HIV-1 capsid (CA) proteins encoded by the viral gag gene have been obtained by incubation of histidine-tagged capsid proteins (His-HIVCA) beneath lipid monolayers containing the nickel-chelating lipid, 1,2-di-O-hexadecyl-sn-glycero-3-(1'-2"-R-hydroxy-3'-N-(5-amino-1- carboxypentyl)iminodiacetic acid)propyl ether. The membrane-bound His-HIVCA proteins formed small crystalline arrays of primitive (p1) unit cells with dimensions of a = 74.2 A, b = 126.2 A, gamma = 89.3 degrees. The image-analyzed two-dimensional projection of His-HIVCA assemblies shows a cage-like lattice, consisting of hexamer and trimer units, surrounding protein-free cage holes. The hexamer-coordinated cage holes of 26.3-A diameter are spaced at 74. 2-A intervals: these distances, and the hexamer-trimer arrangement, are consistent with previous, lower resolution studies on immature HIV-1 virus particles produced in vivo. Additionally, HIV-1 matrix protein trimer unit structures align to the His-HIVCA trimer units such that residues previously shown to interact with the HIV-1 gp120/gp41 envelope protein complex are oriented toward the hexamer cage holes. Our results form a bridge between results from conventional methods for the analysis of HIV particle structure.
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PMID:Organization of HIV-1 capsid proteins on a lipid monolayer. 951 5

Ovarian cancer cells were isolated from ascites fluid of 30 different patients diagnosed with cystadenocarcinoma of ovaries. Large colonies of malignant ASC cells were observed during the first week of cell growth in vitro. Colony formation was followed by fusion of cells and formation of large multinucleated and highly vacuolated syncytia. In contrast, cells isolated from the ascites fluid produced by patients with benign mucinous cystadenoma of ovaries did not form syncytia. Nonmalignant Brenner tumor cells, isolated from the ascites fluid, also did not form syncytia. Syncytia, but not the nonmalignant tumor cells, were immunofluorescence stained with an anti-human immunodeficiency virus type 1 (HIV-1) gp120 monoclonal antibody (MAb) and MAb RAK-BrI. Both MAbs recognized cancer-associated antigens RAK (for Rakowicz markers) p120, p42, and p25. Exposure of ASC cells to either the anti-HIV-1 gp120 MAb or MAb RAK-BrI inhibited syncytium formation. PCR with HIV-1 Env-derived primers revealed DNA sequences with over 90% homology to HIV-1 gp41 in syncytia and in ovarian cancer cells but not in normal ovary cells. Electron microscopic analysis revealed viral particles, hexagonal in shape (90 nm in diameter), with a dense central core surrounded by an inner translucent capsid and dense outer shell with projections. Negative staining detected membrane-covered particles (100 to 110 nm in diameter) in the cell culture medium. Incubation of normal breast cells with viral particles resulted in drastic morphological changes and syncytium formation by the transformed breast cells. The cytopathic effects of the identified virus resembled those of spumaviruses, which, in addition to their epitopic and genetic homology to HIV-1, might suggest a common phylogeny.
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PMID:Giant syncytia and virus-like particles in ovarian carcinoma cells isolated from ascites fluid. 987 74

Children with hypertension, seizures, lethargy, encephalopathy, headache, and occipital blindness are reviewed. After undergoing antihypertensive therapy, most children improve. Some patients have a similar syndrome associated with chemotherapy, transplantation, transfusion, or human immunodeficiency virus-1 (HIV-1) infection. These latter children can develop symptoms with only minimal or no discernible elevations in blood pressure and improve, in the case of cancer-associated encephalopathy, after discontinuing chemotherapy. The reported children with this distinctive clinical condition are compared to adults with reversible posterior leukoencephalopathy syndrome. Since both gray and white matter are involved, we had suggested previously that the name be changed to (reversible) occipitoparietal encephalopathy syndrome. However, reversible posterior leukoencephalopathy has been used in the adult population and probably should be employed in children for the sake of uniformity, since both children and adults have the same clinical presentation and presumably a similar pathophysiology for the encephalopathy syndrome. The diagnosis is confirmed by reversible posterior abnormalities seen on T2-weighted brain magnetic resonance imaging, and by the presence of either headache, altered mental status, seizures, or visual disturbances.
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PMID:Hypertensive encephalopathy, reversible occipitoparietal encephalopathy, or reversible posterior leukoencephalopathy: three names for an old syndrome. 1034 93

An efficient antigen expression system using a recombinant Sendai virus (SeV) has been established recently and its potential to induce resistance against immunodeficiency virus infections in macaques has been shown. SeV replication has been well characterized in mice, the natural host, but not in primates, including humans. Here, primary SeV replication was investigated in macaques. After intranasal immunization with a recombinant SeV expressing simian immunodeficiency virus Gag protein, SeV-Gag, robust gag expression was observed in the nasal mucosa and much lower but significant levels of gag expression were observed in the local retropharyngeal and submandibular lymph nodes (LN). Expression peaked within a week and lasted at least up to 13 days after immunization. SeV-Gag was isolated from nasal swabs consistently at day 4 but not at all at day 13. Gag expression was undetectable in the lung as well as in remote lymphoid tissues, such as the thymus, spleen and inguinal LN, indicating that the spread of the virus was more restricted in macaques than in mice. SeV-specific T cells were detectable in SeV-immunized macaques at day 7. Finally, no naive macaques showed significant levels of anti-SeV antibodies in the plasma, even after living in a cage together with an acutely SeV-infected macaque for 5 weeks, indicating that SeV transmission from SeV-infected macaques to naive ones was inefficient. None of the SeV-immunized macaques displayed appreciable clinical manifestations. These results support the idea that this system may be used safely in primates, including humans.
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PMID:Primary replication of a recombinant Sendai virus vector in macaques. 1202 53

Inadequate attention has been paid to the frequent and often extensive cancer-associated DNA hypomethylation. This hypomethylation usually includes undermethylation of certain DNA repeats in constitutive heterochromatin, although it is not limited to such sequences. Many cancers display an overall deficiency in the levels of genomic 5-methylcytosine compared to a variety of normal postnatal somatic tissues. The immunodeficiency, centromeric region instability, facial anomalies (ICF) syndrome, a rare recessive DNA methyltransferase deficiency disease, results in a small decrease in the extent of global genomic methylation. In ICF, DNA hypomethylation is targeted to the satellite DNA in juxtacentromeric (centromere-adjacent) heterochromatin of chromosomes 1 and 16 (1qh and 16qh), which are prone to rearrangements in ICF lymphoid cells. Also, 1qh and 16qh DNA sequences frequently are hypomethylated in human cancers and rearrangements in their vicinity are overrepresented in cancers. These often lead to chromosome arm imbalances and gene dosage imbalances that could participate in carcinogenesis. Studies of ICF cells suggest that hypomethylation in the normally highly methylated 1qh and 16qh regions predisposes to heterochromatin decondensation in these regions, which in turn leads to elevated levels of rearrangements. Studies of ICF cells also suggest that some of these rearrangements, namely multiradial chromosomes with multiple arms joined in the pericentromeric region, may be unstable intermediates in formation of more stable pericentromeric rearrangements in cancer. Microarray gene expression analysis on ICF and normal lymphoblastoid cell lines suggests that this hypomethylation also may affect gene expression elsewhere in the genome.
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PMID:DNA hypomethylation, cancer, the immunodeficiency, centromeric region instability, facial anomalies syndrome and chromosomal rearrangements. 1216 5

Untreated cultures from normal chorionic villus (CV) or amniotic fluid-derived (AF) samples displayed dramatic cell passage-dependent increases in aberrations in the juxtacentromeric heterochromatin of chromosomes 1 or 16 (1qh or 16qh). They showed negligible levels of chromosomal aberrations in primary culture and no other consistent chromosomal abnormality at any passage. By passage 8 or 9, 82 +/- 7% of the CV metaphases from all eight studied samples exhibited 1qh or 16qh decondensation and 25 +/- 16% had rearrangements in these regions. All six analyzed late-passage AF cultures displayed this regional decondensation and recombination in 54 +/- 16 and 3 +/- 3% of the metaphases, respectively. Late-passage skin fibroblasts did not show these aberrations. The chromosomal anomalies resembled those diagnostic for the ICF syndrome (immunodeficiency, centromeric region instability, and facial anomalies). ICF patients have constitutive hypomethylation at satellite 2 DNA (Sat2) in 1qh and 16qh, generally as the result of mutations in the DNA methyltransferase gene DNMT3B. At early and late passages, CV DNA was hypomethylated and AF DNA was hypermethylated both globally and at Sat2. DNMT1, DNMT3A, or DNMT3B RNA levels did not differ significantly between CV and AF cultures or late and early passages. The high degree of methylation of Sat2 in late-passage AF cells indicates that hypomethylation of this repeat is not necessary for 1qh decondensation. Sat2 hypomethylation may nonetheless favor 1qh and 16qh anomalies because CV cultures, with their Sat2 hypomethylation, displayed 1qh and 16qh decondensation and rearrangements at significantly lower passage numbers than did AF cultures. Also, CV cultures had much higher ratios of ICF-like rearrangements to heterochromatin decondensation in chromosomes 1 and 16. These cultures may serve as models to help elucidate the biological consequences of cancer-associated satellite DNA hypomethylation.
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PMID:Prolonged culture of normal chorionic villus cells yields ICF syndrome-like chromatin decondensation and rearrangements. 1258 36


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