Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used direct microinjection of messenger RNA into individual mouse and human cells to assay for specific translation products. We have been able to detect the synthesis of human fibroblast interferon, thymidine, kinase, hypoxanthine phosphoribosyltransferase, adenine phosphoribosyltransferase, and propionyl-CoA carboxylase in response to injected mRNA. Using the interferon system as a model, we have quantitated interferon synthesis and followed partial purification of interferon mRNA sequences on sucrose density gradients. The methods we have utilized should be applicable to other systems in which sensitive assays exist for gene products and should provide a screening procedure for isolating specific mRNA sequences.
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PMID:Biological detection of specific mRNA molecules by microinjection. 29 82

We have selected mutations in genes encoding components of the signaling pathway for alpha interferon (IFN-alpha) by using a specially constructed cell line. The upstream region of the IFN-regulated human gene 6-16 was fused to the Escherichia coli guanine phosphoribosyltransferase (gpt) gene and transfected into hypoxanthine-guanine phosphoribosyltransferase-negative human cells. These cells express gpt only in the presence of IFN-alpha. They grow in medium containing hypoxanthine, aminopterin, and thymidine plus IFN and are killed by 6-thioguanine plus IFN. Two different types of mutants were obtained after treating the cells with mutagens. A recessive mutant, selected in 6-thioguanine plus IFN, was completely resistant to IFN-alpha but responded normally to IFN-gamma and, unexpectedly, partially to IFN-beta. A constitutive mutant, selected in hypoxanthine-aminopterin-thymidine alone, was abnormal in expressing endogenous genes in the absence of IFN. Both types revert infrequently, allowing selection for complementation of the defects by transfection.
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PMID:Use of a selectable marker regulated by alpha interferon to obtain mutations in the signaling pathway. 251 75

The fusion of thioglycollate-elicited peritoneal macrophages from the lipopolysaccharide (LPS)-nonresponsive C3H/HeJ mouse strain to a hypoxanthine phosphoribosyltransferase (HPRT)-negative variant of the murine macrophage cell line P388D1 has resulted in the derivation of eight hybrid clones following HAT selection. Propidium-Iodide staining followed by flow cytometry has demonstrated that the DNA content of the hybrids represents the sum of the parents. Codominant expression of class I antigens from both parental haplotypes is observed in the hybrids. While class II antigens are inducible following a 72-hr induction with gamma interferon-containing supernatants, the amount of each haplotype varies between clones. These hybrids demonstrate Fc-mediated erythrophagocytosis in contrast to P388D1. In distinction to the C3H/HeJ primary peritoneal-macrophage parent, LPS treatment of the hybrids results in the increased release of both interleukin-1 (IL-1) and cachectin/tumor necrosis factor (TNF) into culture supernatants. Therefore, cell fusion has resulted in the stable restoration of the LPS-responsive phenotype in C3H/HeJ macrophage hybrids. These macrophage hybrids should serve as useful models in understanding the regulation of macrophage effector functions in response to environmental stimuli.
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PMID:Restoration of the lipopolysaccharide-responsive phenotype in C3H/HeJ peritoneal macrophage-P388D1 cell hybrids. 325 49

Alpha and beta interferons control expression of a selectable marker in the human hypoxanthine phosphoribosyltransferase-negative cell line 2fTGH, in which transcription of gpt is regulated by the upstream region of an interferon-responsive human gene. Selection of mutagenized 2fTGH cells in hypoxanthine-aminopterin-thymidine medium yielded mutants in one recessive (C1) and two dominant (C2 and C3) complementation groups. The mutants constitutively expressed low levels of beta interferon (C1), alpha interferon (C2), or both (C3).
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PMID:Constitutive production of alpha and beta interferons in mutant human cell lines. 818 43

In order to quantify in vivo the mRNAs of cytokines which play important roles in leptospirosis, we have developed quantitative real-time PCR assays for interleukin-2 (IL-2), IL-4, IL-10, IL-12p40, tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma), transforming growth factor beta, and two housekeeping genes (encoding beta-actin and hypoxanthine phosphoribosyltransferase). We used a lethal hamster model reflecting severe leptospirosis in humans. The LightCycler system was used to quantify the gene expression levels with the SYBR green I detection format using external standard curves for each target. We compared the expression levels of cytokine mRNA in the peripheral blood mononuclear cells of both control (uninfected) hamsters and Leptospira interrogans-inoculated hamsters from 1 to 24 h and then 1 to 4 days postinfection. In this kinetic study, there was pronounced expression of Th1 cytokine mRNA (TNF-alpha, IFN-gamma, and IL-12), with transcripts being detected as early as 1 h postinfection. Expression of anti-inflammatory cytokines, such as IL-4 and IL-10, was prominent in delayed samples from 1 to 4 days postinfection in response to infection with Leptospira interrogans. Our data are the first to establish that pathogenic leptospires can stimulate in vivo the production of type 1 cytokines involved in cellular immunity by using this informative animal model. Measuring and assessing cytokine profiles may provide a useful method for accurate study of the mechanisms of anti-Leptospira immunity, indications of prognosis factors, and prospective evaluation of leptospirosis vaccine efficacy in humans.
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PMID:Proinflammatory and immunomodulatory cytokine mRNA time course profiles in hamsters infected with a virulent variant of Leptospira interrogans. 1679 Jul 92

A microarray for demonstration of a limited number of porcine cytokines was initiated. Polymerase chain reaction (PCR) products were synthesized for four house-keeping genes, cyclophilin, beta-actin, hypoxanthine phosphoribosyltransferase (HPRT) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and the following cytokines: interleukin (IL)-1beta, IL-4, IL-6, IL-8, IL-10, IL-12 p35, IL-12 p40, IL-18, interferon (IFN)-alpha, IFN-beta, IFN-gamma, tumour necrosis factor (TNF)-alpha, macrophage inhibition factor (MIF) and granulocyte/macrophage colony-stimulating factor (GM-CSF). Cytokine production was induced by incubation of porcine peripheral blood mononuclear cells (PBMC) with Concanavalin A (ConA) or oligodeoxynucleotide (ODN) 2216. RNA was isolated after 6 or 24 h from stimulated cells or unstimulated control cells and from intestinal biopsies. Cytokine expression was analysed using a 3-DNA Array 350(TM) labelling kit from Genisphere. Data were normalized using external control genes and analysed with the genepix pro 5.0 software. All the cytokines could be induced in PBMC and expressed on the array and the cytokines IL-6 and IFN-alpha were also analysed at protein level. All but one cytokine were expressed in samples from intestinal biopsies. Densitometric analyses of PCR products of the house-keeping genes were performed to validate the results from the microarray. Thus, this microarray will enable analyses of the cytokine profile during local and systemic infections in the pig.
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PMID:Development of a microarray for studying porcine cytokine production in blood mononuclear cells and intestinal biopsies. 1738 82