Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inherited human disorders sialidosis and galactosialidosis are the result of deficiencies of glycoprotein-specific alpha-neuraminidase (acylneuraminyl hydrolase, EC 3.2.1.18; sialidase) activity. Two genes were determined to be necessary for expression of neuraminidase by using human-mouse somatic cell hybrids segregating human chromosomes. A panel of mouse RAG-human hybrid cells demonstrated a single-gene requirement for human neuraminidase and allowed assignment of this gene to the (pter----q23) region of chromosome 10. A second panel of mouse thymidine kinase (TK)-deficient LM/TK- -human hybrid cells demonstrated that human neuraminidase activity required both chromosomes 10 and 20 to be present. Analysis of human neuraminidase expression in interspecific hybrid cells or polykaryocytes formed from fusion of mouse RAG (hypoxanthine/guanine phosphoribosyltransferase deficient) or LM/TK- cell lines with human sialidosis or galactosialidosis fibroblasts indicated that the RAG cell line complemented the galactosialidosis defect, but the LM/TK- cell line did not. This eliminates the requirement for this gene in RAG-human hybrid cells and explains the different chromosome requirements of these two hybrid panels. Fusion of LM/TK- cell hybrids lacking chromosome 10 or 20 (phenotype 10+,20- and 10-,20+) and neuraminidase-deficient fibroblasts confirmed by complementation analysis that the sialidosis disorder results from a mutation on chromosome 10, presumably encoding the neuraminidase structural gene. Galactosialidosis is caused by a mutation in a second gene required for neuraminidase expression located on chromosome 20.
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PMID:Sialidosis and galactosialidosis: chromosomal assignment of two genes associated with neuraminidase-deficiency disorders. 308 2

Most drugs available for cancer chemotherapy exert their effects through cytodestruction. Although significant advances have been attained with these cytotoxic agents in several malignant diseases, response is often accompanied by significant morbidity and many common malignant tumours respond poorly to existing cytotoxic therapy. Development of chemotherapeutic agents with non-cytodestructive actions appears desirable. Considerable evidence exists which indicates that (a) the malignant state is not irreversible and represents a disease of altered maturation, and (b) some experimental tumour systems can be induced by chemical agents to differentiate to mature end-stage cells with no proliferative potential. Thus, it is conceivable that therapeutic agents can be developed which convert cancer cells to benign forms. To study the phenomenon of blocked maturation, squamous carcinoma SqCC/Y1 cells were employed in culture. Using this system it was possible to demonstrate that physiological levels of retinoic acid and epidermal growth factor were capable of preventing the differentiation of these malignant keratinocytes into a mature tissue-like structure. The terminal differentiation caused by certain antineoplastic agents was investigated in HL-60 promyelocytic leukaemia cells to provide information on the mechanism by which chemotherapeutic agents induce cells to by-pass a maturation block. The anthracyclines aclacinomycin A and marcellomycin were potent inhibitors of N-glycosidically linked glycoprotein biosynthesis and transferrin receptor activity, and active inducers of maturation; temporal studies suggested that the biochemical effects were associated with the differentiation process. 6-Thioguanine produced cytotoxicity in parental cells by forming analog nucleotide. In hypoxanthine-guanine phosphoribosyltransferase negative HL-60 cells the 6-thiopurine initiated maturation; this action was due to the free base (and possibly the deoxyribonucleoside), a finding which separated termination of proliferation due to cytotoxicity from that caused by maturation.
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PMID:The 1985 Walter Hubert lecture. Malignant cell differentiation as a potential therapeutic approach. 389 54

Using a monoclonal antibody specific for human fibronectin (FN), we screened hybrid clones derived from the fusion of FN+ human fibroblasts, carrying a 11/X translocation, and FN-, HPRT- mouse cells for the production of this glycoprotein. Since no hybrid clone retaining the human der 11 chromosome was found to produce any human fibronectin, the segment of chromosome 11 included in the rearranged chromosome (11qter leads to 11p13) probably does not carry the structural locus for fibronectin.
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PMID:Human fibroblasts X mouse cell hybrids, containing a human 11/X translocation, do not express human fibronectin. 685 Aug 63

Mouse A9 cells, L-cell-derived mutants deficient in hypoxanthine phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) were found to be incapable of binding (125)I-labeled epidermal growth factor (EGF) to the cell surface. The A9 cells were fused with human diploid fibroblasts (WI-38) possessing EGF-binding ability, and human-mouse cell hybrids (TA series) were isolated after hypoxanthine/aminopterin/thymidine/ouabain selection. Analyses of isozyme markers and chromosomes of four representative clones of TA hybrids indicated that the expression of EGF-binding ability is correlated with the presence of human chromosome 7 or 19. Four subclones were isolated from an EGF-binding-positive line, TA-4, and segregation of EGF-binding was found to be concordant with the expression of human mitochondrial malate dehydrogenase (MDHM; L-malate:NAD(+) oxidoreductase, EC 1.1.1.37), a marker for chromosome 7, but not with glucosephosphate isomerase (GPI; D-glucose-6-phosphate ketol-isomerase, EC 5.3.1.9), a marker for chromosome 19. Furthermore, evidence from 27 clones of AUG hybrids that were produced between A9 and another human fibroblast line, GM1696, carrying an X/7 chromosome translocation indicated that EGF-binding ability segregates together with human MDHM and two X-linked markers, HPRT and glucose-6-phosphate dehydrogenase (G6PD; D-glucose-6-phosphate:NADP(+) 1-oxidoreductase, EC 1.1.1.49), that are located on the translocation chromosome 7p(+). These results permit assignment of the gene, designated EGFS, which is associated with the expression of EGF-binding ability, to human chromosome 7 and its localization to the p22-qter region. Because the EGF receptor is reported to be a glycoprotein the EGFS could be either a structural gene(s) for receptor protein or a gene(s) for modifying the receptor protein through glycosylation.
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PMID:Genetics of cell surface receptors for bioactive polypeptides: binding of epidermal growth factor is associated with the presence of human chromosome 7 in human-mouse cell hybrids. 696 72

Laser microdissection combined with real-time RT-PCR represents a powerful method to analyse the transcription efficiency of defined cell types. Therefore, a RNA-preserving immunolabelling method was established to identify neurons and astrocytes in persistently BDV-infected rat brain sections for subsequent laser microdissection and quantitation of viral gene products by real-time RT-PCR. Firstly, to ensure an accurate measurement of viral RNA after immunolabelling, different reference genes (glyceraldehyde-3-phosphate dehydrogenase [GAPDH], succinate-ubiquinone reductase [SDHA], hypoxanthine phosphoribosyl-transferase-1 [HPRT]) were tested. Only normalisation with GAPDH yielded a stable relative expression of viral RNA encoding the nucleoprotein (BDV-N), the matrixprotein and the glycoprotein (intron I and intron II). The two remaining reference genes biased the ratios of BDV-transcripts in the immunolabelled brain sections significantly. Secondly, 100 immunolabelled neurons and astrocytes were harvested using laser microdissection and amplification of all viral transcripts revealed 681 and 168 (BDV-N), 573 and 254 (intron I), 324 and 133 (intron II) and 161 and 36 (GAPDH) absolute copy numbers in neurons and astrocytes, respectively. Thus, laser microdissection combined with real-time RT-PCR provides an effective tool for the analysis of cell-specific viral transcription efficiency and allows elucidating virus-host-interactions and virus persistence mechanisms in the CNS.
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PMID:A rapid method for gene expression analysis of Borna disease virus in neurons and astrocytes using laser microdissection and real-time RT-PCR. 1805 93