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 studied a case of Lesch-Nyhan syndrome with delayed onset of self-mutilation. Athetotic cerebral palsy and mental retardation were diagnosed at 1 year old, but the disease was not suspected until age 8 years when he began biting his lips and fingers. There was no obvious alteration of catecholamine in urine and CSF. We attempted to induce a series of blink reflexes by electric, mechanical and photic procedures. The R1 amplitude increased and the latency of the R2 shortened compared with controls. This shows that not only orbicularis motoneuron itself, but also uncrossed interneurons, are in a state of hyperexcitability. The contralateral R2 was poor which was in favour of hypoexcitability of the crossed interneurons at the brainstem. The significant large response was obtained by photic procedure which was in favour of hyperexcitability of the motoneurons. Therefore, it is demonstrated that a thorough examination of blink reflexes provides a useful method for examination of a state of the underlying neural activity.
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PMID:Lesch-Nyhan syndrome with delayed onset of self-mutilation: hyperactivity of interneurons at the brainstem and blink reflex. 232 43

Purine metabolism in the Lesch-Nyhan syndrome has been re-examined in 10 patients. Hypoxanthine and xanthine concentrations in plasma and CSF and urinary excretion have been studied, on and off allopurinol treatment, using high performance liquid chromatographic methods. Accumulation of the substrate, hypoxanthine, of the missing hypoxanthine guanine phosphoribosyltransferase (HPRT) enzyme, is more marked in urine and in CSF than in plasma. The greater increase in CSF is consistent with the most metabolically active tissue, brain, showing the most marked functional changes. The function of HPRT seems to be the recycling of hypoxanthine which is released from tissues in increasing quantities as energy use, ATP 'turnover', in the tissue increases. The existing screening method for HPRT deficiency, the ratio of the urinary concentration of urate to that of creatinine, shows overlap between the values in severe HPRT deficiency and in controls; this overlap is not found with a urinary hypoxanthine/creatinine molar concentration ratio.
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PMID:Lesch-Nyhan syndrome and its pathogenesis: purine concentrations in plasma and urine with metabolite profiles in CSF. 314 65

Treatment of circulating human neutrophils with recombinant human granulocyte colony-stimulating factor (rhG-CSF) for 30 min augmented superoxide generation and chemotaxis induced by N-formylmethionyl-leucyl-phenylalanine (fMLP) in a dose dependent manner. When neutrophils were treated with 1 microM of methotrexate (MTX) for 60 min after incubation with rhG-CSF (10 ng/ml), the effects of rhG-CSF on superoxide generation and chemotaxis were inhibited by approximately 49 and 29%, respectively. Although inhibitory effects of MTX were also seen in neutrophils not pretreated with rhG-CSF, the degree of inhibition was much less. The addition of either hypoxanthine or guanosine at a concentration of 100 microM to the culture medium significantly attenuated the effects of MTX. However, in neutrophils obtained from a patient with Lesch-Nyhan syndrome, which lacked hypoxanthine-guanine phosphoribosyl transferase activity neither hypoxanthine nor guanosine had any rescue effect. These results suggest that MTX inhibits superoxide generation and chemotaxis in rhG-CSF-activated neutrophils, at least in part, by disturbing purine nucleotide biosynthesis.
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PMID:Methotrexate inhibits superoxide production and chemotaxis in neutrophils activated by granulocyte colony-stimulating factor. 864 14