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

Sleep EEG patterns in 23 mentally retarded children with cerebral palsy (CP) (from 4 months to 5 years of age) and 39 reference mentally retarded children of no abnormality with the exception of psychomotor retardation (from 4 months to 12 years of age) were studied throughout nocturnal sleep, and the following results were obtained. Eleven CP cases and 30 reference cases evidenced normal sleep patterns that could be classified into 6 stages. Twelve other cases in CP and 9 reference cases showed some abnormal sleep EEG patterns as follows: (i) in CP cases absence of EEG patterns characteristic of wakefulness, NREM sleep and REM sleep without spindles (n = 3); porencephaly with microcephaly (n = 1) and cytomegalovirus infection (n = 2), no characteristic EEG patterns of stages 1-4 without spindles (n = 2); cardiac arrest (n = 1) and agenesis of corpus callosum with lissencephaly (n = 1), absence of REM sleep (n = 1); kernicterus, spindles with an extremely low incidence (n = 5); perinatal anoxia (n = 2), kernicterus (n = 1), Lesch-Nyhan syndrome (n = 1) and cerebral palsy due to unknown etiologies (n = 1), and extreme spindles (n = 1); cerebral palsy due to unknown etiologies, (ii) in reference cases no spindles (n = 2), spindles with an extremely low incidence (n = 6), and extreme spindles (n = 1). Short sleep and long waking times during the night were noted in 4 out of 23 CP subjects; kernicterus (n = 2), agenesis of corpus callosum with lissencephaly (n = 1), and porencephaly with microcephaly (n = 1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nocturnal sleep in mentally retarded infants with cerebral palsy. 241 20

The Lesch-Nyhan syndrome is an X-linked disorder caused by a virtually complete absence of the key enzyme of purine recycling, hypoxanthine-guanine phosphoribosyltransferase (HPRT). It is characterized by uric acid overproduction and severe neurological dysfunction. No treatment is yet available for the latter symptoms. A possible long-term solution is gene therapy, and recombinant adenoviruses have been proposed as vectors for gene transfer into postmitotic neuronal cells. We have constructed an adenoviral vector expressing the human HPRT cDNA under the transcriptional control of a short human cytomegalovirus major immediate early promoter (RAd-HPRT). Here we show that infection of human 1306, HPRT-negative cells with RAd-HPRT, expressed high enough levels of HPRT enzyme activity, as to reverse their abnormal biochemical phenotype, thus enhancing hypoxanthine incorporation and restoring purine recycling, increasing GTP levels, decreasing adenine incorporation, and allowing cell survival in HAT medium in which only cells expressing high levels of HPRT can survive. Infection of murine STO cells, increased hypoxanthine incorporation and restored purine recycling, thus allowing cell survival in HAT medium, and reduced de novo purine synthesis. Although both cells were able to survive in HAT medium post infection with RAd-HPRT, some of the biochemical consequences differed. In summary, even though adenoviral vectors do not integrate into the genome of target HPRT-deficient human or murine cells, RAd-HPRT mediated enzyme replacement corrects abnormal purine metabolism, increases intracellular GTP levels, and allows cells to survive in a negative selection medium.
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PMID:Adenoviruses encoding HPRT correct biochemical abnormalities of HPRT-deficient cells and allow their survival in negative selection medium. 1085 May 48