Record 1 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/09
TITLE: Bone marrow transplantation does not ameliorate the neurologic symptoms in mice deficient in hypoxanthine guanine phosphoribosyl transferase (HPRT).
AUTHOR(S): Wojcik-BE; Jinnah-HA; Muller-Sieburg-CE; Friedmann-T
ADDRESS OF AUTHOR: Dept. of Pediatrics, UCSD School of Medicine, La Jolla, CA 92093, USA.
SOURCE (BIBLIOGRAPHIC CITATION): Metab-Brain-Dis. 1999 Mar; 14(1): 57-65
INTERNATIONAL STANDARD SERIAL NUMBER: 0885-7490
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: The use of bone marrow transplantation (BMT) for the treatment of genetic diseases with neurologic involvement has yielded mixed results. We have employed a mouse model of Lesch-Nyhan disease (LND) to assess the efficacy of BMT in ameliorating the neurologic manifestations of the disease. Adult HPRT-deficient mice exhibit a measurable decrease in striatal dopamine levels and a hypersensitivity to amphetamine. Marrow-ablated adult HPRT-deficient mice were transplanted with marrow from congenic HPRT-expressing mice. BMT altered neither the neurochemical nor the behavioral phenotypes in either HPRT-positive or HPRT-deficient mice. Barring any important species differences, these results suggest that BMT in its present form may not be an effective therapy for Lesch-Nyhan syndrome.
MINOR MESH HEADINGS: Behavior,-Animal-drug-effects; Behavior,-Animal-physiology; Dextroamphetamine-pharmacology; Disease-Models,-Animal; Dopamine-metabolism; Lesch-Nyhan-Syndrome-metabolism; Lesch-Nyhan-Syndrome-physiopathology; Lesch-Nyhan-Syndrome-psychology; Lesch-Nyhan-Syndrome-surgery; Mice-; Mice,-Inbred-C57BL; Prosencephalon-metabolism
MAJOR MeSH HEADINGS: *Bone-Marrow-Transplantation; *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Nervous-System-Diseases-etiology
CHECKTAGS: Animal; Female
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: EC 2.4.2.8; 51-61-6; 51-64-9
NAME OF SUBSTANCE: Hypoxanthine-Phosphoribosyltransferase; Dopamine; Dextroamphetamine
MEDLINE ACCESSION NUMBER: 1999276070
UPDATE CODE: 199909
Record 2 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/09
TITLE: Hypoxanthine-guanine phosphoribosyltransferase deficiency and erythrocyte synthesis of pyridine coenzymes.
AUTHOR(S): Micheli-V; Sestini-S; Rocchigiani-M; Jacomelli-G; Manzoni-F; Peruzzi-L; Gathof-BS; Zammarchi-E; Pompucci-G
ADDRESS OF AUTHOR: Dipartimento di Biologia Molecolare-Universita di Siena, Italia. micheli@cuces.unisi.it
SOURCE (BIBLIOGRAPHIC CITATION): Life-Sci. 1999; 64(26): 2479-87
INTERNATIONAL STANDARD SERIAL NUMBER: 0024-3205
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: Purine and pyridine metabolism were studied in ten Lesch-Nyhan patients, with virtually no hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity in erythrocytes. Increased NAD erythrocyte concentrations were found in all patients. Raised activities of two enzymes catalysing NAD synthesis from nicotinic acid (nicotinic acid phosphoribosyltransferase: NAPRT, and NAD synthetase: NADs) was found in erythrocyte lysates from all patients. The two enzymes had normal apparent Km for their substrates and increased Vmax. The rate of synthesis of pyridine nucleotides from nicotinic acid by intact erythrocytes in vitro was also increased in most patients. These findings suggest that raised NAD concentrations in HPRT- erythrocytes are due to enhanced synthesis as a result of increased enzyme activities.
MINOR MESH HEADINGS: Adolescence-; Adult-; Amide-Synthases-blood; Child-; Child,-Preschool; Erythrocytes-metabolism; Infant-; Kinetics-; Lesch-Nyhan-Syndrome-enzymology; Middle-Age; Nicotinic-Acids-blood; NAD-blood; Pentosyltransferases-blood; Purine-Nucleotides-blood; Purines-blood; Pyrimidine-Nucleotides-blood; Tryptophan-blood
MAJOR MeSH HEADINGS: *Erythrocytes-enzymology; *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Lesch-Nyhan-Syndrome-blood; *NAD-biosynthesis; *Pyridines-blood
CHECKTAGS: Female; Human; Male; Support,-Non-U.S.-Gov't
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: EC 2.4.2.; EC 2.4.2.11; EC 2.4.2.8; EC 6.3.1; EC 6.3.1.5; 0; 0; 0; 0; 0; 53-84-9; 73-22-3
NAME OF SUBSTANCE: Pentosyltransferases; nicotinate-phosphoribosyltransferase; Hypoxanthine-Phosphoribosyltransferase; Amide-Synthases; NAD+-synthase; Nicotinic-Acids; Purine-Nucleotides; Purines; Pyridines; Pyrimidine-Nucleotides; NAD; Tryptophan
MEDLINE ACCESSION NUMBER: 1999330301
UPDATE CODE: 199909
Record 3 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/09
TITLE: The molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in French families; report of two novel mutations.
AUTHOR(S): Liu-G; Aral-B; Zabot-MT; Kamoun-P; Ceballos-Picot-I
ADDRESS OF AUTHOR: Laboratoire de Biochimie Genetique Centre National de la Recherche Scientifique, URA 1335, Hopital Necker Enfants-Malades, Paris, France.
SOURCE (BIBLIOGRAPHIC CITATION): Hum-Mutat. 1998; Suppl 1: S88-90
INTERNATIONAL STANDARD SERIAL NUMBER: 1059-7794
PUBLICATION YEAR: 1998
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
MINOR MESH HEADINGS: Base-Sequence; Cells,-Cultured; DNA-Mutational-Analysis; DNA,-Complementary-chemistry; DNA,-Complementary-genetics; Family-Health; Frameshift-Mutation; France-; Hypoxanthine-Phosphoribosyltransferase-genetics; Lesch-Nyhan-Syndrome-enzymology; Mutation-; Mutation,-Missense; Reverse-Transcriptase-Polymerase-Chain-Reaction; Sequence-Deletion
MAJOR MeSH HEADINGS: *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Lesch-Nyhan-Syndrome-genetics
CHECKTAGS: Human; Support,-Non-U.S.-Gov't
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: EC 2.4.2.8; 0
NAME OF SUBSTANCE: Hypoxanthine-Phosphoribosyltransferase; DNA,-Complementary
MEDLINE ACCESSION NUMBER: 1998112430
UPDATE CODE: 199909
Record 4 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/09
TITLE: Fibroblast models of neurological disorders: fluorescence measurement studies.
AUTHOR(S): Connolly-GP
ADDRESS OF AUTHOR: Purine Neuroscience Laboratory, Division of Chemical Pathology, Guy's Hospital, United Medical School, London, UK.
SOURCE (BIBLIOGRAPHIC CITATION): Trends-Pharmacol-Sci. 1998 May; 19(5): 171-7
INTERNATIONAL STANDARD SERIAL NUMBER: 0165-6147
PUBLICATION YEAR: 1998
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: Biochemical studies of human fibroblasts from patients with neurological disorders have revealed a wealth of information on how such disorders occur. In this review, Gerald Connolly describes how recently developed fluorescence video imaging techniques have been used to study the physiology of skin fibroblasts isolated from patients with certain neurological disorders, including those produced by Alzheimer's disease, Lesch-Nyhan syndrome, mitochondrial disorders, amyotrophic lateral sclerosis and lysosomal disorders. The results of these studies indicate disruptions in cell homeostasis, particularly specific changes in Ca2+ homeostasis and autofluorescence, which mirror changes thought to occur in the CNS of neurologically impaired patients. More extensive studies of these 'systemic changes' using new fluorescent indicators, combined with advances in imaging techniques, are predicted to increase the potential usefulness of human skin fibroblasts as experimental models and to help diagnose and treat neurological disorders.
MINOR MESH HEADINGS: Alzheimer-Disease-physiopathology; Amyotrophic-Lateral-Sclerosis-physiopathology; Calcium-metabolism; Cells,-Cultured; Central-Nervous-System-Diseases-diagnosis; Fibroblasts-pathology; Lesch-Nyhan-Syndrome-physiopathology; Lysosomal-Storage-Diseases-physiopathology; Mitochondrial-Myopathies-physiopathology; Potassium-Channels-physiology; Spectrometry,-Fluorescence-methods
MAJOR MeSH HEADINGS: *Central-Nervous-System-Diseases-physiopathology; *Fibroblasts-physiology; *Skin-physiopathology
CHECKTAGS: Human; Support,-Non-U.S.-Gov't
PUBLICATION TYPE: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
CAS REGISTRY NUMBER OR EC NUMBER: 0; 7440-70-2
NAME OF SUBSTANCE: Potassium-Channels; Calcium
MEDLINE ACCESSION NUMBER: 1998316005
UPDATE CODE: 199908
Record 5 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/09
TITLE: Cognitive functioning in Lesch-Nyhan syndrome: a 4-year follow-up study.
AUTHOR(S): Matthews-WS; Solan-A; Barabas-G; Robey-K
ADDRESS OF AUTHOR: The Matheny Institute of Applied Research, Princeton, New Jersey, USA.
SOURCE (BIBLIOGRAPHIC CITATION): Dev-Med-Child-Neurol. 1999 Apr; 41(4): 260-2
INTERNATIONAL STANDARD SERIAL NUMBER: 0012-1622
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: Lesch-Nyhan syndrome (LNS) is a rare disorder of metabolism caused by a defective gene on the X chromosome. It is typically characterized by choreoathetosis, hypertonia, hyperreflexia, and self-mutilation. The present study is a 4-year follow-up investigation of the cognitive status of six subjects with a mean age of 17 years 10 months (range 14 years 9 months to 23 years). The Stanford-Binet Intelligence Scale: IV was used. Each of the four domains assessed by this battery (verbal reasoning, abstract/visual reasoning, quantitative, and short-term memory) was compared with previous findings of the same subjects at their initial test and 2-year follow up; the aim being to gain further insight into the clinical course of LNS over time. The results suggest that while the subjects generally continued to acquire new information and skills over time, their standardized scores declined, indicating that a plateau was reached in their skill levels relative to their peers, as also seen in other developmental disabilities. Deficits were noted in working memory, particularly on tasks that involve considering multiple features simultaneously.
MINOR MESH HEADINGS: Adolescence-; Adult-; Age-Factors; Child-; Child,-Preschool; Follow-Up-Studies; Stanford-Binet-Test
MAJOR MeSH HEADINGS: *Cognition-; *Lesch-Nyhan-Syndrome-psychology
CHECKTAGS: Female; Human; Male
PUBLICATION TYPE: JOURNAL-ARTICLE
MEDLINE ACCESSION NUMBER: 1999281941
UPDATE CODE: 199908
Record 6 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/09
TITLE: In our parents' shadow. Lesch-Nyhan syndrome.
AUTHOR(S): Gelbart-M
ADDRESS OF AUTHOR: Chelsea and Westminster Hospital, London.
SOURCE (BIBLIOGRAPHIC CITATION): Nurs-Times. 1999 Mar 10-16; 95(10): 32
INTERNATIONAL STANDARD SERIAL NUMBER: 0954-7762
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
MINOR MESH HEADINGS: Lesch-Nyhan-Syndrome-diagnosis; Lesch-Nyhan-Syndrome-genetics; Lesch-Nyhan-Syndrome-therapy
MAJOR MeSH HEADINGS: *Lesch-Nyhan-Syndrome
CHECKTAGS: Human
PUBLICATION TYPE: JOURNAL-ARTICLE
MEDLINE ACCESSION NUMBER: 1999230866
UPDATE CODE: 199907
SUBSET: NURSING
Record 7 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/09
TITLE: [Physiopathology of neurological signs of hypoxanthine-guanine phosphoribosyltransferase deficiency]
ORIGINAL TITLE: Fisiopatologia de las manifestaciones neurologicas en la deficiencia de hipoxantina-guanina fosforribosiltransferasa.
AUTHOR(S): Torres-Jimenez-R; Mateos-Anton-F; Arcas-Martinez-J; Pascual-Castroviejo-I; Garcia-Puig-J
ADDRESS OF AUTHOR: Servicio de Bioquimica Clinica, Hospital La Paz, Facultad de Medicina, Universidad Autonoma, Madrid, Espana.
SOURCE (BIBLIOGRAPHIC CITATION): Rev-Neurol. 1998 Dec; 27(160): 1050-4
INTERNATIONAL STANDARD SERIAL NUMBER: 0210-0010
PUBLICATION YEAR: 1998
LANGUAGE OF ARTICLE: SPANISH; NON-ENGLISH
COUNTRY OF PUBLICATION: SPAIN
ABSTRACT: OBJECTIVE: Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is characterized by an increase in renal uric acid excretion, usually with hyperuricemia and may be associated with more or less important neurological symptoms. Based on a series of 20 patients from 16 Spanish families we propose that HPRT deficiency could be clinically classified in four different groups. In the more severe form (classic Lesch-Nyhan syndrome) HPRT deficiency is characterized by choreoathetosis, spasticity, mental retardation and compulsive self-mutilation behavior. The pathophysiology of the neurological symptoms remains unclear and there is no effective therapy. This review is intended to provide a research strategy for a better knowledge of the neurological pathophysiology of HPRT deficiency. DEVELOPMENT: We have analyzed the knowledge on the neurological symptoms of HPRT deficiency. This knowledge comes from histopathological studies of the brains from Lesch-Nyhan patients, chemical studies of the cerebrospinal fluid, experimental animal models (pharmacologic and lesioning and genetic approaches), and human in vivo studies with positron-emission tomography. CONCLUSIONS: The observed findings suggest that the neurological symptoms of Lesch-Nyhan syndrome could be related with the neonatal neuronal and/or dopaminergic terminations damage. This damage could be due to lost or reorganization of dopaminergic system, and is associated with a reduced dopamine levels and with hypersensitivity of the D1 subclass dopamine receptors.
MINOR MESH HEADINGS: Brain-Diseases-diagnosis; Brain-Diseases-enzymology; Dopamine-metabolism; English-Abstract; Hypoxanthine-Phosphoribosyltransferase-genetics; Lesch-Nyhan-Syndrome-diagnosis; Lesch-Nyhan-Syndrome-genetics; Point-Mutation-genetics
MAJOR MeSH HEADINGS: *Brain-Diseases-physiopathology; *Hypoxanthine-Phosphoribosyltransferase-deficiency
CHECKTAGS: English-Abstract; Human; Support,-Non-U.S.-Gov't
PUBLICATION TYPE: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
CAS REGISTRY NUMBER OR EC NUMBER: EC 2.4.2.8; 51-61-6
NAME OF SUBSTANCE: Hypoxanthine-Phosphoribosyltransferase; Dopamine
MEDLINE ACCESSION NUMBER: 1999136185
UPDATE CODE: 199907
Record 8 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/09
TITLE: Polysomnographic studies of Lesch-Nyhan syndrome.
AUTHOR(S): Saito-Y; Hanaoka-S; Fukumizu-M; Morita-H; Ogawa-T; Takahashi-K; Ito-M; Hashimoto-T
ADDRESS OF AUTHOR: Department of Child Neurology, National Center Hospital for Mental, Nervous and Muscular Disorders, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
SOURCE (BIBLIOGRAPHIC CITATION): Brain-Dev. 1998 Dec; 20(8): 579-85
INTERNATIONAL STANDARD SERIAL NUMBER: 0387-7604
PUBLICATION YEAR: 1998
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NETHERLANDS
ABSTRACT: Three cases of Lesch-Nyhan syndrome (LNS) were examined by polysomnography to assess the brainstem function, and to determine the causes of the neurological manifestations and sudden death in this syndrome. In the two older cases, the amount of slow wave and rapid eye movement (REM) sleep, the REM density and the frequency of REM bursts were decreased. In the youngest case, symmetrical phasic movements of all four limbs were observed at all sleep stages other than REM sleep. Although movements other than these symmetrical body movements appeared to be normal in this case, the frequency of twitch movements showed an abnormal pattern in each sleep stage in the two older cases. These findings suggest that in the brainstems of younger cases with LNS the REM-non REM generator as well as multiple neurotransmitter systems influencing body movements during sleep remain relatively normal, but become progressively impaired in adult cases. Severe obstructive apnea was observed in one case with hypothyroidism, but there were no respiratory abnormalities in other two cases.
MINOR MESH HEADINGS: Child,-Preschool; Electroencephalography-; Electromyography-; Infant-; Lesch-Nyhan-Syndrome-drug-therapy; Lesch-Nyhan-Syndrome-psychology; Movement-physiology; Polysomnography-; Sleep-physiology; Sleep,-REM-physiology
MAJOR MeSH HEADINGS: *Lesch-Nyhan-Syndrome-physiopathology
CHECKTAGS: Case-Report; Human; Male
PUBLICATION TYPE: CLINICAL-TRIAL; JOURNAL-ARTICLE
MEDLINE ACCESSION NUMBER: 1999081138
UPDATE CODE: 199905
Record 9 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/09
TITLE: Partial hypoxanthine phosphoribosyltransferase deficiency: unrecognized until adult ages [editorial; comment]
COMMENTS: Comment on: Intern Med 1998 Nov;37(11):945-9
AUTHOR(S): Kamatani-N
SOURCE (BIBLIOGRAPHIC CITATION): Intern-Med. 1998 Nov; 37(11): 905-6
INTERNATIONAL STANDARD SERIAL NUMBER: 0918-2918
PUBLICATION YEAR: 1998
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: JAPAN
MINOR MESH HEADINGS: Adolescence-; Adult-; DNA,-Complementary-analysis; Hypoxanthine-Phosphoribosyltransferase-blood; Hypoxanthine-Phosphoribosyltransferase-genetics; Lesch-Nyhan-Syndrome-diagnosis; Lesch-Nyhan-Syndrome-enzymology; Mice-; Mice,-Knockout; Mutation-
MAJOR MeSH HEADINGS: *Hypoxanthine-Phosphoribosyltransferase-deficiency
CHECKTAGS: Animal; Human
PUBLICATION TYPE: COMMENT; EDITORIAL; REVIEW; REVIEW,-TUTORIAL
CAS REGISTRY NUMBER OR EC NUMBER: EC 2.4.2.8; 0
NAME OF SUBSTANCE: Hypoxanthine-Phosphoribosyltransferase; DNA,-Complementary
MEDLINE ACCESSION NUMBER: 1999084291
UPDATE CODE: 199905
Record 10 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/09
TITLE: Gene therapy for inherited neurological disorders: towards therapeutic intervention in the Lesch-Nyhan syndrome.
AUTHOR(S): Lowenstein-PR; Southgate-TD; Smith-Arica-JR; Smith-J; Castro-MG
ADDRESS OF AUTHOR: Department of Medicine, University of Manchester, UK. lowenstein@man.ac.uk
SOURCE (BIBLIOGRAPHIC CITATION): Prog-Brain-Res. 1998; 117: 485-501
INTERNATIONAL STANDARD SERIAL NUMBER: 0079-6123
PUBLICATION YEAR: 1998
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NETHERLANDS
MINOR MESH HEADINGS: Brain-physiopathology; Gene-Transfer; Hypoxanthine-Phosphoribosyltransferase-metabolism; Models,-Chemical; Models,-Neurological; Recombinant-Proteins-metabolism
MAJOR MeSH HEADINGS: *Brain-metabolism; *Gene-Therapy; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-therapy
CHECKTAGS: Animal; Human; Support,-Non-U.S.-Gov't
PUBLICATION TYPE: JOURNAL-ARTICLE; REVIEW; REVIEW,-ACADEMIC
CAS REGISTRY NUMBER OR EC NUMBER: EC 2.4.2.8; 0
NAME OF SUBSTANCE: Hypoxanthine-Phosphoribosyltransferase; Recombinant-Proteins
MEDLINE ACCESSION NUMBER: 1999131219
UPDATE CODE: 199905
Record 11 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/09
TITLE: Purine metabolism in female heterozygotes for hypoxanthine-guanine phosphoribosyltransferase deficiency.
AUTHOR(S): Puig-JG; Mateos-FA; Torres-RJ; Buno-AS
ADDRESS OF AUTHOR: 'La Paz' University Hospital, Madrid, Spain.
SOURCE (BIBLIOGRAPHIC CITATION): Eur-J-Clin-Invest. 1998 Nov; 28(11): 950-7
INTERNATIONAL STANDARD SERIAL NUMBER: 0014-2972
PUBLICATION YEAR: 1998
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: BACKGROUND: Female carriers of the X-linked recessive disorder hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency show somatic cell mosaicism, and this may cause an increased synthesis of purines. We have examined whether urinary oxypurines could be useful for carrier diagnosis. METHODS: Carrier testing was performed in 35 women belonging to 16 unrelated Spanish families with at least one subject affected by the Lesch-Nyhan syndrome (11 families, 14 patients) or the Kelley-Seegmiller syndrome (five families, six patients) by means of HPRT and adenine phosphoribosyltransferase activities in hair follicles and/or molecular studies. Plasma and 24-h urinary concentrations of hypoxanthine, xanthine and uric acid were measured while subjects were on a purine-restricted diet. RESULTS: Mean plasma urate concentrations and 24-h urinary hypoxanthine, xanthine and uric acid excretion rates were significantly higher in 22 heterozygotes than in 13 non-carriers (P < 0.02). Daily urinary oxypurine excretion rates were also significantly higher in heterozygotes than in 12 normal women (P = 0.0011). Cumulative 5-day radioactivity excretion after [8-14C]-adenine infusion was markedly increased in 10 carrier women compared with five normal women (P = 0.0369). The sensitivity of 24-h urinary hypoxanthine and xanthine excretion rates was 86% and 77%, respectively, and the specificity 100% for both tests. CONCLUSION: Female heterozygotes for HPRT deficiency show an enhanced purine nucleotide degradation and purine overproduction. An elevated hypoxanthine and/or xanthine excretion rate differentiated most heterozygotes for HPRT deficiency from non-carrier women and thus could be useful for carrier diagnosis.
MINOR MESH HEADINGS: Adolescence-; Adult-; Aged-; Case-Control-Studies; Hypoxanthine-urine; Lesch-Nyhan-Syndrome-enzymology; Middle-Age; Spain-; Xanthine-urine
MAJOR MeSH HEADINGS: *Heterozygote-; *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-genetics; *Lesch-Nyhan-Syndrome-metabolism; *Purines-metabolism
CHECKTAGS: Female; Human; Male; Support,-Non-U.S.-Gov't
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: EC 2.4.2.8; 0; 68-94-0; 69-89-6
NAME OF SUBSTANCE: Hypoxanthine-Phosphoribosyltransferase; Purines; Hypoxanthine; Xanthine
MEDLINE ACCESSION NUMBER: 1999041780
UPDATE CODE: 199903
Record 12 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/09
TITLE: Influence of age and strain on striatal dopamine loss in a genetic mouse model of Lesch-Nyhan disease.
AUTHOR(S): Jinnah-HA; Jones-MD; Wojcik-BE; Rothstein-JD; Hess-EJ; Friedmann-T; Breese-GR
ADDRESS OF AUTHOR: Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland 21287, USA.
SOURCE (BIBLIOGRAPHIC CITATION): J-Neurochem. 1999 Jan; 72(1): 225-9
INTERNATIONAL STANDARD SERIAL NUMBER: 0022-3042
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Lesch-Nyhan disease is a neurogenetic disorder caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit a characteristic pattern of neurological and behavioral features attributable in part to dysfunction of basal ganglia dopamine systems. In the current studies, striatal dopamine loss was investigated in five different HPRT-deficient strains of mice carrying one of two different HPRT gene mutations. Caudoputamen dopamine concentrations were significantly reduced in all five of the strains, with deficits ranging from 50.7 to 61.1%. Mesolimbic dopamine was significantly reduced in only three of the five strains, with a range of 31.6-38.6%. The reduction of caudoputamen dopamine was age dependent, emerging between 4 and 12 weeks of age. Tyrosine hydroxylase and aromatic amino acid decarboxylase, two enzymes responsible for the synthesis of dopamine, were reduced by 22.4-37.3 and 22.2-43.1%, respectively. These results demonstrate that HPRT deficiency is strongly associated with a loss of basal ganglia dopamine. The magnitude of dopamine loss measurable is dependent on the genetic background of the mouse strain used, the basal ganglia subregion examined, and the age of the animals at assessment.
MINOR MESH HEADINGS: Age-Factors; Aromatic-L-Amino-Acid-Decarboxylases-analysis; Behavior,-Animal-physiology; Choline-O-Acetyltransferase-analysis; Disease-Models,-Animal; Mice-; Mice,-Inbred-C57BL; Mice,-Inbred-DBA; Neostriatum-enzymology; Species-Specificity; Tyrosine-3-Monooxygenase-analysis
MAJOR MeSH HEADINGS: *Corpus-Striatum-metabolism; *Dopamine-metabolism; *Hypoxanthine-Phosphoribosyltransferase-genetics; *Lesch-Nyhan-Syndrome-metabolism; *Mice,-Knockout
CHECKTAGS: Animal; Comparative-Study; Female; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PUBLICATION TYPE: JOURNAL-ARTICLE
CONTRACT OR GRANT NUMBERS: 1K08NS0198501NSNINDS
CAS REGISTRY NUMBER OR EC NUMBER: EC 1.14.16.2; EC 2.3.1.6; EC 2.4.2.8; EC 4.1.1.28; 51-61-6
NAME OF SUBSTANCE: Tyrosine-3-Monooxygenase; Choline-O-Acetyltransferase; Hypoxanthine-Phosphoribosyltransferase; Aromatic-L-Amino-Acid-Decarboxylases; Dopamine
MEDLINE ACCESSION NUMBER: 1999101164
UPDATE CODE: 199903
Record 13 of 13 in MEDLINE EXPRESS (R) 1999/01-1999/09
TITLE: No self-injurious behavior was found in HPRT-deficient mice treated with 9-ethyladenine.
AUTHOR(S): Edamura-K; Sasai-H
ADDRESS OF AUTHOR: Life Science Research Laboratory, Japan Tobacco Inc., Yokohama, Kanagawa.
SOURCE (BIBLIOGRAPHIC CITATION): Pharmacol-Biochem-Behav. 1998 Oct; 61(2): 175-9
INTERNATIONAL STANDARD SERIAL NUMBER: 0091-3057
PUBLICATION YEAR: 1998
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: It has been reported that 9-ethyladenine (9-EA) is an efficient inhibitor of APRT (adenine phosphoribosyltransferase) and that its administration causes self-injurious behavior (Lesch-Nyhan Syndrome-like symptoms) in HPRT (hypoxanthine-guanine phosphoribosyltransferase)-deficient mice. In contrast, we found neither any self-injurious behavior (SIB), such as visible injury or hair loss, nor any apparent decrease in APRT activity in HPRT-deficient mice treated with 9-EA. We also found that 9-EA has little irreversible or competitive inhibitory effect on APRT in vitro, even at a concentration of 10(-2) M. In light of the negative finding of SIB in APRT/HPRT double-deficient mice, it seems unlikely that SIB in HPRT-deficient mice is caused by lowered APRT activity. It is concluded that 9-EA is not a sufficient APRT inhibitor and cannot be used in experiments that mimic lowered APRT status in an animal model.
MINOR MESH HEADINGS: Adenine-pharmacology; Cell-Extracts; Disease-Models,-Animal; Mice-; Mice,-Inbred-C57BL
MAJOR MeSH HEADINGS: *Adenine-analogs-and-derivatives; *Hypoxanthine-Phosphoribosyltransferase-deficiency; *Lesch-Nyhan-Syndrome-chemically-induced; *Self-Injurious-Behavior
CHECKTAGS: Animal
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: EC 2.4.2.8; 0; 2715-68-6; 73-24-5
NAME OF SUBSTANCE: Hypoxanthine-Phosphoribosyltransferase; Cell-Extracts; 9-ethyladenine; Adenine
MEDLINE ACCESSION NUMBER: 1998408913
UPDATE CODE: 199902