Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms.

The deficient activity of the human lysosomal hydrolase, acid sphingomyelinase (ASM, EC 3.1.4.

The effect of carnitine on the metabolism of valproic acid in epileptic patients.

The half-life of valproic acid (VPA) was studied in 8 epileptic and severely mental retarded patients before and after one month of carnitine supplementation. Serum carnitine concentration was significantly decreased and VPA half-life was prolonged especially in adult patients before carnitine supplementation. After the treatment with carnitine, serum carnitine concentration was increased, and prolonged half-lives of VPA were corrected near to the normal range (from 12.

A case of tubulo-interstitial nephritis with exfoliative dermatitis and hepatitis due to phenobarbital hypersensitivity.

Severe exfoliative dermatitis and liver dysfunction developed in a 5-year-old girl 3 weeks after initiation of phenobarbital therapy. Liver function improved gradually after discontinuation of phenobarbital. During the convalescent stage an initially mild renal dysfunction was exacerbated by episodes of post-transfusion haemolysis.

Isolation and sequence determination of cDNA encoding P2 protein of human peripheral myelin.

A full length cDNA of P2 protein of peripheral myelin has been isolated from a cDNA library of human fetus spinal cord. The clone is 2150 base pairs (bp) in length and contains a 393 bp open reading frame encoding a polypeptide of 131 residues. The deduced amino acid sequence is highly homologous to P2 protein from other species.

Isolation and sequence determination of cDNA encoding the major structural protein of human peripheral myelin.

A full length cDNA of the major structural protein of peripheral myelin (P0 protein) has been isolated from a cDNA library of human fetus spinal cord. The clone is 1948 base pairs (bp) in length and contains a 744 bp open reading frame encoding a polypeptide of 248 residues including 29 signal peptide. The deduced amino acid sequence is highly homologous to P0 protein from other species.

[A case of Ullrich disease with distinct pathological change of muscular dystrophy].

A case of Ullrich disease was presented. The patient was a 3-year-old girl with torticollis, generalized muscle weakness and acroatonia since birth. High-arched palate, protruded calcaneus, and mild contracture of proximal joints were also recognized.

Decrease in cerebral metabolic rate of glucose after high-dose methotrexate in childhood acute lymphocytic leukemia.

We measured changes in the regional cerebral metabolic rate of glucose (rCMRGlu) using 18F-fluorodeoxyglucose and positron emission tomography for the assessment of neurotoxicity in childhood acute lymphocytic leukemia treated with high-dose methotrexate (HD-MTX) therapy. We studied 8 children with acute lymphocytic leukemia (mean age: 9.6 years) treated with HD-MTX (200 mg/kg or 2,000 mg/M2) therapy.

Multiple mitochondrial DNA deletions exist in cardiomyocytes of patients with hypertrophic or dilated cardiomyopathy.

Genetic impairment was revealed in idiopathic cardiomyopathy and the responsible DNA locus was estimated. Mitochondrial DNA were amplified from autopsied cardiac specimens from three patients who died from hypertrophic or dilated cardiomyopathy by using polymerase chain reaction (PCR). By using two novel methods for PCR gene amplification, the pleioplasmic existence of multiple populations of differently deleted mitochondrial DNA in all specimens from the patients was confirmed.

[A case of malignant neuroepithelioma in the retroperitoneum].

Reported is a case of a malignant neuroepithelioma in the retroperitoneum. The patient was a 37-year-old male suffering from lumbago and edema of the lower extremities. After ultrasonography and a CT scan, a diagnosis of a retroperitoneal tumor was made and a surgical resection of the tumor was performed in October, 1985.

Multiple populations of deleted mitochondrial DNA detected by a novel gene amplification method.

A gene amplification method for detecting small populations of deleted mitochondrial DNA was used in analysis of skeletal muscle from a patient with ocular myopathy. Multiple populations of differently deleted mtDNA were detected in the patient muscle. The presence of deleted mtDNAs was further confirmed by comparison of the shift in the sizes of the amplified fragments with the shift in the positions of the primers used for the amplification, (the primer shift PCR method).

Effect of tetrahydrobiopterin and 5-hydroxytryptophan on hereditary progressive dystonia with marked diurnal fluctuation: a suggestion of the serotonergic system involvement.

A daughter and her mother developed hereditary progressive dystonia with marked diurnal fluctuation (HPD) at the age of 4 and 34, respectively. L-Dopa, tetrahydrobiopterin (BH4) or 5-hydroxytryptophan (5-HTP) was orally administered to them. L-Dopa cured completely their symptoms.

Carnitine deficiency in lysinuric protein intolerance: lysine-sparing effect of carnitine.

Plasma carnitine deficiency (41% of normal control) was found in a 9 year-old boy with lysinuric protein intolerance. Following oral carnitine administration, the plasma level of lysine as well as carnitine has significantly increased (p less than 0.05).

Transitory type of sphingomyelinase deficient Niemann-Pick disease: clinical and morphological studies and follow-up of two sisters.

The transitory type is a rare and ill-defined variant of sphingomyelinase deficient NPD. Here reported are full clinical and morphological studies on two sisters with the transitory type. Our cases have the following features in common: 1) prominent visceral involvement from early infancy, such as marked hepatosplenomegaly, pulmonary infiltration, and numerous characteristic foam cells in the bone marrow aspirates; 2) very low sphingomyelinase activities in cultured skin fibroblasts; 3) atypical cherry-red spots in the retina; despite 4) absence of any neurological symptoms even at the age of 5 years and 6 months, and 3 years and 9 months, respectively.

Human alpha-L-iduronidase. II. Comparative biochemical and immunologic properties of the purified low and high uptake forms.

The physicokinetic and immunologic properties of the purified low and high uptake forms of the human lysosomal hydrolase, alpha-L-iduronidase, have been determined and compared. The apparent Km and Vmax values for the low and high uptake forms were similar toward two artificial substrates, 4-methylumbelliferyl-alpha-L-iduronide (0.07 and 0.

Microautoradiographic study on the tissue localization of liposome-entrapped or unentrapped 3H-labeled beta-galactosidase injected into rats.

The localization of intravenously injected liposome-entrapped or unentrapped 3H- beta-ga lactosidase in various tissues of rats was investigated by microautoradiography. The microautoradiographic silver grains, indicating the uptake of both forms of the enzyme were observed in all of the rat tissues studied, such as the liver, kidneys, spleen, lungs, heart, muscle and brain. The liver was found to be the most active in taking up both forms of the enzyme and probably Kupffer cells were primarily involved in the uptake of the enzyme.

Pyruvate decarboxylase deficiency in a patient with Leigh's encephalomyelopathy.

A 23-month-old boy with progressive muscular hypotonia and mental and motor deterioration was described. Four days after the admission he had a respiratory arrest and required the care in a respirator thereafter. Laboratory examinations showed metabolic acidosis and high levels of pyruvate, lactate and alanine in blood and cerebrospinal fluid.