Biomedical subjects

Nobuo Sakura

Publications and source records attributed to Nobuo Sakura.

25 records · Page 2Linked to original sources

PubMed2002

The peak height ratio of S-sulfonated transthyretin and other oxidized isoforms as a marker for molybdenum cofactor deficiency, measured by electrospray ionization mass spectrometry.

Molybdenum cofactor deficiency is a fatal neurological disorder, which follows an autosomal-recessive trait and is characterized by combined deficiency of the enzyme, sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Early detection of molybdenum cofactor-deficient patients is essential for their proper care and genetic counseling of families at risk. We demonstrate the use of S-sulfonated transthyretin (TTR) as a marker for molybdenum cofactor deficiency. Plasma or sera obtained from 4 patients with molybdenum cofactor deficiency and 57 controls were studied by electrospray ionization mass spectrometry (ESIMS) following selective enrichment of TTR by immunoprecipitation using protein G/A agarose. The data obtained from molybdenum cofactor deficiency samples indicated a strong increase in the peak height of S-sulfonated TTR. A more significant difference was revealed if the peak height ratio of S-sulfonated TTR and the sum of the other oxidized TTR were determined. By accurate determination of the ratio, the samples of molybdenum cofactor deficiency patients could clearly be distinguished from controls without molybdenum cofactor deficiency.

Adolescent↗

PubMed2002

Newborn mass screening and selective screening using electrospray tandem mass spectrometry in Japan.

Electrospray tandem mass spectrometry was applied to detect a series of inherited metabolic disorders during a newborn-screening pilot study and a selective screening in Japan. In our mass screening of 102,200 newborns, five patients with propionic acidemia, two with methylmalonic acidemia, two with medium-chain acyl-CoA dehydrogenase deficiency, three with citrullinemia type II, and one with phenylketonuria were identified. In a selective screening of 164 patients with symptoms mainly related to hypoglycemia and/or hyperammonemia, 12 with fatty acid oxidation disorders and six with other disorders were found. The results indicated the importance of newborn screening using this technology in Japan.

Humans↗

PubMed2002

Application of delayed extraction-matrix-assisted laser desorption ionization time-of-flight mass spectrometry for analysis of sphingolipids in pericardial fluid, peritoneal fluid and serum from Gaucher disease patients.

Gaucher disease is a glycolipid storage disorder characterized by the accumulation of glucosylceramide. Using delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry (DE-MALDI-TOF-MS), we analyzed sphingolipids in pericardial fluid, peritoneal fluid, and serum from two patients with Gaucher disease. Crude lipids were extracted from 1 ml each of pericardial fluid, peritoneal fluid, and serum with chloroform and methanol. After mild alkaline treatment of the crude lipids, a sphingolipid fraction was prepared and analyzed by DE-MALDI-TOF-MS. The results were as follows: (a) in all the specimens, peaks of ceramide monohexoside and sphingomyelin were detected in both the controls and Gaucher disease patients; (b) in pericardial fluid, peritoneal fluid, and serum, the ceramide monohexoside/sphingomyelin ratio was increased in the Gaucher disease patients compared with in the controls. It was indicated that the accumulation of ceramide monohexoside in such samples from Gaucher disease patients can be easily detected with this DE-MALDI-TOF-MS method.

Ascitic Fluid↗

PubMed2002

Unexpectedly high prevalence of the mild form of propionic acidemia in Japan: presence of a common mutation and possible clinical implications.

Propionic acidemia [MIM 606054] is a form of organic acidemia caused by genetic deficiency of propionyl-CoA carboxylase (PCC) and characterized by attacks of severe metabolic acidemia and hyperammonemia beginning in the neonatal period or in early infancy. There are, however, patients who have higher PCC activities and present later with unusual symptoms, such as mild mental retardation or extrapyramidal symptoms, sometimes even without metabolic acidosis. Through the neonatal screening of more than 130,000 Japanese newborns we detected a frequency of patients with propionic acidemia more than ten times higher than previously reported, most of them with milder phenotypes. The mutational spectrum was quite different from that of patients with the severe form and there was a common mutation (Y435C) in the beta subunit of the PCC gene (PCCB). Since patients with the mild form could present with unusual symptoms and therefore could easily remain unrecognized, it is important to identify those patients and clarify their natural history. Molecularly, one of the mutations (A1288C) caused an unusual pattern of multiple exon skipping and another unidentified mutation lead to the absence of mRNA. Taking into consideration previous findings regarding PCCB mutations, it appears that this gene is particularly prone to posttranscriptional modifications such as missense mediated exon skipping, mRNA decay, or rapid product degradation.

Adolescent↗

PubMed2002

The C677T mutation in the methylenetetrahydrofolate reductase gene contributes to hyperhomocysteinemia in patients taking anticonvulsants.

Hyperhomocysteinemia, a possible risk factor for vascular disease can result from folate deficiency due to anticonvulsant therapy. A reaction catalyzed by 5,10-methylenetetrahydrofolate reductase (MTHFR) supplies 5-methyltetrahydrofolate, needed to remethylate homocysteine to methionine. MTHFR gene mutation (C677T) also can lead to hyperhomocysteinemia. We examined interaction between anticonvulsant therapy, C677T homozygosity, serum folate concentration, and plasma total homocysteine (tHcy) concentration in 81 epileptic patients. Patients receiving monotherapy showed no difference in occurrence of hyperhomocysteinemia (tHcy>90th percentile for controls) between homozygotes for C677T and heterozygotes or patients with no mutant MTHFR. No monotherapy patient was folate deficient (<3 ng/ml). Among patients receiving multidrug therapy, hyperhomocysteinemia in homozygotes for C677T occured significantly more often than in heterozygotes or patients with no mutant enzyme (88.9 vs. 21.1%). The same was true for folate deficiency (44.4 vs. 0%). The C677T mutation is closely related to hyperhomocysteinemia and folate deficiency in epileptic patients taking multiple anticonvulsants.

Adolescent↗

PubMed2002

Betaine and homocysteine concentrations in foods.

BACKGROUND: Betaine (Bet) supplementation is an effective strategy for dietary treatment of homocystinuria. However,previous reports on diet therapy have only examined methionine (Met)and cystine concentrations, but not those of Bet and homocysteine(Hcy) in food items. We set up a hypothesis that there are some food items, which contain a small amount of Met, but a great amount of Hcy and Bet. METHODS: We measured Bet and Hcy concentrations in 58 food items, which were regarded as containing low Met. RESULTS: Products of wheat flour are rich in Bet. The amount of Bet in food items investigated in this study is much smaller than the dose used to treat homocystinuria patients. Vegetables contained little Hcy, however sprouted beans and sprouted alfalfa seeds contained ample Hcy. CONCLUSION: Patients with homocystinuria do not have to be too concerned about Hcy in food items because the amount is small. Therefore, we encourage homocystinuria patients to continue a low Met diet therapy without anxiety of Hcy and Bet, and if necessary,Bet will be supplemented.

Betaine↗

PubMed2002

A case of MELAS: hyperperfused lesions detected by non-invasive perfusion-weighted MR imaging.

We report a case of MELAS in which lesions were detected by perfusion-weighted MR imaging. Perfusion-weighted MRI using contrast media (PWI) and FAIR (flow-sensitive alternating inversion recovery), an arterial spin labeling method, clearly showed these lesions as hyperperfused areas. One of these lesions, diminished after steroid therapy, could also be detected by FAIR.

Adolescent↗