Biomedical subjects

Akihito Ueta

Publications and source records attributed to Akihito Ueta.

6 recordsLinked to original sources

PubMed2006

A simple quantitative assay for urinary adenosine using column-switching high-performance liquid chromatography.

Adenosine is a physiologically active molecule produced locally in many sites of the body to regulate various cell functions. Measurement of levels of the factor in organs and biological fluids provides clues to its role and we reported an accurate quantitative high-performance liquid chromatography method for urinary adenosine requiring no preliminary sample preparation, other than filtration. Analyses were performed isocratically with a reversed-phase and a molecular exclusion columns connected by a column switch. Each sample was analyzed automatically in 35 min. Linearity could be verified up to 1,000 micromol/L (r = 0.999) and recovery of adenosine was 94.6-98.0%. The coefficients of variation (CV) were established to be 0.56-1.32%, intra-assay, and 1.61-4.67%, inter-assay. Based on analyses of healthy individuals at different ages, we are here able to provide age-related values, infants (1.51 +/- 0.71 micromol/mmol creatinine) and children (1.06 +/- 0.36 and 0.83 +/- 0.27 micromol/mmol creatinine; aged 1-5 and 6-10 years), excreting significantly higher amounts of adenosine than adults (0.44 +/- 0.08 micromol/mmol creatinine). We also measured urinary adenosine from patients suffering from metabolic disease or severe respiratory failure and found that unfavorable pathophysiologic conditions are associated with appreciable elevation of adenosine.

Adenosine↗

PubMed2005

Novel mutations in the cytochrome P450 2C19 gene: a pitfall of the PCR-RFLP method for identifying a common mutation.

CYP2C19 is a clinically important enzyme involved in the metabolism of therapeutic drugs such as (S)-mephenytoin, omeprazole, proguanil, and diazepam. Individuals can be characterized as either extensive metabolizers (EM) or poor metabolizers (PM) on the basis of CYP2C19 enzyme activity. The PM phenotype occurs in 2-5% of Caucasian populations, but at higher frequencies (18-23%) in Asians. CYP2C19*2 and CYP2C19*3, which are single-nucleotide polymorphisms of CYP2C19, are the main cause of PM phenotyping in homozygotes or compound heterozygotes. We report two novel mutations in the CYP2C19 gene identified by direct sequencing and subcloning procedures. One of these mutations was considered to be CYP2C19*3 by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). This result suggests that mutations classed as CYP2C19*3 might include other mutations. Further studies are needed to clarify the relationship between these novel mutations and enzyme activity.

Adult↗

PubMed2005

Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency in the Japanese population.

Inosine triphosphate pyrophosphohydrolase (ITPase) is an enzyme that catalyzes the conversion of inosine triphosphate (ITP) to inosine monophosphate and pyrophosphate. In Caucasian populations it is reported that the frequency of cases showing decreased ITPase activity is 5%. The structure of ITPA gene along with five single nucleotide polymorphisms has been reported in Caucasians. We examined ITPase activity and frequency of two polymorphisms (94C>A and IVS2+21A>C) in 100 Japanese individuals. Among these individuals, we observed that three cases with zero activity were homozygote for 94C>A, and were accompanied by abnormal accumulation of ITP in erythrocytes. The cases included in the low ITPase activity group were heterozygote for 94C>A polymorphism. The activity of the heterozygote cases was approximately 27% of the mean value of the wild type. The allele frequency of the 94C>A polymorphism was 0.155, which was 2.6 times higher than that of the Caucasians (0.06). The IVS2+21A>C was not detected in Japanese cases, although it occurred with a frequency of 0.130 in Caucasians. Furthermore, we identified a novel mutation IVS2+68T>G in intron 2 in the case with the lowest enzyme activity in the 94C>A wild type. Since the frequency of ITPA 94C>A polymorphism is higher in the Japanese population than that in Caucasians, it is more important to examine ITPA 94C>A polymorphism in the Japanese population to prevent thiopurine drug toxicity. Pretherapeutic screening of individuals for ITPA polymorphisms should be considered for safer and more tolerable treatment with thiopurine drugs.

Adult↗

PubMed2005

Urinary uracil in female patients with ornithine transcarbamylase deficiency.

BACKGROUND: Female patients with ornithine transcarbamylase deficiency (OTCD) show a wide range of clinical severity, from asymptomatic to lethal hyperammonemia. It is important to establish a simple method to distinguish symptomatic from asymptomatic patients. METHODS: Uracil and orotic acid concentrations were analyzed in three female patients with OTCD at both the hyperammonemia-attack and interval stages. These concentrations were compared with those in asymptomatic female patients reported previously. RESULTS: Uracil concentrations in symptomatic female patients were uniformly higher than those in asymptomatic female patients at both the hyperammonemia-attack and interval stages. CONCLUSION: Uracil may present a useful index for detecting OTCD female patients who are destined to suffer from hyperammonemia attack. Further data on uracil concentrations are necessary to establish the threshold for distinguishing symptomatic from asymptomatic subjects.

Child, Preschool↗

PubMed2005

Chronic zinc toxicity in an infant who received zinc therapy for atopic dermatitis.

UNLABELLED: In Japan and many other industrialized countries, zinc is readily available as a nutritional supplement, for cosmetic purposes and for the treatment of atopic dermatitis. The potential risks associated with its use are not, however, fully recognized. As a reciprocal relationship exists between copper and zinc, excessive zinc can produce hypocupraemia, which can cause anaemia and neutropenia. We report on a male infant who presented with anaemia and neutropenia and showed signs of developmental delay after dietary restriction for food allergy and eating difficulties and zinc therapy administered for the treatment of atopic dermatitis at a dose nine times the daily dietary allowance for his age group. After 1 mo of zinc withdrawal, copper and ceruloplasmin concentrations had increased, and the blood cell count had improved, activity was increasing but verbal development remained limited. As development improved after withdrawal of zinc, we cannot rule out a relation between developmental delay and hyperzincaemia and/or hypocupraemia. CONCLUSION: Caution must be exercised in administering zinc to children during their neurological development.

Chronic Disease↗

PubMed2005

Vitamin B6-responsive ornithine aminotransferase deficiency with a novel mutation G237D.

Ornithine aminotransferase (OAT) deficiency (MIM: 258870) is a rare congenital metabolic disorder characterized by gyrate atrophy of the choroid and retina. Here, we report a 37-year-old male with gyrate atrophy of the choroid and retina who has been treated for 18 years. At the age of 7 years, the patient consulted an ophthalmologist due to progressive loss of vision. A large atrophied area was observed in his retina, and OAT deficiency was suspected. At the age of 19 years, amino acid analysis revealed high serum ornithine levels (1,140 nmol/ml), with the normal range being 40-100 nmol/ml. He was treated with vitamin B(6) 300 mg/day for 6 months, which successfully reduced his serum ornithine levels by 20-30%. For 18 years since, his serum ornithine levels have been maintained with vitamin B(6) medication. There was no further impairment of vision or increase in the atrophied area, as judged by ophthalmoscopic examination. OAT activity was undetected in white blood cells of the patient and was 105% and 45% of normal values in his wife and son, respectively. OAT gene analysis revealed a novel mutation of Gly237Asp in exon 7 (710G > A) in both alleles of the patient, while his son was a heterozygote for the mutation. Notably, this novel mutation is associated with a vitamin B6-responsive phenotype. Therefore, early diagnosis and treatment with vitamin B(6) may prevent loss of vision in some patients with OAT deficiency.

Adult↗