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Biomedical subjects

Y Matsubara

Publications and source records attributed to Y Matsubara.

At least 163 records · Page 9Linked to original sources

[Interferon treatment for chronic hepatitis C--assessment of 3 regimens in patients received more than 500MU interferon treatment and their effect predictive factors for interferon treatment using multivariate analysis with the logistic regression model].

Chronic hepatitis C patients (n = 115) were treated with interferon (IFN). Total dose employed was more than 500 MU. The response rate was assessed among the three treatment groups: 2W continuous+TIW, 4W continuous+TIW, 8W continuous+TIW. The IFN treatment effect predictive factors were also assessed. Complete response (CR) rate, CR with serum HCV-RNA disappearance rate, responders' histology activity index score changes between before and after treatment, and responders' hepatocytes HCV-RNA disappearance rate did not differ among the three treatment regimens. CR to IFN treatment was dependent on serum HCV-RNA and HCV serotype. Patients of low serum HCV-RNA and serotype II were responsive to IFN treatment.

Chronic Disease↗

[The result of reoperation for lung cancer].

Twenty four patients with recurrent or multiple lung cancer were reoperated in our center. Five-year survival rate was 20% for 11 patients with recurrent, while was 25% for 13 patients with multiple after reoperation. The patients with limited operation had well survival and there was no significant difference in procedure. However all four patients with N2 had poor prognosis. Seven patients (29%) had the post reoperative complication in pulmonary system. All of them had the impairment of pulmonary function (FEV1.0% was less than 50%) or more than 75% perfusion ratio, measured with pulmonary perfusion scintigraphy, in the side of the reoperation.

Adenocarcinoma↗

[Positive expression of c-myc and p53 products in two cases of pulmonary sclerosing hemangioma].

The c-myc and p53 genes are thought to be an oncogene and a tumor suppressor gene, respectively. These genes' products are characteristic of malignant tumors. We quantitatively analyzed the c-myc and p53 products by flow cytometry in two cases of pulmonary sclerosing hemangioma. In case 1, 32.3% of the tumor cells were found to have the c-myc product, and 8.9% were found to have the p53 product. In case 2, 6.7% of the tumor cells were found to have the c-myc product and 15.5% were found to have the p53 product. The percentages in both cases were twice as high as those in a negative control lymphocytes stained with c-myc and p53 products. Therefore, these two cases showed positive expression of the c-myc and p53 products. In addition DNA from six other patients with sclerosing hemangioma was analyzed with paraffin-embedded sections. All six had DNA diploidy, with DNA indexes ranging from 0.91 to 1.03 and coefficients of variation ranging from 3.0 to 5.5. We suggest that pulmonary sclerosing hemangioma is a very weakly malignant tumor.

Adult↗

Analysis of polymerase chain reaction-product by capillary electrophoresis with laser-induced fluorescence detection and its application to the diagnosis of medium-chain acyl-coenzyme A dehydrogenase deficiency.

Capillary gel electrophoresis with laser-induced fluorescence (CGE-LIF) has been developed to detect polymerase chain reaction (PCR) amplified samples. LIF detection was performed using Thiazole Orange as the fluorescent intercalating dye. This method was ca. 100x as sensitive as that with UV detection. The highly sensitive CGE-LIF was applied to the detection of the most prevalent mutation (lysine329-to-glutamic acid substitution) in medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. The disorder, which shows an autosomal recessive inheritance, is known to be highly prevalent among Caucasian population and often mimics as Reye-like syndrome or sudden infant death. A DNA fragment containing the mutation site was PCR-amplified with two sets of allele specific oligonucleotide primers, followed by CGE-LIF. The mutant allele produced a 175-base pairs DNA fragment, which the normal allele generated a 202-base pairs DNA fragment. CGE-LIF clearly distinguished these PCR products, facilitating rapid diagnosis of MCAD deficiency.

Acyl-CoA Dehydrogenase↗

Familial amyotrophic lateral sclerosis (ALS) in Japan associated with H46R mutation in Cu/Zn superoxide dismutase gene: a possible new subtype of familial ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurological disorder that results in relentless damage to the motor neuron system. Although about 5-10% of cases are familial, the pathophysiologic process of ALS remains unknown. We identified a novel point mutation A to G in exon 2 of the Cu/Zn SOD gene, resulting in an amino acid substitution of histidine46 by arginine (H46R), in two Japanese familial ALS (FALS) families. The segregations of the mutation were evident. The enzymatic activities of Cu/Zn SOD of peripheral red blood cell lysate were reduced to about 80% in the affected members, compared with other non-affected family members. The patients in these families are clinically characterized by relative late onset, initial involvement in lower extremities, relative rare impairment of bulbar muscles and much slow progression of muscular weakness and atrophy, compared with other Japanese FALS cases who have no mutation in the Cu/Zn SOD gene. These findings suggest that the H46R mutation in Cu/Zn SOD gene is highly related to this unique subtype of FALS.

Adult↗

Safety evaluation of lipase G from Penicillium camembertii.

Lipase G, a partial glycerides eliminating enzyme produced by Penicillium camembertii, was subjected to safety evaluation studies to establish its safety when used as a processing aid in the food industry. The toxicological studies on the enzyme included a 90-day gavage study with rats, a mutagenicity study using bacteria, and a pathogenicity study using mice. The no-adverse-effect level from the 90-day gavage toxicity study was 2000 mg/kg body weight/day for rats. There was no evidence of mutagenic potential. The micro-organism was evaluated for pathogenicity using mice and classified as a non-pathogen. Results indicate that the production and use of lipase G may be regarded as safe for the enzyme production worker and the consumer.

Animals↗

Isolation and characterization of mutations in the human holocarboxylase synthetase cDNA.

Holocarboxylase synthetase (HCS) plays an essential role in biotin utilization in eukaryotic cells and its deficiency causes biotin-responsive multiple carboxylase deficiency in humans. We have cloned the human HCS cDNA and show that antiserum against the recombinant protein immunoprecipitates human HCS. A one base deletion resulting in a premature termination and a missense mutation (Leu to Pro) were found in cells from siblings with HCS deficiency. Human HCS shows homology to BirA, which acts as both a biotin-[acetyl-CoA-carboxylase] ligase and a biotin repressor in E. coli, suggesting a functional relationship between the two proteins. The human HCS gene maps to chromosome 21q22.1.

Amino Acid Sequence↗

The ergonomic implications of a doorless system in an automobile assembly line.

A doorless assembly system (the Nagamachi System) was first implemented at Nissan Motor's Zama Plant and has since spread throughout Japan and the rest of the world. With this system all doors are taken off a car body in the first process of a car assembly line and assembled in a separate door assembly line. This system aims to obtain an ergonomic profit from the reduction of a worker's workload. The implementation of the system results in such a reduction in workload, as well as an increase in work efficiency, and higher productivity.

Automobiles↗

Identification of two novel mutations in the methylmalonyl-CoA mutase gene with decreased levels of mutant mRNA in methylmalonic acidemia.

Genetic defects in the methylmalonyl-CoA mutase (MCM) gene result in methylmalonic acidemia which is inherited as an autosomal recessive disease. We investigated fibroblast cultures obtained from two Japanese patients with MCM deficiency. MCM mRNA was not detected by Northern blot analysis, suggesting that MCM mRNA was markedly decreased. Reverse transcription/polymerase chain reaction (RT-PCR) of MCM mRNA followed by analysis on a fluorescent fragment analyzer indicated that the level of MCM mRNA in these fibroblasts was less than 1% of normal controls. This minute amount of MCM mRNA was successfully amplified by nested RT-PCR and subjected to primary structure analysis. Sequence analysis revealed two novel mutations: a G-to-T substitution at nucleotide position 425 and a 2 bp deletion at nucleotide positions 769 and 770. The first mutation (G425T) resulted in the substitution of a termination codon for glutamic acid at amino acid position 117. The second mutation (769 delta CA) resulted in a frame shift which created a premature termination codon 508 amino acid upstream of the C-terminus of the protein. Patient 1 was homozygous for G425T and patient 2 was a compound heterozygote for G425T and 769 delta CA. Our report is the first to identify MCM mutations that affect the stability of MCM mRNA. An analysis of 16 Japanese patients revealed the presence of G425T in six patients, suggesting a relatively high incidence of the mutation among Japanese patients. This is in sharp contrast to a previous report describing diverse heterogeneity of MCM mutations among Caucasians.

Amino Acid Metabolism, Inborn Errors↗

Rapid detection of phenylketonuria mutations by non-radioactive single-strand conformation polymorphism analysis.

A non-radioactive single-strand conformation polymorphism (SSCP) method was used to detect various phenylketonuria (PKU) mutations in Japanese and Chinese patients. Arginine413-to-proline (R413P) mutation in exon 12 of the phenylalanine hydroxylase gene was identified in a Japanese patient by this method. The segregation of the R413P mutation in the proband's family was clearly demonstrated and the carrier status of each family member was determined. Analysis of DNA fragments containing exon 7 originated from Chinese patients revealed two mutations, arginine243-to-glutamine (R243Q) and arginine261-to-glutamine (R261Q), and a polymorphism, valine245-to-valine (V245V). Although R261Q has been identified previously among Caucasian subjects, this report is the first to describe this mutation among Orientals. Since the non-radioactive SSCP method employs pre-cast acrylamide gels and pre-made gel buffer strips combined with semi-automated temperature-controlled electrophoresis, it can be performed without much expertise in molecular biological techniques. The ability of this method to detect various mutations as demonstrated in this study and its ease of use make it feasible to detect PKU mutations in a routine DNA diagnostic laboratory.

Asian People↗

Development of early-stage embryos of the Japanese field vole, Microtus montebelli, in vivo and in vitro.

Although ovulation could be easily induced in the Japanese field vole by administering pregnant mares' serum gonadotrophin and hCG, the number of embryos obtained varied from 1 to 47 (mean, 9.6). One-cell embryos were small (57.8-63.3 microns in diameter; mean, 61.0 microns) compared with those in other mammals. Development of the preimplantation vole embryos in vivo was similar to that of mouse embryos. The first cleavage occurred between 24 and 26 h after mating. The second cleavage was between 46 and 52 h after mating, and subsequent cleavages occurred at about 12 h intervals. Blastocysts were clearly observed in the uterus 4 days after mating. Vole embryos could be cultured in vitro from the late two-cell to the blastocyst stage in M16 medium. However, development of one-cell and early two-cell embryos in vitro was limited, and few cleaved beyond the four-cell stage. Eliminating sodium pyruvate from M16 medium significantly improved the development of early two-cell embryos into blastocysts (P < 0.05). The Japanese field vole may be a useful experimental animal for reproductive biology, comparable with the mouse.

Animals↗

Effects of a daily feeding-restriction on the reproductive and development toxicity parameters in female rats.

On the assumption of that the oral administration of an acid-unstable test compound into the empty stomach could enhance the systemic exposure to the test compound, the non-pregnant and pregnant rats had free access to the diet only for five hours per day. Female rats under the restricted feeding for a period of 21 days took diet at two thirds of the daily food-intake by the control animals, and lost their weight more than 10%. The vaginal smear test in these animals revealed a prolonged estrous cycle and diestrous period over four days. On the other hand, the restricted feeding from Day 0 to Day 17 of gestation suppressed the weight gain of pregnant animals but did not cause any significant influence upon the litter data, incidence of external anomalies or fetal skeletal development. The restricted feeding from Day 0 of gestation to Day 7 of lactation seriously disturbed the nursing behavior and the growth of offspring. These results suggested that the dosing method under the above-mentioned restricted feeding might be applicable to the teratology study but could not be applied to the fertility study nor to the peri- and post-natal study.

Abnormalities, Drug-Induced↗

Radiation therapy of adult T-cell leukemia.

Between January, 1983 and December, 1991, 30 adult patients with T-cell leukemia (ATL) and lymph node or skin lesions resistant to chemotherapy were treated by irradiation. Thirty Gy of high energy x-rays, 60Co gamma rays or electrons was delivered to 22 lymph node lesions in 17 patients, for focal cutaneous lesions in 6 patients, and as total skin irradiation in 7 patients. Irradiation therapy was effective in all patients with skin lesions and in 12 of 17 patients with lymph node lesions. Symptoms such as pain or itching diminished in all cases and no severe side effects were observed. Radiation therapy thus achieved good control of ATL associated focal lesions resistant to chemotherapy. Even if the prognosis of ATL is poor, radiation therapy should be considered as a palliative therapy.

Adult↗