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N Okamoto

Publications and source records attributed to N Okamoto.

At least 199 records · Page 11Linked to original sources
PubMed1994

Cloning of a new kinesin-related gene located at the centromeric end of the human MHC region.

We previously reported the presence of a new gene (HSET) with an unknown function, in the centromeric side of the class II gene region of the human major histocompatibility complex (MHC). cDNA clones corresponding to the HSET gene were isolated from a human testis cDNA library. A 2.4 kilobase transcript from the HSET gene was abundantly expressed in testis, B-cell, T-cell, and ovary cell lines but was not detected in lung or stomach. Analysis of the nucleotide sequence of the HSET cDNA clones revealed significant similarity to kinesin-related proteins in yeast, Drosophila, and human. Its predicted amino acid sequence contains a domain with strong sequence similarity to the ATP-binding and motor domains of a plus end-directed microtubule motor protein, kinesin, which might be involved in mitotic chromosome segregation, suggesting that the HSET gene encodes a novel kinesin-related protein.

Amino Acid Sequence↗
PubMed1994

Monoallelic expression of normal mRNA in the PIT1 mutation heterozygotes with normal phenotype and biallelic expression in the abnormal phenotype.

The combined deficiency of thyrotropin, growth hormone and prolactin, caused by PIT1 abnormality manifests in the homozygous or heterozygous state. We studied a patient having an allele with Arg271Trp mutation, which produces clinical symptoms in heterozygotes by a dominant-negative effect. However, in the family, her father, grandmother and aunts had the same mutation without clinical symptoms, although the proband had typical phenotypic expression. We analyzed the PIT1 transcript in peripheral lymphocytes by reverse transcription-polymerase chain reaction and found monoallelic expression of normal allele in the father and grandmother and skewed pattern of biallelic expression in the proband. The phenotypic expression of PIT1 abnormality may depend on different transcription of the PIT1 gene.

Alleles↗
PubMed1994

Three year follow up study of national influenza vaccination practices in Japan.

STUDY OBJECTIVE: To evaluate new national influenza vaccination practices which were started in 1987 under a revised law in Japan. DESIGN: This was a three year, nonrandomised cohort study with information collected by questionnaire between 1989 and 1991. SETTING: Eight primary schools in the city of Yonago, Tottori, Japan. These schools were selected from 23 schools in the city. PARTICIPANTS: Altogether 4251 pupils (1355 boys and 2896 girls) in years 1-4 of the eight primary schools were included in this study, and followed up. Three years later, data for 1619 pupils (768 boys and 851 girls) were obtained and analysed. MAIN RESULTS: The one-winter seasonal incidence rates of influenza-like disease were 13.4%, 29.9%, and 10.3% in 1989, 1990, and 1991 respectively. The incidence rate of influenza-like disease in fully vaccinated pupils was significantly lower than that in unvaccinated pupils in 1990, but not in 1989 or 1991. Stepwise multiple regression analysis showed that the incidence of influenza-like disease had a statistical relationship with the frequency of vaccination and the school year (R2 was 0.0148). Standardised parameters of the frequency of vaccination and the school frequency of vaccination and the school year were -0.089 and -0.080 respectively. CONCLUSIONS: The preventive effects of influenza vaccine are not strong. There must be some unknown factors that affect the incidence of influenza. This vaccine is useful for pupils in the early school years who seem to have less resistance. All pupils should not be inoculated with the vaccine to reduce influenza transmission in the community or school.

Child↗
PubMed1994

Uniquely higher incidence of isolated or combined deficiency of band 3 and/or band 4.2 as the pathogenesis of autosomal dominantly inherited hereditary spherocytosis in the Japanese population.

To clarify the pathogenesis of hereditary spherocytosis (HS), red cell membrane protein components were analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with a 3.5-17% exponential gradient according to the method of Fairbanks et al. and of Laemmli in 47 HS cases from 32 unrelated Japanese families. The relative contents of each membrane protein fraction, which was stained by Coomassie blue, were expressed as their ratios to those of total membrane proteins. The density of each band of red cell membrane proteins in 47 HS patients was compared to that in 10 normal controls or in 4 high-reticulocyte controls. Various isolated or combined deficiencies of membrane proteins in these HS patients were detected by identifying the amounts of membrane proteins, which were > 1 S.D. (91%) or 2 S.D. (53%) of the mean values of normal controls, and > 1 S.D. (100%) or 2 S.D. (98%) of those of high-reticulocyte controls. Contrary to the commonly held belief that most of the autosomal dominantly-inherited HS demonstrate isolated or combined deficiency of ankyrin (ANK) and/or spectrin (SP), a much lower incidence of isolated or combined deficiency of SP and/or ANK was observed in these Japanese HS patients; 19% (> 1 S.D.) or 12% (2 S.D.) compared to normal controls, or 2% (1 S.D.) or 4% (2 S.D.) compared to high-reticulocyte controls. Instead, the incidence of isolated or combined deficiency of band 3 (B3) and/or band 4.2 (B4.2) was markedly elevated in these Japanese HS patients; 50% (1 S.D.) or 39% (2 S.D.) compared to normal controls, or 78% (1 S.D.) or 88% (2 S.D.) compared to high-reticulocyte controls. Other combined deficiencies were also observed, but the incidence was much lower. Therefore, distinct characteristics, i.e., higher incidence of isolated or combined deficiency of B4.2 and/or B3 with much lower incidence of ANK and/or SP deficiency, were observed in Japanese HS patients.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1994

Red cell membrane disorders in the Japanese population: clinical, biochemical, electron microscopic, and genetic studies.

Based on studies on 610 cases of hereditary red cell membrane disorders, the characteristic features of the incidence of these disorders in the Japanese population are described. These patients were screened by a protocol on red cell morphology (scanning electron microscopy), on red cell membrane proteins (sodium dodecylsulfate polyacrylamide gel electrophoresis, and kinetics of membrane proteins), biophysical studies (ektacytometry, mechanical stability and fluorescence recovery after the photobleaching method), membrane transport (sodium influx and efflux, and anion transport), gene analysis (spectrins, band 4.2 and band 3), surface markers (blood type antigens and sialic acid content), and development and expression of membrane proteins (using a two-phase liquid culture system). Among the molecular abnormalities detected, alpha-spectrin mutation appeared rare (only one family with spectrin alpha I/74), as opposed to two beta-spectrin mutations in Japan out of seven worldwide cases. Two unrelated kindreds with a chromosomal abnormality; that is, del (8) (p11.2-p21.1), were found that involved the possible contribution of ankyrin to the pathogenesis of hereditary spherocytosis. Anomalies of a transmembrane domain of band 3 were detected in two independent kindreds with impaired anion transport. Among 16 HE patients, 13 cases were partially band 4.1 deficient. Complete band 4.2 deficiency of the Nippon type (GCT-->ACT at codon 142 in band 4.2 gene) was observed in 17 cases of 13 unrelated kindreds. Other forms of band 4.2 deficiency without the mutation were also detected in three kindreds. Band 7 deficiency was found in seven cases with hereditary stomatocytosis independent of the presence or absence of cation transport abnormalities. A relatively high incidence of hereditary high red cell membrane phosphatidylcholine hemolytic anemia was disclosed by the analysis of red cell membrane lipids.

Anemia, Hemolytic, Congenital↗
PubMed1994

[Molecular analysis of bcr-abl mRNA during long-term follow-up of cases of chronic myelogenous leukemia].

Forty cases of Ph1-positive CML patients, who were followed up for a long period, were evaluated for bcr-abl mRNA using RT-PCR. We analyzed the relation of the bcr-abl mRNA subtype to the duration of chronic phase and blast crisis lineage. The mean duration of the chronic phase was 2 years 3 months (2Y3M) in b2-a cases, 1Y11M in b3-a, and 1Y4M in both b2-a and b3-a cases. The myeloid/lymphoid ratio at the blastic phase was 1.0 in b2-a, 0.33 in b3-a, and 2.5 in both mRNA cases. No significant difference was observed in the mean duration of the chronic phase and the frequency of two kinds of blast crisis lineage among different bcr-abl mRNA cases. We also evaluated CML patients in clinical remission after BMT. Bcr-abl mRNA was detectable in 6 of 7 cases (6/7) within 6 months after BMT, all five cases from 6 months to 1 year (1Y), 2/8 at 1Y, 3/7 at 2Y, and 3/7 over 3Y. It suggested the longer time after BMT, the more patients were negative for RT-PCR. In one patient, RT-PCR signal became undetectable at 9Y. This demonstrated that bcr-abl mRNA-positive residual cells could be eradicated long after BMT.

Adolescent↗
PubMed1994

Electron microscopic and physicobiochemical studies on disorganization of the cytoskeletal network and integral protein (band 3) in red cells of band 4.2 deficiency with a mutation (codon 142: GCT-->ACT).

The role of band 4.2 deficiency in the pathogenesis of red cell membrane dysfunctions was studied in seven unrelated patients with complete band 4.2 deficiency with a point mutation (142 GCT-->ACT; 142 Ala-->Thr) on the cDNA of the band 4.2 gene. Two major types of abnormalities were detected in these patients; (A) abnormalities of the cytoskeletal network in the horizontal dimension, and (B) abnormalities of band 3 in the vertical dimension. Electron microscopy by the surface replica method and the quick-freeze deep-etching method demonstrated the markedly impaired cytoskeletal network (a disorganized cobblestone pattern, uneven distribution of junctional units, and the appearance of bulky aggregates after heat treatment). Ektacytometry showed a markedly decreased red cell deformability especially at 48 degrees C, although the cytoskeletal proteins themselves were essentially normal with normal mechanical stability of the Triton-shells. Electron microscopy by the freeze fracture method revealed a decreased number and a random distribution of intramembrane particles (IMPs) with a shift of the IMPs to a larger size. Fluorescence recovery after photobleaching studies on band 3 indicated the marked increase of its mobile fraction. The extractability of band 3 by Triton X in vitro was markedly enhanced, although the physico-biochemical properties of band 3 itself (the cleavage pattern of band 3 fragments, and the binding properties of band 3 to band 4.2 or ankyrin) were basically normal. These findings demonstrate that band 4.2 plays a crucial role in the maintenance of the normal structure and functions of both the cytoskeletal and integral proteins (band 3).

Anion Exchange Protein 1, Erythrocyte↗
PubMed1994

Effect of 1,6-dihydro-2-[2-(2-methylpropoxy)anilino]-6-oxo-5-pyrimidinecarboxylic acid on gastric mucosal defensive factors and gastric secretion in rats.

1,6-dihydro-2-[2-(2-methylpropoxy)anilino]-6-oxo-5-pyrimidinecarbo xylic acid, (MAR-99, CAS 98772-05-5) (10-30 mg/kg i.g.) improved the reduction of gastric blood flow rate induced by the administration of 99.5% ethanol or acidified-acetylsalicylic acid (ASA). In addition, MAR-99 (3 x 10(-6)-3 x 10(-5) mol/l) protected dose-dependently the damage of epithelial cells induced by ulcerogenic agents such as ethanol or acidified-ASA. MAR-99 (1-10 mg/kg p.o.) prevented dose-dependently the reduction of hexosamine content in glandular stomach. Furthermore, MAR-99 (10-30 mg/kg i.g.) improved the decrease in gastric potential difference induced by 99.5% ethanol and acidified-ASA. MAR-99 (10-30 mg/kg p.o.) significantly inhibited the lesion formation induced by 99.5% ethanol and such effect of this compound was not attenuated by the pretreatment with indomethacin. Furthermore MAR-99 (10 and 30 mg/kg p.o.) had no effect on the prostaglandins (PGE2 and I2) contents in the stomach of normal rats. In pylorus-ligated rats, MAR-99 (3-100 mg/kg i.d.) showed a weak or no effect on acidity and pepsin activity in gastric juice, although this compound decreased dose-dependently the volume of gastric juice. In perfused stomachs, MAR-99 (30-100 mg/kg i.d.) slightly prevented the acid secretion induced by carbachol and pentagastrin. However, MAR-99 did not affect the acid secretion stimulated by histamine. These results indicated that anti-ulcer effect of MAR-99 was mainly due to maintenance of the gastric mucosal resistance.

Animals↗
PubMed1993

Increased risk of lung cancer in Japanese smokers with class mu glutathione S-transferase gene deficiency.

Japanese lung cancer patients (n = 121) and community controls (n = 201), both with current smoking history and aged < or = 69, were compared for the rates of class mu glutathione S-transferase (GSTmu) negative genotype detected by polymerase chain reaction. The prevalence of the GSTmu negative genotype was 45.3% in the community control group and 68.4%, 69.2%, 54.3% and 72.7% in the squamous cell carcinoma, small cell carcinoma, adenocarcinoma and other primary lung cancer groups, respectively. Odds ratios adjusted for age, sex composition and smoking index by multiple logistic regression analysis were 2.71 (1.23-5.99), 2.72 (1.11-6.66), 1.33 (0.68-2.60), and 3.27 (0.83-12.81), respectively. These results suggest that smokers with a GSTmu negative genotype are at higher risk for bronchial carcinoma than smokers with positive genotype.

Adult↗
PubMed1993

The male preponderance in incidence of hepatocellular carcinoma in cirrhotic patients may depend on the higher DNA synthetic activity of cirrhotic tissue in men.

BACKGROUND: The relationship between the DNA synthetic activity of hepatocytes from cirrhotic liver tissue and the incidence of hepatocellular carcinoma (HCC) during a 3-year follow-up period was studied in male and female patients with posthepatitic cirrhosis. METHODS: The bromodeoxyuridine labeling index (BrdU LI) of hepatocytes was estimated in 38 cirrhotic patients (Child A stage, 23 men and 15 women) using a BrdU/anti-BrdU in vitro method. The incidence of HCC was compared between male and female cirrhotic patients during a 3-year follow-up period. RESULTS: Sixteen of 23 (69.6%) male patients belonged to the high-DNA synthesis group (BrdU LI > or = 1.5%), and only 7 (30.4%) were in the low-DNA synthesis group (BrdU LI < 1.5%). Among female patients, only 5 of 15 (33.3%) were in the high-DNA synthesis group, and 10 of 15 (66.7%) were in the low-DNA synthesis group (P < 0.05). Eleven of 23 (47.8%) male patients and 3 of 15 (20.0%) female patients had HCC develop. In the high-DNA synthesis group, 10 of 16 (62.5%) of the men and 3 of 5 (60.0%) of the women had HCC develop during the follow-up period. In contrast, only one of seven (14.3%) male patients and none of ten (0%) female patients in the low-DNA synthesis group had HCC develop. CONCLUSIONS: It was concluded that HCC developed frequently (about 60% of the time within 3 years) in patients of both sexes who were in a high-DNA synthesis group. Thus, the larger proportion of men in the high-DNA synthesis group compared with the number of women in the group (69.6% versus 33.3%) might be one possible reason for the male predominance in the development of HCC in cirrhotic patients.

Adult↗
PubMed1993

DNA synthesis activities of hepatocytes from noncancerous cirrhotic tissue and of hepatocellular carcinoma (HCC) cells from cancerous tissue can predict the survival of hepatectomized patients with HCC.

BACKGROUND: There is a concept that a cancer often maintains some of the traits of the background tissue cells. Thus, the possibility exists that the DNA synthetic activity of the hepatocytes in cirrhotic tissue affects that of hepatocellular carcinoma (HCC) cells. METHODS: DNA synthesis activity of hepatocytes from background cirrhotic tissue and HCC cells from cancerous tissue was studied in 30 patients with liver cirrhosis (LC) and HCC who had undergone hepatectomy; the study was done using the bromodeoxyuridine (BrdU)-anti-BrdU in vitro method. The correlation between the BrdU labeling index (LI) of hepatocytes from noncancerous cirrhotic tissue and that of HCC cells was studied. The relationship between both BrdU LI values and the survival after hepatectomy also was studied. RESULTS: A significant correlation (r = 0.572; P < 0.001) was identified between the BrdU LI for HCC and that for noncancerous cirrhotic tissue. A significant correlation (r = -0.572; P < 0.05) was found between the BrdU LI of HCC cells and the survival after hepatectomy. A significant correlation (r = -0.678; P < 0.01) was observed between the BrdU LI of the noncancerous cirrhotic tissue and the survival. CONCLUSIONS: It was concluded that a significant correlation existed between DNA synthesis of hepatocytes from the background cirrhotic tissue and that of HCC cells and that DNA synthesis activity of hepatocytes from noncancerous cirrhotic tissue and that of HCC cells from cancerous tissue could predict the survival of patients with HCC who had undergone hepatectomy.

Adult↗