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N Mitsuda

Publications and source records attributed to N Mitsuda.

At least 37 records · Page 2Linked to original sources
PubMed1997

A high-density STS map based on a single contig of YAC and P1 clones in the chromosome 8p12-p21 region.

We have constructed a yeast artificial chromosome (YAC) and P1 contig in the 8p12-p21 region. The contig comprises 16 overlapping YAC clones and 44 overlapping P1 clones. Twelve dinucleotide-repeat polymorphic sequence-tagged site (STS)-markers that were previously isolated mainly from these YAC and P1 clones were genetically mapped. A total of 46 nonpolymorphic STS markers were newly established mainly from the YAC and P1 clone end fragments, and 28 of the 46 nonpolymorphic STSs, as well as the 12 polymorphic STSs, were also mapped physically onto the contig based on STS content analysis of YAC pools and of the P1 and YAC clones. As a result, the YAC and P1 clones were assembled into a single contig covering a minimum of 1.5 Mb physically and 2.8 cM genetically with 12 polymorphic and 28 nonpolymorphic STSs within the 8p12-p21 region. Average STS spacing in the contig was estimated to be 40 kb/STS. In addition, further characterization of the contig suggested that this contig includes a region where genetic recombination occurs frequently. Thus, the resulting cloned region, together with densely mapped STS markers on the contig, should help to promote our understanding of this region.

Bacteriophage P1↗
PubMed1997

Effects of autoantibodies on the course of pregnancy and fetal growth.

OBJECTIVE: To assess the effects of autoantibodies on the course of pregnancy and fetal growth. METHODS: One thousand one hundred seventy-nine healthy women with singleton gestations were screened in early pregnancy for seven kinds of autoantibodies: antithyroid microsomal antibody, antithyroglobulin antibody, two kinds of rheumatoid factor, antinuclear antibody, anti-DNA antibody, and antimitochondrial antibody. RESULTS: In 228 cases (19.3%), at least one autoantibody was found; however, overlap of autoantibodies in the same individual was unexpectedly rare, and only two cases were positive for as many as four autoantibodies. A significantly higher rate of spontaneous abortion was observed in antibody-positive subjects, especially those with antithyroid microsomal (10.4%) or antinuclear antibodies (16.0%), compared with all antibody-negative subjects (5.5%). There were no significant differences in any outcome assessed among subjects positive for antithyroglobulin antibody, anti-DNA antibody, or antimitochondrial antibody compared with all antibody-negative subjects. None of the seven autoantibodies affected the rates of preterm delivery, stillbirth, pregnancy-induced hypertension, malformation, or gender ratio. CONCLUSION: Antithyroid microsomal antibody and antinuclear antibody are the only autoantibodies that increase the abortion rate.

Adult↗
PubMed1997

Molecular and epidemiological studies of Werner syndrome in the Japanese population.

Werner syndrome (WS) is an autosomal recessive genetic disease characterized by many age-related features. The gene responsible for WS (WRN) has been isolated and contains a helicase domain, but its function is unknown. Six different mutations throughout the WRN gene have been reported in the Japanese population. We have studied whether patients with a specific mutation exhibit distinct phenotypes from others. Fourteen patients with different mutations showed almost the same signs and symptoms and, therefore, the C terminal part of the product appears to be crucial for its functions, although other parts may be important as well. Haplotype analyses using 13 microsatellites covering the 2.8-3.0 cM WRN region showed that two out of six different mutations had founder chromosomes. These two founder chromosomes may be evenly distributed throughout the western part of Japan, suggesting that these mutations go back to a time earlier than 1400 years ago.

Chromosome Mapping↗
PubMed1997

Changes in T, B, and NK lymphocyte subsets during and after normal pregnancy.

PROBLEM: Pregnancy affects the maternal immune system and the clinical course of maternal diseases. Here we report the changes in the detailed lymphocyte subsets of helper T cells, suppressor T cells, CD5+ B cells, T cell receptor (TCR) alpha beta-positive T cells (T alpha beta cells), TCR alpha beta-negative T cell (T gamma delta cells), and other during and after pregnancy through to one year postpartum, and discuss the significance of the changes. METHOD: The absolute numbers of helper T cells, suppressor T cells, cytotoxic T cells, TCR alpha beta-negative T cells (T gamma delta cells), CD5- B cells, CD5+ B cells, and NK cell subsets were examined by two-color flow cytometry in peripheral blood from 51 healthy non-pregnant women, 106 healthy pregnant women, and 148 healthy postpartum women. RESULTS: In early pregnancy, the numbers of suppressor T cells and NK cells with strong cytotoxicity (NK+3 cells) increased, and the number of cytotoxic T cells decreased. In late pregnancy, the helper T cell and NK+3 cell numbers decreased. T alpha beta, CD5- B and CD5+ B cells decreased during pregnancy. After delivery, helper T cells and cytotoxic T cells increased from 1 to 4 months postpartum, and suppressor T cells increased at 7 months postpartum. TCR alpha beta-negative T cells increased at 4 to 10 months postpartum. Both CD5- and CD5+ B cells decreased further at 1 month postpartum, but CD5+ B cells increased markedly at 7 to 10 months postpartum. CONCLUSIONS: These data indicate that 1) early increases of suppressor T cells and NK+3 cells during pregnancy may be related to the mechanism to accept or reject the fetus in early pregnancy, respectively; 2) late decreases of helper T cells and NK+3 cells may be related to the maintenance of pregnancy: 3) postpartum increases of helper T cells, cytotoxic T cells, TCR alpha beta-negative T cells (T gamma delta cells), and CD5+ B cells may be related to the postpartum aggravation of autoimmune diseases; and 4) the immunological effects of pregnancy remains until about 1 year after delivery.

Adult↗
PubMed1997

Value of the maternal interleukin 6 level for determination of histologic chorioamnionitis in preterm delivery.

The present study examined whether maternal serum cytokine levels are useful for the diagnosis of histologic chorioamnionitis. The blood samples of 29 women who delivered preterm between 22 and 34 weeks of gestation were collected at delivery, and placentas were histopathologically examined for chorioamnionitis. The interleukin (IL) 6 titer was higher in 18 mothers with histologic chorioamnionitis (median 12.0 pg/ml, range 4.9-63.5 pg/ml) than that in 11 mothers without histologic chorioamnionitis (median 3.5 pg/ml, range 1.7-14.9 pg/ml; p < 0.0001). The C-reactive protein (CRP) titer also differed significantly between these two groups (chorioamnionitis group: median 5.2 mg/dl, range 0.1-12.3 mg/dl; no chorioamnionitis group: median 0.2 mg/dl, range 0.1-0.5 mg/dl; p = 0.0001). The IL-6 titer showed better clinical diagnostic indices and a higher odds ratio (9.78, 95% confidence interval 1.50-63.82) than did CRP (3.26, 95% confidence interval 1.22-8.67). The levels of IL-8, monocyte chemotactic and activating factor, and soluble IL-6 receptor did not differ between the two groups. These data suggest that the level of maternal serum IL-6 is more useful than other markers, including CRP, for the identification of women at risk of impending preterm labor with histologic chorioamnionitis.

Adult↗
PubMed1996

Narrowing the position of the Werner syndrome locus by homozygosity analysis-extension of homozygosity analysis.

Werner syndrome (WS) is an autosomal recessive disorder characterized by the premature occurrence of many age-related features. Previously, the WS gene (WRN) was mapped between D8S131 and D8S87, in an 8.3-cM interval. In this study, regions of homozygosity in 36 WS patients from inbred families were searched for by genotyping for 35 dinucleotide repeat polymorphic markers to narrow down the WRN critical region. The region most consistently homozygous in these patients was between the D8S1219/D8S1220 cluster and D8S278, within a 4.4-cM interval. For 16 markers mapped in this interval, 24 WS patients (22 Japanese patients and 2 Caucasian patients) in whom consanguinity failed to be proved were also genotyped, under the assumption that some of these patients might still be from consanguineous marriages. The data were analyzed by Fisher's exact test with a 2 x 2 contingency table for the 22 Japanese patients, excluding the 2 Caucasian patients. The frequencies of homozygosity in the 22 patients at 10 of 16 markers tested were significantly higher than those detected in the general population. Analysis of homozygosity patterns indicated that the region most consistently homozygous was between D8S1445 and D8S278. Thus the WRN locus is most likely between the two markers D8S1445 and D8S278, in a 1.6-cM interval.

Asian People↗
PubMed1996

Changes in soluble CD4 and CD8 proteins in healthy pregnant and postpartum women.

PROBLEM: We examined physiological changes in serum levels of soluble CD4 (sCD4) and soluble CD8 (sCD8) during pregnancy and 1-12 months postpartum to study changes in the maternal immune system during and after pregnancy. METHOD: The serum concentrations of sCD4 and sCD8 were measured by enzyme immunoassay in the sera separated from blood samples withdrawn from healthy women in the 1st, 2nd, and 3rd trimesters of pregnancy and 1, 4, 7, and 10-12 months postpartum (n = 182) and healthy non-pregnant women (n = 25), and in 90 of the women, the changes in sCD4 and sCD8 were compared with changes in the number of peripheral CD4+ and CD8+ cells measured by flow cytometry. RESULTS: The serum concentration of sCD4 decreased throughout pregnancy, from the first trimester, and recovered gradually after delivery. The serum concentration of sCD8 did not change significantly during or after pregnancy compared to the concentration in the non-pregnant controls, but the concentration 1 month postpartum was significantly higher than that in the 3rd trimester. The number of CD4+ and cd8+ cells decreased during pregnancy but did not change significantly after delivery. Interestingly, the ratio of the serum sCD4 level to the number of CD4+ cells decreased and the ratio of the sCD8 level to the number of CD8+ cells increased in the first and second trimesters of pregnancy, but these ratios were within the normal range from the third trimester of pregnancy to 10-12 months postpartum. CONCLUSIONS: Decreases in serum sCD4 concentration and in the ratio sCD4/CD4+ cells, and an increase in the ratio sCD8/CD8+ cells may be important factors in the immunological changes that occur during pregnancy.

Adult↗
PubMed1996

Recurrent left atrial myxoma in a patient with a twin fetus pregnancy.

We experienced a case of a recurrent left atrial myxoma in a pregnant woman with twin fetuses. Normal healthy twins weighing 1430 and 1190 gm were delivered by cesarean section performed under epidural anesthesia at 32 weeks gestation. Neither cardiac failure nor embolisms were observed during pregnancy or delivery. The left atrial myxoma was removed surgically one week after delivery. The infants and mother remain in good health. According to previous reports and our present observations, the decision for cardiac surgery during pregnancy should be based on the maternal and fetal status.

Adult↗
PubMed1995

Genetic association between chromosome 8 microsatellite (MS8-134) and Werner syndrome (WRN): chromosome microdissection and homozygosity mapping.

Werner syndrome (WRN) is an autosomal recessive disorder characterized by premature aging that has been mapped to the short arm of chromosome 8, 8p11.2-p12. To refine the genetic map around the WRN region, we have isolated eight microsatellites for this region from a microdissection library. We typed members of Japanese families with WRN on the basis of homozygosity mapping analysis. There was no obligate recombination between the WRN locus and microsatellite clone, MS8-134 (D8S1055). The maximum lod score was 20.28 at theta = 0.00. Alleles for MS8-134 showed association with WRN in a case-control study (OR = 3.55, 95% CI 1.56-8.07, P < 0.01). Such microsatellites from a microdissection library of the definite chromosome region may be useful for positional cloning of the WRN gene.

Base Sequence↗
PubMed1995

Pathogenic role of asialo human chorionic gonadotropin in gestational thyrotoxicosis.

We reported that gestational thyrotoxicosis is induced by thyroid-stimulating activity (TSA) of circulating hCG. However, the serum immunological hCG concentration did not correlate to TSA. To elucidate this, we examined the relation of carbohydrate moieties of hCG to bioactivity in 79 early pregnant women, divided into 4 groups: no emesis, mild emesis, hyperemesis, and gestational thyrotoxicosis with hyperemesis. Serum free T4 (FT4) and free T3 (FT3) levels were significantly higher and TSH was lower in the hyperemesis (FT4, 23.42 +/- 5.02 pmol/L; FT3, 6.26 +/- 1.80 pmol/L; TSH, 0.30 +/- 0.44 mU/L) and in gestational thyrotoxicosis (FT4, 48.65 +/- 14.80 pmol/L; FT3, 14.71 +/- 3.47 pmol/L; TSH, < 0.04 mU/L) groups than in the no emesis group (FT4, 16.99 +/- 2.48 pmol/L; FT3, 5.51 +/- 0.75 pmol/L; TSH, 1.37 +/- 1.23 mU/L; P < 0.0005). TSA was also significantly higher in the hyperemesis (566 +/- 187%) and gestational thyrotoxicosis (832 +/- 168%) groups than in the no emesis group (321 +/- 135%). We found no significant difference among serum hCG concentrations measured by immunoassay in the four groups. To characterize the carbohydrate chains, serum hCG was fractionated by Concanavalin-A and ricin lectin affinity chromatography. The fraction firmly bound to Con-canavalin-A, which contains hCG with high mannose and hybrid-type carbohydrate chains, was significantly higher in the hyperemesis group (91.07 +/- 2.06%; n = 15) than in the no emesis group (89.61 +/- 2.38%; n = 24; P < 0.04). The fraction firmly bound to ricin column, which contains hCG with asialo-carbohydrate chains, was significantly increased in the gestational thyrotoxicosis group (3.44 +/- 1.70%; n = 5) compared with that in the no emesis group (1.77 +/- 0.49%; n = 24; P < 0.03). Serum FT4 positively correlated to the hCG fraction firmly bound to ricin column (r = 0.61; P < 0.001). We conclude that thyrotoxicosis with hyperemesis may be caused by circulating asialo-hCG with higher thyrotropic bioactivity.

Adult↗
PubMed1995

Leukemia developing after 131I treatment for thyroid cancer in a patient with Werner's syndrome: molecular and cytogenetic studies.

A 40-year-old female patient with Werner's syndrome (WS) suffering from thyroid cancer and myelodysplastic syndrome (MDS) is reported. She had been diagnosed as having WS complicated with thyroid cancer seven years previously. Total thyroidectomy and radioactive iodine (131I, 100 mCi/year) therapy for seven years had slowed the progression of thyroid cancer. She suffered a sudden onset of MDS at the age of 40 years. After six months she died from overt leukemia. We found an additional chromosome aberration of chromosome 10 in the progression of leukemia from MDS.

Adenocarcinoma, Papillary↗
PubMed1995

[Genetic analysis of Werner syndrome in a family].

Werner syndrome (WRN) is a rare autosomal recessive disorder, one of the progeroid syndromes, and is characterized by features of premature aging. The incidence of WRN in the Japanese population, 1 in 200,000, is higher than than that in the Caucasian population. The genetic defect of WRN is unknown. But genetic linkage to several markers on the short arm of chromosome 8 has been reported recently. Here, we studied one family with WRN in which an affected individual had a papillary thyroid carcinoma and myelodysplastic syndrome. Using 4 microsatellites closely located to the WRN locus: D8S360, D8S1055, D8S339 and ANK1, we analyzed the genotypes of this patient, her three siblings and her parents, who were first cousins. The mutative haplotype, identified through the generations in pedigree, helps detect a carrier or a presymptomatic patient. The eldest sister inherited two normal haplotypes, but the second sister inherited one mutative haplotype. There was no difference in clinical signs and symptoms between these sisters. when the WRN gene is isolated, it will help us understand the mechanism of aging.

Adult↗