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Biomedical subjects

N Mitsuda

Publications and source records attributed to N Mitsuda.

At least 55 records · Page 3Linked to original sources
PubMed1995

[Prenatal detection of the growth-retarded fetuses with a serious risk of adverse perinatal outcome by uterine artery Doppler flow velocimetry: a prospective study].

Our objective was to evaluate the predictive value of uterine artery Doppler flow velocimetry with regard to a serious risk of adverse perinatal outcome in growth-retarded fetuses. A prospective comparative study of pregnancies complicated with growth-retarded fetus with normal and abnormal uterine artery blood flow was performed. Ninety-three pregnancies were assessed by Doppler flow velocimetry in terms of the resistance index at 27-36 weeks. The relative risks (95% Confidence Interval) in 52 pregnancies with abnormal uterine artery blood flow compared with 41 pregnancies with normal uterine artery blood flow were as follows: Premature delivery: 2.29 (1.32-3.97), birth weight < 2,000g: 2.94 (1.74-4.97), cesarean section for fetal distress: 2.57 (1.30-5.05), admission to NICU: 3.27 (1.60-6.69). The findings in this study suggest that abnormal uterine artery blood flow is associated with a serious risk of adverse perinatal outcome in a pregnancy complicated with a growth-retarded fetus. Doppler flow velocimetry of the maternal uterine artery is useful for determining the clinical management of a pregnancy complicated with a growth-retarded fetus.

Adult↗
PubMed1994

Lupus anticoagulant autoantibody induces apoptosis in umbilical vein endothelial cells: involvement of annexin V.

The effects of lupus anticoagulant (LAC) on cultured human umbilical vein endothelial cells were studied. All five monoclonal antibodies from a patient with systemic lupus erythematosus (SLE), as well as plasma samples with LAC activity from six SLE patients, induced apoptosis. Anti-annexin V IgG also induced apoptosis. Since monoclonal antibodies and plasma from SLE patients had an affinity for annexin V, an endothelial apoptosis pathway mediated by annexin V was suggested as the molecular pathogenesis of the hemostatic derangement associated with LAC.

Animals↗
PubMed1994

Heterogeneity and diversity of IgM and IgG lupus anticoagulants in an individual with systemic lupus erythematosus.

From one patient with systemic lupus erythematosus retaining lupus anticoagulant (LAC), we established 6 Epstein-Barr virus-transformed human B cell clones secreting antibodies that affect the coagulation assay. Two and 4 of the clones secreted IgM and IgG antibodies, respectively. Although all 6 antibodies displayed anticardiolipin activity in ELISA, the increased binding activity in the presence of beta 2-glycoprotein I was limited only to the IgG antibodies. Five antibodies (two IgM and three IgG) had LAC activity which prolonged the activated partial thromboplastin time (APTT), whereas one IgG antibody shortened the APTT. Two of the IgG producing clones had an identical Ig heavy chain gene rearrangement despite their opposite effects on the coagulation assay. These results demonstrated the heterogeneity of LACs and diversity among their physiological functions.

Adult↗
PubMed1994

Carrier detection of Werner's syndrome using a microsatellite that exhibits linkage disequilibrium with the Werner's syndrome locus.

Werner's syndrome (WS) is a rare autosomal recessive disorder, one of the progeroid syndromes, characterized by features of premature aging. The genetic defect in WS is unknown but recently the genetic linkage of WS to several markers on the short arm of chromosome 8 has been reported. Genetic analysis of 25 families with WS demonstrated that D8S339 was the closest marker linked to the gene locus for Werner's syndrome (WRN), with a peak lod score of 18.29 at recombination frequency 0.001, and showed a linkage disequilibrium with the WRN locus. We studied two unrelated families with WS using ANK1, D8S339, and D8S360. The mutative haplotype identified through the generations in pedigrees provides a means of carrier detection and presymptomatic diagnosis.

Female↗
PubMed1994

Differentiation of postpartum thyrotoxicosis by serum thyroglobulin: usefulness of a new multisite immunoradiometric assay.

Destruction-induced thyrotoxicosis and Graves' thyrotoxicosis must be differentiated, since they are treated differently. To find a useful marker, we examined serial changes in serum thyroglobulin (Tg) concentrations in 20 patients with postpartum thyroid disease (9, euthyroid Hashimoto's disease; 11, Graves' disease in remission in early pregnancy). Serum Tg was measured by a new multisite immunoradiometric assay that allows little influence of anti-Tg autoantibodies. Eight women developed destruction-induced thyrotoxicosis 1 to 4 months postpartum, 6 had relapse of Graves' thyrotoxicosis 2 to 4 months postpartum, and 6 remained euthyroid. In destruction-induced thyrotoxicosis, serum Tg 2 months before the onset was 13.3 +/- 11.4 micrograms/L, then clearly increased 1 month before (34.5 +/- 31.9 micrograms/L) and was even higher at the onset of thyrotoxicosis (116.5 +/- 137.1 micrograms/L). In contrast, serum Tg increased only at the onset in Graves' thyrotoxicosis (from 25.9 +/- 25.2 micrograms/L 1 month before to 76.1 +/- 75.3 micrograms/L at the onset, p < 0.05). There was no difference in serum Tg level at the onset between the two disorders. However, when data were expressed as the percent increase from the level one month before, and the cut-off value were taken at 150%, all 7 patients above the cut-off developed destruction-induced thyrotoxicosis, and 6 of 7 below had recurrent Graves' thyrotoxicosis. Thus, serial measurement of serum Tg is useful for the differentiation of destruction-induced thyrotoxicosis from Graves' thyrotoxicosis after delivery.

Adult↗
PubMed1994

Prediction of post-partum Graves' thyrotoxicosis by measurement of thyroid stimulating antibody in early pregnancy.

OBJECTIVE: Autoimmune thyroid diseases often occur after delivery. However, it has been difficult to predict who will develop Graves' thyrotoxicosis after delivery. We tried to establish a systematic method for predicting post-partum onset of Graves' thyrotoxicosis. DESIGN: We followed up the pregnant women with antithyroid microsomal antibody (MCAb) from early pregnancy to the post-partum period and analysed the relation between the activities of thyroid stimulating antibodies (TSAb) in early pregnancy and post-partum occurrence of Graves' disease. PATIENTS: Seventy-one women with positive MCAb in early pregnancy were studied. They were randomly selected from 262 MCAb-positive subjects found in 3405 consecutive early pregnant women who attended our maternity clinic during the last ten years. MEASUREMENTS: MCAb was measured with a commercially available agglutination kit. For 71 MCAb-positive subjects, TSH-binding inhibitory immunoglobulin (TBII) and TSAb were measured in early pregnancy, and serially until 6 months after delivery for the subjects with either positive TBII or TSAb. Thyroid function and goitre size were recorded at every observation. RESULTS: Among the 71 subjects, 7 showed positive TSAb in early pregnancy without any thyroid dysfunction; all 7 developed thyroid dysfunction in the post-partum period. Five of them (70% of TSAb-positive subjects) developed Graves' disease, two showing persistence and three transiently. None of 64 TSAb-negative subjects developed Graves' thyrotoxicosis, though 44 developed various types of thyroid dysfunction as a result of post-partum autoimmune thyroiditis. CONCLUSION: The individuals at high risk of post-partum onset of Graves' thyrotoxicosis can be found early in their pregnancy by the detection of TSAb. Overall occurrence of post-partum Graves' disease in the general population is estimated above 0.54%, that is, one in 200 post-partum women may develop Graves' thyrotoxicosis, although thyrotoxicosis may be transient in half of the patients.

Autoantibodies↗
PubMed1993

Isolation and mapping of microsatellites from a library microdissected from the Werner syndrome region, 8p11.2-p22.

We have constructed a new genetic linkage map of the Werner syndrome (WRN) region, using microsatellites from a library which was developed by a chromosome microdissection and enzymatic amplification method. These microsatellites were used to genotype members of CEPH families using a simplified detection system of polymerase chain reaction (PCR) products. Two-point analysis was used to assign 4 microsatellite markers relative to each marker and other markers reported in the CEPH public data base. We confirmed that these 4 markers are located to the WRN region, 8p11.2-p22. Such microsatellites microdissected from the definite chromosome region may be useful for positional cloning.

Base Sequence↗
PubMed1993

Crucial role of serum human chorionic gonadotropin for the aggravation of thyrotoxicosis in early pregnancy in Graves' disease.

Thyrotoxicosis in Graves' disease is often aggravated in early pregnancy and is closely associated with postpartum recurrence of stimulative thyrotoxicosis. To examine whether thyroid-stimulating TSH receptor antibody (TSAb) or human chorionic gonadotropin (hCG), which also has thyroid-stimulating activity (TSA), was responsible for this early aggravation, the respective TSA due to TSAb or hCG was evaluated by a highly sensitive cAMP accumulation assay using FRTL-5 cells. TSA was detectable in all of 11 women in normal early pregnancy, correlated positively with serum hCG concentration, and was abolished completely by the pretreatment of serum sample with the solid-phase hCG antibody coupled with Sepharose 4B. The model serum samples of Graves' disease with pregnancy were made by the mixture of normal pregnant and Graves' sera, and their TSA were reduced by the pretreatment with the solid-phase hCG antibody, just corresponding with the reduction in hCG-induced TSA. TSA of early pregnant sera in 20 patients with Graves' disease decreased significantly but were still positive even after the pretreatment with the hCG antibody. Serial changes in TSAb and hCG-induced TSA were measured in 5 of these 20 pregnant patients. hCG-induced TSA increased associated with the increase in free thyroxine, while TSAb did not show striking change in early pregnancy. These data indicate that (1) respective TSA due to TSAb or hCG can be measured distinctively by using the solid-phase hCG antibody and (2) hCG plays a crucial role in the aggravation of Graves' thyrotoxicosis in early pregnancy.

Autoantibodies↗
PubMed1993

Gestational thyrotoxicosis and hyperemesis gravidarum: possible role of hCG with higher stimulating activity.

OBJECTIVE: The thyroid gland is physiologically stimulated in normal early pregnancy. However, clinical thyrotoxicosis in normal pregnancy has not been well described. In order to clarify this we examined thyroid function and thyrotoxic symptoms in relation to emesis in normal pregnancy. We also investigated the possible mechanism of gestational thyrotoxicosis. DESIGN: Thyroid function was evaluated in view of the clinical thyrotoxic symptoms and the severity of gestational emesis in early pregnancy of 51 normal women. Two pregnant women who showed clinical thyrotoxicosis were followed serially during and after pregnancy. MEASUREMENTS: Serum free T4, free T3 and TSH were measured by radioimmunoassay and hCG by fluoroimmunoassay. Thyroid-stimulating activity of pregnancy sera was measured by cAMP increase in cultured FRTL-5 cells. RESULTS: Fifty-one pregnant women were divided into three groups: those without emesis (n = 24), with emesis (n = 19) and with hyperemesis (n = 8). Serum free T4 and free T3 were higher in the hyperemesis group (P < 0.01) and the emesis group (P < 0.01), and serum TSH was suppressed to less than 0.1 mU/l in both groups, while serum hCG was not significantly different among these three groups. However, serum thyroid-stimulating activity was remarkably high in the hyperemesis group (P < 0.01). Thus the ratio of thyroid-stimulating activity to hCG was higher in the hyperemesis group (P < 0.05) and the emesis group (P < 0.05) compared with that in the group without emesis. These thyroid-stimulating activities were abolished by treatment of the serum with anti-hCG antibody. Two of eight women with hyperemesis, who had the highest free T4 and thyroid-stimulating activity/hCG ratio, showed overt clinical symptoms of thyrotoxicosis; all the symptoms disappeared in association with a fall in thyroid-stimulating activity and free T4. CONCLUSION: Clinical thyrotoxicosis is caused by circulating hCG with higher biological activity in pregnant women with hyperemesis. A new clinical entity of 'gestational thyrotoxicosis' is proposed and tentative characteristics are discussed.

Chorionic Gonadotropin↗
PubMed1993

Prenatal detection of ischemic changes in the placenta of the growth-retarded fetus by Doppler flow velocimetry of the maternal uterine artery.

OBJECTIVE: To determine the relationships among the pregnancy outcomes of growth-retarded fetuses, Doppler flow velocimetry of the fetomaternal circulation, and pathologic changes in the placenta. METHODS: Forty-seven fetuses confirmed to be growth-retarded by ultrasonographic biometry were monitored during pregnancy in terms of the resistance indexes of the maternal uterine, fetal umbilical, and fetal middle cerebral arteries. After delivery, the placentas were examined for pathologic changes such as infarction and villous ischemia. RESULTS: Compared with 23 fetuses with nonischemic placentas, 24 growth-retarded fetuses whose placentas showed ischemic lesions were more frequently delivered preterm (P < .001) and by cesarean for fetal distress (P < .01), and they also had lower mean pH, higher carbon dioxide pressure, and lower oxygen pressure values (P < .05). Compared with the fetal umbilical and middle cerebral artery resistance indexes, the uterine artery resistance index showed the highest sensitivity (91.7%), specificity (78.3%), and positive predictive value (81.5%) for detecting placental ischemic changes. Linear discriminative analysis also showed that the uterine artery resistance index had the strongest correlation (P < .00001) with the placental ischemic changes. CONCLUSION: Ischemia of the placenta is associated with an adverse pregnancy outcome in growth-retarded fetuses. The placental ischemic changes can be detected using Doppler flow velocimetry. Measurement of the uterine artery resistance index might be useful for determining the clinical management of growth-retarded fetuses.

Adult↗
PubMed1992

Increase in peripheral natural killer cell activity in patients with autoimmune thyroid disease.

Changes in the activity and number of natural killer (NK) cells in peripheral blood in patients with autoimmune thyroid disease were examined. NK activity was measured in a 4-hr 51Cr-release assay and the number of NK cells was analyzed with FITC-conjugated monoclonal antibodies by use of an automated flow cytometer. NK activity in patients with untreated Graves' disease (n = 25, 39.7 +/- 13.5%, P less than 0.05) and Hashimoto's thyroiditis (n = 18, 41.0 +/- 14.2%, P less than 0.05) was high compared to the activity in non-pregnant controls (n = 61, 32.6 +/- 15.0%). NK activity in patients with postpartum Graves' thyrotoxicosis (n = 11, 48.6 +/- 18.9%) was markedly increased compared to the activity in non-pregnant controls (P less than 0.01) and in postpartum controls (n = 29, 33.8 +/- 15.2%, P less than 0.05), although the mean ages of each group did not differ significantly. Moreover, NK activities in the thyrotoxic state were significantly higher than those in the euthyroid state in the same patients with postpartum Graves' thyrotoxicosis or with postpartum destructive thyrotoxicosis. The number of CD16 positive cells increased in patients with postpartum Graves' thyrotoxicosis. However the number of CD16 and CD57 positive cells were normal in all other groups of patients. These results indicate that an increase of NK activity is associated with exacerbation of autoimmune thyroid disease both in Hashimoto's thyroiditis and in Graves' disease and suggest that NK cells might have an important role for the control of disease activity in autoimmune thyroid disease.

Adult↗
PubMed1992

Risk factors for developmental disorders in infants born to women with Graves disease.

OBJECTIVE: To identify risk factors for disorders of fetal growth and thyroid function in the presence of maternal Graves disease. METHODS: Two hundred thirty pregnancies in gravidas with Graves disease were analyzed. Maternal thyroid status was evaluated by serum free thyroxine (T4) or free T4 index, TSH, and TSH-receptor antibody; personal history of thyrotoxicosis and total dose of antithyroid drugs during pregnancy were also noted. Neonatal thyroid function was assessed at birth and on the fifth day after birth. RESULTS: Fifteen neonates (6.5%) were small for gestational age (SGA), and this occurrence was significantly associated with thyrotoxicosis lasting for 30 weeks or more of pregnancy, TSH-receptor antibody level of 30% or more at delivery, history of Graves disease of 10 years or longer, and onset of Graves disease before 20 years of age. However, no significant correlation was found between maternal thyroid hormone level and SGA neonates. Thyroid dysfunction developed in 38 infants (16.5%), of whom only four were SGA; development of this dysfunction was significantly related to the mother's total dose of antithyroid drugs, duration of thyrotoxicosis in pregnancy, and/or TSH-receptor antibody level at delivery. CONCLUSIONS: Duration of maternal Graves disease or thyrotoxicosis, either mild chemical or overt, in pregnancy is significantly associated with SGA neonates. Neonatal thyroid dysfunction is associated with the maternal thyroid condition, especially the serum TSH-receptor antibody level.

Adult↗
PubMed1992

[Analysis of circulating thyroid-stimulating activities in pregnant women with Graves' disease: differential measurement of activities induced by TSH receptor antibody and hCG].

Thyrotoxicosis in Graves' disease is often aggravated in early pregnancy and this aggravation is associated with postpartum relapse of thyrotoxicosis. To examine whether thyroid-stimulating TSH receptor antibody (TSAb) or human chorionic gonadotropin (hCG), which also has thyroid-stimulating activity (TSA), is responsible for this early aggravation, the respective TSA due to TSAb or hCG were evaluated with a sensitive cAMP accumulation assay using FRTL-5 cells. TSA, which was detectable in all of 11 women in normal early pregnancy, correlated positively with serum hCG level, but was abolished completely by the pretreatment of serum samples with the solid-phase hCG antibody coupled with Sepharose-4B. Total TSA in the model samples of mixture of Graves' and pregnant sera (Gr + Preg), was reduced by the pretreatment with the solid-phase antibody, just corresponding with the reduction in hCG-induced TSA. Total TSA in early pregnant sera in 15 patients with Graves' disease, decreased significantly but was still positive even by the pretreatment with the hCG antibody. Pregnancy-associated changes in TSA was examined serially in a patient with Graves' disease, and hCG-induced TSA increased predominantly along with the serum thyroid hormone in early aggravation period. These data indicate that (1) the respective TSA due to TSAb or hCG can be differentially measured by using the solid-phase hCG antibody and (2) hCG plays an important role for aggravation of Graves' thyrotoxicosis in early pregnancy.

Animals↗
PubMed1991

Changes in natural killer cell activity in normal pregnant and postpartum women: increases in the first trimester and postpartum period and decrease in late pregnancy.

Changes in the activity and number of natural killer (NK) cells in peripheral blood in normal pregnant and postpartum women were examined. NK activity was measured in a 4-h 51Cr-release assay and evaluated by conventional relative lytic units and absolute lytic units which represent the total NK activity within a fixed volume of circulating blood. The number of NK cells was analyzed with FITC-conjugated monoclonal antibodies and by use of an automated flow cytometer. Unexpectedly, the relative NK activity increased in the first trimester and also for 1 month postpartum compared to the activity in normal non-pregnant controls. On the other hand, absolute NK activity decreased in the third trimester compared to the activity in normal non-pregnant controls. The percentage of CD57+ cells decreased in the second trimester, but the percentage of CD16+ cells did not change during pregnancy or the postpartum period. The absolute counts of CD57+ cells and CD16+ cells decreased in the second and third trimesters and increased transiently in the postpartum period. These findings indicate that the increased NK activity in the first trimester and at 1 month postpartum is induced by increased cytotoxic activity of individual NK cells, and that the decreased NK activity in late pregnancy is induced by a decrease in the numbers of NK cells. These physiological changes may play an important role in implantation in early pregnancy, protection of the fetal allograft in late pregnancy and in the natural defense against infection during the puerperal period.

Adult↗