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N Mitsuda

Publications and source records attributed to N Mitsuda.

71 records · Page 4Linked to original sources

[Prenatal evaluation of the platelet counts in the fetuses and the neonates of the mothers complicated with idiopathic thrombocytopenic purpura].

We investigated 25 pregnancies with ITP. The results were as follows. 1. The platelet counts of the maternal blood just before delivery were not correlated with those of the cord blood. 2. It was suggested that the maternal PAIgG value just before delivery could foretell the onset of neonatal thrombocytopenic purpura. 3. The platelet counts in fetal scalp blood were correlated with those of the cord blood, but falsely lower platelet counts were found in the fetal scalp samples. 4. We saw 5 cases of percutaneous umbilical blood sampling (PUBS) in pregnancies with ITP. PUBS was found to be a useful and safe method. The indications for PUBS and fetal platelet transfusion in pregnancy with ITP are discussed.

Cesarean Section↗

Expression of the corticotropin-releasing hormone (CRH) gene in human placenta and amniotic membrane.

Immunoreactive corticotropin-releasing hormone (IR-CRH) in maternal plasma increases progressively during pregnancy and decreases rapidly after delivery, suggesting that IR-CRH is produced in the placenta. We studied the expression of the CRH gene in developing human chorionic tissue, the amniotic membrane, the uterine myometrium and a fresh surgical specimen of hydatidiform mole by Northern blot analysis. Our results were as follows: (1) CRH mRNA was demonstrated in the placenta in the third trimester and at term, but under detectable level in the first and second trimesters. (2) CRH mRNA expression was observed in the amniotic membrane, but its expression in the myometrium in normal pregnancy was under detectable level at term. (3) CRH mRNA was also under detectable level in trophoblasts of a hydatidiform mole. These results suggest that the sources of the increased level of IR-CRH in human plasma and amniotic fluid during pregnancy are the placenta and amniotic membrane, and that gene expression of placental CRH increases during pregnancy.

Amnion↗

Clinical evaluation of a direct colorimetic method for determination of amniotic phospholipids.

Evaluation of amniotic phospholipids, which are a parameter of fetal lung maturation, is important in the management of premature infants. The method available for measuring the lecithin/sphingomyelin (L/S) ratio, which appears to provide an index to fetal lung maturity, is laborious, involving determinations of phospholipids, and so is unsuitable for rapid quantitative measurement of phospholipids in the amniotic fluid in the perinatal period. We developed a simple, sensitive colorimetric assay for phospholipids without their extraction. This assay is based on the fact that phospholipids form stable hydrophobic complexes with Co(SCN)4, Fe(SCN)2- and Fe(SCN)3 within about 1 hr. Amniotic fluid samples (n = 115) were collected from women with normal and abnormal pregnancies in week 16-41 of pregnancy, and these samples were examined both by thin layer chromatography (TLC) and by our method of phospholipid determination. Good correlations were observed between the L/S ratio determined by TLC and the values obtained by this method. Moreover the distributions of the dipalmitoylphosphatidylcholine (DPPC) content and DPPC/sphingomyelin (SM) ratio were similar to those of the PC content and L/S ratio. This method was proved to be more accurate than other methods such as TLC and the shake test for predicting neonatal RDS.

Amniotic Fluid↗

Physiologic thyroid activation in normal early pregnancy is induced by circulating hCG.

In normal early pregnancy, serum free thyroxine (T4) increases and serum TSH decreases, indicating that the thyroid gland is activated physiologically. To identify the factor responsible for this thyroid activation, we measured the serum thyroid-stimulating activity in comparison with the serum level of hCG in 39 normal women in early pregnancy. Serum thyroid-stimulating activity was measured by a sensitive cyclic adenosine 3',5'-monophosphate (cAMP) accumulation assay using a rat thyroid cell line (FRTL-5). Thyroid-stimulating activity was detected in 37 women (95%), and the activities of individuals correlated positively with their serum free T4 levels (r = 0.474; P less than .01) and negatively with their serum TSH levels (r = -0.376; P less than .02). Moreover, serum thyroid-stimulating activity correlated closely with the serum hCG level (r = 0.741; P less than .001), but was completely abolished by pre-treatment of the sera with hCG antibodies. These data indicate that in normal early pregnancy, the thyroid gland is physiologically activated by serum hCG, which has intrinsic thyroid-stimulating activity.

Animals↗

[Effect of low-dose aspirin therapy on utero-placental blood flow and malondialdehyde (MDA) as an indicator of its therapeutic effect].

Pregnancy-induced hypertension (PIH) and preeclampsia develop when an imbalance occurs between prostacyclin (PGI2) and thromboxane A2 (TXA2) production. PGI2 promotes vasodilation and decreases platelet adhesiveness, while TXA2 acts as a vasoconstrictor and enhances platelet aggregation and adhesion to vascular walls. The PGI2/TXA2 ratio appears to be important in pregnancy and the development of the functioning uteroplacental unit. Recently, antiplatelet treatment such as low-dose aspirin therapy has been effective in preventing the development of PIH and preeclampsia. TXA2 breaks down spontaneously into a stable substance, TXB2, which is inactive. Another stable, inactive metabolite, malondialdehyde (MDA), is formed via the same pathway. TXB2 and MDA are produced in approximately equimolar quantities. We studied the effects of a low-dose aspirin prescription. Production of MDA was remarkably suppressed during the low-dose aspirin therapy. Furthermore, pulsed doppler ultrasound assessment of blood flow was performed in the fetal descending aorta, umbilical artery and uterine artery of the low-dose aspirin therapy patients. Doppler abnormalities were improved during the therapy. It is concluded that low-dose aspirin improves the uteroplacental blood flow assessed by pulse doppler waveform and that determination of MDA is useful as an indicator of platelet thromboxane synthesis.

Adult↗

Thyroxine requirement during pregnancy for replacement therapy of hypothyroidism.

We examined the dose requirements of thyroxine (T4) and desiccated thyroid during eight pregnancies of six women who had undergone total thyroidectomy for thyroid carcinoma. In five pregnancies from four patients treated with T4, serum free T4, which was measured by a newly developed radioimmunoassay, decreased during pregnancy but increased above the normal range after delivery. Consistent with these changes in free T4, serum TSH (measured by a highly sensitive immunoradiometric assay) increased during pregnancy but returned to an undetectable level after delivery, with one exception. The serum triiodothyronine (T3)-to-T4 ratio, which is related to peripheral conversion of T4 to T3, was lower in patients treated with T4 than in normal controls, regardless of pregnancy. The ratio decreased further during pregnancy, and so relative deficiency of T3 during pregnancy was suspected, especially in T4-treated patients. On the other hand, in two pregnancies from two other patients treated with desiccated thyroid at a dose most equivalent to that of T4, serum free T4 decreased to a low-normal value during gestation but returned to the normal range after delivery, whereas serum TSH scarcely changed during pregnancy. These findings indicate that replacement therapy for pregnant patients with hypothyroidism after total thyroidectomy should include an increased dose of T4; in contrast, the dose of desiccated thyroid need not be changed.

Female↗

Immunoreactive corticotropin-releasing hormone, adrenocorticotropin and cortisol in human plasma during pregnancy and delivery and postpartum.

The activity of the hypothalamo-pituitary adrenal axis was examined, by measuring the levels of immunoreactive (IR) corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH) and cortisol (F) in human plasma during normal pregnancy and after delivery with or without complications and during normal postpartum using a specific RIA. The level of IR-CRH in maternal plasma increased progressively during pregnancy, increased further at delivery and declined rapidly to the non-pregnant level on the 1st day postpartum. The level of IR-F in maternal plasma also increased progressively during pregnancy, increased further at delivery, but decreased slowly postpartum, not returning to the non-pregnant level within 5 days. Significant correlations were found between the level of IR-CRH and IR-ACTH, IR-CRH and IR-F, and IR-ACTH and IRF in maternal plasma both during pregnancy and after delivery. It is noteworthy that the concentration of IR-CRH in the maternal plasma at delivery was higher in multiple pregnancy than in normal pregnancy, and that the level of IR-CRH in the umbilical cord in uncomplicated cases was much lower than that in the maternal plasma, and was significantly lower than those in the umbilical cord plasma in cases of asphyxia, IUGR or premature delivery. The level of IR-F, not IR-CRH and IR-ACTH, at normal vaginal delivery was significantly higher than that at elective cesarean section. On these results, we investigated the feto-maternal-hypothalamo-pituitary adrenal axis during pregnancy and delivery, in which CRH plays an important role.

Adrenocorticotropic Hormone↗

Evaluation of TSH receptor antibody by 'natural in vivo human assay' in neonates born to mothers with Graves' disease.

Neonatal thyrotoxicosis induced by transferred TSH receptor antibody (TRAb) is the ideal human in-vivo experimental system for the evaluation of TRAb. The clinical significance of circulating TRAb in Graves' disease was evaluated by this 'natural in-vivo human assay'. TRAb activity in vitro was measured by radioreceptor assay (thyrotrophin-binding inhibitor immunoglobulin, TBII) and sensitive cAMP accumulation assay using FRTL-5 cells (thyroid-stimulating antibody, TSAb). Further, the binding-stimulation index (B-S index) was newly introduced, which was the most useful indicator for prediction of neonatal thyrotoxicosis, calculated as the product of TBII and TSAb (Tamaki et al., 1988a). Maternal serum TRAb indices showed highly significant correlations with the serum free T4 index (FT4I) and free T3 index (FT3I) in neonates (5-10 days after birth) born to 20 mothers with Graves' disease who had positive TBII and/or TSAb (FT4I: r = 0.825 for TBII, r = 0.908 for TSAb, r = 0.944 for the B-S index, P less than 0.001; FT3I: r = 0.622 for TBII, P less than 0.01, r = 0.812 for TSAb, r = 0.791 for the B-S index, P less than 0.001; n = 20). In contrast, in 57 untreated adult patients with hyperthyroid Graves' disease, the FT4I and FT3I levels were not correlated with any of the TRAb indices. The linear regression relationship between the B-S index and FT4I found in neonates was applied to values in adult patients with Graves' disease, and the patients were divided into three groups on the basis of the 95% confidence limit: high, normal, and low responders of thyroid hormone (FT4I) secretion to the B-S index. FT4I and the ratio of FT4I to the B-S index were highest and the TRAb indices were lowest in the high responders, while FT4I and the FT4I/B-S index ratio were lowest and the TRAb indices were highest in the low responders. The FT4I/B-S index ratio was inversely correlated with the titres of antithyroid microsomal antibody in all the adult patients with untreated Graves' disease (r = -0.288, P less than 0.05). The results suggest that in-vitro assays using animal thyroid cells and cAMP as an index of response are suitable for detecting circulating thyroid stimulating activity in vivo. Secretion of thyroid hormones in Graves' disease may be regulated not only by circulating thyroid-stimulating antibodies but also by intrathyroidal stimulatory factors or by inhibitory or destructive factors.

Antibodies↗

Plasma concentrations of human atrial natriuretic peptide at vaginal delivery and elective cesarean section.

The change in plasma concentration of atrial natriuretic peptide (hANP) at delivery was examined by measuring the concentrations of hANP in plasma samples from 21 subjects after 36 weeks of normal pregnancy, 22 subjects after normal spontaneous delivery and 20 subjects after elective cesarean section. The maternal plasma concentration of hANP after normal delivery (38.0 +/- 8.2 fmol/ml, mean +/- S.E.M.) was significantly higher than that after 36 weeks of normal pregnancy (16.8 +/- 2.3 fmol/ml), but its concentration after cesarean section was not different from that after 36 weeks of pregnancy. After normal delivery, the plasma concentration of hANP in the umbilical artery (66.9 +/- 11.8 fmol/ml) was also significantly higher than that in the umbilical vein (35.1 +/- 7.3 fmol/ml). In contrast, after elective cesarean section, the hANP levels in the umbilical artery and vein were not significantly different. These results suggest that hANP secretion into the maternal and fetal circulation may be stimulated by the dynamic movement of the mother in labour and the stress of the fetus at delivery, respectively.

Adult↗

Discordant changes in serum anti-TSH receptor antibody and antithyroid microsomal antibody during pregnancy in autoimmune thyroid diseases.

Immunological effect of pregnancy on the level of anti-TSH receptor antibody (TRAb) and antithyroid microsomal antibody (MCAb) was examined serially in twelve patients; ten with active Graves' disease treated with antithyroid drugs for some time during pregnancy, one with previous Graves' disease with stimulating type TRAb, and one with primary atrophic hypothyroidism with blocking type TRAb. TRAb was measured by radioreceptor assay (TSH-binding inhibitor immunoglobulin, TBII) and MCAb was determined by radioimmunoassay. Among the ten patients with active Graves' disease, TBII level decreased as pregnancy progressed in seven but increased during pregnancy in three, whereas MCAb level decreased uniformly during pregnancy in all ten patients. However, possible immunosuppressive effect of antithyroid drugs on these antibody levels could not be completely excluded in these patients. On the other hand, in the two consecutive pregnancies of the patient with previous Graves' disease, TBII level increased "spontaneously" to 10-fold the initial value at 30 weeks during the first pregnancy, while it did not show consistent increase or decrease during the second one. Another patient with primary hypothyroidism showed increase in TBII level during pregnancy to 5-fold the initial value at week 28. In contrast to these TBII changes, MCAb levels and immunoglobulin concentrations decreased consistently during pregnancy in these two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

Changes in concentration of human atrial natriuretic peptide in normal pregnancy and toxaemia.

Changes in concentration of human atrial natriuretic peptide (hANP) in normal and toxaemic pregnancy were examined. The maternal plasma concentration of hANP increased gradually during normal pregnancy to a maximum of 20.0 +/- 2.4 pmol/l (mean +/- S.E.M.) after week 36 of pregnancy. From week 20, the plasma concentrations of hANP were significantly higher than those in non-pregnant women (9.3 +/- 2.0 pmol/l). In toxaemia with hypertension, maternal plasma hANP levels were increased after week 26 of pregnancy (37.7 +/- 6.0 pmol/l) compared with those in normal gravida at the same time (17.1 +/- 1.6 pmol/l). Maternal plasma hANP levels in toxaemia only with oedema were not different from those in normal gravida.

Adult↗

High incidence of respiratory distress syndrome (RDS) in infants born to mothers with placenta previa.

OBJECTIVE: To evaluate the incidence of respiratory distress syndrome (RDS) in infants born to mothers with placenta previa and to assess the risk factors for RDS. METHODS: Ninety-nine pregnant women with placenta previa who delivered by cesarean section at 30-35 weeks of gestation were compared retrospectively with 102 pregnant women matched for week of gestation and birth year, who underwent elective cesarean section. Maternal characteristics, neonatal outcome, and incidence of RDS were analyzed. Umbilical cord blood samples were collected at delivery and were used to determine cortisol, epinephrine, and norepinephrine levels. Student's t-test, the chi-square test, and Fisher's exact test were used for statistical comparisons. P < 0.05 was considered significant. The Mann-Whitney U test was used for comparison of continuous variables. RESULTS: Preeclampsia, histological chorioamnionitis, and premature rupture of membranes were significantly lower in the placenta previa group (placenta previa: 2.0% vs. control: 14.7%, P < 0.01; 14.1% vs. 30.1%, P < 0.01; 7.1% vs. 17.6%, P < 0.05, respectively). The incidence of RDS was significantly higher in the placenta previa group than in the control group (29.3% vs. 6.9%, P < 0.0001). The cortisol level in umbilical cord blood in the placenta previa group was lower than in the control group (median 7.3, range 4.4-14.9 microg/dl vs. median 10.6, range 4.9-30.3 microg/dl, P < 0.05). There were no significant differences in epinephrine or norepinephrine levels between the two groups. CONCLUSIONS: The incidence of RDS in infants delivered at 30-35 weeks' gestation by cesarean section was significantly higher in mothers with placenta previa than in women without placenta previa. This may reflect decreased fetal stress since the cord blood cortisol levels were found to be lower in women with placenta previa.

Cesarean Section↗