Masao Maeyama

Effect of calcium supplementation on the vascular sensitivity to angiotensin II in pregnant women

Pregnant women destined to develop pregnancy-induced hypertension lose refractoriness to the pressor effects of infused angiotensin II. The effect of calcium supplementation on the vascular sensitivity to angiotensin II was investigated in pregnant women. We administered orally 600 mg of calcium L-aspartate daily to 22 pregnant women from 20 weeks of gestation to delivery. The values for the effective pressor dose of angiotensin II in the calcium-supplemented women were compared with those in 72 nonsupplemented pregnant women. The vascular sensitivity was significantly decreased after calcium supplementation. The values for the effective pressor dose of angiotensin II in the calcium-supplemented patients were 18.1 +/- 1.2 ng/kg/min at 20 weeks of gestation, 32.2 +/- 2.6 ng/kg/min at the twenty-sixth week, 41.1 +/- 3.4 ng/kg/min at the thirtieth week, and 25.9 +/- 2.9 ng/kg/min at the thirty-sixth week (mean +/- SEM), while those in the nonsupplemented patients were 17.3 +/- 1.2, 17.7 +/- 1.6, 17.6 +/- 1.2, and 15.0 +/- 1.6 ng/kg/min, respectively. Assessment of the changes in the effective pressor dose of angiotensin II in the individual patients indicated that the percentile changes from 20 weeks of gestation in the calcium-supplemented patients were also significantly greater than those in 22 nonsupplemented patients. These findings suggest that calcium supplementation tends to reduce the vascular sensitivity in pregnancy. The present dosage of calcium did not affect the blood chemical parameters and did not reduce the blood pressure. The incidence of pregnancy-induced hypertension in the calcium-supplemented patients was 4.5%, which was smaller than that (21.2%) in the nonsupplemented patients. Although there is no clear explanation of the mechanisms involved in such an effect of calcium, the present results do provide evidence to support the idea that oral calcium intake can prevent the onset of pregnancy-induced hypertension.

Purification and characterization of myosin light-chain kinase from porcine myometrium and its phosphorylation and modulation by cyclic amp-dependent protein kinase

Myosin light-chain kinase was purified from porcine myometrium to apparent homogeneity at about 262-fold with an Mr of 130 000 as determined by SDS-polyacrylamide gel electrophoresis and a sedimentation coefficient of 4.5 S. The approximate content of the soluble myosin light-chain kinase was estimated to be about 0.85 microM. The purified enzyme exhibited strict substrate specificity only for 20-kDa myosin light chain and Ka values of 0.6 nM and 0.3 microM for calmodulin and Ca2+, respectively. The enzyme was phosphorylated by the catalytic subunit of cyclic AMP-dependent protein kinase, which resulted in a decrease in the affinity for calmodulin of 4-7-fold without effect on the Vmax. The maximal amount of phosphate incorporated into the enzyme was 0.5-0.8 and 1.0-1.4 mol per mol of the enzyme in the presence and absence of Ca2+ and calmodulin, respectively. In the presence of a subsaturating concentration of calmodulin, the enzyme showed a lower sensitivity for Ca2+ by phosphorylation.

Tamoxifen in the treatment of infertility associated with luteal phase deficiency

A group of 17 patients with suspected luteal phase deficiency was treated with tamoxifen. Tamoxifen therapy was found to lengthen the luteal phase in all patients and resulted in pregnancy in 6 of 17 patients. The integrated luteal phase progesterone (P) concentration in the nontreatment cycle of seven patients was significantly lower (P less than 0.01) than that of five normal women. Therapy with tamoxifen increased the P concentration to 186.0 +/- 24.4 ng/ml/cycle (mean +/- standard error of the mean), i.e., twice that of the control cycle. The mean estradiol (E2) concentration at the midcycle peak was about twice that observed during the nontreatment cycle. The glycogen content of the endometrial tissue at the midluteal phase in the tamoxifen cycle was significantly higher (P less than 0.025) than that of endometrial tissue in the nontreatment cycle, indicating improvement of the endometrial function.

Calmodulin and Ca2+- and Calmodulin-Dependent Protein Kinase in Rat Anterior Pituitary Gland

Calmodulin and Ca2+‐ and calmodulin‐dependent protein kinase were identified in the rat anterior pituitary gland. The concentration of calmodulin was 1.18 ± 0.11 μg/mg protein (n = 7) in the cytosol fraction. The calmodulin of the anterior pituitary gland co‐migrated with brain calmodulin on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The Ka value of the partially purified enzyme for Ca2+ was 3.3 μ.M in the presence of 0.30μ.M calmodulin. Trifluoperazine and chlorpromazine, calmodulin‐interacting agents, inhibited enzyme activity, with Ki values of 1.3 and 2.6 x 10‐5M, respectively. The enzyme was resolved into two peaks of activity, with sedimentation coefficients of 5.5 S and 16.5 S, by sucrose density gradient centrifugation. At least nine proteins were phosphorylated by the enzyme in a Ca2+‐ and calmodulin‐dependent manner. In light of these results, the possibility that calmodulin and the calmodulin‐activatable protein kinase system are involved in the mediation of the Ca2+ effect on hormone release from the anterior pituitary gland must be given consideration.

Treatment with danazol of ureteral obstruction caused by endometriosis.

Abstract. A case of unilateral ureteral obstruction in extensive endometriosis in a 21‐year‐old patient is reported. The present patient received danazol therapy following conservative surgery, and restoration of the renal function was achieved 5 months after initiation of the danazol administration.

Small cell carcinoma of the endometrium associated with adenosquamous carcinoma: A light and electron microscopic study

This report describes a 64-year-old woman with a primary small cell carcinoma of the endometrium associated with adenosquamous carcinoma. The light microscopic features resembled those of small cell carcinoma of the lung and those of the uterine cervix, and foci of adenosquamous carcinoma lay scattered sparsely in the small cell carcinoma. Electron microscopy revealed cytoplasmic neurosecretory type granules. The neoplasm behaved in a very aggressive manner such that at 3 months after surgery a metastatic neoplasm appeared in the vagina. This case is a rare example of an endometrial carcinoma with differentiation toward endocrine as well as adeno and squamous cell carcinoma.

Cell-Mediated Immunity in Human Pregnancy

The function of thymus‐dependent lymphocytes (T lymphocytes) was studied in women during pregnancy and labor and postpartum by evaluating the blastogenesis of peripheral lymphocytes, which were stimulated with phytohemagglutinin‐P (PHA‐P) in both whole‐blood semimicroculture and purified lymphocyte culture. Data from 353 random samples (203 women) and 50 serial specimens from 10 women revealed that PHA‐P induced‐lymphocyte blastogenesis was significantly (p<0.005) reduced during pregnancy and labor but rapidly returned to normal several days after artificial termination in the early stage of pregnancy as well as after full‐term delivery. These results indicate that the T‐lymphocyte function in maternal peripheral blood is depressed by causes related to pregnancy. It seems very likely that depressed T‐lymphocyte function during pregnancy is caused by inhibitory factors in the blood plasma derived from the feto‐placental unit. Questions relating to the inhibitory factors in maternal plasma are discussed.

Uterine papillary serous carcinoma with high levels of serum carcinoembryonic antigen. Response to combination chemotherapy

A case of metastatic uterine papillary carcinoma with elevated serum carcinoembryonic antigen (CEA) is reported. The patient presented with ascites and pleural effusions and with a high level of CEA (258 ng/ml) 3 months after primary surgical resection and postoperative irradiation had been performed. Her complete response, although temporary, to two kinds of combination chemotherapy was evaluated using serial estimations of the serum CEA.

A graduated regimen of clomiphene citrate: its correlation to glycogen content of the endometrium and serum levels of estradiol and progesterone in infertile patients at the midluteal phase

The glycogen content, glycogen synthetase level, and glycogen phosphorylase level were studied in endometrial samples obtained from 14 infertile patients during the midluteal phase before and after clomiphene citrate (Clomid, Shionogi & Company, Ltd., Osaka, Japan) treatment, simultaneously with measurement of the serum concentrations of estradiol and progesterone. Increase in the endometrial glycogen content in the clomiphene cycle was accompanied by a corresponding increase of the dosage of clomiphene. Also, the midluteal concentrations of estradiol and progesterone in the clomiphene cycle were significantly higher (P less than 0.005 and P less than 0.005, respectively) than those in the nontreatment cycle. Clomiphene therapy at 50 mg/day resulted in pregnancy in three of ten patients, while clomiphene at 100 mg/day resulted in pregnancy in three of six patients. These results suggest a fair correlation between the dosage of clomiphene and the improvement of endometrial function in infertile patients following stimulated ovarian steroidogenesis.

Action of tamoxifen on folliculogenesis in the menstrual cycle of infertile patients

Daily estimations of follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, and progesterone were made in the serum of eight infertile patients from day 1 through the follicular phase during menstrual cycles before and after tamoxifen therapy. Tamoxifen therapy was found to shorten the follicular phase from 15.4 +/- 0.8 days (mean +/- standard error of the mean) to 14.0 +/- 0.6 days (difference not significant) and to lengthen the luteal phase from 12.8 +/- 0.4 days to 14.1 +/- 0.8 days (P less than 0.05). The mean estradiol concentration in the eight patients during tamoxifen treatment cycles rose on day 8 (3 days after starting tamoxifen treatment) and increased significantly (P less than 0.05) from day 10 to midcycle. The integrated follicular phase estradiol concentration in the tamoxifen treatment cycle increased to 2450.1 +/- 208.1 pg/ml/cycle, and was significantly higher (P less than 0.025) than that in the nontreatment cycle. In contrast, the concentrations of follicle-stimulating hormone, luteinizing hormone, and prolactin during the follicular phase and at the midcycle peak of tamoxifen treatment cycles were not significantly different from those of the nontreatment cycle. These results suggest that the mechanism of tamoxifen in improving folliculogenesis may involve a direct action on the ovary without intervention of the hypothalamic-pituitary system.