Human ovarian aging and mitochondrial DNA deletion.

The functions of human ovary change dynamically around the menopausal period. A decrease of the number of primordial follicles and an increase of fibrous tissues are observed histologically in the aged ovary. As endocrinological aspects at menopause, the synthesis and secretion of ovarian steroid hormones such as estrogens and progesterone decrease, followed with the resultant increases of pituitary gonadotropins.

Randomised study of immunotherapy with OK-432 in uterine cervical carcinoma.

OK-432, a streptococcal preparation, was administered to patients with stage Ib and II cervical carcinoma except for adeno- and adenosquamous carcinomas. To evaluate the efficacy of OK-432 precisely, 177 patients were stratified by clinical stage, radiotherapy, and lymph node metastasis after complete radical hysterectomy and pelvic lymphadenectomy. Within each stratum, patients were divided randomly into OK-432 and control groups.

Source of prolactin in human follicular fluid.

To analyze whether prolactin (PRL) in human follicular fluid (FF) is synthesized locally or derived from the circulation, PRL concentrations of plasma and FF were determined in the patients after ovarian stimulations. The amounts of PRL messenger ribonucleic acid (mRNA) in the follicular tissues during different menstrual phases were also determined. The FF PRL concentration was correlated positively with plasma PRL and highest estradiol levels during the stimulatory cycle.

Gonadotropin induces expression of c-fos and c-jun genes in rat ovaries.

It has been shown that the expression of protooncogenes, c-fos and c-jun, induced by growth factors and hormones plays important roles in cellular proliferation, tissue differentiation and transcription of certain genes. Since gonadotropin stimulates ovarian steroidogenesis and cellular proliferation, we investigated whether gonadotropin affects the expression of c-fos and c-jun genes in rat ovaries. The expression of mRNA coding side chain cleavage enzyme (P450scc), the rate limiting enzyme in ovarian steroidogenesis was also studied.

[Effect of chemotherapy on the prognosis of ovarian cancer].

Through the collaboration of 22 institutions nationwide, a total of 1,185 cases of ovarian cancer treated between January, 1980 and December, 1987, were investigated as to their prognosis from the aspect of the chemotherapeutic effect. (1) An excellent effect of the remission-induction chemotherapy was observed in a group receiving combination therapy with CDDP as the main ingredient. In particular a significant effect was seen in stages III and IV.

Relationship between the changes in placental blood flow resistance assessed by Doppler technique and maternal serum placental aminopeptidases, which degrade vaso-active peptides, in pre-eclampsia.

Our study showed that there were statistically significant correlations between the systolic and diastolic ratio (S/D) of maternal uterine or umbilical artery and the levels of maternal serum aminopeptidase activities in pre-eclampsia. Kininase I was positively correlated with the S/D ratios, whereas placental leucine aminopeptidase (P-LAP) and aminopeptidase A were negatively correlated with the S/D ratios. It is known that the increased S/D ratios reflect the increased utero-placental blood flow resistance.

[A group study on prognosis of ovarian cancer in Japan].

An assessment has been made, with the cooperation of 22 institutes, of 1,185 cases of ovarian cancer as subjects who were treated in the period from January, 1980, to December, 1987. As a result, (1) As for distribution by clinical staging at the initial examination, the cases in Stage III were the most numerous, followed by those in Stage I, and if classified according to the histological type, serous cystadenocarcinoma was the most frequently observed in Stage III, and undifferentiated and unclassified carcinomata were observed in Stages III and IV. (2) In the examination of prognostic factors, it was confirmed that the clinical stage, histological type and diameter of the remaining tumor after the initial operation were important factors.

Degradation of oxytocin by the human placenta: effect of selective inhibitors.

The hydrolysis of oxytocin by human placental subcellular fractions was studied in the presence of selective inhibitors by measuring liberated amino acids by high performance liquid chromatography (HPLC). Oxytocin degradation by microsomal and lysosomal fractions was inhibited by bestatin, amastatin and puromycin. The IC50 values of these inhibitors on oxytocin degradation by both fractions were similar to those of these inhibitors on the human placental aminopeptidase M measured by L-Leu-p-nitroanilide as a substrate (LAP activity), which we reported previously.

The effect of nifedipine and dipyridamole on the Doppler blood flow waveforms of umbilical and uterine arteries in hypertensive pregnant women.

In a study of 45 hypertensive pregnant women, the systolic velocity/diastolic velocity ratio and pulsatility index of the umbilical and uterine arteries showed good correlation with the maternal blood pressure, and they appeared to provide a good parameter for the fetoplacental condition. Using the pulse Doppler method, we studied the effects of the antihypertensive agent nifedipine and of dipyridamole (an agent used to treat proteinuria) on the blood flow of the umbilical and uterine arteries in 16 hypertensive pregnant women. The results proved that both drugs caused a decrease in the vascular resistance of the umbilical artery and suggested that they increased the blood flow volume of this artery and were useful in the treatment of hypertension during pregnancy.

Inhibitory effect of bestatin on the growth of human lymphocytes.

Bestatin at mid to high concentration had inhibitory effect to [3H]thymidine incorporation of human lymphocytes. It also decreased the PHA-P, Con A and PWM-induced mitogenicity of human lymphocytes. On the contrary, bestatin had growth stimulatory effect to murine lymphocytes, and enhanced the Con A, LPS-induced mitogenicity of murine lymphocytes.

Menotropin stimulation after prolonged gonadotropin releasing hormone agonist pretreatment for in vitro fertilization in patients with endometriosis.

Two protocols were scheduled for in vitro fertilization and embryo transfer (IVF-ET) in patients with various stages of endometriosis who were resistant to conventional therapies. In the ultralong protocol (21 patients), gonadotropin releasing hormone agonist (Gn-RHa) was administered for at least 60 days prior to ovarian stimulation along with menotropin until human chorionic gonadotropin was injected. In the long protocol (11 patients), Gn-RHa was started at the midluteal phase and exogenous gonadotropin was commenced between the third and the seventh day of the menstrual cycle after pituitary suppression.

Induction by cortisol of aminopeptidases production from the human placenta in tissue culture.

Human placental aminopeptidase M and A and post-proline endopeptidase are known to act as degrading enzymes of bioactive peptides such as angiotensin II, oxytocin and endogenous opioids. We tested the effects of cortisol on the activities of human placental aminopeptidase A and M and post-proline endopeptidase using short-cultured placental tissues. From 34.

Identification of human placental leucine aminopeptidase as oxytocinase.

Human placental leucine aminopeptidase (P-LAP) was purified from retroplacental serum for the first time by serial chromatography on columns of Matrex Blue A, DEAE-Sepharose CL-6B, phenyl-Sepharose 4B, chelating-Sepharose, and Sepharose CL-6B. The purified P-LAP was apparently homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the apparent molecular weight (Mr) was estimated to be 210,000. By comparing P-LAP activity with cystine aminopeptidase activity, we concluded that both activities were shared by the same molecule.

Transvaginal Doppler ultrasound with color flow imaging in the diagnosis of ovarian cancer.

Transvaginal Doppler ultrasound with color flow imaging is a new technique for the evaluation of gynecologic diseases. This method was used for the diagnosis of ovarian tumors in 24 women treated in the Department of Obstetrics and Gynecology, Nagoya University Hospital, Japan. Waveforms of the parenchymal tumor arteries or tumor surface arteries were compared using values of the pulsatility index (PI).

[Diagnosis of ovarian tumors by transvaginal Doppler ultrasound with color flow imaging].

Ovarian carcinoma is a silent disease with few symptoms. Early detection of ovarian cancer is difficult. Transvaginal Doppler ultrasound with color flow imaging is a new technique in the evaluation of gynecological diseases.

Clinical effect of sizofiran combined with irradiation in cervical cancer patients: a randomized controlled study. Cooperative Study Group on SPG for Gynecological Cancer.

To evaluate the clinical effect of a biological response modifier (BRM), sizofiran (SPG), combined with irradiation, a randomized controlled study was performed in patients with stage II or III cervical cancer involving the collaboration of 52 institutes throughout Japan. Patients were randomly allocated to the control group (radiotherapy only) and the SPG group (radiotherapy + SPG). SPG was given intramuscularly, 40 mg once and 20 mg twice, a week concomitantly with radiotherapy.

[A case of subacute sclerosing panencephalitis developing 8 years after immunosuppressive treatment for acute lymphocytic leukemia].

A 13-year-old girl developed subacute sclerosing panencephalitis (SSPE) with atypical absence attacks as an initial symptom. Eight years earlier she had been treated for acute lymphocytic leukemia with cytotoxic treatment and radiotherapy, which had resulted in complete remission. She was first treated with an anticonvulsant because the atypical absence attacks and the presence of epileptic discharges on an EEG suggested epilepsy.

Rapid determination of fetal sex using amniotic fluid cells and the polymerase chain reaction.

We determined the sex of 50 fetuses by an amplification of the Y-chromosome specific fragment using the polymerase chain reaction (PCR). Amniotic fluid cells were collected by amniocentesis from pregnant women at 14 to 17 weeks of gestation. Total DNA was purified from cells in 1 ml of amniotic fluid.

Prophylactic effect of bestatin on the onset of invasive mole--clinical and fundamental studies.

This study was performed to determine whether bestatin (Ubenimex) has clinical prophylactic effects on the onset of invasive mole and a direct inhibitory effect on the growth of hydatidiform molar cells. A total of 49 patients with hydatidiform mole treated at Nagoya University Hospital from 1984 to 1990 were randomly divided into two groups, a bestatin administered-group and a bestatin non-administered group. Patients in the bestatin group were given 30 mg of bestatin orally and daily for three months just after their molar deliveries.

Further evaluation of the pregnancy-linked down-regulation of the paternal antigen-specific splenic cytotoxic T lymphocyte activity in allogeneically pregnant mice.

Cytotoxic T lymphocyte (CTL) activity directed against paternal alloantigen was examined in allogeneically pregnant mice using various allogeneic combinations. The spleen cells from pregnant C57BL/6 (H-2b) mice mated with BALB/c (H-2d) male mice generated less anti-H-2d CTL after in vitro sensitization than those from unpregnant or syngeneically mated C57BL/6 mice. Different allogeneic combinations including the incompatibility at only D region of H-2 or minor histocompatibility loci were effective for downregulating the anti-paternal CTL activity in pregnancy.