Presence of vasoactive intestinal peptide receptor in the hen hypothalamus.

Radioligand assays of the membrane fraction of hen hypothalamic tissues involving the preoptic (HPOA) or median eminence (HMEA) areas revealed the presence of a specific binding component to chicken vasoactive intestinal peptide (cVIP) having properties of a receptor. The equilibrium dissociation constant (Kd) was 0.70 +/- 0.07 nM (Mean +/- SEM; N = 5) in HPOA and 1.02 +/- 0.15 nM (N = 5) in HMEA as estimated by Scatchard analysis of saturation studies, and was 0.91 +/- 0.11 nM (N = 3) (HPOA) and 1.25 +/- 0.09 nM (N = 3) (HMEA) as determined by a kinetic analysis. The maximum binding capacity (Bmax) obtained by Scatchard analysis was 167 +/- 19 fmol/mg protein (N = 5) (HPOA) and 133 +/- 17 fmol/mg protein (N = 5) (HMEA). The Kd and Bmax values obtained by Scatchard analysis were similar in the two areas of the hypothalamus and in both laying and nonlaying hens. Administration of cVIP in vivo caused a decrease in specific cVIP binding. These results suggest the presence of a VIP receptor in the hen hypothalamus.

Effects of removal of chicks from hens on concentrations of prolactin, luteinizing hormone and oestradiol in plasma of brooding Gifujidori hens.

Gifujidori hens were allowed to repeat a breeding cycle in one season. In the first breeding cycle the duration of the brooding (raising chicks) stage was limited to 3 weeks, whereas in the second breeding cycle it was limited to 1 week by removing all chicks from mother hens. In the first breeding cycle, plasma prolactin (PRL) was high during the incubation period, but rapidly decreased on the day of hatching and reached minimum values about 1 week after hatching. In contrast, plasma luteinizing hormone (LH) concentrations were low during the incubation period, but after hatching they gradually increased and reached peak values immediately after removal of chicks. Concentrations of oestradiol in plasma were low in the incubation and brooding stages but increased significantly immediately after removal of chicks. In the second breeding cycle, changes in PRL and LH concentrations were similar to those observed in the first breeding cycle except that even greater increases in plasma LH and oestradiol concentrations were observed one week after hatching when the chicks were removed. These results suggest that coexistence of newly hatched chicks may suppress LH secretion from the pituitary of the hen in the natural breeding cycle.

[Pharmacokinetic and clinical studies of ceftizoxime in the perinatal period. The Chemotherapy Research Group for Mothers and Children].

Pharmacokinetic and clinical studies of ceftizoxime (CZX) in the perinatal period gave the following results: 1. Peak concentrations of CZX in the maternal serum, umbilical cord serum and amniotic fluid in mothers after one intravenous injection of 1 g were, respectively, 70.2 micrograms/ml at 0 hour; 15.7 micrograms/ml at 0.5 hour; and 10-30 micrograms/ml at 3-6 hours. Concentrations of CZX in the neonatal serum were 0.87-13.5 micrograms/ml during 6-14 hours after parturition. The mean concentration of CZX in the milk in 1-8 hours after injection was less than 0.32-0.52 microgram/ml. 2. Good or excellent clinical efficacy was obtained in 28 of the 29 patients with perinatal infections, with an efficacy rate of 96.6%. Prophylactic effectiveness was obtained in 14 of the 15 patients, with an efficacy rate of 93.3%. 3. No side effects were observed in 44 cases. GOT and GPT values increased slightly in 1 patient. No abnormal values in total serum bilirubin or other parameters were found in any neonates after parturition. 4. The above results suggest that CZX is safe and effective for the treatment and prophylaxis of infection in the perinatal period.

The serum pregnancy-specific beta 1-glycoprotein to beta-human chorionic gonadotrophin ratio as an index of prognosis in patients with choriocarcinoma.

The ratio of serum pregnancy-specific beta 1-glycoprotein (SP1) to the beta-subunit of human chorionic gonadotrophin (beta-hCG) before and after chemotherapy was measured in 12 patients with metastatic choriocarcinoma. The ratios before chemotherapy ranged between 0.03 and 0.75, with a mean value of 0.34 (SD 0.21). The ratio increased to over 1.0 (1.05-53.3) after one or two courses of chemotherapy in seven of the 12 patients. These women achieved complete remission. In the other five patients who died of the disease due to drug resistance of the tumour, the ratio after chemotherapy was low (0.04-0.74) and tended to decline. These data suggest that the serum SP1/beta-hCG ratio can be used to predict the prognosis of patients with choriocarcinoma.

Estrogen formation from cholesterol in rabbit preimplantation blastocysts and corpora lutea in vitro.

Rabbit blastocysts and corpora lutea (CL) obtained six days after coitus were incubated with [4-14C]cholesterol. In the CL, the conversion of [4-14C]cholesterol to radioactive progesterone was about twice that to radioactive estrone. On the other hand, in the preimplantation blastocyst, estrone formation from the substrate was far higher than progesterone formation. Both in the blastocyst and CL, [4-14C]cholesterol was least incorporated into estradiol among the steroids identified. It is suggested that steroids biosynthesized in rabbit preimplantation blastocysts and CL are quite different both in quality and in quantity at the time of implantation.

[Pharmacokinetic and clinical studies of cefuzonam in the field of obstetrics and gynecology].

Pharmacokinetic and clinical studies on cefuzonam (CZON) were performed to evaluate its usefulness in the field of obstetrics and gynecology. A summary of the results is as follows: 1. Concentrations of CZON in female genital organ tissues showed a little variance among organs. Mean concentrations were 3.34-7.83 micrograms/g at 40 minutes, 0.523-1.08 micrograms/g at 2 hours 15 minutes and 0.286 micrograms/g (in the myometrium) at 3 hours 10 minutes after the end of drip infusion. 2. Mean concentrations of CZON in the pelvic dead space exudate were 31.0 micrograms/ml immediately after the end of drip infusion (1 hour after the start of infusion), and 37.2 micrograms/ml 1 hour after the end of infusion, then they gradually decreased to 25.6 micrograms/ml after 3 hours and 21.4 micrograms/ml after 5 hours. Mean serum concentrations of CZON in concurrently collected samples from the peripheral vein were 30.0 micrograms/ml immediately after the end of drip infusion, 14.4 micrograms/ml after 1 hour, 4.00 micrograms/ml after 3 hours and 1.84 micrograms/ml after 5 hours. The T 1/2 beta was 1.03 hours. 3. Clinical trial in 7 patients, with CZON administered at a dose level of 1 g at a time, twice daily, showed "excellent" and "good" efficacy in all the patients. No side effects were noted. From the results of the above studies, CZON seems to be highly useful for infections in the field of obstetrics and gynecology.

[Histopathological characteristics of stromal cells in trophoblastic disease].

The histopathological characteristics of stromal cells in trophoblastic diseases remain unknown, though determination of malignancy depends on the existence of stromal elements in villi. Thus, we tried to clarify the characteristics and role of stromal cells in the development of diseases. The mitosis index (MI) of stromal cells and cytotrophoblasts, and the frequency of vessels observed in the stroma were examined. The results were as follows: 1) Complete moles were characterized by high MI values for stromal cells and cytotrophoblasts. They were similar to the ones from normal villi. 2) In partial moles, the MI values for both cells were remarkably low. 3) Invasive moles showed low stromal MI and high cytotrophoblastic MI values. 4) The frequency of blood vessels observed in the stroma was low in complete and invasive moles, though it was high in partial moles. The present results which showed histopathological differences in stromal elements in partial and complete moles, may correspond to the difference in their pathogenesis. And it is possible to assume that the decrease in stromal MI values in invasive mole play an important role in the abnormal proliferation of trophoblasts.

Ovarian blood flow and oxygen transport to the follicle during the preovulatory period.

The mechanism of ovulation, especially the mechanism of follicle rupture, is still uncertain. Ovarian blood flow, ovarian vessel morphology and oxygen transport to follicle were therefore studied during the preovulatory period. Japanese white rabbits, weighing 3.0-4.4 kg, were used as the experimental animal. Ovulation was induced by the administration of PMS (100 iu, IM) and hCG (100 iu, IV). The ovulation was observed at 10-13 h after hCG administration. Continuous measurement of ovarian blood flow was facilitated by the crossed-thermocouple inserted into the unilateral ovary. The variation of ovarian blood flow was expressed as the percentage ratio based on the post-mortem value ( = 0%) and the initial value prior to hCG administration ( = 100%). Histologic changes of ovarian blood vessels were observed at intervals of every 2 hours after hCG administration. Oxygen transport to follicle was compared at 7 and 12 h after hCG administration. The ovarian blood flow increased rapidly within 1 h following hCG administration. High percentage increases were demonstrated during 2 h to 5 h, showing a peak value of 155.3 +/- 12.7% at 3 h. The ovarian blood flow decreased gradually from 5 h to 8 h and then was maintained at about 110% after 8 h. The perifollicular and stromal vasodilatations were confirmed at 2 h and moderate dilatation was observed during 4 h to 6 h. At 10 h, just prior to ovulation, vasodilatation became most remarkable especially at the apical vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of ovarian metastasis in patients with cancer of the uterine cervix.

During the period from 1970 to 1985, 706 patients with cervical cancer of stage 0 and Ia were treated by a simple hysterectomy without oophorectomy. In 326 patients with invasive carcinoma in stage Ib to stage III, who were treated by a radical hysterectomy from 1977 to 1985, histological examinations were performed to detect ovarian metastasis. A total of 674 autopsy specimens were obtained from the Annual of the Pathological Autopsy Cases in Japan. (Japanese Pathological Society, 1965 to 1978). Follow-up observations on stage 0 and stage Ia revealed no recurrence in the ovaries. In invasive cases of epidermoid carcinoma (stage Ib to stage III), no ovarian metastases were detected, despite discovery of metastases to the pelvic lymph node in 21.6% of the cases. Conversely, in the cases of cervical adenocarcinoma (pure adenocarcinoma and mixed carcinoma), 6 of 48 cases (12.5%) showed ovarian metastases. Ovarian metastases were found in 22 of 77 (28.6%) autopsy cases of adenocarcinoma, but in only 104 of 597 (17.4%) cases of epidermoid carcinoma. This finding is statistically significant (P less than 0.02). Both corpus invasion and metastasis to the ovaries were found in 20 of 54 cases (37.0%). This rate was significantly higher than the rate of ovarian metastasis in cases without corpus invasion (P less than 0.001).

Factors associated with clinical reactions to rubella vaccination in women.

Two types of rubella vaccine were given to 272 seronegative healthy Japanese adult women. Clinical and laboratory studies on clinical reaction after vaccination were carried out on HI antibody response, HLA types, basal body temperature (BBT), menstrual cycles and serum progesterone levels of vaccinees. Clinical reactions were not associated with HLA types of vaccinees, but arthropathy occurred significantly more often in women vaccinated at the progestational stage than in women vaccinated at the estrogenic stage.

PIP: 2 types of rubella vaccine were administered to 272 seronegative healthy Japanese adult women. Among 5 Japanese attenuated rubella vaccines, TO-336 vaccine manufactured by Takeda Chemical Industries Limited and MEQ11 vaccine manufactured by the Research Foundation for Microbial Diseases for Osaka University were used. 0.5 ml in volume specified was administered subcutaneously. TO-366 vaccine was administered to 172 women aged 18-30 years and MEQ11 vaccine to 100 women aged 18-26 years. All of the study subjects were asked to record clinical reactions on charts for 30 days after vaccination. Those who had clinical reactions were asked to consult physicians for examination and medical care as soon as possible. Serums for HI antibody test, slightly modified Stewart's method was principally collected from 6-12 weeks after vaccination. HLA typing was done retrospectively in the majority of those vaccinated. Of 172 women administered TO-336 vaccine, 110 were asked to record menstrual cycles for every 3 cycles and basal body temperature (BBT) for 1 month before and after vaccination. No vaccinees were using oral contraceptives (OCs). Of the 110 vaccinees, 87 were unmarried and 23 married. The most popular contraceptive methods were condom, rhythm, BBT, and their combinations. Serum progesterone was radioimmunoassayed at an interval of every 7 days for weeks after vaccination in 88 of 100 vaccinees. Some of the 88 vaccinees were examined for serum progesterone level 1 week before vaccination. TO-336 vaccine produced detectable HI antibodies in all vaccinees (100%); MEQ11 vaccine produced HI antibody response in 97 cases (97.0%). Clinical reactions were observed in 51 vaccinees (29.7%) of those receiving TO-336 but only in 4 (4.0%) of MEQ11 vaccinees. The most frequently observed clinical reaction was joint symptoms, followed by lymphadenopathy. In 41 vaccinees with joint symptoms, 9 also had lymphadenopathy and 3 had a rash. Clinical reactions appeared generally in the 2nd or 3rd week after vaccination. Rash mainly appeared on the face and trunk from 12-22 days after vaccination and lasted for 2-4 days. Lymphadenopathy occurred commonly in the suboccipital and retroauricular lymph nodes from 8-14 days after vaccination and lasted for 2-5 days. The joint symptom was transient mild arthralgia, but a few cases were typical arthritis with swelling, redness, and pain. Clinical reactions were not associated with HLA types of vaccines, but arthropathy occurred significantly more often in women vaccinated at the progestational stage of their menstrual cycle than in women vaccinated at the estrogenic stage.

The propensity to malignancy of dispermic heterozygous moles.

Complete hydatidiform moles may originate from either the fertilization of an empty egg by a haploid sperm followed by duplication (producing a monospermic, homozygous mole) or the fertilization of such an egg by two haploid sperms (producing a dispermic, heterozygous mole). This difference in the mechanism leading to the formation of complete moles raises the question of whether the risk of subsequent malignancy is influenced by the zygosity of the mole. We have compared the incidence of postmolar sequelae in patients with homozygous and heterozygous moles. Using chromosomal heteromorphisms, human lymphocyte antigen (HLA) and phosphoglucuromutase 1 (PGM1) polymorphisms, we established the androgenetic origin of complete mole in 84 of 91 cases. Homozygosity was confirmed in 51 moles, and we found ten heterozygous moles. Five of ten patients with heterozygous moles developed postmolar trophoblastic disease, whereas only two of the 51 patients with homozygous moles had postmolar trophoblastic disease (an additional five patients showed signs of degenerating residual trophoblasts). The XY sex chromosome constitution of the two in vitro choriocarcinoma cell lines examined here provides further evidence of the propensity to malignancy of heterozygous moles.

[MTX resistant mechanisms in human choriocarcinoma cells].

Choriocarcinoma cells grown in the presence of MTX have developed resistance in two ways. The HCCM derived sublines (relatively high MTX resistant) produced enhanced levels of DHFR and had relatively unimpaired transport of MTX, though altered transport was the primary determinant of response in the CC1 derived sublines (low MTX resistant). Since the selection procedure used was identical, it was assumed that altered MTX transport was insufficient to account entirely for various degrees of resistance. Increased DHFR activity was necessary for the development of high MTX resistance. The overproduction of DHFR was the consequence of amplification of the DHFR gene sequence. The incidence of DMs in metaphases paralleled the degree of resistance. Since DMs were also present in the cells not showing DHFR gene amplification, mechanisms other than DHFR gene multiplication were responsible for the de novo synthesis of DMs.

[Effects of ovarian wedge resection (WR) and spironolactone administration on pulsatile LH release and serum steroid hormone levels in women with polycystic ovarian disease].

The exact mechanism(s) by which WR induces ovulation in women with PCOD is still uncertain. The aim of this study is to observe the change in sex steroids and pulsatile LH release (pul-LH-R) after WR. Before and either 7-8 days after the surgery (n = 8) or after 30 days of spironolactone treatment (n = 4), serum LH levels were measured every 15 min for 2-4 hours in PCOD women. Sex steroids were radioimmunoassayed before, and 3-4 and 7-8 days after WR. Testosterone (T) and androstenedione (A) in 7 women in whom spontaneous ovulation occurred after WR decreased significantly either 3-4 or 7-8 days after the surgery (p less than 0.001). Estrone decreased significantly (p less than 0.001) 7-8 days after the operation. The mean level of LH after WR in the 7 women decreased significantly (p less than 0.001). Furthermore, significant decreases both in the mean values of LH pulse amplitude (p less than 0.001) and frequency (p less than 0.01) were observed after WR. Ovulation occurred after 45 and 58 days of spironolactone administration in 2 PCOD women who showed changes in pul-LH-R and a drop in serum testosterone levels after 30 days of treatment. The data suggested that changes in pul-LH-R and decreased sex steroids after WR seemed to play key roles in the mechanism(s) by which WR induces ovulation.

Nonsurgical therapy to preserve oviduct function in patients with tubal pregnancies.

Surgical treatment for tubal pregnancies greatly impairs the subsequent fertility of patients because of salpingectomy and its complicated adhesions. Nonsurgical methotrexate therapy was developed to avoid such complications. Although early detection was of prime importance, resolution of ectopic pregnancy was obtained in 22 patients (95.7%) with methotrexate administration alone. Patency of the oviducts was evaluated with hysterosalpingography and/or laparoscopy in 19 patients after termination of methotrexate treatment. In 10 of 19 patients (52.6%), complete patency of the involved oviduct confirmed the validity of this regimen. Severe side effects were not observed in any of the 23 patients.

[Pharmacokinetic studies on aztreonam in late pregnancy in sheep and humans].

The transplacental passage of single intravenous doses of aztreonam (AZT), 1 g or 2 g, was examined in 7 sheep and 14 women in late pregnancy, respectively and the obtained data were analyzed by a two-compartment model. The obtained results were summarized as follows. After single 2 g intravenous doses were given to pregnant sheep, the mean peak level of AZT in maternal blood was 83.79 micrograms/ml and the half-life of the beta-phase was 1.525 hours. After single 1 g intravenous doses were administered to pregnant women, the mean peak level of AZT in blood was 102.62 micrograms/ml and the half-life of beta-phase was 2.128 hours. The peak levels in umbilical venous blood and amniotic fluid were 14.43 micrograms/ml and 11.86 micrograms/ml, respectively.

[Studies of aztreonam transfer into the fetus and amniotic fluid in early pregnancy].

The materno-fetal transfer of aztreonam by a single intravenous dose of 1 g was examined in 7 volunteer women undergoing induced abortion in early pregnancy and the following results were obtained. After administration of the drug, maternal blood levels at 15, 30, 60 and 120 minutes were 77.24 +/- 6.09 micrograms/ml (Mean +/- S.E.), 37.84 +/- 5.85 micrograms/ml, 25.62 +/- 3.15 micrograms/ml and 18.10 +/- 2.22 micrograms/ml, respectively. Amniotic fluid level of the drug was low in 3 cases, of which amniotic fluid levels were determined; 0.74 microgram/ml after 229 minutes, 0.83 microgram/ml after 280 minutes and 0.74 microgram/ml after 328 minutes. Fetal tissue concentration of the drug was below our detection limit at 120 minutes. Tissue levels of villus and decidua in 6 cases were also too low to be detectable between 89 and 328 minutes after injection.