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Biomedical subjects

M Motoyama

Publications and source records attributed to M Motoyama.

At least 55 records · Page 3Linked to original sources

Arrest of follicular development in a patient with 17 alpha-hydroxylase deficiency: folliculogenesis in association with a lack of estrogen synthesis in the ovaries.

The degree of follicular development was examined in a patient with 17 alpha-hydroxylase deficiency that accounted for impairment of estrogen and androgen biosynthesis. The ovarian content of P was markedly higher than those of any other steroids requiring 17 alpha-hydroxylation for synthesis. The morphologic analysis of the ovaries demonstrated that normal follicles could not develop to more than 2.2 mm in diameter, and most follicles with diameters of 1.0 mm or more yielded to atresia. It is known that estrogen and FSH act synergistically on the growth of the follicles. Our data suggest that the follicles can develop up to the size of 2.2 mm in diameter at most with the sole stimulation of gonadotropin.

Adolescent↗

Reevaluation of immunoreactive gonadotropin-releasing hormone (GnRH) levels in general circulation in women: changes in levels and episodic patterns before, during and after gonadotropin surges.

In order to reevaluate the earlier varying data regarding circulatory gonadotropin-releasing hormone (GnRH), we assayed extracted GnRH from the plasma frequently collected at mid-cycle in 11 women. For the analysis of episodic GnRH patterns and basal levels, blood samples were obtained at 6 h intervals for 72 h and at 15 min intervals for 2 h every 12 h throughout the experimental period. All blood samples were assayed for GnRH and selected samples for LH, FSH, estradiol and progesterone. For GnRH assay, 5 or 6 ml of blood was mixed with 60 mg of ethylenediaminetetraacetic acid, disodium salt, and 3 mg of phenylmethylsulfonyl floride immediately after blood collection. These enzyme inhibitors prevented the destruction of GnRH in the blood at room temperature for at least 4 h. Plasma GnRH was extracted through several steps including florisil absorption, acidic extraction and washing with organic solvent. Nonspecific immunoreactivity in the plasma was markedly decreased through this extraction process. Our assay values (approximate range, 0.1-2.0 pg/ml) of plasma GnRH in normal women corresponded to the low range of those obtained by others who used the alcohol extraction method. The basal levels of GnRH did not change significantly throughout 3 different periods, i.e., before, during and after the LH surges, and fluctuated between a small range of 0.11 and 1.44 pg/ml. Although the peak levels of GnRH observed in its episodic patterns did not change between the periods before and during the LH surges, they decreased significantly after the LH surge compared with those seen during the LH surges (0.93 +/- 0.07 vs 1.17 +/- 0.09 pg/ml, p less than 0.05). The present data demonstrate that immunoreactive GnRH in the extracted peripheral plasma does not change significantly in its mean, basal and peak levels during the periovulatory period except for a minor but significant decrease in the peak levels shortly after an LH surge.

Adult↗

Reduction in pituitary desensitization and prolongation of gonadotropin release by estrogen during continuous administration of gonadotropin-releasing hormone in women: its antagonism by progesterone.

The present study was designed to elucidate gonadal steroid influences on gonadotropin release and subsequent pituitary desensitization to GnRH. Sixteen women, 10 of whom were normal and 6 of whom had hypogonadism, were infused with GnRH at rates ranging from 0.313-10 micrograms/h via an indwelling iv catheter for 66 h. Blood samples obtained throughout the GnRH infusion were analyzed for LH, FSH, estradiol, and progesterone. A prompt and substantial release of gonadotropin occurred in women with ovarian failure or during the luteal phase in normal women compared with that during the follicular phase of the menstrual cycle. Thereafter, a gradual decrease in gonadotropin secretion occurred due to pituitary desensitization, which was slower in the follicular phase than in other groups. A dose-related increase in integrated LH release occurred during GnRH infusion, but this response tapered off with administration of large doses of GnRH to women with ovarian failure or during the luteal phase. In contrast, it increased linearly up to the maximum dose of GnRH in the follicular phase. These data suggest that 1) basal levels of estrogen suppress the early rapid release of gonadotropin in response to GnRH and reduce subsequent pituitary desensitization, resulting in the prolonged release of LH; 2) estrogen widens the range of dose-related increases in gonadotropin in response to GnRH; and 3) these effects of estrogen are antagonized by progesterone.

Adult↗

Biphasic stimulatory effects of estrogen on gonadotropin surges induced by continuous administration of gonadotropin-releasing hormone in women.

The present experiments were performed to study the effects of preovulatory levels of estrogen on GnRH-induced gonadotropin release. Twelve female volunteers in various phases of the menstrual cycle received estradiol infusion for 66 h at a constant rate of 500 micrograms/24 h which is grossly equivalent to its production rate during the preovulatory follicular phase. In 8 of the women, GnRH was administered concomitantly from 6 h after the initiation of estradiol infusion. The administered doses of GnRH were 2.5 and 5 micrograms/h. Blood samples obtained throughout the infusion were analysed for LH, FSH, estradiol and progesterone. The sole administration of estradiol failed to induce the positive feedback effect on gonadotropin release within the experimental period in the early follicular phase (days 3-7) in 4 women. In 5 women treated during the follicular phase, remarkable LH releases were induced after a lag period by the infusion of both GnRH and estradiol. The induced LH surge formed a prolonged biphasic pattern. Although a similar pattern of FSH was observed in some cases, its response was minimal compared with that of LH. In 3 women during the luteal phase, however, a combined administration of estradiol and GnRH induced only a short term release of LH which was terminated in only 12 h. The present data indicate that 1) Preovulatory levels of estrogen affect the late part of the LH surge which is induced by constant administration of low doses of GnRH resulting in a prolonged biphasic release of LH, and 2) These effects of both hormones are not manifest in the presence of high levels of progesterone. These results indicate the possibility of a role of GnRH and estrogen in the mechanism of the prolonged elevation of a gonadotropin surge at mid-cycle.

Adult↗

Follicular development and a single ovulation induced with pulsatile administration of Gn-RH in anovulatory women: studies of hormonal analysis and follicular sonometry.

The method of pulsatile administration of gonadotropin-releasing hormone (Gn-RH) has been proven as a useful means for induction of ovulation in anovulatory women. In our series of clinical trials, 23 out of 29 anovulatory patients ovulated with pulsatile administration of Gn-RH. Seven patients who ovulated volunteered for the present study with daily hormonal analysis and follicular sonometory . Two patients have oligomenorrhea, 3 patients secondary amenorrhea-1st grade (the sole administration of gestagen required for withdrawal bleeding) and the remaining 2 patients secondary amenorrhea-2nd grade (the combined administration of estrogen and gestagen required for withdrawal bleeding). A diagnosis of hyperprolactinemia was made for one patient with secondary amenorrhea-1st grade. Pulsatile administration of Gn-RH was performed by the use of a self-administered infuser . The infuser was connected to an i.v. indwelling catheter via a specially designed blood backflow eliminater . Five micrograms or less of Gn-RH was given every 2 hr from 07:00 to 23:00 hr daily. Five patients received HCG during the preovulatory period. In one patient, a short term treatment of HMG was added to Gn-RH treatment. Follicular sonometry revealed the development of a single dominant follicle which reached between 20 and 28 mm (23.7 +/- 0.12 mm, mean +/- S.E.) in diameter at the preovulatory period. Disappearance of a dominant follicle was recognized in the early luteal phase. Characteristic increases in estradiol were recognized concomitantly with the development of a dominant follicle. Progesterone levels after ovulation were within the limits of its normal "luteal phase" rise. The present data suggest that pulsatile administration of low dose Gn-RH with nocturnal interruption of treatment is effective for normal progress of follicular development in various types of anovulatory patients, culminating in single ovulation. This paper includes the discussion on our method which may be responsible for a high success rate of ovulation induction.

Adult↗

[Ophthalmic use of clindamycin-2-phosphate (author's transl)].

Bacterial and clinical experiments for ophthalmic use of clindamycin-2-phosphate (CLDM-2-P) were performed and the results were summarized as follows. 1. The distribution of sensitivity for 100 strains of Staphylococcus aureus isolated in 1975 was in the range of less than or equal to 0.19 approximately greater than or equal to 100 mug/ml, and majority of them (96.0%) were in less than or equal to 0.39 mug/ml. 2. The serum concentration by intramuscular injection of 300 mg and 600 mg CLDM-2-P in a single dose respecitvely reached the peak level after 2 hours and decreased gradually until 12 hours in both of them. 3. Ocular penetrations were examined in rabbit eyes. (1) After instillation of 1% CLDM-2-P solution, the aqueous level reached the highest after 1 hour and measurable after 6 hours. (2) After subconjunctival injection of 5 mg/0.5 ml CLDM-2-P, the aqueous level reached the highest after 2 hours and decreased until 6 hours. (3) After intramuscular injection of 100 mg/kg, the aqueous concentration was recognized from 1 to 8 hours, and peak was reached after 1 hour. 1 to 8 hours, and peak was reached after 1 hour. Aqueous-serum ratio in 1 hour was 37.13%. The ocular tissue concentrations at 2 hours showed relatively high levels in both of outer and inner parts of the eye. 4. The intramuscular injection of CLDM-2-P, 300 approximately 1800 mg daily, against suppurative ocular infections revealed excellent effects on cases of external hordeolum, acute chalazion, lid abscess, orbital phlegmone, corneal infiltration, corneal ulcer, and iridocyclitis purulenta. 5. Side effects: Two cases out of 22 cases complained of diarrhoea and bitter taste after injection, and able to be treated continuously by the drug. No abnormal findings in hepatic and renal tests were observed and no servere side effects like allergic reactions were recognized.

Abscess↗