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Biomedical subjects

S Tojo

Publications and source records attributed to S Tojo.

At least 91 records · Page 5Linked to original sources

Ultrastructural study of minute uterine leiomyomas.

Minute uterine leiomyomas, less than 3 mm in diameter, were studied by electron microscopy. In five of 15 cases, morphologically different types of smooth muscle cell were identified. In the central region of leiomyomas, most myoma cells were characterized by filaments sporadically located in the cytoplasm and well-developed organelles. These cells were interpreted as immature smooth muscle cells. In the outer layer of nodules, the cells were a more mature form of smooth muscle cell and resembled normal myometrial cells. The differences suggest that differentiation of the smooth muscle cells occurs early in the growth of uterine leiomyoma.

Adult↗

Plasminogen activator in rat ovary during the ovulatory process: independence of prostaglandin mediation.

To elucidate the possible roles of increased plasminogen activator (PA) in follicular rupture and to investigate whether prostaglandins participate in ovarian PA synthesis in vivo, enzyme activities were sequentially measured by a method using the chromogenic substrate S-2251 in immature rat ovaries primed with pregnant mare serum gonadotrophin (PMSG) followed by human chorionic gonadotrophin (hCG) either alone or with a concurrent injection of indomethacin. Before hCG injection PA activity was 0.006 +/- 0.006 (S.D.) mumol/1.6 mg ovarian tissue (wet wt) per 30 min: PA activity of a saline-treated group remained at low levels (less than 0.018 +/- 0.003 mumol/l X 6 mg tissue per 30 min). In contrast, PA activity of animals given hCG alone increased after the treatment, reaching a peak value of 0.112 +/- 0.071 mumol/l X 6 mg tissue per 30 min 12h later, before decreasing to 0.023 +/- 0.014 mumol/l X 6 mg tissue per 30 min at 32 h. Contrary to expectations, a dose of indomethacin which completely blocked ovulation had no effect on either the magnitude or the time-course of PA synthesis after hCG administration (P greater than 0.05). These results indicate that prostaglandins are not involved in the preovulatory synthesis of PA induced by hCG in rat ovaries and that PA is not a primary proteolytic enzyme for follicular rupture. It is suggested that PA has possible roles in cumulus detachment and/or proliferation of granulosa cells during the ovulatory process.

Animals↗

Discordant pregnancy tests in detection of alpha-subunit--producing tumors.

Ectopic production of isolated alpha-subunit of glycoprotein hormones was detected in a 32-year-old Japanese woman with metastatic lung tumor by a discordance in the immunologic pregnancy tests for native human chorionic gonadotropin (hCG) assays. Quantitative discrepancy of titrations among different types of pregnancy tests, ie, competitive (hemagglutination or latexagglutination inhibition) and noncompetitive (hemagglutination or latexagglutination) reactions, was also confirmed experimentally using a highly purified ectopic alpha-subunit from the patient's urine. Thus the discrepancy between the 2 types of assay systems was due, at least partly, to a cross-reaction of high concentrations (20,000 ng/ml) of ectopically secreted free alpha-subunit of glycoprotein hormones.

Adult↗

[Tumor markers in gynecologic malignancies].

Human chorionic gonadotropin (hCG) is widely used as a tumor specific index substance for the trophoblastic disease. The radioimmunoassay (RIA) of the C-terminal peptide of hCG-beta subunit can detect hCG up to the level of 0.5 IU/day in urine or 0.5mIU/ml in serum without cross-reactivity with luteinizing hormone. Therefore, this RIA would be used as a hCG-specific assay method in order to ensure the disease is in complete remission and to detect early recurrence. Alpha-fetoprotein and lactic dehydrogenase can be used as a sensitive tumor marker for embryonal carcinoma and dysgerminoma respectively. Carcinoembryonic antigen may serve as a valuable aid in monitoring the response to the therapy of the patient with ovarian or cervical carcinoma, but may not be useful for early detection of these diseases.

Carcinoembryonic Antigen↗

[Morphological and endocrinological study of theca cell tumor during pregnancy].

With a theca cell tumor of the ovary associated with pregnancy, an extremely rare occurrence in a 30 years old primigravida at 15 weeks of gestation, morphological and endocrinological studies were performed. The tumor was composed of cell-nests scattered among a fibromatous structure. The round or polygonal cells are rich in eosinophilic cytoplasm, resembling theca internal cells. The histochemical activity of 3 beta-HSD and G-6-PDH was demonstrated in these cells. They had the ultrastructures characteristic for steroid-producing cells, in some of which immature and mature Reinke crystalloid-like structures were identified. Mature ones were infrequently observed in contrast to the numerous immature ones. It is considered that a few cells might have differentiated into Leydig cells in the course of differentiation into thecomatous cells from ovarian stroma or mesenchyme. Judged from the rapid enlargement in early pregnancy, this tumor may depend on hCG. Serum estradiol was decreased immediately after removal of the tumor even at 15 weeks of gestation. Histochemical, ultrastructural and endocrinological findings suggest that the tumor was secreting mainly estradiol at the time of the operation.

3-Hydroxysteroid Dehydrogenases↗

Regulation of biosynthesis of guanidinosuccinic acid in isolated rat hepatocytes and in vivo.

To clarify the metabolic pathway of guanidinosuccinic acid (GSA), we investigated the relationship between GSA synthesis and the urea cycle. In isolated rat hepatocytes, GSA formation increased as urea concentration was raised; the effect of urea was not modified by the addition of ammonium chloride. Other urea cycle intermediates, including arginine and cyanate, a degradation product of urea, failed to stimulate GSA synthesis. Ornithine and arginine, which stimulate urea synthesis, strongly inhibited urea-stimulated GSA synthesis in the presence of 10 mM ammonium chloride, but the inhibitory effect of ornithine was not observed when ammonium chloride was not present. Citrulline (5 mM) strongly inhibited urea-stimulated GSA synthesis with or without ammonium chloride. D,L-norvaline, which inhibits urea cycle enzymes, strongly inhibited GSA synthesis. Following urea injection, hepatic GSA levels also increased in vivo, but there was little change in hepatic arginine. However, the addition of ornithine or D,L-norvaline inhibited the production of hepatic GSA, although arginine was increased substantially. These results indicate that GSA synthesis occurs in rat hepatocytes and is stimulated by urea. The data also suggest that the urea cycle enzymes catalyze some of the biochemical reactions in the GSA synthetic pathway.

Amino Acids↗

Effective extraction and radioimmunoassay of chorionic gonadotropin in human urine.

A single-step procedure for extracting and concentrating hCG from 24hr urine samples was developed. The procedure involves the adsorption chromatography with Vitachange (Permutit). Its hCG recovery was improved to be more than 90% compared with about 50% of a standard kaolin-acetone method. Nonspecific urinary protein concentration in extracts was also reduced. Thus, partial purification and concentration of urinary hCG by this procedure with subsequent RIA using antisera against the unique carboxyl-terminal peptide of hCG beta subunit provides a sensitive and specific method for detecting hCG in urine. In urine samples obtained from normal persons, the upper limit of hCG-immunoreactivity detected by this new system was 1.1 IU/24hr. However, 93% of subjects gave values lower than 0.5 IU/24hr. The urinary hCG level of lower than 1.1 IU/24hr may be designated as normal. This new assay system now provides reliable potentiality in the strict management of patients who are undergoing treatment for gestational trophoblastic neoplasia.

Chorionic Gonadotropin↗

[The influence of bromocriptine-induced pregnancy and delivery on infertile cases with pituitary microadenoma].

Two consecutive pregnancies were induced in three hyperprolactinemic primary infertile patients bearing intrasellar microadenoma without visual disturbance. Pretreatment prolactin levels, 224 -496ng/ml, were normalized by 10-22.5mg/day of bromocriptine and the initial conceptions occurred. No abnormal sign due to pituitary enlargement was detected throughout the period of gestation and they delivered single full-term babies. Since no significant change was observed in puerperium, it was decided to give the second bromocriptine therapy. The prolactin levels, 80-190ng/ml, measured before the second therapy were apparently lower than those seen prior to the first therapy and the minimum effective dose used to induce the second pregnancy (5-7.5mg/day) was identical to 1/3-1/2 of the first one. The course of the second pregnancy of each case was also uneventful and the babies were all normal and mature. The magnitude of the rise in the prolactin level during the second pregnancy was smaller than that observed during the first pregnancy. The present longitudinal study throughout two consecutive pregnancies in three cases indicates that resolution of prolactinoma was resulted in some extent after withdrawal of stimulative factors associated with pregnancy. Hence, hyperprolactinemic infertile cases with intrasellar microadenoma can be subjected to bromocriptine therapies inducing consecutive pregnancies under intensive follow-up.

Adenoma↗

Ultrasonographic observation of ovarian follicular development via vaginal route.

Ovarian follicular growth during periovulatory period was measured using real-time ultrasound via vaginal route. In 15 patients examined preliminarily by the abdominal procedure, the mean follicular diameter increased from 15.6mm on four days before ovulation to a maximum of 21.8mm on the day of ovulation. A clear distinction of follicular development during periovulatory period could be made in 40 patients by the vaginal procedure. The mean distance between follicle and scanner was 5.6cm in the vaginal observation, which was significantly shorter than those observed in the abdominal observation. Thus, real-time ultrasound examination via vaginal route appears to be a useful technique for assessing the ovarian follicular development.

Adult↗

[Visual and neurological disturbances accompanying with pregnancies of hyperprolactinemic patients].

Twenty-three hyperprolactinemic infertile cases become pregnant after surgical treatment and/or bromocriptine administration, and 18 of them accomplished normal full-term deliveries. Serial ophthalmological examination which had been performed monthly throughout pregnancy revealed that four cases bearing pituitary adenomas developed visual disturbances which manifested themselves in the latter part of gestational period. The objective signs detected in these cases were bitemporal hemianopsia, temporal and nasal visual defects and the disappearance of central isopter. Another patient with microadenoma complained of headache at 16 weeks of gestation and it became more severe as gestation progressed. Bromocriptine (1.25 mg/day) was effective in diminishing this symptom. Although all these cases recovered from visual disturbances and headache after delivery, two of them were operated on transsphenoidally when radiological evidence of pituitary enlargement was found in the postpartum period. It is generally accepted that nearly 20% of hyperprolactinemic patients have pituitary adenomas. In view of the limited accuracy of techniques used in diagnosing pituitary tumor, it is legitimate to postulate that most hyperprolactinemic infertile patients have microadenoma to some extent. For this reason, a detailed follow up of visual field and neurological signs throughout pregnancy of hyperprolactinemic patients is important in early detection of changes in pituitary size.

Adenoma↗

[Studies on the secretion of human placental lactogen from human trophoblastic tissues (author's transl)].

In order to study the secretory mechanism of human placental lactogen (hPL:hCS) from trophoblastic tissues, tissue culture and new placental perifusion systems were developed and used to clarify the effect of various substances on the secretion of hPL. These substances were (1), metal ions([Ca2+], [K+], [mg2+], [Na+]); (2) growth hormone and prolactin releasing or inhibiting factors (arginine, TRH, somatostatin, dopamine); (3) LH-RH, dibutyryl cyclic-AMP which stimulates hCG secretion; (4) prostaglandins F2 alpha and E2, bradykinin; (5) EGF and insulin which have the receptors in the placenta; (6) glucose. It was found that most of the substances examined had no effect on the secretion of hPL, except dopamine and glucose. The effect of dopamine in the tissue culture system is dose-dependent. At high concentrations dopamine slightly inhibited hPL secretion(5mM: 38.6 +/- 15.0 and 10mM; 35.7 +/- 19.0 micrograms/g wet tissue) compared with the control (63.2 +/- 29.8 microgram/g wet tissue). However, these effects may be due to the deviation of pH in the medium from the direct addition of dopamine hydrochloride. At a low concentration(1mM) it was observed to have a rather stimulatory effect (125.7 +/- 18.0 micrograms/g wet tissue, p less than 0.05), but in the perifusion system, this effect could not be observed. The addition of glucose in the perifusion system gave a slightly higher hPL secretion than that of the control. Perhaps this resulted from increased cell activity rather than a stimulatory effect. an incorporation experiment of [3H] leucine was also carried out to study the biosynthesis of hPL. Newly synthesized ([3H]-labelled) hPL was secreted into the medium within two hours. Furthermore, a labelled larger molecular weight substance together with the tritiated hPL was also observed on a Sephadex G-100 gel chromatography. These labelled substances were immunoprecipitable using an anti-hPL serum, indicating that the substances contain the same immunological determinants. This result indicates that the larger molecular substance may represent the biosynthetic precursor or the aggregate of hPL. These data indicate that the secretion of hPL has a unique mechanism, different from GH and PRL, and may be self regulated.

Arginine↗