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Biomedical subjects

O Tanizawa

Publications and source records attributed to O Tanizawa.

At least 289 records · Page 16Linked to original sources

Danazol binds to progesterone receptors and inhibits the growth of human endometrial cancer cells in vitro.

Based on our recent findings that danazol, an isoxazol derivative of ethinyltestosterone, has a profound growth-inhibitory effect on an established human endometrial adenocarcinoma cell line, the effects of danazol on cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were investigated in the present study. Of the 22 uterine adenocarcinomas, estrogen, progesterone, and androgen receptors were found in 12, 14, and 4 tumors, respectively. Competitive binding studies showed that danazol specifically binds to progesterone and androgen receptors but not to estrogen receptors. Of the five cancer cells from five patients succeeded in primary cell culture, a marked inhibition of cell growth was demonstrated by addition of danazol in two cancer cells having progesterone but not androgen receptors. However, danazol did not affect the growth of the remaining three cancer cells lacking progesterone receptors. These results strongly suggest that danazol has a significant growth-inhibitory effect on human endometrial adenocarcinoma cells, possibly through progesterone receptors in the cells.

Adenocarcinoma↗

Further characterization of a human sperm coating antigen (gp12).

In our previous paper, we identified a novel sperm-coating antigen with molecular weight of approximately 12,000 daltons that is highly specific to sperm, seminal plasma, and milk from the plasma membrane fraction of human spermatozoa by using rabbit antiseminal plasma antiserum. In the present study, this 12,000-daltons component, termed gp12, has been investigated for its tissue distribution and antigenic stability. The largest amounts of the antigen are found in seminal plasma, although individual variation is rather high. In seminal plasma, the gp12 molecule presents in a large form with a molecular weight of approximately 50,000 daltons. Its antigenicity is stable when treated with acid, alkali, heat, and various protein denaturants.

Antigens, Surface↗

Retinoic acid enhances cell responses to epidermal growth factor in mouse mammary gland in culture.

Addition of epidermal growth factor (EGF) at up to 100 ng/ml to the medium of cultured explants of mouse mammary gland increased thymidine incorporation into DNA dose dependently. Addition of retinoic acid alone at 10 micrograms/ml to the medium had no significant effect on DNA synthesis, but addition of EGF with retinoic acid enhanced the EGF-stimulated DNA synthesis. Furthermore, pretreatment of mammary explants with retinoic acid enhanced the effect of EGF plus retinoic acid on cell growth. EGF inhibited the synthesis of casein and decreased alpha-lactalbumin activity of mammary explants in culture in the presence of insulin, cortisol, and PRL. Retinoic acid alone had no significant effect on the synthesis of casein, but suppressed alpha-lactalbumin activity dose dependently. Concomitant addition of retinoic acid with EGF had no significant effect on EGF-induced inhibition of casein synthesis, but enhanced EGF-induced inhibition of alpha-lactalbumin activity dose dependently. Measurement of specific binding of [125I]EGF to mouse mammary glands in culture demonstrated that pretreatment of the explants with retinoic acid slightly, but significantly, enhanced the specific binding of EGF to its cellular receptors.

Animals↗

Monoamine oxidase in rat ovary during the estrous cycle. A histochemical study by a new coupled peroxidatic oxidation method.

A new coupled peroxidatic oxidation method for histochemical detection of monoamine oxidase (MAO) was applied to rat ovary. With this new method, fixed tissues could be used, and two forms of MAO could be identified by use of selective inhibitors. MAO activity was observed in the corpora lutea, interstitial gland cells, and blood vessels. In the corpora lutea, no activity was detected during the first estrous cycle, but strong activity was observed in the next two cycles. MAO in blood vessels showed characteristic changes of activity during the estrous cycle. The results suggest that MAO activity might possibly be involved in ovulation and progesterone metabolism in the ovary. Like other organs, rat ovary was found to contain two types of MAO; type A MAO was predominant in the corpora lutea. On the other hand, only one type of MAO, type B, was found in the blood vessels.

Animals↗

Clomiphene citrate induces pituitary GnRH receptors in ovariectomized rats: its possible role in induction of ovulation.

Since our previous studies have shown that clomiphene citrate (clomiphene) acts directly on the pituitary gland and exerts a facilitatory role on oestradiol-17 beta (E2)-induced LH surge in chronically ovariectomized rats, the effect of clomiphene on pituitary GnRH receptors was investigated. A single ip injection of either 5 micrograms E2 or 200 micrograms clomiphene did not induce LH release in adult rats ovariectomized 1-2 weeks before the injection. However, a significant increase in serum LH was noted 24 h after a single injection of E2 in the ovariectomized rats, if clomiphene was pre-injected 48 h before the E2 injection. The content of pituitary GnRH receptors in the ovariectomized rats (62 +/- 9 fmol/pituitary) remained almost unchanged until 24 h after a single injection of clomiphene but significantly increased 48 h after the injection (105 +/- 13 fmol/pituitary) without any alterations in the affinity for GnRH. To determine steroid specificity for the increase in pituitary GnRH receptors, other classes of steroids were injected in the ovariectomized rats. A single dose of E2 increased GnRH receptors, but either progesterone or 5 alpha-dihydrotestosterone failed to show any effect on the level of GnRH receptors. These results suggest that clomiphene may augment oestrogen-induced pre-ovulatory LH surge in anovulatory women, at least in part by increasing the number of pituitary GnRH receptors.

Animals↗

Dexamethasone inhibits the effects of oestrogen on the pituitary gland in rats.

The administration of glucocorticoids has been shown to be effective for the induction of ovulation in patients with anovulation. In the present study, we investigated the effects of a glucocorticoid on oestrogen-induced changes in the pituitary gland. A single ip injection of 10 micrograms oestradiol-17 beta (E2) in ovariectomized and adrenalectomized rats resulted in a significant increase in pituitary weight and progesterone receptor (PgR) concentration. In these animals, serum LH level was initially suppressed and restored to control level 24 h after E2 injection. However, 1 mg of dexamethasone (Dex) injected before E2, but not after E2 administration, completely inhibited both the increases in pituitary weight and PgR concentration. The restoration of serum LH level 24 h after E2 was also prevented. These antioestrogenic effects of Dex were blocked by ip administration of the synthetic antiglucocorticoid, RU486. Dex treatment alone did not have any effect on E2-induced changes in the dynamics of pituitary oestrogen receptor. Finally, E2-pellet implanted sc in ovariectomized and adrenalectomized rats for 7 days caused marked increases in pituitary weight and PgR concentration. A single ip injection of 250 micrograms clomiphene citrate (clomiphene) significantly reduced both the pituitary weight and PgR concentration in these animals, but 1 mg of Dex failed to have a similar effect. These results suggest that glucocorticoids antagonize E2 effects on the pituitary by a mechanism different from antioestrogens such as clomiphene. These antioestrogenic effects of glucocorticoid may be involved in induction of ovulation in anovulatory women.

Adrenalectomy↗

Hydatidiform mole in a triplet pregnancy following gonadotropin therapy.

A first case is reported of complete hydatidiform mole with two coexistent fetuses in a triple pregnancy following human menopausal gonadotropin human chorionic gonadotropin (hMG-hCG) therapy. The molar mass and two fetuses were delivered separately at 17 weeks of gestation. The fetuses were female (155 g) and male (160 g) with individual placentae (85 g, 90 g). The hydatidiform mole (650 g) had a normal 46,XX karyotype. The sexes of the two fetuses and the karyotype of the mole are consistent with previous reports that the chromosomes of fetuses and moles are derived from both parents and the father, respectively.

Adult↗

[A case of amylase-producing ovarian tumor].

A 51-year-old woman with ovarian carcinoma with hyperamylasemia is reported. She was admitted to Osaka General (JNR) Hospital in July 1982. A cystic tumor was palpated in the pelvis. Serum amylase, mainly the salivary type, in electrophoresis, had increased to 1583 Smith-Roe units/dL, while the pancreas was normal on ultrasonography and CT. Chemotherapy (MFC) was performed, and laparotomy revealed bilateral ovarian tumors. Histologically, they were serous cystadenocarcinoma. Serum and urinary amylase values dropped to the normal range after chemotherapy and surgery, and varied directly with the clinical course. Immunohistochemically, amylase was demonstrated in the tumor tissue by the PAP method. In conclusion, amylase was a useful marker in the diagnosis and follow-up of the present patient.

Amylases↗

Immunohistochemical demonstration of HNK-1-defined antigen in gynecologic tumors with argyrophilia.

Gynecologic tumors with argyrophilia were tested immunohistochemically for reactivity with monoclonal antibody HNK-1, which detects normal and neoplastic cells derived from the neuroectodermal and the amine-precursor-uptake and decarboxylation (APUD) systems. The tumors included six small cell carcinomas and four adenocarcinomas of the cervix; 23 adenocarcinomas of the endometrium (13 with type I and 10 with type II argyrophil cells); and 11 mucinous tumors (three benign, three borderline, and five malignant), eight endometrioid carcinomas (four with type I and four with type II argyrophil cells), and two carcinoid tumors (one insular and one strumal) of the ovary. HNK-1 reactive cells were found in almost every category of tumor: in four small cell carcinomas and two adenocarcinomas of the cervix; 11 adenocarcinomas of the endometrium (eight with type I and three with type II argyrophil cells); and four mucinous (two benign and two borderline), two endometrioid (one with type I and one with type II argyrophil cells), and two carcinoid tumors of the ovary. These cells corresponded to at least some of the type I argyrophil cells in endometrial and ovarian endometrioid carcinomas and to similar cells in mucinous and carcinoid tumors of the ovary and small cell carcinoma and adenocarcinoma of the cervix. However, the remaining type I and similar argyrophil cells and almost all type II argyrophil cells were HNK-1 negative, and some of the nonargyrophil tumor cells were HNK-1 positive. Although the significance of such discrepancies in reactivity with HNK-1 antibody remains unknown, the present results suggest that some of the gynecologic tumors with argyrophilia are related to APUDomas.

Antigens, Neoplasm↗

[Immunohistological demonstration of peptide hormones and serotonin in ovarian mucinous and endometrioid tumors with argyrophil cells].

The localization of peptide hormones and serotonin in ovarian mucinous and endometrioid tumors with argyrophil cells was examined by immunohistochemistry. All of the 15 mucinous tumors had argyrophil cells which resemble the enterochromaffin cells seen in the gastrointestinal tract, and peptide hormones such as gastrin and somatostatin were found in 3 of 5 benign, in 3 of 5 borderline, and in all of 5 malignant tumors. Serotonin was found in 4 benign, 3 borderline and 2 malignant tumors. Of 19 endometrioid adenocarcinomas, type I argyrophil cells which resemble enterochromaffin cells were found in 4 tumors, type II argyrophil cells which contain argyrophil granules mainly in the apical portion or throughout the whole cytoplasm were found in 14, and mixed type cells were found in one. Somatostatin-positive cells were found only in type I cells of a tumor with mixed type argyrophil cells. Serotonin-positive cells were found in 3 tumors containing type I cells. The results obtained were discussed in the comparison with those of cervical and endometrial adenocarcinomas of the uterus. In conclusion, the present study suggests that type I or similar argyrophil cells in ovarian tumors may have endocrine activity.

Adenocarcinoma↗

Immunoregulatory effects of human cord blood T lymphocytes on mixed lymphocyte reaction.

Fetuses of outbred mammalian species can survive despite disparities of participants' histocompatibility antigens. During pregnancy, maternal immune response is supposed to be suppressed by various immune suppressive mechanisms. In order to know whether fetal lymphocytes can suppress the maternal immune reaction, we investigated the suppressive effect of human newborns' T lymphocytes. Newborn T cells were isolated from the umbilical cord blood by means of the sheep red blood cell rosette forming method and treated with mitomycin C. The newborn T cells were added as regulator cells to one way mixed lymphocyte reaction (MLR) using maternal lymphocytes, paternal lymphocytes and unrelated donor's lymphocytes. In a control study, adult T cells were treated in the same manner. In any combination of the MLR, the response was substantially suppressed by the addition of cord T cells in comparison with the response by the addition of normal adult T cells. The suppression was dose-related with an increasing number of regulator cord T cells. The suppressive activity of cord T cells showed radiation resistance until 1,000 rads irradiation. In the kinetics study, cord T cells were found to suppress the recognition phase of MLR. These results suggest that cord T lymphocytes suppress the mother's immunological reaction to the fetal antigens.

Female↗

Histochemical studies on human placental and chorionic monoamine oxidase.

A new coupled peroxidation method for detection of monoamine oxidase was applied to human chorionic and placental tissues of various weeks of gestation. With this new method, the precise localization of monoamine oxidase activity could be determined and the two isotypes of the enzyme could be identified using selective inhibitors. Significant monoamine oxidase activity was observed in syncytiotrophoblasts of fine villi and budding villi. Monoamine oxidase activity in chorionic and placental tissues remained similar in intensity and localization throughout pregnancy. Only one type of monoamine oxidase, type A, was found in the placenta. The functional role of monoamine oxidase is discussed.

Chorion↗