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Biomedical subjects

O Tanizawa

Publications and source records attributed to O Tanizawa.

At least 235 records · Page 13Linked to original sources

Possible involvement of lipoxygenase pathway of arachidonic acid in rat pituitary hormone release in vitro.

The roles of arachidonic acid (AA) and its lipoxygenase products in control of secretion of anterior pituitary hormones were studied in vitro using cultured cells. AA (10(-4)M) and 5-hydroxy-eicosatetraenoic acid (5HETE) (5 x 10(-6)M) significantly (p less than 0.05) stimulated the releases of LH, TSH, GH, PRL, ACTH and beta-endorphin (beta-E). Added leukotriene B4 (LTB4) (5 x 10(-6)M) also caused significant increases in the secretions of LH, GH, ACTH and beta-E. The other lipoxygenase metabolites tested, 12HETE, 15HETE, LTA4, LTC4 and LTD4, had no effect on the releases of anterior pituitary hormones. These results suggest that AA and 5-lipoxygenase metabolites may be involved in the control of the releases of anterior pituitary hormones.

Adrenocorticotropic Hormone↗

RU486, a progestin antagonist, binds to progesterone receptors in a human endometrial cancer cell line and reverses the growth inhibition by progestins.

The human endometrial cancer cell line, IK-90 cells, contains estrogen-independent progesterone receptors (PR) and is progestin sensitive. Accumulation of glycogen in the cytoplasm of IK-90 cells as well as growth inhibition of the cells in response to progestins are observed. In the present study, the effects of RU486, a progestin antagonist, on IK-90 cells were investigated in a serum-supplemented medium. Scatchard plot analysis of cytoplasmic binding data in the cells revealed a high affinity binding site for RU486 (Kd, 2.6 nM) with maximum binding sites of 169 fmol/mg protein. However, the binding ability to DNA-cellulose of heat activated [3H]RU486-PR complexes was lower when compared with that of the progestin agonist [3H]R5020-PR complexes, suggesting a decrease in progestin activity of RU486 in IK-90 cells. The addition of 1 microM RU486 to culture medium produced periodic acid-Schiff-positive granules in the cytoplasm of the cells. On the other hand, RU486 (1 nM-1 microM) did not significantly inhibit the growth of cells. However, RU486 (0.1-1 microM) totally prevented the growth-inhibitory effect of R5020 (0.1-1 microM) on IK-90 cells. In conclusion, RU486, an antiprogestin, had a dual activity both a progestin antagonist and weak agonist in human endometrial cancer cells, which was not mediated through the estrogen receptor system.

Binding, Competitive↗

Inhibitory effects of danazol and medroxyprogesterone acetate on [3H]thymidine incorporation in human endometrial cancer cells.

Effects of medroxyprogesterone acetate (MPA) and danazol (1 nM-10 microM) on cultured cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were simultaneously investigated. Of twenty-four endometrial adenocarcinomas examined, five tumors were successfully maintained in primary cell culture. The addition of MPA as well as danazol in culture of cells from the five tumors resulted in a significant inhibition of [3H]thymidine incorporation in cancer cells from three tumors having progesterone receptors (PR). The minimum effective concentrations of MPA and danazol for the inhibition of [3H]thymidine incorporation were found to be 10 and 100 nM, respectively. The difference in effective concentration could be explained by a higher affinity of MPA to PR than that of danazol in cancer cells. On the other hand, neither danazol nor MPA affected [3H]thymidine incorporation in cultured cells from the remaining two tumors, in which PR was absent in one but present in the other. These findings, together with our previous findings that danazol inhibited the growth of a human endometrial cancer cell line with PR, suggest that a growth-inhibitory effect of danazol on human endometrial cancer cells is mediated through PR in the cells.

Adenocarcinoma↗

Clinical evaluation of the enzyme-linked immunosorbent assay (ELISA) kit for antisperm antibodies.

A commercially available enzyme-linked immunosorbent assay (ELISA) kit for the detection of antisperm antibodies in serum was compared with standard sperm immobilization test (SIT) with the use of sera from 83 infertile women and 29 control individuals. For the ELISA, 24% of the infertile patients and 10% of the controls showed positive results, whereas 15% of the patients and none of the control were positive in the SIT. Parallel tests carried out on the same sera indicated that these methods detect a different, though often overlapping, spectrum of antibody activity. The presence and number of motile sperm in cervical mucus during postcoital tests were found to be related to the results of the SIT. On the other hand, the ELISA did not appear to be related to the quality of postcoital tests. These data indicate that care must be employed to interpret the results of this ELISA kit for the detection of antisperm antibodies.

Antibodies↗

Second pregnancy with spontaneous ovulation following clomiphene- or gonadotropin-induced pregnancy.

For investigation of the rates of spontaneous pregnancy following termination of pregnancy induced by treatment with clomiphene or human menopausal gonadotropin-human chorionic gonadotropin (hMG-hCG) and of spontaneous abortion in the second pregnancy, 119 women (58 with an anovulatory cycle and 141 with amenorrhea) who desired another pregnancy were studied. The rate of spontaneous pregnancy following pregnancy induced by clomiphene was 46.6%, which was significantly (p less than 0.001) higher than that following pregnancy induced by hMG (14.9%). The mean (+/- SEM) period between the termination of the first induced-ovulation pregnancy and the second spontaneous pregnancy was 16.6 +/- 1.4 months. The spontaneous abortion rates in the second pregnancies after pregnancies induced by clomiphene and hMG were 7.5% and 9.8%, respectively, which were significantly (p less than 0.001, p less than 0.05) lower than those in the first pregnancy (25.7%, 33.0%). There was no difference between the spontaneous abortion rates following a first pregnancy which terminated in abortion and those following a pregnancy which ended in birth. These data suggest that a first pregnancy in anovulatory women may restore the ovulatory cycle and have a beneficial effect on the rates of spontaneous abortion in the second pregnancy.

Clomiphene↗

Universal predictive criteria for neonatal overt thyrotoxicosis requiring treatment.

The universal predictive criteria for neonatal overt thyrotoxicosis requiring treatment were examined in 108 neonates (including a pair of twins) born to mothers with Graves' disease (36 patients under treatment with antithyroid drugs [group A] and 71 in remission [group B]). Anti-thyroid-stimulating hormone (TSH) receptor antibody activity was measured by both radioreceptor assay (TSH-binding inhibitor immunoglobulin [TBII]) and biologic stimulation assay (thyroid stimulating antibody [TSAb]). For generalization of the predictive criteria, the expression of TBII activity was standardized using standard serum made taking units of Medical Research Council long-acting thyroid stimulator, standard B as a reference, and expression of TSAb activity was standardized using bovine TSH as a standard. TBII activity was positive in 22 mothers at delivery, and TSAb activity was positive in 18. In 12 cases, both activities were positive. Both the TBII and the TSAb activity of maternal serum at delivery correlated well with that of the cord serum. Neonatal thyrotoxicosis occurred in 9 of 108 neonates (8%), of whom five (5%) had clinical overt symptoms requiring antithyroid drug treatment. In all nine cases the TBII and TSAb activities were both positive, but no neonate without TBII or TSAb activity developed thyrotoxicosis. The prediction rate (42%) of neonatal overt thyrotoxicosis was higher when both TBII and TSAb were measured than when only TBII (23%) or TSAb (28%) was measured. Clinical overt thyrotoxicosis could be predicted in five of six neonates (83%) of mothers when the cutoff levels of antibody activities were increased to a TBII activity of above 8 U/ml and TSAb activity of above 1.0 TSH microUEq.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

Identification and characterization of a human sperm antigen corresponding to sperm-immobilizing antibodies.

A sperm antigen has been isolated from radiolabeled human sperm cell membrane by detergent solubilization, lectin affinity chromatography, gel filtration, and indirect immune precipitation using sperm-immobilizing antisera from patients with unexplained infertility. Isolated material was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Among 20 infertile women's sera with sperm-immobilizing antibodies, two were found to react predominantly with a sperm membrane polypeptide having the approximate molecular weight of 15,000 daltons. No significant binding to this molecule was observed in any sera from pregnant women, unmarried women, and normal men. By the absorption with spermatozoa, the antisera lost their binding activity to the molecule, while the sera absorbed with seminal plasma did not lose the activity. The results indicated that the molecule is a genuine sperm antigen and not a sperm-coating seminal plasma antigen. By the indirect immunofluorescence of washed ejaculated spermatozoa with the antisera, strong fluorescence was localized only in an equatorial segment of the acrosome, while no specific staining was observed in the controls. The antigen is relatively unstable against acid, alkali, and heat treatment. Treatment with proteolytic enzymes such as pronase and trypsin inactivated the antigen activity, indicating that the antigen epitope could be a peptide portion of the glycoprotein.

Antigens, Surface↗

Changes of lymphocyte subsets in normal pregnant and postpartum women: postpartum increase in NK/K (Leu 7) cells.

Changes in lymphocyte subsets in whole blood of normal pregnant and postpartum women were examined by flow cytometry with an automated leukocyte differential system. From the first trimester and throughout pregnancy, the absolute counts of T(CD3) and B(CD20) and T-cell subsets (CD4, CD8) decreased with a decrease in the absolute lymphocyte count, although the proportions of these cells remained unchanged except for a decrease in the percentage of T helper-inducer (CD4) cells in the first trimester. On the contrary, the percentage of NK/K (Leu 7) cells, but not of NK/K (CD16) cells, increased in the first trimester and then both gradually decreased in the second and third trimesters. In the postpartum period, the percentages and absolute counts of T(CD3) and NK/K (Leu 7) cells, but not of other cells, increased transiently. These changes of lymphocyte subsets may indicate suppression of immunological activity during pregnancy and its "increase" in the postpartum period.

Adult↗

Increase in antideoxyribonucleic acid antibody titer in postpartum aggravation of autoimmune thyroid disease.

Serum antidouble stranded DNA antibody levels were measured during pregnancy and after delivery in women who had postpartum exacerbations of Graves' and Hashimoto's diseases. The changes in serum anti-DNA antibody levels closely paralleled those in the serum free T4 index, significantly increasing in the thyrotoxic phase 3-8 months postpartum in women with postpartum exacerbations of thyrotoxicosis due to Graves' disease and 1-3 months postpartum in women with postpartum destructive thyrotoxicosis of Graves' and Hashimoto's diseases. No change in anti-DNA antibody level was found in women with no postpartum exacerbations of thyroid diseases, nor could we demonstrate significant increases in serum anti-DNA antibody titers in patients with thyrotoxicosis due to subacute thyroiditis or in normal pregnant and postpartum women. The changes in serum anti-DNA antibody titers may reflect some generalized immunological abnormality in women who have postpartum exacerbations of Graves' or Hashimoto's diseases.

Adult↗

Changes in epidermal growth factor receptor and its messenger ribonucleic acid levels in human placenta and isolated trophoblast cells during pregnancy.

We measured the amounts of epidermal growth factor receptor (EGFR) in plasma membrane fractions purified from early, middle, and term placentas and from isolated trophoblast cells, and the amounts of EGFR mRNA were measured in whole placentas. Binding studies were performed using [125I] human EGF as ligand; two classes (high and low) of binding sites were found in placental and trophoblast cell plasma membranes. Although dissociation constants (Kd) were not significantly different in placental plasma membranes from the three stages of pregnancy, the number of binding sites increased significantly during pregnancy. The mean numbers of binding sites were 0.72 +/- 0.18 (+/- SE), 1.02 +/- 0.10, and 1.89 +/- 0.21 pmol/mg protein (high affinity sites) in plasma membrane fractions from early, middle, and term whole placentas, respectively. A similar significant increase was found when the membranes were prepared from isolated trophoblast cells. At the same time, total cellular RNA was isolated, denatured, and blotted onto nitrocellulose membranes. Then, hybridization with 32P-labeled pE 7, a cDNA of EGFR, or 32P-labeled v-erb-B oncogene, autoradiography, and densitometry were performed. The EGFR mRNA increased proportionally to the changes in EGFR during pregnancy. These results indicate that EGF-binding sites and EGFR production increase in human placentas throughout the gestational period.

Blotting, Northern↗

Increase in peripheral large granular lymphocytes in postpartum autoimmune thyroiditis.

In order to elucidate the mechanism of postpartum aggravation of autoimmune thyroid disease (AITD), we serially examined the change in the proportion of peripheral large granular lymphocytes (LGL), which have activities of NK, K and/or cytotoxic T cells, in their postpartum period. Within 6 months postpartum, the percentage of LGL increased transiently in patients with AITD who remained euthyroid, or developed destructive thyrotoxicosis and/or hypothyroidism due to thyroiditis and even in normal controls. These changes in the LGL percentage were more obvious in the patients who had marked postpartum thyroid dysfunction. In contrast, we did not find a definite increase in the LGL percentage within 6 months postpartum in patients with Graves' disease who relapsed into Graves' thyrotoxicosis. These deta suggest that the increase in LGL in the postpartum period may be related to the induction of postpartum destructive thyrotoxicosis and/or hypothyroidism in AITD.

Female↗

Lunch induces an increase in the plasma prolactin concentration, but not vasoactive intestinal peptides or cholecystokinin.

Ingestion of lunch is known to be associated with acute release of prolactin (PRL). The neuroendocrine mechanism of this release was examined by measuring changes in serum vasoactive intestinal peptides (VIP) and cholecystokinin (CCK) after the noon meal in six normal men. The serum PRL concentration was significantly increased (40% above the level before lunch) from 30 min to 1 h 45 min after beginning to eat. However, the ingestion of lunch had no remarkable effects on the plasma immunoreactive concentration of VIP and CCK. Thus the changes in the plasma concentration of these two gut-brain peptides did not coincided with acute PRL release after ingestion of lunch, suggesting either that these two gut-brain peptides are probably not involved in PRL release after lunch, or that the level of these two gut-brain peptides in the general circulation may not represent that in the hypophyseal portal plasma.

Adult↗

Vasoactive intestinal peptide stimulates gonadotropin-releasing hormone release from rat hypothalamus in vitro.

The effects of vasoactive intestinal peptide (VIP) on the releases of LH and GnRH were examined in a sequential double chamber perifusion system by perfusing the medio-basal hypothalamus and/or pituitary excised from normal female rats in diestrus or ovariectomized rats. When the medio-basal hypothalamus and pituitary from normal rats in series were perifused with VIP (10(-6) mol/l), the concentration of LH in the efflux was increased by 59-181% above that before the injection (P less than 0.05), VIP having a dose-dependent effect. VIP had no effect on LH release from the pituitary perifused alone. Infusion of VIP at 10(-6) mol/l induced a significant release (84-159% increase, P less than 0.05) of GnRH from the medio-basal hypothalamus. Infusion of 10(-6) mol/l VIP induced a significant release (41-99% increase, P less than 0.05) of LH in ovariectomized rats. These findings suggest that VIP induces GnRH release from the medio-basal hypothalamus, resulting in LH release from the pituitary, and that this process does not require ovarian estrogen.

Animals↗

17-beta-estradiol treatment maintains differentiative potential of virgin mouse mammary gland in culture and its responsiveness to insulin.

Synthesis of the milk proteins, casein and alpha-lactalbumin was not induced in cultured mammary explants from C3H/HeN castrated virgin mice in the presence of lactogenic hormones such as insulin, cortisol and PRL. Replacement therapy with 17-beta-estradiol to the castrated mice completely restored the differentiative potentials of mammary explants, inducing synthesis of the two milk proteins. [3H]thymidine incorporation into DNA synthesized in cultured mammary explants was also decreased by castration to less than 50% (P less than 0.001) of that obtained in intact mice, and 17-beta-estradiol treatment to castrated animals restored DNA synthesis to 90% of the intact level. The addition of insulin to culture medium significantly (P less than 0.001) enhanced [3H]thymidine incorporation into DNA in cultured mammary explants from both intact and 17-beta-estradiol-treated castrated mice but not from castrated animals. Insulin binding sites (1710 +/- 260 sites/cell) to mammary epithelial cells from castrated mice were significantly (P less than 0.05) lower than those from both intact (2870 +/- 300 sites/cell) and 17-beta-estradiol-treated castrated animals (2860 +/- 190 sites/cell). The present findings suggest that 17-beta-estradiol maintains growth and differentiative responses of mammary epithelial cells to insulin, which may be through preserving the number of insulin binding sites in the cells.

Animals↗

[Expression of blood group antigens A, B, H, Lewis a, Lewis b, in malignant lesions of the uterine cervix].

The fetal, normal adult, and malignant squamous epitheliums of the cervix were immunohistochemically examined by the avidin-biotin-peroxidase complex method with monoclonal antibodies for blood group antigens (BGAs) A, B, H, Lewis a, and Lewis b. The results were as follows. 1) ABH antigen compatible with ABO status was found in most normal squamous epithelium of fetal and adult cervix. 2) Compatible ABH and A antigen were abolished in small cell nonkeratinizing squamous cell carcinomas (SNKCs) and large cell nonkeratinizing squamous cell carcinomas (LNKCs), respectively. But no remarkable change in ABH antigen expression was observed in other types of cervical lesions. 3) Precursor H antigen was accumulated in all types of malignant lesions. 4) Incompatible expression of A or B antigen was observed in some cases of LNKCs and keratinizing squamous cell carcinomas. 5) Lewis antigens were abolished to various degrees in malignant lesions of the cervix. The present study showed the change in BGAs expression during carcinogenesis of the cervix, but further investigation is needed to elucidate the interaction between these changes in BGAs and the biological behavior of cancer cells.

ABO Blood-Group System↗

[Altered expression of Lewis antigens associated with malignant transformation in endometrial tissues].

Fetal, normal adult, and malignant tissues of the uterine endometrium were examined by immunoperoxidase staining for Lewis antigens. Pronounced expression of Lewis-a, Lewis-b, and Lewis-Y antigens in malignant tissues was observed, compared with that in normal adult tissues. Moreover, the amplified expression of Lewis-b antigen was considerably higher than that of Lewis-a and Lewis-Y antigens. On the other hand, Lewis-X antigen was less expressed in malignant tissues than in normal adult tissues. These results suggest that fucose-transferase activity might be increased in malignant tissues and that the type I carbohydrate chain may play a role in the malignant transformation. In addition, Lewis-b and Lewis-Y antigens can be considered to be oncofetal antigens since they were frequently expressed in fetal and malignant tissues, but not in normal adult tissues. However, the functional significance of these changes in the expression of Lewis antigens remains to be investigated.

Cell Transformation, Neoplastic↗

[Method and evaluation of hormone assays in practical obstetrics and gynecology].

Hormone assays are very important in obstetrics and gynecology. Today, I want to talk about how to measure hormones and how to evaluate the data obtained for therapeutic purposes. In humans, there are two mechanisms of control, neural control and endocrine control. Generally speaking, the neural system controls organs directly via various neurotransmitters, while the endocrine system controls organs by hormones transported in the blood. In fact, recent progress in hormone research has shown that this concept should be modified, because some hormones act as neurotransmitters or regulate other cells or even endocrine cells themselves in the same organ. But I shall not go into this. Today's lecture is focused on hormones that are closely related to clinical obstetrics and gynecology. The hormones that are important are those in females, reproduction, and pregnancy, and tumors. First, and most important, is that patients acquire femininity in the physiological and psychological sense by hormones. The hormones closely related to this are estrogens and pituitary hormones. For reproduction, cyclic hormonal change is important. In the reproductive period, women have menstruation and ovulation along with cyclic changes of ovarian and pituitary hormones. After conception, various kinds of hormones, including hCG, HPL and estriol, are secreted from the feto-placental system. These hormones are used clinically as a markers of placental function. Hormones also have important roles in oncology. hCG is an excellent marker of trophoblastic diseases. Endometrial cancer is expected respond to large doses of progestins if they have progesterone receptors. There are three types of hormone assays, biological assays, immunological assays and chemical assays.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗