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Biomedical subjects

O Tanizawa

Publications and source records attributed to O Tanizawa.

At least 73 records · Page 4Linked to original sources
PubMed1992

Induction of uterine cervical neoplasias in mice by human papillomavirus type 16 E6/E7 genes.

We constructed a recombinant retrovirus containing the E6/E7 genes of human papillomavirus (HPV) 16 (ZE67) and examined the morphological changes in the cervicovaginal epithelium induced by inoculation of this virus into the vagina of mice. The ZNeo virus without HPV genes was used as a negative control. Moreover, cotreatment with phorbo-13-myristate-12-acetate or N-methyl-N'-nitro-N-nitrosoguanidine and these viruses was carried out. At the end of the observation period (9 months for CD-1 nu/nu and 15 months for C57BL/6J), of 31 CD-1 nude mice treated with ZE67, 7 and 19 had low-grade and high-grade dysplasia, respectively, while 5 of 22 mice treated with ZNeo had low-grade dysplasia (rank sum test, P less than 0.001). Similarly, 4 and 3 of 8 C57BL mice treated with ZE67 had low-grade and high-grade dysplasias, respectively, whereas 3 of the 8 control mice had low-grade dysplasias (P = 0.049). ZE67 plus phorbol-13-myristate-12-acetate and ZE67 plus N-methyl-N'-nitro-N-nitrosoguanidine cotreatments induced cervical cancers in 2 of 13 CD-1 nude mice and 6 of 15 C57BL mice, respectively. On the contrary, none of 6 CD-1 and 2 of 10 C57BL mice had cancer in the control groups (P = 0.0142 for phorbol-13-myristate-12-acetate treatment; P = 0.0173 for N-methyl-N'-nitro-N-nitrosoguanidine treatment). In addition, the existence and expression of HPV 16 E6/E7 genes were detected in the lesions induced by ZE67 but not in the lesions of the control mice by analysis by polymerase chain reaction and mRNA in situ hybridization. The present results suggest that HPV 16 E6/E7 genes induce dysplastic changes but require additional promoting or mutagenic stimulation for the development of cancer.

Animals↗
PubMed1992

Malignant cell-specific gelatinase activity in human endometrial carcinoma.

BACKGROUND: The protease activity leading to degradation of the extracellular matrix was compared between human endometrial cancer and normal uterine endometrium. METHODS: Conditioned medium from tumor cells and normal endometrial cells was subjected to electrophoresis on sodium dodecyl sulfate (SDS)-polyacrylamide gel containing gelatin as a substrate. After electrophoresis, the gel was stained with Coomassie blue, and then the enzyme activity, expressed as the zone of dye clearing, was analyzed by densitometry. RESULTS: Densitometric analysis showed that all the endometrial cancers expressed a very high molecular weight enzyme activity (Mr 220,000), which was not detected in medium from normal endometrial cells. The analysis also showed that in endometrial cancer the activity of a Mr 92,000 enzyme was always superior to that of a Mr 64,000 enzyme, which was in contrast to the situation for normal endometrium. CONCLUSIONS: These results indicate that the expression of Mr 220,000 enzyme activity and the higher activity of the Mr 92,000 enzyme than the Mr 64,000 enzyme are involved in the malignant phenotype of native endometrial cancer.

Adenocarcinoma↗
PubMed1992

Activin A increases cytosolic free calcium concentration in rat pituitary somatotropes.

The effect of activin A on the cytosolic free calcium concentration ([Ca2+]i) in normal rat pituitary cells was examined using a calcium sensitive fluorescent dye, indo 1 AM, and a digital imaging fluorescent microscope system. The cells showing an increase in [Ca2+]i in response to activin A were then characterized by comparison with cells responding to growth hormone releasing hormone (GRH), thyrotropin releasing hormone (TRH), corticotropin releasing hormone (CRH), and gonadotropin releasing hormone (GnRH) in monolayer cultures of normal rat pituitary cells. Activin A increased [Ca2+]i in some cells in a mixed population of normal rat pituitary cells. The cells that responded to activin A also responded to GRH. Most of these cells were not affected by other tropic hormones (CRH, TRH, and GnRH), but a few cells responded to both GRH and TRH. None of the activin A-responding cells responded to CRH or GnRH, and none of the CRH- or GnRH-responding cells responded to activin A. In a preparation of somatotropes purified 80-90% by fluorescence-activated cell sorting, activin A increased [Ca2+]i in 30% of the cells that shows a [Ca2+]i-response to GRH. These findings suggest direct involvement of somatotropes in activin A-induced biological events in the rat pituitary gland.

Activins↗
PubMed1992

Relationship of age at menarche and subsequent fertility.

We investigated retrospectively the relationship between the age at menarche and reproductive ability in 2278 married women. Those who had a pregnancy experienced menarche at a mean age (+/- SEM) of 13.7 +/- 0.1 years, and those who were infertile had menarche at a mean age of 14.0 +/- 0.2 years, difference in the times of onset of menarche being significant (P less than 0.05). Moreover, a group in whom menstruation started after the age of 18 years had a significantly higher rate of infertility (15.7%) than the others (5.0%). Irregular menstruations during the first few years after menarche was also related to decreased reproductive ability. These findings indicate the importance of menarche before the age of 18 for normal reproductive functioning.

Adolescent↗
PubMed1992

Structure and expression of a human oxytocin receptor.

Just before the onset of labour, uterine myometrium becomes extremely sensitive to oxytocin, for which it is a primary target tissue, because of a dramatic increase in the number of oxytocin receptors. We report here the structure and expression of the human oxytocin receptor complementary DNA isolated by expression cloning. The encoded receptor is a 388-amino-acid polypeptide with 7 transmembrane domains typical of G protein-coupled receptors. The oxytocin receptor, expressed in Xenopus oocytes, specifically responds to oxytocin and induces an inward membrane current. Messenger RNAs for the receptor are of two sizes, 3.6 kilobases in breast, and 4.4 kilobases in ovary, uterine endometrium and myometrium. The mRNA level in the myometrium is very high at term. We conclude that the increase in receptor number in the myometrium at labour is, at least in part, due to the increase in mRNA.

Amino Acid Sequence↗
PubMed1992

Regulation of intracellular Mg2+ by superoxide in amnion cells.

Changes of intracellular free Mg2+ concentration ([Mg2+]i) in human amnion cells induced by superoxide anion were determined using a highly Mg(2+)-sensitive fluorescent dye Mg(2+)-fura2 or Mg(2+)-indol. Superoxide anion, produced by addition of xanthine oxidase to hypoxanthine, induced decrease of [Mg2+]i. The decrease was significantly inhibited by an anion channel blocker, 4,4'diisothiocyano-2,2' disulfonic acid stilbene (DIDS). Superoxide dismutase (SOD), injected into cells by cell fusion, also inhibited the change of [Mg2+]i, but catalase did not. Superoxide anion induced prompt increase of intracellular pH (pHi) as well as decrease of [Mg2+]i and subsequently activated the increase of intracellular free Ca2+ ([Ca2+]i) and the release of arachidonate. In contrast to superoxide anion, NH4Cl which induces increase of pHi in amnion cells increased [Mg2+]i. The elevation of basal level of [Mg2+]i by Mg(2+)-ionophore inhibited the change of [Ca2+]i and the release of arachidonate induced by superoxide anion. These results suggest that superoxide anion, transported through anion channels into cells, decreases [Mg2+]i directly, not due to a pH-effect and that the decrease of [Mg2+]i may regulate biological functions of the cells via increase of [Ca2+]i.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Altered expression of sialyl-Tn, Lewis antigens and carcinoembryonic antigen between primary and metastatic lesions of uterine cervical cancers.

Immunohistochemical examination was performed of serial sections of 24 normal human adult cervical tissues and 53 human cervical carcinomas including 36 cases with lymph node metastasis. For this investigation, monoclonal antibodies directed to Lewis-X, Lewis-Y, sialyl-dimeric Lewis-X (SDLX), sialyl-Tn (STn) and carcinoembryonic antigen (CEA) were used. STn and CEA antigens were expressed very weakly in the normal cervical epithelium but strongly in the cancer cells, indicating the antigens to be oncogenic antigens of cervical squamous cell carcinoma. No significant difference in immunoreactivity was observed between primary and metastatic lesions of carcinoma or between primary lesions with and without metastasis. However, the expression patterns of STn and Lewis-Y antigens were quite different between primary lesions and metastatic lesions. In primary lesions the cancer cell nests tended to be stained centrally, but in metastatic lesions the cancer cell nests tended to be stained peripherally. This finding may reflect an important role of these carbohydrate chains in the process of metastasis of cervical squamous cell carcinoma to regional lymph nodes.

Antibodies, Monoclonal↗
PubMed1992

Triplet pregnancy involving complete hydatidiform mole and two fetuses: genetic analysis by deoxyribonucleic acid fingerprint.

A case of a triplet pregnancy involving a dizygous twin pregnancy and a complete hydatidiform mole after therapy with human menopausal gonadotropin and human chorionic gonadotropin is reported. Two female fetuses, two placentas in one mass with two amnions and two chorions, and a tumor mass with a grapelike appearance were spontaneously delivered at 19 weeks of gestation. The deoxyribonucleic acid fingerprints of the two placentas and tumor tissue were compared with those of the parents. The fingerprints of the placentas showed patterns different from each other; however, all their polymorphic fragments could be traced back to either the father or mother. All polymorphic fragments of the tumor tissue were inherited only from the father (androgenesis). These results indicated that this triplet pregnancy involved a dizygous twin pregnancy and a complete hydatidiform mole.

Adult↗
PubMed1992

Detection of human papillomavirus types 16 and 18 in the exfoliated cervical cells using the polymerase chain reaction.

We applied the polymerase chain reaction (PCR) to detect HPV 16 and 18 in cytological samples obtained from the uterine cervices of Japanese women. HPV infection was detected in 17 (25%) of 67 with CIN and 11 (37%) of 30 with cervical carcinoma. It is notable that 11 (16%) of 69 women with normal cervices were infected with either HPV 16 or 18. The polymerase chain reaction is sensitive and useful for epidemiological studies.

Adolescent↗
PubMed1992

Estimation by an electrophysiological method of the expression of oxytocin receptor mRNA in human myometrium during pregnancy.

In order to evaluate the changes in uterine oxytocin receptor-specific mRNA during pregnancy, receptor expression in Xenopus oocytes are examined electrophysiologically following microinjection of mRNA from human uterus. In voltage-clamped oocytes injected with term myometrial mRNA, oxytocin elicited an inward current response. The amplitude of the oxytocin-induced current increased with increasing dose of oxytocin, but no current was elicited following stimulation with vasopressin. The oxytocin-induced current was completely eliminated as a result of pretreatment with a specific oxytocin antagonist. 21 of 27 oocytes injected with term myometrial mRNA showed a large amplitude (77.0 +/- 16.1 nA) reaction to oxytocin. In comparison, only 3 of 13 oocytes injected with early gestational myometrial mRNA exhibited a small amplitude (4.6 +/- 1.4 nA) reaction to oxytocin. No oxytocin response was observed in oocytes injected with non-pregnant myometrial mRNA. These results indicate that the striking increment in oxytocin sensitivity in term uterus depends on the increase in mRNA encoding oxytocin receptors.

Animals↗
PubMed1992

Inhibitory effect of medroxyprogesterone acetate on angiogenesis induced by human endometrial cancer.

OBJECTIVE: The purpose of this study was to investigate the effect of medroxyprogesterone acetate on angiogenesis induced by endometrial cancer and to elucidate the possible mechanisms by which it inhibits the growth of the cancer. STUDY DESIGN: Tumors were obtained from 29 patients with endometrial adenocarcinoma, and angiogenesis was assayed in corneas of white rabbits. RESULTS: Transplantation of tumor tissues into rabbit corneas induced angiogenesis in 70.4% of the corneas, but their transplantation with a pellet of medroxyprogesterone acetate induced angiogenesis in only 21.5% of the corneas. This compound also inhibited angiogenesis induced by acidic fibroblast growth factor and transforming growth factor-alpha. CONCLUSION: Inhibition of angiogenesis may be one mechanism by which medroxyprogesterone acetate inhibits the growth of endometrial adenocarcinoma, and its inhibition of neovascularization induced by adenocarcinoma may be through its direct action on endothelial cells.

Adenocarcinoma↗
PubMed1992

The fetus as an allograft: immunobiologic role of human trophoblasts for fetal survival.

OBJECTIVE: The hypothesis of this study is that trophoblasts contribute to the survival of the mammalian fetal allograft. STUDY DESIGN: Immunologic and molecular biologic studies were performed with human trophoblasts or trophoblastic tumor cells to investigate the expression of class I human leukocyte antigens, the susceptibility to natural killer and lymphokine-activated cells, the ontogeny of Fc gamma-receptors, and the production of immunosuppressive factors. RESULTS: Heterogeneous expression of class I human leukocyte antigens on trophoblasts was regulated at transcriptional level. Trophoblasts showed low susceptibility to natural killer and lymphokine-activated cells. Trophoblasts expressed natural killer cell-type Fc gamma-receptor III, which mediates phagocytosis. The trophoblast-derived immunosuppressive factor was very similar to transforming growth factor-beta. CONCLUSION: The trophoblasts, which ultimately form the fetoplacental interface, constitute a major immune barrier for the survival of the allogenic conceptus.

Female↗
PubMed1992

Expression of E-cadherin in normal, benign, and malignant tissues of female genital organs.

The expression of human E-cadherin in normal tissues and in benign and malignant tumors of female genital organs was examined immunohistochemically with a monoclonal antibody, HECD-1, specific for human E-cadherin. The normal tissues included the ovary, fallopian tube, uterine endometrium, uterine cervix, and vagina. E-cadherin was detected clearly in the cell-to-cell boundaries of both normal glandular and squamous epithelia obtained from those tissues. The tumor tissues consisted of 9 ovarian, 7 endometrial, and 4 cervical adenocarcinomas, 12 squamous cell carcinomas of the cervix, including 3 cervical intraepithelial neoplasms, and 5 mesenchymal tumors. E-cadherin also was detected in the cell-to-cell borders of all the epithelial tumors tested, with some reactivity in the cytoplasm of malignant cells, whereas mesenchymal tumors showed no expression. It is noteworthy that poorly differentiated areas of both the adenocarcinomas and squamous cell carcinomas showed less expression of E-cadherin. No difference in the expression of E-cadherin between the primary and metastatic lesions was detected in 10 sets of malignant tumors. E-cadherin may be an important factor among a variety of biologic events that occur during the process of metastasis. However, further studies are needed to clarify this.

Antibodies, Monoclonal↗
PubMed1992

Interleukin-8 in cord sera: a sensitive and specific marker for the detection of preterm chorioamnionitis.

Interleukin-8 (IL-8) exerts chemotactic activity on neutrophils at inflammatory sites to eliminate invading bacteria. To investigate whether the preterm fetus with chorioamnionitis produces IL-8, the titers of IL-8 were examined in sera of babies with (n = 38) and without chorioamnionitis (n = 34) using an EIA kit specific for IL-8. The infected babies had a significantly higher IL-8 titer than those not infected at 22-36 gestational weeks. The IL-8 titer was increased even in the mild histologic stage of chorioamnionitis and became much higher in the more severe stage. The IL-8 elevation, however, was remarkably suppressed by infusion of a steroid into the mother to promote fetal lung maturation. This retrospective study demonstrated that titration of IL-8 in cord serum is a more useful marker for the early detection of chorioamnionitis, because of its higher sensitivity and specificity, than conventional markers such as C-reactive protein.

Anti-Bacterial Agents↗
PubMed1992

Human placenta constitutively produces interleukin-8 during pregnancy and enhances its production in intrauterine infection.

Interleukin-8 (IL-8) exerts unique chemotactic and activating activity on neutrophils. To address the significance of IL-8 in the fetoplacental unit during pregnancy, we cultured human placental explants that had been obtained by vaginal delivery, Caesarean section, or artificial abortion and then measured the IL-8 titer in the culture supernatants by enzyme immunoassay (EIA). Chorionic tissue from the first trimester produced a significant amount of IL-8 (2.2 +/- 0.4 ng/ml/10 mg, n = 5), while placentae in the second trimester (8.3 +/- 1.6 ng/ml/10 mg, n = 7) or at term (9.2 +/- 0.7 ng/ml/10 mg, n = 29) produced significantly higher amounts of IL-8. The presence or absence of labor did not affect the amount of placental IL-8 production. However, placentae with chorioamnionitis (25.2 +/- 1.6 ng/ml/10 mg, n = 9) showed significantly higher IL-8 production than those without chorioamnionitis (p less than 0.0001). Northern blot analysis of IL-8 mRNA expression demonstrated a constant level during pregnancy with or without chorioamnionitis, indicating the possibility that the major site of regulation of IL-8 synthesis in the placenta is posttranscriptional. Immunohistochemical analysis of first and third trimester placental tissues with rabbit anti-IL-8 antibody revealed the IL-8 producing cells to be trophoblasts and macrophage-like cells. IL-8 produced by the placental cells might contribute to potentiation of the immunocompetence of placental cells against bacteria invading the fetoplacental unit.

Blotting, Northern↗
PubMed1992

Intermittent intensive combination chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (cyclic PAC chemotherapy) for ovarian cancer.

Despite high primary response rates with cisplatin-based combination chemotherapy, the overall survival rate for advanced ovarian cancer remains unsatisfactory. This prompted us to design a new systematic approach using a combination chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide (PAC), namely, cyclic PAC chemotherapy. This is a 3-step chemotherapy with 3 courses of the PAC regimen in each step. It was administered for 18 months to patients with clinical Stage Ic-IV ovarian cancer, after cytoreductive surgery. In the present study, the cyclic PAC, brief PAC, and FAM (5-Fu, an alkylating agent, and mitomycin C) groups included 27 cases, 34 cases, and 38 cases, respectively. Treatment of Stage Ic-IV disease by cyclic PAC improved the outcome (57% estimated 5-year survival rate) compared to brief-PAC and FAM (20% and 32%, respectively). The outcome for patients with Stage III or IV ovarian cancer was also superior for the cyclic-PAC group compared to the brief-PAC and FAM groups (cyclic-PAC 44%, brief-PAC 9%, and FAM 0% estimated 5-year survival rates). Cyclic PAC chemotherapy was thus found to be capable of dramatically improving the long-term survival rate of ovarian cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Sialyl-Tn, sialyl-Lewis Xi, CA 19-9, CA 125, carcinoembryonic antigen, and tissue polypeptide antigen in differentiating ovarian cancer from benign tumors.

Serum sialyl-Tn, sialyl-Lewis Xi, CA 19-9, CA 125, carcinoembryonic antigen (CEA), and tissue polypeptide antigen were measured in 65 women with early-stage ovarian cancer (45 stage I and 20 stage II cases) and 317 with benign pelvic masses. As a single assay, sialyl-Tn showed the best sensitivity and specificity, 46 and 92%, respectively. CA 19-9 detected the greatest number of cancer patients but had the lowest specificity. The combination of sialyl-Tn, CA 125, tissue polypeptide antigen, and CEA seemed to perform the best, with a sensitivity and specificity of 71 and 76%, respectively. The combination of sialyl-Tn, CA 125, and tissue polypeptide antigen gave similar results and may be more cost-effective. However, one-fifth of the patients with early-stage cancer still showed up as false negatives even with use of the six markers in combination. Approaches other than serum assay alone will be needed to detect all malignant pelvic masses at an early stage.

Antigens, Neoplasm↗