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Biomedical subjects

O Tanizawa

Publications and source records attributed to O Tanizawa.

At least 145 records · Page 8Linked to original sources

[Re-evaluation of hysteroscopy in the diagnosis of uterine endometrial cancer].

To evaluate the clinical value of hysteroscopy in the management of endometrial cancer, findings in 3,681 patients with endometrial cancer treated between 1985 and 1989 at 167 hospitals in Japan were analyzed. In 1,040 of these patients, hysteroscopy was performed before operation. Pre-operative staging by fractional curettage with or without hysteroscopy was compared with post-operative histological diagnoses. The accuracy rates of diagnosis at final stages I and II were 91.4% and 79.4%, respectively, with hysteroscopy. There figures were not significantly different from those of 91.4% and 77.7% without hysteroscopy. The accuracy rate for diagnosis at the final stage I was 98.0% with the hystero-fiberscope and significantly higher than that with rigid hysteroscopy (86.0%). Tumor cells in the pelvic cavity were examined at the time of operation in 1,115 patients. Tumor cells were found in 8.5% of those in stage I, 18.8% of those in stage II, 64.7% of those in stage III and 75.0% of those in Stage IV by hysteroscopy. These values were not significantly different from those of 7.3%, 22.7%, 57.1% and 81.1%, respectively, observed without hysteroscopy. These findings indicate that hystero-fiberscopy might be valuable for the pre-operative diagnosis of endometrial cancer, but has no effect on cytological malignancy in the peritoneal cavity.

Adult↗

[Prenatal evaluation of the platelet counts in the fetuses and the neonates of the mothers complicated with idiopathic thrombocytopenic purpura].

We investigated 25 pregnancies with ITP. The results were as follows. 1. The platelet counts of the maternal blood just before delivery were not correlated with those of the cord blood. 2. It was suggested that the maternal PAIgG value just before delivery could foretell the onset of neonatal thrombocytopenic purpura. 3. The platelet counts in fetal scalp blood were correlated with those of the cord blood, but falsely lower platelet counts were found in the fetal scalp samples. 4. We saw 5 cases of percutaneous umbilical blood sampling (PUBS) in pregnancies with ITP. PUBS was found to be a useful and safe method. The indications for PUBS and fetal platelet transfusion in pregnancy with ITP are discussed.

Cesarean Section↗

Direct measurement of intracellular free calcium in cultured human puerperal myometrial cells stimulated by oxytocin: effects of extracellular calcium and calcium channel blockers.

The changes in intracellular free calcium concentration ([Ca2+]i) induced by oxytocin in single cells of cultured human puerperal myometrium were measured with the calcium-sensitive fluorescent dye fura 2 in a digital imaging fluorescence microscopic system. Oxytocin at concentrations of 30-300 nmol/L induced a dose-dependent increase in [Ca2+]i with a peak at 20 seconds. This increase depended mainly on extracellular calcium ([Ca2+]ex) at concentrations of 0.6-4.8 mmol/L. In the absence of [Ca2+]ex, the increase was only 16% of that in its presence. The voltage-sensitive calcium channel blockers nicardipine, nifedipine, and nitrendipine had similar effects, causing significant suppression of the increase in [Ca2+]i induced by oxytocin. Diltiazem also suppressed the increase in [Ca2+]i, though less than the other calcium channel blockers. These data indicate that the increase in [Ca2+]i induced by oxytocin is predominantly dependent upon [Ca2+]ex. Furthermore, the data explain why calcium channel blockers are effective for weakening uterine muscle contractions and indicate which type of blocker is most effective.

Calcium↗

[Clinical significance of serum sialyl Tn antigen in patients with gynecological cancer. STN Study Group].

Serum sialyl Tn antigen was assayed in gynecological cancer and benign patients by means of "STN OTSUKA" kits. Fifty-eight of 140 (41.1%) ovarian cancer patients showed a significant elevation of sialyl Tn antigen in serum above the cut-off level of 45 unit/ml (mean +2SD) determined from normal controls. There was no feature of positive frequency in tissue type, including serious carcinoma (47.6%), mucinous carcinoma (45.5%), clear cell carcinoma (30.4%) and endometrioid carcinoma (55.6%), but the positive frequency of mucinous carcinoma (36.8%) was higher than that of serous carcinoma (11.1%) in stage I. Compared with other markers, sialyl Tn antigen showed a very much lower false-positive rate (3.6%) in benign gynecological diseases. In the diagnosis of ovarian cancers, the combination assay of sialyl Tn antigen and CA 125 increased diagnostic efficiency compared with any other combination assays. Therefore, sialyl Tn antigen will be a useful tumor marker for ovarian cancers.

Antigens, Neoplasm↗

Superoxide anion increases intracellular free calcium in human myometrial cells.

We investigated the effects of superoxide anion on the intracellular free calcium concentration ([Ca2+]i) in human cultured myometrial cells using a calcium-sensitive fluorescent dye, indo-1, and a digital imaging fluorescence microscopic system. Hypoxanthine (HX) plus xanthine oxidase induced a rise in [Ca2+]i in a manner dose-dependent on xanthine oxidase. The increase in [Ca2+]i in the absence of extracellular calcium ([Ca2+]ex) was 10% of that in the presence of [Ca2+]ex. Nifedipine, which blocks voltage-sensitive calcium channels, also reduced the increase in [Ca2+]i induced by HX-xanthine oxidase. Superoxide dismutase or superoxide dismutase plus catalase, which metabolizes superoxide anion, inhibited the effect of HX-xanthine oxidase on [Ca2+]i. The desensitization of the effect of superoxide anion on [Ca2+]i was investigated by pulsatile administration of HX and xanthine oxidase. Desensitization was observed on pulsatile administration of HX-xanthine oxidase at 2-min intervals. These data suggest that superoxide production may participate in uterine contraction via [Ca2+]i increase.

Calcium↗

Perinatal infection of human T-lymphotropic virus type I, the etiologic virus of adult T-cell leukemia/lymphoma. DNA amplification of specific human T-lymphotropic virus type I sequences.

A gene amplification technique, polymerase chain reaction, was used to detect human T-lymphotropic virus type I (HTLV-I), the etiologic agent of adult T-cell leukemia/lymphoma, in mononuclear cells in peripheral blood and breast milk of ten HTLV-I carrier gravida. The DNA in umbilical cord blood mononuclear cells of the neonates born to the HTLV-I carrier gravida were also amplified and examined for the possibility of HTLV-I infection via placenta during pregnancy. The HTLV-I sequences were detected both in the peripheral blood and milk of all ten carrier gravida by Southern blot analysis of amplified DNA. However, HTLV-I proviral DNA could not be detected in the cord blood of the carriers' neonates, indicating that transplacental infection of HTLV-I should be rare and that postpartum infection via breast milk is a likely major perinatal transmission route.

Antibodies, Neoplasm↗

K-ras activation in neoplasms of the human female reproductive tract.

The role of cellular oncogenes in the development of epithelial tumors of the human female reproductive tract has not previously been extensively studied. DNAs isolated from ten human uterine, 13 ovarian, and four cervical neoplasms and from three cell lines derived from endometrial adenocarcinoma were investigated by dot blot hybridization after polymerase chain reaction amplification of ras gene sequences and in some cases by NIH 3T3 transfection. Transforming activity was found in two of nine endometrial adenocarcinomas, but none of seven ovarian carcinomas and none of four cervical carcinomas showed transforming activity. K-ras sequences with a GGT----GAT mutation in codon 12 were demonstrated in both transformants derived from endometrial carcinoma. K-ras codon 12 mutations were similarly detected in six of 13 endometrial carcinomas (one GAT and GCT, one GTT and GCT, two GAT, two GTT) and two of 13 ovarian tumors (GAT and GCT, GAT), both mucinous adenocarcinomas. Point mutation of K-ras in codon 12 is thus comparably frequent in uterine endometrial carcinomas and in colorectal carcinomas and may have similar significance as an event that contributes to progression of these tumors. Cervical carcinomas and ovarian tumors in general, with the possible exception of mucinous adenocarcinoma of the ovary, do not appear to have this characteristic.

Animals↗

Studies on the pathogenesis of choriocarcinoma by analysis of restriction fragment length polymorphisms.

The association of complete hydatidiform mole with choriocarcinoma has long been recognized, but it is unknown whether the pathogenesis of the two are identical. We investigated the pathogenesis of these trophoblastic tumors by analyzing restriction fragment length polymorphisms using a minisatellite DNA probe to choriocarcinoma, the complete mole, and normal trophoblasts as well as the parental cells. The polymorphic fragments of the complete mole were all transmitted from the paternal DNA, but some polymorphic fragments of the paternal DNA were not recognized in the complete mole. This confirms at a molecular level the androgenetic origin of the complete mole. In some cases of choriocarcinoma, the pattern of inheritance of restriction fragment length polymorphisms was the same as that in the complete mole, whereas in others all the polymorphic fragments in tumor tissues were identical to those in the host DNA. These results suggest that the pathogenesis of choriocarcinoma varies, being completely different from that of the complete hydatidiform mole in some cases.

Choriocarcinoma↗

Altered expression of Lewis blood group and related antigens in fetal, normal adult and malignant tissues of the uterine endometrium.

The expression of the Lewis blood group and its related antigens in fetal, normal adult and malignant tissues of the uterine endometrium was examined immunohistochemically using a panel of mouse monoclonal antibodies with specificities for Lewis-a (La), Sialyl Lewis-a (SLa), Lewis-b (Lb), Lewis-X (LX), Sialyl Lewis-X (SLX) and Lewis-Y (LY) antigens. La, SLa and SLX having one fucose residue were detected in a small number of fetal tissues, while Lb and LY having two fucose residues were found in most cases. In the adult endometrium, expression of Lb and LY was considerably lower than those in fetal tissues, although expression of La and SLa was not different between these two tissues. Expression of LX and SLX was pronounced in adult when compared with fetal tissues. Malignant endometrial glands expressed La, SLa, Lb and LY, extensively, while LX and SLX were expressed less than in normal tissues. Lb and LY can thus be considered oncofetal antigens, extensively expressed in fetal and malignant tissues but not in normal adult tissues. Expression of Lb and LY was greater than that of La and SLA in carcinoma; an increase in the activity of fucose transferase might be associated with malignant transformation in the uterine endometrium.

Adult↗

Effects of danazol, gonadotropin-releasing hormone agonist, and a combination of danazol and gonadotropin-releasing hormone agonist on experimental endometriosis.

Effects of danazol, gonadotropin-releasing hormone agonist (leuprolide), and danazol-leuprolide combination on experimental endometriosis were evaluated in female rats. A complete resorption of the fluid and a marked decrease in the volume of endometrium autotransplanted under the renal capsule were found after castration (1.4 +/- 0.1 mm3 in castrated, n = 14, vs 26.7 +/- 5.6 mm3 in intact control, n = 16). Histologic examination indicated atrophy and regression of the endometrial explant. These atrophic changes of endometrial explant were also induced by danazol, leuprolide, and the combination treatment. However, the volume of explants after combination therapy with danazol and leuprolide (1.8 +/- 1.0 mm3, n = 17) was significantly less than that after therapy with danazol (11.6 +/- 2.8 mm3, n = 20) or leuprolide alone (5.9 +/- 1.4 mm3, n = 24). The combination therapy (16/17) was also shown to be superior to danazol (9/20) or leuprolide alone (14/24) to induce the regression of fluid in experimental endometriosis. As expected, administration of leuprolide decreased the serum estradiol level, but use of danazol did not. These findings suggest that a combination therapy of danazol and gonadotropin-releasing hormone agonist, which show different modes of action, may be a potential modality in treatment of patients with advanced endometriosis.

Analysis of Variance↗

Differential diagnosis between complete mole and hydropic abortus by deoxyribonucleic acid fingerprints.

We used a new method of deoxyribonucleic acid fingerprint analysis to obtain the differential diagnosis between complete mole and hydropic abortus. This method with a deoxyribonucleic acid minisatellite probe requires only a small amount of tissue sample and peripheral blood, and presents individual specific restriction fragment length polymorphisms (deoxyribonucleic acid "fingerprints") by simultaneous detection of many hypervariable regions (minisatellite regions) widely dispersed in the human genome. Southern blot hybridization showed that in cases of complete mole, all polymorphic fragments were exclusively inherited from the father. Some of the polymorphic bands of paternal deoxyribonucleic acid were not observed in molar deoxyribonucleic acid. However, in the hydropic abortus, the polymorphic fragments could be traced back to its parent. These results indicate that deoxyribonucleic acid fingerprints could distinguish the abnormal fertilization of complete mole (androgenesis) from the normal fertilization of hydropic abortus by identifying the difference in genetic variations between complete mole and hydropic abortus at the deoxyribonucleic acid level.

Blotting, Southern↗

In vitro and in vivo production of interleukin-6 by fetal mononuclear cells.

We examined the functional activity of cord mononuclear cells (MNCs) to produce interleukin (IL)-6 in vitro and in vivo. We stimulated fetal T-cell, B-cell, and macrophage fractions with mitogens. The supernatant of each stimulated cord cell fraction contained a comparable amount of IL-6 to that of each adult cell fraction activated similarly, suggesting functional maturity of cord MNCs' ability to produce IL-6. We then examined fetal cells' activities to produce IL-6 in response to perinatal infections, especially to intraamniotic infections (IAI). Among the cord MNCs from fetuses with IAI, macrophages were major cells producing IL-6. The serum IL-6 level in the fetuses with IAI was elevated, but it decreased to normal levels after antibiotic treatment; this finding indicates that IL-6-mediated host defense mechanisms by cord MNCs are triggered by perinatal infections.

Amniotic Fluid↗

Impaired development of mammary glands in scorbutic rats unable to synthesize ascorbic acid.

The effects of ascorbic acid (AsA)-deficiency on the development of mammary glands were investigated using mutant rats (osteogenic disorder syndrome rats; ODS rats) with hereditary inability to synthesize AsA. Female ODS rats of 21 days old were castrated and divided into two groups. One group was given AsA in their drinking water, and the other was not. All the rats received a daily injection of oestradiol-17 beta and progesterone (EP) from day 28 to day 49 of age. After EP treatment, the concentrations of AsA in the mammary glands of rats not given AsA were less than one tenth of those of rats given AsA and the contents of hydroxyproline in the mammary glands of the former rats were about half of those in the latter. Furthermore, the concentration of serum prolactin in rats not given AsA was reduced to about one third of that in rats given AsA. After EP treatment, whole mounts of mammary glands showed that in rats not given AsA the development of ducts was impaired and there was extensive accumulation of endbuds. Consistent with this finding, EP injections did not increase the area of parenchyma in the mammary glands of rats not given AsA, whereas they increased it about 2-fold in rats given AsA. Moreover, after EP treatment the amount of alpha-lactalbumin was significantly less in the mammary parenchyma of rats not given AsA than in that of rats given AsA. On the other hand, AsA deficiency did not impair the response of the mammary cells to insulin or prolactin in terms of DNA synthesis and alpha-lactalbumin production. These findings indicate that AsA deficiency impaired the development of mammary glands. This effect may be partly attributable to a defect in collagen synthesis in the mammary glands and a decrease in the concentration of serum prolactin.

Animals↗

Changes of bioactive luteinizing hormone after laparoscopic ovarian cautery in patients with polycystic ovarian syndrome.

The serum levels of bioactive luteinizing hormone (LH), immunoreactive LH, follicle-stimulating hormone, androstenedione (A), and testosterone (T) were determined in nine anovulatory women with polycystic ovarian syndrome (PCOS) before and after laparoscopic ovarian cautery. Eight ovulated spontaneously and three conceived after treatment. Before treatment, the mean (+/- SEM) levels of bioactive LH, immunoreactive LH, A, and T were 51.4 +/- 8.6 mIU/mL, 36.0 +/- 4.5 mIU/mL, 1.98 +/- 0.35 ng/mL, and 1.18 +/- 0.13 ng/mL, respectively, which were significantly higher than those of five control women (19.2 +/- 1.6 mIU/mL, 21.4 +/- 1.2 mIU/mL, 0.54 +/- 0.03 ng/mL, 0.28 +/- 0.03 ng/mL). After treatment, the mean levels of these hormones had significantly decreased. Decreases in the levels of these hormones by laparoscopic ovarian cautery in women with PCOS may result in both restoration of the ovulatory cycle and achievement of pregnancy.

Adult↗

Expression of the corticotropin-releasing hormone (CRH) gene in human placenta and amniotic membrane.

Immunoreactive corticotropin-releasing hormone (IR-CRH) in maternal plasma increases progressively during pregnancy and decreases rapidly after delivery, suggesting that IR-CRH is produced in the placenta. We studied the expression of the CRH gene in developing human chorionic tissue, the amniotic membrane, the uterine myometrium and a fresh surgical specimen of hydatidiform mole by Northern blot analysis. Our results were as follows: (1) CRH mRNA was demonstrated in the placenta in the third trimester and at term, but under detectable level in the first and second trimesters. (2) CRH mRNA expression was observed in the amniotic membrane, but its expression in the myometrium in normal pregnancy was under detectable level at term. (3) CRH mRNA was also under detectable level in trophoblasts of a hydatidiform mole. These results suggest that the sources of the increased level of IR-CRH in human plasma and amniotic fluid during pregnancy are the placenta and amniotic membrane, and that gene expression of placental CRH increases during pregnancy.

Amnion↗

A novel monoclonal antibody against squamous cell carcinoma.

The monoclonal antibody, INS-2, was raised against rat fibroblasts transformed by open reading frames E6 and E7 of human papillomavirus (HPV) DNA. In immunoperoxidase testing of frozen sections, the INS-2 antibody was reactive with all squamous cell carcinomas of the uterine cervix and esophagus tested. In contrast, no antibody binding was detected with adenocarcinomas of various origins. Similarly, normal tissues, lymphoid cells and erythrocytes from multiple donors were negative, except that binding localized at basal cells in normal squamous epithelium was observed. Interestingly, strong staining was observed in dysplastic cells of cervical intraepithelial neoplasia and at the growing edge of squamous cell carcinomas. The antigen for the INS-2 antibody is a non-sialyl glycoprotein with Mw. 40,000 and appears to be a squamous cell-specific cell differentiation marker, although it is not related to HPV-DNA-derived protein.

Animals↗

Clinical evaluation of a direct colorimetic method for determination of amniotic phospholipids.

Evaluation of amniotic phospholipids, which are a parameter of fetal lung maturation, is important in the management of premature infants. The method available for measuring the lecithin/sphingomyelin (L/S) ratio, which appears to provide an index to fetal lung maturity, is laborious, involving determinations of phospholipids, and so is unsuitable for rapid quantitative measurement of phospholipids in the amniotic fluid in the perinatal period. We developed a simple, sensitive colorimetric assay for phospholipids without their extraction. This assay is based on the fact that phospholipids form stable hydrophobic complexes with Co(SCN)4, Fe(SCN)2- and Fe(SCN)3 within about 1 hr. Amniotic fluid samples (n = 115) were collected from women with normal and abnormal pregnancies in week 16-41 of pregnancy, and these samples were examined both by thin layer chromatography (TLC) and by our method of phospholipid determination. Good correlations were observed between the L/S ratio determined by TLC and the values obtained by this method. Moreover the distributions of the dipalmitoylphosphatidylcholine (DPPC) content and DPPC/sphingomyelin (SM) ratio were similar to those of the PC content and L/S ratio. This method was proved to be more accurate than other methods such as TLC and the shake test for predicting neonatal RDS.

Amniotic Fluid↗