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Biomedical subjects

Y Tomoda

Publications and source records attributed to Y Tomoda.

At least 37 records · Page 2Linked to original sources

Clinical behavior of borderline ovarian tumors: a study of 150 cases.

BACKGROUND: We evaluated the clinical features, treatment, and survival status of the patients with borderline ovarian tumors. METHODS: A retrospective review of the charts of 150 patients with borderline ovarian tumor registered at the Tokai Ovarian Tumor Study Group from January 1, 1980, to December 31, 1994, was conducted to obtain clinical and pathological information. RESULTS: In stage II and III disease, the numbers of patients with no residual tumor, residual tumor of <2 cm, 2-5 cm, and >5 cm were 9, 10, 3, and 3, respectively. The sizes of residual tumors and corresponding clinical response to chemotherapy were as follows: residual tumor of <2 cm, complete response (CR), 6 patients; no change (NC), 2; progressive disease (PD), 2; tumors 2-5 cm, NC, 1 patient, PD, 2; tumors >5 cm, PD, 3 patients. The survival for patients with residual tumor <2 cm was significantly better than for those with residual tumor from 2-5 cm and of >5 cm (P < 0.05). The survival for patients with stage II and III serous tumor was significantly longer than that for patients with stage II and III mucinous tumor (P < 0.05). CONCLUSION: In advanced borderline ovarian tumor, the prognosis of patients with gross residual tumor after initial surgery, and especially with mucinous tumor, was poor.

Adolescent↗

Effects of 17 beta-estradiol and progesterone on migration of human monocytic THP-1 cells stimulated by minimally oxidized low-density lipoprotein in vitro.

OBJECTIVE: Many epidemiological studies have shown that postmenopausal hormone replacement therapy (HRT) has a beneficial effect on atherosclerotic cardiovascular disease. The aim of this study was to investigate the effects of estrogen and progestin on the migration of monocytes induced by minimally oxidized low-density lipoprotein (m-ox-LDL) in vitro. METHODS: Human monocytic THP-1 cells were used for the study. Migration assay was performed using a modified Boyden chamber. RESULTS: The presence of estrogen receptors was determined in THP-1 cells by Western and Northern blot analysis. Although native LDL had no significant effects on the migration of THP-1 cells, m-ox-LDL increased the migration of THP-1 cells in a dose-dependent manner. Although 17 beta-estradiol (E2, 10(-9)-10(-6) M) inhibited the 10 micrograms/ml-induced migration of THP-1 cells in a dose-dependent manner, estrone (E1), estriol (E3) and progesterone (P) had no significant effects. The combination of P (10(-9)-10(-6) M) did not show any effect on the inhibitory effect of 10(-7) M E2. Preincubation of THP-1 cells with the anti-estrogenic agent, tamoxifen (10(-6) M), significantly antagonized the inhibitory effect of 10(-7) M E2. m-ox-LDL stimulated MCP-1 secretion from THP-1 cells, which was reduced by E2. Anti-human MCP-1 neutralizing antibody inhibited the migration of THP-1 cells stimulated by m-ox-LDL. E2 also inhibited the 10 ng/ml MCP-1-induced migration of THP-1 cells in a dose-dependent manner. CONCLUSIONS: These findings suggest that the inhibitory effect of E2 on the migration of monocytes might be one of the factors involved in the decreased incidence of atherosclerotic cardiovascular disease in premenopausal women and postmenopausal HRT.

Adult↗

Fetal heart rate patterns associated with periventricular leukomalacia.

OBJECTIVE: Our purpose was to assess the applicability of fetal heart rate (FHR) monitoring to detect fetuses at risk of developing periventricular leukomalacia (PVL). METHODS: FHR tracings obtained for babies delivered under 33 weeks' gestation and with a birth weight under 2000 g were assessed for baseline heart rate, variability, deceleration and "flip flap' (an oscillatory tracing pattern). RESULTS: PVL developed in 19 of the 103 infants studied. All of these infants were among the fetuses who exhibited average and increased variability. In addition, PVL was detected in 10 (47.6%) of the 21 flip flap positive fetuses, and in 9 (11.0%) of the 82 flip flap negative fetuses. The incidence of PVL was significantly higher in the flip flap positive fetuses (P < 0.005). CONCLUSION: The possibility that an unstable intrauterine environment, reflected by a flip flap pattern, is related to the subsequent development of PVL is indicated.

Female↗

Human amniotic fluid motogenic activity for fetal alveolar type II cells by way of hepatocyte growth factor.

OBJECTIVE: To find out if hepatocyte growth factor (HGF) in amniotic fluid (HGF-AF) has a direct effect on fetal lung development, we investigated the effects of AF as well as recombinant human HGF (rhHGF) on proliferation, migration, and morphogenesis of fetal alveolar type II cells in vitro. METHODS: Amniotic fluid samples were obtained from 37 women at various gestational ages. Mitogenic, motogenic, and morphogenic activity was investigated by 5-bromo-2'-deoxyuridine incorporation, Boyden chamber assay, and culture in collagen-gels, respectively. RESULTS: The motility of AK-D cells was stimulated by AF from 14 to 31 weeks' gestation in proportion to the concentration of HGF-AF, and this effect was comparable to that observed with rhHGF. Furthermore, this activity was neutralized by anti-human HGF antibody. However, AF samples subsequent to 32 weeks had no motogenic influence despite the continued presence of immunoreactive HGF-AF. Neither increased DNA synthesis nor morphogenesis in response to AF was identified under the conditions used. CONCLUSION: The present study suggests that AF stimulates alveolar type II cell migration by way of HGF-AF in vitro.

Amniotic Fluid↗

Squamous cell carcinoma arising from mature cystic teratoma of the ovary: a clinicopathologic analysis.

OBJECTIVE: There have been few studies concerning the clinical pathology of squamous cell carcinoma arising from ovarian mature cystic teratoma. Thus, the objective of this study is to determine clinicopathologic factors affecting survival in this rare tumor. METHODS: From September 1979 to June 1996, 37 patients with squamous cell carcinoma arising from ovarian mature cystic teratoma were treated by the Tokai Ovarian Tumor Study Group. A retrospective clinicopathologic and survival analysis of these patients was performed. The mode of infiltration was classified into expansive, moderately diffused, and diffused patterns. RESULTS: Although the 5-year survival rate was 94.7% and 80.0% for stage I and II patients, respectively, 12 of 13 patients with stage III died within 20 months (P = .0001). A significant difference was also observed between the survival of the groups with and without residual tumor at surgery (P = .0001). Pathologic features, grade, mode of infiltration, and vascular involvement were significant factors by univariate analysis. Multivariate analysis showed significant differences in survival related to grade (P = .0154) and mode of infiltration (P = .0053). The preoperative squamous cell carcinoma antigen level was significantly higher in the patients with squamous cell carcinoma arising from mature cystic teratoma than in patients with mature cystic teratoma (P < .0001). CONCLUSION: This study suggests that pathologic factors, grade, and mode of infiltration can provide valuable information for predicting the survival of patients with squamous cell carcinoma arising from mature cystic teratoma. In addition, squamous cell carcinoma antigen may be a useful marker to detect this disease preoperatively.

Adult↗

Expression of midkine and pleiotropin in ovarian tumors.

OBJECTIVE: To compare the expression of midkine and pleiotropin in malignant ovarian tumors with that in normal and benign ovarian tissue. METHODS: Total RNA was isolated from 23 samples of normal ovaries, 15 benign ovarian tumors, and 36 malignant ovarian tumors. Midkine and pleiotropin gene expression was examined by using Northern blot analysis. To confirm the localization of midkine expression, in situ hybridization and immunohistochemical analyses were performed. The truncated midkine messenger RNA was examined using polymerase chain reaction with complementary DNA synthesized from total RNA with reverse transcriptase. RESULTS: Expression of midkine gene was observed in 19 of 23 normal ovary samples and in 51 of 53 ovarian tumors (13 of 15 benign, both of the two borderline tumors, and all 36 malignant tumors). Pleiotropin gene was expressed in six normal ovaries and in 24 tumors (nine benign, two borderline, and 13 malignant tumors). The expression of midkine in germ cell tumors was significantly lower than in epithelial tumors, whereas expression in malignant epithelial tumors was significantly higher than in benign ones. In germ cell tumors, two samples with differentiated neural tissues showed high levels of pleiotropin gene expression. In situ hybridization and immunohistochemical analysis showed strong expression of midkine in cancer cells. The truncated midkine messenger RNA was not found in any of the normal, benign, or malignant tissues examined. CONCLUSION: These results suggest an association between midkine and carcinogenesis. Expression of pleiotropin is more restricted, and high levels of its expression may be correlated with neural differentiation.

Adult↗

Increased matrix metalloproteinase-9 activity in human ovarian cancer cells cultured with conditioned medium from human peritoneal tissue.

Ovarian cancer cells disseminate by attachment to the peritoneal mesothelial cell surface of the abdominal cavity. We therefore investigated the influence of conditioned medium (CM) from human peritoneal tissues and mesothelial cells on the secretion of matrix metalloproteinases (MMPs) by ovarian cancer cells. The molecular weights of MMPs stimulating factors derived from human peritoneal tissues and mesothelial cells were estimated using microconcentrators with various cut-off membranes. Human peritoneal tissues were obtained from 12 surgical patients, and mesothelial cells were isolated from three peritoneal specimens. Exposure to CM from peritoneal tissue caused a concentration-dependent increase of the MMP-2 and MMP-9 bands in CM from NOM1 ovarian cancer cells, as shown by zymography. There was a significant difference in the increase of MMP-2 and MMP-9 (2.46-fold and 7.14-fold, respectively, at 0.4 mg/ml protein; P < 0.005). CM from mesothelial cells also significantly increased the secretion of MMP-9 by NOM1 cells. The molecular size of possible MMP-9-stimulating factors secreted by peritoneal tissues and mesothelial cells was above M(r) 100000. Further, CM of peritoneal tissues and mesothelial cells also induced the invasiveness of NOM1 cells. These findings suggest that mesothelial cells may secrete some factors which predominantly induce the MMP-9 production and increase invading cell numbers.

Collagenases↗

Alteration of N-linked oligosaccharide structures of human chorionic gonadotropin beta-subunit by disruption of disulfide bonds.

The human chorionic gonadotropin beta-subunit (hCGbeta) is a glycoprotein in which 12 cysteine residues pair to form six intramolecular disulfide bonds. In order to elucidate the effect of each disulfide bond on glycosylation of the molecule, we analysed structures of asparagine-linked oligosaccharides of various recombinant hCGbeta produced in Chinese hamster ovary (CHO) cells: wild-type hCGbeta (betaWT) and mutants in which any one of the six intramolecular disulfide bonds had been disrupted by site-directed mutagenesis. SDS-PAGE analysis of betaWT and these mutants before and after digestion with endoglycosidase F and H revealed structural changes in the oligosaccharide moieties of some mutants. In addition, structural analysis of oligosaccharides obtained from metabolically labeled betaWT and a mutant showed that the mutant contained additional high mannose type oligosaccharides. These results suggest that elimination of a specific disulfide bond, resulting in a change in the protein conformation, disturbs the normal assembly of the mature complex type oligosaccharides in the hCGbeta molecule.

Acetylglucosamine↗

Hyaluronidase activity in gynaecological cancer tissues with different metastatic forms.

We investigated hyaluronidase activity in gynaecological normal and malignant tissues. Hyaluronidase activity in culture medium of tissue specimens was detected by hyaluronic acid zymography and quantified by densitometry. Hyaluronidase activity was shown as one dominant band (molecular weight 65 kDa) at pH 3.5. Hyaluronidase activity was significantly higher in normal ovary (P < 0.05) and normal endometrium (P< 0.05) than in normal cervix. One dominant 65-kDa hyaluronidase was expressed in 100% (14 out of 14) of ovarian cancer tissues and in 91% (10 out of 11) of endometrial cancer tissues. However, hyaluronidase activity was not observed in cervical cancer tissues. Hyaluronidase activity was significantly higher in ovarian (P < 0.001) and endometrial (P < 0.01) cancer tissues than in cervical cancer tissue and was significantly higher in ovarian cancer tissue than in endometrial cancer tissue (P < 0.05). These facts suggest that the cancer cells make use of the original characteristic of the organ to invade and metastasize. Moreover, these results reflect the difference in metastatic forms and are suggestive of a strong relationship between hyaluronidase activity and invasion and metastasis of ovarian and endometrial cancers compared with cervical cancer.

Adult↗

Possible involvement of placental proteases in bradykinin (BK) degradation.

The hydrolysis of bradykinin (BK) by human placental subcellular fractions and pregnancy sera was studied in the presence of inhibitors by measuring amino acids liberated from BK by high-performance liquid chromatography. The effects of the inhibitors DL-2-mercaptomethyl-3-guanidinoethylthiopropionic acid (MGTA, for kininase I), phosphoramidon (for endopeptidase 24.11) and captopril and rentiapril (for angiotensin-converting enzyme [ACE, kininase II]) suggested the essential roles of the above three proteases in BK degradation: among the three proteases, kininase I and endopeptidase 24.11 appeared to be the most important in kininase action in the placenta microsomes, whereas kininase I and ACE appeared to be the most important in kininase action in the placental cytosol, lysosome and pregnancy serum. Measurements of BK concentrations in the umbilical arterial blood, umbilical venous blood and maternal plasma revealed higher concentrations in the mother than in the fetus. The present data suggest that degradation of BK in the placenta and pregnancy serum might contribute to the gradient of BK between mother and fetus.

3-Mercaptopropionic Acid↗

Increased mitochondrial damage by lipid peroxidation in trophoblast cells of preeclamptic placentas.

Lipid peroxides and their related free radicals have been implicated in the pathogenesis of placental dysfunction in preeclampsia. Recent studies suggest that the placenta is a source of the increased lipid peroxides in the maternal circulation of women with preeclampsia. We examined intracellular localization of 4-hydroxy-2-nonenal (HNE: a major aldehydic product of lipid peroxidation)-modified proteins in human placentas by immunohistochemistry, and immunoblotting. The trophoblast layer of the chorionic villi showed intense immunoreactivity for HNE-modified proteins in 4 of 12 preeclamptic placentas, whereas no staining was observed in 12 normal placentas. Immunoblotting revealed that three immunoreactive proteins with apparent molecular mass of 110 kDa, 75 kDa, and 70 kDa were localized in the mitochondrial fraction. The present results indicate that the damage to mitochondrial proteins by lipid peroxidation by products and subsequent dysfunction of trophoblasts contribute to the pathophysiology of preeclampsia.

Aldehydes↗

Effects of all-trans retinoic acid on choriocarcinoma cells in vitro.

OBJECTIVES: To determine the activities of all-trans retinoic acid (RA) on choriocarcinoma cells in vitro. METHODS: The antiproliferative effect of all-trans RA on 4 choriocarcinoma cell lines was measured by the MTT assay. The effect of all-trans RA combined with methotrexate or actinomycin-D was then examined. The effect of all-trans RA on hCG secretion was also studied. The gene expression of retinoic acid receptors (RARs) was examined by RT-PCR. RESULTS: All-trans RA inhibited cell proliferation dose- and time-dependently; a 6-day exposure to 1 microM all-trans RA suppressed the cell growth by 67.8%-82.0% compared to the controls. An enhanced effect was observed in the combined administration of all-trans RA and methotrexate or actinomycin-D. The secretion of hCG increased 4-fold to 9-fold by the addition of 1 microM all-trans RA. RARs genes were expressed in all cell lines. CONCLUSION: The anticancer activity presented here appears to warrant further evaluation of all-trans RA as adjuvant therapy for choriocarcinoma.

Antineoplastic Agents↗

A case of uterine choriocarcinoma with spontaneous rupture twenty-three years following the antecedent pregnancy.

A 53-year-old woman went into shock with a spontaneous uterine rupture due to choriocarcinoma that occurred 23 years after an elective abortion in the first trimester, and she underwent an emergency hysterectomy. After 4 courses of uneventful postoperative chemotherapy, she suffered from severe pneumonia. Fortunately, however, she recovered and has remained in complete remission at 2.5 years follow-up. This is a case of uterine choriocarcinoma with a spontaneous rupture after the longest latent period yet reported.

Abortion, Induced↗

Factors influencing an ultrasound-estimated bone mass in postmenopausal women.

OBJECTIVE: There are various methods for determining bone-mineral density for diagnosing osteoporosis. The most accurate method among them is dual-energy X-ray absorptiometry (DEXA), and the simplest one utilizes an ultrasound bone densitometer. We investigated factors influencing the correlation between bone-density values determined by dual-energy X-ray absorptiometry and by the use of an ultrasound bone densitometer. METHODS: Sixty-seven postmenopausal Japanese women aged from 31 to 68 years old were enrolled in the study. Bone-mineral densities (BMDs) of the lumbar spine (L2-4) measured by DEXA and broadband ultrasound attenuation (BUA) of the right os calcaneus measured by an ultrasound bone densitometer were subjected to statistical analysis. RESULTS: Multivariate analysis indicated that the patient's exercise history was useful-following the number of years since menopause and body weight-for determining lumbar spine bone-mineral density. The influence of hormone replacement therapy (HRT) on bone mass in postmenopausal women is also considered to be marked, but the results of the present multivariate analysis showed almost no influence on BUA or the L2-4 BMD. CONCLUSIONS: The patient's exercise history should be taken into consideration when lumbar spine bone-mineral density is estimated using an ultrasound bone densitometer instead of DEXA.

Absorptiometry, Photon↗

Effects of gonadotropin, estrogen, and progesterone on c-mos gene expression in mouse oocytes in vivo and in vitro.

OBJECTIVE: To analyze the effects of gonadotropin and ovarian steroid hormones on the gene expression of c-mos in mouse oocytes. METHODS: The changes of c-mos messenger RNA (mRNA) levels in oocytes were examined after the administration of pregnant mare's serum gonadotropin (PMSG) in vivo, or after incubation with estrogen and/or progesterone in vitro. Five IU PMSG was injected intraperitoneally to female immature mice, and human chorionic gonadotropin was also injected intraperitoneally 48 hours after the PMSG injection, with or without mating with male mice. The oocytes were collected from follicles or oviducts at 24, 30, 36, 42, 48, 60, 72, and 84 hours after the injection. The RNAs were extracted from 5 oocytes at each time point, and a reverse-transcription polymerase chain reaction using specific primers to c-mos DNA was performed to measure the relative amount of c-mos mRNA. RESULTS: The c-mos mRNA in oocytes at 36 hours after the injection was 2.7 times higher than that at 24 hours. The c-mos mRNA level gradually decreased thereafter, and after ovulation the level was only 1/10 of the peak level. When the oocytes that were retrieved 24 hours after PMSG injection were incubated with 800 ng/ml estradiol 17-beta or 600 ng/ml progesterone for 120 minutes, the c-mos gene expression was significantly suppressed or stimulated, respectively, in comparison with the absence of these substances. CONCLUSION: Although the regulatory mechanism of c-mos gene expression in oocytes is still unclear because the result obtained from the in vitro study, that estrogen suppressed the c-mos gene expression directly, was inconsistent with the result of the in vivo study, that increases of both c-mos mRNA and estrogen occurred simultaneously with PMSG stimulation in the early phase of preovulatory oocytes, our present study revealed that gonadotropin and steroid hormones might affect c-mos gene expression in mouse oocytes indirectly and/or directly.

Animals↗

Epididymal sperm retrieval by epididymal micropuncture combined with intracytoplasmic sperm injection: difference between acquired and congenital irreparable obstructive azoospermia.

To evaluate the differences in fertilization and pregnancy rates following intracytoplasmic sperm injection (ICSI) of retrieved epididymal sperm between congenital (group 1) and acquired (group 2) unreconstructable obstructive azoospermic patients, we compared the outcome of the ICSI procedure between these two groups. Thirty-six patients with obstructive azoospermia received epididymal sperm retrieval by the micropuncture method for the ICSI procedure. Main parameters evaluated were epididymal fluid volume, sperm concentration, sperm-motility; fertilization rate and clinical pregnancy rate. There were no significant differences in epididymal fluid and sperm concentration between the two groups. However, the sperm motility in group 1 was significantly higher than that in group 2. The fertilization rates per couple in groups 1 and 2 were 78.2 and 82% (nonsignificant). The pregnancy rate per couple in group 1 was 37.5% (6/16), while that in group 2 was only 5% (1/20); this difference was statistically significant (p < 0.05). Using epididymal sperm for the ICSI procedure, the chances of pregnancy for couples with congenital absence of the vas deferens were significantly higher compared with couples with acquired unreconstructable obstructive male infertility.

Adult↗

Effects of 17beta-estradiol and progesterone on the adhesion of human monocytic THP-1 cells to human female endothelial cells exposed to minimally oxidized LDL.

It is known that hormone replacement therapy inhibits the progression of atherosclerosis in postmenopausal women. Focal attachment of monocytes to endothelial cells is observed in early atherosclerotic lesions. The aim of this study was to investigate the effects of 17beta-estradiol (E2) and progesterone on the adhesion of human monocytic THP-1 cells to human female aortic endothelial cells (HAECs) in vitro. Minimally oxidized low-density lipoprotein (LDL) significantly increased THP-1 cell adhesion to HAECs as compared with native LDL at the same concentration. Though E2 inhibited minimally oxidized LDL-induced THP-1 cell adhesion in a dose-dependent manner, progesterone had no significant effects. Preincubation of HAECs with tamoxifen significantly antagonized the inhibitory effect of E2. These findings suggest a beneficial effect of hormone replacement therapy on atherosclerosis.

Adult↗

Distribution of platinum in human gynecologic tissues and pelvic lymph nodes after administration of cisplatin.

BACKGROUND: Defining tissue accumulation of platinum may be of importance, since it may provide a pharmacological explanation for organ-specific cisplatin activity. This study was conducted to evaluate the efficacy of cisplatin at the tissue level in different gynecologic organs. The doses administered were equivalent to those used in neoadjuvant chemotherapy regimens. STUDY DESIGN: Cisplatin was administered intravenously to patients with cervical or endometrial cancer 1 h before operation, and platinum accumulations in tissues were assayed by the atomic absorption method. RESULTS: Platinum accumulation was highest in the cervix and next highest in the myometrium in both cancers. Platinum accumulation in ovary and lymph node was only 0.58 and 0.57 times that in the myometrium, respectively. In patients with cervical cancer, the platinum accumulations in the myometrium and cervix were significantly higher than in the ovary and lymph node. Platinum accumulation in cervical cancer tissue was lower than in the myometrium and cervix, suggesting that delivery of cisplatin to a cervical cancer is somewhat more difficult than to the normal cervix. In patients with endometrial cancer, there was significantly more accumulation in the cervix than in the ovary and lymph node. CONCLUSIONS: These data indicated that cisplatin was easily distributed to the cervix and myometrium, but not to the ovary, lymph node, and cancer tissues.

Adult↗