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Y Tomoda

Publications and source records attributed to Y Tomoda.

At least 19 recordsLinked to original sources
PubMed1995

Effect of KN-62, Ca2+/calmodulin-dependent protein kinase II inhibitor, on adriamycin resistance of human ovarian cancer cells.

We examined effects of an isoquinolinesulfonamide derivative, KN-62, on human ovarian cancer cells, NOS3AR, that are resistant to Adriamycin (ADR). MTT assay revealed that 10 microM KN-62 overcame the resistance. KN-62 had little effect on GST activity. In studies on the intracellular accumulation of ADR, KN-62 increased the ADR contents in the resistant cells close to the level seen in the sensitive cells. These results suggest that the reversal of the resistance against ADR in ovarian cancer cells by KN-62 is mainly due to higher accumulation of ADR in NOS3AR cells. Furthermore, we detected Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in NOS3AR cells since KN-62 is a specific inhibitor of the kinase. In this paper, we discussed on modulation of ADR-resistance by KN-62.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Regulatory role of gamma delta T cells in uterine intraepithelial lymphocytes in maternal antifetal immune response.

To elucidate the potential roles of the gamma delta T cells in uterine intraepithelial lymphocytes (IEL) in the regulation of maternal antifetal immune response during pregnancy, we examined the kinetics and function of gamma delta T cells in uterine IEL obtained from (C3H/He x AKR/J) pregnancy. The number of gamma delta T cells increased in the uterine IEL in (C3H/HexAKR/J) pregnancy more than those in (C3H/HexC3H/He) pregnancy and much more than in nonpregnant C3H/He mice. The uterine IEL in (C3H/HexC3H/He) pregnancy significantly proliferated in response to AKR/J stimulator cells. In contrast, the uterine IEL in (C3H/HexAKR/J) pregnancy showed little, if any, proliferation in response to the same stimulator cells. gamma delta T cell depletion from the uterine IEL in (C3H/HexAKR/J) pregnancy restored their responsiveness against AKR/J stimulator cells. Both gamma delta T cell-enriched fraction and alpha beta T cell-depleted fraction, but neither gamma delta T cell-depleted fraction nor alpha beta T cell-enriched fraction in the uterine IEL exhibited suppressive activity against allogeneic responses of nonpregnant C3H/He LN cells. This suppressive activity was shown by transferring the supernatant of culture medium in the uterine IEL stimulated with AKR/J cells that contained a large amount of TGF-beta, and the suppressive activity was significantly blocked by addition of anti-TGF-beta mAb to the culture. Taken together, our results suggest that gamma delta T cells in the uterine IEL suppress the maternal antifetal immune response at the maternal-fetal interface at least in part through TGF-beta production to prevent a rejection of the fetus.

Animals↗
PubMed1995

Association of human leukocyte antigen-B1*03 with cervical cancer in Japanese women aged 35 years and younger.

BACKGROUND: An association of human leukocyte antigen (HLA)-DQw3 alleles with squamous cell carcinoma (SCC) of the cervix has been reported in some European populations, but the significance of HLA-DQw3 has not been examined in other populations to the authors' knowledge. The interaction between HLA-DQw3 and human papillomavirus (HPV) in SCC remains to be clarified. METHODS: To elucidate the association of HLA-DQ alleles with SCC of the cervix, DNA samples extracted from blood lymphocytes of 23 patients with SCC were amplified by the polymerase chain reaction (PCR) using specific primers for the DQB1 genes, and then, each HLA-DQB1 genotype was defined by digestion with restriction enzymes. Human papillomavirus typing also was performed in all cases by PCR, using specific primers for the E6 regions of cancer-associated HPV types (HPV 16, 18 and 33). RESULTS: Twenty patients (87%) carried a DQB1 gene-encoding HLA-DQw3, compared with 49.4% Japanese control subjects in the International Histocompatibility Workshop panel (P = 0.0003). Human papillomavirus 16 or HPV 18 DNA was detected in 86% of the patients. In 13 of the patients with invasive carcinoma with HPV, a high incidence of not only HLA-DQw3 but also of HLA-DQw1 was observed compared with that in control subjects (P = 0.0019, P = 0.047, respectively). The correlation between DQB1*03 alleles and HPV infection was not statistically significant. CONCLUSION: The frequency of HLA-DQw3 alleles was higher in the authors' patient group than in the control group, suggesting that the HLA-DQw3 molecules may influence the development of SCC of the cervix in young Japanese women. In the patients with HPV-positive invasive carcinoma, the association with HLA-DQw1 molecules suggested that it also may influence the progression of SCC.

Adult↗
PubMed1995

Gonadoblastoma with dysgerminoma in one ovary and gonadoblastoma with dysgerminoma and yolk sac tumor in the contralateral ovary in a girl with 46XX karyotype.

A case of gonadoblastoma with dysgerminoma in the left ovary and gonadoblastoma with dysgerminoma and yolk sac tumor in the right of a 10-year-old girl is reported. Her karyotype was 46XX, normal female type. A case of a gonadoblastoma without a Y chromosome is very rare. Furthermore, the prognosis for gonadoblastoma accompanied by germ cell tumors other than dysgerminoma was very poor in the past, but the patient remains well 25 months after the first operation.

Child↗
PubMed1995

A novel human monoclonal antibody against cervical cancer: its immunoreactivity with normal tube and ovary and with ovarian tumor tissue.

1-1-2D, a novel human monoclonal antibody (MAb) raised against cervical cancer, was examined for its immunohistochemical reactivity with ovarian cancer. Six of 10 ovarian cancer cell lines showed positive staining, while 3 of 5 cervical cancer cell lines were positive. Among tumor tissues, 15 of 18 (83%) ovarian serous cystadenocarcinomas and 10 of 12 (83%) ovarian clear cell adenocarcinomas were positive. We also performed immunohistochemical staining of the same cancer specimens with OC 125 and compared their reactivity. The frequency of positivity was similar, but the reactivity of the two MAbs was different. 1-1-2D stained the apical surface of the glandular epithelial cells and secretory products of the gland. On the other hand, OC 125 stained the cytoplasm as well as the plasma membrane of the glandular epithelial cells. These results suggest that 1-1-2D MAb recognizes a different antigen from that recognized by OC 125.

Adenocarcinoma↗
PubMed1995

Levels of hepatocyte growth factor in maternal serum and amniotic fluid.

OBJECTIVE: The purpose of our study was to investigate hepatocyte growth factor levels in maternal serum and amniotic fluid during pregnancy. We also demonstrated production and secretion of hepatocyte growth factor by placenta and amnion at different stages of gestation. STUDY DESIGN: Hepatocyte growth factor levels in maternal serum (n = 219), cord blood (n = 20), and amniotic fluid samples (n = 90) were measured by an enzyme-linked immunosorbent assay. The secretion of hepatocyte growth factor by placenta and amnion was evaluated by measuring the amount released into the culture supernatant. RESULTS: Most hepatocyte growth factor levels in maternal serum were below the detection limit before 10 weeks of pregnancy. Levels increased significantly thereafter and continued to increase until term. On the other hand, levels in amniotic fluid were significantly higher between 20 and 29 weeks of gestation than after 30 weeks. Hepatocyte growth factor secretion from the placental tissue per weight seemed unchanged throughout pregnancy. Its secretion from amnion was, however, approximately 300 to 400-fold higher in the second trimester compared with that at term. CONCLUSION: Both placenta and amnion produce and secrete hepatocyte growth factor, suggesting its role in fetal growth and the growth and differentiation of placenta.

Adult↗
PubMed1995

Suppression of gelatinase production with decreased invasiveness of choriocarcinoma cells by human recombinant interferon beta.

OBJECTIVE: Choriocarcinoma is a highly invasive gynecologic tumor, and hematogenous metastases frequently develop. To establish a molecular basis for antiinvasion therapy of choriocarcinoma, we examined the effects of human recombinant interferons on gelatinase production and invasion by choriocarcinoma cells. STUDY DESIGN: Using five choriocarcinoma cell lines, we measured gelatinase activity by gelatin zymography. The effects of recombinant interferons (rIFN-alpha, rIFN-beta, and rIFN-gamma) were then analyzed by Western blot analysis and chemoinvasion assay. RESULTS: High levels of 72 kd gelatinase activity were detected in the highly invasive choriocarcinoma cell lines, two of which also contained an active form of 72 kd gelatinase with an apparent molecular mass of 68 kd. Gelatinase production was decreased by incubation with rIFN-beta. In the chemoinvasion assay, only rIFN-beta had an inhibitory effect on the invasiveness of tumor cells without a cytotoxic effect. CONCLUSION: Choriocarcinoma cells showed high 72 kd gelatinase activity, which suggested a role for the enzyme in vascular metastasis. Studies on the use of rIFN-beta to inhibit metastasis of choriocarcinoma via suppression of gelatinase production are warranted.

Choriocarcinoma↗
PubMed1995

Postmenopausal bone loss in Japanese women.

OBJECTIVES: Our purpose was to detect anatomic variations in postmenopausal bone loss and to determine the risk factors most affecting bone mass in Japanese women. METHODS: One hundred sixty-six Japanese women (54 premenopausal and 112 postmenopausal), aged 40-68 years, were enrolled in the study. Bone mineral densities (BMD) of the lumbar spine (L2-4) and total body were measured by dual energy X-ray absorptiometry and the results were subjected to statistical analysis. RESULTS: Among the various sites studied, the lumbar spine (L2-4) showed the fastest bone loss after menopause. Multiple regression analysis indicated that two factors, number of years since the menopause and body mass index (BMI), affected lumbar spine (L2-4) BMD. CONCLUSION: Measurement of lumbar spine (L2-4) BMD is suitable for evaluating postmenopausal osteoporosis. The risk factors for postmenopausal bone loss were a long period after menopause and a low BMI.

Adult↗
PubMed1995

Longitudinal monitoring of fetal behavior in twins when one is anencephalic.

BACKGROUND: To our knowledge, there has been no report on longitudinal monitoring of fetal behavior in the anencephalic fetus. CASE: A 30-year-old woman was diagnosed with a twin pregnancy at 8 weeks' gestation; at week 20, one of the twins was identified as anencephalic. From 25-36 weeks' gestation, the behavioral patterns of each fetus were recorded weekly on videotape for 60 minutes, then compared with morphologic findings after birth. CONCLUSION: Our data comparing normal and anencephalic fetuses indicate that the development of the central nervous system above the medulla oblongata plays an important role in the elimination of fetal movements, such as startle, jumping, and writhing, and in the commencement of breathing movements.

Adult↗
PubMed1995

Umbilical plasma concentration of endothelin-1 in intrapartum fetal stress: effect of fetal heart rate abnormalities.

OBJECTIVE: To measure the umbilical plasma concentration of endothelin (ET)-1 in the presence of labor, fetal heart rate (FHR) abnormalities, and fetal hypoxia. METHODS: Umbilical and maternal plasma concentrations of ET-1 were measured in 100 pregnant women at full-term deliveries (60 with vaginal delivery without induction and 40 with elective cesarean delivery without labor). We assessed the FHR pattern, measured umbilical blood gases and plasma concentration of vasopressin, and investigated the relationships between the umbilical vein-artery ET-1 concentration difference and these variables. RESULTS: The concentration of ET-1 in the umbilical vein was higher than in the umbilical artery and the maternal vein in all cases. The umbilical vein-artery ET-1 concentration difference (mean +/- standard error of the mean) was significantly greater in the vaginal delivery group (4.5 +/- 2.0 pmol/L) than in those delivered by elective cesarean (1.7 +/- 1.5 pmol/L) (P < .05). The umbilical vein-artery ET-1 concentration difference was significantly greater when more than three episodes of severe variable decelerations occurred during the 30-minute period before delivery (7.0 +/- 2.0 pmol/L) than in the absence of any decelerations (1.6 +/- 1.5 pmol/L) (P < .05). The umbilical vein-artery ET-1 concentration difference correlated positively with the umbilical arterial concentration of vasopressin (r = 0.45, P < .05) and negatively with the umbilical arterial oxygen pressure (r = -0.47, P < .05). CONCLUSION: In cases of vaginal delivery with FHR abnormalities and with fetal hypoxia, the fetoplacental concentration of ET-1 was increased.

Adult↗
PubMed1995

The study of mitochondrial gene modifications in human placenta.

A quantitative study on the effects of placental senescence on mitochondrial DNA (mtDNA) was carried out by measuring mitochondrial gene mutation, levels of mRNA for the cytochrome c oxidase subunit I (COI) and of mtDNA in normal placental tissues at different stages. Deleted mtDNA, the expression of COI in mitochondria and the amounts of mtDNA per cell were examined by the polymerase chain reaction, northern blot analysis and southern blot analysis, respectively. No accumulation of mutant mtDNA with a 4977 base pair (bp) deletion was detected in the normal placenta during pregnancy. There appeared to be a gradual increase of COI mRNA as pregnancy progressed, while the ratio of mtDNA to total DNA in human placenta tended to decrease with gestation. These results indicate that placental ageing is not associated with the accumulation of mtDNA mutation with the 4977 bp deletion or markedly reduced expression of the mitochondrial genome.

Base Sequence↗
PubMed1995

Screening of the mutations in luteinizing hormone beta-subunit in patients with menstrual disorders.

OBJECTIVE: To evaluate the clinical significance of the LH consisting of a mutant beta-subunit (Trp8 to Arg8 and Ile15 to Thr15). DESIGN: Clinical and biochemical studies. SETTING: Fertility center at the University Hospital and its research laboratory. PATIENTS: Fifty-one patients with menstrual disorders and three homozygote cases and two heterozygote cases of the mutant LH who were reported previously. INTERVENTIONS: Nucleotide mutations of the LH beta gene in patients with menstrual disorders were screened using techniques of the polymerase chain reaction and restriction fragment length polymorphism. Immunologic and biologic activities of the mutant LH and endocrinologic profiles in the affected women were evaluated. MAIN OUTCOME MEASURES: Serum LH levels measured with different immunoassay kits; serum FSH and LH on the GnRH test; serum thyroid-stimulating hormone, PRL, T, and androstenedione; ultrasound examination of the ovaries; clinical hyperandrogenic symptoms; and biologic activity of LH. RESULTS: Two cases of homozygotes and four of heterozygotes affected by the LH beta gene mutations were discovered in the current study through screening of patients with menstrual disorders. Serum LH levels in the homozygote cases were undetectable using a LH immunoassay kit, whereas levels in the heterozygote cases showed reduced detectability with the kit. However, the ratio of the mutant LH values in the bioassay to those in the immunoassay was higher in the homozygote group than that in the control subjects. Response patterns of serum gonadotropins to GnRH in the homozygote were similar to those in patients with polycystic ovary syndrome. CONCLUSION: The mutations of LH beta-subunit might be related to menstrual disorder in some patients.

Adolescent↗
PubMed1995

The concentration of hepatocyte growth factor (HGF) in human amniotic fluid at second trimester: relation to fetal birth weight.

Hepatocyte growth factor (HGF) was measured in 28 samples of amniotic fluid, 1 of fetal urine and 5 of first neonatal urine. The mean level of HGF was 12.4 +/- 4.5 ng/ml (second trimester) and 10.5 +/- 6.6 ng/ml (third trimester). These values were extremely high compared to that in plasma from normal subjects and greater than the plasma levels from patients with acute hepatitis. The concentration of amniotic HGF at second trimester showed a significant inverse correlation both with birth weight (r = 0.47; p < 0.05) and birth weight deviation (r = 0.54; p < 0.02). The level of HGF in fetal urine (0.10 ng/ml) and in the first neonatal urine (0.08 +/- 0.02 ng/ml) were much less than that in amniotic fluid. HGF stimulated DNA synthesis of human fetal liver cells in vitro. While the effect was dose dependent, a maximal response was reached with about 0.2 ng/ml, attaining a 1.3-fold stimulation. The presence of extremely high levels of HGF in the amniotic fluid may be involved not in fetal growth, but rather in maturation of fetal organs such as the lung and the digestive tract.

Amniotic Fluid↗
PubMed1995

Establishment and characterization of acquired resistance to platinum anticancer drugs in human ovarian carcinoma cells.

To investigate differences in resistance to cis-diamminedichloroplatinum(II) (CDDP) and diammine (1,1-cyclobutanecarboxylato)platinum(II) (CBDCA), and their newly developed derivative, ((-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato)platinum (II) (DWA2114R), four types of resistant cell lines were established from a parental cell line (NOS2) of a serous cystadenocarcinoma of the ovary. The cross-resistance of CDDP-resistant cells (NOS2CR1 and NOS2CR2) to DWA2114R was slight (only 25% of the resistance to CDDP), and no cross-resistance was observed to anticancer drugs other than the CDDP derivative, except to camptothecin (CPT-11) in the case of NOS2CR2 cells. The cross-resistance of CBDCA-resistant cells (NOS2CBR) to DWA2114R was slight (only about 1/3 of the resistance to CBDCA), and no cross-resistance was observed among anticancer drugs other than the CDDP derivative. On the other hand, DWA2114R-resistant cells (NOS2DR) showed a high cross-resistance to CDDP, CBDCA, etoposide (VP-16), and CPT-11. Intracellular accumulations of CDDP and CBDCA were markedly reduced in NOS2CR1, NOS2CR2, and NOS2CBR cells compared to those in NOS2 cells, but were reduced only slightly in NOS2DR cells. Intracellular accumulation of DWA2114R was reduced somewhat in the four types of resistant cells. Glutathione S-transferase activity was not increased in any of the four types of resistant cells, and intracellular GSH concentration was increased only in NOS2CR2 cells (by 2.6 fold). From these results, we consider that the resistance mechanisms against CDDP and CDBCA are similar, and reduction of intracellular drug accumulations is a significant factor. Resistance to DWA2114R differed from resistance to CDDP and CBDCA in both cross-resistance spectrum and resistance mechanism, indicating that reduction in intracellular drug accumulation is not the major resistance mechanism.

Camptothecin↗
PubMed1995

Bulk sperm collection by epididymal micropuncture and stimulation of the spermatic nerve; a novel method for sperm retrieval for IVF for surgically irreparable vasal obstruction.

We have developed a new sperm collection method by epididymal micropuncture in conjunction with perivascular nerve stimulation to obtain as many uncontaminated spermatozoa as possible for IVF for patients with surgically unreconstructable vasal obstruction. Fifteen azoospermic men with congenital absence of the vas deferens or vasal obstruction not amenable to surgical repair enrolled in this study. Under general anaesthesia the testis and epididymis were retrieved and stabilized in a testicular holder with the aid of 2% agar. The epididymal micropuncture was performed using a micropipette placed in a micromanipulator. A pair of Ag-AgCl ring electrodes were placed around the spermatic cord for perivascular nerve stimulation with DC (intensity 136 V, frequency 20 Hz) for 30 s. Electrical stimulation was repeated every 1 min until no further fluid was obtained. Epididymal fluid obtained ranged from 78 to 980 microliters (mean 169 microliters). Sperm concentration ranged from 0.7 to 200 million (mean 53.5 million). Sperm motility ranged from 0.5% to 70% (mean: 19.9%). The percentage of spermatozoa with normal morphology ranged from 3% to 32% (mean 16.4%). Of 16 cycles in which spermatozoa and oocytes were retrieved, 56% (9/16) resulted in fertilization and 18.8% (3/16) developed clinical pregnancies. The clinical pregnancy rate per couple was 20% (3/15). This is the first clinical experience of the bulk sperm collection system for IVF for the treatment of unreconstructable obstructive azoospermia. Our results indicate that our new technique, in conjunction with IVF, is clinically useful for patients with surgically irreparable vasal obstruction.

Cell Separation↗
PubMed1995

Clinical value of a new serum tumor marker, CA125II, in gynecologic disease: comparison with CA125.

CA125 II, an improved version of the conventional CA125 was compared with CA125 as to which was more useful in gynecologic disease. In the diagnosis of tumors around the adnexal field (primary epithelial ovarian cancer, metastatic ovarian cancer, benign ovarian tumor and endometrial cyst), CA125 II showed the same sensitivity and specificity as CA125. CA125 II also has high simultaneous reproducibility in the low concentration area. The examination by the receiver operating characteristic curve revealed that CA125 II has higher precision than that of CA125 when it is used for the screening test. In conclusion, CA125 II is a better tumor marker than conventional CA125.

Biomarkers, Tumor↗
PubMed1995

Role of the Pro-Leu-Arg motif in glycosylation of human gonadotropin alpha-subunit.

CG, LH, FSH, and TSH are a family of heterodimeric glycoprotein hormones that contain a common alpha-subunit, but differ in their hormone-specific beta-subunit. Processing of the N-linked oligosaccharide of the glycoprotein family is both tissue and dimer specific. LH, TSH, and free alpha synthesized in pituitary bear oligosaccharide terminating with sulfate (SO4) and N-acetylgalactosamine (GalNAc), whereas the termination of oligosaccharide in CG synthesized in placenta and FSH is sialic acid and galactose (Gal). Using site-directed mutagenesis and gene transfer, we studied the role of the Pro-Leu-Arg motif, which has been shown to be a recognition marker of glycoprotein hormone-specific GalNAc transferase, in sulfation of N-linked oligosaccharide in alpha-subunit. The wild-type or mutated alpha gene was transfected into GH3 cells. Our data revealed that substitution of the Pro-Leu-Arg motif by Ala-Leu-Ala did not affect the sulfation of N-linked oligosaccharide, but generated the attachment of O-linked oligosaccharide. alpha-Subunit containing either of the two N-linked glycosylations is also sulfated. We conclude that in GH3 cells, the Pro-Leu-Arg motif plays no role in the sulfation of oligosaccharide in alpha-subunit, and both N-glycosylations are terminated with SO4.

Amino Acid Sequence↗