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Biomedical subjects

Y Tomoda

Publications and source records attributed to Y Tomoda.

At least 163 records · Page 9Linked to original sources
PubMed1992

Source of prolactin in human follicular fluid.

To analyze whether prolactin (PRL) in human follicular fluid (FF) is synthesized locally or derived from the circulation, PRL concentrations of plasma and FF were determined in the patients after ovarian stimulations. The amounts of PRL messenger ribonucleic acid (mRNA) in the follicular tissues during different menstrual phases were also determined. The FF PRL concentration was correlated positively with plasma PRL and highest estradiol levels during the stimulatory cycle. No PRL mRNA sequence was detected in the RNAs extracted from follicles at any stage in the menstrual cycle, although beta-actin mRNA was detected in all samples. In a comparison with pituitary RNA, the PRL mRNA concentration in ovarian follicular tissues seemed to be 10,000 times less than that in the pituitary. These results suggest that FF PRL may not be synthesized locally, but derived from the pituitary via the circulation through passive diffusion, and thus regulated by estrogen.

Actins↗
PubMed1992

Degradation of oxytocin by the human placenta: effect of selective inhibitors.

The hydrolysis of oxytocin by human placental subcellular fractions was studied in the presence of selective inhibitors by measuring liberated amino acids by high performance liquid chromatography (HPLC). Oxytocin degradation by microsomal and lysosomal fractions was inhibited by bestatin, amastatin and puromycin. The IC50 values of these inhibitors on oxytocin degradation by both fractions were similar to those of these inhibitors on the human placental aminopeptidase M measured by L-Leu-p-nitroanilide as a substrate (LAP activity), which we reported previously. However, purified aminopeptidase M from human placental microsomal fractions could not liberate any amino acid from oxytocin. Since phosphoramidon (1 mumol/l), a putative metalloendopeptidase inhibitor, and N-benzylcarbonyl-valyl-prolinal (Z-Val-prolinal) (14 mumol/l), a selective inhibitor of post-proline endopeptidase, could not significantly influence the degradation of oxytocin by either subcellular fractions, neither enzyme seems to be actively involved in oxytocin degradation. These results strongly suggested the existence of oxytocinase(s) other than the above three enzymes in microsomal and/or lysosomal fractions of human placenta.

Amino Acids↗
PubMed1992

[Effect of chemotherapy on the prognosis of ovarian cancer].

Through the collaboration of 22 institutions nationwide, a total of 1,185 cases of ovarian cancer treated between January, 1980 and December, 1987, were investigated as to their prognosis from the aspect of the chemotherapeutic effect. (1) An excellent effect of the remission-induction chemotherapy was observed in a group receiving combination therapy with CDDP as the main ingredient. In particular a significant effect was seen in stages III and IV. In addition, the effect on the remaining tumors by diameter also showed a significant difference in cases of tumors of not less than 2 cm in diameter. (2) As to the effect on histological types, a comparison in stage III showed a favourable effect on endometroid, serous and mucinous adenocarcinomas, while no effect was observed in clear cell adenocarcinoma. (3) The effect of the remission induction chemotherapy did not always give rise to an improvement in the long-term prognosis of ovarian cancer, and the establishment of a therapeutic method aimed at the prevention of recurrence was desired. (4) To improve the long-term prognosis, intermittent (or cyclic) chemotherapy with CDDP as the main ingredient was found to be very effective, but maintenance chemotherapy with orally administered of 5-Fluorouracil or Tegaful was not effective. (5) The effect of the conventional immunotherapy was not observed at all.

Adenocarcinoma↗
PubMed1992

[A group study on prognosis of ovarian cancer in Japan].

An assessment has been made, with the cooperation of 22 institutes, of 1,185 cases of ovarian cancer as subjects who were treated in the period from January, 1980, to December, 1987. As a result, (1) As for distribution by clinical staging at the initial examination, the cases in Stage III were the most numerous, followed by those in Stage I, and if classified according to the histological type, serous cystadenocarcinoma was the most frequently observed in Stage III, and undifferentiated and unclassified carcinomata were observed in Stages III and IV. (2) In the examination of prognostic factors, it was confirmed that the clinical stage, histological type and diameter of the remaining tumor after the initial operation were important factors. (3) A significant difference was observed between the grade of histomorphological differentiation and prognosis, the difference was chiefly due to the deviated distribution of clinical staging in each group of differentiation. (4) A favorable trend was observed in the prognosis by patient's age toward the younger layer. (5) When the starting time of the therapy is considered, a trend toward improvement has been seen year by year, and it is considered that the beneficial effect of chemotherapy with CDDP contributes to this.

Adult↗
PubMed1992

Clinical effect of sizofiran combined with irradiation in cervical cancer patients: a randomized controlled study. Cooperative Study Group on SPG for Gynecological Cancer.

To evaluate the clinical effect of a biological response modifier (BRM), sizofiran (SPG), combined with irradiation, a randomized controlled study was performed in patients with stage II or III cervical cancer involving the collaboration of 52 institutes throughout Japan. Patients were randomly allocated to the control group (radiotherapy only) and the SPG group (radiotherapy + SPG). SPG was given intramuscularly, 40 mg once and 20 mg twice, a week concomitantly with radiotherapy. A total 315 patients were enrolled for the study but 23 were excluded from analysis. Of the remaining 292 patients, 121 were of stage II (43 controls and 78 SPG) and 171 of stage III (49 controls and 122 SPG). The results were as follows. (1) The complete response (CR) rate among stage II patients was higher in the SPG group (91.0%) than in the control group (79.1%); also the CR rate among stage III patients was significantly higher in the SPG group (77.9%) than in the control group (61.2%). (2) The SPG group showed a significantly rapid recovery from the decreased lymphocyte counts due to radiotherapy (P less than 0.05). (3) Side effects, probably associated with SPG administration, were observed in 11 cases (5.2%).

Adult↗
PubMed1992

[Diagnosis of ovarian tumors by transvaginal Doppler ultrasound with color flow imaging].

Ovarian carcinoma is a silent disease with few symptoms. Early detection of ovarian cancer is difficult. Transvaginal Doppler ultrasound with color flow imaging is a new technique in the evaluation of gynecological diseases. This method was used in the diagnosis of ovarian tumors in 39 women who were treated in the Department of Obstetrics and Gynecology, Nagoya University Hospital. Wave forms of the parenchymal tumor arteries or tumor surface arteries were compared by according to the pulsatility index (PI). 1/PI was 0.69 +/- 0.04 in benign tumor and 2.33 +/- 1.36 in malignant tumors (p less than 0.01). When the cutoff value of 1/PI was set at 0.8 (cutoff value of PI: 1.25), the accuracy of diagnosis was 84.6% (33/39). The accuracy of ultrasonographic pattern classification and CA125 were 74.4% (29/39) and 53.8% (21/39), respectively. In 18 tumors with low CA125 (less than 35 U/ml), 5 of 7 malignant tumors (71.4%) had high 1/PI (greater than 0.8), and benign tumor, low 1/PI (less than 0.8) or non-detectable wave forms. This procedure should prove to be useful in the diagnosis of ovarian cancer.

Adult↗
PubMed1992

Transvaginal Doppler ultrasound with color flow imaging in the diagnosis of ovarian cancer.

Transvaginal Doppler ultrasound with color flow imaging is a new technique for the evaluation of gynecologic diseases. This method was used for the diagnosis of ovarian tumors in 24 women treated in the Department of Obstetrics and Gynecology, Nagoya University Hospital, Japan. Waveforms of the parenchymal tumor arteries or tumor surface arteries were compared using values of the pulsatility index (PI). The value for 1/PI was 0.69 +/- 0.05 in benign tumors and 1.87 +/- 0.65 in malignant tumors (P less than .01). When the cutoff value of 1/PI was set at 0.8 (cutoff value of PI was 1.25), the accuracy of diagnosis was 95.8% (23 of 24). Among 11 tumors with low CA 125 (less than 35 U/mL), all five malignant tumors had high 1/PI (above 0.8), and all benign tumors had low 1/PI (less than 0.8) or nondetectable waveforms. Based on the findings of this study, color flow Doppler proved to be useful for diagnosis of ovarian cancer.

Adult↗
PubMed1992

[A case of subacute sclerosing panencephalitis developing 8 years after immunosuppressive treatment for acute lymphocytic leukemia].

A 13-year-old girl developed subacute sclerosing panencephalitis (SSPE) with atypical absence attacks as an initial symptom. Eight years earlier she had been treated for acute lymphocytic leukemia with cytotoxic treatment and radiotherapy, which had resulted in complete remission. She was first treated with an anticonvulsant because the atypical absence attacks and the presence of epileptic discharges on an EEG suggested epilepsy. However, with this mode of treatment the epileptic discharges did not disappear, but periodic high-voltage slow-wave complex discharges were revealed on subsequent EEGs. The antibody titer for measles virus in the cerebrospinal fluid and serum was elevated, confirming the diagnosis of SSPE. SSPE may arise, though rarely, in an individual in an immunosuppressive state due to congenital immunodeficiency or various kinds of malignancies, and also may arise several years after the contraction of measles infection. Our patient, however, lacked a past history of measles infection or immunization, suggesting the possibility that she had contracted measles during or shortly after the course of treatment for ALL.

Adolescent↗
PubMed1991

Growth inhibitory effect of bestatin on choriocarcinoma cell lines in vitro.

Bestatin, one of the biological response modifiers (BRMs), is an inhibitor of aminopeptidase B (AP-B), leucine aminopeptidase (LAP) and aminopeptidase M (AP-M). In this report, we investigated the direct effect of bestatin on the growth of cancer cells in vitro using established four choriocarcinoma cell lines. In vitro chemosensitivity was evaluated by the succinate dehydrogenase inhibition (SDI) test. Bestatin showed the growth-inhibitory effect on all the choriocarcinoma cell lines dose-dependently, especially on NaUCC-4 cells. Both an isomer of bestatin with no inhibitory activity against aminopeptidases, (2R, 3S)-AHPA-(R)-Leu, and another isomer with stronger inhibitory activity against AP-B than bestatin, (2S, 3S)-AHPA-(R)-Leu, did not show growth inhibition on NaUCC-4 cells. So it is suggested that one of the possible mechanisms responsible for the direct action of bestatin on the choriocarcinoma cells may be related to the inhibition of activity of LAP or AP-M rather than that of AP-B. Furthermore, cytotoxicity of actinomycin D on the choriocarcinoma cells was significantly enhanced by combination with bestatin. These results suggest that bestatin has not only an indirect host-mediated anti-tumor activity, but also a direct growth-inhibitory effect on some kinds of cancer cell lines.

Aminopeptidases↗
PubMed1991

Characterization of an established mouse-human heterohybridoma and its application for production of (mouse-human)-human triple hybridoma secreting human immunoglobulin.

We report the construction of a mouse-human (M-H) heterohybridoma by fusion of the murine myeloma cell line NS-1 and human spleen cells from a 17 week old fetus. The nonsecreting, cloned hybridoma cell line II was resistant to 8-azaguanine (8-AG) and sensitive to hypoxanthine, aminopterin and thymidine (HAT) medium. It grew rapidly in 8-AG containing medium (doubling time 20 hrs.), but did not grow in HAT medium or in non-serum medium. It had a high fusion frequency with human lymphocytes from regional lymph nodes. Five human chromosomes were retained stably for over 6 months by this cell line II. Nine (mouse-human)-human ((M-H)-H) triple hybridomas secreting human IgG 1 or IgM were established by the fusion of this parental cell line II and human lymphocytes from regional lymph nodes. Immunoglobulin secretion was stable and has been maintained for over 8-10 months without recloning in these hybridomas. Secretion of immunoglobulin varies from 2.1-3.0 micrograms/10(6) cells/day, and these hybridomas contain from 3 to 16 human chromosomes, including No. 14. So, this M-H heterohybridoma II is an excellent useful parental cell line for the production of hybridomas secreting human immunoglobulin.

Animals↗
PubMed1991

Sequence-dependent termination of mammalian DNA polymerase reaction by a new platinum compound, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)-2-plati num(II) monohydrate).

We examined the mechanism of the inhibition of DNA synthesis by a new platinum compound, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato+ ++)-2-platinum(II) monohydrate (DWA-2114R), a derivative of the antitumor drug cis-diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryotic DNA polymerases. Preincubating activated DNA with CDDP or DWA-2114R reduced its template activity for prokaryotic and eukaryotic DNA polymerases in a dose-dependent manner. DWA2114R required six times greater drug concentration and two times longer incubation time to show the same decrease of the template activity compared to CDDP. Treatment of primed pUC118 ssDNA templates with the two drugs followed by second-strand synthesis by prokaryotic and eukaryotic DNA polymerases revealed that DWA2114R bound to DNA in a similar manner to CDDP and these adducts blocked DNA elongation by DNA polymerases of eukaryotes as well as of prokaryotes. With these two drugs, the elongations by E. coli DNA polymerase I (Klenow fragment), T7 DNA polymerase and calf thymus DNA polymerase alpha were strongly arrested at guanine-guanine sequences (GG). Stop bands were also observed at adenine-guanine sequences (AG) guanine-adenine-guanine sequences (GAG) and mono-guanine sequence (G). Calf testis DNA polymerase beta was also arrested efficiently at AG, GAG and G, but much more weakly at GG. This pattern was common to DWA2114R and CDDP.

Animals↗
PubMed1991

Purification and properties of human placental aminopeptidase B.

Aminopeptidase B (EC 3.4.11.6; L-arginyl-beta-naphthylamidase) was purified 1,800-fold from human placental cytoplasm and characterized. The enzyme was subjected to ammonium sulfate fractionation and a series of chromatographies on DE-52, hydroxylapatite, Bio-gel A 0.5 m and L-arginine-Sepharose. The native molecular mass of the enzyme was estimated to be 220,000 by gel filtration. The molecular mass was estimated to be about 83,000 by SDS/PAGE in the absence of 2-mercaptoethanol, suggesting that the enzyme exists in a polymeric form. The isoelectric point of the enzyme was 5.4. The purified enzyme was most active at pH 7.2 with L-arginyl-beta-naphthylamide as substrate and the Km value for this enzyme was 0.3 mmol/l. Human placental aminopeptidase B was markedly activity by Cl-. Bestatin and arphamenin, low molecular weight peptides, showed appreciable inhibition of this enzyme. However, amastatin and puromycin did not inhibit the enzyme. Bacitracin markedly activated this enzyme.

Aminopeptidases↗
PubMed1991

Suckling stimulates the expression of vasoactive intestinal polypeptide gene in rats.

The effect of suckling on vasoactive intestinal polypeptide (VIP) gene expression in the hypothalami was studied during the postpartum period in rats. Female rats were divided into two groups immediately after delivery. In one group, a mother was housed with 8 pups, and in the other, without any pups. The former group was named S(+) and the latter S(-). On days 0, 3, 6, 9 and 12 after delivery, the mothers were killed by decapitation. Hypothalamic VIP mRNA was measured by RNA dot hybridization. Although the VIP mRNA level showed no significant change after delivery in the S(-) group, VIP mRNA in the S(+) group on days 6, 9 and 12 increased to 1.6, 3.5 and 2.1 times higher than the level observed on day 0, respectively. These results suggest that suckling induces the synthesis of VIP after 6 postpartum days.

Actins↗
PubMed1991

Antenatal diagnosis of twin-twin transfusion syndrome by Doppler ultrasound.

We evaluated 31 pairs of twins: six with twin-twin transfusion syndrome, four discordant, and 21 concordant twins. The criterion for the retrospective diagnosis of discordancy was a difference in birth weight of 20% of the larger infant's weight. Using pulsed Doppler evaluation of the umbilical artery of each twin, the pulsatility index (PI) was used to evaluate the umbilical arterial waveforms. The differences in the PI from the twin-twin transfusion syndrome cases between 24-31 weeks significantly exceeded those of the cases without this syndrome (P less than .05). Seven cases had inter-twin differences in PI above 0.5, six of which had the twin-twin transfusion syndrome. The difference in PI seemed to predict the risk of twin-twin transfusion syndrome: The difference was high before the appearance of hydrops fetalis in those with this syndrome, whereas the difference in PI from discordant twin cases, except for those with the syndrome, was low.

Female↗
PubMed1990

Selective suppression of human papilloma virus type 18 mRNA level in HeLa cells by interferon.

We have studied the effect of IFN on the transcription of integrated HPV 18 DNA in HeLa cells. We found that the amount of cytoplasmic HPV 18 mRNA was markedly reduced in HeLa cells treated with 10(3) IU/ml of IFN alpha or gamma, and that the inhibitory effect was dose dependent and was detectable by 12h after the addition of IFN. Furthermore, northern blot analysis indicated that IFN remarkably reduced 3.4 kb mRNA species of HPV 18 transcripts in HeLa cells. In contrast, the level of beta-actin mRNA was found to increase in IFN treated cells. The results suggest that IFN alpha and gamma selectively inhibited HPV 18 gene expression at the level of transcription.

Cell Cycle↗
PubMed1990

Mitomycin C cross-resistance induced by adriamycin in human ovarian cancer cells in vitro.

We prepared Adriamycin-resistant cancer cells by exposing an ovarian serous cystadenocarcinoma cell line to the drug. The resistant cells also showed cross-resistance to a wide variety of other compounds, including vincristine, vinblastine, actinomycin D, daunorubicin, mitomycin C and carboquone. Against vincristine, the cells showed a greater than 5,000-fold increase in resistance, far surpassing their resistance to the selection drug. The resistant cells displayed a decrease in intracellular Adriamycin content and an increase in the mRNA of the mdr-1 gene coding for P-glycoprotein, with no amplification of the DNA. In revertant cells, resistance to Adriamycin was lost, but that to mitomycin C was maintained. Adriamycin resistance was partially overcome by the addition of verapamil or cyclosporin A, but cross-resistance to mitomycin C was not influenced at all. These results strongly suggest that the resistance to mitomycin C observed in our Adriamycin-resistant cells was due to some other mechanism than that causing multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Increased serum kininase I activity in pregnancy complicated by pre-eclampsia.

Serum kininase I activity was measured in normal pregnancy and pre-eclampsia. The mean value in nonpregnant controls was 180 +/- 25 (SD) nmol/min/ml. Kininase I activity during normal pregnancy significantly increased after week 14, reaching the highest value (240 +/- 20 nmol/min/ml) at weeks 38 and 40. The kininase I activity in pregnancy complicated by severe pre-eclampsia was higher than that in normal pregnancy. The possible role played by elevated kininase I levels in pre-eclampsia was discussed.

Adult↗