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Biomedical subjects

Y Tomoda

Publications and source records attributed to Y Tomoda.

At least 145 records · Page 8Linked to original sources
PubMed1993

Possible action of human placental aminopeptidase N in feto-placental unit.

Aminopeptidase N purified from human placenta actively hydrolyzed various immunomodulating peptides from their N-terminus such as splenopentin, thymopentin, thymic humoral factor gamma 2, tuftsin and rigin in vitro. Aminopeptidase N also actively hydrolyzed neuropeptide hormones (met-enkephalin, somatostatin and neurokinin A) and vasoactive peptides (lysyl-bradykinin and angiotensin III) from their N-terminus. In addition, angiotensin II, secretin, thymopoietin II peptide fragment, motilin, endothelin-I and insulin were tested for hydrolysis by aminopeptidase N. Km and Vmax values for the N-terminal amino acid, Thr, a liberation from tuftsin were 267 microM and 8.33 mumol/min/mg protein, respectively. L-Leucyl-p-nitroanilidase activity in the human placental membrane fraction was almost completely neutralized by anti-aminopeptidase N antibody. Our present study suggests that possible roles for surface enzyme aminopeptidase N in the human placenta would be to down-regulate the action of immunomodulating peptides as well as vasoactive and neuropeptide hormones, and to control both immunology and endocrinology of pregnancy.

Amino Acid Sequence↗
PubMed1993

Pregnancy after chemotherapy for trophoblastic diseases and psychosomatic development in the progeny.

We treated 542 patients with trophoblastic diseases from 1965 through 1988, and succeeded in preserving fertility in 269 of them (240 cases of invasive mole and 29 cases of choriocarcinoma). Of the 269 patients, 198 (79.5%) conceived after completing treatment. A total of 396 pregnancies in these women resulted in 295 term live births (74.5%), 51 spontaneous abortions (12.9%), and 4 recurrences of moles (1.0%). Four cases (1.32%) of malformations were discovered. The growth conditions of 101 children born in 1976 or later were followed up until the age of 18 months. Their heights or weights did not differ significantly from those of children measured in national infantile-growth surveys. The psychoneurological development of 54 children up to the age of 7 years who were studied by using infantile mental-development questionnaires showed no marked mental retardation. Our results provide strong evidence of the safety of chemotherapy for the treatment of trophoblastic diseases.

Adult↗
PubMed1993

Plasma angiotensin I concentration and serum placental leucine aminopeptidase (P-LAP) activities in puerperal hypertension.

To elucidate the involvement of angiotensin in puerperal hypertension with and without preeclampsia in the course of prior pregnancy, we measured plasma angiotensin I levels and serum placental leucine aminopeptidase (P-LAP) activities in several puerperal hypertensive patients. Placental leucine aminopeptidase (P-LAP) activities of puerperal hypertensive patients with severe preeclampsia during prior pregnancy were equal to or somewhat lower levels than those in normal puerperal women after a normal pregnancy. However, their angiotensin I levels were higher than those in normal puerperal women after a normal pregnancy. In puerperal hypertensive patients with and without preeclampsia during prior pregnancy, P-LAP activities tended to show much lower levels that those in normal puerperal women, while angiotensin I levels tended to show much higher levels than those in normal puerperal women, respectively. Since serum placental leucine aminopeptidase acts as an angiotensinase via degradation of angiotensin III (A-III), our present data suggest the involvement of angiotensin in puerperal hypertension.

Adult↗
PubMed1993

[Studies of prognostic factor and chemotherapeutic effect of epithelial ovarian cancer using Cox's proportional hazard model].

To make clear the prognostic factor and chemotherapeutic effect of epithelial ovarian cancer, a multiple-center study involving 22 hospitals in Japan was conducted using Cox's proportional hazard model. A total of 1,181 cases were reviewed. Clinical stage, histologic type, and residual tumor diameter were significant prognostic factors, but the degree of tissue differentiation was not. The effect of remission induction chemotherapy was assessed with or without CDDP, and a distinct prognostic difference was noted. Among the patients receiving CDDP + ADM + other chemotherapeutic agents (PA group), CDDP + other chemotherapeutic agents (PO group) and CDDP only (P group), the prognosis of the PO group was better than for the P group. The long-term prognosis improving effect of chemotherapy was assessed. Neither maintenance chemotherapy based on oral administration of pyrimidine fluoride nor immunotherapy had any long-term prognosis improving effect, while intermittent chemotherapy based on CDDP resulted in improved prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Determination of intrauterine pressure using catheter-tip transducer inserted outside fetal membranes].

To determining intrauterine pressure outside fetal membranes, we used a catheter-tip transducer to study 20 women before the occurrence membrane rupture. Their mean age was 28.2 +/- 3.4 years and all women were in weeks 37 to 41 of pregnancy when studied. In the first stage of labor, the peak intrauterine pressure was 60.0 +/- 12.5 mmHg (mean +/- SD) when the external os was dilated 4 to 6 cm, 90.0 +/- 14.8 mmHg, at 7 to 8 cm dilation, and 80.0 +/- 11.5 mmHg at 9 cm or greater dilation. Each pressure wave lasted 45 to 55 sec. The highest baseline pressure (28.0 +/- 4.5 mmHg) was obtained when the subjects were sitting. A baseline pressure of 17.0 +/- 4.0 mmHg was obtained in the supine position, as well as a value of 21.0 +/- 3.5 mmHg in the recumbent position. There were no complications related to the catheter-tip transducer. Our findings indicate that this method is both accurate and reliable in determining the amounts of intrauterine pressure to which fetal membranes are subjected.

Adult↗
PubMed1993

[Descriptive epidemiology of malignant neoplasm of the ovary in Japan].

Descriptive-epidemiological analysis of national mortality statistics on malignant neoplasm of the ovary revealed the following major findings. 1. Crude and age-adjusted mortality rates have gradually and constantly increased from 1947 to 1990 by 8.8 times and 5.4 times, respectively. 2. This increasing mortality trend was concluded to be mainly ascribable to the increasing rate of incidence rate and more accurate diagnosis. Eight background factors are generally considered to be determinants of the mortality trend. 3. Individual effects of age, year and birth cohort on mortality were analyzed and found to be constant after 50 years of age, uniformly increasing in 1950-1990, and clearly decreasing in cohorts born after 1931-1935. 4. A high standardized mortality ratio was detected in prefectures with large cities and in the northern part of Japan, with significant geographical clustering of the low standardized mortality ratio in the southern part, particularly in Kyushu Island. 5. The incidence rate of ovarian cancer was found to be relatively low in Japan as compared to the developed countries in Europe and the U.S.A..

Adult↗
PubMed1993

Identification of the pregnancy responsible for gestational trophoblastic disease by DNA analysis.

In three cases of choriocarcinoma, genetic loci including a variable number of tandem repeat regions were amplified by the polymerase chain reaction method on DNA from three established cell lines and from lymphocytes of patients and their husbands to identify the responsible pregnancy. Case 1, from whom NaUCC-3 was derived, had only one full-term fetal death. Case 2, from whom NaUCC-4 was derived, had one normal delivery followed by one complete molar delivery and one normal delivery. Case 3, from whom NaUCC-2 was derived, had one normal delivery followed by one complete molar delivery. In case 1, NaUCC-3 was found to be of parental origin and derived from the pregnancy with full-term fetal death. In cases 2 and 3, NaUCC-4 and NaUCC-2 were of probable androgenetic origin and were derived from the pregnancy with complete hydatidiform mole. We also conducted the restriction fragment length polymorphism method using case 1 samples, and it confirmed the results based on the polymerase chain reaction method product patterns. All nine cases of hydatidiform mole and three cases of invasive mole were of androgenetic origin. The polymerase chain reaction method thus makes it possible to identify easily the pregnancy responsible for choriocarcinoma using only a few specimens without isotopes.

Adult↗
PubMed1992

Identification of human placental leucine aminopeptidase as oxytocinase.

Human placental leucine aminopeptidase (P-LAP) was purified from retroplacental serum for the first time by serial chromatography on columns of Matrex Blue A, DEAE-Sepharose CL-6B, phenyl-Sepharose 4B, chelating-Sepharose, and Sepharose CL-6B. The purified P-LAP was apparently homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the apparent molecular weight (Mr) was estimated to be 210,000. By comparing P-LAP activity with cystine aminopeptidase activity, we concluded that both activities were shared by the same molecule. We also examined the hydrolytic activity of P-LAP using naturally occurring peptide hormones and found that the enzyme hydrolyzed oxytocin, vasopressin, and angiotensin III. These results suggest that P-LAP shows oxytocinase activity and plays an important role in the regulation of the plasma level of these hormones during pregnancy.

Chromatography, Gel↗
PubMed1992

Menotropin stimulation after prolonged gonadotropin releasing hormone agonist pretreatment for in vitro fertilization in patients with endometriosis.

Two protocols were scheduled for in vitro fertilization and embryo transfer (IVF-ET) in patients with various stages of endometriosis who were resistant to conventional therapies. In the ultralong protocol (21 patients), gonadotropin releasing hormone agonist (Gn-RHa) was administered for at least 60 days prior to ovarian stimulation along with menotropin until human chorionic gonadotropin was injected. In the long protocol (11 patients), Gn-RHa was started at the midluteal phase and exogenous gonadotropin was commenced between the third and the seventh day of the menstrual cycle after pituitary suppression. The estradiol response and the number of retrieved oocytes, fertilized oocytes, cleaved oocytes, and transferred embryos were similar in both groups but the clinical pregnancy rate per transfer was superior in the ultralong protocol (67 vs 27%). The miscarriage rate was 14% (2/14) in the ultralong protocol. Prolonged Gn-RHa suppression of ovarian function before superovulation may overcome some causes of infertility in patients with endometriosis.

Adult↗
PubMed1992

Prophylactic effect of bestatin on the onset of invasive mole--clinical and fundamental studies.

This study was performed to determine whether bestatin (Ubenimex) has clinical prophylactic effects on the onset of invasive mole and a direct inhibitory effect on the growth of hydatidiform molar cells. A total of 49 patients with hydatidiform mole treated at Nagoya University Hospital from 1984 to 1990 were randomly divided into two groups, a bestatin administered-group and a bestatin non-administered group. Patients in the bestatin group were given 30 mg of bestatin orally and daily for three months just after their molar deliveries. There was no significant difference in age, gravidity, parity and gestational weeks between the two groups. There was also no significant difference in the duration of human chorionic gonadotropin (hCG) negative conversion in patients without invasive mole between the two groups. However, the incidence of invasive mole in the bestatin group (2/25, 8%) was significantly lower than that of the non-bestatin group (7/24, 29.2%). Nevertheless, there was no significant difference between the two groups in such immunological parameters as PHA skin test, PPD skin test, PHA stimulation index (PHA-SI), white blood cell (WBC) count lymphocytes % per WBC, OKT 3% per lymphocytes, OKT 4% per lymphocytes, OKT4/OKT8 and Leu 11% per lymphocytes. In vitro studies were performed with primary cultured hydatidiform moles. The result was that bestatin inhibited the secretion of hCG and 3H-thymidine uptake of hydatidiform molar cells. Thus, a possibility was suggested that bestatin directly inhibits the growth of hydatidiform molar cells and prevents the onset of invasive mole.

Adolescent↗
PubMed1992

Rapid determination of fetal sex using amniotic fluid cells and the polymerase chain reaction.

We determined the sex of 50 fetuses by an amplification of the Y-chromosome specific fragment using the polymerase chain reaction (PCR). Amniotic fluid cells were collected by amniocentesis from pregnant women at 14 to 17 weeks of gestation. Total DNA was purified from cells in 1 ml of amniotic fluid. When only the expected 130 base pair X-chromosome specific fragment was detected, we identified the fetus as female, while when both the expected 170 base pair Y-chromosome specific and X-chromosome specific fragments were detected, we identified it as male. In all cases, identification was confirmed either by chromosome analysis or post partum.

Amniotic Fluid↗
PubMed1992

Induction by cortisol of aminopeptidases production from the human placenta in tissue culture.

Human placental aminopeptidase M and A and post-proline endopeptidase are known to act as degrading enzymes of bioactive peptides such as angiotensin II, oxytocin and endogenous opioids. We tested the effects of cortisol on the activities of human placental aminopeptidase A and M and post-proline endopeptidase using short-cultured placental tissues. From 34.5 nM to 3.45 microM of cortisol significantly increased the activities of 3 enzymes. Our present data suggest a possible important role of cortisol in the growth of human placenta via induction of placental aminopeptidases.

Aminopeptidases↗
PubMed1992

Relationship between the changes in placental blood flow resistance assessed by Doppler technique and maternal serum placental aminopeptidases, which degrade vaso-active peptides, in pre-eclampsia.

Our study showed that there were statistically significant correlations between the systolic and diastolic ratio (S/D) of maternal uterine or umbilical artery and the levels of maternal serum aminopeptidase activities in pre-eclampsia. Kininase I was positively correlated with the S/D ratios, whereas placental leucine aminopeptidase (P-LAP) and aminopeptidase A were negatively correlated with the S/D ratios. It is known that the increased S/D ratios reflect the increased utero-placental blood flow resistance. Since our previous study showed that placental aminopeptidases degrade vasoactive peptides such as oxytocin, angiotensin and bradykinin, which the fetus actively produces, our present study suggests that the increased vascular resistance in feto-placental circulation in pre-eclampsia is partly controlled by changes in vaso-active peptides, via degradation by placental aminopeptidases.

Adult↗
PubMed1992

Further evaluation of the pregnancy-linked down-regulation of the paternal antigen-specific splenic cytotoxic T lymphocyte activity in allogeneically pregnant mice.

Cytotoxic T lymphocyte (CTL) activity directed against paternal alloantigen was examined in allogeneically pregnant mice using various allogeneic combinations. The spleen cells from pregnant C57BL/6 (H-2b) mice mated with BALB/c (H-2d) male mice generated less anti-H-2d CTL after in vitro sensitization than those from unpregnant or syngeneically mated C57BL/6 mice. Different allogeneic combinations including the incompatibility at only D region of H-2 or minor histocompatibility loci were effective for downregulating the anti-paternal CTL activity in pregnancy. The downregulation of anti-paternal CTL activity induced by allogeneic pregnancy occurred at day 10 to day 18 of pregnancy, most extensively at day 14. The allogeneic pregnancy also downregulated the allogeneic CTL activities that had been amplified by injecting alloantigens before mating.

Animals↗
PubMed1992

The effect of nifedipine and dipyridamole on the Doppler blood flow waveforms of umbilical and uterine arteries in hypertensive pregnant women.

In a study of 45 hypertensive pregnant women, the systolic velocity/diastolic velocity ratio and pulsatility index of the umbilical and uterine arteries showed good correlation with the maternal blood pressure, and they appeared to provide a good parameter for the fetoplacental condition. Using the pulse Doppler method, we studied the effects of the antihypertensive agent nifedipine and of dipyridamole (an agent used to treat proteinuria) on the blood flow of the umbilical and uterine arteries in 16 hypertensive pregnant women. The results proved that both drugs caused a decrease in the vascular resistance of the umbilical artery and suggested that they increased the blood flow volume of this artery and were useful in the treatment of hypertension during pregnancy.

Adult↗
PubMed1992

Gonadotropin induces expression of c-fos and c-jun genes in rat ovaries.

It has been shown that the expression of protooncogenes, c-fos and c-jun, induced by growth factors and hormones plays important roles in cellular proliferation, tissue differentiation and transcription of certain genes. Since gonadotropin stimulates ovarian steroidogenesis and cellular proliferation, we investigated whether gonadotropin affects the expression of c-fos and c-jun genes in rat ovaries. The expression of mRNA coding side chain cleavage enzyme (P450scc), the rate limiting enzyme in ovarian steroidogenesis was also studied. The effect of gonadotropin was examined in female rats whose gonadotrophs were medically ablated by GnRH agonist (TAP-144-SR). After intravenous administration of pregnant mare's serum gonadotropin (PMSG:30 IU/rat), their ovaries were dissected out at various time intervals and total RNA was extracted. Changes in the levels of c-fos, c-jun and P450scc mRNAs were determined by Northern blot analysis. The levels of c-fos and c-jun mRNAs increased rapidly and transiently with the peak levels at 15 min after PMSG administration. The levels of both mRNAs were decreased by 30 to 60 min. On the other hand, the levels of P450scc mRNA started to increase 60 min after PMSG. These results indicate that gonadotropin-induced increase in the expression of c-fos and c-jun genes may play important roles in mediating the action of gonadotropin on the ovaries.

Actins↗