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Biomedical subjects

Y Tomoda

Publications and source records attributed to Y Tomoda.

At least 127 records · Page 7Linked to original sources

Increase in Pit-1 mRNA is not required for the estrogen-induced expression of prolactin gene and lactotroph proliferation.

Estrogen has been shown to stimulate lactotroph proliferation and expression of the prolactin (PRL) gene. Recently it has been established that Pit-1, a pituitary-specific transcription factor, is required for lactotroph proliferation. Furthermore, in vitro studies showed that an increase in the PRL promoter activity caused by estrogen was dependent of the amount of cotransfected Pit-1-expressing plasmid. These findings led us to examine whether the induction of Pit-1 mRNA is required for the estrogen-increased PRL gene expression in the rat anterior pituitary in vivo. Short term estrogen treatment was achieved by means of a single intramuscular injection of estradiol dipropionate. DNA synthesis, the levels of PRL and Pit-1 messenger RNAs in the anterior pituitary were determined. Estradiol dipropionate resulted in a significant increase in DNA synthesis 24 h after administration and in PRL mRNA after 48 h. In contrast, the Pit-1 mRNA level was not altered. Since Pit-1 is expressed not only in lactotroph but also in somatotroph and thyrotroph, and the lactotroph cell population has been reported to be less than 10% in the pituitary, the change in the Pit-1 mRNA level in lactotrophs was not seen following only short term estrogen treatment. An increase in the lactotroph cell population was therefore achieved by chronic estrogen treatment (subcutaneous implantation of a silastic tube containing 17 beta-estradiol powder for 30 days). This treatment resulted in the marked proliferation of lactotrophs and a 3-fold increase in PRL mRNA. However, no alteration in Pit-1 mRNA was observed. These results suggest that the increase in Pit-1 mRNA is not required for the estrogen-induced lactotroph proliferation or PRL gene expression.

Animals↗

Effect of interleukin 2 on the production of progesterone and prostaglandin E2 in human fetal membranes and its consequences for preterm uterine contractions.

Our objective was to clarify the mechanism of uterine contraction induced in pregnant women by intrauterine bacterial infection. The concentration of interleukin 2 (IL-2) was measured in amniotic fluids that had been obtained by amniocentesis, transvaginal amniotomy or by transuterine amniocentesis performed at cesarean section in 50 pregnant women. The concentration of IL-2 in those cases with intrauterine infection was significantly higher than that of those without intrauterine infection at preterm. The same tendency was found at term. Scatchard analysis demonstrated the presence of an IL-2 receptor in the fetal membranes. We collected the fetal membranes aseptically for the measurement of progesterone and prostaglandin E2 by radioimmunoassay following incubation with various concentrations of interleukin 1 (IL-1) and IL-2 at 37 degrees C for 16 h. The production of progesterone was inhibited significantly by 10 pmol/l IL-2 but not by 10 pmol/l IL-1. The production of prostaglandin E2 was accelerated significantly by either IL-1 or IL-2 at a dose of 10 pmol/l. The inhibitory effect of IL-2 on the production of progesterone was unaffected by indomethacin, which inhibits the production of arachidonate cycloxygenase metabolites such as prostaglandin E2. Our present data suggest that the presence of intrauterine bacterial infection may stimulate the intrauterine production of IL-2, and that the stimulation of IL-2 and the reduction of progesterone caused by IL-2 may in part explain the mechanism of uterine contraction associated with intrauterine infection during pregnancy.

Amniotic Fluid↗

[Maternal working status and low birthweight: findings from a cohort study].

To explore possible associations of maternal working status with birthweight, a cohort study was conducted from July, 1989 to June, 1991 in 8 general hospitals in the Tokai district. Using a self-administered questionnaire, data on job employment were collected mostly in the first or second trimester. Information on delivery outcome was recorded by doctors, midwives or nurses after child birth. Included in this analysis were 1,360 pregnants who delivered a live singleton without major malformations at gestation of 37 weeks or more. The following major findings emerged. (1) No significant difference in mean birthweight was detected between working and non-working pregnants. (2) Working pregnants were at greater risk of delivering a low birthweight (< 2,500g) baby. (3) Delivery of a low birthweight baby was more frequent in multiparous than nulliparous mothers. (4) The risks of delivering a low birthweight baby significantly differed according to the maternal working status. (5) These results suggest that not only the maternal working factor itself but the working status should be deliberately taken into consideration in order to provide proper prenatal care.

Adolescent↗

Decrease in cytochrome c oxidase and cytochrome oxidase subunit I messenger RNA levels in preeclamptic pregnancies.

OBJECTIVE: To elucidate the possible relation between mitochondrial gene expression and placental dysfunction. METHODS: We measured the activity of cytochrome c oxidase and the expression of cytochrome oxidase subunit I in mitochondria from human placentas of women whose gestations were appropriate for gestational age (AGA) and those with preeclampsia. In addition, the amounts of normal mtDNA and deleted mitochondrial DNA were examined in the two groups by Southern blot analysis and polymerase chain reaction, respectively. RESULTS: Cytochrome c oxidase activity and expression of cytochrome oxidase subunit I were significantly lower in the preeclamptic group than in the AGA group. There were no differences between the groups in the amounts of mitochondrial DNA. In addition, no mutant mitochondrial DNA with a 4977-base pair deletion was detected in the two groups. CONCLUSION: These results suggest that reduced expression of the mitochondrial gene is involved in placental dysfunction in preeclamptic pregnancy.

Actins↗

Expression of angiotensin-converting enzyme in human placenta and its physiologic role in the fetal circulation.

OBJECTIVE: To clarify the physiologic function of angiotensin-converting enzyme (EC 3.4.15.1) in the human placenta. METHODS: The concentrations of angiotensin I and angiotensin II were measured in the umbilical artery and vein. In addition, the expression of angiotensin-converting enzyme messenger RNA (mRNA) and its activity in the human placenta were studied. The amount of angiotensin-converting enzyme mRNA was measured by Northern blot hybridization with specific human complementary DNA. RESULTS: The mean (+/- standard deviation) level of angiotensin I was significantly higher in the umbilical artery than in the umbilical vein (1044.5 +/- 626.5 versus 796.5 +/- 372.8 pg/mL; P < .05). In contrast, the mean level of angiotensin II was significantly lower in the umbilical artery than in the umbilical vein (97.3 +/- 102.9 versus 129.3 +/- 110.3 pg/mL; P < .05). Angiotensin-converting enzyme mRNA was detected in the human placenta at 4.5 and 3.9 kilobases. The amount of angiotensin-converting enzyme mRNA increased over the course of pregnancy but decreased near term, whereas angiotensin-converting enzyme activity in the human placenta continued to increase from the first trimester to term. CONCLUSION: The placenta appears to contribute to the conversion of angiotensin I to angiotensin II in the fetal circulation.

Angiotensin I↗

Detection of human papillomaviruses from histologically normal lymph nodes of Japanese cervical cancer patients by nested polymerase chain-reaction assay.

To determine the prognostic significance of human papilloma virus (HPV) DNA in histologically normal lymph nodes, we developed a nested polymerase chain-reaction (PCR) method on HPV16,18 and 33 DNAs for formalin-fixed, paraffin-embedded tissues. We investigated 370 histologically normal lymph nodes from 15 patients treated for stage-IB/IIB (FIGO) invasive cervical cancer. HPV16 DNA was detected in 7 (47%) and HPV18 DNA in 3 (20%) of the cervical cancers. Examination of histologically normal lymph nodes from these 10 patients by nested PCR revealed HPV DNA in 5 (50%) of them; in all cases HPV type in lymph nodes and tumor was the same. Two of these 5 patients had a recurrence (pelvic cavity or lung) and died of cancer, although all 5 had had pelvic radiotherapy after radical hysterectomy and lymphadenectomy. These findings indicate that nested PCR is useful for evaluating early lymph-node involvement retrospectively in HPV-positive cases.

Adult↗

Development of postmolar trophoblastic disease after partial molar pregnancy.

We investigated the clinical characteristics of patients with partial molar pregnancy and patients who developed invasive partial mole. Between 1981 and 1990, 349 patients were followed up by the Aichi prefecture trophoblastic disease registration center after partial molar pregnancy. Ten of the 349 patients with partial molar pregnancy developed invasive partial mole, an incidence (2.87%) significantly lower (P < 0.01) than that for the development of invasive complete mole (174/1410, 12.34%) following complete molar pregnancy during the same period. None of the patients had any histologic evidence of choriocarcinoma after partial molar pregnancy. The medical records of these 10 patients were compared with those of 85 of 174 registered patients with invasive complete mole, whose clinical information could be used. The interval from molar delivery to the diagnosis of invasive mole was under 9 weeks (mean, 4.90 weeks) for the patients with invasive partial mole and was significantly shorter than that for the patients with invasive complete mole, from 2 to 18 weeks (mean, 8.12 weeks) (P < 0.01). All 10 patients with invasive partial mole achieved a negative hCG level (< 0.5 mIU/ml) with eight courses or less of chemotherapy (mean, 5.50 courses). The number of courses was the same as that in the invasive complete mole group (mean, 5.70 courses). None of the patients with invasive partial mole developed recurrence. We conclude that all patients with partial molar pregnancy should be followed up as are those with complete molar pregnancy. Some patients with partial molar pregnancy will develop invasive partial mole with a relatively short interval, but remission can be achieved without the recurrence and choriocarcinoma seldom develops after partial molar pregnancy.

Adult↗

Enhanced proliferation of fetal rat hepatocytes in primary culture induced by ritodrine.

OBJECTIVE: Although ritodrine crosses the placenta, its direct effect on fetal cell proliferation has not been reported. We hypothesized that beta 2-adrenergic receptor stimulation could promote fetal liver growth. STUDY DESIGN: Ritodrine was added to serum- and hormone-free primary cultures of fetal, neonatal, or adult rat hepatocytes. We measured both tritiated thymidine incorporation into deoxyribonucleic acid and nucleus number. The effect of ritodrine on cell cycle was also analyzed with flow cytometry. RESULTS: Ritodrine enhanced the proliferation of fetal rat hepatocytes. Ritodrine remarkably stimulated deoxyribonucleic acid synthesis of fetal and neonatal but not adult hepatocytes. The effect was dose dependent and was antagonized by propranolol. Analysis of the nuclear deoxyribonucleic acid content derived from flow cytometry revealed that cells stimulated by ritodrine entered S phase. CONCLUSION: These results indicate that ritodrine may promote the proliferation of fetal hepatocytes through the stimulation of beta 2-adrenergic receptors, followed by induction of deoxyribonucleic acid synthesis.

Animals↗

Pregnancy and successful delivery in a patient with triple heart valve prosthesis.

A 42-year-old patient had a history of rheumatic fever in childhood. At 37 years of age, she underwent a triple heart valve replacement; thereafter, she was followed with the administration of warfarin and methyldigoxin. Her third pregnancy occurred with the last menstruation on 12 March 1990. At the 30th gestational week, she was admitted to the Nagoya University Hospital for the control of anticoagulation and rest. She delivered by cesarean section a healthy male infant weighing 2070 g at 34 weeks of gestation. The post-operative course was uneventful. This report shows that a patient with a three heart valve prosthesis tolerated pregnancy well under intense medical supervision.

Adult↗

Randomised study of immunotherapy with OK-432 in uterine cervical carcinoma.

OK-432, a streptococcal preparation, was administered to patients with stage Ib and II cervical carcinoma except for adeno- and adenosquamous carcinomas. To evaluate the efficacy of OK-432 precisely, 177 patients were stratified by clinical stage, radiotherapy, and lymph node metastasis after complete radical hysterectomy and pelvic lymphadenectomy. Within each stratum, patients were divided randomly into OK-432 and control groups. 85 patients received OK-432 and 92 patients did not. No significant difference was observed in overall 5-year disease free rates between the OK-432 and the control groups, although the mean diameter of erythema on SU-polysaccharide (SU-PS) skin test was larger in the OK-432 group than in the control group. In stage IIb, a significant difference was observed between the OK-432 and control groups. This difference, however, could be attributed in part to the different incidence of the lymph node metastasis. In stage II without lymph node metastasis, 5-year disease free rate was significantly higher in the OK-432 group.

Adult↗

Rapid accumulation of deleted mitochondrial deoxyribonucleic acid in postmenopausal ovaries.

To study the aging process in human ovary, we analyzed the accumulation of mitochondrial DNA (mtDNA) mutation in ovary in women of various ages. Thirty-nine tissues from ovaries and abdominal muscles, ranging from those of a fetus to those of a 77-yr-old woman, were collected at artificial abortion or gynecological surgery. Total DNA was extracted from these tissues, and parts of mtDNA were amplified via polymerase chain reaction. Through these experiments, we found a 4977-bp deletion of mtDNA between the ATPase8 and ND5 genes in ovarian samples obtained from menopausal and postmenopausal women and in all muscle samples. Quantitative analysis of the deleted mtDNA also showed that the accumulation of deleted mtDNA in the ovary occurs rapidly around the menopausal period while the accumulation found in abdominal muscle occurs gradually with aging. These results indicated that the mtDNA deletion occurs in muscular tissues even at very young ages but that accumulation of the deletion in ovarian tissue starts at the menopausal period and may have a relationship to dysfunction of the ovary in aging.

Adult↗

Human ovarian aging and mitochondrial DNA deletion.

The functions of human ovary change dynamically around the menopausal period. A decrease of the number of primordial follicles and an increase of fibrous tissues are observed histologically in the aged ovary. As endocrinological aspects at menopause, the synthesis and secretion of ovarian steroid hormones such as estrogens and progesterone decrease, followed with the resultant increases of pituitary gonadotropins. However, the mechanism of menopause and ovarian aging is not well understood. Thus, to study the regulatory mechanism of ovarian dysfunction by aging, we analyzed the accumulation of mitochondrial DNA (mtDNA) mutation in the human ovary in women of various ages. The amplification of a 5.5-kb region in mtDNA with polymerase chain reaction revealed a 0.5-kb band in ovarian samples obtained from menopausal and postmenopausal women, which means that the 5.0-kb deletion of mtDNA in ovarian tissue starts at the menopausal period. The close relationship between the occurrence of ovarian mtDNA deletion and the menstrual irregularity was also observed. These observations suggest that the accumulation of the deleted mtDNA may be a regulating factor of dysfunction of the ovary by aging.

Adult↗