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Biomedical subjects

N Toyoda

Publications and source records attributed to N Toyoda.

At least 55 records · Page 3Linked to original sources
PubMed1999

Type 1 iodothyronine deiodinase in heart --effects of triiodothyronine and angiotensin II on its activity and mRNA in cultured rat myocytes.

We previously demonstrated that iodothyronine 5'-deiodination (5'D) activity is present and increased by triiodothyronine (T3) and angiotensin II (Ang II) in cultured rat cardiac myocytes. To further elucidate the stimulatory mechanism of Ang II, we investigated the effect of intracellular Ca2+ and protein kinase C on myocardial 5'D activity. Moreover, to elucidate the molecular mechanism of the stimulatory effect of T3 and Ang II, we detected the mRNA levels by means of a reverse-transcriptase polymerase chain reaction (RT-PCR). 5'D activity was increased by adding Bay-k 8644, Ca2+ channel agonist and the effect of Bay-k 8644 was completely blocked by nifedipine, a Ca2+ channel antagonist. 12-O-tetradecanoylphorbol-13-acetate, a protein kinase C activator, similarly stimulated 5'D activity. The addition of a high concentration (20-40 mM) of K+, which caused the depolarization of the membrane had significant stimulatory effects on 5'D activity. Type 1 deiodinase (D1) mRNA was evident in myocardial cells by RT-PCR in a single 758 bp band similar to that in the liver. Cardiac fibroblasts did not express the D1 mRNA. A significant increase in D1 mRNA was also evident after adding T3 and Ang II. These findings indicate that 5'D activity in myocardial cells is increased by activating the voltage sensitive Ca2+ channel, protein kinase C, and membrane depolarization, and that the D1 mRNA is present in cardiac myocytes and is increased by T3 and Ang II. This study therefore suggests that Ang II could affect the action of thyroid hormone on the heart by increasing the D1 gene expression.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1999

[Anti-thyroglobulin antibodies].

Measurement of anti-thyroglobulin antibody(TgAb) is used for diagnosis of autoimmune thyroid disease(AITD). Approximately 82-100% of patients with Hashimoto's thyroiditis and 60-70% of patients with Graves' disease are TgAb positive using high sensitive radioimmunoassay. In patients with subacute thyroiditis(SAT), TgAb is usually negative. Therefore, measurement of TgAb is useful to diagnose painless thyroiditis or acute worsening of Hashimoto's thyroiditis from SAT. To predict the post-partum thyroid dysfunction and thyroid dysfunction after interferon treatment, TgAb measurement is important, since patients with positive TgAb are apt to progress thyroid dysfunction.

Autoantibodies↗
PubMed1999

Gasless laparoscopy under epidural anesthesia for adnexal cysts during pregnancy.

OBJECTIVE: To evaluate laparoscopic adnexal cystectomy during pregnancy using an open technique with a whole abdominal wall-lift method under epidural anesthesia. STUDY DESIGN: Seven cases of adnexal cysts during pregnancy were resected using a gasless laparoscopic (extracorporeal) method with a whole abdominal wall-lift. We performed this procedure without using general anesthesia or CO2 pneumoperitoneum. RESULTS: All operations were performed successfully without complications. All patients resumed normal activity within one week. The subsequent antenatal courses of the patients were uneventful. There were no severe complications during the operations or postoperative courses. Six patients had vaginal deliveries of normal infants at term. No abnormal findings were found in the antenatal course of patient 7 until 30 weeks of gestation. CONCLUSION: Based on our limited experience, this procedure may be safe.

Adnexal Diseases↗
PubMed1999

GnRH agonist. Increasing the pregnancy rate after combined treatment with hMG/hCG and direct intraperitoneal insemination.

OBJECTIVE: To evaluate the efficacy of the GnRH agonist (GnRHa) administered in conjunction with human menopausal gonadotropin/human chorionic gonadotropin hMG/hCG and direct intraperitoneal insemination (DIPI) in women with long-standing unexplained infertility. STUDY DESIGN: A prospective, randomized, non-blind analysis. During the period May 1995-December 1996, couples with unexplained infertility who failed to conceive following superovulation combined with IUI for at least seven cycles were prospectively enrolled and followed. Pregnancy rates per cycle and per patient of DIPI were compared between groups of hMG/hCG with (GnRHa[+] controlled ovarian hyperstimulation [COH] group) or without (GnRHa[-] COH group) GnRHa. RESULTS: Thirty-four women (59 cycles) underwent COH with hMG and GnRHa, and 31 women (49 cycles) received hyperstimulation with hMG alone. The pregnancy rates for the women administered GnRHa significantly exceeded those of the patients who did not receive GnRHa both per treatment cycle (35.6% versus 14.3%) and per couple (55.9% versus 22.5%). CONCLUSION: The use of GnRHa with hMG/hCG and DIPI treatment significantly increased the pregnancy rate in women with long-standing infertility.

Adult↗
PubMed1998

Serum leptin levels do not rise during pregnancy in age-matched rats.

The serum leptin profile and its production in adipose tissue during pregnancy and lactation were investigated along with changes in appetite and factors reflecting nutritional status in 11-week-old rats. Serum leptin levels in pregnant rats were stable except on day 20 of pregnancy and significantly reduced during lactation compared to nonpregnant rats (P < 0.001). Circulating leptin levels corresponded with changes in appetite during pregnancy and postparturition. Leptin mRNA in parametrial adipose tissue reflected the circulating levels, also being significantly reduced during late pregnancy and during lactation (P < 0.05). Leptin mRNA expression was observed in placenta, but the amount suggested little influence on circulating leptin levels. These results indicate that reduction in leptin mRNA in parametrial adipose tissue and circulating leptin levels may increase appetite during late pregnancy and lactation and may play a role in regulating metabolic homeostasis around parturition in rats.

Adipose Tissue↗
PubMed1998

Quantitative measurements for type 1 deiodinase messenger ribonucleic acid in human peripheral blood mononuclear cells: mechanism of the preferential increase of T3 in hyperthyroid Graves' disease.

To evaluate the regulatory mechanism of human Type 1 iodothyronine deiodinase (D1) gene expression, we measured the D1 mRNA levels in peripheral blood mononuclear cells (PBMC) in normal control subjects and in patients with Graves' disease. We used competitive reverse transcriptase-polymerase chain reaction with the deleted complimentary RNA of D1 as the standard for quantification. The D1 mRNA levels in PBMC were increased significantly in patients with Graves' disease compared with that in normal controls. There was a significant (p < 0.01) positive correlation (r=0.698) between D1 mRNA level and serum T3 concentration. When PBMC from the normal volunteers were cultured with various doses of T3, the quantity of D1 mRNA increased significantly in a dose-dependent manner. These findings indicate that PBMC D1 mRNA is actually up-regulated by T3 in vivo, and we postulate that a vicious spiral of increasing T3 and D1 is responsible for the exacerbation of thyrotoxicosis in hyperthyroid Graves' disease.

Gene Expression Regulation↗
PubMed1998

Possible direct effect of gonadotropin releasing hormone on human endometrium and decidua.

Decidualization of endometrial tissues, which is essential for implantation and the continuation of pregnancy, is induced by pituitary hormones that are regulated by gonadotropin releasing hormone (GnRH). Our objective was to determine the role of a direct action of GnRH on endometrial tissues by comparing the characteristics of receptors for GnRH in human endometrial and decidual tissues. Competitive binding studies were performed with the protease-resistant GnRH analogues, buserelin and [125I] buserelin. The effects of buserelin on phosphoinositol turnover were determined by the measurement of inositol 1,4,5-triphosphate(IP3). The values for the dissociation constant (Kd) and number of binding sites (Bmax) per unit protein versus buserelin for endometrial tissues did not differ from the values for decidual tissues. However, the Bmax per unit DNA was significantly higher in endometrial tissues. Also, buserelin induced a significant increase in IP3 in decidual tissue. These results indicate that GnRH may be a potential modulator of the function in human endometrium and decidua. The signal transduction mechanism for GnRH action appeared to involve the accelerated turnover of phosphoinositol.

Binding, Competitive↗
PubMed1998

Maternal thyroid function in multiple pregnancy: the variable thyrotropic activity of human chorionic gonadotropin.

The present study was undertaken to evaluate thyroid function and thyrotropic action of hCG in multiple pregnancy. We examined serum samples from 9 multiple pregnant women (3 triplets and 6 twins) and 27 singleton pregnant women as control subjects. Serum hCG levels in multiple pregnancy were higher than those in singleton pregnancy in the second and third trimesters (P < 0.01). The mean free T3 and T4 concentrations in multiple pregnancy did not differ from those in singleton pregnancy in each trimester. Serum hCG levels showed a statistically significant positive correlation with free T3 and T4 levels in singleton pregnancy (P < 0.001). However, these correlations were not observed in multiple pregnancy. Thyroid stimulation activity (TSA) determined by cAMP accumulation in FRTL-5 cells in multiple pregnancy sera was significantly higher than that in singleton pregnancy in the first trimester (P < 0.05), but did not differ in the second and third trimesters. Moreover, TSA did not show any correlation with serum hCG levels in multiple pregnancy in contrast with the results in normal pregnancy. A bioactivity/immunoreactivity ratio of hCG in multiple pregnancy was lower than in singleton pregnancy in the second and third trimesters. The discrepancy between immunoreactivity and thyrotropic activity of hCG may be caused by the variable thyrotropic potency of heterogeneous hCG molecules in multiple pregnancy.

Adult↗
PubMed1998

Induction of type 2 deiodinase activity by cyclic guanosine 3',5'-monophosphate in cultured rat glial cells.

We investigated the effects of cyclic guanosine 3',5'-monophosphate (cGMP) on type 2 iodothyronine deiodinase (D2) in cultured rat glial cells. Rat glial cells were cultured in Dulbecco's modified Eagle's medium supplemented with 15% fetal bovine serum. When cells were cultured in the presence of 8-bromo cGMP (8-Br cGMP), an analogue of cGMP, D2 activity was increased in a time- and concentration-dependent manner. Lineweaver-Burk plots revealed that the stimulation of D2 activity by 8-Br cGMP (10(-3) M) was associated with fivefold increase in maximum velocity but without a significant change in Michaelis-Menten constant, suggesting that cGMP increases D2 activity via new enzyme synthesis. Both atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) are well known to increase the intracellular cGMP level via their guanylate cyclase-linked receptors in rat glial cells. In the present study, ANP (10(-6) M) and CNP (10(-6) M) significantly increased the D2 activity in rat glial cells (1.9-fold [ANP] or 2.3-fold [CNP] compared with control activity, respectively). Northern blot analysis demonstrated that D2 mRNA level increased in the presence of 8-Br cGMP (10(-3) M), and reached a plateau (six-fold) after 4 hours of incubation. The increment of D2 mRNA level by 8-Br cGMP was comparable with the increase of the D2 activity by this agent. Our data suggest that cGMP induces rat D2 activity, at least in part, at the pretranslational level, and that ANP and CNP increase D2 activity most likely via their guanylate cyclase-linked receptors in rat glial cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Spontaneous rupture of the uterus caused by placenta percreta at 28 weeks of gestation: a case report.

Placenta percreta is a rare complication of pregnancy. Rupture of the uterus due to placenta percreta is one of the most urgent obstetrical catastrophes. Recently, we observed a patient who developed placenta percreta accompanied by spontaneous uterine rupture at 28 weeks of gestation. A 29-year old gravida 3, para 1, who had a history of one cesarean section and one miscarriage with dilatation and curetage, was seen at 28 weeks of gestation. An acute abdomen and shock were diagnosed. Immediate laparotomy revealed a transverse rupture on the fundus of the uterus. A hysterectomy was performed. Pathological examination of the uterus showed placenta percreta. Rupture of the uterus due to placenta percreta before the onset of labor is extremely rare.

Adult↗
PubMed1998

Occult papillary thyroid carcinoma in Hashimoto's thyroiditis presenting as a metastatic bone tumor.

Some occult thyroid carcinomas are hypothesized to regress and be eventually obliterated. We report here a patient whose condition supports this hypothesis. A 51-year-old male with primary hypothyroidism due to Hashimoto's thyroiditis suffered from a rib bone tumor. He had a diffuse goiter with no nodular lesion. Serum FT4 and TSH concentrations were 0.8 ng/dl and 36.4 microU/ml on taking 100 microg/day of T4. Anti-Tg- and -TPO-Ab were strongly positive (99 and 1380 U/ml). The iodine 123 scintigraphy demonstrated clear accumulation in the rib tumor, whereas the thyroid was scarcely visible. Biopsy of the rib tumor showed papillary proliferation of large atypical cells, which were immunohistochemically positive for thyroglobulin. Metastatic bone tumor of papillary thyroid carcinoma was therefore strongly suspected. He underwent a total thyroidectomy and the thyroid was stepwise sectioned completely at 3 mm intervals. The thyroid condition was diagnosed as Hashimoto's thyroiditis demonstrating diffuse and dense fibrosis, lymphocyte infiltration with lymphoid follicles and flattened atrophied follicles, but no carcinomatous foci were found. He was treated with I-131 and scintigraphy after the ingestion showed distinct accumulation in the rib tumors similar to that before thyroidectomy. No other abnormal uptake was observed. It is suggested that the primary occult thyroid papillary carcinoma regressed and was obliterated possibly by some immunologic or other host-resistance factors after it metastasized to the distant bone.

Bone Neoplasms↗
PubMed1998

Variant angina in isolated adrenocorticotropin deficiency, inappropriate vasopressin secretion and Hashimoto's thyroiditis.

We report a 62-year-old male patient who had variant angina and isolated adrenocorticotropic hormone (ACTH) deficiency. His serum sodium concentration was low and vasopressin was inappropriately high for the low plasma osmolality. Serum free thyroxine (FT4) was low and thyroid stimulating hormone (TSH) was high with positive anti-thyroperoxidase antibodies, compatible with Hashimoto's thyroiditis. Treatment with Amrodipine and hydrocortisone relieved chest symptoms and hyponatremia, and hypothyroidism was also normalized. It is suggested that coronary artery spasm may be related to cortisol deficiency and/or inappropriately high vasopressin secretion and that hypothyroidism was ameliorated because the reduced responsiveness to TSH returned to normal due to hydrocortisone supplement.

Adrenocorticotropic Hormone↗
PubMed1998

Clinical features of ovarian cancer in Japanese women with germ-line mutations of BRCA1.

We analyzed the clinical features of 25 ovarian cancer patients who were associated with germ-line mutations of BRCA1 from four site-specific ovarian cancer families and seven breast-ovarian cancer families in Japan. The average age at diagnosis was 51.1 years (range, 38-77 years). Histological examination revealed 24 serous cyst adenocarcinomas in 25 patients. In 23 patients with clear clinical records, 3 patients had stage I disease, 17 had stage III disease, and 3 had stage IV disease. Thirteen patients with stage III disease who were treated with cisplatin-containing chemotherapy following tumor reduction surgery showed more favorable outcomes in both the survival rate and disease-free intervals, compared with age- and treatment course-matched controls (5-year survival rate, 0.786 versus 0.303; median disease-free interval, 91.43 versus 40.92 months; P < 0.05 for both, by logarithmic rank test). Our statistical model for the inheritance of susceptibility to ovarian cancer was derived from the analysis of 26 patients and 19 healthy carriers of 12 families. The expected lifetime risk of ovarian cancer is about 80% for women with mutations of BRCA1. These results suggest that the clinical outcome of ovarian cancer with germ-line mutations of BRCA1 appears to be more favorable than that with sporadic cases and that the disease penetrance among pedigrees with germ-line mutations of the BRCA1 gene is substantially high.

Adult↗
PubMed1997

Effects of epidermal growth factor on preimplantation mouse embryos.

PURPOSE: Our purpose was to clarify the effects of epidermal growth factor (EGF) on mouse preimplantation embryos. METHODS: We examined the effect of EGF on two-cell and four-cell stage mouse embryos cultured in vitro. In preimplantation embryos, we analyzed the binding of 125I-EGF by autoradiography and EGF receptor mRNA by the reverse transcription-polymerase chain reaction. RESULTS: At more than 0.005 ng/ml, EGF relieved the two-cell block and regulated the differentiation of morula-stage embryos. These effects were negated by antiserum. EGF did not exhibit any marked effect on embryos between the four-cell and the morula stages. Specific binding for EGF and EGF receptor mRNA was detected during and after the morula stage. CONCLUSIONS: The effects of EGF on preimplantation mouse embryos differed according to the stage of development, promoting cleavage before the four-cell stage and regulating differentiation after the morula stage. This regulatory action is thought to be transmitted to the cells via EGF receptors.

Animals↗
PubMed1997

Hexokinase II activity and messenger ribonucleic acid abundance in adipose tissue and skeletal muscle during pregnancy and lactation in rats.

OBJECTIVE: Our purpose was to investigate the influence of pregnancy and lactation on hexokinase II activity and gene expression in adipose tissue and skeletal muscle of rats. STUDY DESIGN: Intraabdominal adipose tissue and femoral quadriceps muscle were removed from Sprague-Dawley rats at various times (6 to 10 animals per group) during pregnancy and lactation. Hexokinase II messenger ribonucleic acid was assayed by quantitative ribonuclease protection analysis, and hexokinase activity was measured with the glucose-6-phosphate-coupled assay. RESULTS: The amount of hexokinase II messenger ribonucleic acid in adipose tissue on day 20 of pregnancy was 55.4% +/- 8.4% (p < 0.01, unpaired Student t test) of the value for nonpregnant control rats; hexokinase II activity was also decreased in this tissue at this time (39.34 +/- 3.05 vs 27.81 +/- 3.61 mU x min(-1) x mg protein(-1), p < 0.05). Hexokinase II activity and messenger ribonucleic acid abundance in skeletal muscle were unaffected by pregnancy and lactation. CONCLUSION: Both hexokinase II messenger ribonucleic acid abundance and enzyme activity are reduced in adipose tissue of pregnant rats near term, possibly contributing to the insulin resistance associated with late pregnancy.

Adipose Tissue↗
PubMed1997

Relative expression of insulin genes I and II during pancreatic development in fetuses of rats with streptozotocin-induced diabetes.

The relative expression of insulin genes I and II in the developing pancreas of fetuses from female rats with streptozotocin-induced diabetes was investigated by reverse transcription and polymerase chain reaction analysis. Unlike the fetuses of normal rats, in which the ratio of the pancreatic abundance of insulin I mRNA to that of insulin II mRNA increases during late gestational development, peaks around birth, and then decreases to adult values, the ratio in the offspring of diabetic mothers remained relatively constant (1.6 to 2.2) throughout this period at values similar to those of normal adult animals. These results suggest that changes in the maternal environment attributable to diabetes affect the relative expression of insulin genes I and II, and that the two genes are regulated by distinct mechanisms.

Animals↗
PubMed1997

A new variant of the cytochrome P450c17 (CYP17) gene mutation in three patients with 17 alpha-hydroxylase deficiency.

A new CYP17 gene abnormality was found in three Japanese patients with 17 alpha-hydroxylase deficiency (170HD). These patients were children from consanguineous marriages, but from two apparently unrelated families: one patient with 46, XY karyotype, and two siblings with 46, XX and 46, XY karyotypes. They were all raised as girls and presented with amenorrhea, eunuchoid appearance and hypertension. Gene analysis revealed two base-pair (TG) deletion in exon 5 (codons 300, 301) of the CYP17 gene. This deletion could be expected to alter the reading frame resulting in the lack of a haem-binding region (Cys 442) due to a premature stop codon at position 333. This small mutation may account for the patients' clinical manifestations of 170HD.

Adolescent↗