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Biomedical subjects

N Toyoda

Publications and source records attributed to N Toyoda.

At least 91 records · Page 5Linked to original sources
PubMed1994

Clear cell adenocarcinoma of the vagina in a young female, treated by combination chemotherapy (local and systemic chemotherapy), complicated with chromosomal abnormality.

Although cancer of the vagina, a rare form of genital cancer, is usually squamous cell carcinoma in women over the age of 50 years, vaginal clear cell adenocarcinomas (CCA) are exceedingly rare. The pathogenesis of clear cell adenocarcinoma is uncertain, but as a clinical entity, it is most commonly associated with diethylstilbestrol exposure in utero. We report a rare case of primary vaginal CCA in a 17-year-old female who was not exposed to diethylstilbesterol in utero. The case, which was complicated with chromosomal abnormality, was treated with combination chemotherapy. To our knowledge, this is the first reported case of vaginal CCA in a woman with chromosomal abnormality and bicornate uterus.

Adenocarcinoma, Clear Cell↗
PubMed1994

A case report of placental hemangioma resulting in severe fetal distress.

A 30 year old female was admitted twice during her pregnancy for genital bleeding. An ultrasonography at 19 weeks gestation showed several nodules on the chorionic plate. Cardiotocography during labor at 37 weeks gestation indicated a non-reactive pattern. A 2230 g infant girl was delivered soon after rupture of membranes with asphyxia and hydrops fetalis. The placenta weighed 600 g with a maximal thickness of 6 cm. Nodules occupied about one-third of the placenta and were diagnosed as placental hemangiomas. Postnatal examination revealed that the infant had disseminated intravascular coagulation and cardiac failure. This baby recovered after treatment in the intensive care unit, and was discharged home on the 52nd day of life.

Adult↗
PubMed1994

Autologous blood transfusion using recombinant human erythropoietin in radical hysterectomy.

The possibility of serious complications of infection and GVHD and adverse prognosis in cancer patients resulting from homologous blood transfusions has been reported. We used recombinant human erythropoietin (rHuEPO) in autologous blood transfusions for radical hysterectomies to avoid the risks associated with transfusions. rHuEPO efficacy, stability and influence on hemodynamics were investigated. All patients were able to donate 1,200 ml of autologous blood prior to surgery, and anemia did not result despite phlebotomy three times each week. Elevation in Hb concentration was calculated at 0.78 +/- 0.37 g/dl over the first 7 days, and 2.12 +/- 0.35 g/dl over the first 14 days. No adverse side effects were observed in any patient. The serum EPO level was measured by RIA, and compared to the homologous blood transfusion group. rHuEPO did not influence postoperative EPO secretion. Autologous blood transfusion with rHuEPO in radical hysterectomy was extremely effective in mitigating the risks associated with homologous blood transfusions.

Blood Transfusion, Autologous↗
PubMed1994

Human chorionic gonadotropin secretion and protein phosphorylation in chorionic tissue.

The signal transduction system acts either monodirectionally (synergistically) or bidirectionally (antagonistically) in different tissues. We activated the signal transduction system in BeWo human choriocarcinoma cells and studied the effects on human chorionic gonadotropin (hCG) secretion, cell proliferation, and DNA synthesis. Protein phosphorylation in the cytosolic fraction was also studied by two-dimensional polyacrylamide gel electrophoresis. When phorbol 12-myristate 13-acetate (PMA) was added to cultures, hCG secretion was increased dose-dependently, but cell proliferation and 3H-thymidine uptake were not affected. When only cholera toxin was added, hCG secretion was also stimulated dose-dependently, but when both PMA and cholera toxin were added there was a synergistic potentiation of hCG production. In contrast, Ca ionophore A23187 had almost no effect on hCG secretion. Two-dimensional gel electrophoresis and autoradiography showed that phosphorylation of a 33 kd acidic protein was produced by cholera toxin, while phosphorylation of a 45 kd acidic protein and dephosphorylation of a 14 kd acidic protein were caused by the phorbol ester. These proteins may be specific substrates of protein kinase A and protein kinase C, respectively, in BeWo cells.

Cell Division↗
PubMed1993

Correlation of orbital muscle changes evaluated by magnetic resonance imaging and thyroid-stimulating antibody in patients with Graves' ophthalmopathy.

To evaluate the relationship between eye changes and autoantibody to the thyrotropin receptor in patients with Graves' disease, we evaluated the eye changes using magnetic resonance imaging and the results were correlated with thyroid-stimulating antibody, thyrotropin binding inhibitor immunoglobulin and thyroid growth activity. Subjects were 15 patients with Graves' disease who had Graves' ophthalmopathy, including exophthalmos and other signs and symptoms, and nine patients without ophthalmopathy; all were maintained in a euthyroid state by antithyroid drugs. The thyrotropin-binding inhibitor immunoglobulin was measured by a kit, and thyroid-stimulating antibody and thyroid growth activity were evaluated by cyclic adenosine 3',5'-monophosphate production and [3H]thymidine incorporation, respectively, by cultured functional rat thyroid lined cells. The sum of the swelling ratios (muscle thickness to the diameter of the optic nerve) of the four extraocular muscles correlated well with the degree of exophthalmos. The thyrotropin-binding inhibitor immunoglobulin was positive in nine out of 15 patients with ophthalmopathy; however, no correlation was observed between the activity and exophthalmos or muscle swelling. No significant correlation was observed between muscle changes and thyroid growth activity either. On the other hand, thyroid-stimulating antibody (642 +/- 91%) in Graves' patients with ophthalmopathy was significantly (p < 0.02) higher than that (315 +/- 84%) in patients without ophthalmopathy. Moreover, the level of stimulating activity in Graves' patients with ophthalmopathy showed a significant (p < 0.02) positive correlation with the sum of the swelling ratios of the individual eight eye muscles. These results suggest that thyroid-stimulating antibody has a close relation to Graves' ophthalmopathy.

Adolescent↗
PubMed1992

Human chorionic gonadotropin induces c-myc mRNA expression via TSH receptor in FRTL-5 rat thyroid cells.

To elucidate the gene regulation of the thyroid-cell growth-promoting activity by human chorionic gonadotropin (hCG), we investigated the effect of hCG on c-myc proto-oncogene expression in cultured rat FRTL-5 cells by the Northern blot method. hCG induced c-myc mRNA expression, which peaked at 60-120 min. A dose-dependent increase in c-myc mRNA levels was also ascertained. In the presence of crude immunoglobulin G (IgG) from 2 patients with primary hypothyroidism who had blocking type TSH-receptor antibody, c-myc mRNA expressions induced by hCG were decreased to 82% and 62%, compared with that in the presence of normal IgG. The present results suggest that the expression of c-myc mRNA is a part of the molecular mechanism through which hCG regulates the proliferation of thyroid cells, and that hCG-induced c-myc mRNA expression is presumed to be mediated in part by TSH receptors.

Adenoma↗
PubMed1992

Thyrotropin and triiodothyronine regulate iodothyronine 5'-deiodinase messenger ribonucleic acid levels in FRTL-5 rat thyroid cells.

We investigated the regulation of type I iodothyronine 5'-deiodinase (5'-D) gene expression by TSH and T3 in FRTL-5 rat thyroid cells. Northern blot analysis revealed that these cells express a 5'-D messenger RNA (mRNA) species of 2.1 kilobases. Readdition of TSH to FRTL-5 cells, precultured in both thyroid hormones and TSH-depleted medium for 4 days, increased 5'-D mRNA levels, reaching a maximum (2.8-fold compared to control) after 12 h of TSH (10 microU/ml) stimulation. Dibutyryl cAMP (DBC) and forskolin mimicked this stimulatory effect of TSH on 5'-D mRNA levels. T3 also increased the 5'-D mRNA levels, reaching a maximum (2-fold compared to control) after 8 h of T3 (10(-9) M) stimulation. Addition of TSH (10 microU/ml) or DBC (1 mM) together with T3 (10(-9) M) further increased 5'-D mRNA levels, reaching a maximum (5-fold compared to control) after 12 h of stimulation. Examination of the rate of disappearance of 5'-D mRNA levels after inhibition of mRNA transcription by actinomycin-D revealed that neither TSH nor T3 significantly affected the rate of disappearance. Cycloheximide, a protein synthesis inhibitor, almost completely blocked the induction of 5'-D mRNA by TSH and DBC, but did not block the induction by T3. These results suggest that both TSH and T3 increase 5'-D mRNA levels probably by increasing transcription rate, and that TSH regulates it, in part via the second messenger cAMP, for which cycloheximide-sensitive de novo protein synthesis is required, whereas T3 does without requiring it.

Animals↗
PubMed1992

Identification of a 27-kilodalton protein with the properties of type I iodothyronine 5'-deiodinase in human thyroid gland.

N-Bromoacetyl-[125I]T4(BrAc[125I]T4) was used as affinity label to identify type I 5'-deiodinase (5'-D) in human thyroid glands. Affinity labeled proteins were analyzed by autoradiography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Human thyroid microsomes labeled with BrAc[125I]T4 showed the most prominent radiolabeled band of protein at a mol wt of approximately 27,000 (p27). BrAc[125I]T4 incorporations into p27 were significantly higher in both Graves' and follicular adenomas than in normal thyroids. On the other hand, four cases out of five carcinomas were lower than the least value of normal thyroids. Furthermore, an excellent correlation was observed between 5'-D activities and quantities of p27 in all cases (r = 0.96; P less than 0.001). Labeling of p27 was strongly inhibited by preferred type I 5'-D substrate rT3, but to a lesser extent by poor substrate T4 or T3, and the type I 5'-D inhibitor, propylthiouracil and iopanoic acid, also inhibited the p27 labeling in normal and various diseases. In addition, the rate of enzyme inactivation by BrAcT4 equaled the rate of p27 labeling. These data suggest that p27 may be a type I 5'-D itself or at These data suggest that p27 may be a type I 5'-D itself or at least the substrate-binding subunit of this enzyme in human thyroid, and that both Graves' and follicular adenoma thyroids contain larger amounts of it, and papillary adenocarcinoma thyroids smaller than normal amounts.

Adenocarcinoma, Papillary↗
PubMed1992

3,3',5'-Triiodothyronine inhibits collagen-induced human platelet aggregation.

To clarify further the activity of rT3, we examined the effect of rT3 on collagen-induced platelet activation as reflected by aggregation, serotonin release, and protein phosphorylation. rT3, T4, T3, and triiodothyroacetic acid inhibited collagen-induced platelet aggregation and serotonin release from platelets in a dose-dependent manner. However, thyronine did not inhibit collagen-induced platelet aggregation. The concentration at which rT3 inhibited by 50% collagen-induced platelet aggregation was 30 +/- 4 (mean +/- SE) mumol/L. rT3, T4, and T3 did not differ significantly in their abilities to inhibit platelet aggregation. Moreover, rT3 inhibited collagen-induced phosphorylation of the 20-kilodalton protein (myosin light chain) in platelets. In contrast, rT3 did not inhibit 12-O-tetradecanoylphorbol 13-acetate (TPA)- or thrombin-induced platelet aggregation and inhibited only minimally TPA-induced 40-kilodalton protein phosphorylation. These results suggest that rT3 inhibits collagen-induced platelet activation by inhibiting the activity of myosin light chain kinase and that it may be interesting to investigate some kinds of activity of rT3.

Blood Platelets↗
PubMed1992

Treatment of hairy cell leukemia with deoxycoformycin (YK-176). The Deoxycoformycin (YK-176) Study Group.

Eleven patients with hairy cell leukemia (HCL) were treated with YK-176 (2'-deoxycoformycin) at a dose of 5 mg/m2 by intravenous injection every week or every other week. Patients received a median of eight (range 4-19) injections of YK-176. Five patients had previously been untreated, four of whom had massive splenomegaly. Six patients had previously been treated, four with interferon-alpha (IFN-alpha) or IFN-alpha and chemotherapy and two with prednisolone. Two patients had had splenectomies. Five patients achieved complete remission (CR) and six, partial remission (PR) according to WHO criteria (remission rate 100%, 95% confidence interval (CI) 74-100%). All six neutropenic patients recovered > 1,500/microliters neutrophils, six of seven anemic patients recovered > 12.0 g/dl hemoglobin and five of nine thrombocytopenic patients recovered > 100,000/microliters platelets following the treatment. According to the response criteria for HLC, five patients achieved CR, two PR and four minor response. The overall remission (CR + PR) rate was 64% (95% CI 35-85%). The CR and PR have lasted from > 30 to > 718 days (median, > 281 days) so far with no relapses. Of four patients previously treated with IFN-alpha, two achieved CR and one, PR. All patients were alive with a median survival time of > 290 days from treatment (range > 50- > 763 days). The treatment was generally well tolerated. Mild to moderate nausea, vomiting, appetite loss and general fatigue were experienced in two patients, skin rash in one and a transient fever in three. YK-176 was a highly active agent in the treatment of HCL.

Adult↗
PubMed1991

Postbinding insulin resistance around parturition in the isolated rat epitrochlearis muscle.

To determine whether insulin resistance exists in maternal skeletal muscle during pregnancy and how it returns to normal during the postpartum period, 3-O-methyl[14C]-D-glucose transport and [125I]insulin-binding activities were measured in isolated rat epitrochlearis muscle. Maximally insulin-stimulated methylglucose transport activity was decreased on day 20 of pregnancy and on days 1 and 4 post partum; it returned to the nonpregnant level by day 9. The insulin-binding activity did not change significantly throughout pregnancy, increased on days 1 and 4 post partum, and returned to the nonpregnant level by day 9. There was no significant difference in insulin binding or insulin-stimulated methylglucose transport activity between lactating and nonlactating animals. These results suggest that insulin resistance caused by postbinding changes in epitrochlearis muscle develops during late pregnancy and continues at least until day 4 post partum. Lactation does not appear to have a significant effect on insulin resistance.

Adenosine Triphosphate↗
PubMed1991

Iodothyronine 5'-deiodinase activity in cultured rat myocardial cells: characteristics and effects of triiodothyronine and angiotensin II.

Using a primary culture of neonatal rat heart, we investigated the properties of iodothyronine 5'-deiodinating activity in the heart. 125I- release from [125I] reverse T3 incubated with cell homogenates depended on the concentrations of protein and dithiothreitol, pH, incubation time, and temperature of the incubation mixture. The activity was almost completely inhibited by 10(-3)-10(-5) M propylthiouracil and had the higher affinity for reverse T3 than T4. These findings indicate that type I iodothyronine 5'-deiodinase(I-5'-D) exists in cultured neonatal rat myocardial cells. Then, we studied the direct effects of T3, insulin, glucocorticoid, and angiotensin II (AII) on myocardial I-5'-D. The addition of 10(-9)-10(-7) M T3 or 10(-9)-10(-6) M AII to the culture medium increased I-5'-D activity in a dose-dependent manner. Insulin and dexamethasone, however, had no significant effects. Kinetic studies revealed that maximum velocities in T3- and AII-treated cells were 2.1- and 1.8-fold above the control value, respectively, whereas the apparent Michaelis-Menten constant did not alter significantly both in T3- and AII-treated cells. Moreover, the treatment of cyclohexamide combined with T3 or AII completely abolished the stimulating effect of these agents on I-5'-D activity. From these data, it is suggested that both T3 and AII increase the activity of myocardial I-5'-D by their direct actions to the heart, probably through the new synthesis of I-5'-D.

Angiotensin II↗
PubMed1991

Mechanism of thyroid stimulation by human chorionic gonadotropin in sera of normal pregnant women.

To elucidate the mechanism of thyrotropic activity of human chorionic gonadotropin in sera of normal pregnant women, we examined the effect of blockade of the TSH receptor on the serum-induced cAMP accumulation and the effect of hCG on the TSH binding to FRTL-5 cells. In the presence of crude immunoglobulin fractions in sera from patients with primary hypothyroidism, cAMP accumulation induced by both crude and purified hCG, and normal pregnant women serum were significantly inhibited compared with that in the presence of normal IgGs. The mode of inhibition of these IgGs on the cAMP accumulation was similar for TSH and hCG when analysed by Lineweaver-Burk plots. Moreover, binding of [125I]bTSH to the TSH receptor in porcine thyroid cell membrane was apparently inhibited by adding 4 x 10(6) IU/l of purified hCG. Binding studies of TSH in FRTL-5 cells also indicated the dose-dependent displacements of [125I]TSH by hCG. Although half-maximal inhibitory concentration of hCG was about 20 times as high as that of TSH on a molar basis, displacement of [125I]TSH was observed at a concentration of hCG of 10(5)IU/l or more, which could be a physiological concentration of hCG in sera of normal pregnant women. These results suggest that thyrotropic activity of hCG in sera of normal pregnant women is, at least in a part, mediated by TSH receptors.

Animals↗
PubMed1991

Regulation of atrial natriuretic hormone production by triiodothyronine in cultured rat atrial myocytes.

Since thyroid hormones have been reported to increase the synthesis of rat atrial natriuretic hormone and its mRNA accumulation, we further investigated the mechanism of stimulation of rANH synthesis by T3 using cultured rat atrial myocytes. T3 (10(-9)-10(-7) mol/l) increased cellular content and secretion into the medium of immunoreactive rANH in a dose-dependent manner. However, the ratio of secreted/cellular rANH was not altered by the addition of T3. Furthermore, in both cellular and secreted rANH, the larger molecular form (gamma-rANH) apparently predominated over the smaller one (alpha-rANH), and this profile was not influenced by T3 (10(-7) mol/l). Although T3 (10(-9)-10(-7) mol/l) also increased cellular rANH mRNA accumulation, the ratio of cellular rANH/rANH mRNA was not changed. Moreover, using actinomycin D, we found that T3 (10(-7) mol/l) did not affect the degradation of rANH mRNA. From these findings, we suggest that T3 has no specific effects on the translational and posttranslational processes and the release of rANH, but that T3 stimulates rANH synthesis in the pretranslational levels, probably in the transcriptional level of rANH gene.

Animals↗
PubMed1990

The effects of insulin antibodies during diabetic pregnancy on newborn infants.

Levels of insulin antibody, free insulin, and total insulin in the blood of diabetic mothers and their newborn infants were measured, and the relations of these findings to perinatal complications were studied. The subjects were 35 patients: 8 treated with bovine/porcine insulin, 15 with porcine, and 12 with human insulin. Insulin antibody levels (insulin binding capacity; IBC) in patients injected with bovine/porcine insulin were higher. There was no difference in the insulin antibody levels between the groups treated with porcine and human insulin preparations. Infant insulin antibody levels were close to the mother's levels. Free insulin levels did not correlate with total insulin nor antibody levels, but correlated with plasma glucose levels in the infants. The birth weight did not correlate with insulin antibody levels. The frequency of neonatal hypoglycemia and cord hematocrit levels were increased when the mother's insulin antibody levels were over 20%. We conclude the following: 1) Insulin antibodies are transferred through the placenta; 2) The risk of neonatal hypoglycemia is high if the mother's insulin antibody levels are high; 3) Bovine insulin preparations should not be used.

Female↗
PubMed1990

Stimulation of rat atrial natriuretic peptide (rANP) synthesis by triiodothyronine and thyroxine (T4): T4 as a prohormone in synthesizing rANP.

Thyroid hormones have been reported to increase the secretion and synthesis of atrial natriuretic peptide (ANP) in vitro. In this study, we focused on the role of type I T4 5'-deiodinase to investigate the stimulating effects of T4 on ANP synthesis and secretion by measuring cellular content and secretion into the medium of immunoreactive rat ANP (IR-rANP) and rANP mRNA levels in cultured rat neonatal atrial myocytes. Both T3 (10(-9)-10(-7) M) and T4 (10(-8)-10(-6) M) increased cellular content and secretion into the medium of IR-rANP in a dose-dependent manner. However, these effects of T4 were completely inhibited by the addition of propylthiouracil, which selectively suppressed type I T4 5'-deiodinase activity. Methimazole, which did not alter T4 5'-deiodinase activity, had no effects on T4-induced IR-rANP increase. In the measurements of rANP mRNA levels by dot blot analysis, T3 (10(-8) and 10(-7) M) and T4 (10(-7) and 10(-6) M) increased rANP mRNA levels in the same way as they increased IR-rANP content. Although T4-increased rANP mRNA levels were also inhibited by propylthiouracil, methimazole did not alter the effect of T4. Moreover, T4-induced rANP mRNA accumulation in atrial myocytes was further stimulated by the addition of dithiothreitol, suggesting that the deiodinating activity was thiol sensitive. These data suggest that the stimulating effect of T4 on cellular IR-rANP content and rANP mRNA levels is entirely induced after it is converted to T3 by type I T4 5'-deiodinase in atrial myocytes and that T4 serves as a prohormone for T3 in synthesizing rANP.

Animals↗