Biomedical subjects

T Shiraki

Publications and source records attributed to T Shiraki.

At least 37 records · Page 2Linked to original sources

PubMed1996

Pioglitazone improves insulin signaling defects in skeletal muscle from Wistar fatty (fa/fa) rats.

The effects of pioglitazone, a novel antidiabetic insulin-sensitizing agent, on insulin signaling in skeletal muscles from genetically obese Wistar fatty rats and their lean littermates were studied. Increased tyrosine phosphorylation levels of insulin receptors (IRs) and insulin receptor substrate 1 (IRS-1) in response to insulin were not observed in fatty rats. Insulin-stimulated phosphatidylinositol (PI) 3-kinase activity was reduced in fatty rats. Administration of pioglitazone (3 mg/kg/day) to fatty rats for 10 or 18 days reversed the decline in the insulin-stimulated tyrosine phosphorylated IR and IRS-1 levels and the reduced insulin-stimulated PI 3-kinase activities. In contrast, insulin-stimulated tyrosine phosphorylation of IR and IRS-1 and PI 3-kinase activity in lean rats was not changed by pioglitazone. IR expression in fatty rats was down-regulated, which was not affected by pioglitazone. There was no difference between the PI 3-kinase expression levels in fatty and lean rats and pioglitazone did not change these expression levels. These results indicate that pioglitazone can correct the insulin signaling defects of Wistar fatty rats, thereby ameliorating insulin resistance.

Animals↗

PubMed1996

Stimulating effect of 6R-tetrahydrobiopterin on Ca2+ channels in neurons of rat dorsal motor nucleus of the vagus.

We have recently found that 6R-tetrahydrobiopterin (6R-BH4), a natural cofactor for aromatic L-amino acid hydroxylases and nitric oxide synthase, enhances dopamine release. Here, using a slice patch method, we examined the effect of 6R-BH4 on Ca2+ channels in neurons of rat dorsal motor nucleus of the vagus, where dopaminergic neurons are densely located. 6R-BH4 enhanced N-type Ca2+ channel currents, whereas 6S-BH4, a diastereoisomer of 6R-BH4, had little effect. Neither sodium nitroprusside, a nitric oxide generator, nor L-DOPA, a product of tyrosine hydroxylation, mimicked the effect of 6R-BH4. These findings suggest that 6R-BH4 enhances N-type Ca2+ channel currents in stereospecifically and independently of its cofactor activities as observed in its dopamine releasing action, and raise possibility that 6R-BH4 enhances dopamine release by activating Ca2+ channels.

Animals↗

PubMed1996

Human endothelin converting enzyme gene (ECE1) mapped to chromosomal region 1p36.1.

The chromosomal localization of the human endothelin converting enzyme gene (ECE1) has been identified. Southern blot analysis of human genomic DNA from human x mouse somatic cell hybrids demonstrated that ECE1 maps to chromosome 1. Fluorescence in situ hybridization of a digoxigenin-labeled human ECE1 probe to normal human metaphase chromosomes showed that the gene is located within chromosome band 1p36.1.

Animals↗

PubMed1996

Reduced vasodilator response of the right coronary artery to myocardial ischemia in the hypertrophied right ventricle.

The reduced reactive hyperemic response of the right coronary artery (RCA) to brief coronary occlusion was assessed in dogs with pressure-induced right ventricular hypertrophy (RVH). Right coronary reactive hyperemia was observed in normal dogs and in dogs with pressure-induced RVH. RVH was induced by chronic pulmonary artery banding in eight 3- to 6-month-old dogs, and reactive hyperemia responses to coronary occlusion lasting for 5, 10, 15, 20, 30, 45, and 60 sec were compared to those in normal dogs. In dogs with RVH, the peak reactive flow rate and excess blood flow debt repayment after the release of 5- to 60 sec RCA occlusion were markedly attenuated. The calculated minimum coronary resistance was higher in RVH dogs than in normal dogs (p < 0.02). The occlusion time that produced one-half of the maximum %PRHc, T1/2, was significantly (p < 0.01) shorter in RVH dogs than in normal dogs, where %PRHc = (peak reactive flow rate baseline flow rate)/(baseline flow rate). T1/2 in RVH dogs varied inversely with right ventricular systolic pressure. Therefore, blood flow in the RCA in RVH is characterized by an attenuated flow response to acute myocardial ischemia, suggesting inadequate development of the coronary vasculature supplying the hypertrophied ventricle.

Animals↗

PubMed1996

[Epicardial lipoma].

Explore the source record for details and available documents.

Diagnosis, Differential↗

PubMed1994

cDNA cloning and expression of bovine endothelin converting enzyme.

We have cloned cDNA encoding bovine endothelin converting enzyme (ECE). The predicted amino acid sequence of bovine ECE consisted of 758 amino acid residues. Northern blot analysis revealed that ECE mRNA was abundantly expressed in lung. Co-expression of the cloned cDNA of bovine ECE with human preproET-1 cDNA in CHO-K1 cells resulted in the production of mature ET-1 and this production was inhibited by phosphoramidon.

Amino Acid Sequence↗

PubMed1994

Genetic transfer of endothelin converting enzyme activity to CHO-K1 cells: detection of positive cells by reverse hemolytic plaque assay.

We have established a novel method of molecular cloning of endothelin converting enzyme, a key enzyme in the production of a potent vasoconstrictor endothelin-1, by modification of the reverse hemolytic plaque assay. Also, we demonstrated that a cell line, CHO-K1, showed no detectable activity of endothelin converting enzyme. This cell line was transfected with a cDNA library of bovine endothelial cells. The modified reverse hemolytic plaque assay was shown to detect even a single CHO-K1 cell that was changed to produce mature ET-1 by transfection. Thus, this novel method is suggested to be useful for the molecular cloning of other secreted antigens and their processing enzyme.

Animals↗

PubMed1993

Prostaglandin E2 excites neurons of the nucleus tractus solitarius by activating cation channels.

Nucleus tractus solitarius (NTS) has a high density of prostaglandin E2 (PGE2)-binding sites. Action of PGE2 (10(-9)-10(-6) M) was tested on neurons in a NTS slice with patch-clamp recording under synaptic blockade. PGE2 raised the firing rate in approximately half of the neurons in cell-attached patch mode. In whole-cell current clamp, PGE2 depolarized membrane potential accompanied by an increase in firing rate. In whole-cell voltage clamp (-58 mV), PGE2 induced the inward current with an increase in conductance. The current was linearly related to voltage from -100 mV to -10 mV and suppressed between -10 mV and 20 mV. The current-voltage curve remained similar under low external Cl- or high internal Cl- conditions and after external Na+ was replaced by Cs+. It is concluded that PGE2 excites NTS neurons by activating cation conductance.

Animals↗

PubMed1993

Antihypertensive effects of CS-045 treatment in obese Zucker rats.

The association of hypertension with obesity has been well recognized, but the etiology remains poorly understood. Obesity is characterized by hyperinsulinemia, which reflects peripheral insulin resistance. Insulin resistance may participate in the development of hypertension with obesity. CS-045 [(I)-5-[4-(5-hydroxy-2,5,7,8-tetramethylchroman-2-yl-methoxy)be nzy l]-2,4- thiazolidiendion] is a new orally effective antidiabetic agent that potentiates insulin action and reduces insulin resistance in obese Zucker rats and other obese diabetic animals. In this study, we examined the antihypertensive effect of CS-045 in obese male and female Zucker rats as a model of hypertension associated with obesity. CS-045 was administered as a food admixture (approximately 16 and approximately 70 mg/kg/d) for 4 weeks (female) and (approximately 15 and approximately 67 mg/kg/d) 8 weeks (male) in obese Zucker rats at 5 to 7 months of age. CS-045 slightly but significantly decreased plasma glucose levels. Plasma insulin levels were significantly decreased in obese male rats, but were not significantly decreased in obese female rats. Drug administration led to significant decreases in plasma triglyceride and cholesterol levels and systolic blood pressure (SBP) in a dose-dependent manner from 1 week after administration in obese Zucker rats. CS-045 increased urinary sodium excretion, sodium/potassium ratio, and creatine clearance in a dose-dependent manner, and also led to a remarkable decrease in urinary protein excretion. However, CS-045 did not reduce urinary catecholamine excretion. These data indicate that CS-045 may promote renal sodium excretion and improve decreased glomerular filtration rates, which may reflect the amelioration of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effects of emergency coronary angioplasty on left ventricular volume after acute myocardial infarction compared with intracoronary thrombolysis.

BACKGROUND: The effects of emergency coronary angioplasty on left ventricular remodeling have not been fully evaluated. We compared the effects of emergency coronary angioplasty on left ventricular volume with those of intracoronary thrombolysis in patients suffering from their first acute myocardial infarction (AMI). METHODS: A total of 51 patients who had a culprit lesion at site No 6 of the American Heart Association (AHA) classification were analyzed. Patients with re-obstruction of the culprit lesion after reperfusion were excluded from the study. The coronary angioplasty and the thrombolysis groups consisted of 28 and 23 patients, respectively. Left ventricular volume was measured by left ventriculography at 4 weeks after infarction. RESULTS: Clinical and angiographic background factors showed no significant differences between these two groups. The left ventricular end-systolic volume index was significantly smaller in the angioplasty group than in the thrombolysis group (31 +/- 14 versus 45 +/- 14 ml/m2, P < 0.01). Similarly, the left ventricular end-diastolic volume index was significantly smaller in the angioplasty group (64 +/- 13 versus 82 +/- 13 ml/m2, P < 0.01). Conversely, the left ventricular ejection fraction was larger in the angioplasty group than in the thrombolysis group (54 +/- 13 versus 45 +/- 13%, P < 0.05). Multivariate analysis revealed that the selection of coronary angioplasty was one of the factors significantly associated with a decrease in left ventricular end-systolic and end-diastolic volume. CONCLUSION: These results suggest that emergency coronary angioplasty produces better left ventricular remodeling than intracoronary thrombolysis after AMI.

Adult↗

PubMed1993

[Giant plasmacytoma of the skull which appeared in the clinical course of multiple myeloma--a case report].

A 51-year-old woman with large plasmacytoma occurring from the temporal bone is presented. She has a history of multiple myeloma for 9 years. She manifested marked swelling in the left temporal area with tenderness. Neurological examination revealed no abnormality. She showed monoclonal free light chain (lambda type) in the serum and urine, and had multiple osteolytic lesions in her general bones. T1 WI of MRI exhibited a huge mass showing slightly high intensity in the left middle fossa and infratemporal fossa, and a part of the mass protruded into the extracranial space. The mass was markedly enhanced by Gd-DTPA. Angiography showed a hypervascular mass supplied by the external carotid artery. Biopsy disclosed plasmacytoma. She underwent local irradiation of 30 Gy and chemotherapy of Ranimustine (100 mg) and Cyclophosphamide (400 mg). The tumor reduced its size, and tenderness in her temporal area disappeared.

Cerebral Angiography↗

PubMed1992

C-1' hydrogen abstraction of deoxyribose in DNA strand scission by dynemicin A.

Dynemicin A, which is a hybrid antitumor antibiotic containing anthraquinone and enediyne cores, abstracts the C-1' hydrogen of DNA deoxyribose and then the damaged DNA leads to strand breaks with the formation of 5'- and 3'-phosphate termini. The lesions of C-4' hydrogen also occur at 3' side of G.C base pairs (i. e., 5'-CT and 5'-GA), leading to 5'-phosphate and 3'-phosphoglycolate termini or 4'-hydroxylated abasic sites. The C-1' hydrogen abstraction by dynemicin A is distinct from the preferential C-5' hydrogen abstraction of calicheamicin and neocarzinostatin.

Anthraquinones↗

PubMed1992

A case of Graves' disease and papillary thyroid carcinoma with predominant production of thyroid-stimulation-blocking antibodies (TSBAb) persisted after total thyroidectomy.

A 42-year-old female with Graves' disease and papillary thyroid carcinoma with lung metastasis was referred to our hospital. After treatment of thyrotoxicosis with methimazole and Lugol's solution, she underwent total thyroidectomy. She was then given 131I twice to treat lung metastasis. However, 131I uptake into the lung was not clear in the scintigram. Both thyroid-stimulating antibodies (TSAb) and thyroid-stimulation-blocking antibodies (TSBAb) were detected in her sera before and after the treatments. Compared with TSAb activities, TSBAb activities were extremely high. Changes in the titers of these two antibodies were not clear after total thyroidectomy. These results indicate that lymphocytes outside the thyroid gland are the major source of TSAb and TSBAb in this patient.

Adult↗

PubMed1991

Reductive and nucleophilic activation products of dynemicin A with methyl thioglycolate. A rational mechanism for DNA cleavage of the thiol-activated dynemicin A.

The reaction products of methyl thioglycolate with dynemicin A, dynemicin H and dynemicin S, were isolated by HPLC purification and identified spectroscopically. The major product, dynemicin H (C30H23NO9), was determined to be a C-8 hydrogen analogue of dynemicins L and N in which the enediyne core is aromatized. The minor product, dynemicin S (C33H27No11S), is an adduct of methyl thioglycolate at the C-8 position. By using NADPH instead of methyl thioglycolate, the reaction with dynemicin A also gives the same major product (dynemicin H). The nucleotide-specific cleavage of dynemicin A induced by addition of methyl thioglycolate is remarkably similar to that induced by addition of NADPH, whereas dynemicins H and S show no DNA cleavage activities. The formation of dynemicins H and S provides a rationale for the reductive and nucleophilic activations of dynemicin A.

Alkenes↗

PubMed1991

Reproducibility of diurnal variation of heart rate.

Heart rate variation has been utilized as a parameter for validating autonomic nerve and sinus node function. However, few reports are available on the reproducibility of such data. In the present study, we studied the reproducibility of the diurnal variation of heart rate in 15 patients, and the effect of age differences on the variation in 30 normal men using a Holter ECG monitoring method. For investigating reproducibility, Holter ECG monitoring was performed twice, the two measurements being separated by a short interval. A moving average method applied on heart rate of every 3h exhibited essentially the same diurnal pattern of heart rate between two records in each patient. Excellent reproducibility of the pattern was also demonstrated by a lag correlation analysis. Variability of heart rate in normal men was independent of age. These results suggest that heart rate variation was essentially constant in each subject, at least within a short period.

Adult↗

PubMed1990

Visible light induced DNA cleavage by the hybrid antitumor antibiotic dynemicin A.

Dynemicin A, which is a hybrid antitumor antibiotic containing anthraquinone and enediyne cores, effectively breaks DNA strands upon irradiation with visible light of long wavelength. The preferential cutting sites of visible light induced DNA cleavage with dynemicin A are on the 3'-side of purine bases such as in 5'-AT and 5'-GT sequences. The observed nucleotide cutting specificity is remarkably similar to that of NADPH- (or thiol) induced DNA breakage with dynemicin A, suggesting the presence of the same DNA-cleaving intermediate. Indeed, the photoproduct of dynemicin A is chromatographically identical with the reaction product (dynemicin H) of the thiol-activated dynemicin A. On the basis of the present results, a reasonable mechanism for the visible light induced DNA cleavage of dynemicin A has been proposed.

Anthraquinones↗

PubMed1990

DNA intercalation and cleavage of an antitumor antibiotic dynemicin that contains anthracycline and enediyne cores.

Dynemicin is a hybrid containing anthraquinone and enediyne cores, which contribute to binding and cleavage of DNA, respectively. DNA strand scission by the antitumor antibiotic is significantly enhanced by the addition of NADPH or thiol compounds. The preferential cutting site of dynemicin is on the 3' side of purine bases (i.e., 5'-GC, -GT, and -AG) and is clearly different from the cutting sites of esperamicin and calicheamicin. The double-stranded and the stem regions of single-stranded DNAs are preferentially cleaved by dynemicin. Therefore, dynemicin may be a useful reagent for probing secondary structures of DNA. Pretreatment of DNA with Adriamycin and actinomycin D alters the cutting mode of dynemicin. Dynemicin-mediated DNA breakage is strongly inhibited by pretreatment of the DNA with distamycin A and anthramycin, suggesting that dynemicin interacts with the minor groove of the DNA helix. Intercalation of the anthraquinone core into the DNA followed by the attack of the phenyl diradical formed from the enediyne core is considered as a possible mechanism of action of dynemicin.

Anthraquinones↗

PubMed1990

[A malignant thymoma combined with sarcoidosis].

A case of 69-year-old female of malignant thymoma with sarcoidosis was experienced. Although many diseases such as myasthenia gravis are associated with thymoma, sarcoidosis is a rare thymoma-associated disease. Only one case of thymoma with sarcoidosis was reported all over the world, and our case is the first case in Japan. As thymus is essential for the development of T lymphocytes, thymoma may cause T lymphocytes disorder and sarcoidosis. So, we consider thymoma with sarcoidosis as a syndrome rather than as a spectrum of coincidental disease.

Aged↗