Search PubMed⌕ Search

Biomedical subjects

Y Seino

Publications and source records attributed to Y Seino.

At least 91 records · Page 5Linked to original sources
PubMed2000

Prevalence of idiopathic hypoparathyroidism and pseudohypoparathyroidism in Japan.

A nationwide epidemiologic survey of idiopathic hypoparathyroidism and pseudohypoparathyroidism was conducted in 1998 to clarify the prevalence of the two disorders in Japan. From a total of 14,100 departments of pediatrics, internal medicine, neurology, and endocrinology in whole Japan, 2952 (20.9%) study departments were selected at random. Of these departments receiving the first questionnaire, 1855 (62.8%) responded. From these departments 390 patients with idiopathic hypoparathyroidism and 203 with pseudohypoparathyroidism who visited the hospitals in 1997 were reported. The total numbers of patients were estimated to be 900 (690-1100) for idiopathic hypoparathyroidism and 430 (330-520) for pseudohypoparathyroidism (95% confidence intervals in parentheses). Using these data, the period prevalence of the diseases were 7.2 (5.5-8.8) per million population in idiopathic hypoparathyroidism, and 3.4 (2.6-4.2) in pseudohypoparathyroidism (95% confidence intervals in parentheses).

Adolescent↗
PubMed2000

Activating transcription factor-2 is a positive regulator in CaM kinase IV-induced human insulin gene expression.

Insulin plays a crucial role in the regulation of glucose-homeostasis, and its synthesis is regulated by several stimuli. The transcription of the human insulin gene, enhanced by an elevated intracellular concentration of calcium ions, was completely blocked by Ca2+/calmodulin-dependent protein kinase inhibitor. The activity of the transcription factor activating transcription factor-2 (ATF-2), which binds to the cAMP responsive elements of the human insulin gene, was enhanced by Ca2+/calmodulin-dependent protein kinase IV (CaMKIV). Mutagenesis studies showed that Thr69, Thr71, and Thr73 of ATF-2 are all required for activation by CaMKIV. CaMKIV-induced ATF-2 transcriptional activity was not altered by activation of cJun NH2-terminal protein kinase (JNK) or p38 mitogen-activated protein (MAP) kinase. Furthermore, when transfected into rat primary cultured islets, ATF-2 enhanced glucose-induced insulin promoter activity, whereas cAMP response element-binding protein (CREB) repressed it. These results suggest a mechanism in which ATF-2 regulates insulin gene expression in pancreatic beta-cells, with the transcriptional activity of ATF-2 being increased by an elevated concentration of calcium ions.

Activating Transcription Factor 2↗
PubMed2000

[Genetic factors and insulin resistance].

Diabetes is characterized by impaired insulin secretion from pancreatic beta-cell and/or insulin resistance in peripheral tissues. Genetic factors affecting the insulin sensitivities have been described, including the mutations of genes of insulin receptor, insulin receptor substrate-1, glycogen synthase, uncoupling proteins, beta3-adrenergic receptor, and peroxisome proliferator-activated receptor gamma. Mutant insulin receptors might act as a monogenic factor, but most of the others act as one of the genetic factors of a polygenetic disease.

Carrier Proteins↗
PubMed2000

[Osteoporosis].

Explore the source record for details and available documents.

Calcitonin↗
PubMed2000

[Clinical investigation of inhomogeneity of washout rate in dipyridamole stress thallium scintigraphy: implication of new parameter for the indication of coronary intervention].

OBJECTIVES: The standard deviation of the washout rate in dipyridamole stress thallium-201 myocardial single photon emission computed tomography (SPECT) was correlated with the severity of coronary artery lesions and the viability of ischemic myocardium to provide a new quantitative parameter for judging indications for coronary intervention therapy. METHODS: Dipyridamole stress thallium-201 SPECT was performed in 233 patients for differential diagnosis of angina pectoris during the 40 months beginning in October 1995, and 57 patients were investigated who underwent coronary angiography within 6 months of the SPECT. The washout rate standard deviation (WRSD) in 720 fractions in the bull's-eye view of the SPECT was determined. The conventional washout rate extent score (WRES) and washout rate severity score (WRSS) on the washout rate map were also determined. Based on the coronary angiography findings, patients were divided into 3 groups: zero-vessel group (zero-vessel disease, n = 20), one-vessel group (one-vessel disease, n = 18), and multivessel group (two- or three-vessel disease, n = 19). The patients were also divided into 2 other groups: Int group (n = 21), who underwent coronary intervention therapy, and Med group (n = 36), in whom intervention therapy was not indicated. RESULTS: All 3 parameters, WRSD, WRES and WRSS, showed significant differences between the 3 groups, and more coronary arteries affected by coronary artery stenosis were associated with higher WRSD (zero-vessel group: 5.4 +/- 1.5, one-vessel group: 7.0 +/- 3.7, multivessel group 11.4 +/- 6.7; p < 0.001), WRES (3.3 +/- 5.0, 15.5 +/- 18.1, 23.0 +/- 25.4; p < 0.01), and WRSS (1.4 +/- 2.8, 25.4 +/- 40.2, 84.8 +/- 114.5; p < 0.01). WRSD (Med group: 5.9 +/- 2.7, Int group: 11.3 +/- 6.4; p < 0.001), WRES (7.3 +/- 12.0, 24.7 +/- 24.9; p < 0.01), and WRSS (9.9 +/- 29.3, 82.9 +/- 108.2; p < 0.01) were all significantly higher in the Int group compared with the Med group. There were significant correlations between Gensini's score and WRSD (r = 0.51, p = 0.00005), WRES (r = 0.37, p = 0.005), and WRSS (r = 0.29, p = 0.03). The cutoff values for the indications for coronary intervention therapy were established for each of the 3 parameters as the maximum value of average sensitivity and specificity as follows: WRSD > 9.0 (sensitivity 0.62, specificity 0.89, positive predictive value 0.76, negative predictive value 0.24); WRES > 10.0 (0.62, 0.69, 0.54, 0.46, respectively); WRSS > 13.0 (0.62, 0.83, 0.68, 0.32, respectively). WRSD > 9.0 had the highest specificity and positive predictive value for judging indications. CONCLUSIONS: A new quantitative parameter, WRSD > 9.0, suggests the presence of viable and curable ischemic myocardium as an indication for coronary intervention therapy.

Aged↗
PubMed1999

Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice.

Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic beta cells. GIPR-/- mice have higher blood glucose levels with impaired initial insulin response after oral glucose load. Although blood glucose levels after meal ingestion are not increased by high-fat diet in GIPR+/+ mice because of compensatory higher insulin secretion, they are significantly increased in GIPR-/- mice because of the lack of such enhancement. Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes.

Administration, Oral↗
PubMed1999

Troglitazone but not pioglitazone affects ATP-sensitive K(+) channel activity.

We compared the effects of the two thiazolidinedione derivatives, troglitazone and pioglitazone, on ATP-sensitive K(+) (K(ATP)) channel activities. Pancreatic beta-cell type and cardiac type K(ATP) channels were reconstituted in COS-1 cells (SV 40-transformed African green monkey kidney (AGMK) cells) by heterologously expressing sulfonylurea receptor 1 (SUR1) plus Kir6.2 and sulfonylurea receptor 2A (SUR2A) plus Kir6.2, respectively. Troglitazone inhibited [86Rb(+)] efflux in both K(ATP) channel types in the presence of metabolic inhibitors, which was confirmed by electrophysiological techniques. The [86Rb(+)] efflux increased by the channel openers diazoxide and pinacidil was abolished by troglitazone. In contrast, pioglitazone did not affect these channel activities in either type K(ATP) channel. These results suggest that troglitazone modulates the various cellular functions including insulin secretion by inhibiting the K(ATP) channels, while pioglitazone has no effect on K(ATP) channel activity.

ATP-Binding Cassette Transporters↗
PubMed1999

Regulation of intracellular ATP concentration under conditions of reduced ATP consumption in pancreatic islets.

ATP is the most important factor in glucose-induced insulin secretion in pancreatic beta-cells, but examination of intracellular differences in ATP concentration is difficult because ATP production and consumption occur simultaneously. In the present study, we measured the ATP concentration under the condition of a reduced ATP requirement by omitting extracellular Ca(2+) and inhibiting Na-K ATPase. The ATP concentration in islets incubated with 16.7 mM glucose in the absence of Ca(2+) for 30 min was increased by about 1. 9-fold more than in the presence of Ca(2+). The increment was extracellular Ca(2+)-dependent, and was completely abolished by the metabolic inhibitors dinitrophenol and iodoacetic acid. The Ca channel blockers including nitrendipine and Ni(2+) did not affect the ATP concentration in islets incubated with 16.7 mM glucose in the presence of Ca(2+). However, when thapsigargin and suramin, inhibitors of Ca-ATPase at the endoplasmic reticulum, were added to Ca channel blockers in the presence of ambient Ca(2+), the intraislet ATP content was increased, similarly to that under Ca-free conditions. But thapsigargin did not further augment the ATP concentration in the islet with 16.7 mM glucose in the absence of Ca(2+). On the other hand, the suppression of Na-K ATPase by ouabain rather reduced the ATP concentration augmented by omission of extracellular Ca(2+). In addition, vanadate, a blocker of Ca-ATPase at the plasma membrane, failed to increase the ATP concentration in the islets. These data suggest that the increment of ATP concentration in the absence of Ca(2+) is attributable to the reduced ATP requirement due to stopping of the Ca-ATPase activity at the endoplasmic reticulum, and that the intracellular ATP concentration is differently regulated by Na-K ATPase at plasma membrane and by Ca-ATPase at endoplasmic reticulum.

Adenosine Triphosphate↗
PubMed1999

The cyclic AMP response element modulator family regulates the insulin gene transcription by interacting with transcription factor IID.

We analyzed a mechanism of transcriptional regulation of the human insulin gene by cyclic AMP response element modulator (CREM) through four cyclic AMP response elements (CREs). We isolated two novel CREM isoforms (CREMDeltaQ1 and CREMDeltaQ2), which lack one of the glutamine-rich domains, Q1 and Q2 respectively, and six known isoforms (CREMtaualpha, CREMalpha, inducible cyclic AMP early repressor (ICER) I, ICER Igamma, CREM-17X, and CREM-17) from rat pancreatic islets and the RINm5F pancreatic beta-cell line. CREM isoforms functioned as efficient transcriptional activators or repressors to modulate insulin promoter activity by binding to all of the insulin CREs. The binding activity of repressors is higher than that of activators and suppressed not only basal activity but also activator-induced activities. Furthermore, CREM activator interacted directly with the transcription factor IID components hTAF(II)130 and TATA box-binding protein (TBP). These results suggest that the activation of the insulin gene transcription by CREM activator is mediated by not only direct binding to the CREs but also by recruiting transcription factor IID to the insulin promoter via its interaction with hTAF(II)130 and TBP. On the other hand, the CREM repressor ICER competitively interrupts the binding of the activators to CREs and does not interact with either TBP or hTAF(II)130; therefore, it might fail to stabilize the basal transcriptional machinery and repress transactivation.

Animals↗
PubMed1999

Lowering barometric pressure aggravates mechanical allodynia and hyperalgesia in a rat model of neuropathic pain.

To examine the effects of meteorological change on the pain-related behaviors of neuropathic rats, animals with a chronic constriction injury (CCI) to the sciatic nerve were exposed to low barometric pressure (LP), 20 mmHg below the natural atmospheric pressure in a climate-controlled room. CCI caused a decreased hindpaw withdrawal threshold to von Frey hair (VFH) stimulation (mechanical allodynia) and prolonged duration of hindpaw withdrawal in response to pinprick stimulation (mechanical hyperalgesia). When the CCI rats were exposed to LP, both these pain-related behaviors were aggravated, whereas no change was seen in a group of controls. In the CCI rats sympathectomy inhibited this LP-induced augmentation of pain-related behaviors. These results show that LP intensifies the abnormalities in the pain-related behaviors of neuropathic rats, and that sympathetic activity contributes to the LP effect.

Animals↗
PubMed1999

The MH1 domains of smad2 and smad3 are involved in the regulation of the ALK7 signals.

The biological responses of the transforming growth factor beta (TGF-beta) superfamily are induced by activation of a receptor complex and Smad proteins. We surveyed the TGF-beta superfamily receptors using the degenerate PCR strategy, and found activin receptor-like kinase 7 (ALK7) to be abundantly expressed in fetal rat pancreatic islets. ALK7 is also expressed in adult rat islets and pancreatic beta-cell-derived MIN6 cells. The constitutively active form of ALK7, ALK7(T194D), activated Smad3 and a chimeric Smad protein, Smad3-2, containing the MH1 domain of Smad3 and the MH2 domain of Smad2, and translocated them to nuclei and then induced activation of the human PAI-1 promoter. However, neither Smad2 nor Smad2-3 protein, containing the MH1 domain of Smad2 and the MH2 domain of Smad3 were activated. These results indicate that the ALK7 signal regulates nuclear localization and activation of Smad2 and Smad3, and the MH1 domain of Smad2 has inhibitory effects on the nuclear localization.

Activin Receptors↗