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Biomedical subjects

Y Seino

Publications and source records attributed to Y Seino.

At least 37 records · Page 2Linked to original sources
PubMed2001

Recovery of function and mass of endogenous beta-cells in streptozotocin-induced diabetic rats treated with islet transplantation.

Islet transplantation corrects chronic hyperglycemia by augmentation of insulin supply from the graft tissue, but the role of endogenous beta-cells after transplantation is not clear. In the present study, we examined endogenous beta-cell function after glucose homeostasis had been reestablished by islet graft in streptozotocin (STZ)-induced diabetic rats. Fed plasma glucose levels in diabetic rats transplanted with a large number of islets (2500 islets) into the left kidney capsule soon became lower (139.8 +/- 8.2 mg/dl) and close to the level in controls (129.7 +/- 11.3 mg/dl), and IPGTT exhibited a pattern of plasma glucose response almost identical to control. The insulin and DNA contents, islet area, and the distribution of beta-cells that were markedly deteriorated in islets of STZ rats were significantly restored in transplanted rats. The insulin release in response to glucose or alpha-ketoisocaproate was less in STZ rats, while in islets of transplanted rats the secretion recovered to levels similar to controls. On the other hand, arginine-induced insulin release was conversely hyperresponsive in STZ rats, but in transplanted rats, the response was decreased similar to controls. Thus, as the plasma glucose level normalizes, residual beta-cells show a recovery of function that cannot be accounted for by the increase in mass alone.

Animals↗
PubMed2001

Maternal origin of a unique extra chromosome, der(9)(pter-->q13::q13-->q12:) in a girl with typical trisomy 9p syndrome.

We report on a girl with the typical trisomy 9p syndrome who had an additional E-sized metacentric chromosome. On the basis of GTG- and CBG-banding, her karyotype was considered to be 47,XX,+der(9)(pter-->q13::q13-->q12:) de novo. Results of a fluorescence in situ hybridization study using a chromosome 9-specific painting probe were compatible with this cytogenetic interpretation. Molecular analyses of six highly polymorphic dinucleotide repeat loci on the short arm and the proximal long arm of chromosome 9 demonstrated that the girl inherited one allele from her father and two identical or different alleles from the mother. We speculated that the extra chromosome may have resulted from either nondisjunction of chromosome 9 followed by a U-type exchange and a crossing-over between different sister chromatids during maternal meiosis I and subsequent breakage and malsegregation during meiosis II, or nondisjunction during meiosis II followed by isochromosome formation in one of the two maternal chromosomes 9 and subsequent breakage.

Alleles↗
PubMed2001

Heat shock restores insulin secretion after injury by nitric oxide by maintaining glucokinase activity in rat islets.

Heat shock protein (hsp), including hsp70, has been reported to restore the glucose-induced insulin release suppressed by nitric oxide (NO). However, the mechanism underlying this recovery remains unclear. In the present study, we examine the effects, in rat islets, of heat shock on insulin secretion inhibited by a small amount of NO and also on glucose metabolism, the crucial factor in insulin release. Exposure to a higher dose (15 U/ml) of interleukin-1beta (IL-1beta) abolished the insulin release by stimulation of glucose or KCl in both control and heat shocked islets. In rat islets exposed to a lower dose (1.5 U/ml) of IL-1beta, insulin secretion in response to glucose, but not to glyceraldehydes (GA), ketoisocaproate (KIC), or KCl, was selectively impaired, concomitantly with lower ATP concentrations in the presence of 16.7 mM glucose, while such suppression of insulin secretion and ATP content was not observed in heat shock-treated islets. NO production in islets exposed to 1.5 U/ml IL-1beta was significantly, but only partly, decreased by heat shock treatment. The glucose utilization rate measurement using [5-3H]-glucose and [2-3H]-glucose and the glucokinase activity in vitro were reduced in islets treated with 1.5 U/ml IL-1beta. In heat shock-treated islets, glucose utilization and glucokinase activity were not affected by 1.5 U/ml IL-1beta. These data suggest that heat shock restores glucose-induced insulin release inhibited by NO by maintaining glucokinase activity and the glucose utilization rate in islets in addition to reducing endogenous NO production.

Animals↗
PubMed2001

Molecular detection of metastatic retinoblastoma cells by reverse transcription polymerase reaction for interphotoreceptor retinoid-binding protein mRNA.

BACKGROUND: In the current study, the authors report a 4 year old girl with disseminated retinoblastoma. To find sensitive and specific molecular markers for detection of retinoblastoma cells in blood and marrow, the authors evaluated three photoreceptor-associated gene transcripts by using reverse transcription polymerase chain reaction (RT-PCR). METHOD: Samples of bone marrow and blood were obtained from healthy donors and the patient. RT-PCR was performed to detect the cone alpha'-subunit of cGMP phosphodiesterase (cone alpha'-PDE), the rod beta-subunit of cGMP (rod beta-PDE), and the interphotoreceptor retinoid-binding protein (IRBP) gene transcript in RNA extracted from the samples. RESULTS: While no expression of rod beta-PDE or IRBP was detected in any of the normal samples, expression of cone alpha'-PDE was detected in two out of seven normal marrow samples. Expression of rod beta-PDE was not detected in the patient samples. Expression of IRBP was detected in the patient samples obtained from iliac bone marrow before intensive chemotherapy but not thereafter. CONCLUSION: RT-PCR for IRBP was a useful method for detecting metastatic retinoblastoma cells as well as for evaluating the therapeutic effects of treatment in this particular case.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Expression of very low density lipoprotein receptor mRNA in circulating human monocytes: its up-regulation by hypoxia.

Although very low density lipoprotein (VLDL) receptor expression by macrophages has been shown in the vascular wall, it is not clear whether or not circulating monocytes express the VLDL receptor. We investigated the expression of VLDL receptor mRNA in human peripheral blood monocytes and monocyte-derived macrophages by reverse transcriptase polymerase chain reaction (RT-PCR) and nucleotide sequencing after subcloning of PCR product. VLDL receptor mRNA was detected both in peripheral blood monocytes and monocyte-derived macrophages. Expression of VLDL receptor mRNA was upregulated by hypoxia in monocytes, whereas treatment with oxidized LDL, interleukin-1beta or monocyte chemoattractant protein-1 did not affect the levels of VLDL receptor mRNA in monocytes and macrophages. The present study shows a novel response of VLDL receptor mRNA to hypoxia, suggesting a role for VLDL receptor in the metabolism of lipoproteins in the vascular wall and the development of atherosclerosis.

Adult↗
PubMed2001

Distinct effect of diazoxide on insulin secretion stimulated by protein kinase A and protein kinase C in rat pancreatic islets.

Protein kinase activation is known to stimulate glucose-induced insulin secretion in the presence of diazoxide. Diazoxide opens the ATP-sensitive K(+) channel and inhibits FAD-linked glycerophosphate dehydrogenase activity in a concentration-dependent manner. In the present study, we examined the effect of lower (100 microM) and higher (250 microM) concentrations of diazoxide on insulin release by protein kinase A (PKA) and protein kinase C (PKC) activation. Forced depolarization by a high potassium concentration, augmented the intracellular Ca(2+) concentration ([Ca(2+)](i)) similarly in the presence of both concentrations of diazoxide. Under this condition, 250 microM diazoxide inhibited insulin release enhanced by PKA activation but not that by PKC. Under a basal concentration of [Ca(2+)](i), PKC activation elicited glucose-induced insulin secretion at 100 and 250 microM diazoxide, while PKA activation did so only at 100 microM. These augmentations were completely inhibited by mannoheptulose, a glucokinase inhibitor. Glyceraldehyde, in place of glucose, enhanced insulin secretion by PKC activation under both concentrations of diazoxide. On the other hand, it did not affect PKA-stimulated insulin release under either conditions, but in the case of 100 microM, glucose augmented the insulin secretion in the presence of glyceraldehyde and db-cAMP concentration-dependently. These data suggest that insulin release stimulated by PKA and PKC activation under diazoxide is dependent on glucose metabolism, and that a signal derived from proximal steps in glycolysis may be necessary for the secretion by PKA activation.

Animals↗
PubMed2001

Case report: pulmonary embolism from thrombosis in a duplicated inferior vena cava developing after an electrophysiologic procedure.

Duplicated inferior cava (IVC) is an anomaly we rarely encounter during electrophysiologic procedures. We report a case with duplicated IVC who developed thrombosis of the left IVC following an electrophysiologic procedure, which resulted in an asymptomatic pulmonary embolism. It is speculated that several catheters placed in the torturous route through the left IVC caused either endothelial damage to the vessel wall, or hemostasis in the relatively narrow portion of the vessel, resulting in thrombus formation. Since the prevalence and characteristics of thrombo-embolic complications during electrophysiologic procedures in patients with a duplicated IVC remain unknown, we believe this case should be reported.

Electrophysiologic Techniques, Cardiac↗
PubMed2001

Disopyramide and its metabolite enhance insulin release from clonal pancreatic beta-cells by blocking K(ATP) channels.

In an insulin-secreting pancreatic beta-cell line (MIN6), insulin release was caused by disopyramide, an antiarrhythmic drug with Na-channel blocking action, and its main metabolite mono-isopropyl disopyramide (MIP). Insulin secretion, measured as immunoreactive insulin (IRI), was accelerated to 265.7% of the control by disopyramide and to 184.4% by MIP, with half-effective concentrations (EC50) of 30.9 +/- 1.5 microM and 92.4 +/- 2.2 microM. We tested the possibility that these drugs induce insulin release by inhibiting ATP-sensitive K+ (K(ATP)) channels of MIN6 cells. In the cell-attached or ATP-free inside-out mode with patch membranes on MIN6 cells, K-selective channels were recorded with unitary conductance of 70.5 +/- 3.5 pS (150 mM external K+ ions at room temperature). The channels were concluded to be MIN6-K(ATP) channels because they were closed by extracellular high glucose (11.0 mM) or glibenclamide (200 nM) and were reversibly activated by diazoxide (50 microM). In the inside-out patch mode, they were inhibited by micromolar ATP. In both cell-attached and insideout mode, disopyramide and MIP inhibited single MIN6-K(ATP) channels. In the inside-out mode, they produced a dose-dependent inhibition of channel activity: the half-blocking concentrations (IC50) were 4.8 +/- 0.2 microM for disopyramide and 40.4 +/- 3.1 microM for MIP. It was therefore concluded that both agents exert insulinotrphic effect through the inhibition of membrane K(ATP) channels in MIN6 cells.

ATP-Binding Cassette Transporters↗
PubMed2001

Synergistic effect of polymorphisms of uncoupling protein 1 and beta3-adrenergic receptor genes on autonomic nervous system activity.

OBJECTIVE: To investigate the association of the promoter region -3826 A to G polymorphism of the uncoupling protein 1 (UCP1) gene with autonomic nervous system (ANS) activity and the interaction of the polymorphism with the Trp64Arg polymorphism of the beta3 adrenergic receptor (beta3AR). SUBJECTS: Three-hundred and forty-nine young (mean age 20.4+/-2.1 y old), healthy Japanese males. MEASUREMENTS: DNA was extracted from whole blood and genotyped by polymerase chain reaction restriction fragment length polymorphism. Plasma glucose, plasma insulin and body mass index (BMI) were measured. Frequency of family history of diabetes or obesity was determined by interview. Subjects randomly chosen from each genotype were examined for ANS activity during supine rest and standing by electrocardiogram power spectral analysis of heart rate variability. RESULTS: UCP1 or beta3AR polymorphism was not associated with BMI, plasma glucose, plasma insulin and frequency of family history of diabetes or obesity. The inhibitory effect of UCP1 polymorphism on ANS activity was observed only with occurrence of the variant of beta3AR. The very low frequency component associated with thermoregulation in the sympathetic nervous system of homozygotes of UCP1 (GG) at supine rest was significantly lower than normal (AA, 203.2+/-50.3 vs 462.2+/-83.6 ms(2); mean+/-s.e., P=0.021). A higher response to postural change to standing was also observed in both sympathetic and parasympathetic nervous activities of AA than of GG. CONCLUSION: While UCP1 polymorphism alone does not affect ANS activity, it has a synergistic effect with beta3AR polymorphism in decreasing sympathetic nervous system activity.

Adult↗
PubMed2001

An ultrasensitive assay revealed age-related changes in serum oestradiol at low concentrations in both sexes from infancy to puberty.

OBJECTIVE: Intensive studies of oestrogen receptors have suggested extragonadal functions of oestrogen. However, the in vivo extragonadal functions of oestradiol remain unclear because of the lack of an adequate assay system at low concentrations. In this study, we assessed the usefulness of a new ultra-sensitive assay for children. METHODS: Serum oestradiol was measured with an ultrasensitive assay (assayable concentration: 5-1,835 pmol/l: ESTR-US-CT, CIS biointernational, France). Intra- and interassay coefficients of variation at low concentrations (< 36.7 pmol/l) were 8.2 +/- 6.8 (0.1-31.2)% and 8.3 +/- 3.7 (7.5-12.9)%, respectively. SUBJECTS: Sera from 88 healthy children (55 males and 33 females; 1 month to 16 years old) and 31 patients who underwent gonadal suppression therapy were analysed. RESULTS: Age-related changes were observed in both sexes. Serum oestradiol concentrations in childhood decreased slightly compared to those in infancy, then increased at puberty. Most prepubertal children showed oestradiol concentrations lower than 36.7 pmol/l. A study on patients who underwent gonadal suppression therapy revealed oestradiol changes within low concentrations, depending on the stage of the therapy. CONCLUSIONS: The new assay was considered precise enough for the assessment of oestradiol secretion at low concentrations in childhood. Age-related changes in serum oestradiol suggested gonadal activity in the prepubertal period. This assay could be a powerful tool for investigating novel oestradiol functions in vivo.

Adolescent↗
PubMed2001

Genetic variation in the hepatocyte nuclear factor (HNF)-3alpha gene does not contribute to maturity-onset diabetes of the young in Japanese.

Heterozygous mutations in the genes encoding transcription factors in the hepatocyte nuclear factor (HNF) cascade are associated with maturity-onset diabetes of the young (MODY), a monogenic form of diabetes mellitus. However, these genes are responsible for only approximately 20% of the cases of MODY in Japanese patients. Searching for a novel MODY gene in this population, we investigated a candidate for encoding the forkhead transcription factor HNF-3alpha, which also belongs to the HNF-transcription cascade. The human HNF-3alpha gene, which was assigned to the segment near microsatellites D14S75 and AFM200ZH4 on chromosome 14 by radiation hybrid mapping, spans approximately 5 kb and consists of two exons. Ninety-five Japanese subjects with MODY/early-onset non-ketotic diabetes were screened for mutations in this gene. Direct sequencing of the exons and flanking regions identified one missense mutation (Ala-83-Thr) in exon 2 and three nucleotide alterations in the non-coding regions. However, their frequencies were not significantly different between MODY and control subjects, indicating that mutations in the HNF-3alpha gene are not a major cause of MODY in Japanese patients.

DNA-Binding Proteins↗
PubMed2001

Abnormal axonal inward rectifier in streptozocin-induced experimental diabetic neuropathy.

In order to explore the pathophysiology of diabetic neuropathy, we studied serial changes of axonal excitability in 20 adult Wistar rats with streptozocin-induced diabetes using the technique of threshold electrotonus (TE). After persistent hyperglycaemia had developed, rats were divided into two groups: nine were fed a diet containing aldose reductase inhibitor (Epalrestat 30 mg/kg/day) (ARI(+) group) and 11 were fed a diet without the inhibitor (ARI(-) group). Eight normal control rats of similar age (NC group) were also studied. We monitored membrane properties of motor axons in the tail for 3 months using TE to measure the changes in excitability induced by subthreshold polarizing currents while recording compound muscle action potentials (CMAPs) in the tail muscle. The ARI(-) group showed a significant increase in CMAP latency 1 month after streptozocin injection, and by 3 months there was significantly lower excitability after hyperpolarization for 100 ms compared with the NC group. A similar change in TE was reproduced by injection of caesium chloride, an inhibitor of inward rectification. By contrast, the ARI(+) group exhibited no significant change in TE or latency at 3 months, although they showed significant body weight loss and hyperglycaemia. These findings indicate that inward rectification is reduced in an experimental model, as in human diabetes, and that blocking the polyol pathway with an ARI prevents this reduction. Reduced inward rectification potentiates conduction block caused by activity-dependent hyperpolarization and may underlie the decreased vibratory sensation seen in the early stage of diabetic neuropathy.

Action Potentials↗
PubMed2001

Effects of blockade of the renin-angiotensin system on tissue factor and plasminogen activator inhibitor-1 synthesis in human cultured monocytes.

OBJECTIVES: To clarify the pathophysiological significance of the renin-angiotensin system (RAS) in monocytes, we examined the effect of its blockade on tissue factor and plasminogen activator inhibitor-1 (PAI-1) synthesis in human cultured monocytes. METHODS: Monocytes were isolated from healthy volunteers and cultured. Tissue factor and PAI-1 antigens in culture medium and cells were measured by enzyme-linked immunosorbent assay and Western blotting, and mRNA levels were assessed by reverse-transcriptase polymerase chain reaction. RESULTS: We show that the RAS is present in isolated human peripheral blood monocytes. Exogenous angiotensin II increased the levels of tissue factor antigen and mRNA in cultured monocytes, but not of PAI-1 synthesis. An angiotensin converting enzyme (ACE) inhibitor (captopril) and an angiotensin II type 1 (AT1) receptor antagonist (candesartan) decreased the levels of tissue factor protein and mRNA in cultured monocytes. These alterations were accompanied by a reduction in the levels of tumour necrosis factor-alpha protein and mRNA. The levels of PAI-1 protein were reduced by captopril, but not by candesartan. A bradykinin B2 receptor antagonist abolished the suppressive effect of captopril on PAI-1 antigen. CONCLUSIONS: An ACE inhibitor and an AT1 receptor antagonist reduced tissue factor synthesis in these cells. We show different actions of these agents on PAI-1 synthesis. ACE inhibition decreased PAI-1 synthesis mediated by bradykinin production, but AT1 receptor inhibition had no effect.

Angiotensin II↗
PubMed2001

Antidiabetic activity of the rhizoma of Anemarrhena asphodeloides and active components, mangiferin and its glucoside.

The antidiabetic activity of the rhizoma of Anemarrhena asphodeloides was investigated in KK-Ay mice, an animal model of genetic type 2 diabetes. The water extract of the rhizoma (AA) (90 mg/kg) reduced blood glucose levels from 570 +/- 29 to 401 +/- 59 mg/dl 7 h after oral administration (p<0.05) and also tended to reduce serum insulin levels in KK-Ay mice. AA-treated KK-Ay mice had significantly reduced blood glucose levels in an insulin tolerance test. Based on these results, the antidiabetic mechanism of AA may be due to decreased insulin resistance. In addition, the active components of AA were confirmed to be mangiferin and its glucoside.

Animals↗
PubMed2001

Cardiac emergency triage and therapeutic decisions using whole blood rapid troponin T test for patients with suspicious acute coronary syndrome.

Emergency triage and therapeutic decisions using the recently developed whole blood rapid troponin T test were evaluated and compared with conventional electrocardiographic (ECG) diagnosis in a total of 155 patients with chest pain who visited 16 emergency outpatient clinics in the Tokyo metropolitan area. Thirty-seven patients (23.9%) had a final diagnosis of acute myocardial infarction or high-risk unstable angina requiring emergency coronary intervention and these events were defined as acute coronary syndrome. Diagnostic values using the second-generation rapid troponin T test were evaluated according to 3 time-windows in 85 patients. The sensitivity of the test was 10% for patients assessed within 3 h after the onset, 62.5% for 3-6 h after, and 75% for more than 6h, whereas conventional ECG diagnosis had 100% sensitivity at any time-window. In contrast, the specificity of the rapid troponin T test was 100%, 100%, and 97.4%, whereas that of conventional ECG diagnosis was 25%, 57.1%, and 42.2%, respectively for the 3 time-windows. The positive predictive value of ECG diagnosis was inferior to the rapid troponin T test, which reflected the prudent attitude of physicians taking ECG decisions as positive when myocardial ischemia was suspected. The diagnostic efficacy of the rapid troponin T test was remarkable in patients with the non-ST elevation type of acute coronary syndrome. A questionnaire survey on therapeutic decisions revealed that only 10% of Tokyo outpatient institutes performed prehospital thrombolytic therapy, 30-33% administered aspirin or nitrate, and 16.7% gave heparin. The rapid troponin T test is extremely useful for cardiac emergency triage and therapeutic decision making. There is a requirement for practical guidelines for the primary therapeutic decisions for patients with suspicious acute coronary syndrome.

Acute Disease↗
PubMed2001

Impairment of insulin-stimulated GLUT4 translocation in skeletal muscle and adipose tissue in the Tsumura Suzuki obese diabetic mouse: a new genetic animal model of type 2 diabetes.

BACKGROUND: In skeletal muscle and adipocytes, insulin-stimulated glucose transport has been known to occur through the translocation of glucose transporter (GLUT) 4 from the intracellular pool to the plasma membrane. The Tsumura Suzuki obese diabetic (TSOD) mouse, a new genetic animal model of type 2 diabetes, develops moderate degrees of obesity and diabetes that are especially apparent in animals more than 11 weeks old. A defect in insulin stimulation of GLUT4 translocation also contributes to the characteristics of type 2 diabetes. OBJECTIVE: To characterize this mouse further, we examined the alteration in insulin-stimulated GLUT4 translocation in the skeletal muscle and adipose tissue. METHODS: For glucose and insulin tolerance tests, the mice were given glucose or insulin and blood samples were collected. After isolation of low-density microsomal membrane and plasma membrane from skeletal muscle and adipose tissue, insulin-stimulated translocation of GLUT4 in these TSOD mice was examined by Western blot. RESULTS AND CONCLUSIONS: TSOD mice showed a significant increase in blood glucose after the glucose load, and exhibited a significantly attenuated decrease in blood glucose concentrations after administration of insulin, compared with that in control Tsumura Suzuki non-obese (TSNO) mice. The insulin-stimulated translocation of GLUT4 from low-density microsomal membranes to plasma membrane was significantly reduced in both skeletal muscle and adipose tissue of TSOD mice. These results indicate that the reduced insulin sensitivity in diabetic TSOD mice is presumably due, at least in part, to the impaired GLUT4 translocation by insulin in both skeletal muscle and adipocytes.

Adipocytes↗