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Chiaki Shigemasa

Publications and source records attributed to Chiaki Shigemasa.

At least 19 recordsLinked to original sources
PubMed2006

Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin.

Organic cation transporters (OCTs) are responsible for the hepatic and renal transport of metformin. In this study we analyzed variants of OCT1 and OCT2 genes in 33 patients (24 responders and nine non-responders) based on the hypothesis that polymorphisms in both genes contribute to large inter-patient variability in the clinical efficacy of metformin. The sequences of the 5'-flanking and coding regions of the two genes of interest were screened by single-strand conformation polymorphism (SSCP) analysis. To compare the causative factors between responders and non-responders, we performed stepwise discriminant functional analysis. Age, body mass index (BMI) and treatment with lipid-lowering agents were demonstrated as positive predictors, and two mutations in the OCT1 gene, -43T > G in intron 1 and 408Met > Val (1222A > G) in exon 7, were negative and positive predictors, respectively, for the efficacy of metformin; the predictive accuracy was 55.5% (P < 0.05). Subsequent study indicated that OCT1 mRNA levels tended to be lower in human livers with the 408Met (1222A) variant, though the differences did not reach the level of significance. In this study it is suggested that OCT1 and OCT2 gene polymorphisms have little contribution to the clinical efficacy of metformin.

Adult↗
PubMed2006

Delayed onset of beating and decreased expression of T-type Ca2+ channel in mouse ES cell-derived cardiocytes carrying human chromosome 21.

The mouse ES cell line hcgp7/#21, which carries a human chromosome 21 (hChr.21), was used as an in vitro model to examine the effects of hChr.21 on cardiomyocyte differentiation. Cardiomyocytes derived from hcgp7/#21 showed a significant delay in the onset of spontaneous beating. The number of Nkx2.5/GFP(+) cardiac progenitor cells was comparable to that in control ES cells and they also expressed comparable mRNA levels for mesodermal markers, cardiac specific transcription factors, contractile proteins, and L-type Ca(2+) channels. However, cells from hcgp7/#21 expressed significantly reduced levels of mRNA for Cav3.1 and Cav3.2, which was consistent with the decreased number of cells expressing T-type Ca(2+) channels and decreased T-type Ca(2+) channel currents. These findings suggest that the presence of human chromosome 21 suppresses expression of T-type Ca(2+) channels in cardiomyocytes during differentiation, which may be responsible for delayed onset of spontaneous beating.

Animals↗
PubMed2006

Pharmacogenetic determinants of variability in lipid-lowering response to pravastatin therapy.

Pravastatin is mainly taken up from the circulation into the liver via organic anion-transporting polypeptide 1B1 (SLCO1B1 gene product). We examined the contribution of genetic variants in the SLCO1B1 gene and other candidate genes to the variability of pravastatin efficacy in 33 hypercholesterolemic patients. In the initial phase of pravastatin treatment (8 weeks), heterozygous carriers of the SLCO1B1*15 allele had poor low-density lipoprotein cholesterol (LDL-C) reduction relative to non-carriers (percent reduction: -14.1 vs -28.9%); however, the genotype-dependent difference in the cholesterol-lowering effect disappeared after 1 year of treatment. Cholesterol 7alpha-hydroxylase (CYP7A1) and apolipoprotein E (APOE) are known to contribute to lipid metabolism. Homozygous carriers of the CYP7A1 -204C allele or heterozygotes for both CYP7A1 -204C and APOE epsilon4 alleles showed significantly poorer LDL-C reduction compared to that in other genotypic groups after 1 year of treatment (-24.3 vs -33.1%). These results suggest that the SLCO1B1*15 allele is associated with a slow response to pravastatin therapy, and the combined genotyping of CYP7A1 and APOE genes is a useful index of the lipid-lowering effect of pravastatin.

Adult↗
PubMed2006

[Cretinism].

Explore the source record for details and available documents.

Congenital Hypothyroidism↗
PubMed2006

Autoperipheral blood mononuclear cell transplantation improved giant ulcers due to chronic arteriosclerosis obliterans.

We report the case of a 74-year-old man with Fontaine stage IV chronic arteriosclerosis obliterans who had been suffering from inveterate giant skin ulcers on the dorsum and heel of the right foot. As conventional medical treatments had not improved these ulcers and surgical treatment was considered unfeasible, amputation of the right lower limb below the knee appeared to represent the only option. The patient was admitted to Tottori University Hospital to attempt a new angiogenic therapy using auto-mononuclear cell transplantation to avoid amputation. On admission, neither right ankle blood pressure nor transcutaneous partial pressure of oxygen at the right toe were detectable. The patient had a history of multiple cerebral infarctions, and collection of mononuclear cells from bone marrow was considered too difficult, so collection of peripheral blood mononuclear cells was selected. Transcutaneous partial pressure of oxygen and skin temperature in the treated limb started to improve from 2 weeks after implantation. Ulcer size was recognizably reduced by 1 month after treatment. Partial auto-skin implantation on the right heel was performed 2 months after treatment, and the giant skin ulcer was finally completely covered. No adverse effects were noted during follow-up lasting 1 year. These results suggest that peripheral blood mononuclear cell implantation may offer a suitable alternative rescue therapy for patients with critical limb ischemia whose general condition is not good.

Aged↗
PubMed2006

Catabolism of adenine nucleotides favors adenosine production following exercise in patients with chronic heart failure.

BACKGROUND: Adenosine 5'-triphosphate is catabolized to adenosine 5'-monophosphate (AMP), which is further degraded by 2 pathways: deamination to inosine 5'-monophosphate and ammonia by AMP deaminase, or dephosphorylation to adenosine and inorganic phosphate by 5'-nucleotidase. Because adenosine is believed to be cardioprotective and we have reported that ammonia production decreased after exercise in patients with chronic heart failure (CHF), we determined if plasma adenosine levels after exercise increases in patients with CHF. METHODS AND RESULTS: Maximal ergometer exercise tests with expired gas analysis were performed in 51 patients with CHF (age = 61 +/- 2 years, New York Heart Association [NYHA] class I/II/III = 19/18/14) and 20 age-matched normal controls. Serial changes in both plasma ammonia and adenosine levels were determined. The ratio for delta ammonia to peak work rate became smaller (control, NYHA I/II/III: 0.59 +/- 0.13/0.41 +/- 0.06/0.37 +/- 0.10/0.22 +/- 0.11 microg/dL x watts, respectively) and the ratio for delta adenosine to peak work rate was significantly higher in class III CHF (control, NYHA I/II/III: 0.93 +/- 0.21/0.86 +/- 0.14/1.11 +/- 0.27/2.92 +/- 0.67 nmol/L x watts, respectively). CONCLUSION: In patients with CHF after exercise, the plasma levels of adenosine increased along with the decrease in the plasma levels of ammonia. Considering the physiologic cardioprotective actions of adenosine, the enhanced adenosine production after exercise may be an important adaptive response in patients with CHF.

Adenine Nucleotides↗
PubMed2006

Small extra-adrenal pheochromocytoma causing severe hypertension in an elderly patient.

We report the case of a 67-year-old woman with severe hypertension caused by an extra-adrenal pheochromocytoma. The tumor was detected by 131I metaiodobenzylguanidine scintigraphy and it was found to be small (2 cm ø) by enhanced CT. After the extirpation of the tumor, the blood pressure of the patient immediately normalized. It should be taken into account that a small extra-adrenal pheochromocytoma can be one of the causes of secondary hypertension in elderly patients. Since small extra-adrenal pheochromocytomas are difficult to detect, it is also important to perform suitable examinations to establish the diagnosis. Furthermore, we emphasize the importance of an accurate diagnosis in elderly patients with pheochromocytoma, for they often have less symptomatology and more severe cardiovascular complications due to refractory hypertension than younger patients.

3-Iodobenzylguanidine↗
PubMed2005

Status of endothelial dependent vasodilation in patients with hyperuricemia.

Hyperuricemia has been associated with an increased risk for cardiovascular disease and increased mortality. However, the biologic mechanisms that link elevated serum uric acid to cardiovascular disease are uncertain. This study tested the hypothesis that elevated serum uric acid is associated with impaired endothelial function in hyperuricemic patients without any overt cardiovascular disease. Seventeen male patients with hyperuricemia (mean age 42+/-4 years) and 9 control subjects (mean age 45+/-5 years) were studied. All subjects were nonsmokers. All patients had never been treated for hyperuricemia, were on no medications, and were free of any other known diseases. Endothelial function was evaluated by flow-mediated dilation measured by ultrasound. Flow-mediated dilation was significantly impaired in patients with hyperuricemia (4.0+/-0.7%) compared with control subjects (6.4+/-0.8%) (p=0.044). Flow-mediated dilation correlated inversely with uric acid levels (r=-0.4, p=0.05). Nitrate-induced dilation was 12.3+/-1.0% in patients with hyperuricemia and 11.8+/-2.3% in control subjects (p=0.82). Impaired endothelial-dependent vasodilation is present in hyperuricemic patients even in the absence of any overt cardiovascular disease. The elevated serum uric acid, per se, may constitute a novel risk factor for endothelial dysfunction.

Adult↗
PubMed2005

Proteasomal degradation of Kir6.2 channel protein and its inhibition by a Na+ channel blocker aprindine.

ATP-sensitive K+ channels (K(ATP):SUR2A+Kir6.2) play a pivotal role in cardiac protection against ischemia and reperfusion injury. When expressed in COS cells, Kir6.2 was short-lived with a half-life time of 1.9 h. The half-life time of Kir6.2 was prolonged by proteasome inhibitors MG132, ALLN, proteasome inhibitor 1, and lactacystine, but not at all by a lysosomal inhibitor chloroquine. MG132 also increased the level of ubiquitinated Kir6.2 without affecting its localization in the endoplasmic reticulum and Golgi apparatus. In electrophysiological recordings, MG132 augmented nicorandil-activated K(ATP) currents in COS cells expressing SUR2A and Kir6.2 as well as the same currents in neonatal rat cardiomyocytes. Like MG132, a Na+ channel blocker aprindine prolonged the half-life time of Kir6.2 and augmented K(ATP). Finally, both aprindine and MG132 inhibited the 20S proteasome activity in vitro. These results suggest a novel activity of aprindine to enhance K(ATP) currents by inhibiting proteasomal degradation of Kir 6.2 channels, which may be beneficial in the setting of cardiac ischemia.

Animals↗
PubMed2005

Acute myocardial infarction in a patient with essential thrombocythemia: successful treatment with percutaneous transluminal coronary recanalization.

A 65-year-old woman with essential thrombocythemia (ET) was admitted to hospital where she was diagnosed as acute myocardial infarction (AMI). Because of abundant thrombus of right coronary arteries, percutaneous transluminal coronary recanalization by administration of urokinase was selected as the reperfusion therapy, resulting in successful revascularization with Thrombolysis in Myocardial Infarction grade III coronary flow. The maximum creatine kinase reached 507 IU/L, and left ventriculography performed at 1 month after initiation of both anticoagulant and antiplatelet therapies revealed reduced motion in the inferior wall with an ejection fraction of 57%. Despite good recovery of left ventricular function, bleeding complications, such as epistaxis or ecchymoma, which did not require blood transfusion, occurred during the clinical course. Because ET causes not only thrombus formation but also bleeding tendency, it is very important to carefully follow-up any clotting abnormality in AMI patients with ET.

Aged↗
PubMed2005

Subtype switching of T-type Ca 2+ channels from Cav3.2 to Cav3.1 during differentiation of embryonic stem cells to cardiac cell lineage.

BACKGROUND: The developmental changes of Ni(2+)-sensitivity to automaticity of Nkx2.5-positive cells derived from mouse embryonic stem cell have been identified, suggesting developmental regulation of expressing Ni(2+)-sensitive T-type Ca(2+) channel, although the mechanism of the change has not been fully studied. METHODS AND RESULTS: Transcripts of Cav3.2, Cav3.1 and Cav1.2 genes of beating Nkx2.5-positive cells, which encode the Ni(2+)-sensitive T-type Ca(2+) channel, Ni(2+)-insensitive T-type Ca(2+) channel, and L-type Ca(2+) channel, respectively, were investigated by real-time reverse-transcriptase-polymerase chain reaction, and the current density of each channel was measured by patch-clamp techniques at the early and late stages of differentiation. The expression of the Cav3.2 transcript predominated in the early stage whereas those of Cav3.1 and Cav1.2 transcripts were upregulated in the late stage, which was consistent with the change in each current density, suggesting the expression of channel proteins is largely determined at the transcriptional level. CONCLUSION: The results indicate that the mechanism of change of Ni(2+)-sensitivity is partly, if not completely, the subtype switch of T-type Ca(2+) channel from Cav3.2 to Cav3.1 at the transcriptional level, and that the expression of the L-type Ca(2+) channel might have an attenuating effect on Ni(2+)-sensitivity to automaticity in the late stage of differentiation.

Animals↗
PubMed2005

Effects of angiotensin II on the action potential durations of atrial myocytes in hypertensive rats.

Angiotensin II (Ang II) has been reported to indirectly influence atrial electrical activity and to play a critical role in atrial arrhythmias in hypertensive patients. However, it is unclear whether Ang II has direct effects on the electrophysiological activity of the atrium affected by hypertension. We examined the effects of Ang II on the action potentials of atrial myocytes enzymatically isolated from spontaneous hypertensive rats (SHRs). The action potentials were recorded by the perforated patch-clamp technique and the atrial expression of the receptors AT1a and AT2 was measured by radioimmunoassay. Ang II significantly shortened the action potential durations (APDs) of SHRs without changes in the resting membrane potentials (RMPs). Pretreatment with selective AT1a blockers abolished the Ang II-induced reduction of atrial APDs of SHRs; however, a selective AT2 blocker did not, which was consistent with the results of the receptor assay. Pretreatment with phosphatidylinositol 3 (PI3)-kinase inhibitor, phospholipase C inhibitor, or protein kinase C (PKC) inhibitor abolished the Ang II-induced shortening of atrial APDs, but pertussis toxin and protein kinase A (PKA) inhibitor did not. To study the effects of chronic AT1a inhibition on Ang II-induced shortening of atrial APD, SHRs were treated with AT1a blocker for 4 weeks. AT1a blocker abolished the Ang II-induced reduction of atrial APDs of SHRs and also significantly lowered their blood pressure. In conclusion, Ang II shortened atrial APDs of SHRs via AT1a coupled with the Gq-mediated inositol triphosphate (IP3)-PKC pathway. Our findings indicated that Ang II caused atrial arrhythmias in hypertensive patients by shortening the effective refractory period of the atrium.

Action Potentials↗
PubMed2005

[Alteration of education programs for anesthesia after the start of the obligatory postgraduate clinical training in Japan: survey at affiliated teaching hospitals of medical schools].

BACKGROUND: There is little information on education programs for anesthesia evaluating the present educational contents of early postgraduate clinical training period. METHODS: A questionnaire that consisted of 40 questions graded from 1 (absolutely unnecessary) to 5 (absolutely necessary) was send to 80 medical universities in Japan to investigate the alterations of education programs for anesthesia at their affiliated teaching hospitals after the start of the obligatory early postgraduate clinical training. RESULTS: Answers were obtained from 59 of 80 universities (74%). Educational necessities after the obligation were significantly reduced at the following items compared with pre-obligation; intravenous anesthesia technique (P<0.05), epidural (P<0.01) and spinal (P<0.05) anesthesia technique, anesthesia for cesarean section (P<0.01), and adult patients of more than ASA PS 3 (P<0.01) and pediatric patients (P<0.05). Contrarily, educational necessities increased significantly in the attending (P<0.01) and presentation (P<0.05) at the academic meetings. CONCLUSIONS: Clinical anesthesia education after the obligation was likely to change the direction to establish the safer anesthesia in patients with low anesthetic risk(s) along with encouraging the trainees to be interested in medicine.

Anesthesiology↗
PubMed2004

Detection of the novel autoantibody (anti-UACA antibody) in patients with Graves' disease.

Uveal autoantigen with coiled coil domains and ankyrin repeats (UACA) is an autoantigen in patients with panuveitis such as Vogt-Koyanagi-Harada disease. The prevalence of IgG anti-UACA antibodies in patients with uveitis is significantly higher than healthy controls, suggesting its potential role as an autoantigen. Originally, UACA was cloned from dog thyroid tissue following TSH stimulation. So, we presumed UACA could be a novel autoantigen in autoimmune thyroid diseases. We measured serum anti-UACA antibody titer using ELISA in patients with autoimmune thyroid diseases (Graves' disease, Hashimoto's thyroiditis, subacute thyroiditis, and silent thyroiditis). The prevalence of anti-UACA antibodies in Graves' disease group was significantly higher than that in healthy group (15% vs. 0%). Moreover, the prevalence of anti-UACA antibodies in Graves' ophthalmopathy was significantly higher than that in Graves' patients without ophthalmopathy (29% vs. 11%). Especially, 75% of severe ocular myopathy cases showed high UACA titer. Immunohistochemical analysis revealed that UACA protein is expressed in eye muscles as well as human thyroid follicular cells. Taken together, UACA is a novel candidate for eye muscle autoantigens in thyroid-associated ophthalmopathy.

Adult↗
PubMed2004

Mechanism of iodide/chloride exchange by pendrin.

We performed an electrophysiological study to investigate ion transport of pendrin and thereby understand the pathogenesis of Pendred syndrome. Using pendrin-transfected COS-7 cells, we could show that pendrin transports both iodide and chloride measured as voltage-dependent inward and outward membrane currents. Chloride in the culture medium, [Cl-]o, was efficiently exchanged with cytoplasmic iodide, [I-]i, under physiological concentrations, indicating that pendrin is important for chloride uptake and iodide efflux. Although exchange of iodide in the medium, [I-]o, with cytoplasmic chloride, [Cl-]i, was observed, a significantly high concentration of iodide (10 mm) was required. In addition, either iodide or chloride was required on both sides of the cell membrane for the anion exchange activity of pendrin, indicating that iodide and chloride activate the exchange activity of pendrin while they are transported. The present study further supports that pendrin is responsible for the iodide efflux in thyroid cells where intracellular iodide concentration is high and that the general function of pendrin in other tissues is to transport chloride through exchange with other anions.

Animals↗
PubMed2004

Protective effect of edaravone against hypoxia-reoxygenation injury in rabbit cardiomyocytes.

1 We examined whether edaravone (Eda), a clinically available radical scavenger, directly protects cardiomyocytes from ischemia/reperfusion (I/R) injury, and whether the timing of its application is critical for protection. 2 Cardioprotective effects of edaravone were tested in the modified cell-pelleting model of ischemia and under exogenous oxidative stress (hydrogen peroxide: H2O2) in isolated adult rabbit ventricular cells. Cell death and reactive oxygen species (ROS) generation were detected using propidium iodide (PI) and DCFH-DA, respectively. These parameters were evaluated objectively using flow cytometory. 3 Hypoxia and reoxygenation aggravated the proportion of dead cells from 32.2+/-1.8% (Baseline) to 51.3+/-2.7% (Control). When 15 microm edaravone was applied either throughout the entire experiment (Through) or only at reoxygenation (Reox), cell death was significantly reduced to 39.9+/-1.8% (P<0.01 vs Control) and 43.3+/-2.5% (P<0.05 vs Control), respectively. In contrast, when edaravone was applied 10 min after reoxygenation, its protective effect disappeared. Cardioprotection by edaravone was more remarkable than that afforded by other free radical scavengers, such as ascorbate and superoxide dismutase (SOD). There is a positive correlation between the cardioprotective effect of edaravone and the extent of ROS reduction. 4 Edaravone blunted the H2O2-induced changes in electrical properties, and significantly prolonged the time to contracture induced by H2O2 in single ventricular myocytes. 5 Taken together, edaravone directly protects cardiomyocytes from I/R injury by attenuating ROS production, even when applied at the time of reoxygenation, suggesting that edaravone could be a potent cardioprotective therapeutic agent against hypoxia-reoxygenation injury.

Action Potentials↗