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Hiroyuki Kamiya

Publications and source records attributed to Hiroyuki Kamiya.

At least 19 recordsLinked to original sources
PubMed2006

Crystallization and preliminary X-ray analysis of human MTH1 complexed with two oxidized nucleotides, 8-oxo-dGMP and 2-oxo-dATP.

Human MutT homologue 1 (hMTH1) hydrolyzes a variety of oxidized purine nucleoside triphosphates, including 8-oxo-dGTP, 2-oxo-dATP, 2-oxo-ATP and 8-oxo-dATP, to their corresponding nucleoside monophosphates, while Escherichia coli MutT possesses prominent substrate specificity for 8-oxoguanine nucleotides. Three types of crystals were obtained corresponding to the following complexes: selenomethionine-labelled hMTH1 with 8-oxo-dGMP (SeMet hMTH1-8-oxo-dGMP), hMTH1 with 8-oxo-dGMP (hMTH1-8-oxo-dGMP) and hMTH1 with 2-oxo-dATP (hMTH1-2-oxo-dATP). Crystals of the SeMet hMTH1-8-oxo-dGMP complex belong to space group P4(1)2(1)2, with unit-cell parameters a = b = 45.8, c = 153.6 A, and diffracted to 2.90 A. Crystals of hMTH1-8-oxo-dGMP and hMTH1-2-oxo-dATP belong to space groups P2(1) and P2(1)2(1)2(1), with unit-cell parameters a = 34.0, b = 59.0, c = 65.9 A, beta = 90.7 degrees and a = 59.2, b = 67.3, c = 80.0 A, respectively. Their diffraction data were collected at resolutions of 1.95 and 2.22 A, respectively.

Crystallization↗
PubMed2006

Recognition of nucleotide analogs containing the 7,8-dihydro-8-oxo structure by the human MTH1 protein.

The MTH1 protein catalyzes hydrolysis of oxidatively damaged purine nucleotides including 8-hydroxy-dGTP to the monophosphates. The MTH1 protein seems to act as an important defense system against mutagenesis, carcinogenesis, and cell death induced by oxidized purine nucleotides. We previously reported that the functional groups at the 2- and 6-positions of the purine ring affect the recognition by the human MTH1 protein. 8-Hydroxy-dGTP and 8-hydroxy-dATP are substrates of MTH1, and both have the "7,8-dihydro-8-oxo structure." In this study, three nucleotide analogs containing this motif were examined. A synthetic purine analog containing the 7,8-dihydro-8-oxo structure and the 2-amino function (dJTP) was hydrolyzed to the monophosphate with high efficiency by MTH1. On the other hand, two analogs that lack the two-ring system of their bases [formamidopyrimidine-dGTP (FAPY-dGTP) and 2-OH-dYTP] were poor substrates. FAPY-dGTP is a mixture of conformers and was hydrolyzed more than ten-fold less efficiently than 8-hydroxy-dGTP. These results clarify the effects of the 2-amino group and the two-ring system of the purine base on the recognition by the human MTH1 protein.

DNA Repair Enzymes↗
PubMed2006

Creatine kinase isoenzyme MB relative index as predictor of mortality on extracorporeal membrane oxygenation support for postcardiotomy cardiogenic shock in adult patients.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) has been used as initial, biventricular circulatory support for patients with severe postcardiotomy cardiogenic shock (PCS). Due to its aggressiveness and limited weaning quote, concerns have been raised about maintenance of ECMO support regarding duration. However, it is frequently hazardous for physicians to make an individualized decision, whether and when discontinuation of ECMO support should be considered. We tried to find measurable values during ECMO support that could predict the patient mortality on ECMO support. METHODS: During a 9-year period, 32 patients (mean age 55.4+/-11.9; ranging from 30 to 75 years) with ECMO support for postcardiotomy cardiogenic shock were included in this study. RESULTS: Eighteen patients died without weaning (group I, 56.25%), while 14 patients could be weaned off the ECMO support (group II, 43.75%). In the group II, six patients (18.75%) died later in the postoperative course and eight patients (25%) survived to be discharged from hospital. The overall survival of all 32 patients at 30 days was 31.25% (n=10). At a follow-up period of 3.88+/-1.58 years, the overall survival rate was 12.5% (n=4). Mean duration of ECMO support was 2.7+/-1.7 days. The following variables were significantly different between the two groups: blood lactate level and the level of MB isoenzyme of creatine kinase (CK-MB) 48 h after ECMO initiation (p<0.01, p=0.001) as well as the CK-MB relative index as the ratio of CK-MB to total CK (p<0.001). Logistic regression identified that only the CK-MB relative index 48 h after ECMO initiation was associated with mortality on ECMO support (p=0.011, odds ratio=1.219, 95% confidence interval: 1.046-1.421). CONCLUSION: For adult non-transplantation patients with postcardiotomy cardiogenic shock, the CK-MB relative index 48 h after ECMO initiation can be a predictor of mortality on ECMO support. This might be a useful tool for considering a patient either for discontinuation of ECMO support or further treatment.

Adult↗
PubMed2006

Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: is deep hypothermia required?

OBJECTIVE: To investigate whether deep (<20 degrees C) hypothermia is necessary in patients undergoing pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. METHODS: Between January 2004 and February 2005, 30 patients (New York Heart Association (NYHA) class III or IV) were randomly assigned to increasing (1 degrees C) levels of moderate (28-32 degrees C) hypothermic cardiopulmonary bypass (CPB), each study group including six patients. Primary study endpoint was adverse neurological outcome. Overall preoperative total pulmonary vascular resistance was 1110+/-192 dynes cm(-5). RESULTS: Mean CPB and cross-clamp times, and core temperature at the time of circulatory arrests were 129+/-39 min and 92+/-24 min, and 30.1+/-1.5 degrees C, respectively. Circulatory arrest was induced 2+/-0.7 times and its mean total duration was 10.3+/-5.2 min (range, 2-19 min). Postoperatively, three patients (10%) belonging to the 31 degrees C (n=1) and 32 degrees C (n=2) groups suffered from temporary neurological dysfunction. Postoperative mechanical ventilatory support and ICU stay were 26.3+/-18.9 h and 6.6+/-8.5 days, respectively, and uninfluenced by degree of hypothermia. There were no lung reperfusion injuries or any other major complications. All patients had a significant hemodynamic improvement. CONCLUSION: Results suggest that pulmonary endarterectomy can be safely performed with moderate hypothermia and short periods of circulatory arrests without the need of profound hypothermia.

Adult↗
PubMed2006

Tuberous sclerosis complex complicated by pulmonary multinodular shadows.

A 41-year-old woman with a history of epilepsy was referred for multiple nodular ground-glass opacities on a chest computed tomography (CT) scan. They were initially suspected of representing atypical adenomatous hyperplasia or well-differentiated adenocarcinoma. However, the subsequent brain CT and magnetic resonance imaging (MRI) scans revealed a coarse nodular calcification and cortical tubers. A subungual fibroma was also noted. Histological examination of a video-assisted thoracoscopic lung biopsy specimen disclosed multiple nodules of type II pneumocyte hyperplasia with septal thickening. Based on all of these findings taken together, a diagnosis of tuberous sclerosis complex with multifocal micronodular pneumocyte hyperplasia (MMPH) was made.

Adult↗
PubMed2006

Intranuclear disposition of exogenous DNA in vivo: silencing, methylation and fragmentation.

The intranuclear disposition of exogenous DNA is highly important for the therapeutic effects of the administrated DNA. Naked luciferase-plasmid DNA was delivered into mouse liver by a hydrodynamics-based injection, and the amounts of intranuclear plasmid DNA, luciferase, and its mRNA were quantitated at various time points. Methylation of the promoter of the luciferase gene was also analyzed. Expression efficiency from one copy of the exogenous DNA dramatically decreased over time, and the DNA was methylated and degraded into fragments. Unexpectedly, methylation of the intact plasmid DNA was low and did not increase over time. Rather, the fragmented DNA was methylated more frequently than the intact plasmid. These results suggest that the CpG methylation and the degradation of exogenous DNA, and its 'silencing', occurred in parallel in the nucleus.

Animals↗
PubMed2006

Hybrid surgical angiogenesis: omentopexy can enhance myocardial angiogenesis induced by cell therapy.

BACKGROUND: The conditions at the injection site are important in cell transplantation for severe ischemic heart disease. The omentum is both a well-vascularized tissue and a source of angiogenic factors. We examined the effectiveness of autologous bone marrow-derived mononuclear cells (BM-MNCs) with or without omentopexy in a large animal model. METHODS: Myocardial infarction was generated in the lateral wall by ligation of coronary artery branches in miniswine. Animals received BM-MNC injection with or without omentopexy. Controls received saline only. Three weeks after surgery, regional myocardial blood flow and contractility were measured, and density of arterioles was evaluated immunohistologically. Angiography and postmortem examinations were performed to determine collateral communication. RESULTS: Regional myocardial contractility was significantly improved by BM-MNC transplantation both with and without omentopexy (0.29 +/- 0.02 vs 0.11 +/- 0.03, p < 0.01, 0.30 +/- 0.02 vs 0.12 +/- 0.01, p < 0.01, respectively). Relative regional myocardial blood flow in the combined omentopexy group was significantly higher than the controls both at rest (1.05 +/- 0.11 vs 0.57 +/- 0.07, p < 0.01) and under stress (1.09 +/- 0.08 vs 0.40 +/- 0.10, p < 0.01). The number of arterioles (< 50 microm) in both groups were higher than the controls (88.1 +/- 5.00 vs 38.1 +/- 8.99, p < 0.01 and 109.2 +/- 9.91 vs 38.1 +/- 8.99, p < 0.01, respectively). The number of large arterioles (> 50 microm) in the combined omentopexy group was significantly higher than in both BM-MNC alone (26.9 +/- 2.4 vs 17.6 +/- 1.8, p = 0.011) and controls (26.9 +/- 2.4 vs 10.0 +/- 1.3, p < 0.01). Collateral communication between the omentum and myocardium was demonstrated by angiography and postmortem injection. CONCLUSIONS: The BM-MNC transplantation may attenuate cardiac contractile dysfunction, and omentopexy may enhance angiogenesis induced by BM-MNC transplantation.

Angiography↗
PubMed2006

Cerebral microembolization during antegrade selective cerebral perfusion.

BACKGROUND: This study quantified the number of intraoperative microemboli in patients undergoing aortic arch surgery using selective cerebral perfusion (SCP) in comparison with those in patients undergoing ascending aortic replacement without circulatory arrest and SCP. METHODS: A transcranial Doppler monitoring of the medial cerebral artery was performed in 15 patients undergoing proximal arch replacement with SCP (SCP group) and 15 patients undergoing replacement of the ascending aorta (control group). RESULTS: There was no significant difference in the high-intensity transient signal counts between the SCP group and the control group at any phase. In the SCP group, 4.8% of microemboli occurred during cross-clamping, and only 0.6% occurred during SCP. In the control group, 4.6% occurred during cross-clamping. Most microemboli occurred after removing the cross-clamps in both groups; 92.2% in the SCP group and 92.1% in the control group. CONCLUSIONS: The present study demonstrated that outbreak frequency of microemboli during SCP was very low, and thus implies that the risk of embolic event that may be caused by SCP is very low.

Aged↗
PubMed2006

Surgical treatment of aberrant right subclavian artery (arteria lusoria) aneurysm using three different methods.

BACKGROUND: Here we report our surgical experiences with aberrant right subclavian artery (ARSA) aneurysm in 8 patients. METHODS: Eight patients underwent surgical treatment for ARSA aneurysm between March 1994 and June 2005. The age of these patients ranged from 20 to 75 years. The mean size of the ARSA aneurysm was 3.3 cm, ranging from 2 to 5 cm. The ARSA aneurysm was completely resected through a left posterolateral thoracotomy after reconstruction of the right subclavian artery through the supraclavicular approach in 4 patients (group 1). The ARSA aneurysm was excluded through a left posterolateral thoracotomy without revascularization of the right subclavian artery in 2 patients (group 2). The distal site of the ARSA aneurysm was closed followed by revascularization through a median sternotomy, and the ARSA aneurysm was left as a blind sack in 2 patients (group 3). RESULTS: None of the patients in group 1 or 3 had any postoperative complications. In group 2, 1 had a steal syndrome caused by the exclusion of the ARSA aneurysm, and the other died of sepsis 2 months after the operation. CONCLUSIONS: Complete anatomical repair of the ARSA aneurysm could be performed through the combination of the supraclavicular approach and the left posterolateral thoracotomy, with excellent results. Exclusion of the ARSA aneurysm without revascularization resulted in a suboptimal outcome. Surgical results of simple closure of the ARSA followed by revascularization were uneventful, but the ARSA aneurysm was left as a blind sack.

Adult↗
PubMed2006

Transient expression of Drosophila melanogaster deoxynucleoside kinase gene enhances cytotoxicity of nucleoside analogs.

The Drosophila melanogaster deoxynucleoside kinase gene was introduced into HeLa cells with cationic lipids to allow its transient expression, and cytotoxic effects of several nucleoside analogs in the transfected cells were examined. Of the analogs tested, cytotoxicities of 1-beta-D-arabinofuranosylcytosine (araC), 5-fluorodeoxyuridine (FUdR), and 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytosine (DMDC) were increased by the deoxynucleoside kinase gene. These results suggest that the combination of the transient expression of the Drosophila deoxynucleoside kinase gene and these nucleoside analogs is a candidate for the suicide gene therapy.

Animals↗
PubMed2006

Mutagenic properties of oxidized GTP and ATP in in vitro transcription-reverse transcription.

Oxidation of RNA precursors may disturb genetic information by mispair formations. In this study, effects of oxidized ribonucleoside triphosphates on in vitro transcription catalyzed by T7 RNA polymerase were examined. 8-Hydroxyguanosine 5'-triphosphate (8-OH-GTP) and 2-hydroxyadenosine 5'-triphosphate (2-OH-ATP) reduced amount of RNA. In addition, mRNA was converted to cDNA by reverse transcriptase, and the cDNA was then amplified by PCR. The PCR product was subsequently cloned into plasmid DNA and sequence of DNA was analyzed for each bacterial colony. The two oxidized ribonucleotides induced mutations in cDNA, suggesting disturbance of genetic information during transcription and/or reverse transcription. 8-OH-GTP induced T-->G plus T-->C mutations and 2-OH-ATP caused T-->C mutations. These results indicate that formation of these oxidized RNA precursors in cells affects transcription quantitatively and qualitatively. In addition, they are potential antiviral drugs that cause mutations in genomic RNA.

Adenosine Triphosphate↗
PubMed2006

Involvement of Y-family DNA polymerases in mutagenesis caused by oxidized nucleotides in Escherichia coli.

Escherichia coli DNA polymerase IV incorporated 2-hydroxy-dATP opposite template guanine or thymine and 8-hydroxy-dGTP exclusively opposite adenine in vitro. Mutator phenotypes in sod/fur strains were substantially diminished by deletion of dinB and/or umuDC. DNA polymerases IV and V may be involved in mutagenesis caused by incorporation of the oxidized deoxynucleoside triphosphates.

DNA Polymerase beta↗
PubMed2006

Effects of overexpression and antisense RNA expression of Orf17, a MutT-type enzyme.

The Escherichia coli Orf17 (NtpA, NudB) protein, a MutT-type enzyme, hydrolyzes oxidized deoxyribonucleotides, including 8-hydroxy-2'-deoxyadenosine 5'-triphosphate and 8-hydroxy-2'-deoxyguanosine 5'-triphosphate, in vitro. To examine its in vivo role(s) in bacteria, plasmid DNAs containing the orf17 gene in the sense and antisense orientations were introduced. When the Orf17 protein was overexpressed in mutT cells, the rpoB mutant frequency was decreased. On the other hand, similar effects were not observed when Orf17 was overexpressed in wild type and orf135 cells. Expression of the antisense RNA of the orf17 gene did not produce an obvious phenotype, such as increased mutant frequency and resistance to ionizing radiation. These results suggest that the role of the Orf17 protein is to back up the MutT function, and to assist in the elimination of 8-hydroxy-2'-deoxyguanosine nucleotides.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Silencing of exogenous DNA in cultured cells.

The intranuclear disposition of exogenous DNA is highly important for the therapeutic effects of the administrated DNA. Naked luciferase-plasmid DNA was transfected into cultured cells including HeLa by electroporation, and the amounts of intranuclear plasmid DNA and luciferase were quantitated at various time points. Decrease in expression efficiency from one copy of the exogenous DNA over time occurred as the case of mouse liver, and its degrees varied between cell lines. These results suggest that exogenous DNA is 'silenced' in the cultured cells as well as in mouse hepatocytes.

Animals↗
PubMed2006

Genome wide expression analysis of white blood cells and liver of pre-diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats using a cDNA microarray.

In a prior study, we reported on a significant decrease in calpain10 gene expression in white blood cells (WBC) as well as the major insulin-target tissues including liver and adipose tissue, before the onset of diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. In this study, we extended our hypothesis that some type 2 diabetes mellitus (NIDDM) susceptible genes are up/down-regulated before the onset in WBC of OLETF rats, reflecting their up/down-regulation in major insulin-target tissues, such as the liver. We tested this hypothesis using rat cDNA microarrays. The findings show that 1080 genes are up/down-regulated by more than 2-fold compared to the controls, Long-Evans Tokushima Otsuka rats, before the onset in WBC and liver under fasted or insulin administered condition. Fifty-seven of the 1080 genes were up/down-regulated in both WBC and the liver. More than half have been reported to NIDDM susceptible genes and the remainder have not been reported to be related to NIDDM. These results indicate that there some NIDDM related genes are up/down-regulated in WBC before the onset of diabetes.

Animals↗
PubMed2006

Short moderate hypothermic circulatory arrest without any adjunctive cerebral protection for surgical repair of the ascending aorta extending into the proximal aortic arch: is it safe?

INTRODUCTION: We have been using only moderate hypothermic circulatory arrest (HCA) for patients with ascending aortic aneurysms extending into the proximal aortic arch if the distal anastomoses seem to be simple and easy. The aim of this study is to evaluate the early and midterm results of the use of moderate HCA without any adjunctive cerebral protection in such patients. METHODS: Between October 2000 and March 2005, 23 patients with an age range of 39 to 77 years (mean, 59.7 +/- 12.2 years) received surgical repair of the ascending aorta extending into the proximal aortic arch using HCA without any adjunctive cerebral protection. Mean circulatory arrest time was 7.5 +/- 2.0 minutes (range, 2-13 minutes), and mean core temperature at induction of the circulatory arrest was 26.7 +/- 1.4 degrees C (range, 24-30 degrees C). RESULTS: Operative mortality was 4.3% (1/23) due to unknown cause after successful extubation. Temporary neurological dysfunction was observed in only 1 patient (4.3%), and no persistent neurologic event was observed in any of the patients. One patient died 3 months after the operation due to a mediastinitis. No other cardiac or neurologic event was observed in the 21 surviving patients. CONCLUSION: Our results suggest that moderate HCA at 26 degrees C to 28 degrees C without any adjunctive cerebral protection within 10 minutes is safe in selected patients.

Adult↗