Biomedical subjects

Hiroshi Nakashima

Publications and source records attributed to Hiroshi Nakashima.

At least 19 recordsLinked to original sources

PubMed2006

Electron transport in self-assembled polymer molecular junctions.

A molecular junction of a poly(p-phenyleneethynylene)s derivative with thioacetate end groups (TA-PPE) was fabricated by self-assembling. Nanogap electrodes made by electroplating technique was used to couple thiol end groups of TA-PPE molecules. Room temperature current-voltage characteristics of the molecular junction exhibited highly periodic, repeatable, and identical stepwise features. First-principles calculations suggest that one possibility for the equidistant step is due to the opening of different conducting channels that corresponds to the unoccupied molecular orbitals of the polymer in the junction. It is interesting to see that an 18 nm long polymer is of quantized electronic structures and behaves like a quantum transport device.

Journal Article↗

PubMed2006

Predictors of sub-acute stent thrombosis in acute myocardial infarction patients following primary coronary stenting with bare metal stent.

BACKGROUND: The aim of the present study was to identify the relationship between sub-acute stent thrombosis (SAT) and acute-phase inflammatory reactants, such as high-sensitivity C-reactive protein (hs-CRP) and serum amyloid-A protein (SAA), in patients with acute myocardial infarction (AMI) successfully treated with primary coronary stenting. METHODS AND RESULTS: The 381 consecutive AMI subjects were reperfused by primary coronary stenting within 24 h of onset. SAT was confirmed angiographically in 10 patients (2.6%). There were no significant differences between the patients with or without SAT in terms of patient characteristics, Killip classification on admission, or stent diameter, nor were there significant differences between the 2 groups in terms of left ventricular function soon after stenting (left ventricular ejection fraction) or end-diastolic volume index. The plasma levels of both hs-CRP and SAA were significantly higher in the SAT patients than in the others (hs-CRP: 6.7+/-6.7 mg/dl vs 3.3+/-3.8 mg/dl, p=0.007; SAA: 699+/-812 mug/dl vs 208+/-273 mug/dl, p<0.0001). Multivariate analysis identified SAA as an independent predictor of SAT (risk ratio: 4.9, 95% confidence interval: 1.7-14.9, p<0.05). CONCLUSION: In patients with AMI who are treated with primary coronary stenting, inflammation may be closely related to SAT, for which SAA is a useful predictor.

Acute Disease↗

PubMed2006

Serum amyloid a protein as a predictor of cardiac rupture in acute myocardial infarction patients following primary coronary angioplasty.

BACKGROUND: The predictors of cardiac rupture (CR) in patients with acute myocardial infarction (AMI) treated with successful primary coronary angioplasty have not been identified. METHODS AND RESULTS: Of 433 consecutive AMI subjects who underwent reperfusion by primary coronary angioplasty within 24 h of onset, CR occurred in 11 (2.5%), free wall rupture in 9, and ventricular septal perforation in 2. Rates of females, diabetes mellitus and anterior infarction were higher in the group of CR patients than in the others (p < 0.05). There were no significant differences between the 2 groups in terms of left ventricular (LV) function soon after recanalization, such as LV ejection fraction, regional wall motion, or end-diastolic volume index. Plasma levels of both high-sensitivity C-reactive protein (hsCRP) and serum amyloid-A protein (SAA) were significantly higher in the CR patients than in the others (hsCRP: 6.7 +/- 6.7 mg/dl vs 3.3 +/- 3.8 mg/dl, p = 0.007; SAA: 699 +/- 812 microg/dl vs 208 +/- 273 microg/dl, p < 0.0001). Multivariate analysis identified SAA as an independent predictor of CR (risk ratio: 8.8, 95% confidence interval: 1.7-25.6, p < 0.05). Conclusions In patients with AMI treated with primary coronary angioplasty, inflammation may be closely related to CR, for which SAA is a useful predictor.

Aged↗

PubMed2005

Assembly of additional heterochromatin distinct from centromere-kinetochore chromatin is required for de novo formation of human artificial chromosome.

Alpha-satellite (alphoid) DNA is necessary for de novo formation of human artificial chromosomes (HACs) in human cultured cells. To investigate the relationship among centromeric, transcriptionally permissive and non-permissive chromatin assemblies on de novo HAC formation, we constructed bacterial artificial chromosome (BAC)-based linear HAC vectors whose left vector arms are occupied by beta geo coding genes with or without a functional promoter in addition to a common marker gene on the right arm. Although HACs were successfully generated from the vectors with promoter-less constructs on the left arm in HT1080 cells, we failed to generate a stable HAC from the vectors with a functional promoter on the left arm. Despite this failure in HAC formation, centromere components (CENP-A, CENP-B and CENP-C) assembled at the integration sites correlating with a transcriptionally active state of both marker genes on the vector arms. However, on the stable HAC, chromatin immunoprecipitation analysis showed that HP1alpha and trimethyl histone H3-K9 were enriched at the non-transcribing left vector arm. A transcriptionally active state on both vector arms is not compatible with heterochromatin formation on the introduced BAC DNA, suggesting that epigenetic assembly of heterochromatin is distinct from centromere chromatin assembly and is required for the establishment of a stable artificial chromosome.

Cell Line, Tumor↗

PubMed2005

Clinical significance of nuclear expression of spleen tyrosine kinase (Syk) in gastric cancer.

Spleen tyrosine kinase (Syk) expression was immunohistochemically examined in 250 gastric cancer patients. The rate of positive Syk expression was 42.4%. Syk expression was significantly associated with T1 tumors, lymphatic invasion, venous invasion and lymph node metastasis (P<0.0001). The 5-year survival rate was significantly higher among patients with nuclear Syk expression than among those who were negative for Syk expression (P=0.0003). However, Syk expression was not an independent prognostic factor. Loss of Syk expression was closely related to the malignant property of gastric cancer in the context of tumor depth and lymph node metastasis, especially in early gastric cancer.

Adult↗

PubMed2005

A self-assembled nano optical switch and transistor based on a rigid conjugated polymer, thioacetyl-end-functionalized poly(para-phenylene ethynylene).

A nanometer-scale optical switch and transistor were fabricated with thioacetyl-end-functionalized poly(para-phenylene ethynylene)s and Au nanogap electrodes by self-assembly. With photoirradiation, the switch can be switched on/off quickly with a switching ratio as high as 1000. Moreover, the device works well as a p-type transistor. With an increase in gate bias, strong conductance oscillation was observed in this self-assembled transistor (under low temperature 147 K), which is very likely due to single-electron charging oscillations arising from electron tunneling through the nanometer-scale transistor.

Journal Article↗

PubMed2005

Effects of docetaxel on antigen presentation-related functions of human monocyte-derived dendritic cells.

PURPOSE: Docetaxel (TXT) is a unique chemotherapeutic agent that has been approved for treating various types of malignancies. TXT stabilizes microtubule assembly in cells and causes various dysfunctions of microtubule-dependent cellular events. Patients with advanced malignancies are beginning to receive TXT in combination with immunotherapy; however, the influence of TXT at clinically achievable serum concentrations (less than 10(-6) M) on antigen presentation-related functions of human monocyte-derived dendritic cells (Mo-DCs) remains unclear. METHODS: Immature Mo-DCs (imMo-DCs) were generated from peripheral blood monocytes with interleukin-4 and granulocyte-macrophage colony-stimulating factor in vitro. Mature Mo-DCs (mMo-DCs) were induced from imMo-DCs with tumor necrosis factor-alpha and prostaglandin E(2). RESULTS: TXT at concentrations lower than 10(-7) M did not significantly affect cellular viability, phagocytosis, or expression of antigen presentation-related molecules of Mo-DCs. In contrast, TXT at concentrations lower than 10(-9) M significantly suppressed directional motility of imMo-DCs toward MIP-1alpha and of mMo-DCs toward MIP-3beta. However, TXT had no effect on either CCR1 expression by imMo-DCs or CCR7 expression by mMo-DCs. No gross changes in the microtubule skeleton were evident by immunofluorescence microscopy after treatment with TXT at less than 10(-8) M. However, reduced numbers of imMo-DCs with podosomes localized primarily in one cell region were observed. CONCLUSIONS: The present results indicate that different concentrations of TXT influence antigen presentation-related functions differently. In particular, TXT at relatively low therapeutic doses disrupts chemotactic motility of Mo-DCs.

Antineoplastic Agents, Phytogenic↗

PubMed2005

Selective chemisorption of end-functionalized conjugated polymer on macro- and nanoscale surfaces.

Linear and conjugated poly(p-phenylene ethynylene)s (PPEs) with three different types of functionalized end groups (thiolacetate, isocyanide, and carboxylic acid groups) were synthesized, and their selective chemisorption behavior on various substrate surfaces were investigated using UV/vis transmission absorption spectroscopy. The UV/vis spectra of the PPEs were clearly dependent on the chemical affinity between the PPE end group and the solid surfaces. Furthermore, regarding the chemisorption of thiolacetate modified polymer on a nanoscopic gold particle surface, we visualized novel polymer-colloid nanoarchitectures such as a barbell-type nanohybrid and interconnected polymer nanowire structures that are successively linked through gold nanoparticles.

Letter↗

PubMed2005

Measurement and analysis of induced activities in concrete irradiated using high-energy neutrons at KENS Neutron Spallation Source Facility.

Precise estimation of induced activities in concrete shields for high-energy accelerator facilities is one of the most important issues that need to be solved, not only for the reduction of exposure for workers, but also for the reduction of radioactive wastes. Irradiation experiments have been performed by using the 500 MeV Neutron Spallation Source Facility in KEK. The large concrete assembly was placed in the direction of 0 degrees to the beamline. Two kinds of samples were placed at several positions in the assembly. The irradiation period was about 1 week and induced activities in the samples were measured until approximately 1.5 y after irradiation. From the comparison between the experiment and the available Monte Carlo calculation code system, good agreement was obtained for 24Na, 47Sc, 47Ca and 54Mn within a factor 2; however, large discrepancies were observed for some other nuclides.

Computer Simulation↗

PubMed2005

Neurotrophic effect of magnolol in the hippocampal CA1 region of senescence-accelerated mice (SAMP1).

Magnolol has neurotrophic effects in primary cultured rat cortical neurons, which are expressed as the promotion of neurite outgrowth and neuronal survival. In this study, we investigated the protective effect of magnolol against age-related neuronal loss in the hippocampus using senescence-accelerated mouse (SAMP1). Magnolol (5, 10 mg/kg) was orally administered once a day for 14 d to 2- or 4-month-old mice, and evaluation was carried out when the mice were 4 or 6 months old. The density of neurofibrils decreased with aging in the stratum radiatum of the CA1 region in the hippocampus of SAMP1, not SAMR1. Treatment with magnolol significantly prevented the decrease of neurofibrils in the CA1, when it was administered in 2-month-olds. However, administration at 4 months of age did not result in a preventive effect. These findings suggest that the administration of magnolol before the initiation of neuronal loss may result in a protective effect in the hippocampus.

Aging↗

PubMed2005

Prognostic value of serum amyloid A protein in patients with acute myocardial infarction.

BACKGROUND: The relationship between plasma levels of serum amyloid A protein (SAA) concentrations and clinical course (including mortality) was investigated in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The study enrolled 280 consecutive AMI patients who were admitted within 10 h of onset and were successfully reperfused by primary percutaneous coronary intervention. Plasma SAA concentrations were evaluated at 24 h after onset. The threshold of the upper quintile (325 mug/dl) was used to divide patients into 2 groups: either a high SAA (H group: > or =325 mug/dl; n=56) or low SAA (L group: <325 microg/dl; n=224). (I) Left ventricular (LV) ejection fraction in the chronic phase was significantly less in the H group than in the L group (52+/-14% vs 57+/-13%, p=0.03). (II) There were significantly more major complications in the H group than in the L group (cardiac rupture: p=0.0007, cardiogenic shock: p<0.0001; subacute thrombosis: p=0.0007; cardiac death: p=0.0003). (III) Multivariate analysis identified SAA as an independent predictor of 6-month mortality in AMI patients (risk ratio: 5.8, 95%confidence interval: 1.3-27.7, p=0.03). CONCLUSIONS: In the setting of AMI, plasma SAA concentrations may be closely related to LV systolic dysfunction and poor patient outcomes, including mortality.

Acute Disease↗

PubMed2005

Clinical significance of acute-phase endothelin-1 in acute myocardial infarction patients treated with direct coronary angioplasty.

BACKGROUND: The aim of the present study was to investigate the relationship between plasma concentrations of endothelin (ET)-1 and clinical outcome (including mortality) and left ventricular (LV) systolic function in acute myocardial infarction (AMI). METHODS AND RESULTS: The study group comprised 110 consecutive first-AMI patients who were successfully reperfused by primary coronary intervention. Plasma ET-1 concentrations were evaluated 24 h from onset and the patients were divided into 2 groups according to the median value, either a high group (H group: > or = 2.90 pg/ml plasma ET-1; n = 55) or low group (L group: < 2.90 pg/ml plasma ET-1; n = 55). Major complications and LV systolic function were monitored in the 2 groups. Both highly sensitive C-reactive protein (hs-CRP) and brain natriuretic peptide (BNP) showed a significant positive correlation with ET-1 (BNP: r = 048, p < 0.0001, hs-CRP: r = 0.43, p < 0.001). Chronic stage left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume index (LVEDVI) were significantly poorer in the H group (LVEF: 51+/-15% vs 60+/-13%, p = 0.003, LVEDVI: 74+/-19 ml/m2 vs 66+/-14 ml/m2, p < 0.05). There were significantly more major complications in the H group than in the L group (cardiogenic shock: 18% vs 5%, p = 0.04; cardiac death: 13% vs 0%, p < 0.01). CONCLUSIONS: In the setting of AMI, plasma ET-1 concentrations may be closely related to LV systolic dysfunction and poor patient outcome, including mortality.

Aged↗

PubMed2005

Predictors of mortality in patients with acute myocardial infarction and cardiogenic shock.

BACKGROUND: Although cardiogenic shock (CS) is the leading cause of death for acute myocardial infarction (AMI) patients, reliable predictive factors in the acute stage, such as cardiovascular peptides, have not yet been identified. METHODS AND RESULTS: In 42 consecutive AMI patients with CS on admission, successfully treated by primary percutaneous coronary intervention (PCI) within 12 h of onset, related factors including brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), renin, aldosterone, catecholamines, and adrenomedullin, were investigated 24 h from onset, as well as the 1-year mortality rates. During the 12-month follow-up period, 15 patients died from cardiovascular causes (group D). There were no significant differences in patient characteristics, angiographic findings, and left ventricular systolic function between group D subjects and the survivors (group S: n=27). Multivariate analysis identified high levels of adrenomedullin as an independent predictor of 1-year mortality (risk ratio: 6.42, 95% confidence interval, 1.49-43.31, p<0.05). CONCLUSIONS: The acute-phase plasma concentration of adrenomedullin may be a reliable predictor of mortality in patients with AMI complicated by CS and successfully treated by direct PCI, as may be BNP concentration, peak-creatine kinase value, and ventricular fibrillation.

Angioplasty, Balloon↗

PubMed2005

Clinical outcomes and left ventricular function in diabetic patients with acute myocardial infarction treated by primary coronary angioplasty.

The objective of the present study was to compare left ventricular (LV) function and clinical outcomes in diabetics versus nondiabetics with acute myocardial infarction (AMI) treated by primary coronary angioplasty. A total of 327 consecutive AMI subjects were reperfused by primary coronary angioplasty within 12 hours from onset. Diabetes mellitus (DM) was present in 104 of the 327 patients. LV function was serially determined by left ventriculograms taken in the acute and chronic phases (6 months after onset). (I) The early ST-segment resolution rate was lower in DM patients compared with non-DM patients (59% versus 83%, P < 0.0001). (II) During a 6-month follow-up, the percentages of target vessel revascularization (TVR), coronary aorta bypass grafting (CABG), and cardiac death were higher in the DM patients compared with the non-DM patients (TVR: 29% versus 19%; P < 0.05, CABG: 10% versus 5% ; P < 0.05, cardiac death: 12% versus 4%; P = 0.01). (III) The differences in left ventricular ejection fraction (LVEF) between two stages (delta-LVEF) were significantly lower in the DM patients than the non-DM patients (1 +/- 9% versus 7 +/- 10%, P < 0.0001). (IV) Multivariate analysis identified DM as an independent predictor of cardiac death (Odds ratio 5.5, 95% CI, 1.3-23.7, P < 0.05) and as a sole independent predictor of LVEF deterioration (Odds ratio 5.8, 95% CI, 2.8-11.8, P < 0.001). In patients with AMI treated using primary coronary angioplasty, DM is closely related to left-ventricular systolic dysfunction and a poor patient outcome, including mortality.

Adult↗

PubMed2005

Prognostic significance of time-delay to peak creatine kinase after direct percutaneous coronary intervention in acute myocardial infarction patients.

The aim of the present study was to investigate the prognostic significance of time-delay to peak creatine kinase (CK) after successful direct percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Our 240 consecutive first AMI attack subjects admitted within 5 hours from onset were successfully reperfused by direct PCI therapy. Subjects were divided into two groups according to the upper quartile value of peak-CK time from onset, the early peak-CK group (peak-CK time < or = 16 hours from onset, n = 180) and the late peak-CK group (peak-CK time > 16 hours, n = 60). (I) The early ST-segment resolution rate was lower in the late peak-CK group compared with the early peak-CK group (P < 0.05), and there were significantly fewer patients with preinfarction angina pectoris in the late peak-CK group than in the early peak-CK group (P < 0.01). (II) LVEF in the chronic stage was significantly lower in the late peak-CK group than in the early peak-CK group (49 +/- 13% versus 57 +/- 13%, P < 0.001). (III) There were significantly more patients with major complications in the late peak-CK group than in the early peak-CK group (required CABG: 10% versus 3%, P < 0.05; cardiac death: 18% versus 3%, P = 0.0001). (IV) Multivariate analysis identified late peak-CK as an independent predictor of cardiac death (Odds ratio 7.91, 95% C.I. 1.40-44.11, P < 0.05). In patients with AMI, the time-delay to peak-CK after successful direct PCI may be closely related to left-ventricular systolic dysfunction and poor patient outcome, including mortality.

Adult↗

PubMed2005

A 13-week toxicity study of bismuth in rats by intratracheal intermittent administration.

Although bismuth is widely used as a lead substitute in the industrial field, the toxicity of bismuth by inhalation is little known. We performed a 13-wk intratracheal intermittent bismuth dose toxicity study. Bismuth was administered at dose levels of 0, 0.8, 4, 20 mg/kg to male Crj:CD(SD)IGS rats (SPF) by intratracheal intermittent administration once a week for thirteen weeks to investigate its potential toxic effects; especially for specific adverse effects and changes related to pre-neoplastic lesions. Our results showed foreign body inflammation in the lungs, which was caused by intratracheal administration of bismuth, and physical changes related to pulmonary lesions; however, there were no serious changes in other organs. We concluded that dose-dependent, but not specific adverse effects, were attributable to bismuth inhalation in the rat.

Administration, Inhalation↗

PubMed2005

Oral toxicity of bismuth in rat: single and 28-day repeated administration studies.

The consumption and production of bismuth are increasing, however there is very little information about the direct toxic effect of bismuth. The present study aimed to characterize the potential toxic effects of bismuth through oral administration and observation for fourteen days following single dose of 0 and 2,000 mg/kg (acute oral toxicity study), and repeated oral administration for twenty-eight days at dose levels of 0, 40, 200, and 1,000 mg/kg daily (28-d repeated oral dose toxicity study) to male and female Crj:CD (SD) IGS rats (SPF). We found no deaths and no abnormalities in clinical signs, body weights, and necropsy findings for any of the animals in the acute oral toxicity study and no changes attributable to bismuth in either males or females in the dose group up to 1,000 mg/kg of the 28-d repeated-dose toxicity study. Therefore, we determined that the lethal dose with a 50% mortality rate (LD50) is greater than 2,000 mg/kg and the no-observed-adverse-effect level (NOAEL) of bismuth is 1,000 mg/kg in both sexes. We conclude that the adverse toxic effects of bismuth as a simple metal substance are low compared to lead toxicity under the conditions tested in our studies.

Administration, Oral↗

PubMed2004

Paclitaxel probably enhances cytotoxicity of natural killer cells against breast carcinoma cells by increasing perforin production.

Paclitaxel, a semisynthetic taxane, is one of the most active chemotherapeutic agents for the treatment of patients with breast cancer. We focused on the effect of paclitaxel on the cytotoxicity of natural killer (NK) cells. NK cells were purified by negative selection with magnetic beads from peripheral blood mononuclear cells of healthy volunteers. A human breast carcinoma cell line BT-474 and an NK cell-sensitive erythroleukemia cell line K562 were used as targets. Cytotoxicity of NK cells was determined by 51Cr-release assay with labeled target cells. Paclitaxel (1-100 nM) did not affect cellular viability, and significantly enhanced cytotoxicity of NK cells in a dose-dependent manner. Although paclitaxel did not affect Fas-ligand expression of NK cells, paclitaxel induced mRNA and protein production of perforin, an effector molecule in NK cell-mediated cytotoxicity. Concanamycin A, a potent inhibitor of the perforin-mediated cytotoxic pathway, inhibited paclitaxel-dependent NK cell-mediated cytotoxicity. Furthermore, paclitaxel induced activation of nuclear factor kappa B (NF-kappa B) in NK cells. NF-kappa B inhibitor pyrrolidine dithiocarbamate significantly suppressed both paclitaxel-induced perforin expression and NK cell cytotoxicity. Our results show for the first time that paclitaxel enhances in vitro cytotoxicity of human NK cells. Moreover, our results suggest a significant association between enhanced NK cell cytotoxicity, increased perforin production, and NF-kappa B activation.

Adenocarcinoma↗