Biomedical subjects

Hiroshi Nakashima

Publications and source records attributed to Hiroshi Nakashima.

At least 19 recordsLinked to original sources

PubMed2006

Obstructive sleep apnoea inhibits the recovery of left ventricular function in patients with acute myocardial infarction.

AIMS: It has been suggested that obstructive sleep apnoea syndrome (OSA) may be a direct cause of left ventricular (LV) systolic dysfunction. This study was designed to examine our hypothesis that OSA inhibits the recovery of LV function in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Our 86 consecutive first-AMI patients underwent primary percutaneous coronary intervention (PCI). All patients underwent polysomnography and OSA was defined as an apnoea-hypoapnoea index (AHI) > or =15 events/h, of which more than 50% were obstructive. Left ventriculograms immediately after PCI and at 21 days were used to evaluate LV ejection fraction (LVEF), LV end-diastolic volume index, and regional wall motion (RWM) within the infarct area. OSA was observed in 37 patients (43%). All three indices of LV function after primary PCI were comparable between the two groups. Increases in LVEF and RWM during admission were significantly lower in OSA patients than those without OSA (delta LVEF: -0.3+/-9.6 vs. 7.4+/-7.2%, P < 0.001; delta RWM: 0.26+/-1.04 SD/chord vs. 1.16+/-1.20 SD/chord, P = 0.002). Multiple regression analysis showed that AHI correlated negatively with delta LVEF and delta RWM. CONCLUSION: The novel finding is that OSA may inhibit the recovery of LV function in patients with AMI.

Aged↗

PubMed2006

Nuclear factor-kappaB contributes to hedgehog signaling pathway activation through sonic hedgehog induction in pancreatic cancer.

The hedgehog (Hh) signaling pathway, which functions as an organizer in embryonic development, is implicated in the development of various tumors. In pancreatic cancer, pathway activation is reported to result from aberrant expression of the ligand, sonic Hh (Shh). However, the details of the mechanisms regulating Shh expression are not yet known. We hypothesized that nuclear factor-kappaB (NF-kappaB), a hallmark transcription factor in inflammatory responses, contributes to the overexpression of Shh in pancreatic cancer. In the present study, we found a close positive correlation between NF-kappaB p65 and Shh expression in surgically resected pancreas specimens, including specimens of chronic pancreatitis and pancreatic adenocarcinoma. We showed that blockade of NF-kappaB suppressed constitutive expression of Shh mRNA in pancreatic cancer cells. Further activation of NF-kappaB by inflammatory stimuli, including interleukin-1beta, tumor necrosis factor-alpha, and lipopolysaccharide, induced overexpression of Shh, resulting in activation of the Hh pathway. Overexpression of Shh induced by these stimuli was also suppressed by blockade of NF-kappaB. NF-kappaB-induced Shh expression actually activated the Hh pathway in a ligand-dependent manner and enhanced cell proliferation in pancreatic cancer cells. In addition, inhibition of the Hh pathway as well as NF-kappaB suppressed the enhanced cell proliferation. Our data suggest that NF-kappaB activation is one of the mechanisms underlying Shh overexpression in pancreatic cancer and that proliferation of pancreatic cancer cells is accelerated by NF-kappaB activation in part through Shh overexpression.

Animals↗

PubMed2006

Microchannel device using self-spreading lipid bilayer as molecule carrier.

We propose a microchannel device that employs a surface-supported self-spreading lipid bilayer membrane as a molecule carrying medium. The device has a micropattern structure fabricated on a SiO2 surface by photolithography, into which a self-spreading lipid bilayer membrane is introduced as the carrier medium. This system corresponds to a microchannel with a single lipid bilayer membrane height of approximately 5 nm, compared with conventional micro-fluidic channels that have a section height and width of at least several microm. The device is beneficial for detecting intermolecular interactions when molecules carried by the self-spreading lipid bilayer collide with each other in the microchannel. The validity of the device was confirmed by observing the fluorescence resonance energy transfer (FRET) between two dye molecules, coumarin and fluorescein.

Coumarins↗

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↗

PubMed2006

[Clinical manifestations and outcome of acute myocardial infarction in young adults treated with primary coronary angioplasty].

OBJECTIVES: This study investigated the differences in presentation, complications, and outcome of young patients with acute myocardial infarction compared to other patients. METHODS: Our series of 379 consecutive patients with acute myocardial infarction, who were admitted within 12 hr of onset and successfully reperfused by primary percutaneous coronary intervention, included 28 (7.4%) young patients (< 50 years). RESULTS: There were significantly more male patients, current smokers, and hyperlipidemia in the young group than in the other patients (p < 0.01). The levels of acute phase brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) were significantly lower (BNP: 128 +/- 103 vs 379 +/- 470 pg/ml, p = 0.009, ANP: 17 +/- 11 vs 66 +/- 81 pg/ml, p = 0.004) and peak creatine kinase value was significantly higher (3,824 +/- 3,459 vs 2,413 +/- 2,023 IU/l, p = 0.009) in the young group than in the other patients. The increase (chronic phase-acute phase) of left ventricular ejection fraction was significantly better in the young group (8 +/- 9% vs 4 +/- 10%, p < 0.05). There were significantly fewer patients with ventricular arrhythmia in the young group than in the other patients (10.7% vs 33.0%, p = 0.04). The cardiac mortality rate in the first 6 months was only 3.6% in the young group. CONCLUSIONS: Young patients with acute myocardial infarction, in spite of higher peak creatine kinase value, seemed to have excellent prognosis, with lower BNP and good recovery of left ventricular ejection fraction.

Adult↗

PubMed2006

[Clinical manifestations and acute myocardial infarction in women treated with primary coronary angioplasty].

OBJECTIVES: The differences in presentation, complications, and outcome of acute myocardial infarction treated with primary coronary angioplasty were compared in male and female patients. METHODS: Consecutive patients with acute myocardial infarction who were admitted within 12 hr of onset underwent primary percutaneous coronary intervention, including 120 female (31%) and 264 male (69%) patients. RESULTS: There were significantly more patients with diabetes mellitus (42% vs 31%, p = 0.03), and hyperlipidemia(56% vs 38%, p = 0.001), and fewer patients with current smoking (10% vs 60%, p < 0.0001) in the female group than in the male group (p < 0.01). The female group was significantly older (75 +/- 11 vs 67 +/- 12 years, p < 0.0001). The value of acute phase brain natriuretic peptide was significantly higher (483 +/- 543 vs 306 +/- 404 pg/ml, p = 0.001), and peak creatine kinase value was significantly lower (1,743 +/- 1,732 vs 2,855 +/- 2,997 IU/l, p = 0.0003) in the female group than in the male group. Both Killip's classification on admission (p = 0.04) and Thrombolysis in Myocardial Infarction grade soon after mechanical reperfusion therapy (p = 0.03) were significantly worse in the female group. There were significantly more patients with heart failure in the female group (40% vs 27%, p = 0.04). The cardiac mortality rates during 6 months was significantly higher in the female group (11% vs 5%, p = 0.02). However, multivariate analysis showed that female sex was not an independent predictor of cardiac death. CONCLUSIONS: Female patients with acute myocardial infarction seemed to have a poor prognosis, in spite of lower peak creatine kinase value and higher brain natriuretic peptide value. The reasons for poorer outcomes in women were considered to be patient background, such as higher age and diabetes mellitus, and condition of heart failure on admission.

Age Factors↗

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↗