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Yoshihiko Ikeda

Publications and source records attributed to Yoshihiko Ikeda.

15 recordsLinked to original sources
PubMed2006

Tissue-specific renin-angiotensin system in pulmonary lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM), a multisystem disease found in middle-aged women, is characterized by cystic lung destruction and abdominal tumors (e.g., angiomyolipomas, lymphangioleimyomas), resulting from proliferation of abnormal-appearing, smooth muscle-like cells (LAM cells). The LAM cells, in combination with other cells, form nodular structures within the lung interstitium and in the walls of the cysts. LAM cells contain mutations in the tuberous sclerosis complex TSC1 and/or TSC2 genes, which lead to dysregulation of the mammalian target of rapamycin, affecting cell growth and proliferation. Proliferation and migration of vascular smooth muscle cells and production of angiogenic factors are regulated, in part, by angiotensin II. To determine whether a LAM-specific renin-angiotensin system might play a role in the pathogenesis of LAM, we investigated the expression of genes and gene products of this system in LAM nodules. mRNA for angiotensinogen was present in RNA isolated by laser-captured microdissection from LAM nodules. Angiotensin I-converting enzyme and chymase-producing mast cells were present within the LAM nodules. We detected renin in LAM cells, as determined by the presence of mRNA and immunohistochemistry. Angiotensin II type 1 and type II receptors were identified in LAM cells by immunohistochemistry and immunoblotting of microdissected LAM nodules. Angiotensin II is localized in cells containing alpha-smooth muscle actin (LAM cells). A LAM-specific renin-angiotensin system appears to function within the LAM nodule as an autocrine system that could promote LAM cell proliferation and migration, and could represent a pharmacologic target.

Actins↗
PubMed2006

Sex differences in early mortality of patients undergoing primary stenting for acute myocardial infarction.

BACKGROUND: Limited information exists regarding the impact of gender on in-hospital outcome after primary stenting for acute myocardial infarction (AMI). METHODS AND RESULTS: A total of 2,981 patients (790 women and 2,191 men) participated in the study who were admitted within 24 h after symptom onset and underwent emergency primary stenting for AMI. Compared with men, women were significantly older; had higher incidences of hypertension, diabetes mellitus, hyperlipidemia, Killip class > or =2, and cardiogenic shock; had a higher blood glucose level and a lower serum creatinine level on admission. Other baseline characteristics, including the incidences of ST-segment elevation AMI, anterior infarction, 3-vessel disease, initial or final Thrombolysis in Myocardial Infarction (TIMI) flow grade did not significantly differ between the sexes. The in-hospital mortality rate was significantly higher in women than in men (9.4% vs 5.2%, p<0.001). On multivariate analysis, age, Killip class, blood glucose level, serum creatinine level, and final TIMI grade were independent predictors of in-hospital death, but female gender was not (odds ratio 1.01, p=0.69). CONCLUSIONS: Our findings suggest that in patients undergoing primary stenting for AMI, women have higher in-hospital mortality than men, but female gender itself is not independently associated with increased in-hospital mortality after adjustment for baseline differences.

Acute Disease↗
PubMed2005

Acute hyperglycemia is associated with adverse outcome after acute myocardial infarction in the coronary intervention era.

PURPOSE: This study was undertaken to assess the association between acute hyperglycemia and inhospital outcome after acute myocardial infarction (AMI) in the percutaneous coronary intervention (PCI) era. We also assessed outcome of patients with a history of diabetes mellitus in the PCI era. METHODS: Between January 2001 and December 2001, 1253 patients were admitted to the hospitals within 48 hours after the onset of AMI. Plasma glucose was measured at hospital admission. Acute hyperglycemia was defined as plasma glucose of > 11 mmol/L (198 mg/dL), regardless of the diabetic status. Primary PCI was performed in 898 (72%) patients. RESULTS: The inhospital mortality rate was significantly higher in patients with acute hyperglycemia than in patients without (16% vs 6%, P < .001). However, there was no significant difference in mortality between diabetic and nondiabetic patients (8% vs 9%, P = .54). Acute hyperglycemia was associated with a higher inhospital mortality rate both in nondiabetic patients (24% vs 6%, P < .001) and in diabetic patients (10% vs 5%, P = .039). Acute hyperglycemia was associated with a higher incidence of no reflow during PCI (21% vs 12%, P < .001), but diabetes was not (14% vs 15%, P = .71). CONCLUSION: Acute hyperglycemia, but not diabetes, was a predictor for inhospital mortality after AMI in the PCI era. No reflow occurred more frequently during PCI in patients with acute hyperglycemia, suggesting that microvascular dysfunction might have contributed to adverse outcome of these patients.

Acute Disease↗
PubMed2005

Activation of toll-like receptor-mediated NF-kappa beta by zymosan-derived water-soluble fraction: possible contribution of endotoxin-like substances.

Zymosan is a well-known reagent for the examination of inflammatory response and is prepared from yeast, Saccharomyces cerevisiae. In the activation process, Toll-like receptor (TLR) 2 and TLR6 act as functional receptors for NF-kappaB activation. Although zymosan is primarily composed of beta-glucans, little is known about the active component of zymosan-mediated biological activities. The active moiety of zymosan was fractionated by its solubility in water, and its biological activity on macrophages and TLRs-transfectants examined. The macrophage cell line, RAW264.7, was treated with zymosan-derived preparations, and tumor necrosis factor alpha (TNF-alpha) produced in the culture supernatant was measured by ELISA. Increased TNF-alpha production was observed by stimulation with water-soluble (ZWS) or water-insoluble fraction (ZWIS). ZWS showed higher activity in TNF-alpha production. NF-kappaB activation via TLR2, TLR1/ TLR2, TLR2/TLR6, and TLR4/MD-2/CD14 also was enhanced by stimulation with ZWS and ZWIS. In particular, ZWS showed higher activity via TLR1/TLR2, TLR2/TLR6, and TLR4/MD-2/CD14 than other preparations. ZWS activity was decreased by treatment with polymyxin B, but not with lysozyme and zymolyase. Furthermore, ZWS contained significant more endotoxin than any other preparations. Therefore, we suggest that the active moiety of ZWS for the NF-kappaB activation has an endotoxin-like substance, that is abundantly observed in Gram-negative bacteria. These results imply that the inflammatory activity of zymosan is induced not only by beta-glucans, but also by other endotoxin-like water-soluble substances.

Animals↗
PubMed2005

Effects of glucose abnormalities on in-hospital outcome after coronary intervention for acute myocardial infarction.

BACKGROUND: The effects of glucose abnormalities on outcomes after percutaneous coronary intervention (PCI) remain unclear. We examined the association between glucose abnormalities and in-hospital outcome in patients undergoing PCI for acute myocardial infarction (AMI). METHODS AND RESULTS: A total of 849 patients with AMI who were admitted within 12 h after symptom onset and underwent emergency PCI were classified according to the presence or absence of admission hyperglycemia, defined as a blood glucose level on admission of >11 mmol/L and whether they had a history of diabetes mellitus: group 1 (n = 504), non-diabetic patients without admission hyperglycemia; group 2 (n = 111), diabetic patients without admission hyperglycemia; group 3 (n = 87), non-diabetic patients with admission hyperglycemia; and group 4 (n = 147), diabetic patients with admission hyperglycemia. Among groups 1, 2, 3 and 4, in-hospital mortality was 2.6, 2.7, 11.5 and 8.8%, respectively (p < 0.01). Multivariate analysis showed that compared with group 1 patients, the odds ratio (95%confidence interval) for in-hospital mortality among those in groups 2, 3, and 4 were 0.80 (0.24-2.60, p = 0.708), 2.29 (1.10-5.49, p = 0.039), and 2.14 (1.14-4.69, p = 0.048), respectively. CONCLUSIONS: In-patients undergoing PCI for AMI, admission hyperglycemia, irrespective of the presence or absence of diabetes, is associated with increased in-hospital mortality, whereas diabetes without admission hyperglycemia is not.

Adult↗
PubMed2005

Beneficial effect of preinfarction angina on in-hospital outcome is preserved in elderly patients undergoing coronary intervention for anterior acute myocardial infarction.

BACKGROUND: Preinfarction angina improves survival after acute myocardial infarction (AMI) in nonelderly but not elderly patients in the thrombolytic era. However, it remains unclear whether preinfarction angina has a beneficial effect on clinical outcome in elderly patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: The study group comprised 484 anterior AMI patients who were admitted within 24 h of onset and underwent emergency PCI. Patients were divided into 2 groups: those aged < 70 years (nonelderly patients, n = 290) and those aged > or = 70 years (elderly patients, n = 194). Angina within 24 h before AMI was present in 42% of nonelderly patients and in 37% of elderly patients. In nonelderly patients, preinfarction angina was associated with a lower in-hospital mortality rate (1% vs 7%, p = 0.02). Similarly, in elderly patients, preinfarction angina was associated with a lower in-hospital mortality rate (6% vs 16%, p = 0.03). Multivariate analysis showed that the absence of preinfarction angina was an independent predictor of in-hospital mortality in both nonelderly (odds ratio 4.20; 95% confidence interval (CI) 1.20-10.6; p = 0.04) and elderly patients (odds ratio 3.04; 95%CI 1.06-18.1; p = 0.04). CONCLUSIONS: Angina within the 24 h before AMI is associated with better in-hospital outcomes in elderly and nonelderly patients.

Aged↗
PubMed2005

Apoptotic myocardial cell death in the setting of arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disease characterized by progressive atrophy of the right ventricular myocardium accompanied by fibro-fatty replacement. We examined whether the loss of myocardial cells in the setting of ARVC could result from cell death by apoptosis as demonstrated by the detection of DNA fragmentation and the expression of apoptosis regulatory proteins (e.g. CPP-32, Bcl-2, and Bax). METHODS: Specimens obtained from the right ventricular myocardium of 11 patients with ARVC (ARVC group) and 10 age-matched normal individuals (control group) were analysed. To identify individual cells undergoing apoptosis, paraffin sections were examined with the TdT-mediated dUTP-biotin nick end labelling method (TUNEL) and the rabbit polyclonal anti-single stranded DNA method (ssDNA). The apoptotic index was calculated as the percentage of nuclei staining positive by the TUNEL or ssDNA method. We also used immunohistochemical techniques to examine the levels of CPP-32, Bcl-2, and Bax expression. RESULTS: Apoptosis was detected in the ARVC group with a mean apoptotic index of 5.7 +/- 4.5% (ssDNA) and 23.8 +/- 7.5% (TUNEL), but not in the control group (p < 0.01). CPP-32 expression and Bax overexpression were observed in the ARVC group. However, Bcl-2 expression was not seen in either group. CONCLUSIONS: Apoptotic myocardial cell death occurs in the setting of ARVC and may contribute to the loss of myocardial cells.

Adult↗
PubMed2004

The white blood cell count is an independent predictor of no-reflow and mortality following acute myocardial infarction in the coronary interventional era.

BACKGROUND: In the era before the use of coronary reperfusion therapy, an elevated white blood cell (WBC) count was associated with a higher risk of adverse events following acute myocardial infarction (AMI). However, the relationship between WBC count and prognosis after AMI has not been investigated since coronary intervention was introduced. AIM: To evaluate whether a high WBC count within 48 hours of the onset of AMI predicts future adverse events in patients undergoing percutaneous coronary intervention (PCI). METHOD: We evaluated 1,016 patients who underwent PCI in the acute phase of MI using the Japanese Acute Coronary Syndrome Study (JACSS) database. RESULTS. WBC count was significantly associated with smoking, sudden onset AMI, and the no-reflow phenomenon during PCI, as were age, peak creatine kinase level, and Killip class. An elevated WBC count was significantly associated with higher risk of in-hospital mortality. Patients in the highest quartile of WBC count were about three times more likely to have a poor prognosis after AMI compared to those in the lowest quartile. CONCLUSIONS: The WBC count is of great significance for stratifying patient risk and can be used as a universal marker for predicting future adverse events following any treatment for AMI.

Age Factors↗
PubMed2004

Characterization of beta-glucan recognition site on C-type lectin, dectin 1.

Dectin 1 is a mammalian cell surface receptor for (1-->3)-beta-d-glucans. Since (1-->3)-beta-d-glucans are commonly present on fungal cell walls, it has been suggested that dectin 1 is important for recognizing fungal invasion. In this study we tried to deduce the amino acid residues in dectin 1 responsible for beta-glucan recognition. HEK293 cells transfected with mouse dectin 1 cDNA could bind to a gel-forming (1-->3)-beta-d-glucan, schizophyllan (SPG). The binding of SPG to a dectin 1 transfectant was inhibited by pretreatment with other beta-glucans having a (1-->3)-beta-d-glucosyl linkage but not by pretreatment with alpha-glucans. Dectin 1 has a carbohydrate recognition domain (CRD) consisting of six cysteine residues that are highly conserved in C-type lectins. We prepared 32 point mutants with mutations in the CRD and analyzed their binding to SPG. Mutations at Trp(221) and His(223) resulted in decreased binding to beta-glucan. Monoclonal antibody 4B2, a dectin- 1 monoclonal antibody which had a blocking effect on the beta-glucan interaction, completely failed to bind the dectin-1 mutant W221A. A mutant with mutations in Trp(221) and His(223) did not have a collaborative effect on Toll-like receptor 2-mediated cellular activation in response to zymosan. These amino acid residues are distinct from residues in other sugar-recognizing peptide sequences of typical C-type lectins. These results suggest that the amino acid sequence W221-I222-H223 is critical for formation of a beta-glucan binding site in the CRD of dectin 1.

Amino Acid Sequence↗
PubMed2004

Remodeling of the chronic severely failing ischemic sheep heart after coronary microembolization: functional, energetic, structural, and cellular responses.

The mandatory use of pharmacotherapy in human heart failure (HF) impedes further study of natural history and remodeling mechanisms. We created a sheep model of chronic, severe, ischemic HF [left ventricular (LV) ejection fraction (LVEF) <35% stable over 4 wk] by selective coronary microembolization under general anesthesia and followed hemodynamic, energetic, neurohumoral, structural, and cellular responses over 6 mo. Thirty-eight sheep were induced into HF (58% success), with 23 sheep followed for 6 mo (21 sheep with sufficient data for analysis) after the LVEF stabilized (median of 3 embolizations). Early doubling of LV end-diastolic pressure persisted, as did increases in LV end-diastolic volume, LV wall stress, and LV wall thinning. Contractile impairment (LV end-systolic elastance, LV preload recruitable stroke work, and dobutamine-responsive contractile reserve) and diastolic dysfunction also remained stable. Cardiac mechanical energy efficiency did not recover. Plasma atrial natriuretic peptide levels remained elevated, but rises in plasma aldosterone and renin activity were transient. Collagen content increased 170%, the type I-to-III phenotype ratio doubled in the LV, but right ventricular collagen remained unaltered. Fas ligand cytokine levels correlated with expression of both caspase-3 and -2, suggesting a link in the apoptotic "death cascade." Caspase-3 activity also bore a close relationship to LV meridional wall stress calculated from echocardiographic and intraventricular pressure measurements. We concluded that the stability of chronic untreated severe ischemic HF depends on the recruitment of myocardial remodeling mechanisms that involve an interaction among hemodynamic load, contractile efficiency/energetics, neurohumoral activation, response of the extracellular matrix, wall stress, and the myocyte apoptotic pathway.

Aldosterone↗
PubMed2004

Clinical efficacy and safety of rosuvastatin in Japanese patients with heterozygous familial hypercholesterolemia.

Rosuvastatin is a new statin that has been shown to produce substantial dose-dependent reductions in low-density lipoprotein cholesterol (LDL-C) in Western and Japanese hypercholesterolemic patients. Rosuvastatin efficacy and safety were assessed in an open-label, dose-titration trial of 37 Japanese patients with heterozygous familial hypercholesterolemia. After an 8-week dietary lead-in period, patients received rosuvastatin on the following schedule: 10 mg/day during weeks 0-6; 20 mg/day during weeks 6-12, and 40 mg/day for weeks 12-18. Mean percentage reductions from baseline in LDL-C (49.2-56.7%), total cholesterol (39.4-45.4%), and non-high-density lipoprotein cholesterol (non-HDL-C) (46.7-54.3%) were highly significant at each dose (p < 0.0001). Similar significant reductions in triglycerides (18.2-25.0%; p < 0.006) and increases in HDL-C (9.6-13.6%; p < 0.005) were observed. Rosuvastatin was well tolerated. Two patients withdrew from the study because of adverse events unrelated to the study treatment. No patients had clinically significant elevations in liver transaminases. Two patients exhibited a single increase in creatine kinase (one unrelated to study treatment, the other possibly related) with no muscle symptoms. Rosuvastatin produced significant beneficial changes in all lipid parameters in Japanese patients with heterozygous familial hypercholesterolemia and was well tolerated.

Asian People↗
PubMed2003

Effects of preinfarction angina pectoris on infarct size and in-hospital mortality after coronary intervention for acute myocardial infarction.

We studied the effect of preinfarction angina on in-hospital outcomes after percutaneous coronary intervention for anterior and nonanterior acute myocardial infarction. Beneficial effects of preinfarction angina on infarct size and in-hospital outcome are evident in patients with anterior infarction, but not in those with nonanterior infarction.

Aged↗
PubMed2002

Tissue factor pathway inhibitor gene delivery using HVJ-AVE liposomes markedly reduces restenosis in atherosclerotic arteries.

OBJECTIVE: Tissue factor pathway inhibitor (TFPI), as a primary inhibitor of TF-induced coagulation, reduces neointimal formation and luminal stenosis by inhibiting coagulation and thrombosis after vessel wall injury. Here, we investigated the effect of TFPI gene delivery with a HVJ-AVE liposome vector on restenosis in atherosclerotic arteries after angioplasty in rabbits. We also evaluated the safety of the novel gene therapeutic strategy to prevent restenosis. METHODS: Local iliac artery atherosclerosis was induced by a combination of balloon denudation and high-cholesterol diet in Japanese white rabbits, which were then subjected to angioplasty. Infusion of an HVJ-AVE liposome containing the TFPI gene or an "empty" pcDNA 3.1 expression vector, or HVJ-liposome vector only, or saline was performed at the site of angioplasty using a Dispatch((R)) catheter. Quantitative angiography and histopathology were performed before and after gene delivery and at 4 weeks follow-up. The safety of the gene therapy was evaluated over a 6-month observation period. RESULTS: TFPI mRNA and protein were detected in local TFPI gene transferred vessels after gene transfer. The mean minimal luminal diameter of the TFPI group was markedly greater than that of the control groups (P<0.01) at 4 weeks after gene transfer. The mean neointimal area, the ratio of the neointimal to medial areas, and percent of stenosis in the TFPI group were all significantly reduced compared with the control groups (each P<0.01). The external elastic luminal area, internal elastic luminal area, and luminal area were larger in the TFPI groups versus controls (each P<0.01). Thrombosis was found in five empty plasmid control group animals, but in only one in the TFPI group (P=0.05). The systemic coagulation status of the treated animals were not significantly changed in either the TFPI group or the control groups; no toxicity was observed after HVJ-AVE liposome-mediated TFPI gene transfer. CONCLUSIONS: HVJ-AVE liposome-mediated TFPI gene transfer significantly reduced neointimal hyperplasia, inhibited thrombosis, and attenuated vascular remodeling and lumimal stenosis after angioplasty in atherosclerotic arteries without any significant adverse effects.

Angioplasty, Balloon↗