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Biomedical subjects

Yukio Maruyama

Publications and source records attributed to Yukio Maruyama.

At least 19 recordsLinked to original sources
PubMed2006

RhoA-dependent PAI-1 gene expression induced in endothelial cells by monocyte adhesion mediates geranylgeranyl transferase I and Ca2+ signaling.

We investigated the role of RhoA activation and its mechanism in plasminogen activator inhibitor-1 (PAI-1) gene expression induced in endothelial cells by monocyte adhesion. Isolated human peripheral blood monocytes were added to cultured human coronary endothelial cells. Monocyte adhesion to endothelial cells increased PAI-1 expression at the transcriptional level and activated RhoA which was accompanied by an increase in the activity of geranylgeranyl transferase I (GGTase I), an enzyme responsible for geranylgeranylation, and actin stress fiber formation. Inhibition of RhoA by C3 exoenzyme or by adenovirus-mediated expression of N19RhoA, as well as by pravastatin, prevented the upregulation of PAI-1 induced by monocyte adhesion. GGTI-286, an inhibitor of GGTase I, prevented the monocyte-induced RhoA activation and PAI-1 expression in endothelial cells. Monocyte attachment induced an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in endothelial cells and Ca(2+) chelation prevented the increased promoter activity and expression of PAI-1 induced by monocyte adhesion. C3 exoenzyme and GGTI-286 also suppressed endothelial intracellular Ca(2+) mobilization and Ca(2+) entry induced by monocytes. The present study shows that GGTase I plays a role in the RhoA activation in endothelial cells induced by monocyte adhesion and that GGTase I-mediated Ca(2+) signaling may contribute to RhoA-dependent PAI-1 gene expression.

Actins↗
PubMed2006

The frequency of HLA class I alleles in Japanese patients with bone marrow failure.

The frequencies of the HLA-B*4002 and HLA-A*0206 alleles in patients with aplastic anemia (AA) (n=32; 21.9%) and paroxysmal nocturanl hemoglobinuria (PNH) (n=24; 22.9%), respectively, were significantly different from those in controls (n=371; 8.6%, p<0.002 and 7.7%, p<0.001, respectively), suggesting that each specific allele in AA or PNH may be related to the immunologic pathophysiology of these disorders.

Anemia, Aplastic↗
PubMed2006

Attenuated cardioprotection by ischemic preconditioning in coronary stenosed heart and its restoration by carvedilol.

OBJECTIVE: Infarct size (IS) reduction by ischemic preconditioning (IPC) has been assessed in the heart in which coronary stenosis (CS)-induced chronic ischemia was not present. The aim of this study is to assess whether and how IS reduction by IPC is modified in the heart in which CS has occurred, and how further therapeutics, if any, modify it. METHODS: We assessed the IS produced by a 30-minute acute coronary occlusion and a 24-hour reperfusion (COR) in rat hearts in which CS had developed for 1-12 weeks. Modifications of IS by IPC and the mitochondrial KATP channel (mitoKATP) opener and blocker, and the effects of daily beta-blocker treatment with carvedilol on them, were also assessed. Myocardial protein kinase C (PKC)-epsilon activities in the risk areas were measured by Western blotting. RESULTS: One to 4 weeks after CS induction, myocardial PKC-epsilon was activated in the risk area of CS even without IPC, but such CS-induced PKC activation as well as that by IPC was attenuated 8-12 weeks after CS. The IS reductions by the mitoKATP opener as well as by IPC were attenuated 8-12 and 4-12 weeks after CS, respectively. Daily carvedilol treatment after inducing CS restored the malfunctioning PKC-mitoKATP signal cascade and the attenuated IPC and mitoKATP effect on IS. CONCLUSION: CS activates the PKC-mitoKATP signal cascade, mimicking the IPC effect, whereas this cardioprotective effect is attenuated late after CS via their downregulation. Restoration of these changes may be a novel mechanism for cardioprotection by carvedilol in the CS-induced ischemic heart.

Adrenergic beta-Antagonists↗
PubMed2006

Carbon monoxide and bilirubin from heme oxygenase-1 suppresses reactive oxygen species generation and plasminogen activator inhibitor-1 induction.

Heme oxygenase-1 (HO-1) responds to a variety of oxidative stresses. We examined whether HO-1 expression influences pro-thrombotic processes, in which the involvement of oxidative stress has been reported. Since HO-1 knockout mice with a C57/BL6J background were not viable, embryonic cells from HO-1 deficient mice (E11.5) were used. Cell viability, the level of plasminogen activator inhibitor-1 (PAI-1) expression and reactive oxygen species (ROS) generation of HO-1 deficient cells in response to the exposures to hydrogen peroxide and oxidized LDL were compared to those with wild-type cells. We also examined the effects of glutathione (GSH), desferrioxamine (DFO) and diphenyleneiodonium (DPI: an NADPH oxidase inhibitor) as well as of the HO reaction products, bilirubin (BR) and carbon monoxide (CO) on PAI-1 expression and ROS generation. PAI-1 expression and ROS generation were markedly elevated in HO-1 deficient cells compared to wild-type cells. Exposure to oxidized LDL significantly elevated PAI-1 expression and ROS production in HO-1 deficient cells. Interestingly, these increases in HO-1 deficient cells were significantly lowered by BR, CO, GSH and DPI while DFO had little effect. Furthermore, BR and CO were effective to improve viabilities of HO-1 deficient cells. These results suggest that HO-1 may be required to suppress ROS generation and the production of pro-thrombotic molecules such as PAI-1.

Animals↗
PubMed2006

Quantitative assessment of the peritoneal vessel density and vasculopathy in CAPD patients.

BACKGROUND: Peritoneal sclerosis (PS) complicates continuous ambulatory peritoneal dialysis (CAPD). Exploring the peritoneal vascular changes, which are characteristic histological findings in long-term PD, may give new insight into the basic pathological process leading to PS. We present a quantitative analysis of peritoneal vascular density as well as vasculopathy grades in relation to PD duration. METHODS: Peritoneal samples from 56 stable CAPD patients were analysed, and cases with membrane failure were excluded. Patients were classified into four groups according to CAPD duration in years: group A (n = 12), 0 year; group B (n = 11), 1-5 years; group C (n = 17), 5-9 years; and group D (n = 16), >9 years. The total density, of microvessels (capillaries, post-capillary venules and venules) and the density of each vasculopathy grade (0 = intact, 1 = mild, 2 = moderate and 3 = severe) in the compact zone were calculated (numbers/mm(2)) in each sample and the percentage ratio of each grade in relation to the total vessel density was also determined. RESULTS: There was no significant difference in the total vessel density (P-value = 0.64). In the grade of vasculopathy (density and percentage ratio), there were significant differences among groups, with grade 0 highest in group A, grade 1 highest in group C and grade 3 highest in group D. CONCLUSION: The results of this study indicate that vascular density does not increase, at least in stable uncomplicated PD, and that intact vessels decrease with time on PD, while the severe grades of vasculopathy predominate especially on a long-term basis.

Adult↗
PubMed2006

Differing effects of metoprolol and propranolol on large vessel and microvessel responsiveness in a porcine model of coronary spasm.

OBJECTIVES: The purpose of this study is to assess the effect of beta1-selective blocker on coronary vasospasm. MATERIALS AND METHODS: Balloon epicardial coronary artery endothelial denudation was performed at the left anterior descending coronary artery every 2 weeks for a total of 4 times in pigs. Changes in denuded site diameter and left anterior descending coronary artery blood flow caused by acetylcholine or serotonin were assessed before each endothelial denudation and at week 8 in untreated pigs (ED group) and in those treated with metoprolol (Meto group) or propranolol (Pro group). RESULTS: In the ED group, decreased blood flow response to acetylcholine enhanced from -20+/-10% before the first ED to -100% (i.e. zero flow) at week 8 without denuded site narrowing, suggesting microvascular spasm, and serotonin-induced left anterior descending coronary artery diameter reduction at week 8 was -92+/-15%. In the Pro group, blood flow reduction by acetylcholine and left anterior descending coronary artery diameter reduction by serotonin did not change compared with those of the ED group. In the Meto group however, blood flow reduction by acetylcholine (week 8, -70+/-16%) and left anterior descending coronary artery diameter reduction by serotonin (week 8, -64+/-15%) were blunted (P<0.01) compared with those of ED and Pro groups. CONCLUSION: The beta1-selective blocker metoprolol was effective to prevent coronary vasospasm.

Acetylcholine↗
PubMed2006

Complete donor chimaerism of Langerhans cells in lymph node early after allogeneic bone marrow transplantation.

Host-derived Langerhans cells (LCs) are crucial antigen-presenting cells that cause graft-vs.-host disease after allogeneic haematopoietic stem cell transplantation (HSCT). However, chimaerism of LCs after allogeneic HSCT is largely unknown in humans. We here report a case that developed dermatopathic lymphadenitis accompanied by an accumulation of donor-derived LCs in the second month after allogeneic HSCT with reduced-intensity conditioning. This is the first case to show that donor LCs have the ability to migrate into draining lymph nodes and replace host LCs early after HSCT in humans.

Adult↗
PubMed2006

Neutropenia due to parvovirus B19 infections in patients with paroxysmal nocturnal hemoglobinuria. Blood transfusion and natural infection cases.

Two patients with paroxysmal nocturnal hemoglobinuria (PNH) and parvovirus B19 (PVB19) infection are reported. One was infected by PVB19-contaminated blood transfusion, whereas the other had become infected naturally. Both patients completely recovered after transient pancytopenia, but showed severe and intermediate neutropenia (0.216 and 0.768 x 10(9)/l, respectively) at the nadirs of aplastic crises. In the literature, PNH cases also showed neutropenia (0 and 0.54 x 10(9)/l) at aplastic crises. When patients with PNH are infected by PVB19, they may show severe neutropenia and mild thrombocytopenia in addition to severe reticulocytopenia. Therefore, these patients might have to be treated with granulocyte colony-stimulating factor to be able to recover from severe neutropenia.

Aged↗
PubMed2006

Left ventricular dysfunction and remodeling in streptozotocin-induced diabetic rats.

BACKGROUND: It is not fully clarified how diabetes mellitus (DM)-induced cardiac dysfunction is associated with histopathological changes of the heart in a long lasting period of DM. METHODS AND RESULTS: Eighteen weeks after a streptozotocin injection was given to Wistar - Kyoto rats (D rats), echocardiography and hemodynamic studies including the dobutamine infusion test were performed. After perfusion fixation, immunofluorescent staining and histopathology of the heart were analyzed, and analysis with electron microscopy was also conducted. Systolic blood pressure in the conscious state and left ventricular (LV) ejection fraction by 2-dimensional echocardiography were reduced in D rats. LV mechanical responses to dobutamine assessed by maximal LV pressure derivative (+LVdP/dt) also decreased with higher dobutamine doses in D rats. Although LV and right ventricular (RV) wall thickness were smaller in D rats, there were increased RV volumes, indicating LV and RV dilatational remodeling in D rats. The cardiomyocyte transverse diameter and actin staining in cardiomyocytes in both the LV and RV were significantly reduced, and capillary tortuosity and type IV collagen were increased, indicating microangiopathy in D rats. CONCLUSIONS: Advanced insulin-dependent DM incurred not only RV remodeling but also overt resting LV systolic dysfunction and decreased LV responsiveness to beta adrenergic stimulation with dilatational remodeling, accompanied by pathological changes of capillaries and cardiomyocytes including actin filaments.

Actin Cytoskeleton↗
PubMed2006

Recurrent extramedullary relapse of acute promyelocytic leukemia after allogeneic stem cell transplantation: successful treatment by arsenic trioxide in combination with local radiotherapy.

Isolated extramedullary relapse is rare in patients with acute promyelocytic leukemia (APL) after allogeneic stem cell transplantation (SCT), and an optimal therapy for it has not been established. We describe a patient with APL who developed serially occurring extramedullary disease (EMD) after SCT. We confirmed that EMD had arisen from the recipient's APL blasts by detecting t(15;17) and PML/RARalpha from the tumor cell suspension. The patient displayed EMD 4 times at different sites. Administration of all-trans retinoic acid with local radiotherapy and with chemotherapy for the first to third EMDs resulted in regression of the tumors. However, these regimens did not prevent the subsequent occurrence of new EMD. For the fourth EMD, intravenous administration of arsenic trioxide followed by local radiotherapy resulted in the disappearance of EMD, and no further EMD has developed to date. In the present case, the bone marrow was in morphologic and molecular remission during the course of recurrent EMD. The accumulation of detailed cases is needed to elucidate the pathogenesis, predisposing factors, and optimal therapy for EMD in APL after SCT.

Antineoplastic Agents↗
PubMed2006

Effects of angiotensin-converting enzyme inhibitors or an angiotensin receptor blocker in combination with aspirin and cilostazol on in-stent restenosis.

It remains to be determined whether adding an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) to antiplatelet therapy has a therapeutic benefit on in-stent restenosis. After successful coronary stenting, 165 patients (167 lesions) were randomly assigned to a basal (aspirin 162 mg + cilostazol 200 mg/day), ACEI (basal treatment + quinapril 10 mg or perindopril 4 mg/day), or ARB (basal treatment + losartan 50 mg/day) treatment group. Quantitative coronary angiography was performed before, immediately following, and 6 months after stenting. Follow-up coronary angiography was completed in 126 patients (128 lesions). Restenosis rates tended to be higher (12, 26, and 12% for the basal, ACEI, and ARB groups, respectively), and target lesion revascularization rates were higher in the ACEI group than in the other groups (9, 23,* and 5%, respectively, *P < 0.05 versus basal group). Moreover, late lumen loss was higher in the ACEI group than in the basal group (0.60 +/- 0.55, 0.98 +/- 0.61* and 0.73 +/- 0.64 mm in the basal, ACEI, and ARB groups, respectively). The combinations of an ACEI or ARB with aspirin and cilostazol are ineffective for the prevention of in-stent restenosis, and an ACEI may even promote intimal proliferation after stent implantation.

Aged↗
PubMed2006

Specificity of vascular reactivity and remodeling after repeated endothelial injury in a swine model.

We investigated the difference in vascular responses and remodeling between coronary and iliac arteries after repeated endothelial denudation. Endothelial denudation of the left anterior descending coronary artery (LAD) and the right common iliac artery (RIA) was repeated 4 times twice a month using a Fogarty catheter in 21 pigs. Vascular responses to vasoactive drugs were evaluated as % luminal diameter changes on contrast angiography 2 weeks after the last denudation. Corresponding nondenuded sites, ie, the left circumflex coronary artery (LCX) and the left common iliac artery (LIA), were used as references. Acetylcholine (1 microg/kg) did not constrict the LCX (0 +/- 1%) and the LAD (1 +/- 1%, P < 0.05), whereas it constricted the RIA (20 +/- 6%) but not the LIA (-3 +/- 3%, P < 0.01). Alternatively, serotonin (10 microg/kg) constricted the LAD strikingly (88 +/- 5%, P < 0.01 versus LCX and RIA), as well as the RIA (35 +/- 10%, P < 0.05 versus LIA). Vasodilator responses to substance P and isosorbide dinitrate were not different after injury in both arteries. The intima-to-media ratio and adventitia-to-media ratio of the relevant site in cross section of tissue sample from LAD were greater than those from LCX, and were more prominent than those from RIA. The results show that vascular tone regulation after the endothelial injury and vascular remodeling might be altered in a vessel-specific manner.

Acetylcholine↗
PubMed2006

[Heart failure in the elderly].

Heart failure (HF) is a major disease of the elderly. Since their symptoms of HF are generally light, on admission of the hospitals HF is sometimes in an advanced stage. Therefore, preventive medicine for those with the risk factors of HF is needed as a future strategy of cardiac gerontology. The routine assessment of the HF severity may be performed noninvasively by Nohria's profiles rather than other invasive methods. HF is worsened by the interaction with the co-morbidity factors, such as renal dysfunction and anemia. The interaction between HF and kidney disease (and anemia) is called 'cardiorenal (anemia) syndrome.' Recurrent hospitalization due to HF is common, and the period of hospitalization tends to be long in this syndrome. One of the hopeful therapeutic agents is carperitide, a recombinant human atrial natriuretic peptide. In cardiorenal syndrome, much lower initial doses of carperitide, such as 0.0125 microg/kg/min is recommended for treatment of HF in order to avoid possible worsening of renal dysfunction. In cardiorenal anemia syndrome, supplement of iron, careful blood transfusion in severe cases, administration of recombinant human erythropoietin, should be performed if indicated. However, the possibility of anemia unrelated to HF, such as due to gastrointestinal carcinoma, is also considered in the elderly. In such cases, finding a decrease of serum ferritin preceding that of hemoglobin may contribute to a differential diagnosis of anemia in elderly HF patients. Thus, the therapies considering several features of HF in elderly will contribute to improving quality of life and outcome.

Aged↗
PubMed2005

Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial.

BACKGROUND AND PURPOSE: Although the efficacy of anticoagulant therapy for primary prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF) has been established, efficacy of antiplatelet therapy for low-risk patients is disputable in Japanese patients because of the frequent hemorrhagic complications. We examined the efficacy and safety of aspirin therapy in Japanese patients with NVAF in a prospective randomized multicenter trial. METHODS: Patients with NVAF were randomized to an aspirin group (aspirin at 150 to 200 mg per day) or a control group without antiplatelet or anticoagulant therapy. Primary end points included cardiovascular death, symptomatic brain infarction, or transient ischemic attack. RESULTS: A total of 426 patients were randomized to aspirin group and 445 to no treatment. The trial was stopped earlier because there were 27 primary end point events (3.1% per year; 95% CI, 2.1% to 4.6% per year) in the aspirin group versus 23 (2.4% per year; 95% CI, 1.5% to 3.5% per year) in the control group, suggesting a low possibility of superiority of the aspirin treatment for prevention of the primary end point. In addition, treatment with aspirin caused a marginally increased risk of major bleeding (7 patients; 1.6%) compared with the control group (2 patients; 0.4%; Fisher exact test P=0.101). CONCLUSIONS: For prevention of stroke in patients with NVAF, aspirin at 150 to 200 mg per day does not seem to be either effective or safe. Further prospective studies are needed to determine the best preventive therapy for cerebrovascular events in Japanese patients with NVAF.

Aged↗
PubMed2005

Transforming activity of the lymphotoxin-beta receptor revealed by expression screening.

Pancreatic ductal carcinoma (PDC) remains one of the most intractable human malignancies. To obtain insight into the molecular pathogenesis of PDC, we constructed a retroviral cDNA expression library with total RNA isolated from the PDC cell line MiaPaCa-2. Screening of this library with the use of a focus formation assay with NIH 3T3 mouse fibroblasts resulted in the identification of 13 independent genes with transforming activity. One of the cDNAs thus identified encodes an NH(2)-terminally truncated form of the lymphotoxin-beta receptor (LTBR). The transforming activity of this short-type LTBR in 3T3 cells was confirmed by both an in vitro assay of cell growth in soft agar and an in vivo assay of tumorigenicity in nude mice. The full-length (wild-type) LTBR protein was also found to manifest similar transforming activity. These observations suggest that LTBR, which belongs to the tumor necrosis factor receptor superfamily of proteins, may contribute to human carcinogenesis.

3T3 Cells↗
PubMed2005

Interleukin-1 gene cluster polymorphisms are associated with nutritional status and inflammation in patients with end-stage renal disease.

BACKGROUND: Wasting and inflammation are two common risk factors for death in patients with end-stage renal disease (ESRD). Interleukin-1beta (IL-1beta) and its receptor antagonist (IL-1Ra) may play a pivotal role in the pathogenesis of wasting and inflammation. METHODS: To investigate effects of the IL-1 gene cluster polymorphisms on wasting and inflammation, we studied 189 ESRD patients (52+/- 12 years, 62% males) close to the start of renal replacement therapy. 205 healthy volunteers served as controls. We analyzed the IL-1B -511C/T, -31C/T, and +3954C/T polymorphisms as well as a variable number of a tandem repeat (VNTR) in IL-1RN. Nutritional parameters included serum albumin level, subjective global nutritional assessment (SGA), and body composition evaluated by dual-energy X-ray absorptiometry (DXA). We used serum high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation. RESULTS: Wasting (SGA>1) was present in 31%, whereas inflammation (CRP>/=10 mg/l) was present in 36% of the patients. The male carriers of the -511T/T and -31C/C genotypes had a lower prevalence of wasting (p<0.05), higher body mass index (BMI) (p<0.05), and higher lean body mass (LBM) (p<0.01). In a stepwise multiple regression model, age (p<0.05), BMI (p<0.01) and the IL-1B -511 genotype (p<0.01) were independently associated with LBM. The carriers of the +3954T allele had a lower prevalence of inflammation (p<0.05) and lower serum hsCRP (p<0.05). The VNTR in IL-1RN was not associated with any markers. CONCLUSION: The investigated IL-1 gene cluster polymorphisms were associated with nutritional status and inflammation in ESRD patients, but marked differences were found between the genders. These polymorphisms could have prognostic utility for predicting wasting and inflammation in ESRD patients.

Adult↗