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Biomedical subjects

S Sasayama

Publications and source records attributed to S Sasayama.

At least 91 records · Page 5Linked to original sources
PubMed2000

Hepatitis C virus from the hearts of patients with myocarditis and cardiomyopathy.

The myocardium may be the target of several types of viral infections. The importance of hepatitis C virus (HCV) infection has been recently noted in patients with myocarditis and in patients with dilated or hypertrophic cardiomyopathy. The present study sought to detect HCV genomes in formalin-fixed paraffin sections of autopsied hearts from patients with myocarditis and patients with dilated or hypertrophic cardiomyopathy. Paraffin sections were deparaffinized, RNA was extracted, and the positive and negative strands of HCV RNA were detected by performing reverse transcription and nested polymerase chain reaction. The polymerase chain reaction products were cloned and sequenced. beta-actin gene was used as a control for the successful amplification of a housekeeping gene. Among 106 hearts examined, beta-actin gene was amplified in 61 hearts (57.5%). Among the latter, HCV RNA was detected in 13 hearts (21.3%), and negative strands in 4 hearts (6.6%). HCV RNA was found in 4 hearts (33.3%) with myocarditis, in 3 hearts (11.5%) with dilated cardiomyopathy, and in 6 hearts (26.0%) with hypertrophic cardiomyopathy. The sequences recovered from nine patients were highly homologous to the standard strain of HCV. HCV genomes were not found in either 35 hearts from patients with myocardial infarction or 20 hearts from patients with noncardiac diseases. These HCV RNA positive samples were obtained from 1 heart in 1979, 7 hearts between 1980 and 1989, and 5 hearts since 1990, indicating that HCV RNA can be amplified from paraffin-embedded hearts preserved for many years. This method of detecting HCV genomes in formalin-fixed paraffin cardiac specimens has enabled us to widen our research into HCV infection and has been helpful in identifying the presence of HCV infection in cardiac myopathic disorders.

Adolescent↗
PubMed2000

Mesangial factor V expression colocalized with fibrin deposition in IgA nephropathy.

BACKGROUND: Factor V in its active form (Va) plays a key role at the termination of the intrinsic coagulation pathway, serving as a membrane-bound cofactor for the conversion of prothrombin to thrombin by factor Xa. Cross-linked fibrin (XFb) is often observed in mesangial areas in active types of human glomerulonephritis. In this study, to clarify contribution of factor V in intramesangial coagulation, mesangial factor V expression and its relationship to mesangial proliferation and fibrin deposition in IgA nephropathy (IgAN) were investigated. METHODS: Twenty-two patients with IgAN were studied. XFb was detected in renal biopsy specimens using anti-d-dimer antibody combined with plasmin exposure, and factor V was detected with rabbit antibody against human factor V. Double-labeling immunohistochemistry was used to investigate the relationship of the glomerular distribution of factor V to XFb. The relationship of factor V staining to the activity index or XFb deposition was evaluated. The expression of factor V mRNA was assessed by in situ hybridization in relationship to the antigen staining of alpha-smooth muscle actin (alpha-SMA). The ultrastructural distribution of factor V in glomeruli was studied by immunoelectron microscopy. RESULTS: XFb and factor V were observed in the mesangium and along capillary loops in seven and nine specimens, respectively. Factor V had intense, frequent expression in the proliferating and necrotizing areas, showing a significant relationship to XFb (P < 0.05). Furthermore, XFb deposition and factor V expression were markedly correlated with disease activity (P = 0.005 and P = 0.008, respectively). By double-labeling experiments, XFb and factor V were often seen colocalized in mesangial areas of the glomeruli, which showed necrotizing lesions and/or intense cellular proliferation. By in situ hybridization, factor V mRNA was detected mainly in the mesangial cells, which were positive for alpha-SMA, and partly in the endothelial cells. By immunoelectron microscopy, factor V presence was confirmed in the mesangium and endothelium. CONCLUSION: The present findings suggest that factor V is strongly expressed in mesangial cells in active IgAN accompanied with mesangial proliferation and may exert procoagulant activity, leading to intramesangial coagulation.

Actins↗
PubMed2000

Inhibitory effects of rosmarinic acid on the proliferation of cultured murine mesangial cells.

BACKGROUND: Rosmarinic acid is a phenolic compound widely distributed in Labiatae herbs such as rosemary, sweet basil, and perilla, which are frequently used with meat and fish dishes in Western and Asian countries. In the present study we investigated the effects of rosmarinic acid on cultured murine mesangial cell proliferation. METHODS: Cultured murine mesangial cells were stimulated by growth factors with or without rosmarinic acid, and [(3)H]thymidine incorporation was measured in regard both to signal transduction and to cell cycle dependency. In other experiments, mRNA extracted from the cells was analysed by Northern blotting. RESULTS: Rosmarinic acid inhibited the cell proliferation induced by platelet-derived growth factor (PDGF) (P<0.01; IC(50) values, 1.4 microg/ml) or tumour necrosis factor-alpha (P<0.01; IC(50) values, 3. 8 microg/ml), and these effects involved both the G(0)/G(1) and G(1)/S phases of the cell cycle. Rosmarinic acid also suppressed the mRNA expressions of PDGF and c-myc in PDGF-stimulated mesangial cells. CONCLUSIONS: Rosmarinic acid inhibits cytokine-induced mesangial cell proliferation and suppresses PDGF and c-myc mRNA expression in PDGF-stimulated mesangial cells. Rosmarinic acid in Labiatae herbs might be a promising agent to prevent mesangial cell proliferation.

Animals↗
PubMed2000

Interleukin 12 induces crescentic glomerular lesions in a high IgA strain of ddY mice, independently of changes in IgA deposition.

BACKGROUND: Our recently established high immunoglobulin (Ig)A inbred strain (HIGA) of ddY mice showed constantly high serum IgA levels, progressive mesangial sclerosis accompanied by IgA deposits, and elevated renal expression of transforming growth factor (TGF)-beta, mimicking IgA nephropathy. In the present study, we assessed the role of the immune system, especially of T cells, in this strain. METHODS: The in vitro production of interferon (IFN)-gamma, interleukin (IL)-4 and TGF-beta1 by splenic CD4+ T cells was assessed in HIGA mice at 14 and 28 weeks of age by comparison with age-matched C57BL/6 and BALB/c mice, T-helper (Th) 1, and Th2 prone controls respectively. Moreover, recombinant murine IL-12 was administered intraperitoneally to HIGA mice and serum IgA and renal lesions were analysed. RESULTS: The production of IFN-gamma by splenic CD4+ T cells was markedly upregulated in HIGA mice at both ages as compared with age-matched C57BL/6 and BALB/c mice. Although splenic CD4+ T cells from HIGA mice produced less IL-4 than those from BALB/c mice at both ages, the former produced significantly more IL-4 with age, which contrasted with the age-associated decrease in the latter. Moreover, TGF-beta1 production of these cells in HIGA mice was equal to or greater than that in the two groups of control mice at both ages. Daily intraperitoneal administration of IL-12 for 1 week significantly enhanced crescent formation with glomerular macrophage accumulation and interstitial cell infiltration, whereas it reduced the serum IgA level. CONCLUSIONS: In HIGA mice, Th1 is markedly upregulated from a young age and there is an age-associated Th2 increase with TGF-beta1 upregulation in helper T cells. The former may be related to the exacerbation of inflammatory renal lesions on IL-12 administration, while the latter may contribute to increased IgA production, leading to glomerular IgA deposition and progressive glomerulosclerosis in HIGA mice. The pathogenic role of T cell function and fluctuation of these subsets, especially the Th1/Th2 balance, is crucial to the immunopathological phenotype of the renal lesions in HIGA mice.

Animals↗
PubMed2000

Blockade of cardiac ATP-sensitive K+ channel by cibenzoline targets its pore-forming subunit.

Several antiarrhythmic agents with Na-channel blocking action have been shown to inhibit cardiac K(ATP) channels. We used cibenzoline to examine its precise target site using patch-clamp techniques and receptor binding assays in guinea-pig ventricular myocytes. Exposure of myocytes to a glucose-free perfusate containing 1 mM cyanide produced a time-dependent shortening of the action potential duration (APD) in the current-clamp mode. Cibenzoline (30 microM) slowed the development of APD shortening (APD90 to approximately 91% vs. approximately 55% control 16 min after metabolic inhibition) at pHo 7.4, but not at pHo 6.4 (to approximately 60%). The pinacidil (30 microM)-induced K(ATP) currents were inhibited by cibenzoline in a pHo-dependent manner: the higher the pHo, the stronger the blocking effect of cibenzoline. The binding of [3H]-labeled cibenzoline was prevented by cibenzoline, but not by glibenclamide. Alkalinization produces a higher concentration of the uncharged form of cibenzoline, which can more easily permeate the cell membrane than the charged form. In NIH3T3 cells stably expressing Kir6.1, a putative pore-forming subunit of K(ATP) channel, cibenzoline but not glibenclamide inhibited the K conductance. Thus cibenzoline interacts with the channel pore-forming subunit of the K(ATP) channel (Kir6.2), but not the sulfonylurea receptor, from the cytosolic side after it permeates into the cell interior via the membrane lipid bilayer.

Action Potentials↗
PubMed2000

Significant suppressive effect of low-dose temocapril, an ACE inhibitor with biliary excretion, on FGS lesions in hypertensive rats.

To investigate how the interruption of the renin-angiotensin system (RAS) and reduction of blood pressure (BP) affect the lesions of chronic focal and segmental glomerulosclerosis (FGS), we studied the effects of high and low doses of angiotensin-converting enzyme inhibitors (temocapril - TEM) a newly developed ACE inhibitor with biliary tract excretion, on the hypertensive model of FGS. A high dose of TEM significantly lowered BP and suppressed both intense proteinuria and glomerular extracapillary lesions including macrophage infiltration. On the other hand, although a low dose of TEM did not significantly lower BP throughout the experimental period, it prevented renal lesions almost in the same manner as high-dose TEM with suppression of c-myc gene expression in glomeruli. These findings suggest that in PAN-induced chronic FGS, the systemic BP elevation could not be the major factor for the progression of renal damage which TEM could prevent without significant lowering of BP.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Role of p38 mitogen-activated protein kinase in neointimal hyperplasia after vascular injury.

p38 mitogen-activated protein kinase (MAPK) is involved in intracellular signals that regulate a variety of cellular responses during inflammation. However, the role of p38 MAPK in atherosclerosis, a chronic inflammatory disorder, remains uncertain. The aim of the present study was to examine the role of p38 MAPK in the development of neointimal hyperplasia in balloon-injured rat carotid arteries. Immunohistochemical studies indicated that p38 MAPK was rapidly activated in the majority of medial cells in injured arterial walls. Rats treated with FR167653, a selective inhibitor of p38 MAPK, at a dosage of 10 mg x kg(-1) x d(-1), had a 29.4% lower intima-to-media ratio than the untreated controls at 14 days after balloon injury (P:<0.05). The percentage of proliferating nuclear antigen-positive cells in the media at 48 hours was significantly lower in the FR167653-treated group than in the control group. Quantitative competitive reverse transcription-polymerase chain reaction analysis revealed that interleukin-1beta mRNA expression in arteries was significantly inhibited by FR167653 (to 18.1% of control, P:<0.05) at 8 hours after balloon injury. Moreover, p38 MAPK activation and interleukin-1beta production by lipopolysaccharide-stimulated vascular smooth muscle cells were inhibited by FR167653 in a concentration-dependent manner in vitro. These results indicate that p38 MAPK is activated in vascular walls after injury and promotes neointimal formation and suggest that selective inhibition of p38 MAPK may be effective in the prevention of restenosis after percutaneous transluminal coronary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed2000

[Effect of itraconazole on digoxin clearance in patients with congestive heart failure].

We showed a digoxin-itraconazole interaction in three patients in whom digoxin serum concentrations were increased. Their electrocardiograms revealed arrhythmias such as ventricular premature contraction, atrioventricular block, and ST depression. The elimination half-life of digoxin in case 3 patient who continued itraconazole therapy was 8.4 days, which was estimated by nonlinear least squares method from the serum concentrations of digoxin versus time curve. In order to evaluate the influence of itraconazole on pharmacokinetic parameters of digoxin, we estimated digoxin clearance by the Bayesian method using the population pharmacokinetic parameters in Japanese patients. During the concomitant use of itraconazole and digoxin, the digoxin clearance in all patients decreased to 50.5 +/- 8.8% (mean +/- S.D.) of the clearance without itraconazole. When digoxin and itraconazole are used concomitantly, careful monitoring of digoxin serum concentrations is necessary. Based on our results of digoxin clearance evaluation, the dose of digoxin should be reduced to 50% of original dose after itraconazole is started, and digoxin serum concentration might be controlled at the same level before the concomitant use.

Aged↗
PubMed2000

Effect of long-term cholesterol-lowering treatment with HMG-CoA reductase inhibitor (simvastatin) on myocardial perfusion evaluated by thallium-201 single photon emission computed tomography.

Fifteen patients with either angina pectoris or old myocardial infarction, who had positive 201Tl single photon emission computed tomography (SPECT) imaging and coronary sclerosis of more than 50%, were treated with an HMG-CoA reductase inhibitor (simvastatin) for more than 1 year. They were compared with an untreated control group (n = 25). Total cholesterol decreased 22% and high-density lipoprotein (HDL) increased 9% with simvastatin; both changes were significantly different from those in controls. Long-term simvastatin induced improvement of myocardial perfusion on 201Tl SPECT images both during exercise and at rest, which was also significantly different from controls. In addition, the improvement of myocardial perfusion on 201Tl SPECT images was clearly related to the improvements in cholesterol values, especially nonHDL cholesterol. Thus, the greater the decrease in nonHDL cholesterol, the greater the improvement in myocardial perfusion at rest or during exercise with long-term treatment using an HMG-CoA reductase inhibitor. These findings indicate that the improvements in cholesterol values caused by HMG-CoA reductase inhibitor therapy are related to improvements of myocardial perfusion seen on 201Tl SPECT images.

Angina Pectoris↗
PubMed2000

Strain difference in rats with experimental giant cell myocarditis.

Immunogenetic mechanisms may be involved in the pathogenesis of myocarditis and dilated cardiomyopathy. The present study investigated the incidence, histopathology and histocompatibility characteristics of experimental giant cell myocarditis in various strains of rats. Experimental giant cell myocarditis was induced by immunization with porcine cardiac myosin in Lewis (RT-1(l)), Dahl (DIR/Eis) (RT-1(l)), Fisher (RT-1(lv 1)) rats, but not in Dahl (DIS/Eis) (RT-1(l)) or Brown Norway (RT-1(n)). Myocarditis was most severe in the Lewis rats and their heart weight/body weight ratio was significantly higher than that of control rats immunized with Freund's complete adjuvant alone. In conclusion, this study provides evidence that the expression and severity of experimental giant cell myocarditis may be determined mainly by genetic factors, including both major histocompatibility complex genes as well as other genes, which may be controlled by an immune mechanism.

Animals↗
PubMed2000

Interferon treatment for dilated cardiomyopathy and striated myopathy associated with hepatitis C virus infection based on serial measurements of serum concentrations of cardiac troponin T.

The present authors recently suggested, on the basis of studies using polymerase chain reaction (PCR), that hepatitis C virus (HCV) infection is involved in the etiology or pathogenesis of cardiomyopathic disorders. They have also reported that the serum concentration of cardiac troponin T is an indicator of ongoing myocyte degeneration in patients with dilated cardiomyopathy (DCM) and hypothesized that its serial measurement may be a marker of therapeutic efficacy. This is the first case report of DCM and striated myopathy, associated with HCV infection, treated with interferon therapy guided by monitoring of serial serum concentrations of cardiac troponin T. Positive-plus strands of HCV RNA were found in the patient's myocardium, as well as plus and minus strands in the quadriceps muscle specimens. Serum levels of creatine kinase (CK), CK-MB and cardiac troponin T fell as serum HCV titers decreased during treatment with interferon, whereas conventional treatment of heart failure had no effect. Monitoring of serial serum concentrations of cardiac troponin T may allow the earlier diagnosis and treatment of patients with HCV-associated cardiomyopathy and improve their clinical course.

Antiviral Agents↗
PubMed2000

Pericardial fluid from patients with ischemic heart disease accelerates the growth of human vascular smooth muscle cells.

The strong association between severe coronary stenosis and collateral growth continues to be a paradigm in this field of investigation. The present study was based on the hypothesis that angiogenic growth factors are produced by ischemic cardiac tissue, are diffusible and more concentrated in pericardial fluid, and accelerate the growth of vascular smooth muscle cells (VSMC). Pericardial fluid from 17 patients with stable or unstable angina or acute myocardial infarction (group A) and from 10 patients with nonischemic heart disease (group B) were collected at the time of open heart surgery. Cultured human aortic VSMC were plated at the third passage at a density of 5x10(3)/100 microl and allowed to attach for 24 h. The 3-day growth assay was preceded by 72 h of growth arrest with 0.4% fetal calf serum (FCS). Growth was restarted by the addition of 90 microl of medium containing 0.4% FCS, and 1O microl of each pericardial fluid. Cell counts on triplicate wells were performed using a dimethylthiazol (MTT) method on days 0 and 3. The effect of pericardial fluid on the growth of VSMC was evaluated as a ratio (R) of cell numbers on day 3 to those on day 0. The concentration of basic fibroblast growth factor (bFGF) in pericardial fluid was measured by an enzyme-linked immunosorbent assay. The concentration of bFGF in pericardial fluid of group A was 633+/-127 pg/ml, and significantly (p=0.003) higher than that of group B (86+/-23 pg/ml). R in group A was 2.29+/-0.18 and significantly (p=0.019) higher than that in group B (1.68+/-0.11). The level of bFGF positively correlated with R (p=0.009). These findings indicate that pericardial fluid from patients with ischemic heart disease contains some substances that mediate collateral development, and bFGF might be one of them.

Aged↗
PubMed2000

Dilated phase of hypertrophic cardiomyopathy with mid-ventricular obstruction after 20-year follow-up.

This paper reports a case of dilated phase in hypertrophic cardiomyopathy with mid-ventricular obstruction. Following the first cardiac catheterization and endomyocardial biopsy, the patient was diagnosed as having hypertrophic cardiomyopathy (HCM) with mid-ventricular obstruction. He had been first diagnosed at the age of 38 years and was subsequently followed for 20 years. Echocardiogram revealed gradually progressive dilatation of the left ventricle, associated with disappearance of the mid-ventricular obstruction. The second cardiac catheterization and endomyocardial biopsy performed at the age of 58 disclosed that the patient was in the dilated phase of HCM with a dip-and-plateau pattern diastolic pressure trace.

Adult↗
PubMed2000

Hypertrophic cardiomyopathy as a manifestation of cardiac sarcoidosis.

The present study aimed to clarify whether cardiac sarcoidosis causes changes that mimic hypertrophic cardiomyopathy. Eighty-two consecutive patients (35 men, 47 women), who were referred to the Department of Cardiovascular Medicine, with a diagnosis of pulmonary and/or ocular sarcoidosis (average age, 49.5 years, range 20-74), underwent detailed clinical, electrocardiographic, and echocardiographic evaluations; in some patients, right and left heart catheterization, selective coronary artery cineangiography, and right and left endomyocardial biopsies were performed. Over a 15-month period of observation, 6 of these 82 patients (7.3%) were found to have echocardiographic abnormalities: increased thickness of the interventricular septum was found in 4 patients, asymmetric septal hypertrophy in 2, localized septal hypertrophy in 1 and apical hypertrophy in 1 patient. One patient had an 'ace-of-spades' deformity of the left ventricle. Cardiac sardoidosis can mimic, and even present as, hypertrophic cardiomyopathy.

Adult↗
PubMed2000

Circulating hepatocyte growth factor as a marker of thrombus formation in unstable angina pectoris.

A new enzyme-linked immunosorbent assay can detect 10 pg/ml of human hepatocyte growth factor (HGF). Circulating HGF was significantly higher in patients with unstable angina (296+/-184 pg/ml, mean+/-SD, n=36) than in healthy volunteers (201+/-64 pg/ml, n=250, p<0.0001). Individual concentrations exceeded the mean control value +2 SD (329 pg/ml) in 12 of the 36 (33%) patients with unstable angina. The present study indicates that this new, sensitive HGF assay can successfully detect thrombosis in patients with unstable angina.

Adolescent↗
PubMed2000

Significance of pericardial cytokines in giant cell myocarditis in rats--pathological comparison to viral myocarditis in mice.

To investigate the precise disease progression in myocarditis, Lewis rats were injected with porcine cardiac myosin, and C3H/He mice were inoculated with coxsackievirus B3. Both were killed serially, and the hearts were stained with hematoxylin-eosin to compare their pathological characteristics. In viral myocarditis, viral replication in the myocardium resulted in myocardial necrosis with inflammation, and the lesions were distributed transmurally, as previously reported. On the other hand, in giant cell myocarditis, inflammatory lesions appeared at first around the capillaries in the epicardium, and thereafter spread transmurally. Pericardial effusion was noticed in all the rats with myocarditis in the fulminant stage. Levels of interleukin (IL) -1beta and IL-6 in the pericardial effusion were elevated compared with the serum cytokines at the peak of inflammation. However, interferon-gamma in both the pericardial effusion and serum was not elevated. The cause of the myocardial lesions that developed in rats with giant cell myocarditis may be some active inflammatory process via the pericardial effusion.

Animals↗