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Kazuyuki Shimada

Publications and source records attributed to Kazuyuki Shimada.

At least 19 recordsLinked to original sources
PubMed2006

Morphometric analysis of fibers of the human vestibular nerve: sex differences.

The aim of this study was to analyze myelinated axons in the human vestibular nerve (VN). We assumed that a smaller total number and average transverse area of myelinated axons in the female than male VN, would partly explain the female preponderance of vestibular disorders. The materials were obtained from 24 cadavers (12 females and 12 males) aged 54-90 years (average 74.8 years). We counted the myelinated axons, measured the transverse area of the myelinated axons, and analyzed morphological differences between the female and male specimens. The total number differed significantly between the female and male specimens. The older generation of both sexes tended to have lower total counts, but there was no significant difference among the generations. The average transverse area of the myelinated axons did not differ significantly between the female and male specimens. The older generation of both sexes tended to have a smaller average transverse area, and there was a significant difference among the generations. The presented results indicated that the lower total number, not the average transverse area, of myelinated axons in the female VN might be one of the reasons why vestibular disorders have a female preponderance.

Aged↗
PubMed2006

Circulating endothelial progenitor cells in congestive heart failure.

BACKGROUND: Endothelial progenitor cells (EPCs) circulate in the adult peripheral blood and contribute to neovascularization. EPCs are considered to be included in CD34 positive mononuclear cells (CD34+ MNCs). Kinetics of circulating EPCs in congestive heart failure (CHF) has not been fully investigated. METHODS: We determined the numbers of white blood cells (WBCs), plasma brain natriuretic peptide (BNP), serum erythropoietin, vascular endothelial growth factor (VEGF) and thrombomodulin levels in 16 mild CHF patients (NYHA I, II), 10 severe CHF patients with acute exacerbation (NYHA III, IV), and 22 control subjects. The number of CD34+ MNCs in peripheral blood was quantified by flow cytometry. RESULTS: The ratio of CD34+ MNCs:10(3) WBCs in mild CHF patients was higher than that in control subjects (P<0.05). Interestingly, the ratio of CD34+ MNCs:10(3) WBCs in severe CHF patients at admission was significantly lower than that in control subjects (P<0.005) or in mild CHF patients (P<0.05). Levels of BNP and erythropoietin in severe CHF patients were significantly higher than those in mild CHF patients. However, VEGF and thrombomodulin levels were not different between mild and severe CHF patients. In addition, the ratio of CD34+ MNCs:10(3) WBCs in severe CHF patients increased in proportion to the amelioration of CHF during hospitalization, and this increase correlated with the decrease in BNP level. CONCLUSIONS: The ratio of CD34+ MNCs:10(3) WBCs was decreased in severe CHF. These findings suggest that impaired EPC recruitment might be involved in the pathophysiology of severe CHF.

Aged↗
PubMed2006

Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats.

Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.

Animals↗
PubMed2006

An intronic variable number of tandem repeat polymorphisms of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene modifies gene expression and is associated with essential hypertension.

Cold-induced autoinflammatory syndrome 1 (CIAS1) gene is a member of the NALP subfamily of the CATERPILLER protein family that is expressed predominantly in peripheral blood leukocytes, which is to regulate apoptosis or inflammation through the activation of NF-kappaB and caspase. Recent genetic analyses suggested an association between inflammation and oxidative stress-related genes in the development of hypertension. This is the first genetic study indicating an association between the CIAS1 gene and susceptibility to essential hypertension (EH). The frequency of subject with the homozygote of 12 repeat allele was significantly higher in patients with hypertension compared with control subjects (987 cases, 924 controls) (P=0.030; odds ratio=1.24) at a novel VNTR polymorphism of CIAS1 intron 4 loci. We also found that the mean of systolic blood pressure of homozygotes of 12 repeat allele was 6.4 mmHg higher than those of homozygotes of non-12 repeat allele in male random population (P=0.009). The frequency of six SNPs spanning of the CIAS1 gene was not significantly between patients and controls. The real-time PCR analysis showed that among healthy young adults, 12-12 subjects expressed CIAS1 mRNA in peripheral leukocytes significantly more abundantly than homozygote of non-12 repeat alleles subjects (P<0.05). Reporter gene assay of the CIAS1-VNTR in HL60 stimulated by lipopolysaccharides showed that the intronic sequence involving 12 repeat increased the expression of luciferase compared with 9, 7, and 6 repeats. Thus, we propose here the CIAS1 is associated with EH through the dominant expression of transcripts, which may depend on the CIAS1-VNTR genotype.

Alleles↗
PubMed2006

Efficacy of mycophenolic acid combined with KRP-203, a novel immunomodulator, in a rat heart transplantation model.

BACKGROUND: To explore a more effective and less toxic immunosuppressive strategy in organ transplantation, we recently developed the novel sphingosine-1-phosphate receptor agonist KRP-203. This study examined the efficacy of KRP-203 combined with mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil, in rat heart allografts. METHODS: Heterotopic heart transplantation was performed in a rat combination of DA (MHC haplotype: RT1(a)) to Lewis (RT1). The recipients were divided into 12 groups (n = 5-7): Syngeneic (Lewis to Lewis), Vehicle, KRP-203 (0.3 and 1 mg/kg), MPA (10 and 20 mg/kg), 10 mg/kg MPA with KRP-203 (0.03, 0.3, 1, and 3 mg/kg), and 20 mg/kg MPA with KRP-203 (0.3 and 1 mg/kg). MPA, KRP-203, and vehicle were given orally. RESULTS: The mean days of survival were 5.8 (vehicle), 7 and 7.9 (0.3 and 1 mg/kg KRP-203, respectively), 12.7 and >54.4 (10 and 20 mg/kg MPA), >39.6 and >30.5 (10 mg/kg MPA with 1 and 3 mg/kg KRP-203), >100 and >87.8 (20 mg/kg MPA with 0.3 and 1 mg/kg KRP-203). Histologic and immunohistochemical analysis revealed that diffuse mononuclear cell infiltration (macrophages and T cells), hemorrhage, myocardial necrosis and fibrosis, and expression of endothelin-1, transforming growth factor-beta1, monocyte chemoattractant protein-1, interleukin-8, and E-selectin were markedly diminished in the allografts treated with MPA combined with KRP-203. Pharmacokinetic experiments indicated no interaction between MPA and KRP-203, and both combination regimens were well tolerated. CONCLUSIONS: Combination therapy of MPA with KRP-203 has a therapeutic potential as a novel immunosuppressant strategy in clinical transplantation.

Animals↗
PubMed2006

Preoperative cardiac evaluation: when should the surgeon consult the cardiologist?

PURPOSE: We compiled a manual aimed at reducing preoperative cardiac assessment costs and defining the roles of surgeons and cardiologists. We tested prospectively and retrospectively if this manual achieved these goals. METHODS: Using the Guidelines for Perioperative Cardiovascular Evaluation for Noncardiac Surgery of the American College of Cardiology (ACC) / American Heart Association (AHA), and other articles as a reference, we compiled the Jichi Medical School Hospital (JMSH) Manual in September 2002. This manual contains a novel checklist and flowcharts and includes all past and present cardiac disorders, complications, abnormalities in electrocardiograms (ECGs) and chest X-rays, and evaluation of daily activity. Using this manual, we prospectively studied 1087 surgical candidates from September 2002 to August 2003, and retrospectively analyzed 927 surgical candidates from September 2001 to August 2002. RESULTS: In the prospective study, 39 (3.6%) patients were deemed to require further cardiac assessment and 4 (0.37%) suffered postoperative complications. In the retrospective study, 108 (11.7%) were deemed to require further cardiac assessment and 20 (2.2%) suffered postoperative complications. Using this manual reduced preoperative cardiac examination costs by 1323,600 Japanese yen, representing a 70.5% reduction. CONCLUSIONS: The JMSH Manual defines the roles of surgeons and cardiologists and is useful for assessing preoperative cardiac function and surgical risks. This manual dramatically reduced the costs associated with preoperative cardiac examinations.

Cardiology↗
PubMed2006

Impact of blood pressure vs. glycemic factors on target organ damage in patients with type 2 diabetes mellitus.

The hypothesis that three measures of target organ damage in type 2 diabetics would be more closely related to blood pressure (BP) than to glycemic factors was tested by recording 24-hour ambulatory BP and glycosylated hemoglobin. The prevalence of silent cerebral infarcts with brain magnetic resonance imaging, left ventricular mass index with cardiac ultrasonography, and albuminuria in 244 asymptomatic diabetics (mean age, 65.4+/-9 years; 122 men and 122 women; hypertension, 73%) were evaluated. Multivariate analysis showed that age (standard partial regression coefficient: b=0.299; p<0.001), duration of hypertension (b=0.176; p=0.007), and 24-hour systolic BP (b=0.195; p=0.004) were significantly associated with the number of silent cerebral infarcts, but glycosylated hemoglobin (b=0.104; p=0.109) and duration of diabetes were not. Left ventricular mass index was associated with 24-hour systolic BP (b=0.377; p<0.001) and male sex (b=0.172; p=0.019). Presence of albuminuria was significantly associated with 24-hour systolic BP (b=0.209; p=0.003), duration of diabetes (b=0.154; p=0.022), cholesterol (b=0.132; p=0.042), and insulin use (b=0.150; p=0.026). In conclusion, all three measures of target organ damage were related to 24-hour BP, but only albuminuria was related to glycosylated hemoglobin in type 2 diabetics. BP may be more important than glycemic factors for predicting future cardiovascular complications.

Age Factors↗
PubMed2006

The Japan Morning Surge-1 (JMS-1) study: protocol description.

Morning blood pressure is reported to be more closely related to hypertensive organ damages such as left ventricular mass index, microalbuminuria and silent cerebral infarcts, than blood pressure at other times of the day. Morning blood pressure may play an important role in the pathogenesis of hypertensive target organ damage. Increased sympathetic nerve activity is reported to be one of the mechanisms of morning hypertension; however, there are no available data that show whether strict home blood pressure control, especially in the morning period, can reduce target organ damage. The Japan Morning Surge-1 (JMS-1) study includes hypertensive outpatients with elevated morning systolic blood pressure (>or=135 mmHg) as assessed by self-measured blood pressure monitoring at home. All enrolled patients are under stable antihypertensive medication status. Exclusion criteria are arrhythmia, chronic inflammatory disease, and taking alpha-blockers or beta-blockers. The target number of patients to be enrolled in the JMS-1 study is 600, and the aim is to evaluate differences in the markers of hypertensive target organ damage, such as brain natriuretic peptide and the urinary albumin excretion/creatinine ratio. All of the patients are randomized to an experimental group or a control group, with randomization to be carried out by telephone interviews with the patients' physicians. In the experimental group, patients begin taking additional antihypertensive medication just before going to bed. This consists of doxazosin 1 mg/day, which then is increased to 2 mg/day and 4 mg/day, with a beta-blocker added after a 1-month interval until the morning systolic blood pressure is controlled to less than 135 mmHg. Patients in the control group continue the treatment they are receiving at the enrollment for 6 months. Blood pressure levels, adverse effects, and hypertensive target organ damage before and after the study are evaluated. In the JMS-1 study, we will evaluate whether strict morning blood pressure control by sympathetic nervous system blockade using an alpha-blocker, doxazosin, and with the addition of a beta-blocker if needed, can reduce hypertensive target organ damage.

Albuminuria↗
PubMed2006

Morning hypertension: the strongest independent risk factor for stroke in elderly hypertensive patients.

Stroke occurs most frequently in the morning hours, but the impact of the morning blood pressure (BP) level on stroke risk has not been fully investigated in hypertensives. We studied stroke prognosis in 519 older hypertensives in whom ambulatory BP monitoring was performed, and who were followed prospectively. During an average duration of 41 months (range: 1-68 months), 44 stroke events occurred. The morning systolic BP (SBP) was the strongest independent predictor for stroke events among clinic, 24-h, awake, sleep, evening, and pre-awake BPs, with a 10 mmHg increase in morning SBP corresponding to a relative risk (RR) of 1.44 (p<0.0001). The average of the morning and evening SBP (Av-ME-SBP; 10 mmHg increase: RR=1.41, p=0.0001), and the difference between the morning and evening SBP (Di-ME-SBP; 10 mmHg increase: RR=1.24, p=0.0025) were associated with stroke risks independently of each other. The RR of morning hypertension (Av-ME-SBP > or = 135 mmHg and Di-ME-SBP > or = 20 mmHg) vs. sustained hypertension (Av-ME-SBP > = 135 mmHg and Di-ME-SBP < or = 20 mmHg) for stoke events was 3.1 after controlling for other risk factors (p=0.01). In conclusion, morning hypertension is the strongest independent predictor for future clinical stroke events in elderly hypertensive patients, and morning and evening BPs should be monitored in the home as a first step in the treatment of hypertensive patients.

Aged↗
PubMed2006

Morphological evaluation of the human facial muscles.

The facial muscles are composed of striated muscle fibers, as well as other skeletal muscles, and can produce more delicate and complex expressions. We studied 12 facial muscles of 10 Japanese cadavers (8 males and 2 females, average 74.7 years old) by histological techniques. We measured the cross-sectional area of the muscle belly (mm2), number of muscle fibers per mm2, total number of muscle fibers, and muscle fiber size (microm2). The depressor anguli oris m. was predominant for the cross-sectional area and the total number of muscle fibers than other facial muscles. For the muscle fiber size, muscles inserted to the angle of the mouth were larger than those inserted to the lip. The orbicularis oculi and orbicularis oris muscles were the smallest facial muscles. The muscle fiber sizes in the facial muscles were less than other skeletal muscles.

Aged↗
PubMed2006

[Dipper and non-dipper].

Explore the source record for details and available documents.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Redox imbalance in patients with coronary artery disease showing progression of atherosclerotic lesions.

OBJECTIVES: To clarify the relationship between changes in redox balance and the development of new coronary lesions in patients with coronary artery disease (CAD). METHODS: We studied 82 CAD patients (70 males and 12 females, mean age 61.8 +/- 9.2 years) who underwent repeated coronary angiography within 1 year after percutaneous coronary intervention. Levels of serum lipid peroxide, erythrocyte glutathione peroxidase activity, and the redox state of erythrocyte (ratio of reduced to oxidized glutathione, the GSH/GSSG ratio) were measured at the time of follow-up coronary angiography. According to the development of significant stenotic lesions, we divided the patients into two groups: 57 patients without the development of new stenotic lesions (group A) and 25 patients showing new significant stenotic lesions within 1 year (group B). RESULTS: The serum lipid peroxide level in group B was significantly higher than those of group A (2.61 +/- 0.32 vs 1.74 +/- 0.16 nmol/ml, p < 0.01). Erythrocyte glutathione peroxidase activity did not differ significantly between two groups. The erythrocyte GSH/GSSG ratio in group B was significantly lower than that of group A (83 +/- 9.6 vs 126 +/- 7.3, p < 0.01). The sensitivity and specificity of GSH/GSSG ratio to detect CAD patients with the development of significant coronary stenosis were 80.0% and 61.4%, respectively. CONCLUSIONS: CAD patients who showed development of new coronary lesions within 1 year have increased oxidative stress and imbalanced erythrocyte redox state. The GSH/GSSG ratio, an indicator for redox balance, could be a useful marker to identify high-risk CAD patients.

Adult↗
PubMed2006

[Cholesterol pericarditis identified by increased cardiothoracic ratio on chest radiography: a case report].

A 72-year-old man with no symptoms was admitted to our hospital to investigate increased cardiothoracic ratio on chest radiography. There were no specific physical findings but the cardiac sound was weak. Electrocardiography showed low voltage in all leads. Thyroid function was within normal limits. Echocardiography revealed massive pericardial effusion. Pericardiocentesis was performed, and 1,800ml of gold paint-like opaque fluid was drained. Microscopic examination revealed cholesterol crystals, so the diagnosis was cholesterol pericarditis. Cytologic examination revealed no malignant cells, and no bacteria was cultured. Mycobacterium tuberculosis was not amplified using the polymerase chain reaction method of pericardial fluid. Further analysis showed reduction of apo-B in the pericardial fluid, suggesting involvement in the precipitation of cholesterol.

Aged↗
PubMed2005

Gene expression profiling of human atrial myocardium with atrial fibrillation by DNA microarray analysis.

BACKGROUND: Atrial fibrillation (AF) is the most frequently encountered arrhythmia in the clinical setting. However, a comprehensive investigation of the molecular mechanism of AF has not been performed. The aim of this study was to clarify transcriptional profiling of genes modulated in the atrium of AF patients using DNA microarray technology. METHODS: We obtained 17 fresh cardiac specimens, right atrial appendages, isolated from 10 patients with normal sinus rhythm and seven chronic AF patients who underwent cardiac surgery. Affymetrix GeneChip (Human Genome U95A) investigating 12,000 human genes was used for each specimen. Quantitative analysis of selected genes was performed by the real-time PCR method. RESULTS: The left atrial diameter in the AF group was greater than that in the sinus rhythm group. We could identify 33 AF-specific genes that were significantly activated (>1.5-fold), compared with the sinus rhythm group, including an ion channel, an antioxidant, an inflammation, three cell growth/cell cycle, three transcription such as nuclear factor-interleukin 6-beta, several cell signaling and several protein genes, and seven expressed sequence tags (ESTs). In contrast, we found 63 sinus rhythm-specific genes, including several cell signaling/communication such as sarcoplasmic reticulum Ca2+-ATPase 2, several cellular respiration and energy production and two antiproliferative or negative regulator of cell growth genes, and 22 ESTs. CONCLUSIONS: The present study demonstrated that about one hundred genes were modulated in the atria of AF patients. These findings suggest that these genes may play critical roles in the initiation or perpetuation of AF and the pathophysiology of atrial remodeling.

Adolescent↗
PubMed2005

Genome-wide screening for target regions of histone deacetylases in cardiomyocytes.

The acetylation status of core histones in cardiomyocytes has been linked to the development of cardiac hypertrophy and heart failure. Little is known, however, of the genes affected by abnormal histone acetylation in such pathological conditions. We recently developed a genome-wide screening method, differential chromatin scanning (DCS), to isolate genomic fragments associated with histones subject to differential acetylation. We have now applied DCS to H9C2 rat embryonic cardiomyocytes incubated with or without trichostatin A (TSA), a specific inhibitor of histone deacetylase (HDAC) activity. About 200 genomic fragments were readily isolated by DCS on the basis of the preferential acetylation of associated histones in TSA-treated cells. Quantitation of the amount of DNA in chromatin immunoprecipitates prepared with antibodies to acetylated histone H3 revealed that 37 of 38 randomly chosen DCS clones were preferentially precipitated from the TSA-treated cells, thus verifying the high fidelity of DCS. Epigenetic regulation of DCS clones was further confirmed in cells treated with sodium butyrate, another HDAC inhibitor, as well as in cardiac myocytes isolated from neonatal rats. The mRNA level of 9 (39%) of 23 genes corresponding to DCS clones changed in parallel with the level of histone acetylation in H9C2 cells. Furthermore, a physiological hypertrophic stimulus, cardiotrophin-1, affected the acetylation level of histones associated with genomic regions corresponding to certain DCS clones. Our data thus establish a genome-wide profile of HDAC targets in cardiomyocytes, which should provide a basis for further investigations into the role of epigenetic modification in cardiac disorders.

Acetylation↗
PubMed2005

Diabetic brain damage in hypertension: role of renin-angiotensin system.

Diabetes and hypertension are potent risk factors for cerebrovascular disease. We studied the effects of an angiotensin II type 1 receptor blockade (ARB) on brain damage in hypertensives in relation to diabetes. We studied cerebral metabolism (by proton magnetic resonance spectroscopy) and hemodynamics (by phase-contrast magnetic resonance angiography) before and 3 to 4 months after candesartan therapy in 20 diabetic hypertensives (DHTs) and 20 matched nondiabetic hypertensives (HTs). Silent multiple cerebral infarcts detected by brain MRI were more common in DHTs than in HTs (50% versus 25%). Cerebral N-acetyl aspartate (NAA; an indicator of functional neuronal mass) was lower in DHTs than in HTs (8.35 versus 9.58 mmol/kg; P=0.007). Baseline quantitative volume flow in the internal carotid arteries (ICAs) and the middle cerebral arteries (MCAs) was comparable between the 2 groups, whereas cerebrovascular reserve (CVR) assessed using acetazolamide (a cerebral arteriolar dilator) in ICAs (25% versus 35%; P=0.03) and MCAs (20% versus 31%; P=0.01) was lower in DHTs than in HTs. These baseline CVR and NAA values of DHT group were lower than those of 12 matched normotensives (CVR: 44% for ICA; 41% for MCA; NAA: 10.5 mmol/kg; all P<0.005). After candesartan therapy, CVR in ICAs and MCAs was significantly increased (P=0.001) independently of the reduction of the 24-hour blood pressure level, whereas the cerebral NAA level did not change. In conclusion, brain damage is advanced in DHTs. ARB partly improved the impaired cerebral microvascular function in DHTs.

Aged↗
PubMed2005

Type 2 diabetes is associated with left ventricular concentric remodeling in hypertensive patients.

BACKGROUND: Left ventricular (LV) geometric remodeling is associated with cardiovascular prognosis in hypertensive patients. It is uncertain how LV remodeling is modulated by diabetes in hypertensive patients. In this study, we investigated the impact of diabetes and ambulatory blood pressure (BP) on LV geometric remodeling in hyptensives with/without diabetes. METHODS: Ambulatory BP monitoring and echocardiography were performed to compare 24-h BP levels and LV measurements in 400 uncomplicated hypertensives (mean age, 67 years, 152 men and 248 women) between diabetic (n = 161) and nondiabetic (n = 239) patients. RESULTS: The age (67 v 68 years), percentage of men (43% v 34%), body mass index (24.5 v 24.0 kg/m(2)), 24-h systolic BP (144/80 v 144/82 mm Hg), LV mass index (128 v 130 g/m(2)) were similar between the groups. Diabetic patients had higher relative wall thickness (0.50 v 0.44, P < .001) and higher prevalence of concentric LV hypertrophy (39.4% v 26.8%, P < .001) than nondiabetic patients. The presence of diabetes (odds ratio [OR] = 2.76; 95% confidence interval [CI] = 1.73-4.41, P < .001) and 24-h systolic BP (OR for 10 mm Hg increase = 1.17; 95% CI = 1.01-1.37, P < .05) were independently associated with the higher relative wall thickness (>/=0.45). On the other hand, 24-h systolic BP was independently associated with LV hypertrophy (OR for 10 mm Hg increase = 1.32; 95% CI = 1.14-1.52, P < .05). CONCLUSIONS: Among hypertensive patients, type 2 diabetes was associated with concentric LV geometry independent of ambulatory BP.

Adult↗