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Biomedical subjects

Kazuyuki Shimada

Publications and source records attributed to Kazuyuki Shimada.

At least 37 records · Page 2Linked to original sources
PubMed2005

Determinants of exaggerated difference in morning and evening blood pressure measured by self-measured blood pressure monitoring in medicated hypertensive patients: Jichi Morning Hypertension Research (J-MORE) Study.

BACKGROUND: Morning blood pressure (BP) surge in ambulatory BP monitoring was a risk factor for stroke in our previous study. We studied the determinants of the morning minus evening systolic BP difference (ME difference) in self-measured BP monitoring, as a possible risk factor for stroke in medicated hypertensive patients. METHODS: Nine hundred sixty-nine hypertensive outpatients receiving stable antihypertensive drug treatment were studied using self-measured BP monitoring in the morning and evening. RESULTS: The ME difference ranged from -37.3 to 53.3 mm Hg (mean 7.9 mm Hg). The highest quartile (Q4) of the ME difference group (>15.0 mm Hg) had older age (68.0+/-9.8 years v 66.2+/-10.3 years, P=.01) and higher prevalence of men (48.3% v 39.9%, P=.02), regular alcohol drinkers (34.7% v 26.0%, P=.01) and beta-blocker use (26.9% v 19.9%, P=.03) than the other quartile groups (Q1 to Q3), whereas there was no significant difference in the average of morning and evening (ME average) BP. In logistic regression analysis controlling for ME average and other confounding factors, independent risks for Q4 of ME difference were older age (10 years older: odds ratio [OR] 1.21, P=.01, 95% confidence interval (CI) 1.04-1.42), regular alcohol drinker (OR 1.51, P=.04, 95% CI 1.01-2.26), and beta-blocker use (OR 1.50, P=.02, 95% CI 1.06-2.12). CONCLUSIONS: Older age, beta-blocker use, and regular alcohol drinking were significant determinants of the exaggerated ME difference in medicated hypertensive patients.

Adrenergic beta-Antagonists↗
PubMed2005

Nocturnal hypoxia is associated with silent cerebrovascular disease in a high-risk Japanese community-dwelling population.

BACKGROUND: Sleep-disordered breathing (SDB) is recognized as a risk factor for cerebrovascular disease. The objective of this study was to investigate the relationship between nocturnal hypoxia and silent cerebral infarct (SCI) in the general population. METHODS: In the 2001 annual health check in Nishiarita, Japan, 170 individuals at high risk were screened who met more than three of the following criteria: high blood pressure, hypercholesterolemia, left ventricular hypertrophy by electrocardiography, hemoglobinA(1)c >6.5%, proteinuria, central obesity, heavy smoking habit, heavy drinking, and family history of stroke. Overnight pulse oximetry, brain magnetic resonance imaging, and carotid/cardiac ultrasonography were performed in 146 (mean age 67.4 +/- 9.0 years) of the 170 individuals in whom pulse oximetry was successfully performed. RESULTS: Subjects were classified into a nocturnal hypoxia group (n = 36) and a nonhypoxia group (n = 110) based on a 3% oxygen desaturation index (ODI) 5.6 times per hour during sleep (highest quartile) by pulse oximetry. The presence of silent cerebral infarct (SCI) (57% v 35%, P = .03) was significantly higher in the hypoxia group than in the nonhypoxia group. The number of SCI was positively correlated with age (r = 0.23, P < .01), systolic blood pressure (r = 0.196, P < .05), and 3% ODI (r = 0.318, P < .001). Even after adjustment for confounding factors using logistic regression analysis, nocturnal hypoxia (odds ratio = 2.2, 95% confidence interval = 1.10 to 5.30, P = .026) as well as systolic blood pressure and age (10-year increase: odds ratio = 1.22, 95% confidence interval 1.00 to 1.48, P = .048) were independently associated with SCI in the study subjects. CONCLUSIONS: Based on the study results, SDB assessed by overnight pulse oximetry was associated with silent cerebral disease in a high-risk, community-dwelling Japanese population.

Adult↗
PubMed2005

Morning blood pressure hyper-reactivity is an independent predictor for hypertensive cardiac hypertrophy in a community-dwelling population.

BACKGROUND: Morning blood pressure (BP) surge seems to be a risk factor for cardiovascular events. Although physical activity after arising significantly affects morning BP surge, it has remained unclear whether morning BP surge after controlling for physical activity (morning BP reactivity) is associated with target organ damage. METHODS: We performed ambulatory BP monitoring with simultaneous actigraphy and echocardiography in 120 community-dwelling Japanese subjects. We determined the waking time by actigraphy, and defined morning BP surge (MBPS) as the average of systolic BP during the 2 h after awakening minus the average of systolic BPs during the 1 h that included the lowest sleep BP. The ratio of MBPS/(sum of the 2-h physical activity after the arising time)0.5 was calculated as the morning BP reactivity (MBPR). RESULTS: In all the subjects studied (n = 120), MBPR was positively associated with left ventricular (LV) mass index (r = 0.30, P = .001). The MBPR had a positive association with both 24-h BP variability (SD) (r = 0.373, P < .001) and awake BP variability (r = 0.20, P < .05). The MBP hyper-reactive group (the highest quartile [Q4] of MBPR: n = 30) had significantly higher LV mass index than the nonreactive group (the other quartiles [Q1 to 3]: n = 90) (140 v 113 g/m(2), P < .001). Even after controlling for age, body mass index, gender, and 24-h systolic BP, the MBP hyper-reactive status still remained a strong predictor for LV hypertrophy. CONCLUSIONS: Exaggerated MBPS, adjusted for physical activity, is associated with cardiac hypertrophy independent of ambulatory BP level in a community-dwelling population.

Age Factors↗
PubMed2005

An anti-ulcer drug, geranylgeranylacetone, suppresses inducible nitric oxide synthase in cultured vascular smooth muscle cells.

OBJECTIVE: Geranylgeranylacetone (GGA) is commonly used as an anti-ulcer drug. If GGA affects inducible nitric oxide synthase (iNOS) in the vascular tissue, it could influence disease progression in coronary arteries. We investigated the effects of the anti-ulcer drug GGA on iNOS activity in vascular smooth muscle cells. METHODS: We measured the production of nitrite, a stable metabolite of nitric oxide, in cultured rat vascular smooth muscle cells with the Griess reagent. iNOS protein and mRNA expressions were assayed by western blotting and northern blotting, respectively. The levels of nuclear factor (NF)-kappaB proteins in nuclear extracts were analyzed by gel retardation assay. Heat shock protein 70, a cytoprotective molecule, was evaluated by western blotting. RESULTS: Incubation of cultures with interleukin-1beta for 24 h caused a significant increase in nitrite generation. Interleukin-1beta-induced nitrite production by vascular smooth muscle cells was significantly suppressed by GGA in a dose-dependent manner. GGA-suppressed nitrite production was accompanied by decreased iNOS mRNA and protein accumulations. GGA by itself did not modulate the basal level of nitrite production. Interleukin-1beta induced NF-kappaB activation in vascular smooth muscle cells, and the addition of GGA further inhibited this NF-kappaB activation. GGA itself induced heat shock protein 70 expression in a dose-dependent manner. CONCLUSION: These findings demonstrated that GGA suppresses iNOS expression in cytokine-stimulated cultured vascular smooth muscle cells partially through the suppression of NF-kappaB activation, suggesting that GGA may modulate the pathophysiology of cardiovascular diseases including atherosclerosis. In addition, this effect may be associated with heat shock protein 70 production by GGA.

Animals↗
PubMed2005

Comparison of the effects of cilnidipine and amlodipine on ambulatory blood pressure.

Cilnidipine is a novel and unique 1,4-dydropyridine derivative calcium antagonist that exerts potent inhibitory actions not only on L-type but also on N-type voltage-dependent calcium channels. Blockade of the neural N-type calcium channel inhibits the secretion of norepinephrine from peripheral neural terminals and depresses sympathetic nervous system activity. The purpose of this study was to assess the effect of cilnidipine and amlodipine on ambulatory blood pressure (BP) levels. We performed 24-h ambulatory BP monitoring before and after once-daily use of cilnidipine (n=55) and amlodipine (n=55) in 110 hypertensive patients. Both drugs significantly reduced clinic and 24-h systolic BP (SBP) and diastolic BP (DBP) (p < 0.005). However, the reductions of 24-h (-1.19+/-6.78 vs. 1.55+/-6.13 bpm, p=0.03), daytime (-1.58+/-6.72 vs. 1.68+/-7.34 bpm, p=0.02) and nighttime (-1.19+/-5.72 vs. 1.89+/-6.56 bpm, p=0.01) pulse rate (PR) were significantly greater in the cilnidipine group than the amlodipine group. There was no correlation between the degree of daytime SBP change and that of daytime PR change after amlodipine treatment (r=-0.08, n.s.), but there was a significant negative correlation between the degree of daytime SBP change and that of day-time PR change after cilnidipine treatment (r=-0.27, p<0.05). N-type calcium channel blockade by cilnidipine may not cause reflex tachycardia, and may be useful for hypertensive treatment.

Aged↗
PubMed2005

Altered aortic properties in elderly orthostatic hypertension.

To investigate the impact of arterial properties on orthostatic blood pressure (BP) dysregulation in older hypertensives, orthostatic BP dysregulation, a common phenomenon in elderly hypertensives, is associated with target organ damage and falls. However, the mechanism of orthostatic BP dysregulation remains unclear. The pulse wave velocity (PWV), related arterial stiffness, and the augmentation index (AI), a measure of arterial wave reflection, were measured in 365 older hypertensives. We classified the study patients into an orthostatic hypertension (OHT) group with orthostatic increase of systolic BP (SBP) of > or = 220 mmHg (n = 27) and an orthostatic normotension (ONT) group with an orthostatic increase of SBP of < 20 mmHg and orthostatic SBP decrease of < 20 mmHg (n = 338). Orthostatic AI was significantly greater in the OHT group than in the ONT group (OHT: 6.5 +/- 12% vs. ONT: -5.6 +/- 12%, p < 0.001), while supine AI and supine and orthostatic pulse rate were comparable between the two groups. There was no significant difference in the PWV between the OHT and ONT groups. Orthostatic hypertension was affected by altered aortic properties and associated with augmented wave reflection of arterial pressure.

Aged↗
PubMed2005

The combination therapy of hypertension to prevent cardiovascular events (COPE) trial: rationale and design.

A number of major clinical trials have demonstrated the clinical benefits of lowering blood pressure and have indicated that a majority of patients with hypertension will require more than one drug to achieve optimal blood pressure control. However, there is little data showing which antihypertensive combination best protects patients from cardiovascular events and which best achieves the target blood pressure with the fewest adverse events. The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial is the first large-scale investigator-initiated multicenter study with a prospective, randomized, open, blinded endpoint evaluation (PROBE) design to directly compare cardiovascular mortality and morbidity, incidence of adverse drug reaction, and degree of blood pressure reduction in Japanese hypertensive patients for a combination of angiotensin receptor blockers, beta-blockers or thiazide diuretics in addition to a calcium antagonist, benidipine hydrochloride, with a response-dependent dose titration scheme. The COPE trial is being conducted with the cooperation of more than 100 centers and clinics in Japan and involves 3,000 patients, who will be followed for 3 years. Eligible patients are being enrolled from May 2003 until May 2006. Results from the COPE trial should provide new evidence for selecting optimal combination therapies for hypertensive patients.

Antihypertensive Agents↗
PubMed2005

A case of reversible posterior leukoencephalopathy syndrome caused by transient hypercoagulable state induced by infection.

We report a normotensive case of reversible posterior leukoencephalopathy syndrome caused by transient hypercoagulable state. Hypertension is the main risk factor for reversible posterior leukoencephalopathy syndrome, which is believed to occur as a result of high blood pressure-related dysfunction of cerebrovascular endothelial cells, because it commonly appears in hypertensive emergency. However, in this completely normotensive case, the typical clinical findings of reversible posterior leukoencephalopathy syndrome were triggered by transient hypercoagulable state without any blood pressure variation. The case was successfully treated with anticoagulation therapy using heparin. Thus, this case indicates that reversible posterior leukoencephalopathy syndrome is induced by cerebrovascular endothelial dysfunction, which is induced not only by high blood pressure but also hemostatic dysfunction.

Aged↗
PubMed2005

Smoking and antihypertensive medication: interaction between blood pressure reduction and arterial stiffness.

To investigate how cigarette smoking and antihypertensive drug therapy may interact to affect cardiovascular disease, in this prospective study we administered amlodipine to hypertensive smokers and non-smokers and compared blood pressure reduction and indices of arterial stiffness. We measured blood pressure (BP), heart rate (HR), brachial-ankle pulse wave velocity (baPWV), and the carotid augmentation index (AIx) by using a non-invasive automated device in 101 hypertensive patients at baseline and at 1, 3, and 6 months of amlodipine administration (5.0 mg). At baseline, the AIx was significantly lower in smokers (n=27) than in non-smokers (n=74) (27.3% +/- 13.3% vs. 33.3% +/- 11.4%). After amlodipine administration, in both the groups, the mean BP, baPWV, and AIx were significantly reduced; however, the HR did not show a statistically significant difference. The reduction in the baPWV (cm/s) at 1 and 3 months was less marked in smokers than in non-smokers (mean +/- SD: -186.6 +/- 36.5 vs. -283.6 +/- 24.5 at 1 month; -136.6 +/- 42.2 vs. -280.1 +/- 29.6 at 3 months, respectively, both p<0.05). At 6 months, these intergroup differences in the reductions of baPWV disappeared. The blunted reduction of baPWV, particularly at 3 months, was significantly associated with the extent of smoking (lifetime pack-years smoked). Changes observed in the AIx and mean BP were similar between groups throughout the study period. In the short term, cigarette smoking blunts the effect of amlodipine on the reduction of arterial stiffness, independently of the mean BP level.

Aged↗
PubMed2005

A case of vertebral artery dissection associated with morning blood pressure surge.

We report a case of a middle-aged man who suffered a cerebral infarction resulting from dissection of a vertebral artery associated with morning blood pressure surge. A 56-year-old man was transferred to our hospital with dizziness and vomiting in the early morning on a cold day in winter. He reported that he had been standing in front of the sink after bathing when he suddenly felt dizzy and fell down. He did not lose consciousness, and by the time he reached the hospital by ambulance, his dizziness had subsided, but he complained of severe headache and vomited 3 times. On admission, he was alert, and there were no neurological or radiological abnormalities (CT, MR angiography) in the brain. However, infarction in the left cerebellar hemisphere was detected by brain MRI on the 5th day of hospitalization. String sign of the left vertebral artery was noted by angiography, confirming the diagnosis of dissection of the left vertebral artery. Ambulatory blood pressure monitoring was performed after discharge. Although the mean 24-h blood pressure was in the normal range, a marked morning blood pressure rise was observed. We speculated that the acute rise of blood pressure in the early morning might have contributed to the dissection of the vertebral artery.

Atherosclerosis↗
PubMed2005

Collagen metabolism in extracellular matrix may be involved in arterial stiffness in older hypertensive patients with left ventricular hypertrophy.

Collagen metabolism in the extracellular matrix (ECM) is related to the pathogenesis of cardiovascular stiffness and remodeling in hypertension. We evaluated the association between collagen metabolism markers and the newly developed parameter, brachial-ankle pulse wave velocity (baPWV), in older hypertensive patients with left ventricular hypertrophy (LVH). We performed echocardiography and baPWV measurement using a new device, form PWV/ABI (Colin Medical Technology, Komaki, Japan), and measured plasma levels of markers of collagen metabolism such as procollagen type I C-terminal propeptide (PICP: a marker of collagen synthesis), collagen type I pyridinoline cross-linked C-terminal telopeptide (ICTP: a marker of collagen type I degradation), matrix metalloproteinase-1 (MMP-1: a marker of collagen degradation) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in 46 hypertensive patients with LVH. BaPWV was correlated with the plasma level of PICP (r=0.33, p=0.03) and ICTP (r=0.29, p=0.05) and the total TIMP-1/MMP-1 ratio (an index of collagen turnover; r=0.30, p=0.04). BaPWV was negatively correlated with the E/A ratio of left ventricular inflow (r=-0.36, p<0.05), while baPWV was not correlated with left ventricular mass index (LVMI; r=-0.175, p=0.25) or deceleration time of the mitral E wave (DCT; r=0.15, p=0.31). The measures of hypertensive heart disease, such as the E/A ratio, DCT or LVMI were not correlated with any collagen markers in this study. In multiple regression analysis adjusted for confounding factors such as age, sex, pulse pressure, mean blood pressure, pulse rate, LVMI, E/A ratio and DCT, the positive correlation between baPWV and total TIMP-1/MMP-1 ratio remained significant (p<0.05). In conclusion, arterial stiffness in high-risk older hypertensive patients may involve ECM collagen metabolism.

Aged↗
PubMed2005

Repair of infarcted myocardium mediated by transplanted bone marrow-derived CD34+ stem cells in a nonhuman primate model.

Rodent and human clinical studies have shown that transplantation of bone marrow stem cells to the ischemic myocardium results in improved cardiac function. In this study, cynomolgus monkey acute myocardial infarction was generated by ligating the left anterior descending artery, and autologous CD34(+) cells were transplanted to the peri-ischemic zone. To track the in vivo fate of transplanted cells, CD34(+) cells were genetically marked with green fluorescent protein (GFP) using a lentivirus vector before transplantation (marking efficiency, 41% on average). The group receiving cells (n = 4) demonstrated improved regional blood flow and cardiac function compared with the saline-treated group (n =4) at 2 weeks after transplant. However, very few transplanted cell-derived, GFP-positive cells were found incorporated into the vascular structure, and GFP-positive cardiomyocytes were not detected in the repaired tissue. On the other hand, cultured CD34(+) cells were found to secrete vascular endothelial growth factor (VEGF), and the in vivo regional VEGF levels showed a significant increase after the transplantation. These results suggest that the improvement is not the result of generation of transplanted cell-derived endothelial cells or cardiomyocytes; and raise the possibility that angiogenic cytokines secreted from transplanted cells potentiate angiogenic activity of endogenous cells.

Animals↗
PubMed2005

[Reduced arterial compliance with advancing age].

The term "compliance" is generally used as softness of the arterial wall. Fundamentally, compliance characterizes property of a chamber, being defined as deltaV/deltaP. It implies that how easily volume (V) of the chamber changes in response to unit pressure (P) change. However, in reality, the arterial system is not such a simple chamber but a complicated branched tubing system, in which compliance components are distributed along the tubing. It can be simplified as a single tube model, in which we can regard compliance as the sum of proximal portion as a determinant of characteristic impedance of the aorta and distal portion consisting of terminal impedance of the peripheral arterial bed. Such distributed model enables us to simulate pulse wave propagation and reflection, actually occurred in real arteries. This paper deals with parameters relating to arterial compliance corresponding to such distributed model. Arterial compliance is reduced with advancing age. This phenomenon has been widely recognized by epidemiological studies on blood pressure, in which systolic and pulse pressures are increased with aortic reflection without significant change in diastolic pressure. Also, many investigators reported age-dependent compliance declines by assessing compliance-relating parameters including cross-sectional compliance, pulse wave velocity and augmentation index. This reduced compliance may affect the heart as a pulsatile afterload and adversely alter myocardial energy balance.

Aged↗
PubMed2005

Drug-recommendation system for patients with infectious diseases.

We developed a decision support system that helps doctors select appropriate first-line drugs. The system classifies patients' abilities to protect themselves from infectious diseases as a risk level for infection. In an evaluation of the prototype system, the risk level it determined correlated with the decisions of specialists. The system is very effective and convenient for doctors to use.

Communicable Diseases↗
PubMed2004

The important role for betaVLDLs binding at the fourth cysteine of first ligand-binding domain in the low-density lipoprotein receptor.

The low-density lipoprotein (LDL) receptor (LDLR) is a crucial role for binding and uptaking apolipoprotein (apo) B-containing lipoproteins, such as very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and LDL. The defect function of the LDLR causes familial hypercholesterolemia (FH), the phenotype of which is elevated plasma cholesterol and premature coronary heart disease (CHD). In the present study, we characterize the role of the cysteine residue of the ligand-binding domain of the LDLR. The mutant LDLR protein of cysteine for serine at codon 25 (25S-LDLR) was expressed in Chinese hamster ovary (CHO) cell line, ldl-A7. By Western blot analysis, the 25S-LDLR was detected with monoclonal antibody IgG-12D10, which reacts with the linker site of the LDLR but not with IgG-C7, which reacts with the NH2 terminus of the receptor. The 25S-LDLR bound LDL similarly to the wild-type LDLR, but the rate of uptake of LDL by the mutant receptor was only about half of that by the wild-type receptor. In contrast, the 25S-LDLR bound and internalized beta VLDL more avidly than LDL. These results suggest that the fourth cysteine residue of the first ligand-binding domain of the LDLR might be important for the internalization of atherogenic lipoproteins by vascular cells despite reduced LDL uptake, leading to atherosclerosis and premature cardiovascular disease.

Animals↗
PubMed2004

Cardiac function-related gene expression profiles in human atrial myocytes.

To obtain insights into the molecular pathogenesis of heart failure in humans, we have analyzed the expression profiles of>12,000 genes in a total of 17 human specimens of right atrial myocytes. From this large data set, we here tried to identify gene clusters, expression level of which is correlated precisely with clinical parameter values of cardiac function. We could reveal that cardiac myocytes with normal sinus rhythm were clearly differentiated, in the point of view of gene expression, from those with atrial fibrillation. Further, an expression profile-based prediction of arrhythmia by a newly developed "weighted-distance method" could efficiently diagnose our samples. We could even construct calculation formulae for the values of left ventricular ejection fraction based on the expression level of selected genes. To our best knowledge, this is the first report to indicate that pumping ability of heart can be predicted by any measures of atrium.

Adolescent↗