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Biomedical subjects

Kazuyuki Shimada

Publications and source records attributed to Kazuyuki Shimada.

At least 91 records · Page 5Linked to original sources
PubMed2003

Associations between nondipping of nocturnal blood pressure decrease and cardiovascular target organ damage in strictly selected community-dwelling normotensives.

BACKGROUND: In hypertensives, nondippers are more likely than dippers to suffer silent, as well as overt, hypertensive target organ damage. In this study, we investigated whether a nondipper status was associated with target organ damage in normotensives. METHODS: We performed ambulatory blood pressure (BP) monitoring, echocardiography, and carotid ultrasonography and measured natriuretic peptides and urinary albumin (UAE) in 74 normotensive subjects with the following criteria: 1) clinical BP <140/90 mm Hg; 2) average 24-h ambulatory BP <125/80 mm Hg. RESULTS: The left ventricular mass index (LVMI) and the relative wall thickness (RWT) measured by echocardiography were greater in nondippers than dippers (LVMI: 103 +/- 26 v 118 +/- 34 g/m(2), P <.05; RWT: 0.38 +/- 0.07 v 0.43 +/- 0.09, P <.01). Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were higher in nondippers than dippers (ANP: 14 +/- 10 v 36 +/- 63 pg/mL, P <.01; BNP: 16 +/- 12 v 62 +/- 153 pg/mL, P <.05). There were no significant differences in UAE and intima-media thickness measured by carotid ultrasonography. CONCLUSIONS: Normotensive nondipping may not reflect renal damage, but may have a predominant effect on cardiac damage. Nondipping of nocturnal BP seems to be a determinant of cardiac hypertrophy and remodeling, and may result in a cardiovascular risk independent of ambulatory BP levels in normotensives.

Aged↗
PubMed2003

Effects of olmesartan, an angiotensin II receptor blocker, on mechanically-modulated genes in cardiac myocytes.

BACKGROUND: Angiotensin II plays an important role in cardiac hypertrophy or remodeling. Angiotensin II receptor blockers (ARB) are clinically useful for the treatment of hypertension and heart failure. However, the molecular effects of ARB in the mechanically-stressed myocardium have not been completely defined. We investigated the effects of ARB on mechanically-modulated genes in cardiac myocytes. METHODS: We used powerful DNA microarray technology to study the effects of the ARB, CS-886 (olmesartan), on genes modulated in neonatal rat cardiac myocytes using mechanical stimuli. Mechanical deformation was applied to a thin and transparent membrane on which neonatal rat cardiac myocytes were cultured in the presence or absence of RNH-6270, an active metabolite of CS-886. Expression profiles of 8000 rat genes using the Affymetrix GeneChip (Rat Genome U34A) were investigated with mRNA obtained from the samples above. RESULTS: Nine genes induced under 4% mechanical strain were significantly suppressed by RNH-6270 in rat cardiac myocytes: monoamine oxidase B, neuromedine B receptor, olfactory receptor, synaptotagmin XI, retinol-binding protein, and 4 expressed sequence tags (ESTs). In contrast, 21 genes suppressed under mechanical strain were significantly restored by RNH-6270: major acute phase alpha 1-protein, Sp-1, Bcl-Xalpha, JAK2, 2 genes encoding detoxification, few genes for receptor, structure, metabolism or ion channel, and 10 ESTs. CONCLUSIONS: As some of these genes may be involved in promoting or modulating cardiac remodeling, these findings suggest that ARB may affect cardiovascular morbidity and mortality partially via these molecular alterations.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2003

Serum MCP-1 and VEGF levels are not affected by inhibition of the renin-angiotensin system in patients with acute myocardial infarction.

Monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) stimulate angiogenesis in ischemic tissues, and both of their expression are stimulated by angiotensin II. We measured the serum concentrations of MCP-1 and VEGF in patients with acute myocardial infarction (AMI) and investigated the effects of an early administration of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor blocker (ARB) on their levels. Thirty-six patients with AMI were divided randomly into 3 therapeutic groups; the ACEI perindopril, the ARB candesartan and control (without perindopril and candesartan), and the drugs were administered within 36 hours after the onset of AMI. Peripheral blood mononuclear cells (PBMC) obtained from the patients were incubated for 24 hours. The levels of MCP-1 and VEGF in the serum and the supernatant of PBMC were measured by ELISA. The serum MCP-1 and VEGF levels in AMI patients at the time of admission were not significantly different from those in healthy control subjects, but both MCP-1 and VEGF levels in the patients were increased significantly after 7 days. There was no significant difference in the serum MCP-1 and VEGF levels among the 3 therapeutic groups. The production of MCP-1 and VEGF by PBMC was also increased in AMI patients compared with healthy control subjects, and there was also no difference in their production among the 3 therapeutic groups. In conclusion, circulating MCP-1 and VEGF levels and their production by PBMC are elevated during the course of AMI, and early administration of ACEI and ARB does not affect their levels.

Aged↗
PubMed2003

Intravenous prostaglandin E1 reduces monocyte chemoattractant protein-1 levels in peripheral arterial obstructive disease.

OBJECTIVES: Blood monocytes are the precursors of the lipid-laden foam cells that are the hallmark of early atherosclerotic lesions, and monocyte chemoattractant protein-1 (MCP-1) plays important roles in their recruitment to the vessel wall. In this study, we measured serum levels of MCP-1 in patients with peripheral arterial obstructive disease (PAOD) and investigated whether intravenous prostaglandin E1 (PGE1) treatment, which produces clinical benefits in PAOD, might decrease such levels. METHODS: Eight patients with PAOD at Fontaine stage II to IV were treated with a daily intravenous infusion of 10 microg of PGE1 for 7 consecutive days. Blood samples before and after 7-day PGE1 treatment were used for assays of MCP-1, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), von Willebrand factor (vWF), and endothelin-1 (ET-1). RESULTS: Serum MCP-1 levels in patients with PAOD were significantly higher than those in healthy control subjects (263.8 +/- 52.8 vs 136.5 +/- 15.0 pg/mL, P =.002). PGE1 administration for 7 days resulted in a significant decrease in the MCP-1 level, from 263.8 +/- 52.8 to 196.1 +/- 25.5 pg/mL (P =.02), whereas levels of IL-6, hs-CRP, and ET-1 and the activity of vWF were not affected. CONCLUSIONS: Serum MCP-1 levels were elevated in patients with PAOD, indicating the involvement of activation of monocytes in the pathogenesis of this disorder. Parenteral administration of PGE1 appeared to decrease circulating MCP-1 levels, which might lead to the suppression of the development of atherosclerotic lesions in patients with PAOD.

Adult↗
PubMed2003

Adrenomedullin expression in coronary circulation after stent implantation as a prognostic factor for restenosis.

The authors determined the changes in adrenomedullin (AM) expression in the coronary circulation of patients with ischemic heart disease who underwent coronary stent implantation. Blood samples were drawn from the coronary sinus before, immediately after and four hours after coronary stent implantation, and plasma levels of AM were measured. AM levels in the coronary sinus blood were significantly increased four hours after stent implantation. On the other hand, in the femoral arterial blood, no significant changes in AM levels were observed. A significant positive correlation was found between AM level in the coronary sinus blood four hours after stent implantation and late loss index six months after the procedure. These results suggest that inflammation after coronary stent implantation induces AM expression, which might play an important role in restenosis after stenting.

Adrenomedullin↗
PubMed2003

Inhibition of the renin-angiotensin system: no effect on circulating macrophage colony-stimulating factor levels in acute myocardial infarction.

Macrophage colony-stimulating factor, which induces proliferation and differentiation, and activation of monocytes and macrophages, plays an important role in the vulnerability of atheromatous plaques as well as the formation of atherosclerotic lesions. We measured serum concentrations of macrophage colony-stimulating factor in patients with acute myocardial infarction and also investigated the effects of early administration of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker on circulating macrophage colony-stimulating factor levels in these patients. The patients were divided randomly into 3 therapeutic groups; perindopril, candesartan, and control (without perindopril and candesartan) groups, and the drugs were administered within 24 to 36 hours after the onset of acute myocardial infarction. Serum macrophage colony-stimulating factor concentrations in acute myocardial infarction patients at the time of admission were significantly higher than those in healthy control subjects. The macrophage colony-stimulating factor levels in the patients decreased gradually after admission, but remained significantly higher than those in control subjects for 14 days. There were no significant differences in serum macrophage colony-stimulating factor levels among the 3 therapeutic groups during this study period. In conclusion, circulating macrophage colony-stimulating factor levels are elevated during the course of acute myocardial infarction, and inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitor or angiotensin receptor blocker does not affect these levels.

Adult↗
PubMed2003

C-reactive protein directly inhibits nitric oxide production by cytokine-stimulated vascular smooth muscle cells.

C-reactive protein (CRP) is an important risk factor for atherosclerosis and coronary artery disease. The authors investigated the effects of CRP on nitric oxide (NO) synthesis in vascular smooth muscle cells (VSMCs). Production of nitrite, a stable metabolite of NO, was measured, as was the expression of inducible NO synthase (iNOS) messenger RNA and protein in cultured rat VSMCs. Incubation of cultures with interleukin (IL)-1beta (10 ng/mL) caused a significant increase in nitrite production. C-reactive protein significantly decreased the IL-1beta-induced nitrite production by VSMCs in a dose-dependent manner (10-100 microg/mL). Incubation with IL-1beta induced expression of iNOS mRNA and protein in VSMCs, whereas CRP showed a suppressive effect on their expression. Addition of IL-1beta activated nuclear factor-kappaB (NFkappaB) in VSMCs, whereas CRP did not affect IL-1beta-induced NFkappaB activation. In conclusion, CRP acts on VSMCs and inhibits NO synthesis, which might contribute to the development of atherosclerosis and vascular events.

Animals↗
PubMed2003

Clinical implication of morning blood pressure surge in hypertension.

Cardiovascular events occur most frequently in the morning. The morning surge in blood pressure may be associated with hypertensive target organ damage and subsequent cardiovascular risk in hypertensive patients. In our prospective study on elderly hypertensive patients, the morning blood pressure surge (defined as the increase from the lowest blood pressure during sleep to the average of the first 2 h after waking) was significantly associated with silent hypertensive cerebrovascular disease and subsequent stroke risk. This association was independent of age and 24-h ambulatory blood pressure levels. In addition, even after controlling for these factors and status of silent cerebrovascular disease, the contribution of the morning blood pressure surge remained significant, and a 10 mmHg increase in systolic morning blood pressure surge increase the stroke risk by 22%. A related factor is orthostatic hypertension, which might be associated with increased sympathetic activity, and which is significantly associated with an increase in morning blood pressure surge and ambulatory blood pressure variability. A possible implication is that, in addition to strict blood pressure control, antihypertensive medication that targets exaggerated morning blood pressure may achieve more effective prevention of cardiovascular events in hypertensive patients.

Blood Pressure↗
PubMed2003

Circulating endothelial progenitor cells are reduced in hemodialysis patients.

OBJECTIVE: The risk of cardiovascular disease in hemodialysis patients is far greater than in the general population. Endothelial progenitor cells (EPCs) circulating in the peripheral blood contribute to neovascularization in the ischemic tissue. EPCs are considered to be included in CD34 positive (CD34+) or AC133 positive (AC133+) mononuclear cells (MNCs). This study's aim was to determine the number and functional activity of EPCs in hemodialysis patients and age-matched control subjects. METHODS: The numbers of CD34+ MNCs and AC133+ MNCs in the peripheral blood were quantified by flow cytometry. The peripheral blood EPCs were also examined by an in vitro culture assay. The levels of serum vascular endothelial growth factor (VEGF) were measured by sandwich enzyme immunoassay. RESULTS: The numbers of CD34+ MNCs and AC133+ MNCs were significantly reduced by 56% and 49%, respectively, in hemodialysis patients (n = 50) compared with control subjects (n = 36). The number of EPCs determined by the culture assay was also significantly reduced by 41% in hemodialysis patients compared with control subjects. Multivariate analysis revealed that none of the atherosclerotic risk factors were independent predictors of reduced CD34+ MNC counts. The serum VEGF levels in hemodialysis patients were not different from those in control subjects and did not correlate with CD34+ MNC counts. CONCLUSION: Circulating EPCs are significantly reduced in hemodialysis patients, which might be related to impaired neovascularization and cardiovascular disease in these patients.

Antigens, CD34↗
PubMed2003

Serum concentrations of vascular endothelial growth factor and monocyte-colony stimulating factor in peripheral arterial disease.

Vascular endothelial growth factor (VEGF) strongly promotes angiogenesis, and monocyte-colony stimulating factor (M-CSF) regulates the differentiation, proliferation, and survival of monocytes. Both VEGF and M-CSF are expressed in atherosclerotic lesions. The present study was performed to clarify the role of VEGF and M-CSF in the development of peripheral artery disease (PAD). The serum VEGF and M-CSF concentrations were determined in patients with arteriosclerosis obliterans (ASO) and thromboangitis obliterans (TAO). In both patient groups the serum VEGF concentrations were significantly higher than those in the control subjects. In contrast, the serum M-CSF concentrations in the ASO patients were significantly higher than those in both the TAO patients and control subjects, but there were no differences in the M-CSF concentrations between the TAO patients and control subjects. There was no correlation between the serum concentrations of VEGF and M-CSF. In conclusion, the serum VEGF concentration was increased in ASO and TAO patients, but increased concentration of M-CSF was seen only in ASO patients. These results may reflect a difference between ASO and TAO in disease pathogenesis.

Arteriosclerosis Obliterans↗
PubMed2003

Japanese society of hypertension (JSH) guidelines for self-monitoring of blood pressure at home.

UNLABELLED: Home blood pressure (BP) measurements are indispensable for the improvement of hypertension management in medical practice as well as for the recognition of hypertension in the population. The Working Group for Establishment of Guidelines for Measurement Procedures of Self-Monitoring of Blood Pressure at Home of the Japanese Society of Hypertension has established standards for all techniques and procedures of home BP measurements. The recommendations are as follows. RECOMMENDATION: 1) Arm-cuff devices based on the cuff-oscillometric method that have been validated officially, and the accuracy of which has been confirmed in each individual, should be used for home BP measurement. 2) The BP should be measured at the upper arm. Finger-cuff devices and wrist-cuff devices should not be used for home BP measurements. 3) Devices for home BP measurement should be adapted to the American Association for Medical Instrumentation (AAMI) standards and the British Hypertension Society (BHS) guidelines. In addition, the difference between the BP measured by the auscultatory method and that measured using the device should be within 5 mmHg in each individual. The home measurement device should be validated before use, and at regular intervals during use. 4) Home BP should be monitored under the following conditions. The morning measurement should be made within 1 h after waking, after micturition, sitting after 1 to 2 min of rest, before drug ingestion, and before breakfast. The evening measurement should be made just before going to bed, sitting after 1 to 2 min of rest. 5) Home BP should be measured at least once in the morning and once in the evening. 6) All home BP measurements should be documented without selection, together with the date, time, and pulse rate. Use of devices with a printer or an integrated circuit memory is useful to avoid selection bias. 7) The home BP in the morning and that in the evening should be averaged separately for a certain period. The first measurement on each occasion should be used for totaling. 8) Home BP values averaged for a certain period indicate hypertension when 135/80 mmHg and over and definite hypertension when 135/85 mmHg and over. Normotension is defined as less than 125/80 mmHg and definite normotension as less than 125/75 mmHg. Home BP measurements based on these guidelines can be considered an appropriate tool for clinical decision-making, and it is hoped that these guidelines will serve to reduce confusion and confirm the place of home BP measurement in clinical practice.

Blood Pressure↗
PubMed2003

Primary cutaneous diffuse large B cell lymphoma: a clinically aggressive case.

An 80-year-old woman was diagnosed with primary cutaneous B cell lymphoma. She had multifocal cutaneous tumors, but no nodal lymphadenopathy or bone marrow involvement. Histopathological examination of a biopsy specimen showed diffuse large B cell lymphoma without a bcl-2 expression. Complete resolution of hypercalcemia and disappearance of tumors were achieved with CHOP therapy, but a rapidly progressive skin lesion was observed soon after the completion of the therapy. The clinical manifestation of primary cutaneous diffuse large B cell lymphoma is diverse and the treatment strategy is not entirely clarified. This case represents another example of this rare lymphoma.

Aged↗
PubMed2003

Postpartum acute myocardial infarction induced by ergonovine administration.

We report a primigravida woman with acute myocardial infarction caused by coronary artery spasm induced by intravenous administration of methyl ergometrine maleate just after delivery. Despite the frequent usage of ergot derivatives to promote uterine contractions, cardiac complications related to this drug are rare. Myocardial infarction may be overlooked in young women in the early postpartum period. Careful monitoring and prompt evaluation should be performed when this drug is administered for obstetrical purposes.

Adult↗
PubMed2003

Role of mechanical stress in monocytes/macrophages: implications for atherosclerosis.

Hypertension is a well-known risk factor for atherosclerosis, but the molecular mechanisms that link elevated blood pressure to atherosclerosis progression remain uncertain. The interactions of mechanical forces and cells of the vasculature are relevant to many cardiovascular diseases. Once a monocyte infiltrates a tissue, it establishes extracellular matrix contacts and is subjected to deformation through those contacts. Macrophages participate in atherogenesis and commonly localize at sites of coronary plaque rupture. Although macrophages may be subjected to excess mechanical stress in these conditions, how biomechanical forces affect macrophage function remains incompletely defined. Recent work demonstrates that human monocytes/macrophages respond to mechanical deformation with selective augmentation of matrix metalloproteinases and induction of immediate-early genes. In human monocytes/macrophages and THP-1 cells, biomechanical strain can induce expression of the class A scavenger receptor, an important lipoprotein receptor in atherogenesis. In addition, DNA microarray analysis reveals that cyclic mechanical strain induces only a few genes (>2.5-fold), including interleukin-8 and IEX-1 in THP-1 cells. Thus, biomechanical deformation of monocytes/macrophages contributes to degradation of extracellular matrix, monocyte differentiation, and promotion of atherosclerosis. These findings suggest that mechanical stress in vivo, such as hypertension, may play an important role in atherogenesis and instability of coronary-artery plaques through biomechanical effects on vascular macrophages.

Animals↗
PubMed2003

Abnormal nocturnal blood pressure falls in elderly hypertension: clinical significance and determinants.

Abnormal patterns of diurnal blood pressure variation have been reported to be related to advanced target organ damage and poor cardiovascular prognosis. We studied silent cerebrovascular disease and stroke events in older Japanese patients with different nocturnal blood pressure dipping. There was a J-shaped relationship of nocturnal dipping status with silent cerebral infarcts detected by brain magnetic resonance imaging at baseline, and with stroke incidence during the follow-up period. The extreme-dippers (with marked nocturnal blood pressure dipping) and the risers (with higher nocturnal blood pressure than awake blood pressure) had a higher prevalence of silent cerebral infarcts and a poorer stroke prognosis than those with appropriate nocturnal blood pressure dipping (dippers). The extreme-dippers tended to have predominant systolic hypertension and increased blood pressure variability. Several factors affect the diurnal blood pressure variation pattern. The non-dipping pattern is associated with autonomic nervous dysfunction and poor sleep quality due to nocturnal behavior and sleep apnea. The extreme-dippers might have increased arterial stiffness with reduced circulating blood volume in addition to an excessive morning surge due to alpha-adrenergic hyperactivity. Anti-hypertensive medication that normalizes the diurnal blood pressure variation might improve the cardiovascular prognosis in high-risk hypertensive patients.

Aged↗
PubMed2003

[Incidence and risk indicators of thromboembolism during the acute phase of single chamber ventricular pacing].

BACKGROUND: The incidence of thromboembolism may be higher in single chamber ventricular pacing than in physiological pacing. However, the incidence of thromboembolism during the acute phase of single chamber ventricular pacing (within 14 days) is not known. OBJECTIVES: The incidence and the risk indicators of thromboembolism were investigated during the acute phase of single chamber ventricular pacing. METHODS: Fifty-five consecutive patients (22 males, 33 females, mean age 67 +/- 9 years) who required VVI pacemakers due to brady-tachy sick sinus syndrome (42 patients) or brady atrial fibrillation (13 patients) in the period from April 1975 to December 2000 were retrospectively reviewed. The patients were divided into groups with thromboembolism and without thromboembolism, and the risk indicators for thromboembolism were analyzed. RESULTS: Seven patients (13%) suffered systemic thromboembolism. Three patients had thromboembolic events during temporary ventricular pacing, and four patients had thromboembolic events just after permanent VVI pacemaker implantation. The following risk indicators were identified in the patients with thromboembolism: hyperlipidemia, hypertension, organic heart disease (p < 0.05, respectively), and diabetes mellitus (p < 0.0005). CONCLUSIONS: Patients with brady-tachy sick sinus syndrome and brady atrial fibrillation have a significant risk of thromboembolism during the acute phase of single chamber ventricular pacing. Effective anticoagulation is needed in these patients.

Aged↗
PubMed2003

[Systemic infection of Aspergillus flavus in a patient with acute lymphoblastic leukemia].

A 57-year-old woman with acute lymphoblastic leukemia (ALL) developed an antibiotics-resistant fever after remission induction therapy. Chest X-ray and computed tomography scan revealed multiple consolidations and cavities. Successively, numerous subcutaneous nodules and a thyroid mass emerged. Aspergillus flavus (A. flavus) was cultured from both sites. Despite the patient's granulocyte recovery, the fever persisted and multiorgan function deteriorated rapidly. However, she was successfully treated with intensive supportive therapy including continuous hemodialysis and filtration. Prolonged use of amphoterin B and itraconazole failed to cure her aspergillosis, but the illness remained indolent thereafter.

Amphotericin B↗