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Biomedical subjects

Kazuyuki Shimada

Publications and source records attributed to Kazuyuki Shimada.

122 records · Page 7Linked to original sources
PubMed2002

HMG-CoA reductase inhibitors reduce interleukin-6 synthesis in human vascular smooth muscle cells.

Interleukin-6 (IL-6) is a key molecule in chronic inflammation and has been implicated in the progression of atherosclerosis. HMG-CoA reductase inhibitors (statins) may reduce the cardiovascular risk and vulnerability of atherosclerotic plaque through nonlipid as well as lipid-lowering mechanisms, but their anti-inflammatory effects on the vascular tissue have not been fully elucidated. We investigated the effects of fluvastatin on IL-6 synthesis in human vascular smooth muscle cells (VSMCs). Addition of fluvastatin decreased IL-6 synthesis in VSMCs in a time (0-24 hours)- and dose (10(-8)-10(-5) mol/L)-dependent manner. Fluvastatin also decreased IL-6 mRNA expression in VSMCs. The effects of fluvastatin on IL-6 expression were completely reversed in the presence of mevalonate or geranylgeranyl-pyrophosphate, but not squalene. Inhibition of Rho by C3 exoenzyme or Rho kinase by Y-27632 significantly decreased IL-6 expression in VSMCs. In conclusion, fluvastatin decreases IL-6 synthesis in human VSMCs through inhibition of Rho pathway. These findings suggested that reduction of IL-6 expression by statins may partially explain their therapeutic effects in patients with coronary artery disease.

ADP Ribose Transferases↗
PubMed2002

Identification of mechanically induced genes in human monocytic cells by DNA microarrays.

BACKGROUND: Hypertension is a risk factor for coronary heart disease. Macrophages are critically involved in both atherogenesis and plaque instability. Although macrophages may be subjected to excess mechanical stress in these diseases, the way in which biomechanical forces affect macrophage function remains incompletely defined. OBJECTIVE: To investigate the molecular response to mechanical force in macrophages. DESIGN AND METHODS: We used a DNA microarray with 1056 genes to describe the transcriptional profile of mechanically induced genes in human monocytic THP-1 cells. Mechanical deformation was applied to a thin and transparent membrane on which cells were cultured. After THP-1 cells were pre-incubated in the presence of phorbol 12-myristate 13-acetate (0.2 micromol/l) for 24 h, THP-1 cells attached to the membrane were subjected to biaxial mechanical strain. Interleukin-8 concentrations were determined using an enzyme-linked immunosorbent assay. RESULTS: In DNA microarray analysis, cyclic mechanical strain at 1 Hz induced only three genes more than 2.5-fold at 3 and 6 h in THP-1 cells: prostate apoptosis response-4 (3.0-fold at 3 h, 6.7-fold at 6 h), interleukin-8 (4.3-fold at 6 h) and the immediate-early response gene, IEX-1 (2.6-fold at 6 h). Real-time reverse transcriptase polymerase chain reaction analysis confirmed the amplitude-dependent induction of these three genes. In addition, mechanical strain increased interleukin-8 protein expression. CONCLUSION: The present study demonstrates that human monocytic cells respond to mechanical deformation with induction of immediate-early and inflammatory genes. These findings suggest that mechanical stress in vivo, such as that associated with hypertension, may play an important part in atherogenesis and instability of coronary artery plaques, through biomechanical effects on vascular macrophages.

Apoptosis Regulatory Proteins↗
PubMed2002

Fluvastatin enhances apoptosis in cytokine-stimulated vascular smooth muscle cells.

Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have been shown to attenuate proliferation of vascular smooth muscle cells (VSMCs) by mechanisms independent of lipid reduction. In the current study, we investigated the effect of lipophilic and hydrophilic statins (fluvastatin and pravastatin) on apoptosis in unstimulated or cytokine-stimulated VSMCs. The presence of apoptosis in rat VSMCs was evaluated by electrophoresis of DNA fragments and 4'6'-diamidine-2'-phenylindole staining and quantified by flow cytometry. Fluvastatin but not pravastatin enhanced apoptosis in interleukin-1beta-stimulated VSMCs. The proapoptotic effect of fluvastatin was fully reversed by mevalonate and geranylgeranyl-pyrophosphate, and partially by farnesyl-pyrophosphate, but not by squalene. Inhibition of the extracellular signal-regulated protein kinase (ERK1/2) pathway significantly increased fluvastatin-enhanced apoptosis, whereas inhibition of the p38-mitogen-activated protein kinase (MAPK) pathway significantly prevented this increase. However, fluvastatin showed no effect on the activity of ERK1/2 and p38-MAPK. Furthermore, fluvastatin-induced apoptosis was inhibited by YVAD-FMK (a caspase-1/interleukin-1beta-converting enzyme-like protease inhibitor) and DEVD-FMK (a caspase-3/CPP32 inhibitor), indicating involvement of an important segment in the apoptosis signaling pathway. These findings suggest that fluvastatin enhances apoptosis in cytokine-stimulated VSMCs and that protein prenylation, MAPK (ERK1/2 and p38-MAPK), and caspases are critically involved in the pathways of fluvastatin-enhanced apoptosis.

Animals↗
PubMed2002

Fluvastatin induces apoptosis in rat neonatal cardiac myocytes: a possible mechanism of statin-attenuated cardiac hypertrophy.

Hydroxymethylglutaryl CoA (HMG-CoA) reductase inhibitors (statins) have been shown to reduce atherosclerotic cardiovascular mortality and morbidity. Recent evidence indicates that statins may also exert direct effects on vascular wall cells (including endothelial cells and smooth muscle cells) independently of their hypocholesterolemic properties. However, little is known about whether statins have direct effects on myocardium. The effect of lipophilic and hydrophilic statins (fluvastatin and pravastatin) on apoptosis and protein synthesis in rat neonatal cardiac myocytes was investigated. The presence of apoptosis was evaluated by morphologic criteria, electrophoresis of DNA fragments, 4",6"-diamidine-2"-phenylindole (DAPI) staining, and TUNEL assay. Protein synthesis was measured by H-leucine incorporation into the cells. Fluvastatin, but not pravastatin, induced apoptosis in cardiac myocytes in a time- and dose-dependent manner. The pro-apoptotic effect of fluvastatin was reversed in the presence of mevalonate or geranylgeranyl-pyrophosphate (GGPP), but not in the presence of squalene. The addition of protein prenylation inhibitor perillic acid and Rho-kinase inhibitor Y27632 significantly increased apoptosis. Fluvastatin decreased RhoA protein in the membrane fraction, whereas there were no significant changes of the RhoA protein in the cytosol fraction. Interleukin-1beta-stimulated H-leucine incorporation was completely inhibited by fluvastatin, but not by pravastatin. The findings suggest that fluvastatin induces apoptosis in cardiac myocytes via protein prenylation and the subsequent inhibition of Rho, and may play a role in the pathogenesis of cardiac hypertrophy and remodeling.

Animals↗
PubMed2002

Transient complete atrioventricular block occurring 1 week after radiofrequency ablation for the treatment of atrioventricular nodal re-entrant tachycardia.

Atrioventricular (AV) block following radiofrequency (RF) ablation for the treatment of AV nodal re-entrant tachycardia (AVNRT) is a rare but serious complication of this procedure. Almost all such cases occur during or immediately after radiofrequencey (RF) energy application, followed by prompt recovery. The present report describes a 22-year-old woman with first-degree AV block on electrocardiography, who developed complete AV block 1 week after RF ablation for the treatment of the uncommon form of AVNRT (slow/slow). The patient's complete AV block persisted for another 1 week before she recovered.

Adult↗
PubMed2002

Differential effects of a long-acting angiotensin converting enzyme inhibitor (temocapril) and a long-acting calcium antagonist (amlodipine) on ventricular ectopic beats in older hypertensive patients.

We studied differences in the effects of a long-acting angiotensin-converting enzyme (ACE) inhibitor (temocapril) and a long-acting calcium channel blocker (amlodipine) on ventricular ectopic beats (VEB) in relation to sympathetic nerve activity in 46 patients with essential hypertension. We performed 24-h Holter electrocardiography and ambulatory blood pressure (BP) monitoring simultaneously, and examined blood samples during the baseline, temocapril and amlodipine treatment periods. The ambulatory BP was lower in the amlodipine period than in the temocapril period. However, the number of VEB was significantly increased in the amlodipine period compared to that in the baseline period (11.9 vs. 7.4/day, p<0.05). In the temocapril period, the number of VEB was not significantly increased compared to that in the baseline period (8.6 vs. 7.4/day, p=0.30). Ambulatory heart rate (HR) was significantly increased in the amlodipine period compared to that in the baseline period (24-h HR: 70 vs. 66 bpm, p<0.001; daytime HR: 75 vs. 71 bpm, p<0.001; nocturnal HR: 60 vs. 58 bpm, p<0.05). Plasma norepinephrine (NE) also was significantly increased in the amlodipine period compared to that in the baseline period (457 vs. 369 pg/ml, p<0.001). However, when patients receiving amlodipine were divided into a high dose group (8.6 +/- 1.2 mg/day) and a low dose group (4.6 +/- 1.2 mg/day), increases in HR and plasma NE levels were found only in the high dose group. These results indicate that amlodipine is effective at lowering BP in older hypertensives, although it may increase VEB, especially when given at a high dose.

Aged↗
PubMed2002

Two cases of malignant hypertension with reversible diffuse leukoencephalopathy exhibiting a reversible nocturnal blood pressure "riser" pattern.

We report two cases of malignant hypertension with reversible diffuse leukoencephalopathy demonstrating a nocturnal blood pressure (BP) rising pattern ("riser" pattern). Case 1 was a 54-year-old man diagnosed with malignant hypertension who presented with diffuse leukoencephalopathy and nocturnal BP rise during the acute phase. These abnormal findings diminished after treatment of hypertension. Case 2 was a 50-year-old woman diagnosed with malignant hypertension in association with leukoencephalopathy, heart failure and acute renal failure. She also presented with a "riser" pattern during the acute phase. In contrast to case 1, the leukoencephalopathy and "riser" pattern in case 2 were not improved even after 1 month of treatment. Following intensive antihypertensive treatment, renal failure was improved in case 1, but renal failure was not improved after 1 month in case 2. In conclusion, a possible explanation of this phenomenon is that a causative volume overload due to renal dysfunction produced the temporal leukoencephalopathy-like brain edema and "riser" pattern in these cases.

Blood Pressure↗
PubMed2002

Questionnaire survey on the Japanese guidelines for treatment of hypertension in the elderly: 1999 revised version.

A questionnaire survey was administered to Japanese clinical specialists in hypertension in order to gauge their opinions on the 1999 revised version of the Guidelines for Hypertension in the Elderly prepared by the Comprehensive Research Project on Aging and Health of the Ministry of Health and Welfare. Out of 162 council members of the Japanese Society of Hypertension, 122 (75%) replied. The majority (93%) of respondents approved of the guidelines in general, and 72% of them approved of the age-related setting of a therapeutic goal for blood pressure. Sixty-five percent of respondents selected long-acting Ca antagonists, ACE inhibitors and low-dose diuretics as first-line agents for hypertension without complications in the elderly. The results of the questionnaire survey should be reflected in the next version of the guidelines.

Aged↗
PubMed2002

[Silent and clinically overt stroke in older Japanese subjects with white-coat and sustained hypertension].

BACKGROUND: Whether white-coat hypertension in older subjects is a benign condition or is associated with an increased risk for stroke remains uncertain. White-coat hypertension as a risk factor for stroke was investigated in relation to silent cerebral infarct in the older Japanese population. METHODS: The prognosis for stroke was studied in 958 older Japanese subjects [147 normotensives (NT), 236 white-coat hypertensives (WCHT), and 575 sustained hypertensives (SHT)] in whom ambulatory blood pressure monitoring was performed in the absence of antihypertensive treatment. Silent cerebral infarct was also assessed using brain magnetic resonance imaging in 585 subjects (61%). RESULTS: Silent cerebral infarcts were found in 36% of NT (n = 70), 42% of WCHT (n = 154), and 53% of SHT (n = 361), and multiple silent cerebral infarcts(presence of > or = 2 silent cerebral infarcts) were found in 24% of NT, 25% of WCHT, and 39% of SHT. During a mean 42-month-follow-up period, clinically overt strokes occurred in 62 subjects [NT 3(2.0%), WCHT 5(2.1%), SHT 54(9.4%)], with 14 fatal cases [NT 1(0.7%), WCHT 0(0%), SHT 13 (2.3%)]. Cox regression analysis showed that age (p = 0.0001) and SHT [RR(95% confidence interval): 4.3 (1.3-14.2), p = 0.018] were independent stroke predictors, whereas WCHT was not significant. Adding presence/absence of silent cerebral infarct at baseline into this model, the RR (95% confidence interval) for silent cerebral infarct was 4.6 (2.0-10.5) (p = 0.003), and that of SHT was 5.5 (1.8-18.9) vs WCHT (p = 0.004) and 3.8 (0.88-16.7) vs NT (p = 0.07). CONCLUSIONS: The incidence of stroke in WCHT is similar to that of NT, and one fourth the risk in SHT in older subjects. Although silent cerebral infarct is a strong predictor of stroke, the difference in stroke prognosis between SHT and WCHT was independent of silent cerebral infarct. It is clinically important to distinguish WCHT from SHT even after assessment of target organ damage in the elderly.

Aged↗
PubMed2002

[Beneficial effect of ARB for ischemic stroke].

Angiotensin II plays a pathophysiological role for the development of cardiovascular disease. Angiotensin receptor blocker(ARB) is an antihypertensive drug that blocks the angiotensin II receptor. Recently, according to the reports of basic research, ARB has various cerebrovascular-protective-effects such as improvement of cerebrovascular auto-regulation, stroke prevention, reduction of brain edema, improvement of neurological outcome in cerebral ischemia and so on. There is no report of ARB being used for the acute stage of stroke. In an ongoing ACCESS(Acute Candesartan Cilexetil Evaluation in Stroke Survivors) trial, the ARB candesartan is being used to treat the acute stage of stroke. This trial is expected to clarify whether early treatment with candesartan during the acute stage of stroke is beneficial for the neurological outcome or prognosis.

Angiotensin Receptor Antagonists↗
PubMedDate not supplied

Corrosion casts of convoluted testicular arteries in mice and rats.

The preparation of vascular corrosion casts enables us to observe the minute features of blood vessels. For mice and rats, reports on the macroscopical appearance of testicular arteries with the cast technique have been quite limited. Therefore, in the present study, we tried to prepare corrosion casts of such arteries in order to observe the three-dimensional structures in mice and rats. Vascular casts of testicular arteries were produced by intravenous injection of a polymethylmethacrylate solution, followed by treatment of the whole animal bodies with NaOH. Additionally, the gross appearance of human testicular arteries in cadavers was compared with that of the vascular casts. The results showed that the testicular arteries of humans, mice, and rats run from the abdominal aorta to the testes, with various configurations (straight, meandering, spiral, or coiled forms), and each species exhibits a specific pattern. The specific forms of testicular arteries may play several roles in protection of normal spermatogenesis, such as allowing wide mobility of the testes on physical attack, heat emission with the entwined pampiniform plexus, and reduction of the blood flow rate. The great extension of the testicular arteries during the fetal period from the upper abdomen to the scrotum when the testes descend might be another feature of the specific development of their running configuration.

Animals↗
PubMedDate not supplied

Circadian variation of blood pressure and neurohumoral factors during the acute phase of stroke.

This study was to investigate the relationship between circadian blood pressure (BP) variation and circadian variation of neurohumoral factors during the acute phase of stroke. We studied 17 patients with cerebral infarction in 16 and cerebral hemorrhage in one. We performed 24-hour ambulatory BP monitoring and examined plasma renin activity (PRA), catecholamine, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), endothelin 1 (ET1) and prothrombin fragment 1+2 (PT F1+2) and urinary catecholamine. Our result showed that the circadian variation of BP, neurohumoral and coagulation factors were diminished. There were significant relationships between BP levels and plasma BNP levels, nocturnal urinary adrenalines and ET1s. There were also significant relationships between night/day ratio of BP and plasma ET1 level. In conclusion the abnormal patterns of circadian BP rhythm were frequently observed during the acute phase of stroke. The cause of this abnormality may result from the diminished circadian rhythms of neurohumoral factors.

Aged↗