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Biomedical subjects

K Shimamoto

Publications and source records attributed to K Shimamoto.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Cardioprotective mechanism of ischemic preconditioning is impaired by postinfarct ventricular remodeling through angiotensin II type 1 receptor activation].

BACKGROUND: Activation of protein kinase C-linked receptors and subsequent opening of the mitochondrial adenosine triphosphate-sensitive K+ (mitoKatp) channel is crucial in preconditioning. This study examined whether post-infarct ventricular remodeling interferes with the preconditioning mechanism. METHODS AND RESULTS: Two weeks before isolation of hearts, rabbits underwent a sham operation or coronary ligation (COL) to induce remodeling. Isolated buffer perfused hearts were subjected to 30-min global ischemia/2-hr reperfusion, and infarct size was expressed as a percentage of the left ventricle (%I/LV), from which the scarred infarct by COL was excluded. Although %I/LV was similar in sham-operated and remodeled hearts (52.9 +/- 6.5% vs 45.8 +/- 5.2%), preconditioning with 2 episodes of 5-min ischemia protected sham-operated but not remodeled hearts (%I/LV = 18.1 +/- 2.5% vs 54.8 + 2.9%, p < 0.05). Infusion of valsartan (10 mg/kg/day; Val), an angiotensin II type 1 receptor blocker, for 2 weeks after COL prevented the ventricular remodeling and preserved the response to preconditioning (%I/LV = 27.4 +/- 3.8%), though Val alone did not change %I/LV. Diazoxide, a mitoKatp channel opener, protected both sham-operated and remodeled hearts (%I/LV = 14.1 +/- 3.1% and 8.3 +/- 3.6%). CONCLUSIONS: The myocardium remodeled after infarction is refractory to preconditioning, which is probably due to interruption of cellular signaling by preconditioning upstream of mitoKatp channels. An angiotensin II type 1 receptor blocker is beneficial not only for suppression of ventricular remodeling but also for preservation of the preconditioning mechanism.

Angiotensin Receptor Antagonists↗
PubMed2001

[Night-eating syndrome].

Morning anorexia, evening hyperphagia and insomnia characterized night-eating syndrome. This syndrome is described in 1955 by Stunkard, et al. It occurred during periods of stress and was associated with a poor outcome of efforts at weight reduction. The prevalence of this syndrome was about 26% of severely obese population in US. In Japan, there is few clinical study of this syndrome. It is thought that this syndrome increases in prevalence with increasing adiposity. The behavior study showed that a coherent pattern of behavior was found in subjects with night-eating syndrome. And neuroendocrine study indicated that the leptin, which was produced from the adipocyts, related this syndrome and night eating behavior.

Feeding and Eating Disorders↗
PubMed2001

[Usefulness of right ventricular Doppler index for predicting outcome in patients with dilated cardiomyopathy].

OBJECTIVES: Left ventricular Doppler index (LVDI) is believed to be a useful echocardiographic index of systolic and diastolic ventricular function. However, the usefulness of right ventricular Doppler index (RVDI) remains uncertain, especially in dilated cardiomyopathy. The predictive value of RVDI for estimating long-term cardiac events, including cardiac death, was investigated. METHODS: Fifty-nine consecutive patients with dilated cardiomyopathy (41 males and 18 females, mean age 52 +/- 15 years) were enrolled in this follow-up study. RVDI and LVDI were calculated as follows: DI = (isovolumic contraction time + isovolumic relaxation time)/ejection time. RESULTS: During a follow-up period of 3.7 +/- 3.0 years, 27 (46%) of the patients exhibited cardiac events, including cardiac death (n = 9), heart failure (n = 16) and tachyarrhythmias (n = 2) requiring in-hospital treatment. Patients with these cardiac events had higher LVDI and RVDI at the initial follow-up examination, and RVDI had a significant linear correlation with LVDI (LVDI = 0.550 + 0.452 x RVDI, r = 0.530, p = 0.0001). The 6-year survival rate was significantly lower in patients with both LVDI > or = 0.78 and RVDI > or = 0.49 than in other patients (50% vs 75%, respectively, p = 0.009). Cox proportional hazards model analysis showed that RVDI > or = 0.49 was the independent predictor of cardiac events (p = 0.0153) and cardiac death (p = 0.0003). CONCLUSIONS: RVDI is clinically useful for estimating the outcome of patients with dilated cardiomyopathy.

Adult↗
PubMed2001

Defect in human myocardial long-chain fatty acid uptake is caused by FAT/CD36 mutations.

Because of the importance of long-chain fatty acids (LCFAs) as a myocardial energy substrate, myocardial LCFA metabolism has been of particular interest for the understanding of cardiac pathophysiology. Recently, by using radiolabeled LCFA analogues, myocardial LCFA metabolism has been clinically evaluated, which revealed a total defect of myocardial LCFA accumulation in a small number of subjects. The mechanism for the cellular LCFA uptake process is still disputable, but recent results suggest that fatty acid translocase (FAT)/CD36 is a transporter in the heart. In the present study, we analyzed mutations and protein expression of the FAT/CD36 gene in 47 patients who showed total lack of the accumulation of a radiolabeled LCFA analogue in the heart. All the patients carried two mutations in the FAT/CD36 gene, and expression of the FAT/CD36 protein was not detected on either platelet or monocyte membranes. Our results showed the link between mutations of the FAT/CD36 gene and a defect in the accumulation of LCFAs in the human heart.

Adolescent↗
PubMed2001

[Insulin resistance syndrome].

Insulin resistance and hyperinsulinemia have been observed in essential hypertension. The selective impairment of glucose metabolism in skeletal muscle may accompanied hyperinsulinemia and raise blood pressure through sympathetic nervous system and/or renin-angiotensin system activation, renal sodium retention, proliferation of vascular smooth muscle and leptin. Recently, molecular techniques have applied for investigating the mechanisms of insulin resistance. The mutation of insulin receptor gene, changes of muscle fiber composition and muscle blood flow, abnormalities of insulin signal transduction, and TNF-alpha are considered as involvement of insulin resistance in the skeletal muscle. While further study will be necessary to clarify the mechanisms of insulin resistance and hypertension.

Animals↗
PubMed2001

Assessment of underlying etiology and cardiac sympathetic innervation to identify patients at high risk of cardiac death.

UNLABELLED: Cardiac (123)I-labeled metaiodobenzylguanidine (MIBG) activity has significant incremental prognostic value, but the difference between the long-term prognostic value of MIBG imaging for ischemic cardiomyopathies and the long-term prognostic value of MIBG imaging for idiopathic cardiomyopathies is not clear. This study aimed to determine whether assessment of cardiac (123)I-MIBG activities in ischemic and idiopathic cardiomyopathies have equally prognostic values and whether the kinetics are different because of the underlying etiologies. METHODS: After quantitative (123)I-MIBG imaging, 76 ischemic and 56 idiopathic cardiomyopathy patients were prospectively followed up for 54 mo. In addition to conventional parameters, cardiac (123)I-MIBG activity was quantified as a heart-to-mediastinum ratio (H/M) for early and late images and the washout kinetics were calculated using tomographic imaging. The data were compared with those obtained from 16 healthy volunteers. RESULTS: During follow-up, 29 deaths from heart failure, 11 sudden cardiac deaths, 2 deaths from arrhythmia, and 5 deaths from acute myocardial infarction were documented. Multivariate discriminant analysis using the Cox proportional hazards model showed that, in comparison with other variables, late H/M was the most powerful independent predictor of a lethal clinical outcome in ischemic (Wald chi(2) = 18.6502; P = 0.0000) and idiopathic (Wald chi(2) = 5.3394; P = 0.0208) groups. When patients with left ventricular ejection fraction (LVEF) < 40% were considered, late H/M had the greatest statistical power in both groups. Kaplan-Meier analysis showed late H/M to have an identical threshold (1.82) for both groups for identifying patients at risk of cardiac death. Likewise, when analysis was restricted to patients with an LVEF < 40%, the upper cutoff value of late H/M was 1.50 (P = 0.0358; log rank = 4.41) for ischemic patients and 2.02 (P = 0.0050; log rank = 7.86) for idiopathic patients. For patients with an LVEF < 40% and a late H/M less than the identified threshold of late H/M, the annual rate of cardiac death was greatest, 18.2%/y for the ischemic group and 11.9%/y for the idiopathic group. CONCLUSION: Cardiac (123)I-MIBG activity has the most powerful independent long-term prognostic value for both ischemic cardiomyopathy patients and idiopathic cardiomyopathy patients, indicating that both disease processes have common pathophysiologic and prognostic implications of impaired cardiac sympathetic innervation. Although combined testing of cardiac function and (123)I-MIBG activity is most likely to identify patients at increased risk of cardiac death, the underlying etiology of cardiac dysfunction may affect the threshold of (123)I-MIBG activity for the differentiation of high-risk patients.

3-Iodobenzylguanidine↗
PubMed2001

[The role of renal vasodepressor and natriuretic systems and ouabain-like factor on the early phase of hypertension in two-kidney, one-clip hypertensive rats].

Recent studies have shown that not only an enhanced renin-angiotensin system, but also relative volume retention might contribute to hypertension even in the early phase of a two-kidney, one-clip hypertensive model. To evaluate the role of renal depressor and natriuretic systems in the development of high blood pressure in the early phase of this model, we measured urinary excretion of kallikrein(uKAL), prostaglandin E2(uPGE2), and dopamine(uDA) in male Sprague-Dawley rats instrumented with a 0.2 mm diameter clip on the left renal artery(2K1C) and compared the results with those of sham-operated rats(sham). We also measured ouabain-like factor(OLF) in the plasma(pOLF) and urine(uOLF) in both groups. In 2K1C, systolic blood pressure(SBP) progressively increased and plasma renin activity was higher than the sham in the 3rd week. UDA and uPGE2 were not different between these groups, but uKAL attenuated in 2K1C in the 1st and 3rd week compared to the sham. There was a negative correlation between %delta SBP and %delta uKAL. On the other hand, uOLF increased in 2K1C in the 1st, 2nd and 3rd week compared to the sham. There was a positive correlation between SBP and uOLF. And pOLF was higher in 2K1C than in the sham. Furthermore there was a negative correlation between %delta uKAL and %delta uOLF. These results indicated that even in the early phase, suppression of the renal kallikrein-kinin system would contribute to high blood pressure in part, and OLF might play a compensatory role against the impaired natriuretic system in the kidney. However, OLF might contribute to blood pressure elevation through vasoconstriction in 2K1C.

Animals↗
PubMed2000

Right ventricular abnormalities assessed by myocardial single-photon emission computed tomography using technetium-99m sestamibi/tetrofosmin in right ventricle-originated ventricular tachyarrhythmias.

OBJECTIVES: We sought to determine whether right ventricular (RV) perfusion imaging with technetium-99m (Tc-99m) sestamibi or tetrofosmin single-photon emission computed tomography has diagnostic benefit for RV-originated ventricular tachyarrhythmias (RVT). BACKGROUND: Identification of RV abnormalities is clinically important to establish RVT etiology. METHODS: Forty-seven patients with RVT (23 with idiopathic and 24 with organic RVT due to arrhythmogenic RV or dilated cardiomyopathy, cardiac sarcoidosis or myocarditis) were compared to 25 control subjects. Right ventricular uptake score, as assessed by modified tomographic imaging, and regional RV count relative to peak left ventricular (LV) count (RV/LV count ratio) were compared with RV regional and global function. RESULTS: Regional RV uptake score correlated well with the RV/LV count ratio, and segmental abnormality was more frequently (p = 0.001) detected in the organic RVT group (22 [92%] of 24 patients) than in the idiopathic RVT group (4 [17%] of 23 patients) or the control group (8 [32%] of 25 patients). The total RV score (8.4+/-3.8) in the organic RVT group was significantly lower than that in the idiopathic RVT group (15.6+/-1.6) or the control group (15.1+/-1.8). The total RV score correlated with RV EF (r = 0.702, p<0.001). A total RV score <12 differentiated the organic RVT group from the other two groups, with a sensitivity of 79% and a specificity of 100%. The asynergic RV regions had a significantly lower RV/LV count ratio and RV score as compared with the nonasynergic regions and were identified by RV assessment, with a sensitivity of 76.1% and a specificity of 76.6%. CONCLUSIONS: Right ventricular perfusion tomography using a Tc-99m-labeled tracer is clinically useful for the noninvasive detection of RV myocardial damage in patients with RVT and for differentiating organic from idiopathic RVT.

Adolescent↗
PubMed2000

Syntheses of optically pure beta-hydroxyaspartate derivatives as glutamate transporter blockers.

DL-threo-beta-benzyloxyaspartate (DL-TBOA) is a non-transportable blocker of the glutamate transporters that serves as an indispensable tool for the investigation of the physiological roles of the transporters. To examine the precise interaction between a blocker and the transporters, we synthesized the optically pure isomers (L- and D-TBOA) and its erythro-isomers. L-TBOA is the most potent blocker for the human excitatory amino acid transporters (EAAT1-3), while D-TBOA revealed a difference in the pharmacophores between EAAT1 and EAAT3. We also synthesized the substituent variants (methyl or naphthylmethyl derivatives) of L-TBOA. The results obtained here suggest that bulky substituents are crucial for non-transportable blockers.

ATP-Binding Cassette Transporters↗
PubMed2000

Cardioprotective mechanism of ischemic preconditioning is impaired by postinfarct ventricular remodeling through angiotensin II type 1 receptor activation.

BACKGROUND: Activation of protein kinase C-linked receptors and subsequent opening of the mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel are crucial in preconditioning (PC). This study examined whether postinfarct ventricular remodeling interferes with the PC mechanism. METHODS AND RESULTS: Two weeks before isolation of hearts, rabbits underwent a sham operation or coronary ligation (COL) to induce remodeling. Isolated buffer-perfused hearts were subjected to 30-minute global ischemia/2-hour reperfusion, and infarct size was expressed as a percentage of the left ventricle (%I/LV), from which the scarred infarct by COL was excluded. Although %I/LV was similar in sham-operated and remodeled hearts (52.9+/-6.5% versus 45.8+/-5.2%), PC with 2 episodes of 5-minute ischemia protected sham-operated but not remodeled hearts (%I/LV=18.1+/-2.5% versus 54.8+/-2.9%, P<0.05). Infusion of valsartan (10 mg x kg(-1). d(-1), an angiotensin II type 1 (AT(1)) receptor blocker, for 2 weeks after COL prevented the ventricular remodeling and preserved the response to PC (%I/LV=27.4+/-3.8%), although valsartan alone did not change %I/LV. Diazoxide, a mitoK(ATP) channel opener, protected both sham-operated and remodeled hearts (%I/LV=14.1+/-3.1% and 8.3+/-3.6%). CONCLUSIONS: The myocardium remodeled after infarction is refractory to PC, which is probably due to interruption of cellular signaling by PC upstream of mitoK(ATP) channels. An AT(1) receptor blocker is beneficial not only for suppression of ventricular remodeling but also for preservation of the PC mechanism.

Angiotensin II↗
PubMed2000

Electrocardiographic and echocardiographic abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy and in their pedigrees.

Electrocardiographic and echocardiographic evaluations in 18 patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and 29 family members (25 males and 25 females from 7 pedigrees) aged 5 to 64 years (mean +/- 1 SD 30 +/- 16) revealed that 5 of 28 ARVC family members (17%) fulfilled ARVC Task Force criteria. Indexes on late potentials of the signal-averaged electrocardiogram had a significant linear correlation with the age of patients with ARVC and of family members with echocardiographic wall motion abnormality.

Adolescent↗
PubMed2000

Impaired myocardial accumulation of 15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid in a patient with hypertrophic cardiomyopathy and exercise-induced ischemia due to vasospasm.

We encountered a patient with hypertrophic cardiomyopathy complicated with exercise-induced myocardial ischemia. Exercise-stress 99mTc-tetrofosmin imaging demonstrated reversible ischemia in the lateral wall, whereas resting fatty acid imaging with a new beta-methyl branched fatty acid analogue, I-123-15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid (123I-9-MPA), showed impaired uptake and accelerated washout kinetics in the inferoapical and posteroseptal walls but not in the ischemia-related region. These findings suggest that the metabolic derangement is closely related to cardiomyopathy per se rather than exercise-induced myocardial ischemia in this patient with hypertrophic cardiomyopathy and a spastic coronary lesion so that myocardial perfusion and 123I-9-MPA imagings may contribute to clarifying the etiological background of impaired myocardial fatty acid metabolism.

Aged↗
PubMed2000

Role of ultrasonography in the detection of intraductal spread of breast cancer: correlation with pathologic findings, mammography and MR imaging.

The purpose of this study was to assess the role of US in the detection of intraductal spread of breast cancer in comparison with mammography (MMG) and MRI. In 46 patients with breast cancer, US features of the intraductal component were classified as ductal type or distorted type. Histopathologically, 29 of 46 (63%) cases had intraductal components, and the sensitivity, specificity, and accuracy rates in detection of intraductal spread were 89, 76, and 85%, respectively. Each US pattern demonstrated good correspondence to the histologic components, and the distorted type correlated well with comedo-type carcinoma. Mammography was performed in all cases, and the sensitivity, specificity, and accuracy rates in detection of intraductal spread were 55, 100, and 72%, respectively. In comedo type, MMG could diagnose the extent of intraductal spread more accurately compared with US examination. Magnetic resonance imaging comparison was available in 25 cases. Magnetic resonance imaging depicted intraductal extension as an enhanced area during the early phase of a contrast enhancement study with a sensitivity of 93%. Ultrasound and MRI were closely related in terms of morphologic characteristics: the ductal type of US image correlated well with linear enhancement on MRI, whereas the distorted type correlated with regional or segmental enhancement. Current US examination is useful in depicting the intraductal spread of breast cancer; however, US has a tendency to underestimate intraductal component of comedo type compared with MMG and MRI.

Breast↗
PubMed2000

Roles of mitochondrial ATP-sensitive K channels and PKC in anti-infarct tolerance afforded by adenosine A1 receptor activation.

OBJECTIVES: This study intended to assess the role of mitochondrial ATP-sensitive potassium (mitoK ATP) channels and the sequence of signal transduction with protein kinase C (PKC) and adenosine A1 receptors in rabbits. BACKGROUND: To our knowledge, the link between trigger receptors of preconditioning, PKC and mitoK ATP channels has not been examined in a whole heart model of infarction. METHODS: In the first series of experiments, myocardial infarction was induced in isolated buffer-perfused rabbit hearts by 30-min global ischemia and 2-h reperfusion. Infarct size in the left ventricle was determined by tetrazolium staining and expressed as a percentage of area at risk (i.e., the whole left ventricle) (%IS/AR). In the second series of experiments, mitochondria were isolated from the heart, and their respiratory function was examined using glutamate as a substrate. RESULTS: Pretreatment with R-phenylisopropyladenosine (R-PIA, 1 micromol/liter), an A1-receptor agonist, reduced %IS/AR from 49.8 +/- 6.5% to 13.4 +/- 2.9%. This protection was abolished by calphostin C, a PKC inhibitor, and by 5-hydroxydecanoate (5-HD), a selective inhibitor of mitoK ATP channels. A selective mitoK ATP channel opener, diazoxide (100 micromol/liter), mimicked the effect of R-PIA on infarct size (%IS/AR = 11.6 +/- 4.0%), and this protective effect was also abolished by 5-HD. However, calphostin C failed to block the infarct size-limiting effect of diazoxide. Neither calphostin C nor 5-HD alone modified %IS/AR. State III respiration (QO2) and respiratory control index (RCI) were reduced after 30 min of ischemia (QO2 = 147.3 +/- 5.3 vs. 108.5 +/- 12.3, RCI = 22.3 +/- 1.1 vs. 12.1 +/- 1.8, p < 0.05). This mitochondrial dysfunction was persistent after 10 min of reperfusion (QO2 = 96.1 +/- 15.5, RCI = 9.5 +/- 1.9). Diazoxide significantly attenuated the respiratory dysfunction after 30 min of ischemia (QO2 = 142.8 +/- 9.7, RCI = 16.2 +/- 0.8) and subsequent 10-min reperfusion (QO2 = 135.3 +/- 7.2, RCI = 19.1 +/- 0.8). CONCLUSIONS: These results suggest that mitoK ATP channels are downstream of PKC in the mechanism of infarct-size limitation by A1-receptor activation and that the anti-infarct tolerance afforded by opening of mitoK ATP channels is associated with preservation of mitochondrial function during ischemia/reperfusion.

Adenosine Triphosphate↗