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Biomedical subjects

Issei Komuro

Publications and source records attributed to Issei Komuro.

At least 73 records · Page 4Linked to original sources
PubMed2006

[Pharmacological therapeutics based on molecular mechanisms].

Pharmacological treatment of chronic heart failure has considerably changed according as a shift of the pathophysiological concept. During the past two decades, it became clear that neurohumoral stimulations play an important role in the progression of heart failure by promoting cardiac remodeling. Administration of angiotensin-converting enzyme-inhibitors, angiotensin II receptor blockers, and beta blockers is now an essential treatment that reduces morbidity and mortality. In spite of an increase in available treatments, the prognosis of symptomatic heart failure remains to be poor. To establish newer and successful treatments, further advancement in our understanding of the molecular mechanisms underlying the pathogenesis of heart failure will be required. Currently, several novel approaches are being tested targeting prevention of cardiac remodeling and myocardial dysfunction. Cardiomyocyte protection by hematopoietic cytokines and stem cell-based therapy may have a promising therapeutic potential.

Cell Death↗
PubMed2006

A novel mechanism of mechanical stress-induced hypertrophy.

Angiotensin II (AII) type 1 (AT1) receptor plays a critical role in load-induced cardiac hypertrophy. We have recently found a novel mechanism of mechanical stress-induced activation of the AT1 receptor, which is independent of AII. Mechanical stretch did not activate ERKs in HEK293 cells and COS7 cells which had no AT1 receptor, but when AT1 receptor was overexpressed in these cells, stretch activated ERKs, Galphaq and JAK2. An AT1 receptor blocker, candesartan, inhibited stretch-induced activation of ERKs in these cells. Stretch also activated ERKs in COS7 cells expressing AT1 mutant which did not bind AII and in cardiac myocytes prepared from angiotensinogen null mice. Stretch did not activate ERKs in COS7 cells which overexpressed ETA receptor and beta-adrenergic receptor. Pressure overload induced cardiac hypertrophy in angiotensinogen null mice as well as in wild-type mice, which was significantly inhibited by candesartan. These results suggest that mechanical stress activates AT1 receptor independently of AII, which is inhibited by an inverse agonist candesartan.

Animals↗
PubMed2005

Retrospective ECG-gated left ventriculography using multislice CT following left ventricular bolus injection and evaluation of its utility and motion artifact at every cardiac phase.

Following left ventricular bolus injection of contrast material, multislice CT scanning was performed. With retrospective ECG-gated reconstruction, we could acquire volume data for the heart at any cardiac phase and selectively depict only the left ventricle and aorta with maximum intensity projection. Temporal resolution of multislice CT was not sufficient to eliminate motion artifact except just before atrial contraction periods.

Aged↗
PubMed2005

Influence of heart rate on the detectability and reproducibility of multislice computed tomography for measuring coronary calcium score using a pulsating calcified mock-vessel in comparison with electron beam tomography.

BACKGROUND: The influence of heart rate on detectability and reproducibility of multislice computed tomography (MSCT) for measuring coronary calcium score was evaluated using pulsating calcified mock-vessels and compared with electron beam tomography (EBT). MATERIALS AND METHODS: Four calcified mock-vessels with 200-350 HU were made to pulsate at a rate of 40-80 beat/min. Retrospective ECG-gating MSCT (Light Speed Ultra 16) scanning with 0.625 mm slice-thickness was performed twice at each pulsation rate. For comparison, EBT (Imatron C150 XP) was performed with 3 and 1.5 mm beam collimation with prospective ECG-gating and calcium scores were measured. RESULTS: The comparison revealed that MSCT did not have better reproducibility than EBT, but the calcium scores with MSCT were less influenced by pulsation rates than those with EBT. Especially in mild calcification, the calcium scores decreased with EBT with 3 mm beam collimation with increasing pulsation rate, but the scores were stable in any rate with MSCT. CONCLUSION: MSCT effectively detects coronary calcification, especially mild calcification, without being influenced by heart rate. This is accomplished by reducing the partial volume effect in the through plane using sub millimeter slice thickness, and using appropriate reconstruction methods, which improve temporal resolution.

Calcinosis↗
PubMed2005

Utility of triple channel injection of contrast material with mixture of saline, with acquisition in the cephalic direction for arterial trees in the thorax using multislice computed tomography.

BACKGROUND: If contrast material is injected into the cubital vein, artifacts due to high concentration of the contrast material in the vein lead to deterioration of the opacification of the thoracic aorta and the major branches. We describe a new protocol employing a combination of triple channel contrast material injection and a mixture of saline with acquisition in the cephalic direction utilizing capability of 16-slice multislice CT. MATERIALS AND METHODS: Of 35 subjects who underwent thoracic CT, 18 were injected with 70 ml contrast each prior to scanning with acquisition in the cephalic direction during the injection of 30 ml contrast diluted 50/50 with saline, followed by the injection of 20 ml of saline (new protocol). Seventeen subjects were injected each with 100 ml contrast at 3 ml/s, with scanning in the caudal direction (ordinary protocol). RESULTS: In the new protocol, the major branches of the aorta and the left ventricle were more opacified, but the veins were less opacified compared with the ordinary protocol, resulting in clear delineation of the thoracic aorta and the major branches without artifacts. CONCLUSIONS: A new acquisition protocol is described in which the thoracic aorta and the major branches can be evaluated without artifact due to high CT values in the veins. Faster, more informative CT scans can be performed using diluted contrast.

Contrast Media↗
PubMed2005

Cardiac developmental biology: from flies to humans.

The heart is the first organ to form during embryogenesis, and heart formation is essential for subsequent embryonic development. Since the identification of a cardiac-restricted transcription factor Csx/Nkx-2.5 in the early 1990s, extensive studies on cardiac development have been done in various species ranging from flies to humans. Molecular dissection of regulatory pathways that control multiple steps of cardiogenesis will not only advance our understanding of cardiac development and congenital heart diseases, but will also provide an important clue to novel therapeutic strategies for heart diseases.

Animals↗
PubMed2005

Direction, location, and size of shunt flow in congenital heart disease evaluated by ECG-gated multislice computed tomography.

OBJECTIVE: To demonstrate the utility of multislice computed tomography (MSCT) in the evaluation of direction, location, and size of shunt flow in congenital heart disease. BACKGROUND: Transthoracic and transesophageal echocardiography, magnetic resonance imaging, and conventional angiography has been used to evaluate congenital heart disease; however, some are invasive and some do not provide accurate information about the spatial relationship to other organs. METHODS: Three patients with typical presentation of ventricular septal defect, atrial septal defect, and patent ductus arteriosus were recruited. Enhanced MSCT (Light Speed Ultra 16, General Electric) was performed with a 1.25-mm slice thickness, helical pitch 3.25. Following intravenous injection of 100 ml of iodinated contrast material (350 mg I/ml) at a rate of 3 ml/s, CT scanning was performed with retrospective ECG-gated reconstruction at 5 s and 30 s after injection. RESULTS: In all cases the information of direction, location, and size of shunt flow including left-to-right and right-to-left shunt with spatial relationship to other organs could be obtained non-invasively. CONCLUSION: ECG-gated MSCT is a useful tool to evaluate congenital heart diseases with shunts.

Adult↗
PubMed2005

Effect of mental stress on coronary flow velocity reserve in healthy men.

The effect of mental stress on coronary flow velocity reserve (CFVR) was examined in healthy men using transthoracic Doppler echocardiography. In the mental stress group (n = 31), CFVR was significantly reduced at 15 (to 3.3 +/- 0.8, p <0.001) and 30 (to 3.7 +/- 0.8, p <0.01) minutes after mental stress testing, compared with before mental stress (4.3 +/- 0.9), whereas it did not change in each of 3 measurements in control subjects (n = 10). Mental stress impaired coronary circulation even after a certain interval after the stress.

Adult↗
PubMed2005

Phosphatidylinositol 3-kinase-Akt pathway plays a critical role in early cardiomyogenesis by regulating canonical Wnt signaling.

We have recently reported that activation of phosphatidylinositol 3-kinase (PI3K) plays a critical role in the early stage of cardiomyocyte differentiation of P19CL6 cells. We here examined molecular mechanisms of how PI3K is involved in cardiomyocyte differentiation. DNA chip analysis revealed that expression levels of Wnt-3a were markedly increased and that the Wnt/beta-catenin pathway was activated temporally during the early stage of cardiomyocyte differentiation of P19CL6 cells. Activation of the Wnt/beta-catenin pathway during this period was required and sufficient for cardiomyocyte differentiation of P19CL6 cells. Inhibition of the PI3K/Akt pathway suppressed the Wnt/beta-catenin pathway by activation of glycogen synthase kinase-3beta (GSK-3beta) and degradation of beta-catenin. Suppression of cardiomyocyte differentiation by inhibiting the PI3K/Akt pathway was rescued by forced expression of a nonphosphorylated, constitutively active form of beta-catenin. These results suggest that the PI3K pathway regulates cardiomyocyte differentiation through suppressing the GSK-3beta activity and maintaining the Wnt/beta-catenin activity.

Animals↗