Biomedical subjects

Shigeru Kanda

Publications and source records attributed to Shigeru Kanda.

22 records · Page 2Linked to original sources

PubMed2002

Angiopoietin 2 stimulates migration and tube-like structure formation of murine brain capillary endothelial cells through c-Fes and c-Fyn.

The angiopoietin (Ang)/Tie2 system is exclusively involved in vasculogenesis and angiogenesis. Ang2 is known to inhibit Ang1-mediated phosphorylation of Tie2 as well as cellular responses during embryonic development. Recent studies have demonstrated that Ang2 has angiogenic activities in adult tissues and cultured endothelial cells. In the present study, we examined the downstream signaling pathways involved in Ang2-mediated cellular responses by murine brain capillary cell line, IBE cells. Tie2 was tyrosine phoshorylated by Ang2. Ang2 showed no effect on proliferation, but stimulated chemotaxis and tube-like structure formation. Phosphoinositide 3-kinase (PI 3-kinase) was activated by Ang2 through c-Fes and was involved in chemotaxis toward Ang2. Ang2 also activated c-Fyn in IBE cells. Cells expressing kinase-inactive c-Fyn attenuated Ang2-induced tube formation, suggesting that c-Fyn was responsible for Ang-2-mediated tube formation. Collecting these data, Ang2 activates c-Fes and c-Fyn, leading to migration and tube formation by murine capillary endothelial cells.

Angiopoietin-2↗

PubMed2002

Transient decrease in gap junction expression during compensatory renal growth in mice.

OBJECTIVES: To examine gap junction expression during compensatory renal growth. Compensatory renal growth is a normal response to the removal of renal cells. Gap junctional intercellular communication plays important roles in homeostatic regulation, differentiation, and synchronization of cellular electronic and metabolic functions. METHODS: The right ureters of 5-week-old ddy mice were dorsally incised and unilaterally obstructed, and the animals were killed at varying intervals. The control group underwent a sham operation. Freeze-fractured kidney tissue samples were studied using electron microscopy. The amount of proliferative cell nuclear antigen-positive cells and connexin 43 (Cx43) protein was studied by immunohistochemistry and Western blotting, respectively. RESULTS: Proliferative cell nuclear antigen-positive cells in the renal tubules increased on days 1 and 2 after surgery that obstructed the ureter, and decreased to normal levels by day 14. The number of gap junctions significantly decreased on days 1 and 2, and then gradually increased to normal levels from days 3 to 14 after surgery. The amount of Cx43 protein in the renal tubules decreased until day 2 and recovered to the same level as that of the control by day 14 after surgery. Significantly, a hyperphosphorylated band of Cx43 in the control kidney was not detected in the operated kidney. CONCLUSIONS: These data suggest that the gap junctional intercellular communication of renal tubular cells during compensatory renal growth after unilateral ureteral obstruction could be temporarily reduced concomitant with a decrease of the expression of a phosphorylated Cx43 protein in renal cortical tubular cells after unilateral ureteral obstruction of the contralateral kidney.

Adaptation, Physiological↗

PubMed2002

Standardization of plasma brain natriuretic peptide concentrations in older Japanese-relationship to latent renal dysfunction and ischemic heart disease.

OBJECTIVES: To determine the contributors to elevating plasma brain natriuretic peptide (BNP) concentrations in older people with normal systolic function. To investigate the relationship between cyclic guanosine monophosphate (cGMP) and BNP in older people with and without ischemic heart disease (IHD). DESIGN: Observational study. SETTING: Hospitalized patients in Nagoya University Hospital from November 1997 to May 2000. PARTICIPANTS: Younger patients (<65) without IHD (n = 31), older patients (> or=65) without IHD (n = 37), and older patients with stable IHD (n = 32). All participants showed 45% or greater of their left ventricular ejection fraction (LVEF). MEASUREMENTS: LVEF, peak atrial velocity/peak early velocity (A/E) ratio at the mitral valve, and left ventricular mass volume were measured using transthoracic echocardiogram. Plasma BNP level, cGMP, and serum creatinine (Scr) were measured. Creatinine clearance (CLcr) was calculated based on 24-hour urine collection. RESULTS: Plasma BNP levels in older people with and without IHD were significantly greater than in younger patients (mean +/- standard deviation = 76.4 +/- 96.0 (P <.001), 165.2 +/- 200.6 (P <.001), and 8.1 +/- 7.0, respectively). By simple regression analysis, in the groups without IHD, the logarithm of plasma BNP (Log BNP) concentrations had a significant positive relationship with age (R = 0.657, P <.001), Scr (R = 0.449, P <.001), and A/E ratio (R = 0.326, P =.003) and a significant negative relationship with CLcr (R = -0.663, P <.001). A stepwise multiple regression analysis with Log BNP level as the dependent variable and age, Scr, CLcr, and A/E ratio as independent variables showed that CLcr was a significant independent contributor in groups without IHD (R = -0.766, P <.001). In this analysis, the regression coefficient of the intercept was 2.006, and that of CLcr was -0.010. The cGMP/BNP ratio in older subjects with stable IHD tended to be lower than in those without IHD (P =.063). CONCLUSIONS: Elevated BNP levels in older patients with normal systolic function may be in part due to latent renal dysfunction, despite normal Scr levels. In healthy older people, it is important to exclude the effects of latent renal function in assessing cardiac function according to BNP level. In older subjects with stable IHD, the cGMP/BNP ratio tended to be lower than in those without IHD. This may be a reflection of a poor response of cGMP to BNP.

Aged↗

PubMed2002

[Effects of carvedilol on the hemodynamics and its tolerance in elderly patients].

Clinical trials have shown that beta-blockers can produce symptomatic improvement and decrease the risk of death in chronic heart failure patients. However, the side effects of beta-blockers including worsening heart failure, AV-block, contracting peripheral vessels and unfavorable effects on glucose and cholesterol metabolism tend to make physicians hesitate to prescribe beta-blockers for elderly patients. Carvedilol is a novel non-selective beta-blocker without intrinsic sympathomimetic activity (ISA) and has vasodilating effect through blocking alpha 1 receptor. We examined the effects of carvedilol on cardiac parameters in order to clarify whether beta-blocker may affect left ventricular function in elderly Japanese patients with hypertension, angina pectoris, or both. We examined the hemodynamic effect of carvedilol in 16 patients with hypertension, angina patients or both, aged 65 and over (75.5 +/- 5.6 y.o.). After 12 weeks treatment with 10-20 mg daily oral administration, echocardiography was performed and hemodynamic parameters were calculated to evaluate their cardiac functions. Blood pressure was significantly decreased, especially in systolic pressure (163.8/87.6 +/- 15.6/11.2 mmHg to 141.6/76.9 +/- 16.6/11.7 mmHg, p < 0.001/p < 0.01, respectively). Ejection fraction increase (65.8 +/- 11.8% to 71.2 +/- 11.4%, p < 0.05) accompanied heart rate decrease (72.0 +/- 16.1 bpm to 63.9 +/- 11.4 bpm, p < 0.05). Carvedilol increased ejection fraction and decreased blood pressure safely in elderly patients with hypertension, angina pectoris, or both. Taking the condition of each patient into consideration, alpha-beta-blocker can be beneficial in elder patients.

Adrenergic beta-Antagonists↗