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Articles by Y Tamaki
Total Records ( 4 ) for Y Tamaki
  Y Inuzuka , J Okuda , T Kawashima , T Kato , S Niizuma , Y Tamaki , Y Iwanaga , Y Yoshida , R Kosugi , K Watanabe Maeda , Y Machida , S Tsuji , H Aburatani , T Izumi , T Kita and T. Shioi
 

Background— Heart failure is a typical age-associated disease. Although age-related changes of heart are likely to predispose aged people to heart failure, little is known about the molecular mechanism of cardiac aging.

Methods and Results— We analyzed age-associated changes in murine heart and the manner in which suppression of the p110 isoform of phosphoinositide 3-kinase activity modified cardiac aging. Cardiac function declined in old mice associated with the expression of senescence markers. Accumulation of ubiquitinated protein and lipofuscin, as well as comprehensive gene expression profiling, indicated that dysregulation of protein quality control was a characteristic of cardiac aging. Inhibition of phosphoinositide 3-kinase preserved cardiac function and attenuated expression of the senescence markers associated with enhanced autophagy. Suppression of target of rapamycin, a downstream effector of phosphoinositide 3-kinase, also prevented lipofuscin accumulation in the heart.

Conclusions— Suppression of phosphoinositide 3-kinase prevented many age-associated changes in the heart and preserved cardiac function of aged mice.

  T Kato , S Niizuma , Y Inuzuka , T Kawashima , J Okuda , Y Tamaki , Y Iwanaga , M Narazaki , T Matsuda , T Soga , T Kita , T Kimura and T. Shioi
  Background—

Congestive heart failure (CHF) is associated with a change in cardiac energy metabolism. However, the mechanism by which this change is induced and causes the progression of CHF is unclear.

Methods and Results—

We analyzed the cardiac energy metabolism of Dahl salt-sensitive rats fed a high-salt diet, which showed a distinct transition from compensated left ventricular hypertrophy to CHF. Glucose uptake increased at the left ventricular hypertrophy stage, and glucose uptake further increased and fatty acid uptake decreased at the CHF stage. The gene expression related to glycolysis, fatty acid oxidation, and mitochondrial function was preserved at the left ventricular hypertrophy stage but decreased at the CHF stage and was associated with decreases in levels of transcriptional regulators. In a comprehensive metabolome analysis, the pentose phosphate pathway that regulates the cellular redox state was found to be activated at the CHF stage. Dichloroacetate (DCA), a compound known to enhance glucose oxidation, increased energy reserves and glucose uptake. DCA improved cardiac function and the survival of the animals. DCA activated the pentose phosphate pathway in the rat heart. DCA activated the pentose phosphate pathway, decreased oxidative stress, and prevented cell death of cultured cardiomyocytes.

Conclusions—

Left ventricular hypertrophy or CHF is associated with a distinct change in the metabolic profile of the heart. DCA attenuated the transition associated with increased energy reserves, activation of the pentose phosphate pathway, and reduced oxidative stress.

  T Tanei , K Morimoto , K Shimazu , S. J Kim , Y Tanji , T Taguchi , Y Tamaki and S. Noguchi
 

Purpose: Breast cancer stem cells have been shown to be associated with resistance to chemotherapy in vitro, but their clinical significance remains to be clarified. The aim of this study was to investigate whether cancer stem cells were clinically significant for resistance to chemotherapy in human breast cancers.

Experimental Design: Primary breast cancer patients (n = 108) treated with neoadjuvant chemotherapy consisting of sequential paclitaxel and epirubicin-based chemotherapy were included in the study. Breast cancer stem cells were identified by immunohistochemical staining of CD44/CD24 and aldehyde dehydrogenase 1 (ALDH1) in tumor tissues obtained before and after neoadjuvant chemotherapy. CD44+/CD24 tumor cells or ALDH1-positive tumor cells were considered stem cells.

Results: Thirty (27.8%) patients achieved pathologic complete response (pCR). ALDH1-positive tumors were significantly associated with a low pCR rate (9.5% versus 32.2%; P = 0.037), but there was no significant association between CD44+/CD24 tumor cell proportions and pCR rates. Changes in the proportion of CD44+/CD24 or ALDH1-positive tumor cells before and after neoadjuvant chemotherapy were studied in 78 patients who did not achieve pCR. The proportion of ALDH1-positive tumor cells increased significantly (P < 0.001) after neoadjuvant chemotherapy, but that of CD44+/CD24 tumor cells did not.

Conclusions: Our findings suggest that breast cancer stem cells identified as ALDH1-positive, but not CD44+/CD24, play a significant role in resistance to chemotherapy. ALDH1-positive thus seems to be a more significantly predictive marker than CD44+/CD24 for the identification of breast cancer stem cells in terms of resistance to chemotherapy.

  S Niizuma , Y Iwanaga , T Yahata , Y Tamaki , Y Goto , H Nakahama and S. Miyazaki
 

Background: Plasma B-type natriuretic peptide (BNP) is a diagnostic and prognostic marker in heart failure (HF). Although renal function is reported as an important clinical determinant, precise evaluations of the relationships of renal function with hemodynamic factors in determining BNP have not been performed. Therefore, we evaluated the association of plasma BNP concentrations with LV end-diastolic wall stress (EDWS) in a broad range of HF patients including those with chronic kidney disease (CKD) and end-stage renal disease (ESRD).

Methods: In 156 consecutive HF patients including those with CKD and ESRD, we measured plasma BNP and performed echocardiography and cardiac catheterization. LV EDWS was calculated as a crucial hemodynamic determinant of BNP.

Results: Plasma BNP concentrations increased progressively with decreasing renal function across the groups (P < 0.01) and were correlated with LV EDWS (r = 0.47) in the HF patients overall. This relationship was also present when patients were subdivided into systolic and diastolic HF (P < 0.01). In multivariable analysis, higher EDWS was associated with increased BNP concentration independently of renal dysfunction (P < 0.01). Anemia, systolic HF, and decreased BMI also contributed to increased BNP concentrations.

Conclusions: These results suggest that LV EDWS is a strong determinant of BNP even in patients with CKD and ESRD. Anemia, obesity, and HF type (systolic or diastolic) should also be considered in interpreting plasma BNP concentrations in HF patients. These findings may contribute to the clinical management of HF patients, especially those complicated with CKD and ESRD.

 
 
 
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