No abstract

Marked changes in intermediary metabolism occur during development of the heart. In the fetus, the heart utilises lactate and glucose as its main energy substrates, while in the adult, fatty acids are the main energy substrate. The transition from carbohydrate to fatty acid metabolism is a complex process which involves maturation of mitochondrial processes and dramatic changes in circulating levels of fatty acids and lactate. In addition, developmental changes in the use of energy substrates also involve changes in the regulation of the enzymes involved in both carbohydrate and fatty acid utilisation. This paper reviews these changes in intermediary metabolism which occur during myocardial development. The metabolic differences that exist between immature and adult hearts may explain the observed differences in the ability of immature hearts to withstand hypoxaemia or ischaemia.

No abstract

The death receptor Fas (Apo1/CD95) and Fas ligand (FasL) system is recognised as a major pathway for the induction of apoptosis in vivo, and antiapoptosis via its blockade plays a critical role in carcinogenesis and progression in several malignancies. However, the function of Fas -FasL system in urothelial cancer (UC) has not been elucidated. We therefore investigated the expression of Fas, FasL and Decoy receptor 3 for FasL (DcR3) in UC specimens and cell lines, and examined the cytotoxic effect of an anti-Fas-activating monoclonal antibody (mAb) in vitro. Immunohistochemical examinations of Fas-related molecules were performed on 123 UC and 30 normal urothelium surgical specimens. Normal urothelium showed Fas staining in the cell membrane and cytoplasm. In UC, less frequent Fas expression was significantly associated with a higher pathological grade (Po0.0001), a more advanced stage (P ¼ 0.023) and poorer prognosis (P ¼ 0.010). Fas and the absence thereof were suggested to be crucial factors with which to select patients requiring more aggressive treatment. Moreover, low-dose anti-Fas-activating mAb sensitised resistant cells to adriamycin, and this synergistic effect could be applied in the development of new treatment strategy for UC patients with multidrug-resistant tumours.

Previously, we reported that Bcl-2 was frequently expressed in renal cell carcinoma (RCC) specimens, but p53 mutation was a rare event. However, it was unclear whether Bcl-2 positivity was associated with the clinicopathological characteristics and prognosis in RCC. Therefore, we investigated the expression of Bcl-2 protein and its roles in 101 RCC specimens. In addition, the proliferation index (PI), apoptotic index (AI), caspase-3 and p53 expression were examined. The immunohistochemical method was applied for Bcl-2, caspase-3 and p53 protein expression. To investigate the proliferation activity and apoptosis of tumour cells, PI and AI were calculated based on Ki-67 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL)-positive cells, respectively. Bcl-2 expression was detected in 72 out of 101 (71.3%) specimens. Bcl-2 positivity was inversely correlated with PI (Po0.0001) and AI (P ¼ 0.0074). Furthermore, Bcl-2 positivity was significantly correlated with better survival (P ¼ 0.0014), and was associated with lower stage (P ¼ 0.0301) and grade (P ¼ 0.0020). In RCC, frequent Bcl-2 expression was correlated with favourable character without higher PI and AI. Thus, Bcl-2 expression might be applied as a novel predictor of better prognosis in RCC patients.