経食道超音波法による心筋コントラストエコー法

心コントラストエコー法は,心エコー図検査の際に超音波用の造影剤を使用する画像診断法である.近年の心コントラストエコー法の技術的進歩は,経胸壁心エコー図法による局所心筋潅流の定量評価を可能にした.しかし,経食堂超音波法(TEE : transesophageal echocardiography)による心筋コントラストエコー法についての報告は1報告のみで,特に第二世代経静脈性超音波造影剤や,セカンドハーモニック法を使用した経食道心筋コントラストエコー法についての報告は無い.本研究では第二世代経静脈性超音波造影剤(FS069)と,セカンドハーモニック法を使用して,TEEによる心筋コントラストエコー法の可否を確認するとともに,心筋局所血流灌流の定量化が可能であるかどうかを検討し、以下の結論を得た.1)セカンドハーモニック法と第二世代経静脈性超音波造影剤(OPTISON^[○!R])を用いることにより,探触子に近い左室下壁領域においてTEEによる心筋コントラストエコー法が可能である.2)この方法により,左室下壁領域の冠血流予備能の定量化が可能である.Contrast echocardiography is an echocardiographic imaging technique using contrast agents. Recently, the technical advances in contrast echocardiography have made possible quantification of myocardial perfusion abnormalities by transthoracic echocardiography However, there has been only one report on myocardial contrast echocardiography (MCE) using transesophageal echocardiography (TEE), and no reports regarding MCE employing TEE with a second harmonic imaging technique or second generation contrast agents. In the present study, we evaluated whether it is possible to perform MCE using TEE with a second harmonic imaging technique and second contrast agents (OPTISON^[○!R]) and to quantify myocardial perfusion abnormalities in vivo. We concluded that 1) MCE using TEE with such an imaging technique and such contrast agents is possible in only the left ventricular inferior wall near a transducer, and 2) coronary flow reserve can be assessed by this method in the left ventricular inferior wall

Fibroblasts Show More Potential as Target Cells than Keratinocytes in COL7A1 Gene Therapy of Dystrophic Epidermolysis Bullosa

Dystrophic epidermolysis bullosa (DEB) is an inherited blistering skin disorder caused by mutations in the type VII collagen gene (COL7A1). Therapeutic introduction of COL7A1 into skin cells holds significant promise for the treatment of DEB. The purpose of this study was to establish an efficient retroviral transfer method for COL7A1 into DEB epidermal keratinocytes and dermal fibroblasts, and to determine which gene-transferred cells can most efficiently express collagen VII in the skin. We demonstrated that gene transfer using a combination of G protein of vesicular stomatitis virus-pseudotyped retroviral vector and retronectin introduced COL7A1 into keratinocytes and fibroblasts from a DEB patient with the lack of COL7A1 expression. Real-time polymerase chain reaction analysis of the normal human skin demonstrated that the quantity of COL7A1 expression in the epidermis was significantly higher than that in the dermis. Subsequently, we have produced skin grafts with the gene-transferred or untreated DEB keratinocytes and fibroblasts, and have transplanted them into nude rats. Interestingly, the series of skin graft experiments showed that the gene-transferred fibroblasts supplied higher amount of collagen VII to the new dermal–epidermal junction than the gene-transferred keratinocytes. An ultrastructural study revealed that collagen VII from gene-transferred cells formed proper anchoring fibrils. These results suggest that fibroblasts may be a better gene therapy target of DEB treatment than keratinocytes

Evaluation of Longitudinal Conversion Loss (LCL) for Indoor AC Mains Line

Influence to electromagnetic environment has been studied for power line communication (PLC). Longitudinal conversion loss (LCL) and input impedance are important parameters to evaluate the influence. Indoor AC mains line is modeled considering with typical conditions of Japanese house. The modeled line and electric equipment are presented with 4-port F-matrixes. The parameters of 4-port F-matrix are determined from calculation and measurement. Using this model, the input impedance and the LCL are calculated. The analysis model is examined by a simple network, and the results show that the calculation values almost agree with the measured values. The input impedance and the LCL are investigated for actual AC mains line, and the measured results almost agree with the calculated value.2003 IEEE Symposium on Electromagnetic Compatibility, August 18-22, 2003, Boston, MA, US

Thymidine Catabolism as a Metabolic Strategy for Cancer Survival

Thymidine phosphorylase (TP), a rate-limiting enzyme in thymidine catabolism, plays a pivotal role in tumor progression; however, the mechanisms underlying this role are not fully understood. Here, we found that TP-mediated thymidine catabolism could supply the carbon source in the glycolytic pathway and thus contribute to cell survival under conditions of nutrient deprivation. In TP-expressing cells, thymidine was converted to metabolites, including glucose 6-phosphate, lactate, 5-phospho-α-D-ribose 1-diphosphate, and serine, via the glycolytic pathway both in vitro and in vivo. These thymidine-derived metabolites were required for the survival of cells under low-glucose conditions. Furthermore, activation of thymidine catabolism was observed in human gastric cancer. These findings demonstrate that thymidine can serve as a glycolytic pathway substrate in human cancer cells

Thymidine catabolism promotes NADPH oxidase-derived reactive oxygen species (ROS) signalling in KB and yumoto cells

Thymidine phosphorylase (TP) is a rate-limiting enzyme in the thymidine catabolic pathway. TP is identical to platelet-derived endothelial cell growth factor and contributes to tumour angiogenesis. TP induces the generation of reactive oxygen species (ROS) and enhances the expression of oxidative stress-responsive genes, such as interleukin (IL)-8. However, the mechanism underlying ROS induction by TP remains unclear. In the present study, we demonstrated that TP promotes NADPH oxidase-derived ROS signalling in cancer cells. NADPH oxidase inhibition using apocynin or small interfering RNAs (siRNAs) abrogated the induction of IL-8 and ROS in TP-expressing cancer cells. Meanwhile, thymidine catabolism induced by TP increased the levels of NADPH and intermediates of the pentose phosphate pathway (PPP). Both siRNA knockdown of glucose 6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme in PPP, and a G6PD inhibitor, dihydroepiandrosterone, reduced TP-induced ROS production. siRNA downregulation of 2-deoxy-D-ribose 5-phosphate (DR5P) aldolase, which is needed for DR5P to enter glycolysis, also suppressed the induction of NADPH and IL-8 in TP-expressing cells. These results suggested that TP-mediated thymidine catabolism increases the intracellular NADPH level via the PPP, which enhances the production of ROS by NADPH oxidase and activates its downstream signalling