Although there are numerous reports on the electrical heterogeneity of the myocardium, little has been given attention to its relation to cardiovascular mechanics, because of difficulties of simultaneously observing multiple effects in vivo. In this research, a multi-scale cardiovascular simulation model, which describes the myocyte physiology, left ventricular structural dynamics, and hemodynamics, was used to theoretically investigate the relationship between the electrical transmural heterogeneity of myocytes and ventricular energetics. The parameters which describe the characteristics of ion channels of an existing myocyte model were changed to create endo-, mid-, and epi-cardium myocyte models. Simulations were performed with electrically heterogeneous and homogeneous models. As a result, the heterogeneous model had lower contractility and higher total mechanical energy generation per ATP consumption. These findings indicate that electrical heterogeneity contribute to cardiac efficiency.
We have previously reported the initial results of applying the fast Fourier transform (FFT) method to DNA ploidy analysis using a flow cytometer, aiming to develop a device that supports the diagnosis of solid tumors. In the present study, the diagnostic accuracy was improved by further increasing the number of cases and introducing additional analyses using screening, the domain method, and a tree-based model. In screening, tissues displaying clear aneuploidy on the histograms obtained (primary histograms)(the address of the maximum peak on the primary histogram deviates greatly from 200) were judged to be cancer. For the remaining tissues, the primary histograms were normalized (by setting the address of the maximum peak to 200, and the height of the maximum peak to 1) and analyzed using the FFT method. In addition, normalized histograms were separated into domains based on the cell cycle, and the integrated values of these domains were determined. Tissues collected from 46 patients who underwent resection of colorectal cancer at the Cancer Institute Hospital of JFCR were analyzed. Each resected tissue was divided into two pieces;one piece was subjected to hematoxylin and eosin staining for pathological diagnosis, and the remaining piece was analyzed for DNA ploidy by preparing a cell suspension and staining the nuclei using an automatic cell isolation and staining system and freeze-dry reagent. All 17 cases identified as cancer during screening were subsequently diagnosed as cancer pathologically. By the FFT method, the sensitivity and specificity using the Slope value (Maxdif in previous studies) were higher than 90%. Using the integrated values of the S and G2/M domains in the histograms, the sensitivity and specificity were both approximately 85%. Sensitivity and specificity of ≥95% were obtained using a combination of the FFT and domain methods. Furthermore, when all the parameters were used to construct a tree-based model, the cases were accurately classified into cancer, suspected cancer, and normal. These results indicate the potential clinical utility of this method.
Visual impairment has serious impact on our quality of life. Although stem cell-based therapies contribute to improve retinal diseases, it is essentially critical to have quantitative data of the physiological characteristics of retinal cellular functions and related neural networks for reliable treatment. In the phototransduction system of retinal photoreceptor cells, visual pigments are activated by the incident light and stimulate transducin, which in turn send electrical signals to downstream neural networks. A single visual pigment may activate hundreds of transducin, amplifying the incoming signal. Efficacy of the signal amplification system has been reported to be light intensity-dependent. Experimentally, a positive correlation between light intensity and activated transducin has been observed at a lower stimulation intensity range, whereas activated transducin starts to decrease at very high intensity light stimulation. Since none of the proposed phototransduction models were able to reproduce the complex characteristics of the signal transduction system of retinal photoreceptor cells, we propose a model that may reproduce the light intensity-dependent amplification of incoming signals in both rods and cones. The present model successfully reproduced the experimental data.