A role of constraint in self-organization

In this paper we introduce a neural network model of self-organization. This model uses a variation of Hebb rule for updating its synaptic weights, and surely converges to the equilibrium status. The key point of the convergence is the update rule that constrains the total synaptic weight and this seems to make the model stable. We investigate the role of the constraint and show that it is the constraint that makes the model stable. For analyzing this setting, we propose a simple probabilistic game that models the neural network and the self-organization process. Then, we investigate the characteristics of this game, namely, the probability that the game becomes stable and the number of the steps it takes.Comment: To appear in the Proc. RANDOM'98, Oct. 199

Stimulus-Dependent State Transition between Synchronized Oscillation and Randomly Repetitive Burst in a Model Cerebellar Granular Layer

Information processing of the cerebellar granular layer composed of granule and Golgi cells is regarded as an important first step toward the cerebellar computation. Our previous theoretical studies have shown that granule cells can exhibit random alternation between burst and silent modes, which provides a basis of population representation of the passage-of-time (POT) from the onset of external input stimuli. On the other hand, another computational study has reported that granule cells can exhibit synchronized oscillation of activity, as consistent with observed oscillation in local field potential recorded from the granular layer while animals keep still. Here we have a question of whether an identical network model can explain these distinct dynamics. In the present study, we carried out computer simulations based on a spiking network model of the granular layer varying two parameters: the strength of a current injected to granule cells and the concentration of Mg2+ which controls the conductance of NMDA channels assumed on the Golgi cell dendrites. The simulations showed that cells in the granular layer can switch activity states between synchronized oscillation and random burst-silent alternation depending on the two parameters. For higher Mg2+ concentration and a weaker injected current, granule and Golgi cells elicited spikes synchronously (synchronized oscillation state). In contrast, for lower Mg2+ concentration and a stronger injected current, those cells showed the random burst-silent alternation (POT-representing state). It is suggested that NMDA channels on the Golgi cell dendrites play an important role for determining how the granular layer works in response to external input

心臓MRIにおける二つの異なる撮像シーケンス間の左室心筋容積ならびに左室内腔容積の換算方法の確立と、それを用いた非閉塞性肥大型心筋症におけるアンジオテンシンII受容体拮抗薬の効果に関する研究 : 左室形態・機能の長期定量的評価に基づく知見

学位の種別: 論文博士審査委員会委員 : （主査）東京大学教授 山崎 力, 東京大学教授 小山 博史, 東京大学講師 山内 治雄, 東京大学准教授 山内 敏正, 東京大学特任准教授 脇 嘉代University of Tokyo(東京大学

Effects of dietary inulin, statin, and their co-treatment on hyperlipidemia, hepatic steatosis and changes in drug-metabolizing enzymes in rats fed a high-fat and high-sucrose diet

<p>Abstract</p> <p>Background</p> <p>Rats fed a high-fat and high-sucrose (HF) diet develop hepatic steatosis and hyperlipidemia. There are several reports that a change in nutritional status affects hepatic levels of drug-metabolizing enzymes. Synthetic inulin is a dietary component that completely evades glucide digestion. Supplementing a HF diet with inulin ameliorates hypertriglycemia and hepatic steatosis, but not hypercholesterolemia. This study aimed at distinguishing the effects of synthetic inulin and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), which inhibit cholesterol biosynthesis.</p> <p>Methods</p> <p>We examined effects of co-treatment with synthetic inulin (5%) and fluvastatin (0, 4, and 8 mg/kg, <it>per os</it>) on body weight, epidydimal white adipose tissue weight, serum and hepatic lipid profiles, and hepatic cytochrome P450 (CYP) mRNA and protein profiles in rats fed a standard diet or a HF diet for 3 weeks.</p> <p>Results</p> <p>Treatment with the synthetic inulin (5%) or fluvastatin at 4 mg/kg (lethal dose in rats fed the HF diet, 8 mg/kg) ameliorated the elevation in hepatic triacylglycerol and total cholesterol levels in rats fed the HF diet. Whereas co-treatment with the inulin (5%) and fluvastatin (4 mg/kg) had a tendency to more strongly suppress the elevation in serum levels of very low density lipoprotein triacylglycerol than either treatment alone, no additive or synergistic effect was found in decrease in hepatic lipid levels. Hepatic levels of CYP1A1/2 and CYP2E1 mRNA and protein and methoxyresorufin <it>O</it>-demethylase and ethoxyresorufin <it>O</it>-deethylase activities were reduced in rats fed the HF diet. The synthetic inulin alleviated the reduction in hepatic levels of CYP1A1/2 and CYP2E1 mRNA and protein more strongly than fluvastatin, and no synergistic effects were observed on co-treatment. Furthermore, hepatic levels of aryl hydrocarbon receptor mRNA were decreased in rats fed the HF diet and recovered to near normal values with the intake of dietary inulin, which correlated with change in CYP1A1/2.</p> <p>Conclusions</p> <p>Dietary inulin alone was effective to prevent the development of hepatic steatosis, ameliorate nutritional effects, and alleviate the hepatic change in the expression of CYP1A1/2 and CYP2E1, while co-treatment with statin did not have additive or synergistic effects and statin may cause adverse effects in rats fed the HF diet.</p

Light and Electron Microscopic Studies of Microcalcifications Appearing in Monomorphic Adenomas

Microcalcifications appearing in two cases of monomorphic adenomas were studied histopathologically, electron microscopically, and electron-microanalytically. One case was basal cell adenoma that occurred in a 56-year-old man and the other was canalicular adenoma in a 71-year-old woman. The calcified granules were observed both in the lumina formed by the tumor cells and in the stromal tissues. The surroundings of the granules were stained by alcian blue and showed a sulfur peak by EPMA. These facts suggest that the surroundings contain sulfated glycosaminoglycans and that sulfur has a significant role in the mechanisms of pathological calcification as well as physiological calcification

Novel device prototyping for endoscopic cell sheet transplantation using a three-dimensional printed simulator

手術負担の少ない内視鏡による心臓表面への細胞シート移植デバイスを開発 --心臓再生医療への応用を目指して--. 京都大学プレスリリース. 2020-11-20.Introduction: Considering higher risks of candidates for cardiac regenerative therapy with compromised cardiac function, it is anticipated to develop less invasive surgical procedures. In the present study, we aimed to develop a prototype of totally endoscopic cell sheet delivery device and evaluate the surgical technique for epicardial cell sheet placement using three-dimensional (3D) printed simulators based on human computed tomography data. Methods: We designed an endoscopic cell sheet delivery device with outer and inner frame with self-expandable applicator which can be opened in thoracic cavity. We launched spout line to provide liquids on the applicator surface and tension line to gently bend the applicator dorsally. We prepared human mesenchymal stem cell (MSC) sheets and compared wet/dry conditions of 3D printed heart/porcine heart and applicator to identify suitable conditions for cell sheet transplantation. Finally we validated the feasibility of endoscopic transplantation to anterior and lateral wall of left ventricle using 3D printed simulators. Results: Moist condition of both 3D printed heart/porcine heart surface and applicator at transplantation yielded highest successful rate (100%, p = 0.0197). For both endoscopic transplantation sites, MSC sheets were successfully deployed. The procedure duration was 157 ± 23 s for anterior wall and 123 ± 13 s for the lateral wall in average, respectively. Conclusions: We developed a novel prototype of endoscopic cell sheet delivery device for minimally-invasive cardiac regenerative therapy utilizing a 3D printed simulator. The commercialization of the prototype may provide a safe minimally-invasive method to deliver potential cardiac regenerative therapy in the future

Age-Specific Prevalence of Glaucoma is Determined by the Presence of Refractive Errors Among Japanese Workers

To develop appropriate glaucoma mass screening programs for occupational health among Japanese workers, we estimated the prevalence of glaucoma and the increase rate by age. A total of 10,579 Japanese general workers (men/women = 9292/1287) underwent frequency doubling technology (FDT) perimetry testing. Visual field abnormalities (VFA) were identified by the FDT-based glaucoma screening protocol (FDT-VFA). Subjects with FDT-VFA were ophthalmologically diagnosed and classified as "normal," "glaucomatous VFA" (preperimetric, suspicious, and definitive glaucoma) or "other ocular diseases." Prevalence of FDT-VFA and positive predictive values for "glaucomatous VFA" and "definitive glaucoma" were calculated by five-year age intervals, and then the prevalence of "glaucomatous VFA" and "definitive glaucoma" in each age interval was estimated. Prevalence of "glaucomatous VFA" and "definitive glaucoma" in workers younger than 30 years old was approximately 1.5% and 0.5%, respectively. Interestingly, the increase in prevalence of glaucoma by age was significantly different between workers with and without refractive errors (RE). From ages 30 to 55 years, the estimated prevalence of "definitive glaucoma" linearly increased with a regression coefficient (%/age in years) that was 2.5-fold higher in subjects with RE than in those without RE {regression coefficient = 0.131 [95% confidence interval (CI) = 0.109, 0.152; R2 = 0.980]vs. 0.047 [95% CI = 0.026, 0.068; R2 = 0.869]for subjects with RE vs. those without RE, respectively}. Further, among workers older than 55 years, the prevalence of glaucoma continued increasing in workers with RE, whereas it plateaued in those without RE. From these estimates, we propose that FDT testing should be conducted as follows: 1) once in workers under the age of 30 years, 2) according to both age and the presence of RE in 30-55 years old, and 3) by age only in those over 55 years old

Synergistic inhibitory effect of gemcitabine and angiotensin type-1 receptor blocker, losartan, on murine pancreatic tumor growth via anti-angiogenic activities.

Pancreatic cancer is one of the leading causes of cancer death, and represents a challenging chemotherapeutic problem. The crucial role of angiogenesis in tumor growth has been widely recognized, and several reports have revealed that the combination treatment of the conventional chemotherapeutic drugs and anti-angiogenic agents exerted synergistic anti-cancerous effects. It has been reported that the clinically used angiotensin type-1 receptor blocker (ARB) exerted potent anti-angiogenic activity. The aim of our current study was to examine the combination effect of gemcitabine (GEM), a widely used conventional chemotherapeutic drug against pancreas cancer, and losartan (Lo), an ARB, on murine pancreatic tumor growth, especially in conjunction with angiogenesis. When used individually, GEM and Lo at clinically comparable low doses moderately suppressed pancreatic tumor development. The combination treatment with GEM and Lo exerted a marked inhibitory effect as compared with single agent treatments even after the tumor was fully established. Neovascularization and the expression of the vascular endothelial growth factor (VEGF), a central angiogenic factor, in the tumor were both markedly suppressed in a magnitude similar to the inhibitory effects against the tumor growth. Since both agents are widely used in the clinical practice, the combination regimen of GEM and Lo may represent a potential new therapeutic strategy for pancreatic cancer in the future

A novel approach for the endothelialization of xenogeneic decellularized vascular tissues by human cells utilizing surface modification and dynamic culture

Decellularized xenogeneic vascular grafts can be used in revascularization surgeries. We have developed decellularization methods using high hydrostatic pressure (HHP), which preserves the extracellular structure. Here, we attempted ex vivo endothelialization of HHP-decellularized xenogeneic tissues using human endothelial cells (ECs) to prevent clot formation against human blood. Slices of porcine aortic endothelium were decellularized using HHP and coated with gelatin. Human umbilical vein ECs were directly seeded and cultured under dynamic flow or static conditions for 14 days. Dynamic flow cultures tend to demonstrate higher cell coverage. We then coated the tissues with the E8 fragment of human laminin-411 (hL411), which has high affinity for ECs, and found that Dynamic/hL411showed high area coverage, almost reaching 100% (Dynamic/Gelatin vs Dynamic/hL411; 58.7 ± 11.4 vs 97.5 ± 1.9%, P = 0.0017). Immunostaining revealed sufficient endothelial cell coverage as a single cell layer in Dynamic/hL411. A clot formation assay using human whole blood showed low clot formation in Dynamic/hL411, almost similar to that in the negative control, polytetrafluoroethylene. Surface modification of HHP-decellularized xenogeneic endothelial tissues combined with dynamic culture achieved sufficient ex vivo endothelialization along with prevention of clot formation, indicating their potential for clinical use as vascular grafts in the future