Rigidity Matching between Cells and the Extracellular Matrix Leads to the Stabilization of Cardiac Conduction

Biomechanical dynamic interactions between cells and the extracellular environment dynamically regulate physiological tissue behavior in living organisms, such as that seen in tissue maintenance and remodeling. In this study, the substrate-induced modulation of synchronized beating in cultured cardiomyocyte tissue was systematically characterized on elasticity-tunable substrates to elucidate the effect of biomechanical coupling. We found that myocardial conduction is significantly promoted when the rigidity of the cell culture environment matches that of the cardiac cells (4 kiloPascals). The stability of spontaneous target wave activity and calcium transient alternans in high frequency-paced tissue were both enhanced when the cell substrate and cell tissue showed the same rigidity. By adapting a simple theoretical model, we reproduced the experimental trend on the rigidity matching for the synchronized excitation. We conclude that rigidity matching in cell-to-substrate interactions critically improves cardiomyocyte-tissue synchronization, suggesting that mechanical coupling plays an essential role in the dynamic activity of the beating heart

ボールミリング法で改質したβ-TCPセメントの諸特性への粉液比の影響

The authors have developed a β-tricalcium-phosphate (β-TCP) powder modified mechano-chemically through the application of a ball-milling process (mβ-TCP). The resulting powder can be used in a calcium-phosphate-cement (CPC). In this study, the effects of the powder-to-liquid ratio (P/L ratio) on the properties of the CPCs were investigated, and an appropriate P/L ratio that would simultaneously improve injectability and strength was clarified. The mβ-TCP cement mixed at a P/L ratio of 2.5 and set in air exhibited sufficient injectability until 20 min after mixing, and strength similar to or higher than that mixed at a P/L ratio of 2.0 and 2.78. Although the mβ-TCP cements set in vivo and in SBF were found to exhibit a lower strength than those set in air, it did have an appropriate setting time and strength for clinical applications. In conclusion, P/L ratio optimization successfully improved the strength of injectable mβ-TCP cement

強度と注入性に優れるβ-TCP基セメントへのジルコニア添加の効果

Injectable calcium phosphate cements (CPCs) exhibit many advantages as bone substitution materials. However, the strength of injectable CPCs after setting are often insufficient. In our previous studies, mechano-chemically modification of β-tricalcium phosphate cement powder through a planetary ball-milling process exhibited simultaneous improvement in the strength and injectability of CPC. Two plausible effects of this process are: changes in the CPC powder properties and zirconia abrasion powder contamination from the milling pot and balls. The objective of the present study is to separately evaluate these two effects on the strength and injectability of CPCs. The calculated injectability of the cement paste with and without the addition of zirconia powder were higher than 65% at 6 h after mixing. These values were much higher than that of the CPC paste without mechano-chemically modification, and similar to that of CPC with zirconia abrasion powder contamination. By contrast, the compression strength of the set CPC with zirconia powder additives were higher than that without the addition, and similar to that of CPC with zirconia abrasion powder contamination. These results suggest that the changes in the CPC powder properties due to mechano-chemically modification mainly affected the injectability of the CPC paste, and the zirconia abrasion powder contamination of the CPC powder affected the strength of the set CPC

Accuracy of ventricular volume and ejection fraction measured by gated myocardial SPECT: Comparison of 4 software programs

金沢大学大学院医学系研究科Gated myocardial perfusion SPECT has been used to calculate ejection fraction (EF) and end-diastolic volume (EDV) and has correlated well with conventional methods. However, the comparative accuracy of and correlations across various types of gated SPECT software are not well understood. Methods: Mathematic phantoms of cylindric-hemispheric hybrid models, ranging in volume from 34 to 266 mL, were generated. The clinical cases consisted of 30 patients who participated in a radionuclide angiography and gated blood-pool (GBP) study in addition to undergoing 99mTc-sestamibi gated SPECT. Four kinds of software, Quantitative Gated SPECT (QGS), the Emory Cardiac Toolbox (ECT), 4D-MSPECT, and Perfusion and Functional Analysis for Gated SPECT (pFAST) were used to compute EF and EDV, and the results were analyzed by multiple comparisons tests. Patients were classified into 4 groups (i.e., no defect, small defect, large defect, and small heart) so that factors affecting variation could be analyzed. Results: In mathematic models ≥74 mL, volume error was within ±15%, whereas for a small volume (34 mL), QGS and 4D-MSPECT underestimated the volume and pFAST overestimated it. The respective intra- and interobserver reproducibility of the results was good for QGS (r=0.99 and 1.00), ECT (r=0.98 and 0.98), and 4D-MSPECT (r=0.98 and 0.98) and fair for pFAST (r=0.88 and 0.85). The correlation coefficient for EF between gated SPECT and the GBP study was 0.82, 0.78, 0.69, and 0.84 for QGS, ECT, 4D-MSPECT, and pFAST, respectively. The correlation coefficient for EDV between gated SPECT and the GBP study was 0.88, 0.89, 0.85, and 0.90, respectively. Although good correlation was observed among the 4 software packages, QGS, ECT, and 4D-MSPECT overestimated EF in patients with small hearts, and pFAST overestimated the true volume in patients with large perfusion defects. Correlation coefficients among the 4 kinds of software were 0.80-0.95 for EF and 0.89-0.98 for EDV. Conclusion: All 4 software programs showed good correlation between EF or EDV and the GBP study. Good correlation was observed also between each pair of quantification methods. However, because each method has unique characteristics that depend on its specific algorithm and thus behaves differently in the various patient subgroups, the methods should not be used interchangeably

Textual Variations and Readings among the Manuscripts and Editions of The Canterbury Tales: With Special Reference to The Knight’s Tale

This is a revised version of the paper presented at the 20th congress of the New Chaucer Society at Queen Mary University of London on 12 July 2016. This research was supported by Grant-in-Aid for Scientific Research (C) (Grant Number 15K02304) from the Japan Society for the Promotion of Science

Optimizing Charge Switching in Membrane Lytic Peptides for Endosomal Release of Biomacromolecules.

Endocytic pathways are practical routes for the intracellular delivery of biomacromolecules. Along with this, effective strategies for endosomal cargo release into the cytosol are desired to achieve successful delivery. Focusing on compositional differences between the cell and endosomal membranes and the pH decrease within endosomes, we designed the lipid-sensitive and pH-responsive endosome-lytic peptide HAad. This peptide contains aminoadipic acid (Aad) residues, which serve as a safety catch for preferential permeabilization of endosomal membranes over cell membranes, and His-to-Ala substitutions enhance the endosomolytic activity. The ability of HAad to destabilize endosomal membranes was supported by model studies using large unilamellar vesicles (LUVs) and by increased intracellular delivery of biomacromolecules (including antibodies) into live cells. Cerebral ventricle injection of Cre recombinase with HAad led to Cre/loxP recombination in a mouse model, thus demonstrating potential applicability of HAad in vivo

Dual-radionuclide simultaneous gastric emptying and bile transit study after gastric surgery with double-tract reconstruction

金沢大学医学部附属病院核医学診療科木南, 伸一Objective: The physiology of gastrointestinal transfer function after proximal gastrectomy with bypass-tract reconstruction is not well understood. We applied a simultaneous dual-radionuclide method with a hepatobiliary imaging and gastric emptying study to evaluate physiologic alterations occurring after surgery. Methods: Nineteen patients with early gastric cancer, including 9 preoperative control patients and 10 who had proximal gastrectomy and double-tract reconstruction surgery were examined by dual-radionuclide hepatobiliary and gastric emptying studies (99mTc PMT and 111In DTPA). Retention fraction in the stomach at 3 minutes (R3) and 60 minutes (R60) and gastric emptying half-time (GET) were calculated. Bile reflux and mixture of bile and food were also evaluated. Results: The retention fractions of R3 and R60 were significantly lower in the double-tract reconstruction group than those in the preoperative group. GET differed significantly between the double-tract and preoperative groups (20.7 min ± 7.1 min and 36.2 min ± 11.0 min, p = 0.0018). The mixture of bile and food was not good in the double-tract reconstruction group (p = 0.014 vs. preoperative). Patients with a large residual stomach showed slower initial emptying (p = 0.0068) and a better mixture of bile and food (p = 0.058) compared to those with a small residual stomach. The bile reflux was not significantly increased after surgery. Conclusion: The dual-radionuclide gastrointestinal and hepatobiliary imaging was feasible and could demonstrate characteristic transit patterns of the foods and bile in the double-tract reconstruction procedure. A larger residual stomach, if possible, is desirable to provide better transfer and mixing of bile and foods

A Case of Autoimmune Hepatitis Associated with Idiopathic Thrombocytopenic Purpura and Chronic Thyroiditis

Autoimmune hepatitis (AIH) is frequently associated with extrahepatic autoimmune disorders such as rheumatoid arthritis, Sjogren\u27s syndrome, and chronic thyroiditis, but the association with idiopathic (immune) thrombocytopenic purpura (ITP) is rare. We report a 46-year-old Japanese woman who presented with severe thrombocytopenia, elevated levels of aminotransferases, immunoglobulin (Ig) G, and platelet-associated IgG (PAIgG), positive anti-nuclear antibody, and hypothyroidism. After a diagnosis of coexisting AIH, ITP, and chronic thyroiditis, the patient was treated with 30 mg/day of prednisolone orally. The patient responded to such treatment: showing an increase in the number of platelets and decrease of serum levels of aminotransferases, IgG, and PAIgG to within normal ranges. Discrimination of ITP from liver cirrhosis as a cause of severe thrombocytopenia seen in chronic liver disease is important because complications and therapy are quite different. Prednisolone as a treatment for All should be also effective for ITP, and therefore, ITP should be considered when liver dysfunction is accompanied by severe thrombocytopenia, particularly in the autoimmune types of liver diseases

Diastolic dysfunction in patients with systemic sclerosis detected by gated myocardial perfusion SPECT: An early sign of cardiac involvement

金沢大学大学院Diagnosis of cardiac involvement is important for the management of patients with systemic sclerosis (SSc). This study was undertaken to determine the significance of gated myocardial perfusion SPECT in patients with SSc and whether diastolic function measured by gated SPECT is an early sign of cardiac complications. Methods: Thirty-four patients with SSc and 16 control patients were studied using exercise nongated and resting gated myocardial perfusion SPECT. The SSc was classified by the modified Rodnan total skin score (TSS) into high-TSS (score ≥ 10; n = 18) and low-TSS (score < 10; n = 16) groups. Gated SPECT was performed using 99mTc-methoxyisobutyl-isonitrile with 16 frames per cardiac cycle and quantitatively analyzed by QGS software and Fourier filtering of the volume curve. The parameters of ejection fraction (EF), peak filling rate (PFR), one-third mean filling rate, and time to PFR (TPFR) were calculated. Results: A slight perfusion abnormality was observed in four and five patients in the low-TSS and high-TSS groups, respectively (not statistically significant). A decreased resting EF less than 55% was found in no and two patients in the low-TSS and high-TSS groups, respectively. TPFR was 166 ± 22, 168 ± 38, and 216 ± 82 ms (P = 0.05, high-TSS group versus low-TSS group; P = 0.04, control group versus high-TSS group) and TPFR/R-R interval was 0.18 ± 0.02, 0.19 ± 0.04, and 0.26 ± 0.09 (P = 0.01, high-TSS group versus low-TSS group; P = 0.005, control group versus high-TSS group) for the control, low-TSS, and high-TSS groups, respectively. Conclusion: Diastolic function can be evaluated by gated myocardial perfusion SPECT. Significant diastolic abnormalities were shown even in patients with normal perfusion and systolic function and were related to the severity of SSc