Quantitative Analysis of Endocardial and Epicardial Left Ventricular Myocardial Deformation in Patients with Cardiac Amyloidosis

Article信州医学雑誌 67(1): 49-62(2019)journal articl

A computational framework for bioimaging simulation

Using bioimaging technology, biologists have attempted to identify and document analytical interpretations that underlie biological phenomena in biological cells. Theoretical biology aims at distilling those interpretations into knowledge in the mathematical form of biochemical reaction networks and understanding how higher level functions emerge from the combined action of biomolecules. However, there still remain formidable challenges in bridging the gap between bioimaging and mathematical modeling. Generally, measurements using fluorescence microscopy systems are influenced by systematic effects that arise from stochastic nature of biological cells, the imaging apparatus, and optical physics. Such systematic effects are always present in all bioimaging systems and hinder quantitative comparison between the cell model and bioimages. Computational tools for such a comparison are still unavailable. Thus, in this work, we present a computational framework for handling the parameters of the cell models and the optical physics governing bioimaging systems. Simulation using this framework can generate digital images of cell simulation results after accounting for the systematic effects. We then demonstrate that such a framework enables comparison at the level of photon-counting units.Comment: 57 page

Left ventricular deformation and torsion assessed by speckle-tracking echocardiography in patients with mutated transthyretin-associated cardiac amyloidosis and the effect of diflunisal on myocardial function

AbstractBackgroundMutated transthyretin-associated (ATTRm) amyloidosis with heart failure is associated with decreased longitudinal left ventricular (LV) myocardial contraction, as measured by strain Doppler echocardiography. We sought to clarify whether speckle-tracking echocardiography (STE) would provide useful information in patients with ATTRm cardiac amyloidosis.MethodsOne hundred twenty-three consecutive patients with ATTRm amyloidosis were divided into 3 groups. Group 1 had no evidence of cardiac involvement (n=47), group 2 had heart involvement but no congestive heart failure (CHF) and/or serum brain natriuretic peptide (BNP) levels <100pg/mL (n=35), and group 3 had heart involvement and CHF and/or serum BNP levels ≥100pg/mL (n=41). All patients underwent standard 2-dimensional (2D), Doppler echo, and STE.ResultsBy standard 2D and Doppler echo, differences in parameters were only apparent between group 3 and groups 1 and 2. Global circumferential strains by STE at each LV level and LV torsion were different between group 1 and groups 2 and 3, but not between group 2 and group 3. In contrast, global longitudinal LV strain showed significant intergroup differences (−17.3±2.3%, −13.3±2.3%, −9.9±3.3% for groups 1 to 3, respectively, P<0.0001). Radial strain also showed significant intergroup differences for each basal LV segment. Among 41 patients who could have been followed up after 1year, 34 patients with diflunisal treatment had shown improvement in apical rotation and torsion without deterioration in multidirectional strains.ConclusionATTRm cardiac amyloidosis is characterized by progressive impairment in longitudinal and basal LV radial function when global circumferential shortening and torsion remain unchanged

Assessment of the intrapulmonary ventilation-perfusion distribution after the Fontan procedure for complex cardiac anomalies: Relation to pulmonary hemodynamics

AbstractIn 12 patients who underwent the Fontan procedure for complex cardiac anomalies, lung scanning with xenon-133 was performed to assess the intrapulmonary ventilation-perfusion distribution, and comparison was made with a control group. All data were then analyzed in relation to either pre- or postoperative pulmonary hemodynamic data. In ventilation scans, the intrapulmonary distribution in the right lung was almost normal.In perfusion scans, an abnormal increased upper to lower lobe perfusion ratio greater than the normal value found in the control group was noted in seven patients (58.3%). There was a significant correlation (p < 0.02) between the upper to lower lobe perfusion ratio and postoperative pulmonary vascular resistance. Furthermore, this perfusion ratio correlated inversely with the preoperative (p < 0.005) and postoperative (p < 0.02) right pulmonary artery area index, defined as the ratio of cross-sectional area to the normal value. Of five patients with < 90% arterial oxygen saturation, four showed an abnormal distribution of pulmonary blood flow greater than the normal perfusion ratio. No patient had evidence of a pulmonary arteriovenous fistula by the echocardiographic contrast study.These results suggest that abnormal distribution of pulmonary blood flow to the upper lung segment may develop in patients after the Fontan procedure, and that insufficient size of the pulmonary artery before operation and the consequent postoperative elevation of pulmonary vascular resistance may be responsible for this perfusion abnormality

Phytochrome regulates cellular response plasticity and the basic molecular machinery of leaf development

Plants are plastic organisms that optimize growth in response to a changing environment. This adaptive capability is regulated by external cues, including light, which provides vital information about the habitat. Phytochrome photoreceptors detect far-red light, indicative of nearby vegetation, and elicit the adaptive shade-avoidance syndrome (SAS), which is critical for plant survival. Plants exhibiting SAS are typically more elongated, with distinctive, small, narrow leaf blades. By applying SAS-inducing end-of-day far-red (EoD FR) treatments at different times during Arabidopsis (Arabidopsis thaliana) leaf 3 development, we have shown that SAS restricts leaf blade size through two distinct cellular strategies. Early SAS induction limits cell division, while later exposure limits cell expansion. This flexible strategy enables phytochromes to maintain control of leaf size through the proliferative and expansion phases of leaf growth. mRNAseq time course data, accessible through a community resource, coupled to a bioinformatics pipeline, identified pathways that underlie these dramatic changes in leaf growth. Phytochrome regulates a suite of major development pathways that control cell division, expansion, and cell fate. Further, phytochromes control cell proliferation through synchronous regulation of the cell cycle, DNA replication, DNA repair, and cytokinesis, and play an important role in sustaining ribosome biogenesis and translation throughout leaf development

Phosphoproteomics-Based Modeling Defines the Regulatory Mechanism Underlying Aberrant EGFR Signaling

BACKGROUND: Mutation of the epidermal growth factor receptor (EGFR) results in a discordant cell signaling, leading to the development of various diseases. However, the mechanism underlying the alteration of downstream signaling due to such mutation has not yet been completely understood at the system level. Here, we report a phosphoproteomics-based methodology for characterizing the regulatory mechanism underlying aberrant EGFR signaling using computational network modeling. METHODOLOGY/PRINCIPAL FINDINGS: Our phosphoproteomic analysis of the mutation at tyrosine 992 (Y992), one of the multifunctional docking sites of EGFR, revealed network-wide effects of the mutation on EGF signaling in a time-resolved manner. Computational modeling based on the temporal activation profiles enabled us to not only rediscover already-known protein interactions with Y992 and internalization property of mutated EGFR but also further gain model-driven insights into the effect of cellular content and the regulation of EGFR degradation. Our kinetic model also suggested critical reactions facilitating the reconstruction of the diverse effects of the mutation on phosphoproteome dynamics. CONCLUSIONS/SIGNIFICANCE: Our integrative approach provided a mechanistic description of the disorders of mutated EGFR signaling networks, which could facilitate the development of a systematic strategy toward controlling disease-related cell signaling