Flow-induced Alignment of Amyloid Protofilaments Revealed by Linear Dichroism

This research was originally published in the Journal of Biological Chemistry. Rumi Adachi, Kei-ichi Yamaguchi, Hisashi Yagi, Kazumasa Sakurai, Hironobu Naiki and Yuji Goto. Flow-induced Alignment of Amyloid Protofilaments Revealed by Linear Dichroism. J. Biol. Chem. 2007; 282, 8978-8983. © the American Society for Biochemistry and Molecular Biolog

Onset heart rate of microvolt-level T-wave alternans provides clinical and prognostic value in nonischemic dilated cardiomyopathy

AbstractObjectivesThis study was designed to determine the prognostic value of onset heart rate (OHR) in T-wave alternans (TWA) in patients with nonischemic dilated cardiomyopathy (DCM).BackgroundOne of the current major issues in DCM is to prevent sudden cardiac death (SCD). However, the value of the OHR of TWA as a prognostic indicator in DCM remains to be elucidated.MethodsWe prospectively investigated 104 patients with DCM undergoing TWA testing. The end point of this study was defined as SCD, documented sustained ventricular tachycardia/ventricular fibrillation. Relations between clinical parameters and subsequent outcome were evaluated.ResultsForty-six patients presenting with TWA were assigned to one of the following two subgroups according to OHR for TWA of ≤100 beats/min: group A (n = 24) with OHR ≤100 beats/min and group B (n = 22) with 100 < OHR ≤ 110 beats/min. T-wave alternans was negative in 37 patients (group C) and indeterminate in 21 patients. The follow-up result comprised 83 patients with determined TWA. During a follow-up duration of 21 ± 14 months, there was a total of 12 arrhythmic events, nine of which included three SCDs in group A, two in group B and one in group C. The forward stepwise multivariate Cox hazard analysis revealed that TWA with an OHR ≤100 beats/min and left ventricular ejection fraction were independent predictors of these arrhythmic events (p = 0.0001 and p = 0.0152, respectively).ConclusionsThe OHR of TWA is of additional prognostic value in DCM

Antioxidant α-tocopherol ameliorates glycemic control of GK rats, a model of type 2 diabetes

AbstractWe have shown recently that oxidative stress by chronic hyperglycemia damages the pancreatic β-cells of GK rats, a model of non-obese type 2 diabetes, which may worsen diabetic condition and suggested the administration of antioxidants as a supportive therapy. To determine if natural antioxidant α-tocopherol (vitamin E) has beneficial effects on the glycemic control of type 2 diabetes, GK rats were fed a diet containing 0, 20 or 500 mg/kg diet α-tocopherol. Intraperitoneal glucose tolerance test revealed a significant increment of insulin secretion at 30 min and a significant decrement of blood glucose levels at 30 and 120 min after glucose loading in the GK rats fed with high α-tocopherol diet. The levels of glycated hemoglobin A1c, an indicator of glycemic control, were also reduced. Vitamin E supplementation clearly ameliorated diabetic control of GK rats, suggesting the importance of not only dietary supplementation of natural antioxidants but also other antioxidative intervention as a supportive therapy of type 2 diabetic patients

Complete Fracture-Dislocation of the Thoracolumbar Spine with No Critical Neurological Deficit : A Case Report

Fractures at the thoracolumbar junction are the most common spinal column fractures. Among type C fractures in the Arbeitsgemeinschaft für Osteosynthesefragen Spine Classification, cases with complete fracture-dislocations of the spinal column often result in a critical neurological deficit despite surgical treatment. We present a case of an 18-year-old man who had a complete fracture-dislocation of the T12 vertebral body and multiple injuries following high-energy trauma but no critical neurological deficits. Because of active bleeding in the left thoracic cavity, the patient underwent open reduction of the T12 vertebral body and anterior spinal fusion of the T11-L1 vertebral bodies via an anterior approach between the T9 and T10 ribs within 24 h of the accident. Four months postoperatively, the patient could ambulate independently, with a slight disturbance of light touch. At 6 months postoperatively, plain computed tomography scans showed bony union of the T12 vertebral body. We postulated two reasons for the absence of critical neurological dysfunction : (1) spontaneous spinal canal sparing because of the fracture of the right superior articular process in the L1 vertebral body and (2) fracture morphology, that is, a rotational fracture with mild to moderately strong shearing stress to the dura mater

Magnetic thickness measurement for various iron steels using magnetic sensor and effect of electromagnetic characteristics

The diagnosis and prevention of the deterioration of iron-steel infrastructure has become an important social issue in recent years. The thickness measurement technique (extremely low-frequency eddy current testing (ELECT)) using a magnetic sensor for detecting steel corrosion at extreme frequency ranges has been previously reported. Using the calibration curves based on the correlation between the phase of the detected magnetic signal and the plate thickness, the plate thickness reduction caused by corrosion can be estimated from the detected phase signal. Iron-steel materials have large changes in electromagnetic characteristics; therefore, the reference calibration data for each type of iron-steel are required for plate thickness estimation. In this study, the effect of electromagnetic characteristics on the magnetic thickness measurement was investigated to improve the thickness estimation. Four types of iron-steel plates (SS400, SM400A, SM490A, and SMA400AW) with thicknesses ranging from 1 mm to 18 mm were measured by ELECT, and the phase change at multiple frequencies of each plate were analyzed. The shift in the phase and linearity regions of the calibration curves for each type of steel plate was observed. To analyze this shift phenomenon, the electromagnetic characteristics (permeability μ and conductivity σ) of each type of steel were measured. Compared with the permeability μ and conductivity σ of each steel plate in the applied magnetic field strength range, the product (σμ) for various steel plates decreased in the following order: SM400 > SS400 >SMA400AW > SM490A. The product of μ and σ is related to the skin depth, indicating the electromagnetic wave attenuation and eddy current phase shift in the material. Therefore, each shift in the calibration curve of each type of iron steel is explained by the changes in the parameters σ and μ

Radiographic changes of cervical destructive spondyloarthropathy in long-term hemodialysis patients : A 9-year longitudinal observational study

Analyses of radiographic changes and clinical symptom of destructive spondyloarthropathy (DSA) on consecutive 42 patients managed with long-term hemodialysis were performed to elucidate radiographic changes of DSA and the factors that influence to the destructive changes. Patients underwent plain radiographs of the cervical spine with 9 years interval. Grading of radiological feature from lateral view was classified into grade 0 to grade 3. Clinical symptom was evaluated using modified Japanese Orthopaedic Association scoring system for cervical myelopathy (mJOA score). Destructive changes were observed in 3 patients at the first examination, and those were observed in 15 patients 9 years after the first examination. There is no statistically significant difference between the duration of hemodialysis and the grade. The mean age at the onset of hemodialysis, however, was significantly higher in patients of grade 2 and 3 than those of grade 1. Older patients with long-term hemodialysis had destructive changes. Destructive changes commonly observed in lower cervical spine. The average numbers of the involved disc level were 1.6 in grade 2 and 1.0 in grade 3. Clinical symptoms were varied in each grade and there was no statistically significant difference in total mJOA score among these grades

Supersaturation-limited and unlimited phase transitions compete to produce the pathway complexity in amyloid fibrillation

Although amyloid fibrils and amorphous aggregates are two types of aggregates formed by denatured proteins, their relationship currently remains unclear. We used β2-microglobulin (β2m), a protein responsible for dialysis-related amyloidosis, to clarify the mechanism by which proteins form either amyloid fibrils or amorphous aggregates. When ultrasonication was used to accelerate the spontaneous fibrillation of β2m at pH 2.0, the effects observed depended on ultrasonic power; although stronger ultrasonic power effectively accelerated fibrillation, excessively strong ultrasonic power decreased the amount of fibrils formed, as monitored by thioflavin T fluorescence. An analysis of the products formed indicated that excessively strong ultrasonic power generated fibrillar aggregates that retained β-structures but without high efficiency as seeds. On the other hand, when the spontaneous fibrillation of β2m was induced at higher concentrations of NaCl at pH 2.0 with stirring, amorphous aggregates became more dominant than amyloid fibrils. These apparent complexities in fibrillation were explained comprehensively by a competitive mechanism in which supersaturation-limited reactions competed with supersaturation-unlimited reactions. We link the kinetics of protein aggregation and a conformational phase diagram, in which supersaturation played important roles.This research was originally published in the Journal of Biological Chemistry. Masayuki Adachi, Masatomo So, Kazumasa Sakura, József Kardos and Yuji Goto. Supersaturation-limited and Unlimited Phase Transitions Compete to Produce the Pathway Complexity in Amyloid Fibrillation. J. Biol. Chem. 2015; 290, 18134-18145. © the American Society for Biochemistry and Molecular Biolog