Akira Kitamura

The current results indicate that diabetic autonomic neuropathy is associated with more severe intraoperative hypothermia. We postulate that diabetic patients become more hypothermic because their peripheral neuropathy delays the onset of thermoregulatory vasoconstriction and reduces its efficacy once triggered. These patients may therefore fail to develop a normal core temperature plateau.

A hallmark of amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is formation of inclusion bodies (IBs) from misfolded proteins in neuronal cells. TAR RNA/DNA-binding protein 43 kDa (TDP43) is an ALS-causative protein forming IBs in ALS patients. The relation between localization of the IBs and neurotoxicity remains largely unknown. We characterized aggregation of fluorescently tagged TDP43 and its carboxyl-terminal fragments (CTFs) by analytical fluorescence imaging t

Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, and Huntington's disease, are devastating proteinopathies with misfolded protein aggregates accumulating in neuronal cells. Inclusion bodies of protein aggregates are frequently observed in the neuronal cells of patients. Investigation of the underlying causes of neurodegeneration requires the establishment and selection of appropriate methodologies for detailed investigation of t

A hallmark of protein conformational disease, exemplified by neurodegenerative disorders, is the expression of misfolded and aggregated proteins. The relationship between protein aggregation and cellular toxicity is complex, and various models of experimental pathophysiology have often yielded conflicting or controversial results. In this study, we examined the biophysical properties of amyotrophic lateral sclerosis (ALS)-linked mutations of Cu/Zn superoxide dismutase 1 (SOD1) expressed in human

In Brief Halothane and propofol enhance the activity of the γ-aminobutyric acid (GABA) system, which is one of the most important systems in the mechanism of anesthesia. To determine whether halothane and propofol enhance GABAergic responses by the same mechanism, we performed single-channel patch-clamp experiments with rat cortical neurons in primary culture. Each of the open-time and closed-time distributions of GABAA receptor single channels was expressed by a sum of fast and slow time consta

Cellular homeostasis is maintained by several types of protein machinery, including molecular chaperones and proteolysis systems. Dysregulation of the proteome disrupts homeostasis in cells, tissues, and the organism as a whole, and has been hypothesized to cause neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). A hallmark of neurodegenerative disorders is formation of ubiquitin-positive inclusion bodies in neurons, suggesting that the aggr

Hyperosmotic stress activates in live cells numerous processes and also promotes intracellular protein/RNA aggregation and phase separation. However, the time course and the extent of these changes remain largely uncharacterized. To investigate dynamic changes in intracellular macromolecular crowding (MMC) induced by hyperosmotic stress in live cells, we used fluorescence lifetime imaging microscopy and fluorescence correlation spectroscopy (FCS) to quantify changes in the local environment by m

Fluorescence recovery after photobleaching (FRAP) enables characterization of quantitative dynamic properties such as diffusion coefficients of fluorescent molecules in living cells by analyzing the recovery of fluorescence intensity after photobleaching in a specific cellular compartment or area. To quantitatively determine high intracellular diffusion coefficients, a suitable optical system as well as an appropriate model for fast diffusion analysis is necessary. Here, we propose a procedure t

The accumulation of misfolded proteins in the cytosol and nucleus of neuronal cells leads to neurodegenerative disorders. Polyglutamine diseases are caused by polyglutamine-expanded proteins, whereas mutations in superoxide dismutase 1 lead to amyotrophic lateral sclerosis. These structurally unstable mutant species perturb essential interactions between normal proteins and tend to aggregate because of the presence of exposed hydrophobic surfaces. Accumulating evidence suggests that soluble spec

Using a superfine fiberscope with an outer diameter of 0.75 mm, the effect of repeated injections through a single epidural catheter on the epidural space was examined in 18 patients. The subjects were divided into a control group of 10 patients who had not previously received epidural anesthesia (EA) and an EA group of 8 patients who had received repeated EA with 4-6 mL 0.25% bupivacaine through an epidural catheter, two to three times per day for 7-14 days. The epidural space was observed thro