Mapping of a gene responsible for twy (tip-toe walking Yoshimura), a mouse model of ossification of the posterior longitudinal ligament of the spine (OPLL).
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Biomedical subjects
Publications and source records attributed to S Goto.
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We investigated the neurotoxicity evoked by N-methyl-D-aspartate (NMDA) receptor stimulation in the organotypic static slice cultures of rat cerebral cortices. We also examined whether the gamma-aminobutyric acid (GABA)A receptor agonist muscimol has a protective effect on the NMDA-mediated neurotoxicity in this culture system. NMDA-mediated cytotoxicity was evaluated histologically and quantified by the measurement of lactate dehydrogenase (LDH) release into the culture medium. There was an NMDA-induced, dose-dependent leakage of LDH release and neuronal cell death, which were not attenuated by muscimol treatment. The results suggested that NMDA neurotoxicity is reproduced in the organotypic culture, and that GABA(A) receptor activation exerted no protective action against the NMDA cytotoxicity.
It is known that acute physical exercise may have diverse pathophysiological consequences in various organs due to free radical formation. We have investigated whether a period of anaerobic running to exhaustion in rats results in oxidative modification of proteins in the lungs. Six rats of an exercised group (E) ran for two periods of 5 min at a speed of 30 m.min-1 followed by a recovery period of 5 min, and then by a third period of running to exhaustion. Reactive carbonyl derivatives (RCD) were measured by the Western blot technique on lungs of E and control (C) rats. In addition, the activity of glutamine synthetase (GS) was also monitored as marker of oxidative damage to proteins. This investigation revealed significant exercise-induced increases in accumulation of RCD in the lungs of the E group compared with the C group. The RCD signals were visibly stronger in proteins with molecular weight of 55 kDa and 32 kDa. The activity of GS was higher by about 30% in E rats than in C rats. The present data suggest that anaerobic exercise induces protein oxidation in the lungs.
The aim of this study was to investigate the expression of the immediate early genes (IEGs), c-fos and c-jun, in the rat kidney and liver in two types of hemorrhage shock/resuscitation models. In the first group, hemorrhagic shock was induced by the withdrawal of blood through the carotid artery. A mean arterial blood pressure (MAP) of 40mmHg was maintained for 1h before blood was reperfused. In the second group, the MAP was maintained at the same level for 2h. Animals were resuscitated with Ringer's lactate solution. In the first group, a rapid and transient induction of c-fos and c-jun mRNAs in both the liver and kidney was observed, peaking 0 to 2 h after reperfusion. In the second group, a more protracted pattern of induction was evident in both organs. In both models, the induction of c-fos mRNA was distinctly different in the liver and kidney. These results indicated, first, that with respect to IEG expression, organs respond differently to a systemic shock/resuscitation stimuli, and second, that alterations in the pattern of IEG expression might represent an indication of the degree of organ damage or the repair processes subsequent to hypotension/reperfusion.
In the present study, we investigated the effect of a nitric oxide (NO) scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide [carboxy-PTIO], on endothelium-dependent relaxation of a series of blood vessels from rabbits, such as thoracic aorta and femoral, renal, mesenteric, and pulmonary arteries, using a functional muscle bath technique. Carboxy-PTIO produced concentration-dependent contractions in various vessels. The contractile responses in renal, mesenteric, and pulmonary arteries were significantly greater than those in the aorta and femoral artery. Similarly, phenylephrine-induced contractions in renal, mesenteric, and pulmonary arteries were markedly enhanced after pretreatment with carboxy-PTIO. Also, carboxy-PTIO inhibited acetylcholine-induced relaxation in various blood vessels. The maximum inhibitions in aorta and femoral artery were significantly greater than those in renal, mesenteric, and pulmonary arteries. The present data demonstrate that carboxy-PTIO reduces basal, phenylephrine-, and acetylcholine-induced release of NO in rabbit blood vessels. However, different degrees of inhibition of endothelium-dependent vasorelaxation were observed in various vessels. Specifically, the thoracic aorta and femoral artery are less susceptible to the action of carboxy-PTIO without acetylcholine than renal, mesenteric, and pulmonary arteries. Conversely, the most potent carboxy-PTIO-induced inhibition of acetylcholine-induced vasorelaxation was observed with aorta and femoral arteries. Thus, it is suggested that the contribution of endogenous NO to vascular tone and regional blood flow may vary among different rabbit blood vessels.
Both exposure to high altitude (HA) and caloric restriction (CR) may influence free radical generation. The aim of the present study was to evaluate the effects of 4 wk chronic exposure to 4,000m of HA and CR (60% of CR of control (C) rats) on protein oxidation in brain. Eighteen rats with similar body mass were assigned to CR, HA and C rats. Reactive carbonyl derivatives (RCD), marker of protein oxidation, were measured by Western blot. In addition, the activity and protein content of glutamine synthetase (GS) were determined. The body mass of C rats was significantly higher (P< 0.001) than that of HA and CR groups. The quantified signal intensity of RCD was significantly stronger in C rats than in HA and CR rats. The activity of GS was significantly increased in CR rats, while the protein content of GS was decreased in HA rats compared to C group. The data suggest that both HA and CR decreases the accumulation of RCD in the brain, however the mechanism of the decrease seems to be different during HA and CR.
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