There are eight thermosensitive TRP (transient receptor potential) channels in mammals, and there might be other TRP channels sensitive to temperature stimuli. Here, we demonstrate that TRPM2 can be activated by exposure to warm temperatures (4351C) apparently via direct heatevoked channel gating. b-NAD þ -or ADP-ribose-evoked TRPM2 activity is robustly potentiated at elevated temperatures. We also show that, even though cyclic ADPribose (cADPR) does not activate TRPM2 at 251C, coapplication of heat and intracellular cADPR dramatically potentiates TRPM2 activity. Heat and cADPR evoke similar responses in rat insulinoma RIN-5F cells, which express TRPM2 endogenously. In pancreatic islets, TRPM2 is coexpressed with insulin, and mild heating of these cells evokes increases in both cytosolic Ca 2 þ and insulin release, which is K ATP channel-independent and protein kinase A-mediated. Heat-evoked responses in both RIN-5F cells and pancreatic islets are significantly diminished by treatment with TRPM2-specific siRNA. These results identify TRPM2 as a potential molecular target for cADPR, and suggest that TRPM2 regulates Ca 2 þ entry into pancreatic b-cells at body temperature depending on the production of cADPR-related molecules, thereby regulating insulin secretion.

No abstract

Profound abnormalities of the brain were noted in a 6-year-old Japanese boy with congenital muscular dystrophy (CMD). Pathological alterations included diffuse cerebral and cerebellar micropolygyria, with bilateral temporal agyria, and abnormal fusion of gray matter in the basal portions of both frontal hemispheres. Microscopically, the architecture of both cerebral and cerebellar cortices was severely distorted, with irregular arrangement of neurons and increased vascularization. Skeletal muscles showed dystrophic changes rather than neurogenic atrophy. Eight autopsy cases of CMD with similar pathologic findings have been reported in Japan, although the lesions in the brain are quantitatively different from case to case. The findings indicate that CMD is a dysplastic disease of the central nervous system, with dystrophic involvement of skeletal muscles.

No abstract

This study was conducted to elucidate the relationship between the presence of occlusal support in edentulous subjects and their ability for physical exercise. Ten complete denture wearers were selected and instructed to jump vertically while standing on a force plate with and without occlusal support (i.e. dentures). On the curve recorded by the force plate (1) reaction time (latency) (2) jump elevation time and (3) maximum kicking force were analysed. The reaction time, which is an index of physical quickness, was significantly prolonged when the subjects lost their occlusal support. This result suggests that reconstruction of occlusal support at a desirable mandibular position has significance not only for the restoration of masticatory function but also for the maintenance of physical exercise.