Relationship between inositol 1,4,5-trisphosphate receptor isoforms and subcellular Ca2+ signaling patterns in nonpigmented ciliary epithelia.

PURPOSE: Subcellular Ca2+ signaling patterns, such as Ca2+ waves, gradients, and oscillations, are an important aspect of cell regulation, but the molecular basis for these signaling patterns is not understood. Because Ca2+ release patterns differ among isoforms of the inositol 1,4,5-trisphosphate (InsP3) receptor, the relationship between the distribution of these isoforms and subcellular Ca2+ signaling patterns in nonpigmented epithelial (NPE) cells was investigated. METHODS: The distributions of the types I, II, and III InsP3 receptors were determined in NPE cells by immunofluorescence, and subcellular Ca2+ signaling patterns in these cells were examined by confocal line scanning microscopy. RESULTS: The type I InsP3 receptor was concentrated at the basal pole of NPE cells, whereas the type III receptor was localized to the apical pole. The type II InsP3 receptor was not expressed in detectable amounts. Acetylcholine induced increases in Ca2+ that were mediated by InsP3, and these Ca2+ increases began as Ca2+ waves that were initiated at the apical pole, in the region of the type III InsP3 receptor. Acetylcholine occasionally induced sustained or repetitive Ca2+ increases that were prominent at the basal pole, in the region of the type I InsP3 receptor, but only subtle or absent apically. CONCLUSIONS: Because the type I InsP3 receptor is thought to be responsible for repetitive Ca2+ release events, and the type III InsP3 receptor instead is suited to initiate Ca2+ signals, the subcellular distribution of these two isoforms corresponds to the Ca2+ signaling patterns observed in this cell type. Differential subcellular expression of InsP3 receptor isoforms may be an important molecular mechanism by which NPE cells organize their Ca2+ signals in space and time.     

Total quality management: rhetoric and reality

TQM in health care today is still more rhetoric than reality. Changing the typical health care organization's culture and installing the infrastructure needed to support TQM will be expensive and time consuming, and will require a new technology of health care quality control that is still developing. TQM will achieve its considerable potential only if management stays the course, invests the time and money--and reins in Ruby and her ilk.     

Seizures of axial structures. Presumptive evidence for brain stem origin.

Scattered reports, both clinical and experimental, have been accumulating in the past 20 years indicating that true seizures may, indeed, originate from the brain stem and its immediate connections. Four cases are reported that give further strong presumptive evidence that this is so. All the seizures were confined to axial structures (face, tongue, palate, pharynx, diaphragm, and abdomen), and in one case each seizure had an identical "Jacksonian march." The phenomena were documented by 16-mm motion pictures, brain stem signs, and electroencephalography. The EEG consisted of periods of burst activity followed by relative interictal electrocerebral silence.