The mechanical properties of human erythrocyte membrane are largely regulated by submembranous protein skeleton whose principal components are alpha- and beta-spectrin, actin, protein 4.1, adducin, and dematin. All of these proteins, except for actin, are phosphorylated by various kinases present in the erythrocyte. In vitro studies with purified skeletal proteins and various kinases has shown that while phosphorylation of these proteins can modify some of the binary and ternary protein interactions, it has no effect on certain other interactions between these proteins. Most importantly, at present there is no direct evidence that phosphorylation of skeletal protein(s) alters the function of the intact membrane. To explore this critical issue, we have developed experimental strategies to determine the functional consequences of phosphorylation of beta-spectrin on mechanical properties of intact erythrocyte membrane. We have been able to document that membrane mechanical stability is exquisitely regulated by phosphorylation of beta-spectrin by membrane-bound casein kinase I. Increased phosphorylation of beta-spectrin decreases membrane mechanical stability while decreased phosphorylation increases membrane mechanical stability. Our data for the first time demonstrate that phosphorylation of a skeletal protein in situ can modulate physiological function of native erythrocyte membrane.

4-chloro-m-cresol is a trigger of malignant hyperthermia in susceptible swine, but only when serum concentrations are far above those likely to be encountered in humans. A relatively low concentration of 4-chloro-m-cresol, 50 micromol, is sufficient to activate sarcoplasmic [Ca+2] release in vitro (e.g., contractures); this same bolus dose administered in vivo (0.57 mg/kg) has minimal effects due to the rapid decrease in its plasma levels.

Abstract.Gastrointestinal stromal tumors (GISTs) are the most frequently diagnosed mesenchymal tumors of the GI tract. GISTs usually arise from the stomach, followed by the small intestine, rectum and other locations in the GI tract. The most common metastatic sites are the liver and peritoneum, whereas GISTs rarely metastasize to the bone. Although a small number of previous studies have described bone metastases originating from GISTs, the true prevalence is yet to be elucidated. The present study describes two cases of bone metastasis in patients with GISTs and reviews the relevant literature. Case one was of a 78-year-old male who presented with bone metastasis to the femoral neck five years after the resection of a GIST. The metastasis was completely resected and the patient remains alive nine years after the initial diagnosis of the GIST. Case 2 was of a 41-year-old male who presented with bone metastases to the ribs following resection of GISTs seven and 17 years earlier. The metastases were completely resected and the patient remains alive 17 years after the initial diagnosis. In total, only 10 cases of GISTs with metastases to the bone have been reported in the English literature. The possibility of bone metastases originating from a GIST should be considered during clinical follow-up, particularly in the presence of liver metastases. If feasible, bone metastases should be completely surgically excised.