Carol F. Whitfield

SPECTRIN AND RELATED MOLECULES

This review begins with a complete discussion of the erythrocyte spectrin membrane skeleton. Particular attention is given to our current knowledge of the structure of the RBC spectrin molecule, its synthesis, assembly, and turnover, and its interactions with spectrin-binding proteins (ankyrin, protein 4.1, and actin). We then give a historical account of the discovery of nonerythroid spectrin. Since the chicken intestinal form of spectrin (TW260/240) and the brain form of spectrin (fodrin) are the best characterized of the nonerythroid spectrins, we compare these molecules to RBC spectrin. Studies establishing the existence of two brain spectrin isoforms are discussed, including a description of the location of these spectrin isoforms at the light- and electron-microscope level of resolution; a comparison of their structure and interactions with spectrin-binding proteins (ankyrin, actin, synapsin I, amelin, and calmodulin); a description of their expression during brain development; and hypotheses concerning their potential roles in axonal transport and synaptic transmission.

Regulation of Sugar Transport in Eukaryotic Cells

Publisher Summary This chapter describes the control of passive transport of sugar in erythrocytes, muscle, adipose tissue, and other tissues. Transport is passive in the sense that under ordinary conditions, the sugar moves from a region of higher to one of lower concentration. Transport is a major rate-limiting step for glucose uptake in a large variety of eukaryotic cells. Existing kinetic data are compatible with a simple carrier model for passage of the sugar through the membrane. Nonhormonal control of transport is the most basic type of regulation, because it is present in both unicellular organisms and in cells of mammalian tissues. The conditions involved in this type of regulation are decreased energy production, increased energy expenditure, or utilization of other substrates. These conditions are brought about by anoxia and inhibitors of oxidative phosphorylation, by increased ATP consumption from muscle contraction and greater rates of ion pumping, and by providing fatty acids as substrates. The anoxic effect on transport is related to ATP depletion, but the effect cannot be considered to be due to ATP levels alone. Insulin is the major hormone that accelerates transport in muscle and adipose tissue. Growth hormone modifies insulin sensitivity, as does cortisol. The inhibitory effect of cortisol in adipose tissue, diaphragm, and thymocytes may involve synthesis of an inhibitory protein. Epinephrine increases sugar transport in heart, adipose tissue, skeletal muscle, and avian red blood cells.

Effect of anoxia on sugar transport in avian erythrocytes.

Abstract 1. 1. Simple anoxia, without additon of metabolic poisons, was found to stimulate carrier-mediate sugar transport. 2. 2. Development of an anoxic stimulation of transport immediately followed changes in intracellular levels of low and high energy intermediates, suggesting a role for these compounds as regulators of transport. 3. 3. Adenine and ATP were the only metabolites found to alter transport rates, when they were added exogenously. Adenine partially inhibited the anoxic stimulation of transport while ATP stimulated sugar entry in both aerobic and anerobic cells. 4. 4. Neither monovalent nor divalent cations were absolutely required for the development of the faster rate of transport in anoxic cells.

Tracking development of clinical reasoning ability across five medical schools using a progress test.

Purpose Little is known about the acquisition of clinical reasoning skills in medical school, the development of clinical reasoning over the medical curriculum as a whole, and the impact of various curricular methodologies on these skills. This study investigated (1) whether there are differences in clinical reasoning skills between learners at different years of medical school, and (2) whether there are differences in performance between students at schools with various curricular methodologies. Method Students (n = 2,394) who had completed zero to three years of medical school at five U.S. medical schools participated in a cross-sectional study in 2008. Students took the same diagnostic pattern recognition (DPR) and clinical data interpretation (CDI) tests. Percent correct scores were used to determine performance differences. Data from all schools and students at all levels were aggregated for further analysis. Results Student performance increased substantially as a result of each year of training. Gains in DPR and CDI performance during the third year of medical school were not as great as in previous years across the five schools. CDI performance and performance gains were lower than DPR performance and gains. Performance gains attributable to training at each of the participating medical schools were more similar than different. Conclusions Years of training accounted for most of the variation in DPR and CDI performance. As a rule, students at higher training levels performed better on both tests, though the expected larger gains during the third year of medical school did not materialize.

Simulation of diabetic ketoacidosis for cellular and molecular basics of medical practice.

DEMOGRAPHICS Patient Name: Tiffany. Scenario Name: Interactive Discussion on Diabetic Ketoacidosis presented in synthetic Emergency Department Bay: making a problem-based learning (PBL) session “come alive.” Date of Development: January 2007, January 2008. Appropriate for Following Learning Groups: medical students (year): 1, 2; nursing students (year): 1, 2; specialty areas: all acute care areas including primary care. Appropriate Class Size: The medical students attend the sessions mostly in their existing PBL groups which consist of 6 to 8 students which seem to be an ideal group size. Up to 10 students have been accommodated.

Sugar transport in reversibly hemolyzed avian erythrocytes.

The technique of reversible hemolysis represents one approach which may be used to study transport regulation in nucleated red cells. After 1 h of incubation at 37 degrees C, 88% of the ghosts regained their permeability barrier to L-glucose. In these ghosts, the carrier-mediated rate of entry of 3-O-methylglucose was more than 10-fold greater than the rate in intact cells. Glyceraldehyde-3-phosphate dehydrogenase prevented ghosts from resealing when it was present at the time of hemolysis. Albumin, lactic dehydrogenase and peroxidase did not have this effect. Sugar transport rate could not be tested in the unsealed ghosts. Two possible mechanisms for the effect of hypotonic hemolysis on sugar transport rate were discussed: (1) altered membrane organization and (2) loss of intracellular compounds which bind to the membrane and inhibit transport in intact cells.