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A national panel on medical education was appointed as a component of the AAMC's Mission-based Management Program and charged with developing a metrics system for measuring medical school faculty effort and contributions to a school's education mission. The panel first defined important variables to be considered in creating such a system: the education programs in which medical school faculty participate; the categories of education work that may be performed in each program (teaching, development of education products, administration and service, and scholarship in education); and the array of specific education activities that faculty could perform in each of these work areas. The panel based the system on a relative value scale, since this approach does not equate faculty performance solely to the time expended by a faculty member in pursuit of a specific activity. Also, a four-step process to create relative value units (RVUs) for education activities was developed. This process incorporates quantitative and qualitative measures of faculty activity and also can measure and value the distribution of faculty effort relative to a school's education mission. When adapted to the education mission and culture of an individual school, the proposed metrics system can provide critical information that will assist the school's leadership in evaluating and rewarding faculty performance in education and will support a mission-based management strategy in the school.

Incubation of astrocytoma cells with catecholamines results in a decrease in catecholamine-stimulated adenylate cyclase activity and a concomitant alteration in the sedimentation properties of particulate beta-adrenergic receptors. The altered receptors exhibit agonist binding properties similar to those of receptors that are "uncoupled" from adenylate cyclase.

The quenching of protein fluorescence that occurs when dihydrofolate reductase is titrated with

Rabbit skeletal muscle phosphorylase kinase was treated with sodium dodecyl sulfate and fractionated by gel filtration chromatography into two peaks. Peak I was shown to consist of previously identified subunits A and B having molecular weights of 118,000 and 108,000, respectively. Peak II was shown to consist of subunit C having a molecular weight of 41,000. Peak I showed slight heterogeneity on sedimentation equilibrium. The average molecular weight for this fraction was found to be 103,000 in 0.1 % sodium dodecyl sulfate and 113,000 in buffer at pH 10.3. Peak II showed a molecular weight of 43,000 in 0.1% sodium dodecyl sulfate. The amino acid composition of peak I was shown to differ T A he preceding paper (Hayakawa et al., 1973) described a purification procedure for rabbit skeletal muscle phosphorylase kinase (ATP-phosphorylase phosphotransferase, EC 2.7.138) which yielded an essentially homogeneous enzyme. Physicochemical characterization of the kinase showed it to have a molecular weight of 1.33 X 106 and to be composed of three types of subunits with molecular weights of 118,000, 108,000. and 41,000 as revealed by disc gel electrophoresis in the presence of sodium dodecyl sulfate. These subunits, referred to as A, B, and C, respectively, were found to be present in amounts suggesting that the quaternary structure of the intact enzyme can be expressed by the formula, A4B4CV In the present paper an effort has been made to characterize more fully the subunits of phosphorylase kinase. Enzyme dissociated by sodium dodecyl sulfate was divided into a heavy (mixture of subunits A and B) and a light fraction (subunit C) by gel filtration chromatography. Each of these fractions was characterized by sedimentation equilibrium and amino acid analysis. Activation of the kinase by enzymatic phosphorylation was studied as a function of phosphate uptake in the individual subunits. Preliminary observations were made as to the effect of tryptic activation on the subunit structure of phosphorylase kinase. Experimental SectionMaterials. The purification of nonactivated rabbit skeletal muscle phosphorylase kinase was carried out as described t From the

Rabbit skeletal muscle phosphorylase kinase has been obtained in a homogeneous form having a sedimentation coefficient, J20,w> of 26.1 S and a molecular weight of 1.33 X 106. The enzyme is subject to pressure denaturation which leads to the formation of polydisperse aggregated material which can be separated from the major fraction of the enzyme by gel filtration using Sepharose 4B. Three types of subunits are present in phosphorylase kinase as determined by disc gel electrophoresis in the presence of sodium dodecyl sulfate. These subunits (A, B, and C) have molecular weights of 118,000, 108,000, and 41,000, respectively. Molar amounts of P .L hosphorylase kinase (ATP-phosphorylase phosphotransferase, EC 2.7.138) which catalyzes the conversion of phos-Recently the binding of Ca2+ to the enzyme has been studied t From the

Norepinephrine, epinephrine, and histamine cause a rapid increase in the concentration of adenosine 3':5'-cyclic monophosphate (cAMP) in a tumor astrocyte cell line derived from a primary culture of a human glioblastoma multiforme. The catecholamine-induced increase in cAMP is dependent on the cell density, being far greater in cells in the log phase of growth than in cells near terminal density. The response to norepinephrine is inhibited 50% by 0.01 pM propranolol, a blocking agent of #-adrenergic receptors. In contrast, the effect of histamine on cAMP concentration varies only slightly from log-phase growth to terminal density, and is not inhibited by 10 All of the known components of the cAMP regulatory system, adenylate cyclase (1), a cAMP-dependent protein kinase (2), and a cAMP-specific phosphodiesterase (3), are demonstrable in brain. Furthermore, the adenylate cyclase of brain generates cAMP in response to various effectors: e.g., putative neurotransmitters such as norepinephrine, histamine, and serotonin (4), depolarizing agents such as K + and veratridine (5), and the nucleoside, adenosine (6). However, elucidation of the exact role of cAMP has been hampered because of the anatomic and cellular complexity of brain. For example, there is great variation in the response of the adenylate cyclase system to these effectors within different brain regions (7), within the same region in different species (5), and at different stages of brain development (8). Further, since brain is composed of a number of cell types, primarily neurons and glia, measurements of enzyme activities in homogenates or of cAMP concentrations in slices will include contributions from both of these cell populations. To our knowledge, no report has appeared describing attempts to differentiate the response of the adenylate cyclase system in the two major cell types. Since neurons and glia probably have distinctly different functional capacities, an increase in the intracellular concentration of cAMP would presumably be mediated by cell-specific stimuli. In view of these considerations, studies with homogeneous cell populations of either neurons or glia should reveal whether one cell type or both are responsive to the various effectors, and ultimately should provide a rational approach to the determination of the role of cAMP in brain function. For this reason, we are characterizing the cAMP regulatory system of a human astrocytoma cell line, 1181N1, maintained in continuous culture. Adenylate cyclase, cAMP phosphodiesterase, and cAMP-dependent protein kinase are present 2757 (9), and the growth pattern and morphology of the cells is altered by N6, 02 '-dibutyryl cAMP (10). Here, we report the effects of catecholamines and histamine on the intracellular concentrations of cAMP. A preliminary report of some of the results of this investigation has appeared (11). MATERIALS AND METHODSThe cloned tumor astrocyte line, 1181N1, was originally derived from a human cerebral glioblastoma multiforme (12). The cells are grown in Eagle's mi...

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