Principal/agent theory and decision making in health care

Principal/agent theory, an economics concept that defines an agency relationship as "a contract under which one or more persons engage another person (the agent) to perform some service on their behalf which involves delegating some decision-making authority to the agent," is held to be applicable to the patient/physician relationship, in contrast to the view that this is a fiduciary relationship, not a contractual one. The distinction between fiduciary and contractual relationships is illuminated in the process of evaluating objections to the application of the principal/agent theory to the patient/physician relationship. The ability of the principal/agent theory to reveal important features of advance directives, understood as public documents rather than as confidential instructions from patient to physician, is also examined.     

A novel hsp70-like protein (P70) is present in mouse spermatogenic cells.

Mouse spermatogenic cells contain relatively large amounts of a 70-kilodalton protein (P70) that is closely related to hsp70, the major inducible heat shock protein. When hsp70 from spermatogenic cells is heat induced, it migrates to the same location as does P70 on two-dimensional polyacrylamide gels, indicating that it has an apparently identical mass and isoelectric point. P70 reacts strongly and specifically with an anti-Drosophila hsp70 monoclonal antibody that is specific for products of the hsp70 gene family. Both P70 and hsp70 are also ATP-binding proteins and are purified by using ATP-affinity chromatography. However, P70 and hsp70 are unique proteins on the basis of peptide map analysis and are regulated differently in germ cells. P70 appears to be a novel heat shock protein of spermatogenic cells which is synthesized in association with germ cell differentiation.     

Copper deficiency depresses rat aortae superoxide dismutase activity and prostacyclin synthesis

Prostaglandin synthesis shows dependence on lipid hydroperoxides and resultant oxygen derived radical formation. In view of the importance of dietary copper in cytosolic copper dependent superoxide dismutase (Cu/Zn SOD) activity and the role of SOD in oxygen radical formation, the influence of dietary copper on prostacylin (PGI2) synthesis and SOD activity in rat aorta was examined. Copper deficient (0.5 micrograms Cu/g diet) rats showed a significant 47% reduction in PGI2 synthesis rates by aortic ring incubations in comparison to copper adequate (6.0 micrograms Cu/g diet) animals. Aortic SOD activity was reduced by 46% in copper deficiency in comparison to copper adequate animals. Marginal dietary copper (1.6 micrograms Cu/g diet) significantly reduced aortic SOD activity by 32% but was without effect on aortic ring incubation PGI2 synthesis. These results indicate that dietary copper deficiency, and the resultant decrease in SOD activity, depresses aortic PGI2 synthesis.     

Agroinfection and nucleotide sequence of cloned wheat dwarf virus DNA

Cloned DNA of the geminivirus wheat dwarf virus (WDV) was successfully used to infect seedling wheat plants. The clone was derived from circular double-stranded viral DNA isolated from naturally infected tissue. The initiation of infection was mediated by Agrobacterium tumefaciens using cloned dimeric WDV genomes in a binary Agrobacterium vector. The WDV DNA which comprised the infectious clone was sequenced and is compared with the published sequence of a Swedish isolate of the same virus. The results confirm that the single WDV genome component of 2.75 kb carries all the information necessary for production of viral symptoms, virus particles and viral double- and single-stranded DNA forms.     

Genetic information could be integrated extrinsically for simplest life forms

Polynucleotides and proteins coupled in mutual synthesis are widely believed to have been needed for the origin of life, but this theory encounters grave problems. Simple catalysts reproducing by positive feedback, sometimes advocated as an alternative, lack a built-in mechanism for generating and accumulating genetic information. Modern organisms, however, integrate genetic information by extrinsic in addition to intrinsic mechanisms, and extrinsic mechanisms were available even at the beginning of chemical evolution for any self-reproducing entities that might have appeared. Novel molecules were generated by reactions among prevailing molecules, and a catalyst multiplying by positive feedback would have transmitted structural information not only to progeny molecules of its kind, but to derivatives and by-products. New molecules derived immediately or remotely from successfully reproducing catalysts would be favored to have catalytic properties. New catalysts with effective positive feedback would increase autocatalytically and be integrated with others into a metabolizing system by natural selection.     

Two Developmentally Regulated Isoenzymes of Calmodulin-Stimulated Protein Kinase II in Rat Forebrain

Soluble calmodulin-stimulated protein kinase II has been purified from adult and 10-day-old rat forebrain. By autoradiography, the alpha/beta subunit ratios of the 10-day and adult enzymes were 0.67 +/- 0.03 and 2.20 +/- 0.15, respectively. By silver staining, the alpha/beta subunit ratios were 1.02 +/- 0.06 and 2.36 +/- 0.10, respectively. The apparent holoenzyme molecular masses of the purified 10-day and adult enzymes were 500,000 daltons and 700,000 daltons. However, varying the purification conditions revealed higher and lower molecular mass forms at both ages and suggested that the form of the kinase that is usually purified is merely that which has the highest affinity for calmodulin-Sepharose and may not be the form of the kinase that exists in vivo. The subunits of the adult and 10-day enzymes were indistinguishable by one- and two-dimensional electrophoresis and one-dimensional proteolytic peptide maps. These results are consistent with the suggestion that at least two developmentally regulated isoenzymes of this kinase exist in rat forebrain.     

Differential Regulation by Calmodulin of Basal, GTP-, and Dopamine-Stimulated Adenylate Cyclase Activities in Bovine Striatum

The concentration requirements of calmodulin in altering basal, GTP-, and dopamine-stimulated adenylate cyclase activities in an EGTA-washed particulate fraction from bovine striatum were examined. In the bovine striatal particulate fraction, calmodulin activated basal adenylate cyclase activity 3.5-fold, with an EC50 of 110 nM. Calmodulin also potentiated the activation of adenylate cyclase by GTP by decreasing the EC50 for GTP from 303 +/- 56 nM to 60 +/- 10 nM. Calmodulin did not alter the maximal response to GTP. The EC50 for calmodulin in potentiating the GTP response was only 11 nM as compared to 110 nM for activation of basal activity. Similarly, calmodulin increased the maximal stimulation of adenylate cyclase by dopamine by 50-60%. The EC50 for calmodulin in eliciting this response was 35 nM. These data demonstrate that calmodulin can both activate basal adenylate cyclase and potentiate adenylate cyclase activities that involve the activating GTP-binding protein, Ns. Mechanisms that involve potentiation of Ns-mediated effects are much more sensitive to calmodulin than is the activation of basal adenylate cyclase activity. Potentiation of GTP-stimulated adenylate cyclase activity by calmodulin was apparent at 3 and 5 mM MgCl2, but not at 1 or 10 mM MgCl2. These data further support a role for calmodulin in hormonal signalling and suggest that calmodulin can regulate cyclic AMP formation by more than one mechanism.