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Biomedical subjects

J W Mitchell

Publications and source records attributed to J W Mitchell.

At least 37 records · Page 2Linked to original sources

Phosphorylation of heart glycogen synthase by cAMP-dependent protein kinase. Regulatory effects of ATP.

Glycogen synthase I, purified from bovine heart, had a specific activity of 33 units/mg and gave a single band on sodium dodecyl sulfate gel electrophoresis with a subunit molecular weight of 86,000. The enzyme was phosphorylated with cAMP-dependent protein kinase catalytic subunit, also isolated from heart. With 10 microM ATP, only one phosphate group was incorporated per subunit of glycogen synthase. The phosphorylation decreased the per cent of glycogen synthase I from 0.95 to 0.50 when activity was determined by assays with Na2SO4 and glucose 6-phosphate. Glycogen synthase containing one phosphate per subunit was designated GS-1. One additional phosphate was incorporated per synthase subunit when ATP was increased to 0.5 mM and the percent glycogen synthase I decreased from 0.50 to < 0.05. This enzyme form was designated GS-1,2. Conversion of GS-1 to Gs-1,2 gave cooperative kinetics with ATP concentration and a half-maximal stimulation at approximately 40 microM. Phosphorylation of GS-1 could also be achieved by adding other non-substrate nucleotide triphosphates such as ITP and UTP along with 10 microM ATP. Glucose-6-P and Na2SO4 were without effect on this phosphorylation reaction. Two separate peptides were obtained after CNBr cleavage of 32P-labeled GS-1,2 and only one from GS-1. Both enzyme forms contained a single phosphorylated peptide in common. Thus, heart glycogen synthase may be phosphorylated specifically in either of two different sites using appropriate concentrations of ATP. ATP acts as a substrate for the protein kinase and also affects the availability of a second site to phosphorylation by cAMP-dependent protein kinase.

Adenosine Triphosphate↗

A ten year experience with cadaver kidney preservation using cryoprecipitated plasma.

Between August 1967 and January 1977, 699 cadaver kidneys were preserved and transplanted in our hospital after continuous perfusion with cryoprecipitated plasma. Overall graft survival of primary transplants was 55 +/- 2 per cent at one year and 41 +/- 2 per cent at four years. The results with ninety-six second transplants were similar. The number of HLA antigens shared and the duration of preservation did not influence graft survival. Patient survival among 426 cadaver graft recipients since September 1972, when lower dose immunosuppression was started, was 91 +/- 1 per cent at one year and 84 +/- 2 per cent at four years, significantly better than survival before then. Survival of fifty-two recipients of cadaver retransplants since September 1972 was 86 +/- 5 per cent at one year and 86 +/- 5 per cent at four years, which was better than before. The incidence of posttransplantation dialysis was 30 per cent and did not correlate with the length of preservation. Primary wound infections, primary ureteral extravasation, and vascular complications each occurred with an incidence of 1.1 per cent or less in patients treated with lower dose immunosuppression. Only four kidneys were lost because of complications, and in no instance was the need for transplant nephrectomy directly related to the method of preservation. Perfusion preservation with cryoprecipitated plasma gives excellent results compared with alternative methods.

Adolescent↗

Heat transfer from spheres and other animal forms.

A general predictive relation for the convection heat transfer from animal forms is developed. This relation is based on the convection equation for a sphere, and employs a simple, unique characteristic dimension to represent the animal which is the cube root of the animal volume. The accuracy of this relation is established through comparison with available convection results from animal shapes ranging in size and shape from spiders to cows. This relation allows an extrapolation to animal shapes for which data are not available. Results are also presented for the enhancement of convection heat transfer due to natural turbulence. A procedure is outlined for estimating the convecture heat loss from an animal in the natural outdoor environment.

Animals↗

Model simulation of blood flow and oxygen uptake during exercise.

We developed a dynamic model to account for blood flow in the working muscle during step changes in work rate. The model contains a proportional controller based on oxygen tension in the muscle and a description of the various oxygen-equivalent energy stores. Because of nonlinearities only particular solutions can be obtained. Such solutions were obtained via the finite difference method for various work levels and regimens. Model predictions are presented in comparisons with new experimental data, and with data reported in the literature. The changes in oxygen-equivalent energy stores and in muscle blood flow occur very rapidly after onset of exercise, with at least 90% of the steady-state response being reached within 90 sec.

Blood Flow Velocity↗