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D G Knox

Publications and source records attributed to D G Knox.

5 recordsLinked to original sources
PubMed1982

Thermodynamics of structural fluctuations in lysozyme as revealed by hydrogen exchange kinetics.

A new method is described that makes use of the empirical enthalpy--entropy compensation behavior of a related series of processes for deriving the activation enthalpy and entropy probability density functions from the corresponding rate constant density function. The method has been applied to data obtained from a study of the temperature dependence of hydrogen-tritium exchange in lysozyme. Analysis of the temperature dependence of tj, the time required to reach a particular number of hydrogens remaining unexchanged, provides estimates of delta G#, delta H#, and delta S# for the exchange process. The results are consistent with the notion of two mechanisms of exchange characterized by different activation energies. Increases in delta H# are compensated by corresponding increases in delta S#. The compensation plot, however, reveals two distinct apparent compensation temperatures, which reflect the operation of two qualitatively different mechanisms of exchange. The faster hydrogens exchange with delta H# values between 8 and 18 kcal X mol-1 and are characterized by a high compensation temperature of 470 K. The slower hydrogens exchange with delta H# values that reach 40 kcal X mol-1 and display a compensation temperature of congruent to 360 K. The latter is associated with a thermal unfolding mechanism of exchange.

Hydrogen↗
PubMed1978

Pressure effects on folded proteins in solution. Hydrogen exchange at elevated pressures.

The observed rate constants for base-catalyzed hydrogen exchange reactions between solvent water and peptide nitrogen in lysozyme, ribonculease A, oxidized ribonuclease A, and poly(DL-lysine) are all enhanced by an increase in pressure. Activation volumes have been calculated from the pressure effect on these rate constants. For the folded proteins lysozyme and ribonuclease A, deltaV for base-catalyzed exchange changes from about +9 ml/mol at atmospheric pressure -3 ml/mol at 2500 kg/cm2. The same quantity, determined for the random coil polypeptides oxidized ribonuclease A and poly(DL-lysine), does not show this dependence upon pressure. These effects can be understood either in terms of solvent penetration on the folded proteins or the onset of a small degree of pressure induced unfolding. Possible mechanisms by which such penetration could occur are discussed.

Hydrogen Bonding↗
PubMed1975

Portacaval shunt as emergency procedure in unselected patients with alcoholic cirrhosis.

A prospective evaluation of emergency portacaval shunt has been conducted during a 12 year period in 138 unselected, consecutive patients with alcoholic cirrhosis and bleeding esophageal varies. An extensive diagnostic evaluation was completed within seven hours of hospital admission, and the shunt operation was undertaken within a mean of 8.5 hours. Follow-up study was conducted in a special clinic, and the current status of 97.1 per cent of the patients had jaundice, ascites or encephalopathy alone or in combination on admission. Systemic intravenous administration of posterior pituitary extract temporarily controlled the hemorrhage in 94 per cent of the patients, and the emergency portacaval shunt promptly and permanently controlled the varix bleeding in 96 per cent of the patients. Contrary to recent proposals, patients with the highest portal perfusion pressure and, presumably, the largest hepatopetal portal flow had the highest survival rate and those who were presumed from pressure measurements to sustain the smallest portal flow diversion from the shunt had the lowest survival rate. The operative survival rate was 51 per cent, the predicted seven year survival rate for those operated upon seven or more years ago was 42.5 per cent. Encephalopathy requiring dietary protein restriction developed at some time in 17 per cent of the survivors. Sixty per cent of the survivors abstained from alcohol, and 53 per cent resumed gainful employment or full time housekeeping. Preoperative factors that adversely influenced survial rate were ingestion of alcohol within one month of bleeding, ascites, severe muscle-wasting and a small liver. Postoperatively, the single most important factor that compromised long term survival was resumption of alcoholism. In comparisons with our previous prospective studies, emergency portacaval shunt resulted in a significantly greater long term survival rate than did either emergency medical therapy or emergency varix ligation, followed by elective shunt. It is concluded that emergency portacaval shunt is the most effective treatment of bleeding esophageal varices in patients with alcoholic cirrhosis. Criteria for exclusion of those patients who are unlikely to derive long term benefits from portacaval shunt remain to be defined by further studies.

Adult↗