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Biomedical subjects

H A Johnson

Publications and source records attributed to H A Johnson.

At least 73 records · Page 4Linked to original sources

Injury of the cell's respiratory system by heat and by formaldehyde. Thermokinetics and early molecular events.

This is a study of the manner in which the respiratory system of the cell is injured either by elevated temperature or by exposure to diluted formaldehyde. Molecular mechanisms were identified by thermokinetic measurements. The rates at which respiratory failure developed in mouse liver slices in an injurious environment were measured at various temperatures. The data were fitted to the Arrhenius equation, and the effective activation energies of the injury processes were calculated. These data show that (1) the thermokinetics of injury to the cell's respiratory system, whether by thermal or chemical means, follows the Arrhenius law. (2) Thermal injury of the cell's respiratory system has a high activation energy, indicating that the critical, rate-determining event is a protein denaturation. Other mechanisms such as imbalance of metabolic reaction rates and thermal liquefaction of membrane lipids can be ruled out. (3) Repression of cell respiration by diluted formaldehyde has an activation energy compatible with a chemical reaction but low enough to exclude protein denaturation as a mechanism.

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On the thermodynamics of cell injury. Some insights into the molecular mechanisms.

A method is presented for determining the thermodynamic parameters of the rate-limiting chemical reaction in cell injury. From these parameters one can deduce certain molecular details of this reaction, such as the number of molecular events required for a specific observable injury, the approximate number of the chemical bonds broken and the degree of molecular configurational change involved. Inactivation of cell division in vitro by heat and by an alkylating agent have been studied by this method. In each case cell injury involved only one to three catastrophic molecular events, which were irreparable within a 3-day period. This suggests that in each case there had been an alteration of a genome essential for cell division. In the case of thermal injury this critical molecular event had the thermodynamic characteristics of a massive configurational change, compatible with the uncoiling of a DNA segment. In the case of alkylation injury the thermodynamic parameters were those of a small localized event with little configurational change and energetically compatible with an alkylation-depurination of DNA.

Animals↗