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D Crane

Publications and source records attributed to D Crane.

71 records · Page 4Linked to original sources
PubMed1983

Decrease of flux through pyruvate dehydrogenase and branched-chain 2-oxo-acid dehydrogenase by nitrofurantoin in perfused rat liver.

Addition of nitrofurantoin to isolated perfused rat liver leads to an inhibition of 14CO2 production from [1-14C]pyruvate, 2-oxo-[1-14C]isocaproate and 2-oxo-[1-14C]isovalerate, indicating a decreased flux through the corresponding mitochondrial 2-oxo-acid dehydrogenases. This is in agreement with a decreased tissue level of the active (dephospho)form of pyruvate dehydrogenase in presence of nitrofurantoin. 2) Evidence is presented for an inhibition of the monocarboxylate translocator in the mitochondrial membrane during addition of nitrofurantoin by comparing the effects of alpha-cyanocinnamate as a transport inhibitor with those of nitrofurantoin. 3) It is concluded that nitrofurantoin-induced hepatocyte toxicity may include mitochondrial effects due to decreased oxo-acid dehydrogenase flux.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1983

Decreased flux through pyruvate dehydrogenase by thiol oxidation during t-butyl hydroperoxide metabolism in perfused rat liver.

Addition of t-butyl hydroperoxide to isolated perfused rat liver leads to a decreased flux through pyruvate dehydrogenase, shown by a decreased 14CO2 release from [1-14C]pyruvate. The effect is observed at rates of infusion of t-butyl hydroperoxide exceeding 0.7 mumol per min per g liver in normal livers and at significantly lower rates in glutathione-depleted livers. The effect is absent in livers from Se-deficient rats in which the hepatic Se-dependent glutathione peroxidase activity is very low, indicating that reduction of t-butyl hydroperoxide by glutathione peroxidase is a necessary prerequisite for the inhibition. With isolated mitochondria, decreased 14CO2 release from [1-14C]pyruvate during t-butyl hydroperoxide metabolism correlates with decreased GSH and increased GSSG contents, respectively. The addition of various disulfide compounds, including GSSG, inhibits activity of the enzyme in mitochondrial extracts. In both mitochondria and perfused liver, t-butyl hydroperoxide-mediated decrease of pyruvate dehydrogenase flux is relieved by thiol reductants. The active (dephospho)form of pyruvate dehydrogenase as measured in freeze-stopped liver samples is actually increased from 46% to 72% during t-butyl hydroperoxide metabolism. The tissue levels of ATP and ADP and perfusate beta-hydroxybutyrate/acetoacetate ratio are not markedly perturbed by addition of the hydroperoxide (10 min). It is concluded that the decreased flux through pyruvate dehydrogenase during t-butyl hydroperoxide metabolism results from oxidation of critical thiol group(s) of the enzyme complex consequential to a decrease in mitochondrial GSH/GSSG.

Animals↗
PubMed1982

Synthesis and incorporation of phospholipid by peroxisomes of mouse liver.

The uptake of radioactively labelled glycerol into the phospholipid fractions of mouse liver has been studied. The incorporation of phospholipid into peroxisomal and microsomal membranes was found to be rapid, and of a similar timescale, whereas mitochondrial membranes were appreciably slower in their uptake of label. Discernible differences were shown to exist between these membrane types in relation to phospholipid composition and lipid turnover. These data are interpreted as supportive of a model for peroxisomal biogenesis which involves formation of these organelles by a budding process from the smooth endoplasmic reticulum.

Animals↗
PubMed1982

Rise of coenzyme A-glutathione mixed disulfide during hydroperoxide metabolism in perfused rat liver.

The hepatic metabolism of an externally added hydroperoxide, t-butyl hydroperoxide, results in substantial decreases in CoASH and acetyl-CoA and a concomitant increase in CoA-disulfides. The principal CoA-disulfide which is formed under these conditions was identified as CoASSG, the mixed disulfide of coenzyme A and glutathione; CoASSCoA levels were unchanged. The perturbation in the coenzyme A system was absent when the hydroperoxide was infused into livers from rats maintained on a selenium-deficient diet. In these livers. Se-dependent glutathione peroxidase is lowered to less than 5% of control levels; the observed effects can be attributed to flux through Se-dependent GSH peroxidase.

Acetyl Coenzyme A↗
PubMed1975

Decisions to treat critically ill patients: a comparison of social versus medical considerations.

A questionnaire survey shows that physicians in four medical specialties evaluate chronically and terminally ill patients not only in terms of the physiological aspects of illness but also in terms of the extent to which they are capable of interacting with others. A patient's potential capacity to perform his social roles depends upon his "salvageability," i;e., the likelihood that he will be able to resume his roles and the degree of irreversible physical or mental damage which indicates his capacity for resuming them. The priorities in terms of treatment are the following: (1) salvageable patients with physical damage; (2) salvageable patients with mental damage and unsalvageable patients with physical damage; (3) unsalvageable patients with mental damage. Within these catagories variables such as patient attitude, family attitude, age, and social class, which define the social environment of the patient, also influence the physician's decision to treat him. Studies of hospital records of cases in two of the specialties were consistent with they survey findings. The findings suggest that there is a disparity between the traditional ethic concerning the treatment of such patients and the actual behavior of many physicians. As a solution to the inconsistencies between ideal and actual behavior, the development of medical guidelines for the withdrawal of treatment with respect ot certain specifically defined conditions is recommended.

Adult↗