Physiological chemistry and physics最新文献

Probable mitochondrial damage in brain and possibly in other tissues of an elderly woman after open heart surgery was treated by therapy aimed at providing the cell with materials necessary to synthesize new mitochondria to replace those damaged by imperfect perfusion of body tissues with blood by the artificial heart-lung machine. Large quantities of B-complex vitamins for Krebs cycle enzyme cofactors, vitamin C for protein synthesis, and ribonucleic acid for templates for protein synthesis were provided. With this therapy started 5 days post-operatively, marked acceleration of clinical recovery from a previously static state of presumed mitochondrial damage occurred. On the basis of animal experiments, a diagnosis of mitochondrial damage is suggested to be reasonable in appropriate human patients. On the basis of the successful result reported here, specific mitochondrial therapy is suggested as feasible and probably beneficial for patients with a diagnosis of mitochondrial damage.

By dynamic simulation of molecular structures in a digital computer, search was made for all possible ways of superposing a phenyl ring of a tricyclic antidepressant on the phenyl ring of norepinephrine. Using all available structure activity data and deductive reasoning, attempt was then made to reject all but one superposition. A significant outcome was information regarding 2-hydroxydesipramine. Although manifestly inactive when administered, this drug is likely to be potent if delivered at the neuronal site of action. From the chosen superposition a dihydroxy derivative is predicted to be even more potent if it can be endogenously generated or suitably modified to enable delivery at the site of action. Among the various superpositions obtained, it was indirectly possible to make a Monte Carlo type of conformational analysis on the side chain of norepinephrine. Previous conformational studies on norepinephrine are reviewed in this context.

A procedure is described for characterization of the proteinic, peptidic, and amino-acidic components of human placental extracts. Four different preparations were analyzed. The first was an extract prepared in our laboratory from fresh on-term placenta. The other three were commercial products obtained by different procedures including autolysis and sterilization. The patterns given by each type of preparation are reproducible and characteristic.

In 1838 a differential equation was developed by Verhulst to explain what is currently termed the S-shaped curve. Reviewed here are his application of the equation to population data and significant later applications by various workers to problems in physics, chemistry, and biology. The usefulness, versatility, and convenience of this integrated equation are illustrated by examples from our own work, including superimposition of data by use of reduced variables.

Sarcoplasmic reticulum preparations from rabbit cardiac and fast skeletal muscle react differentially with low concentrations of 1-fluoro- and 1,5-difluoro-2,4-dinitrobenzene. Dinitrophenylation of cardiac sarcoplasmic reticulum by 1-fluoro-2,4-dinitrobenzene is not affected by Ca2+ and is limited to the lipoprotein-lipid region. This contrasts sharply with the predominant Ca2+-dependent dinitrophenylation of the ATPase protein of rabbit skeletal sarcoplasmic reticulum by this reagent. Formation of non-serial high mol. wt. oligomers by 1,5-difluoro-2,4-dinitrobenzene is significantly greater in cardiac than in skeletal vesicles. Substrate MgATP2- does not protect rabbit cardiac sarcoplasmic reticulum ATPase activity or Ca2+ uptake from dinitrophenylation when monofunctional and bifunctional reagents are used. Chemical differences in the overall structure of the two kinds of membrane preparations can be ascertained from a comparison of the effects of Ca2+ and MgATP2- on the reactivity of these reagents.

Following the observation of polysome disaggregation by vanadate, when Neuro-2a cells were incubated with vanadate, incorporation of 3H-leucine into protein was markedly inhibited. The inhibition of protein synthesis was dependent on vanadate concentration and on time of incubation. Inhibition of cell growth was also observed. Simultaneous measurements on vanadate-treated cells showed decreased Na,K-ATPase activity. Rats given sodium vanadate as their sole drinking fluid also showed an inhibition of brain protein synthesis (18 and 20% after 30 and 60 days, respectively, of treatment). Possible implications of the inhibition of Na,K-ATPase and of protein synthesis by vanadate are discussed.

Immunological studies are reported showing that ascorbic acid, like selected sulfhydryl inhibitors, can induce immunity against some cancers in mice. Accompanying this immunizing action are changes in the surface structure of the cancer cells, as revealed by scanning electron microscopy. Electron spin resonance measurements show that the ascorbate anion free radical is readily produced in oxygenated cancer tissue and that this radical can react with sulfhydryl groups which are free radical scavengers. It is proposed that ascorbate acts as an effective thiolprive in oxygenated cancer tissues. This action is thought to lead to the observed changes in the cancer cell surface structure and to the concomitant immunological response.

Use of buffers in homogenization media can result in loss of considerable particulate enzyme activity even with low-speed centrifugation. Addition of tris chloride buffer to 0.25 M sucrose homogenization media resulted in precipitation of 80 to 95% of the activity of two mitochondrial marker enzymes (3-hydroxy-3-methylglutaryl CoA lyase and citrate synthase) with the nuclear fraction during differential centrifugation. Lactate dehydrogenase, a cytoplasmic marker, was not precipitated under the same conditions, indicating that the precipitated enzymes were not associated with intact cells. Photomicrographs showed that tris chloride buffers resulted in mitochondrial aggregation. Isolated mitochondria resuspended in tris chloride or potassium phosphate buffer also aggregated, which resulted in a marked decrease in assayable mitochondrial enzyme activity.