Biomedical subjects
Publications and source records attributed to K Butler.
A perfusion technique applicable to metabolic studies by NMR is described in detail. The utility and versatility of the approach are demonstrated by following gluconeogenesis from [2-13C]pyruvate in the perfused, isolated mouse liver, and lipogenesis from [2-13C]acetate in perfused Acanthamoeba castellanii cells embedded in agarose filaments.
Using 13C nuclear magnetic resonance, we have compared the gluconeogenic activity of perfused livers isolated from normal starved mice and mice highly parasitized with Plasmodium berghei, using [2-13C]pyruvate as substrate. In both types of livers, 13C labeling of glucose carbons occurred in positions 1, 2, 5, and 6. The equal proportions of [1,6-13C]- and [2,5-13C]glucose in livers from malarial and normal mice suggests that pyruvate enters the gluconeogenic pathway directly and, to an equal extent, via the tricarboxylic acid cycle. The normalized signal heights indicated that at a given time after the addition of [2-13C]pyruvate the degree of 13C labeling in glucose carbons was reduced in livers from malarial animals, when compared to livers from normal animals. During the course of the perfusion experiment, the [2-13C]lactate resonance signal was always more intense from livers of malarial animals than from normal animals. A reduced activity of hepatic gluconeogenesis in malarial animals was further confirmed by a separate set of perfusion experiments which showed a 56% reduction of the measured rate of glucose production in livers from malarial animals, with respect to that of normal animals. A lowered NAD/NADH ratio in livers from malarial animals would explain the increased proportion of lactate observed in the spectra and be related to a decreased gluconeogenic rate. A more reduced oxidoreduction level in the hepatocytes of a malarial animal would result from a defect in the oxidative phosphorylation activity of mitochondria.
The LVAS utilizing an intrathoracic blood pump and a parathoracic, electrohydraulic energy converter has a number of promising features. These include: transcutaneous energy transmission and an implanted variable volume device which eliminate the need for percutaneous access; utilization of an intrathoracic blood pump and variable volume device which allow the diaphragm and abdominal cavity to remain intact; parathoracic or subcutaneous location of the transformer secondary, energy converter, internal battery and interconnecting elements allowing replacement with a minor surgical procedure; employment of the "biolized" continuous blood contacting surface which has the potential of long-term use without anticoagulants and utilization of an electrohydraulic energy converter which provides synchronization without requiring transducers and associated electronics and which provides lubrication of mechanical components. The development effort, which began separately in 1977 and has been conducted jointly by Nimbus and the Cleveland Clinic since 1980, has demonstrated that the above features can be incorporated in a reliable LVAS. In particular, the system in vivo test series have demonstrated the soundness of the basic concepts and led to refinements which were demonstrated in the 6-1/2 mo test. All elements of the system have been utilized during the in vivo test program. Component tests of significance include: LVAS and total heart blood pump in vivo experiments of up to 7 mos duration which demonstrate the blood compatibility of the biolized surface without the use of long-term anticoagulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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A/J and C57BL/6J mice behave differently in tests for alcohol preference, open-field activity, defecation in the open field, cricket attacking, and rope climbing. Chimeric mice, i.e., mice containing both A/J cells and C57BL/6J cells, were constructed and tested for these behaviors. Patterns of behavior among A/J in equilibrium with C57BL/6J chimeras are such as to suggest that none of these behavior differences is controlled by a single cell or clone and that the same cell population that gives rise to the strain difference in alcohol preference also gives rise to the differences in open-field activity and defecation, while separate cell populations control cricket killing and rope climbing.
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The effect of anti-inflammatory drugs on the biochemical changes in the Arthus reaction have been studied and correlated to changes in the pathology of the reaction. In the Arthus reaction all the non-steroidal anti-inflammatory drugs inhibited the migration of cells into the lesion and reduced the lysosomal enzyme concentration at the Arthus site. The steroids did not inhibit the cellular inflitration or the total lysosomal enzyme concentration in the skin but did reduce the concentration of cathepsin D in the oedema fluid. In addition, prednisolone and, to a lesser extent, hydrocortisone reduced the degree of oedema formation. The results suggest that non-steroidal anti-inflammatory drugs inhibit the Arthus reaction by reducing the cellular infiltration whereas anti-inflammatory steroids act by preventing these cells secreting their lysosomal enzymes and thus causing tissue damage.
The object of this investigation was to determine whether the pathological events which occur during the Arthus and mixed hypersensitivity reaction could be monitored biochemically and whether changes in enzyme concentrations would reflect the severity of tissue damage either in the skin itself or in the lymph draining the lesion. The initial increase in vascular permeability which resulted in oedema formation in the tissue was reflected by a large increase in the water and protein content of the tissues, however, there was no increase in either the protein concentration or flow of the lymph. The increases in the total enzyme content in the lesion could not always be related to the macroscopic appearance of the reaction site. However, the severity of the reaction did appear to be related to the concentration of cathepsin D in the oedema fluid present at the reaction site. Although the release of enzymes was reflected in the local lymph in the case of LDH and beta-glucuronidase there was no increase in of the concentration cathepsin D in the lymph draining the lesion.
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1. Lymph was collected directly from the hind limbs of rabbits anaesthetized with pentobarbitone and from unanaesthetized rabbits before and after one hind limb was injured by immersion in water at 60 degrees C for 1 minute.2. Rabbits were treated with anti-inflammatory agents hydrocortisone or indomethacin which, in acute experiments, were infused close-arterially into the limb either at the time of the injury or 90 min later. In chronic experiments hydrocortisone was given intravenously three times a day.3. When given at the time of the injury both drugs reduced the subsequent mean increases in the lymph of the intracellular enzymes lactate dehydrogenase and glutamic pyruvate transaminase but not those of beta-glucuronidase and protein; whereas when given 90 min after the injury only the increase in lymph protein concentration was reduced.4. The results indicate that these anti-inflammatory agents probably inhibit the second phase of increase in vascular permeability which occurs after injury and in addition, reduce the leakage of intracellular protein by a non-specific effect on membrane permeability.5. The pronounced variability of the response of individual animals and the complexity of the experiments preclude the method as a suitable model for the estimation of anti-inflammatory activity.
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