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Biomedical subjects

D J Miller

Publications and source records attributed to D J Miller.

At least 235 records · Page 13Linked to original sources

The effects of very low external calcium and sodium concentrations on cardiac contractile strength and calcium-sodium antagonism.

1. The tension levels of the contractures induced in frog atrial trabeculae by reduction of the bathing Na concentration have been investigated over a wide range of [Na+]o and [Ca2+]o, making use of EGTA to buffer [Ca2+]o under 10(-5)M. 2. The relationship between tension and the quotient [Ca2+]o/[Na+]2o is only an apparent one, and holds approximately for Na concentrations as low as 1-5 mM. 3. However, for low Na concentrations tension depends on the absolute values of both [Ca2+]o and [Na+]o. 4. Extracellular Ca is the essential factor in tension production. The results indicate an apparent threshold for tension near 5 X 10(-8) M-[Ca2+]o. 5. It can be shown that, under the present experimental conditions, the Na concentration around the cells must be lower than about 0-1 mM in 'zero' Na+ solutions. 6. It is shown that the over-all process leading to tension production can be explained in terms of a reaction involving two Ca ions. 7. To account for the results, a modification of the reaction scheme put forward by Lüttgau & Niedergerke (1958) is proposed, involving a competitive action between Ca and Na ions at a free receptor site. 8. To account for the scheme, an example of a mechanism involving both internal and external Na and Ca concentrations is considered.

Animals↗

Serial habituation in two-, three-, and four-month-old infants.

Serial habituation of visual fixations in 2-, 3-, and 4-month-old infants was investigated through a design permitting cross-sectional, within-subject longitudinal, cohort longitudinal, and time-lag analyses. The components of the standard stimulus were displayed individually before and after successive exposures of the standard for familiarization. Relative saliencies of the components for each child were indexed by magnitude of responding to these parts in the initial presentation. Comparisons of the pre- and postexposure fixation times suggest that for all ages habituation was under way to the parts of the stimulus in orders of the relative saliencies. The nature of the data in general did not appear to be influenced significantly by any 1 methodology.

Attention↗

Individual differences in habituation rates and object concept performance.

The scores from object concept tasks for 15 infants at 14 months of age were analyzed with respect to their habituation rates at 4 months of age. Partitioning of the data according to subjects categorized as fast and slow habituators brought some organization consistent with the notion that the former are more advanced than the latter. Statistical differences between groups did not obtain, but a significant correlation between ranked task scores and habituation ratios offers some support to the interpretation. The possibility of using habituation rates or ratios as an index of differences in processing, perhaps with some predictive value, may be considered if further evidence of relations to later cognitive performanceis found.

Concept Formation↗

An animal model of fulminant hepatic failure: a feasibility study.

An attempt was made to produce animal model of fulminant hepatic failure in the pig by intragastric administration of acetaminophen (N-acetyl-p-aminophenol). The effect of varying doses was observed in phenobarbital-pretreated and untreated animals. Assessment of optimal dose was made in terms of duration of survival and coma in animals exhibiting biochemical and histological evidence of liver necrosis. Significant liver necrosis was observed in enzyme-induced pigs only, whereas in the noninduced pigs respiratory arrest was considered a likely cause of death. Although liver necrosis occurred consistently at a dose of 0.5 to 1.1 g per kg of acetaminophen in phenobarbital-pretreated animals, survival time and coma duration were unpredictable. Only one-fifth of the total number of phenobarbital-pretreated pigs administered acetaminophen in this dose range fulfilled the prescribed criteria for a satisfactory model. There was a good correlation between survival time and duration of coma, although survival time did not correlate with acetaminophen dose, or with any of the following: peak plasma acetaminophen levels, thrombocytopenia, fall in hematocrit or fibrinogen, or alteration in other biochemical parameters. In addition to the unpredictable duration of survival and coma, the occurrence of acute anemia in 60% of the enzyme-induced animals was a major detraction from the possible usefulness of this model to evaluate various therapeutic regimes.

Acetaminophen↗

Jaundice in severe bacterial infection.

Thirty patients are described who developed jaundice during the course of severe bacterial infection. Although the infecting organism was variable, as was the site of infection, the patients were generally ill and pyrexial. The group had a very high mortality rate (43%). A positive blood culture was obtained in 11 patients. Biochemical abnormalities noted were those of an increased concentration of conjugated bilirubin in the serum with only a modest increase in alkaline phosphatase and transaminase levels. Serum cholesterol was found to be normal. The mean serum urea level was significantly elevated, as were creatine phosphokinase and lactic dehydrogenase. Most patients exhibited a neutrophil leukocytosis and an elevated sedimentation rate, and the mean hemoglobin level was low. Liver histology was studied in 13 patients. There was evidence of mild bile stasis in 5 and moderate bile stasis in 2. Findings were otherwise nonspecific and were characterized by fatty change and/or inflammatory cells in the portal areas. There was no correlation between degree or duration of juandice and prognosis, although all patients who died remained jaundiced until death. It is suggested that this syndrome is not one of true cholestasis in that all biliary substances were not shown to be elevated in the serum, but that it is rather a selective defect in the excretion of conjugated bilirubin.

Adolescent↗

The effects of caffeine on the contraction of the frog heart.

1. The force of contraction and the membrane potentials have been measured from preparations of frog heart, with methods that also allow the rapid exchange of the extracellular fluid.2. In regularly beating preparations, caffeine induces only weak contractures at temperatures above 15 degrees C, but it does cause a marked potentiation of the twitch responses; longer exposure results in a depression of contraction. The build up and decline of the twitch strength, on addition and on removal of caffeine approximates to a single exponential, time constant 26-45 sec, and this time constant is not altered by variation of the [Ca](o), the stimulus rate or the caffeine concentration. This time course of the change of twitch strength is less complex than the changes seen when either [Ca](o) or the stimulus rate is altered, suggesting a more direct action of caffeine on excitation-contraction coupling.3. Caffeine increases the strength of the contractures initiated by potassium-rich or sodium-depleted solutions in isolated atrial trabeculae.4. After the spontaneous relaxation of the contracture, evoked by either sodium-free or potassium-rich fluids, the application of caffeine initiates a redevelopment of tension. This caffeine contracture is transient and its strength is dependent on the caffeine concentration. The response in sodium-free solution can be elicited in the virtual absence of extracellular calcium.5. Local anaesthetics antagonize the caffeine contracture.6. The results suggest that the sarcoplasmic reticulum of frog heart muscle plays an important role in the initiation and control of contraction and relaxation.

Action Potentials↗

Structure-activity relations for caffeine: a comparative study of the inotropic effects of the methylxanthines, imidazoles and related compounds on the frog's heart.

1. The ability of several groups of compounds, related to caffeine, to induce contractures in isolated frog auricular trabeculae has been tested.2. Of the methylxanthines, theophylline, theobromine and paraxanthine are of similar potency to caffeine. This applies to contractures produced in either high-potassium or in sodium-free solution, and to the twitch responses in normal Ringer.3. Xanthines in which the 9-position nitrogen is combined and is, therefore, without an ethylene bond do not affect contraction.4. The hypothesis is put forward that a double-bonded nitrogen, in an imidazole ring, is required for activity of the methylxanthine. This hypothesis is supported by the ability of imidazole and several close derivatives (e.g. histamine), as well as imidazolines, to evoke contractures. As predicted by the hypothesis, imidazolidines and imidazolidones, in which all the nitrogen atoms have single bonds, fail to initiate tension development.5. The activity of histamine and histidine is only demonstrable at high pH ( bumpy equals, equals 9.0).6. Raising the pH in sodium-free solution induces a transient contracture.7. Several arguments suggest that cyclic AMP is probably not an intermediate in the response to the methylxanthines. The activity of cyclic AMP (and adenosine) in eliciting contractures is predicted by the hypothesis because they contain an imidazole moiety as part of their molecular structure.

Adenosine↗

Biochemical and physical changes in shaken suspensions of Pasteurella pestis.

Pasteurella pestis, harvested after 24 to 30 hr of growth in a casein hydrolysate medium at 26 C, was resuspended and shaken in 3% lactose-0.1 m phosphate buffer for 4 hr at the same temperature. Certain characteristics of these starved cells were compared with those of control cells. No differences in the amounts of cellular carbohydrate or lipid were detected. The concentrations of the principal free amino acids were greater in the shaken cells, except that they contained no measureable arginine, and the normally large pools of intracellular tricarboxylic acid cycle intermediates were reduced. Greater viable-cell counts resulted with the cells that were shaken in lactose buffer than with the control cells when each was incubated at 5 C for several weeks. However, the reduced viabilities were apparent losses caused by the formation of aggregates of cells. The clumping of cells was caused by the polymerization of extracellular nucleic acids, principally deoxyribonucleic acid, that were excreted by the cells. Cell clumping could be partially prevented by prior shaking of the suspended cells, which removed some of the deleterious material, or by the action of crystalline deoxyribonuclease.

Acids↗