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Biomedical subjects

C Johnson

Publications and source records attributed to C Johnson.

At least 487 records · Page 27Linked to original sources

Hypernatremia induced by maximal exercise.

A short burst of intensive exercise (100-m swim lasting one minute and resulting in a 12-fold rise in the level of blood lactate) resulted in frank hypernatremia (serum sodium level, greater than 150 mEq/L) in 30% to 40% of well-trained athletes. In contrast, less intensive exercise (800-m swim lasting ten minutes and resulting in a sevenfold rise in the level of blood lactate) failed to cause a rise in serum sodium level despite comparable elevations in hematocrit reading and serum protein levels. Hypernatremia induced by intensive exercise cannot be explained by losses in body fluid or solute ingestion, but is probably a consequence of a shift of hypotonic fluid from the extracellular to the intracellular compartment. Thus, the mechanism of exercise-induced hypernatremia may be unique, as compared with other clinically recognized forms of hypernatremia.

Adolescent↗

Bulimia: an analysis of moods and behavior.

An innovative sampling method was used to compare normal-weight bulimic patients to normal controls on four dimensions: (1) overall moods, (2) extent of mood fluctuating, (3) degree of social isolation, and (4) extent of food-related behavior. In addition, a sequence analysis was conducted to explore the impact of binging and purging episodes on various affective states among the bulimics. Results indicated that the bulimics experienced significantly more dysphoric and fluctuating moods than normal controls and that they spent much more time alone and in food-related behavior than the control group. The discussion presents a hypothetical integration regarding the etiology and maintenance of the bulimic behavior based on the results of the data and post-trial interviews with the bulimic patients.

Adult↗

Oxidation of fatty acids in cultured fibroblasts: a model system for the detection and study of defects in oxidation.

A number of recently described inherited disorders interfere with the oxidation of fatty acids. In these disorders at least three different metabolic steps may be affected: (1) transport of long chain fatty acids into the mitochondria as in carnitine deficiency and carnitine palmitoyl transferase deficiency (CPT); (2) multiple acyl CoA dehydrogenase deficiency or glutaric aciduria type II (GAII) due presumably to a defective common electron transfering flavoprotein or iron sulfur flavoprotein; (3) specific long or medium chain fatty acyl CoA dehydrogenase deficiency as in inherited dicarboxylic aciduria. In order to develop a system for the detection and the study of the consequences of defects such as these on the oxidation of fatty acids, we investigated the metabolism of oleate (18 carbons), octanoate (eight carbons) and butyrate (four carbons) in intact cultured fibroblasts from patients with CPT deficiency, GAII, and dicarboxylic aciduria. In CPT deficient cells there was a markedly deficient ability to oxidize [1-14C] and [U-14C] oleate (19 and 5% of normal, respectively), whereas oxidations of [1-14C] octanoate and [1,4-14C] succinate were significantly increased (150 and 222%, respectively), and [1-14C] butyrate oxidation was normal. GAII cells displayed a nearly complete defect in the oxidation of [1-14C] and [U-14C] oleate (8 and 1%, respectively), as well as of [1-14C] octanoate and [1-14C] butyrate (8 and 5% of normal, respectively). The oxidation of [1,4-14C] succinate by GAII cells was normal. Cells from a patient with dicarboxylic aciduria showed a significant reduction in [14CO2] production from [U-14C] oleate (57%) and [1-14C] octanoate (31%) and a normal oxidation of [1-14C] oleate, [1-14C] butyrate, and [1,4-14C] succinate. These observations are consistent with available information on the normal metabolism of fatty acids in liver and muscle and also with the hypothesis about the molecular localization of the defects in GAII and inherited dicarboxylic aciduria. They demonstrate that intact cultured skin fibroblasts represent a reliable and convenient model for the investigation of fatty acid oxidation in man. Many aspects of the human acyl CoA dehydrogenases and their physiologic functions remain unknown, among them the problem of their acyl chain length specificity. Studies in cultured fibroblasts from patients with presumed mutations affecting the metabolism of fatty acids provide a means for the elucidation of these defects and at the same time give information on normal metabolic functions. It appears likely that a number of previously unrecognized defects in this area of metabolism remain to be found. The availability of a model system for their study in cultured fibroblasts should facilitate their discovery.

Carnitine O-Palmitoyltransferase↗

The myth of formal operations: rethinking adolescent cognition in clinical contexts.

There has been growing interest in the application of Piaget's theory to understanding children's thinking in clinical contexts. However, many such applications have been naive and accompanied by misconceptions. The present article deals specifically with the period of formal operations and its usefulness in understanding adolescent thinking. Literature is reviewed which leads to the conclusion that the formal operations concept has little clinical explanatory power. Formal operations represents an ideal description of intellectual competence, whereas clinicians must deal with factors influencing actual performance. Three performance factors are described which are especially relevant to understanding cognition in clinical situations.

Adolescent↗

Histamine-mediated adenylate cyclase stimulation in human myocardium.

We evaluated the mechanisms of histamine-mediated adenylate cyclase stimulation in 18 human hearts obtained from cardiac transplant recipients or prospective donors. Mg2+ and guanyl nucleotide were required for histamine stimulation. In the presence of 10-5 M GTP, histamine produced a maximal stimulation of 1.54 +/- 0.06 times basal activity in left ventricle (39% of the isoproterenol maximum), which rose to 1.75 +/- 0.14 times basal activity (68% of the isoproterenol maximum) in the presence of a 10-5M concentration of the synthetic guanyl nucleotide 5'-guanylyl imidodiphosphate. Histamine stimulation of adenylate cyclase was antagonized by cimetidine (KB = 1.58 X 10-6 M) but not by H1-blocking doses of mepyramine or pyrrobutamine. The selective H2 agonist dimaprit stimulated adenylate cyclase to approximately the same extent as histamine, whereas a selective H1 agonist produced only minimal stimulation that was H2-mediated. The selective H2 agonist impromidine was a partial agonist and produced approximately 20-40% of maximal histamine stimulation at lower concentrations (10-7 and 10-6 M) and inhibition of histamine stimulation at higher concentrations (10-5 and 10-4 M). Histamine stimulated adenylate cyclase activity over the same dose range as that which produced a positive inotropic response in isolated papillary muscles. Under one set of assay conditions, contractile response and adenylate cyclase does-response curves were essentially super-imposable. We conclude that human myocardial adenylate cyclase is coupled to the H2 receptor and linked to the contractile response, whereas the H1 receptor does not mediate a biochemical or mechanical effect.

Adenylyl Cyclases↗

The regulation of T cell responses by spontaneously active suppressor cells.

In studying T cell regulation, peripheral blood mononuclear cells from normal subjects were examined for 'spontaneous', rather than mitogen-induced, suppressor cell activity. Normal blood leucocytes from 30 subjects included a subpopulation of cells capable of suppressing the response of lymphocytes to the T cell mitogen phytohaemagglutinin by 21-35%. The indicator system for these studies consisted of fresh normal lymphocytes stimulated by three concentrations of PHA in the presence or absence of normal but mitomycin C treated peripheral blood lymphocytes. To measure accurately the spontaneous suppressor cell activity, additional cultures were needed to control for the suppressive effects of crowding and metabolic competition. Allogeneic, cryopreserved 'B' cell enriched populations, supplied satisfactory control cells for this purpose. While allogeneic culture systems could induce significant suppressor cell activity after 7 days of co-culture, they could not induce this activity in the 3 days required to assay spontaneous suppressor cell effects. In developing this assay we noted that (a) crowding became a factor in the cellular response to mitogens with concentrations higher than 2 X 10(4) cells/well, (b) spontaneous suppressor cell activity decreased rapidly once cells were placed in culture and (c) both spontaneous and concanavalin A (Con A) activated suppressor cells could significantly reduce the response to PHA even when added to cultures established with mitogens 72 hr earlier. The ability to measure spontaneous suppressor cell activity in vitro will allow more physiological studies of the membrane markers and functional characteristics of these cells than is possible in conventional studies utilizing Con A. In addition, this assay allows the detection of enhanced in vivo activity of suppressor cells not easily detected in assays relying on mitogen induction of suppression. Such increased activity is thought to be an important factor in the pathogenesis of a number of human diseases.

Cells, Cultured↗

Immunoregulatory abnormalities in children with thrombocytopenic purpura.

Twenty-eight children with idiopathic thrombocytopenia and 51 members of their immediate families were studied for immunologic function and expression of autoimmune phenomena and disease. Among patients with active ITP, 64% had defective immunoregulatory lymphocytes. The majority of patients (23/28) and family members had one or more immunologic abnormalities, including autoantibodies, other autoimmune disorders, and abnormalities in complement, immunoglobulins, or regulatory T lymphocytes. These data suggest that a genetic predisposition to autoimmunity is present in the majority of children with ITP.

Adolescent↗

Stimulus dominance in dichotic listening.

Twenty-four listeners received 20 dichotic-listening runs of natural stop-vowel syllables. Listeners marked two responses for each of 30 pairs of syllables per run, which yielded 480 pairs of responses for each of the 30 pairs of syllables. The principal analysis focused on "stimulus dominance" wherein a significantly higher score occurs for one of the competing syllables in a pair regardless of the ear to which that syllable is presented. With 30 pairs of syllables, there were 15 possible instances of stimulus dominance; 11 were observed. The voicing feature was contrasted for 9 of the 15 pairs. Seven of those pairs resulted in significantly higher scores (dominance) for the voiceless stop than for the voiced, one resulted in a higher score for the voiced member of the pair, and for one pair the scores for the two members were essentially the same. Stimulus dominance cannot, however, be characterized sufficiently as a dominance of voiceless over voiced stops; three of the six pairs in which voicing was shared also produced significant stimulus dominance. Stimulus dominance for a given pair of syllables may interact with, and in some cases override, the ear advantage. Of the 30 pairs of syllables, 11 produced a significant right ear advantage (REA), 9 produced a significant left ear advantage (LEA), and for 10 pairs the ear advantage was not significantly different from zero. For a specific pair of syllables, the direction of ear with, and in some cases override, the ear advantage. Of the 30 pairs of syllables, 11 produced a significant right ear advantage (REA), 9 produced a significant left ear advantage (LEA), and for 10 pairs the ear advantage was not significantly different from zero. For a specific pair of syllables, the direction of ear with, and in some cases override, the ear advantage. Of the 30 pairs of syllables, 11 produced a significant right ear advantage (REA), 9 produced a significant left ear advantage (LEA), and for 10 pairs the ear advantage was not significantly different from zero. For a specific pair of syllables, the direction of ear advantage usually corresponded to the ear that received the dominant syllable.

Adolescent↗

A common mutant EcoRI restriction endonuclease site in the 5' flanking portion of the human alpha-globin gene.

A mutant EcoRI endonuclease restriction site has been identified in 3 of 37 Black subjects and in 2 sibs of one of these persons. This mutation was not encountered in 13 Whites. It is located approximately 6 kilobases "inside" the normal site in the 5' flanking sequence of the alpha-globin chain complex. The shortened alpha-globin gene-bearing segment produced in the EcoRI digest produces a restriction map similar to that observed for the common alpha-globin gene deletion observed in the Black population. However, the restriction map with BamHI is normal, confirming that all four alpha loci are present.

Base Sequence↗

Insulin binding, internalization, and receptor regulation in cultured human fibroblasts.

Insulin binding to receptors was studied using monolayers of cultured normal human fibroblasts. Binding was rapid and inversely related to the incubation temperature; prolonged periods of steady-state binding were achieved at all temperatures studied and the amount of degradation of extracellular insulin was minimal. Competition curves demonstrated half-maximal inhibition of 125I-insulin binding at an unlabeled insulin concentration of 125I-insulin binding at an unlabeled insulin concentration of 7 ng/ml. Scatchard plots of the binding data were curvilinear and revealed that fibroblasts contained about 7,000 receptor sites per cell. Bound 125I-insulin dissociated from fibroblasts with a t 1/2 of 10 min at 30 degrees C and 35 min at 16 degrees C. After 60 min dissociation at 30 degrees C, 45% of the dissociated radioactivity consisted of 125I-insulin degradation products, whereas only 8% of the dissociated material was in the form of degraded products after 60 min of dissociation at 16 degrees C. This indicates that fibroblasts possess a temperature-sensitive receptor-mediated process for insulin degradation. Preincubation of the monolayers with insulin led to a hormone-induced loss of insulin receptors. Thus, incubating cells with 25 ng/ml insulin for 6 h at 37 degrees C caused a 50% reduction in subsequently measured 125I-insulin binding. This hormone-induced receptor loss was sensitive to physiologic insulin levels, with approximately 5 ng/ml causing a half-maximal receptor loss. When monolayers were treated with the lysosomotropic agent chloroquine and subsequently incubated with 5 X 10(-11) M 125I-insulin, a 130% increase in cell-associated radioactivity was observed after 120 min at 30 degrees C. In summary, 1) cultured normal human fibroblasts possess insulin receptors that exhibit kinetic properties and specificity identical to that of other insulin target cells; 2) incubation of fibroblasts with physiologic concentrations of insulin causes a marked loss of cell-surface insulin receptors; and 3) receptor-bound 125I-insulin is internalized through an energy-dependent endocytotic pathway and subsequently degraded by a chloroquine-sensitive reaction.

Cells, Cultured↗

Acute effects of caffeine in normal prepubertal boys.

A recent study demonstrated that dextroamphetamine has an effect in normal prepubertal boys similar to that seen in hyperactive children. The purpose of the present study was to see whether the effects of caffeine are similar to those of amphetamine in normal children. The authors observed 19 prepubertal boys following administration of a single dose of placebo, 3 mg/kg of caffeine, and 10 mg/kg of caffeine in a double-blind, crossover design. Caffeine produced increased vigilance and decreased reaction time, as does amphetamine. Unlike amphetamine, however, the higher dose of caffeine did not have a motor calming effect but increased motor activity. Separate biological systems, therefore, may be differentially affected by the two substances.

Attention↗