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Biomedical subjects

M Caplan

Publications and source records attributed to M Caplan.

At least 37 records · Page 2Linked to original sources
PubMed1991

Conflict and its resolution in small groups of one- and two-year-olds.

48 1- and 48 2-year-olds were observed in groups of 3 for 25 min on 2 consecutive days, once with ample resources and once with scarce resources. The triads were composed of either 2 girls and a boy or 2 boys and a girl, and duplicate copies of toys were available for half the groups. Their conflicts contained interpersonal features and were more affected by social influences than by the availability of resources. Contrary to expectations, scarcity of resources did not result in increased conflict. In fact, 2-year-olds were more likely to resolve conflict by sharing when toys were scarce. The provision of duplicates decreased the probability of conflict, but many conflicts occurred even when a duplicate was easily accessible. The form of conflict depended on the children's age and the gender composition of the group. Older children and groups dominated by boys, relative to younger children and groups dominated by girls, were less likely to use force and more likely to resolve disputes in prosocial ways. Taken together, these findings provide further evidence for the social nature of conflict in the first few years of life.

Child, Preschool↗
PubMed1990

Serum PAF acetylhydrolase increases during neonatal maturation.

Acetylhydrolase is an acid-labile, 43 kd protein that catalyzes the degradation of platelet activating factor (PAF), a potent phospholipid inflammatory mediator, to its biologically inactive metabolite lysoPAF. PAF has a short half-life, thus acetylhydrolase plays an important role in its regulation. Since previous work suggests that PAF may be involved in certain neonatal diseases such as necrotizing enterocolitis, we studied the effect of age on acetylhydrolase activity. Serum acetylhydrolase activity was quantified using radio-labelled PAF and measuring reaction products. Serum samples were obtained prospectively from 70 subjects ranging in age from 4 hr to 48 yr. Acetylhydrolase activity was lower for newborns (less than 3 wk) than all other age ranges (8.2 +/- 1.4 nmole/ml/min vs 30.0 +/- 1.6 nmole/ml/min, p less than .01). Furthermore, enzyme activity increased linearly with respect to the natural logarithm of age from 0 days to 6 weeks (r = 0.65, p less than .001). By 6 weeks of life acetylhydrolase activity approached values of older children and adults. Newborn acetylhydrolase activity was similar between term and preterm infants (8.6 +/- 1.9 nmole/ml/min vs 7.2 +/- 2.4 nmole/ml/min, p = NS). We conclude that acetylhydrolase activity is low in human neonates and increases during the first 6 weeks of life. These results suggest that newborn infants may be at increased risk for pathophysiologic processes mediated by PAF.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1990

Cerebrospinal fluid cachectin/tumor necrosis factor-alpha and platelet-activating factor concentrations and severity of bacterial meningitis in children.

In prospective studies, tumor necrosis factor (TNF alpha) was detected in cerebrospinal fluid (CSF) of 33 of 38 children with bacterial meningitis (BM) but in none of 15 with viral meningitis/encephalitis (P less than .001). BM CSF TNF alpha (less than 35 to greater than 25,500 pg/ml) correlated with CSF bacterial density (P less than .01), CSF protein (P less than .001), endotoxin (LPS) in gram-negative disease (P less than .01), and consecutive febrile hospital days (P less than .001); initial CSF TNF alpha greater than 1000 pg/ml was associated with seizures (P less than .05). Only 5 children with BM (13%) had detectable plasma TNF alpha activity on admission. A higher proportion who died had detectable plasma TNF alpha activity compared with survivors (3/4 vs. 2/34, P less than .005). Platelet-activating factor (PAF) in CSF was higher in 19 children with Haemophilus influenzae meningitis than in 17 controls (P less than .01) and correlated with bacterial density (P less than .01), CSF LPS (P less than .01), CSF TNF alpha levels (P less than .01), and the Herson-Todd severity score (P less than .01). Elevated CSF TNF alpha and PAF are often present in children with BM and are associated with seizures and severity of disease. Detectable CSF TNF alpha appears to distinguish BM from viral meningitis.

Adolescent↗
PubMed1989

Polarized distribution of Na+,K+-ATPase in giant cells elicited in vivo and in vitro.

Giant cell formation was analyzed to determine whether it results in the high level of Na+,K+-ATPase expression that characterizes multinucleated cells such as osteoclasts. Giant cells and fusing alveolar macrophages were subjected to morphological, immunological, and biochemical studies. Both subunits of the Na+,K+-ATPase were found to be present on the plasma membrane of giant cells. Their localization was restricted to the non-adherent domain of the cell surface. Dynamic studies of giant cell differentiation demonstrated that on culture and/or multinucleation, an increase in sodium pump alpha-subunit synthesis occurred and led to a high level of expression of Na pumps. Conversely, the adherent plasma membrane of giant cells was enriched in a lysosomal membrane antigen. This study demonstrates that culture and/or multinucleation induces a significant increase in the expression of sodium pumps. The polarized distribution of these pumps and of a lysosomal component suggests that fusing macrophages undergo biochemical and morphological alterations which prepare them for a new and specialized function in chronic inflammatory reactions. Giant cells may offer a suitable model system to study the differentiation of other related multinucleated cells, such as osteoclasts.

Animals↗
PubMed1986

Evidence for a high and specific concentration of (Na+,K+)ATPase in the plasma membrane of the osteoclast.

During bone resorption, the osteoclast actively acidifies a limited extracellular compartment. We hypothesized that, like other cells engaged in ion transport and proton translocation, the osteoclast's membrane might be highly enriched in sodium pumps. Using monoclonal antibodies to both the alpha and the beta subunits, immunoblot analysis, and [3H]ouabain binding, we have demonstrated that the osteoclast plasma membrane is both highly and specifically enriched in (Na+,K+)ATPase, compared with other bone cells, monocytes, macrophages, and other blood and bone marrow cells. The density of binding sites on the osteoclast is equivalent to that of kidney tubule cells. This observation is consistent with the hypothesis that the (Na+,K+)ATPase plays a role in the mechanism of bone resorption, possibly coupled with secondary active calcium and/or proton transport. Monoclonal antibodies against the (Na+,K+)ATPase can therefore be used as specific markers for the osteoclast in bone and bone marrow preparations.

Animals↗
PubMed1985

Monoclonal antibody to Na,K-ATPase: immunocytochemical localization along nephron segments.

To obtain a highly specific reagent that could be utilized for ultrastructural localization of Na,K-ATPase, monoclonal antibodies were produced using microsomal preparations of outer renal medulla of dog and rat enriched for Na,K-ATPase. The monoclonal antibody (C62.4) raised against dog antigen, immunoprecipitated a 96,000 Dalton protein from membranes labeled either with 35S methionine or 3H NAB ouabain. Na,K-ATPase, Na-ATPase, and KpNPPase activity were 25, 60, and 100% maximal after reaction with C62.4. Na,K-ATPase activated with SDS was inhibited, but Na,K-ATPase in tight right-side-out membrane vesicles was not. C62.4 inhibited ouabain binding in the presence of Na,K, and Mg, but did not inhibit ouabain binding in the presence of Mg and Pi. Labeling of broken membranes was readily seen using C62.4 labeled with colloidal gold. Intact right-side-out vesicles showed no evidence of labeling, demonstrating that the antibody is directed to an epitope of the cytoplasmic domain of the enzyme. Differential localization of C62.4 along the nephron was identified. Glomeruli showed no significant antibody binding except by occasional cells in the mesangial regions. Only basal lateral membranes of cells from all tubule segments labeled with C62.4. There was no evidence of specific apical labeling. The thick ascending limb of Henle's loop demonstrated the greatest concentration of antibody binding. In the cortical and outer medullary collecting duct, only principal cells showed abundant antibody binding. Intercalated cells showed no detectable evidence of antibody binding on any surface. These studies demonstrate that Na,K-ATPase is localized exclusively to the basal lateral membrane of renal tubular epithelial cells and varies in density and distribution in different nephron segments.

Animals↗
PubMed1985

Molecular cloning of rat brain Na,K-ATPase alpha-subunit cDNA.

We have isolated a cDNA clone for the rat brain Na,K-ATPase alpha subunit. A lambda gt11 cDNA expression library constructed from mRNA of 1- and 2-week-old rat brains was screened with an antibody reactive with rat brain Na,K-ATPase. A positive phage clone, lambda rb5, containing a 1200-base-pair cDNA insert expressed a beta-galactosidase-cDNA fusion protein that was reactive by immunoblotting with the Na,K-ATPase antibody. This fusion protein was also reactive in ELISA with a monoclonal antibody directed against the alpha subunit of the Na,K-ATPase. A 27S mRNA species exhibiting sequence hybridization to the cDNA insert of lambda rb5 was identified in rat brain, kidney, and liver, as well as in dog kidney. This 27S mRNA exhibited a tissue-specific pattern of abundance consistent with the relative abundance of Na,K-ATPase polypeptides in vivo: kidney greater than brain greater than liver. In a ouabain-resistant HeLa cell line, C+, which contains minute chromosomes and at least a 10-fold greater number of sodium pumps than parental HeLa cells, DNA sequences complementary to lambda rb5 cDNA were amplified approximately 40-fold. Analysis of the lambda rb5 cDNA sequence demonstrated a perfect nucleotide sequence match between a portion of the cDNA and the amino acid sequence of the Na,K-ATPase alpha-subunit fluorescein isothiocyanate binding site. Taken together, the data presented here demonstrate that the lambda rb5 cDNA clone is a portion of the gene coding for the rat brain Na,K-ATPase alpha subunit. The ATPase gene appears to be present in one or very few copies in the rat and human genomes and to be transcriptionally regulated in different rat tissues. In a ouabain-resistant human cell line, on the other hand, ouabain resistance appears to involve an increase in the number of gene copies coding for the Na,K-ATPase.

Animals↗
PubMed1985

Identification of hydrogen peroxide and hydroxyl radicals as mediators of leukocyte-induced myocardial dysfunction. Limitation of infarct size with neutrophil inhibition and depletion.

Neutrophil infiltration of the myocardium is an important component of such diverse disease entities as myocarditis, ischemia, and ischemia-reperfusion injury. We have hypothesized that activated neutrophils are capable of disrupting myocardial function via an oxygen free-radical mechanism. Human neutrophils activated with phorbol myristate acetate disrupted calcium transport by canine cardiac sarcoplasmic reticulum, and this process was inhibited by a combination of superoxide dismutase and catalase. In addition, the activated neutrophil system was also inhibited by the combination of cyclooxygenase inhibitors (ibuprofen and indomethacin) and catalase and accelerated by MK-447. These results incriminate both hydrogen peroxide and the hydroxyl radical as mediators of neutrophil-induced myocardial dysfunction. A test of this hypothesis in vivo was performed by neutrophil-depleting dogs with anti-canine leukocyte antisera prior to coronary artery ligation. Following 6 hr of reperfusion, there was a 43% reduction in infarct size compared to non-immune-sera-injected animals. We conclude that oxygen free radicals generated by neutrophils are capable of inducing significant myocardial injury and play an important role in the pathophysiology of ischemia reperfusion injury.

Adenosine Triphosphatases↗
PubMed1983

Hydrogen peroxide and hydroxyl radical mediation of activated leukocyte depression of cardiac sarcoplasmic reticulum. Participation of the cyclooxygenase pathway.

Human peripheral blood leukocytes, activated by phorbol myristate acetate, disrupt canine sarcoplasmic reticulum calcium transport, in vitro, by an oxygen-derived free radical mechanism. Activated leukocytes significantly depress Ca++ uptake activity and Ca++ -stimulated, Mg++ -dependent ATPase activity. The depression is completely inhibited by sodium-azide (0.1 mM) or the combination of superoxide dismutase (10 micrograms/ml) and catalase (10 micrograms/ml). Exogenous hydrogen peroxide (0.441-4.41 mM) uncoupled Ca++ uptake activity from ATP hydrolysis, and this effect was inhibited by catalase. Mannitol alone did not inhibit the effects of activated leukocytes, but superoxide plus mannitol (20-100 mM) resulted in normal ATPase activity, while Ca++ uptake remained depressed. In the presence of indomethacin and ibuprofen, activated leukocytes depressed Ca++ uptake and had no effect on ATPase activity. 2-Amino-methyl-4-t-butyl-6-iodophenol (MK-447) further depressed Ca++ uptake and partially inhibited the effect on ATPase activity. Indomethacin plus catalase completely inhibited the effects of activated leukocytes on cardiac sarcoplasmic reticulum. We conclude, first, that activated leukocytes depress canine cardiac sarcoplasmic reticulum Ca++ transport by an oxygen-free radical mechanism with the generation of hydrogen peroxide and hydroxyl radical. In addition to the classical membrane NADPH oxidase system, significant oxygen radical generation can occur through the cyclooxygenase pathway of arachidonic acid metabolism, and seems to be responsible for the generation of the hydroxyl radical.

Adenosine Triphosphatases↗
PubMed1983

Absence of pH effect on creatine kinase leakage from mouse skeletal muscle.

Skeletal muscle enzyme leakage has been found to be independent of extracellular pH (6.6 - 8.2), changes in ionic strength, osmolarity, and the weight changes that occur during in vitro incubation. This is in contrast to the effect of pH and ionic strength on heart, and no change in heart weight, during incubation in similar media. These observations further emphasize the disparate responses of heart and skeletal muscle to changes in the extracellular environment.

Animals↗
PubMed1982

Response manipulation on the depression Adjective Check List.

Explored response manipulation on the Depression Adjective Check List (DACL) in a 2 (trials) x 3 (instructions to fake) x 2 (sex) x 2 (order) mixed factorial, counterbalanced design in which 240 college students, 120 males and 120 females, were assigned randomly to one of six conditions with 20 males and 20 females per condition. For conditions 1, 2, and 3, each session consisted of two trials. In trial 1, Ss completed DACL, E, F, and G as they actually felt and in trial 2 they were instructed to either "fake good," "fake bad," or "fake average." The order of "actual" and "faked" trials was reversed for conditions 4, 5, and 6. The significant findings for "fake bad" and "fake good" were discussed in terms of the ability of an examiner to detect the manipulative set by means of the grossly deviant scores.

Adult↗
PubMed1977

Enhanced response acceleration or suppression produced by response-independent food presentations in rats with septal lesions.

In two separate experiments, the response rates of rats with septal lesions were compared with those of control rats when response-independent food was presented while subjects were responding on a differential-reinforcement-of-low-rate schedule of reinforcement (Experiment 1) or according to a conjunctive differential-reinforcement-of-high-rate, fixed-ratio schedule (Experiment 2). Free-food deliveries resulted in acceleration of responding of subjects working on the low-rate schedule and in suppression of responding of those animals working on the high-rate schedule. Both of these effects were localized to a brief time period immediately following the free-food deliveries, and baseline rates of responding were not altered. The acceleration and suppression of responding that occurred on the respective schedules were greatly enhanced in rats with septal lesions. This finding supports the suggestion that these animals are hyperreactive to the reinforcing and/or eliciting properties of discrete stimulus events.

Animals↗