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Biomedical subjects

M Siegal

Publications and source records attributed to M Siegal.

17 recordsLinked to original sources
PubMed1991

Where to look first for children's knowledge of false beliefs.

Recent research has shown that, although young children have a substantial knowledge of beliefs as internal mental states, they have considerable difficulty in understanding how a false belief can lead to an outcome which is in conflict with a desire. However, this evidence has come from tasks which assume that children follow an experimenter's "implicatures" in conversation and interpret the question "Where will a person (with the false belief) look for the object?" to mean "Where will the person look first?" rather than "Where will the person have to look (or go to look) to find the object?" In our investigation, even 3-year-olds often responded correctly when asked to predict the initial behavior of a story character with a false belief. We discuss these results in terms of the conversational worlds of children and adults.

Adult↗
PubMed1991

Antiarrhythmic actions of the ATP-regulated K+ current activated by pinacidil.

We tested the hypothesis that a selective increase in membrane current, as contrasted with the decreases in currents caused by most antiarrhythmic agents, would be an effective antiarrhythmic intervention. We studied models of early afterdepolarizations (EADs), delayed afterdepolarizations (DADs), and abnormal automaticity in single canine ventricular myocytes using intracellular microelectrodes or patch electrodes. EADs were induced by injected current, Bay K 8644 (0.5-1 microM), or ketanserin (1.0 microM); DADs were induced by ouabain intoxication (2 x 10(-7) M); and abnormal automaticity was induced by exposure to barium (0.25 mM). To increase outward K+ current, we used pinacidil and the protein kinase C activator 4 beta-phorbol 12,13-dibutyrate (PDBu). Under control conditions, 10-100 microM pinacidil caused a concentration-dependent and reversible decrease in action potential duration and an increase in steady-state outward current; both effects were blocked by glibenclamide and thus presumably reflected changes in the ATP-regulated potassium current. Pinacidil increased the current required to induce EADs and abolished EADs caused by Bay K 8644 or ketanserin. After exposure of myocytes to ouabain, pinacidil caused a decrease in action potential duration and diminished or abolished DADs. Finally, pinacidil arrested abnormal automaticity caused by Ba2+. PDBu (30 nM) shortened action potential duration without altering plateau amplitude in some of the myocytes. In these cells the depolarizing current needed to produce an EAD was increased by over 70%; outward potassium current tails were also increased, an effect consistent with an increase of the repolarizing potassium current (IK). These findings show that each of the mechanisms for abnormal impulse generation can be effectively antagonized by an increase in outward current and suggest to us that selective augmentation of a repolarizing current, possibly IK, might be a reasonable antiarrhythmic intervention.

Action Potentials↗
PubMed1991

Counting by children with Down syndrome.

Children's understanding of one-to-one, stable order, and cardinal principles was tested through error-detection and self-performance counting tasks. Gelman's modified counting task was used to test understanding of the order irrelevance principle. There were no significant differences between the mean task scores of 15 children with Down syndrome and 15 preschoolers with similar revised Peabody Picture Vocabulary test (PPVT-R) scores (mean age equivalent, 4 years, 7 months). Partial correlations showed several significant associations between counting principles and PPVT-R that were independent of chronological age. The results support the view that counting by children with Down syndrome can be guided by counting principles and that developmental level rather than the syndrome is associated with counting behavior.

Attention↗
PubMed1988

Children's knowledge of contagion and contamination as causes of illness.

Children's knowledge of contagion and contamination as causes of illness was examined in 3 experiments. In Experiment 1, preschoolers and children in grades 1 and 3 were shown videotaped segments of puppets with colds and toothaches who explained their ailments in terms of contagion and immanent justice. The children were instructed to evaluate and correct the puppets' explanations and, in addition, to indicate the possible effects on health of drinking milk that had come into contact with objects such as a cockroach, used comb, and spoon. Even preschoolers displayed some knowledge of contagion and contamination. However, compared to the third graders, younger children were less likely to reject proximity to a sick person and naughty behavior as causes of toothaches. They were also more likely to indicate that to drink milk that had come into contact with a spoon was unhealthy. In Experiment 2, preschoolers rejected the proposition that an ailment caused by accident (i.e., a scraped knee) is contagious and, in Experiment 3, they generally accepted that contamination through contact with a dirty spoon can be prevented by washing. Altogether, preschoolers have a more substantial knowledge of contagion and contamination than has been estimated previously. The results are discussed in terms of children's ability to understand causal relations.

Accidents↗
PubMed1984

Diminished responsibility as a mitigating circumstance in juvenile offenders' legal judgments.

The legal judgments of 20 juvenile offenders and 20 non-offenders were examined for three types of crimes: assault, arson and treason. Mitigating circumstances cast in the form of an inability to control events consisted of brain damage, passion and economic need, in contrast to a situation in which no mitigating circumstances were offered. The results indicated that despite the often-made legal argument, neither group regarded passion and economic need as circumstances warranting the reduction of sentencing. Compared to the non-offender group, offenders rated brain damage as less mitigating. While non-offenders rated passion and economic need more severely than brain damage, offenders' ratings of the three circumstances did not differ significantly. The findings are discussed in terms of perceptions of control and structural-developmental approaches to socialization.

Adolescent↗
PubMed1982

Helper cell function of Leukemic Leu-2a+, histamine receptor+, T gamma lymphocytes.

Leukemic cells from a patient with an 11-yr history of chronic lymphocytic leukemia (CLL) were found to have the surface phenotype Leu-1+, Leu-2a+, Leu-3a-, sheep erythrocyte rosette+, IgGFc receptor+. The cells also bore a receptor for histamine inhibitable by cimetidine (H-2). The clonal nature of the proliferation was documented by the presence of a consistent marker chromosome (22-trisomy) in metaphases elicited by culture with T cell growth factors. Although the surface phenotype suggested that these cells might function as suppressor lymphocytes, they had an enhancing effect on the pokeweed- mitogen- (PWM) driven generation of plasma cells and reverse hemolytic plaque-forming cells in vitro. This helper activity was modified neither by irradiation of the leukemic cells nor by removal of a minor population of Leu-3a+ cells, suggesting that the effects were attributable to the CLL cells themselves. In addition to these functions, the CLL cells were active in antibody-dependent cellular cytotoxicity (ADCC) assays in association with expression of Fc receptors for IgG. The ADCC was diminished when a transient loss of the Fc receptor expression was observed. No activity in natural killer cell assays employing K-562 cells or herpes simplex virus- (HSV) infected cells as targets could be attributed to the leukemic clone. These studies indicate that the cell surface phenotype, as defined by monoclonal antibodies, may not always predict the functional state of a particular cell, and suggest that within the Leu-2a+ (TH-2+) population of human lymphocytes, some helper as well as suppressor/cytotoxic cells are to be found.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

Role of helper, suppressor and B-cell defects in the pathogenesis of the hypogammaglobulinemias.

We investigated suppressor and helper T cells in 19 patients with variable immunodeficiency to assess the possibility that defective interactions among these cells and B lymphocytes are the chief cause of the inadequate plasma-cell development and hypogammaglobulinemia characterizing these syndromes. We accomplished functional separation of the two T-cell subsets, using irradiation, which selectively inactivates T-cell suppressors. The patient B lymphocytes were usually capable of some differentiation into plasma cells when co-cultured with T cells manipulated to optimize helper effects. Eighteen of 19 patients showed quantitatively poor plasma-cell production even under these conditions. However, only one had defective enough helper function, and only one sufficiently excessive suppressor activity for these factors to be considered the major pathogenetic process in each case. Since neither an absolute defect in B cells nor consistent abnormalities in modulator T cells were demonstrable in most patients, other explanations must be sought for the mechanisms underlying this form of primary immune deficiency.

Adolescent↗
PubMed1977

Enhancement by irradiated T cells of human plasma cell production: dissection of helper and suppressor functions in vitro.

The addition of irradiated T-enriched lymphocytes to B cell-enriched fractions of human peripheral blood or to unseparated mononuclear cells stimulated the differentiation of plasmacytoid cells in culture with pokeweek mitogen beyond the synergy obtained by the addition of unirradiated T cells. This stimulation was observed in both the proportion and absolute number of plasmacytoid cells recovered from the cultures, and in the amount of IgM detected in culture supernatants by a hemagglutination inhibition assay. Irradiation-induced enhancement was observed with normal and hypogammaglobulinmic T cells, but not with monoclonal T cells from two patients. Inactivation of T cells by heating or by repeated freezing and thawing did not produce the same effects as did irradiation. These data suggest that cell-mediated suppressor function in man is selectively radiosensitive, while helper activity is not. Irradiation may be a useful method for the functional isolation of helper cells and for the manipulation of the balance between suppressor and helper cell activities.

B-Lymphocytes↗
PubMed1976

Association of a chromosomal abnormality with lymphocytes having both T and B markers in a patient with lymphoproliferative disease.

The lymphocytes of a patient with leukemic lymphosarcoma were found to have an unusual surface phenotype in that they bound both sheep erythrocytes (a T cell marker) and complement-coated erythrocytes (a B cell marker) but lacked other B cell surface characteristics. Marker chromosomes were present in these cells, but not in other, phenotypically normal cells from the same patient. This case may provide a clue to the chromosomal origin of some lymphocyte surface markers in man.

Aged↗
PubMed1976

Suppression of B-cell differentiation by leukocytes from hypogammaglobulinemic patients.

Leukocytes from patients with several forms of immunodeficiency characterized by apparently differing defects in B-lymphocyte maturation produced few or no plasmacytoid cells in vitro, and were capable of suppressing the generation of plasma cells in co-culture with cells of normal persons, in the presence of pokeweed mitogen. Such inhibition was commonly observed in cultures which included cells from patients with primary immunoglobulin deficiency, but was not seen to a significant degree in identical co-cultures of cells from normals. The suppression observed was not dependent upon mixed leukocyte culture reactivity. Both sheep erythrocyte-rosetting lymphocytes and adherent cells appeared to participate in these effects in some patients. In one patient with common variable immunodeficiency, but not in several others, removal of suppressing cells permitted the patient's remaining cells to differentiate into plasma cells in vitro. Because of the diverse syndromes in which suppression was observed, it is likely that, in at least some hypogammaglobulinemic patients, the suppression is secondary to the disease process rather than being the primary pathogenic mechanism.

Agammaglobulinemia↗
PubMed1975

A scanning electron microscopy and immunological study of 84 cases of lymphocytic leukaemia and related lymphoproliferative disorders.

The surface features of cells from 84 cases of lymphocytic leukaemia, and related lymphoproliferative disorders are described as seen by scanning electron microscopy (SEM). Most of the 46 cases of CLL were shown to be B-derived, but rare cases of mixed B and T cell leukaemia and leukaemia with cells bearing both B and T markers were also encountered. Despite the existence of a spectrum of cell surface morphology, it was possible in many cases to identify a dominant cell type. Cells from cases of B derived malignancies were most frequently of the 'predominantly villous' type while a smaller proportion of cases were of the predominantly 'smoother' or 'mixed villous and smooth' type. Variations in surface morphology also occurred with progression of the disease. In most cases of acute lymphoblastic leukaemia (ALL) 'smoother' cells predominated. However, more cases of ALL and T derived leukaemia need to be examined before definite conclusions can be drawn concerning the surface of these cell types. This study also illustrates the importance of examining large numbers of cases of leukaemia, before conclusions are drawn concerning their surface features and indicates that SEM cannot consistently distinguish between leukaemic B and T cells. It will be of interest to determine whether the surface architecture of the leukaemic cell is related to the degree of cell differentiation and eventual prognosis in these cases.

B-Lymphocytes↗