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Biomedical subjects

M A Campbell

Publications and source records attributed to M A Campbell.

At least 19 recordsLinked to original sources

Tyrosine phosphorylation of CD22 during B cell activation.

Ligation of the antigen receptor on B cells induces the rapid phosphorylation of tyrosine on a number of cellular proteins. A monoclonal antibody that recognized a tyrosine-phosphorylated cell surface protein that was present in activated B cells was generated. Amino acid sequence analysis showed that this 140-kilodalton protein was CD22, a B cell-specific cell surface glycoprotein and putative extracellular ligand of the protein tyrosine phosphatase CD45. Tyrosine phosphorylation of CD22 may be important in B cell signal transduction, possibly through regulation of the adhesiveness of activated B cells.

Antigens, CD

Association between B-lymphocyte membrane immunoglobulin and multiple members of the Src family of protein tyrosine kinases.

Treatment of B lymphocytes with antibodies to membrane immunoglobulin (Ig) stimulates protein tyrosine phosphorylation. We have examined the phosphorylation in vitro of proteins associated with membrane Ig. The Src family protein tyrosine kinases p53/56lyn, p59fyn, and p56lck are associated with membrane Ig in spleen B cells and B-cell lines and undergo phosphorylation in vitro. The pattern of expression of Src family protein tyrosine kinases in B cells varied. Our studies suggest that multiple kinases can potentially interact with membrane Ig and that within any one B-cell type, all of the Src family kinases expressed can be found in association with membrane Ig. We also observed that the Ig-associated Ig alpha protein, multiple forms of Ig beta, and proteins of 100 and 25 kDa were tyrosine phosphorylated in vitro. The 100- and 25-kDa proteins remain unidentified.

Animals

Work stress, burnout, and sense of coherence among dialysis nurses.

The overall goal of this study was to examine the relationship among work stressors, burnout, and sense of coherence (SOC) in dialysis nurses. Two hundred thirty-eight registered nurses from 56 dialysis units completed a demographic data form, the Nursing Stress Scale, the Maslach Burnout Inventory, and Antonovsky's Sense of Coherence Scale. The results indicated that work load was the major contributing factor to both overall stress and burnout. Understanding the stressors that affect responses to the work environment will allow for successful interventions to alter the risk of exhaustion and burnout.

Adult

Protein tyrosine phosphorylation is induced in murine B lymphocytes in response to stimulation with anti-immunoglobulin.

Activation of both T and B lymphocytes through their membrane receptors for antigen is known to induce breakdown of inositol phospholipids. In addition, T cell activation by antigen is accompanied by increased protein tyrosine phosphorylation of components of the T cell antigen receptor. We now provide evidence that B cell activation through membrane immunoglobulin is also coupled to stimulation of protein tyrosine kinase activity. One potential candidate for a B lymphocyte protein tyrosine kinase is an 80 kd molecule that is itself phosphorylated at tyrosine residues in response to stimulation with anti-immunoglobulin antibodies.

Animals

Rational selective exploitation and distress: employee reactions to performance-based and mobility-based reward allocations.

Prior research has demonstrated that allocators frequently distribute greater rewards to persons with high professional and geographic mobility than to persons with constrained mobility, especially among the very competent. This phenomenon has been termed rational selective exploitation. Do the recipients of such allocations actually experience this distribution rule as unjust and distressing, or is it a misnomer to refer to this phenomenon as exploitation? Two studies were conducted to explore this question. Study 1 was a laboratory experiment in which we manipulated relative performance level, relative mobility level, and allocation standard: performance based versus mobility based. Study 2 was a cross-sectional survey of actual employees in which subjects reported the degree to which performance and mobility were the basis for pay decisions at their places of employment, as well as the degree to which they perceived each standard to be fair. Both studies demonstrated that people regard mobility-based allocations as less fair and more distressing than performance-based allocations. Furthermore, the degree of distress resulting from mobility-based allocations is greater among persons who are disadvantaged by that standard: among people with constrained mobility, especially those who perform at high levels. These findings provide good support for the assertion that so-called rational selective exploitation is indeed distressing to employees. Reactions to this form of distress are also explored, and the implications of these findings for the allocation process are discussed.

Adaptation, Psychological

Elastase and cathepsin G of human monocytes. Quantification of cellular content, release in response to stimuli, and heterogeneity in elastase-mediated proteolytic activity.

Human peripheral blood monocytes contain human leukocyte elastase (HLE) and cathepsin G (CG), serine proteinases originally described in azurophil granules of polymorphonuclear neutrophils (PMN). Immunoreactive HLE and CG of freshly harvested monocytes have been quantified in this study; to begin to elucidate potential roles for these enzymes in extracellular events, release in response to stimuli has been measured, along with proteolytic activity of monocytes toward surface-bound proteins. Our results indicate that whole-cell extracts of monocytes contain approximately 6% of the amount of HLE as do extracts of comparable numbers of PMN. In response to PMA in vitro, monocytes released 39 to 53% of their content of HLE and CG within 60 min, a fractional release greater than that of PMN. Furthermore, when phorbol-stimulated monocytes were adherent to a fibronectin-coated surface, extensive HLE-mediated proteolysis of the surface-bound protein was observed. Proteolysis by such cells in the presence of proteinase inhibitors was of considerable interest, since a subpopulation (15 to 20% of the total) expressed marked but localized proteolytic activity, possibly escaping inhibition through contact-mediated mechanisms. These data indicate that a subpopulation of freshly harvested monocytes is rich in HLE and CG (serine proteinases traditionally associated with PMN), can promptly release HLE and CG in response to stimuli, and can utilize HLE for extracellular proteolysis. Monocyte-derived serine proteinases may participate in extracellular events formerly associated with PMN-derived HLE and CG.

Cathepsin G

Turnover of proteoglycans in articular-cartilage cultures. Characterization of proteoglycans released into the medium.

By using an e.l.i.s.a. method it was demonstrated that the majority of proteoglycans released into the medium of both control and retinoic acid-treated explant cultures of bovine articular cartilage did not contain a hyaluronate-binding region. This supports our previous findings [Campbell & Handley (1987) Arch. Biochem. Biophys. 258, 143-155] that proteoglycans released into the medium of both cultures were of smaller hydrodynamic size, more polydisperse and unable to form aggregates with hyaluronate. Analysis of 35S-labelled core proteins associated with proteoglycans released into the medium of both cultures by using SDS/polyacrylamide-gel electrophoresis and fluorography indicated the presence of a series of core-protein bands (Mr approx. 300,000, 230,000, 215,000, 200,000, 180,000, 140,000, 135,000, 105,000, 85,000 and 60,000) compared with three core proteins derived from the proteoglycans remaining in the matrix (Mr 300,000, 230,000 and 215,000). Further analysis of the core proteins released into the medium indicated that the larger core proteins associated with medium proteoglycans contain both chondroitin sulphate and keratan sulphate glycosaminoglycans whereas the smaller core proteins contain only chondroitin sulphate chains. These experiments provide definitive evidence that the loss of proteoglycans from the matrix involves proteolytic cleavage at various sites along the proteoglycan core protein.

Animals

Y-79 retinoblastoma cells: isolation and characterization of clonal lineages.

Y-79 cells are generally undifferentiated, but can be induced to express characteristics of various retinal cell types. Since specific changes occur in only low percentages of cells, it has not been clear whether different agents select different lineages, or if the same cells are differentially responsive. In order to answer this question, we isolated 16 clonal lineages and characterized their responses to various treatment regimes. Dibutyryl cyclic AMP (4 mM) had little effect on cell viability, but treatment with butyrate (1 mM), caused mortality ranging from 20 to 84%. Laminin (100 micrograms ml-1) did not decrease cell growth, and in some cases increased it. The frequency of attachment to a laminin-coated substrate also varied between clones. Comparison of the results for each clone, under all these conditions, indicated that the parental Y-79 line contains at least two different cell types. On the other hand, no obvious differences were found between clones in the morphological changes induced by different agents, evidencing the very plastic nature of Y-79 cells.

Bucladesine

Effects of laminin on attachment, growth and differentiation of cultured Y-79 retinoblastoma cells.

In vitro, as in vivo, the attachment, growth and differentiation of many cell types are dependent upon the availability of appropriate extracellular matrix (ECM) molecules. Here we have studied the effects of ECM components, including fibronectin and laminin on cultured Y-79 retinoblastoma cells. Both in 2 hr and in 3 day studies, the highest frequencies of attachment were seen with a laminin substrate (50 micrograms/35 mm culture dish). Attachment was significantly inhibited by specific anti-laminin antibodies. In longer studies of up to 1 week, laminin or fibronectin was added directly to the culture medium. Neither molecule significantly stimulated cell growth, but laminin continued to promote the highest frequencies of attachment (20% to 30% greater than any other substrate). Laminin exposure also caused morphological changes in Y-79 cells. Many cells became flattened and extended long, branching, neurite-like processes. These changes could be inhibited by inclusion of anti-laminin antibodies. Such studies may provide information about events occurring during normal eye development as well as about tumor cell attachment and growth.

Animals

A radioimmunometric assay for the detection and characterization of lung cancer-associated antibodies in sera of lung cancer patients.

A radioimmunometric assay was developed from P3 lung carcinoma target cells to detect anti-lung cancer antibodies. Of 100 sera from lung cancer patients tested, 80 (80%) were positive. However, only 6/30 (20%) sera from cancer patients with other cancers, 1/25 (4%) of sera from patients with nonmalignant lung disease, and 0/20 sera from healthy donors were positive. Quantitative absorptions showed that sera from lung cancer patients cross-reacted with other lung cancers, gastrointestinal cancers, and/or fetal lung tissues, but not with breast carcinomas, melanomas, sarcomas, fetal skin, or normal lung tissues. Two lung cancer antigens were defined: LCA-1, which shared antigenic determinants with GI tumors and fetal lung tissues, and LCA-2, which showed cross-reactivity only with GI tumors.

Adult

Thymosin-inducible 'null' cells in atopic eczema.

Thirty children with atopic eczema were compared with an equal number of age-matched healthy children. The mean peripheral blood T-lymphocyte level was lower in the eczema group (mean 1,197/mm2 as against 1,702/mm3; P = 0 . 003). This difference was abolished in vitro by thymosin, a thymic hormone extract. Positive correlations were found between eczema severity and: eosinophilia; hyperimmunoglobulinaemia E; but not T lymphopaenia. Thymosin-inducible T-cell (Ti) counts correlated with plasma IgE levels, suggesting that these Ti cells may be immature suppressor T cells. If this T-cell deficiency represents inadequate suppression of IgE responses, then a trial of treatment with thymosin appears to be warranted.

Adolescent

T-cell depletion and in vitro thymosin inducibility in asthmatic children.

Thirty asthmatic children were compared with an equal number of age-matched healthy children. The mean peripheral blood T-lymphocyte level without foetal calf serum was lower in the asthmatic group (mean 970/mm3, as against 1740/mm3; P less than 0.0001), but this difference was abolished by adding foetal calf serum or thymosin, thus explaining how quite severe T-cell deficiency can be missed by widely used methods. The degree of eosinophilia and the degree of elevation of the plasma IgE level in the asthmatic patients were positively correlated. Positive correlations were also shown between the degree of severity of the asthma, the degree of eosinophilia and the degree of elevation of the plasma IgE level, but not the degree of depression of the T-cell numbers. If this T-cell deficiency reflects an inadequate suppression of IgE responses, a clinical trial of thymosin appears to be warranted.

Adolescent

Thymosin-inducible lymphocytes in the peripheral blood of patients with malignant melanoma.

E rosette-forming (T) lymphocytes and surface immunoglobulin-bearing lymphocytes were estimated in 85 patients with malignant melanoma. The melanoma patient group had lower mean levels of T lymphocytes and higher mean levels of immunoglobulin-bearing (? B) lymphocytes than did normal subjects. The absolute and percentage depressions of T-cell levels in the melanoma patients were stage-related, as was the depression of total lymphocyte and B-lymphocyte levels. The T lymphopenia in the melanoma patients could, in vitro, be partially abolished by fetal calf serum (as used in many E rosetting methods), and could be totally abolished by thymosin fraction 5 (Hoffmann-La Roche) at optimum concentration. In view of the ability of thymosin to restore T cells to normal levels in all of the T-lymphopenic patients, a clinical trial of this hormone in selected melanoma patients of all stages appears to be warranted.

Adolescent