The relative effects of perceived personal control and responsibility on health and health-related behaviors in young and middle-aged adults.

We examined whether perceptions of personal control over health and perceptions of personal responsibility for well-being were related, whether they had independent or interactive effects on health and health-related behaviors, and whether the effects of the perceptions varied by income. Young and middle-aged employees of a technology company (N = 186; aged 20-63) completed a questionnaire about perceived control and responsibility, health, health-related behaviors, and demographic information. Correlation analysis indicated that the perceived control and perceived responsibility variables were unrelated. Regression analysis indicated that a main effect of perceived control--but not responsibility--contributed significantly to the explanation of variance in health and several health-related behaviors (medical checkup, breast self-examination, exercise, and health promotion program membership). Perceived control and responsibility did not interact in their influences over health and behavior; however, the hypothesis that the variables would interact with income was partially confirmed. Overall, the results suggest that the sense of control rather than sense of responsibility should be targeted for health promotion efforts.

Role of endothelium in chronic inflammatory synovitis.

The rheumatoid synovial membrane is infiltrated by chronic inflammatory cells. The major fraction of the infiltrating lymphocytes is composed of CD4+ cells. A large number of studies of the composition of the T cell receptors of these lymphocytes have failed to demonstrate evidence of a dominant clonal population of T cells which is characteristic of rheumatoid synovitis. Most of the T cells are polyclonal in nature. This report discusses the basis for this polyclonality. Current evidence is reviewed which supports the conclusion that T cells emigrate from postcapillary venules because they are in an activated state. The activated T cell is characterized by elevated expression and avidity of adhesion receptors capable of reacting with counterreceptors on the endothelial cells of postcapillary venules, leading to binding and emigration from the blood. The T cells are retained in the perivascular connective tissue because their adhesion receptors interact with counterreceptors on other mononuclear cells and on matrix proteins. The increased expression of adhesion receptors on the T cells may be a result of prior contact with antigen; increased expression of counter-receptors on the endothelial cells results from stimulation by cytokines released by local inflammatory cells. The interaction between T cell adhesion molecules and counterreceptors is independent of the immunological specificity of the T cell. Hence, the T cells of the rheumatoid synovium are largely polyclonal memory cells.

Role of endothelium in the pathogenesis of rheumatoid synovitis.

The rheumatoid mononuclear cell infiltrate has a number of features of a cellular immune response. In the latter, the immunological specificity of the lymphocytic infiltrate is largely independent of the inciting antigen. Extensive investigation of the possible clonal or oligoclonal dominance of T-cell populations of the rheumatoid synovial infiltrate has demonstrated either no clonality or a dominance of T-cell populations with T-cell receptor V regions which have varied from patient group to patient group and, frequently, from patient to patient within a given group. These findings suggest that the basis for the mobilization of the synovial T-cell population is the activation state of the circulating T cells, not their immunological specificity, which makes them eligible for endothelial binding and transmigration. The specificity of the activated T cells of the circulating T-cell pool appears to be determined by the immunological history of the host.

Documented clinical side-effects to dental amalgam.

Since all dental restorative materials are foreign substances, their potential for producing adverse health effects is determined by their relative toxicity and bioavailability, as well as by host susceptibility. Adverse health effects to dental restoratives may be local in the oral cavity or systemic, depending on the ability of released components to enter the body and, if so, on their rate of absorption. The medical scientific community is now in general agreement that patients with dental amalgam fillings are chronically exposed to mercury, that the average daily absorption of mercury from dental amalgam is from 3 to 17 micrograms per day, and that the amalgam mercury absorption averages 1.25-6.5 times the average mercury absorption from dietary sources (World Health Organization, 1991). The health significance of this chronic mercury exposure is now being investigated by several medical research groups.

Effect of inflammatory cytokines on human endothelial cell proliferation.

Neovascularization, a common occurrence in chronic inflammatory lesions, requires endothelial cell (EC) proliferation. Because this form of inflammation is often mediated by immunologically generated cytokines, the effects of such cytokines on human umbilical vein EC proliferation in vitro were investigated. Low concentrations of recombinant interferon gamma (rIFN-gamma) (10-100 U/ml), but not a higher concentration (1,000 U/ml), enhanced both basal and endothelial cell growth factor (ECGF)-stimulated EC proliferation. Recombinant interleukin 1 (rIL-1) and recombinant tumor necrosis factor-alpha (rTNF) had minor effects on basal EC proliferation, but significant inhibition was observed in the presence of ECGF. A combination of rIFN-gamma and rTNF induced marked suppression of EC proliferation, which appeared to be due to a cytotoxic effect on the EC, as demonstrated by 51Cr release. In contrast, the combination of rIFN-gamma and rIL-1 had only an additive effect on EC proliferation, with no evidence of cytotoxicity. These results suggest that cytokines have important regulatory roles in local vascular proliferation. These effects varied not only with the individual cytokine, but also with the combination of cytokines used. The most striking effects were 1) the stimulation of proliferation by IFN-gamma at a low concentration and 2) the inhibition by both rIL-1 and rTNF of ECGF-stimulated proliferation.

T cell inhibitor secreted by macrophages and endothelial cells.

On stimulation with lipopolysaccharide (LPS), normal human macrophages (M phi) and endothelial cells (EC) produced factors which inhibited interleukin 2 (IL-2)-dependent lymphocyte proliferation and PHA plus interleukin 1 (IL-1)-dependent mouse thymocyte proliferation but not IL-1-dependent human fibroblast proliferation, suggesting that they were inhibitors of the IL-2 response. In addition, these factors inhibited the production of IL-2 by normal human peripheral blood mononuclear cells (PBMC). The factors also inhibited PBMC proliferation in response to PHA and concanavalin (Con A) but did not inhibit the proliferation of EC, U937 cells, or Epstein-Barr virus-transformed B cells. On Sephadex G200 gel filtration, the inhibitory factors from both M phi and EC were detected almost entirely in a 130- to 150-kDa fraction, but active material was also detected in a 15- to 20-kDa fraction. On isoelectric chromatofocusing of the 130- to 150-kDa fraction, inhibitory activity was associated with fractions eluted at three isoelectric points, pH 7.0, 5.4, and 4.8. The isoelectric fractions isolated from M phi and EC showed similar patterns of inhibition. When 130- to 150-kDa fractions from Sephadex G200 of the M phi and EC supernatants were treated with an antibody against a macrophage-derived suppressor factor produced by the human monocytic leukemia cell line THP-1, the activity of both fractions was neutralized. The above findings suggest that normal M phi and EC secrete an identical or closely related inhibitor of IL-2 synthesis and IL-2 response, and this inhibitor regulates these IL-2-related functions by a suppressive action on the T lymphocyte.

Endothelial cell activation induced by tumor necrosis factor and lymphotoxin.

Alterations in the morphology and histochemistry of vascular endothelial cells (EC) have been repeatedly observed at sites of chronic inflammation and immune reactions. These changes, which are most prominent in the EC postcapillary venules present in areas with large lymphocytic infiltrates, include the acquisition of a columnar or cuboidal morphology, the development of ribonuclease-sensitive metachromasia, and an increase in intracellular organelles. Thus, EC at sites of inflammation appear to be activated and to demonstrate increased metabolic activity. This study reports that both tumor necrosis factor-alpha (TNF) and lymphotoxin (LT) can activate cultured human umbilical vein EC, as measured by: 1) increased adhesiveness for lymphocytes, 2) increased cell metabolism, as measured by RNA and protein synthesis, and 3) increased cell volume. Although gamma interferon (IFN-gamma) and interleukin-1 (IL-1) have been shown previously to stimulate EC adhesiveness for lymphocytes, these two cytokines had only marginal effects on EC RNA and protein synthesis, and both caused a decrease in EC volume. These findings suggest that TNF and LT play a role in the type of activation of EC in vivo that leads to the development of tall endothelium and increased lymphocyte emigration.

Role of endothelium in chronic inflammation.

The character of the immunologically stimulated chronic inflammatory infiltrate is to a considerable extent determined by nonspecific factors governing mononuclear cell traffic. The volume, composition and distribution of this traffic is strongly dependent on an initial adhesive interaction between circulating mononuclear cells and the EC of the PCV of the involved tissues. The emigration of lymphocytes from the PCV is preceded by binding of the lymphocytes to the endothelial lining cell. This binding is enhanced by lymphokines (IFN-gamma, TNF-beta) and monokines (IL-1, TNF-alpha), secreted by perivascular inflammatory cells and acting on the EC. This enhancement may permit an initial, immunologically generated small focus of mononuclear cells to amplify itself to a larger infiltrate. Movement of the EC-bound lymphocyte through the endothelium may be facilitated by IFN-gamma, as suggested by evidence that T cells, bound to the surface of EC monolayers overlying nitrocellulose filters, migrate through these monolayers in increased numbers in the presence of IFN-gamma. Movement of the lymphocyte through the wall of the PCV and subsequently through the perivascular space toward the inflammatory focus may be enhanced by the chemotactic action of IL-1, generated by the macrophages of the perivascular infiltrate. The lining layer of the synovial membrane may play an important role in the development of synovitis. Hyperplasia of the synovial lining layer is associated with the secretion of chemotactic agents which can attract monocytes from the PCV toward the lining. The continuous movement of monocytes from PCV to lining may establish a steady-state population of macrophage-like cells in the interstitium of the synovium. These may provide the accessory cell population required for the immune responses which give rise to the various chronic inflammatory synovitides. The sublining layer of the rheumatoid synovium does, in fact, contain large numbers of DR+macrophage+ cells which may represent this accessory cell population. Since the cytokines mediate the inflammatory effects of the cellular immune response, it follows that when injected intraarticularly they should produce synovial inflammation. Such inflammation has, in fact, been produced in experimental animals by the intraarticular injection of supernatants of antigen-stimulated PBMC or of rIL-1. A cytokine-mediated chronic inflammatory reaction may be expected to assemble a polyclonal population of lymphocytes around the PCV. However, the fraction of the accumulated T cells which is antigen reactive is not entirely a random one as indicated by the following.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition of human endothelial cell proliferation in vitro and neovascularization in vivo by D-penicillamine.

To investigate the effects of D-penicillamine (D-Pen) on angiogenesis, we have studied the effects of this drug on in vitro proliferation of human endothelial cells (EC) and in vivo corneal neovascularization. D-Pen, in the presence of copper sulfate, suppressed tritiated thymidine ([3H]TdR) incorporation into EC in a dose-dependent manner. Significant inhibition was observed with D-Pen concentrations attainable in the serum and tissues of treated patients. Neither D-Pen nor copper ion alone significantly affected [3H]TdR incorporation into EC. The inhibition by D-Pen and copper was blocked by catalase (CAT) or horseradish peroxidase but not by boiled CAT or SOD. When rabbits were daily injected intravenously with D-Pen at the per kilogram dosage administered to rheumatoid patients, neovascularization as quantitated by the proliferation of corneal new blood vessels was significantly inhibited. These results suggest that hydrogen peroxide generated by D-Pen and copper exerts a pronounced antiangiogenic effect through inhibition of EC proliferation. It is, therefore, considered that D-Pen may suppress rheumatoid synovitis by reducing the number of small blood vessels available for the emigration of chronic inflammatory cells, and the proliferation of the synovial tissue.

Pathways of mononuclear cell infiltration in rheumatoid synovitis.

The mononuclear cell infiltration which characterizes the chronic inflammatory reaction results from the migration of lymphocytes and monocytes through the endothelium of the postcapillary venule. The initial step in the emigration of these cells in their binding to the vascular endothelium. The binding capacity of the endothelial cell (EC) for lymphocytes and monocytes is increased by IFN-gamma, IL-1, TNF alpha, and TNF beta. Production of these cytokines by chronic inflammatory cells may be expected to amplify the chronic inflammatory reaction. Initiation of the chronic synovitis of rheumatoid and other chronic synovitides probably results from the interaction of antigen with sensitized T cells in the sublining region of the synovium. This interaction is facilitated by the presence of substantial numbers of DR + macrophage + accessory cells in the synovial interstitial space. It is likely that these accessory cells are bone marrow derived monocytes migrating to the synovial lining layer in response to chemotactic factors released by the hyperplastic synovial lining cells. Lymphocytes differ in their binding affinity for ECs, and more strongly binding lymphocytes may be preferentially bound. Since binding is the first step in lymphocyte emigration, this event may lead to the selection of more strongly binding lymphocytes in the perivascular infiltrate. The T cells present in the mononuclear cell infiltrates of rheumatoid arthritis, other chronic synovitides, and multiple sclerosis have been shown to be composed largely of the CDw29 + CD4+, helper-inducer, memory cell subset. The predominance of this T-cell subset may result from its demonstrated greater binding affinity for ECs.(ABSTRACT TRUNCATED AT 250 WORDS)

T-cell adhesion to endothelial cells in systemic lupus erythematosis.

To investigate the pathogenesis of the lymphopenia in systemic lupus erythematosus (SLE), we examined the adhesion of these T cells to endothelial cells (EC). T cells from 10 lymphopenic patients with active SLE showed significantly reduced adhesion to unstimulated and interleukin-1 (IL-1)-stimulated human EC monolayers when compared with T cells from age, sex, and race matched normal control individuals. Percentage decreases from control values (delta) in the measured percentage of T cells adherent to unstimulated and IL-1-stimulated EC were 36.4% (P less than 0.025) and 34.0% (P less than 0.005), respectively. Percentage adhesion of phorbol ester-treated T cells of SLE patients was also reduced compared with similarly treated T cells of control patients; the decrease was 22.8% (P less than 0.025). No abnormality was detected in the adhesion to EC of T cells from patients with asthma who were receiving corticosteroids, suggesting that the abnormality in the SLE T cells was related to the disease process itself. The reduced adhesion of the circulating T cells may be a consequence of the withdrawal from the blood of more strongly adherent cells in the course of the inflammatory response. The loss of strongly adherent lymphocytes may contribute to the lymphopenia of SLE.

Stimulation of mononuclear cell binding to human endothelial cell monolayers by thrombin.

The common occurrence of fibrin deposits in chronic inflammatory lesions suggests a possible role for thrombin in the mobilization of mononuclear cell infiltrates. For this reason, the effect of thrombin on the binding of mononuclear cells to endothelial cells (EC) was investigated. Incubation of confluent monolayers of human umbilical vein endothelial cells with thrombin markedly enhanced EC adhesiveness for both T lymphocytes and U937 cells (a monocyte-like cell line) in a time- and dose-dependent fashion. This effect was EC specific: 1) treatment of the T cells or the U937 cells with thrombin did not stimulate their adherence to EC, and 2) treatment of human foreskin fibroblasts with thrombin did not stimulate their inherently low adhesiveness for T cells. Fixation of EC monolayers with paraformaldehyde after pre-incubation with thrombin did not affect the increased adhesiveness for T cells. mAb against the LFA-1 antigen (mAb 60.3 (anti-CD18) or mAb TS1/22 (anti-CD11a), which inhibit the binding of T cells to unstimulated EC, failed to block the increased adhesion induced by thrombin, indicating that the increased binding induced by thrombin is similar to that induced by IL-1 and TNF, which showed similar resistance. These results suggest that thrombin may have a role in the extravascular emigration of mononuclear cells from post-capillary venules by virtue of its ability to stimulate the adhesiveness of EC for both lymphocytes and monocytes.

Separation and characterization of human T lymphocytes with varying adhesiveness for endothelial cells.

Previous studies in this laboratory have demonstrated that the adhesion of T lymphocytes to endothelial cell (EC) monolayers in vitro can be increased by preincubation of the EC with interferon-gamma, interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF), or lipopolysaccharide (LPS), or by stimulation of the T cells with phorbol esters. In this report, we have demonstrated that three subpopulations of human peripheral blood T cells can be identified on the basis of their abilities to bind to EC: (1) a strongly binding group which binds to unstimulated EC; (2) an intermediately binding subset which adheres to EC only if these cells have been stimulated with IL-1, TNF, or LPS; and (3) a weakly binding subpopulation which adheres poorly to either unstimulated or stimulated EC. The more adhesive subgroups had larger cellular volumes than the less adhesive cells, were relatively enriched in cells bearing the OKM1 surface marker, and expressed relatively greater amounts of the lymphocyte-function-associated-1 molecule. Stimulation of the EC to bind increased numbers of T cells by IL-1, TNF, and LPS appeared to be mediated by the expression of a common adhesion molecule on the EC.

Interleukin 1 derived from human endothelial cells enhances the binding and chemotactic step of T lymphocyte emigration.

Recent evidence indicates that interleukin 1 (IL-1) from different sources has varying molecular weights, amino acid and gene sequences and biological properties. In previous experiments, it has been shown that monocyte derived IL-1 was chemotactic for lymphocytes and stimulated their binding to endothelial cells (EC). These phenomena are important in the emigration of lymphocytes in inflammatory states. In the present investigation, EC were stimulated with LPS and from the supernatants the IL-1 activity was isolated. After AcA 54 gel filtration, the active 17 kD fraction was further purified by chromatofocusing, yielding active fractions with pI of 7.0 and 5.0. All of these fractions showed T lymphocyte chemotactic activity, stimulated the binding of T cells to EC and the proliferation of fibroblasts. It is concluded, therefore, that EC-derived IL-1 has similar biological activity to that of monocyte-derived IL-1 and that it can exert a true autocrine effect at the blood-tissue endothelial interface.

Migration of lymphocytes through endothelial cell monolayers: augmentation by interferon-gamma.

During normal lymphocyte recirculation and in chronic inflammation, lymphocytes emigrate from blood into the perivascular tissue. The mechanism of lymphocyte migration through the endothelial cell (EC) layer of blood vessels is poorly understood. To identify factors that control lymphocyte emigration, a method has been developed to measure human peripheral blood lymphocyte migration through monolayers of human umbilical vein EC and into nitrocellulose (NC) filters located below the EC monolayer. Counts were made of lymphocytes that had migrated into the NC filter using a particle counter. T lymphocytes attached to and migrated through EC monolayers in a T-cell-number- and time-dependent fashion. Migration required viable EC since lymphocytes failed to migrate through formaldehyde-fixed EC monolayers or monolayers of dermal fibroblasts. Interferon-gamma (IFN-gamma) markedly augmented the migration in a dose- and time-dependent manner when preincubated with the EC. When T lymphocytes were pretreated with IFN-gamma, no increase in migration was observed. Finally, IFN-gamma augmented the migration of T cells prebound to the EC, indicating that the IFN-gamma-enhanced migration was not due to increased binding of T cells to the EC, but rather to an action on the EC to facilitate subsequent migration.