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Biomedical subjects

J R Bender

Publications and source records attributed to J R Bender.

At least 55 records · Page 3Linked to original sources
PubMed1994

Epican, a heparan/chondroitin sulfate proteoglycan form of CD44, mediates cell-cell adhesion.

Epican is a heparan/chondroitin sulfate proteoglycan form of CD44 and is expressed on the surface of keratinocytes from the basal layer to the granular layer of the epidermis. To analyze the adhesive properties of epican apart from the influence of other adhesive molecules found on keratinocytes, mouse L cell fibroblasts were transfected with CD44Epican cDNA. The epican expressed on the surface of transfected L cells was predominantly a heparan or chondroitin sulfate proteoglycan. The CD44Epican-transfected L cells acquired: (a) a self-aggregating phenotype that required hyaluronan but was calcium-independent; and (b) a new capacity to adhere to keratinocytes, a property that was blocked by an anti-epican antibody. Both aggregation and adhesion of CD44Epican-transfected cells were completely prevented by pretreatment with hyaluronidase, but were totally restored by the addition of exogenous hyaluronan. Aggregation of transfected L cells was minimally influenced by other glycosaminoglycans, but adhesion of transfected L cells to keratinocytes was substantially inhibited by heparin.

Animals↗
PubMed1994

Glass fiber manufacturing and fiber safety: the producer's perspective.

Historically, the potential health effects of airborne fibers have been associated with the dose, dimension, and durability. Increasing focus is being placed on the latter category. Concern about airborne fiber safety could be reduced by manufacturing fibers that are not respirable; however, due to performance and manufacturing constraints on glasswool insulations, this is not possible today. These products are an important part of today's economy and as a major manufacturer, Owens-Corning is committed to producing and marketing materials that are both safe and effective in their intended use. To this end, manufacturing technology seeks to produce materials that generate low concentrations of airborne fibers, thus minimizing exposure and irritation. The range of fiber diameters is controlled to assure effective product performance and, as far as possible, to minimize respirability. Glass compositions are designed to allow effective fiber forming and ultimate product function. Fiber dissolution is primarily a function of composition; this too, can be controlled within certain constraints. Coupled with these broad parameters is an extensive product stewardship program to assure the safety of these materials. This article will discuss the factors that influence glasswool insulation production, use, and safety.

Air Pollutants↗
PubMed1994

Science, public policy, and stewardship.

Synthetic vitreous fibers play an important role in today's economy. Glass fibers, as an example, have found uses in more than 30,000 products that include insulations, reinforcements, fire resistant fabrics, and protective armor. Vitreous fibers also play a direct role in energy conservation. For example, in 1992, a study by Arthur D. Little found that the annual production of fiber glass batts and blowing wool used in U.S. buildings--only a fraction of the current production and use of glass wool--saved the equivalent of 33.4 million barrels of oil in 1992, avoiding the need for nearly 6800 megawatts of power. This is equivalent to 34 new 200-megawatt power plants. An ongoing commitment by the manufacturers to assure the safety of their products paralleled the growth of the vitreous fiber industry. Soon after commercialization of glass wool manufacturing in the mid-1930s, worker concerns about silica gave rise to the first study on the health of fiber glass workers (Siebert, 1942). Since that time, there have been hundreds of studies, published papers, and international reviews that have evaluated potential health effects and exposures associated with synthetic vitreous fibers.

Air Pollutants, Occupational↗
PubMed1994

Measurement of respirable glass and total fiber concentrations in the ambient air around a fiberglass wool manufacturing facility and a rural area.

Little data are available on ambient concentrations of glass fibers which along with other manmade vitreous fibers are receiving increased regulatory attention. The purpose of this study was to measure glass and total respirable fibers around a large fiberglass wool manufacturing plant and a rural area. Samples were collected on mixed esters of cellulose filters using high-volume air samplers at flow rates of 1.2 m3/min. Fibers were counted using a modified NIOSH 7400B procedure. Glass fibers were found in very low concentrations for both areas sampled; 90% of the samples were below the detectable limit of 0.00001 fibers/cc. Average glass fiber concentrations accounted for less than 1% of the total fibers measured. Dispersion modeling was used to estimate ambient glass fiber concentrations around the plant. Predicted and measured results showed relatively good agreement.

Air Pollutants, Occupational↗
PubMed1993

Heterogeneity of dermal microvascular endothelial cell antigen expression and cytokine responsiveness in situ and in cell culture.

Microvascular endothelial cells (EC) recruit circulating leukocytes at sites of inflammation, in part through cytokine-regulated expression of endothelial-leukocyte adhesion molecules. Adhesion molecule expression varies among vascular beds and among EC within microvessels of a particular vascular bed. In the present study, we have examined the patterns of antigen expression and cytokine responsiveness of dermal microvascular endothelial cells (DMEC) in a skin organ culture model and, for comparison, in cell culture. Within the superficial vascular plexus (SVP) of normal skin, CD36 molecule expression is undetectable on capillary loops and is expressed on DMEC in only 20% of the larger, horizontal vessels. CD36 expression is not modulated by cytokines. Endothelial-leukocyte adhesion molecule-1 (ELAM-1) expression induced at 6 and 24 h by TNF or IL-1, is restricted to the venular side of the capillary loop and to the venules proper. Vascular cell adhesion molecule-1 (VCAM-1) expression is not inducible on EC of the SVP in normal skin by TNF, IL-1, or IL-4, alone or in combination at either time point. When inflamed skin is examined in organ culture, SVP EC are cytokine responsive regarding VCAM-1 expression. Within the deep vascular plexus (DVP). CD36 molecules are expressed on EC in all capillaries and small vessels. Both ELAM-1 and, to a lesser extent, VCAM-1 expression are inducible by TNF, IL-1, and/or IL-4 on capillaries and larger microvessels at 6 and 24 h. The larger vessels at the dermal-subcutaneous border were found to be CD36-/ELAM-1+/VCAM-1+ after cytokine treatment. CD36 expression of DMEC in cell culture varies from 47 to 98% of cells (mean 75%) in seven separate isolates and is not modified by cytokines. Upon TNF or IL-1 activation, 50 to 90% of DMEC express ELAM-1 molecules at 6 h and expression persists at high levels for 24 h. VCAM-1 expression is negligible at both times. These results with DMEC differ from human umbilical vein EC analyzed in parallel, which are completely CD36- and show transient ELAM-1 and sustained VCAM-1 expression in response to TNF and IL-1. In summary, we have demonstrated that DMEC comprise a heterogeneous population that differ from umbilical vein EC.

Animals↗
PubMed1993

Recent studies of man-made vitreous fibers. Chronic animal inhalation studies.

The history of asbestos use and asbestos-related disease is replete with comments that the public health would have been better protected if the results of laboratory investigation, epidemiologic surveys, and clinical studies were made available at appropriate intervals during the ongoing research, rather than in the generally accepted method of awaiting completion of studies prior to reporting medical and scientific findings. No substantive evidence of long-term adverse effects has been published in workers exposed to man-made vitreous fibers. Nevertheless, in an effort to preclude a repetition of this error of omission that occurred with asbestos exposure and use, the Thermal Insulation Manufacturers Association is regularly reporting interim and final data from ongoing animal studies. A significant segment of man-made vitreous fibers have now been tested in state-of-the-art chronic studies. This paper includes the recently completed animal inhalation studies on refractory ceramic fibers and fibrous glass. It also reviews interim data on mineral wool studies.

Air Pollutants, Occupational↗
PubMed1992

Early recognition of a discordant xenogeneic organ by human circulating lymphocytes.

Cell-mediated immune mechanisms underlying discordant xenograft rejection are poorly characterized. In our study, using a human to rat xenogeneic ex vivo model, we show that a fraction of human lymphocytes, when perfused through the coronary system of a rat heart, rapidly and specifically adheres to the vascular endothelium and infiltrates the myocardium. Lymphocyte phenotypic analysis before and after perfusion, as well as the use of purified cell subpopulations, demonstrate preferential adhesion of CD3- CD16+ NK cells. NK cell adhesion occurs via xenoreactive antibody-dependent and -independent pathways, because the selective removal of human IgG from the perfusion buffer markedly reduces but does not completely abrogate NK cell sequestration. However, T lymphocytes are retained in the xenoorgan via an antibody-independent pathway, as assessed by the lack of influence of IgG removal. Leukocyte integrins appear to play a crucial role in mediating adhesion of both lymphocyte subsets, because the pretreatment of lymphocytes with anti-CD11a, anti-CD11b, and anti-CD18 antibodies markedly reduces their retention into the xenogeneic organ. Retained human lymphocytes mediate rapid and direct damage of the xenoorgan, as demonstrated by histologic and functional alterations of the endothelium, impaired vascular resistance and in vitro lysis of rat endothelial cells by human NK cells. Taken together, these findings suggest a role for cell-mediated mechanisms in the rapid recognition and rejection of vascularized xenografts.

Animals↗
PubMed1992

Regulatory mechanisms in leukocyte adhesion: flexible receptors for sophisticated travelers.

Unstimulated leukocytes spend extended periods circulating in the blood, punctuated by migration through lymphoid areas and peripheral tissues. During transit, strong cell-cell interactions control immune surveillance and specialized effector functions. The structures and mechanisms that allow this flexible adhesion and migration behavior are the subject of this review.

Allosteric Regulation↗
PubMed1992

Antigen-receptor complex stimulation triggers protein kinase C-dependent CD11a/CD18-cytoskeleton association in T lymphocytes.

Although it is well accepted that intercellular adhesion involving the CD11a/CD18 (LFA-1) complex is critical in a wide array of T cell-dependent processes, recent demonstrations of an LFA-1 high avidity state, induced by triggering the T cell receptor (TCR) complex, has raised questions about the intracellular signals generated and molecular events leading to effective cell coupling, as well as their orderly sequence. In this study, we assessed the effects of T cell activation on the actin-based cytoskeleton, and LFA-1, as well as their interaction. Crosslinking the TCR complex with anti-CD3 mAb resulted in actin polymerization and colocalization with LFA-1, as detected by fluorescence microscopy. This association was confirmed by immunoprecipitating LFA-1 from the detergent insoluble, cytoskeletal-associated membrane fraction after TCR crosslinking. These consequences were inhibited by the protein kinase C (PKC) inhibitor staurosporine or by PKC desensitization, as was a transient CD11a hyperphosphorylation, induced by monoclonal anti-CD3. Furthermore, a small percentage of beta 2-deficient T cells maintained the ability to rearrange the cytoskeleton in response to TCR complex activation, with F-actin-VLA4 colocalization. These results provide evidence that the important consequences of TCR-induced signal transduction include a PKC-dependent cytoskeletal rearrangement, involving an association between leukocyte integrins and F-actin. We discuss the implications of these findings with respect to effective T cell functions.

Actins↗
PubMed1991

Signal requirements for the generation of CD4+ and CD8+ T-cell responses to human allogeneic microvascular endothelium.

Microvascular endothelium has been implicated as a major target in the rejection of vascularized allografts. In an attempt to dissect the stepwise generation of the T-cell-mediated immune response to microvascular endothelial cells (ECs), we analyzed the requirements for the two major T-cell subsets, CD4+ and CD8+, in the triggering of proliferative and cytotoxic responses to allogeneic ECs in vitro. Results demonstrate that resting ECs are unable to stimulate a functional response by purified T, CD4+, and CD8+ cells in the absence of costimulatory signals. T cells and CD8+ cells develop both proliferative and cytotoxic anti-EC responses by the addition of as little as 2 units/ml interleukin-2, 10 units/ml interleukin-1, or irradiated monocytes autologous to the responder lymphocytes, whereas only autologous monocytes are capable of triggering CD4+ T-cell precursors to proliferate and become anti-EC-specific effector cytotoxic T lymphocytes. CD8+ cell-mediated anti-EC cytotoxicity is directed toward allogeneic major histocompatibility complex (MHC) class I determinants on ECs and involves recognition by the CD3/T-cell receptor complex and the CD8 molecule on the effector T cells. CD4+ cells can be driven to proliferate, produce interleukin-2, and become anti-EC-specific cytotoxic T lymphocytes despite the lack of detectable membrane MHC class II determinants on the target cells. Chloroquine inhibition experiments demonstrate that autologous monocytes/macrophages are required by CD4+ T-cell precursors for the processing of EC-derived alloantigens and their subsequent presentation in the context of self-MHC molecules. These results are in agreement with the adoptive transfer experiments in experimental allograft models and suggest that the coordinate engagement of cells of the CD4, CD8, and monocyte/macrophage series is more effective than the individual cell subsets in the

Antibody Formation↗
PubMed1990

T-cell receptor-negative natural killer cells display antigen-specific cytotoxicity for microvascular endothelial cells.

Based upon prior demonstrations that human microvascular endothelial cells (ECs) could serve as natural killer (NK) cell targets, we established NK cell lines and clones by repeated stimulation of highly purified CD16-positive, CD3/T-cell receptor (Ti)-negative cells with allogeneic ECs. After 3 weeks in culture these lymphoid cells, which neither expressed surface CD3/Ti molecules nor rearranged Ti beta- or gamma-chain genes and which lysed K562 human erythroleukemia cells, displayed specific cytotoxicity for the stimulating ECs. Furthermore, freshly isolated NK cells bound and then removed from each of several allogeneic EC lines displayed selective cytotoxicity for the adsorbing EC line. These results provide evidence for alloantigen-specific recognition of microvascular ECs by NK cells that appears to be determined, at least in part, at the level of adherence. We discuss the implications of these findings with respect to the rejection of vascularized organ allografts.

Antibodies, Monoclonal↗
PubMed1989

Heterogeneous distribution and transmembrane signaling properties of lymphocyte function-associated antigen (LFA-1) in human lymphocyte subsets.

The role of LFA-1, a member of the integrin supergene family, in intercellular adhesion, including lymphocyte-endothelial cell (EC) binding, has been established. We now demonstrate that differences in LFA-1 cell surface density are responsible for the variable adhesion efficiency of lymphocyte subsets to EC. Electrophoretic analysis revealed multiple glycosylated isoforms of both alpha and beta subunits, largely as a result of different degrees of sialylation, with variable expression among different lymphocyte subsets. Neuraminidase digestion before EC adhesion increased the binding efficiency of all lymphocyte subsets, although the relative increase in each subset was proportional to the initial LFA-1 sialic acid content. LFA-1 cross-linking resulted in phosphoinositide hydrolysis and a rise in [Ca2+]i when using anti-alpha but not anti-beta subunit antibodies. These findings indicate that the density of LFA-1 on lymphocyte subsets controls their adhesive properties, and that the LFA-1 alpha subunit has transmembrane signaling properties that may result in activation events after interaction with its natural ligands.

Adult↗
PubMed1989

Evidence that cytotoxic lymphocytes alter and traverse allogeneic endothelial cell monolayers.

In an attempt to study the effects of allogeneic lymphocytes on endothelial cells (EC) and analyze the mechanism whereby such lymphocytes traverse an EC barrier, we have established human microvascular EC monolayers, in vitro, and analyzed the effects of lymphocyte subpopulations on such monolayers. Previous studies have shown that CD16+ (natural killer) and CD8+ (cytotoxic) lymphocytes but not CD4+ (helper) cells bind and induce the appearance of class II major histocompatibility complex antigens on allogeneic EC. The current findings indicate that these same lymphocyte subsets induce marked swirling and elongation of allogeneic EC, and traverse intact EC monolayers. In contrast, none of the functional consequences of the initial lymphocyte-EC adhesion were observed using autologous combinations, despite the presence of significant intercellular binding. Scanning and electron micrographs demonstrate extensive areas of lymphocyte-EC surface contact and EC-coated pit formation, whereas a panel of recombinant cytokines known to alter the surface phenotype of EC fail to induce the same morphologic changes whether used singly or in combination. We postulate that the cellular interactions observed here, in vitro, may represent the initial steps in the rejection of vascularized allografts in vivo.

Animals↗
PubMed1989

Development of an evaluation model for computer foodservice management systems.

Business evaluation practices were used to develop a model for postimplementation of a computer system in a foodservice. Four levels of success with a corresponding indicator for evaluation were identified as: I. Management Action--management implements data and reports; II. Management Change--management initiates use of system to find solutions to problems; III. Management Uses Analytical Approach--management uses system as a routine part of problem-solving; and IV. Management Change in Task-management's role changes as a result of the computer system. Five computer functions were identified for evaluation: integrity, performance, use, efficiency, and effectiveness. Criteria, measurements, standards, and actual sections were then developed for each function. An instrument was developed on the basis of the evaluation, including forms, questionnaires, learning experiences, and scenarios. The instrument was then applied to two computer foodservice management systems--a custom-designed system and a packaged software system. The instrument was applied to software systems by the scenario method. Five criteria with key indicators were developed to determine successful application of the instrument. The evaluation model and the final instrument developed and applied in this study should be useful to dietitians evaluating a computer system 6 to 12 months after implementation in their foodservice.

Computer Systems↗