Faculty

Dennis J. Beer, M.D.

Specialty: Allergy and Pulmonary Medicine

Newton-Wellesley Hospital

2014 Washington Street
Newton, MA 02462

Publications

The following is a list of publications for which this Partners Asthma Center physician has been cited as an author in PubMed databases. Study abstracts have been provided for your convenience.

Levin, M. S., I. Vernovsky, et al. (1996). "Recent Dieulafoy’s lesion bleeding and massive pulmonary emboli. Successful use of thrombolytic therapy." Chest 110(2): 567-70.

A massive GI bleed secondary to a Dieulafoy’s lesion developed in a 77-year-old woman. Fifteen days later, massive pulmonary emboli developed. We describe successful thrombolytic treatment of her pulmonary emboli without complicating GI hemorrhage.

Laberge, S., W. W. Cruikshank, et al. (1996). "Secretion of IL-16 (lymphocyte chemoattractant factor) from serotonin-stimulated CD8+ T cells in vitro." J Immunol 156(1): 310-5.

At sites of inflammation, mononuclear cells are in close contact with aggregated platelets. Although the physiologic role of this association is not clear, this proximity suggests that platelet-derived mediators may play a role in chemoattraction of T lymphocytes. In the current study we investigated serotonin receptor-bearing lymphocyte modulation of T cell migration. Serotonin-stimulated human blood mononuclear cells secrete lymphocyte chemoattractant activity with selective activity for CD4+ T cells. This chemoattractant activity was observed within 2 h of exposure to serotonin and was blocked by serotonin type 2 receptor antagonists. Molecular sieve chromatography of supernatant from serotonin-stimulated PBMCs revealed a single peak of T cell chemoattractant activity with an apparent molecular mass of 56 kDa and a pl of 9.1. Neutralizing experiments with specific mAbs indicated that the serotonin-induced chemotactic factor was the previously characterized lymphocyte chemoattractant factor (LCF), recently designated IL-16. Serotonin induced secretion of IL-16 from CD8+, not CD4+, T cells which did not require the de novo protein synthesis. These studies suggest that serotonin, via serotonin type 2 receptors, may promote the recruitment of CD4+ T lymphocytes into an inflammatory focus.

Jack, G. W. and D. J. Beer (1996). "Immunoaffinity chromatography." Methods Mol Biol 59: 187-96.

Beer, D. J., A. M. Yates, et al. (1995). "A comparison of the leakage of a monoclonal antibody from various immunoaffinity chromatography matrices." Bioseparation 5(4): 241-7.

Antibody leakage from immunoaffinity chromatography (IAC) matrices could reduce the working life of the IAC matrix and/or contaminate parenteral products, purified by IAC. There is therefore a need to measure the leakage of antibody from IAC matrices and to reduce such leakage. Using sensitive ELISAs it was found that the type of activated matrix, the buffer, the presence of proteases in the feedstock and the storage of IAC matrices between runs could all effect antibody leakage.

Katz, M. F., H. W. Farber, et al. (1994). "Serotonin-stimulated aortic endothelial cells secrete a novel T lymphocyte chemotactic and growth factor." J Leukoc Biol 55(5): 567-73.

Atherosclerotic lesions contain multiple cell types including smooth muscle cells, macrophages, and T lymphocytes. The development of an extralymphatic T lymphocyte focus of inflammation in this condition requires chemoattractant-induced cell migration and growth factor-induced cell activation. In a previous study, we described a novel 13-15-kDa T lymphocyte-specific chemotactic cytokine, endothelial cell-derived lymphocyte chemoattractant activity (ED-LCA), secreted by serotonin-stimulated bovine aortic endothelial cells that is distinct from previously identified endothelial cell-derived interleukins (IL) 1, 6, and 8. Because of the association between T lymphocyte chemotactic and growth factor activity, in the current study we investigated the effect of ED-LCA on T cell growth. We assessed its capacity to induce markers of the passage of T cells from the resting (G0) state into the G1 phase of the cell cycle, such as receptors for IL-2 (IL-2R) and transferrin (TFR) and class II major histocompatibility complex antigens (HLA-DR). Incubation of G0 freshly isolated human T lymphocytes for 48 h with chromatographically resolved, partially purified ED-LCA resulted in a threefold increase in expression of the p55 subunit of IL-2R, a threefold increase in TFR, and a twofold increase in HLA-DR. Passage into the G1 phase of the cell cycle was confirmed by cell cycle analysis employing acridine orange. Evaluation of CD4+ and CD8+ T cell subsets by double-antibody labeling demonstrated that the p55 subunit of IL-2R was induced in both T cell subsets. Although incubation of human T cells with ED-LCA alone did not induce proliferation, addition of exogenous IL-2 to T cells pulsed with ED-LCA for 24 h caused a proliferative response with a stimulation index of 3. By up-regulating functional cell surface receptors for IL-2, ED-LCA is a competence growth factor for T lymphocytes and primes them to respond to IL-2. By virtue of its effect on T cells, as a chemotactic and competence factor, this endothelial cell-derived mitoattractant could participate with other T cell growth factors like IL-2 in the recruitment and amplification of the extralymphatic T cell component of atherosclerosis.

Katz, M. F., D. J. Beer, et al. (1994). "Secretion of a novel T-lymphocyte cytokine possessing both chemotactic and growth factor activity by serotonin-stimulated human aortic endothelial cells." Exp Cell Res 212(1): 113-9.

The development of an extralymphatic T-lymphocyte focus of inflammation requires chemoattractant-induced cell migration and growth factor-induced cell proliferation. In a previous study, we identified a novel 13- to 15-kDa T-lymphocyte-specific chemotactic cytokine, endothelial cell-derived lymphocyte chemoattractant activity (ED-LCA), secreted by serotonin-stimulated human aortic endothelial cells. Based on its physicochemical and functional characteristics and antibody inhibition studies, ED-LCA is distinct from previously identified endothelial cell-derived IL-1, IL-6, and IL-8. Because of the association between T-lymphocyte chemotactic and growth factor activity, in the current study, we investigated the effect of ED-LCA on T cell growth by assessing its capacity to induce markers of the passage of T cells from the resting (G0) state into the G1 phase of the cell cycle, such as receptors for IL-2 (IL-2R) and transferrin (TFR), and class II major histocompatibility complex antigens (HLA-DR). Incubation of G0 freshly isolated human T lymphocytes for 48 h with chromatographically resolved, partially purified ED-LCA resulted in a threefold increase in expression of IL-2R, a threefold increase in TFR, and a twofold increase in HLA-DR. Double antibody labeling demonstrated that IL-2R was induced in both CD4+ and CD8+ T cell subsets. Although incubation of human T cells with ED-LCA alone did not induce DNA synthesis, addition of exogenous IL-2 to T cells pulsed with ED-LCA for 24 h caused an increase in DNA synthesis with a stimulation index of 3.5. By up-regulating functional cell surface receptors for IL-2 on T lymphocytes and priming them to respond to exogenous IL-2, ED-LCA is a competence growth factor. By virtue of its effect on T cells, as a chemotactic and competence factor, this endothelial cell-derived mitoattractant could participate with other T-cell growth factors like IL-2 in the generation of an extralymphatic T-lymphocyte inflammatory response.

Beer, D. J., A. M. Yates, et al. (1994). "Development of enzyme-linked immunosorbent assays (ELISAs) for the detection of monoclonal antibody leakage from immunoaffinity chromatography matrices." J Immunol Methods 173(1): 103-9.

Antibodies can leak from immunoaffinity chromatography (IAC) matrices, reducing the working life of the IAC matrix and/or compromising the purity of the product, purified by IAC, for therapeutic use. There is therefore a need to monitor the leakage of antibody from IAC matrices. Antibody leakage from a model IAC system was measured using two-site “non-competitive” ELISAs. Two assays were developed to measure the leakage of intact and fragmented antibody from the IAC matrix. By measuring the leakage of intact and fragmented antibody the mechanisms underlying antibody leakage from solid-supports could be elucidated.