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Biomedical subjects

D J Beer

Publications and source records attributed to D J Beer.

36 records · Page 2Linked to original sources
PubMed1986

Pharmacotherapy of chronic obstructive pulmonary disease.

The pharmacologic treatment of the reversible elements of chronic obstructive pulmonary disease is discussed in this article. Discussion focuses on three classes of bronchodilator drugs--the sympathomimetic agents, the methylxanthines, and the anticholinergic agents. A section on corticosteroid use in patients with chronic airflow limitation is included. An integrated approach to pharmacotherapy is suggested that allows a treatment program to be designed to meet the needs of the individual patient.

Adrenergic Fibers↗
PubMed1985

Chemoattractant lymphokines specific for the helper/inducer T-lymphocyte subset.

The cellular content of T-lymphocyte-rich inflammatory sites is dependent in part on the in situ elaboration of chemoattractant factors. We have previously described three T-lymphocyte-specific chemoattractant lymphokines; a chemokinetic factor, lymphocyte chemoattractant factor (LCF, MW 56,000), and two distinct lymphocyte migration inhibitory factors (LyMIF75K, MW 75,000; and LyMIF35K, MW 35,000). These factors are produced by human T cells in response to antigen, concanavalin A, or histamine stimulation. In this communication, we report that LCF and LyMIF35K are produced by OKT8+ (suppressor/cytotoxic) and OKT4+ (helper/inducer) lymphocytes, respectively, and are selectively chemoattractant for the OKT4+ lymphocyte subset. LyMIF75K is produced by OKT4+ cells and inhibits both OKT4+ and OKT8+ lymphocyte migration. Production of LCF and LyMIF35K by infiltrating lymphocyte subsets may be one mechanism whereby unactivated helper/inducer T lymphocytes are selectively recruited to sites of inflammation.

Antibodies, Monoclonal↗
PubMed1985

Induction of human T lymphocyte motility by interleukin 2.

Interleukin 2 (IL 2) is known to have multiple immunoenhancing activities that are related to its ability to promote the proliferation and the expression of effector functions of human T lymphocytes. We investigated the potential of IL 2 to induce human T lymphocyte migration. Unstimulated T cells did not respond to IL 2, but T cells exposed to dextran or phytohemagglutinin did respond to IL 2 concentrations from 0.01 to 10.0 U/ml, with significantly increased migration. This activity could be specifically blocked with anti-Tac antibody. Analysis of T lymphocyte subsets revealed that OKT4+ but not OKT8+ lymphocytes responded to IL 2 in the chemotaxis assay. Checkerboard analysis demonstrated that the IL 2-induced chemoattractant activity was predominantly chemotactic rather than chemokinetic in nature. The activity of IL 2 was compared with that of another chemoattractant lymphokine, lymphocyte chemoattractant factor, which was found to stimulate lymphocyte migration without prior exposure to mitogen, and which was not inhibited by anti-Tac. Our data suggest that the lymphocyte migratory response to IL 2 is under the control of the inducible receptor recognized by anti-Tac in a manner similar to the proliferative response to IL 2, but differs from proliferation in its OKT4+ cell specificity.

Adjuvants, Immunologic↗
PubMed1984

Errant placement of nasoenteric tubes. A hazard in obtunded patients.

We describe a case of intubation of both main-stem bronchi with a narrow-bore nasoenteric tube on two separate occasions, with the subsequent development of pleural effusions of enteral solution, in an elderly semicomatose woman with a properly positioned cuffed endotracheal tube. Neither aspiration of fluid from the tube nor propulsion of air with auscultation of gastric borborygmi are positive proof of proper positioning. We recommend that in obtunded patients, especially if there is the possibility of impaired mucosal integrity, appropriate placement of the tube should be confirmed by chest roentgenogram.

Aged↗
PubMed1984

Functional characteristics of histamine receptor-bearing mononuclear cells. II. Identification and characterization of two histamine-induced human lymphokines that inhibit lymphocyte migration.

Although functional histamine receptors have generally been restricted to those human T lymphocytes expressing suppressor cell functions, more recent evidence suggests that histamine receptor-bearing human T lymphocytes are functionally heterogeneous and capable of other immunomodulatory activities. Lymphocyte chemoattractant factor (LCF) is a cationic sialoprotein with an apparent m.w. of 56,000, whose production is limited to histamine-type 2 receptor-bearing human T cells. LCF is selectively chemokinetic for T lymphocytes, and presumably contributes to the recruitment of unsensitized effector lymphocytes at inflammatory sites. In addition to LCF, Sephadex G-100 gel filtration of histamine-induced lymphocyte supernatants revealed two regions of migration inhibitory activity for human blood T and rat splenic lymphocytes. These regions corresponded to m.w. of 70,000 to 80,000 (LyMIF75K) and 30,000 to 40,000 (LyMIF35K). LyMIF75K had a single pI of 7.5 to 8.0, and its biologic activity was sensitive to trypsin but not to neuraminidase or heat (56 degrees C). LyMIF35K had a single pI of 8.5 to 8.8, and its biologic activity was sensitive to neuraminidase and heat but not to trypsin. These LyMIFs therefore appeared to be distinct from one another and physicochemically different from other migration inhibitory lymphokines. All three lymphokine activities appeared within 4 hr of incubation. The minimum concentration of histamine required to stimulate production of the LyMIF was 10(-6) M. Lymphocytes that did not adhere to a histamine affinity matrix were unable to produce either LyMIF upon subsequent stimulation with histamine or concanavalin A (Con A). Lymphocytes incubated with histamine and diphenhydramine produced LCF but neither LyMIF, whereas cells incubated with histamine in the presence of cimetidine produced both LyMIF but not LCF. These data suggest that a subset of lymphocytes defined by the presence of histamine-type 1 receptors are capable of producing two distinct species of lymphocyte migration inhibitory activity. These cells may contribute to the immobilization of effector T lymphocytes chemokinetically attracted to certain inflammatory sites.

Adult↗
PubMed1983

Augmentation of prostaglandin and thromboxane production in vitro by monocytes exposed to histamine-induced suppressor factor (HSF).

A possible mechanism to explain the suppression of mitogen-induced lymphocyte proliferation in vitro by histamine-stimulated mononuclear cells was investigated. In initial experiments, the inhibitory action of histamine-induced suppressor factor (HSF) on lymphocyte proliferation was documented to be reduced by the addition of indomethacin (1 microgram/ml). Moreover, the addition of exogeneous PGE2 (10(-7)-10(-8) M) to mononuclear cell cultures reconstituted HSF activity in the presence of indomethacin. In order to ascertain the nature of the target cell responding to HSF, control and suppressor supernatants were incubated with human lymphocytes or monocytes (5 X 10(6) cells/ml) for 24 hr. Following incubation, the supernatants were assayed for their content of prostaglandin E2, F2 alpha, and thromboxane B2. Monocytes (but not lymphocytes) incubated with supernatants containing HSF increased their production of prostaglandin E2, F2 alpha, and thromboxane B2 by 169, 53, and 49%, respectively. Suppressor supernatants were generated with histamine or an H-2 agonist (dimaprit) and chromatographed by gel filtration on Sephadex G-100. The elution profiles for the factor(s) inducing suppression of lymphocyte proliferation (25-40,000 daltons) and augmenting PGE2 production (25,000 daltons) overlapped but were not identical. Collectively, these data suggest that HSF-mediated inhibition of lymphocyte proliferation may occur in part through the augmented production of prostaglandins and/or thromboxane B2 by human monocytes.

Dinoprostone↗
PubMed1983

Functional characteristics of histamine receptor-bearing mononuclear cells. I. Selective production of lymphocyte chemoattractant lymphokines with histamine used as a ligand.

Mitogens and antigens have been the traditional ligands for activating lymphocytes in vitro for the elaboration of lymphokines. Recently, histamine, by interaction with histamine-type 2 receptors on T lymphocytes, has been found to induce the production of one lymphokine, histamine-induced suppressor factor (HSF), that inhibits lymphocyte proliferation and lymphokine production in vitro. Because the biologic effects of HSF appear to be confined to alterations in lymphocyte function, we assessed the ability of soluble products of histamine-stimulated human blood mononuclear cells to affect another lymphocyte function, motility. Utilizing a modified Boyden chamber assay to assess lymphocyte migration, we identified chemoattractant activity for human blood and rat splenic T lymphocytes in histamine-induced mononuclear cell supernatants. No neutrophil or monocyte chemoattractant activity was present. Sephadex G-100 gel filtration of histamine-induced supernatants showed the lymphotactic activity eluted with a 56,000 m.w. This activity was cationic as determined by its elution pattern from a Sephadex QAE anion exchange matrix with a single pl of 9.0 to 9.4 determined by isoelectric focusing in sucrose. Its biologic activity is predominantly chemokinetic in nature, is stable to heating at 56 degrees C for 30 min, but is sensitive to the effects of trypsin and neuraminidase. These physicochemical and functional characteristics establish it as identical to a recently described concanavalin A-induced (Con A) lymphotactic lymphokine (LCF). Mononuclear cells that did not adhere to a histamine affinity matrix were unable to produce LCF when subsequently stimulated with histamine or Con A. Mononuclear cells incubated with histamine and diphenhydramine produced LCF; the addition of cimetidine eliminated LCF production. In fact, supernatants from cells incubated with histamine and cimetidine significantly inhibited lymphocyte migration, a phenomenon explainable by the two regions of lymphocyte migration inhibitory activity that were present in the Sephadex G-100 chromatography of crude histamine-induced supernatants. These data suggest that a subset of lymphocytes defined by the presence of histamine-type 2 receptors is capable of producing LCF while cells that bear histamine-type 1 receptors produce lymphocyte migration inhibitory activity.

Adult↗
PubMed1982

Abnormal histamine-induced suppressor-cell function in atopic subjects.

To detect a potential defect in immunoregulatory function in atopic subjects, we studied histamine-induced suppressor-T-cell activity and histamine Type 1 and Type 2 receptors on T cells. Peripheral-blood mononuclear cells from 16 atopic subjects generated less histamine-induced suppressor activity than did those from 20 nonatopic normal controls (P less than 0.005). The percentage of T lymphocytes bearing histamine Type 2 receptors was lower in the atopic group than in the control group (P less than 0.001), but the percentage of cells with Type 1 receptors was the same in both groups. In the atopic subjects, the functional suppressor-cell abnormality positively correlated with the decreased phenotypic expression of histamine Type 2 receptors. No abnormality in concanavalin A-induced suppressor activity was detected in these subjects. Nonatopic control subjects with systemic mastocytosis had normal functional and phenotypic data, suggesting that chronic activation of atopic T cells in vivo by circulating histamine does not explain the abnormal histamine-induced suppressor response.

Adolescent↗
PubMed1982

Pneumocystis carinii and cytomegalovirus pneumonia in a previously healthy adult.

A case of Pneumocystis carinii pneumonia and cytomegalovirus infection occurring in a previously healthy adult male homosexual who was not receiving known immunosuppressive therapy is described. This 35-year-old man had been treated with metronidazole and tetracycline for an intermittent diarrheal illness of 5 months' duration. He was then admitted to the hospital where he was found to have a small infiltrate in the left lower lobe, and this process soon involved both lungs. Initially, Pneumocystis carinii infection and later cytomegalovirus infection were diagnosed by lung biopsy and culture. Peripheral blood lymphopenia was present and he had in vivo and in vitro abnormalities of his cellular immune responses. He was unresponsive to Bactrim as well as pentamidine and pyrimethamine therapy and died 7 wk after hospitalization.

Adult↗
PubMed1982

Human monocyte-derived soluble product(s) has an accessory function in the generation of histamine- and concanavalin A-induced suppressor T cells.

We have analyzed the cellular interactions required for the generation of histamine- and concanavalin A (Con A)-induced suppressor T cells by employing a co-culture assay and techniques for fractionation of human blood mononuclear cells (PBMC). PBMC cultured in the presence of histamine (0.1 mM-1 mM) or Con A (20 micrograms/ml) for 24 h, mitomycin treated and subsequently combined with autologous mitogen-stimulated mononuclear cells, significantly suppressed a subsequent blastogenic response. PBMC fractionated over nylon wool columns and depleted of adherent cells and enriched for T cells (NWNA-T) were unable to generate suppressor activity. However, suppressor cell function by NWNA-T cells was reconstituted by the addition of autologous monocytes. In both the histamine and ConA suppressor systems, the requirement for monocytes in the activation process was enhanced by suspending the NWNA-T population in supernatants derived from allogeneic monocytes stimulated with heat-killed Staphylococcus albus. These crude supernatants contained leukocytic pyrogen (LP) and lymphocyte activating factor (LAF). Sequential purification and separation of the crude supernatants using gel-filtration, immunoadsorption, and isoelectric focusing demonstrated that only those fractions containing LP and LAF were capable to reconstituting NWNA-T cell histamine and Con A-induced suppressor activity. Thus, these studies suggest that the accessory role of supernatants derived from activated monocytes in the generation of suppressor cells may be mediated by LP/LAF. Further studies are in progress to explore the mechanism by which soluble factors stimulate suppressor T cells.

Animals↗
PubMed1978

Pleural effusion associated with primary lymphedema: a perspective on the yellow nail syndrome.

A 28-year-old woman with bilateral pleural effusions and generalized, primary lymphedema beginning with facial erysipelas at 6 years of age is presented. The pleural effusions were exudates with 250 cells per mm3, 92 per cent of which were lymphocytes. Lymphatic stasis was demonstrated by persistence of the blue dye in the dorsa of her feet 3 months after a lymphangiogram of both lower extremities, pelvis, and abdomen. Her nails were not remarkable. Our patient represents the twentieth recorded case of pleural effusion in association with primary lymphedema. Women have been afflicted more than twice as often as men, and the age of onset has varied from birth to the eighth decade. Yellow dystrophic nails may precede or follow lymphedema or the pleural effusion and have occurred in only 11 of the 20 patients.

Adult↗