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Biomedical subjects

N J Roberts

Publications and source records attributed to N J Roberts.

At least 73 records · Page 4Linked to original sources

Influenza virus infection of human alveolar and blood-derived macrophages: differences in accessory cell function and interferon production.

Influenza virus infection in vitro depresses accessory cell function of human peripheral blood-derived macrophages (PBM phi) for lymphocyte proliferative responses, but effects on such functions of alveolar macrophages (AlvM phi) have not been described. AlvM phi were obtained by bronchoalveolar lavage from normal young volunteers, and the effects of influenza virus infection of AlvM phi and autologous PBM phi were compared by measuring the accessory support provided by these cells for phytohemagglutinin-induced proliferation of purified autologous lymphocytes. Accessory cell function of AlvM phi was not altered by viral infection; in contrast, this function was significantly depressed with autologous virus-infected PBM phi. Virus-infected PBM phi produced greater amounts of interferon than did autologous AlvM phi. However, synthesis of interferon or prostaglandins by virus-infected cells could not account, per se, for depression of lymphocyte responses in the presence of PBM phi. These studies detail functional heterogeneity of autologous PBM phi and AlvM phi in response to a common respiratory-tract pathogen, influenza virus.

Adult↗

Influenza virus infection of human alveolar and peripheral blood-derived macrophages. Production of factors that alter fibroblast proliferation.

Influenza virus infection of the lung has been shown, in animal models as well as in isolated human case reports, to cause a long-term alveolitis characterized by increased numbers of free lung macrophages. Recruitment of peripheral blood monocytes into the interstitial spaces, with subsequent maturation into tissue macrophages, accounts for most of the observed increase in cell numbers. The current studies examined the release of soluble factors by lavage-derived alveolar macrophages from healthy volunteers, and by peripheral blood-derived macrophages from the same subjects. Cell-free supernatant fluids generated by the macrophages after in vitro exposure or sham exposure to influenza virus were tested for effects on human fibroblast proliferation. The data indicated that autologous human alveolar macrophages and peripheral blood-derived macrophages both produce fibroblast-stimulating factor(s) in response to in vitro infection. The data suggest that macrophage release of fibroblast-stimulating factor(s) may play a role in the development of end-stage fibrotic lung disease occasionally seen as a sequela of influenza pneumonia.

Adult↗

Bronchoalveolar lavage in gold lung.

We report the results of bronchoalveolar lavage in a patient with gold salt-induced interstitial pneumonitis. The presence of elevated numbers of lymphocytes in the lavage specimen supports a hypersensitivity-related pathogenesis of this disease. Such findings may help distinguish pulmonary complications of gold therapy from interstitial disease due to rheumatoid arthritis.

Adult↗

Human leukocyte functions and the U.S. safety standard for exposure to radio-frequency radiation.

Human mononuclear leukocytes were exposed to microwaves at energies relevant to current public safety recommendations. No detectable effects on viability or function of the leukocytes resulted from exposure to microwaves at specific absorption rates up to 4 milliwatts per milliliter. The results were highly reproducible and provided no evidence that current safety standard recommendations are inappropriate insofar as leukocyte function is concerned.

DNA↗

A dual vial waveguide exposure facility for examining microwave effects in vitro.

A waveguide exposure system operated between 2 and 4 GHz was assembled in a laboratory incubator in order to study potential temperature-dependent and temperature-independent actions of microwaves. Two vials containing cell cultures were exposed simultaneously in a single waveguide in order to reduce the space required, and to allow concurrent study of autologous cell cultures in two different functional states (resting and stimulated) during exposure. Dosimetry was performed using three techniques with different underlying assumptions, as well as the technique of differential power measurement. Each of the four techniques yielded different results, although differences between the two vials using any single technique were negligible. A significant 'hot spot' occurred at the center of each vial. The ratio between maximum and minimum absorption rate within a single vial was 33-fold using a vial of 1.2-cm diameter and 1.6-cm height. With agitation and exposure at specific absorption rate (SAR) equal to 21 mW/ml, the thermal gradient was less than 0.1 degrees C between these two points. The averaged SAR can be determined by steady-state heating analysis. The exposure system can be calibrated readily by calculation for the measured powers, but not by differential power measurement.

Cells, Cultured↗

Human alveolar macrophage support of lymphocyte responses to mitogens and antigens. Analysis and comparison with autologous peripheral-blood-derived monocytes and macrophages.

Observations from animal studies and investigations using human peripheral-blood-derived macrophages may not be representative of human alveolar macrophage functions. Thus, we extensively examined and compared accessory cell functions of autologous human alveolar macrophages and peripheral-blood-derived monocytes and macrophages obtained from healthy, nonsmoking volunteer subjects. The alveolar and peripheral-blood-derived cells differed in ability to enhance mitogen- and antigen-stimulated transformation responses of purified autologous lymphocytes. Peripheral-blood-derived cells supported greater lymphocyte responses to optimal concentrations of several mitogens, but alveolar macrophages supported much greater responses to suboptimal concentrations of the mitogen phytohemagglutinin. Peripheral-blood-derived macrophages supported, but alveolar macrophages did not support, lymphocyte responses to streptococcal and influenza virus antigens. Such relative accessory cell functions of the different macrophages and monocytes were not due to different kinetics of response, nor were they due to differences in the proportion of macrophages required to support the lymphocyte responses. These data indicate that human alveolar macrophages have functional characteristics different from autologous peripheral-blood-derived monocytes and macrophages. Such differences may be important in both pulmonary immune homeostasis and in the pathogenesis of pulmonary disease.

Adult↗

Different effects of influenza virus, respiratory syncytial virus, and Sendai virus on human lymphocytes and macrophages.

Influenza virus, respiratory syncytial virus, and Sendai virus depress human cell-mediated immune responses, such as mitogen-induced lymphocyte transformation, but differ in their ability to induce other immune defense mechanisms, such as interferon production. Exposure to the different viruses resulted in depressed transformation responses to the mitogen phytohemagglutinin by affecting the function of lymphocytes, or macrophages, or both cell types.

Adult↗

Interferon production by human mononuclear leukocytes: differences between respiratory syncytial virus and influenza viruses.

The ability of respiratory syncytial virus (RSV) to induce interferon production by human mononuclear leukocytes was compared with that of influenza viruses. Cell culture fluids were assayed for interferon activity 1, 3 and 7 days after exposure to RSV or to one of two subtypes of influenza A virus (H0N1 and H3N2). RSV induced interferon production inconsistently and in low titers. Varying the multiplicity of infection did not improve the ability of RSV to induce interferon production. In contrast, influenza viruses were effective inducers of interferon production. Seropositivity to the influenza virus strains was not associated with increased interferon titers. Interferon produced after exposure to RSV or to the influenza viruses was resistant to low pH treatment. The data suggest that interferon production may not be a major component of human immunological defense against RSV infection.

Adult↗

Mitogen responses and interferon production after exposure of human macrophages to infectious and inactivated influenza viruses.

Human macrophages were exposed to two influenza A viruses representing different subtypes. The donors were likely to have been exposed to one subtype (H3N2) but not to the other (H0N 1). Similar effects upon the macrophages were observed for both subtypes: macrophage enhancement of mitogen-stimulated lymphocyte transformation responses was depressed, and the macrophages produced interferon. In contrast, macrophages exposed to inactivated virus exhibited normal enhancement of lymphocyte transformation response, yet produced interferon, although in lower titers than did macrophages exposed to infectious virus.

Hot Temperature↗

Variability of results of lymphocyte transformation assays in normal human volunteers. Responses of mononuclear leukocytes to mitogen stimulation.

Human mononuclear leukocyte transformation responses were tested in a microassay system using measurement of tritiated thymidine incorporation stimulated by different mitogens. A wide range of results was found using cells isolated by Ficoll-Hypaque separation of blood from normal volunteer donors. Considerable variation was seen in the responses of different individuals tested concurrently, and in the responses of single individuals tested sequentially. Wide variation in responses existed even when dose-response curves were produced. There was little variation in the cell concentrations or mitogen concentrations that produced optimal responses in this assay. Caution in comparing responses of mononuclear leukocytes obtained at different venipunctures is advised.

Adolescent↗

The absence of differences in cellular immunity in elderly individuals with and without delayed local cutaneous reactions to influenza vaccine.

Two groups of elderly subjects who received bivalent influenza virus vaccine were identified. Those in Group I manifested marked local reactions, suggestive of delayed hypersensitivity reactions, whereas those in Group II, matched with Group I for vaccine preparation, had no cutaneous reactions. In vitro assays of immune function were performed on pairs of subjects from the two groups and included serum immunoglobulin and complement levels, antibody response to vaccine, lymphocyte transformation to mitogens (phytohemagglutinin, pokeweed mitogen and concanavalin A) and antigens (streptokinase-streptodornase, influenza virus vaccine antigens and multiple mixed lymphocytes), and polymorphonuclear leukocyte chemotactic responsiveness. There was no demonstrable correlation between delayed local cutaneous reaction and preservation of in vitro cell-mediated immune function in these elderly individuals.

Age Factors↗