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Biomedical subjects

D M Lewis

Publications and source records attributed to D M Lewis.

186 records · Page 11Linked to original sources
PubMedDate not supplied

Modification of alveolar macrophage function with bis-basic ethers of fluorene and fluoren-9-substituted derivatives.

Bis-basic ethers of fluorene and fluoren-9-substituted derivatives such as tilorone have been reported to inhibit silica-induced fibrosis in rats. The potential antifibrotic potency of 2,7-bis(diethylamino)ethoxy fluorene (F-9-H,H), fluorenone (F-9-one), fluorenoxime (F-9-oxime), and fluorenol (F-9-ol) was F-9-oxime > F-9-one approximately F-9-H,H >> F-9-ol. Since the release of reactive oxygen species and growth factors from alveolar macrophages (AM) in response to silica exposure has been linked to the development of pulmonary fibrosis, the present study was carried out to determine the inhibitory effects of these compounds on rat AM activity in vitro. The following parameters were monitored: (1) cellular viability; (2) zymosan-induced respiratory burst activity (superoxide and hydrogen peroxide release, chemiluminescence, and oxygen consumption) of AM; (3) drug binding to AM; and (4) lipopolysaccharide (LPS)-stimulated interleukin-1 (IL-1) release from AM. The bis-basic ethers, at 40 microM, did not affect cell viability when incubated with AM for 30 min, but significantly inhibited zymosan-induced macrophage respiratory burst activity. The inhibitory effect of these agents was F-9-oxime > F-9-one approximately F-9-H,H >> F-9-ol. Binding of these drugs to AM was time and dose dependent, and exhibited the following binding affinity: F-9-oxime > F-9-one > F-9-H,H > F-9-ol. F-9-oxime was shown to inhibit LPS-stimulated IL-1 release by AM in a dose-dependent manner. This inhibition of IL-1 release by AM cannot be explained as a decrease in viability. In addition, these drugs were also shown to impair human fibroblast proliferation in response to serum stimuli without impairing cell viability. These results indicate a positive correlation between drug binding to AM or other cell types and their inhibitory effects on cellular activities including oxygen consumption, superoxide release, hydrogen peroxide secretion, chemiluminescence, IL-1 release, and proliferation. The ability of these bis-basic ethers to modify AM and fibroblast functions in vitro suggests that further investigation of their reported antifibrotic potency in vivo is warranted.

Animals↗
PubMedDate not supplied

Is specific antibody determination diagnostic for asthma attributable to low-molecular-weight agents?

It is important to understand a medical testís performance characteristics, so that it can be used appropriately. Performance characteristics of tests for antibodies specific to low-molecular-weight (LMW) agents in predicting asthma caused by these agents differ in the study population. In general, currently published data supporting the use of tests to detect specific IgE and IgG to LMW agents in the diagnosis of occupational asthma is limited and inconclusive. However, a few general statements can be made. The most promising results have been achieved for agents such as acid anhydrides and platinum salts, where specific IgE responses appear to play a significant pathogenic role in causing occupational asthma. Results have been less promising for agents such as isocyanates and plicatic acid, for which antibody responses do not appear to underlie the development of asthma in most individuals. In the case of isocyanates, determination of antigen-specific IgG might have some utility as a biomarker of exposure.

Antibody Specificity↗
PubMedDate not supplied

Peripheral giant cell granuloma: a case report.

The peripheral giant cell granuloma is a reactive lesion of the soft tissue of the oral cavity. Clinical appearance ranges from normal tissue coloration to dark red or purplish. These are elevated lesions generally 5-15 mm in diameter. Etiology is considered to be chronic irritation. To decrease the risk of clinical recurrence, treatment is complete excision to include the underlying periosteum. Histologic features of the peripheral giant cell granuloma include multinucleated giant cells with a stroma that may contain osteoblasts, myofibroblasts, macrophages, and Langerhans cells. A case report is presented.

Adult↗
PubMedDate not supplied

Experimental otitis media in chinchillas. II. Comparison of the middle ear immune responses to S pneumoniae types 3 and 23.

The present study shows that two different serotypes of Streptococus pneumoniae (type 3 and 23) when inoculated through the bulla elicit distinctly different immune responses in chinchillas. The passive hemagglutination assay shows that type 3 is a better immunogen than type 23 and that type 3 primarily elicits immune responses in the middle ear. When class-specific antibody activity was measured with the red cell linked antigen-antibody reaction test, antibody activities of serum IgG to type 3 slightly declined and of effusion IgM and IgA to type 3 increased following type 3 infection, whereas following type 23 infection antibody activities of serum IgG to type 23 increased and no antibody activities of IgA and IgM to type 23 were present in the effusions.

Animals↗
PubMedDate not supplied

Chemotaxis of alveolar macrophages and neutrophils in response to microbial products derived from organic dust.

Mechanisms of chemotaxis of alveolar macrophages (AMs) and neutrophils (PMNs) in response to microbial products derived from organic dust were studied using the blindwell chemotaxis chamber technique. Seven different known etiological agents causing respiratory symptoms were used for experiments: cell extract and endotoxin from Pantoea agglomerans (synonyms: Erwinia herbicola, Enterobacter agglomerans), cell extracts from Thermoactinomyces vulgaris and Aspergillus fumigatus, protease from Bacillus thermoproteolyticus rokko and two preparations of glucans. These agents were evaluated for their ability to direct attraction of alveolar macrophages and neutrophils and stimulation of alveolar macrophages to release chemotactic factors for other alveolar macrophages and neutrophils. The microbial products were able to attract both alveolar macrophages and neutrophils directly in a dose-dependent manner, and the exposure of cultured alveolar macrophages to most agents stimulated chemotactic activity for for alveolar macrophages and neutrophils. The generation and release of this activity by alveolar macrophages may provide a mechanism for the initiation and amplification of inflammatory reactions in the lung after inhalation of organic dust. Results of these in vitro studies may be relevant to the pathogenesis of alveolitis in organic dust-induced lung diseases.

Animals↗