Biomedical subjects

G Lark

Publications and source records attributed to G Lark.

3 recordsLinked to original sources

PubMed1998

Allergen-stimulated leukotriene B4 and interleukin-8 levels in patients with asthma and allergic rhinitis-modulation by a lipid pathway inhibitor.

BACKGROUND: Leukotriene B4 (LTB4), a potent chemokinetic mediator for neutrophils, is enhanced by interleukin-8 (IL-8) and may play a key role in the inflammatory response of asthma. OBJECTIVE: The aim of the present study was to investigate whether zileuton, a 5-lipoxygenase antagonist known to inhibit LTB4 production and recruitment of eosinophils/neutrophils in bronchoalveolar fluid, could affect the production of LTB4 and IL-8 by allergen-stimulated peripheral blood mononuclear cells in vitro from patients with asthma and/or allergic rhinitis. METHODS: Peripheral blood mononuclear cells were isolated using Ficoll-Hypaque density gradient from 14 subjects (2 with asthma, 11 with asthma and allergic rhinitis, and 1 with allergic rhinitis) and were stimulated by selected allergens (grass, tree, mite, and mold) in the absence or presence of 1 and 10 microM of zileuton. Supernatants were collected and assayed for LTB4 and IL-8 levels using RIA and ELISA, respectively. RESULTS: Levels of LTB4 were significantly elevated in peripheral blood mononuclear cells stimulated with mold, grass, and tree compared with the unstimulated control group (P<.05). Levels of IL-8 were significantly elevated in all allergen-stimulated peripheral blood mononuclear cells, except mold, compared with the unstimulated control group (P<.05). Zileuton significantly reduced production of LTB4 by mold and tree-stimulated peripheral blood mononuclear cells. By contrast, no effect of zileuton on IL-8 production was observed in allergen-stimulated peripheral blood mononuclear cells. CONCLUSIONS: The zileuton-induced attenuation of LTB4 production by allergen-stimulated peripheral blood mononuclear cells from patients with asthma and/or allergic rhinitis occurs independently from the allergen-stimulated IL-8 production.

Adult↗

PubMed1992

Differences in snRNP localization between transformed and nontransformed cells.

We have examined the localization of snRNPs in a variety of mammalian cells and have observed differences in the organization of these factors in transformed cells, immortal cells, and cells of defined passage number. Cells of defined passage number exhibit a speckled staining pattern after immunolabeling with anti-Sm, anti-B'', or anti-m3G antibodies. Furthermore, 2-3% of the cells, in a given population, exhibit labeling of 1 or 2 round coiled bodies in addition to the speckled-labeling pattern. However, transformed cells exhibited 1-4 intensely stained coiled bodies, in 81-99% of the cells, in addition to the speckled-labeling pattern. Immortal cells exhibited 1-4 intensely stained smaller coiled bodies in 4-40% of the cells, in addition to the speckled-labeling pattern. When immortal cells (REF-52) that had been transformed by adenovirus (REF-52Ad5.4) were examined, these cells exhibited an increase in the percentage of cells containing 1 or 2 intensely stained coiled bodies, in addition to the speckled labeling, from 24 to 99%. On the basis of this study, we conclude that the organization of snRNPs within the mammalian cell nucleus is a reflection of the physiology of the cell that may change upon transformation or immortalization.

Animals↗

PubMedDate not supplied

Late phase response during nasal challenge: effect of astemizole on leukotriene B4 levels.

Nasal provocation (NP) in allergic rhinitis patients can elicit a late phase inflammatory response in which interleukins (IL), leukotrienes (LT), and neutrophils have been implicated. Certain antihistamines have been shown to have anti-inflammatory properties. The objective was to determine whether astemizole at 10 mgs/day has any anti-inflammatory characteristics. We clinically evaluated 20 patients with allergic rhinitis and measured nasal IL-8 and LTB4 during NP with increasing doses of grass and ragweed antigen in a double-blind placebo-controlled fashion after a 4-week course of treatment. Clinical symptom scores for sneezing, pruritus, and rhinorrhea were evaluated. Nasal fluid was examined by ELISA and RIA for IL-8 and LTB4 levels along with neutrophil assessment before NP and at 3, 6, and 8 hours. Symptom scores for nasal sneezing, pruritus, rhinorrhea, and nasal LTB4 levels at 6 and 8 hours and IL-8 at 3, 6, and 8 hours were generally lower in astemizole-treated patients compared to those on placebo. Nasal IL-8 levels corresponded to LTB4 levels at diluent and at 6 hours in the placebo group (P = 0.01). The percentage of neutrophils correlated with LTB4 levels at baseline, coefficient = 0.76, P = 0.02 and at 6 hours, coefficient = 0.62, P = 0.035 in the placebo group. This study is the first to demonstrate an effect of astemizole during NP on IL-8 and LTB4 levels with a significant correlation of neutrophil numbers in untreated patients during the nasal late phase response.

Adult↗