Minati Dhar

Administration of antisense oligonucleotides to GαQ/11 reduces the severity of murine lupus

Our principle hypothesis is that the hypothalamic hormone, gonadotropin-releasing hormone (GnRH), is an immunostimulatory hormone and plays a pivotal role in the gender differences in immunity and/or autoimmunity. As a general rule, females display heightened immune responses and heightened endocrinological responsiveness to GnRH compared to males. We have previously demonstrated that GnRH receptor antagonists are effective in ameliorating murine lupus and that GnRH receptor agonists exacerbate murine lupus. GnRH exerts its actions via stimulatory G proteins, specifically via Galpha(s) and the homologous G proteins Galpha(q) and Galpha(11) (referred to together as Galpha(q/11)). We have previously demonstrated that females express higher levels of Galpha(q/11) mRNA and protein compared to males. We hypothesized that antisense inhibition of these specific G proteins would lead to a reduction in inflammatory cytokines and to an amelioration of disease in a mouse model of lupus. We randomized gonadectomized female (NZB x NZW) F1 hybrid mice to treatment with antisense oligonucleotides to Galpha(q/11) or to missense oligonucleotides. Administration of antisense oligonucleotides to Galpha(q/11) led to significant reductions in autoantibody levels, serum IgG levels, hematuria, and proteinuria compared to missense oligos. A trend toward prolonged survival was also noted. In vitro co-culture experiments demonstrated that antisense to Galpha(q/11) significantly inhibited IL-6 production compared to control.

Alternaria and Cladosporium Fungal Allergen Epitopes are Denatured by Sodium Hypochlorite

BackgroundFungal allergens are ubiquitous; however, little progress has been made understanding fungal allergenic material removal from indoor environments.PurposeWe investigated removal of environmental allergenic material derived from Alternaria and Cladosporium using sodium hypochlorite in vivo and in vitro.MethodsFreeze dried allergen extract from Alternaria alternata and Cladosporium herbarum was treated with hypochlorite concentrations of 322, 88, 38, 16, 3, 0.3, and 0 mM, respectively. Remaining native allergenic material was quantified using enzyme immunoassay and remaining viable fungal material was evaluated.ResultsThe results of treating Alternaria or Cladosporium extract with sodium hypochlorite are immediate and obvious. Concentrations greater than 100 mM remove color and concentrations between 100 and 38 mM partially uncolored the extract. Immunoassay for total antigenic and allergenic material remaining after treatment with sodium hypochlorite including 2 concentrations recommended for killing fungus confirmed a general destruction of antigenic and allergenic material at concentrations of 38 mM or greater.ConclusionsThis work confirms the ability of solutions of sodium hypochlorite to denature fungal allergenic material from common outdoor and indoor fungi A. alternata and C. herbarum. Destruction of recognized antigenic and allergenic epitopes occurs at hypochlorite concentrations commonly used for household cleaning.

Relation of indoor and outdoor airborne fungal spore levels in the Kansas City metropolitan area

BACKGROUND Environmental control is an important component of asthma management for persons with asthma. A damp indoor environment and elevated airborne spore levels are factors in housing environmental control. OBJECTIVES We investigated if indoor airborne fungal spore levels correlated with outdoor ground-level airborne fungal spores or outdoor centrally collected spore levels as to types and abundance. METHODS Air collections were taken from home interiors, outdoor areas adjacent to the homes, and at a central location in the metropolitan area at the approximate same time. All air collections were examined and enumerated microscopically, and airborne spore estimates per cubic meter of air were reported for total fungal spores and for 11 identifiable spore groups. RESULTS The 244 homes in the study were typical of the North American Midwest. The overall mean total spore counts in spores per cubic meter of air was indoors (4076 spores/m3), outdoors at ground level (8899 spores/m3), and outdoor metropolitan area (8342 spores/m3). All of the major indoor taxa were strongly correlated with the mean total spores present in the home. Total outdoor ground spore levels were highly correlated with levels of major outdoor taxa, such as ascospores and Cladosporium. Correlations of indoor spore levels with outdoor spore levels are strong for most major outdoor taxa. Indoor Aspergillus-Penicillium and Chaetomium are significantly correlated between indoor and local ground-level outdoor air. CONCLUSION Although conditions may exist where indoor or outdoor spore levels were not well aligned, in most circumstances, the outdoor airborne spore community was reflected in the indoor airborne spore community.