The epidermal growth factor receptor mediates allergic airway remodelling in the rat.

The chronicity of bronchial asthma is attributed to persistent airway inflammation and to a variety of structural changes, or remodelling, that includes smooth muscle and goblet cell hyperplasia. To investigate the mechanisms of airway remodelling, the current authors used an established allergen (ovalbumin; OVA)-driven rodent model (the Brown Norway rat). Brown Norway rats were sensitised to OVA and challenged three times at 5-day intervals to evoke airway remodelling. The effects of an epidermal growth factor (EGF) receptor inhibitor, AG1478, and a cysteinyl leukotriene-1 receptor antagonist, montelukast, on epithelial and airway smooth muscle (ASM) cell proliferation in vivo in response to repeated OVA challenge were tested. Three challenges with leukotriene (LT)D(4) were given, to examine their effects on remodelling with and without AG1478 pretreatment. OVA challenges caused ASM hyperplasia, with an increase in mass, epithelial cell proliferation and goblet cell proliferation. AG1478 prevented the changes, as did montelukast. Multiple OVA challenges increased heparin-binding EGF-like growth factor but not EGF expression by airway epithelium. LTD(4) reproduced the changes in remodelling induced by OVA and this was blocked by AG1478. Allergen-induced airway epithelial and airway smooth muscle remodelling is mediated by cysteinyl leukotrienes via the cysteinyl leukotriene-1 receptor with downstream effects on the epidermal growth factor receptor axis.

T-helper type 2-dependent early recruitment of antigen non-specific CD4+ T cells in experimental asthma.

BACKGROUND: Following antigen challenge, adoptively transferred antigen-specific CD4(+) T cells induce allergic airway inflammation, comprised primarily of an increase in lymphocytes and eosinophils. OBJECTIVE: Our goal was to better understand the contribution of the GATA-3 transcription factor to the ability of adoptively transferred T cells to induce airway inflammation in the Brown Norway rat model of adoptively transferred asthma. METHODS: We transduced antigen-stimulated CD4+ T cells with recombinant retroviruses encoding enhanced green fluorescent protein (EGFP) only or EGFP and the GATA-3 transcription factor. Each population of transduced cells was adoptively transferred to naïve recipients that were then challenged with antigen. Airway inflammatory responses were then quantified. RESULTS: Our data indicate that T cells transduced with retroviruses encoding GATA-3 expressed high levels of GATA-3 protein as well as T-helper type 2 cytokines. Following adoptive transfer and airway antigen challenge, these gene-modified T cells induced robust inflammatory responses in the lungs and draining lymph nodes. Increased numbers of total inflammatory cells and eosinophils were recovered in the bronchoalveolar lavage fluid (BALF). In addition, the number of antigen non-specific CD4+ T cells recovered in the BALF as well as the lung and draining lymph nodes was enhanced in recipients of GATA-3 overexpressing T cells following antigen challenge. Nevertheless, the transduced CD4+ T cells comprised only a small percentage of the population of CD4+ T cells infiltrating the lung and were not detectable at all in the draining lymph nodes. CONCLUSION: These data provide evidence that GATA-3 plays a significant role in the ability of antigen-specific T cells to amplify allergic inflammatory responses in vivo by promoting the recruitment of endogenous antigen non-specific T cells to the lung.

[A case of localized fibrous tumor of the pleura after four years follow up and evaluate the doubling time with computed tomography].

Thirty-five-year female had taken video assisted thoraco-surgery (VATS) and resected her localized fibrous tumor of parietal pleura. She suspected chest tumor with annual X-ray survey for lung disease four years ago. She complained of left side back pain recently. Her chest CT revealed that the tumor enlarged than before. She was performed video assisted thoraco-surgery. The tumor was solid hard and connected to the parietal pleura with pedicle, which was resected easily from her pleural cavity. Histrogical examination detected that her tumor was localized fibrous tumor of parietal pleura. CD 34 and Vimentin were positive and cytokeratin was negative in this case. Four year and two examinations of the chest CT later, we could determine the doubling time (800.7 days) of localized fibrous tumor in this case.

Cephalosporins having a heterocyclic catechol in the C3 side chain. II. Improvement of pharmacokinetic profile.

7-[(Z)-2-(2-Aminothiazol-4-yl)-2-methoxy-(or hydroxy)-iminoacetamido]-3- [propen-1-yl]-cephalosporins having a variety of heterocyclic catechol in 3-position of the propenyl group were synthesized. Among them, 6,7-dihydroxyisoquinoline derivatives, 2a and 2b, showed very high and prolonged blood levels after intramuscular administration to mice and higher in vivo antibacterial activity than expected from their in vitro activity. The former cephalosporin (2a) gave well-balanced in vitro and in vivo antibacterial spectra including anti-methicillin-resistant Staphylococcus aureus (MRSA) activity. The latter cephalosporin (2b) also showed good in vitro and in vivo activities against Gram-positive bacteria, especially against S. aureus A15036, a strain of MRSA, the in vivo activity being comparable to vancomycin but was lacking in anti-pseudomonal activity.