No abstract

Idiopathic pulmonary fibrosis is a fibrotic lung disease characterized by an increased number of mesenchymal cells in the alveolar walls. Alveolar macrophages constitutively express low levels of c-sis, the protooncogene coding for the B chain of platelet-derived growth factor, a protein with chemotactic and mitogenic activity toward mesenchymal cells. We therefore hypothesized that alveolar macrophages in patients with idiopathic pulmonary fibrosis may release increased amounts of platelet-derived growth factor, which might help to explain the accumulation of mesenchymal cells and the fibrosis of the lower respiratory tract in the disease. Evaluation of alveolar macrophages recovered from the lungs of patients with idiopathic pulmonary fibrosis demonstrated that these cells spontaneously released four times more platelet-derived growth factor than did alveolar macrophages recovered from normal persons (P less than 0.01). That the platelet-derived growth factor molecules were potentially active was shown by their chemotactic activity for smooth-muscle cells and their ability to act as a "competence" factor for fibroblast growth. These observations suggest the possibility that the accumulation of mesenchymal cells within the alveolar walls in patients with idiopathic pulmonary fibrosis may result partly from the exaggerated release of the potent mitogen platelet-derived growth factor by mononuclear phagocytes in the lower respiratory tract.

No abstract

Treatment with the nicotine inhaler plus nicotine patch resulted in significantly higher cessation rates than inhaler plus placebo patch.

Women are less successful than men at quitting smoking. We examined whether the male vs. female cessation outcome was influenced by baseline smoking behavior in participants who attempted to quit by using nicotine inhaler (NI) plus nicotine patch (NP) combination therapy. This double-blind, randomized, placebo-controlled trial enrolled 196 men and 204 women. Group 1 (99 men, 101 women) received NI plus NP (15 mg nicotine/16 h) for 6 weeks, then NI plus placebo patch (PP) for 6 weeks, then NI alone for 14 weeks. Group 2 (97 men, 103 women) received NI plus PP for 12 weeks, then NI alone for 14 weeks. Outcome measures were continuous self-reported abstinence and expired carbon monoxide concentration < 10 ppm. Baseline nicotine dependence was assessed by the Fagerström Test for Nicotine Dependence (FTND), and behavioral dependence by the 18-question Glover-Nilsson Smoking Behavioral Questionnaire (GN-SBQ). Male vs. female complete abstinence rates, regardless of treatment group, were 61.7% vs. 46.6% at 6 weeks (p = .0022), 42.3% vs. 30.9% at 12 weeks (p = .017), 30.1% vs. 17.6% at 6 months (p = .003), and 23.0% vs. 10.8% at 12 months, respectively (p = .001). Men had significantly higher baseline FTND (p = .0180) and lower total GN-SBQ (p < .0001) scores than women. In conclusion, women appear to have higher behavioral, and lower nicotine, dependence than men according to the GN-SBQ and the FTND; thus both nicotine and behavioral treatment should be tailored to women to increase their chances of abstinence.

Current ideas about the mechanism of wound healing and the pathogenesis of atherosclerosis, pulmonary fibrosis and hepatic fibrosis suggest a central role for the mononuclear phagocyte in attracting and/or stimulating the proliferation of mesenchymal cells. We demonstrate here that activated human blood monocytes, but not resting monocytes, release a mediator that attracts smooth muscle cells and cooperates with other mediators to stimulate fibroblast proliferation. This mediator is very similar to platelet-derived growth factor (PDGF): its chromatographic properties and chemical stability are similar to those of PDGF, it competes with 125I-PDGF for binding to fibroblasts and it immunoprecipitates with anti-PDGF antibodies. In parallel, stimulated monocytes, but not resting monocytes, express the c-sis proto-oncogene, a gene coding for one of the PDGF chains, consistent with the concept that expression of the c-sis proto-oncogene may be involved in the ability of mononuclear phagocytes to modulate the accumulation of mesenchymal cells.

To evaluate the contribution of mononuclear phagocytes, and particularly alveolar macrophages, to alpha-l-antitrypsin (alAT) production in normal and alAT-deficient individuals, Northern analysis with a human alAT complementary DNA was used to demonstrate that alAT messenger RNA (mRNA) can be detected in liver, blood monocytes, and alveolar macrophages.Quantification of alAT mRNA expression demonstrated that: (a) type PiMM monocytes and alveolar macrophages expressed, respectively, 200-fold and 70-fold less alAT mRNA per cell than the liver, (b) the level of expression of the alAT gene was increased during the in vitro maturation of blood monocytes; and (c) blood monocyte and alveolar macrophage levels of expression of the alAT gene were the same in PiMM and PiZZ individuals. However, the amount of newly synthesized alAT secreted by ZZ alveolar macrophages was 10 times lower than that secreted by MM alveolar macrophages. Thus, mononuclear phagocytes of PiZZ individuals express a secretory defect in alAT in a fashion similar to hepatocytes. Not only do mononuclear phagocytes provide a readily accessible cell to evaluate the regulation of alAT gene expression, but these cells may contribute to the levels of alAT present in the lower respiratory tract in the nornul and ZZ states.

Expression of RARalpha and RXRalpha is either normal or elevated in NSCLC. In contrast, a large percentage of tumors show a marked decrease in the expression of RARbeta, RARgamma, and RXRbeta as well as a high frequency of LOH at 3p24, which was also observed in non-neoplastic lesions. These data suggest that altered retinoid receptor expression may play a role in lung carcinogenesis.