Methacholine bronchial provocation test in patients with asthma: serial measurements and clinical significance.

Background/Aims: The methacholine bronchial provocation test (MBPT) is used to detect and quantify airway hyper-responsiveness (AHR). Since improvements in the severity of asthma are associated with improvements in AHR, clinical studies of asthma therapies routinely use the change of airway responsiveness as an objective outcome. The aim of this study was to assess the relationship between serial MBPT and clinical profiles in patients with asthma. METHODS: A total of 323 asthma patients were included in this study. The MBPT was performed on all patients beginning at their initial diagnosis until asthma was considered controlled based on the Global Initiative for Asthma guidelines. A responder was defined by a decrease in AHR while all other patients were considered non-responders. RESULTS: A total of 213 patients (66%) were responders, while 110 patients (34%) were non-responders. The responder group had a lower initial PC20 (provocative concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20%) and longer duration compared to the non-responder group. Members of the responder group also had superior qualities of life, compared to members of the non-responder group. Whole blood cell counts were not related to differences in PC20; however, eosinophil concentration was. No differences in sex, age, body mass index, smoking history, serum immunoglobulin E, or frequency of acute exacerbation were observed between responders and non-responders. Conclusions: The initial PC20, the duration of asthma, eosinophil concentrations, and quality-of-life may be useful variables to identify improvements in AHR in asthma patients.

Prognostic value of baseline carcinoembryonic antigen and cytokeratin 19 fragment levels in advanced non-small cell lung cancer.

BACKGROUND: Serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) levels are prognostic predictors in non-small cell lung cancer (NSCLC). However, even in patients with the same stage of cancer, the serum levels of those markers often vary. OBJECTIVE: We investigated the association between the initial biomarker levels and prognosis. METHODS: We retrospectively reviewed 445 patients with advanced NSCLC and their baseline serum CEA and CYFRA 21-1 levels. Patients were divided into four groups according to the initial levels of those markers: the NN, HN, NH, and HH group. Kaplan-Meier survival analysis with Log-rank test and Cox proportional hazards regression analysis were performed. RESULTS: The 5-year overall survival (OS) rate in the HN group was the highest (32.2%). Multivariate analyses indicated that the HN group (HR 0.520, 95% CI 0.309-0.878, P= 0.014), female sex (HR 0.685, 95% CI 0.498-0.944, P= 0.021), serum CRP level (HR 1.057, 95% CI 1.034-1.080, P< 0.001), chemotherapy (HR 0.324, 95% CI 0.228-0.460, P< 0.001), and chemotherapy/radiotherapy (HR 0.266, 95% CI 0.171-0.414, P< 0.001) were independent prognostic factors for overall survival. CONCLUSIONS: In advanced NSCLC, patients with baseline high serum CEA but low CYFRA 21-1 level have a significant longer overall survival regardless of clinical stage.

Apolipoprotein A1 Inhibits TGF-ß1-Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ß1 (TGF-ß1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-ß1-induced EMT in experimental lung fibrosis and clarify its mechanism of action. METHODS: The A549 alveolar epithelial cell line was treated with TGF-ß1 with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and α-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-ß1 receptor type 1 (TßRI) and type 2 (TßRII) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. RESULTS: TGF-ß1-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-ß1-induced change of the EMT phenotype. ApoA1 inhibited the TGF-ß1-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-ß1-induced increase in TßRI and TßRII expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. CONCLUSION: Our data demonstrate that ApoA1 inhibits TGF-ß1-induced EMT in experimental lung fibrosis.

Serum sickness reaction with skin involvement induced by bee venom injection therapy.

Bee venom injection therapy is an alternative treatment sometimes used for chronic inflammatory diseases, including rheumatoid arthritis and multiple sclerosis, to reduce pain. Several chemical components of bee venom have anti-inflammatory effects, and apitoxin, one of the mixed components, has been used for pain prevention therapy. However, there have been no large-scale investigations regarding the efficacy or side effects or apitoxin. In this study, a case of serum sickness reaction that developed after receiving bee venom injection therapy is reported.

Transcriptional regulation of Niemann-Pick C1-like 1 gene by liver receptor homolog-1.

Factors that modulate cholesterol levels have major impacts on cardiovascular disease. Niemann-Pick C1-like 1 (NPC1L1) functions as a sterol transporter mediating intestinal cholesterol absorption and counter-balancing hepatobiliary cholesterol excretion. The liver receptor homolog 1 (LRH-1) had been shown to regulate genes involved in hepatic lipid metabolism and reverse cholesterol transport. To study whether human NPC1L1 gene is regulated transcriptionally by LRH-1, we have analyzed evolutionary conserved regions (ECRs) in HepG2 cells. One ECR was found to be responsive to the LRH-1. Through deletion studies, LRH-1 response element was identified and the binding of LRH-1 was demonstrated by EMSA and ChIP assays. When SREBP2, one of several transcription factors which had been shown to regulate NPC1L1 gene, was co-expressed with LRH-1, synergistic transcriptional activation resulted. In conclusion, we have identified LRH-1 response elements in NPC1L1 gene and propose that LRH-1 and SREBP may play important roles in regulating NPC1L1 gene.