Allergic airway diseases are related to exposure to atmospheric pollutants, which have been suggested to be one factor in the increasing prevalence of asthma. Little is known about the effect of ozone and diesel exhaust particulates (DEP) on the development or aggravation of asthma. We have used a mouse asthma model to determine the effect of ozone and DEP on airway hyperresponsiveness and inflammation. Methacholine enhanced pause (P(enh)) was measured. Levels of IL-4 and IFN-gamma were quantified in bronchoalveolar lavage fluids by enzyme immunoassays. The OVA-sensitized-challenged and ozone and DEP exposure group had higher P(enh) than the OVA-sensitized-challenged group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone exposure group. Levels of IFN-gamma were decreased in the OVA-sensitized-challenged and DEP exposure group and the OVA-sensitized-challenged and ozone and DEP exposure group compared to the OVA-sensitized-challenged and ozone exposure group. Levels of IL-4 were increased in the OVA-sensitized-challenged and ozone exposure group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone and DEP exposure group compared to OVA-sensitized-challenged group. Co-exposure of ozone and DEP has additive effect on airway hyperresponsiveness by modulation of IL-4 and IFN-gamma suggesting that DEP amplify Th2 immune response.
Air Pollutants, Environmental/toxicity ; Animals ; Asthma/*chemically induced/*immunology ; Disease Models, Animal ; Drug Combinations ; Drug Synergism ; Female ; Hypersensitivity/complications/*etiology/*immunology ; Interferon Type II/immunology ; Interleukin-4/immunology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; Ozone/*toxicity ; Pneumonia/*chemically induced/complications/*immunology ; Research Support, Non-U.S. Gov't ; Respiratory Hypersensitivity/chemically induced/complications/immunology ; Vehicle Emissions/*toxicity

Allergic asthma is associated with persistent functional and structural changes in the airways and involves many different cell types. Many proteins involved in allergic asthma have been identified individually, but complete protein profiles (proteome) have not yet been reported. Here we have used a differential proteome mapping strategy to identify tissue proteins that are differentially expressed in mice with allergic asthma and in normal mice. Mouse lung tissue proteins were separated using two-dimensional gel electrophoresis over a pH range between 4 and 7, digested, and then analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MS). The proteins were identified using automated MS data acquisition. The resulting data were searched against a protein database using an internal Mascot search routine. This approach identified 15 proteins that were differentially expressed in the lungs of mice with allergic asthma and normal mice. All 15 proteins were identified by MS, and 9 could be linked to asthma-related symptoms, oxidation, or tissue remodeling. Our data suggest that these proteins may prove useful as surrogate biomarkers for quantitatively monitoring disease state progression or response to therapy.
Animals ; Asthma/genetics/immunology/*metabolism ; Comparative Study ; Disease Models, Animal ; Electrophoresis, Gel, Two-Dimensional ; Gene Expression/immunology ; Gene Expression Profiling ; Lung/immunology/metabolism/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Ovalbumin/immunology ; Proteome/*analysis/genetics/immunology ; Proteomics/methods ; RNA, Messenger/genetics/metabolism ; Research Support, Non-U.S. Gov't ; Reverse Transcriptase Polymerase Chain Reaction ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Presence of persistent left superior vena cava(PLSVC) is considered to be one of the most frequently encountered anomalies of the systemic venous return. The incidence of PLSVC is reported to be 0.3% to 0.5% in the general population, and in 3% to 10% of patients with congenital heart disease. The presence of PLSVC draining into the coronary sinus is of no hemodynamic significance. However, it is important to recognize this condition, as it can have important clinical implications. The diagnosis can be established by two demensional echocardiography. It should be suspected by the presence of dilated coronary sinus, and confirmed by contrast echocardiography. A 61-year-old man with chronic atrial fibrillation was diagnosed as PLSVC by contrast transthoracic echocardiography(TTE) using agitated saline. Contrast TTE allowed visualization of the time sequence of the echo-contrast within the right atrium first following injection of right antecubital vein. Following injection of left antecubital vein, opacification of the dilated coronary sinus first and then the right atrium was seen.
Atrial Fibrillation* ; Coronary Sinus ; Diagnosis ; Dihydroergotamine ; Echocardiography* ; Heart Atria ; Heart Defects, Congenital ; Hemodynamics ; Humans ; Incidence ; Middle Aged ; Veins ; Vena Cava, Superior*

DNA methylation may regulate gene expression by restricting the access of transcription factors. We have previously demonstrated that GATA-1 regulates the transcription of the CCR3 gene by dynamically interacting with both positively and negatively acting GATA elements of high affinity binding in the proximal promoter region including exon 1. Exon 1 has three CpG sites, two of which are positioned at the negatively acting GATA elements. We hypothesized that the methylation of these two CpGs sites might preclude GATA-1 binding to the negatively acting GATA elements and, as a result, increase the availability of GATA-1 to the positively acting GATA element, thereby contributing to an increase in GATA-1-mediated transcription of the gene. To this end, we determined the methylation of the three CpG sites by bisulfate pyrosequencing in peripheral blood eosinophils, cord blood (CB)-derived eosinophils, PBMCs, and cell lines that vary in CCR3 mRNA expression. Our results demonstrated that methylation of CpG sites at the negatively acting GATA elements severely reduced GATA-1 binding and augmented transcription activity in vitro. In agreement, methylation of these CpG sites positively correlated with CCR3 mRNA expression in the primary cells and cell lines examined. Interestingly, methylation patterns of these three CpG sites in CB-derived eosinophils mostly resembled those in peripheral blood eosinophils. These results suggest that methylation of CpG sites at the GATA elements in the regulatory regions fine-tunes CCR3 transcription.
Binding Sites ; Cell Line ; *CpG Islands ; DNA Methylation ; Enhancer Elements, Genetic ; Eosinophils/cytology/*metabolism ; Exons ; Fetal Blood/cytology/metabolism ; GATA1 Transcription Factor/*genetics/metabolism ; Gene Expression Regulation ; Humans ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Receptors, CCR3/*genetics/metabolism ; Sequence Analysis, DNA ; *Transcription, Genetic

OBJECTIVE: Previous pathologic and roentgenographic studies have suggested a relation between aortic plaque and coronary artery disease but have lacked clinical utility. The study was undertaken to elucidate whether atherosclerotic aortic plaque detected by transesophageal echocardiography can be a clinically useful marker for significant obstructive coronary artery disease. METHODS: Clinical and angiographic features and intraoperative transesophageal echocardiographic findings were prospectively analyzed in 131 consecutive patients (58 women and 73 men, aged 17 to 75 years [mean 54 +/- 12]) undergoing open heart surgery. Significant obstructive coronary artery disease was defined as > or = 50% stenosis of > or = 1 major branch. RESULTS: Seventy-six (58%) of 131 patients were found to have obstructive coronary artery disease. In 76 patients with significant coronary artery disease, 71 had thoracic aortic plaque. In contrast, aortic plaque existed in only 10 of the remaining 55 patients with normal or minimally abnormal coronary arteries. The presence of aortic plaque on transesophageal echocardiographic studies had a sensitivity of 93%, a specificity of 82% and positive and negative predictive values of 88% and 90%, respectively, for significant coronary artery disease. There was a significant relationship between the degree of aortic intimal changes and the severity of coronary artery disease (r = 0.74, P < 0.0001). Multivariate logistic regression analysis of patient age, sex, risk factors of cardiovascular disease and transesophageal, echocardiographic findings revealed that atherosclerotic aortic plaque was the most significant independent predictor of coronary artery disease. CONCLUSION: This study indicates that transesophageal echocardiographic detection of atherosclerotic plaque in the thoracic aorta is useful in the noninvasive prediction of the presence and severity of coronary artery disease.
Adolescence ; Adult ; Aged ; Aorta, Thoracic/ultrasonography* ; Arteriosclerosis/ultrasonography ; Coronary Disease/ultrasonography* ; Echocardiography, Transesophageal ; Female ; Human ; Male ; Middle Age ; Prospective Studies ; Risk Factors

BACKGROUND: Coronary artery disease (CAD) has recently become one of the major causes of mortality and morbidity in Korea. However, not much epidemiologic and demographic data has yet been reported. The purpose of this study was to investigate the clinical features as well as the prognostic factors of patients with CAD. METHODS: We prospectively enrolled 1,665 consecutive patients with CAD who had been admitted to the Catholic University Hospitals from December 1999 to April 2003. RESULTS: Acute myocardial infarction (AMI) was the most common cause of admission (n=715, 42.9%). Dyslipidemia, hypertension and smoking were the most common risk factors. More than 70% of the patients who underwent percutaneous coronary intervention (PCI) received stent implantation. A total of 965 (612 males) patients were followed at least for 6 months (the mean follow-up duration was 23.8+/-12.2 months). The incidence rates of major adverse cardiac events (MACE: cardiac death, acute myocardial infarction, target vessel revascularization) and cardiac death were 15.1% (n=146) and 2.2% (n=21), respectively. There was no difference in overall survival between the patients treated with medical therapy and those treated with PCI. By Cox regression analysis, the independent prognostic factors for MACE were PCI (95% CI: 1.75-4.85; p<0.01) and multivessel disease (95% CI: 1.03-2.04; p<0.05), and the independent prognostic factors for cardiac death were medical therapy (95% CI: 1.08-14.41; p<0.05) and old age (95% CI: 1.13-16.13; p<0.05). CONCLUSIONS: There was no difference in overall survival between the patients treated with medical therapy and those treated with PCI. However, PCI was superior to medical therapy for preventing death of the patients with acute coronary syndrome.
Acute Coronary Syndrome ; Coronary Artery Disease* ; Coronary Disease ; Coronary Vessels* ; Death ; Dyslipidemias ; Follow-Up Studies ; Heart* ; Hospitals, University ; Humans ; Hypertension ; Incidence ; Korea ; Mortality ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Prognosis ; Prospective Studies ; Risk Factors ; Smoke ; Smoking ; Stents