Astrocytes play important roles in normal brain development and the physiological processes. In particular, 30% of the brain volume consists of astrocytes, and they are the primary target cell in the brain for cellular injuries from chemical exposures. The present study attempts to establish an immortalized murine astrocyte cell line to study the mechanisms of chemical-induced carcinogenesis of astrocytes. Primary astrocytes isolated from mice were transfected with plasmid carrying the SV40 T antigen. Clonal cells obtained after G418 selection were continuously subcultured to establish an immortalized astrocyte cell line. The cell line was positive on GFAP expression and was sensitive to exposure to such chemicals as MNNG. Cells were treated with MNNG for 5 days, with doses ranging from 0.001ug/ml to 1ug/ml. Dose-dependent cellular transformations of astrocytes were observed. Treatments at 0.01ug/ml showed the most distinct characteristics of neoplastic transformation. Subsequent treatment with TPA produced higher levels of neoplastic cell transformation than MNNG treatment alone, as evidenced by increases of saturation density, soft-agar colony formation and cell aggregation. Promotional effects of TPA on cell transformation was further demonstrated by the shortening duration of foci appearance. Addition of hydrocortisone to the culture media resulted in further promotion of cell transformation in astrocytes treated with MNNG and TPA, suggesting that glucocortocoid also plays a role in the promotion of chemical-induced astrocyte transformation. The present study demonstrates that astrocytes are susceptible to chemical-induced carcinogenicity and subject to mechanisms of multistage carcinogenesis. Analysis of MNNG-transformed astrocytes showed that, while the expression of TGF-beta was decreased, expression of GFAP, IL-1betaand fibronectin were increased. The results suggest that these factors are associated with mechanisms of MNNG-induced astrocyte transformation and may be used as potential candidates for biomarkers representing astrocyte-related tumors and cell toxicities. The study showed scientific evidence that growth factors, cytokine and the extracellular matrix are involved in processes of chemical-induced transformation of astrocytes. In addition, the present work provided an excellent opportunity to develop an immortalized astrocyte cell line that can be used for studying mechanisms of astrocyte-related diseases.
Animals ; Antigens, Viral, Tumor ; Astrocytes* ; Biomarkers ; Brain ; Carcinogenesis* ; Cell Aggregation ; Cell Line ; Cell Transformation, Neoplastic ; Culture Media ; Extracellular Matrix ; Fibronectins ; Hydrocortisone ; Intercellular Signaling Peptides and Proteins ; Methylnitronitrosoguanidine ; Mice ; Physiological Processes ; Plasmids ; Transforming Growth Factor beta

BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is known to induce chronic rhinosinusitis (CRS). Nasal polyp, which is frequently found in patients with CRS, seems to have close relationship with COPD, but little is known about its relationship with COPD. In this study, we investigated the relationship between COPD and nasal polyp in middle aged and elderly CRS patients. SUBJECTS AND METHOD: We analyzed the clinical data of 174 patients (age of over 50 years) with CRS. Patients were divided as COPD [forced expiratory volume (FEV1)/forced vital capacity (FVC)<70%, n=30] and non-COPD group (FEV1/FVC≥70%, n=144) according to the pulmonary function test results. Binary logistic regression analysis was used to describe the relationships between clinically relevant factors related to nasal polyp. RESULTS: On logistic regression analysis, no significant relationship was found between age [adjusted odds ratio (AOR): 1.058, 95% confidence interval for the difference (CI)=0.995-1.126, p=0.073], sex AOR: 0.897, 95% CI=0.366-2.415, p=0.897), smoking (AOR: 0.434, 95% CI=0.154-1.219, p=0.113) and obesity (underweight AOR: 3.833, 95% CI=0.781-18.808, p=0.098, overweight AOR: 5.169, 95% CI=0.996-26.814, p=0.051, obese AOR: 2.911, 95% CI=0.335-25.329, p=0.333) with polyp. However, there was a negative correlation between COPD history and nasal polyp with statistical significance (AOR: 0.288, 95% CI=0.102-0.809, p=0.018). CONCLUSION: Our findings suggest that patients with COPD are less likely to have nasal polyp than patients without COPD.
Aged* ; Humans ; Logistic Models ; Middle Aged* ; Nasal Polyps* ; Obesity ; Odds Ratio ; Overweight ; Polyps ; Pulmonary Disease, Chronic Obstructive* ; Respiratory Function Tests ; Sinusitis ; Smoke ; Smoking ; Vital Capacity

PURPOSE: Malignant tumors of the hand occurred very rarely and optical surgical treatment and prognosis are not clearly established. We report the clinical characteristics and treatment outcomes of primary and metastatic bone and soft tissue tumors during last twenty years with a review of literatures. MATERIALS AND METHODS: We reviewed 20 cases of malignant tumors in the hand (7 cases of acrometastasis, 9 cases of malignant melanoma, 2 cases of chondrosarcoma and 2 cases of squamous cell carcinoma) retrospectively. RESULTS: Patients of early Clark stage (I to III) of malignant melanoma survived after wide resection or ray amputation. But patients with late Clark stage (IV to V) expired associated with distant metastasis. All seven patients with acrometastasis expired in 6.3 months after diagnosis of metastasis. Two patients with chondrosarcoma survived without recurrence. Among patients with squamous cell carcinoma, one patient is free of disease after wide resection, but the other was dead due to metastasis. CONCLUSION: Good results might be attained after surgical treatment of malignant tumors of the hand by proper surgical technique to minimize loss of hand function and systemic evaluation of metastasis.
Amputation ; Carcinoma, Squamous Cell ; Chondrosarcoma ; Hand ; Humans ; Melanoma ; Neoplasm Metastasis ; Prognosis ; Recurrence

OBJECTIVES: To correlate Frey's syndrome with subjective symptoms, Minor's starch iodine test results, and infrared thermography measurements, and to discuss the utility of thermography as a quantitative diagnostic method. METHODS: This study included 59 patients who underwent unilateral parotidectomy. A subjective clinical questionnaire and an objective Minor's starch iodine test were performed to evaluate the incidence of Frey's syndrome. Infrared thermography was performed, and the subjects were divided into seven groups according to the temperature differences between operated and unoperated sites. The thermal differences were correlated with the results from Minor's starch iodine test and the subjective symptoms questionnaire. RESULTS: Of the 59 patients, 20 patients (33.9%) reported subjective symptoms after eating; 30 patients (50.8%) tested positive for Minor's starch iodine test, 19 patients (63.3%) of which reported subjective symptoms. Of the 29 patients who were negative for the iodine test, 2 patients (6.9%) reported subjective symptoms. Thus, subjective symptoms were well correlated with Minor's starch iodine test (r=0.589, P<0.001). As the thermal differences with infrared thermography increased, the number of patients with subjective symptoms increased (chi2=22.5, P<0.001). Using infrared thermography, the mean temperature difference in the positive group for the iodine test was 0.82degrees C+/-0.26degrees C, and that in the negative group was 0.10degrees C+/-0.47degrees C. With increased thermal differences, more patients showed positivity in the iodine test (chi2=29.9, P<0.001). CONCLUSION: Subjective symptoms, Minor's starch iodine test, and infrared thermography are well correlated with one another. Quantitative thermography provides clues for the wide variation in the incidence of Frey's syndrome, and could be a useful method for diagnosing and studying Frey's syndrome.
Eating ; Humans ; Incidence ; Iodine* ; Parotid Gland ; Starch* ; Sweating ; Sweating, Gustatory* ; Thermography* ; Surveys and Questionnaires

We have reported that hypoxia stimulates EDRF(s) release from endothelial cells and the release may be augmented by previous hypoxia. As a mechanism, it was hypothesized that reoxygenation can stimulate EDRF(s) release from endothelial cells and we tested the hypothesis via bioassay experiment. In the bioassay experiment, rabbit aorta with endothelium was used as EDRF donor vessel and rabbit carotid artery without endothelium as a bioassay test ring. The test ring was contracted by prostaglandin F2a (3 X 10-6 M) which was added to the solution perfusing through the aorta. Hypoxia was evoked by switching the solution aerated with 95% O2/5% CO2 mixed gas to one aerated with 95% N2/5% CO2 mixed gas Hypoxia/reoxygenation were interexchanged at intervals of 2 minutes (intermittent hypoxia). In some experiments, endothelial cells were exposed to 10-minute hypoxia (continuous hypoxia) and then exposed to reoxygenation and intermittent hypoxia. In other experiments, the duration of re oxygenation was extended from 2 minutes to 5 minutes. When the donor aorta was exposed to intermittent hypoxia, hypoxia stimulated EDRF(s) release from endothelial cells and the hypoxia-induced EDRF(s) release was augmented by previous hypoxia/reoxygenation. When the donor aorta was exposed to continuous hypoxia, there was no increase of hypoxia-induced EDRF(s) release during hypoxia. But, after the donor aorta was exposed to reoxygenation, hypoxia-induced EDRF(s) release was markedly increased. When the donor aorta was pretreated with nitro-L-arginine (10-5 M for 30 minutes), the initial hypoxia-induced EDRF(s) release was almost completely abolished, but the mechanism for EDRF(s) release by the reoxygenation and subsequent hypoxia still remained to be clarified. TEA also blocked incompletely hypoxia-induced and hypoxia/reoxygenation-induced EDRF(s) release EDRF(s) release by repetitive hypoxia and reoxygenation was completely blocked by the combined treatment with nitro-L-arginine and TEA. Cytochrome P450 blocker, SKF-525A, inhibited the EDRF(s) release reversibly and endothelin antgonists, BQ 123 and BQ 788, had no effect on the release of endothelium-derived vasoactive factors. Superoxide dismutase (SOD) and catalase inhibited the EDRF(s) release from endothelial cells. From these data, it could be concluded that reoxygenation stimulates EDRF(s) release and hypoxia/reoxygenation can release not only NO but also another EDRF from endothelial cells by the production of oxygen free radicals.
Anoxia ; Aorta* ; Biological Assay ; Carotid Arteries ; Catalase ; Cytochrome P-450 Enzyme System ; Endothelial Cells* ; Endothelins ; Endothelium ; Free Radicals ; Humans ; Oxygen ; Proadifen ; Superoxide Dismutase ; Tea ; Tissue Donors

Various cell types in higher multicellular organisms are genetically homogenous, but are functionally and morphologically heterogeneous due to the differential expression of genes during development, which appears to be controlled by epigenetic mechanisms. However, the exact molecular mechanisms that govern the tissue-specific gene expression are poorly understood. Here, we show that dynamic changes in histone modifications and DNA methylation in the upstream coding region of a gene containing the transcription initiation site determine the tissue-specific gene expression pattern. The tissue-specific expression of the transgene correlated with DNA demethylation at specific CpG sites as well as significant changes in histone modifications from a low ratio of methylated H3- lysine 4 or acetylated H3-lysine 9, 14 to acetylated H4 to higher ratios. Based on the programmed status of transgene silenced in cloned mammalian ear-derived fibroblasts, the transgene could be reprogrammed by change of histone modification and DNA methylation by inhibiting both histone deacetylase and DNA methylation, resulting in high expression of the transgene. These findings indicate that dynamic change of histone modification and DNA methylation is potentially important in the establishment and maintenance of tissue-specific gene expression.
Transgenes/*genetics ; Swine ; Organ Specificity/genetics ; Methylation ; Lysine/*metabolism ; Histones/*metabolism ; Histone Deacetylases/metabolism ; Gene Silencing ; *Gene Expression ; Fibroblasts ; Ear ; *DNA Methylation ; Cells, Cultured ; Animals, Genetically Modified ; Animals ; Acetylation

BACKGROUND AND OBJECTIVES: In patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease, complete revascularization (CR) for non-culprit lesions is not routinely recommended. The aim of this study was to compare the clinical outcomes of multivessel compared with infarct-related artery (IRA)-only revascularization in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI. SUBJECTS AND METHODS: From the Korean Acute Myocardial Infarction Registry (KAMIR) database, 1,094 STEMI patients with multivessel disease who underwent primary PCI with drug-eluting stents were enrolled in this study. The patients were divided into two groups: culprit-vessel-only revascularization (COR, n=827) group; multivessel revascularization, including non-IRA (MVR, n=267) group. The primary endpoint of this study included major adverse cardiac events (MACEs), such as death, myocardial infarction, or target or nontarget lesion revascularization at one year. RESULTS: There was no difference in clinical characteristics between the two groups. During the one-year follow-up, 102 (15.2%) patients in the COR group and 32 (14.2%) in the MVR group experienced at least one MACE (p=0.330). There were no differences between the two groups in terms of rates of death, myocardial infarction, or revascularization (2.1% vs. 2.0%, 0.7% vs. 0.8%, and 11.7% vs. 10.1%, respectively; p=0.822, 0.910, and 0.301, respectively). The MACE rate was higher in the incompletely revascularized patients than in the completely revascularized patients (15% vs. 9.5%, p=0.039), and the difference was attributable to a higher rate of nontarget vessel revascularization (8.6% vs. 1.8%, p=0.002). CONCLUSION: Although multivessel angioplasty during primary PCI for STEMI did not reduce the MACE rate compared with culprit-vessel-only PCI, CR was associated with a lower rate of repeat revascularization after multivessel PCI.
Angioplasty ; Arteries ; Coronary Artery Disease ; Drug-Eluting Stents ; Follow-Up Studies ; Glycosaminoglycans ; Humans ; Myocardial Infarction ; Percutaneous Coronary Intervention