A TFG-TEC nuclear localization mutant forms complexes with the wild-type TFG-TEC oncoprotein and suppresses its activity.

Human EMCs (extraskeletal myxoid chondrosarcomas) are soft tissue tumours characterized by specific chromosomal abnormalities. Recently, a proportion of EMCs were found to harbour a characteristic translocation, t(3;9)(q11-12;q22), involving the TFG (TRK-fused gene) at 3q11-12 and the TEC (translocated in extraskeletal chondrosarcoma) gene at 9q22. The present study used both in vitro and in vivo systems to show that the TFG-TEC protein self-associates, and that this is dependent upon the CC (coiled-coil) domain (amino acids 97-124), the AF1 (activation function 1) domain (amino acids 275-562) and the DBD (DNA-binding domain) (amino acids 563-655). The TFG-TEC protein also associated with a mutant NLS-TFG-TEC (AAAA) protein, which harbours mutations in the NLS (nuclear localization signal). Subcellular localization assays showed that the NLS mutant TFG-TEC (AAAA) protein interfered with the nuclear localization of wild-type TFG-TEC. Most importantly, the mutant protein inhibited TFG-TEC-mediated transcriptional activation in vivo. Thus mutations in the TFG-TEC NLS yield a dominant-negative protein. These results show that the biological functions of the TFG-TEC oncogene can be modulated by a dominant-negative mutant.

The TFG-TEC fusion gene created by the t(3;9) translocation in human extraskeletal myxoid chondrosarcomas encodes a more potent transcriptional activator than TEC.

The t(3;9)(q11-q12;q22) translocation associated with human extraskeletal myxoid chondrosarcomas results in a chimeric molecule in which the N-terminal domain (NTD) of the TFG (TRK-fused gene) is fused to the TEC (Translocated in Extraskeletal Chondrosarcoma) gene. Little is known about the biological function of TFG-TEC. Because the NTDs of TFG-TEC and TEC are structurally different, and the TFG itself is a cytoplasmic protein, the functional consequences of this fusion in extraskeletal myxoid chondrosarcomas were examined. The results showed that the chimeric gene encoded a nuclear protein that bound DNA with the same sequence specificity as the parental TEC protein. Comparison of the transactivation properties of TFG-TEC and TEC indicated that the former has higher transactivation activity for a known target reporter containing TEC-binding sites. Additional reporter assays for TFG (NTD) showed that the TGF (NTD) of TFG-TEC induced a 12-fold increase in the activation of luciferase from a reporter plasmid containing GAL4 binding sites when fused to the DNA-binding domain of GAL4, indicating that the TFG (NTD) of the TFG-TEC protein has intrinsic transcriptional activation properties. Finally, deletion analysis of the functional domains of TFG (NTD) indicated that the PB1 (Phox and Bem1p) and SPYGQ-rich region of TFG (NTD) were capable of activating transcription and that full integrity of TFG (NTD) was necessary for full transactivation. These results suggest that the oncogenic effect of the t(3;9) translocation may be due to the TFG-TEC chimeric protein and that fusion of the TFG (NTD) to the TEC protein produces a gain-of-function chimeric product.

The Effect of Discrimination on Stress among Public Housing Residents: A Comparative Study between Social-Mix and Independent Public Housing Complexes.

This study aims to examine the differential effect of discrimination on stress between social-mix and independent public housing complexes. We analyzed the 2017 Seoul Public Housing Residents Panel Study data that were collected from public housing residents living in Seoul, Korea by running ordinal logit analyses. The empirical analysis shows that discrimination has a lower effect on stress in social-mix housing complexes than in independent public housing complexes. In addition, the moderating effect of community-based activities on the relationship between discrimination and stress was found in the independent public housing complex model.

A fiberoptic orotracheal intubation successfully performed using a modified Guedel airway in a sedated emergency patient - A case report.

BACKGROUND: Fiberoptic intubation is a powerful and safe technique to deal with airway difficulty, but it requires a lot of training to be able to perform correctly. There are various specialized oral airways for fiberoptic intubation, but none of them have perfect functionality. CASE: A 75-year-old male (body weight 71.6 kg, height 159.3 cm, body mass index 28.22 kg/m2) was diagnosed with acute appendicitis, and it was decided to do a laparoscopic appendectomy. After the induction of general anesthesia, it was impossible to insert the direct laryngoscope deep enough for vocal cord visualization without damaging the teeth because of limited mouth opening. We successfully performed fiberoptic intubation with a newly modified Guedel airway via a longitudinal channel on the convex side and a distal opened lingual end. CONCLUSIONS: Our modified Guedel airway can be useful in assisting fiberoptic intubation in unexpectedly difficult airway situations.

The Effect of Cross-Level Interaction between Community Factors and Social Capital among Individuals on Physical Activity: Considering Gender Difference.

This study examines the effect of cross-level interaction between community physical environment and social capital among individuals on physical activity by considering gender difference. In this regard, we ask two research questions: (1) What is the effect of cross-level interaction between community factors and social capital among individuals on physical activity? (2) Is there gender difference in the effect of the cross-level interaction? To examine the research questions, this study used the 2015 Korea Community Health Survey and used multi-level analyses. The empirical analyses show that while there are both positive and negative cross-level interaction effects between physical activity-supportive community environment and social capital among individuals on physical activity, the positive cross-level interaction effect is more pronounced for women than for men. These findings suggest that local efforts to improve public health should take into account the cross-level interaction effect between community physical environment and social capital among individuals as well as gender difference.

The hTAF II 68-TEC fusion protein functions as a strong transcriptional activator.

Human extraskeletal myxoid chondrosarcoma (EMC) is caused by a chromosomal translocation that involves TEC (translocated in extraskeletal myxoid chondrosarcoma), and either EWS (Ewing's sarcoma) or hTAF(II)68 (human TATA-binding protein-associated factor II 68), which generates EWS-TEC or hTAF(II)68-TEC fusion proteins, respectively. Although there has been a great deal of progress in characterizing EWS-TEC, there is relatively little known about the biological function of hTAF(II)68-TEC. We have examined the functional consequences of the fusion of the amino terminal domain (NTD) of hTAF(II)68 to TEC in EMC. The chimeric gene encodes a nuclear protein that binds DNA with the same sequence specificity as parental TEC. Nuclear localization of hTAF(II)68-TEC was dependent on the DNA binding domain, and we identified a cluster of basic amino acids in the DNA binding domain, KRRR, that specifically mediate the nuclear localization of hTAF(II)68-TEC. The transactivation activity of hTAF(II)68-TEC was higher than TEC towards a known target promoter that contained several TEC binding sites. Finally, deletion analysis of hTAF(II)68-TEC indicated that the hTAF(II)68 NTD, and the AF1 and AF2 domains of hTAF(II)68-TEC are necessary for full transactivation potential. These results suggest that the oncogenic effect of the t(9;17) translocation may be due to the hTAF(II)68-TEC chimeric protein and that fusion of the hTAF(II)68 NTD to the TEC protein produces a gain of function chimeric product.

Gender Difference and Spatial Heterogeneity in Local Obesity.

This study asks if there is gender-specific spatial heterogeneity in local obesity. By using the 2015 Korea Community Health Survey and employing spatial analyses, this study found that there is considerable gender-specific spatial heterogeneity in local obesity rates. More specifically, we found that: (1) local obesity rates are more spatially dependent for women than for men; (2) environmental factors, in general, have stronger effects on local obesity rates for women than for men; (3) environmental factors have more spatially varying effects on local obesity rates for women than for men. Based on these findings, we suggest that policies for obesity prevention should not be based on the assumption of spatial homogeneity and gender indifference, but rather should be refined based on gender-specific spatial heterogeneity in local obesity.

The complex association of metabolic syndrome and its components with computed tomography-determined emphysema index.

BACKGROUND: Recent reports have suggested the association between emphysema and cardiovascular disease (CVD); however, there are few reports regarding association of emphysema severity with metabolic syndrome and its components representing CVD risk factors. METHODS: A retrospective cross-sectional study was performed in 2814 adult male subjects over age 40 who visited the Health Promotion Center in Samsung Medical Center for a health checkup program. RESULTS: We classified patients according to the quintiles of forced expiratory volume in 1 sec (FEV1) and emphysema index (EI). FEV1 percentage predicted values (% pred) was inversely associated with prevalence of metabolic syndrome and most of its components, such as abdominal obesity, hypertension, fasting hyperglycemia, and low high-density lipoprotein cholesterol. Although there was no association between prevalence of metabolic syndrome and EI, hypertension was positively associated with EI (P<0.001) and high triglycerides (TGs) were inversely associated with EI (P=0.021). These associations persisted after adjustment of other variables (P<0.001 in hypertension and P=0.039 in high TGs). CONCLUSION: The computed tomography-determined EI has a complex association with components of metabolic syndrome that is associated with increased prevalence of hypertension but decreased prevalence of high TGs, whereas FEV1 (% pred) has an inverse association with metabolic syndrome and most of its components with consistent direction.

Adherence to varenicline and abstinence rates for quitting smoking in a private health promotion center-based smoking cessation clinic.

BACKGROUND: Varenicline is an effective smoking cessation aid. However, smokers prescribed with varenicline do not always receive varenicline for 12 weeks, as recommended. This study analyzed the subjects who received varenicline and investigated the effect of varenicline treatment duration on the success rate of 6-month smoking cessation. METHODS: This study retrospectively analyzed 78 subjects, who received varenicline, out of the 105 smokers that had visited the smoking cessation clinic after medical examination from September 2007 to December 2009. RESULTS: The subjects were all males. Twenty-two subjects (28.2%) had varenicline treatment for 12 weeks or longer; 18 subjects (23.1%) for 8~12 weeks; 22 subjects (28.2%) for 4~8 weeks; and 16 subjects (20.5%) for less than 4 weeks. The total success rate of the 6-month smoking cessation was 47.4%. The success rate of the 6-month smoking cessation was 63.6% in the group that received varenicline for 12 weeks or longer, which was higher than 41.1% of the group that early terminated the varenicline treatment (p=0.074). The period of varenicline treatment was extended for one more week, the odds ratio of the 6-month smoking cessation success increased to 1.172-folds (p=0.004; 95% confidence interval, 1.052~1.305). Adverse events occurred in 30.8% of the subjects who received varenicline, but no serious adverse events were found. CONCLUSION: If varenicline treatment period is extended, the odds ratio of the success rate for the 6-month smoking cessation increases. Therefore, an effort to improve drug compliance for varenicline in clinical practices could be helpful for the long-term success of smoking cessation.

Successful treatment of Mycobacterium celatum pulmonary disease in an immunocompetent patient using antimicobacterial chemotherapy and combined pulmonary resection.

Mycobacterium celatum is a nontuberculous mycobacterium that rarely causes pulmonary disease in immunocompetent subjects. We describe the successful treatment of M. celatum lung disease with antimicobacterial chemotherapy and combined pulmonary resection. A 33-year-old woman was referred to our hospital with a 3-month history of a productive cough. Her medical history included pulmonary tuberculosis 14 years earlier. Her chest X-ray revealed a large cavitary lesion in the left upper lobe. The sputum smear was positive for acid-fast bacilli, and M. celatum was subsequently identified in more than three sputum cultures, using molecular methods. After 1 year of therapy with clarithromycin, ethambutol, and ciprofloxacin, the patient underwent a pulmonary resection for a persistent cavitary lesion. The patient was considered cured after receiving 12 months of postoperative antimycobacterial chemotherapy. There has been no recurrence of disease for 18 months after treatment completion. In summary, M. celatum is an infrequent cause of potentially treatable pulmonary disease in immunocompetent subjects. Patients with M. celatum pulmonary disease who can tolerate resectional surgery might be considered for surgery, especially in cases of persistent cavitary lesions despite antimycobacterial chemotherapy.

Anesthetic experience of methemoglobinemia detected during general anesthesia for gastrectomy of advanced gastric cancer -A case report-.

Methemoglobinemia is an uncommon but potentially fatal disorder. Most cases have no adverse clinical consequence and require no treatment, but methemoglobinemia is often overlooked as a cause of low oxygen saturation, and often mistaken for the more common causes of hypoxia by anesthesiologists despite simple bedside tests that indicate the presence of this treatable abnormality. We present a 68-year-old female patient who underwent gastrectomy for advanced gastric cancer with bleeding. In the preoperative period, the patient showed cyanosis and oxygen saturation was 85% by pulse oximeter, but oxygen saturation by arterial blood gas analysis was 100%. After tracheal intubation, the methemoglobin level was 18.3%. Ascorbic acid and methylene blue were administered. During preanesthetic evaluation, the patient had not informed the anesthesiologist that she had been taking dapsone.

Airway obstruction by extrinsic tracheal compression during spinal surgery under prone position -A case report-.

Tracheal compression by vascular anomalies in adults is uncommon and most related reports are of children. A 79-year-old woman without any respiratory history underwent a lumbar spine surgery under general anesthesia. She suddenly developed airway obstruction after a position change from supine to prone. A fiberoptic bronchoscopy showed the obstruction of endotracheal tube. The obstruction was relieved after we changed the depth of endotracheal tube and supported the patient's neck with a cotton roll. The surgery ended without any other event and the patient recovered safely. A computed tomography revealed the rightward tracheal deviation and tortuous innominate artery contact with trachea. The patient didn't manifest any respiratory related symptoms during postoperative period, and she was discharged without any treatment.

Nontuberculous mycobacteria isolated during the treatment of pulmonary tuberculosis.

BACKGROUND: The significance of nontuberculous mycobacteria (NTM) isolated from a patient during therapy for pulmonary tuberculosis (TB) is uncertain. We investigated the frequency and clinical significance of NTM isolated from patients receiving anti-TB treatment. METHODS: We conducted a retrospective cohort study of all patients with culture-confirmed pulmonary TB, and identified patients with respiratory cultures positive for NTM during therapy for pulmonary TB. RESULTS: From January 2003 to December 2005, 958 patients were diagnosed with culture-confirmed pulmonary TB. NTM were isolated from 113 specimens in 68 (7.1%) patients during anti-TB treatment. The most frequently isolated NTM species were Mycobacterium abscessus (n=35, 31%), Mycobacterium fortuitum (n=17, 15%), Mycobacterium avium complex (n=9, 8%), and Mycobacterium gordonae (n=9, 8%). Forty-eight (71%) patients had only one positive culture, while 20 (29%) had two or more positive cultures for NTM. Only two (3%) patients who had two or more positive culture after anti-TB treatment showed the same NTM species, which were M. abscessus. CONCLUSION: The isolation of NTM in patients with pulmonary TB is not uncommon during anti-TB treatment. However, this is likely the result of colonization, a transient infection, or specimen contamination. The co-existence of pulmonary TB and NTM lung disease may be rare but should be considered in patients with relatively virulent NTM species such as M. abscessus.

Suspicious stress induced cardiomyopathy following hemorrhoidectomy under spinal anesthesia: A case report.

A 48-year-old healthy woman was admitted in our hospital for elective hemorrhoidectomy. She developed sudden headache and chest pain, and showed sinus bradycardia, arrhythmia and hypotension forty minutes after spinal anesthesia with 0.5% hyperbaric bupivacaine. An EKG showed ST depression and an transthoracic echocardiogram performed in PACU demonstrated mild LV dysfunction with hypokinesia of LV inferolateral wall. An coronary angiography on postoperative day 1 revealed normal coronary vessel and akinesia of LV inferior wall. Levels of CK-MB and Troponin I were mildly elevated. With medical therapy, the patient's symptoms improved and recovered without any complication.

Combined effects of p73 and MDM2 polymorphisms on the risk of lung cancer.

p73, a structural and functional homologue of p53, plays an important role in modulating cell-cycle control and apoptosis. MDM2 represses the transcriptional activity of p73 and thus attenuates its activity. Based on the interaction between p73 and MDM2 in cell-cycle control and apoptosis, we investigated the association between p73 G4C14-to-A4T14 and MDM2 309T > G polymorphisms, alone and in combination, on the risk of lung cancer in a Korean population. The p73 and MDM2 genotypes were determined in 582 lung cancer patients and in 582 healthy control subjects who were frequency-matched for age and gender. The p73 AT/AT and MDM2 309 GG genotypes were associated with a nonsignificant increased risk of lung cancer (adjusted odds ratio [OR] = 1.37, 95% confidence interval [CI] = 0.83-2.24; and adjusted OR = 1.29, 95% CI = 0.92-1.80, respectively), compared with their wild-type genotypes, respectively. When the p73 and MDM2 polymorphisms were combined, the risk of lung cancer increased in a dose-dependent manner as the number of variant alleles increased (Ptrend = 0.01). Subjects with three or four variant alleles were at a significantly increased risk of lung cancer (adjusted OR = 1.74, 95% CI = 1.11-2.74, P = 0.02) compared to subjects with zero variant allele. These results suggest an additive effect of the p73 and MDM2 variant alleles on an increased risk of lung cancer.