Downregulation of Heat Shock Protein 72 Contributes to Fibrostenosis in Crohn’s Disease

Background/Aims@#Crohn’s disease (CD) with recurrent inflammation can cause intestinal fibrostenosis due to dysregulated deposition of extracellular matrix. However, little is known about the pathogenesis of fibrostenosis. Here, we performed a differential proteomic analysis between normal, inflamed, and fibrostenotic specimens of patients with CD and investigated the roles of the candidate proteins in myofibroblast activation and fibrosis. @*Methods@#We performed two-dimensional difference gel electrophoresis and identified candidate proteins using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and orbitrap liquid chromatography-mass spectrometry. We also verified the levels of candidate proteins in clinical specimens and examined their effects on 18Co myofibroblasts and Caco-2 intestinal epithelial cells. @*Results@#We identified five of 30 proteins (HSP72, HSPA5, KRT8, PEPCK-M, and FABP6) differentially expressed in fibrostenotic CD. Among these proteins, the knockdown of heat shock protein 72 (HSP72) promoted the activation and wound healing of myofibroblasts. Moreover, knockdown of HSP72 induced the epithelial-mesenchymal transition of intestinal epithelial cells by reducing E-cadherin and inducing fibronectin and α-smooth muscle actin, which contribute tofibrosis. @*Conclusions@#HSP72 is an important mediator that regulates myofibroblasts and epithelial-mesenchymal transition in fibrosis of CD, suggesting that HSP72 can serve as a target for antifibrotic therapy.

Behavior, PET and Histology in Novel Regimen of MPTP Marmoset Model of Parkinson's Disease for Long-Term Stem Cell Therapy

Stem cell technologies are particularly attractive in Parkinson's disease (PD) research although they occasionally need long-term treatment for anti-parkinsonian activity. Unfortunately, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) widely used as a model for PD has several limitations, including the risk of dose-dependent mortality and the difficulty of maintenance of PD symptoms during the whole experiment period. Therefore, we tested if our novel MPTP regimen protocol (2 mg/kg for 2 consecutive days and 1 mg/kg for next 3 consecutive days) can be maintained stable parkinsonism without mortality for long-term stem cell therapy. For this, we used small-bodied common marmoset monkeys (Callithrix jacchus) among several nonhuman primates showing high anatomical, functional, and behavioral similarities to humans. Along with no mortality, the behavioral changes involved in PD symptoms were maintained for 32 weeks. Also, the loss of jumping ability of the MPTP-treated marmosets in the Tower test was not recovered by 32 weeks. Positron emission tomography (PET) analysis revealed that remarkable decreases of bindings of ¹⁸F-FP-CIT were observed at the striatum of the brains of the marmosets received MPTP during the full period of the experiment for 32 weeks. In the substantia nigra of the marmosets, the loss of tyrosine hydroxylase (TH) immunoreactivity was also observed at 32 weeks following the MPTP treatment. In conclusion, our low-dose MPTP regimen protocol was found to be stable parkinsonism without mortality as evidenced by behavior, PET, and TH immunohistochemistry. This result will be useful for evaluation of possible long-term stem cell therapy for anti-parkinsonian activity.

Modeling Parkinson's disease in the common marmoset (Callithrix jacchus): overview of models, methods, and animal care / 한국실험동물학회지

The common marmoset (Callithrix jacchus) is a small-bodied, popular New World monkey and is used widely in reproductive biology, neuroscience, and drug development, due to its comparative ease of handling, high reproductive efficiency, and its unique behavioral characters. In this review, we discuss the marmoset models in Parkinson's disease (PD), which is a neurological movement disorder primarily resulting from a degeneration of dopaminergic neurons with clinical features of tremor, rigidity, postural instability, and akinesia. The most common PD models involve the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine to study the pathogenesis and to evaluate novel therapies. Following the systemic or local administration of these neurotoxins, the marmosets with very severe Parkinson's symptoms are recommended to be placed in an intensive care unit with artificial feeding to increase survival rate. All procedures with MPTP should be conducted in a special room with enclosed cages under negative-pressure by trained researchers with personal protection. Behavioral tests are conducted to provide an external measure of the brain pathology. Along with several biomarkers, including alpha-synuclein and DJ-1, non-invasive neuroimaging techniques such as positron emission tomography and magnetic resonance imaging are used to evaluate the functional changes associated with PD. With the recent growing interest in potential and novel therapies such as stem cell and gene therapy for PD in Korea, the marmoset can be considered as a suitable non-human primate model in PD research to bridge the gap between rodent studies and clinical applications.

Influence of the Flushing Response in the Relationship between Alcohol Consumption and Cardiovascular Disease Risk / 가정의학회지

BACKGROUND: The purpose of this study was to examine the relationship between cardiovascular disease risk and alcohol consumption according to facial flushing after drinking among Korean men. METHODS: The subjects were 1,817 Korean men (non-drinker group, 283 men; drinking-related facial flushing group, 662 men; non-flushing group, 872 men) >30 years who had undergone comprehensive health examinations at the health promotion center of a Chungnam National University Hospital between 2007 and 2009. Alcohol consumption and alcohol-related facial flushing were assessed through a questionnaire. Cardiovascular disease risk was investigated based on the 2008 Framingham Heart Study. With the non-drinker group as reference, logistic regression was used to analyze the relationship between weekly alcohol intake and cardiovascular disease risk within 10 years for the flushing and non-flushing groups, with adjustment for confounding factors such as body mass index, diastolic blood pressure, low density lipoprotein cholesterol, triglycerides, and exercise patterns. RESULTS: Individuals in the non-flushing group with alcohol consumption of < or =4 standard drinks (1 standard drink = 14 g of alcohol) per week had significantly lower moderate or high cardiovascular disease risk than individuals in the nondrinker group (adjusted odds ratio, 0.51; 95% confidence interval, 0.37 to 0.71). However, no significant relationship between the drinking amount and cardiovascular disease risk was observed in the flushing group. CONCLUSION: Cardiovascular disease risk is likely lowered by alcohol consumption among non-flushers, and the relationship between the drinking amount and cardiovascular disease risk may differ according to facial flushing after drinking, representing an individual's vulnerability.

The Use of Greater Saphenous Vein In Situ Graft in Arterial Occlusive Disease of Lower Extremity / 대한흉부외과학회지

BACKGROUND: Distal anastomosis using artificial vascular graft is difficult when luminal size mismatch occurred owing to severe occlusion of popliteal artery and its branches. So we reconstructed blood flow to ischemic lower limb by using autologous greater saphenous vein in situ graft (GSVISG) as vascular graft material. MATERIAL AND METHOD: From July 2000 to July 2005, 26 patients treated using GSVISG. We analyzed clinical results retrospectively by chart review. RESULT: There was no in hospital or early postoperative death and 6 late deaths occurred during follow up period. Postoperative complications were 5 cases of early graft obstruction, 2 cases of wound dehiscence, 1 case of graft aneurysmal change, 1 case of seroma formation at inguinal wound and 1 case of graft injury during valvulotomy. Overall patency rate during follow up period was 69.3%. CONCLUSION: Greater saphenous vein in situ graft is acceptable vascular graft for arterial occlusive disease of lower extremity.

Clinical Analysis of Arteriovenous Fistula in Chronic Renal Failure Patients / 대한흉부외과학회지

BACKGROUND: Owing to the fact that the average life span has increased and the progress in medical science has been made, the number of patients with chronic renal failure (CRF) who have to take hemodialysis (HD) has been going up gradually. Accordingly, it is considered to be as a significant issue to obtain blood vessels which can be used repetitively and supply enough blood flows. Therefore, there have been various kinds of study on an inosculation rate andfactors influencing it following an arteriovenous fistula (AV fistula) and lots of studies are ongoing for the purpose of escalating the inosculation rate. The authors analyzed the effects of short-term result, age, sex, diabetes and hypertension on arteriovenous inosculations in 134 anatomical snuffbox operated subjects among the patients who have taken an AV fistula at this center. MATERIAL AND METHOD: Based on 134 patients who underwent an AV fistula at the department of thoracic surgery of this center from July, 2000 to May, 2004, the difference in arteriovenous inosculation rate was compared and analyzed depending on age (discriminated by 65-year-old), sex and the condition of the presence or absence of diabetes and hypertension. Correlation analyses were conducted for each parameter and statistical tests were performed by using SPSS for windows Release 11.0.1, which were determined to be statistically significant if p value was below 0.05. RESULT: The total number of operations was 169 including 35 of re-operations. The male/female rate was 70:64 (52%:48%). The average age was 56.3+/-12.26 years and there were 33 (24%) old aged patients above 65-year-old; there were 103 (71%) patients with hypertension and 90 (67%) patients with diabetes. Overall arteriovenous inosculation rate was 93+/-2.4%, 91+/-2.7%, 89+/-3.0% at 6, 12, 24 months, respectively. The arteriovenous inosculation rate of above 65-year-old patient group was 85+/-4.8%, 80+/-5.8%, 80+/-5.8% and below 64-year-old patient group's was 85+/-4.8%, 80+/-5.8%, 80+/-5.8% at given time points, respectively, which showed higher inosculation rate in below 64-year-old patient group with a statistical significance (p=0.0034). However, no statistical significance was found between the patients with hypertension and diabetes and the patients with no complication. In addition, there was no statistical significance in inosculation rate between male and female. CONCLUSION: The arteriovenous inosculation ratewas higher in the treated patient below 64-year-old than in the treated patient above 65-year-old. Thus it is advantageous for increase in long-term inosculation rate to obtain hemodialysis routes at an early age. The conditions of sex and the presence or absence of diabetes and hypertension do not make statistically significant effect on the arteriovenous inosculation rate.

Curved Axillary Thoracotomy in Patent Ductus Arteriosus / 대한흉부외과학회지

Muscle sparing thoracotomy is known as alternative of posterolateral thoracotomy because of less postoperative pain, preservation of muscle power and better cosmetic outcome. Curved axillary thoracotomy (CAT) is a type of muscle sparing thoracotomy. Between July 2003 and August 2004, 5 patients diagnosed as pure patent ductus arteriosus (PDA) treated by CAT and we reviewed results retrospectively by clinical record. The operative procedures were ligation of ductus in 4 cases and division of ductus in 1 case. There were no postoperative complication. Curved axillary thoracotomy is considerable alternative for surgical treatment of PDA with merits of muscle sparing effect and cosmetic benefit.

Clinical Analysis of the Early Result of Coronary Artery bypass Graft / 대한흉부외과학회지

BACKGROUND: Recently, coronary artery obstructive disease and coronary artery bypass graft surgery have increased, and the operative result has been improved. We reviewed 154 cases of coronary artery bypass graft surgery from Jan. 1985 to Jun. 2004. MATERIAL AND METHOD: We reviewed 148 patients, 154 cases of coronary artery bypass surgery from Jan. 1985 to Jun. 2004. This investigation is designed to illustrate the preoperative diagnosis, severity of disease, operative method, the kind of used bypass graft used, number of distal anasomosis, associated surgery, and postoperative morbidity and mortality. RESULT: There were 84 males, 64 females and the average age was 58.9+/-8.3 years old. Preoperative clinical diagnosis were unstable angina in 97 cases (63.0%), stable angina in 31 cases (20.1%), acute myocardial infarction in 12 cases (7.8%) and postinfartion angina in 14 cases (9.1%). Preoperative angiographic diagnosis were three-vessel disease in 68 (44.2%), two-vessel disease in 39 (25.3%), one-vessel disease in 35 (22.7%), and left main disease in 12 (7.8%) cases. There were 78 cases of on-pump coronary artery bypass graft surgery and 76 cases of off-pump coronary artery bypass graft surgery. The total distal anastomoses number was 319, mean number of anastomoses was 2.06+/-0.96. There were 10 concomitant procedures. Postoperative intra-aortic balloon pump was used in 21 (13.6%) cases, but only 4 cases were used at off-pump coronary artery bypass surgery. Total early mortality was 7.8%. The mortality was decreased as 4.5% from Jan. 2001 to Jun. 2004. Post operative complication was perioperative myocardial infarction in 9 cases (5.8%), low cardiac output syndrome in 17 cases (11%), and arrhythmia in 30 cases (19.5%) cases. CONCLUSION: Since 1985, The result of coronary artery bypass graft surgery has been improved because of more refined technique, use of off-pump coronary artery bypass surgery, use of internal thoracic artery and radial artery as bypass graft. We should study the long-term follow up more for better operative results.

Clinical Analysis of Bronchogenic Cyst / 대한흉부외과학회지

BACKGROUND: Bronchogenic cyst is a rare and benign disease. Because of its complication or associated disease, Bronchogenic cyst requires surgical treatment. Recently, with the development of diagnostic methods, its incidence has increased. So we reviewed our results from the past 30 years. MATERIAL AND METHOD: We reviewed 27 cases surgically treated from March 1971 to March 2003. This investigation is designed to illustrate the peak age incidence, sex ratio, symptoms, anatomic location, radiologic imagings, associated diseases, operative methods, postoperative pathologic findings and postoperative complications. RESULT: The peak age incidence laid in the 1st to 3rd decade and the ratio of male and female was 1:1.5. The most common complaints were cough and dyspnea, but some had hemoptysis. There were 22 cases (81%) of Intrapulmonary bronchogenic cysts and 5 cases(19%) of mediastinal bronchogenic cysts. Thirteen cases (48.1%) showed cystic lesion in simple chest X-ray. Ten cases showed cystic lesion among 13 cases that had taken computed tomography. We found associated disease in 15cases (56%). The inflammatory diseases from infection were many in intrapulmonary bronchogenic cysts and especially, one case showed carcinosarcoma. Mitral regurgitation and Bronchial obstruction could be seen in mediastinal bronchogenic cysts. The 13 cases (48%) were managed by lobectomy, and cystectomy, pneumonectomy, and segemental resection were done in 7 cases (26%), 4 cases (15%), 3 cases (11%) respectively. Cystic contents were mucus in 9 cases, pus in 9 cases, blood in 2 cases, and carcinosarcoma in 1 case. Bronchotracheal communications were in 13 cases (48%). Five cases showed Postoperative complications, which were pneumothorax, empyema, bleeding. Postoperative death could not be found. CONCLUSION: Almost all patients had clinical symptoms. Severe complications could be associated with bronchogenic cysts. Recently, With the development of diagnostic methods, preoperatively accurate diagnosis is possible; therefore, invasive study has decreased. Bronchogenic cyst is a benign disease. However, because of its clinical symptoms, complications, and possibility of malignant change, immediate surgical treatment is needed.

Pulmonary Arteriovenous Fistula with Hemothorax: A case report / 대한흉부외과학회지

Pulmonary arteriovenous fistula is usually considered as a subset of congenital anomalies or acquired causes which can produce a variety of conditions such as dyspnea, cyanosis, and pulmonary vascular bruit. The diagnostic methods can be diverse such as arterial blood gas analysis (ABGA), chest X-ray, chest CT and pulmonary angiogram but the most accurate diagnostic modality is thought to be the pulmonary angiogram. The complications of this disease are a rupture that can cause hemothorax, brain abscess, and cardiovascular accident, and the treatment options are either segmental resection or therapeutic embolization. A twenty-six year old female developed sudden dyspnea and visited our emergency room. The patient was diagnosed as having pulmonary arteriovenous fistula (size; 4x4x3 cm) in the superior segment of the right lower lobe, evidenced by chest CT and pulmonary angiogram. Consequently, she underwent an emergency right lower lobectomy. We report this rare case of combined hemothorax that we have experienced, from diagnosis to treatment.

The In-hospital Analysis of Outcome of Off-pump CABG and On-pump CABG / 대한흉부외과학회지

Background: With the developement of non-invasive surgical techeniques, coronary artery bypass graft without cardiopulmonary bypass has become popular. We compared the preoperative risk factors and in-hospital outcomes of patients having off-pump CABG with those having on-pump CABG. Material and Method: From January 2001 to June 2003, 87 patients underwent CABG. Thirty-six patients underwent on-pump CABG, fifty-one patinents underwent off-pump CABG. Preoperative risk factors, extent of coronary disease, operative time, postoperative endotracheal intubation time, duration of ICU stay & hospital stay, the amount of bleeding and postoperative levels of cardiac enzymes were compared in both groups. Result: There were no differences in their sex ratios, ages, preoperative risk factors, preoperative MI, Canadian classes, extent of coronary artery diseases and, echocardiographic ejection fraction between Off-pump CABG and On-pump CABG groups. Off-pump CABG group had significantly lower mean operative time (270+/-79.3 min vs 372+/-142.2 min, p<0.001), mean ventilation time (17.1+/-13.1 hr vs 24.3+/-17.8 hr) and CK-MB level (8.9+/-18.7 IU/L vs 25.7+/-8.4 IU/L) than on-pump CABG groups. On-pump CABG group had more distal grafts (2.2+/-0.5 vs 1.7+/-0.7) than Off-pump CABG groups did. There were no differences in their postoperative complications and outcomes including amount of postoperative bleeding for 24 hrs, reoperation for bleeding control, mean in-hospital days, postoperative infection, renal failure and neurologic complications between Off-pump CABG and On-pump CABG groups. Conclusion: This study showed that patients who underwent Off-pump CABG had less operation time & intubation time and lower CK-MB level; however, they also have less distal graft. Even though CABG without CPB provided satisfactory results, more clinical experience & longer follow-up is required.