Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates a wide variety of cellular functions, including cell growth, cellular differentiation, apoptosis, and wound healing. TGF-beta1, the prototype member of the TGF-beta superfamily, is well established as a central mediator of renal fibrosis. In chronic kidney disease, dysregulation of expression and activation of TGF-beta1 results in the relentless synthesis and accumulation of extracellular matrix proteins that lead to the development of glomerulosclerosis and tubulointerstitial fibrosis, and ultimately to end-stage renal disease. Therefore, specific targeting of the TGF-beta signaling pathway is seemingly an attractive molecular therapeutic strategy in chronic kidney disease. Accumulating evidence demonstrates that the multifunctionality of TGF-beta1 is connected with the complexity of its cell signaling networks. TGF-beta1 signals through the interaction of type I and type II receptors to activate distinct intracellular pathways. Although the Smad signaling pathway is known as a canonical pathway induced by TGF-beta1, and has been the focus of many previous reviews, importantly TGF-beta1 also induces various Smad-independent signaling pathways. In this review, we describe evidence that supports current insights into the mechanism and function of TGF-beta-activated kinase 1 (TAK1), which has emerged as a critical signaling molecule in TGF-beta-induced Smad-independent signaling pathways. We also discuss the functional role of TAK1 in mediating the profibrotic effects of TGF-beta1.
Apoptosis ; Extracellular Matrix Proteins ; Fibrosis ; Kidney ; Kidney Diseases ; Kidney Failure, Chronic ; MAP Kinase Kinase Kinases ; Negotiating ; Phosphotransferases ; Renal Insufficiency, Chronic ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; Wound Healing

There are various etilogic factors concerned in the formation of pulmonary edema but it is rare that pulmonary edema is elicited as a consequence of direct current shock. The cause of this complication is unknown. The mechanism of pulmonary edema is suspected that acute alteration or disparities in atrial or ventricular mechanical function of the heart consequent to the application of electrical discharge precipitate pulmonary congestion. A case of acute pulmonary edema following the use of direct current shock during anesthesia for mitral commissurotomy was experienced. The patient was treated with oxygen, diuretics, steroid, continuous positive pressure ventilation and partial cardiopulmonary bypass. The patient recovered without further event.
Anesthesia ; Cardiopulmonary Bypass ; Diuretics ; Estrogens, Conjugated (USP) ; Heart ; Humans ; Oxygen ; Positive-Pressure Respiration ; Pulmonary Edema* ; Shock* ; Thoracic Surgery*

BACKGROUND: Dendritic cells (DCs) are the most potent stimulators of immune response including antitumor response. DCs are currently being pursued clinically in the development of cancer vaccines; therefore there are demands for large-scale and clinical-grade generation of DCs. In the present study, to find out the most efficient separation method of DC precursors, we compared two separation methods, namely, based on magnetic based selection and plastic adherence selection. METHODS: MNCs were collected by leukapheresis from healthful donors and separated by CD14 + immunomagnetic adsorption or plastic adherence. DC precursors separated using the two methods were differenciated in the same condition. Matured DCs were compared in terms of yield, viability, the expression of surface markers and ability to induce immune reaction. RESULTS: This study demonstrated that mature DCs from CD14 + monocytes separated using CD14 + immunomagnetic adsorption had higher expression of surface markers of DCs, yield (1.9 +/-0.5% vs. 0.5 +/-0.2%), viability (94.7 +/-2.5% vs. 72.8 +/-7.5%) and better functionality in inducing immune reaction than those from plastic adherent cells. CONCLUSION: These results demonstrated that CD14 + immunomagnetic adsorption was found to be more effective than the adherent selection for the generation of DCs. This study will allow researcher to facilitate choosing the appropriate protocol to obtain DCs.
Adsorption* ; Cancer Vaccines ; Dendritic Cells* ; Humans ; Leukapheresis ; Monocytes* ; Plastics ; Tissue Donors

PURPOSE: Missing cervical pathology after injury may lead to disability and influence long-term survival. Controversies continue to evolve concerning the initial screening methods used to predict cervical spine injury. Through a retrospective chart review, we attempted to analyze and propose factors predictive of cervical trauma. METHODS: Of all the patients who had visited the Emergency Department of Korea University, from January 2009 to December 2009, a retrospective review of the clinical records of the 217 patients who had undergone cervical spine computed tomography was done. We investigated whether we could predict the need for cervical spine computed tomography shortly after presentation in trauma patients by comparing the group with fractures and group without fractures and by finding risk factors showing significant differences between the two groups that might be used as guides in decision making. RESULTS: Of the 217 subjects who underwent cervical spine computed tomography scans, 33 were identified with fractures of the cervical spine while 184 were not. The most common mechanisms of trauma, in order, for those with fractures were falls, followed by traffic accidents. We found that the injury severity score, multiple injuries, a high-energy injury mechanism, neurologic deficit, and pain and tenderness of the cervical spine showed statistically significant differences between the two groups. CONCLUSION: Fractures of the cervical spine that are not observed with simple radiography occur with a relatively high frequency in trauma patients. Consideration should be given to the risk factors for cervical spine fracture, and if pertinent, cervical spine computed tomography should be performed with speed for early diagnosis of cervical spine fractures.
Accidents, Traffic ; Early Diagnosis ; Emergencies ; Humans ; Injury Severity Score ; Korea ; Mass Screening ; Multiple Trauma ; Neurologic Manifestations ; Retrospective Studies ; Risk Factors ; Spine

BACKGROUND/AIMS: Immune thrombocytopenic purpura (ITP) is an autoimmune disease that is mediated by anti-platelet antibodies. Based on the pathogenesis of ITP we evaluated the efficacy of intravenous anti-D immunoglobulin for adult chronic ITP. METHODS: Fourteen patients (4 without splenectomy and 10 with splenectomy) with refractory chronic ITP were treated with 50-70 microgram/kg of intravenous anti-D immunoglobulin only once. Treatment effects were evaluated by measuring the platelet counts and hemoglobin levels. RESULTS: Five patients (36%) showed a response; improvement in the platelet count lasted for on average 7 days (range: 2~24 days). There were no serious adverse effects. CONCLUSION: Anti-D immunoglobulin, which is associated with an Fc receptor blockade, appeared to be safe and effective for the treatment of adults with chronic ITP. Further studies are needed to confirm these findings and define further potentially effective treatment protocols with intravenous anti-D immunoglobulin.
Adult ; Antibodies ; Autoimmune Diseases ; Clinical Protocols ; Hemoglobins ; Humans ; Immunoglobulins ; Isoantibodies ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; Receptors, Fc ; Rho(D) Immune Globulin ; Splenectomy

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common benign tumor in older men; the etiology of this disease remains poorly understood. Testosterone and dihydrotestosterone (DHT) both act as androgen via a single androgen receptor. Testosterone is converted to DHT by 5alpha-reductase in prostatic stromal cells. Progesterone has been reported to inhibit DHT conversion; howevwe, its effect on prostatic stromal cells remains to be elucidated. MATERILAS AND METHODS: In this experiment, we investigated the effect of progesterone on androgen receptor expression induced by DHT. We also tested the effect of progesterone on cyclooxygenase-2 (COX-2) expression, as well as prostate stromal cell proliferation using the cell count kit-8. RESULTS: Progesterone did not cause an increase of prostate stromal cell proliferation. The mRNA expression of the androgen receptor and COX-2 were not changed by progesterone; the expressions of androgen receptor and COX-2 proteins were decreased by progesterone in prostate stromal cells. CONCLUSION: These results suggest that in prostate stromal cells, progesterone decreases androgen receptor protein expression, which results in decrement of COX-2 protein expression. This effect might be mediated by post-transcriptional regulation.
Cell Count ; Cyclooxygenase 2 ; Dihydrotestosterone ; Humans ; Male ; Progesterone* ; Prostate* ; Prostatic Hyperplasia ; Receptors, Androgen ; RNA, Messenger ; Stromal Cells* ; Testosterone

BACKGROUND: Dermoscopy has been suggested as a useful tool for diagnosing various skin diseases. Recently, the possibility of using dermoscopy to predict the response to treatment has emerged. OBJECTIVE: The purpose of this study was to determine whether dermoscopic findings corresponded to clinical acne scar types. This study also aimed to discover which dermoscopic findings predict the response to acne scar treatment. METHODS: The dermoscopic findings of 39 participants undergoing atrophic acne scar treatment with fractional photothermolysis were evaluated. Patients were divided into two groups according to the duration of acne scar persistence. RESULTS: Patients with a relatively short duration of acne scar persistence usually achieved better treatment outcomes. Dermoscopic findings showed no obvious differences according to clinical acne scar type. But high hair follicle density can be considered a predictive factor of treatment effects. CONCLUSION: Our study indicated that acne scar improvements can be predicted by dermoscopically observing hair follicle density.
Acne Vulgaris* ; Cicatrix* ; Dermoscopy ; Hair Follicle ; Humans ; Pilot Projects* ; Skin Diseases

PURPOSE: I-131 labeled (2'-deoxy-2-iodo-p-D-arabinofuranosyl) adenine (IAD) may be involved in DNA synthesis during active proliferation of tumor cells. We conducted this study to find out the biodistribution of IAD and its feasibility for scintigraphic tumor imaging. MATERIALS AND METHODS: Tosyl acetyl-adenosine was dissolved in acetonitrile, and I-131-NaI was added and heated to synthesize IAD. Female Fisher 344 rats innoculated with breast tumor cells were injected witb 0.27 MBq of IAD. Rats were sacrificed at 0.5, 1, 2, 4, 24h and the % of injected dose per gram of tissue (%ID/g) was determined. For scintigraphy, rats bearing breast cancer were administered with 1.11 MBq of IAD and imaging was perforrned after 2 and 24h. Then, rat body was fixed and rnicrotomized slice was placed on radiographic film for autoradiography, RESULTS: %ID/g of tumor wa.' 0.74 (0.5h), 0.73 (1h), 0.55 (2h), 0.38 (4h), and 0.05 (24h), respectively. At 1h after injection, %ID/g of tumor was higher than that of heart (0.34), liver (0.42), spleen (0.47), kidney (0,69), muscle (0.14), bone (0.33) and intestine (0.51). However, %1D/g of tumor was lower than blood (1.06), lung (0.77), and thyroid (177.71). At 4h, %ID/g of tumor in comparison with other tissue did not change. Tumor contrast expressed by tumor to blood ratio was 0.69 and tumor to muscle ratio was 5.11 at 1h. However, these ratios did not improve through 24h. On autoradiogram and scintigraphy at 2 and 24 hour, the tumor was well visualized. CONCLUSION: This results suggest that Ial) may have a potential for tumor scintigraphy. However, further work is needed to improve localization in tumor tissue.
Adenine ; Animals ; Autoradiography ; Breast Neoplasms* ; Breast* ; DNA ; Female ; Heart ; Hot Temperature ; Humans ; Intestines ; Kidney ; Liver ; Lung ; Radionuclide Imaging* ; Rats* ; Spleen ; Thyroid Gland ; X-Ray Film

BACKGROUND AND OBJECTIVES: The objective of this study was to determine whether long-term exercise training will improve age-related cardiac metabolic derangement using proton magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Young and old male Fischer 344 rats were assigned to sedentary controls groups {young control (YC) group-3 months of age: YC, n=10; old control (OC) group-22 months of age: OC, n=10}, and an exercise training group (OT, n=5). After 12-week of treadmill exercise training, MR spectroscopy at 4.7 T was performed to assess myocardial energy metabolism: measurements of myocardial creatine-to-water ratio (Scr/Sw) were performed using the XWIN-NMR software. RESULTS: Exercise capacity was 14.7 minutes greater in OT than that in OC (20.1+/-1.9 minutes in OT, 5.4+/-2.3 minutes in OC; p<0.001). The 12-week exercise training rendered the old rats a maximum exercise capacity matching that of untrained YC rats (17.9+/-1.5 minutes in YC, 20.1+/-1.9 minutes in OT; p>0.05). The creatine-to-water ratios in the interventricular septa of YC did not differ significantly from that of OT (0.00131+/-0.00025 vs. 0.00127+/-0.00031; p=0.37). However, OC showed significant reduction in creatine-to-water ratio compared to OT (0.00096+/-0.00025 vs. 0.00127+/-0.00031; p<0.001). Mean total creatine concentrations in the myocardium were similar between YC and OT (13.3 +/-3.6 vs. 11.5+/-4.1 mmol/kg wet weight; p=0.29). In contrast, the mean total creatine concentration of OC was significantly reduced compared to OT (6.8+/-3.2 vs. 11.5+/-4.1 mmol/kg wet weight; p=0.03). CONCLUSION: Our findings suggest that long-term exercise training in old rats induced prevention of age-related deterioration in myocardial metabolism.
Animals ; Creatine ; Humans ; Magnetic Resonance Spectroscopy ; Magnetics ; Magnets ; Male ; Myocardium ; Protons ; Rats ; Spectrum Analysis

A 25-year-old man with viral cardiomyopathy and chronic active hepatitis successfully underwent dynamic cardiomyoplasty for the first time in Korea on July 30, 1996. The patient had been intermittently dyspneic for 5 years and was admitted to our center twice because of heart failure. For the past 2 years, he was NYHA functional class III status with a left ventricular ejection fraction (LVEF) of around 30%. The patient was born with scoliosis and showed a short stature. The liver function showed elevated liver enzymes, and hepatitis B antigen was positive. The liver biopsy revealed chronic active hepatitis. The preoperative echocardiogram showed decreased left ventricular function with grade II mitral and grade II tricuspid regurgitation with dilated left and right atrium. Recently his symptoms worsened and we decided to perform a dynamic cardiomyoplasty. The left latissmus dorsi muscle (LDM) was mobilized and tested with lead placement on his right lateral decubitus position. The patient was positioned into supine and, after median sternotomy, the heart was wrapped with the mobilized muscle. The Russian made cardiomyostimulator (EKS-445) and leads (Myocardial PEMB for heart and PEMP-1 for LDM) were used. The total operation time was 8 hours and there were no perioperative episodes. Postoperatively the LDM had been trained for a 10 week period and currently the stimulation ratio is maintained at 1:4. The postoperative LVEF did not increase with the value of 30-35%. However, the patient feels better postoperatively with slightly increased activity.
Adult ; Biopsy ; Cardiomyopathies ; Cardiomyoplasty* ; Heart ; Heart Atria ; Heart Failure ; Hepatitis B ; Hepatitis, Chronic ; Humans ; Korea* ; Liver ; Scoliosis ; Sternotomy ; Stroke Volume ; Tricuspid Valve Insufficiency ; Ventricular Function, Left