Immunologists have activated T cells in vitro using various stimulation methods, including phorbol myristate acetate (PMA)/ionomycin and αCD3/αCD28 agonistic antibodies. PMA stimulates protein kinase C, activating nuclear factor-κB, and ionomycin increases intracellular calcium levels, resulting in activation of nuclear factor of activated T cell. In contrast, αCD3/αCD28 agonistic antibodies activate T cells through ZAP-70, which phosphorylates linker for activation of T cell and SH2-domain-containing leukocyte protein of 76 kD. However, despite the use of these two different in vitro T cell activation methods for decades, the differential effects of chemical-based and antibody-based activation of primary human T cells have not yet been comprehensively described. Using single-cell RNA sequencing (scRNA-seq) technologies to analyze gene expression unbiasedly at the single-cell level, we compared the transcriptomic profiles of the non-physiological and physiological activation methods on human peripheral blood mononuclear cell–derived T cells from four independent donors. Remarkable transcriptomic differences in the expression of cytokines and their respective receptors were identified. We also identified activated CD4 T cell subsets (CD55+) enriched specifically by PMA/ionomycin activation. We believe this activated human T cell transcriptome atlas derived from two different activation methods will enhance our understanding, highlight the optimal use of these two in vitro T cell activation assays, and be applied as a reference standard when analyzing activated specific disease-originated T cells through scRNA-seq.

Despite a low risk of liver failure and preserved liver function, non-cirrhotic hepatocellular carcinoma (HCC) has a poor prognosis. In the current study, we evaluated an active regulator of SIRT1 (AROS) as a prognostic biomarker in non-cirrhotic HCC. mRNA levels of AROS were measured in tumor and non-tumor tissues obtained from 283 non-cirrhotic HCC patients. AROS expression was exclusively up-regulated in recurrent tissues from the non-cirrhotic HCC patients (P=0.015) and also in tumor tissues irrespective of tumor stage (P<0.001) or BCLC stage (P<0.001). High mRNA levels of AROS were statistically significantly associated with tumor stage (P<0.001), BCLC stage (P=0.007), alpha fetoprotein (AFP) level (P=0.013), microvascular invasion (P=0.001), tumor size (P=0.036), and portal vein invasion (P=0.005). Kaplan-Meir curve analysis demonstrated that HCC patients with higher AROS levels had shorter disease-free survival (DFS) in both the short-term (P<0.001) and long-term (P=0.005) compared to those with low AROS. Cox regression analysis demonstrated that AROS is a significant predictor for DFS along with large tumor size, tumor multiplicity, vascular invasion, and poor tumor differentiation, which are the known prognostic factors. In conclusion, AROS is a significant biomarker for tumor aggressiveness in non-cirrhotic hepatocellular carcinoma.
Adult ; Age Distribution ; Aged ; Biomarkers, Tumor/*metabolism ; Carcinoma, Hepatocellular/*epidemiology/*metabolism/pathology ; Disease-Free Survival ; Female ; Humans ; Liver Cirrhosis/epidemiology/metabolism/pathology ; Liver Neoplasms/*epidemiology/*metabolism/pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Nuclear Proteins/*metabolism ; Prevalence ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Factors ; Sensitivity and Specificity ; Sex Distribution ; Transcription Factors/*metabolism ; Young Adult

PURPOSE: Radiofrequency ablation (RFA) is a widely accepted to treat the varicose vein. However, outcome studies for occlusion rate and patterns of the saphenous vein after RFA are scarce. The purpose of our study is to report the results of RFA in patients with varicose vein. METHODS: We retrospectively reviewed the clinical outcomes after RFA using ClosureFAST (Covidien) catheter. We evaluated the occlusion rate and patterns with duplex scanning after RFA. RESULTS: A total of 200 limbs (148 patients) underwent RFA. The truncal veins were ablated in 163 great saphenous veins (GSV) and 41 small saphenous veins (SSVs). The mean age was 52.1 +/- 11.9 years and female to male ratio was 125 : 87. At the mean follow-up of 13.9 months, the CEAP score, VCSS, and QoL score were significantly improved 2.33 +/- 0.78 to 1.29 +/- 0.96 (P < 0.0001), 3.48 +/- 0.98 to 0.63 +/- 1.16 (P < 0.0001), and 6.91 +/- 6.69 to 3.38 +/- 4.74 (P < 0.0001), respectively. The occlusion rate was 94.6% (53/56) in GSV and 94.5% (17/18) in SSV. The most common occlusion pattern in GSV was total occlusion of main trunk with patent superficial inferior epigastric vein in 41.1%. And, the most common pattern in SSV was the total occlusion of SSV with stump in 66.7%. CONCLUSION: RFA is an effective modality in the treatment of varicose vein. At the mean follow-up of 13.9 months, the occlusion rate was 94.6%in GSV and 94.5% in SSV. There are several patterns of saphenous occlusion after RFA.
Catheter Ablation ; Catheters ; Extremities ; Female ; Follow-Up Studies ; Humans ; Male ; Outcome Assessment (Health Care) ; Retrospective Studies ; Saphenous Vein ; Varicose Veins ; Veins

PURPOSE: Radiofrequency ablation (RFA) has been used as an alternative to conventional high ligation and stripping surgery for the treatment of saphenous vein insufficiency. A Korean clinical registry was established in 2012. The purpose of our study is to report the clinical outcomes of RFA from the Korean RFA Registry. METHODS: Data were collected in a multicenter, retrospective registry. All patients were treated before March 31, 2013. The indication for RFA was clinical, etiology, anatomy, and pathophysiology (CEAP) clinical class C2-C6 and patients with disease-associated symptoms, complications, or cosmetic concerns. We retrospectively reviewed the clinical outcomes, such as CEAP score, venous clinical severity score (VCSS), and quality of life (QoL) score after RFA using ClosureFAST (Covidien) catheter. The paired and independent t-test using IBM SPSS ver. 19.0 (IBM Co.) was used for the statistical analysis to evaluate the clinical improvement after treatment. RESULTS: There were 698 patients (890 limbs) treated with RFA at 5 centers in Korea. The average age was 53.7+/-12.0 years (range, 19 to 89 years) with a body mass index of 23.1+/-2.8 kg/m2, 58.2% of the patients were female. All saphenous veins with reflux > or =0.5 seconds were ablated simultaneously. The most common complication was ecchymosis, which occurred in 41 patients (5.9%). All clinical parameters were significantly improved. At the mean follow-up of 13.9 months, the occlusion rate was 94.6% in great saphenous vein and 94.5% in small saphenous vein. CONCLUSION: RFA is an effective modality in the treatment of saphenous vein insufficiency. The clinical parameters including CEAP class, VCSS and QoL score showed significant improvement after RFA.
Body Mass Index ; Catheter Ablation ; Catheters ; Ecchymosis ; Female ; Follow-Up Studies ; Humans ; Korea ; Ligation ; Quality of Life ; Retrospective Studies ; Saphenous Vein ; Varicose Veins

BACKGROUND/AIMS: Acute hemorrhagic rectal ulcer (AHRU) is an important etiology of lower gastrointestinal bleeding in intensive care unit patients and hospital inpatients. Moreover, with increasing elderly populations, and improved survival in critically ill patients, the incidence of AHRU has increased. The aim of this study is to determine rebleeding risk and prognostic factors of AHRU patients. METHODS: We retrospectively reviewed 32 patients with AHRU in Severance Hospital from February 2006 to October 2010, collected clinical data, and analyzed their association with the recurrence of bleeding and mortality of patients. RESULTS: The mean age of patients was 65.5 years, and 27 patients (84.4%) showed Eastern Cooperative Oncology Group performance status 3-4. Nineteen patients (59.4%) had recurrent bleeding. Hypoalbuminemia (< or =2.5 g/dL) was a risk factor of rebleeding in univariate and multivariate analysis. For patients with chronic liver disease, hypoalbuminemia (< or =2.5 g/dL), renal dysfunction (>2 mg/dL) and thrombocytopenia (<150,000/microL) showed relatively earlier rebleeding than those without (P=0.007, P=0.009, P=0.027 and P=0.043, respectively). The endoscopic hemostasis at the first bleeding event was associated with lower early rebleeding rate (P=0.048). In univariate analysis, chronic liver disease, hypoalbuminemia (< or =2.5 g/dL) and the prolongation of activated partial thromboplastin time (>40 seconds) increased mortality (P=0.028, P=0.008 and P=0.027, respectively) and the patients with rebleeding showed a tendency toward higher mortality, compared to those without (57.9% vs. 23.1%, P=0.051). CONCLUSIONS: In AHRU patients, hypoalbuminemia was a risk factor of rebleeding, and chronic liver disease, hypoalbuminemia, renal dysfunction, thrombocytopenia and no endoscopic treatment at the first bleeding event was correlated with relatively earlier rebleeding.
Aged ; Critical Illness ; Gastrointestinal Hemorrhage ; Hemorrhage ; Hemostasis, Endoscopic ; Humans ; Hypoalbuminemia ; Incidence ; Inpatients ; Intensive Care Units ; Liver Diseases ; Multivariate Analysis ; Partial Thromboplastin Time ; Prognosis ; Rectum ; Recurrence ; Retrospective Studies ; Risk Factors ; Thrombocytopenia ; Ulcer

Sudden sensorineural hearing loss has been reported to occur following anesthesia and various non-otologic surgeries, mostly after procedures involving cardiopulmonary bypass. Unilateral sensorineural hearing loss resulting from microembolism is an infrequent complication of cardiopulmonary bypass surgery that has long been acknowledged. Moreover, there are few reports on the occurrence of bilateral sensorineural hearing loss without other neurologic deficits and its etiology has also not been determined. We describe here a rare case of bilateral hearing loss without other neurologic deficits in an otherwise healthy 27-year-old woman who underwent cardiopulmonary bypass surgery for repair of severe mitral valve stenosis. The patient suffered from profound sensorineural hearing loss in both ears that was recognized immediately upon extubation, and audiometry tests confirmed the diagnosis. Without any treatment, her hearing recovered almost completely by the time of her discharge one week after surgery.
Adult ; Anesthesia ; Audiometry ; Cardiopulmonary Bypass ; Ear ; Female ; Hearing ; Hearing Loss ; Hearing Loss, Bilateral ; Hearing Loss, Sensorineural ; Humans ; Mitral Valve Stenosis ; Neurologic Manifestations ; Postoperative Complications

PURPOSE: Many researchers have tried to develop animal models that mimic the human immune system, e.g. a humanized mouse model, to improve the engraftment of hematopoietic stem cells and develop human immune cells in an animal model. This study evaluated the feasibility of the cultured human umbilical cord blood (hUCB)-derived CD34(+) cells for cell expansion, in Rag2(-/-)gamma(c)(-/-) mice, and establish co-transplantation with human fetal thymus/liver tissue (Thy/Liv) under the kidney capsule. METHODS: Co-transplantation of hUCB-derived CD34(+) cells with Thy/Liv was performed. The hUCB-derived CD34(+) cells were prepared by freshly thawing (G1) and culturing for 7 days with two types of cytokine combinations (G2, G3). The CD45(+) cell populations were measured at 6, 8, 10 and 16 weeks in the peripheral blood. The splenocytes were cultured with mitogenic stimuli (PHA -L or IL-2) at 20 weeks post- transplantation, and the proliferation of human immune cells was evaluated. RESULTS: There were no significant differences in the human CD45(+) cell populations at 6, 8, 10 and 16 weeks post-transplantation between the groups. In the cultured splenocytes at 20 weeks post-transplant with PHA-L or IL-2, there was remarkable expansion of CD3(+) cells in the three groups. Although no CD19(+) cells were detected in the spleen, human Ig G was detected in the sera of these mice. CONCLUSION: The cultured and expanded hUCB-derived cells with cytokine combinations might be a feasible cell source in humanized mouse modeling. In addition, human immune cells can be reconstituted from the co-transplantation of Thy/Liv and cultured hUCB-derived CD34(+) cells.
Animals ; Fetal Blood ; Hematopoietic Stem Cells ; Humans ; Hydrazines ; Immune System ; Interleukin-2 ; Kidney ; Mice ; Models, Animal ; Phytohemagglutinins ; Spleen ; Transplants ; Umbilical Cord

Various bacteria were isolated from the casing layer soil of the culture bed of P. ostreatus and their role in fruiting body induction of the edible mushroom, P. ostreatus, was investigated. Analysis of the bacterial community isolated from the casing layer soil revealed that the composition of genera and number of cultivable bacteria were different for each sterilizing treatment. Bordetella was predominant in the bulk soil whereas Flavobacterium was predominant after sterilization of the casing layer soil. Fluorescent Pseudomonas was predominant in the non-sterilized casing layer soil. Total number of the bacterial genera in the casing layer soil was higher than that in the bulk soil. In particular, an increase in the fluorescent Pseudomonas population was observed in the non-sterilized casing layer accompanied by induction of fruiting body and enhanced mushroom production yield. The results suggested that specific bacterial populations in the casing layer play an important role in the formation of primodia and the development of basidiome in P. ostreatus.
Agaricales ; Bacteria ; Bordetella ; Flavobacterium ; Fruit ; Pleurotus ; Pseudomonas ; Soil ; Sterilization

PURPOSE: To evaluate the feasibility and clinical efficacy of transrectal drainage of a deep pelvic abscess using combined transrectal sonographic and fluoroscopic guidance. MATERIALS AND METHODS: From March 1995 and August 2004, 17 patients (9 men; 8 women; mean age, 39years) suffering from pelvic pain, fever and leukocytosis were enrolled in this retrospective study. Ultrasound (US) or computed tomography (CT), which was obtained prior to the procedure, showed pelvic fluid collections that were deemed unapproachable by the percutaneous transabdominal routes. Transrectal drainage of the pelvic abscess was performed under combined transrectal sonographic and fluoroscopic guidance. The causes of the deep pelvic abscess were postoperative complications (n=7), complications associated with radiation (n=3) and chemotherapy (n=1) as well as unknown causes (n=6). A 7.5-MHz end-firing transrectal US probe with a needle biopsy guide attachment was advanced into the rectum. Once the abscess was identified, a needle was advanced via the biopsy guide and the abscess was punctured. Under US guidance, either a 0.018"or 0.035" guidewire was passed through the needle in the abscess. Under fluoroscopic guidance, the tract was dilated to the appropriate diameter with sequential fascial dilators, and a catheter was placed over the guide wire within the abscess. Clinical success of drainage was determined by a combination closure of the cavity on the follow up images and diminished leukocytosis. The technical and clinical success rate, complications, and patient's discomfort were analyzed. RESULTS: Drainage was technically successful in all patients and there were no serious complications. Surgery was eventually performed in two cases due to fistular formation with the rectum and leakage of the anastomosis site. The procedure was well tolerated in all but one patient who complained of discomfort while the catheter was inserted. The catheter did not interfere with defecation and there was no incidence of catheter expulsion by defecation. CONCLUSION: Transrectal drainage of deep pelvic abscesses using ultrasound and fluoroscopic guidance is a safe, feasible procedure that is well tolerated by patients and is relatively easy to perform.
Abscess* ; Biopsy ; Biopsy, Needle ; Catheters ; Defecation ; Drainage* ; Drug Therapy ; Female ; Fever ; Follow-Up Studies ; Humans ; Incidence ; Leukocytosis ; Male ; Needles ; Pelvic Pain ; Postoperative Complications ; Rectum ; Retrospective Studies ; Ultrasonography*

BACKGROUND: The introduction of new immunosuppressants has prompted several trials of steroid withdrawal immunosuppression. However, several groups have reported a higher incidence of rejection. METHODS: We conducted a randomized two-arm, parallel group, open label, prospective study to compare steroid withdrawal (at 6 months post-transplant) regimens: tacrolimus+mycophenolate mofetil (MMF) (FK group) vs cyclosporine+MMF (CyA group). Entry criteria were: first living donor transplant recipient, no diabetes mellitus (DM), no congestive heart failure, no chronic liver disease, and no acute rejection by 6 months post-transplant. The primary endpoint was a biopsy-proven acute rejection episode or treatment failure within 1 year post- transplant. RESULTS: While eighty-seven recipients were assigned to FK (n=43) and CyA group (n=44) before transplantation, seventy-six recipients (FK 39, CyA 37) could taper off steroid at 6 months post-transplant since eleven were excluded due to acute rejection within 6 months post-transplant (FK 2, CyA 3), protocol violation (FK 2, CyA 1), drug change due to side effect (CyA 2) and follow-up loss (CyA 1). After steroid withdrawal, acute rejection episode was 0% in FK group and 13.5% in CyA group (p<0.05). Other results at 12 months post-transplant are comparable: incidence of DM 7.8 vs 0% (FK group vs CyA group), incidence of hypercholesterolemia 41.0 vs 59.5%, proportion of use antihypertensives 48.7 vs 59.6%, plasma creatinine 1.21+-0.24 vs 1.31+-0.50 mg/dL (p>0.05 in every variable). CONCLUSION: These data suggest that steroid withdrawal are successful in first living donor renal transplant recipients and tacrolimus may be more effective than cyclosporine significantly in preventing acute rejection after steroid withdrawal.
Antihypertensive Agents ; Creatinine ; Cyclosporine* ; Diabetes Mellitus ; Follow-Up Studies ; Heart Failure ; Humans ; Hypercholesterolemia ; Immunosuppression ; Immunosuppressive Agents ; Incidence ; Liver Diseases ; Living Donors* ; Plasma ; Prospective Studies ; Tacrolimus* ; Transplantation* ; Treatment Failure