BACKGROUND: Brown adipocytes have thermogenic characteristics in neonates and elicit anti-inflammatory responses. We postulated that thermogenic brown adipocytes produce distinctive intercellular effects in a hypobaric state. The purpose of this study is to analyze the correlation between brown adipocyte and regulatory T cell (T(reg)) expression under intermittent hypobaric conditions. METHODS: Brown and white adipocytes were harvested from the interscapular and flank areas of C57BL6 mice, respectively. Adipocytes were cultured with syngeneic splenocytes after isolation and differentiation. Intermittent hypobaric conditions were generated using cyclic negative pressure application for 48 h in both groups of adipocytes. Expression levels of T(regs) (CD4 + CD25 + Foxp3 + T cells), cytokines [tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10), and the programmed death-ligand 1 (PD-L1)] co-inhibitory ligand were examined. RESULTS: Splenocytes, cultured with brown and white adipocytes, exhibited comparable T(reg) expression in a normobaric state. Under hypobaric conditions, brown adipocytes maintained a subset of T(regs). However, a decrease in T(regs) was found in the white adipocyte group. TNF-α levels increased in both groups under hypobaric conditions. In the brown adipocyte group, anti-inflammatory IL-10 expression increased significantly; meanwhile, IL-10 expression decreased in the white adipocyte group. PD-L1 levels increased more significantly in brown adipocytes than in white adipocytes under hypobaric conditions. CONCLUSION: Both brown and white adipocytes support T(reg) expression when they are cultured with splenocytes. Of note, brown adipocytes maintained T(reg) expression in intermittent hypobaric conditions. Anti-inflammatory cytokines and co-inhibitory ligands mediate the immunomodulatory effects of brown adipocytes under altered atmospheric conditions. Brown adipocytes showed the feasibility as a source of adjustment in physical stresses.
Adipocytes ; Adipocytes, Brown ; Adipocytes, White ; Animals ; Coculture Techniques ; Cytokines ; Humans ; Infant, Newborn ; Interleukin-10 ; Ligands ; Mice ; Necrosis

PURPOSE: Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC. MATERIALS AND METHODS: Chemotherapy-naive patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m2 oxaliplatin (day 1), 135 mg/m2 irinotecan (day 1), and 40 mg/m2 S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue. RESULTS: In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07). CONCLUSION: OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.
Biliary Tract Neoplasms* ; Biliary Tract* ; Cholangiocarcinoma ; Cisplatin ; Diarrhea ; Disease-Free Survival ; Drug Therapy ; Drug Therapy, Combination ; Exome ; Humans ; Male ; Neutropenia ; Peripheral Nervous System Diseases ; Prognosis ; Triplets

BACKGROUND: Psoriasis is an immune-mediated, chronic inflammatory disease affecting multiple aspects of patients' lives. Its epidemiology varies regionally; however, nationwide epidemiologic data on psoriasis depicting profile of Korean patients has not been available to date. OBJECTIVE: To understand nationwide epidemiologic characteristics and clinical features of adult patients with psoriasis visited university hospitals in Korea. METHODS: This multicenter, non-interventional, cross-sectional study recruited 1,278 adult patients with psoriasis across 25 centers in Korea in 2013. Various clinical data including PASI, BSA, DLQI, SF-36 and PASE were collected. RESULTS: A total of 1,260 patients completed the study (male:female=1.47:1). The mean age was 47.0 years with a distribution mostly in the 50s (24.9%). Early onset (<40 years) of psoriasis accounted for 53.9% of patients. The mean disease duration was 109.2 months; mean body mass index was 23.9 kg/m²; and 12.7% of patients had a family history of psoriasis. Plaque and guttate types of psoriasis accounted for 85.8% and 8.4%, respectively. Patients with PASI ≥10 accounted for 24.9%; patients with body surface area ≥10 were 45.9%. Patients with DLQI ≥6 accounted for 78.8%. Between PASI <10 and PASI ≥10 groups, significant difference was noted in age at diagnosis, disease duration, blood pressure, waist circumference of female, and treatment experiences with phototherapy, systemic agents, and biologics. CONCLUSION: This was the first nationwide epidemiologic study of patients with psoriasis in Korea and provides an overview of the epidemiologic characteristics and clinical profiles of this patient population.
Adult ; Biological Products ; Blood Pressure ; Body Mass Index ; Body Surface Area ; Cross-Sectional Studies* ; Diagnosis ; Epidemiologic Studies ; Epidemiology ; Female ; Hospitals, University ; Humans ; Korea* ; Phototherapy ; Psoriasis* ; Waist Circumference

BACKGROUND: Antimicrobials have been a mainstay of inflammatory acne treatment for more than 30 years. However, antibiotic-resistant propionibacteria had been isolated with increased frequency, and associated with failure to respond to antibiotic therapy. OBJECTIVE: The aim of this study was to investigate the clinical efficacy and tolerance of 1% nadifloxacin cream. METHODS: In the final analysis, 197 patients with mild to moderate facial acne vulgaris were enrolled. The patients were instructed to apply 1% nadifloxacin cream twice daily to the affected skin after washing the face. Following 2 and 4 weeks of treatment, patients were observed for clinical response: number of the acne lesions, Korea acne grading system (KAGS), global improvement, and occurrence of adverse reactions. RESULTS: During 4 weeks of treatment, nadifloxacin caused significant reduction in the number of inflamed papulo-pustular lesions and open/closed comedones. In addition, significant reduction of KAGS was observed. About 96% of patients showed clinical improvement in the overall evaluation of the therapeutic effect by physicians. All reported adverse events were mild. CONCLUSION: This study shows that 1% nadifloxacin cream can be an effective and safe treatment for mild to moderate acne vulgaris.
Acne Vulgaris ; Fluoroquinolones ; Humans ; Korea ; Quinolizines ; Republic of Korea ; Skin

Hurthle cell carcinoma, an oncocytic variant of follicular thyroid carcinoma, has a higher malignancy potential than well differentiated thyroid carcinomas. It has a tendency to metastasize easily to the lungs and bones, although isolated sacral bone metastasis has been rarely reported. Hurthle cell carcinoma has been characterized by increased mitotic activity and abundant abnormal mitochondria, which have profound mitochondrial DNA (mtDNA) alterations. In general, a well-known hypothesis is that genomic alteration, especially microsatellite instability of the mtDNA D-loop, might result in whole mtDNA instability as seen in Hurthle cell carcinoma. Recently, we experienced a case of Hurthle cell carcinoma that presented with extensive sacral bone metastasis. To investigate the relationship between mtDNA genomic instability and metastatic potential in this case, we performed direct sequencing of the mtDNA D-loop in samples extracted from normal thyroid tissue, thyroid carcinoma tissue, and sacral bone metastasis tissue. Here, we describe the results of mtDNA D-loop sequencing and present a literature review.
Adenocarcinoma, Follicular ; DNA ; DNA, Mitochondrial ; Genomic Instability ; Humans ; Lung ; Microsatellite Instability ; Mitochondria ; Neoplasm Metastasis ; Oxyphil Cells ; Sacrum ; Thyroid Gland ; Thyroid Neoplasms

BACKGROUND: Although oral isotretinoin is an effective established therapy for acne, Korean data related with this therapy is very limited. Moreover, there is no published data available on the efficacy of this drug that uses a grading system suitable for Korean acne patients. OBJECTIVE: The purpose of this study is to evaluate the efficacy of oral isotretinoin (Roaccutane?) by using the Korean Acne Grading System (KAGS) and the general satisfaction of patients in treating acne. METHODS: In this multicenter and prospective clinical study, 499 patients with acne, who visited at 5 dermatologic clinics during 11 months, were enrolled. The drug dosage was 0.2~1.0 mg/kg/day over 4 months. The efficacy assessment was performed at baseline and monthly after, with an acne grading based on the KAGS and the patient satisfaction questionnaire. RESULTS: Out of the 499 patients, 435 and 371 have completed the 3-month and 4-month treatments, respectively. After the 4-month treatment, the mean acne grades significantly decreased from 2.71 to 0.68, thus showing a 75.9% reduction in pretreatment scores. The mean patient satisfaction scores improved at the end of 4-month treatment, showing a 4.42 out of 5. CONCLUSION: In this paper, we describe the efficacy of oral isotretinoin by using the KAGS, which has not been previously reported in the Korean literature. Our results show that oral isotretinoin is an effective and satisfactory treatment modality for acnes of all grades in Korean patients, regardless of the dosage.
Acne Vulgaris ; Humans ; Isotretinoin ; Patient Satisfaction ; Prospective Studies

Members of the inhibitors of differentiation (Id) family of helix-loop-helix (HLH) proteins are known to play important roles in the proliferation and differentiation of many cell types. Thyroid-stimulating hormone (TSH) regulates proliferation and differentiation by activating TSH receptor (TSHR) in thyrocytes. In this study, we found that Id2, one of the Id family proteins, is a major target for regulation by TSH in FRTL-5 thyroid cells. TSH rapidly increases the Id2 mRNA level in FRTL-5 thyroid cells but the Id2 protein showed biphasic regulatory patterns, being transiently reduced and subsequently induced by TSH treatment. Transient reduction of Id2 protein was noted within 2 hr of TSH treatment and was mediated by proteasomal degradation. Moreover, reduced Id2 expression correlated with the activity of the phosphatidylinositol 3 kinase pathway, which is activated by TSH. Although TSH increases the activity of the Id2 promoter, TSH-induced activation of this promoter was independent of c-Myc. Id2 did not alter TTF-1- and Pax-8-mediated effects on the regulation of the Tg promoter. Thus, in summary, we found that TSH regulates Id2 expression, but that Id2 does not alter the expression of thyroid-specific genes, such as Tg, in FRTL-5 thyroid cells.
1-Phosphatidylinositol 3-Kinase/metabolism ; Animals ; Cattle ; Cell Differentiation ; Cell Proliferation ; *Gene Expression Regulation ; Inhibitor of Differentiation Protein 2/metabolism ; Insulin/metabolism ; Paired Box Transcription Factors/metabolism ; Promoter Regions, Genetic ; Proto-Oncogene Proteins c-myc/metabolism ; Rats ; Thyroglobulin/metabolism ; Thyroid Gland/*cytology ; Thyrotropin/*metabolism

Retroperitoneal hemorrhage caused by intra-abdominal vascular injury during pregnancy or puerperium is rare, but a very fatal complication. Massive retroperitoneal hemorrhage causes the high mortality rate of mother and fetus. But the difficulty of diagnosis and rarity may delay prompt treatment. We experienced a case of massive retroperitoneal hemorrhage, which was caused by a suspected left lumbar artery aneurysm rupture on the fifth day of vaginal delivery. The patient was successfully treated by surgery and arterial embolization. We reported this case with a brief review of literature.
Aneurysm* ; Arteries* ; Diagnosis ; Fetus ; Hemorrhage ; Humans ; Mortality ; Mothers ; Postpartum Hemorrhage ; Postpartum Period ; Pregnancy ; Rupture ; Rupture, Spontaneous* ; Vascular System Injuries

BACKGROUND: Fine needle aspiration(FNA) is an accurate and safe method for the diagnosis of thyroid nodules. One of the limitations of FNA is the variable rate of unsatisfactory specimens, especially in small sized, deep seated or complex cystic nodules. To overcome this problem, ultrasound-guided FNA(US-FNA) has been widely used. In this study, the adequacy of cytologic specimens by US-FNA was compared with that of conventional palpation-guided FNA(P-FNA). METHODS: The medical records of all patients who were engaged in FNA due to thyroid nodules at Chungnam National University Hospital from January 2003 to July 2004 were retrospectively examined. The US-FNA and P-FNA were performed in 114 and 185 patients, respectively. RESULTS: Comparison of the adequacy of the two techniques in providing sufficient material for the cytologic diagnosis showed that specimens in 24(13.0%) and 6(5.3%) patients collected by P-FNA and US-FNA, respectively, were unsatisfactory(P=0.031). A total of 23 patients underwent thyroid surgery due to strong suspicion of malignancy at cytologic finding and/or on clinical judgement. Seventeen patients belonged to the P-FNA group and 6 patients to the US-FNA group. In the P-FNA group, a histologic diagnosis revealed two false-negative cytologic findings, but no false-negative findings were found in the US-FNA group. CONCLUSION: Compared with P-FNA, US-FNA may reduce the possibility of unsatisfactory cytologic specimens and the rate of false-negative diagnosis, and may improve the diagnostic accuracy in investigating thyroid nodules
Biopsy, Fine-Needle* ; Chungcheongnam-do ; Diagnosis ; Humans ; Medical Records ; Needles ; Retrospective Studies ; Thyroid Gland* ; Thyroid Nodule*

BACKGROUND: Thyroid cancers account for about 1% of all human malignancies, with papillary thyroid carcinomas being the most common istotype. Several investigators have recently identified the most common BRAF mutation, the T1796A transversion mutation, in 29~69% of papillary thyroid cancers. The BRAF mutation has been demonstrated as a novel prognostic biomarker for the prediction of poor clinicopathological outcomes, such as increased incidence of extrathyroid invasion and distant metastasis of the tumor. In this study, we investigated the prevalence of the BRAF mutation of thyroid tissues obtained by a thyroidectomy, and its correlation with the clinicopathological outcomes. METHODS: We studied 36 thyroid tissues obtained from 24 women and 12 men by thyroidectomies, including 30 papillary carcinomas, 3 follicular carcinomas, 1 medullary carcinoma and 2 nodular hyperplasia. The mutation was sought in all specimens using DNA sequencing. RESULTS: We studied the BRAF exon 15 T1796A in these 36 thyroid tissues. The mean age at surgery was 46.6, ranging from 18 to 72 years, with a median tumor size of 2.79, ranging from 1.5 to 4.5cm. At the time of diagnosis, 27 of the 34 patients presented with some kind of extrathyroidal invasion of the tumor, and 16 had lymph node metastases. 16, 2 and 16 patients were in stages I, II and III, respectively. There was no distant metastasis. A missense mutation was found at T1796A in exon 15 in 21 of the 30 papillary carcinomas(70%). The other thyroid diseases, including the 3 follicular carcinomas, 1 medullary carcinoma and 2 nodular hyperplasia show no exon 15 T1759A transversion mutation. No statistically significant association was found between the BRAF mutations and clinicopathological characteristics of papillary carcinomas. CONCLUSION: The BRAF mutation is a important genetic alteration, with a high prevalence in papillary thyroid carcinomas. However, there was no significant association between the BRAF mutation and any of the clinicopathological factors. Further, large scale studies will be needed to evaluate the correlation between the BRAF mutation and the clinicopathological factors
Carcinoma, Medullary ; Carcinoma, Papillary* ; Diagnosis ; Exons ; Female ; Humans ; Hyperplasia ; Incidence ; Lymph Nodes ; Male ; Mutation, Missense ; Neoplasm Metastasis ; Prevalence ; Research Personnel ; Sequence Analysis, DNA ; Thyroid Diseases ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroidectomy