PURPOSE: This study investigated the clinical significance of AN in children and adolescents with obesity induced metabolic complications. METHODS: Forty-nine patients who had obesity induced metabolic complications were participated in this cross-sectional study. Obesity induced metabolic complications are as follows: hypertension, dyslipidemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), nonalcoholic steatohepatitis (NASH), homeostasis model assessment of insulin resistance (HOMA-IR)>3.16. Clinical characteristics, such as, age, percentage-weight-for-height (PWH), pubertal status, blood pressure (BP), fasting plasma insulin level, fasting and post-oral glucose tolerance test 2-hour glucose levels, liver function test, lipid profile, HOMA-IR were compared according to the presence of AN. RESULTS: Sixty-five percent of patients had AN, 57.1% NASH, 57.1% dyslipidemia, 55.1% hypertension, 46.9% IFG, 24.5% HOMA-IR>3.16 and 16.2% IGT. The patients who were moderately to severely obese with AN had higher incidence of IGT and HOMA-IR>3.16. The patients with AN had significantly higher diastolic BP (79.4+/-6.9 vs 75.4+/-5.6 mmHg), fasting levels of plasma insulin (10.6+/-6.0 vs 6.2+/-5.4 microIU/mL), HOMA-IR index (2.6+/-1.4 vs 1.4+/-1.3) and PWH (42.4+/-13.0 vs 34.3+/-1.8%). The increasing tendency for the presence of AN was significantly related to the cumulative number of obesity induced metabolic complications. Binary logistic regression analysis revealed that the presence of AN was significantly associated with fasting plasma insulin level, PWH and IFG. CONCLUSION: AN could be useful as a clinical surrogate of obesity induced metabolic complications.
Acanthosis Nigricans* ; Adolescent* ; Blood Pressure ; Child* ; Cross-Sectional Studies ; Dyslipidemias ; Fasting ; Fatty Liver ; Glucose ; Glucose Tolerance Test ; Homeostasis ; Humans ; Hypertension ; Incidence ; Insulin ; Insulin Resistance ; Liver Function Tests ; Logistic Models ; Obesity* ; Plasma

PURPOSE: The purpose of this study is to evaluate the result of primary total knee arthroplasty(TKA) with using NexGen CR-Flex(R) (Zimmer, Warsaw, IN, USA) after a follow-up of at least 2 years. MATERIALS AND METHODS: A total of 63 patients (98 knees) were included in this study. The same surgeon performed all the TKAs between August 2005 and May 2006 with using NexGen CR-Flex(R). The patients' age ranged from 52 to 81 years, and the mean follow-up period was 28 months. The patients were assessed clinically and radiographically with using the HSS score, the possibility that they could squat or kneel, the tibiofemoral angle, the radiolucency and the posterior condylar offset. RESULTS: The mean HSS score was 58.3 points preoperatively, and it was 91.1 points at the last follow-up. The mean range of motion improved from 123.2degrees preoperatively to 137.1degrees postoperatively. Forty-nine patients (78%) were able to squat and 24 patients (38%) could kneel down at the last follow-up. The mean tibiofemoral angle was 6degrees of varus preoperatively, and 7degrees of valgus postoperatively. And there was no radiolucency in any case. The mean posterior condylar offset was 26.1mm preoperatively and 27.2 mm postoperatively. CONCLUSION: TKA with using NexGen CR-Flex(R) showed favorable results at a mean follow-up of 28 months. Adequate patient selection, restoration of the posterior condylar offset and thorough clearing of posterior condylar osteophytes are thought to be the key elements to achieve a satisfactory range of motion after TKAs.
Arthroplasty ; Follow-Up Studies ; Humans ; Knee ; Knee Joint ; Osteophyte ; Patient Selection ; Range of Motion, Articular

Phosphoinositide 3-kinase (PI3K) is considered as a promising therapeutic target for rheumatoid arthritis (RA) because of its involvement in inflammatory processes. However, limited studies have reported the involvement of PI3KC2γ in RA, and the underlying mechanism remains largely unknown. Therefore, we investigated the role of PI3KC2γ as a novel therapeutic target for RA and the effect of its selective inhibitor, PBT-6. In this study, we observed that PI3KC2γ was markedly increased in the synovial fluid and tissue as well as the PBMCs of patients with RA. PBT-6, a novel PI3KC2γ inhibitor, decreased the cell growth of TNF-mediated synovial fibroblasts and LPS-mediated macrophages. Furthermore, PBT-6 inhibited the PI3KC2γ expression and PI3K/AKT signaling pathway in both synovial fibroblasts and macrophages. In addition, PBT-6 suppressed macrophage migration via CCL2 and osteoclastogenesis. In CIA mice, it significantly inhibited the progression and development of RA by decreasing arthritis scores and paw swelling. Three-dimensional micro-computed tomography confirmed that PBT-6 enhanced the joint structures in CIA mice. Taken together, our findings suggest that PI3KC2γ is a therapeutic target for RA, and PBT-6 could be developed as a novel PI3KC2γ inhibitor to target inflammatory diseases including RA.

Mycobacterium szulgai is a rare nontuberculous mycobacterium found in Korea. It is an opportunistic pathogen and is usually isolated from patients with a history of alcoholism, chronic pulmonary disease, or an immunocompromising condition. We present here a case of M. szulgai isolated from a patient with a history of pulmonary tuberculosis. A 54-year-old man was admitted with dyspnea and febrile sensation. He had a history of pulmonary tuberculosis which occurred 30 years earlier and treatment with anti-tuberculosis medication. His chest computed tomography scan showed cavitary consolidation in both upper lungs. A sputum acid-fast bacilli (AFB) smear was positive and anti-tuberculous medication was started. However, a polymerase chain reaction for mycobacterium tuberculosis was negative and anti-tuberculous medication was stopped. M. szulgai was isolated on 3 separate sputum and bronchial wash fluid AFB cultures. He was treated with clarithromycin, rifampicin, and ethambutol. After 1 month, a sputum AFB smear and culture became negative and no additional M. szulgai were isolated during a 16-month treatment.
Alcoholism ; Clarithromycin ; Dyspnea ; Ethambutol ; Humans ; Invasive Pulmonary Aspergillosis ; Korea ; Lung ; Lung Diseases ; Middle Aged ; Mycobacterium ; Mycobacterium tuberculosis ; Nontuberculous Mycobacteria ; Polymerase Chain Reaction ; Rifampin ; Sensation ; Sputum ; Thorax ; Tuberculosis ; Tuberculosis, Pulmonary

The aim of this study was to identify the risk factors for presence and severity of diabetic ketoacidosis (DKA) at the onset of type 1 diabetes mellitus (T1DM) in Korean children and adolescents. A retrospective chart review of children and adolescents newly diagnosed with T1DM was conducted in seven secondary and tertiary centers in Korea. Eligible subjects were < 20 years of age and had records on the presence or absence of DKA at the time of T1DM diagnosis. DKA severity was categorized as mild, moderate, or severe. Data were collected on age, height, body weight, pubertal status, family history of diabetes, delayed diagnosis, preceding infections, health insurance status, and parental education level. A total of 361 patients (male 46.3%) with T1DM were included. Overall, 177 (49.0%) patients presented with DKA at T1DM diagnosis. Risk factors predicting DKA at T1DM diagnosis were age ≥ 12 years, lower serum C-peptide levels, presence of a preceding infection, and delayed diagnosis. Low parental education level and preceding infection increased the severity of DKA. These results suggest that alertness of the physician and public awareness of diabetes symptoms are needed to decrease the incidence and severity of DKA at T1DM diagnosis.
Adolescent* ; Body Height ; C-Peptide ; Child* ; Delayed Diagnosis ; Diabetes Mellitus, Type 1 ; Diabetic Ketoacidosis* ; Diagnosis* ; Education ; Humans ; Incidence ; Insurance, Health ; Korea ; Parents ; Retrospective Studies ; Risk Factors

Neurogenesis is the process that develops neuroectoderm from ectoderm. Bone morphogenetic protein (BMP) inhibition in ectodermal cells is necessary and sufficient for neurogenesis in Xenopus embryos. To isolate genes involved in early neurogenesis, Xenous Affymetrix gene chips representing 14,400 genes were analyzed in early stage of neuroectodermal cells that were produced by inhibition of BMP signaling with overexpression of a dominant-negative receptor. We identified 265 candidate genes including 107 ESTs which were newly expressed during the early neurogenesis by blocking BMP signaling. The candidates of 10 ESTs were selected and examined for upregulation in neuroectoderm. Five EST genes were confirmed to be upregulated in neuroectoderm and examined for time-dependent expression patterns in intact embryos. Two EST genes were cloned and identified as a homology of CYP26c (Xl.1946.1.A1_at) and Kielin containing VWC domain (Xl.15853.1.A1_at). One of them, CYP26c, was further characterized for its transcriptional regulation and role of anterior-posterior patterning during neurogenesis. Taken together, we analyzed and characterized genes expressed in early neurogenesis. The results suggest that neurogenesis by inhibition of BMP provides useful system to isolate genes involved in early events of neurogenesis during early vertebrate embryogenesis.
Bone Morphogenetic Proteins ; Clone Cells ; DNA, Complementary ; Ectoderm ; Embryonic Development ; Embryonic Structures ; Expressed Sequence Tags ; Female ; Neural Plate ; Neurogenesis ; Oligonucleotide Array Sequence Analysis ; Pregnancy ; Up-Regulation ; Vertebrates ; Xenopus

PURPOSE: Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic pneumonia syndrome (IPS), are serious side effects of total body irradiation (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical factors associated with IP and IPS following TBI. MATERIALS AND METHODS: Fifty-eight patients with hematologic malignancies who underwent TBI before allogeneic hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary toxicities were diagnosed based on either radiographic evidence or reduced pulmonary function, and were subdivided into IP and IPS based on the presence or absence of concurrent infection. RESULTS: Pulmonary toxicities developed in 36 patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly associated with increased treatment-related mortality (p = 0.028) and decreased survival (p = 0.039). Multivariate analysis revealed that the risk of developing IPS was significantly higher in patients who received stem cells from a matched unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] = 12.67; 95% confidence interval [CI], 1.46–110.30). Combining other conditioning agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064; HR = 6.19; 95% CI, 0.90–42.56). CONCLUSION: IP and IPS involve different risk factors and distinct pathogeneses that should be considered when planning treatments before and after TBI.
Cyclophosphamide ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Mortality ; Multivariate Analysis ; Pneumonia ; Risk Factors ; Siblings ; Stem Cell Transplantation ; Stem Cells ; Tissue Donors ; Unrelated Donors ; Whole-Body Irradiation*

PURPOSE: Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic pneumonia syndrome (IPS), are serious side effects of total body irradiation (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical factors associated with IP and IPS following TBI. MATERIALS AND METHODS: Fifty-eight patients with hematologic malignancies who underwent TBI before allogeneic hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary toxicities were diagnosed based on either radiographic evidence or reduced pulmonary function, and were subdivided into IP and IPS based on the presence or absence of concurrent infection. RESULTS: Pulmonary toxicities developed in 36 patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly associated with increased treatment-related mortality (p = 0.028) and decreased survival (p = 0.039). Multivariate analysis revealed that the risk of developing IPS was significantly higher in patients who received stem cells from a matched unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] = 12.67; 95% confidence interval [CI], 1.46–110.30). Combining other conditioning agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064; HR = 6.19; 95% CI, 0.90–42.56). CONCLUSION: IP and IPS involve different risk factors and distinct pathogeneses that should be considered when planning treatments before and after TBI.
Cyclophosphamide ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Mortality ; Multivariate Analysis ; Pneumonia ; Risk Factors ; Siblings ; Stem Cell Transplantation ; Stem Cells ; Tissue Donors ; Unrelated Donors ; Whole-Body Irradiation*

Dysfunction or loss of blood vessel causes several ischemic diseases. Although endothelial progenitor cells (EPCs) are a promising source for cell-based therapy, ischemia-induced pathophysiological condition limits the recovery rate by causing drastic cell death. To overcome this issue, we attempted to develop a cell-targeted peptide delivery and priming system to enhance EPCbased neovascularization using an engineered M13 bacteriophage harboring nanofibrous tubes displaying ∼ 2700 multiple functional motifs. The M13 nanofiber was modified by displaying RGD, which is an integrin-docking peptide, on the minor coat protein, and bymutilayering SDKPmotifs,which are the key active sites for thymosin b4, on themajor coat protein. The engineered M13 nanofiber dramatically enhanced ischemic neovascularization by activating intracellular and extracellular processes such as proliferation, migration, and tube formation in the EPCs. Furthermore, transplantation of the primed EPCs with the M13 nanofiber harboring RGD and SDKP facilitated functional recovery and neovascularization in a murine hindlimb ischemia model. Overall, this study demonstrates the effectiveness of theM13 nanofiber-based novel peptide deliveryandprimingstrategy inpromotingEPC bioactivity and neovessel regeneration. To our knowledge, this is first report onM13 nanofibers harboring dual functional motifs, the use of which might be a novel strategy for stem and progenitor cell therapy against cardiovascular ischemic diseases.
Animals ; Bacteriophages ; Blood Vessels ; Catalytic Domain ; Cell Death ; Endothelial Progenitor Cells* ; Hindlimb ; Ischemia ; Nanofibers* ; Regeneration ; Stem Cells ; Thymosin

There is a minor spelling error in the last of name of the 9th author in the originally published article.