Sang-Guk Lee

The new definition of metabolic syndrome by the international diabetes federation is less likely to identify metabolically abnormal but non-obese individuals than the definition by the revised national cholesterol education program: the Korea NHANES study.

Objective:The new definitions for metabolic syndrome (MS) proposed by the IDF and revised NCEP have caused some confusion because patients have emerged that have satisfied the revised NCEP but not the IDF criteria. We performed this study to compare the prevalence of these criteria and to investigate the characteristics of discrepant cases.Research design and methods:A total of 7962 individuals aged ⩾ 20 years (3597 men; 4365 women) who participated in the 1998 Korean NHANES were included. We assessed the agreement between the revised NCEP and IDF criteria and investigated the characteristics of cases satisfying the revised NCEP criteria but not the IDF criteria.Results:The prevalence of MS by the revised NCEP (25.7% of men and 31.9% of women) was higher than that according to the IDF (14.2% of men and 26.6% of women). The IDF criteria failed to identify 44.9% of men and 16.6% of women identified as having MS according to the revised NCEP criteria. The discrepant group showed more adverse metabolic profiles and unfavorable lifestyles despite lower waist circumference as compared with those having MS by both the IDF and revised NCEP criteria. The prevalence of discrepant cases was higher among the elderly.Conclusions:The IDF criteria were inferior to the revised NCEP criteria in identifying the metabolically abnormal but nonobese groups known to be predisposed to type 2 diabetes and cardiovascular disease. Further research regarding the appropriateness of central obesity as an obligatory criterion proposed by the IDF seems to be warranted.

Association between betatrophin/ANGPTL8 and non-alcoholic fatty liver disease: animal and human studies.

Betatrophin/angiopoietin-like protein 8 (ANGPTL8) is a liver-secreted protein recently identified as a potent stimulator of beta cell proliferation in mice. However, it is unclear how betatrophin is regulated in humans with non-alcoholic fatty liver disease (NAFLD). We investigated the role of betatrophin in mice and in humans with and without NAFLD. Serum betatrophin levels were examined by ELISA in 164 subjects, including 96 patients with NAFLD. Levels were significantly elevated in subjects with NAFLD compared with controls (1.301 ± 0.617 vs. 0.900 ± 0.574 μg/L, P < 0.001), even after stratification by diabetic or obesity status. Circulating betatrophin positively correlated with obesity or glycemic indices, liver enzyme profiles, and NAFLD status, and was confirmed by multivariate regression analyses (β = 0.195, P = 0.040). However, when including insulin resistance index in the model, the significant association between betatrophin level and NAFLD was diminished due to a mediation effect of insulin resistance on this relationship. Palmitate or tunicamycin increased betatrophin expression in HepG2 cells, while a chemical chaperone blocked its induction. Hepatic expression of betatrophin was elevated in mice with NAFLD including db/db or ob/ob mice and mice with a high-fat or methionine-choline deficient diet. In conclusion, circulating betatrophin was increased in mice and humans with NAFLD and its expression was induced by endoplasmic reticulum stress in hepatocytes (Clinical trial no. NCT02285218).

Serum Cholesterol Concentration and Prevalence, Awareness, Treatment, and Control of High Low‐Density Lipoprotein Cholesterol in the Korea National Health and Nutrition Examination Surveys 2008–2010: Beyond the Tip of the Iceberg

Background The mortality rate from cardiovascular disease (CVD) among young adults has declined less than that in the older population, raising concerns about the increasing prevalence of obesity‐related conditions including hypercholesterolemia in the younger population. We investigated the age‐standardized mean levels of serum cholesterols and the prevalence, awareness, treatment and control rates of hyper‐low‐density lipoprotein (LDL)‐cholesterolemia based on age. Methods and Results Nationally representative samples of 19 489 subjects aged ≥20 years were analyzed from the Korea National Health and Nutrition Examination Surveys 2008–2010. Hyper‐LDL‐cholesterolemia was individually evaluated by the 2004 National Cholesterol Education Program Adult Treatment Panel III guidelines. Age‐standardized mean levels of total cholesterol, high‐density lipoprotein‐cholesterol, LDL‐cholesterol, and triglycerides were 186.8, 48.0, 112.9, and 136.0 mg/dL, respectively. Age‐standardized prevalence of hyper‐LDL‐cholesterolemia was 23.2% (men, 25.5%; women, 21.8%). Among subjects with hyper‐LDL‐cholesterolemia, awareness and treatment rates were significantly lower in younger adults (<50 years) compared to older adults ≥50 years (awareness, 8.0% versus 21.5%; treatment, 5.1% versus 18.5%, all Ps<0.001), indicating significant discrepancies in awareness and treatment rates of hypercholesterolemia between younger and older adults. Among subjects aware of their hyper‐LDL‐cholesterolemia, younger adults were more likely to have controlled LDL‐cholesterol than the elderly (82.1% versus 67.5%, P<0.001). Conclusions Compared to the elderly, significant proportions of young and middle‐aged adults are unaware of their hypercholesterolemia and are not treated with proper lipid‐lowering medications. Early screening, education, and proper management should be stressed in national public healthcare policies to reduce the increasing burden of CVD in the younger population with undiagnosed hypercholesterolemia.

Establishing pediatric reference intervals for 13 biochemical analytes derived from normal subjects in a pediatric endocrinology clinic in Korea

OBJECTIVES Defining pediatric reference intervals is one of the most difficult tasks for laboratory physicians. The continuously changing physiology of growing children makes their laboratory values moving targets. In addition, ethnic and behavioral differences might also cause variations. The aim of this study was to establish age- and sex-specific partitioned reference intervals for 13 serum biochemical analytes in Korean children. DESIGN AND METHODS A total of 2474 patients, girls aged 2-14 years and boys aged 2-16 years, who underwent a short stature workup but were diagnosed as normal at the Pediatric Endocrinology Clinic of Severance Hospital (Seoul, Korea) between September 2010 and June 2012 were included in this study. The levels of serum calcium, inorganic phosphorus, blood urea nitrogen, creatinine, uric acid, glucose, total cholesterol, total protein, albumin, alkaline phosphatase, aspartic aminotransferase, alanine aminotransferase, and total bilirubin were measured using a Hitachi 7600 analyzer (Hitachi High-Technologies Corporation, Tokyo, Japan). Reference intervals were partitioned according to sex or age subgroups using the Harris and Boyd method. RESULTS Most analytes except calcium and albumin required partitioning either by sex or age. Age-specific partitioned reference intervals for alkaline phosphatase, creatinine, and total bilirubin were established for both males and females after being partitioned by sex. Additional age-specific partitioning of aspartic aminotransferase in females and total protein and uric acid in males was also required. Inorganic phosphorus, total cholesterol, alanine aminotransferase, blood urea nitrogen, and glucose were partitioned only by sex. CONCLUSIONS This study provided updated age- and sex-specific pediatric reference intervals for 13 basic serum chemistry analytes from a sufficient number of healthy children by using a modern analytical chemistry platform.

Preceding orbital granulocytic sarcoma in an adult patient with acute myelogenous leukemia with t(8;21): a case study and review of the literature

A 25-year old man with a 30 month history of proptosis and pain of the right eye was referred to Severance Hospital of Yonsei University. Orbital computed tomography (CT) demonstrated a huge mass in the right retrobulbar orbit; an incisional biopsy and orbitotomy were performed for diagnosis and orbital soft tissue decompression. Subsequent histopathology disclosed sheets of mononuclear cells in the orbital mass, and immunohistochemical stains demonstrated positive results for myeloperoxidase and CD43, which supported the diagnosis of granulocytic sarcoma (GS). After his 1-year follow-up, the patient presented with pancytopenia, and an ensuing bone marrow aspiration revealed markedly hypercellular marrow replaced by many large abnormal myeloblasts. The patient was diagnosed with acute myelogenous leukemia with t(8;21) preceded by orbital GS. Orbital GS is primarily a disease of children, and extremely rare in adults. To the best of our knowledge, only four cases of this disease in adults have been reported in the literature. Our case is the first report of preceding orbital GS in an adult patient with a complex karyotype including t(8;21).

Genomic breakpoints and clinical features of MLL-TET1 rearrangement in acute leukemias

Recent rapid developments in new technology such as whole genome/exome sequencing have revealed that novel mutations in genes such as DNMT3A , IDH1 , IDH2 and TET2 contribute to the main process of leukemogenesis in patients with normal karyotype acute myeloid leukemia (AML).[1][1] Among these genes

Validation of a liquid chromatography tandem mass spectrometry method to measure oxidized and reduced forms of glutathione in whole blood and verification in a mouse model as an indicator of oxidative stress

As a possible marker of oxidative stress, many studies have measured whole blood reduced glutathione (GSH) and oxidized glutathione (GSSG). However, large differences in GSH and GSSG levels reported in different studies, calls for a reliable standardized method. In this study, we validate not only analytical performance of new measurement method for GSH and GSSG, but also the clinical utility of these markers in a mouse model with chronic oxidative stress. Twenty mice were randomized into four treatment groups according to iron burden: 0mg, 5mg, 10mg, or 15 mg of iron were injected into the peritoneum per day over 4 weeks. To prevent artifactual GSH auto-oxidation, we pretreated the sample with N-ethylmaleimide (NEM) immediately after sample collection. After protein precipitation using sulfosalicylic acid, GSSG and GSH-NEM were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The mean GSH/GSSG ratios of the mouse model were 163.1, 31.0, 27.9, and 12.8 for control, 5mg, 10mg, and 15 mg injection groups, respectively, showing a decrease in the GSH/GSSG ratios according to the amount of oxidative stress induced. Inter-assay coefficients of variation were 4.1% for GSH-NEM and 7.3% for GSSG. Recoveries were 98.0-105.9% for GSH-NEM and 98.0-107.3% for GSSG. No ion suppression was observed at the retention time for GSH-NEM and GSSG. This study suggests an accurate method that can be used for glutathione measurement using LC-MS/MS, and showed that GSH/GSSG ratio could provide an assessment of the degree of oxidative stress.

Association of urinary sodium/creatinine ratio and urinary sodium/specific gravity unit ratio with blood pressure and hypertension: KNHANES 2009–2010

BACKGROUND We investigated the association between urinary sodium/creatinine ratio (U[Na(+)]/Cr) or urinary sodium/specific gravity unit ratio (U[Na(+)]/SGU), estimated from spot urine, and blood pressure (BP) and hypertension. METHODS The study population consisted of a total of 9674 adults (4478 men, 5196 women) who participated in the Korea National Health and Nutrition Examination Surveys conducted in 2009 and 2010. Urine levels of sodium and creatinine, urine specific gravity (SG), and BP were measured along with other risk factors of hypertension. SGU is the calculated parameter of (SG-1)×100. RESULTS There were significant trends of increasing mean systolic and diastolic BPs and prevalence of hypertension with increasing quartile of U[Na(+)]/Cr and U[Na(+)]/SGU. After adjusting for age, total cholesterol, alcohol drinking, obesity, current smoking, mild renal dysfunction, and diabetes mellitus, the odds ratios (ORs) for hypertension in the top quartile of U[Na(+)]/Cr compared with the bottom quartile were 1.40 in men and 2.68 in women. Similarly, the ORs for hypertension in the top quartile of U[Na(+)]/SGU were 1.29 in men and 3.02 in women after adjustment. CONCLUSIONS U[Na(+)]/Cr and U[Na(+)]/SGU are associated with BP and hypertension, supporting the possible clinical value of U[Na(+)]/Cr and U[Na(+)]/SGU in general medical facilities.

Rare translocations involving chromosome band 8p11 in myeloid neoplasms.

Two types of distinct clinical syndromes are associated with abnormalities of chromosomal band 8p11 [1]. The first is 8p11 myeloproliferative syndrome (EMS)estem cell leukemia-lymphoma syndrome (SCLL), an aggressive chronic myeloproliferative disorder characterized by myeloid hyperplasia, eosinophilia, and lymphoblastic lymphoma. The second clinical syndrome is an acute myeloid leukemia (AML) of monocytoid phenotype (FAB type M4 or M5) with erythrophagocytosis. The abnormalities of chromosome band 8p11 target two different genes, FGFR1 in EMS and MYST3 (alias MOZ ) in AML. Rosati et al. [2] reported NSD3 (nuclear receptor-binding su(var)3-9, enhancer of zeste, trithorax [SET] domain containing gene 3) as the third translocation target in chromosome 8p11wp12 region, which is telomeric to FGFR1. (Note that NSD3 has since been classified as WHSC1L1; accession no. AF_332469.) Here, we report two rare translocations involving chromosome band 8p11 in myeloid neoplasms: t(8;22)(p11;q11) and t(8;11)(p11;p15). The first patient was a 50-year-old Korean woman, with no relevant past history, who presented with general weakness. An initial complete blood count showed a hemoglobin level of 9.5 g/dL, a platelet count of 596,000/mL, and a white blood cell count of 51,630/mL with 1% myeloblasts, 1% promyelocytes, 5% myelocytes, 6% metamyelocytes, 78% neutrophils, 4% lymphocytes, 1% monocytes, 2% eosinophils, and 2% basophils. A subsequent bone marrow biopsy revealed hypercellular marrow (O90%) with 18% blast cells and eosinophilia. An initial diagnosis of chronic myelogenous leukemia (CML), accelerated phase (AP), was made; however, the results of reverse transcriptasee polymerase chain reaction analysis (RT-PCR) for both major and minor BCReABL were negative. Three months later, transformation to blast phase (BP) occurred and the patient died of sepsis. The second patient was a 37-year-old Korean woman who was admitted with a complaint of abdominal pain and fever. She had been diagnosed with left-side breast cancer 11 years before and underwent a modified radical mastectomy. The patient was subsequently treated with chemotherapy and radiotherapy, when multiple metastases had developed. On presentation at our institution, many abnormal blasts (69%) were observed in the peripheral blood smear. An ensuing bone marrow aspiration revealed

Acute erythroleukemia with der(1;7)(q10;p10) as a sole acquired abnormality after treatment with azathioprine

To our knowledge, at least 11 different unbalanced wholearm translocations including der(1;7)(q10;p10), der(1;15) (q10;q10), der(1;16)(q10;p10), and der(1;19)(q10;p10) have been reported in hematologic malignancies, and some whole-arm translocations have now been documented as primary changes associated with specific disease entities [1e4]. Among these whole-arm translocations, der(1;7) (q10;p10) is the karyotypic aberration most associated with a previous history of chemotherapy or radiation therapy (i.e., in more than half the cases). This aberration is extremely rare, however, in association with acute erythroleukemia (AMLM6); only three cases have been reported in the literature [1,5e7]. Here, we report on a novel case of AML-M6 with der(1;7)(q10;p10) as a sole acquired abnormality in a patient treated with azathioprine for a long duration. A 64-year-old Korean woman with edema and suspected cellulitis of her right third finger was admitted to Severance Hospital of Yonsei University in February 2008. During her hospitalization, she sustained severe neutropenia. Approximately 2 weeks later, a gradual increase in immature cells in the peripheral blood smear compelled us to perform a bone marrow examination. In bone marrow aspiration, erythroid hyperplasia was observed (O50% of all nucleated cells) with abnormal blasts, which constituted 44% of nonerythroid cells, consistent with a morphology of AML-M6 with multilineage dysplasia. The patient exhibited an unbalanced translocation between the whole arms of chromosomes 1 (long arm) and 7 (short arm); the detailed karyotype of this patient was 46,XX,þ1,der(1;7)(q10;p10),inv(9)(p11q13)c in 20 cells analyzed (Fig. 1). Fluorescence in situ hybridization (FISH) analysis for chromosome 7 (Vysis LSI D7S486 (7q31), SpectrumOrangeeCEP 7 SpectrumGreen probe set; Abbott Molecular, Des Plaines, IL) yielded nuc ish (D7S486 1),(CEP7 2)[249/ 300]. Thus, the FISH results were consistent with the cytogenetic karyotype. The patient was treated with fludarabine, cytarabine, and idarubicin, but failed to achieve remission and died of pulmonary hemorrhage and septic shock 38 days after the initial diagnosis of AML-M6. In 1989, the patient had been diagnosed with idiopathic hypereosinophilic syndrome and vasculitis, and was treated