Objective: Ceramide is a signaling molecule that contributes to insulin resistance and hepatosteatosis. In the present study, we activated de novo ceramide synthesis by inducing the hepatic expression of Sptlc2 to investigate the role of ceramide in glucose and lipid metabolism. Methods: We first constructed an adenovirus containing Sptlc2 (AdSptlc2), which encodes a major catalytic subunit of serine palmitoyltransferase (SPT). We then infected hepatocytes and mice fed a regular diet with AdSptlc2 to activate de novo ceramide biosynthesis. The liver-specific effects of ceramide biosynthesis on glucose and lipid metabolism were investigated by measuring changes in insulin signaling, lipid droplet formation, and very low-density lipoprotein (VLDL) secretion. Results: In HepG2 hepatocytes, adenoviral Sptlc2 expression inhibited insulin signaling and increased ceramide levels via activation of c-Jun N-terminal kinase and serine phosphorylation of insulin receptor substrate 1. In contrast, in mice, AdSptlc2 infection decreased plasma glucose levels by downregulating gluconeogenic genes and increased plasma triglyceride levels by increasing VLDL secretion. In mice infected with AdSptlc2, glucose intolerance and insulin sensitivity improved, while pyruvate utilization via gluconeogenesis decreased. Conclusion Hepatic ceramide was found to modulate hepatosteatosis and the insulin response via increased VLDL secretion and inhibition of gluconeogenesis in vivo. Although inhibition of the insulin response was observed in vitro, the compensatory mechanism of relieving ceramide-induced stress and reducing ceramide levels resulted in improvements of glucose and lipid metabolic profiles in vivo. This discrepancy between in vitro and in vivo regulation mechanisms suggests that ceramide plays a role in non-alcoholic fatty liver disease and insulin resistance.

Atherosclerosis is the deposition of plaque in the main arteries. It is an inflammatory condition involving the accumulation of macrophages and various lipids (low-density lipoprotein [LDL] cholesterol, ceramide, S1P). Moreover, endothelial cells, macrophages, leukocytes, and smooth muscle cells are the major players in the atherogenic process. Sphingolipids are now emerging as important regulators in various pathophysiological processes, including the atherogenic process. Various sphingolipids exist, such as the ceramides, ceramide-1-phosphate, sphingosine, sphinganine, sphingosine-1-phosphate (S1P), sphingomyelin, and hundreds of glycosphingolipids. Among these, ceramides, glycosphingolipids, and S1P play important roles in the atherogenic processes. The atherosclerotic plaque consists of higher amounts of ceramide, glycosphingolipids, and sphingomyelin. The inhibition of the de novo ceramide biosynthesis reduces the development of atherosclerosis. S1P regulates atherogenesis via binding to the S1P receptor (S1PR). Among the five S1PRs (S1PR1-5), S1PR1 and S1PR3 mainly exert anti-atherosclerotic properties. This review mainly focuses on the effects of ceramide and S1P via the S1PR in the development of atherosclerosis. Moreover, it discusses the recent findings and potential therapeutic implications in atherosclerosis.

Atherosclerosis is the deposition of plaque in the main arteries. It is an inflammatory condition involving the accumulation of macrophages and various lipids (low-density lipoprotein [LDL] cholesterol, ceramide, S1P). Moreover, endothelial cells, macrophages, leukocytes, and smooth muscle cells are the major players in the atherogenic process. Sphingolipids are now emerging as important regulators in various pathophysiological processes, including the atherogenic process. Various sphingolipids exist, such as the ceramides, ceramide-1-phosphate, sphingosine, sphinganine, sphingosine-1-phosphate (S1P), sphingomyelin, and hundreds of glycosphingolipids. Among these, ceramides, glycosphingolipids, and S1P play important roles in the atherogenic processes. The atherosclerotic plaque consists of higher amounts of ceramide, glycosphingolipids, and sphingomyelin. The inhibition of the de novo ceramide biosynthesis reduces the development of atherosclerosis. S1P regulates atherogenesis via binding to the S1P receptor (S1PR). Among the five S1PRs (S1PR1-5), S1PR1 and S1PR3 mainly exert anti-atherosclerotic properties. This review mainly focuses on the effects of ceramide and S1P via the S1PR in the development of atherosclerosis. Moreover, it discusses the recent findings and potential therapeutic implications in atherosclerosis.

BACKGROUND: The purpose of this study was to examine the prevalence and distribution of unexpected antibodies detected in the Korean population with race-specific RBC panel cells. In spite of a relatively high prevalence of Dia and Mia antigen phenotype in the Korean and Southeast Asian population, there has been little documented research on the prevalence and clinical significance of anti-Dia and anti-Mia in Korea. METHODS: We analyzed the results of 17, 664 antibody screening tests performed during the recent 30-month period from March 2001 to September 2003. Antibodies were screened and identified by using LISS/Coombs gel card with DiaMed-ID system (DiaMed AG, Cressier, Morat, Switzerland) including Dia and Mia panel cells. RESULTS: The prevalence of unexpected antibodies was 1.2% (214/17, 664); antibodies detected most frequently were anti-Rh (74 patients), followed by anti-Lewis (21 patients) and anti-Dia (15 patients). Out of 6, 345 patients, anti-Mia was detected in three patients (0.047%). Anti-Dia and anti-Mia had the specificity of IgG. Anti-Dia was thought as an immune-mediated antibody, whereas anti-Mia was considered as a mixed type with immune and natural antibodies. CONCLUSIONS: This study shows that anti-Dia and anti-Mia antibodies are detected frequently in the Korean population; hence, it seems that Dia and Mia panel cells should be incorporated into antibody screening panels in Korea for safe transfusion.
Antibodies ; Asian Continental Ancestry Group ; Humans ; Immunoglobulin G ; Korea ; Mass Screening* ; Phenotype ; Prevalence* ; Sensitivity and Specificity*

Myelodysplastic syndrome (MDS) is a hematologic disorder characterized by peripheral cytopenia and histologic feature of hematologic dysplasia. MDS has rarely been reported in association with Behcet's disease. We describe a patient with MDS associated Behcet's disease and a review of the literature.
Humans ; Myelodysplastic Syndromes*

Myelodysplastic syndrome (MDS) is a group of hematopoietic disorders characterized by ineffective hematopoiesis and peripheral cytopenia associated with dysplastic hypercellular marrow. Anemia is a frequent finding and reticulocytes are usually normal or slightly decreased in the patients with MDS. "Pseudoreticulocytosis" is a rare abnormality of patients with MDS. In these patients, the delayed maturation of reticulocytes is revealed and unusual reticulocytosis occurs with the decreased red cell production. We report a case of MDS characterized by the anemia associated with high reticulocyte count. 'In vitro reticulocyte survival test' showed that the reticulocytosis was a consequence of delayed maturation.
Anemia ; Bone Marrow ; Hematopoiesis ; Humans ; Myelodysplastic Syndromes* ; Reticulocyte Count ; Reticulocytes ; Reticulocytosis

PURPOSE: The purpose of this study was to demonstrate the effectiveness of combined exercise for 12 weeks on the adiponectin and obesity related variables in overweight and obese children. METHODS: Eighteen children in 5th grade in a certain elementary school in Busan were recruited. They were all overweight or obese children(more than 85 percentile in body mass index). Nine children in the experimental group were given exercises consisting of walking and band resistant training for 12 weeks. Auxological data(including height, weight and body fat mass) and laboratory data (fasting blood sugar, insulin, adiponectin) were checked at baseline and at the 1 week, and at the 4 weeks and 12 weeks stages of their exercise program. Insulin resistance and sensitivity were evaluated indirectly using HOMA index and QUICKI index. RESULTS: Adiponectin gradually decreased until the 4 weeks point and gradually increased thereafter to the starting level at the 12 weeks stage. Body weight, body mass index(BMI) and HOMA index significantly decreased more at the 1 week, 4 weeks, and 12 weeks stages in the experimental group than in the control group. Body fat mass significantly decreased at 12 weeks. The change of insulin was significantly correlated with changes of body weight and BMI. But there was no correlation between changes of adiponectin and changes of insulin. CONCLUSION: Exercise seems to effect the adiponectin concentration. And it might be assumed that exercise increases the adiponectin concentration if it is continued for long time(may be more than 12 weeks). More studies may be necessary to draw that conclusion.
Adiponectin ; Adipose Tissue ; Blood Glucose ; Body Weight ; Busan ; Child* ; Exercise ; Humans ; Insulin ; Insulin Resistance ; Obesity ; Overweight* ; Walking

PURPOSE: Interleukin-6 (IL-6) can stimulate a variety of tumors including prostatic carcinoma. Research has recently shown that IL-6 may act to stimulate the progression of prostatic cancer. IL-6 is elevated in the sera of patients with metastatic prostatic cancer and it has been shown to be a candidate marker of disease activity. To date, little work has been performed to characterize the nature of granulocyte macrophage colony-stimulating factor (GM-CSF) and the expression of IL-6. The aim of this study is to evaluate the effects of GM-CSF on the expression of IL-6 in PC-3 cells. MATERIALS AND METHODS: The bone-derived PC-3 cell line was used in this study. Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the GM-CSF and also the IL-6 mRNA expression. The IL-6 protein was measured by enzyme-linked immunosorbent assay (ELISA) after treatments with the hGM-CSF. RESULTS: hGM-CSF was expressed in the PC-3 cell line. Our data indicated that the IL-6 mRNA expression was not increased at 4, 8 and 12 hours by the hGM-CSF in comparison to the control group, but it was slightly increased at 24 and 48 hours. The expression of IL-6 protein was increased at 4, 8, 12, 24 and 48 hours after hGM-CSF treatment, in comparison with the control group. CONCLUSIONS: The IL-6 mRNA expression was slightly increased by hGM-CSF at 24 and 48 hours in comparison to the control group. Yet the IL-6 protein expression increased before the IL-6 mRNA expression. Therefore, hGM-CSF may modulate the post-transcription pathway of the IL-6 expression in prostate carcinoma cells. Our data suggest that GM-CSF may have a possible IL-6 mediated pathophysiologic role in prostate cancer.
Cell Line* ; Enzyme-Linked Immunosorbent Assay ; Granulocyte-Macrophage Colony-Stimulating Factor ; Granulocytes* ; Humans ; Interleukin-6* ; Macrophage Colony-Stimulating Factor* ; Macrophages* ; Polymerase Chain Reaction ; Prostate* ; Prostatic Neoplasms* ; Reverse Transcription ; RNA, Messenger

We report a Korean family in which the interaction of a triplicated alpha-globin locus and a heterozygous beta-thalassemia gives rise to a clinical phenotype of thalassemia intermedia. The propositus, a 36year-old woman, was evaluated because of moderately severe chronic anemia. Molecular analysis revealed heterozygosity for a single beta-thalassemia mutation, IVSII-1 (G->A). Additionally, she was found to have co-inherited a triplicated alpha-globin gene (alphaalpha/alphaalphaalphaanti3.7). In contrast, her brother heterozygous for the same triplicated alpha-locus and beta-thalassemia was clinically normal, suggesting that the delicate balance between alpha- and beta-chains is controlled by other currently not identified factors. Thalassemia intermedia due to co-inheritance of alphaalpha/alphaalphaalphaanti3.7 and IVSII-1 (G->A) was rare, and in Korea, this patient is the first case of thalassemia intermedia attributable to this combined abnormalities.
alpha-Globins* ; Anemia ; beta-Thalassemia* ; Female ; Humans ; Korea ; Phenotype ; Siblings ; Thalassemia*

Low dose methotrexate (MTX) is widely used for treatment of rheumatoid arthritis (RA) due to prompt clinical response, relatively lack of serious side effects, tolerability and simplicity of medication. However, several serious adverse effects have been reported with the use of MTX. The prevalence of hematologic toxicity, including leukopenia, thrombocytopenia, megaloblastic anemia, and pancytopenia, is estimated to be 3% in MTX-treated RA patients. Pancytopenia, which occurs unpredictably, is one of the most serious adverse effects and the prevalence is estimated to be 1.4% and fatal pancytopenia reported to occur in 17% of these patients. Old age, impaired renal function, concurrent infection, hypoalbuminemia, increased mean corpuscular volume of red blood cell, concomitant medication such as trimethoprim-sulfamethoxazole and nonsteroidal antiinflammatory drug, are the risk factors of MTX induced pancytopenia. We experienced a case of fatal MTX induced early aplastic anemia in RA patients who medicated 3 times MTX (7.5mg/weekly, 22.5mg of cumulative dose) refractory to treatment with steroid pulse, recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) and immunoglobulin.
Anemia, Aplastic* ; Anemia, Megaloblastic ; Arthritis, Rheumatoid* ; Erythrocyte Indices ; Erythrocytes ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Hypoalbuminemia ; Immunoglobulins ; Leukopenia ; Methotrexate* ; Pancytopenia ; Prevalence ; Risk Factors ; Thrombocytopenia ; Trimethoprim, Sulfamethoxazole Drug Combination