There have been several studies supporting a possible relationship between high suicide rate and high altitude. However socioeconomic status may confound this association because low socioeconomic status, which is known to be related to a high suicide rate, is also associated with living at high altitude. This study aims to explore whether the relationship between high altitude and high suicide rate remains after adjusting for socioeconomic status in South Korea. We collected demographic data of completed suicides, the mean altitude of the district where each suicide took place, and the mean income of each district. We analyzed the data using regression analysis before and after adjustment for mean income. We found that there is a positive correlation between altitude and suicide rate, even after adjustment for mean income. Thus, altitude appears to be an independent risk factor for suicide.
Altitude* ; Korea ; Risk Factors ; Social Class* ; Suicide*

The association between celebrity suicide and subsequent increase in suicide rates among the general population has been suggested. Previous studies primarily focused on celebrity suicides in the 2000s. To better understand the association, this study examined the impacts of celebrity suicides on subsequent suicide rates using the data of Korean celebrity suicides between 1990 and 2010. Nine celebrity suicides were selected by an investigation of media reports of suicide deaths published in three major newspapers in Korea between 1990 and 2010. Suicide mortality data were obtained from the National Statistical Office of Korea. Seasonal autoregressive integrated moving average models with intervention analysis were used to test the impacts of celebrity suicides, controlling for seasonality. Six of the 9 celebrity suicides had significant impacts on suicide rates both in the total population and in the same gender- or the same age-subgroups. The incident that occurred in the 1990s had no significant impact on the overall suicide rates, whereas the majority of the incidents in the 2000s had significant influences for 30 or 60 days following each incident. The influence of celebrity suicide was shown to reach its peak following the suicide death of a renowned actress in 2008. The findings may suggest a link between media coverage and the impact of celebrity suicide. Future studies should focus more on the underlying processes and confounding factors that may contribute to the impact of celebrity suicide on subsequent suicide rates.
Adult ; Aged ; *Famous Persons ; Female ; Humans ; Male ; Middle Aged ; Newspapers as Topic ; Republic of Korea ; Suicide/psychology/*statistics & numerical data ; Young Adult

TGF-beta1-induced glomerular mesangial cell (GMC) injury is a prominent characteristic of renal pathology in several kidney diseases, and a ternary protein complex consisting of PINCH-1, integrin-linked kinase (ILK) and alpha-parvin plays a pivotal role in the regulation of cell behavior such as cell proliferation and hypertrophy. We report here that PINCH-1-ILK-alpha-parvin (PIP) complex regulates the TGF-beta1-induced cell proliferation and hypertrophy in cultured rat GMCs. When GMCs were treated with TGF-beta1 for 1, 2 and 3 days, the PIP complex formation was up-regulated after 1 day, but it was down-regulated on day 2. Cell numbers were significantly elevated on day 2, but dramatically decreased on day 3. In contrast, a significant increase in cellular protein contents was observed 3 days after TGF-beta1-treatment. TGF-beta1 induced early increase of caspase-3 activity. In GMCs incubated with TGF-beta1 for 2 days, cytosolic expression of p27(Kip1) was dramatically reduced, but its nuclear expression was remarkably elevated. A significantly decreased expression of phospho-Akt (Ser 473) was observed in the cells treated with TGF-beta1 for 1 day. TGF-beta1 induced early increase of phospho-p27(Kip1) (Thr 157) expression with subsequent decrease, and similar responses to TGF-beta1 were observed in the p38 phosphorylation (Thr 180/Thr 182). Taken together, TGF-beta1 differently regulates the PIP complex formation of GMCs in an incubation period-dependant fashion. The TGF-beta1-induced up- and down-regulation of the PIP complex formation likely contributes to the pleiotropic effects of TGF-beta1 on mesangial cell proliferation and hypertrophy through cellular localization of p27(Kip1) and alteration of Akt and p38 phosphorylation. TGF-beta1-induced alteration of the PIP complex formation may be importantly implicated in the development and progression of glomerular failure shown in several kidney diseases.
Animals ; *Cell Enlargement ; *Cell Proliferation ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p27/metabolism ; Cytoskeletal Proteins/*metabolism ; DNA-Binding Proteins/*metabolism ; Male ; Mesangial Cells/drug effects/*physiology ; Microfilament Proteins/*metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/*metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Transforming Growth Factor beta1/*pharmacology ; p38 Mitogen-Activated Protein Kinases/metabolism

BACKGROUND: Although organotin compounds are widely used as PVC stabilizers, catalysts and biocides, their effects on humans are not well known. However, their acute intoxication is known to cause neurotoxicity in the central nervous system, renal toxicity, and hepatotoxicity. As there has been no previously published case of organotin intoxication in Korea, we report here the first Korean case of acute exposure to organotin. CASE REPORT: A 43-year-old male with disorientation and behavioral change was admitted to a hospital. He had been working as a tank cleaner for several different companies in the previous 8 years and a week before admission, he had cleaned a tank containing dimethyltin (DMT) for 4 days. A day after finishing the job, he suffered decreased memory, behavioral change and progressive mental deterioration when he arrived at the emergency room. The result of spinal tapping was negative but on the 4th day of admission he deteriorated into a state of coma along with metabolic acidosis and severe hypokalemia. High levels of DMT and trimethyltin (TMT) were detected in a highly sensitive urine analysis. After conservative treatment and chelation therapy, the patient showed some clinical improvement but the neurological defects persisted. CONCLUSION: The patient appeared to have been intoxicated from the acute exposure to a high level of organotin while cleaning the tank.
Acidosis ; Adult ; Central Nervous System ; Chelation Therapy ; Coma ; Disinfectants ; Emergency Service, Hospital ; Humans ; Hypokalemia ; Korea ; Male ; Memory ; Organotin Compounds ; Poisoning* ; Spinal Puncture

Situs inversus is an extremely rare autosomal recessive disease with left-right inversion of internal organs. It carries technical difficulties in diagnostic or therapeutic procedures. There have been a few case reports on stone extraction by ERCP in situs inversus patients. ERCP techniques in situs inversus can be classified into conventional method and mirror image method. In mirror image method, the procedure is performed with the patient in the right lateral decubitus position and the endoscopist on the patient's left side. Until now, there is no consensus about which method is better. Herein, we report an unusual case of choledocholithiasis in a patient with situs inversus who underwent ERCP for stone extraction by both conventional method and mirror image method.
Aged ; Balloon Occlusion ; Cholangiopancreatography, Endoscopic Retrograde ; Gallstones/complications/*diagnosis/therapy ; Humans ; Male ; Situs Inversus/complications/*diagnosis ; Stents ; Tomography, X-Ray Computed

B lymphocytes are produced from hematopoietic stem cells (HSCs) through the highly ordered process of B lymphopoiesis, which is regulated by a complex network of cytokines, chemokines and cell adhesion molecules derived from the hematopoietic niche. Primary osteoblasts function as an osteoblastic niche (OBN) that supports in vitro B lymphopoiesis. However, there are significant limitations to the use of primary osteoblasts, including their relative scarcity and the consistency and efficiency of the limited purification and proliferation of these cells. Thus, development of a stable osteoblast cell line that can function as a biomimetic or artificial OBN is necessary. In this study, we developed a stable osteoblastic cell line, designated OBN4, which functions as an osteoblast-based artificial niche that supports in vitro B lymphopoiesis. We demonstrated that the production of a B220⁺ cell population from Lineage⁻ (Lin⁻) Sca-1⁺ c-Kit⁺ hematopoietic stem and progenitor cells (HSPCs) was increased ~1.7-fold by OBN4 cells relative to production by primary osteoblasts and OP9 cells in coculture experiments. Consistently, OBN4 cells exhibited the highest production of B220⁺ IgM⁺ cell populations (6.7±0.6–13.6±0.6%) in an IL-7- and stromal cell-derived factor 1-dependent manner, with higher production than primary osteoblasts (3.7±0.5–6.4±0.6%) and OP9 cells (1.8±0.6–3.9±0.5%). In addition, the production of B220⁺ IgM⁺ IgD⁺ cell populations was significantly enhanced by OBN4 cells (15.4±1.1–18.9±3.2%) relative to production by primary osteoblasts (9.5±0.6–14.6±1.6%) and OP9 cells (9.1±0.5–10.3±1.8%). We conclude that OBN4 cells support in vitro B lymphopoiesis of Lin⁻ Sca-1⁺ c-Kit⁺ HSPCs more efficiently than primary osteoblasts or OP9 stromal cells.
B-Lymphocytes ; Biomimetics ; Cell Adhesion Molecules ; Cell Line ; Chemokines ; Coculture Techniques ; Cytokines ; Hematopoietic Stem Cells ; In Vitro Techniques* ; Lymphopoiesis* ; Osteoblasts ; Stem Cells ; Stromal Cells

Stem cells are used for the investigation of developmental processes at both cellular and organism levels and offer tremendous potentials for clinical applications as an unlimited source for transplantation. Gangliosides, sialic acid-conjugated glycosphingolipids, play important regulatory roles in cell proliferation and differentiation. However, their expression patterns in stem cells and during neuronal differentiation are not known. Here, we investigated expression of gangliosides during the growth of mouse embryonic stem cells (mESCs), mesenchymal stem cells (MSCs) and differentiated neuronal cells by using high-performance thin-layer chromatography (HPTLC). Monosialoganglioside 1 (GM1) was expressed in mESCs and MSCs, while GM3 and GD3 were expressed in embryonic bodies. In the 9-day old differentiated neuronal cells from mESCs cells and MSCs, GM1 and GT1b were expressed. Results from immunostaining were consistent with those observed by HPTLC assay. These suggest that gangliosides are specifically expressed according to differentiation of mESCs and MSCs into neuronal cells and expressional difference of gangliosides may be a useful marker to identify differentiation of mESCs and MSCs into neuronal cells.
Neurons/*cytology/*metabolism ; Mice ; Mesenchymal Stem Cells/*cytology/*metabolism ; Gangliosides/*metabolism ; Embryonic Stem Cells/*cytology/*metabolism ; Cells, Cultured ; Cell Differentiation ; Animals

Bortezomib is a proteasome inhibitor used for the treatment of relapsed/refractory multiple myeloma (MM). However, intrinsic and acquired resistance to bortezomib has already been observed in MM patients. In a previous report, we demonstrated that changes in the expression of mitochondrial genes lead to changes in mitochondrial activity and bortezomib susceptibility or resistance, and their combined effects contribute to the differential sensitivity or resistance of MM cells to bortezomib. Here we report that the combination treatment of bortezomib and 2-methoxyestradiol (2ME), a natural estrogen metabolite, induces mitochondria-mediated apoptotic cell death of bortezomib-resistant MM KMS20 cells via mitochondrial reactive oxygen species (ROS) overproduction. Bortezomib plus 2ME treatment induces a higher level of cell death compared with treatment with bortezomib alone and increases mitochondrial ROS and Ca2+ levels in KMS20 cells. Pretreatment with the antioxidant N-acetyl-L-cysteine scavenges mitochondrial ROS and decreases cell death after treatment with bortezomib plus 2ME in KMS20 cells. Moreover, we observed that treatment with bortezomib plus 2ME maintains the activation of c-Jun N-terminal kinase (JNK) and mitogen-activated protein kinase kinase kinase 4/7 (MKK4/7). Collectively, combination treatment with bortezomib and 2ME induces cell death via JNK-MKK4/7 activation by overproduction of mitochondrial ROS. Therefore, combination therapy with specific mitochondrial-targeting drugs may prove useful to the development of novel strategies for the treatment of bortezomib-resistant MM patients.
Acetylcysteine/pharmacology ; Apoptosis/*drug effects ; Boronic Acids/*pharmacology ; Calcium/metabolism ; Cell Line, Tumor ; *Drug Resistance, Neoplasm ; Drug Synergism ; Estradiol/*analogs & derivatives/pharmacology ; Humans ; Mitochondria/drug effects/metabolism ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Pyrazines/*pharmacology ; Reactive Oxygen Species/metabolism

Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc (Zn2+) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of Zn2+ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular Zn2+ levels are largely regulated by metallothioneins (MTs), Zn2+ importers (ZIPs), and Zn2+ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of Zn2+. However, these regulatory actions of Zn2+ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular Zn2+ levels, Zn2+-mediated signal transduction, impacts of Zn2+ on ion channels and mitochondrial metabolism, and finally, the implications of Zn2+ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of Zn2+.
Central Nervous System ; Heart ; Immune System ; Ion Channels ; Mammary Glands, Human ; Metabolism ; Metallothionein ; Oxidation-Reduction ; Pancreas ; Prostate ; Protein Conformation ; Signal Transduction ; Zinc*