Selectins, carbohydrate-binding molecules, bind to fucosylated and sialylated glycoprotein ligands, and are found on endothelial cells, leukocytes and platelets. They can be classified into E-, L- and P-selectins, and are involved in trafficking of cells of the innate immune system, T lymphocytes and platelets via binding with specific ligands. An absence of selectins or selectin ligands has serious consequences in mice or humans, leading to recurrent bacterial infections and persistent disease. Selectins are involved in constitutive lymphocyte homing and chronic and acute inflammation processes, including post-ischemic inflammation in muscle, kidney, heart, skin inflammation, atherosclerosis, glomerulonephritis and lupus erythematosus. Selectin-neutralizing monoclonal antibodies, recombinant soluble P-selectin glycoprotein ligand 1 and small-molecule inhibitors of selectins have been tested in clinical trials on patients with multiple trauma, cardiac indications and pediatric asthma, respectively. Anti-selectin antibodies have also been successfully used in preclinical models to deliver imaging contrast agents and therapeutics to sites of inflammation. The contributions of selectins and selectin ligands to signalling deserve further study, which will allow a much more detailed analysis of the contributions of selectins in models of inflammation, haemostasis, haematopoiesis, wound healing, atherogenesis, and tumor metastasis.
Animals ; Antibodies ; Antibodies, Monoclonal ; Asthma ; Atherosclerosis ; Bacterial Infections ; Contrast Media ; Endothelial Cells ; Glomerulonephritis ; Glycomics* ; Glycoproteins ; Heart ; Hematopoiesis ; Humans ; Immune System ; Inflammation ; Kidney ; Leukocytes ; Ligands ; Lymphocytes ; Mice ; Multiple Trauma ; Neoplasm Metastasis ; P-Selectin ; Selectins ; Skin ; T-Lymphocytes ; Wound Healing

OBJECTIVE: This study investigated the putative association between type-D personality and suicidality, including the history of suicide attempt and suicidal ideation in patients with major depressive disorder (MDD). METHODS: Eighty-six outpatients aged between 18 and 65 years with MDD were recruited for this study from Ilsan Paik Hospital. The cohort was stratified into two subgroups according to the presence of type-D personality and history of suicide attempt (yes vs. no). Depression severity was evaluated using the Hamilton Depression Rating Scale. The type-D Personality Scale-14 (DS-14), the Beck Hopelessness Scale (BHS), the Barratt Impulsiveness Scale (BIS), the Hamilton Anxiety Scale, and the Beck Scale for Suicidal Ideation (BSS) were also applied. RESULTS: The total BSS, BHS, and BIS scores were higher for the group with type-D personality than for the group without this personality (p=0.004, 0.01, and 0.003, respectively). In addition, the total scores for the BSS, BHS, and social inhibition (SI; subscale of DS-14) were higher for the group with a history of suicide attempt than for the group without this history (p=0.0000004, 0.003, and 0.033, respectively). There were positive correlations between the total DS-14 score and the total BSS, BHS, and BIS scores (r=0.413 and p=0.000077, r=0.404 and p=0.00012, and r=0.245 and p=0.024, respectively). CONCLUSION: Depressed patients with type-D personality are more vulnerable to suicidality than those without type-D personality, even when the MDD severity is identical. In addition, the SI score was higher in patients with a history of suicide attempt than in those without this history.
Anxiety ; Cohort Studies ; Depression ; Depressive Disorder, Major* ; Humans ; Outpatients ; Suicidal Ideation ; Suicide

OBJECTIVE: This study investigated the putative association between type-D personality and suicidality, including the history of suicide attempt and suicidal ideation in patients with major depressive disorder (MDD). METHODS: Eighty-six outpatients aged between 18 and 65 years with MDD were recruited for this study from Ilsan Paik Hospital. The cohort was stratified into two subgroups according to the presence of type-D personality and history of suicide attempt (yes vs. no). Depression severity was evaluated using the Hamilton Depression Rating Scale. The type-D Personality Scale-14 (DS-14), the Beck Hopelessness Scale (BHS), the Barratt Impulsiveness Scale (BIS), the Hamilton Anxiety Scale, and the Beck Scale for Suicidal Ideation (BSS) were also applied. RESULTS: The total BSS, BHS, and BIS scores were higher for the group with type-D personality than for the group without this personality (p=0.004, 0.01, and 0.003, respectively). In addition, the total scores for the BSS, BHS, and social inhibition (SI; subscale of DS-14) were higher for the group with a history of suicide attempt than for the group without this history (p=0.0000004, 0.003, and 0.033, respectively). There were positive correlations between the total DS-14 score and the total BSS, BHS, and BIS scores (r=0.413 and p=0.000077, r=0.404 and p=0.00012, and r=0.245 and p=0.024, respectively). CONCLUSION: Depressed patients with type-D personality are more vulnerable to suicidality than those without type-D personality, even when the MDD severity is identical. In addition, the SI score was higher in patients with a history of suicide attempt than in those without this history.
Anxiety ; Cohort Studies ; Depression ; Depressive Disorder, Major* ; Humans ; Outpatients ; Suicidal Ideation ; Suicide

BACKGROUND: Previous reports have demonstrated a bidirectional relationship between depression and diabetes mellitus (DM), accentuating a need for more intensive depression screening in DM patients. There is a relative paucity of data on the mortality of depressed DM patients in Korea. METHODS: Retrospective data from January 2003 to December 2013 were collected for adult type 2 diabetes mellitus (T2DM) patients older than 30 years using the National Health Information database maintained by the Korean National Health Insurance Service (NHIS). Demographic characteristics were analyzed with descriptive statistics, and the annual prevalence of depression was estimated. Mortality rates and hazard ratios for each age group (stratified into six age groups) of patients diagnosed with T2DM in 2003 were estimated using a Cox proportional hazard method, with the Kaplan-Meier cumulative survival curve showing the overall survival rates according to the T2DM status until the given year of 2013. RESULTS: The annual prevalence of depression was consistently higher in T2DM group from 2003 to 2013. The mortality hazard ratio was higher in the depressed in all age groups, and the risk was higher in male groups and in younger-aged groups. CONCLUSION: Depression was significantly associated with a high mortality risk in T2DM patients; hence, a more systematic surveillance of T2DM patients to identify risk factors for depression might contribute significantly to reducing mortality risk in this group of patients.
Adult ; Cohort Studies* ; Depression* ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Humans ; Korea ; Male ; Mass Screening ; Methods ; Mortality* ; National Health Programs ; Prevalence ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Rate

Bis (Bag-3, CAIR), a Bcl-2-interacting protein, promotes the anti-apoptotic activity of Bcl-2 and increased levels of Bis have been observed in several disease models. The involvement of Bcl-2 and some Bcl-2-binding proteins in differentiation has recently been reported. However, the relevance of Bis to cellular differentiation remains unknown. The findings herein show that Bis expression is up-regulated during the differentiation of HL-60 cells. To investigate the effect of Bis expression on differentiation, we established Bis-overexpressing HL-60 cells (HL-60-bis). HL-60-bis cells have a low nuclear: cytoplasmic ratio and indented nucleus in Wright- Giemsa staining, and an increased expression of CD11b in immunofluorescence study, indicating the promotion of differentiation. The overexpression of Bis also resulted in a retarded cell growth rate, accompanied by the accumulation of HL-60 cells at the G0/G1 phase of the cell cycle, which was sustained during the differentiation process. Western blot analysis revealed that the expression of p27, a representative inducer of cell cycle arrest at the G1 phase, was increased 2.5-fold in HL-60-bis cells compared to HL-60-neo cells. These results suggest that the Bis induced growth inhibition of HL-60 cells promotes G0/G1 phase arrest via up-regulation of p27, which seems to be a prerequisite for differentiation. Further studies will be required to define the exact roles of Bis on cellular differentiation more precisely.
Carrier Proteins/*metabolism ; *Cell Differentiation ; Cell Proliferation ; Cell Shape ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p27/*metabolism ; Flow Cytometry ; Gene Expression ; HL-60 Cells ; Humans ; Research Support, Non-U.S. Gov't ; *Up-Regulation

B-cell lymphoma (BCL)-2-interacting cell death suppressor (BIS) has diverse cellular functions depending on its binding partners. However, little is known about the effects of biochemical modification of BIS on its various activities under oxidative stress conditions. In this study, we showed that H₂O₂ reduced BIS mobility on SDS–polyacrylamide gels in a time-dependent manner via the activation of extracellular signaling-regulated kinase (ERK). The combined results of mass spectroscopy and computational prediction identified Thr285 and Ser289 in BIS as candidate residues for phosphorylation by ERK under oxidative stress conditions. Deletion of these sites resulted in a partial reduction in the H₂O₂-induced mobility shift relative to that of the wild-type BIS protein; overexpression of the deletion mutant sensitized A172 cells to H₂O₂-induced cell death without increasing the level of intracellular reactive oxygen species. Expression of the BIS deletion mutant decreased the level of heat shock protein (HSP) 70 mRNA following H₂O₂ treatment, which was accompanied by impaired nuclear translocation of heat shock transcription factor (HSF) 1. Co-immunoprecipitation assays revealed that the binding of wild-type BIS to HSF1 was decreased by oxidative stress, while the binding of the BIS deletion mutant to HSF1 was not affected. These results indicate that ERK-dependent phosphorylation of BIS has a role in the regulation of nuclear translocation of HSF1 likely through modulation of its interaction affinity with HSF1, which affects HSP70 expression and sensitivity to oxidative stress.
Cell Death ; Gels ; Heat-Shock Proteins ; Hot Temperature ; Immunoprecipitation ; Lymphoma, B-Cell ; Mass Spectrometry ; Oxidative Stress* ; Phosphorylation* ; Phosphotransferases ; Reactive Oxygen Species ; RNA, Messenger ; Shock ; Transcription Factors

The expression of BCL-2 interacting cell death suppressor (BIS), an anti-stress or anti-apoptotic protein, has been shown to be regulated at the transcriptional level by heat shock factor 1 (HSF1) upon various stresses. Recently, HSF1 was also shown to bind to BIS, but the significance of these protein-protein interactions on HSF1 activity has not been fully defined. In the present study, we observed that complete depletion of BIS using a CRISPR/Cas9 system in A549 non-small cell lung cancer did not affect the induction of heat shock protein (HSP) 70 and HSP27 mRNAs under various stress conditions such as heat shock, proteotoxic stress, and oxidative stress. The lack of a functional association of BIS with HSF1 activity was also demonstrated by transient downregulation of BIS by siRNA in A549 and U87 glioblastoma cells. Endogenous BIS mRNA levels were significantly suppressed in BIS knockout (KO) A549 cells compared to BIS wild type (WT) A549 cells at the constitutive and inducible levels. The promoter activities of BIS and HSP70 as well as the degradation rate of BIS mRNA were not influenced by depletion of BIS. In addition, the expression levels of the mutant BIS construct, in which 14 bp were deleted as in BIS-KO A549 cells, were not different from those of the WT BIS construct, indicating that mRNA stability was not the mechanism for autoregulation of BIS. Our results suggested that BIS was not required for HSF1 activity, but was required for its own expression, which involved an HSF1-independent pathway.
Carcinoma, Non-Small-Cell Lung* ; Cell Death ; Down-Regulation ; Glioblastoma ; Heat-Shock Proteins ; Homeostasis ; Hot Temperature ; Oxidative Stress ; RNA Stability ; RNA, Messenger ; RNA, Small Interfering ; Shock ; Transcriptional Activation*

Immunoglobulin G4-related disease is a recently recognized entity characterized by a mass-forming or regional lesion that contains an extensive infiltration of IgG4-producing plasma cells with dense fibrosis. Immunoglobulin G4-related disease can affect any organ system, but solitary hepatic lesion of Immunoglobulin G4-related disease is very rare. This entity mimics primary malignant hepatic tumor, such as hepatocellular carcinoma or intrahepatic cholangiocarcinoma. We experienced a case of hepatic IgG4-related inflammatory pseudotumor in a 50-year-old woman, mimicking hepatocellular carcinoma.
Carcinoma, Hepatocellular* ; Cholangiocarcinoma ; Female ; Fibrosis ; Granuloma, Plasma Cell* ; Humans ; Immunoglobulins* ; Middle Aged ; Plasma Cells

OBJECTIVE: PCB cervical instrument is a newly introduced fusion device which comprises cervical plate, cage (spacer) and screw system. It is developed to enhance fusion rate and stability, as well as to reduce complications related to hardware failure. We investigated the efficacy of clinical and radiological results of PCB instrument and Lubboc bone. METHODS: From August, 1998 to October, 1999, authors performed 54 cases of anterior cervical interbody fusion with PCB instrument and Lubboc bone. Retrospective analysis was undertaken based on clinical and radiological findings. Clinical improvement was evaluated according to Odom's criteria. Cervical plain films and tomography were taken every 2 months to evaluate the degree of interbody fusion and disc height changes. RESULTS: Bone fusion was observed in 36 cases(90%) over 6 months after operation, and during which time there was no significant interval change. There were 3 cases of hardware dislodgement. Disc height was increased significantly and preserved in all cases. Clinical outcome over good degree was seen more than 94% of patients. CONCLUSION: Longer follow-up period and comparative studies to similar instrument appear to be necessary, but this instrumentation system has shown high fusion rate and fewer adverse effects in our series. We believe this system might be indicated for the treatment of cervical trauma and degenerative disease in selective cases.
Follow-Up Studies ; Humans ; Retrospective Studies

OBJECTIVES: Although many reports have been written on seasonal variations in mood and behavior in foreign countries, few reports have dealt with Korean adolescents, except medical students. The goal of this study was to estimate the frequency of seasonal variations in mood and behavior among Korean high school students. METHODS: A total of 656 high school students living in southeastern Seoul participated in this study. The subjects were investigated with the Korean translated version of the Seasonal Pattern Assessment Questionnaire (SPAQ), and their responses were evaluated for seasonal patterns in mood and behavior change according to Kasper's criteria to make SAD (seasonal affective disorder) or SSAD (subclinical seasonal affective disorder) diagnosis. RESULTS: A total of 565 subjects completed the questionnaire and the responses (M: F=324: 241) were collected and used for analysis. The mean age was 16.73 (SD=0.65) years, and mean global seasonality score 5.88 (SD=4.72). Of the respondents, 413 (73.1%) reported problems related with seasonal changes. Total prevalence rates were 13.6% for SAD, 10.8% for S-SAD. The estimated frequencies were 5.1% for summer SAD, 3.2% for summer S-SAD, 0.5% for winter SAD and 1.1% for winter S-SAD. The prevalence rate of summer SAD or S-SAD was higher than winter SAD or S-SAD. CONCLUSION: The subjects showed a higher prevalence rate of summer type than winter type in SAD or S-SAD. These results were similar to those of other studies carried out in East Asian countries. However, the unpleasant feelings resulting from high temperature and humidity in summer rather than depression may have influenced the results. Therefore, it is necessary to make new SAD criteria of the SPAQ suitable for East Asian countries.
Adolescent ; Asian Continental Ancestry Group ; Depression ; Diagnosis ; Epidemiology ; Humans ; Humidity ; Prevalence ; Surveys and Questionnaires ; Seasonal Affective Disorder ; Seasons* ; Seoul ; Students, Medical