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

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

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

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

PURPOSE: We investigated the prevalence of lower urinary tract symptoms (LUTS), and the inconvenience of each symptom, using an ICS-male Questionnaire (ICS-mQ) in Korean man. We also evaluated the relationships between symptoms, prostate volume and urodynamic parameters of a bladder outlet obstruction (BOO). MATERIALS AND METHODS: 180 male LUTS patients, from 7 urological institutions, were enrolled in this study. The ICS-mQ was used to measure the severity of the symptoms, with a bothersomeness scale. Transrectal sonography and urodynamic studies, including Schaefer linear passive urethral resistance relation (L-PURR), were performed. RESULTS: The 5 most frequent symptoms were voiding symptoms, such as reduced stream, terminal dribbling, incomplete emptying, intermittency and hesitancy, in that order. However, the 5 most bothersome symptoms included 2 voiding, and 3 storage, symptoms, such as incomplete emptying, urge incontinence, pain in bladder, nocturnal incontinence and hesitancy. 34.4% of the nocturia patients felt quite, or severely, bothered, but only 1.1% felt no problem. The mean value of estimated prostate volume, by sonography, was 29.8+/-14.1ml. There were no correlations between the severity of symptoms and the prostate size. There were also little, or no, correlations between a wide range of symptoms and the urodynamic parameters of BOO. CONCLUSIONS: The most frequent symptoms of male patients with LUTS are voiding symptoms, but they suffered more from storage, than from voiding, symptoms. The severities of the symptoms, or the bothersomeness, were not correlated with the prostate size or the urodynamic parameters of a bladder outlet obstruction. Therefore, the relief of a bladder outlet obstruction is not crucial to relieve the symptoms.
Humans ; Korea* ; Lower Urinary Tract Symptoms* ; Male ; Nocturia ; Prevalence ; Prostate ; Surveys and Questionnaires* ; Rivers ; Urinary Bladder Neck Obstruction* ; Urinary Bladder* ; Urinary Incontinence, Urge ; Urodynamics

PURPOSE: We investigated the prevalence of lower urinary tract symptoms (LUTS), and the inconvenience of each symptom, using an ICS-male Questionnaire (ICS-mQ) in Korean man. We also evaluated the relationships between symptoms, prostate volume and urodynamic parameters of a bladder outlet obstruction (BOO). MATERIALS AND METHODS: 180 male LUTS patients, from 7 urological institutions, were enrolled in this study. The ICS-mQ was used to measure the severity of the symptoms, with a bothersomeness scale. Transrectal sonography and urodynamic studies, including Schaefer linear passive urethral resistance relation (L-PURR), were performed. RESULTS: The 5 most frequent symptoms were voiding symptoms, such as reduced stream, terminal dribbling, incomplete emptying, intermittency and hesitancy, in that order. However, the 5 most bothersome symptoms included 2 voiding, and 3 storage, symptoms, such as incomplete emptying, urge incontinence, pain in bladder, nocturnal incontinence and hesitancy. 34.4% of the nocturia patients felt quite, or severely, bothered, but only 1.1% felt no problem. The mean value of estimated prostate volume, by sonography, was 29.8+/-14.1ml. There were no correlations between the severity of symptoms and the prostate size. There were also little, or no, correlations between a wide range of symptoms and the urodynamic parameters of BOO. CONCLUSIONS: The most frequent symptoms of male patients with LUTS are voiding symptoms, but they suffered more from storage, than from voiding, symptoms. The severities of the symptoms, or the bothersomeness, were not correlated with the prostate size or the urodynamic parameters of a bladder outlet obstruction. Therefore, the relief of a bladder outlet obstruction is not crucial to relieve the symptoms.
Humans ; Korea* ; Lower Urinary Tract Symptoms* ; Male ; Nocturia ; Prevalence ; Prostate ; Surveys and Questionnaires* ; Rivers ; Urinary Bladder Neck Obstruction* ; Urinary Bladder* ; Urinary Incontinence, Urge ; Urodynamics