BACKGROUND: Cholesterol is a major component of specialized membrane microdomains known as lipid rafts or caveolae, which modulate the fluidity of biological membranes. Membrane cholesterol therefore plays an important role in cell signaling and vesicular transport. OBJECTIVE: In this study, we investigated the effects of cholesterol on matrix metalloproteinase-1 (MMP-1) expression in human dermal fibroblasts. METHODS: MMP-1 mRNA and protein expression were determined by RT-PCR and Western blotting, respectively. AP-1 DNA binding activity was detected by electrophoretic mobility shift assays. The amount of cholesterol was analyzed by cholesterol assay kit. RESULTS: We observed that MMP-1 mRNA and protein expression was dose-dependently decreased by cholesterol treatment. In contrast, cholesterol depletion by a cholesterol depletion agent, methyl-beta-cyclodextrin (M beta CD) in human dermal fibroblasts, increased MMP-1 mRNA and protein expression in a dose-dependent manner. Also, we investigated the regulatory mechanism of M beta CD-induced MMP-1 expression: cholesterol depletion by M beta CD, activated ERK1/2 and JNK, but not p38 MAPK cascade, and it also significantly increased c-Jun phosphorylation, c-Fos expression and activator protein-1 binding activity. Furthermore, the inhibition of ERK or JNK with specific chemical inhibitors prevented M beta CD-induced MMP-1 expression, which indicates that ERK and JNK play an important role in cholesterol depletion-mediated MMP-1 induction. In addition, M beta CD-induced phosphorylation of ERK and JNK and MMP-1 expression were suppressed by cholesterol repletion. CONCLUSION: Our results suggest that cholesterol regulates MMP-1 expression through the control of ERK and JNK activity in human dermal fibroblasts.
beta-Cyclodextrins ; Blotting, Western ; Caveolae ; Cholesterol ; DNA ; Electrophoretic Mobility Shift Assay ; Fibroblasts ; Humans ; Matrix Metalloproteinase 1 ; Membrane Microdomains ; Membranes ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation ; RNA, Messenger ; Transcription Factor AP-1

OBJECTIVES: Impairment of social cognition affects the social functioning of patients with schizophrenia. For example, patients with schizophrenia have been shown to display abnormal eye contact during a one-on-one conversation. This study was designed to investigate the behavioral characteristics of patients with schizophrenia while talking with two people. METHODS: Twenty six patients with schizophrenia and 26 normal controls performed virtual reality conversation tasks, in which they talked with main and assistant avatars under positive or negative emotional conditions. While listening and speaking, the durations of eye gaze with the main and minor avatars were measured from the head orientations of the participants using a positional tracker. RESULTS: Compared with normal controls, the patient group showed a shorter duration of gaze towards the main avatar and a longer duration of gaze towards the assistant avatar. This pattern was more apparent in the negative situation. CONCLUSION: The results suggest a defect in social cognition, in which patients with schizophrenia fail to distribute their gaze appropriately during a conversation with more than one other person.
Cognition ; Eye ; Head ; Humans ; Orientation ; Schizophrenia

OBJECTIVES: Mobile healthcare applications are becoming a growing trend. Also, the prevalence of dementia in modern society is showing a steady growing trend. Among degenerative brain diseases that cause dementia, Alzheimer disease (AD) is the most common. The purpose of this study was to identify AD patients using magnetic resonance imaging in the mobile environment. METHODS: We propose an incremental classification for mobile healthcare systems. Our classification method is based on incremental learning for AD diagnosis and AD prediction using the cortical thickness data and hippocampus shape. We constructed a classifier based on principal component analysis and linear discriminant analysis. We performed initial learning and mobile subject classification. Initial learning is the group learning part in our server. Our smartphone agent implements the mobile classification and shows various results. RESULTS: With use of cortical thickness data analysis alone, the discrimination accuracy was 87.33% (sensitivity 96.49% and specificity 64.33%). When cortical thickness data and hippocampal shape were analyzed together, the achieved accuracy was 87.52% (sensitivity 96.79% and specificity 63.24%). CONCLUSIONS: In this paper, we presented a classification method based on online learning for AD diagnosis by employing both cortical thickness data and hippocampal shape analysis data. Our method was implemented on smartphone devices and discriminated AD patients for normal group.
Alzheimer Disease* ; Artificial Intelligence ; Brain Diseases ; Classification* ; Delivery of Health Care ; Dementia ; Diagnosis ; Discrimination (Psychology) ; Hippocampus ; Humans ; Learning* ; Magnetic Resonance Imaging ; Methods ; Mobile Health Units ; Prevalence ; Principal Component Analysis ; Sensitivity and Specificity ; Statistics as Topic

PURPOSE: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and lymph node (LN) metastasis is common in PTC. Lateral LN metastasis is associated with local recurrence of PTC. The aim of this study is to evaluate the patterns of lateral LN metastasis of PTC. METHODS: One-hundred seventy four patients who undergone total thyroidectomy, central LN and ipsilatereal or bilateral LN dissection due to PTC 'from 2007 to 2008 in Seoul National University Hospital were retrospectively reviewed. The average age of the patients was 50.4 years and the male to female ratio was 1:4.12. Sixty-seven patients (38.5%) had central LN metastasis and 47 patients (27.0%) had lateral node metastasis. RESULTS: The factors related with lateral LN metastasis of PTC are male gender, the tumor size, extrathyroidal extension, multifocality and central LN metastasis. The level III LN group was the most frequent site of lateral LN metastasis followed by the jugular, level IV, level II, and level V groups. The jugular LN metastasis is mainly related with the metastasis of the upper lateral neck area, including level II LNs, and the lymphatic pathway to the lower lateral neck area, including level IV, seems to be independent from the jugular LNs. Ten cases had lateral LN metastasis without central LN metastasis (skip metastasis). CONCLUSION: Lateral LN metastasis of PTC has a certain pattern. The operator must consider this pattern when managing patients with lateral LN metastasis of PTC.
Female ; Humans ; Lymph Nodes* ; Male ; Neck* ; Neoplasm Metastasis* ; Recurrence ; Retrospective Studies ; Seoul ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

OBJECTIVE: To investigate the analgesic effect of transcranial direct current stimulation (tDCS) over the primary motor (M1), dorsolateral prefrontal cortex (DLPFC), and sham tDCS in patients with painful diabetic polyneuropathy (PDPN). METHODS: Patients with PDPN (n=60) were divided randomly into the three groups (n=20 per group). Each group received anodal tDCS with the anode centered over the left M1, DLPFC, or sham stimulation for 20 minutes at intensity of 2 mA for 5 consecutive days. A blinded physician rated the patients' pain using a visual analog scale (VAS), Clinical Global Impression (CGI) score, anxiety score, sleep quality, Beck Depression Inventory (BDI), and the pain threshold (PT) to pressure. RESULTS: After the tDCS sessions, the M1 group showed a significantly greater reduction in VAS for pain and PT versus the sham and DLPFC groups (p<0.001). The reduction in VAS for pain was sustained after 2 and 4 weeks of follow-up in the M1 group compared with the sham group (p<0.001, p=0.007). Significant differences were observed among the three groups over time in VAS for pain (p<0.001), CGI score (p=0.01), and PT (p<0.001). No significant difference was observed among the groups in sleep quality, anxiety score, or BDI score immediately after tDCS. CONCLUSION: Five daily sessions of tDCS over the M1 can produce immediate pain relief, and relief 2- and 4-week in duration in patients with PDPN. Our findings provide the first evidence of a beneficial effect of tDCS on PDPN.
Anxiety ; Chronic Pain ; Depression ; Diabetic Neuropathies* ; Electrodes ; Follow-Up Studies ; Humans ; Pain Threshold ; Prefrontal Cortex ; Visual Analog Scale

Overexpression of HER2 correlates with more aggressive tumors and increased resistance to cancer chemotherapy. However, a functional comparison between the HER2high/HER3 and the HER2low/HER3 dimers on tumor metastasis has not been conducted. Herein we examined the regulation mechanism of heregulin-beta1 (HRG)-induced MMP-1 and -9 expression in breast cancer cell lines. Our results showed that the basal levels of MMP-1 and -9 mRNA and protein expression were increased by HRG treatment. In addition, HRG-induced MMP-1 and -9 expression was significantly decreased by MEK1/2 inhibitor, U0126 but not by phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294002. To confirm the role of MEK/ERK pathway on HRG-induced MMP-1 and -9 expression, MCF7 cells were transfected with constitutively active adenoviral-MEK (CA-MEK). The level of MMP-1 and -9 expressions was increased by CA-MEK. MMP-1 and -9 mRNA and protein expressions in response to HRG were higher in HER2 overexpressed cells than in vector alone. The phosphorylation of HER2, HER3, ERK, Akt, and JNK were also significantly increased in HER2 overexpressed MCF7 cells compared with vector alone. HRG-induced MMP-1 and -9 expressions were significantly decreased by lapatinib, which inhibits HER1 and HER2 activity, in both vector alone and HER2 overexpressed MCF7 cells. Finally, HRG-induced MMP-1 and MMP-9 expression was decreased by HER3 siRNA overexpression. Taken together, we suggested that HRG-induced MMP-1 and MMP-9 expression is mediated through HER3 dependent pathway and highly expressed HER2 may be associated with more aggressive metastasis than the low expressed HER2 in breast cancer cells.
Breast Neoplasms/enzymology/*genetics/*metabolism ; Butadienes/pharmacology ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/pharmacology ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MAP Kinase Signaling System ; MCF-7 Cells ; Matrix Metalloproteinase 1/*genetics/metabolism ; Matrix Metalloproteinase 9/*genetics/metabolism ; Neuregulin-1/*pharmacology ; Nitriles/pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Multimerization ; Proto-Oncogene Proteins c-akt/metabolism ; Quinazolines/pharmacology ; Receptor, erbB-2/genetics/*metabolism ; Receptor, erbB-3/*metabolism

BACKGROUND: Recently, VE1, a monoclonal antibody against the BRAFV600E mutant protein, has been investigated in terms of its detection of the BRAFV600E mutation. Although VE1 immunostaining and molecular methods used to assess papillary thyroid carcinoma in surgical specimens are in good agreement, evaluation of VE1 in thyroid cytology samples is rarely performed, and its diagnostic value in cytology has not been well established. In present study, we explored VE1 immunoexpression in cytology samples from ex vivo papillary thyroid carcinoma specimens in order to minimize limitations of low cellularity and sampling/targeting errors originated from thyroid fineneedle aspiration and compared our results with those obtained using the corresponding papillary thyroid carcinoma tissues. METHODS: The VE1 antibody was evaluated in 21 cases of thyroid cytology obtained directly from ex vivo thyroid specimens. VE1 immunostaining was performed using liquid-based cytology, and the results were compared with those obtained using the corresponding tissues. RESULTS: Of 21 cases, 19 classic papillary thyroid carcinomas had BRAFV600E mutations, whereas two follicular variants expressed wild-type BRAF. VE1 immunoexpression varied according to specimen type. In detection of the BRAFV600E mutation, VE1 immunostaining of the surgical specimen exhibited 100% sensitivity and 100% specificity, whereas VE1 immunostaining of the cytology specimen exhibited only 94.7% sensitivity and 0% specificity. CONCLUSIONS: Our data suggest that VE1 immunostaining of a cytology specimen is less specific than that of a surgical specimen for detection of the BRAFV600E mutation, and that VE1 immunostaining of a cytology specimen should be further evaluated and optimized for clinical use.
Biopsy, Fine-Needle ; Immunohistochemistry ; Mutant Proteins ; Sensitivity and Specificity ; Thyroid Gland* ; Thyroid Neoplasms*