Neural stem cells (NSCs) have the ability to self-renew and differentiate into neurons, oligodendrocytes, and astrocytes. Highly dynamic nature of NSC differentiation requires the intimate involvement of catabolic processes such as autophagy. Autophagy is a major intracellular degradation pathway necessary for cellular homeostasis and remodeling. Autophagy is important for mammalian development and its role in neurogenesis has recently drawn much attention. However, little is known about how autophagy is associated with differentiation of NSCs into other neural lineages. Here, we report that autophagy plays a critical role in differentiation of adult rat hippocampal neural stem (HCN) cells into astrocytes. During differentiation, autophagy flux peaked at early time points, and remained high. Pharmacological or genetic suppression of autophagy by stable knockdown of Atg7, LC3 or CRISPR-Cas9-mediated knockout (KO) of p62 impaired astrogenesis, while reintroduction of p62 recovered astrogenesis in p62 KO HCN cells. Taken together, our findings suggest that autophagy plays a key role in astrogenesis in adult NSCs.
Adult Stem Cells ; Adult ; Animals ; Astrocytes ; Autophagy ; Cell Differentiation ; Homeostasis ; Humans ; Neural Stem Cells ; Neurogenesis ; Neurons ; Oligodendroglia ; Rats ; Suppression, Genetic

PURPOSE: This study was to develop evidence-based clinical practice guideline in order to prevent contrast-induced nephropathy (CIN) for patients undergoing percutaneous coronary intervention (PCI). METHODS: The guideline was developed based on the “Scottish Intercollegiate Guidelines Network (SIGN)”. The first draft of guideline was developed through 5 stages and evaluated by 10 experts.(1) Clinical questions were ensured in PICO format.(2) Two researchers conducted a systematic search through electronic database, identifying 170 studies. We selected 27 full text articles including 16 randomized clinical trials, 7 systematic reviews, and 4 guidelines. Quality of each studies were evaluated by the Cochran's Risk of Bias, AMSTAR, K-AGREEII. Among the studies, 11 studies were excluded.(3) The strength of recommendations were classified and quality of recommendations were ranked.(4) Guideline draft was finalized.(5) Content-validation was conducted by an expert group. All contents were ranked above 0.8 in CVI. RESULTS: Evidence-based clinical practice guideline to prevent CIN was dveloped.(1) The guideline for preventing CIN recommends using 0.9% saline.(2) Standardized rate of fluid therapy is 1 to 1.5ml/kg/hr.(3) Execute hydration for 6~12hrs before PCI and after PCI. CONCLUSION: This study suggests evidence-based clinical practice guideline for preventing CIN which can be more efficiently used in clinical practice.
Acute Kidney Injury ; Bias (Epidemiology) ; Contrast Media ; Evidence-Based Practice ; Fluid Therapy ; Humans ; Percutaneous Coronary Intervention

BACKGROUND/AIMS: Fibroblast growth factor signaling is involved in hepatocarcinogenesis. The aim of this study was to determine the fibroblast growth factor receptor (FGFR) isotype expression in hepatocellular carcinoma (HCC) and neighboring nonneoplastic liver tissue, and elucidate its prognostic implications. METHODS: Immunohistochemical staining of FGFR1, -2, -3, and -4 was performed in the HCCs and paired neighboring nonneoplastic liver tissue of 870 HCC patients who underwent hepatic resection. Of these, clinical data for 153 patients who underwent curative resection as a primary therapy were reviewed, and the relationship between FGFR isotype expression and overall survival was evaluated (development set). This association was also validated in 73 independent samples (validation set) by Western blot analysis. RESULTS: FGFR1, -2, -3, and -4 were expressed in 5.3%, 11.1%, 3.8%, and 52.7% of HCCs, respectively. Among the development set of 153 patients, FGFR2 positivity in HCC was associated with a significantly shorter overall survival (5-year survival rate, 35.3% vs. 61.8%; P=0.02). FGFR2 expression in HCC was an independent predictor of a poor postsurgical prognosis (hazard ratio, 2.10; P=0.02) in the development set. However, the corresponding findings were not statistically significant in the validation set. CONCLUSIONS: FGFR2 expression in HCC could be a prognostic indicator of postsurgical survival.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blotting, Western ; Carcinoma, Hepatocellular/metabolism/mortality/*pathology ; Female ; Hepatectomy ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms/metabolism/mortality/*pathology ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Protein Isoforms/metabolism ; Receptors, Fibroblast Growth Factor/*metabolism ; Young Adult

BACKGROUND/AIMS: The role of prostaglandin E2 (PGE2) in the modulation of cell growth is well established in colorectal cancer. The aim of this study was to elucidate the significance of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) down-regulation on the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: The expression of 15-PGDH in HCC cell lines and resected HCC tissues was investigated, and the correlation between 15-PGDH expression and HCC cell-line proliferation and patient survival was explored. RESULTS: The interleukin-1-beta-induced suppression of 15-PGDH did not change the proliferation of PLC and Huh-7 cells in the MTS [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The induction of 15-PGDH by transfection in HepG2 cells without baseline 15-PGDH expression was suppressed at day 2 of proliferation compared with empty-vector transfection, but there was no difference at day 3. Among the 153 patients who received curative HCC resection between 2003 and 2004 at our institution, 15-PGDH expression was observed in resected HCC tissues in 56 (36.6%), but the 5-year survival rate did not differ from that of the remaining 97 non-15-PGDH-expressing patients (57.1% vs 59.8%; P=0.93). Among 50 patients who exhibited baseline 15-PGDH expression in adjacent nontumor liver tissues, 28 (56%) exhibited a reduction in 15-PGDH expression score in HCC tissues, and there was a trend toward fewer long-term survivors compared with the remaining 22 with the same or increment in their 15-PGDH expression score in HCC tissues. CONCLUSIONS: The prognostic significance of 15-PGDH down-regulation in HCC was not established in this study. However, maintenance of 15-PGDH expression could be a potential therapeutic target for a subgroup of HCC patients with baseline 15-PGDH expression in adjacent nontumor liver tissue.
Adolescent ; Adult ; Aged ; Carcinoma, Hepatocellular/*diagnosis/mortality/pathology ; Down-Regulation ; Female ; Hep G2 Cells ; Humans ; Hydroxyprostaglandin Dehydrogenases/*metabolism ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms/*diagnosis/mortality/pathology ; Male ; Middle Aged ; Prognosis ; Young Adult

The neurological manifestations caused by Epstein-Barr virus (EBV) occur only rarely in association with its primary infection or reactivation. The mechanism by which EBV produces neurological disease is unknown. This article describes two cases of polymerase-chain-reaction-proven EBV brainstem encephalitis. The sera of both patients contained autoantibodies against N-methyl-D-aspartate receptor (NMDAR), suggesting the presence of a secondary immunological mechanism. Prospective studies are needed to reveal whether the subgroup of patients with EBV encephalitis and anti-NMDAR antibodies have different clinical presentations and would benefit from immunotherapy.
Antibodies ; Autoantibodies ; Brain Stem ; Encephalitis ; Herpesvirus 4, Human ; Humans ; Immunotherapy ; N-Methylaspartate ; Neurologic Manifestations

The neurological manifestations caused by Epstein-Barr virus (EBV) occur only rarely in association with its primary infection or reactivation. The mechanism by which EBV produces neurological disease is unknown. This article describes two cases of polymerase-chain-reaction-proven EBV brainstem encephalitis. The sera of both patients contained autoantibodies against N-methyl-D-aspartate receptor (NMDAR), suggesting the presence of a secondary immunological mechanism. Prospective studies are needed to reveal whether the subgroup of patients with EBV encephalitis and anti-NMDAR antibodies have different clinical presentations and would benefit from immunotherapy.
Antibodies ; Autoantibodies ; Brain Stem ; Encephalitis ; Herpesvirus 4, Human ; Humans ; Immunotherapy ; N-Methylaspartate ; Neurologic Manifestations

BACKGROUND/AIMS: Stercoral colitis is an inflammatory condition related to increased intraluminal pressure, itself caused by impacted fecal material. Stercoral colitis is a rare condition and has a generally poor prognosis. The aims of this study were to investigate the clinical characteristics and outcomes of stercoral colitis according to management strategy. METHODS: From January 2004 to August 2009, 11 patients were diagnosed with stercoral colitis at our center. The medical records of these individuals were reviewed retrospectively with regard to the clinical characteristics, management strategy, and clinical outcomes. We defined severe stercoral colitis as stercoral colitis complicated by systemic inflammatory response syndrome, sepsis, or septic shock. RESULTS: Eleven patients (three men and eight women) with a mean age of 70+/-8 years were included. Ten patients were elderly with constipation as a predisposing factor. Nine patients had severe stercoral colitis according to out criteria. Of these, five patients underwent surgery, and the other four were treated with a conservative management strategy. One patient (20%) in the surgical group and all patients in the conservative management group (n=4) died. CONCLUSIONS: Stercoral colitis should be considered in elderly patients with predisposing factors and presents as fecal impaction with colonic wall thickening or pericolic fat stranding on CT scan. In patients with severe stercoral colitis, early surgery may be effective in reducing mortality.
Aged ; Colitis ; Colon ; Constipation ; Fecal Impaction ; Humans ; Intestinal Perforation ; Male ; Medical Records ; Prognosis ; Retrospective Studies ; Sepsis ; Systemic Inflammatory Response Syndrome

BACKGROUND/AIMS: The treatment response to interferon could differ with mutations in the interferon-sensitivity-determining region (ISDR) in patients infected with hepatitis C virus (HCV) genotype-1b (HCV-Ib). We examined the pattern of ISDR mutations and analyzed whether the number of amino acid substitutions influences the treatment response to peginterferon plus ribavirin in chronic hepatitis or cirrhotic patients infected with HCV-Ib. METHODS: The study population comprised 52 patients who visited Seoul Asan Medical Center and Seoul National University Bundang Hospital from January 2006 to December 2008 and who received peginterferon alpha-2a (n=37) or -2b (n=15) plus ribavirin, and whose serum was stored. We analyzed the early virologic response, end-of-treatment response, and sustained virologic response (SVR), and examined the ISDR using direct sequencing. RESULTS: The proportions of patients with ISDR mutation types of wild (0 mutations), intermediate (1-3 mutations), and mutant (> or =4 mutations) were 50.0%, 42.3%, and 7.7%, respectively, and the corresponding SVR rates were 63%, 50%, and 67% (p>0.05). The SVR rates were 59.4% and 50.0% in patients with <2 and > or =2 mutations, respectively (p>0.05). On univariate analysis, age was the only predictive factor for SVR (p=0.016). The pretreatment HCV RNA titer tended to be lower in those with SVR, but without statistical significance (p=0.069). CONCLUSIONS: The frequency of ISDR mutations was low in our cohort of Korean patients infected with HCV-Ib. Therefore, ISDR mutations might not contribute to the response to treatment with peginterferon plus ribavirin.
Adult ; Aged ; Amino Acid Sequence ; Antiviral Agents/*therapeutic use ; Drug Resistance, Viral/genetics ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/*genetics ; Hepatitis C, Chronic/*drug therapy/virology ; Humans ; Interferon Alfa-2a/*therapeutic use ; Interferon Alfa-2b/*therapeutic use ; Male ; Middle Aged ; Molecular Sequence Data ; *Mutation ; Polyethylene Glycols/*therapeutic use ; Republic of Korea ; Ribavirin/therapeutic use

BACKGROUND: Systemic lymphoma can be difficult to recognize due to its diverse manifestations. Paraneoplastic leukoencephalopathy has rarely been reported in the context of lymphoma. CASE REPORT: We report a 45-year-old man with systemic lymphoma whose initial manifestation was sudden-onset leukoencephalopathy, mimicking stroke. This patient, who was eventually diagnosed with diffuse large B-cell lymphoma, initially presented with sudden cognitive impairment and gait disturbance. Radiological studies suggested a paraneoplastic leukoencephalopathy. Chemotherapy for lymphoma resulted in clinical and radiological improvement. CONCLUSIONS: The presented case indicates that diffuse large B-cell lymphoma may initially appear as a treatable leukoencephalopathy.
B-Lymphocytes ; Cerebral Infarction ; Gait ; Humans ; Leukoencephalopathies ; Lymphoma ; Lymphoma, B-Cell ; Middle Aged ; Stroke

BACKGROUND/AIMS: Osteopontin (OPN) is overexpressed in hepatocellular carcinoma (HCC) with postoperative recurrence or extrahepatic metastasis. However, its prognostic value in patients treated with transarterial chemoembolization (TACE) is unclear. We investigated the utility of serum OPN levels and changes therein as prognostic markers in HCC patients who have received TACE. METHODS: Forty-six patients with HCC were enrolled. Serum OPN levels were measured before and 4 weeks after TACE. Serum biochemistry and computed tomography (CT) scans were analyzed. We evaluated baseline serum OPN levels and subsequent changes therein in relation to tumor responses and cumulative survival rates following TACE. A decreasing pattern was defined as a decrease after TACE of more than 10% relative to baseline levels. A "responder" was defined as a patient who exhibited a tumor necrosis rate of higher than 50% on the follow-up CT scan. RESULTS: Higher initial serum OPN levels were associated with a large tumor, portal vein invasion, and an advanced tumor stage. Patients who had lower initial serum OPN levels and those who exhibited decreasing patterns after TACE tended to have more favorable tumor responses (P=0.043 and 0.055, respectively) and exhibited better cumulative survival rates (P=0.036 and 0.030, respectively). However, the initial serum OPN level and subsequent changes in serum OPN levels were not independent predictors for survival on multivariate analysis. CONCLUSIONS: Serum OPN levels were significantly higher in patients with advanced HCC. In addition, HCC patients with low pretreatment serum OPN levels and those for whom serum OPN declined following TACE exhibited better tumor responses and survived for longer.
Adult ; Aged ; Area Under Curve ; Carcinoma, Hepatocellular/metabolism/secondary/*therapy ; *Chemoembolization, Therapeutic ; Female ; Humans ; Liver Neoplasms/metabolism/pathology/*therapy ; Male ; Middle Aged ; Neoplasm Staging ; Osteopontin/*blood ; Portal Vein/pathology ; Prognosis ; Severity of Illness Index ; Survival Rate ; Tomography, X-Ray Computed