Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis.

Background: Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades.

Accumulation of citrullinated glial fibrillary acidic protein in a mouse model of bile duct ligation-induced hepatic fibrosis.

Hepatic stellate cells (HSCs) play pivotal roles in hepatic fibrosis as they synthesize glial fibrillary acidic protein (GFAP), which is increased in activated HSCs. GFAP-expressing HSCs and myofibroblasts accumulate in and around hepatic fibrosis lesions. Peptidylarginine deiminase 2 (PAD2) is responsible for the citrullination of GFAP (cit-GFAP).

Myelin Basic Protein Citrullination, a Hallmark of Central Nervous System Demyelination, Assessed by Novel Monoclonal Antibodies in Prion Diseases.

Myelin basic protein (MBP) citrullination by peptidylarginine deiminase (PAD) enzymes leads to incomplete protein-lipid bilayer interactions and vulnerability to proteolytic enzymes, resulting in disorganization of the myelin sheath in the central nervous system. Therefore, citrullinated MBP (citMBP) has been suggested as a hallmark of demyelination, but how citMBP is implicated in prion diseases remains unknown. For the first time, we developed mouse monoclonal anti-citMBP IgG1 (clones 1B8, 1H1, and 3C6) and IgM (clone 3G5) antibodies that recognize human citMBP at its R25, R122, and R130 residues and at its C-terminal region (or the corresponding sites in mouse MBP), respectively.

Upregulation of Connexin 43 Expression Via C-Jun N-Terminal Kinase Signaling in Prion Disease.

Prion infection leads to neuronal cell death, glial cell activation, and the accumulation of misfolded prion proteins. However, the altered cellular environments in animals with prion diseases are poorly understood. In the central nervous system, cells connect the cytoplasm of adjacent cells via connexin (Cx)-assembled gap junction channels to allow the direct exchange of small molecules, including ions, neurotransmitters, and signaling molecules, which regulate the activities of the connected cells.

Mass spectrometric identification of citrullination sites and immunohistochemical detection of citrullinated glial fibrillary acidic protein in Alzheimer's disease brains.

Peptidylarginine deiminases (PADs) are posttranslational modification enzymes that convert protein arginine to citrulline residues in a calcium ion-dependent manner. Previously, we reported the abnormal accumulation of citrullinated proteins and the increase in the amount of PAD2 in hippocampi from Alzheimer's disease (AD) patients. Moreover, glial fibrillary acidic protein (GFAP), an astrocyte-specific marker protein, and vimentin were identified as citrullinated proteins by using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry.

[A case of spontaneous bacterial peritonitis caused by Listeria monocytogenes].

Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with ascites caused by advanced liver disease. While gram negative bacteria, such as Escherichia coli and Klebsiella pneumonia are the common pathogens, Listeria monocytogenes has been recognized as a very rare pathogen. Empirical treatment with third generation cephalosporins does not provide adequate antibiotics coverage against L.

Pathological characterization of TgElk mice injected with brain homogenate from elk with chronic wasting disease.

Chronic wasting disease (CWD) is classified as a transmissible spongiform encephalopathy or prion disease that affects cervids. CWD has been reported in 15 US states, two Canadian provinces, and in imported elk on several farms in Korea. This study was conducted to examine the molecular biological and pathogenic characteristics of a CWD-associated prion isolated in Korea.

Familial Creutzfeldt-Jakob disease with a mutation at codon 180 presenting with an atypical phenotype.

The clinical features of familial Creutzfeldt-Jakob disease (fCJD) with a mutation at codon 180 (V180I) are less typical than those of patients with sporadic CJD. We describe a patient with pathologically confirmed CJD carrying the V180I mutation who had atypical cerebrospinal fluid and electroencephalography findings. Similar to other prion protein mutations, this report suggests that the V180I mutation is not the exclusive determinant of the phenotype.

Peptidylarginine deiminase modulates the physiological roles of enolase via citrullination: links between altered multifunction of enolase and neurodegenerative diseases.

The citrullination of enolase by PAD (peptidylarginine deiminase) has emerged as an important post-translational modification in human disorders; however, the physiological function of citrullination remains unknown. In the present study, we report that citrullination diversely regulates the biological functions of ENO1 (α-enolase) and NSE (neuron-specific enolase). We developed three mouse IgG1 monoclonal antibodies with specificity to the following: (i) citrullination of Arg9 of ENO1 [ENO1Cit9; anti-CE1 (citrullinated enolase 1) antibody]; (ii) citrullination of Arg9 in ENO1 and NSE (ENO1Cit9/NSECit9; anti-CE1/2 antibody); and (iii) citrullination of Arg429 of NSE (NSECit429; anti-CE2 antibody).

Dura mater graft-associated Creutzfeldt-Jakob disease: the first case in Korea.

Since 1987, dura mater graft-associated iatrogenic Creutzfeldt-Jakob disease (dCJD) has been reported in many countries. We report the first case of dCJD in Korea. A 54-yr-old woman, who underwent resection of the meningioma in the left frontal region and received a dura mater graft 23 yr ago presented with dysesthesia followed by psychiatric symptoms and ataxia.

A Drosophila model of GSS syndrome suggests defects in active zones are responsible for pathogenesis of GSS syndrome.

We have established a Drosophila model of Gerstmann-Sträussler-Scheinker (GSS) syndrome by expressing mouse prion protein (PrP) having leucine substitution at residue 101 (MoPrP(P101L)). Flies expressing MoPrP(P101L), but not wild-type MoPrP (MoPrP(3F4)), showed severe defects in climbing ability and early death. Expressed MoPrP(P101L) in Drosophila was differentially glycosylated, localized at the synaptic terminals and mainly present as deposits in adult brains.

Association of endothelial nitric oxide synthase and mitochondrial dysfunction in the hippocampus of scrapie-infected mice.

The elevation of nitric oxide (NO) within the central nervous system (CNS) is known to be associated with the pathogenesis of neurodegenerative diseases such as HIV-associated dementia (HAD), brain ischemia, Parkinson's disease, and Alzheimer's disease. NO is enzymatically formed by the enzyme nitric oxide synthase (NOS). There are two forms of NOS, the constitutive and the inducible form.

Involvement of peptidylarginine deiminase-mediated post-translational citrullination in pathogenesis of sporadic Creutzfeldt-Jakob disease.

Peptidylarginine deiminases (PADs)-mediated post-translational citrullination processes play key roles in protein functions and structural stability through the conversion of arginine to citrulline in the presence of excessive calcium concentrations. In brain, PAD2 is abundantly expressed and can be involved in citrullination in disease. Recently, we have reported pathological characterization of PAD2 and citrullinated proteins in scrapie-infected mice, but the implication of protein citrullination in the pathophysiology in human prion disease is not clear.

Spontaneous immortalization of oligodendroglial cells derived from an SV40 T antigen-positive human glioblastoma multiforme.

The polyoma group of viruses, including SV40, is known to be oncogenic in certain species. Here we report for the first time naturally occurring, immortalized tumor cells from a patient with glioblastoma multiforme (GBM); the cells were shown to be oligodendroglia; cells had developed remarkable chromosomal changes and were positive for SV40 T antigen. Therefore, we postulated that the main cause of immortalization of these cells was the expression of SV40 T antigen gene and protein.

3D polycaprolactone scaffolds with controlled pore structure using a rapid prototyping system.

Designing a three-dimensional (3-D) ideal scaffold has been one of the main goals in biomaterials and tissue engineering, and various mechanical techniques have been applied to fabricate biomedical scaffolds used for soft and hard tissue regeneration. Scaffolds should be biodegradable and biocompatible, provide temporary support for cell growth to allow cell adhesion, and consist of a defined structure that can be formed into customized shapes by a computer-aided design system. This versatility in preparing scaffolds gives us the opportunity to use rapid prototyping devices to fabricate polymeric scaffolds.

[Abdominal obesity, insulin resistance, and the risk of colonic adenoma].

Background/aims: Abdominal obesity and hyperinsulinemia or insulin resistance are of interest in connection with colon carcinogenesis. We conducted a prospective case controlled study for the evaluation of relationship between abdominal obesity, insulin resistance, and colorectal adenoma.

Methods: Fifty patients with colorectal adenoma and fifty healthy subjects were included in this study.

[A case of primary omental torsion presenting as an acute abdominal pain].

Torsion of greater omentum is a rare cause of acute abdomen. However, it should be included in the differential diagnoses in addition to acute cholecystitis, acute appendicitis, cecal diverticulitis, and other variable causes of acute abdomen. Diagnosis is usually made at laparotomy for suspected appendicitis.

[A case of appendicular tuberculosis presenting as acute appendicitis].

Tuberculosis may affect primarily all organs and tissues of the body, although some of these show high immunity against the infection. The most common forms of non-pulmonary tuberculosis are tuberculosis of bones and joints (30%), urinary system (24%), lymph nodes (13%), sexual organs (8%), cerebrospinal meninges (4%), and alimentary system (3%). Especially, the commonest presentation of abdominal tuberculosis is ileocecal disease, but isolated appendicular involvement is also rarely seen, occurring in only 1.

[Pulmonary toxicity by pegylated interferon alpha-2a in a patient with chronic hepatitis C].

The combination therapy with pegylated interferon alpha and ribavirin has increasingly prescribed for chronic hepatitis C. Although many side effects of interferon such as flu-like symptoms, gastrointestinal and neuropsychiatric symptoms are well known, only several cases of interferon-induced pulmonary toxicity have been reported. Interferon-induced pulmonary toxicity usually develops from 2 weeks to 12 weeks after treatment for HCV infection.

[Comparison of model for end-stage liver disease score with discriminant function and child-Turcotte-Pugh scores for predicting short-term mortality in Korean patients with alcoholic hepatitis].

Background/aims: Alcoholic hepatitis is an acute or acute-on-chronic inflammatory syndrome associated with significant morbidity and mortality. Traditionally, Maddrey discriminant function (DF) score and Child-Turcott-Pugh (CTP) score have been used for stratifying the prognosis of alcoholic hepatitis. Recently, the model for end-stage liver disease (MELD) score has been applied to alcoholic hepatitis and some investigators consider MELD score as a better prognostic indicator for severe alcoholic hepatitis.

[A case of acute cholecystitis secondary to hemobilia after percutaneous liver biopsy].

Percutaneous liver biopsy is well established for the diagnosis and follow-up of many liver diseases. Although it is rather safe, major complications, such as bleeding into the peritoneal or thoracic cavity, hemobilia, enteric perforation and intrahepatic hematoma, have been reported related to the procedure. Recently, incidence of such major complications has been decreased since the introduction of ultrasonography-guided liver biopsy.

[A case of primary hepatic leiomyosarcoma presenting with multiple subcutaneous scalp mass].

Leiomyosarcoma is an uncommon tumor which arises from various sites including uterus, stomach, retroperitoneum, superficial soft tissues, bladder, kidney, and lung. Primary hepatic leiomyosarcoma is a very rare tumor and fewer than 70 cases of primary hepatic leiomyosarcoma have been reported since the first publication in Japan. And there was only one case report of cutaneous metastasis from hepatic leiomyosarcoma.

[A case of nodular regenerative hyperplasia of liver that mimicked primary biliary cirrhosis].

Nodular regenerative hyperplasia (NRH) of the liver is a rare disease that is characterized by multiple regenerative nodules in the hepatic parenchyma without fibrosis. The exact pathogenesis of NRH has not been established, but it's been suggested that obliteration of portal veins may initiate the nodular transformation. It is also known that this disease is associated with autoimmune disease, myeloproliferative disease, lymphoproliferative disease, primary biliary cirrhosis, and some chemotherapy agents.

[Importance of age and other risk factors in NSAID-induced gastropathy].

Background/aims: It is clinically important to analyze the risk factors of NSAID-induced gastropathy because there could be no symptoms. Age is the most important risk factor according to previous reports. The aim of this study was to find risk factors of NSAID-induced gastropathy and to confirm the association between NSAID-induced gastropathy and age.