No abstract available.
Animals ; Burns* ; Rats*

Chronic exposure to high levels of manganese (Mn) leads a pronounced and debilitating disorder known as manganism. Research on the toxic manifestation of manganese have focused primarily on its neurological effects because exposure to high levels of the metal produces a distinct and irreversible extrapyramidal dysfunction resembling the dystonic movements associated with Parkinson's physiological and biochemical systems in the body. The purpose of this study is to determine the effects of Mn on mineralization in primary rat calvarial cells. The experimental groups were in concentration of 0, 10, 30 and 60 micrometer. The results were as follows: 1. ALP activity was decreased in concentration of 30 and 60 micrometer (p<0.01). 2. Bone nodule formation was depressed in concentration of 30 and 60 micrometer at day 14 and 21 (p<0.01). 3. RT-PCR results showed an altered expression of bone matrix proteins. These result suggested that manganese might decrease or alter the expression of the osteoblast phenotype.
Animals ; Bone Matrix ; Manganese ; Osteoblasts ; Osteogenesis* ; Phenotype ; Rats*

PURPOSE: Recent studies have suggested microscopic positive resection margin should be revised according to the presence of tumor cells within 1mm of the margin surface in resected specimens of pancreatic cancer. However, the clinical meaning of this revised margin status for R1 resection margin was not fully clarified. METHODS: From July 2012 to December 2014, the medical records of 194 consecutive patients who underwent pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head were analyzed retrospectively. They were divided into 3 groups on margin status; revised microscopic negative margin (rR0) – tumor exists more than 1 mm from surgical margin, revised microscopic positive margin (rR1) – tumor present within less than 1 mm from surgical margin, classic microscopic positive margin (cR1) – tumor is exposed to surgical margin. RESULTS: There were 76 rR0 (39.2%), 100 rR1 (51.5%), and 18 cR1 (9.3%). There was significant difference in disease-free survival rates between cR1 vs. rR1 (8.4 months vs. 24.0 months, P = 0.013). Margin status correlated with local recurrence rate (17.1% in rR0, 26.0% in rR1, and 44.4% in cR1, P = 0.048). There is significant difference in recurrence at tumor bed (11.8% in rR0 vs. 23.0 in rR1, P = 0.050). Of rR1, adjuvant treatment was found to be an independent risk factor for local recurrence (hazard ratio, 0.297; 95% confidence interval, 0.127–0.693, P = 0.005). CONCLUSION: Revised R1 resection margin (rR1) affects recurrence at the tumor bed. Adjuvant treatment significantly reduced local recurrence of rR1. Accordingly, adjuvant chemoradiation for rR1 group should be taken into account.
Adenocarcinoma* ; Carcinoma, Pancreatic Ductal ; Disease-Free Survival ; Head* ; Humans ; Medical Records ; Pancreatic Neoplasms ; Pancreaticoduodenectomy ; Recurrence ; Retrospective Studies ; Risk Factors

OBJECTIVE: This study was designed to estimate the chemosensitivity by a quantitative evaluation of the apoptotic cell fractions using flow cytometry. METHODS: The OVCAR-3 cells were exposed to 20 nM or 30 nM taxol for 0 (control), 24 and 48 hours, then removed the taxol contained media, and cultured further with fresh media without taxol. (1) Fluorescein isothiocyanate-conjugated Annexin V (Annexin V-FITC) and propidium iodide (PI) were added to one test tube to detect the apoptotic cell fractions and at the same time, PI was added to the other tube to stain the DNA. (2) Annexin V-FITC and cytokeratin (clone CAM5.2 and MNF116) were added to the test tube. They were fixed and permeabilized with 1% paraformaldehyde solution and 100% methanol. They were then incubated with phycoerythrin (PE)-conjugated goat anti-mouse immunoglobulin G (GAM IgG1-PE or GAM IgG2a-PE) and sequentially stained with PI for DNA. All the stained cells were analyzed by a FACScan flow cytometer. RESULTS: (1) After treatment of 20 nM or 30 nM of taxol, G2M arrest was observed in both of treatment groups, which increased with time. (2) The G0G1 sub-fraction indicative of apoptosis increased with increase of culturing time from 24 hrs to 48 hrs. (3) The early apoptotic cell fraction with positive annexin V-FITC and negative PI increased with increase of culturing time. (4) In cells stained sequentailly with annexin V-FITC, cytokeratin (CAM5.2 and MNF116), and PI after 30 nM taxol treatment, the early apoptotic cell fractions increased with increase of culturing time. However, their extent was somewhat lower than those observed by positive annexin V-FITC and negative PI in cells treated with 20 nM of taxol. CONCLUSION: The results of sequential stainings with annexin V-FITC, cytokeratin, and PI were consistent with the those of annexin V-FITC and PI with parallel DNA staining. Our results suggested that the level of apoptosis detected by flow cytometry could be a marker of chemosensitivity which could select the sensitive anti-cancer agents before administration to gynecologic cancer patients.
Annexin A5* ; Apoptosis* ; Cell Line* ; DNA ; Evaluation Studies as Topic ; Flow Cytometry ; Fluorescein ; Goats ; Humans ; Immunoglobulin G ; Keratins* ; Methanol ; Ovarian Neoplasms* ; Paclitaxel ; Phycoerythrin ; Propidium*

We report here on a case of genetically confirmed type Ia glycogen storage disease (GSD) that was diagnosed in the military hospital. A twenty-year old soldier was admitted to the hospital with abdominal fullness. He had a past medical history of hepatomegaly that was firstly recognized at six months after birth, and he had been followed-up at an outpatient clinic with the presumptive diagnosis of type III GSD. He also had a history of growth hormone therapy because of growth retardation. However, he arbitrarily refused medical observation from 14 years of age. On the physical examination, the height of the patient was 163.1 cm and significant hepatomegaly was observed. Significantly abnormal liver-associated paramters were observed on the laboratory findings and multiple hepatic adenomas were observed on the CT exam and MRI scan. To determine the proper treatment, we tried to confirm the exact type of GSD in the patient. By mutational analysis, we found the c.648G>T homozygote splicing mutation in the G6PC gene and the patient was confirmed as having the type Ia GSD.
Adenoma ; Ambulatory Care Facilities ; Chromosome Disorders ; Glycogen ; Glycogen Storage Disease ; Growth Hormone ; Hepatomegaly ; Homozygote ; Hospitals, Military ; Humans ; Magnetic Resonance Imaging ; Military Personnel ; Parturition ; Physical Examination

In diabetic patients who were being treated with hemodialysis, coma and other neurological deficits did not occur in spite of extremely elevated serum glucose levels. In this report, we compared diabetic patients with renal failure in severe hyperglycemia with nonketotic hyperosmolar coma patients with normal renal function to know what affect mental changes. Mental changes were not present in diabetic patients with renal failure. These patients with renal failure showed more severe hyperglycemia, but corrected serum sodium concentration and calculated effective serum osmolality were low. So it is suggested that corrected serum sodium concentration and effective serum osmolality are more important factor affecting mental changes than high blood glucose levels in diabetic patients with renal failure, due to absence of osmotic diuresis.
Blood Glucose ; Coma ; Diuresis ; Humans ; Hyperglycemia* ; Osmolar Concentration ; Renal Dialysis ; Renal Insufficiency* ; Sodium

Trefoil factor 1 (TFF1, also known as pS2) is strongly expressed in the gastrointestinal mucosa and plays a critical role in the differentiation of gastric glands. Since approximately 50% of all human gastric cancers are associated with decreased TFF1 expression, it is considered a tumor suppressor gene. TFF1 deficiency in mice results in histological changes in the antral and pyloric gastric mucosa, with severe hyperplasia and dysplasia of epithelial cells, resulting in the development of antropyloric adenoma. Here, we generated TFF1-knockout (KO) mice, without a neomycin resistant (NeoR) cassette, using the clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRSIPR/Cas9) system. Though our TFF1-KO mice showed phenotypes very similar to the previous embryonic stem (ES)-cell-based KO mice, they differed from the previous reports in that a reduction in body weight was observed in males. These results demonstrate that these newly established TFF1-KO mice are useful tools for investigating genetic and environmental factors influencing gastric cancer, without the effects of artificial gene insertion. Furthermore, these findings suggest a novel hypothesis that TFF1 expression influences gender differences.
Adenoma ; Animals ; Body Weight* ; Carcinogenesis* ; Epithelial Cells ; Gastric Mucosa ; Genes, Synthetic ; Genes, Tumor Suppressor ; Humans ; Hyperplasia ; Lotus ; Male ; Mice* ; Mucous Membrane ; Neomycin ; Phenotype ; Stomach Neoplasms

Recombination activating gene-2 (RAG-2) plays a crucial role in the development of lymphocytes by mediating recombination of T cell receptors and immunoglobulins, and loss of RAG-2 causes severe combined immunodeficiency (SCID) in humans. RAG-2 knockout mice created using homologous recombination in ES cells have served as a valuable immunodeficient platform, but concerns have persisted on the specificity of RAG-2-related phenotypes in these animals due to the limitations associated with the genome engineering method used. To precisely investigate the function of RAG-2, we recently established a new RAG-2 knockout FVB mouse line (RAG-2(−/−)) manifesting lymphopenia by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease. In this study, we further characterized their phenotypes focusing on histopathological analysis of lymphoid organs. RAG-2(−/−) mice showed no abnormality in development compared to their WT littermates for 26 weeks. At necropsy, gross examination revealed significantly smaller spleens and thymuses in RAG-2(−/−) mice, while histopathological investigation revealed hypoplastic white pulps with intact red pulps in the spleen, severe atrophy of the thymic cortex and disappearance of follicles in lymph nodes. However, no perceivable change was observed in the bone marrow. Moreover, our analyses showed a specific reduction of lymphocytes with a complete loss of mature T cells and B cells in the lymphoid organs, while natural killer cells and splenic megakaryocytes were increased in RAG-2(−/−) mice. These findings indicate that our RAG-2(−/−) mice show systemic lymphopenia with the relevant histopathological changes in the lymphoid organs, suggesting them as an improved Rag-2-related immunodeficient model.
Animals ; Atrophy ; B-Lymphocytes ; Bone Marrow ; Genome ; Homologous Recombination ; Humans ; Immunoglobulins ; Killer Cells, Natural ; Lymph Nodes ; Lymphocytes ; Lymphopenia* ; Megakaryocytes ; Methods ; Mice* ; Mice, Knockout ; Negotiating ; Phenotype ; Receptors, Antigen, T-Cell ; Recombination, Genetic ; Sensitivity and Specificity ; Severe Combined Immunodeficiency ; Spleen ; T-Lymphocytes ; Thymus Gland

Background/Aims: As pancreatic mucinous cystic neoplasms (MCNs) are considered premalignant lesions, the current guidelines recommend their surgical resection. We aimed to investigate the concordance between preoperative and postoperative diagnoses and evaluate preoperative clinical parameters that could predict the malignant potential of MCNs. Methods: Patients who underwent surgical resection at Samsung Medical Center for pancreatic cystic lesions and whose pathology was confirmed to be MCN, between July 2000 and December 2017, were retrospectively analyzed. Results: Among a total of 132 patients 99 (75%) were diagnosed with MCN preoperatively. The most discordant preoperative diagnosis was an indeterminate pancreatic cyst. The proportion of male patients was higher (24.2% vs 7.1%, p=0.05) in the diagnosis-discordance group and the presence of worrisome features in radiologic imaging studies, such as wall thickening/enhancement (12.1% vs 37.4%, p=0.02) or solid component/mural nodule (3.0% vs 27.3%, p=0.02), was lower in the diagnosis-discordance group. The presence of symptoms (57.7% vs 34.9%, p=0.02), tumor size greater than 4 cm (80.8% vs 55.7%, p=0.04), and radiologic presence of a solid component/mural nodule (42.3% vs 16.0%, p=0.01) or duct dilatation (19.2% vs 6.6%, p=0.01) were significantly associated with malignant MCNs. Conclusions In our study, the overall diagnostic concordance rate was confirmed to be 75%, and our findings suggest that MCNs have a low malignancy potential when they are less than 4cm in size, are asymptomatic and lack worrisome features on preoperative images.

Background/Aims: Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. Methods: Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of Ecadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. Results: Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0–2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0–2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). Conclusions This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.