• Journal of Veterinary Clinics
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• v.20 no.4
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• pp.443-448
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• 2003

To determine whether localization of tartrate-resistant acid phosphatase (TRAP) and cathepsin K was associated with rupture of the cranial cruciate ligament (CCL) in dogs. Tissue specimens were obtained from 30 dogs with CCL rupture during surgical treatment, 8 aged normal dogs, and 9 young normal dogs that were necropsied for reasons unrelated to this study and unrelated to musculoskeletal disease. The cranial cruciate ligament was examined histologically. $TRAP^+$ cells and cathepsin $K^+$ cells were identified by histochemical staining and immunohistochemical staining respectively. TRAP and cathepsin $K^+$ were co-localized within the same cells principally located within the epiligamentous region and to a lesser extent in the core region of ruptured CCL. Localization of $TRAP^+$ cells (P < 0.05) and cathepsin $K^+$ cells (P =0.05) within CCL tissue was significantly increased in dogs with CCL rupture, compared with aged-normal dogs, and young normal dogs (P < 0.05 - TRAP, P < 0.001 - cathepsin K). Localization of $TRAP^+$ cells and cathepsin $K^+$ cells within the CCL tissue of aged-normal dogs was also increased compared with young normal dogs (P < 0.05). Small numbers of $TRAP^+$ cells and cathepsin $K^+$ cells were seen in the intact ligaments of aged-normal dogs, which were associated with ligament fasicles in which there was chondroid transformation of ligament fibroblasts and disruption of the organized hierarchical structure of the extracellular matrix. $TRAP^+$ cells and cathepsin $K^+$ cells were not seen in CCL tissue from young-normal dogs. Localization of the proteinases $TRAP^+$ and cathepsin $K^+$ in CCL tissue was significantly associated with CCL rupture. Small numbers of proteinase positive cells were also localized in the CCL of agednormal dogs without CCL rupture, but were not detected in CCL from young-normal dogs. Taken together, these findings suggest that the cell signaling pathways that regulate expression of these proteinases in CCL tissue may form part of the mechanism that leads to upregulation of collagenolytic ligament remodeling and progressive structural failure of the CCL over time.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.1.1-1.14
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• 2018

DNA methylation is a regulatory mechanism in epigenetics that is frequently altered during human carcinogenesis. To detect critical methylation events associated with gastric cancer (GC), we compared three DNA methylomes from gastric mucosa (GM), intestinal metaplasia (IM), and gastric tumor (GT) cells that were microscopically dissected from an intestinal-type early gastric cancer (EGC) using methylated DNA binding domain sequencing (MBD-seq) and reduced representation bisulfite sequencing (RRBS) analysis. In this study, we focused on differentially methylated promoters (DMPs) that could be directly associated with gene expression. We detected 2,761 and 677 DMPs between the GT and GM by MBD-seq and RRBS, respectively, and for a total of 3,035 DMPs. Then, 514 (17%) of all DMPs were detected in the IM genome, which is a precancer of GC, supporting that some DMPs might represent an early event in gastric carcinogenesis. A pathway analysis of all DMPs demonstrated that 59 G protein-coupled receptor (GPCR) genes linked to the hypermethylated DMPs were significantly enriched in a neuroactive ligand-receptor interaction pathway. Furthermore, among the 59 GPCRs, six GI hormone receptor genes (NPY1R, PPYR1, PTGDR, PTGER2, PTGER3, and SSTR2) that play an inhibitory role in the secretion of gastrin or gastric acid were selected and validated as potential biomarkers for the diagnosis or prognosis of GC patients in two cohorts. These data suggest that the loss of function of gastrointestinal (GI) hormone receptors by promoter methylation may lead to gastric carcinogenesis because gastrin and gastric acid have been known to play a role in cell differentiation and carcinogenesis in the GI tract.

• Journal of Gastric Cancer
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• v.21 no.2
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• pp.142-154
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• 2021

Purpose: Screening image-enhanced endoscopy for gastrointestinal malignant lesions has progressed. However, the influence of the color enhancement settings for the laser endoscopic system on the visibility of lesions with higher color contrast than their surrounding mucosa has not been established. Materials and Methods: Forty early gastric cancers were retrospectively evaluated using color enhancement settings C1 and C2 for laser endoscopic systems with blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI). The visibilities of the malignant lesions in the stomach with the C1 and C2 color enhancements were scored by expert and non-expert endoscopists and compared, and the color differences between the malignant lesions and the surrounding mucosa were assessed. Results: Early gastric cancers mainly appeared orange-red on LCI and brown on BLI-bright or BLI. The surrounding mucosae were purple on LCI regardless of the color enhancement but brown or pale green with C1 enhancement and dark green with C2 enhancement on BLI-bright or BLI. The mean visibility scores for BLI-bright, BLI, and LCI with C2 enhancement were significantly higher than those with C1 enhancement. The superiority of the C2 enhancement was not demonstrated in the assessments by non-experts, but it was significant for experts using all modes. The C2 color enhancement produced a significantly greater color difference between the malignant lesions and the surrounding mucosa, especially with the use of BLI-bright (P=0.033) and BLI (P<0.001). C2 enhancement tended to be superior regardless of the morphological type, Helicobacter pylori status, or the extension of intestinal metaplasia around the cancer. Conclusions: Appropriate color enhancement settings improve the visibility of malignant lesions in the stomach and color contrast between the malignant lesions and the surrounding mucosa.

• Journal of Digestive Cancer Reports
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• v.8 no.2
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• pp.81-90
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• 2020

We performed a comprehensive meta-analysis on whether Helicobacter pylori (H. pylori) eradication can prevent gastric cancer in individuals with precancerous lesions (chronic atrophic gastritis, intestinal metaplasia, and dysplasia). The studies evaluating the effect of H. pylori eradication on gastric cancer were searched from PubMed, KoreaMed, EMBASE, and Cochrane Library. Subgroup analyses by precancerous lesions, regions and follow-up time were performed. Six randomized clinical trials were included. In the overall population, H. pylori eradication significantly decreased the risk of gastric cancer (risk ratio [RR]=0.56; 95% confidence interval [CI]: 0.41-0.77, p<0.01). Eradication therapy significantly reduced the risk of gastric cancer in Asian and group who followed up more than 10 years (RR=0.51; 95% CI: 0.35-0.73, p<0.01; I²=0%, p=0.46). However, subgroup analysis according to the precancerous lesions did not show any significant results (p>0.05). In the general population especially in Asian population, H. pylori eradication can reduce the risk of gastric cancer. The effect of the eradication treatment is remarkable upon the long-term follow-up. In contrast, there is insufficient evidence whether the eradication should be recommended for the individuals with precancerous lesions.

• Applied Microscopy
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• v.39 no.2
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• pp.117-124
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• 2009

Clonorchis sinensis is the most important widely distributed parasite of the human bile duct in East Asia and the most prevalent parasitic helminth in Korea. The prevalence rate of human clonorchiasis has remained at about 2.9% in Korea. C. sinensis induces dilatation of the duct, hyperplasia of the mucosa, metaplasia or neoplasia of the mucosal epithelium, periductal inflammation and fibrosis, and thickening of the ductal wall. Fibroblast are the most common cells in connective tissue and are responsible for the synthesis of extracellular matrix components. The fibrosis associated with chronic inflammation and injury may also contribute to cholangiocarcinoma pathogenesis, particularly through an increase in extracellular matrix components, which participate in the regulation of bile duct differentiation during development. In this study, ultrastructural changes, the distribution of lectin receptors and actin protein in cultured SD rat bile duct fibroblast after infection of C. sinensis were observed. Experimental group had been divided into four groups: normal bile duct fibroblast cultured in basal media (G1); C. sinensis infected bile duct fibroblast cultured in basal media (G2); normal bile duct fibroblast cultured in basal media containing excretory-secretory product (ESP) (G1-1); C. sinensis infected bile duct fibroblast cultured in basal media containing ESP (G2-1). Overall, once a host is infected by C. sinensis, it affects the host to the extent that sialic acid of ductal fibroblast is increased. Number of cytoplasmic process of SD rat bile duct fibroblast was increased. Actin protein and sialic acid were located in cell surface. Fibroblast induced by C. sinensis was not recovered to normal fibroblast. The cytoplasm bulk and cytoplasmic process were increased whereas the growth rate of the fibroblast of infected SD rat was reduced rather than that of normal fibroblast. In result, it inhibits fibroblast proliferation and increases actin protein on fibroblast cytoplasm, and so causes fibroblast metamorphosis and cellular mutation.

• Journal of Chest Surgery
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• v.39 no.12 s.269
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• pp.920-926
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• 2006

Background: Mortality and morbidity of anastomotic complications after esophagectomy have gradually decreased in recent years. However, swallowing difficulties and reflux symptoms after esophagogastrostomy continue to be a burden jeopardizing the quality of life. In the present study, we evaluated the quality of esophagogastrostomy by analyzing anastomotic stenosis and reflux esophagitis. Material and Method: A retrospective analysis was made in 74 patients who underwent esophagogastrostomy after esophagectomy by one surgeon between January 1995 and December 2004. 53 patients of them received endoscopic examination during follow-up($29{\pm}23.6$ months, range $5{\sim}111$ months). Reflux esophagitis and stenosis at anastomostic site were analyzed according to the techniques and locations of esophagogastrostomy. Result: The median age at the time of repair was $60.3{\pm}8.87$ years(range $39{\sim}81$ years). 23 patients received a hand-sewn esophagogastric anastomosis and 30 patients a circular stapled one. There was no significant statistical difference in terms of anastomotic stenosis(p=0.64) and reflux esophagitis(p=0.41) between the two groups. Cervical anastomosis was peformed in 26 patients and intrathoracic anastomosis in 27 patients. No significant statistical difference in anastomotic stenosis between the two groups was found(p=0.44), but reflux esophagitis was noted in 3 patients in the cervical anastomosis group and 14 patients in the intrathoracic anastomosis group(p=0.003). Conclusion: Cervical anastomosis was supposed to have a better quality of esophagogastrostomy by lowering the risk of reflux esophagitis. In the future, the comprehensive study including a patient's subjective symptom and Barrett's metaplasia should be performed in larger cases.

• Journal of Gastric Cancer
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• v.1 no.1
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• pp.55-59
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• 2001

Purpose: Several studies of an endoscopic mucosal resection(EMR) have been reported, but reports about benign protruding lesions that arise at the scar of EMR for early gastric cancer (EGC) or a gastric adenoma are rare. The purpose of this study was to elucidate endoscopic and histological characteristics of benign protruding lesions which arise at the scar of an EMR for EGC and a gastric flat adenoma. Materials and Methods: In 101 lesions (73 gastric flat adenomas and 28 EGCs) from 96 patients, 16 lesions developed new protruding lesions that arose at the scar of the EMR. We retrospectively analyzed the endoscopic findings of initial and protruding lesions, and several other clinical factors (H. pylori infection, eradication therapy, and proton pump inhibitor (PPI) or H2-blocker use). Results: 1. The mean duration until detection of the protruding lesion was 8.9 months ($1.5\∼27$). Protruding lesions arose at the scar of the EMR in 1 of 28 EGCs ($3.6\%$) and from 15 of 73 gastric flat adenomas ($20.5\%$). All of the patients were men. 2. With respect to the endoscopic findings, the shapes of the protruding lesions were as follows: 10 Yamada (Y) I, 4 Y-II, 1 Y-III, and 1 flat lesion. Histological examination of the protruding lesions revealed regenerating hyperplasia in 5 lesions, intestinal metaplasia in 5, and both in 6. 3. The incidence of these lesions was higher in cases of tubular adenomas with focal high-grade dysplasia than in cases of tubular adenomas without dysplasia (p<0.05). 4. The incidence of H. pylori infection was higher in patients ($81.7\%$) who developed a protruding lesion than in those ($51.8\%$) who did not develop (p=0.029); also, the incidence of use of PPI was higher in those patients (p=0.045). However, eradication therapy for H. pylori and duration of use of PPI or H2-blocker showed no difference between groups. Conclusions: It may be possible that the potential hyperplasia that may reside in normal mucosa surrounding EGC or a gastric adenoma might awaken during the healing process of the EMR ulcer and develop to benign protruding lesions. And, H. pylori and PPI might also be related to the development of the protruding lesions.

• Journal of Yeungnam Medical Science
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• v.16 no.2
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• pp.169-180
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• 1999

Background: Uterine cervical cancer is the most common malignant tumor of the women in Korea. This study was undertaken to evaluate the usefulness of the cervicography as a screening test of cervical cancer. Materials and Methods: Cervicography was taken from 482 women at department of obstetrics and gynecology, at Yeungnam University Hospital from March 1, 1998 to October 31, 1999. Of the 482 women, 172 women were exc1uded from the study for various reasons, and 310 women completed the study. Three-hundred and ten women had cervical cytology (Papanicolaou smear), cervicography and colposcopy, and punch biopsy was undertaken if any of the test result was abnormal. Results: The most common age group was 35-39, and 40-44, 45-49 in order and most common reason for having a screening test was regular check for cervical cancer. The mean duration from the last Pap smear was 17.1 months, and 64 women(20.4%) never had any prior screening tests. Of the 310 women, 254 women were categorized as normal or having benign disease such as cervicitis, erosion or metaplasia. Biopsy was taken from 56 patients and the results were 26 chronic cervicitis, 4 mild dysplasia, 6 moderate dysplasia, 2 severe dysplasia, 14 carcinoma in situ and 4 invasive carcinoma. The results of cytology and cervicography were well correlated(p<0.05). The sensitivity and specificity of cytology were 86.7% and 76.9%, respectively and the sensitivity and specificity of cervicography were 56.7% and 96.2%, respectively. False negative rate of cervicography(43.3%) was much higher than those of cytology(13. 3%) (p<0.05), but false positive rate of cervicography(3.8%) was much lower than that of cytology(23.1%) (p<0.05). Conclusion: It seems inappropriate to use cervicography as a single screening test for cervival cancer, but it may be an effective complementary test for cytology to lower the false negative rate of cytology.

• Journal of Life Science
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• v.11 no.6
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• pp.582-594
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• 2001

This experiment was performed to investigate the effects of sulfur dioxide on the histological changes, properties of mucosubstances and glycoconjugates of the nasal respiratory mucosa in the rat. Sprague-Dawley male rats weighing about 200~250g were divided into a control group and SO$_2$ exposed groups. Again SO$_2$ exposed groups were divided into 10 ppm, 25 ppm, 50 ppm, 100 ppm, and 200 ppm subgroups, according to concentrations of SO$_2$ and each SO$_2$exposed groups were divided into 1, 3 and 6 hours groups. For the histological changes, hematoxylin-eosin(H-E) and periodic acid Schiff's(PAS) stainings were used, and for the properties of mucosubstances, PAS, alcian blue (AB) pH 2.5, pH 2.5-PAS, AB pH 1.0 and aldehyde fuchsin (AF) pH1.7-AB pH 2.5 were used. In all the SO$_2$ exposed groups, loss of cilia and detachment of epithelial cells, vacuolation of goblet cells were observed in the respiratory epithelium while epithelial squamous metaplasia and intraepthelial mucous cells were observed in the higher concentration of SO$_2$ and the degree of the loss cilia was higher according as concentration was higher and exposed time was longer. The intraepitheial mucous cells appeared most remarkable in the 50 ppm SO$_2$ exposed group. The numbers of goblet cells and acini of nasal septal gland were varied according to concentration of SO$_2$ and exposed time, but the numbers in the 25 ppm and 50 ppm, SO$_2$ exposed increased remarkably. However, the numbers in the 100 ppm and 200 ppm SO$_2$ exposed group had a tendency to decrease noticeably, or disappeared.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.5 no.1
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• pp.1-10
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• 2002

Purpose; Dysregulation of gastric epithelial cell proliferation and apoptosis are important in development of ulcer, atrophy and neoplasia in Helicobacter pylori (H. pylori) infection. The aim of this study was to investigate the effect of infection of H. pylori on gastric epithelial cell proliferation and apoptosis in children. Methods: Histological grading by updated Sydney system, PCNA immunostaining and TUNEL method were performed in H. pylori positive (N=58) and negative (N=40) gastric biopsy specimens. Results: In H. pylori positive children, there were significantly higher grade of polymorphonuclear neutrophil activity (P=0.000), chronic inflammation (P=0.000), epithelial damage (P=0.000) and lymphoid follicles (P=0.000) than in H. pylori negative children. Intestinal metaplasia was not seen in H. pylori positive children. PCNA index was significantly different between H. pylori positive children ($67.8{\pm}18.13$) and H. pylori negative children ($54.8{\pm}14.46$, P=0.000). There was positive correlation between PCNA index and H. pylori density (r=0.277, P=0.007), polymorphonuclear neutrophil activity (r=0.280, P=0.007) and chronic inflammation (r=0.284, P=0.006). Apoptosis index of H. pylori positive children ($0.44{\pm}0.447$) was significantly higher than of H. pylori negative children ($0.14{\pm}0.196$, P=0.000). There was positive correlation between apoptosis index and H. pylori density (r=0.472, P=0.000), polymorphonuclear neutrophil activity (r=0.370, P=0.001) and chronic inflammation (r=0.483, P=0.000). There was positive correlation between PCNA index and apoptosis index (r=0.353, P=0.003). Conclusion: The PCNA and apoptosis index in H. pylori positive children were significantly higher than in H. pylori negative children. This study suggested that gastric epithelial cell proliferation and apoptosis are important to pathogenesis of H. pylori infection in children.