Gastrokine 1 Expression in the Human Gastric Mucosa Is Closely Associated with the Degree of Gastritis and DNA Methylation

PURPOSE: Gastrokine 1 plays an important role in gastric mucosal defense. Additionally, the Gastrokine 1-miR-185-DNMT1 axis has been shown to suppress gastric carcinogenesis through regulation of epigenetic alteration. Here, we investigated the effects of Gastrokine 1 on DNA methylation and gastritis. MATERIALS AND METHODS: Expression of Gastrokine 1, DNMT1, EZH2, and c-Myc proteins, and the presence of Helicobacter pylori CagA protein were determined in 55 non-neoplastic gastric mucosal tissue samples by western blot analysis. The CpG island methylation phenotype was also examined using six markers (p16, hMLH1, CDH1, MINT1, MINT2 and MINT31) by methylation-specific polymerase chain reaction. Histological gastritis was assessed according to the updated Sydney classification system. RESULTS: Reduced Gastrokine 1 expression was found in 20 of the 55 (36.4%) gastric mucosal tissue samples and was closely associated with miR-185 expression. The Gastrokine 1 expression level was inversely correlated with that of DNMT1, EZH2, and c-Myc, and closely associated with the degree of gastritis. The H. pylori CagA protein was detected in 26 of the 55 (47.3%) gastric mucosal tissues and was positively associated with the expression of DNMT1, EZH2, and c-Myc. In addition, 30 (54.5%) and 23 (41.9%) of the gastric mucosal tissues could be classified as CpG island methylation phenotype-low and CpG island methylation phenotype-high, respectively. Reduced expression of Gastrokine 1 and miR-185, and increased expression of DNMT1, EZH2, and c-Myc were detected in the CpG island methylation phenotype-high gastric mucosa. CONCLUSIONS: Gastrokine 1 has a crucial role in gastric inflammation and DNA methylation in gastric mucosa.

Neurologic Manifestations during the Course of Neuroblastoma in Children

PURPOSE: The aim of this study is to analyze the frequency and characteristics of neurologic manifestations in patients with neuroblastoma, retrospectively. METHODS: Eighty children with neuroblastoma who were diagnosed and treated in the Department of Pediatrics, Asan Medical Center between January 1995 and June 2009 were included. RESULTS: Neurologic manifestations were present in 21(26%) of the 80 children. Twelve children presented neurologic manifestations at diagnosis(lower limb paresis and bladder dysfunction in 7 children; diplopia, nystagmus and ptosis in 4 children; opsoclonus and truncal ataxia in one child). And 9 children presented neurologic manifestations during treatment(seizure in 5 children; hemiparesis in 2 children; Horner's syndrome in one child; right upper limb paresis in one child). Ten of 12 children with neurologic manifestations at diagnosis recovered and 4 of 9 children with neurologic manifestations during treatment recovered, eventually. All of the patients with neurologic manifestations at diagnosis were consistent with advanced neuroblastoma, either stage III or IV. Five of the 12 children with neurologic manifestations at diagnosis expired and 6 of the 9 children with neurologic manifestations during treatment expired. CONCLUSION: Neurologic manifestations at diagnosis suggest the high likelihood of advanced stage neuroblastoma. Neurologic manifestations during treatment may indicate poor prognosis.

A Case of Silver-Russell Syndrome Diagnosed in the Patient Admitted with Hypoglycemic Seizure

The Silver-Russell syndrome(SRS) is a clinically heterogeneous syndrome characterized by intrauterine and postnatal growth retardation with spared cranial growth, characteristic facial features, and body asymmetry. Although mild to moderate hypoglycemic symptoms occasionally appear in children with SRS especially those who are not fed frequently and regularly, hypoglycemic seizures rarely occur. We report a rare case of SRS which was diagnosed in a 4-year-old female who admitted with hypoglycemic seizure. The patient showed the characteristic features of SRS. Endocrinologic studies were normal except for partial growth hormone insufficiency. To prevent seizures and chronic neurologic deficits in children with SRS, the early recognition and appropriate management of hypoglycemia is critical.

The Usefulness of an Phadiatop(R)Infant as a Allergic Screening Test in Korean Children / 소아알레르기및호흡기학회지

PURPOSE: Atopy is a prerequisite for IgE-mediated allergic disease and also a significant prognostic factor. Phadiatop(R)Infant (phadia AB, uppsala, sweden) is a new blood test designed for the detecting the presence of IgE sensitization in young children. This study aims to investigate the usefulness of Phadiatop(R)Infant test in Korea. METHODS: Among the patients who visited Childhood Asthma Atopy Center, Asan Medical Center between January 2008 and August 2008, young children under 6 years of age who had eczema or wheezing were enrolled. Ninety-three patients were tested using specific IgE antibody tests with 6 aeroallergen including Dermatophagoides pteronyssinus (D.p), Dermatophagoides farinae (D.f), cat, dog, cockroach and alternaria, and 6 food allergen including egg, milk, soybean, wheat, fish and peanut as well as Phadiatop(R)Infant test. RESULTS: The study group was consisted of 54 males and 39 females, with a mean age of 32.4+/-20.4 months. By specific IgE antibody test, 38.7% were sensitized to aeroallergen, 53.8% to food allergen, 71% to at least one allergen. Positive rate of Phadiatop(R)Infant was 66.9%. There were 9 discrepant cases: 4 cases with positive Phadiatop(R)Infant but negative specific IgE antibody test and 5 cases with negative Phadiatop(R)Infant but positive specific IgE antibody test. The former cases except one were older than 36 months and all the latter cases were sensitized to house dust mite. The kappa value between Phadiatop(R)Infant and specific IgE antibody test was 0.768. When the age was considered, the younger children showed the better agreement rate [kappa value=0.933 (48 months)]. CONCLUSION: Phadiatop(R)Infant may be a useful screening test for atopy in Korean children, especially in younger children. It is presumed that the rates of sensitization to local inhalant allergen become higher with increasing age.

An Analysis of p53, bcl-2 and Ki-67 Expressions, and Apoptosis in Rectal Cancer: Their Correlation with the Tumor Response after Preoperative Radiochemotherapy

Background : Preoperative radiochemotherapy (RCT) has been administered for locally advanced rectal cancer to increase the therapeutic benefits, and to preserve the sphincter in low-lying tumors, however, tumor responses after RCT are variable. Methods : Apoptotic index (AI), and expressions of Ki-67, p53 and bcl-2 were analyzed in pretreatment biopsies from 69 patients with rectal cancer by immunohistochemistry. Tumor response was graded in surgically resected specimens by using a three-scale grading system: no response (NR), partial remission (PR) and complete remission (CR). Results : CR was identified in 19 cases (28%), PR in 24 cases (35%), and NR in 26 cases (38%) of 69 cases. p53 protein was expressed in 49 cases (71%), whereas bcl-2 was in 42 cases (61%). The pretreatment Ki-67 labeling index was 65.4+/-3.4%. The tumor response was not associated with any of these markers. Tumors with CR/PR showed a higher AI (0.84+/-.84%/0.66+/-.52%) than that of tumors with NR (0.58+/-0.54%). There was a significant correlation between tumor response and the histologic differentiation (p=0.008) or recurrence (p=0.039). Conclusions : The AI revealed a tendency to increase in tumors with CR/PR, while expressions of p53 and bcl-2, and Ki-67 labeling index had little direct association with tumor response.

Loss of Heterozygosity on Chromosomes 3p,8p,9p and 17p in the Progression of Squamous Cell Carcinoma of the Larynx

Previous molecular genetic studies of laryngeal squamous cell carcinoma (SCC)have shown certain chromosomal regions with recurring alterations. But studies of sequential molecular alterations and genetic progression model of laryngeal SCC have not been clearly defined. To identify the chromosomal alterations associated with the carcinogenesis of laryngeal SCC, we analyzed genomic DNA from microdissected squamous metaplasia, squamous dysplasia, invasive SCC, and metastatic carcinoma samples from 22 laryngeal SCC patients for loss of heterozygosity (LOH) at microsatellite loci. Ten microsatellite markers on chromosome 3p, 8p, 9p, and 17p were used. LOH at 9p21 was observed in the all stages including squamous metaplasia, squamous dysplasia, invasive SCC and metastatic carcinoma. LOH at 17p13.1, 3p25 and 3p14.2 was observed from the squamous dysplasia, invasive SCC and metastatic carcinoma. LOH at 8p21.3-p22 was observed mainly from the invasive SCC and metastatic carcinoma. The results suggest that 9p21 in the early event, 17p13.1, 3p25 and 3p14.2 in the intermediate event and 8p21.3- p22 in the late event may be involved in the laryngeal carcinogenesis.

Loss of Heterozygosity on Chromosome 9p21, 17p13 and 3p in Human Astrocytic Tumor

BACKGROUND: The purpose of this study was to determine the genetic abnormalities of chromosomes 9p21, 17p13.1, 3p25 and 3p14.2 in the development and progression of astrocytic tumors. METHODS: We performed loss of heterozygosity (LOH) analysis in 41 astrocytic tumors, including 20 astrocytomas, 11 anaplastic astrocytomas and 10 glioblastomas, and correlated the results of LOH at different histopathologic grades. LOH was determined by multiplex polymerase chain reaction analysis of the DNA, which was extracted by microdissection. RESULTS: LOH of 9p21 was found in 55.6% of astrocytomas, 54.6% of anaplastic astrocytomas and 100.0% of glioblastomas. LOH of 17p13.1 was found in 21.4% of astrocytomas, 28.6% of anaplastic astrocytomas, and 66.7% of glioblastomas. LOH of 3p25 was found in 37.5% of astrocytomas, 16.7% of anaplastic astrocytomas, and 14.3% of glioblastomas. LOH of 3p14.2 was found in 16.7% of astrocytomas, 40.0% of anaplastic astrocytomas, and 42.9% of glioblastomas. LOH on chromosome 9p21 and 17p13.1 was closely related with the histopathologic grades. CONCLUSIONS: These results may suggest that LOH of 9p21, 17p13.1, 3p25 and 3p14.2 involves an early event of astrocytoma development and accumulates during progression. LOH of 3p25 may be involved in the tumorigenesis of astrocytoma. Identification of these LOH may illuminate the stepwise pathogenesis of astrocytic tumors and predict the possibility of malignant transformation.

A Case of Intrahepatic Cholangiocarcinoma Developed in a Remote Region from the Site of Hepatolithiasis / 대한소화기내시경학회지

An association of hepatolithiasis and cholangiocarcinoma is thought to be rare, with a rate reported to be 2.36%-10%. Most of the cholangiocarcinomas concurrent with intrahepatic stones are found in the vicinity of the hepatolithiasis, and the diagnosis of intrahepatic cholangiocarcinoma in cases with hepatolithiasis is very difficult to detect preoperatively in spite of recent developments in techniques of imaging studies. Recently, the development of cholangiocarcinoma was reportd even after the complete removal of the hepatic stones. Thus, bile stasis and bacterial infecton appear to be important causative factors causing cholangiocarcinoma rather than the stone itself. A rare case is reported on intrahepatic cholangiocarcinoma developed in a remote region from the site of the hepatolithiasis. Therefore, the possible presence of cholangiocarcinoma should always be considered and sought during the diagnosis and treatment of hepatolithiasis.

Colorectal Rupture: an Unusual Complication of Anorectal Manometry / 대한소화관운동학회지

Anorectal manometry is now widely performed to evaluate anorectal physiology in a variety of clinical conditions. No adverse consequence related with this procedure has been reported yet. There has been no known guideline or precaution regarding the upper limit of the volume inflating the rectal balloon in measuring maximum tolerable volume. We experienced 2 cases of colorectal rupture during measuring maximum tolerable volume. Both cases were in their early postoperative period, 1 month after low anterior resection due to rectal cancer and 3 months after Delorme's procedure due to rectal prolapse, respectively. The rectal sensory and anorectal motor responses to rectal distension are known to depend on the rate and pattern of distension. Therefore, results of different examiners and laboratories cannot be compared directly unless the pattern and rate of distension are the same. Wide intersubject and intrasubject variations in maximum tolerable volume have been also reported, and differentiation between patients and normal subjects is not necessarily possible. Measuring maximum tolerable volume is painful and unpleasant, and some authors believe that maximum tolerable volume in addition to the other steps of rectal sensations does not contribute any additional information. Based on our experience and literature, we suggest that measuring maximum tolerable volume might be better to be omitted, or if it be done, rectal balloon should be inflated with great care especially in early postoperative period or in those who cannot feel or express their symptoms clearly, such as elderly or infants.

The Clinical Significance of Pancreas Divisum / 대한소화기내시경학회지

BACKGROUND/AIMS: Pancreas divisum is a congenital anomaly caused by failure of fusion of the ventral and dorsal pancreatic anlagen during the sixth and seventh week of gestation. With widespread use of endoscopic retrograde cholangiopancreatography(ERCP), pancreas divisum is being detected with increasing frequency. Pancreas divisum is the most common congenital pancreatic anatomic variant, occuring in approximately 4.7~14% of necropsy series and has been demonstrated 1.3~6.7% of patients undergoing ERCP, The condition is seen least frequently in Asian(1~2%). It has been postulated that this anomaly may be a cause of obstructive pancreatic pain and pancreatitis on the basis of impaired drainage through the minor papilla. But there is a controversy as to whether pancreas divisum is associated with an increased incidence of pancreatitis. This study is performed to evaluate the clinical presentation and significance of pancreas divisum. METHODS: 27 cases of pancreas divisum detected among 1,718 ERCP examinations performed from June, 1993 to December, 1996 at our institution were critically analyzed. RESULTS: Overall incidence of pancreas divisum was 1.6%. Among them, 13 cases(48.1%) were classified as complete type, 14 cases(51.9%) were classified as incomplete type. There was a significantly high incidence of pancreatitis, 22.2% in pancreas divisum compared with 5.6% in fused pancreas. Pancreas divisum was misdiagnosed as pancreatic head mass on radiological imaging study in 4 cases(25%). CONCLUSIONS: Pancreas divisum may be predispose to development of pancreatitis, and that its presence may lead to misinterpretation of ultrasonographic and CT scan findings.

Prediction and Management of Choledocholithiasis in Patients Undergoing Laparoscopic Cholecystectomy due to Cholelithiasis / 대한소화기내시경학회지

BACKGROUND/AIMS: Endoscopic retrograde cholangiopancreatography(ERCP) or operative cholangiography is the procedure to demonstrate and remove stones of the biliary tree in patients undergoing laparoscopic cholecystectomy(LC) due to cholelithiasis. However, ERCP or operative cholangiography is an invasive procedure. The next question then is when and for what indication should ERCP or operative cholangiography be performed. The aims of this study were to assess whether prediction of common bile duct(CBD) stones by the noninvasive method such as liver function test and/or clinical findings is possible, and to investigate which method is more adequate for removal of CBD stones found on ERCP or operative cholangiography. METHODS: A total 207 patients with symptomatic cholelithiasis scheduled for LC were enrolled from September 1993 to August 1996. Patients who were already found to have either extrahepatic or intrahepatic biliary stones on sonogram were excluded. Patients were classified into risk group and non-risk group. Patients who belong to the risk group were those having CBD dilatation by ultrasonography, history of jaundice or cholangitis, gallstone pancreatitis, or elevated transaminases. RESULTS: 54 cases were confirmed to have CBD stones by preoperative ERCP(49 cases) and operative cholangiography(5 cases). Detection rate of CBD stones in risk group was 26.8%(22.2% in CBD dilatation, 50.0% in jaundice, 42.9% in history of cholangitis, and 0% in history gallstone pancreatitis or elevated transaminase). Detection rate of CBD stones in non-risk group was 7.7%. All of 12 patients who had CBD stones were successfully removed(10 with preoperative endoscopic removal, 1 with postoperative endoscopic removal, and 1 with CBD exploration). CONCLUSIONS: Jaundice or cholangitis need the preoperative ERCP and, if stones are found, they can be revoved endoscopically. CBD dilatation may be an indication for operative cholangiography rather than preoperative ERCP, and, if CBD stones were found, they can be revoved by laparoscopic CBD exploration or postoperative ERCP. But history of gallstone pancreatitis, elevated transaminases, or patients with no risk factors may not need preoperative ERCP or operative cholangiography considering the cost-effectiveness or possible morbidity.

A Case of D-Penicillamine Induced Iga Nephropathy in a Patients with Scleroderma / 대한류마티스학회지

IgA nephropathy can occur rarely as a complication of D-penicillamine treatment, but it is exact pathogenesis remains unclear. If a patients has gross or microscopic hematuria during D-penicillamine treatment, D-penicillamine induced IgA nephropathy should be suspected as a cause of hematuria. In those cases, renal biopsy should be taken for diagnosis and proper management. We experienced a case of IgA nephropathy confirmed by renal biopsy in a 39-years-old female patient with scleroderma during D-penicillamine therapy and report this case with a review of literature.

The Efficacy and Safety of Needle-Knife Papillotomy for Endoscopic Sphincterotomy and Cholangiography / 대한소화기내시경학회지

BACKGROUND: Conventional endoscopic sphincterotomy with papillotome(CES) is an established method of management for patients with biliary obstruction from various causes. However, an alternative treatment to CES must be considered when antecedent cholangiagraphy is unsuccessful or when cannulatian with the conventional papillotome fails. The needle-knife papillotomy(NKP) is one of the alternative methods to CES. Recently, it has been suggested that NKP can be used to achieve diagnostic cholangiography. But NKP is controversial because results from studies assessing its efficacy and safety are conflicting. The current study was undertaken to assess retrospectively the efficacy and safety of NKP and CES. METHODS: All enrolled patients(CES group 113, NKP group 105) underwent ERCP between September 1993 and August 1996 at Korea Univeisity Guro Hospital. NKP for cannulation was used only when biliary tract disease was suspected but deep canulation failed inspite of several attempts. The efficacy and safety of NKP and CES were evaluated according to the rate of success of performing purposes(removal of common bile duct stones, inser tion of endoscopic nasobiliary drainage or endoprosthesis, treatment of sphincter of Oddi dysfunction, and cannulation) and complications(bleeding, perforation, pancreatitis). RESULTS: 1. Overall success rates of performing purposes were 92.9% in CES group(removal of common bile duct stones 95.2%, insertion of endoscopic nasobiliary drainage or endoprosthesis 84.6%, treatment of sphincter of Oddi dysfunction 100%) and 80.0% in NKP group(removal of common bile duct stone 86.7%, insertion of endoscopic nasobiliary drainage or endoprosthesis 80.6%, treatment of SO dysfunction 100%, cannulation 70.6%). The success rate of CES was significantly higher than that of NKP(p=0.04). 2. The morbidity rate of NKP was 10.5%(8 bleeding cases, 1 perforation case, 2 pancreatitis cases) but was not significantly different from that of rate for CES 8.0%(9 bleeding dases). 19 patients with complications recovered uneventfully with conservative treatment. Only 1 patient(ampullary carcinoma) undertwent operation due to severe bleeding after NKP. There was no procedure-related mortality in both groups. CONCLUSION: NKP is an effective endoscopic tool allowing successful endoscopic sphincterotomy when conventional technique fails. And, in carefully selelected cases, NKP is a useful aid for a successful diagnostic cholangiograph.

Primary Ovarian Leiomyosarcoma: A case report

Primary leiomyosarcoma is a rare tumor of the ovary. We experienced a case of primary ovarian leiomyosarcoma in a 68 year old woman. Microscopically, the tumor was characterized by interlacing bundles of plump spindle cells that showed immunoreactivity for alpha-smooth muscle actin, pleomorphic multinucleated giant cells and an increased mitotic rate. Ultrastructural features included abundant smooth muscle type filaments and irregular bodies. Consequently, this case has led us to propose ultrastructural and immunohistochemical criteria for primary ovarian leiomyosarcoma.

Malignant Peripheral Nerve Sheath Tumor Arising from Neurofibromatosis

A 65-year-old woman complained of a pedunculated, huge mass on the anterior chest associated with neurofibromatosis type 1. The clinical and histological data showed the possibility of a malignant peripheral nerve sheath tumor. On electron microscopy, we found the characteristic findings of a malignant peripheral nerve sheath tumor, such as the foci of en-tangled cytoplasmic processes, undifferentiated spindle cells having large pleomorphic nuclei with prominent nucleoli, distinct basal cell lamina, rudimentary cell junctions, intermediate filaments and clumps of glycogen in the tumor cells. We, herein, report a case of malignant peripheral nerve sheath tumor arising from neurofibromatosis, studied by electron microscopy.

Production of PGE2 and H2O2 from Alveolar Macrophage Stimulated by Silica / 결핵

BACKGROUND: The pathogenesis of silicosis has been focused on the interaction between alveolar macrophages and silica particle. Although fibrosis in silicosis has been studied extensively, the mechanism is still not fully understood. There is increasing evidence that monokines and arachidonic acid metabolites produced by macrophage are involved in pathogenesis of silicosis. Recently, it was reported that prostaglandin E2 produced from macrophage counteracts the stimulatory effects of other monokines on fibroblast proliferation or collagen production. Until now, it was remained uncertain by which mechanism silica particle may activate alveolar macrophage to an enhanced release of prostaglandin E2. METHODS: In order to investigate the relationship between the activity of alveolar macrophage and the production of PGE2 from activated alveolar macrophage, the authors measured hydrogen peroxide and PGE2 from alveolar macrophages activated by silica in vitro and from alveolar macrophages in the silicotic nodules from rat. Experimental silicosis was induced by intratracheal infusion of silica(SiO2) suspended in saline (50 mg/ml) in Sprague-Dawley rats. RESULTS: 1) The silicotic nodules with fibrosis were seen from the sections of rat lung at 60 days after intratracheal injection with 50 mg aqueous suspension of silica. 2) In vitro, silica caused the dose dependent increase of hydrogen peroxide(p0.05) release from alveolar macrophages. Alveolar macrophages from rats with silicotic nodules released more hydrogen peroxide and PGE2 than those of control group(p<0.05). CONCLUSION: These results suggest that silica particle could activate macrophage directly and enhanced the release of PGE2 and hydrogen peroxide from the alveolar macrophage.

Acardiac Fetus with Encephalocele: A case report

The acardiac fetus is a rare type of fetal monster in which, as the name implies, the heart is completely absent. Acardius occurs only in a pair monozygotic twin, and shows various other defects in addition to the absence of the heart. Our autopsy case is acardiac anceps. He weighed 1,980 gm and the height was 33 cm. The brain is poorly developed, 60 gm in weight and similar to reversed snowman (3.5x2.8x2.8, 1.5x1.5x1.3 cm). Encephalocele, 6 cm in diameter, was communicated with the brain by a tract which contains nervous tissue and primitive choroid plexus. The upper extremities were absent, while the vertebrae and lower extremities were relatively well developed. The heart, lungs, stomach, liver, and spleen were absent, but the kidney, genital organs and urinary bladder were present. The intestine was seperated into two segments which were blindly ended, 32 cm and 15 cm in length, respectively.

Loss of heterozygosity affecting MCC and APC loci in Korean colorectal adenocarcinomas / 대한암학회지

No abstract available.

Occult Hepatocellular Carcinoma Metastasized to Heart: A case report

We have experienced a case of occult hepatocellular carcinoma metastasized to the heart in a 41 year old female. The hepatocellular carcinoma invaded the hepatic vein, grew in a snakelike fashion up the inferior vena cava and reached the right atrium. Ultrastural examination in this case confirmed the hepatocellular origin of the tumor.