DNA Methylation Patterns of Ulcer-Healing Genes Associated with the Normal Gastric Mucosa of Gastric Cancers

Recent evidence suggests that gastric mucosal injury induces adaptive changes in DNA methylation. In this study, the methylation status of the key tissue-specific genes in normal gastric mucosa of healthy individuals and cancer patients was evaluated. The methylation-variable sites of 14 genes, including ulcer-healing genes (TFF1, TFF2, CDH1, and PPARG), were chosen from the CpG-island margins or non-island CpGs near the transcription start sites. The healthy individuals as well as the normal gastric mucosa of 23 ulcer, 21 non-invasive cancer, and 53 cancer patients were examined by semiquantitative methylation-specific polymerase chain reaction (PCR) analysis. The ulcer-healing genes were concurrently methylated with other genes depending on the presence or absence of CpG-islands in the normal mucosa of healthy individuals. Both the TFF2 and PPARG genes were frequently undermethylated in ulcer patients. The over- or intermediate-methylated TFF2 and undermethylated PPARG genes was more common in stage-1 cancer patients (71%) than in healthy individuals (10%; odds ratio [OR], 21.9) and non-invasive cancer patients (21%; OR, 8.9). The TFF2-PPARG methylation pattern of cancer patients was stronger in the older-age group (> or =55 yr; OR, 43.6). These results suggest that the combined methylation pattern of ulcer-healing genes serves as a sensitive marker for predicting cancer-prone gastric mucosa.

DNA Methylation and Expression Patterns of Key Tissue-specific Genes in Adult Stem Cells and Stomach Tissues

CpG-island margins and non-island-CpG sites round the transcription start sites of CpG-island-positive and -negative genes are methylated to various degrees in a tissue-specific manner. These methylation-variable CpG sites were analyzed to delineate a relationship between the methylation and transcription of the tissue-specific genes. The level of tissue-specific transcription was estimated by counting the number of the total transcripts in the SAGE (serial analysis of gene expression) database. The methylation status of 12 CpG-island margins and 21 non-island CpG sites near the key tissue-specific genes was examined in pluripotent stromal cells obtained from fat and bone marrow samples as well as in lineage-committed cells from marrow bulk, stomach, colon, breast, and thyroid samples. Of the 33 CpG sites examined, 10 non-island-CpG sites, but none of the CpG-island margins were undermethylated concurrent with tissue-specific expression of their nearby genes. The net methylation of the 33 CpG sites and the net amount of non-island-CpG gene transcripts were high in stomach tissues and low in stromal cells. The present findings suggest that the methylation of the non-island-CpG sites is inversely associated with the expression of the nearby genes, and the concert effect of transitional-CpG methylation is linearly associated with the stomach-specific genes lacking CpG-islands.

Comparison of Quantitative Results among Two Automated Rapid Plasma Reagin (RPR) Assays and a Manual RPR Test / 대한진단검사의학회지

BACKGROUND: We compared two automated Rapid Plasma Reagin (RPR) assay kits with a manual RPR assay kit to evaluate the possibility of using the two automated RPR assays as an alternative to the manual RPR assay for a quantitative monitoring. METHODS: One hundred eighty-five samples were analyzed, including 16 sera from patients with primary, secondary, and latent syphilis. Measured RPR unit (R.U.) values of two automated RPR assay kits, Mediace RPR (Sekisui Chemical Co., Ltd, Japan) and HBi Auto RPR (HBI Co., Ltd, Korea), were compared with the RPR titers of Macro-Vue RPR card test (Becton Dickinson BD Microbiology systems, USA). As a confirmatory test, Anti-Treponema pallidum EUROLINE WB (IgG) and Anti-Treponema pallidum EUROLINE WB (IgM) (Euroimmun, Germany) were used. RESULTS: There was a prozone effect with Mediace RPR at RPR titer (card test) of 1:16, but not with HBi Auto RPR. The R.U. values of the two automated RPR assays did not show proportional increase to the RPR titer. Agreement between manual RPR and two automated RPR assay kits, Mediace RPR assay and HBi Auto RPR assay, were 83.8% and 83.2%, respectively. CONCLUSIONS: The two automated RPR assay kits could not be used as an alternative to manual RPR test for quantitative analysis of RPR titer. As Mediace RPR shows a prozone effect at relatively low RPR titer, caution is needed in the interpretation of the measured values.

Intracystic Papillary Carcinoma in the Male Breast: A Case Report / 한국유방암학회지

Intracystic papillary carcinoma of the breast is a variant of ductal carcinoma in situ (DCIS) characterized by the presence of papillary carcinoma within a cystically dilated duct. DCIS of the male breast is an uncommon disease, accounting for approximately 7% of all male breast carcinomas. Most DCIS in men is of the papillary type. We experienced one case of intracystic papillary carcinoma in the right breast of a 49-yr-old male and report the case with a review of the literature.

A Case of Eosionophilic Gastroenteritis Involving EntireGastrointestinal Tract with Eosinophilic Ascites / 대한소화기내시경학회지

Eosinophilic gastroenteritis is a rare condition of unknown cause characterized by pheripheral eosinophilia and eosinophilic infiltration of the gastrointestinal tract. Eosonophilic gastroenteritis is generally classified according to the layer of the gastrointestinal tract that is involved. Serosal eosinophilic infiltration is the rarest form of presentation and can result in the development of eosinophilic ascites. We experienced a case of eosinophlilic gastroenteritis involving the entire gastrointestinal tract in a 34-year-old female patient with abdominal pain that was confirmed by multiple biopsies of the gastrointestinal tract with eosinophilic ascites. The patient was successfully treated with corticosteroids. We report this case with a brief review of the literature.

Borderline Clear Cell Adenofibromatous Tumors of the Ovary: Two Case Reports

Borderline clear cell adenofibromatous tumors are rare with only 26 cases reported in the English literature. Five of these cases exhibited microinvasion and 4 demonstrated intraepithelial carcinoma. We report 2 cases, one typical case and the other with microinvasion. The histological findings revealed widely spaced and focally crowded, variably-sized atypical glands or tubules lined by clear, eosinophilic or hobnail cells set in a dense fibrous stroma. One of the two cases had small solid nests or single cells in the stroma around the proliferative glands less than 1 mm in length that was considered to be a microinvasion.

Comparison of Two Plastic Vacuum Tubes and Glass Tube for Use in Thyroid Hormone Tests / 임상검사와정도관리

BACKGROUND: Plastic tubes have recently been used for blood collection tubes in clinical laboratories. The silicone coated plastic tube is said to be very similar with the glass tube and to show no difference with the glass tube in routine blood test except for some tests such as hormone tests and drug monitoring. So, we investigated the influence of plastic tube on the thyroid hormone test using two types of plastic vacuum tubes. METHODS: A total of 105 cases for the total triiodothyronine (T3), total thyroxine (T4), and thyroid stimulating hormone (TSH) were studied. The glass tube was a plain glass tube, and the plastic tube was a serum separator tube with gel. The plastic vacuum tubes used in this study were the SST II plus tube (Becton Dickinson, Franklin Lakes, USA) and the Vacuette tube (Greiner Bio-One, Kremsmunster, Austria). An IMMULITE 2000 analyzer (Diagnostic Products Corporation, Los Angeles, USA) was used to measure the total T3, total T4 and TSH. RESULTS: Comparisons of the measured values within 1 hour of blood collection in the plastic tube with that in the glass tube are as follows. There was no difference between the Vacuette tube and the glass tube for the three tests, while there was statistically significant difference between the SST II plus tube and the glass tube for the total T3 and total T4. CONCLUSIONS: It might need more cautious interpretation of the results by a solid-phase, competitive chemiluminescent enzyme immunoassay, when the plastic vacuum tube is used as a blood collection tube instead of the glass tube.

Evaluation of BD Lab Reagents for Chemistry Analyzers / 임상검사와정도관리

BACKGROUND: Many modern chemistry analyzers are open systems and they can use reagents other than those supplied by the manufacturer of the analyzer. There are many generic reagents for use in open systems. The objective of this study was to evaluate the analytical performance of the BD Lab reagents (BD Lab co., Korea) which were generic reagents. METHODS: Sixteen kinds of reagents of total protein, albumin, blood urea nitrogen (BUN), creatinine, glucose, uric acid, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, alkaline phosphatase (ALP), lactate dehydrogenase (LD), gamma glutamyl transferase (GGT), calcium, inorganic phosphorus, total cholesterol, triglycerides were tested for precision, linearity and correlation according to the NCCLS guidelines (EP5-A, EP6-A, EP9-A2). Toshiba 200-FR Neo (Toshiba Medical Systems Co., Japan) was used in this evaluation. RESULTS: All reagents showed acceptable precision with total coefficients of variation less than 7%. Comparison of BD Lab reagents with the current reagents by regression analysis resulted in slopes ranging from 0.86 to 1.06 and correlation coefficients more than 0.975. Fifteen of sixteen reagents showed good linearity in broad range. CONCLUSIONS: BD Lab reagents showed good precision, linearity, and correlation. Therefore, we conclude that the BD Lab reagents can be an alternative of currently used reagents in chemistry analyzers.

Comparison of Common Clinical Chemistry Analyte Levels between Greiner Bio-One Vacuette Tube and Glass Tube / 임상검사와정도관리

BACKGROUND: Serum separator tubes were introduced 25 years ago and are widely used in the clinical laboratory for collection of blood. Recently, the plastic serum separator tube has become available for blood collection for lightening and flexibility and suitability for automation. However few studies have been reported on stability of the common analytes in this tube. METHODS: We evaluated the concentrations of seventeencommonly ordered analytes: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein, albumin, sodium, chloride, calcium, phosphorus, triglyceride, low density lipoprotein (LDL)-cholesterol, potassium, uric acid, blood urea nitrogen (BUN), total cholesterol, glucose, creatinine in sera separated in plain glass tubes (no gel) and in sera separated in the plastic Greiner Bio-One Vacuette tubes containing serum separator gel (Greiner Bio-One, Kremsm?nster, Austria) by Toshiba 200-FR Neo. RESULTS: Results were analyzed using two-tailed paired t-tests and Bland-Altman plots. Results from 9 common analytes (glucose, total cholesterol, BUN, potassium, LDL-cholesterol, inorganic phosphorus, calcium, sodium, chloride) were statistically different between glass tube and plastic Greiner Bio-One Vacuette tube, but the differences were not considered to be clinically significant. CONCLUSIONS: We conclude that the plastic Greiner Bio-One Vacuette tubes are suitable for collection of blood and storage of serum for common analytes.

Acute Myocardial Infarction Associated with Secondary Hypertension by Renal Juxtaglomerular Cell Tumor

Most patients with hypertension and no definable cause are said to primary or essential hypertension, while other patients with hypertension and specific causes are siad to secondary hypertension. Approximately 5% fo patients with hypertension have specific causes. The patients of secondary hypertension should not be ignored for the reason: The elimination of cause for hypertension can normalize the blood pressure. Juxtaglomerular cell tumor is a rare condition of secondary hypertension, with only approximately 70 cases reported to date. The higher the level of blood pressure, the most likely that various cardiovascular diseases will develop prematurely through acceleration of atherosclerosis. But Acute myocardial infarction in young hypertensives has been reported rarely. We describe the rare case of a young patient with acute myocardial infarction associated with secondary hypertension by renal juxtaglomerular cell tumor.

The Expression of Matrix Metalloproteinase-9 and Tumor Angiogenesis in Human Osteosarcoma

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is a matrix-degrading enzyme that's believed to play a crucial role not only for tumor invasion and metastasis, but also for a variety of stromal reactions, including neovascularization. The aim of this study was to investigate the expression of MMP-9 and to compare its expression with the angiogenesis activity in human osteosarcoma. METHODS: Archival tumor tissue samples from 20 patients with osteosarcoma were analyzed by performing immunohistochemistry for the expression of MMP-9 and CD34. The vascularity was measured as the average microvascular density (MVD) of the CD34-positive vessels. The clinical information was obtained through searching the computerized retrospective database from the tumor registry. RESULTS: MMP-9 was expressed in 90% (18/20) of the tumors we examined. The MVD ranged from 10.5 to 179.7 with a mean of 64.9. There was no significant correlation between the MMP-9 expression and the MVD (p=.613). The MMP-9 expression was not associated with any of the clinicopathologic variables, whereas the MVD showed an increasing tendency according to the metastasis status (p=.073). CONCLUSIONS: We demonstrated that MMP-9 activation is likely to occur in human osteosarcoma. However, there was no direct involvement of MMP-9 with tumor angiogenesis. It is noteworthy that MVD may aid physicians to predict the presence of distant metastasis in osteosarcoma patients.

A case of Crohn disease presenting as intussusception / 대한내과학회지

Intussusception is unusual in adults and rarely reported in patients with Crohn disease. There are a few reports that patients with Crohn disease had intussusception, but all the reported cases have occurred in adult patients who have had prior surgery due to complications of Crohn disease or in children with no prior surgery. We have experienced a case of 51-year-old man who was presented with acute abdominal pain without any other gastrointestinal symptoms, such as hematochezia, diarrhea. Emergency surgery was performed, because there was an evidence of a small intestinal obstruction in the CT scan, resulting from enteroenteric intussusception. The pathologic report was Crohn disease. In this case, the first manifestation of the Crohn disease was an intussusception leading to a small intestinal obstruction. It is worth to report a case of enteroenteric intussusception in an adult with no prior history of Crohn disease or surgery. We believe that this is the first case report of Crohn disease showing intussusception as its first manifestation in Korea.

Genetic Classification of Breast Cancer based on Unilateral Chromosomal Loss / 한국유방암학회지

PURPOSE: The extent of the loss of heterozygosity (LOH) has been used as the genetic parameter for the classification and staging of some solid tumors. Breast cancers such as ductal carcinoma in situ (DCIS), and invasive and metastatic lesions, are frequently observed to contain heterogeneous tumor foci. To delineate the relation between the LOH and the progression of breast cancers, three successive histological sites in a tumor lesion were analyzed for LOH events. METHODS: We tested 111 tumor site including DCIS, and invasive, and metastatic lymph nodes from 50 breast cancers for LOH using 5 microsatellite makers on 8 chromosomal arms (3p, 4p, 5q, 8p, 9p, 13q, 17p, & 18q). RESULTS: Twenty-four of 34 breast cancers showing intratumoral histological heterogeneity had common chromosomal losses in the heterogeneous tumor sites, as well as having divergent losses that were restricted to a part of tumor lesion (mean divergent loss, 2.32). The number and frequency of heterogeneous chromosomal losses were not significantly related with age, tumor size, and stage. Overall, at least one chromosomal loss was detected in 48 cases, and incidences of LOH in each chromosome were 27.1~63.3%. A large fraction (58%) of breast cancer patients had 2 to 4 chromosomal losses, and chromosome 8p was most frequently lost (63%). When comparing the number of chromosomal losses in nine cases with all of three progressive lesions, the lost extent was greater in the DCIS (mean losses, 4.44) than in the invasive sites (mean losses, 3.1) and the metastatic lymph nodes (mean losses, 2.9). Moderate-level chromosomal losses involving 3-5 chromosomes were significantly related with lymph node metastasis (p=0.006) and the advanced tumor stage (p<0.005), whereas low-level losses involving 1~2 chromosomes and high-level losses involving 6~7 chromosomes were more common in DCIS and early-stage diseases. CONCLUSION: The DCIS, invasive, and metastatic sites of a breast cancer patient contained common and divergent chromosomal losses. This indicates the concurrent expansion of different subclones was derived from a common ancestor clone, in which an optimal range of chromosomal losses, rather than high-level chromosomal losses, was more frequently associated with lymph node metastasis and the advanced tumor stages.

A case of mixed prolactin and growth hormone-secreting pituitary microadenoma presenting galactorrhea / 대한내과학회지

We report a case of galactorrhea with acromegaly from the mixed prolactin and GH secreting pituitary microadenoma managed with a successful surgical complete removal. A 31-year-old woman visited our hospital complaining galactorrhea for more than 6 months after delivery. The physical findings of the patient were a prominent galactorrhea and mild acromegalic features of face and extremities. The laboratory findings of hematology and blood chemistry were normal. In addition, the basal levels of prolactin and GH were slightly elevated. The thyroid is in euthyroid state. The results of the combined anterior pituitary hormone-stimulation tests were that the prolactin and GH responses were stimulated exaggeratedly and the other hormonal ones were normal responses. The oral glucose loading test for acromegaly revealed non-responder results. The sellar MRI showed the 6 X 5 mm-sized pituitary microadenoma. She was operated for surgical removal of the lesions of which the immunohistochemistry findings were consistent with the positive findings for both prolactin and GH. She discharged without post-operative complication and has done well with normalized hormonal levels at outpatient department.

Fate of Atrial Myocardium in Severe Mitral Regurgitation in the Aspect of Programmed Cell Death

BACKGROUND AND OBJECTIVES: From the view point of the molecular aspects, the fate of long standing pressure and volume overloaded atrium in severe MR has not been evaluated. This study was performed to elucidate whether apoptosis of right atrial myocytes is related to atrial changes. SUBJECTS AND METHODS: The medical records of 16 patients (M: F=8: 8, mean age=52+/-12), with severe MR having undergone valve replacement surgery, were retrospectively reviewed. The subjects were divided into 2 groups according to the duration of their symptoms (group I, symptom duration less than 12 months, n=10 and group II, more than 12 months, n=6). Using the atrial myocardium specimens obtained during surgery, TUNEL assays and immunohistochemical staining were performed for the expressions of Fas, Bax and the Bcl family. RESULTS: Apoptotic indices of TUNEL assay were 31.1+/-12.6 and 4.9+/-4.3% in groups I and II, respectively (p<0.01). The Fas expressions were 42.1+/-14.4 and 27.8+/-10.5% in groups I and II, respectively (p<0.05), but in group I, with atrial fibrillation (AF), was 49.3+/-6.9%, which was higher than the 29.2+/-12.5% in group I without AF and group II (p<0.001). The Bax expression in group I patients with a left atrial size less than 4 cm was 19.2+/-10.7%, which was higher than the 7.2+/-6.2% in group I with a left atrial size more than 4 cm and group II (p<0.05). CONCLUSION: Programmed cell death of the atrial myocardium, in severe MR, might be an early molecular pathological change rather than the late sequelae. The causality between programmed cell death and electrical and structural changes of the atrium should be further investigated.

A Case of Desmoplastic Nevus / 대한피부과학회지

Desmoplastic nevus, a benign melanocytic neoplasm characterized by predominantly spindle-shaped nevus cells within a fibrotic stroma without junctional activity, nesting, or pigmentation, can be confused with fibrous lesions and other melanocytic proliferations, including desmoplastic melanoma. We report a rare case of desmoplastic nevus occurring in the left helix of the ear of a 25-year-old woman, which has typical histopathologic features of desmoplastic nevus.

Omental Cyst

An omental cyst is an uncommon intra-abdominal tumor. The pathogenesis of omental cysts are unknown, as the majority are asymptomatic and if found at all are discovered incidentally during abdominal exploration or radiologic examination. A correct preoperative diagnosis of an omental cyst is very difficult as the information provided by CT and ultrasound imaging is often insufficient to support a differential diagnosis. However, with the increasing availability of ultrasound and CT, preoperative diagnoses of omental cysts are being made more frequently. An exception to this occurs in children, in whom abdominal pain secondary to the cyst may be dominant, necessitating surgical intervention. The most common symptoms and physical findings are abdominal pain and a smooth, non-tender, mobile, palpable mass. Recently, we encountered a case of an omental cyst in a surgically removed omentum. This case is reported with a review of the literature.

Effects of Delayed Test, Hemolysis and Turbidity on Measurement of PT and aPTT / 대한임상병리학회지

BACKGROUND: Sometimes we receive specimens collected several hours ahead, hemolyzed, or turbid. To decide to analyze the samples or not, the influence of storage time, hemolysis, and turbidi-ty on PT and PTT were studied. METHODS: Total of 198 cases for PT and 192 for aPTT were studied to clarify the effect of storage time on PT and aPTT. We performed the tests of PT and aPTT at 0, 2, 4, and 8 hours after collection of specimens. For the hemolysis effect study, we used 31 cases. Slightly, moderately, and severely hemolyzed plasma were obtained by adding hemolysate to plasma. For the turbidity effect study, we used 30 cases. Slightly, moderately, and severely turbid plasma were obtained by adding Intrali-pos (20% soybean oil) to plasma. RESULTS: Delayed test time affected the aPTT results after 8 hours. Hemolysis affected the PT and aPTT results. Turbidity did not affect the PT and aPTT results; however, the Coagrex-100s rejected to analyze the severely turbid samples. CONCLUSIONS: It is recommended that specimens be evaluated immediately or within 4 hours and that hemolysed or severely turbid specimens for PT and aPTT tests not be used.

Primary Choriocarcinoma of the Stomach: A Case Report

A case of primary gastric choriocarcinoma with multiple liver metastases is described. A 54-year-old man underwent gastrectomy for an advanced cancer. An ulcerofungating tumor with extensive hemorrhagic necrosis was found in the anterior wall of the prepyloric antrum. The histologic examination revealed a biphasic pattern composed of uninucleated cyto or intermediate trophoblasts and syncytiotrophoblasts. A small area of the adenocarcinoma forming glandular structures and poorly differentiated solid sheets was also noted on the superficial portion of the tumor. Immunohistochemical staining for the beta human chorionic gonadotropin (-hCG) and the human placental lactogen (hPL) showed strong immunoreactivity, particularly in the cytoplasms of the syncytiotrophoblasts and intermediate trophoblasts, respectively. A diagnosis of the choriocarcinoma was made. Multiple hepatic nodules consistent with metastases were noted on the abdominal sonogram. The serum -hCG level of the patient was significantly increased.

Juxtaglomerular cell tumor of the kidney: a case report

We report a case of renin-secreting juxtaglomerular cell tumor which developed in a hypertensive 47-yr-old Korean man. Presumptive clinical diagnosis was made before surgery based on the high level of plasma renin and the radiologic evidence of renal mass. Grossly, a round, bulging, well-encapsulated mass of 3x3 cm was located in the mid-portion of the right kidney. On microscopic examination, the tumor was composed of ovoid to polyhedral cells with bland nuclei, indistinct nucleoli and light eosinophilic cytoplasm. The immunostaining for renin showed strong positivity in the cytoplasm of tumor cells. The characteristic rhomboid shaped renin protogranules were observed in ultrastructural analysis.