Eun Joo Seo

Methylation of p16INK4A and p57KIP2 are involved in the development and progression of gastric MALT lymphomas

p16INK4A and p57KIP2 are inhibitors of cyclin-dependent kinases and their inactivation by methylation has been reported as a major tumorigenic mechanism in tumors. To examine whether methylation of p16INK4A and p57KIP2 is involved in the development and progression of gastric MALT lymphomas, 24 gastric low-grade lymphomas of MALT, 11 diffuse large B-cell lymphomas, and 10 each case of gastric lymphoid follicles with and without Helicobacter pylori infection were studied. H. pylori infection was positive in 85.7% of the gastric lymphomas. In the gastric lymphoid follicles positive for H. pylori, methylation of p16INK4A was detected in 10% of cases, while methylation of p57KIP2 was not detected. In low-grade MALT lymphomas, p16INK4A and p57KIP2 were methylated in 41.7 and 29.2% of the cases, respectively. In diffuse large B-cell lymphomas, methylation of p16INK4A and p57KIP2 was found in 72.7 and 36.4% of the cases, respectively. All but one case with p16INK4A and p57KIP2 methylation was H. pylori positive and most of them were stage I. Our results indicate that methylation of p16INK4A followed by p57KIP2 methylation involves during the tumorigenesis of gastric MALT lymphomas associated with H. pylori infection. As methylation of these two genes was more frequent in the higher grade (P<0.05), it may contribute to the malignant progression of gastric MALT lymphomas.

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

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.

Nasal Angiocentric Lymphoma With Hemophagocytic Syndrome

Objectives Hemophagocytic syndrome(HS) is a fatal complication of nasal angiocentric lymphoma (AL) and difficult to distinguish from malignant histiocyosis. Epstein-Barr virus(EBV)-associated HS is frequently observed in lymphoma of T-cell lineage and EBV is highly associated with nasal AL. Clinicopathologic features of 10 nasal ALs with HS were reviewed to determine the clinical significance and the pathogenetic association with EBV. Methods Ten patients of HS were identified from a retrospective analysis of 42 nasal ALs diagnosed from 1987 to 1996. Immunohistochemical study and in situ hybridization were performed on the paraffin-embedded tumor specimens obtained from 10 patients. Serologic study of EBV-Ab was performed in 3 available patients. Results Five patients had HS as initial manifestation, 3 at the time of relapse and 2 during the clinical remission of AL. Four patients were treated by combination chemotherapy (CHOP) and others had only supportive care. The median survival of all patients with HS was 4.1 months (range 2 days–36.5 months) and all had fatal outcome regardless of the treatment-modality. AH cases were positive for UCHL1 (CD45RO) and EBV by EBER in situ hybridization. The data of serologic tests indicated the active EBV infection. Conclusions HS is a fatal complication of nasal AL and has a high association with EBV. Reactivation of EBV may contribute to HS and further investigation of predictive factors and effective treatment of HS should be pursued in the future.

Erdheim-Chester Disease With Lung Involvement Mimicking Pulmonary Lymphangitic Carcinomatosis

Erdheim-Chester disease (ECD) is a rare proliferative non-Langerhans cell histiocytosis of multiple organs with unknown etiology. Around 20% of ECD cases are reported to be associated with lung involvement and there are very few cases manifested solely by nonspecific respiratory symptoms. A 50-year-old woman presented with dry cough and dyspnea for 2 weeks. Chest computed tomography (CT) revealed diffuse interlobular septal and fissural thickening with perilymphatic and subpleural nodular opacities, suggesting pulmonary lymphangitic spread of metastatic carcinoma. Bone scintigraphy and positron emission tomography/CT showed multiple skeletal and lymph node involvement. The patient underwent surgical lung biopsy and the pathologic feature was consistent with ECD. We describe this case to emphasize that ECD should be included in the differential diagnosis of cases suspected to have lymphangitic lung carcinomatosis. Moreover, the findings of positron emission tomography/CT scan, which showed hot uptakes in the affected areas, are also described.

Increased Expression of Connexin43 on the Aortic Valve in the Hypercholesterolemic Rabbit Model

Background: Aortic valve sclerosis is associated with increased risk of cardiovascular death and myocardial infarction. However, the relevance of connexin43 in aortic valve sclerosis remains unclear. We hypothesized that the mechanism regulating aortic valve sclerosis is associated with the alteration of cell-to-cell communication. Methods: Twenty male New Zealand rabbits were divided into two groups. Group 1 (n = 10) were fed a normal chow diet, while those in group 2 (n = 10) received a diet containing 1% cholesterol for 12 weeks. After utanizing the animals, the aortic valves were excised for analysis. Results: Myofibroblasts and macrophages were more highly expressed in the cholesterol diet group. Osteopontin and connexin43 were found to concentrate within the endothelial layer on the aortic side of the valve leaflets in the cholesterol diet group. A real-time polymerase chain reaction revealed increased connexin43 and osteopontin mRNA levels in the hypercholesterolemic aortic valves. Conclusions: The present study demonstrates that hypercholesterolemia increases the expression of connexin43 in the rabbit aortic valve. The results suggest that alterations in gap junctional intercellular communication via connexin43 gap junctions may play a role in the development of aortic valve sclerosis.

Myocardial infarction in a young female with reninoma induced hypertension and myocardial bridging

We present a case of myocardial infarction in a young female with reninoma induced hypertension and myocardial bridging. Reninoma is a rare and curable cause of secondary hypertension. Currently developed multi-detector computed tomography (MDCT) has permitted better evaluation of myocardial infarction and myocardial bridging. Myocardial infarction associated with reninoma and myocardial bridging has not been reported, and we report this interesting case.