Association between the MUC1 rs4072037 Polymorphism and Risk of Gastric Cancer and Clinical Outcomes

Purpose@#Mucin 1 (MUC1) was identified as a gastric cancer (GC) susceptibility gene by genome-wide association studies in Asians and candidate gene studies in Europeans. This study aimed to investigate the association between the MUC1 rs4072037 polymorphism and GC in terms of the Lauren classification and long-term clinical outcomes. @*Materials and Methods@#A total of 803 patients with GC and 816 unrelated healthy controls were enrolled in the study. The association between the MUC1 rs4072037 variant and GC histological types and clinical outcomes, including tumor recurrence and prognosis was investigated. @*Results@#The major A allele of rs4072037 was associated with increased GC risk (P0.05). Cox proportional hazards analysis revealed the heterozygote AG rs4072037 allele as an independent risk factor influencing tumor recurrence and disease-related death in diffuse-type GC (P0.05). @*Conclusions@#The exonic single nucleotide polymorphism rs4072037 in MUC1 was associated with diffuse-type GC and was an independent risk factor influencing tumor recurrence and disease-related death in diffuse-type GC.

A Case of Behçet's Disease Mimicking Vertebral Invasion of a Mycotic Aneurysm / 대한내과학회지

Behçet's disease is a systemic vasculitis of unknown etiology characterized by recurrent oral and genital ulcers and uveitis. The vascular involvement of Behçet's disease affects arteries, veins, and blood vessels of all sizes, and it can include venous or arterial thrombosis and arterial aneurysms. There are only a few reports of an aortic aneurysm invading a vertebral body in a patient with Behçet's disease. Here, we report the case of a 45-year-old man who was initially diagnosed with vertebral invasion of a mycotic aneurysm. He underwent vascular surgery and received empirical antibiotics, but all cultures were negative. However, he had persistent, recurrent deep vein thrombosis and elevated inflammatory markers. After reviewing the pathology, a final diagnosis of Behçet's disease was made. He was successfully treated with corticosteroids. This report presents a rare case of Behçet's disease mimicking vertebral invasion of a mycotic aneurysm.

Is Whole Exome Sequencing Clinically Practical in the Management of Pediatric Crohn's Disease?

BACKGROUND/AIMS: The aim of this study was to identify the profile of rare variants associated with Crohn's disease (CD) using whole exome sequencing (WES) analysis of Korean children with CD and to evaluate whether genetic profiles could provide information during medical decision making. METHODS: DNA samples from 18 control individuals and 22 patients with infantile, very-early and early onset CD of severe phenotype were used for WES. Genes were filtered using panels of inflammatory bowel disease (IBD)-associated genes and genes of primary immunodeficiency (PID) and monogenic IBD. RESULTS: Eighty-one IBD-associated variants and 35 variants in PID genes were revealed by WES. The most frequently occurring variants were carried by nine (41%) and four (18.2%) CD probands and were ATG16L2 (rs11235604) and IL17REL (rs142430606), respectively. Twenty-four IBD-associated variants and 10 PID variants were predicted to be deleterious and were identified in the heterozygous state. However, their functions were unknown with the exception of a novel p.Q111X variant in XIAP (X chromosome) of a male proband. CONCLUSIONS: The presence of many rare variants of unknown significance limits the clinical applicability of WES for individual CD patients. However, WES in children may be beneficial for distinguishing CD secondary to PID.

Lamin A/C mutations associated with familial and sporadic cases of dilated cardiomyopathy in Koreans

Dilated cardiomyopathy (DCM) is characterized by cardiac dilation and systolic dysfunction. So far sixteen genes have been shown to cause autosomal dominant familial dilated cardiomyopathy (FDC). We identified a large Korean family from the Jeju island showing a clear Mendelian inheritance of FDC. A genomewide linkage scan at 9 cM marker density identified a peak multipoint LOD score of 2.82 at D1S195. Haplotyping of the region with 15 additional markers defined a candidate interval that included a known candidate gene encoding the lamin A/C (LMNA). Sequencing of the LMNA exons revealed one missense mutation at C568T (Arg190Trp) in the alpha-helical rod domain of the LMNA gene cosegregating with FDC with conduction-system disease. The same mutation was found in patients of another Korean family with FDC without conduction-system disease. Upon screening 14 sporadic DCM cases, we found three LMNA mutations including a case having a previously described (Glu161Lys) mutation and two having novel mutations (Glu53Val and Glu186Lys). Our results suggest that variable genotypes of laminopathy are implicated in not only familial but also considerable proportion of sporadic DCM.

Bronchiolitis Obliterans Organizing Pneumonia:Clinicopathologic Review of a Series of 45 Korean Patients Including Rapidly Progressive form

Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinicopathological syndrome associated with a variety of disease entities. The aim of this study was to review cases with initial diagnosis of BOOP applying uniform histopathologic criteria, and analyze the clinical characteristics of proven cases of BOOP including rapidly progressive form. A total of 81 cases, initially diagnosed as BOOP and with available tissue sections, was collected. Thirty six cases (44.4%) were excluded from the study, more than two thirds of which were given a revised diagnosis of interstitial pneumonitis/fibrosis other than BOOP. Thirty one patients were classified as idiopathic BOOP, 8 patients as secondary BOOP, and 6 patients as rapidly progressive BOOP. Open lung biopsy specimen from all six cases with lethal outcome showed more severe interstitial inflammation and septal fibrosis and/or alveolar exudate with a varying degree than those with good prognosis. There was no difference by the sexes. The two most frequent presenting symptoms were cough and dyspnea. Bilateral multifocal consolidation was a common radiological finding. More than 70% cases of idiopathic BOOP experienced clinical improvements. The diagnosis of BOOP is usually suggested by clinicoradiologic findings, but needs to be confirmed histopathologically, preferably through surgical open or video-assisted thoracoscopic biopsy.

Cardiac Sarcoidosis Treated by Cardiac Transplantation: A Case Report

Sarcoidosis, in general, has a low mortality rate. But cardiac sarcoidosis (CS) is a serious condition which may lead to death. Here, we report a rare case of CS that was treated by heart transplantation. A 47-year-old male had occasional syncopes and atypical chest pain. Ventricular tachycardia with right bundle branch block was noted by electrocardiogram. Multiple fixed myocardial perfusion defects in the interventricular septum and both the inferior-posterior ventricular walls were observed by thallium scan. Coronary angiography was unremarkable. Neither perihilar nor mediastinal lymphadenopathy was noted. The patient also suffered three times from tonic-clonic generalized seizures in 3 years, but no neurologic abnormalities were detected. The explanted heart displayed multiple white patches on the endomyocardial surface, measuring up to 8x7 cm. On microscopic examination, the lesion consisted of multiple well-formed and confluent granulomas with numerous scattered multinucleated giant cells, CD68-positive epithelioid histiocytes, and T-lymphocytes. Neither microorganisms nor foreign material was identified on special stain and culture study. It has been six months since the heart transplant, and the patient has been doing well.

An Imported Case of Intestinal Capillariasis Presenting as Protein-Losing Enteropathy

Intestinal capillariasis is caused by a small trichurid nematode, Capillaria philippinensis, which infects freshwater fish as intermediate hosts and subsequently fish eating birds as definitive hosts. It has occurred in areas such as the Philippines and Thailand where people eat raw fish. We report an imported case of intestinal capillariasis in a 31-year-old Korean man who lived in Saipan for ten years. He suffered from diarrhea with weight loss, abdominal distension, and pitting edema in the lower extremities for two years. He ate raw freshwater fish in the Saipan 2 years ago. The diagnosis was confirmed by jejunal biopsy. Flat mucosal surface without villi contained sections of numerous round worms with stichosome, larvae, and eggs which were identified as Capillaria philippinensis. The patient was successfully treated with albendazole.

The first imported case of pulmonary coccidioidomycosis in Korea

Coccidioidomycosis is an endemic disease found in the southwestern part of North America. Travellers who visit the endemic area may carry the infection. We report a case of pulmonary coccidioidomycosis in a 74-year-old woman. She was healthy before visiting Arizona, U.S.A twice. After returning home, she began to complain of intermittent dry coughing. The symptom was mild, however, and she was treated symptomatically. Later a chest radiograph, which was taken 4 years after the onset of the symptom, showed a solitary pulmonary nodule in the right upper lobe. By percutaneous needle aspiration, a few clusters of atypical cells were noted in the necrotic background. A right upper and middle lobectomy was done. A 1.5 x 1.5 x 1.2 cm sized tan nodule was present in otherwise normal lung parenchyma. Microscopically, the nodule consisted of aggregates of multiple solid granulomas inside of which was mostly necrotic. Neutrophils and nuclear debris were scattered along the periphery of the necrotic foci. Numerous multinucleated giant cells were associated with the granulomas. In the necrotic area, mature spherules of Coccidioides immitis, which were 30-100 microm in diameter, were present. They contained numerous endospores which ranged from 5 to 15 microm and were also noted in multinucleated giant cells. The diagnosis of coccidioidomycosis was made. She is doing well after the resection.

Morphological and biochemical analysis of anti-nuclear matrix protein antibodies in human sera

Autoimmune sera have been used in the diagnosis of autoimmune diseases as well as the analysis of nuclear substructures. In an attempt to study the biological characteristics of the nuclear matrix, we screened human sera using immunofluorescent staining and immunoblot. We detected antibodies against nuclear matrix (NM), a remnant nonchromatin protein compartment after the treatment of detergent, salt and nuclease, in 212 out of 284 tested sera (74.6%) by immunoblot. Peptides with molecular weights of 70 kDa, 50 kDa and 25 kDa were detected in the order of frequency. Clinical informations of 198 out of 212 cases were available and went as follows: 38 cases were autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis; 132 non-autoimmune and non-neoplastic diseases; 16 neoplastic diseases and 12 cases unclassified. The immunofluorescent staining intensity by anti-nuclear matrix protein (NMP) antibodies decreased variably, but fibrillogranular, speckled and nucleolar immunolocalization patterns were retained after in situ fractionation. Ku70 and La protein were detected by anti-NMP antibodies. Immunolocalization by anti-NMP antibodies indicates that the NMPs constitute a variety of characteristic nuclear substructures and may serve as autoantigens in diverse human diseases. In addition, the presence of Ku70 and La protein as NMPs suggests that the NM can be functionally active in association with DNA or RNA.

Insertion of a Self-expandable Metallic Stent in Canine Lacrimal Sac: A long-term Evaluation

PURPOSE: To evaluate the feasibility and long-term outcome of the use of self-expandable metallic Z-stents inthe canine lacrimal sac. MATERIALS AND METHODS: Stents were constructed using 0.1 mm stainless steel wire in acylindric zigzag configuration of four bends; their diameter when fully expanded was 2.4 to 3mm, their length was6.0 to 8.0mm, and they were coated with 24-karat gold. Under fluoroscopic guidance and using a 3F cutdown tube, atotal of 12 stents were placed in 12 lacrimal sacs of six adult dogs, which were observed for tearing. After onemonth to three years of observation, the dogs were sacrified and examined grossly and histologically. RESULTS: Stent placement was technically succussful and well tolerated in all but one lacrimal sac, in which the stent wasmisplaced. At three and six months after stent placement, stent wires were not encased by epithelium, but at ninemonths, and one, two and three years after placement, six of the 12 stents had become encased in a proliferationof this where the stent wires contacted the lacrimal sac wall. In no lacrimal system in which stent placement hadbeen successful was migration, stenosis or obstruction of the lacrimal system observed. One misplaced stent causedobstruction of the lacrimal sac, however. CONCLUSION: In 11 of 12 case (92%), fluoroscopic placement of anexpandable metallic stent in the canine lacrimal sac was successful; in 6 of 8 cases (75%), the stent wires becameencased by a proliferation of mucosa, but during long-term follow-up of 9 months to 3 years, no obstruction wasobserved.

S100 Protein Positive Dendritic Cells in Liver Diseases

We describe S100 protein positive dendritic cells (S100+DCs) in various liver diseases including chronic viral hepatitis B and C (20 cases), liver cirrhosis (3 cases), hepatocellular carcinoma (2 cases), hepatolithiasis (6 cases), primary biliary cirrhosis (PBC) (2 cases), liver allograft rejection (9 cases), bile duct paucity (1 case), and Wilson's disease (1 case). By immunohistochemical analysis, S100+DCs were absent in fetal and normal livers, while they were variably present in inflammatory liver diseases. In chronic hepatitis and active cirrhosis, S100+DCs were most frequently located in periportal area, at lymphoid follicles within the portal tract, and at foci of spotty necrosis within the lobule. Frequency and intensity of S100+DCs were not related to etiologies of liver diseases, but they were correlated with the activity of hepatitis. In PBC, S100+DCs were found between biliary epithelial cells of the septal bile ducts, as well as, the periductal area of the portal tracts. A posttransplantation liver with features of moderate acute rejection revealed many S100+DCs in polymorphous portal infiltrates. In hepatocellular carcinomas, many S100+DCs were scattered between tumor cells. In the case of the Wilson's disease, S100+DCs were not noted. Presence of S100+DCs in various inflammatory liver diseases indicates that they play a central role as antigen presenting cells in immune responses of inflammatory liver diseases.

Effect of Protein Kinase C Inhibitor (Staurosporine) in Human Invasive Bladder Tumor Cells / 대한비뇨기과학회지

Protein Kinase C which is a Ca++ -activated, phospholipid - dependent enzyme phosphorylates numerous protein substrates and participates in intracellular signaling processes. Protein kinase C is associated with a wide range of biological effects including stimulus-secretion coupling, induction of cellular proliferation and differentiation, activation of nuclear transcription factors and cell surface receptors and tumor promotion. Programmed cell death, referred to apoptosis is an active, energy-dependent process in which the cell participates in its own destruction during apoptosis. There is condensation and fragmentation of nuclear chromatin, accompanied by a marked decline in total cell volume, dilation of the endoplasmic reticulum and general compacting of cellular organelles. Thereafter, there is fragmentation of both nucleus and cytoplasm to give rise to small membrane-bound vesicles known as apoptotic bodies. Protein kinase C may have the regulatory role in apoptosis. Staurosporine is a potent protein kinase C inhibitor. Staurosporine inhibited the growth of human invasive bladder tumor cells, T24 in MTT test. The survival fractions of human invasive bladder tumor cells T24 were 100.0%, 76.0%, 62.5% and 18.1% with staurosporine concentration 0nM, 10nM, 100nM and 1000nM, respectively. From the results we identified that staurosporine inhibited the growth of T24 cells markedly in a dose dependent manner(P<0.05). 12-hour exposure of T24 cells to staurosporine failed to induce DNA fragmentation at the concentrations of 0nM, 10nM and 100nM but promoted fragmentation at the concentration of 1000nM, showing typical ladder pattern on agarose gel electrophoresis. On the examination of cellular morphology, T24 cells showed the features of apoptosis such as cell shrinkage, nuclear condensation and formation of bleb and apoptotic bodies after exposure to staurosporine of 10nM, 100nM and 1000nM concentrations. These results suggest that staurosporine have remarkable cytotoxic effect against human invasive bladder tumor cells T 24 and the mechanism of cytotoxicity may be apoptosis.

Pathological Analysis of Post-Transplantation Endomyocardial Biopsies

Heart transplantation was first performed in 1967. It is now regarded as a well-established treatment modality for end-stage cardiac diseases. Once the transplantation is performed, endomyocardial biopsy(EMB) is the examination of choice in monitoring the transplanted heart. We analyzed the pathological findings of follow-up EMB of 6 heart transplant patients. All patients have been suffered from severe heart failure. Four patients were adult male and two were adult females. All the hearts, except for one, displayed characteristic features of dilated cardiomyopathy. The remaining heart was diagnosed as having giant cell myocarditis. Post-transplantion EMBs were performed according to the protocol and standard cardiac biopsy grading of ISHT (1990). The standards were applied for grading of cellular rejection. In five patients, there were one or two episodes of biopsy proven acute rejection, grade II or IIIA without any clinical symptoms of rejection. Immediate "pulse therapy" was performed and follow-up biopsies were done. All episodes of rejection were cleared in subsequent biopsies. All patients are doing well without evidence of cardiac problem. The postoperative monitoring of acute rejection is critical since clinical signs of rejection are usually absent. At present, EMB is regarded as the most reliable method for diagnosis and grading of acute rejection and is an efficient guide to the monitoring of the cardiac recipients. Our experience of post-transplantation EMB corresponds with previously published reports.

Cytologic Features of Primary Tumors in Central Nervous System / 대한세포병리학회지

There has been a marked increase in the utility of aspiration cytology for pathologic diagnosis. It may be applied to any kinds of organs and substitutes surgical biopsy. Because of the high risk of complication and difficulties in localization, aspiration cytology in the central nervous system(CNS) has been used with less frequency compared to other sites. However, with the advent of sophisticated imaging instruments, aspiration cytology of lesions in the CNS is being used increasingly. Cytologic features of the CNS neoplasms were quite similar to those of histology except one spindle cell tumor. Reviewing various CNS neoplasms, it appears that cytology may be a useful diagnostic method.

Extrafollicular reticulum cells in pathologic lymph nodes

Extrafollicular reticulum cells in lymph nodes are heterogeneous. They express cytokeratins, desmin, and/or vimentin as their intermediate filament profile. Using those markers, we undertook an immunohistochemical study of human lymph nodes under various pathologic conditions. Samples included 15 simple reactive lymph nodes, 7 follicular hyperplasia, 1 necrotizing lymphadenitis, 4 tuberculous lymphadenitis, 13 malignant lymphoma (9 non-Hodgkin's and 4 Hodgkin's lymphomas), and 11 metastatic adenocarcinoma. In lymph nodes with follicular hyperplasia, cytokeratin and/or desmin expressing reticulum cells displayed a characteristic dendritic meshwork in the subcapsular, perisinusoidal, and paracortical regions. In other forms reactive lymph nodes, they were similarly distributed but were less prominent. By SDS-PAGE and immunoblotting, cytokeratin polypeptides were identified. In necrotizing lymphadenitis, they were increased and the pattern of distribution was disturbed. In tuberculous lymphadenitis, they were also increased and located at nongranulomatous as well as in perigranulomatous areas. In lymphomas the reticular meshwork was entirely obliterated. Cytokeratin or desmin expressing reticulum cells were rarely seen within tumors. The reticular meshwork was also obliterated in metastatic carcinoma. However, the meshwork was maintained in uninvolved areas. In conclusion, extrafollicular reticulum cells displayed characteristic patterns of distribution under various pathologic conditions, and may be implicated in the pathogenesis of those pathologic conditions in human lymph nodes.

Thymic epithelial cells of severe combined immunodeficiency (SCID) mice

To characterize thymic epithelial cells of SCID (severe combined immunodeficiency) mice in comparison with those of Balb C mice, we did an immunohistochemical study using cortical and medullary epithelial cell specific monoclonal antibodies (MoAbs), Th-3 and Th-4, as well as gel electrophoresis and immunoblotting. The thymi of SCID mice were composed of epithelial cells and a few lymphocytes. Most epithelial cells were immunostained diffusely with Th-3, which indicated that they might be "cortical-type" epithelial cells. There were a few clusters of stellate cells with dendritic processes which were negative with Th-3 but stained strongly with Th-4. Cortical type epithelial cells and most of the Th-4 reacting cells were strongly immunostained with cytokeratin antibody MNF116. By immunoblotting, cytokeratin polypeptides No. 10 and 18 were detected in both SCID and Balb C mice; however, the relative amounts of each cytokeratin polypeptides were different. With immunohistochemical and immunoblotting results, we conclude; 1) Th-3 and Th-4 are reliable markers for cortical and medullary thymic epithelial cells in SCID mice; 2) disorganization of cells thymic structure is mostly due to maldevelopment of medullary epithelial and T lymphocytes; and 3) the composition of cytokeratin subfamilies of SCID mice thymi may represent a phenotypic marker of the maldevelopment of medullary epithelial cells.

Endodermal sinus tumor: immunophenotypic expression of a carcinoma

A series of five endodermal sinus tumors was studied for their cytoskeletal and other phenotypic markers. They included 2 ovarian, 2 testicular, and 1 inguinal tumors. The cytoskeletal expression was also studied by gel electrophoresis and immunoblotting. Every tumor was diffusely and strongly immunostained for cytokeratin. By SDS-PAGE and immunoblotting, cytokeratins 8 & 18 were detected. Vimentin was focally coexpressed in 4 cases. The stroma was diffusely immunostained for vimentin. None of them expressed desmin, neurofilament, or glial filament protein. Desmoplakin was expressed only in one ovarian tumor. Alpha-fetoprotein and S-100 protein were also diffusely positive among the neoplastic cells; intracytoplasmic globules were especially strongly immunostained. These findings suggest that endodermal sinus tumors represent a group of pure malignant epithelial neoplasms, and may be regarded as primitive carcinomas.

In Vitro Intrinsic Radiosensitivity Of Human Squamous Cell Carcinoma in Primary Culture / 대한치료방사선과학회지

There are a number of reports suggesting that there may be a correlation between the clinical response to radiotherapy in various tumors and the clonogenic survival of cell lines derived from these tumor following exposure to 2 Gy (SF2). Authors conducted this study to determine SF2 for cells in primary culture from surgical specimens. The tumor tissues with squamous cell carcinoma of uterine cervix and head and neck were obtained. The tumor tissues were disaggregated to single cells by incubating with collagenase typeIV for 2 hours with constant stirring. Single cell suspensions were inoculated in four 24-well plates precoated with cell adhesive matrix. After 24 hours of incubation at 37degree C, rows of four wells were then irradiated, consisting of control set and five other sets each receiving doses of 1,2,3,4, and 6 Gy. After incubation for a total of 13 days, the cultures were stained with crystal violet determine whether cell growth was of epithelial origin, immunocytochemical staining with a mixture of cytokeratin and epithelial monoclonal antibodies were performed on cell cultures. During the period of this study, we received 5 squamous cell carcinoma specimens of head and neck and 20 of uterine cervical carcinoma. Of these, 15 yielded enough cells for radiosensitivity testing. This resulted an overall success rate of 60%. The mean SF2 value for 15 tumors was 0.55+/-0.17 ranging from 0.20 to 0.79. These results indicate that there is a broad range of sensitivities to radiation in same histologic type. So with a large patient population, we plan to determine whether a different SF2 value is associated with tumors that are controlled with radiotherapy than those that are not.

Reticular network of the human thymus

To investigate the development of the reticular network of the thymus with aging and under pathologic conditions, we performed reticulin stains on the following samples; 5 fetal thymi (22 to 33 weeks of gestational age) and 35 postnatal thymi (less than 1 month to 33 years of age). The latter included 1 hyperplastic thymus, 4 pathologically involuted thymi and 1 physiologically involuted thymus as well as 29 normal thymi. Reticulin fibers were invariably seen along the capsule and interlobular septae of all the thymi. In fetal thymi, reticulin fibers circumscribed only cortical blood vessels and Hassall's corpuscles. Postnatal thymi from the children aged less than 1 month showed discontinuous reticulin fibers along the blood vessels of the corticomedullary junction. With aging, the amount of reticulin fibers increased and formed a "fibroreticular network(FRN)" from the branching point of the interlobular septae along the corticomedullary junction. It completely circumscribed the outer medulla in fully developed thymi. In the hyperplastic thymus, the reticular network retained its original structure. Both pathologically and physiologically involuted thymi revealed irregularly collapsed reticulin fibers. These findings suggest that the reticular network of the thymus consists of FRNs as well as capsule and interlobular septae and matures with aging before involution.

Cardiac transplantation / 대한흉부외과학회지

No abstract available.