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Volume 33(8); August 1999
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Original Articles
Expression of TGF-beta and PDGF in Monocrotaline-Induced Pulmonary Hypertension in Rats.
Min Sun Cho, Sang Ho Cho, Woo Ick Yang, Woon Sup Han
Korean J Pathol. 1999;33(8):545-554.
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Pulmonary vascular hypertension is characterized by migration and proliferation of smooth muscle cells accompanying abnormal synthesis and accumulation of extracellular proteins in vascular wall. The aim of this study is to define the role of endogneous TGF-betas and PDGF in the process of remodeling vessels through determining the temporal and spatial distribution of these growth factors in hypertensive pulmonary vessels in monocrotaline-induced pulmonary hypertension in rat. Sprague-Dawley rats were sacrificed 12 hours, 1, 2, 4, 7, 10, 14, 21, 28, and 56 days after treatment. The morphometric analysis of medial thickening and immunohistochemical study using antibodies to TGF-beta1, TGF-beta2, TGF-beta3, and PDGF were performed. Immunoreactivities for TGF-beta1 and TGF-beta3 were increased from the 14th day in the medial smooth muscle cells and PDGF showed increased expression from the 21st day in the medial smooth muscle cells. No difference in TGF-beta2 immunoreactivity was found between control and experimental groups. The expression of TGF-beta1, TGF-beta3 and PDGF increased in medial layers with the progressive thickening of pulmonary arteries which was considered to have close relation to medial hypertrophy of pulmonary arterioles. In the case of PDGF, however, the morphologic change occurred before increase in immunoreactivity was observed in the medial layer of pulmonary arterioles. Moreover, the function of isoforms of TGF-beta has yet to be completely elucidated; the different affinity to receptors and the degree of expression of these receptors that are supposed to affect the function of growth factors. Thus, further studies are needed.
Morphologic Change of Proximal Convoluted Tubules in Radiation-Induced Renal Injury in Rats.
Eun Sook Chang, Kun Young Kwon, Ok Bae Kim
Korean J Pathol. 1999;33(8):555-569.
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Experimental studies suggest that captopril plays an important preventive role in radiation induced renal injury (RRI). To elucidate the pathogenesis of RRI and effect of captopril, one subgroup was irradiated with a single dose of 9 gray (Gy) total body irradiation and another subgroup with 17 Gy local irradiation in the right kidney. Twenty-four healthy looking Sprague-Dawley rats, weighing 200~250 g, were divided into one control and three experimental group (EG)s for this study. The control group, composed of 2 rats, was maintained on stock diet and drinking tap water. EG was divided into three. EG 1 composed of two subgroups, the first subgroup, 3 rats each, was sacrificed within 12 hours after 9 Gy and 17 Gy single dose irradiation only and the second subgroup, 2 and 1 rats each, was sacrificed 8 weeks after the same doses irradiation. EG 2 composed of subgroups of 2 and 3 rats was given 500 mg/L of captopril in the drinking water after irradiating them with 9 Gy and 17 Gy and sacrificed in the 8th week. EG 3 was subdivided into four subgroups by captopril doses given, 62.5 mg/L, 125 mg/L and 250 mg/L and sacrificed 20 weeks after 9 Gy and 17 Gy irradiation. On light microscopy proximal convoluted tubules showed cytoplasmic vacuolization and focal necrosis in the subcapsular region in EG 1 sacrificed within 12 hours after 9 Gy and 17 Gy irradiation only (sham) and very mild fibrosis in juxtamedullary regions in rats sacrificed 8 weeks after irradiation. In EG 3 these changes were severely increased with additional increased fibrosis in the juxtamedullary region in the group given captopril 62.5 mg/L. On transmission electron microscopy, there were various degenerative changes of organelle. Among the captopril administered EG 2 and EG 3, rats given a high dosage revealed milder degree of damage compared to that of rats given a low dosage, and thickening of basement membrane was remarkable in rats given a low dosage. There was a reduction in tubular damage related to the captopril dosage. According to the above findings, administration of a high dose of captopril might preserve the ultrastructure in RRI and the possible mechanism of captopril was discussed.
Abnormal Development and Apoptosis Observed in Brains of the Trisomy 16 Mouse.
Eun youn Cho, Yeon Lim Suh, Je Geun Chi
Korean J Pathol. 1999;33(8):570-580.
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We have studied morphologic characteristics and apoptosis on the fetal brain of the trisomy 16 mouse, a model for human trisomy 21 syndrome. This study was based on serial sections of the whole brain from a sample of sixteen trisomy 16 mice and forty-six age-matched control littermates from embryonic day (ED) 12 to ED 18. Trisomy 16 brains showed a reduction of telencephalic size and abnormal cortical development. At ED 13 trisomy 16 and control brains appeared similar. By ED 14 difference in the cortical thickness and telencephalic growth became evident, and by ED 16 a marked size difference had developed between the trisomy 16 and control brains. By ED 18, however, the thickness of the trisomy 16 cortex had increased considerably and was not significantly different with respect to the thickness and cross-sectional areas of the pallium and its constituent cortical layers. The cell density of the trisomy 16 cortex had persistently decreased before ED 17, when the cell density of control and trisomy 16 corteces was similar within each layer. At ED 18 cell density of trisomy 16 cortex in each layer increased. There was inverse relationship between a number of TUNEL positive apoptotic cells and cell density in the trisomy 16 brains. Our results suggest that developmental abnormalities of the trisomy 16 brain indicated developmental delay of the telencephalon growth, which may be caused by apoptosis rather than by a proliferation defect.
Detection Rate of Helicobacter Pylori in Gastric Adenocarcinoma and Effect of Helicobacter Pylori Infection on Proliferative Activity of Gastric Epithelium.
Young Lyun Oh, Geung Hwan Ahn
Korean J Pathol. 1999;33(8):581-588.
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AbstractAbstract PDF
Helicobacter pylori infection has been shown to be associated with gastric carcinoma. However, despite the frequent detection of seropositivity for H. pylori and histologic detection in biopsy specimen, histologic detection rate of H. pylori in surgical specimens has been low. In this study, we investigated the prevalence of H. pylori infection in gastrectomy specimens bearing gastric adenocarcinoma and compared it with both endoscopic biopsy and serologic results. H. pylori infection was identified by Giemsa stain in the mucosa stripped from the tumor, body, and antrum in 61 gastrectomy specimens. We evaluated the effect of H. pylori infection on gastric mucosal cell proliferation by using monoclonal antibody for Ki-67. H. pylori detection rate using Giemsa stain was higher in gastrectomy specimens (67.3%) compared to that (48.1%) of biopsy specimens (p=0.006). The detection rate was higher in body than that of antrum or tumor site in the same patients (p=0.001). The H. pylori seropositivity was 60.5% and relatively nonspecific. The mean value of Ki-67 labeling index in the H. pylori-positive group was higher than that in the H. pylori-negative group (p<0.05). The increase in gastric epithelial cell proliferation was not influenced by the location of the tumor or the site of the specimen. The results suggest that the actual prevalence of H. pylori infection in patients with gastric carcinoma is considerably higher than that evaluated on endoscopic biopsy specimens. In addition, the increased cell proliferation in the H. pylori-positive group suggests some evidence that H. pylori may be involved in gastric carcinogenesis.
Expressions of p53 and MIB-1 in Glandular Lesions of the Uterine Cervix.
Seo Young Park, Mee Young Sol, Hye Kyoung Yoon
Korean J Pathol. 1999;33(8):589-595.
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The glandular lesions of the uterine cervix can be classified into endocervical glandular dysplasia (EGD), adenocarcinoma in situ (AIS) and adenocarcinoma, but the diagnostic criteria and the continuity of endocervical glandular lesions are still controversial. The aim of this study was to evaluate the significance of immunohistochemical findings of p53 and MIB-1 in the discrimination and the continuity of EGD, AIS and adenocarcinoma. The materials for the study included 11 cases of adenocarcinoma, 7 cases of AIS, 12 cases of high grade EGD, and 19 cases of low grade EGD. Also included were eleven benign glandular lesions (5 cases of tuboendometrial metaplasia, 3 cases of mesonephric remnant, 3 cases of microglandular hyperplasia). A strong reaction of more than 5% of the glandular epithelial nuclei was interpreted as positive for p53 protein. MIB-1 expression was analyzed semiquantitatively as negative, 1 , 2 , 3 , depending on the percentage of positive nuclei (less than 1%, 1~9%, 10~39%, > or = 40%, respectively). p53 protein expression was found in 3 (27.3%) out of 11 cases of adenocarcinoma, and 2 (28.6%) out of 7 cases of AIS. But all of high and low grade EGD cases were negative. High MIB-1 labelling index (> or =10%) was found in all adenocarcinoma cases and in 3 (42.9%) out of 7 cases of AIS. But only 2 (17.7%) out of 12 cases of high grade EGD showed high MIB-1 labelling index, and all of low grade EGD and benign lesions showed negligible MIB-1 positivities. In summary, MIB-1 labelling index might be valuable in the discrimination of malignant glandular lesions and endocervical glandular dysplasia from benign lesions, but p53 expression could be a useful parameter in the discrimination of malignant glandular lesions from endocervical glandular dysplasia and benign lesions.
Tumor Angiogenesis and Stage in Ovarian Carcinoma.
Eun Sook Chang, Hyun Chang Joo, Tae Sung Lee
Korean J Pathol. 1999;33(8):596-602.
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Tumor angiogenesis has been found to have prognostic significance in many tumor types for predicting an increased risk of metastasis. We assessed tumor vascularity in 28 cases of borderline malignancy and 71 cases of carcinoma of the ovary which had been resected and diagnosed, using the highly specific endothelial cell marker CD34. The numbers of microvessels were counted in 200 magnification in three highly vascularised areas. The numbers of microvessels in carcinomas were higher than that in the borderline malignancy of serous and mucinous tumors. The number of microvessels of mucinous carcinomas was significantly higher than that of serous carcinomas. There were neither significant differences in the number of microvessels according to histological tumor types (p=0.075) nor significant differences in the number of microvessels according to FIGO stages (p=0.072). But in serous carcinomas, the number of microvessels was higher in the FIGO III-IV stage than in the FIGO I-II stage (p=0.017). This study showed higher neovascularization in malignant tumor than borderline malignancy, and in the advanced stage (FIGO III-IV) than less advanced stage (FIGO I-II) of serous carcinomas.
Analyses of Genetic Alterations in Breast Cancers by Comparative Genomic Hybridization.
Jin Man Kim, Young Mi Jeon, Young Hyeh Ko, Kyu Sang Song, Howe J Ree, Joo Seob Keum, Jae Hyuk Lee, Sun Hoe Koo
Korean J Pathol. 1999;33(8):603-613.
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AbstractAbstract PDF
Transformation and progression of breast cancer are thought to be caused by an accumulation of complex genetic alterations, but little is known about specific changes. In this study, the author has undertaken a genome-wide screening to detect genetic changes in 20 cases of breast cancer among Koreans, including 16 infiltrating ductal carcinomas, 2 medullary carcinomas, 1 invasive lobular carcinoma, and 1 borderline phyllodes tumor. Comparative genomic hybridization (CGH) was used to screen for DNA sequence gains and losses across all human chromosomes. Simultaneous immunohistochemical staining for c-erbB-2 (Her-2/neu), c-myc, cyclin D1, and p53 protein was done to make comparisons with nuclear grade and that with CGH results. Biotin-labeled tumor DNA and digoxigenin-labeled normal DNA were hybridized to normal metaphase cells. The fluorescence signals were captured by fluorescence microscope after detection by avidin-FITC and anti-digoxigenin rhodamine. Then, the ratio of fluorescence was calculated by an image analyzer. The immunohistochemical staining was done in paraffin-embedded tissue with an LSAB kit and avidin-biotin complex (ABC) method. The CGH results showed gains on chromosomes 8q (40%), 1q (30%), 17q (15%), 20q (15%), 18q (15%), 5p (15%), and 13q (15%). Deletions were on chromosomes 17p (45%) and 22q (20%). High-level amplifications (green/red ratio >1.5) were noted on chromosomes 1p31, 1q, 3q25-qter, 5p, 7q31-qter, 8q, 9p22-qter, 10p, 11p, 11q22-qter, 12p, 12q24, 14q21-qter, 15q23-qter, 17q, 18p, 18q12-qter, 20p, and 20q. By comparison with infiltrating ductal carcinoma, the two medullary carcinomas showed high-level amplification on chromosomes 1p31, 1q, 8q, 10p, 11p and 12p. c-erbB-2, c-myc, cyclin D1, and p53 protein expression was immunohistochemically detected in 9 of 20 (45%), 8 of 20 (40%), 10 of 20 (50%), and 13 of 20 (65%), respectively. The results indicate that the amplification on chromosome 8q, 1q and the deletions on chromosomes 17p and 22q are the most frequent genetic alterations in breast cancers among Koreans. The results reveal a different pattern of genetic alteration from previous studies. The CGH results were not correlated with the immunohistochemical profiles. The amplification pattern of medullary carcinomas was quite different from the pattern of infiltrating ductal carcinomas. The CGH was thought to be very useful in the screening of genetic alterations of solid tumors.
Expression of Maspin Protein in Ductal Hyperplasia, Intraductal Carcinoma and Invasive Ductal Carcinoma of the Breast.
Young Chae Chu, In Seo Park, Yoon Ju Kim, Joon Mee Kim, Hye Seung Han, Jee Young Han, Young Bae Kim
Korean J Pathol. 1999;33(8):614-619.
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AbstractAbstract PDF
Maspin is a recently described gene with tumor suppressor activity. The gene product is a 42 kD protein with homology to the serpin family of protease inhibitors and may play a role as an inhibitor of tumor cell invasion. The prior observation that invasive breast cancers and their metastases showed decreased maspin protein expression by immunostaining supports this speculation. However, the role of maspin in breast cancer progression has not been studied in detail. We, therefore, studied maspin protein expression in a series of hyperplasia, atypical ductal hyperplasia, intraductal carcinoma and invasive carcinomas. Immunohistochemical staining (IHC) for maspin was performed on paraffin sections of 136 breast specimens using a commercially available monoclonal antibody. Among the 106 cases studied were 36 moderate/florid ductal hyperplasia, 11 atypical ductal hyperplasia (ADH), 29 intraductal carcinoma (IDC) (4 low grade, 13 intermediate grade, 12 high grade) and 30 invasive ductal carcinomas. Thirty cases of normal breast were also studied as control group. IHC stains were scored using a semiquantitative scoring system. The mean IHC scores for maspin for normal, moderate/florid hyperplasia, atypical ductal hyperplasia, intraductal carcinoma, and invasive carcinoma were 5.51 1.30, 7.36 0.72, 3.82 1.60, 4.48 2.69, 3.97 3.30, respectively. These scores for each category were statistically significant (p<0.05), except between ADH and IDC. Maspin protein expression was increased in most cases of moderate/florid hyperplasia, while maspin expression was more heterogeneous in ADH and IDC. In high grade IDC, maspin protein expression was stronger than low and intermediate grade IDC, and this suggests the possibility of a compensatory cellular response against the forces driving further tumor progression. Two thirds of invasive ductal carcinomas expressed maspin protein weakly and focally. All metastatic carcinomas of lymph nodes were negative for maspin. It is possible that high grade IDC with strong maspin expression may represent a subset less likely to progress to invasive cancer. This speculation merits investigation in clinical outcome studies.
Case Reports
Tracheobronchial Aspergillosis An autopsy case report.
Tae jung Kwon, Dong Joo Lee, Il Hoon Kwon
Korean J Pathol. 1999;33(8):620-623.
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AbstractAbstract
Tracheobronchial aspergillosis is an unusual form of invasive aspergillosis characterized by noninvasive or only superficially invasive tracheobronchitis with a propensity for dissemination. We report a two-year-old male who suddenly died of respiratory failure. Postmortem examination revealed a pseudomembrane covering the mucosa of larynx, trachea and bronchial tree of both lungs. This pseudomembrane was composed predominantly of Aspergillus hyphae. There was transmural necrotizing bronchitis with fungal invasion to the narrow zone of peribronchial tissue, and dissemination to the stomach and kidney. This form of pulmonary aspergillosis had not been reported in this country.
Chronic Hepatitis in the Idiopathic Hypereosinophilic Syndrome: A case report .
Kyeong Hee Kim, Hae Joung Sul, Sung Chul Jun, Dae Young Kang
Korean J Pathol. 1999;33(8):624-626.
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Chronic hepatitis associated with the idiopathic hypereosinophilic syndrome has been very rarely reported worldwide. Recently, we experienced a case of chronic hepatitis with piecemeal necrosis as the clinical feature of the idiopathic hypereosinophilic syndrome. The patient was a 49-year-old woman who complained of a mild fever, nausea, vomiting, and pain in the right upper quadrant. The eosinophil count of peripheral blood increased up to 14,020/microliter (64% of WBC). Liver biopsy specimen showed severe porto-periportal inflammation with marked eosinophilic infiltration and ballooning degeneration of hepatocytes. Corticosteroid therapy significantly normalized the eosinophil count of peripheral blood.
Sex Cord Tumor with Annular Tubules and Serous Surface Papillary Carcinoma of the Ovary: A case report.
Dae su Kim, Sang Yong Song, Geung hwan Ahn
Korean J Pathol. 1999;33(8):627-630.
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Sex cord tumor with annular tubules (SCTAT) is a rare ovarian neoplasm which usually occurs in two forms. In patients associated with Peutz-Jeghers syndrome, the tumors are usually small, bilateral or multifocal, and show benign clinical course. However, tumors from patients without the syndrome are often large, usually unilateral, and rarely show malignant behavior. Serous surface papillary carcinoma (SSPC) is an aggressive neoplasm which involves peritoneal linings, including ovarian surface. Recently, we encountered a case of an unusual combination of SCTAT and SSPC in the ovary of a 55-year-old Korean woman presented with abdominal distention for one year. Systemic review and physical examination were within normal limit, except for abdominal discomfort and distention. There was no stigmata of Peutz-Jeghers syndrome in all diagnostic examinations, including gastroscopy and colonoscopy. Pelvic computed tomography showed adnexal mass with multiple peritoneal nodules. Exploration revealed uterine and ovarian surfaces covered with multiple, yellow-white papillary nodules. However, the sizes of both ovaries were within normal limit. Typical serous papillary carcinomas were identified in nodules from peritoneum and ovarian surfaces. Well-circumscribed columnar epithelial cell nests composed of ring-shaped tubules encircling hyalinized basement membrane-like materials were found in the ovary away from serous surface papillary carcinoma.
Primitive Neuroectodermal Tumor of the Ovary: A case report .
Chan Kwon Jung, Eun Sun Jung, Youn Soo Lee, Byung Kee Kim, Sun Moo Kim
Korean J Pathol. 1999;33(8):631-635.
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AbstractAbstract PDF
Primitive neuroectodermal tumors (PNET) of the ovary are rare tumors with an exclusive or almost exclusive malignant neuroectodermal composition, and are generally regarded as a monodermal expression of an ovarian teratoma. The tumors are basically identical with the lesions of the same name occuring typically in the central nervous system of children. These tumors consist chiefly of undifferentiated small cells resembling neuroblasts. There are also mature, well- differentiated neuroectodermal cells, such as astrocytes and ependymal cells. We report a case of ovarian PNET with glial and neuroblastic differentiation and focal teratomatous foci of non-neural tissue in a 17-year-old female.

J Pathol Transl Med : Journal of Pathology and Translational Medicine