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Volume 32(12); December 1998
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Original Articles
Identification of Zinc Finger Genes that are Differentially Expressed upon Apoptosis of Ramos B Cells.
Min Sun Shin, Su Young Kim, Seung Myung Dong, Eun Young Na, Sug Hyung Lee, Won Sang Park, Jung Young Lee, Nam Jin Yoo
Korean J Pathol. 1998;32(12):1043-1048.
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AbstractAbstract
Typical programmed cell death requires de novo macromolecular synthesis and shares common morphological changes referred to as apoptosis. To elucidate the molecular mechanism of apoptosis, we isolated 13 cDNA clones of zinc finger genes that are differentially expressed in calcium ionophore-induced apoptosis of Ramos human B cell by 'targeted RNA fingerprinting' protocol (Stone & Wharton, 1993). According to DNA sequence analysis of the 13 cDNA clones, three clones are identical with ZNF7, ZNF143 and MTB-Zf, respectively, and 8 out of the other 10 clones showed partial homology to known zinc finger genes. Differential expression was confirmed in the three known zinc finger genes by ribonuclease protection assay. ZNF7 and ZNF143 are up-regulated after induction of apoptosis, and, in contrast, MTB-Zf is down-regulated. According to the previous reports on these three genes, all of the three genes have been suspected to be tumor suppressor genes, but their functions have not been identified yet. Taken together, our results suggest that many of the novel and known zinc finger genes might play important roles in regulation of apoptosis and that these findings also provide clues as to the functions of the three putative tumor suppressor genes, ZNF7, ZNF143 and MTB-Zf in terms of apoptosis. In addition, the isolation of zinc finger genes by targeted RNA fingerprinting could be a straightforward approach for the identification of novel candidate genes associated with apoptosis.
The Role of Cell Proliferation and Apoptosis in the Cardiac Development.
Eo Jin Kim, Hyo Soo Kim, Jeong Wook Seo
Korean J Pathol. 1998;32(12):1049-1057.
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AbstractAbstract
The functional and morphologic cardiac developments are determined by the morphogenesis, growth and remodeling of the heart resulted from the cell proliferation and apoptosis. We studied the distribution of the proliferation and apoptotic activity of myocardial cells according to the developmental stages in embryos of C57bl/6 mice. Serial histologic sections were stained with PCNA and TUNEL method and were analyzed with image analyzer (BMI, Seoul). The ventricular myocardium of an embryonic heart could be divided into trabecular, inner compact and outer compact layers. Proliferation indices at layers of the left ventricular myocardium on embryonal days (ED) 13, 14, 16, 17 and 18 were 19.9%/47.4%/60.4%, 16.1%/45.8%/60.3%, 24.6%/45.6%/38.1%, 23.3%/17.7%/18.3% and 31.2%/28.0%/19.4% (trabecular/ inner compact/ outer compact) and the right ventricle, 11.0%/34.4%/60.5%, 23.0%/44.0%/69.0%, 29.2%/42.9%/35.1%, 30.4%/30.5%/22.3% and 32.4%/28.4%/16.3%. The apoptotic indices of the left ventricle/VIF were 0.23%/3.66% on ED 13-14, 0.42%/1.31% on ED 16 and 0.05%/0.60% on ED 17-18. The results show that the proliferation of the myocytes was maximal at the outer compact layer on ED 13 and 14 but lowest on ED 17 and 18. This decrease was more pronounced at the left ventricle. The innermost trabecular layer showed a constant proliferation activity of 11.0-32.4%. The presence of spatiotemporal differences in the cell proliferation reveals regional regulation in the developmental timing of cardiac development. Functional maturation is considered to be responsible for the change of proliferation activity. The apoptosis was most frequent and intense in the VIF and crux throughout the periods of each embryonal day where as rarely seen in the ventricular myocardium, especially in the trabecular layer of myocardium. These findings suggest that the apoptosis plays the role in the development of atrioventricular, ventriculoarterial septation and valve formation. Our results also reveal that the participation of apoptosis in formation of the trabeculation can be denied.
The Effects of Angiotensin Converting Enzyme Inhibitor on Progressive Glomerular Sclerosis.
Mi Ok Park, Yong Jin Kim, Hoon Kyu Oh, Chul Ho Lee, Byung Hwa Hyun, Jung Sik Kwak
Korean J Pathol. 1998;32(12):1058-1065.
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AbstractAbstract
Almost all advanced glomerular diseases have glomerular sclerotic changes to varying degrees whatever causes their primary glomerular disease are. Pathogenesis of these sclerosis has been thought of as the hyperfiltration in the primary glomerulosclerosis due to development of glomerular hypertension in each insulted glomeruli. This background gave the theoretical bases for antihypertensive therapies for supporting chronic renal insufficient patients. Angiotensin converting enzyme (ACE) inhibitor, one of the antihypertensive drugs, has received attention recently for its effectiveness. The aims of this study determined the effects and mechanism of the ACE inhibitor, enalapril, on the glomerulosclerosis in FGS/NgaKist mice, which was an animal model of chronic renal failure by generating spontaneously heavy proteinuria and progressive glomerulosclerosis. Five-week-old FGS/NgaKist mice (n=38) were assigned to four groups. Group 1a (n=6) and group 2a (n=8) fed with a vehicle, were sacrificed at the end of 10 weeks and 15 weeks, respectively. Group 1b (n=12) and 2b (n=12) received enalapril (100 mg/L) in drinking water for 5 weeks and 10 weeks from 6th week of age respectively, and were sacrified on the same day as the control groups. Doses of enanapril were maintained to 2 mg/kg/day by measuring the amount of water consumption. In enalapril groups 1b and 2b, systemic blood pressure (74.7 14.0 mm Hg, 74.3 15.9 mmHg) were significantly lower than control group 2a (116.1 4.6 mmHg, P<0.001). Similarly, degree of proteinuria lowered in enalapril group 2b versus control group 2a (0% and 50.0%, P<0.001). Glomerulosclerosis percentage significantly decreased (P<0.001) (group 1b and 2b; 1.9 6.5, 5.6 7.0 vs control 1a and 2a; 32.8 15.5, 31.4 13.8). Glomerulosclerosis score also decreased (P<0.001) (group 1b and 2b; 0.02 0.08 vs control 1a and 2a; 0.48 0.12, 0.30 0.14). The immunofluorescent staining of enalapril groups showed negative for mesangial deposition of IgG, IgA, IgM, and C3 which were positive in control groups. Immunohistochemical staining with TGF-beta1 was negative in enalapril groups and sclerotic glomeruli both enalapril groups and control groups. These results support that the ACE inhibitor has a renoprotective effect on glomerulosclerosis not only by decreasing the blood pressure but also by suppressing the immune deposits on glomeruli.
The Value of Immunohistochemistry on Paraffin Embedded Tissue Sections in the Differentiation of Subgroups of Low Grade B-Cell Lymphomas.
Tae Sook Hwang, Seung Sook Lee, Ji Eun Kim, Hye Seung Han, Chul Woo Kim
Korean J Pathol. 1998;32(12):1066-1073.
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AbstractAbstract
There had been a continuous evolution of lymphoma classification and recently a Revised European-American Lymphoma Classification was proposed by the International Lymphoma Study Group. This new classification often requires information on immunophenotypic and molecular biologic markers in addition to the usual histologic findings. Recent advances in the production of commercially available monoclonal antibodies reactive on formalin-fixed paraffin-embedded tissues provide us a great help to classify the non-Hodgkin's lymphoma. We have analyzed 31 low grade B-cell lymphomas by the schemes proposed by the International Lymphoma Study Group using antibodies to CD3, CD5, CD20, CD23, CD43, cyclin D1, and bcl-2 protein, and have analyzed the immunophenotypic features. Among 31 low grade B-cell lymphomas, 8 small lymphocytic lymphomas, 5 mantle cell lymphomas, 7 follicle center lymphomas (2 grade I, 3 grade II, and 2 grade III), and 11 marginal zone B-cell lymphomas (all of which were extranodal) were identified. Among 8 small lymphocytic lymphomas, 5 cases were positive for CD5; 6 cases were positive for CD23; 7 cases were positive for CD43; all 8 cases were negative for cyclin D1; and 7 cases were positive for bcl-2. Among 5 mantle cell lymphomas, 4 cases were positive for CD5 and CD43; all five cases were negative for CD23; 4 cases were positive for cyclin D1 and bcl-2. All 7 follicle center lymphomas were negative for CD5, CD43 and cyclin D1 and 2 cases were positive for CD23; and 6 cases were positive for bcl-2. All marginal zone B-cell lymphomas were negative for CD5, CD23 and cyclin D1; 3 cases were positive for CD43 and 9 cases were positive for bcl-2. Diagnostic utility for CD5 antigen detection on paraffin embedded tissue has a limitation due to weak antigen expression in tumor cells of B-cell lymphomas; however, still be useful in differentiating small lymphocytic lymphoma and mantle cell lymphoma from other B-cell lymphomas when applied in conjunction with CD43. CD23, CD43, and cyclin D1 appear to be of great help in differentiating subgroups of low grade B-cell lymphomas. Bcl-2, as known, is found to be useful to rule out reactive follicular hyperplasia.
p53 Mutation and Expression of Rb Protein in Germ Cell Tumors.
Ju Han Lee, Mee Yon Cho, Hae Hyeog Lee, Bom Woo Yeom, Nam Hee Won
Korean J Pathol. 1998;32(12):1074-1080.
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AbstractAbstract
We investigated the role of the tumor suppressor genes in the germ cell tumor. Immunohistochemistry (IHC) and polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) for p53 mutation were done in 46 cases of the germ cell tumor with paraffin embedded tissue. The immunohistochemical staining for Rb protein was also performed in the same specimens. The following results were obtained. The overexpression of the p53 protein was detected in 7 of 46 cases (15%). p53 mutation by PCR-SSCP was detected in 1 of 46 cases (2.2%). Expression of Rb protein was negative in 19 cases (41%). These results suggest that p53 mutation does not play an important role in the initiation and progression of germ cell tumors.
Significance of the Expression of Cyclin-Dependent Kinase Inhibitor, p27Kip1, in Human Breast Cancer.
Sang Yong Song, Duck Hwan Kim, Yeon Lim Suh, Young Hyeh Ko, Dae Shick Kim, Seok Jin Nam, Jung Hyun Yang
Korean J Pathol. 1998;32(12):1081-1088.
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AbstractAbstract
p27Kip1 protein, a negative cell cycle regulator in G1 progression, has been reported to be related with human cancers including colon, breast and non-small cell lung carcinomas. To elucidate a possible prognostic indicator, we studied 49 cases of human breast carcinoma for expression of p27Kip1 protein using an immunohistochemical method, and compared these results with known prognostic parameters of the breast cancer. p27Kip1 protein was intensely stained in nuclei of carcinoma cells in 26 cases (53.1%). The expression rate of p27Kip1 protein was significantly higher in higher nuclear grade (p<0.05), lower histologic grade (p<0.01), lower N classification (p<0.001) and lower clinical stage (p<0.05) than in lower nuclear grade, higher histologic grade, higher N classification and higher clinical stage, respectively. p27Kip1 protein expression was significantly correlated with progesterone receptor status (p<0.05) or cyclin D expression (p<0.05). No statistical correlations were found between expression of p27Kip1 protein and other parameters including tumor size, estrogen receptor status, p53 overexpression and c-erbB-2 expression. The results suggest that reduced expression of p27Kip1 protein plays a role in biologically aggressive behavior of breast carcinoma and might contribute in predicting breast cancer patient's survival.
Case Reports
Melanosis Duodeni.
Sun Hoo Park, So Yeon Park, Yong Il Kim, Woo Ho Kim
Korean J Pathol. 1998;32(12):1089-1091.
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AbstractAbstract
Melanosis duodeni is an uncommon pathologic condition characterized by diffuse small black spots on the first and second portions of the duodenum. It occurs predominantly in elderly patients and is linked to chronic renal failure, use of antihypertensive drug and oral iron supplementation, and/or presence of gastric hemorrhage. We report a case of melanosis duodeni in a 60-year-old woman diagnosed with hypertension 20 years ago and chronic renal failure 6 years ago. She has taken antihypertensive drugs for many years. On endoscopy, speckled black pigmentation of duodenal mucosa was detected. Microscopically, this duodenal lesions showed numerous coarse pigments in macrophages confined within the lamina propria. By ultrastructural study, macrophages contained electron-dense granules admixed with lipofuscin-like material in residual bodies.
Primary Hepatic Leiomyosarcoma.
Won Mi Lee, Chan Kum Park, Eun Kyung Hong, Moon Hyang Park, Jung Dal Lee
Korean J Pathol. 1998;32(12):1092-1094.
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AbstractAbstract
Primary hepatic sarcoma is a rare tumor, with fewer than 60 previously reported cases. It is thought to arise from hepatic connective tissue or vascular channels. The tumor is located usually in the intrahepatic area. Pedunculated or bulging lesion is also reported. We report a case of primary leiomyosarcoma of the liver occuring in a 62-year-old Korean woman. A pedunculated, 21 16 cm sized mass is located in the left lateral segment of the liver. Microscopically, the tumor is hypercellular and composed of elongated, partly pleomorphic spindle cells with blunt-ended nuclei, which are focally reactive for muscle specific actin. Mitotic figures are 5/10 high power fields (HPFs). No other primary site is recognized on clinical study.
Adreno-Hepatic Fusion.
So Yeong Oh, Woo Sung Moon, Ho Yeul Choi
Korean J Pathol. 1998;32(12):1095-1097.
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AbstractAbstract
We report a rare case of adreno-hepatic fusion in a 63-year-old man with a traumatic hepatic rupture. The adrenal tissue was located beneath the Glisson's capsule of the liver, and measured 3.5x2x0.3 cm. On histologic examination, the ectopic tissue was composed of both adrenal cortex and medulla surrounded by a delicate capsule of connective tissue.
Malignant Mixed Mullerian Tumor Arising from Adenomyosis of Uterus.
Yoon Ju Kim, Jung Il Suh
Korean J Pathol. 1998;32(12):1098-1100.
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AbstractAbstract
Malignant mixed mullerian tumor (MMMT) is an unusual tumor composed of malignant epithelial and nonepithelial components in the same lesion and is subdivided into homologous and heterologous types. Epidemiologically, these tumors are associated with prior pelvic irradiation, functioning ovarian lesions, exogenous estrogen therapy and rarely endometriosis. We experienced a case of uterine MMMT which arose from adenomyosis in a 47-year-old woman who had no specific past medical history. The posterior uterine corpus showed a 3.5x3.0x2.0 cm sized, relatively well defined tumor mass within the background of the adenomyosis. The tumor was composed of well differentiated endometrial adenocarcinoma and sarcomatous stroma with foci of rhabdomyosarcomatous differentiation confirmed by immunohistochemical and electron microscopic studies. Through the immunohistochemical study, both the epithelial and nonepithelial components were positive for cytokeratin and it suggested that the sarcomatous area originated from metaplasia of the adenocarcinoma component. From the overall findings, it is regarded as an uterine heterologous MMMT which arose from adenomyosis.
Hairy Polyp of Soft Palate in an Infant.
Kyeongmee Park, Yeonmee Kim, Hoonyoung Woo
Korean J Pathol. 1998;32(12):1101-1103.
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AbstractAbstract
Hairy polyp is an uncommon lesion of the nasopharynx and oropharynx. It is most frequently seen as a pedunculated mass at birth or in the first year of life. It generally has been classified as dermoid derived from the ectoderm and mesoderm. The symptoms depend on the size and location of the lesion. We report the clinico-pathological features of a hairy polyp arising from the right nasopharyngeal side of soft palate in a 21-day-old girl. Grossly, a well demarcated brownish yellow solid mass, measuring 2.7x1.5x1.2 cm, showed fine hairs on the surface. The cut surface was a yellowish brown solid appearance. Microscopically, it was covered with keratinizing squamous epithelium and was composed of mature adipose tissue, skeletal muscle, a few peripheral nerve bundles, and blood vessels in the center and mature pilosebaceous units in the periphery. Knowledge of this type of malformation facilitates early intervention and avoids significant morbidity.
Papillary Adenocarcinoma of Nonpigmented Ciliary Epithelium of the Eye.
Hyun Joo Choi, Yeong Jin Choi, Youn Soo Lee, Eun Jung Lee, Seok Jin Kang, Byung Kee Kim, Sang In Shim
Korean J Pathol. 1998;32(12):1104-1107.
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AbstractAbstract
Adenocarcinoma of the ciliary epithelium is a rare tumor, usually occuring in elderly patients who have a history of severe ocular trauma or chronic inflammation. We report an adenocarcinoma of the nonpigmented ciliary epithelium found within the phthisical globe of a 36-year-old female whose eye had been loss of vision since infancy. The mass, measured 4.0 x 4.0 cm, was relatively limited by sclera but had invasion to posterior portion. Histologically, the tumor was a compact mass which consisted of tubular and papillary structures with foci of the pleomorphic area. Strands of cells and individual cells were invested with thick basement membrane that have positivity for periodic acid-Schiff stain. Immunohistochemical staining showed strong reactivity for cytokeratin and epithelial membrane antigen, and focal for neuron-specific enolase and S-100 protein.

JPTM : Journal of Pathology and Translational Medicine