Journal of Pathology and Translational Medicine

Kwan Kyu Park

33 Articles

Transcriptional Regulation of Hepatic Stellate Cell Activation by siRNA for TGF-beta1.: Hoon Kyu Oh, Kyung Hyun Kim, Yoon Sup Keum, Chang Ho Cho, Jae Bok Park, Kwan Kyu Park; Korean J Pathol. 2009;43(6):503-508.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.503

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BACKGROUND
The cytokine-induced activation of hepatic stellate cells (HSC) plays a major role in liver fibrosis. Quiescent HSCs undergo phenotypic transformation called "transdifferentiation" in response to viral, chemical or immune insults to the liver. The cytokine TGF-beta1 plays a key role in progressive liver fibrosis. Since small interfering RNA (siRNA) is a powerful tool for silencing gene expression post-transcriptionally, the present study aimed to determine whether synthetic TGF-beta1 siRNA down-regulates the expression of the TGF-beta1 gene in immortalized and activated rat HSCs (HSC-T6s). The study examined whether synthetic TGF-beta1 siRNA prevents rat HSCs activation and extracellular matrix (ECM) production.
METHODS
TGF-beta1 siRNA or a control (pU6) siRNA was added to HSC-T6 culture media. We then performed RT-PCR and western blot analyses for TGF-beta1 and ECM components (fibronectin, type-I collagen, and TIMP-1). RESULTS: TGF-beta1 siRNA significantly down-regulated expression of TGF-beta1 mRNA and protein and attenuated mRNA and protein expressions of type-I collagen, fibronectin, and TIMP-1, as compared to the control. CONCLUSIONS: TGF-beta1 siRNA can effectively down-regulate the expression of TGF-beta1 in rat HSC, resulting in significant inhibition of HSC activation and of ECM production. These data indicate that synthetic TGF-beta1 siRNA can be a useful treatment modality to prevent liver fibrosis.

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Glaucocalyxin A Attenuates the Activation of Hepatic Stellate Cells Through the TGF-β1/Smad Signaling Pathway
Zhichao Dong, Qi Gao, Hao Guo
DNA and Cell Biology.2018; 37(3): 227. CrossRef

Immunohistochemical Study about the Origin of Bile Ductules Proliferation in Obstructive Liver Disease.: Hyun Jung Sung, Byung Chul Ann, Jae Tae Lee, Yoon Seup Kum, Jae Bok Park, Kwan Kyu Park; Korean J Pathol. 2009;43(2):126-132.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.126

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Abstract PDF: BACKGROUND
The relationship between bile duct proliferation and portal fibrosis in obstructive liver diseases remains unclear. The purpose of this study is to analyze the relationship between hepatic stellate cells (HSC), hepatocytes and bile ductule proliferation in obstructive liver disease using immunoreactivity for alpha-SMA (alpha-smooth muscle actin), CK7, and CK19.
METHODS
We used 20 human tissue samples with hepatic fibrosis due to intrahepatic stones and liver cirrhosis. Immunohistochemical staining was performed using the streptavidin-biotin method.
RESULTS
Proliferations of bile ductules at the periphery of the hepatic lobules, and diffuse HSC activation in the perisinusoidal spaces were observed in all cases. Immunoreactivity of the hepatocytes for CK7 and CK19 suggested a possible phenotypic transformation into bile duct epithelium during fibrogenesis. Immunohistochemical-analyses of alpha-SMA expression profiles showed that intralobular HSCs and some hepatocytes underwent early phenotypic changes, and that the accumulation of collagen coincides with that of alpha-SMA-labeled myofibroblasts around portal/septal ductular structures.
CONCLUSIONS
Our results showed the possibility of a phenotypic transformation of hepatocytes into bile ductular epithelium. It is suggested that hepatocytes might play a role in bile ductule proliferation in obstructive liver disease.

Nasal Type NK/T Cell Lymphoma with Pseudoepitheliomatous Hyperplasia: A Case Report.: Hoon Kyu Oh, Jeong Kyu Kim, Kwan Kyu Park; Korean J Pathol. 2006;40(3):250-254.

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Abstract PDF: A case of prominent pseudoepitheliomatous hyperplasia (PEH), that was misdiagnosed as squamous cell carcinoma (SCC) on the frozen section occured in the nasal mucosa of a patient suffering with nasal type NK/T cell lymphoma. To prevent misdiagnosis of this lesion, pathologists should be aware that NK/T cell lymphoma may be associated with overlying mucosal PEH, and so the physician must adhere to strict diagnostic criteria for making the diagnosis of SCC. The pathogenesis of PEH associated with NK/T cell lymphoma is not still clear, but it may be related to the production of growth factors, especially epidermal growth factor and transforming growth factor, by the underlying tumors.

The Effect of Ribbon-Type Antisense Oligodeoxynucleotides for Transforming Growth Factor-beta1 in Unilateral Ureteral Obstruction .: Sang Mi Han, Eun Joo Kim, Hyo Soon Jeoung, Byung Yuk Lee, Sang Sook Lee, Kwan Kyu Park, Hyun Chul Kim; Korean J Pathol. 2002;36(2):84-92.

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Abstract PDF: BACKGROUND
In unilateral ureteral obstruction (UUO), the obstructed kidney is characterized by interstitial fibrosis and an increase in transforming growth factor (TGF)-beta1. Interstitial expression of TGF-beta1 is important in tublointerstitial fibrosis. The objectives of this study is to make new ribbon-type antisense oligodeoxynucleotides (ODN) for TGF-beta1 which are resistant to exonuclease and to examine the effcets of TGF-beta1 on reducing tubulointerstitial fibrosis of the kidney.
METHODS
We introduced a new ribbon-type antisense ODN for TGF-beta1 in rats using the UUO model to block interstitial fibrosis by tail vein injection. A combination of one antisense sequences for TGF-beta1 was adopted to construct a large antisense molecule with a loop and stem. Artificial viral envelope (AVE)-type hemagglutinating virus of Japan (HVJ)-liposomes were used as a vector system for the delivery of antisense ODN.
RESULTS
The levels of TGF-beta1 mRNA was decreased more in the cultured mesangial cells treated with ribbon-type antisense ODN than in that of a linear-type antisense ODN for TGF-beta1. TGF-beta1 mRNA was increased markedly in the interstitium of untreated obstructed kidneys. Northem analysis revealed that the levels of TGF-beta1 mRNA were decreased in the obstructed kidneys treated with antisense ODN. The fibrosis of the obstructed kidneys treated with ribbon-type antisense ODN was dramatically less than that of the untreated group.
CONCLUSIONS
These results demonstrate that the introduction of new ribbon-type antisense ODN for TGF-beta1 may be a potential therapeutic maneuver for preventing interstitial fibrosis.

The Effect of Antibody and Gene Therapy for Transforming Growth Factor- 1 on Scar Formation.: Jun Hyung Kim, Ki Hwan Han, Jong Duck Ahn, In Kyu Lee, Eun Joo Kim, Mee Yul Hwang, Kwan Kyu Park; Korean J Pathol. 2001;35(5):424-432.

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Abstract PDF: BACKGROUND
Transforming growth factor (TGF)- has a large variety of biological functions, including the modulation of inflammation and the immune system, and is presumed to play important roles in repairing wounds and reducing scarring. The objective of this study is to examine the effects of TGF-1 on healing wounds and reducing scarring. We have also analysed the ability of the hemagglutinating virus of Japan (HVJ) liposome mediated antisense oligodeoxynucleotides (ODNs) to specifically inhibit wound-induced expressions of TGF-1 proteins and mRNA in the rat skin.
METHODS
Skin wounds were created on the backs of 80 anesthetized rats. The first group of wounds, as the controls, was unmanipulated. The second group of wounds, as positive controls or an excessive scarring model, was injected with TGF-1 subcutaneously. The third group of wounds was injected with anti-TGF-1 antibody subcutaneously. The fourth group of wounds was injected with HVJ liposome mediated antisense ODNs for TGF-1 subcutaneously. The wounds of all groups were bisected and analysed histologically 5, 10, 15, 30, and 50 days after the wounds were made.
RESULTS
All control wounds (TGF-1 or no injection) healed with scarring, whereas the wounds treated with the antibody or antisense ODNs healed with less scar formation compared to the control group. The wounds treated with the antibody or antisense ODNs had fewer macrophages, less collagen and fibronectin contents than the other wounds. Northern blotting and in situ hybridization analysis showed that wound sites treated with HVJ liposome mediated antisense ODNs for TGF-1 exhibited decreased levels of TGF-1 mRNA after injury.
CONCLUSIONS
These findings suggest an important new approach to controlling scarring in normal wound healing, complementing the practice of adding exogenous growth factors to chronic wounds in the attempt to inhibit collagen deposition.

Early Detection of Metastasis by Immunohistochemistry in Uterine Cervical Carcinoma.: Kwan Kyu Park, Sun Young Kwon, Eun Sook Chang, Moon Young Jegal, Sang Mi Han, Soon Do Cha, In Sook Han; Korean J Pathol. 2001;35(5):391-340.

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Abstract PDF: BACKGROUND
Adhesion molecules are important in the maintenance of normal epithelial structure, and altered expression of these molecules may be important in epithelial tumors, particularly in the processes of invasion and metastasis.
METHODS
We have examined the expression of E-cadherin, cathepsin-D, CD44, CD44v6, nm23 and transforming growth factor-1 (TGF-1) proteins in the cervical squamous cell carcinoma to evaluate the prognostic significance of these molecules.
RESULTS
Immunostain for E-cadherin was highly expressed in the majority of cases of cervical carcinomatous lesions (85.7-100%), but cathepsin-D was very low (7.1-32%). Immunostain for CD44 showed a lower expression in invasive carcinoma with and without metastasis (50.4 and 52.2%) than in carcinoma in situ (68.0%). CD44v6 protein showed some controversy of expression between invasive carcinoma with metastasis (35.7%) without metastasis (56.5%). Staining for nm23 was observed in the high expression of invasive lesions (85.7%). TGF-1 and C-erbB-2 protein were highly expressed, especially in the microinvasive carcinoma (81.8%, 42.8%, respectively).
CONCLUSIONS
These results suggest that CD44 and CD44v6 were not highly expressed in the invasive squamous carcinoma of the uterine cervix. However, it is notable that TGF-1 and c-erbB-2 in the microinvasive carcinoma and nm23 in invasive carcinoma were highly expressed compared to these of the other lesions of the uterine cervix.

Expression of p27kip1 and Cyclin D1 in Serous Epithelial Ovarian Tumors.: Sun Young Kwon, Eun Sook Chang, Kun Young Kwon, Kwan Kyu Park, Soo Kyung Kim; Korean J Pathol. 2001;35(3):220-225.

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Abstract PDF: BACKGROUND
p27kip1 is a member of the Cip/Kip family of the cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. Decreased expression of p27kip1 is associated with high histologic grade and poor prognosis in a variety of human tumors.
METHODS
Sixty-six cases of serous epithelial ovarian tumors were investigated by immunohistochemical staining for p27kip1, cyclin D1, and Ki-67. Clinicopathologic parameters (WHO classification, histologic grade and FIGO stage) were compared with the incidence of p27kip1, cyclin D1 and Ki-67 protein expression in ovarian serous tumors.
RESULTS
Reduced expression of p27kip1 was found more freguently in serous cystadenocarcinoma than in serous cystadenoma and borderline malignancy (p<0.05). The decreased expression of p27kip1 was correlated with a high histologic grade and an advanced FIGO stage. Overexpression of cyclin D1 is associated with borderline malignancy and grade I serous cystadenocarcinoma. An inverse relationship was observed between the p27kip1 protein and the Ki-67 labeling index within serous cystadenocarcinoma, but it was not significant.
CONCLUSIONS
Reduced expression of p27kip1 protein plays an important role in the biologically aggressive behavior of serous epithelial ovarian tumors and might represent a useful prognostic marker for predicting the recurrence in primary ovarian tumors.

Expression of Transforming Growth Factor-beta1 in Cyclosporine-Induced Nephropathy in Rats.: Yu Na Kang, Kwan Kyu Park, Mee Yul Hwang, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Hyun Chul Kim; Korean J Pathol. 2000;34(9):642-651.

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Abstract PDF: Cyclosporine nephropathy was induced by intraperitoneal injection of cyclosporine 25 mg/kg in Sprague-Dawley rats daily for 1, 4, 8, and 12 weeks to clarify the relationship between cyclosporine nephropathy and the expression of TGF-beta1 with extracellular matrix deposition. On light microscopic examination, the kidneys in the 12 week cyclosporine-treated rats showed focal or striped fibrosis, vacuolization of tubular cells, and injury of endothelial cells. Immunohistochemically, TGF-beta1 protein was strongly expressed in the cyclosporine-treated rat kidneys, especially in the glomerular endothelial cells, interstitial endothelial cells, tubular epithelial cells, and parietal cells in the Bowman's capsule of the glomerulus as well as the periglomerular arterioles. The amount of TGF-beta1 expression was correlated with the morphological change in the cyclosporine-treated rats. Extracellular matrix, such as fibronectin and collagen IV, was also expressed in the endothelial cells of the glomerulus and the interstitium. It can be concluded, therefore that TGF-beta1 protein is probably involved in the early stage of fibrogenesis in cyclosporine nephropathy. It can be postulated that cyclosporine nephropathy results from the accumulation of extracellular matrix associated with the increase of TGF-beta1 transcription. Therefore, these results could be used in reducing fibrosis in cyclosporine nephropathy.

Expression of bcl-2 and p53 Protein in Premalignant Lesion and Invasive Squamous Cell Carcinoma of the Uterine Cervix.: Hyun Chang Joo, Kwan Kyu Park, Sang Sook Lee, Eun Sook Chang, Tae Sung Lee, Soon Do Cha, Young Jae Lee; Korean J Pathol. 2000;34(4):280-287.

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Abstract PDF: In order to understand the possible involvement of bcl-2 and p53 proteins in the tumorigenesis of the cervical cancer and precancerous lesion, we studied the expression patterns of bcl-2 and p53 proteins in 25 cases of carcinoma in situ, 12 cases of microinvasive cervical carcinoma, and 37 cases of invasive cervical carcinoma, respectively. By immunohistochemistry, 76% of in situ carcinoma, 83.3% of microinvasive cervical carcinoma, and 60.9% of invasive cervical carcinoma were positive for bcl-2, while the staining of basal cell layers, columnar cells, and squamous metaplastic epithelium of normal cervical epithelium were positive for bcl-2 in 91.9%, 73.1%, and 81.8% of cases, respectively. Furthermore, two out of fourteen cases of invasive cervical carcinoma with lymph node metastasis were positive for bcl-2. p53 was expressed in 72.7% of condyloma or dysplasia, 12% of in situ carcinomas, 33.3% of microinvasive cervical carcinoma, and 43.5% of invasive cervical carcinomas without metastasis. Six out of fourteen cases of invasive cervical carcinoma with lymph node metastasis were positive for p53 immunostaining. In contrast, 5.4% of basal cells and 9.1% of squamous epithelium, and none of the columnar cells in normal cervical epithelium were positive for p53. In summary, the bcl-2 protein was highly expressed in the proliferative lesion of reserve cells, such as normal reserve cells, columnar cells, squamous metaplasia, carcinoma in situ, and microinvasive squamous cell carcinoma. p53 expression was increased in condyloma, carcinoma in situ, and invasive carcinoma where the reserve cells were non-proliferative. Based on these findings, we propose that bcl-2 and p53 protein are involved in the development and progression of uterine cervical carcinoma.

Ultrastructural Changes in Glomerular Anionic Sites in Puromycin Aminonucleoside Nephropathy.: Hyun Chul Kim, Chan Oh Choi, Young Ho Kim, Kwan Kyu Park; Korean J Pathol. 2000;34(1):56-67.

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Abstract PDF: An ultrastructural study was done on puromycin aminonucleoside (PAN) nephropathy which was induced in a group of Sprague-Dawley rats by a single intraperitoneally injected dose. To study the ultrastructural alteration of glomerular anionic sites renal tissue was stained with polyethyleneimine (PEI) as a cationic probe. The PEI method seemed to selectively stain heparan sulfate proteoglycan in the basement membrane and has been widely used to evaluate the changes of the basement membrane in human diseases as well as in experimental work. The experimental rats developed proteinuria three days after the PAN injection. Electron microscopic studies of glomeruli showed the loss of epithelial foot processes, formation of cytoplasmic vacuoles, microvillous formation, and increased numbers of lysosomes in the cytoplasm of podocytes. The anionic sites on the basement membrane with foot process fusion were mostly indistinguishable from those seen in control rats, but focal areas of loss or disarray of anionic sites were noted. The anionic sites were not seen on the basement membrane where the overlying epithelium was detached. The results suggest that proteinuria in PAN nephrosis may be primarily due to a glomerular epithelial lesion, leading to focal disarray of anionic sites or focal defects in the epithelial covering of the basement membrane. The loss of anionic sites in the basement membrane may result partially from the foot process fusion, but mostly from the epithelial detachment.

Histomorphologic Changes of Small Intestinal Mucosa after Irradiation in Rats.: Chan Hwan Kim, Eun Sook Chang, Keon Young Kwon, Kwan Kyu Park, Ok Bae Kim; Korean J Pathol. 1999;33(9):639-651.

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Abstract PDF: Inadvertent application of ionizing radiation, a valuable tool in diagnostic radiology and radiotherapy, results in injury and death of adjacent normal cells, inducing gene mutations or even producing latent cancers. Captopril, an angiotensin I converting enzyme (ACE) inhibitor, has been reported to prevent the structural and functional changes in variable organs, such as lung and kidney, from radiation injury in different experimental animal models. An experiment was carried out to elucidate the radiation-induced histomorphologic changes of small intestine, especially jejunum, and to determine whether captopril can reduce or prevent the radiation-induced injuries in jejunum. Twenty-six healthy Sprague-Dawley rats were used. Experimental group (n=24) was divided into two large groups: the first one (n=16) was treated with two different single dose (9 Gy, 17 Gy) irradiation only and was sacrificed at 12 hours and at 8 weeks following irradiation; the second one (n=8) received captopril 500 mg/l per oral continuously after same doses of irradiation and was sacrificed at 8 weeks. The control group (n=2) was maintained on a stock diet in a same period of experimental group and sacrificed coincidentally. On light and electron microscopy, the 9 Gy and 17 Gy 12 hours groups revealed frequent apoptosis and necrosis but extremely decreased mitotic figures of the crypt cells. However, the 9 Gy and 17 Gy 8 weeks groups and the combined irradiation with captopril groups showed extremely reduced apoptosis and necrosis with increased mitotic figures. There was good correlation between experimental groups in apoptotic count and mitotic count (p<0.05). In the 9 Gy and 17 Gy 12 hours groups, the mucosal surface was focally or diffusely fragmented and the villi were slightly to moderately distorted. Collagen deposition was very mild and confined to the lower portion of the lamina propria. The 9 Gy and 17 Gy 8 weeks groups showed more severe mucosal surface fragmentation even with foci of erosion, short and distorted villi, and more intense collagen deposition. In contrast, the combined irradiation with captopril groups revealed complete regeneration of the mucosal surface epithelium and absent collagen deposition. These findings suggest that the acute radiation injuries to small intestine occur principally in the mucosal crypt cells. Captopril, the ACE inhibitor, might provide a useful intervention in the radiation injuries of intestinal mucosa.

Expression of Surfactant-D Protein and TNF-alpha in the Interaction of Pneumocystis Carinii and Alveolar Macrophages in Pneumocystis Carinii Pneumonia.: Kun Young Kwon, Kwan Kyu Park, Chang Kwon Park, Young June Jeon, Eun Sook Chang; Korean J Pathol. 1999;33(9):684-694.

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Abstract PDF: Alveolar macrophages participate in the host defense against P. carinii, but the mechanisms in degradation and clearance of the organism from lung has not been well established. We observed the transmission and scanning electron microscopic features and evaluated the expression of TNF-alpha and Surfactant-D in the interaction of P. carinii with alveolar macrophages. Expression of TNF-alpha and Surfactant-D in the experimentally induced P. carinii pneumonia in rat was examined by immunohistochemistry and immunoelectron microscopy. Electron microscopically, the alveolar macrophages phagocytized trophozoites and cysts of P. carinii micro-organisms. Immunohistochemically TNF-alpha was strongly expressed in the cytoplasms of alveolar macrophages. Postembedding immunogold labeling for Surfactant-D protein was expressed on the pellicles of trophozoites and cysts, P. carinii micro-organisms in the cytoplasms of macrophages, free floating surfactant materials and multilamellar bodies of type II epithelial cells. We conclude that alveolar macrophages interacted with P. carinii micro-organisms respond with increased expression of TNF-alpha. TNF-alpha may bind to P. carinii and exert a direct toxic effect upon the micro-organisms. Surfactant-D protein may augment binding of P. carinii to the alveolar macrophages and enhance the clearance of the micro-organisms.

Morphologic Changes of Pulmonary Tissue Secondary to Sidestream Cigarette Smoke.: Kun Young Kwon, Ji Min Jeon, Sang Pyo Kim, Kwan Kyu Park, Dae Hyun Kim; Korean J Pathol. 1999;33(6):395-403.

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Abstract PDF: Chronic bronchiolitis is a condition associated with cigarette smoking, and later associated with pulmonary parenchymal alteration and progressive deterioration of lung function. Early respiratory bronchiolitis was produced in Sprague-Dawley rats by indirect inhalation of cigarette smoke daily in a smoke exposure chamber designed by authors for 1 month. Experimental group A (n=5) was sacrificed after having smoked 30 cigarettes, group B (n=5) after 80 cigarette, and group C (n=7) after 140 cigarettes, respectively. Examination of morphologic changes in the lungs was done on light microscope, transmission and scanning electron microscopes. Light microscopically, increase in number of goblet cells in the bronchial mucosa, brown-pigmented macrophages in the alveoli, multifocal alveolar collapse adjacent to the bronchioles, dilatation of alveolar ducts and alveolar spaces were observed. Transmission electron microscopically, irregularly shaped Clara cells, alveolar wall collapse, and focally type I epithelial cell injury were seen. Scanning electron microscopically, scattered alveolar collapse, irregular dilatation of alveolar ducts, alveolar spaces and interalveolar pores (pores of Kohn) were seen. The terminal and respiratory bronchioles showed morphological alteration of Clara cells, but no evidence of cellular bronchiolitis or bronchiolar obstruction. We conclude that sidestream smoke induces an early respiratory bronchiolitis including aggregates of brown pigmented macrophages and varying degrees of structural alteration of adjacent pulmonary parenchyma.

Undescended Testis in the Complete Testicular Feminization Syndrome A report of three cases.: Yu Na Kang, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Jung Ho Lee, Jong In Kim; Korean J Pathol. 1999;33(5):371-375.

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Abstract PDF: The testicular feminization is the most common type of male pseudohermaphroditism. Mutation of androgen receptor gene impairs normal sexual differentiation in genetic male (46, XY) and subsequently develops secondary female characteristics. We report three cases of complete testicular feminization syndrome with normal development of female external genitalia, but with blindly ended vagina and inguinal or pelvic masses. Microscopic examination of the testes and their adnexa had three components: 1) A testis composed of immature tubules, prominent Leydig cells and a spindle cell stroma resembling ovarian stroma with hamartomatous nodule or Sertoli cell adenoma, 2) a white, whorled, firm, smooth muscle body in the medial pole of the testis, and 3) a lateral adnexal cysts of varying sizes.

bcl-2 and p53 Protein Expression in Multiple Myeloma and Non-tumorous Plasma Cells A study related to survival.: Yu Na Kang, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Young Jae Lee; Korean J Pathol. 1999;33(3):179-186.

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Abstract PDF: The gene product of bcl-2 (B-cell leukemia/lymphoma-2) was suggested to suppress programmed cell death (apoptosis) of tumor cells and be involved in the development of multiple myeloma. However, the normal plasma cells also express the protein. It is unclear whether the expression of bcl-2 in multiple myeloma is of normal character or of regulatory adaptation in association with neoplastic transformation. p53 was also suggested to be involved in tumor progression since mutations on p53 were found in multiple myeloma. In order to find the relationship between the expression patterns of bcl-2 and p53 in tumor cells of multiple myeloma and non-neoplastic plasma cells, we examined 38 cases of multiple myeloma and 10 cases of nasal polyp immunohistochemically. Furthermore, expression of bcl-2 and p53, mitosis, clinical stage and infiltrative pattern of tumor cells in bone marrow were also evaluated in association with the survival of patients. By immunostaining with anti-bcl-2 and p53 monoclonal antibody, 37 out of 38 cases of multiple myeloma and all of 10 cases of nasal polyp were positive for bcl-2 but only 7 cases of multiple myeloma were positive for p53. Marked dysplasia, low percentage of bcl-2 expression, and increased mitoses were correlated with poor prognosis. Based on these observations, we suggest that bcl-2 and p53 are involved in tumorigenesis of multiple myeloma and the survival of patients would be influenced by dysplastic change, mitosis and degree of bcl-2 expression.

Expression of Antigenic Surface Molecules of Pneumocystis Carinii by Immunoelectron Microscopic Examination.: Kun Young Kwon, Seung Che Cho, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang; Korean J Pathol. 1998;32(6):393-403.

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Abstract: This study was carried out to investigate the morphologic characteristics and localization of antigenic molecules of Pneumocystis carinii in experimentally induced P. carinii pneumonia in rats. After six weeks of administration of low protein diet and dexamethasone, Sprague-Dawley rats were sacrificed to submit lungs or bronchoalveolar lavage for the study. Monoclonal (092, 900, 902, and 904) and polyclonal (SP-D) antibodies were used for immunohistochemistry and immunoelectron microscopy (ITEM and ISEM). Immunohistochemically P. carinii organisms were well identified as clusters or separated forms in the alveolar spaces being frequently attached to the alveolar walls. Immunoelectron microscopically the adherences of gold particles were observed on the surface of all stages of the P. carinii. Occasionally positive immunogold labeling was observed in the cytoplasm of the trophozoites and on the pellicle of the intracystic bodies within the cysts. The monoclonal antibodies 092, 900, 902, and 904 reacted mainly with pellicles of P. carinii, whereas SP-D labeled on the pellicles, intracystic bodies, cytoplasms of the alveolar macrophages, and free floated surfactant material in the alveolar spaces. The immunogold particles were observed more diffusely and intensely in the cysts than in the trophozoites. These results indicate that antigen is mainly localized on the pellicles, and accumulated during development from the trophozoite to the cyst stages.

An Anion Site Change of the Glomerular Basement Membrane on Various Glomerular Diseases.: Yu Na Kang, Kwan Kyu Park, Seung Pil Kim, Sung Bae Park, Hyun Chul Kim, Eun Sook Chang, In Soo Suh; Korean J Pathol. 1997;31(8):765-772.

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Abstract PDF: We studied the ultrastructural alteration of glomerular anionic sites in 6 patients with minimal change nephrotic syndrome, 5 patients with membranous glomerulonephritis, 4 patients with focal segmental glomerulosclerosis, and 4 patients with IgA nephropathy by staining with polyethyleneimine (PEI) as a cationic probe. The control study was examined by using a nephrectomy specimen of non-glomerular disease which had no proteinuria. This method seems to selectively stain heparan sulphate in the basement membranes and has been widely used to evaluate changes in basement membrane charge in various human diseases as well as in experimental studies. The anionic sites in the lamina rara interna and lamina densa of normal glomerular basement membrane were always less numerous and less regularly distributed than those in the lamina rara externa. Characteristic common findings in these glomeruli showed a marked decrease of glomerular anionic sites in the regions with immune-complex deposits and normal distribution in the regions with focally those being absorbed and newly forming glomerular basement membrane. They were not detected in the gap of the basement membrane and on the area of the detached overlying epithelium using the PEI method. But the foot process fusion of epithelial cells seems not to influence the loss of anionic sites on the glomerular basement membrane.

Immunocytochemical Detection of Pneumocystis Carinii in Bronchoalveolar Lavage .: Kun Young Kwon, Seung Che Cho, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang, Chung Sook Kim; Korean J Cytopathol. 1997;8(1):27-34.

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Abstract PDF: Pneumocystis carinii is an established cause of pulmonary infections in immuno- compromised hosts. Several cytological stains, such as Papanicolaou, Gomori methenamine silver(GMS) and Diff-Quik have been used for detection of the organism, but occasionally can be laborious and, due to a degree of nonspecificity, may be misleading. We evaluated the diagnostic utility of immunocytochemical stains that recognize P. carinii in bronchoalveolar lavage from experimentally induced P. carinii pneumonia rats(n=15). In addition to routine stains for diagnosis by morphologic recognition of P. carinii on Papanicolaou, GMS and Diff-Quik stains, bronchoalveolar lavage samples were reacted with immunocytochemical stains using monoclonal antibodies(MAB) 092 and 902. In bronchoalveolar lavage P. carinii organisms were detected in 9 of 10 cases (90%) using each MAB 092 and 902, whereas GMS and Diff-Quik stains demonstrated P. carinii in 13(86%) and 11(73%) of 15 cases respectively. In lung tissue specimens(n=15) P. carinii organisms were well identified on GMS stain and immunohistochemical stains using MAB 092 and 902 in all cases. We believe that the immunocytochemical staining using MAB 092 and/or 902 is a very useful and diagnostic tool in addition to GMS and Diff-Quik stain to detect P. carinii organisms in bronchoalveolar lavage.

Non-neoplastic Lesions in Temporal Lobe Epilepsy: A Pathologic Review of 64 cases.: Sang Pyo Kim, Kun Young Kwon, Eun Sook Chang, Kwan Kyu Park, Sang Do Yi, Eun Ik Son; Korean J Pathol. 1996;30(4):281-292.

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Abstract PDF: Temporal lobe epilepsy is characterized by complex partial seizures with either primary intracranial neoplasms or other non-neoplastic lesions. We reviewed 64 cases of surgically resected temporal lobes and amygdalo-hippocampal regions for temporal lobe epilepsy ansed by non-neoplastic lesions to elucidate the incidence and histologic features of each histologic group for a period of 2 years. The patient's age ranged from 12 to 49 years and the ratio of male to female was 42:22. There were 37 cases(57.8%) with single pathology and an additional 20 cases(31.3%) with dual pathology. The emaining 7 cases(10.9%) had no structural alternations. The most common temporal lobe pathology was hippocampal sclerosis in 41 cases(64.1%), diagnosed alone in 21 cases and as dual lesions in 20 cases. The hippocampal neuron loss was most pro,omemt in CA1, followed by CA4, CA3, and CA2. Amygdaloid sclerosis was present in 28 cases(43.8%), lases had 13 dual lesions, 25 cases also had hippocampal sclerosis. The 20 dual lesions showed that 6 cortical dysplasia, 10 microdysgenesis, 1 chronic non-specific inflammatory lesion, and 3 cysticercosis were associated with the various degree of mesial temporal sclerosis. Neuronoglial malformative lesions were identified in 21 cases(32.8%) including 16 dual lesion cases, which composed of 15 microdysgenesis and 6 cortical dysplasia. Neurofilament immunostain for cortical dysplasia revealed abnormally beaded disarray of axons in dysplastic pyramidal cells. The remaining pathologic lesions observed were 1 cysticercosis, 1 chronic non-specific inflammatory lesion, 3 arteriovenous malformation, 2 fibrous nodule, and 1 fibrous adhesions of the arachnoid.

Sertoli-Leydig Cell Tumor with a Coexisting Brenner Tumor of the Ovary.: Ji Youn Bae, Sang Pyo Kim, Kwan Kyu Park, Soon Do Cha; Korean J Pathol. 1996;30(3):266-268.

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Abstract PDF: Sertoli-Leydig cell tumor or Brenner tumor is a relatively rare ovarian tumor. Other associated elements in the form of epithelial, mesenchymal, and tumor components of each tumor have been reported. The Sertoli-Leydig cell tumor with a Brenner tumor element has not been documented in the literature, so we are reporting on a case of Sertoli-Leydig cell tumor coexisting with a Brenner tumor. This 62-year-old woman presented with a 4 year history of lower abdominal mass and vaginal bleeding. Exploratory laparotomy was done. The left ovary showed a multiseptated, cystic, yellow-white solid mass, measuring 17.0x13.0x5.0 cm and weighing 985.0 gm. Microscopic examination revealed a tubular or trabecular arrangement of the Sertoli cells and variable numbers of Leydig cells. There were several tumor nests with cystic spaces composed of ovoid cells showing longitudinal nuclear grooving. Sarcomatoid or heterologous elements were not found.

Ultrastructural Changes in Rat Kidney after Lead Acetate Administration.: Hyun Chul Kim, Seung Pil Kim, Kwan Kyu Park; Korean J Pathol. 1996;30(2):73-88.

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Abstract PDF: This study was carried out to investigate the ultrastructural findings of rats after administration of 0.5% lead acetate with drinking water. The Sprague-Dawley rats were divided into control and experimental groups. The control group was composed of 12 rats and was orally administered with 0.5% sodium acetate. The experimental group was composed of 36 rats and orally administered with 0.5% lead acetate. Two rats in the control group and four rats in the experimental group were sacrificed on day 2, and week 1, 2, 4, 6 and 8 after administration. The kidney was extirpated and examined by electron microscopy. The results obtained were as follows: The blood lead concentration in the experimental group began to increase from the second day after administration and it increased gradually until the 6th week and it decreased at the 8 week. The urinary excretion of delta-ALA also increased from the secondary and gradually increased up to the 8th week. On electron microscopic examination, the proximal tubular cells showed fat droplets, dilatation of the endoplasmic reticulum, mitochondrial swelling, increased numbers of secondary lysosomes and myelin figure-like residual bodies and intranuclear inclusion bodies. All these findings peaked at the eighth week after administration. Ultrastructural findings after Timm sulphide silver reaction revealed the lead granules in the proximal tubular lumen and between the microvilli of the proximal tubular cells without membrane-bounded. It can be concluded that most of the changes of micro-organelles are compatible with degenerative changes of lead exposure and passive diffusion of lead granules are involved in the proximal tubular cells.

Cytologic Analysis of Malignant Effusion.: Sang Pyo Kim, Ji Yeon Bae, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Chung Sook Kim; Korean J Cytopathol. 1995;6(2):116-124.

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Abstract PDF: Eighty cases of malignant effusion were cytologically studied to elucidate the incidence of primary tumor site and cytologic characteristics of each tumor types. Eighty fluid specimens were composed of 43 ascitic, 35 pleural, and 2 pericardial effusion and primary tumor site had been confirmed by histology. The frequent primary sites were stomach (22 cases, 28%), lung (21 cases, 26%), ovary (11 cases, 14%), liver (7 cases, 9%), and breast (4 cases, 5%). The principal malignant tumors were adenocarcinoma (56 cases, 70%), squamous cell carcinoma (7 cases, 9%), liver cell carcinoma (7 cases, 9%), small cell carcinoma (4 cases, 5%), and non-Hodgkin}s lymphoma (4 cases, 5%). The distinctive cytologic findings according to primary tumor types were as follows ; the gastric adenocarcinomas were mainly characterized by isolated cells and irregular clusters sometimes with signet ring cells. Papillary serous cystadenocarcinoma of ovary showed frequently papillary clusters and occasional psammoma bodies. Breast carcinoma of ductal type showed cell balls with smooth margins. Colonic adenocarcinoma showed rather irregular clusters or palisading pattern of cylindrical cells. Metastatic squamous cell carcinoma, liver cell carcinoma, small cell carcinoma, and non-Hodgkin}s lymphoma showed also characteristic features. These findings indicate that the cytological features observed in the great majority of malignant effusion are similar to those of primary tumor types, which are very helpful to indentify the primary tumor site.

Congenital Cytomegalic Inclusion Disease combined with Hydrocephalus: A case report.: Kam Rae Cho, Cheol Hee Yun, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang, Taek Hoon Kim; Korean J Pathol. 1994;28(4):439-441.

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Abstract PDF: This is an autopsy-verifed case of the generalized cytomegalic inclusion disease occuring in a male fetus of a weeks gestation. The fetus revealed hydrocephalus and focal necrosis of brain, focal subcapsular necrosis of liver, and the typical cytomegalic inclusion cells having large acidophilic intranuclear inclusions in the liver, brain, kidney, lung, adrenal gland, pancreas and chorionic villi. Prominent extramedullary hematopoiesis was noted in the liver and kidney. Immuohistochemical staining using anti-cytomegalovirus antibody revealed intranuclear or occasionally intracytoplasmic immunoreactivity in brain, liver, pancreas, lung, kidney, and intestine.

Overexpression of Mutant p53 in Human Anaplastic Astrocytoma and Glioblastoma Multiforme.: Sang Sook Lee, Kam Rae Cho, Cheoul Hee Yun, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang, Eun Ik Sohn; Korean J Pathol. 1994;28(4):376-380.

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Abstract PDF: A total of 30 cases of cerebral gliomas, including 6 cases of low grade astrocytomas, 6 anaplasticastrocytoomas and l8 glioblastomas multiforme, was examined immunohistochemically to demonstrate the overexpression of mutant forms of p53 protein and to evaluate their relationships with histological subtypes. A p53 monoclonal antibody was applied to the routine formalin fixed, paraffin-embedded tissues for this study using microwave-assisted avidin-biotin method. Overexpression of p53 protein was identified in 4 out of 6 anaplastic astrocytomas (66.7%) and in l3 out of l8 glioblastomas multiforme (72.2%). No immunohistochemical positivity of p53 was found in adjacent normal brain tissue, gliosis and 6 cases of astrocytoma. These results suggest that overexpression of mutant p53 may be an important step in the development and progression of malignant astrocytoma, especially of the aggressive subtypes of glioma, including glioblastoma multiforme.

Bronchoalveolar Lavage of Pneumocystis carinii Pneumonia: Cytological and Ultrastructural Features.: Kun Young Kwon, Cheol Hee Yun, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang; Korean J Cytopathol. 1994;5(1):1-9.

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Abstract PDF: The cytological and ultrastructural findings of Pneumocystis carinii(PC) obtained from rats by bronchoalveolar lavage(BAL) are described. All developmental forms of the PC organisms were obtained in the lavage fluid. Ultrastructurally, the cysts were almost circular in shape, and were nearly devoid of surface tubular extensions. The wall of the cyst was composed of an unit membrane, and intermediate electron lucent layer and an external electron dense layer. The cysts frequently contained intracystic bodies, so called sporozoites. Occasionally empty or collapsed cysts with no intracystic bodies, and precysts were found. Trophozoites were variable in size and shape with abundant tubular extensions along the single electron dense pellicle. BAL is a useful method for concentrating the various morphologic forms of PC organisms, and is a rapid diagnostic method for PC pneumonia.

A Comparative Study of PCNA Immunostaining, AgNOR Scores Hormone Receptors and Histology in Human Breast Cancer.: Eun Sook Chang, Kwan Kyu Park; Korean J Pathol. 1993;27(6):605-617.

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Abstract PDF: This study was performed on 50 cases of primary breast cancer removed surgically during the period 1990~1991 and compared the results of four morphologic methods developed for the detection of estrogen receptors, progesterone receptors, monoclonal antibody PCNA immunoreactivity, and the mean number of argyrophilic nucleolar organizer regions(mAgNORs) to ascertain the prognostic significance and also to detect highly malignant heterogenous cancer. To determine the validity of these measurements, a variance analysis was done with Kruskal-Wallis 1-way ANOVA. The results showed that the significant correlation between histologic grade and ER/PR status(P=0.005/P=0.015), the borderline significant correlation between mAgNORs and ER/PR status(P=0.08), and between AgNORs and stage(P=0.07), PCNA has no correlation with ER/PR status(P=0.25), clinical stage and histologic grade. In follow up, four cases of invasive ductal carcinoma with ER/PR, developed early and rapid metastasis within 2 years, three of them were classified as histologic grade 3 and another case was grade 2, whereas two of them were classified ans stage III(+) and the rest were in stage IIB(+) and stage IIA(-). The mAgNOR count of these four cases were ranged from 3.32 to 4.29 which were in the aneuploid category most likely. One of them had rather stormy rapid course with multiple organ metastases resulting death within one year. These results indicated that ductal carcinoma(>2cm size) with ER-/PR- and high mAgNOR level or high PCNA grade, and hihg histologic grade had h highly malignant course, marked by rapidly developing metastases. Thus we concluded that the status of ER/PR alone in tumor tissue is an important information for selecting hormone treatment btu, for the ultimate prognosis, is a weak indicator. Therefore for early detection of such heterogenous tumor, besides ER/PR, AgNORs or PCNA, histologic grade and tumor size are very useful as biological indicators of prognosis. The status ER/PR in combination with these indicators are more accurate and provide better basis on which to base a decision for early implementation of chemotherapy from which to give probably benefit by inhibition of rapid progress.

Capillary Plexus and Vasa of the Rat Lung as Revealed by Scanning Electron Microscope of Corrosion Casts.: Kun Young Kwon, Kam Rae Cho, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang; Korean J Pathol. 1993;27(1):11-18.

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Abstract PDF: The pulmonary microvasculatures of rats were studied by injection replicas prepared from Mercox. This medium enabled us to easily obtain consistent, stable, and complete injected replicas of the pulmonary vasculature. In order to investigate the three dimensional structures of the tributaries of the bronchial artery, such as the capillary plexus and vasa vasorum, we performed a scanning electron microscopic(SEM) study of the vascular casts, using Mercox CL-2B as a media. The alveolar capillaries revealed hexagonal or pentagonal rings of vascular networks. In some areas, the vascular rings composed a square network, The bronchial tree was supplied by the bronchial arteries which form a coarse capillary extending as far as the terminal bronchioles. Occasionally the capillary plexus was connected with adjacent capillary networks in and around the alveolar walls. The walls of the pulmonary artery revealed only a single layer of the vasa vasorum, but those of the pulmonary vein were surrounded by more complicated and well developed vasa vasorum than the pulmonary arterial side. The mean diameters of the venous vasa vasorum are greater than the arterial vasa vasorum.

Fine needle aspiration cytology of endodermal sinus tumor of the mediastinum.: Kam Rae Cho, Sang Pyo Kim, Kwan Kyu Park, Kun Young Kwon, Eun Sook Chang; Korean J Cytopathol. 1993;4(1):57-61.

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Abstract PDF: No abstract available.

Light Electron Microscopic Study in Rat Livers Following Cadmium Chloride Administration.: Kwan Kyu Park, Young Ho Kim, Kun Young Kwon, Eun Sook Chang, Moo Ung Chang; Korean J Pathol. 1992;26(1):28-39.

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Abstract PDF: This study was carried out to investigate the light and electron microscopic findings of the livers of rats after an intraperitoneal injection of cadmium chloride. The Sprague-Dawley rats were intraperitoneally injected with cadmium chloride dissolved in water, once a day for three days. These animals were sacrificed at 1, 3, 8, and 24 hr after the last injection. Control groups of the rats were also sacrificed in the same manner. The liver was extirpated and examined by both light and electron microscopy. The results obtained are as follows: The parenchyma of the liver shows focal neutrophilic infiltration and spotty necrosis. The hepatocytes show fatty change, ballooning degeneration, swelling of the endoplasmic reticulum and mitochondria, increase numbers of secondary lysosomes and residual bodies. Focal patic venules and sinusoids of the liver are congested. The Kupffer cells are increase in number. Therefore, it can be concluded that the cadmium is directly acted to hepatocytes resulting in cellular injuries and deposits in the fat droplets of the cytoplasm of the hepatocytes, not Ito cells as previously suggeted.

An Ultrastructural Study of Bleomycin-Induced Interstitial Pulmonary Fibrosis in the Rat.: Seung Che Cho, Kwan Kyu Park, Kun Young Kwon, Eun Sook Chang; Korean J Pathol. 1991;25(6):539-550.

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Abstract PDF: This study was carried out to investigate the mechanisms of interstitial pulmonary fibrosis of rats after the intratracheal administration of bleomycin. Both lungs after bleomycin injection were examined by light and electron microscopy. The results are as follows: Light microscopically, 1 or 2 weeks after bleomycin injection acute and chronic inflammatory infiltrates and edema in the interstitium and alveolar spaces were observed. Proliferation of alveolar type II pneumocytes was also found at 4 to 6 weeks after bleomycin injection, chronic inflammatory infiltrates with interstitial fibrous thickening were noted. Electron microscopically, the number of type II pneumocytes and irregular lamellar bodies were increased and blunted microvilli were noted at 2 weeks. 4 to 8 weeks, proliferation of fibroblasts with deposition of abundant collagen fibrils in the thickened interstitium revealing irregular or collapsed alveolar spaces were observed. Based on these findings, it can be concluded that bleomycin-induced interstitial pulmonary fibrosis is considered to pass from an early acute inflammation of the interstitium and alveolar spaces to an interstitial fibroblast proliferation and collagen deposition to the length of the period after injection.

The Spontaneously Occurred Apoptosis in Squamous Carcinoams of the Uterine Cervix.: Chan Hwan Kim, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang; Korean J Pathol. 1990;24(3):254-266.

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Abstract PDF: The apoptosis, a distinctive type of individual cell necrosis, has been considered to play a complementary but opposite role to mitosis in the regulation of animal cell populations. It can be initiated or inhibited by a variety of environmental stimuli, physiologically and pathologically. Apoptosis seems to appear in either non-neoplastic or neoplastic tissues, even malignant tumors in the state of untreatment or irradiation. This study was carried out to investigate the spontaneous occurrence of apoptosis in squamous carcinomas of the uterine cervix and its mechanisms. Light microscopically, noted were the condensation and fragmentation of individual tumor cells with formation of apoptotic bodies that were frequently phagocytosed by nearby intact tumor cells. They were commonly seen in the neighbourhood of coagulative necrosis. Electron microscopically (TEM and SEM), noted were nuclear condensation, margination toward the nuclear membrane and fragmentation of membrane-bounded apoptotic bodies that were well preserved. The intracellular apoptotic bodies were phagosomes and reduced to electron-dense lysosomal residual bodies. The conclusion obtained was as follow: Apoptosis was found in all cases of squamous carcinoma of the uterine cervix, of which the frequency was higher in tumors of poor differentiation than those of well to moderate differentiation. The process of the apoptosis is considered to pass through the step of formation of the apoptotic bodies, phagocytosis by adjoining tumor cells or histiocytes, and then degradation as lysosmal residual bodies.

Cytologic Findings of Bronchoalveolar Lavage.: Kun Young Kwon, Seung Che Cho, Kwan Kyu Park, Eun Sook Chang; Korean J Cytopathol. 1990;1(2):129-138.

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Abstract PDF: Bronchoalveolar lavage (BAL) has emerged as a useful technique for the study of pulmonary interstitial disorders. Several types of information are provided by the evaluation of lavage fluid. Identification of cellular constituents helps to separate inflammatory process. Recently we have studied cellular constituents of BAL from three cases with histologically confirmed pulmonary sarcoidosis, idiopathic pulmonary fibrosis and hypereosinophilic syndrome. Pulmonary sarcoidosis showed a marked increase in lymphocytes, idiopathic pulmonary fibrosis revealed a predominance of neutrophils, and hypereosinophilic syndrome presented a marked increase in eosinophils in the lavage fluids.

Ovarian Pregnancy: 12 cases analysis.: Kwan Kyu Park, Sang Sook Lee, Eun Sook Chang, Chae Hong Chung; Korean J Cytopathol. 1985;19(3):339-344.

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Abstract PDF: From January, 1972 to August 1983, 12 cases of ovarian pregnancy out of 1202 total ectopic pregnancy were studied and the incidence constituted 0.9%. The gross and microscopic findings were reviewed according to gross description and gross photographs, and microscopic description and reviewing all microscopic slides. All cases were shown to meet Spiegelberg's criteria for primary ovarian pregnancy.

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