- Effect of Probucol and Verapamil on Injury to Myocardium and Nerve Fibers in Rat Heart Induced by Doxorubicin.
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Sang Yeop Yi, Sang Ho Cho, Woo Ick Yang
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Korean J Pathol. 2004;38(6):378-387.
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- BACKGROUND
Doxorubicin is considered to be one of the most effective drugs to treat a variety of human cancers.
However, the dose-dependent cardiotoxicity of doxorubicin limits its clinical usefulness. This study aimed to evaluate the effect of probucol and verapamil on the cardiac neurotoxicity and cardiomyopathy induced by the long-term use of doxorubicin.
METHODS
Sprague-Dawley male rats were grouped as the control group, the doxorubicin treated group, the doxorubicin treated with probucol group, and the doxorubicin treated with verapamil group. The rats were treated for 4, 6, 8 and 10 weeks. H&E staining and immunohistochemical staining for protein gene product 9.5, caspase-3, heat shock protein 70, and hsp 25 were performed.
RESULTS
The degree of interstitial inflammatory cell infiltration was mildest in the probucol treated group. The reduction in the number of nerve fibers in the probucol treated group was less than the other treatment groups.
There was a negative correlation between the treatment duration and stained nerve fibers in all the treatment groups. The number of caspase-3 positive cells was more increased in the doxorubicin group and the verapamil treated group than in the control and probucol treated group.
CONCLUSION
It is suggested that probucol partly contributed to the inhibition of doxorubicin-induced cardiac neurotoxicity and cardiomyopathy, whereas the verapamil had no effect.
- Pseudofungi Associated with a Granulomatous Response in a Lymph Node: A Case Report.
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Haeryoung Kim, Ja Seung Koo, Hyosup Shim, Gijong Yi, Sang Ho Cho
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Korean J Pathol. 2004;38(1):64-67.
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We present herein a case of pseudofungi incidentally found in the mediastinal lymph nodes of a 31-year-old woman who had a left pneumonectomy for a pulmonary blastoma. The pseudofungi were located in the subcapsular sinuses of the lymph nodes with an associated granulomatous reaction. They revealed yellowish-brown hyphae-like structures with pseudosepta and irregular branching at various angles intermingled with round yeast-like forms. These structures stained positively with periodic acid-Schiff and Gomori methenamine silver, but also stained strongly positive for Prussian blue suggesting that they contain iron. The characteristic morphological features of pseudofungi are discussed with emphasis on the features that distinguish them from true fungal organisms.
- The Expression of Extracellular Signal Regulated Kinase (ERK) in Non-Small Cell Lung Carcinoma.
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Se Hoon Kim, Hyung Jung Kim, Young Nyun Park, Sang Ho Cho
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Korean J Pathol. 2001;35(5):361-367.
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- BACKGROUND
Although it was suggested that constitutive extracellular signal regulated kinase (ERK) activation plays a pivotal role in intracellular signal transduction related to oncogenesis, a consistent relationship between constitutive ERK activation and oncogenesis has not yet been clearly demonstrated. The purpose of this study is to evaluate the expression frequencies and pattern of phosphorylated ERK (p-ERK) in the non-small cell lung carcinoma (NSCLC) and to evaluate whether p-ERK is a useful prognostic factor.
METHODS
One hundred sixty cases of NSCLC tissue specimens were investigated by immunohistochemical staining for p-ERK.
Clinicopathologic values (tumor stage, cell type, differentiation and presence of metastasis) and p-ERK expression of normal alveolar pneumocytes around NSCLC were compared with the incidence of tumor p-ERK expression.
RESULTS
Fifty-three out of 160 cases (33%) of NSCLC showed expression of p-ERK. There was no statistical correlation between the expression of p-ERK in the NSCLC neoplastic cells and the corresponding tumor stage, cell type and presence of metastasis. There was statistical significance between the expressions of p-ERK in alveolar pneumocytes around NSCLC (odds ratio: 6.130).
CONCLUSIONS
Based on these results, we suggest that p-ERK expression is not useful in predicting the prognosis of NSCLC. In regard to the theory of "field cancerization" and the phenomenon of "allele-specific loss or allele-specific mutations", the statistically significant p-ERK expression in alveolar pneumocytes around NSCLC suggests that constitutive ERK activation is involved in the early stage of NSCLC carcinogenesis rather than in proliferation, differentiation or metastasis of NSCLC.
- Nevus Cell Inclusions in the Lymph Node: A Report of Two Cases.
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Ji Sun Song, Tae Woong Noh, Yoon Mee Kim, Sang Ho Cho, Kwang Gil Lee
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Korean J Pathol. 2001;35(3):245-247.
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- Nevus cell inclusion in the lymph node is an uncommon histologic finding and usually is an incidental finding in the capsule, fibrous trabeculae, perinodal adipose tissue, and parenchyma of the axillary, inguinal, or cervical lymph nodes which are removed as part of cancer diagnostic or therapeutic procedures. The aggregated pigmented nevus cells in the lymph node resemble the cells of the cutaneous nevi. It is important to differentiate them from metastatic carcinoma or malignant melanoma. The characteristic features of nevus cell inclusions are presence of nevus cells within the capsule and supporting stroma, without presence in the marginal sinus of the lymph node, and the absence of cytological atypia or mitosis of nevus cells. We report two cases of nevus cell inclusions, in the axillary lymph nodes in a patient with breast carcinoma and in an enlarged inguinal lymph node in a patient without a malignant tumor.
- Relationship among the Expression of Cyclin D1, p21, and p53 Protein, and Prognosis in Non-Small Cell Lung Carcinomas.
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Seok Woo Yang, Sang Ho Cho, Woo Ick Yang, Woo Hee Jung, Chul Min Ahn, Doo Yun Lee
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Korean J Pathol. 1999;33(12):1120-1130.
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- Recently, cell cycle regulators have been suggested as new prognostic factors of the lung cancer. In this study, we evaluated the expression of cyclin D1, p21, and p53 using the X2-test, with regard to the stage of the patients, histologic type, and histologic differentiation in the 135 cases of non-small cell lung carcinomas (NSCLC). To evaluate the confounding effects among cyclin D1, p21, and p53 on X2-test analysis, we used the Mantel-Haenzel test. The NSCLC in this study included 82 cases of squamous cell carcinoma and 53 cases of adenocarcinoma. Each nuclear staining of cyclin D1, p21, and p53 was observed in 65 cases (48.1%), in 54 cases (40.0%), and in 81 cases (60.0%) of NSCLCs, respectively. Only p53 expression was significantly associated with the stage (stage I, II, IIIa) (p<0.05) and squamous cell carcinoma (p<0.05). On the other hand, cyclin D1 expression was significantly associated with the histologic differentiation. The confounding effects among cyclin D1, p21, and p53 revealed that only p21 expression changed the relationship between p53 and stage. In this regard, further study is needed.
- Williams Syndrome in an Infant An autopsy case report .
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Jeong Hae Kie, Se Hoon Kim, Jae Young Choi, Sang Ho Cho
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Korean J Pathol. 1999;33(11):1090-1093.
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- Williams syndrome is a congenital disorder characterized by mental retardation, loquacious personalities, dysmorphic face, and vascular and valvular abnormalities. The etiology of this syndrome was one allelic loss of elastin gene, exhibiting a submicroscopic deletion, at 7q11.23.
Sudden death is an infrequently recognized complication. The mechanism of sudden death is explained by myocardial ischemia, decreased cardiac output, and arrhythmia by anatomical abnormality of coronary artery stenosis and severe biventricular outflow tract obstruction. We report an autopsy case of a 80 day-old male with Williams syndrome. Five days before admission, cardiac murmur was detected incidentally on ascultation at a local clinic during a visit for vaccination. He was transferred to our hospital and cardiac catheterization was done.
He died suddenly next day. Postmortem examination revealed a dysmorphic face and multiple cardiovascular abnormalities including supravalvular aortic stenosis with narrowed coronary artery ostia, supravalvular pulmonic stenosis, secundum type of atrial septal defect, right ventricular hypertrophy, and renal artery stenosis.
Histologically, aorta and pulmonary, bronchial, and renal arteries showed markedly hyperplastic medial elastic laminae approximately three times thick compared to those of age-matched normal artery. The elastic fibers of the innermost two thirds of media were disposed in a normal orderly parallel fashion. In outer third of the media, the elastic fibers had lost the normal orderly arrangement.
- Expression of TGF-beta and PDGF in Monocrotaline-Induced Pulmonary Hypertension in Rats.
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Min Sun Cho, Sang Ho Cho, Woo Ick Yang, Woon Sup Han
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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.
- Adenoid Cystic Carcinoma of the Male Breast: A case report.
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Mi Kyung Lee, In Chul Hong, Woo Ick Yang, Sang Ho Cho
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Korean J Pathol. 1999;33(5):389-392.
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- A 65 year-old male patient presented with a large palpable mass beneath the areola of the right breast for 7 years. The resected breast tissue was almost totally replaced by a round large solid mass (9 6 cm) with a pink-gray to yellow firm, partly nodular cut surface. Microscopically, the tumor revealed the diagnostic biphasic cellular pattern of adenoid cystic carcinoma, which consisted of both cribriform pattern of myoepithelial cells and tubular pattern of epithelial cells.
On immunohistochemistry, the tumor revealed immunoreactivities for alpha-smooth muscle actin and S-100 protein in the myoepithelial cells and for AE1/AE3 in the epithelial cells.
Mitoses were scarce.
Multifocal lymphatic permeation and foci of perineural invasion were also found.
Underlying resection margins and overlying skin were invaded by the tumor. We diagnosed this tumor as grade II adenoid cystic carcinoma according to the system utilized for the salivary gland tumors.
- Relation of Heart Weight to Body Weight, Body Surface Area, Height, and Age in Normal Korean Men and Women.
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Hee Soo Yoon, Hea Soo Koo, Joong Seok Seo, Sang Yong Lee, Jung Duck Park, Moo Yeol Lee, Sang Ho Cho
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Korean J Pathol. 1999;33(1):1-8.
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- Cardiovascular diseases have been the most serious threat to life and health. The socioeconomic ramifications of heart disease have long been a source of vexing legal as well as medical problems with no easy resolution as yet in hand.
Heart weight, one of the important factors for the diagnosis of cardiomegaly and various heart diseases, shows extreme variability according to the height, weight, age, sex, nutritional status of individuals as well as other various factors. The purpose of this investigation was to find a practical method for calculating expected normal range of heart weight in a given individual. The study was performed on 259 autopsy cases of normal Korean men and women, consisting of 123 men and 136 women in age from newborn to 77 years old. Height, body weight, and heart weight were measured and the body surface area was calculated by height (cm)0.725 x weight (kg)0.425 x 71.84 and height (cm)0.7763 x weight (kg)0.4081 x 71.84 in men and women, respectively.
The results showed that the mean heart weight of men and women older than 20 years old were 316.20 +/- 51.15 g (n=96) and 275.87 +/- 44.69 g (n=108), respectively. Heart weight was gradually increased according to the age. The body weight (men: r=0.81, women: r=0.84) and body surface area (men: r=0.83, women: r=0.83) were better univariate predictors of normal heart weight than body height (men: r=0.78, women: r=0.75) and age (men: r=0.42, women: r=0.57).
No significant difference was found in predictive precision between body weight and body surface area. Since the body surface area was calculated from body weight and height, measuring the body weight was essential for calculating expected normal range of heart weight in a given individual, and calculation of expected normal range of heart weight using body weight was simpler method than using body surface area.
- A Histologic Classification of Diffuse Interstitial Lung Disease and Its Clinical Significance.
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Eun Suk Koh, Dong Wha Lee, So Young Jin, Sang Ho Cho
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Korean J Pathol. 1996;30(11):998-1010.
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- Diffuse interstitial lung disease(DILD) is a large group of heterogeneous diseases that diffusely involve the pulmonary connective tissues, principally subpleural, interlobular and alveolar wall portions. Terminology and classification of these diseases are not uniform, and the cause and the pathogenesis are unknown in many entities. It is generally accepted that the response to therapy is related to the relative degree of cellularity and fibrosis present, therefore a histologic evaluation of the relative extent and severity of these changes is required. We reviewed 52 cases of DILD from January 1990 to May 1995 diagnosed by open lung biopsy to reappraise classification and quantitative assessment of the histopathologic features. Differential histopathologic features between usual interstitial pneumonia(UIP) and nonspecific interstitial pneumonia(NIP) were examined with a correlation of HRCT findings and clinical findings. Among 52 cases of DILD, 18 cases(34.6%) were UIP, 6 cases(11.5%) were hypersensitivity pneumonia was NIP was 5 cases(9.6%), interstitial lung diseases associated with the connective tissue diseases were 5 cases(9.6%), inorganic dusts were 4 cases(7.7%), infections were 4 cases(7.7%), durgs were 2 cases(3.8%), acute interstitial pneumonia was 1 case(1.9%), sarcoidosis was 1 case(1.9%) in order of frequency plus 6 other cases(11.5%). UIP was the most frequent DILD in this study which seemed to be a criteria bias of patient selection on open lung biopsy.
Quantitative assessment of histopathologic features was useful in the differential diagnosis of DILD and differentiation of UIP from NIP was possible based on histopathologic features and supported by HRCT. UIP disclosed a significantly high score of fibrotic changes, especially in the interstitial fibrosis, smooth muscle proliferation and honeycombing, otherwise NIP appeared relatively high score in inflammatory changes. Correlation between histopathologic scores and the clinical outcome after steroid therapy or no therapy in UIP was not evident.
- Common Arterial Trunk: Report of Five Atopsied Cases.
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Gil Hyun Kang, Yong Hee Lee, Chong Woo Yoo, Choong Sik Lee, Hong Ryang Kil, Sang Ho Cho, Jeong Wook Seo
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Korean J Pathol. 1996;30(11):1027-1033.
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- The common arterial trunk is a congenital cardiovascular malformation in which one arterial trunk gives origin to the aortic arch, pulmonary and coronary arteries. Other cardiovascular malformations are often associated, such as ventricular septal defect, aortic arch interruption, patent arterial duct and so on. During the early period of life, the persistence of the increased pulmonary arteriolar resistance results in cyanosis. As the pulmonary vascular resistance decreases, the cyanosis disappears but signs of congestive heart failure become the main problems. We report five cases of common arterial trunk that was confirmed by autopsy at Chungnam National University Hospital, Seoul National University Hospital, and Yonsei University Severance Hospital between 1983 and 1995. The ages of these patients at autopsy were 8-28 days and four of them were male. Pulmonary arteries arose as a pulmonary trunk in two cases but three cases showed two arteries arising separately from the posterior wall of the common trunk. The type of ventricular septal defect was juxtatruncal in every case. All five cases had three leaflet truncal valves but three cases showed dysplasia of the leaflets. Interruption of aortic arch was associated in two cases. The cause of death was renal failure in two cases, cardiac failure after corrective surgery in two cases, and pulmonary edema and failure in one case.
- Ectopic Umbilical Liver Associated with Intrauterine Fetal Death: An autopsy case.
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Jai Hyang Go, Sang Ho Cho
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Korean J Pathol. 1996;30(3):269-271.
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- Ectopic liver in the umbilicus is very rare, and a few cases have been reported in the world. It is thought that an increased intraabdominal pressure resulting in entrapment of liver cell nests causes the presence of liver in the umbilicus. It relates to neonatal problem such as infection.
We report a case of ectopic umbilical liver in a stillborn male of 28 gestational weeks. His mother discovered loss of fetal movement 2 days before admission, and intrauterine fetal death was diagnosed by ultrasonography. Grossly, the umbilical cord was markedly swollen. On cut section, a well circumscribed, oval round, tan-colored soft mass was noted within the cord. Histologically, it consisted of hepatic cords without bile ducts. The umbilical vessels were distorted by the ectopic liver, and contained thrombi. These findings suggest that ectopic umbilical liver results in the intrauterine fetal death
- A Morphological Study of the Pulmonary Endothelium and Neuroendocrine Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension.
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Woo Ick Yang, Sang Ho Cho, In Joon Choi, Yoo Bock Lee
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Korean J Pathol. 1992;26(6):582-592.
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- To investigate the mechanism of monocrotaline-induced pulmonary arterial hypertension, authors performed immunohistochemical study using antibody to von Willebrand factor(vWF), cell kinetic study using 5-bromodeoxyuridine and ultrastructural study after single subcutaneous injection of monocrotaline(MCT) to Wistar rats. The results of this study demonstrated that the expression of vWF by pulmonary endothelial cells was markedly increased from day 3 until 2 months after MCT injection. The labeling index of pulmonary microvessel endothelium began to increase after six days and was maximal on the third weeks, and thereafter it remained slightly increased above basal level. Electron microscopic study revealed attachment of inflammatory cells an platelets to endothelium from 6 hours and degranulation of attached platelets 24 hours after MCT injection.
Evidences of endothelial injury began to appear from 12 hours after MCT injection. Evidences of endothelial injury began to appear from 12 hours and was maximal after 48 hours. From the third day, ultrastructural change of cell regeneration and hypertrophy began to appear and was continuosly observed until 2 months. In addition, we evaluated the changes in the number of pulmonary neuroendocrine cells using antibody to gastrin releasing peptide but it demonstrated no change until 2 months suggesting no role of neuroendocrine cells in the development of pulmonary hypertension of Wistar rats at early stage. In conclusion, the results indicate that pulmonary hypertension by MCT injection is due to increased vascular resistance caused by vasoconstriction and hyperplasia of endothelium with musculariz ation of the pulmonary arterioles induced by endothelial dysfunction and some biologic substances released form endothelium and platelets.
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