- The Effects of CD11c/CD18 and CD14 Blocking on Lipopolysaccharide-induced Endotoxemia.
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O Jun Kwon, Jong Kuk Kim, Jyung Sik Kwak
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Korean J Pathol. 2000;34(1):11-19.
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- We studied the morphologic changes and the expression of cytokines of major organs by blocking CD14 and CD11c/CD18, which are known to be receptors of lipopolysaccharide (LPS), in the LPS induced endotoxemic mice. In 2 and 8 hours after initial intraperitoneal injection of 10 mg/kg of LPS into the mice, 500 microgram/kg of anti-CD14 antibody (Ab) and/or the same dosage of the anti-CD11c/CD18 Ab were administered intravenously, respectively or concomitantly. Under the light microscope, the LPS only and the LPS with the anti-CD14 Ab injected groups (group 1 and 2) showed marked acute inflammation in the organs, especially in the lung and liver, but the LPS with the anti-CD11c/CD18 Ab only or with both anti-CD14 and anti-CD11c Abs injected groups (group 3 and 4) revealed only mild acute inflammation. Under the electron microscope, there was marked inflammation in the group 1 and 2 such as marked infiltration of neutrophils, monocytes/ macrophages, lymphocytes, aggregation of platelets, and marked edematous change of endothelial cells with separation from the basement membrane. However in the group 3 and 4, there was only mild inflammation such as mild infiltration of neutrophils in the tissue or aggregation of neutrophils in the capillaries and sinusoids with mild endothelial swelling. The expressions of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1alpha (IL-1alpha), detected by RT-PCR method, was remarkable in the group 2, but minimal in the group 3 and 4. We conclude that blocking the CD11c/CD18 with anti-CD11C/CD18 Ab is effective for the prohibition of biologic reactions and diminution of the inflammation induced by the LPS, even in the LPS induced endotoxemia.
- Cytokine Expression on Microglial Proliferation and Apoptosis in Rat Lumbar Spinal Cord Following Unilateral Sciatic Nerve Transection.
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Sang Pyo Kim, Seung Il Suh, Young Rok Cho, Seung Che Cho, Seung Pil Kim, Jong Wook Park, Jyung Sik Kwak
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Korean J Pathol. 1998;32(2):94-103.
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- This study was carried out to elucidate the cytokine mRNAs expression and morphological features according to a microglial proliferation and apoptosis in a rat lumbar spinal cord, after a right sciatic nerve transection. The control group was composed of 5 rats (Spraque-Dawley) and the experimental group was composed of 70 rats. On post operation day (pod) 1, 2, 3, 5, and 7 eight rats were sacrificed on those days. On pod 10 five rats were sacrificed as well as five rats sacrificed on post operation weeks 2, 3, 4, 5, and 6. On light microscopy, activated microglia were often found in a perineuronal position around motoneurons in the ventral gray matter and more randomly distributed throughout the neuropil in the dorsal gray matter of lumbar spinal cord. GSA I-B4-positive microglia began to increase from 1 day after transection, and reached peak at 2~3 days and it persisted at 5~7 days and decreased thereafter. TUNEL-positive microglia was not observed in control group and began to increase from 5 days after transection and increased gradually until 3 weeks and decreased thereafter. On in situ RT-PCR, the positive signal for IL-1alpha and IL-6 mRNA was found mainly in the cytoplasm of the activated microglia and astrocytes at 1 day after transection and showed stronger signal at 3 days and decreased gradually until 10 days. TNF-alpha mRNA was detected 1 day after transection and remained for 7 days and localized to activated microglia as well as probably some astrocytes. The signal intensity of IL-1alpha and IL-6 mRNA was generally stronger than TNF-alpha mRNA. On transmission electron microscopy, there were chromatin condensation with margination toward nuclear membrane and condensation of cytoplasm at 3 days after transection. Apoptotic bodies were found after 5 days and increased gradually until 3 weeks.
According to the above findings, it is concluded that apoptosis appears to be one mechanism by which activated microglia are gradually eliminated and cytokine expression seems to played an active role in the microglial turnover.
- The Morphologic Changes of the Sinusoidal Endothelial Cells in N-diethylnitrosamine Induced Cirrhotic Rat Liver.
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Ok Ji Paik, Hee Kyung Park, Jong Min Chae, Jyung Sik Kwak, Tae Joong Sohn
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Korean J Pathol. 1996;30(7):604-615.
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- The purpose of this study is to investigate the morphologic changes of the sinusoidal endothelial cells and the associated structures of the cirrhotic rat liver induced by repeat intraperitoneal injections of N-diethylnitrosamine (DEN) (100 mg/kg/week). One day to 6 weeks later, rat livers were observed under the light, transmission and scanning electron microscopy, and immunostained with laminin antibody. Two weeks after DEN treatment, the fibrillar material in Disse's space was noted, and then a basement membrane-like structure was found at 4 weeks after treatment. Laminin was detected in perisinusoidal areas after 4 weeks. Laminin was strongly positive on the fibrous septum and in the sinusoidal wall of cirrhotic nodules after 6 weeks of treatment. The diameters and numbers of sinusoidal endothelial fenestrations did not change significantly until 2 weeks. They decreased within 4 weeks, and then the sinusoidal endothelium was poorly fenestrated at 6 weeks after DEN treatment. These results suggest that as fibrosis develops in cirrhosis, the deposit of extracellular matrix such as laminin within Disse's space is a major contributing factor in the structural alteration of sinusoidal endothelial cells, and the capillarization of the sinusoidal endothelial cells may be a contributor to impairment of the hepatic function in cirrhosis.
- Paraganglioma of Cauda Equina: A case report.
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Ji Hwa Kim, Sang Han Lee, Yoon Kyung Shon, Jyung Sik Kwak, Tae Joong Shon
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Korean J Pathol. 1994;28(5):528-532.
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- The clinical and pathological features of a paraganglioma arising in the cauda equina is described and compared with previous reports. The right microscopic fetures were similar to those of paragangliomas from other sites, with a 'Zellballen' pattern of cells containing arzyrophil granules. Immunohistocytochemical stains for neurone specific enolase, S-100 protein, cytokeratin were positive, but stains for glial fibrillary acidic protein were negative. Electron microscopy showed densely staining membrane-bound granules, cilia like structures and fibros bodies in the cytoplasm. The last two features only occur in paragangliomas from this site. The pathological findings suggest that paragangliomas in this site arise from pre-existing paraganglia, possibly of the visceral autonomic group.
- An Immunohistochemical Study on the Distribution of Endotoxin.
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Tae In Park, Jung Ja Park, Jyung Sik Kwak, In Soo Suh
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Korean J Pathol. 1994;28(3):260-271.
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- This study was performed to investigate the distribution of endotoxin in various organs after intraperitoneal injection of E. coli homogenator(0111:B4, 3X10(9)cells/200g of body weight). Sprague-Dawley rats were intraperitoneally injected with E. coli homogenator and sacrificed 1 and 3 hours after injection. The lung, liver, and kidney were immunohistochemically stained with avidin-biotin complex method and observed by light and electron microscopy. On the light microscopy, granular deposits of reaction products of immunohistochemical stain were found on the cytoplasmic membrane of endothelial cells and some of parenchymal cells of all organs observed. Electron microscopic study revealed finely granular reaction products on the surface of endothelial cells and some of parenchymal cells. The pinocytotic vesicles of endothelial cells demonstrated reaction products in the early phase of experiment. The distribution of reaction products were prominent in the liver among three organs. The Kupffer cells showed the most sensitive and strongest positive reaction. The hepatocytes and endothelial cells revealed weak positive reaction 3 hours later. The alveolar macrophages of the lung were also positive from the early phase of endotoxemia, while the pneumocytes and alveolar septa demonstrated weakly positive reaction in the later phase. The capillary endothelium of the kidney revealed positive reaction from the early phase.
According to above results, it is concluded that the endotoxin entered into the systemic circulation was captured in the liver and lung. And both mononuclear phagocytic system and endothelial cells could be activated or damaged by endotoxin.
- Pulmonary Alveolar Proteinosis: A case report.
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Chang Ho Cho, Yoon Kyung Sohn, Jyung Sik Kwak, Jung Yoon Choi, Won Sik Lee, Tae Hoon Jung
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Korean J Pathol. 1991;25(3):263-268.
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- A case of pulmonary alveolar proteinosis is reported. Most of the alveolar spaces were filled with amorphous deep eosinohilic material which revealed strong positive reaction to periodic acid-Schiff staining. Electron microscopic observation of this material showed numerous lamellar bodies in the alveolar spaces and cytoplasms of alveolar macrophages. A part of them were concentric multilamellated type A lamellar bodies and the other were finger printlike type B bodies. Combined type A and type B lamellar bodies were rarely present. From the above features it is suggested that both type A and B lamellar bodies could be transformed one another and those lamellar bodies may be originated from pulmonary surfactant.
- The Effects of Proteolytic Agent on the Lung Injured by Endotoxemia.
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Chang Ho Cho, Yoon Kyung Sohn, Jyung Sik Kwak, Tae Joong Sohn
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Korean J Pathol. 1991;25(3):215-222.
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- The authors studied the lung injury induced by endotoxemia and the effects of proteolytic agent on the lung changed by endotoxemia. Sprague-Dawley rats were intraperitoneally administrated with a single dose of endotoxin (4 mg/kg, E.
coli 025 : B6 lipopolysaccharide) or with endotoxin and gabexate mesilate (200 mg/kg), a proteolytic agent, concomitantly. Rats of each group were scarificed at 9, 18, and 27 hours after injection. Light and electron microscopic examination were done. The results obtained were summarized as follows: Light microscopic exmination revealed congested capillaries and neutrophilic infiltration in both groups.
Electron microscopic findings were interstitial and alveolar neutrophilic infiltration, endothelial swelling with increased pinocytotic vesicles and cytoplasmic process formation, and interstitial edema. Decrease of osmiophilic bodies in the type II pneumocytes had appeared at 9 hours after endotoxin injection. These changes were increased in severity at 18 hours and 27 hours after endotoxin injection.
In the group of concomitant treatment of gabexate mesilated and endotoxin, there was no edema at 9 hours after injection. After 18 hours welling of endothelial cell and interstitial edema had appeared. However, the severity of the edema was markedly decreased. Type II pneumocytes showed well preserved osmiophilic bodies. According to these results, it is considered that administration of gabexate mesilate can significantly redeced the lung injury induced by endotoxemia.
- Ultrastructural Studies of Aortic Endothelial Injury and Regeneration.
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Gium Mi Jang, Dong Hoon Kim, Jyung Sik Kwak, Tae Joong Sohn
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Korean J Pathol. 1990;24(4):337-348.
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- Author performed this experiment to define the most important factor preventing the intimal thickening. An endothelium of abdominal aorta in the rat was denuded by two different wires having same caliver. The degree of injury was limited to the endothelial cells in one, and extended to the internal elastic lamina in another. The results showed that at 72 hours, in the case of superficial injury, the entire injury site was covered by new regenerating cells, but in the case of disruption of the internal elastic lamina, the migrating smooth muscle cell completely reached into the intima and resulted in intemal thickening. Similar findings persisted to 1 week later. Above results suggest the most important factor preventing the intimal thickening in endothelial injury is the depth of the injury which limited within the endothelial cells without extending into the internal elastic lamina and medial smooth muscle cells.
- Ultrastructure of Adenocarcinoma of the Stomach by Scanning Electron Microscope.
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Kyung Rak Sohn, Jyung Sik Kwak, Tae Joong Sohn
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Korean J Cytopathol. 1985;19(1):13-26.
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- The author studied 11-cases of adenocarcinoma of the stomach confirmed by gastrofiberscopic biopsy before in order to differentiate between differentiated and undifferentiated adenocarcinoma by scanning electron microscope. Light and transmission electron microscopie examination were done, too. Seven of them are differentiated accompanied by severe intestinal metaplasia and four of them are undifferentiated with rearly focal intestinal metaplasia. Two of the undifferentiated cases shows focal tubular differentiation on the superficial region of the mucosa. Microvilli on the free border are long, regular on the differentiated type but in state of variable loss of microvilli under the transmission electron microscope. Number and density of the mucous granules are variable. Scanning electron microscopic examination shows prominent disorganization of the folds, cellular pleomorphism and pleomorphic microvilli are suggestive of early marker of neoplastic transformation. The size of them are 0.6 micrometer and 1.2 micrometer on the differentiated type respectively. Disorganization of the folds is an important differential point between differentiated and undifferentiated type on the lower power examination. Development of folds, furrow, and hemispheric colliculi are more porminent on the differentiated adenocarcinoma. Presence of striated border, partial or complete loss of microvilli and intestinal metaplasia on the undifferentiated and differentiated adenocarcinomas are consisent with origin from common precursor cells.
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