• Journal of Acupuncture Research
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• v.22 no.2
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• pp.71-81
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• 2005

Objective : Dear antler (Cervus korean TEMMINCK var. mantchuricus Swinhoe) used for traditional immunosuppressive and immuno-activating action. The effect of deer antler herbal-acupuncture(DAH) solution, prepared by water extract method, on cathepsin activities in bone tissues (cartilage and synovial) cells from mouse rheumatoid arthritis (RA) model was studied. The cysteine endoprotease cathepsin mediates degradation of the MHC class II invariant chain (Ii) in human and mouse antigen-presenting cells. The studies described here examine the functional significance of cathepsin inhibition on autoantigen presentation and organ-specific autoimmune diseases in a murine model for RA. Methods : An animal model for RA in BALB/c mice thymectomized 3 days after birth (3d-Tx) was constructed All 3d-Tx BALB/c mice developed autoimmune lesions in the bone tissue cells, starting at 3 weeks of age, and the disease mediated by CD4+ T cells was chronic and progressive. Significant inhibitory effects of DAH solution on cathepsin S and L were observed in each organ in a dose-dependent manner. Moreover, we confirmed that cathepsin S and L activity in each organ were clearly inhibited by DAB solution. When we examined the inhibitory effects of DAH solution against autoantigen-specific T cell responses in vitro, in regional lymph node cells, but not in spleens, from model mice, a significant inhibitory effect of DAB solution was observed in a dose-dependent manner. DAH solution do not block T cell proliferation to Con A, indicated that the dose of DAB solution 10 to $20\;{\mu}g/m{\ell}$ was sufficient to inactivate the autoantigen-specific T cell responses in vitro. In vivo therapeutic effects of DAB solution were examined in a murine model for RA, autoantigen-specific (C-II-specific) T cell response were significantly inhibited in LNCs from DAH solution-treated mice. Results : Iinhibition of cathepsin S and L in vivo alters autoantigen presentation and development of organ-specific autoimmunity in RA model. Conclusion : These data identify selective inhibition of cysteine protease cathepsin S and L as a potential therapeutic strategy for autoimmune disease process such RA. Thus, DAH solution will served as a potent anti-inflammatory and anti-arthritic agents for treatment of human RA.

• Tuberculosis and Respiratory Diseases
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• v.40 no.2
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• pp.197-202
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• 1993

Polymyositis (PM) is a inflammatory connective tissue disease involving predominantly skeletal muscles, characterized by symmetrical, proximal muscle weakness, inflammation, and frequently, degeneration. Interstitial lung disease in association with PM occurs in 5~10% of cases and carries an especially grave prognosis. Although the cause of lung involvement in PM is not known, the underlying pathologic process in the lung is an immune mediated inflammation of alveolar structures, alveolitis. It is of interest, therefore, that cyclophosphamide, an immune modulating agent, has been reported to be effective in the treatment of PM. We report a case of corticosteroid resistant PM associated with interstitial lung disease, successfully treated with cyclophosphamide. A 37-year-old female was presented with 8 months duration of cough, exertional dyspnea, and muscle weakness. She had typical symptoms, physical findings, and elevated muscle enzyme levels in serum with characteristic findings of muscle biopsy. She also had typical interstitial lung disease pattern on chest X-ray and high resolution CT with restrictive pattern on pulmonary function test. The findings of transbronchial lung biopsy was compatible with interstitial lung disease. She failed to respond to corticosteroid initially. Subsequently steroids and cyclophosphamide were given with excellent clinical improvement.

• Tuberculosis and Respiratory Diseases
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• v.38 no.2
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• pp.143-154
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• 1991

Pneumconiosis is a sort of pulmonary fibrosis consequent to the inhalation of the respirable dusts. Thus, the pathogenesis of silicosis have concentrated largely on the early response of alveolar macrophage and the later fibroblastic stimulation. But the role of the other cells and continuing cell injury in the pathogenesis has not been fully studied. And the chemical factors such as prostaglandin, fibroblast stimulating factor and inhibiting factor and chemotaxin are also participated in the mechanism of pulmonary fibrosis in silicosis. In order to clarify the role of alveolar cells and prostaglandin, we investigated the changes of the cellularities in bronchoalveolar lavage fluid and tissue pathology in the experimental silicosis with the time sequence. The experimental animals were divided into 3 groups; control group received only intratracheal injection of 0.5 ml saline, silica group received the intratracheal instillation of 40 mg silica with the same amount saline, and aspirin group received 450 mg/kg of aspirin after silica instillation. The results were as follows: 1) The total cells of bronchoalveolar lavage fluid in the silica group markedly increased in comparison with the control group, but there was no significant difference between the silica and aspirin groups. 2) The percentages of alveolar macrophages to the total number of cells in the silica group tended to be lower than those in the control group and also lower than those in the aspirin group at the 1st week after silica instillation. 3) The percentages of neutrophils to the total number of cells in the silica group were significantly higher than those in the control group during the entire period and also higher than those in the aspirin group at the 3rd day after silica instillation. 4) In the silica group, the percentages of lymphocytes to the total number of cells were increased 143 progressively with the time course and those were significantly higher than those in the control group from the 3rd week after silica administration. There were marked differences of lymphocyte percentages between the silica and aspirin groups at the 1st week after silica instillation. 5) The inflammatory change was observed in the rat lung at the 1st day after silica instillation. Also the silicotic nodule appeared in the silica group at the 1st week but we could not find out that nodule in the aspirin group at that time. The fibrotic changes in the rat lung tended to be increased progressively with the time course, therefore, the diffuse fibrotic pattern appeared in the whole field at the 20th week after silica instillation. 6) By the electron microscopy, there were gradual increases of phagosomes and vacuoles in the alveolar macrophage in the silica group as compared with the control group. These results suggest that the neutrophils and the lymphocytes have also participated in the pulmonary fibrosis even though the alveolar macrophage has a major role, and prostaglandin mediate the inflammation and pulmanary fibrosis in the experimental silicosis.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.284-289
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• 2017

Background: Compound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated. Methods: LLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay. Results: The reduction in LLC-PK1 cell viability by $60{\mu}M$ FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with $60{\mu}M$ FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by $60{\mu}M$ FK506 treatment, whereas it was decreased after cotreatment with KRG. Conclusion: Taken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1981.05a
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• pp.39.3-40
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• 1981

Concerning the pathogenesis of acquired cholesteatoma in attic, there has been postulated theories by immigration from the Shrapnell's portion of the tympanic membrane, posterosuperior quardrant of the deep meatal skin and invagination of the margin of the central perforation. Otherwise, squamous metaplasia of the epithelium lining the middle ear cleft has been supported as a possible cause of cholesteatoma. Clinically, there has been known of the facts that cholesteatoma is formed in the attic but the pathogenesis concerning the acquired cholesteatoma is not still exactly reported. Recently, authors analyzed 170 cases of cholesteatomatous middle ear performed the operation to the middle ear cleft. On the operation finding, when the primary focus of the cholesteatoma was in the attic, we observed two types of perforation, marginal and central perforation in the Shrapnell's portion, and retraction to the Prussak's space, bony defect on the Rivinus notch. Among 36 cases of the cholesteatoma, the perforation of the Shrapnell's portion are 5 cases. Bony defect on the Rivinus notch and marginal perforation on the posterosuperior quadrant of the Shrapnell's portion are 21 cases. Among these cases, 3 cases are combined with central perforation of the Shrapnell's portion. Conclusively, the reasons that cholesteatoma is favorable site in the attic: 1) Excretion of the inflammatory discharge in the attic is difficult because of the distance of the E-tube. 2) The Shrapnell's portion has less collagen fiber than the pars tensa and it is thin because the elastic fibers are rich in it. It is easy to retract within the Prussak's space to the cases of keratinizing hyperplasia. 3) The epidermis attached at the Rivinus notch of the superior portion on the Shrapnell's portion is invaginated through the destructed bony wall of the Rivinus notch and the margin of the tympanic membrane in the response to the keratinizing hyperplasia.

• Molecules and Cells
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• v.41 no.8
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• pp.742-752
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• 2018

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive degeneration of dopaminergic (DAergic) neurons, particularly in the substantia nigra (SN). Although circadian dysfunction has been suggested as one of the pathophysiological risk factors for PD, the exact molecular link between the circadian clock and PD remains largely unclear. We have recently demonstrated that $REV-ERB{\alpha}$, a circadian nuclear receptor, serves as a key molecular link between the circadian and DAergic systems. It competitively cooperates with NURR1, another nuclear receptor required for the optimal development and function of DA neurons, to control DAergic gene transcription. Considering our previous findings, we hypothesize that $REV-ERB{\alpha}$ may have a role in the onset and/or progression of PD. In the present study, we therefore aimed to elucidate whether genetic abrogation of $REV-ERB{\alpha}$ affects PD-related phenotypes in a mouse model of PD produced by a unilateral injection of 6-hydroxydopamine (6-OHDA) into the dorsal striatum. $REV-ERB{\alpha}$ deficiency significantly exacerbated 6-OHDA-induced motor deficits as well as DAergic neuronal loss in the vertebral midbrain including the SN and the ventral tegmental area. The exacerbated DAergic degeneration likely involves neuroinflammation-mediated neurotoxicity. The $REV-erb{\alpha}$ knockout mice showed prolonged microglial activation in the SN along with the over-production of interleukin $1{\beta}$, a pro-inflammatory cytokine, in response to 6-OHDA. In conclusion, the present study demonstrates for the first time that genetic abrogation of $REV-ERB{\alpha}$ can increase vulnerability of DAergic neurons to neurotoxic insults, such as 6-OHDA, thereby implying that its normal function may be beneficial for maintaining DAergic neuron populations during PD progression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.973-981
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• 2007

In the present study, we investigated the antiproliferative activity of the water extract of Samgibopae-tang (SGBPT) in NCI-H460 and A549 non-small-cell lung cancer cell lines. We found that exposure of A549 cells to SGBPT resulted in the growth inhibition in a dose-dependent manner as measured by MTT assay, however SGBPT did not affect the growth of NCI-H460 cells. The antiproliferative effect by SGBPT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. SGBPT treatment did not induce the cell cycle arrest in both cell lines, however the frequency of sub-G1 population was concentration-dependently increased by SGBPT treatment in A549 cells. SGBPT treatment partially induced the expression of tumor suppressor p53 in A549 cells and the expression of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) was markedly increased in both transcriptional and translational levels in A549 cells. The up-regulation of p21 by SGBPT occurred in a similar a concentration dependent manner to that observed with the inhibition of cell viability and induction of sub-G1 population of the cell cycle. However SGBPT treatment did not affect other growth regulation-related genes such as early growth response-1 (Egr-1), nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), inducible nitric oxide synthease (iNOS), cyclooxygenases (COXs), telomere-regulatory factors in A549 as well as NCI-H460 cells. Taken together, these findings suggested that SGBPT-induced inhibition of human lung carcinoma A549 cell growth was aoosciated with the induction of p21 and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of SGBPT.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.5
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• pp.289-295
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• 2006

Sodium fluoride (NaF) has been shown to be cytotoxic and elicit inflammatory response in human. However, the cellular mechanisms underlying NaF-induced cytotoxicity in periodontal tissues have not yet been elucidated. This study is aimed to investigate the mechanisms of NaF-induced apoptosis in human gingival fibroblast (HGF). NaF decreased the cell viability of HGF in a dose- and time-dependent manner. NaF gave rise to apoptotic morphological changes including cell shrinkage, chromatin condensation, and DNA fragmentation. However, NaF did not affect the production of ROS. In addition, NaF augumented cytochrome c release from mitochondria into the cytosol, and enhanced caspase -9 and -3 activities., cleavage (85 kDa fragments) of poly (ADP-ribose) polymerase (PARP) and upregulation of voltage-dependent anion channel (VDAC) 1. These results demonstrated that NaF-induced apoptosis in HGF may be mediated with mitochondria. Furthermore, NaF elevated caspase-8 activity and upregulated Fas-ligand (Fas-L), suggesting involvement of death receptor mediated pathway in NaF-induced apoptosis. Expression of Bcl-2, an anti-apoptotic Bcl-2 family, was downregulated, whereas expression of Bax, a pro-apoptotic Bcl-2 family, was not affected in NaF-treated HGF. These results suggest that NaF induces apoptosis in HGF through both mitochondria- and death receptor-mediated pathway mediated by Bcl-2 family.

• Restorative Dentistry and Endodontics
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• v.20 no.2
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• pp.399-422
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• 1995

The purpose of this study was to investigate a fragment of possibility of pulpotomy with the Nd-YAG laser by the observation of pulpal healing process and the fine structural changes of the fibroblasts of the remaining pulpal tissues. Class V cavities on !55 teeth from 4 adult dogs were prepared and the pulp chambers were opened with a sterilized round bur. In the control group(19 teeth), the exposed coronal pulps were excised by a sharp excarvator. After bleeding was controlled with the sterilized cotton pellets, calcium hydroxide powder was applied on the remaining pulpal tissues and the cavities were sealed with Z.O.E. In the experimental group 1 : the pulpotomy with laser-calcium hydroxide powder application group(l9 teeth), the exposed coronal pulps were excised by Nd-YAG laser(10 watts power, 2 psi water, 20 psi air) for 2 or 3 seconds and calcium hydroxide powder was applied on the remaining pulpal tissues and the cavities were sealed with Z.O.E. In the experimental group 2 : the pulpotomy with laser-no calcium hydroxide powder application group(17 teeth), after amputating the coronal pulps with Nd-YAG laser as the experimental group 1, the remaining pulpal tissues were covered with stenilized aluminum foil and the cavities were filled with Z.O.E. The animals were sacrificed at the intervals of 1, 2, 3 and 4 weeks. All the teeth were rouutinely processed and the remaining pulpal tissues were observed by the light microscope and electron microscope. The results were as follows : 1. In light microscopic findings, there was no significant difference of the inflammatory response in the remaining pulpal tissues between the control group and the experimental groups. In both of the experimental group 1 : pulpotomy with laser-calcium hydroxide powder application group and the control group, the dentin bridges were observed after 2 weeks and the structure of the dentin bridge was almost same. In the experimental group 2 : pulpotomy with laser-no calcium hydroxide powder application group, the fibrous layers instead of dentin bridge were observed on the superficial portion of the remaining pulpal tissues after 2 weeks and they were consisted with densely crowded active fibroblasts. 2. In the electronmicroscopic findings, the active fibroblasts in the experimental groups were more frequently observed than in the control group at 1 week. But active fibroblasts were found with same frequency after 2 weeks in all of the control group and the experimental groups. 3. General distortions of the cell such as loss of the cell membrane, vaculoization of the cell etc. were observed at the suberficial layer of the remaining pulpal tissues and the carbonization was found in the dentinal wall in 1 week of the experimental groups. 4. In the experimental group 2 : pulpotomy with laser-no calcium hydroxide powder application group, the activity and the density of the fibroblasts in the fibrous layer were more than those in the deep portion of the remaining pulpal tissues after 2 weeks. 5. In the control group, bacteria such as cocci and bacilli were observed frequently, but in the experimntal groups, they could not be observed.

• Journal of Veterinary Clinics
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• v.32 no.6
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• pp.544-547
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• 2015

An 11-year-old, intact male Pekingese was brought to the Veterinary Teaching Hospital of Kangwon National University with a 10-day history of seizures. Fifteen days before coming to Kangwon National University, the dog had visited a local animal hospital for lameness, and non-steroidal anti-inflammatory drugs were prescribed to treat this symptom. However, 10 days before coming to our hospital, the dog experienced generalized seizures. Two days before his arrival, generalized ataxia and mental dullness also occurred. Our examinations revealed no remarkable findings on a routine blood test or X-ray. However, the neurological examinations confirmed mental dullness, generalized ataxia, and a lack of menace response and pupillary light reflexes. Nine hours later, dyspnea occurred, and 12 hours after that, the patient was euthanized per the client's request. A necropsy of transverse sections confirmed the presence of a prominent midline shift due to extended tumor growth. On histopathological analyses, pseudopalisading necrosis of the glial cells and microvascular proliferation were observed. In immunohistochemical analysis, glial fibrillary acidic protein, proliferating cell nuclear antigens, and ionized calcium binding adaptor molecule 1 immunoreactive cells were observed in the tumor area. Based on the results, the tumor was confirmed to be a glioblastoma. Primary intracranial tumors are rare in the veterinary field. This case report describes the clinical and histopathological findings of glioblastoma in a Pekingese.