• The Journal of Internal Korean Medicine
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• v.35 no.1
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• pp.92-105
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• 2014

Objectives : Cisplatin is a widely used cancer therapy drug. However, nephrotoxicity resulting in increased oxidative stress is a major side effect of cisplatin chemotherapy, thereby limiting its chemotherapeutic use. Lycium chinense Miller (LCM) has been used as a traditional herbal medicine in various febrile and inflammatory diseases such as night sweat, cough, nosebleed, bronchitis, pulmonary tuberculosis, etc. In this study we investigated the protective and antioxidative potential of LCM against cisplatin-induced nephrotoxicity in rats. Methods : Twenty-four 8-week-old male Wistar rats were divided into four groups: normal untreated; cisplatin treatment only; LCM 10 mg/kg plus cisplatin treatment; and LCM 30 mg/kg plus cisplatin treatment. Twenty-four hours after the last cisplatin injection, all the rats were sacrificed, and serological changes were evaluated. The levels of NF-${\kappa}B$ activity and NOX-4, $p47^{phox}$, $p22^{phox}$, COX-2, iNOS, SOD, catalase expressions were analyzed in Western blot analysis. Results : Cisplatin injection caused an increase in the BUN level, which is a reliable indicator of renal toxicity. The levels of BUN, renal ROS, and renal TBARS were significantly reduced in the LCM groups compared with the cisplatin-only groups. The levels of $p47^{phox}$ and $p22^{phox}$, which are NADPH oxidase subunits, were increased in the cisplatin-only groups, whereas they were decreased in the LCM groups. The levels of renal NF-${\kappa}B$ activity and COX-2, iNOS expressions were increased significantly in the cisplatin-only groups compared with the normal groups, whereas they were decreased in the LCM groups. Compared with the cisplatin-only groups, renal GSH and GSH/GSSG increased in the LCM groups. Also, the administration of LCM increased levels of SOD and catalase as compared with the cisplatin-only groups. Conclusions : These results suggest that LCM protects cisplatin-induced nephrotoxicity via a mechanism that may involves the inhibition of oxidative stress by the activation of antioxidants.

• Tuberculosis and Respiratory Diseases
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• v.56 no.1
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• pp.51-66
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• 2004

Objectives : The matrix metalloproteinases (MMPs) that participate in the extracellular matrix metabolism play a important role in the progression of pulmonary fibrosis. The effects of the MMPs are regulated by several factors including Th-1 cytokines, $interferon-{\gamma}$ ($IFN-{\gamma}$). Up to now, $IFN-{\gamma}$ is known to inhibit pulmonary fibrosis, but little is known regarding the exact effect of $IFN-{\gamma}$ on the regulation of the MMPs. This study investigated the effects of $interferon-{\gamma}$ on the pulmonary fibrosis and the expression of the lung MMP-2,-9, TIMP-1,-2, and Th-2 cytokines in aa rat model of bleomycin induced pulmonary fibrosis. Materials and methods : Male, specific pathogen-free Sprague-Dawley rats were subjected to an intratracheal bleomycin instillation. The rats were randomized to a saline control, a bleomycin treated, and a bleomycin+$IFN-{\gamma}$ treated group. The bleomycin+$IFN-{\gamma}$ treated group was subjected to an intramuscular injection of $IFN-{\gamma}$ for 14 days. At 3, 7, 14, and 28 days after the bleomycin instillation, the rats were sacrificed and the lungs were harvested. In order to evaluate the effects of the $IFN-{\gamma}$ on lung fibrosis and inflammation, the lung hydroxyproline content, inflammation and fibrosis score were measured. Western blotting, zymography and reverse zymography were performed at 3, 7, 14, 28 days after bleomycin instillation in order to evaluate the MMP-2,-9, and TIMP-1,-2 expression level. ELISA was performed to determine the IL-4 and IL-13 level in a lung homogenate. Results : 1. 7 days after bleomycin instillation, inflammatory changes were more severe in the bleomycin+$IFN-{\gamma}$ group than the bleomycin group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$2.08{\pm}0.15:2.74{\pm}0.29$, P<0.05), but 28 days after bleomycin instillation, lung fibrosis was significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$3.94{\pm}0.43:2.64{\pm}0.13$, P<0.05). 2. 28 days after bleomycin instillation, the lung hydroxyproline content was significantly reduced as a result of $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$294.04{\pm}31.73{\mu}g/g:194.92{\pm}15.51{\mu}g/g$, P<0.05). 3. Western blotting showed that the MMP-2 level was increased as a result of the bleomycin instillation and highest in the 14 days after bleomycin instillation. 4. In zymography, the active forms of MMP-2 were significantly increased as a result of the $IFN-{\gamma}$ treatment 3 days after the bleomycin instillation, bleomycin+$IFN-{\gamma}$ group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$209.63{\pm}7.60%:407.66{\pm}85.34%$, P<0.05), but 14 days after the bleomycin instillation, the active forms of MMP-2 were significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$159.36{\pm}20.93%:97.23{\pm}12.50%$, P<0.05). 5. The IL-4 levels were lower in the bleomycin and bleomycin+$IFN-{\gamma}$ groups but this was not significant, and the IL-13 levels showed no difference between the experiment groups. Conclusion : The author found that lung inflammation was increased in the early period but the pulmonary fibrosis was inhibited in the late stage as a result of $IFN-{\gamma}$. The inhibition of pulmonary fibrosis by $IFN-{\gamma}$ appeared to be associated with the inhibition of MMP-2 activation by $IFN-{\gamma}$. Further studies on the mechanism of the regulation of MMP-2 activation and the effects of MMP-2 activation on pulmonary fibrosis is warranted in the future.

• Clinical and Experimental Reproductive Medicine
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• v.12 no.1
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• pp.47-70
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• 1985

This study was presented of the 1,872 cases of infertile couples who visited and examined at the sterility clinic of Department of Obstetrics & Gynecology, Seoul National University Hospital from Sept., 1980 to Dec., 1983. Age, duration of infertility, past medical history, and other general factors were analyzed, and the factors responsible for infertility were classified and discussed. Mode of treatment, outcome of pregnancy, pregnancy rate responsible for each factor were also presented. The results were as follows: 1) The infertility was primary in 1,128, or 60.3% and secondary in 744, or 39.7%. 2) The age between 26 and 30 years of age comprised about one half of the total patients. 3) The duration of infertility between 1 and 4 years comprised about three quarters of the total patients, and the mean duration was 3.8 years. 4) The most common medical history in primary infertility was tuberculous disease, and that in secondary infertility was history of previous laparotomy. 5) About two thirds of antecedent pregnancies were abortion. 6) The major etiologic factor of infertility were male factor in 12.3%, tubal factor in 38.8%, ovulatory failure in 25.4%, uterine factor in 8.8%, cervical factor in 5.2%, peritoneal factor in 9.5%, and no demonstrable cause in 11.3%. 7) The types of male factor were azoospermia in 61.6%, oligospermia in 25.8%, low motility in 11.6%, and other abnormality in 1.0%. 8) The types of ovulatory failure were ovarian failure in 7.4%, hypothalamo-pituitary failure in 8.1 %, hypothalamo-pituitary dysfunction (including Polycystic ovarian syndrome) in 30.2%, and hyperprolactinemia in 22.4%. 9) The types of uterine factor were endometrial tuberculosis in 27.5%, uterine synechia in 33.8%, uterine anomaly in 19.7%, myoma and polyp in 9.1 %, and luteal phase defect in 9.9%. 10) The types of peritoneal factor were pelvic adhesion in 80.9% and endometriosis in 19.6%. 11) Surgeries were done in 408 patients, and they were salpingolysis, lysis of extraadnexal adhesion, salpingostomy, fimbrioplasty, ovarian wedge resection for polycystic ovarian disease, tubo-tubal anastomosis, and tubo-uterine implantation in orders. 12) 243 pregnancies were achieved during the infertility work-up, of which livebirth was 46.5%, ectopic pregnancy was 7.4%, spontaneous abortion was 7.8%, and on-going pregnancy or lost to follow-up was 36.2%. 13) Pregnancy rates in various factors were male factor in 18.7%, ovulatory factor in 31.7%, tubal factor in 24.2%, uterine factor in 34.6%, cervical factor in 19.0%, peritoneal factor in 29.0%, combined factors in 10.5%, and unexplained infertility in 37.1%. Pregnancy rate in whole patients was 25.2%.

• IMMUNE NETWORK
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• v.2 no.3
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• pp.142-149
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• 2002

Background: Our previous study showed that purified protein derivative (PPD)-stimulated pleural mononuclear cells (PMC) from tuberculous pleurisy (Tbp) produced significantly more $IFN-{\gamma}$ (10- to 70-fold) after in vitro PPD stimulation than freshly isolated pleural cells from malignant pleurisy. The present study was designed to determine whether blocking the CD40-CD40 ligand (CD40L) interaction decreases $IFN-{\gamma}$ production by altering IL-12 levels. Methods: IL-12 and $IFN-{\gamma}$ production after neutralizing anti-CD40L antibody treatment was compared to the efficacy of anti-CD80, anti-CD86, and a combination of anti-CD80 and CD86 (CD80+86) monoclonal antibodies (mAb). These activities were measured by enzyme-linked immunosorbent assays (ELISAs) and reverse transcription-polymerase chain reaction (RT-PCR), after in vitro stimulation with PPO antigen (Ag). Results: Neutralization of CD80, CD86 and CD80+86 did not decrease $IFN-{\gamma}$ and IL-12 production in Tbp-PMC, whereas neutralization of CD40L significantly depressed IL-12 p40 and $IFN-{\gamma}$. In addition, neutralization of CD40L completely inhibited IL-12 p40 and $IFN-{\gamma}$ mRNA expression. Conclusion: The CD40-CD40L interaction might play a major role in IL-12 and $IFN-{\gamma}$ production in Tbp-PMC, thus contributing to protective immunity in human tuberculosis.

• Journal of Chest Surgery
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• v.10 no.2
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• pp.205-213
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• 1977

In order to evaluate the therapeutic effect of thoracostomy on the patients with pathological changes in pleural cavity which were caused by various etiological factors, a clinical study was carried out during a period of 5 and half years from May 1972 to September 1977 in the department of thoracic surgery, Hanyang University Hospital, and the following results were obtained. Of a total of 264 patients, 205 cases were male, and 59 female, exhibiting the ratio of male to female being 3.5 to 1. The pathological changes in pleural cavity could occur at any age from 4 months after birth to 76 years old, the peak incidence being in the third decade in either male or female. The incidence decreased in the second, fifth and fourth decade in order. The type of pathological changes observed and their frequencies of occurrences were 93 cases [35.2%] in pneumothorax, 62 cases [23.5%] in hemothorax, 48 cases [18.2%] in pyothorax, 46 cases [17. 4%] in hemopneumothorax, 13 cases [4.9%] in hydropneumothorax, and one case each in hydrothorax and chylothorax. The incidence of the primary diseases which predisposed the pathological changes in pleural cavity were, 119 cases [45-1%] in trauma, 64 cases [24.2%]in lung tuberculosis, 38 cases [14.4%] in pneumonia or empyema, 14 cases [5.3%] in lung emphysema and blebs, 13 cases [4.9%] in process after thoracotomy, 3 cases [1.1%] each in lung malignant tumor and lung paragonimiasis, one case in mechanical ventilator and 9 cases [3.4%] in unknown origin. The pathological changes in pleural cavity were located in the right side of the cavity in 124 cases, in the left side in 133 cases and in both sides in 7 cases, indicating that the difference between the incidence of the left and rightside occurences was insignificant. Of 93 cases of pneumothorax studied, 63 cases were found to have been tension pneumothorax and 30 cases non-tension pneumothorax, showing greater prevalence of tension type over non-tension type. Of 119 cases of trauma observed, 82 cases were accompanied with rib fractures and 37 cases were without any fracture [non-bone fracture]. Patients with the rib fractures were characterized by multiple rib fractures and multiple double fractures of ribs, accompanying with or without fracture of bones other than ribs, and patients with non-bone fracture were characterized by penetrating stab wound and blunt trauma. Of 264 cases who received thoracostomy, 207 cases [78.4%] demonstrated that their pathological changes in pleural cavity were removed and subsided by a simple measure of thoracostomy. In 43 cases [16.3%], various surgical measures including radical operation and thoracotomy were required for complete healing, since their pathological changes were not abolished by thoracostomy alone. The rest 14 cases [5.3%] were expired following thoracostomy.

• Journal of Chest Surgery
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• v.8 no.2
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• pp.109-118
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• 1975

This is a report on four cases of the lobar emphysema due to proximal bronchial obstruction in the Department of Thoracic Surgery, Hanyang University Hospital, during the period of three and half years from 1972 to 1975. First case, a two years old male child was referred to our Department with the lobar emphysema of the lower lobe of the right lung with pneumonia. This emphysema was developed after aspiration of a piece of peanut. Bronchoscopy revealed that the bronchus of the right lower lobe was obstructed with the foreign body, however removal of the peanut through bronchoscope was not attempted because of corruption and softening of the peanut. The removal of the peanut by bronchotomy was performed after subsiding of acute phase of pulmonary infection. Postoperative course was uneventful and the emphysema was disappeared. Second case, a twenty months old female baby was referred to our Department with lobar emphysema of the lower lobe of the left lung. The emphysema was suddenly developed with coughing and dyspneic symptoms and the diagnosis was made roentgenologically. She gave a history of reccurrent infections of the respiratory tract after birth. Bronchoscopy showed an obstruction of the left main bronchus with the growing of fibrinous tissue on the bronchial mucosa. The protruded tissue in the left main bronchus taken out about O.8ml with biopsy forceps for histological examination. After this procedure, the emphysema of the left lung was disappeared. Histological finding was reported to be a chronic inflammatory granulation tissue. Third case, a two and half years old male child was referred to our Department with roentgenological lobar emphysema. Two weeks prior to admission he had an episode of sudden onset of coughing attack with dyspnea. Bronchoscopy revealed that the bronchus of the left lower lobe was obstructed with a mass which was strongly suspected of a neoplastic tissue. At operation, there was found a perforation of enlarged tuberculous lymph node in the bronchus of the left lower lobe and protrusion of granulation tissue into the bronchus. Ruptured orifice on themembranous wall of the left lower lobe bronchus was closed with interrupted suture after the" removal of a perforated tuberculous lymph node. Postoperative course was uneventful and antituberculous chemotherapy was given. Fourth case, a 47 years old man was admitted to our Department with the complaint of severe dyspnea of few months duration. Twenty years ago, he had a history of lung tuberculosis and was treated for many years. X-ray examination including tomography and bronchography revealed that the upper lobe of the right lung was destroyed with cavities, the lower lobe was completely shrunk, and the right middle lobe was strongly overdistended with narrowing bronchial trees. Differential bronchospirometry and lung scanning confirmed that the respiratory function of the affected lung was impaired almost totally. The value of the right lung was calculated on 6% of oxygen uptake, 1% of Minute volume, and 32% of vital capacity. The right pneumonectomy was performed under the careful consideration of anesthetic and surgical procedures. Postoperative course was uneventful and the respiratory function was improved nearly to the normal level.evel.

• Journal of Chest Surgery
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• v.31 no.11
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• pp.1076-1080
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• 1998

Background: Spontaneous hemopneumothorax, occurring in 1% to 12% of patients with spontaneous pneumothorax, is a rare disorder that can potentially lead to life-threatening complications. Materials and methods: We have experienced 15 cases (2.28%) with spontaneous hemopneumothorax among 659 episodes of spontaneous pneumothorax for eight years, from 1990 to 1997, at our hospital. We studied our previously treated patients by retrospective case studies to determine the nature of optimal management. Results: There were 14 male and 1 female patients whose mean age was 27.5 years, ranging from 19 to 58. The sides with disorder were as following: right in 10 cases and left in 5, unilaterally. The amount of initial bleeding ranged from 400 to 1,500 mL and 8 patients received a homologous blood transfusion. Patients exhibited symptoms of chest pain, dyspnea, chest discomfort, and hypovolemic shock. We concluded that causes of this disease in our patients were a torn pleural adhesion (14 cases) and a rupture of vascularized bullae (1 case with an underlying intrinsic lung disease, tuberculosis). All patients underwent closed thoracostomy and had good results except for 3. One patient underwent thoracotomy within 3 days from the onset because of continuous active hemorrhage. Decortication was required in one case because of a reactive fluid collection in the pleural space, which led to impaired lung expansion. Another patient underwent thoracotomy due to a ipsilateral recurrent pneumothorax without blood collection. Conclusions: The goals of treatment include hemostasis and reexpansion of the collapsed lung. Thus, if patients arrive early at hospital, closed thoracostomy and transfusion are thought to be sufficient treatments, although early surgical repair has been considered recently.

• Journal of Chest Surgery
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• v.31 no.8
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• pp.792-798
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• 1998

Background: There are various tracheal diseseas which cause the obstruction of the trachea: postintubation tracheal stenosis, tracheal cancer, thyroid cancer, endotracheal tuberculosis, et al. Recently surgical resection and reconstruction of the trachea has been adopted as the safe method for tracheal lesions. Materials and methods: We report our experience and results of resection and reconstruction for various obstructive tracheal lesions in 38cases from 1985 to 1996. Length of resection of the trachea was up to 6 cm. Twenty lesions were approached by cervical collar incision, 12 lesions by cervicosternal incision and 4cases needed transthoracic approach. Surgical procedures consisted of resection and tracheotracheal anastomosis in 32 cases, resection and laryngotracheal anastomosis in 6cases and in addition laryngeal release was necessary to release anastomotic tension in 3cases. Results: The complications were 4 minor wound infections, 2 mild suture line granulomas, 1 vocal cord palsy, 2 pneumonias and 1 systemic candidiasis. Two patients who had poor consciousness and pnemonia and one who developed systemic candidiasis were expired after operation. Conclusion: We suggests resection and reconstruction of trachea is optimal procedure for up to 6cm long tracheal lesions. However, for the patients with poor consciousness or poor general conditions would be the conservative treatment preferred to the tracheal reconstruction because of high serious complications and mortalities.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.475-482
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• 2009

Rifampicin is a macrocyclic antibiotic which is used extensively for treatment against Mycobacterium tuberculosis and other mycobacterial infections. Recently, a number of studies have focused on the immune-regulatory effects of rifampicin. Therefore, we hypothesized that rifampicin may influence the TLR2 expression in LPS-activated RAW 264.7 cells. In this study, we determined that rifampicin suppresses LPS-induced TLR2 mRNA expression. The down-regulation of TLR2 expression coincided with decreased production of TNF-$\alpha$ Since NF-${\kappa}B$ is a major transcription factor that regulates genes for TLR2 and TNF-$\alpha$, we examined the effect of rifampicin on the LPS-induced NF-${\kappa}B$ activation. Rifampicin inhibited NF-${\kappa}B$ DNA-binding activity in LPS-activated RAW 264.7 cells, while it did not affect IKK$\alpha/\beta$ activity. However, rifampicin slightly inhibited the nuclear translocation of NF-${\kappa}B$ p65. In addition, rifampicin increased physical interaction between pregnane X receptor, a receptor for rifampicin, and NF-${\kappa}B$ p65, suggesting pregnane X receptor interferes with NF-${\kappa}B$ binding to DNA. Taken together, our results demonstrate that rifampicin inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF-${\kappa}B$ DNA-binding activity in RAW 264.7 cells. Thus, the present results suggest that the rifampicin-mediated inhibition of TLR2 via the suppression of NF-${\kappa}B$ DNA-binding activity may be a novel mechanism of the immune-suppressive effects of rifampicin.

• Korean Journal of Pharmacognosy
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• v.34 no.4 s.135
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• pp.327-334
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• 2003

We evaluated the anti-arthritic effect of a new diet-supplement product containing red ginseng, glucosamine, shark cartilage, ascorbic acid and manganese chloride for the relieving arthritic symptoms. Anti-inflammatory activities of the aqueous extract of red ginseng (250 and 500 mg/kg), glucosamine (240 mg/kg) and shark cartilage (240 mg/kg) were tested individually on vascular permeability and carrageenan-induced paw edema. Glucosamine and shark cartilage showed the inhibition of vascular permeability by 29.6 and 32.9%, respectively. Red ginseng (500 mg/kg) and shark cartilage showed the inhibition of carrageenan-induced paw edema at 0.5, 1, 2 and 3 hr. The supplement (red ginseng mixture: RGM) composed of red ginseng (43.5%), glucosamine (25.0%), shark cartilage (25.0%), ascorbic acid (5.0%) and manganese chloride (1.5%) was prepared and its inhibitory activities including vascular permeability and carrageenan-induced paw edema were comparable to anti-inflammatory drugs such as diclofenac and ibuprofen. It was also tested on adjuvant-induced arthritis in rats as one of chronic arthritic tests and Randall-Selitto assay as an analgesic test. RGM showed the inhibition against the swelling of rat paws induced by Mycobacterium tuberculosis at a dose of 1,500 mg/kg. Determination of cytokines of the sera sampled from arthritis-induced animals indicated that RGM increased the levels of $interferon-{\gamma}$ and interleukin-6, representing the immunostimulatory effect by red ginseng. RGM treatment moderately reduced the production of NO in RAW 264.7 cells in a dose-dependent manner. Taken together, these results support that RGM can be applicable for the improvement of arthritic as a new diet-supplement.