• Title/Summary/Keyword: Disease Progression

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The Effect of PDGF-Loaded Biodegradable Membrane on Early Healing Stage in Guided Tissue Regeneration (흡수성 차폐막의 치주조직 재생에 혈소판유래 성장인자가 미치는 영향)

  • Rhyu, In-Chul;Bae, Kyoo-Hyun;Seol, Yang-Jo;Ku, Young;Lee, Seung-Jin;Han, Soo-Boo;Choi, Sang-Mook;Chung, Chong-Pyoung
    • Journal of Periodontal and Implant Science
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    • v.29 no.3
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    • pp.507-519
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    • 1999
  • The ultimate objective of periodontal treatment is to stop disease progression and to regenerate destroyed periodontal tissues and thereby regain normal function. Growth factors are naturally found polypetides which stimulate many cellular activities pertaining to wound healing by acting as signal molecule in controlling cell movement, proliferation, and matrix production. Platelet derived growth factor (PDGF) is 28,000-35,000 Da molecular weight dimeric protein with 2 long positively charged polypeptide chains connected by sulfide bonds. The purpose of this study is to evaluate histologically the initial guided tissue regeneration in a periodontal defect f a beagle dog treated with a biodegradable membrane formed with polylactic acid (poly-L-lactic acid) and polyglycolic acid loaded with 200ng/$cm^2$ platelet derived growth factor. 2 beagle dogs were used in he experiment. $5mm{\times}6mm$ alveolar bone defect was formed in upper and lower canines and third premolars and a reference notch was placed. PDGF-BB non-containing membrane was used as control. Each defect was randomly assigned to the test roup or the control group. The dogs were sacrificed 3 weeks after membrane placement. Toluidine blue and multiple staining was done for histological analysis. In the 3 week specimen in the control group, no new one formation could be seen. Small amount f bone resorption below the notch could be seen. In the notch, loose connective tissue with infiltration of inflammatory cells could be seen. Also thin discontinuous new cementum could be seen and the membrane still retained its structure. Where PDGF-BB containing membrane was used, new bone formation could be seen in the notch at weeks and also continuous thin cementum could be seen. PDL cells were observed between new bone and new cementum and some were attached to bone and cementum. These results suggest that new bone and cementum formation seen when PDGF-BB loaded membrane was used was due to inhibition of downgrowth of epithelial cells and also due to continuous release of the growth factor. Further study on the resorption characteristics of the membrane nd the release characteristics of the PDGF-BB is necessary. Also, development of a membrane easier to use clinically is necessary.

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EXPRESSION OF THE GENES OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND VON WILLEBRAND FACTOR IN SALIVARY GLAND TUMORS (타액선 종양에서 혈관내피성장인자와 von Willebrand 인자 유전자 발현에 관한 연구)

  • Chung, Ji-Hun;Kim, Ji-Hyuk;Park, Young-Wook
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.30 no.1
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    • pp.41-51
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    • 2008
  • Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor which compromises about 6$\sim$8% of all tumors followed by the adenoid cystic carcinoma (ACC) and adenocarcinoma. Most deaths from salivary carcinomas are caused by recurrent or metastatic lesions that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the vascular metastasis is important for the design of more effective therapy of salivary carcinomas. Neoangiogenesis is essential for tumor growth, which is postulated to be fundamentally dependent on the induction of stromal neovascularization. However, how neovascularization takes place in live tissue has not been fully established, especially in recruitment and differentiation of endothelial cells in the salivary gland tumors. Vascular endothelial growth factor (VEGF) is a heparin-binding, dimeric polypeptide growth factor known to exert its mitogenic activity specifically on endothelial cells. VEGF has been shown th be directly involved in angiogenesis, which in essential for the pathogenesis of many solid tumors. von Willebrand factor (vWF) is a large multimeric protein synthesized by megakaryocytes and endothelial cells that enable platelets to adhere to exposed subendothelium and, as well, to respond to changes in the blood flow. Recent studies suggest that increased levels of vWF correlate with progression of disease, metastasis, or survival time and thus may have a prognostic significance. vWF is explained as an acute phase proteins which is increased in cancer or as a result of increased endothelial cell synthesis associated with tumor-induced angiogenesis. Due to adhesive properties of vWF, its increased concentrations may also contribute metastasis of tumor. In this study, we determined the mRNA expression of VEGF and vWF in salivary ACC, MEC and pleomorphic adenoma by in situ hybridization. As a result, stronger expression of VEGF and vWF was seen in salivary ACC and MEC which has more invasive nature than the salivary benign tumor.

MiR-204 acts as a potential therapeutic target in acute myeloid leukemia by increasing BIRC6-mediated apoptosis

  • Wang, Zhiguo;Luo, Hong;Fang, Zehui;Fan, Yanling;Liu, Xiaojuan;Zhang, Yujing;Rui, Shuping;Chen, Yafeng;Hong, Luojia;Gao, Jincheng;Zhang, Mei
    • BMB Reports
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    • v.51 no.9
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    • pp.444-449
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    • 2018
  • Acute myeloid leukemia (AML) is one of the most common hematological malignancies all around the world. MicroRNAs have been determined to contribute various cancers initiation and progression, including AML. Although microRNA-204 (miR-204) exerts anti-tumor effects in several kinds of cancers, its function in AML remains unknown. In the present study, we assessed miR-204 expression in AML blood samples and cell lines. We also investigated the effects of miR-204 on cellular function of AML cells and the underlying mechanisms of the action of miR-204. Our results showed that miR-204 expression was significantly downregulated in AML tissues and cell lines. In addition, overexpression of miR-204 induced growth inhibition and apoptosis in AML cells, including AML5, HL-60, Kasumi-1 and U937 cells. Cell cycle analysis further confirmed an augmentation in theapoptotic subG1 population by miR-204 overexpression. Mechanistically, baculoviral inhibition of apoptosis protein repeat containing 6 (BIRC6) was identified as a direct target of miR-204. Enforcing miR-204 expression increased the luciferase activity and expression of BIRC6, as well as p53 and Bax expression. Moreover, restoration of BIRC6 reversed the pro-apoptotic effects of miR-204 overexpression in AML cells. Taken together, this study demonstrates that miR-204 causes AML cell apoptosis by targeting BIRC6, suggesting miR-204 may play an anti-carcinogenic role in AML and function as a novel biomarker and therapeutic target for the treatment of this disease.

Protective Effects of Curcumin on CCl4-Induced Hepatic Fibrosis with High Fat Diet in C57BL/6 Mice (C57BL/6 마우스에서 고지방 식이와 CCl4로 유발한 간섬유증에 미치는 커큐민의 보호효과)

  • Jekal, Seung-Joo;Min, Byung Woon;Park, Ho
    • Korean Journal of Clinical Laboratory Science
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    • v.47 no.4
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    • pp.251-258
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    • 2015
  • Curcumin, a major polyphenolic compound of turmeric, is well known to prevent non-alcoholic steatohepatitis (NASH) related to obesity. The aim of the study was to investigate the effect of curcumin on hepatic fibrosis induced by carbon tetrachloride ($CCl_4$) in obese mice. $CCl_4$ was administrated in mice fed a normal diet (ND) or a high fat diet (HFD) for 7 weeks together with or without curcumin. It was conducted to examine for metabolic profiles, adipocyte size, and liver fibrosis by serum biochemistry, histology and immunohistochemistry. Also, Apoptosis of hepatic cells was determined by the TUNEL method. Treatment with curcumin significantly lowered the body weight, fasting glucose, serum AST and ALT, and decreased the adipocyte size, the number of macrophage and mast cells in adipose tissue, and collagen deposition in liver tissue in the HFD+$CCl_4$ group compared with the findings of the HFD+$CCl_4$ group. In contrast, treatment with curcumin on the ND+$CCl_4$ group did not show a significant difference except the body weight and mast cell number when compared with the ND+$CCl_4$ group. Furthermore, curcumin significantly reduced the number of parenchymal apoptotic cells, whereas it increased the number of non-parenchymal apoptotic cells, especially resembling an activated hepatic stellate cell in the liver. Taken together, this data suggests that curcumin might be an effective antifibrotic drug for the prevention of liver disease progression in obese mice. Thus, the development of curcumin as a therapy for obesity and liver fibrosis is supported.

Histopathological observation of liver in cultured black rock fish Sebastes schlegeli in low temperature season (저수온기 양식 조피볼락, Sebastes schlegeli 간에 대한 조직병리학적 연구)

  • Choi, Hye-Sung;Huh, Min-Do;Lee, Mu-Kun;Choi, Hee-Jung;Park, Myung-Ae
    • Journal of fish pathology
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    • v.24 no.3
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    • pp.225-236
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    • 2011
  • This study was aimed to determine the fish physical status according to the gross and histopathological findings of liver in cultured black rock fish, Sebastes schlegeli. All 47 fish submitted had no marked abnormalities in the external findings. 42.55% of fish showed normal liver, 25.53% yellow liver, 25.53% atrophic brown liver, 4.26% yellowish-green liver and 2.13% fatty liver in gross examination. Grossly normal liver showed no remarkable change in lobular structure but many vacuoles were found in hepatic cell. Hepatic cells took normal roundish, polygonal shapes containing spherical nuclei. In group of yellow-brown liver, many brown pigments were seen in hepatic cells, MMCs and brown-colored hyaline droplets within cytoplasm of hepatocytes. Yellowish green pigments were seen in hepatic cells and MMCs of yellow green liver and green colored hyaline droplets within hepatocytes. The dilated central veins are highlighted with atrophy of hepatic cells. Outline of atrophic hepatocyte became ambiguous and nucleus frequently become small and pyknotic. Fatty liver showed prominent vacuolar structures in cells as clear spaces or foamy cytoplasm with degenerative nuclei. From these results, it was strongly suggested that hepatic gross and histological findings could be used as important and critical health parameters of fish prior to progression to substantial manifestation as clinical disease.

Study of Sophorae Radix on $H_2O_2$-mediated Apoptosis and Total Protein Expression Pattern in Vascular Smooth Muscle Cells (고삼이 $H_2O_2$에 의한 대동맥 평활근세포 고사 및 전체 단백질 발현에 미치는 영향)

  • Jeon In Cheol;Jeong Jae Eun;Son In Hwan;Lee Ju Seok;Jeong Seung Won;Jang Jae Ho;Lee Seon U;Lee In;Moon Byun Soon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1652-1660
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    • 2004
  • Apoptosis of vascular smooth muscle cells(VSMCs) is essential in atherogenesis, being a factor that modulates its early progression rather than a terminal event in the course of the disease. Various stimuli, including oxide lipoproteins, altered hemodynamic stress and free radical, can induced VSMCs apoptosis in vitro. The protective effects of Sophorae Radix (SR) on apoptotic cell death induced by H₂O₂ were investigated in VSMCs. The viability of VSMCs was markedly decreased by H₂O₂. Sophorae Radix protected the H202-induced apoptotic death of VSMCs, which was characterized as nuclear fragmentation and increase of sub-G0/G1 fraction .. Sophorae Radix decreased the activation of caspase-3 like protease induced by H₂O₂ and recovered control level from H202-induced PARP, Bak, Bcl-XL and mitochondrial membrane potential. These results suggest that Sophorae Radix protected VSMCs apoptotic death induced by H₂O₂ via inactivation of caspase-3 and modulation of mitochondrial function. Also, the expression profile of proteins by using two-dimensional (2-D) gel electrophoresis was screened. Future investigations will need to explore the use of an anti atherosclerotic therapy of Sophorae Radix, which relies on inhibition of the proapoptotic activation of the vascular smooth muscle cells.

Nicotine Suppresses TNF-${\alpha}$ Expression in Human Fetal Astrocyte through the Modulation of Nuclear Factor-${\kappa}B$ Activation

  • Son, Il-Hong;Park, Yong-Hoon;Yang, Hyun-Duk;Lee, Sung-Ik;Han, Sun-Jung;Lee, Jai-Kyoo;Ha, Dae-Ho;Kang, Hyung-Won;Park, Joo-Young;Lee, Sung-Soo
    • Molecular & Cellular Toxicology
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    • v.4 no.2
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    • pp.106-112
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    • 2008
  • Parkinson's disease (PD) progresses severely by a gradual loss of dopaminergic neurons in the substantia nigra (SN). Epidemiological studies showed that the incidences of PD were reduced by smoking of which the major component, nicotine might be neuroprotective. But the function of nicotine, which might suppress the incidences of PD, is still unknown. Fortunately, recently it was reported that a glial reaction and inflammatory processes might participate in a selective loss of dopaminergic neurons in the SN. The levels of tumour necrosis factor (TNF)-${\alpha}$ synthesised by astrocytes and microglia are elevated in striatum and cerebrospinal fluid (CSF) in PD. TNF-${\alpha}$ kills the cultured dopaminergic neurons through the apoptosis mechanism. TNF-${\alpha}$ release from glial cells may mediate progression of nigral degeneration in PD. Nicotine pretreatment considerably decreases microglial activation with significant reduction of TNF-${\alpha}$ mRNA expression and TNF-${\alpha}$ release induced by lipopholysaccharide (LPS) stimulation. Thus, this study was intended to explore the role of nicotine pretreatment to inhibit the expressions of TNF-${\alpha}$ mRNA in human fetal astrocytes (HFA) stimulated with IL-$1{\beta}$. The results are as follows: HFA were pretreated with 0.1, 1, and $10{\mu}g/mL$ of nicotine and then stimulated with IL-$1{\beta}$ (100 pg/mL) for 2h. The inhibitory effect of nicotine on expressions of TNF-${\alpha}$ mRNA in HFA with pretreated $0.1{\mu}g/mL$ of nicotine was first noted at 8hr, and the inhibitory effect was maximal at 12 h. The inhibitory effect at $1{\mu}g/mL$ of nicotine was inhibited maximal at 24 h. Cytotoxic effects of nicotine were noted above $10{\mu}g/mL$ of nicotine. Moreover, Nicotine at 0.1, 1 and $10{\mu}g/mL$concentrations significantly inhibited IL-$1{\beta}$-induced TF-${\kappa}B$ activation. Collectively, these results indicate that in activated HFA, nicotine may inhibit the expression of TNF-${\alpha}$ mRNA through the pathway which suppresses the NF-${\kappa}B$ activation. This study suggests that nicotine might be neuroprotective to dopaminergic neurons in the SN and reduce the incidences of PD.

Evaluation of Therapeutic Effect of the Extract from Rhubarb (Rheum officinalis) in Dogs with Chronic Renal Failure (개의 만성 신부전에서 대황 추출물의 치료학적 효과의 평가)

  • Kim, Ye-Won;Hyun, Changbaig
    • Journal of Veterinary Clinics
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    • v.29 no.6
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    • pp.435-440
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    • 2012
  • This study was designed to evaluate the clinical efficacy and safety of Rhubarb extracts ($Rubenal^{(R)}$) in dogs with chronic renal failure (CRF). Client-owned 40 dogs with CRF graded International renal interest Society (IRIS) II-III were enrolled in this study. The dogs were equally allocated and blindly administered with $Rubenal^{(R)}$ or placebo. The following items were evaluated at day 0, 30, 90 and 180: body condition score (BCS), clinical score (appetite, polydipsia/polyuria, quality of life score), hemogram (WBC, RBC, PCV), serum biochemistry (ALT/AST, ALP, Creatinine/BUN, total protein, albumin), serum electrolyte (Na, K, Cl, Ca, P), systolic blood pressure, urinalysis (UPC, USG) and IRIS stage. In this study, we found that the $Rubenal^{(R)}$ preparation was well tolerated by dogs and induced no adverse effects. Statistically significant improvements were observed in clinical score (quality of life score by vet and clients), serum BUN and creatinine levels, serum phosphorus concentration, level of proteinuria, and the IRIS score of CRF in dogs after 6 month of treatment of $Rubenal^{(R)}$. Those findings suggested that the Rhubarb extracts can improve the clinical signs of CRF (i.e. azotemia, hypertension, proteinuria, hyperphosphoremia) and the quality of life (i.e. BCS, clinical score) and can retard the progression of CRF in dogs. Therefore the Rhubarb extracts can be a good supplementary drug for treating dogs with subclinical and clinical renal diseases. However, care should be taken for interpreting our result, because this study is not double-blinded controlled study but pilot study.

Proteomic-determined Alteration of Synovial Fluid on Induced Model of Transected Ligament of Head of Femur (개의 대퇴골두인대 절단 모델에서 프로테오믹스로 관찰한 관절액의 변화)

  • Kim, Se-Hoon;Shin, Ki-Uk;Ji, Joong-Ryong;Shim, Kwan-Seob;Kim, Nam-Soo
    • Journal of Veterinary Clinics
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    • v.27 no.6
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    • pp.679-685
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    • 2010
  • Many animal models of osteoarthritis (OA) have been developed, aimed at understanding the long-term progression of OA and difficulty of identifying patients in the initial stage of the disease. In canines, coxofemoral luxation and hip dysplasia are common orthopedic ailments related to OA in the hip joint. Transecting the ligament of the head of the femur (LHF) aids in diagnosis of coxofemoral joint OA. Presently, mobility of this joint was increased by transected LHF in 10 mature, 2-3-year-old (average $2.57{\pm}0.20$ years), healthy male beagles. The animals were normally gaited 1-week post-operatively. During the experimental period, examinations including X-ray, complete blood count and serum chemistry were unremarkable. Proteomic examination revealed protein alterations in synovial fluid, with significant increases in Vitamin D-binding protein precursor (ANOVA, p < 0.004) and Kinogen-1 (ANOVA, p < 0.039). Both proteins correlated with arthritis.

Congenital cystic adenomatoid malformation (선천성 낭포성 선종양기형 -1례 보고-)

  • Sun, Kyung;Baek, Kwang-Je;Lee, Chol-Sei;Chae, Sung-Soo;Kim, Hark-Jei;Kim, Hyung-Mook
    • Journal of Chest Surgery
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    • v.17 no.1
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    • pp.118-124
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    • 1984
  • Congenital Cystic Adenomatiod Malformation (C.C.A.M.) is rare, but one of the most common congenital pulmonary anomalies that cause acute respiratory distress in the newborn infants. It is characterized and differentiated from the diffuse pulmonary cystic disease pathologically, i.e. adenomatoid appearance due to marked proliferation of the terminal respiratory components. An 2/12 year old male patient was suffered from respiratory distress and cyanosis on crying since birth, but no specific therapy was given. With progression of symptoms, he came to Korea University Hospital for further evaluation and then transfered to Dept. of Chest Surgery for operative correction under the impression of Congenital Obstructive Emphysema suggested by a pediatrician. On gestational and family history, there was nothing to be concerned such as congenital anomaly. Physical examinations showed; moderate nourishment and development (Wt. 5.5kg), cyanosis on crying, both intercostal and lower sternal retraction on inspiration, Lt. chest building with tympany, Rt. shifting of cardiac dullness, decreased breathing sound with expiratory wheezing on entire Lt. lung field, decreased breathing sound on Rt. upper lung filed, and tachycardia. The remainders were nonspecific. Laboratory findings were normal except WBC $14000/mm^3$ (lymphocyte 70%), Hgb 9.8m%, Hct 28%, negative Mantaux test, and sinus tachycardia and counter-clockwise rotation on EKG. Preoperative simple Chest PA revealed marked hyperlucent entire Lt. lung, herniation of Lt. upper lobe to Rt., collapsed Rt. upper lobe, tracheal deviation and mediastinal shifting to Rt., and no pleural reaction. At operation, after Lt. posterolateral thoracotomy, 4th rib was resected. Operative findings were severe emphysematous changes limited to both lingular segmentectomy was done. The resected specimen showed slight solidity, measuring $8{\times}4.5{\times}2cm$ in size, and small multiple cystic spaces filled with air. Microscopically, entire tissue structures were glandular in appearance, cyst were lined by ciliated columnar epithelium, and occasional cartilages were noted around the cystic spaces. Bronchial elements were dilated but normal pattern on histologically. The patient had a good postoperative courses clinically and radiologically, and discharged on POD 10th without event. The authors report a case of Cogenital Cystic Adenomatoid Malformation (C.C.A.M.)

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