• Title/Summary/Keyword: pathological response

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Correlation between Clinicopathology and Expression of HSP70, BAG1 and Raf-1 in Human Diffuse Type Gastric Carcinoma (미만형 위암에서 임상병리학적 인자와 Hsp70, BAG1과 Raf-1 발현간의 상관성)

  • Jung, Sang Bong;Lee, Hyoun Wook;Chung, Kyung Tae
    • Journal of Life Science
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    • v.26 no.1
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    • pp.101-108
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    • 2016
  • The aim of this study was to evaluate the relationships between the expression of Heat shock protein70 (HSP70), Raf-1 and Bcl-2-associated athanogene-1 (BAG1) protein in diffuse type gastric carcinoma and examine association of HSP70, Raf-1 and BAG1 expression with various clinic-pathological factors and survival. Heat shock protein70 is induced in the cells in response to various stress conditions, including carcinogens. Overexpression of heat shock protein 70 has been observed in many types of cancer. The proto-oncoprotein Raf is pivotal for mitogen-activated protein kinase (MAPK) signaling, and its aberrant activation has been implicated in multiple human cancers. Overexpression of BAG1 protein has been documented in some type of human cancer. BAG1 has been reported to interact with protein involved with a variety of signal pathway, and regulation of cell differentiation, survival and apoptosis. These interaction partners include HSP70 and Raf-1. The percentage of tumors exhibiting HSP70 positivity was significantly in cases of positive lymph node metastasis (64.9%) compared to cases without lymph node metastasis (35.1%, p=0.007). HS70 expression was correlated with pathological N-stage (p=0.006). Expression of BAG1 was detected in the majority of diffuse type gastric carcinoma tissues (71.7%), especially in younger patients (80% vs 52.6%, p=0.035). Furthermore BAG1 expression was correlated with tumor size (p=0.020). Raf-1 expression was found to be significantly associated with tumor size (p=0.005). The result indicate that HSP70 was significantly correlated the progression of diffuse type gastric cancer. Expression of BAG1 and Raf-1 may be used as diagnostic markers for gastric carcinoma.

Toxico-pathological Study p,p-DDE After Experimental Aerosol Exposed to ICR Mouse (환경호르몬인 p,p-DDE의 흡입 시 ICR 마우스의 폐에 미치는 독성병리학적 연구)

  • Choi Hae-Yun;Jung Tae-Young;Ku Sae-Kwang;Yang Hee-Bog;Lee Hyeung-Sik
    • Toxicological Research
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    • v.21 no.2
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    • pp.151-160
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    • 2005
  • In order to monitor the histological and general profiles of lung after direct expose of p,p-DDE, 1, 5 and 10 mg/ml of p,p-DDE were sprayed to male ICR mouse, and seven days after exposure, changes of body weight, lung weight, clinical signs, histological profiles of lung and total WBC in blood were investigated with changes of total cell number and their differential count in bronchoalveolar lavage fluid (BALF). In the present study, a significant and dosage-dependent decrease of body weight was detected in p,p-DDE exposed groups and body weight gains during observational periods (7 days) were also significantly and dosage-dependently decreased in p,p-DDE exposed groups compared to that of vehicle control group. In addition general depression signs were detected in all p,p-DDE exposed groups with dosage-dependent manners, and lung weights were also increased in p,p-DDE exposed groups. Congestion, hemorrhage and severe exudate were observed in the lung of p,p-DDE exposed groups with sarcomatous changes and these signs were also showed by dosage-dependent manners. In addition, foreign body pneumonia signs were observed in the lung of p,p-DDE exposed groups in histological levels. The percentage of ALSA (Area of luminal surface of alveoli) was also significantly and dosage-dependently decreased in p,p-DDE exposed groups and total blood WBC and BALF cell numbers were significantly and dosage-dependently increased in p,p­DDE exposed groups compared to that of vehicle control group and increase percentage of neutrophil, eosinophil, and lymphocyte in BALF were monitored in p,p-DDE exposed groups compared to that of vehicle control group. In conclusion, severe allergic response and/or foreign body pneumonitic changes were induced by direct exposure of p,p-DDE containing beverage. So it is considered that strong and powerful regulation was need to control production of residence of environmental pollutant especially to p,p-DDE.

Physiological Roles of Phospholipase Cγ and Its Mutations in Human Disease (Phospholipase Cγ의 생리적 기능과 질병과 연관된 돌연변이)

  • Jang, Hyun-Jun;Choi, Jang Hyun;Chang, Jong-Soo
    • Journal of Life Science
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    • v.30 no.9
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    • pp.826-833
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    • 2020
  • Phospholipase C gamma (PLCγ) has critical roles in receptor tyrosine kinase- and non-receptor tyrosine kinase-mediated cellular signaling relating to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] to produce inositol 1,4,5 trisphosphate (IP3) and diacylglycerol (DAG), which promote protein kinase C (PKC) and Ca2+ signaling to their downstream cellular targets. PLCγ has two isozymes called PLCγ1 and PLCγ2, which control cell growth and differentiation. In addition to catalytically active X- and Y-domains, both isotypes contain two Src homology 2 (SH2) domains and an SH3 domain for protein-protein interaction when the cells are activated by ligand stimulation. PLCγ also contains two pleckstrin homology (PH) domains for membrane-associated phosphoinositide binding and protein-protein interactions. While PLCγ1 is widely expressed and appears to regulate intracellular signaling in many tissues, PLCγ2 expression is restricted to cells of hematopoietic systems and seems to play a role in the regulation of immune response. A distinct mechanism for PLCγ activation is linked to an increase in phosphorylation of specific tyrosine residue, Y783. Recent studies have demonstrated that PLCγ mutations are closely related to cancer, immune disease, and brain disorders. Our review focused on the physiological roles of PLCγ by means of its structure and enzyme activity and the pathological functions of PLCγ via mutational analysis obtained from various human diseases and PLCγ knockout mice.

Chronic Ca2+ influx through voltage-dependent Ca2+ channels enhance delayed rectifier K+ currents via activating Src family tyrosine kinase in rat hippocampal neurons

  • Yang, Yoon-Sil;Jeon, Sang-Chan;Kim, Dong-Kwan;Eun, Su-Yong;Jung, Sung-Cherl
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.2
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    • pp.259-265
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    • 2017
  • Excessive influx and the subsequent rapid cytosolic elevation of $Ca^{2+}$ in neurons is the major cause to induce hyperexcitability and irreversible cell damage although it is an essential ion for cellular signalings. Therefore, most neurons exhibit several cellular mechanisms to homeostatically regulate cytosolic $Ca^{2+}$ level in normal as well as pathological conditions. Delayed rectifier $K^+$ channels ($I_{DR}$ channels) play a role to suppress membrane excitability by inducing $K^+$ outflow in various conditions, indicating their potential role in preventing pathogenic conditions and cell damage under $Ca^{2+}$-mediated excitotoxic conditions. In the present study, we electrophysiologically evaluated the response of $I_{DR}$ channels to hyperexcitable conditions induced by high $Ca^{2+}$ pretreatment (3.6 mM, for 24 hours) in cultured hippocampal neurons. In results, high $Ca^{2+}$-treatment significantly increased the amplitude of $I_{DR}$ without changes of gating kinetics. Nimodipine but not APV blocked $Ca^{2+}$-induced $I_{DR}$ enhancement, confirming that the change of $I_{DR}$ might be targeted by $Ca^{2+}$ influx through voltage-dependent $Ca^{2+}$ channels (VDCCs) rather than NMDA receptors (NMDARs). The VDCC-mediated $I_{DR}$ enhancement was not affected by either $Ca^{2+}$-induced $Ca^{2+}$ release (CICR) or small conductance $Ca^{2+}$-activated $K^+$ channels (SK channels). Furthermore, PP2 but not H89 completely abolished $I_{DR}$ enhancement under high $Ca^{2+}$ condition, indicating that the activation of Src family tyrosine kinases (SFKs) is required for $Ca^{2+}$-mediated $I_{DR}$ enhancement. Thus, SFKs may be sensitive to excessive $Ca^{2+}$ influx through VDCCs and enhance $I_{DR}$ to activate a neuroprotective mechanism against $Ca^{2+}$-mediated hyperexcitability in neurons.

Effects of Polychlorinated Biphenyls and Phenols on the Biosynthesis of 6-Methoxymellein, a Phytoalexin (당근 Phytoalexin 6-Methoxymellein 생합성에 미치는 Polychlorinated Biphenyls 및 Phenol의 영향)

  • Lim, Do-Hyung;Lim, Da-Som;Keum, Young-Soo
    • Korean Journal of Environmental Agriculture
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    • v.35 no.3
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    • pp.216-222
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    • 2016
  • BACKGROUND: Polychlorinated biphenyls (PCBs) are one of the most common environmental contaminants. Because of their recalcitrant properties and long-term toxicity, numerous studies have been performed. The toxicological concerns are focused on endocrinological effects of animal. Several different metabolites have been reported, including hydroxy PCBs, PCB quinones, and methylsulfonyl PCBs from animal tissues. However, details in plants have never been studied. It is well-known that plants can produce phytoalexin in response to chemical, physical, or pathological stress.METHODS AND RESULTS: In this study, the several PCBs and hydroxy derivatives were prepared by chemical syntheses. Their effects on secondary metabolite biosynthesis were determined in carrot roots. The levels of 6-methoxymellein were determined in several different treatments, using gas chromatography-mass spectrometry. In general, the concentration of 6-methoxymellein reached a maximum at 2 days and gradually decreased to trace level at 5 days in control experiments. However, the effects of PCBs or hydroxy derivatives were highly dependent on compounds. For example, the maximum concentrations of 6-methoxymellein were observed at 3 days for 2-hydroxy/4-hydroxybiphenyl, while 3,3',4,4',5-pentachlorobiphenyl and 3,5-dichloro-2-hydroxybiphenyl showed a rapid accumulation within 1 day, followed by rapid dissipation to undetectable levels.CONCLUSION: Biphenyl derivatives were effective elicitor of 6-methoxymellein accumulation. In general, hydroxybiphenyls (phenols) more efficiently induced phytoalexin biosynthesis than those without hydroxy groups. It can be concluded that PCBs or their possible metabolites could change the plant secondary metabolism.

Indicators for the Quantitative Assessment of Tree Vigor Condition and Its Theoretical Implications : A Case Study of Japanese Flowering-cherry Trees in Urban Park (도시공원에 식재된 왕벚나무 수종을 중심으로 한 수목활력도의 정량평가지표 개발 및 이론적 고찰에 관한 연구)

  • Song, Youngkeun
    • Journal of the Korean Society of Environmental Restoration Technology
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    • v.17 no.4
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    • pp.57-67
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    • 2014
  • The vigor condition of trees is an important indicator for the management of urban forested area. But difficulties in how to assess the tree vigor condition still remain. Previous efforts were limited in the 1) measurement of single indicator rather than using multiple indices, 2) purpose-oriented measurement such as for air-pollution effect or specific pathological symptom, and 3) ordinal-scale evaluations by field crews 4) despite human errors based on his/her experiences or prior knowledge. Therefore, this study attempted to develop a quantitative and objective methodology for assessing tree vigor condition, by measuring multiple modules and building the profile inventory. Furthermore, the possibility and limitations were discussed in terms of schematic frames describing tree vigor condition. The vigor condition of 56 flowering cherry plants in urban park were assessed by in-situ measurements of following eight items; growth of crown(Gc), growth of shoots, individual tree volume(Vol), plant area index, woody area index, leaf area index, leaf chlorophyll content(Lc) and leaf water content(Lw). For validation, these measurements were compared with the ranks of holistic tree vigor condition, which were visually assessed using a 4-point grading scale based on the expert's knowledge. As a result, the measures of each evaluation item successfully highlighted a variety of aspects in tree vigor condition, including the states of both photosynthetic and non-photosynthetic parts. The variation in the results depending on evaluated parts was shown within an individual tree, even though the broad agreement among the results was found. The result of correlation analysis between the tested measurements and 4-point visual assessment, demonstrated that the state of water-stressed foliage of the season (Lw) or the development of plant materials since sapling phase (Vol) could be better viewed from the outer appearance of trees than other symptoms. But only based on the visual assessment, it may be difficult to detect the quality of photosynthesis (Lc) or the recent trend in growth of trees (Gc). To make this methodology simplified for the broad-scale application, the tested eight measurements could be integrated into two components by principal component analysis, which was labelled with 'the amount of plant materials' and 'vigor trend', respectively. In addition, the use of these quantitative and multi-scale indicators underlies the importance of assessing various aspects of tree vigor condition, taking into account the response(s) on different time and spatial scale of pressure(s) shown in each evaluated module. Future study should be advanced for various species at diverse developing stages and environment, and the application to wide areas at a periodic manner.

Altering of Collagens in Early Pregnant Mouse Uterus (착상전 생쥐 자궁에서 콜라겐의 변화)

  • Cheon, Yong-Pil
    • Development and Reproduction
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    • v.11 no.1
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    • pp.1-11
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    • 2007
  • Specific endometrial preparation should occur during periimplantation period. That is a progress of serial differentiation and is absolute in implantation of embryo and successful pregnancy. Remodeling of tissues shown during embryogenesis is regulated by various factors including extracellular matrix (ECM). Marked changes during pregnancy are including embryo migration, decidual response, and differentiation of placenta in placental animals including human. These changes to successful implantation in embryo and uterus have to prepare the competence for attachment of embryo and uterus, and invasion defense of uterus. During these changes, ECM dramatically changes for maintaining the uterine and embryonic functions. The major component of most connective tissue is collagens. It is very complex and hard to explore the mechanisms for ECM modulation. Recently using high throughput methodology, PCR-select cDNA subtraction method, microarray, many candidate genes have been identified. Steroid hormones have fundamental role in implantation and maintenance of pregnancy. Dermatopontin, a regulator of collagen accumulation, is regulated spatio-temporally in the uterus by primarily progesterone through progesterone receptors at the time of implantation. Modulation of extracellular matrix is critically regulated by cascade of gene net-works which are regulated by cascade of sex steroid hormones. Pathological regulation of uterine extracellular matrix reported in diabetic patients. To know the extracellular modulation is essential to understanding implantation, feto-placental development and overcome the paths involved in female reproduction. Though ECM composed with very various components and it is complex, the present review focused on the fate of collagens during periimplantation period.

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Gene Expression Profiling in Diethylnitrosamine Treated Mouse Liver: From Pathological Data to Microarray Analysis (Diethylnitrosamine 처리 후 병리학적 결과를 기초로 한 마우스 간에서의 유전자 발현 분석)

  • Kim, Ji-Young;Yoon, Seok-Joo;Park, Han-Jin;Kim, Yong-Bum;Cho, Jae-Woo;Koh, Woo-Suk;Lee, Michael
    • Toxicological Research
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    • v.23 no.1
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    • pp.55-63
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    • 2007
  • Diethylnitrosamine (DEN) is a nitrosamine compound that can induce a variety of liver lesions including hepatic carcinoma, forming DNA-carcinogen adducts. In the present study, microarray analyses were performed with Affymetrix Murine Genome 430A Array in order to identify the gene-expression profiles for DEN and to provide valuable information for the evaluation of potential hepatotoxicity. C57BL/6NCrj mice were orally administered once with DEN at doses of 0, 3, 7 and 20 mg/kg. Liver from each animal was removed 2, 4, 8 and 24 hrs after the administration. The histopathological analysis and serum biochemical analysis showed no significant difference in DEN-treated groups compared to control group. Conversely, the principal component analysis (PCA) profiles demonstrated that a specific normal gene expression profile in control groups differed clearly from the expression profiles of DEN-treated groups. Within groups, a little variance was found between individuals. Student's t-test on the results obtained from triplicate hybridizations was performed to identify those genes with statistically significant changes in the expression. Statistical analysis revealed that 11 genes were significantly downregulated and 28 genes were upregulated in all three animals after 2 h treatment at 20 mg/kg. The upregulated group included genes encoding Gdf15, JunD1, and Mdm2, while the genes including Sox6, Shmt2, and SIc6a6 were largely down regulated. Hierarchical clustering of gene expression also allowed the identification of functionally related clusters that encode proteins related to metabolism, and MAPK signaling pathway. Taken together, this study suggests that match with a toxicant signature can assign a putative mechanism of action to the test compound if is established a database containing response patterns to various toxic compounds.

Preparation and Biocompatibility of Medical Fiber from Novel Regenerated Cellulose from Styela clava tunic (미더덕껍질의 재생셀룰로오스를 이용한 의료용 섬유의 제조 및 생체적합성)

  • Song, Sung Hwa;Kim, Ji Eun;Choi, Jun Young;Park, Jin Ju;Lee, Mi Rim;Song, Bo Ram;Lee, Yechan;Kim, Hong Sung;Lee, Jae Ho;Lim, Yong;Hwang, Dae Youn;Jung, Young Jin
    • Textile Coloration and Finishing
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    • v.30 no.2
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    • pp.117-129
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    • 2018
  • Cellulose has been widely applied into various medical fields including scaffolding, tissue engineering and tissue formation. In this study, we manufactured cellulose medical fiber from Styela clava tunics(SCT-CS) and analyzed the tensile strength, elongation at break, fluid uptake and surface morphology. And then, the biocompatibility and toxicity of SCT-CS were measured in Sprague-Dawley(SD) rats after the implantation for 30, 60 and 90 days. The level of tensile strength and fluid uptake were lower in SCT-CS than chromic catgut(CCG), while elongation at break level were maintained the higher in SCT-CS. Also, the roughness with pronounced surface patterns as a result of in vivo degradation was significantly greater in CCG than this of SCT-CS although these levels gradually appeared with time in both groups. After implantation for 90 days, SCT-CS and CCG was successfully implanted around muscle of thigh without any significant immune response. Furthermore, no significant alterations were measured in serum parameters and the specific pathological features induced by most toxic compounds for liver and kidney toxicity. Therefore, these results suggest that SCT-CS showing good biocompatibility and non-toxicity can be successfully prepared from cellulose powder of SCT as well as has the potential for use as a powerful biomaterial for medical sutures.

Novel and Effective Almagate Enema for Hemorrhagic Chronic Radiation Proctitis and Risk Factors for Fistula Development

  • Yuan, Zi-Xu;Ma, Teng-Hui;Zhong, Qing-Hua;Wang, Huai-Ming;Yu, Xi-Hu;Qin, Qi-Yuan;Chu, Li-Li;Wang, Lei;Wang, Jian-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.631-638
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    • 2016
  • Radiation proctitis is a common complication after radiotherapy for pelvic malignant tumors. This study was conducted to assess the efficacy of novel almagate enemas in hemorrhagic chronic radiation proctitis (CRP) and evaluate risk factors related to rectal deep ulcer or fistula secondary to CRP. All patients underwent a colonoscopy to confirm the diagnosis of CRP and symptoms were graded. Typical endoscopic and pathological images, risk factors, and quality of life were also recorded. A total of 59 patients were enrolled. Gynecological cancers composed 93.1% of the primary malignancies. Complete or obvious reduction of bleeding was observed in 90% (53/59) patients after almagate enema. The mean score of bleeding improved from 2.17 to 0.83 (P<0.001) after the enemas. The mean response time was 12 days. No adverse effects were found. Moreover, long-term successful rate in controlling bleeding was 69% and the quality of life was dramatically improved (P=0.001). The efficacy was equivalent to rectal sucralfate, but the almagate with its antacid properties acted more rapidly than sucralfate. Furthermore, we firstly found that moderate to severe anemia was the risk factor of CRP patients who developed rectal deep ulcer or fistulas (P= 0.015). We also found abnormal hyaline-like thick wall vessels, which revealed endarteritis obliterans and the fibrosis underlying this disease. These findings indicate that almagate enema is a novel effective, rapid and well-tolerated method for hemorrhagic CRP. Moderate to severe anemia is a risk factor for deep ulceration or fistula.