• Title/Summary/Keyword: Lethal necrosis

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Development of human tumor necrosis factor-α muteins with improved therapeutic potential

  • Jang, Seung-Hwan;Kim, Hyo-Jin;Cho, Kwang-Hwi;Shin, Hang-Cheol
    • BMB Reports
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    • v.42 no.5
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    • pp.260-264
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    • 2009
  • Tumor necrosis factor-$\alpha$ (TNF-$\alpha$) exhibits cytotoxicity towards various tumor cells in vitro and induces apoptotic necrosis in transplanted tumors in vivo. It also shows severe toxicity when used systemically for the treatment of cancer patients, hampering the development of TNF-$\alpha$ as a potential anticancer drug. In order to understand the structure-function relation of TNF-$\alpha$ with respect to receptor binding, we selected four regions on the bottom of the TNF-$\alpha$ trimer that are in close contact with the receptor and carried out mutagenesis studies and computational modeling. From the study, various TNF-$\alpha$ muteins with a high therapeutic index were identified. These results will provide a structural basis for the design of highly potent TNF-$\alpha$ for therapeutic purposes. By conjugating TNF-$\alpha$ muteins with a high therapeutic index to a fusion partner, which targets a marker of angiogenesis, it could be possible to develop TNF-$\alpha$ based anticancer drugs.

Modification of Tomato Aspermy Virus Symptom by Cucumber Mosaic Virus- Associated Satellite RNA (Cucumber Mosaic Virus-associated Satellite RNA에 의한 Tomato Aspermy Virus의 병징변화)

  • Lee Hyun Sook
    • Korean Journal Plant Pathology
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    • v.2 no.3
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    • pp.145-149
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    • 1986
  • A tomato Aspermy Virus (TAV-B) served as a helper virus for multiplication and encapsidation of satellite RNAs which were isolated from two different CMV isolates, D and K. These two satellite RNAs induced renarkable attenuation of TAV symptoms in infected tobacco, which was correlated with a reduction of virus content in the plant. The CMV satellite RNAs also caused lethal necrosis in TAV-infected tomato as in the case of CMV system.

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ACUTE MAMMALIAN TOXICITY OF O-CHLOROBENZYLIDENE MALONONITRILE(CS)

  • Rim, Byung-Moo;Rim, Chae-Woong
    • Toxicological Research
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    • v.5 no.1
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    • pp.49-52
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    • 1989
  • Acute inhalation intoxication of CS (O-chlorobenzylidene malononitrile) occurred among the 192 animals in confined animal cages of farm as the result of prolonged exposure. A total of 8 animals (3 silver foxes, 3 fitches and 2 minks) died in 15 hours after the exposure. Distinct evidences of pulmonary atelectasis were observed as with hepatorenal damages. The lethal toxicity of CS was considered to be due to early severelung damages leading to asphyxia, accompanying acute toxic hepatitis and nephritis.

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Characterization of an Isometric virus Infecting Paprika (Capsicum annuum var. glosum) in Korea

  • Kim, Jae-Hyun;Kim, Jeong-Soo;Park, Gug-Seoun;Soo- Young Chae;Lee, Sin-Ho;Park, Jang-Kyung
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 2003.10a
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    • pp.140.1-140
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    • 2003
  • An Isometric virus was isolated from Paprika (Capsicum annuum var. glossum) showing necrosis spot and malformation on the fruit and the leaves, respectively, at yecheon in Korea. The virus could infect locally on Chenopodium amaranticolr, C. quinoa, Petunia x hybrida and Nicotiana glutinosa, but could not infect on Gomphrena globosa and Physalis floridana. The virus could infect systemically on red pepper and Lycopersicon esculentum. Datura stramonium, N. cleuarandii, N. rustim and N. tabacum cvs. were produced necrosis or necrotic ring spot lesions on the inoculated leaves and mosaic, vein necrosis or lethal death on the upper leaves. The virus was not related serologically to cucumber mosaic virus (CMV). In RT-PCR assay, it could not detected with specific primers of CMV and BBWV-II. The virions contain one molecule of genomic RNA, Which was approximately 3.8Kb and the coat protein (CP) of the purified virion migrated as a single band with molecular wight of about 29KDa in SDS-PAGE.

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Characterization of an Isolate of Cucumber mosaic virus Isolated from Chinese aster (Callistephus chinensis) (과꽃에서 분리한 Cucumber mosaic virus의 성질)

  • Oh, Sun-Mi;Kim, Sung-Ryul;Hong, Jin-Sung;Ryu, Ki-Hyun;Lee, Gung-Pyo;Choi, Jang-Kyung
    • Research in Plant Disease
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    • v.14 no.3
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    • pp.229-232
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    • 2008
  • An isolate of Cucumber mosaic virus (CMV), designated as Cas-CMV, was isolated from Chinese aster (Callistephus chinensis) showing severe mosaic symptom, and its properties was compared to the well-characterized Fny-CMV (subgroup IA) and As-CMV (subgroup IB) by host reaction in several indicator plants, dsRNA analysis, RT-PCR analysis, and restriction enzyme profile of the PCR products. Cas-CMV differed markedly in their host reaction to Fny-CMV or As-CMV in Cucurbita pepo cv. Black beauty. In the zucchini squash, all strains induced chlorotic spot on inoculated leaves and mosaic symptoms on upper leaves. However, symptoms induced by Cas-CMV were developed lethal necrosis on the young plants 15 to 20 days after inoculation. In experiments of dsRNA analysis and RT-PCR analysis, properties of Cas-CMV was come within subgroup I CMV. Moreover, restriction enzyme analysis using HindIII of the RT-PCR products showed that Cas-CMV belong to a member of CMV subgroup IA.

The Effect of Dietary Safflower Seed Supplementation on the $CCl_4$-Induced Hepatic Injury in Rats: Histopathological Observation (홍화씨 식이가 사 염화탄소에 의한 랫트 간손상에 미치는 영향: 병리조직학적 관찰)

  • Ha, Tae-Young;Jeong, Won-Il;Park, Sang-Joon;Jeong, Kyu-Shik;Lee, Cha-Soo
    • Korean Journal of Veterinary Pathology
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    • v.5 no.1
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    • pp.9-16
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    • 2001
  • To investigate the effects of safflower seed supplementation diet on the hepatic injury of rats administered with carbon tetrachloride (CCI$_4$), histopathological changes were assessed following acute and chronic administration in rats. In acute cases, all rats in group fed with 10% safflower seed supplementation diet survived despite the administration of lethal doses of $CCl_4$. However, most rats in group fed with control diet died. The hepatic injuries of survived rats, in the histopathological findings, were mild compared to those of dead rats. In the chronic cases, livers of group 2 fed with control diet were more progressive in fatty changes and centrilobular necrosis than those of group 3 fed with 20%safflower seed diet. However, after six weeks, livers of group 2 and 3 showed severe necrosis and mild fibrosis at the same time. Group 5 fed with 10% safflower seed supplementation diet and water containing 0.05% phenobarbital sodium showed mild fatty changes and necrosis compared with group 4 fed with control diet and water containing 0.05% phenobarbital sodium at sixth week. At 8 to 10 wee71s after the administration of $CCl_4$, severe fibrosis. fatty changes and marked necrosis were observed in group 4, but hepatic injuries were less severe in group 5. The present results suggested that safflower seed has some protective effect in hepatic lesions and consequently delay the progression of hepatic fibrosis.

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Organophosphate Poisoning in a Hooded Crane (유기인제에 중독된 흑두루미(Grus monachus) 증례)

  • Kim, Yong-Hwan;Cho, Kyoung-Oh;Park, Nam-Yong
    • Korean Journal of Veterinary Pathology
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    • v.5 no.2
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    • pp.75-78
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    • 2001
  • A dead nine-month-old female hooded crane (Grus monachus) fecund in Chonnam province was examined pathologically, bacteriologically and toxicologically. Pathologically multiple necrotic foci consisting of infiltration of heterophil, lymphocytes and macrophages, and exudation of fibrin were observed in liver. Kidney had multiple hemorrhagic foci. Aeromonas hydrophila identified by biochemical properties was isolated. Phosphamidon, a kind of organophosphate, was detected massively in feed content of gizzard. From these results, lethal ingestion of phosphamidon was a causative agent of death. In addition, future study has to be done about correlation between liver necrosis and A. hydrophila infection.

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Toxicity and Effects of the Herbicide Glufosinate-Ammonium (Basta) on the Marine Medaka Oryzias dancena

  • Kang, Gil Ran;Song, Ha Yeun;Kim, Dong Soo
    • Fisheries and Aquatic Sciences
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    • v.17 no.1
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    • pp.105-113
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    • 2014
  • Glufosinate-ammonium, a component of the herbicide Basta, is one of the most extensively used pesticides worldwide. In this study, we assessed subchronic and chronic toxicities of Basta and its histopathological effects on the marine medaka Oryzias dancena. Marine medaka were exposed to 0, 2, 4, or 8 mg/L of Basta for 28 or 42 days. The lethal concentration ($LC_{50}$) of Basta for 96 h is 8.76 mg/L. Histological changes in the gills and liver were evaluated with histopathological indices, allowing quantification of the damage to fish exposed to Basta. Blood congestion, lamellar fusion, and epithelial lifting were observed in the gills, and hydropic degeneration, fibrosis, lipid degeneration, leukocyte infiltration, and necrosis were found in the liver. These responses could be useful indicators of Basta toxicity in this species.

Single Oral Dose Toxicity Study of the Methylcyclohexane in Female Rats (암컷 랫드에서 Methylcyclohexane의 단회 경구투여 독성시험)

  • Kim, Sung-Hwan;Lim, Jeong-Hyeon;Shin, In-Sik;Moon, Changjong;Kim, Sung-Ho;Shin, Dong-Ho;Kim, Jong-Choon
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.21 no.1
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    • pp.33-39
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    • 2011
  • The present study was carried out to investigate the potential acute toxicity of methylcyclohexane (MCH) by a single oral dose in female rats. The test chemical was administered once by gavage to female rats at dose levels 0, 1,250, 2,500, and 5,000 mg/kg. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period following the administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem and histopathological examinations were performed. Treatment-related clinical signs, as evidenced by depression, soft feces, decreased locomotion activity, solid perineal region, crouching position, and anorexia were observed in all treatment groups in a dose-dependent manner. At the dose level of 5,000 mg/kg, decreased or suppressed body weight gain was found during the study period. At the scheduled necropsy, one case of congestion of the intestine and an increase in the weights of liver and kidney were observed in the 5,000 mg/kg group. Histopathological examinations exhibited an increased incidence of glomerular atrophy, congestion/hemorrhage, and focal degeneration/necrosis in the liver and an increased incidence of congestion, and inflammatory cell infiltration in the kidney. On the basis of the results, it was concluded that a single oral administration of MCH resulted in some adverse effects on clinical sign, body weight gain, and organ weight and histopathology in the liver and kidney in female rats. In the experimental conditions, the minimal lethal dose ($LD_{10}$) of MCH was greater than 5,000 mg/kg.

Compound K Rich Fractions Regulate NF-κB-dependent Inflammatory Responses and Protect Mice from Endotoxin-induced Lethal Shock

  • Yang, Chul-Su;Yuk, Jae-Min;Ko, Sung-Ryong;Cho, Byung-Goo;Sohn, Hyun-Joo;Kim, Young-Sook;Wee, Jae-Joon;Do, Jae-Ho;Jo, Eun-Kyeong
    • Journal of Ginseng Research
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    • v.32 no.4
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    • pp.315-323
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    • 2008
  • In the previous studies, we isolated the compound K rich fractions (CKRF) and showed that CKRF inhibited Toll-like receptor (TLR) 4- or TLR9-induced inflammatory signaling. To extend our previous studies,1) we investigated the molecular mechanisms of CKRF in the TLR4-associated signaling via nuclear factor (NF)-${\kappa}B$, and in vivo role of CKRF for induction of tolerance in lipopolysaccharide (LPS)-induced septic shock. In murine bone marrow-dervied macrophages, CKRF significantly inhibited the induction of mRNA expression of proinflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, CKRF significantly attenuated the transcriptional activities of TLR4/LPS-induced NF-${\kappa}B$. Nuclear translocation of NF-${\kappa}B$ in response to LPS stimulation was significantly abrogated by pre-treatment with CKRF. Furthermore, CKRF inhibited the recruitment of p65 to the interferon-sensitive response element flanking region in response to LPS. Finally, oral administration of CKRF significantly protected mice from Gram-negative bacterial LPS-induced lethal shock and inhibited systemic inflammatory cytokine levels. Together, these results demonstrate that CKRF modulates the TLR4-dependent NF-${\kappa}B$ activation, and suggest a therapeutic role for Gram-negative septic shock.