• Title/Summary/Keyword: Barrier test

Search Result 741, Processing Time 0.033 seconds

The Relationship between Intracellular Protein Kinase C Concentration and Invasiveness in U-87 Malignant Glioma Cells (교모세포종 세포주 U-87에서 세포내 PKC 농도와 종양침습성과의 상관 관계)

  • Ji, Cheol;Cho, Kyung-Keun;Lee, Kyung Jin;Park, Sung Chan;Cho, Jung Ki;Kang, Joon Ki;Choi, Chang Rak
    • Journal of Korean Neurosurgical Society
    • /
    • v.30 no.3
    • /
    • pp.263-271
    • /
    • 2001
  • Objective : Glioblastomas, the most common type of primary brain tumors, are highly invasive and cause massive tissue destruction at both the tumor invading edges and in areas that are not in direct contact with glioma cells. As a result, patients with high-grade gliomas are faced with a poor prognosis. Such grim statistics emphasize the need to better understand the mechanisms that underlie glioma invasion, as these may lead to the identification of novel targets in the therapy of high grade gliomas. Protein kinase C(PKC) is a family of serine/threonine kinases and an important signal transduction enzyme that conveys signals generated by ligand-receptor interaction at the cell surface to the nucleus. PKC appears to be critical in regulating many aspects of glioma biology. The purpose of this study was to assess accurately the role of PKC in the invasion regulation of human gliomas based on hypothesis that protein kinase C(PKC) is functional in the process of glial tumor cell invasion. Method : To test this hypothesis, U-87 malignant glioma cell line intracellular PKC levels were up and down regulated and their invasiveness was tested. Intracellular PKC level was characterized using PKC activity assays. Invasion assays including barrier migration and spheroid confrontation were used to study the relationship between PKC concentration and invasiveness. Result : The cell line which were treated by PKC inhibitor tamoxifen and hypericin exhibited decreased PKC activity and decreased invasive abilities dose dependently both in matrigel invasion assay and tumor spheroid fetal rat brain aggregates(FRBA) confrontation assay. However, the cell line that was treated by PKC activator 12-O-tetradecanylphorbol-13acetate(TPA) did not exhibit increases in either PKC activity or invasive ability. Conclusion : These studies suggest that PKC may be a useful molecular target for the chemotherapy of glioblastoma and other malignancies and that a therapeutic approach based on the ability of PKC inhibitors may be helpful in preventing invasion.

  • PDF

Switching and Leakage-Power Suppressed SRAM for Leakage-Dominant Deep-Submicron CMOS Technologies (초미세 CMOS 공정에서의 스위칭 및 누설전력 억제 SRAM 설계)

  • Choi Hoon-Dae;Min Kyeong-Sik
    • Journal of the Institute of Electronics Engineers of Korea SD
    • /
    • v.43 no.3 s.345
    • /
    • pp.21-32
    • /
    • 2006
  • A new SRAM circuit with row-by-row activation and low-swing write schemes is proposed to reduce switching power of active cells as well as leakage one of sleep cells in this paper. By driving source line of sleep cells by $V_{SSH}$ which is higher than $V_{SS}$, the leakage current can be reduced to 1/100 due to the cooperation of the reverse body-bias. Drain Induced Barrier Lowering (DIBL), and negative $V_{GS}$ effects. Moreover, the bit line leakage which may introduce a fault during the read operation can be eliminated in this new SRAM. Swing voltage on highly capacitive bit lines is reduced to $V_{DD}-to-V_{SSH}$ from the conventional $V_{DD}-to-V_{SS}$ during the write operation, greatly saving the bit line switching power. Combining the row-by-row activation scheme with the low-swing write does not require the additional area penalty. By the SPICE simulation with the Berkeley Predictive Technology Modes, 93% of leakage power and 43% of switching one are estimated to be saved in future leakage-dominant 70-un process. A test chip has been fabricated using $0.35-{\mu}m$ CMOS process to verify the effectiveness and feasibility of the new SRAM, where the switching power is measured to be 30% less than the conventional SRAM when the I/O bit width is only 8. The stored data is confirmed to be retained without loss until the retention voltage is reduced to 1.1V which is mainly due to the metal shield. The switching power will be expected to be more significant with increasing the I/O bit width.

Establishment and Characterization of Bone Marrow Mesenchymal Stromal/Stem Cells (MSCs) Derived from ${\alpha}$-1,3-Galactosyltransferase Knock Out(GalT KO) Pig (${\alpha}$-1,3-Galactosyltransferase Knock Out(GalT KO) 돼지유래 골수 중간엽 줄기세포의 특성 규명)

  • Ock, Sun-A;Oh, Keon Bong;Hwang, Seongsoo;Im, Seoki;Kim, Youngim;Park, Jin-Ki
    • Journal of Embryo Transfer
    • /
    • v.28 no.3
    • /
    • pp.281-287
    • /
    • 2013
  • A major barrier to progress in pig to primate organ transplantation or cell therapy is the presence of terminal ${\alpha}$-1,3-galactosyl epitopes on the surface of pig cells. Therefore, the purpose of this experiment was to establish and cha- racterize mesenchymal stromal/stem cells (MSCs) derived from ${\alpha}$-1,3-galactosyltransferase (GalT) knock out (GalT KO) pig to confirm their potential for cell therapy. Bone marrow (BM)-MSCs from GalT KO pig of 1 month old were isolated by Ficoll-Paque PLUS gradient and cultured with A-DMEM + 10% FBS on plastic dishes in 5% $CO_2$ incubator at 38.5. GalT KO BM-MSCs were analyzed for the expression of CD markers ($CD45^-$, $29^+$, $90^+$ and $105^+$) and in vitro differentiation ability (adiopogenesis and osteogenesis). Further, cell proliferation capacity and cell aging of GalT KO BM-MSCs were compared to Wild BM-MSCs by BrdU incorporation assay (Roche, Germany) using ELISA at intervals of two days for 7 days. Finally, the cell size was also evaluated in GalT KO and Wild BM-MSCs. Statistical analysis was performed by T-test (P<0.05). GalT KO BM-MSCs showed fibroblast-like cell morphology on plastic culture dish at passage 1 and exhibited $CD45^-$, $29^+$, $90^+$ and $105^+$ expression profile. Follow in ginduction in StemPro adipogenesis and osteogenesis media for 3 weeks, GalT KO BM-MSCs were differentiated into adipocytes, as demonstrated by Oilred Ostaining of lipid vacuoles and osteocytes, as confirmed by Alizarinred Sstaining of mineral dispositions, respectively. BrdU incorporation assay showed a significant decrease in cell proliferation capacity of GalT KO BM-MSCs compared to Wild BM-MSCs from 3 day, when they were seeded at $1{\times}10^3$ cells/well in 96-well plate. Passage 3 GalT KO and Wild BM-MSCs at 80% confluence in culture dish were allowed to form single cells to calculate cell size. The results showed that GalT KO BM-MSCs($15.0{\pm}0.4{\mu}m$) had a little larger cell size than Wild BM-MSCs ($13.5{\pm}0.3{\mu}m$). From the above findings, it is summarized that GalT KO BM-MSCs possessed similar biological properties with Wild BM-MSCs, but exhibited a weak cell proliferation ability and resistance to cell aging. Therefore, GalT KO BM-MSCs might form a good source for cell therapy after due consideration to low proliferation potency in vitro.

Preoperative Evaluation of Brain Lesion with $^{201}Tl$ Brain SPECT: Is It Useful to Differentiate Benign and Malignant Lesions? (수술 전 뇌 병변의 $^{201}Tl$ 뇌 SPECT: 양성과 악성 병변을 감별하는데 유용한가?)

  • Sohn, Hyung-Sun;Kim, Euy-Neyng;Kim, Sung-Hoon;Chung, Yong-An;Chung, Soo-Kyo;Bong, Yong-Gil;Lee, Youn-Soo
    • The Korean Journal of Nuclear Medicine
    • /
    • v.34 no.5
    • /
    • pp.371-380
    • /
    • 2000
  • Purpose: Thallim-201 ($^{201}Tl$) brain SPECT, which can represent cellular activity of brain lesions, may provide more useful information in differentiating between benign and malignant brain lesions more so than CT of MRI, that merely represents anatomic changes or breakdown of blood brain barrier. We used $^{201}Tl$ brain SPECT prospectively to evaluate the utility of $^{201}Tl$-indices as an indicator of benign or malig nant lesions. Materials and Methods: We studied 28 patients. There were 13 cases of benign lesions (3: nonspecific benign lesion, 3: meningioma, 2: low grade glioma, 1: tuberculoma, central neurocytoma, hemangioblastoma, radiation necrosis, and choroid plexus papilloma) and 15 cases of malignant lesions (6: glioblastoma multiforme, 5: anaplastic glioma, 2: medulloblastoma, 1: metastasis and lymphoma). In all patients, CT and/or MRI were obtained and then $^{201}Tl$ brain SPECT was obtained with measuring mean $^{201}Tl$ index and peak $^{201}Tl$ index. An unpaired t-test was performed to compare the $^{201}Tl$-indices and pathologic diagnoses to evaluate the utility of $^{201}Tl$-indices as all indicator of benign or malignant lesions. Results: There were no statistically significant difference in $^{201}Tl$-indices between benign and malignant brain lesion (p>0.05). Conclusion: These results demonstrated that we could not use $^{201}Tl$ indices on brain SPECT alone as an indicator of benign or malignant brain lesions.

  • PDF

The Impact of Perceived Risks Upon Consumer Trust and Purchase Intentions (인지된 위험의 유형이 소비자 신뢰 및 온라인 구매의도에 미치는 영향)

  • Hong, Il-Yoo B.;Kim, Woo-Sung;Lim, Byung-Ha
    • Asia pacific journal of information systems
    • /
    • v.21 no.4
    • /
    • pp.1-25
    • /
    • 2011
  • Internet-based commerce has undergone an explosive growth over the past decade as consumers today find it more economical as well as more convenient to shop online. Nevertheless, the shift in the common mode of shopping from offline to online commerce has caused consumers to have worries over such issues as private information leakage, online fraud, discrepancy in product quality and grade, unsuccessful delivery, and so forth, Numerous studies have been undertaken to examine the role of perceived risk as a chief barrier to online purchases and to understand the theoretical relationships among perceived risk, trust and purchase intentions, However, most studies focus on empirically investigating the effects of trust on perceived risk, with little attention devoted to the effects of perceived risk on trust, While the influence trust has on perceived risk is worth studying, the influence in the opposite direction is equally important, enabling insights into the potential of perceived risk as a prohibitor of trust, According to Pavlou (2003), the primary source of the perceived risk is either the technological uncertainty of the Internet environment or the behavioral uncertainty of the transaction partner. Due to such types of uncertainty, an increase in the worries over the perceived risk may negatively affect trust, For example, if a consumer who sends sensitive transaction data over Internet is concerned that his or her private information may leak out because of the lack of security, trust may decrease (Olivero and Lunt, 2004), By the same token, if the consumer feels that the online merchant has the potential to profit by behaving in an opportunistic manner taking advantage of the remote, impersonal nature of online commerce, then it is unlikely that the merchant will be trusted, That is, the more the probable danger is likely to occur, the less trust and the greater need to control the transaction (Olivero and Lunt, 2004), In summary, a review of the related studies indicates that while some researchers looked at the influence of overall perceived risk on trust level, not much attention has been given to the effects of different types of perceived risk, In this context the present research aims at addressing the need to study how trust is affected by different types of perceived risk, We classified perceived risk into six different types based on the literature, and empirically analyzed the impact of each type of perceived risk upon consumer trust in an online merchant and further its impact upon purchase intentions. To meet our research objectives, we developed a conceptual model depicting the nomological structure of the relationships among our research variables, and also formulated a total of seven hypotheses. The model and hypotheses were tested using an empirical analysis based on a questionnaire survey of 206 college students. The reliability was evaluated via Cronbach's alphas, the minimum of which was found to be 0.73, and therefore the questionnaire items are all deemed reliable. In addition, the results of confirmatory factor analysis (CFA) designed to check the validity of the measurement model indicate that the convergent, discriminate, and nomological validities of the model are all acceptable. The structural equation modeling analysis to test the hypotheses yielded the following results. Of the first six hypotheses (H1-1 through H1-6) designed to examine the relationships between each risk type and trust, three hypotheses including H1-1 (performance risk ${\rightarrow}$ trust), H1-2 (psychological risk ${\rightarrow}$ trust) and H1-5 (online payment risk ${\rightarrow}$ trust) were supported with path coefficients of -0.30, -0.27 and -0.16 respectively. Finally, H2 (trust ${\rightarrow}$ purchase intentions) was supported with relatively high path coefficients of 0.73. Results of the empirical study offer the following findings and implications. First. it was found that it was performance risk, psychological risk and online payment risk that have a statistically significant influence upon consumer trust in an online merchant. It implies that a consumer may find an online merchant untrustworthy if either the product quality or the product grade does not match his or her expectations. For that reason, online merchants including digital storefronts and e-marketplaces are suggested to pursue a strategy focusing on identifying the target customers and offering products that they feel best meet performance and psychological needs of those customers. Thus, they should do their best to make it widely known that their products are of as good quality and grade as those purchased from offline department stores. In addition, it may be inferred that today's online consumers remain concerned about the security of the online commerce environment due to the repeated occurrences of hacking or private information leakage. Online merchants should take steps to remove potential vulnerabilities and provide online notices to emphasize that their website is secure. Second, consumer's overall trust was found to have a statistically significant influence on purchase intentions. This finding, which is consistent with the results of numerous prior studies, suggests that increased sales will become a reality only with enhanced consumer trust.

Modelling of Fault Deformation Induced by Fluid Injection using Hydro-Mechanical Coupled 3D Particle Flow Code: DECOVALEX-2019 Task B (수리역학적연계 3차원 입자유동코드를 사용한 유체주입에 의한 단층변형 모델링: DECOVALEX-2019 Task B)

  • Yoon, Jeoung Seok;Zhou, Jian
    • Tunnel and Underground Space
    • /
    • v.30 no.4
    • /
    • pp.320-334
    • /
    • 2020
  • This study presents an application of hydro-mechanical coupled Particle Flow Code 3D (PFC3D) to simulation of fluid injection induced fault slip experiment conducted in Mont Terri Switzerland as a part of a task in an international research project DECOVALEX-2019. We also aimed as identifying the current limitations of the modelling method and issues for further development. A fluid flow algorithm was developed and implemented in a 3D pore-pipe network model in a 3D bonded particle assembly using PFC3D v5, and was applied to Mont Terri Step 2 minor fault activation experiment. The simulated results showed that the injected fluid migrates through the permeable fault zone and induces fault deformation, demonstrating a full hydro-mechanical coupled behavior. The simulated results were, however, partially matching with the field measurement. The simulated pressure build-up at the monitoring location showed linear and progressive increase, whereas the field measurement showed an abrupt increase associated with the fault slip We conclude that such difference between the modelling and the field test is due to the structure of the fault in the model which was represented as a combination of damage zone and core fractures. The modelled fault is likely larger in size than the real fault in Mont Terri site. Therefore, the modelled fault allows several path ways of fluid flow from the injection location to the pressure monitoring location, leading to smooth pressure build-up at the monitoring location while the injection pressure increases, and an early start of pressure decay even before the injection pressure reaches the maximum. We also conclude that the clay filling in the real fault could have acted as a fluid barrier which may have resulted in formation of fluid over-pressurization locally in the fault. Unlike the pressure result, the simulated fault deformations were matching with the field measurements. A better way of modelling a heterogeneous clay-filled fault structure with a narrow zone should be studied further to improve the applicability of the modelling method to fluid injection induced fault activation.

Improving Corsican pine somatic embryo maturation: comparison of somatic and zygotic embryo morphology and germination

  • Wtpsk, Senarath;Shaw, D.S.;Lee, Kui-Jae;Lee, Wang-Hyu
    • Proceedings of the Plant Resources Society of Korea Conference
    • /
    • 2003.04a
    • /
    • pp.61-62
    • /
    • 2003
  • Clonal propagation of high-value forest trees through somatic embryogenesis (SE) has the potential to rapidly capture the benefits of breeding or genetic engineering programs and to improve raw material uniformity and quality. A major barrier to the commercialization of this technology is the low quality of the resulting embryos. Several factors limit commercialization of SE for Corsican pine, including low initiation rates, low culture survival, culture decline causing low or no embryo production, and inability of somatic embryos to fully mature, resulting in low germination and reduced vigour of somatic seedlings. The objective was to develop a Corsican pine maturation medium that would produce cotyledonary embryos capable of germination. Treatments were arranged in a completely randomized design. Data were analyzed by analysis of variance, and significant differences between treatments determined by multiple range test at P=0.05. Corsican pine (Pinus nigra var. maritima) cultures were initiated on modified !P6 medium. Modifications of the same media were used for culture multiplication and maintenance. Embryogenic cultures were maintained on the same medium semi solidified with 2.5 g/l Gelrite. A maturation medium, capable of promoting the development of Corsican pine somatic embryos that can germinate, is a combination of iP6 modified salts, 2% maltose, 13% polyethylene glycol (PEG), 5 mg!l abscisic acid (ABA), and 2.5 g/l Gelrite. After initiation and once enough tissue developed they were grown in liquid medium. Embryogenic cell suspensions were established by adding 0.951.05 g of 10- to 14-day-old semisolid-grown embryogenic tissue to 9 ml of liquid maintenance media in a 250ml Erlenmeyer flask. Cultures were then incubated in the dark at 2022$^{\circ}$C and rotated at 120 rpm. After 2.53 months on maturation medium, somatic embryos were selected that exhibited normal embryo shape. Ten embryos were placed horizontally on 20 ml of either germination medium ($\frac{2}{1}$strength Murashige and Skoog (1962) salts with 2.5 g/l activated charcoal) or same medium with copper sulphate adjusted to 0.25 mg/1 to compensate for copper adsorption by activated carbon. 2% and 4% maltose was substituted by 7.5% and 13% PEG respectively to improve the yield of the embryos. Substitution of' maltose with PEG was clearly beneficial to embryo development. When 2% of the maltose was replaced with 7.5% PEG, many embryos developed to large bullet-shaped embryos. At latter stages of development most embryos callused and stopped development. A few short, barrel-shaped cotyledonary embryos formed that were covered by callus on the sides and base. When 4% of the maltose was removed and substituted with 13% PEG, the embryos developed further, emerging from the callus and increasing yield slightly. Microscopic examination of the cultures showed differing morphologies, varying from mostly single cells or clumps to well-formed somatic embryos that resembled early zygotic embryos only liquid cultures with organized early-stag. A procedure for converting and acclimating germinants to growth in soil and greenhouse conditions is also tested. Seedling conversion and growth were highly related to the quality of the germinant at the time of planting. Germinants with larger shoots, longer, straighter hypocotyls and longer roots performed best. When mature zygotic embryos germinate the root emerges, before or coincident with the shoot. In contrast, somatic embryos germinate in reverse sequence, with the cotyledons greening first, then shoot emergence and then, much later, if at all, the appearance of the root. Somatic seedlings, produced from the maturation medium, showed 100% survival when planted in a field setting. Somatic seedlings showed normal yearly growth relative to standard seedlings from natural seed.

  • PDF

Reinforcing Effects around Face of Soil-Tunnel by Crown & Face-Reinforcing - Large Scale Model Testing (천단 및 막장면 수평보강에 의한 토사터널 보강효과 - 실대형실험)

  • Kwon Oh-Yeob;Choi Yong-Ki;Woo Sang-Baik;Shin Jong-Ho
    • Journal of the Korean Geotechnical Society
    • /
    • v.22 no.6
    • /
    • pp.71-82
    • /
    • 2006
  • One of the most popular pre-reinforcement methods of tunnel heading in cohesionless soils would be the fore-polling of grouted pipes, known as RPUM (reinforced protective umbrella method) or UAM (umbrella arch method). This technique allows safe excavation even in poor ground conditions by creating longitudinal arch parallel to the tunnel axis as the tunnel advances. Some previous studies on the reinforcing effects have been performed using numerical methods and/or laboratory-based small scale model tests. The complexity of boundary conditions imposes difficulties in representing the tunnelling procedure in laboratory tests and theoretical approaches. Full-scale study to identify reinforcing effects of the tunnel heading has rarely been carried out so far. In this study, a large scale model testing for a tunnel in granular soils was performed. Reinforcing patterns considered are four cases, Non-Reinforced, Crown-Reinforced, Crown & Face-Reinforced, and Face-Reinforced. The behavior of ground and pipes as reinforcing member were fully measured as the surcharge pressure applied. The influences of reinforcing pattern, pipe length, and face reinforcement were investigated in terms of stress and displacement. It is revealed that only the Face-Reinforced has decreased sufficiently both vertical settlement in tunnel heading and horizontal displacement on the face. Vertical stresses along the tunnel axis were concentrated in tunnel heading from the test results, so the heading should be reinforced before tunnel advancing. Most of maximum axial forces and bending moments for Crown-reinforced were measured at 0.75D from the face. Also it should be recommended that the minimum length of the pipe is more than l.0D for crown reinforcement.

The Usefulness of Product Display of Online Store by the Product Type of Usage Situation - Focusing on the moderate effect of the product portability - (사용상황별 제품유형에 따른 온라인 점포 제품디스플레이의 유용성 - 제품 휴대성의 조절효과를 중심으로 -)

  • Lee, Dong-Il;Choi, Seung-Hoon
    • Journal of Distribution Research
    • /
    • v.16 no.2
    • /
    • pp.1-24
    • /
    • 2011
  • 1. Introduction: Contrast to the offline purchasing environment, online store cannot offer the sense of touch or direct visual information of its product to the consumers. So the builder of the online shopping mall should provide more concrete and detailed product information(Kim 2008), and Alba (1997) also predicted that the quality of the offered information is determined by the post-purchase consumer satisfaction. In practice, many fashion and apparel online shopping malls offer the picture information with the product on the real person model to enhance the usefulness of product information. On the other virtual product experience has been suggested to the ways of overcoming the online consumers' limited perceptual capability (Jiang & Benbasat 2005). However, the adoption and the facilitation of the virtual reality tools requires high investment and technical specialty compared to the text/picture product information offerings (Shaffer 2006). This could make the entry barrier to the online shopping to the small retailers and sometimes it could be demanding high level of consumers' perceptual efforts. So the expensive technological solution could affects negatively to the consumer decision making processes. Nevertheless, most of the previous research on the online product information provision suggests the VR be the more effective tools. 2. Research Model and Hypothesis: Presented in

    , research model suggests VR effect could be moderated by the product types by the usage situations. Product types could be defined as the portable product and installed product, and the information offering type as still picture of the product, picture of the product with the real-person model and VR. 3. Methods and Results: 3.1. Experimental design and measured variables We designed the 2(product types) X 3(product information types) experimental setting and measured dependent variables such as information usefulness, attitude toward the shopping mall, overall product quality, purchase intention and the revisiting intention. In the case of information usefulness and attitude toward the shopping mall were measured by multi-item scale. As a result of reliability test, Cronbach's Alpha value of each variable shows more than 0.6. Thus, we ensured that the internal consistency of items. 3.2. Manipulation check The main concern of this study is to verify the moderate effect by the product type of usage situation. indicates that our experimental manipulation of the moderate effect of the product type was successful. 3.3. Results As
    indicates, there was a significant main effect on the only one dependent variable(attitude toward the shopping mall) by the information types. As predicted, VR has highest mean value compared to other information types. Thus, H1 was partially supported. However, main effect by the product types was not found. To evaluate H2 and H3, a two-way ANOVA was conducted. As
    indicates, there exist the interaction effects on the three dependent variables(information usefulness, overall product quality and purchase intention) by the information types and the product types. As predicted, picture of the product with the real-person model has highest mean among the information types in the case of portable product. On the other hand, VR has highest mean among the information types in the case of installed product. Thus, H2 and H3 was supported. 4. Implications: The present study found the moderate effect by the product type of usage situation. Based on the findings the following managerial implications are asserted. First, it was found that information types are affect only the attitude toward the shopping mall. The meaning of this finding is that VR effects are not enough to understand the product itself. Therefore, we must consider when and how to use this VR tools. Second, it was found that there exist the interaction effects on the information usefulness, overall product quality and purchase intention. This finding suggests that consideration of usage situation helps consumer's understanding of product and promotes their purchase intention. In conclusion, not only product attributes but also product usage situations must be fully considered by the online retailers when they want to meet the needs of consumers.

  • PDF
  • The Ability of Anti-tumor Necrosis Factor Alpha(TNF-${\alpha}$) Antibodies Produced in Sheep Colostrums

    • Yun, Sung-Seob
      • 한국유가공학회:학술대회논문집
      • /
      • 2007.09a
      • /
      • pp.49-58
      • /
      • 2007
    • Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

    • PDF

    (34141) Korea Institute of Science and Technology Information, 245, Daehak-ro, Yuseong-gu, Daejeon
    Copyright (C) KISTI. All Rights Reserved.