• Title/Summary/Keyword: Dose analysis

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Effect of Resveratrol on the Induction of Cdk Inhibitor p21 and Pro-apoptotic Bax Expression by amyloid-β in Astroglioma C6 Cells (신경교 세포에서 resveratrol이 amyloid-β에 의해 유도되는 Cdk inhibitor p21 및 Bax 발현의 감소 효과)

  • Kim Young Ae;Lim Sun-Young;Ko Woo Shin;Choi Byung Tae;Lee Yong Tae;Rhee Sook-Hee;Park Kun-Young;Lee Won-Ho;Choi Yung Hyun
    • Journal of Life Science
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    • v.15 no.2 s.69
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    • pp.169-175
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    • 2005
  • Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. $Amyloid-\beta$ deposition and senile plaque-associated astrocytes are common neuropathological features of Alzheimer's disease. In this study, we have explored the effects of resveratrol on $amyloid-\beta-peptide-mediated$ cytotoxicity in vitro and modulation of cell growth-regulatory gene products in astroglioma C6 cells to elucidate its possible mechanism for anti-cytotoxicity. Exposure of C6 cells to $Amyloid-\beta$ resulted in dose-dependent growth inhibition and morphological changes of C6 cells, which were recovered by pre-treatment with resveratrol. The anti-proliferative effect of $amyloid-\beta$ was associated with the induction of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) expression assessed by RT-PCR and Western blot analysis in time-dependent manner in C6 cells. In addition, the pro-apoptotic Bax expression was also up-regulated in $amyloid-\beta-treated$ C6 cells without alteration of anti-apoptotic Bcl-2 and $Bcl-X_L$ expression. However, pre-treatment of resveratrol significantly inhibited $amyloid-\beta-induced$ p53, p21 and Bax levels, suggesting that the modulation of p53, p21 and Bax levels could be one of the possible pathways by which resveratrol functions as anti-cytotoxic agent. Our results demonstrate that resveratrol may enhance the protection against $amyloid-\beta-induced$ cytotoxicity by promoting the survival of glial cells.

The Physical and Chemical Properties and Cytotoxic Effects of Acer tegmentosum Maxim. Extracts (산겨릅나무 추출물의 이화학적 특성과 암세포 성장 억제 효과)

  • Shin, In-Cheol;Sa, Jae-Hoon;Shim, Tae-Heum;Lee, Jin-Ha
    • Applied Biological Chemistry
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    • v.49 no.4
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    • pp.322-327
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    • 2006
  • Food constituents analysis of Acer tegmentosum. Maxim.(Acer TM) stem was carried out according to AOAC method, and the antiradical activity on DPPH and cytotoxicity on human cell lines (AGS, HepG2, A549, MCF-7 and Chang) for the 80% ethylalcohol(EtOH) extracts of Acer TM stem were studied. The antiradical activity on DPPH radical of the ethylacetate(EtOAc) fraction of the bark showed a higher activity than that of $\alpha$-tocopherol, ascorbic acid and BHT. The inhibition activity of the 80% EtOH extracts from Acer TM stem on human cancer cell lines by SRB assay indicated a dose-dependent growth inhibition on most human carcinoma cells. The growth inhibition rate of each human cancer cell line showed 91.3% to AGS, 75.0% to A549, 74.1% to HepG2, and 70.2% to MCF-7 cells, respectively, when the 80% EtOH extract(1 mg/ml) of Acer TM stem was added.

Therapeutic Efficacy of Alendronate for Glucocorticoid Induced Metabolic Bone Disease in Children with Nephrotic Syndrome (신증후군 환아에서 스테로이드 유발 대사성 골질환에 대한 Alendronate의 치료 효과)

  • Lee Ji-Eun;Lee Hyun-Ok;Paik Kyung-Hoon;Lee Suk-Hyang;Jin Dong-Kyu
    • Childhood Kidney Diseases
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    • v.8 no.1
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    • pp.33-42
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    • 2004
  • Purpose : Children with nephrotic syndrome(NS) are under high risk for metabolic bone disease(MBD) as a complication of long-term glucocorticoid therapy. We prospectively evaluated the effect of oral bisphosphonate(alendronate) therapy in children with NS, which has proven efficacy in adult patients with glucocorticoid induced MBD. Methods : Among 58 children with NS, aged 5 to 8 years and haying a disease duration of more than 2 years, 30(51.7%) were enrolled to meet the selection criteria, less than -1.0 Z-scores of lumbar spine bone mineral density(BMD) by dual energy X-ray absorptiometry (DEXA). These 30 children were divided into three groups and each were assigned to receive alendronate, calcitriol, and no-medication, respectively for one year. Lumbar spine BMD was followed up every 6 months and the biochemical indexes were measured before and 1 year after the treatment. There were no significant difference among groups with respect to the average age, the initial BMD, and the cumulative steroid doses. Analysis of the treatment efficacy was done by the % change of BMD and by the changes in Z-scores of lumbar spine BMD. Results : Mean age and disease duration of patients at the initial lumbar spine BMD evaluation was $7.4{\pm}1.7$ years and $2.2{\pm}1.2$ years, respectively. Twenty-three of 30 children(76%) had osteopenia, and seven(23%) had osteoporosis. There was no difference in the biochemical values among the groups, before and 1 year after the treatment(P<0.05). Twenty two children(73.3%) with frequent relapsing or steroid dependant NS had more frequent MBD, compared to the 8 children(26.6%) with infrequent relapsing NS. The one year % changes of BMD were 8.56 in alendronate group, 5.79 in calcitriol group, and 1.9 in no-medication group. The changes in Z-score of lumbar spine BMD increased in the alendronate group and the calcitriol group, but not in the no-medication group. One year % changes of BMD were different among groups(P=0.0002). Significant differences were found between the alendronate and the no-medication group, and between the calcitriol and the no-medication group(P<0.05). There was no difference between the alendronate and the calcitriol group. No serious adverse effect was observed in the alendronate group. Conclusion : Children with NS receiving high dose steroids are under the high risk of BMD and should undergo regular BMD evaluation. Z-score of lumbar spine BMD was a useful parameter in diagnosing low bone mass in children. Alendronate weekly oral therapy was effective and relatively safe in increasing the lumbar spine BMD in children with NS having steroid induced MBD.

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Concurrent Chemoradiation for Unresectable Pancreatic Cancer (절제 불가능한 췌장암의 동시항암화학방사선요법)

  • Kim, Yong-Bae;Seong, Jin-Sil;Song, Si-Young;Park, Seung-Woo;Suh, Chang-Ok
    • Radiation Oncology Journal
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    • v.20 no.4
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    • pp.328-333
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    • 2002
  • Purpose : To analyze the treatment results of concurrent chemoradiation with oral 5-FU plus Gemcitabine or Paclitaxel for unresectable pancreatic cancer. Materials & Methods : The patients, who were diagnosed by imaging modalities or by explo-laparotomy, were treated with concurrent chemoradiation. Radiotherapy was delivered to primary tumor and regional lymph nodes, and the total dose was 45 Gy. Patients received Gemcitabine $1,000\;mg/m^2$ or Paclitaxel $50\;mg/m^2$ weekly and oral 5-FU daily The total number of cycles of chemotherapy ranged from 1 to 39 (median, 11 cycles). The follow-up period ranged from 6 to 36 months, Survival was analyzed using the Kaplan-Meier method. Results : Fifty-four patients between Jan. 1999 to Nov. 2001 were included in this study. Forty-two patients who completed the planned treatment were included in this analysis. The patients' age ranged from 37 to 73 years (median, 50 years) and the male to female ratio was 30:12. Treatment was interrupted for 12 patients due to: disease progression for 6 $(50\%)$, poor performance status for 4 $(33.3\%)$, intercurrent disease for 1 $(8.3\%)$, and refusal for 1 $(8.3\%)$. Response evaluation was possible for 40 patients. One patient gained complete remission and 24 patients gained partial remission, hence the response rate was $59\%$. The survival rates were $46.7\%\;and\;17.0\%$ at 1 year and 2 years, respectively with a median survival time of 12 months. Patients treated with Paclitaxel showed superior outcomes compared to those patients treated with Gemcitabine, in terms of both response rate and survival rate although this difference was not statistically significant. Grade III or IV hematologic toxicity was shown in 8 patients $(19\%)$, while grade III or IV non-hematologic toxicity was shown in 5 patients $(12\%)$. Conclusion : Concurrent chemoradiation with oral 5-FU and Gemcitabine or Paclitaxel improves both the response rate and survival rate in patients with unresectable pancreatic cancer. A prospective study should be investigated in order to improve both the patient selection and the treatment outcome as well as to reduce the toxicity.

The Result of Radiotherapy for Pituitary Adenoma (뇌하수체 선종의 방사선치료 결과)

  • Lee, Hyun-Joo;Yang, Kwang-Mo;Cho, Heung-Lae;Shon, Seung-Chang;Suh, Hyun-Suk
    • Radiation Oncology Journal
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    • v.15 no.4
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    • pp.297-303
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    • 1997
  • Purpose : To evaluate the prognostic factors for disease-free survival and long-term results of radiotherapy for pituitary adenoma. Methods and Materials : The study involved a retrospective review of out-come in a series of 27 patients with pituitary adenoma, between 1984 and 1995 at Paik hospital. The study included 20 patients treated with surgery and postoperative radiotherapy and 7 with radiotherapy alone. The patients were followed for 12-146 months (median : 97 months). Seventeen were men and 10 were women. The numbers of functioning and nonfunctioning pituitary adenorna were 22 and 5 respectively and those of microadenoma and macroadenoma were 4 and 23 respectively. The radiation doses of 5040-5580cGy (median : 5040cGy) were deliverd over 5-7 weeks, using 4MV LINAC. The prognostic factors were analyzed by log-rank test. Results: For radiation therapy alone, the 5YSR was 100% and progression free survival rate was 85.8%, The tumor was controlled in 6/7 (85.8%). For surgery and postoperative radiotherapy. the 5YSR, progression free survival rate and local control rate were 95%, 84.8%, and 89.5% respectively. The parameters of tumor size, hormone secretion, radiation dose. radiotherapy field size were evaluated in a uni- and multivariate analysis and all the factors were not statisticaIty significant (P>0.05). Eleven of 12 (92%) with visual field defect experienced normalization or improvement, and 5 for 7 evaluabie patients with hyperprolactinoma achived normalization in 4 and decrement in S patients. Only 2 patients developed mild degree of Panhypopituitarism. Conclusion: The radiotherapy appears to be effective in controiling clinical symptoms and signs resulting from pituitary adenoma. Local control rate with radiotherapy alone or with surgery and postoperative radiotherauy was comparable. There was a trend toward high recurrence rate in Patients with nonfunctioning or prolactin secretion tumor and larger radiation field sizes.

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A Novel Chenodeoxycholic Derivative HS-1200 Induces Apoptosis in Human HT-29 Colon Cancer Cells (인체 대장암 세포주(HT-29)에서 담즙산 합성유도체(HS-1200)의 세포 사망 기전)

  • Oh Sin Geun;Yang Kwang Mo;Hur Won Joo;Yoo Young Hyun;Suh Hong Suk;Lee Hyung Sik
    • Radiation Oncology Journal
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    • v.20 no.4
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    • pp.367-374
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    • 2002
  • Purpose : To investigate the growth inhibitory effects, and the underlying mechanism of human colon cancer cell (HT-29) death, induced by a new synthetic bile acid derivative (HS-1200). Materials and Methods : Human colon cancer cells (HT-29), in exponential growth phase, were treated with various concentrations of a new synthetic bile acid derivative (HS-1200). The growth inhibitory effects on HT-29 cells were examined using a frypan blue exclusion assay. The extent of apoptosis was determined using agarose gel electrophoresis, TUNEL assays and Hoechst staining. The apoptotic cell death was also confirmed by Western blotting of PARP, caspase-3 and DNA fragmentation factor (DFF) analysis. To investigate the involvement of mitochondria, we employed immunofluorescent staining of cytochrome c and mitochondrial membrane potential analyses. Results : The dose required for the half maximal inhibition $(IC_{50})$ of the HT-29 cell growth was $100\~150\;{\mu}M$ of HS-1200. Several changes, associated with the apoptosis of the HT-29 cells, were reveal by the agarose gel eletrophoresis, TUNEL assays and Hoechst staining, following their treatment with $100\;{\mu}M$ of HS-1200. HS-1200 treatment also induced caspase-3, PARP and DFF degradations, and the western blotting showed the processed caspase-3 p20, PARP p85 and DFF p30 and p11 cleaved products. Mitochondrial events were also demonstrated. The cytochrome c staining indicated that cytochrome c had been released from the mitochondria in the HS-1200 treated cells. The mitochondrial membrane potential $(\Delta\Psi_m)$ was also prominently decreased in the HS-1200 treated cells. Conclusion : These findings suggest that the HS-1200 - induced apoptosis of human colon cancer cells (HT-29) is mediated via caspase and mitochondrial pathways.

The Results of Postoperative Radiotherapy for Endometrial Carcinoma (자궁 내막암의 수술 후 방사선치료 결과)

  • Noh, O-Kyu;Lee, Sang-Wook;Ahn, Seung-Do;Choi, Eun-Kyung;Kim, Jong-Hyeok;Kim, Yong-Man;Nam, Joo-Hyun;Mok, Jung-Eun;Kim, Jong-Hoon;Shin, Seong-Soo
    • Radiation Oncology Journal
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    • v.25 no.2
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    • pp.93-100
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    • 2007
  • [ $\underline{Purpose}$ ]: To evaluate the outcome and prognostic factors of postoperative radiotherapy in endometrial carcinoma. $\underline{Materials\;and\;Methods}$: From September 1991 to August 2003, 76 patients with endometrial carcinoma received postoperative adjuvant radiotherapy after hysterectomy at Asan Medical Center. Stage was classified as FIGO I in 41 (53.9%), II in 12 (53.9%), and III in 23 (30.3%). Histologic grade 1, 2 and 3 were in 29 (38.2%), 20 (26.3%), and 27 (35.5%) respectively. Forty two patients received both external beam radiation therapy (EBRT) and intracavitary radiation (ICR), 34 patients were treated with EBRT or ICR alone. EBRT dose was 50.4 Gy, ICR was performed in $4{\sim}6$ fractions with $4{\sim}5\;Gy$ per fraction. Median follow-up period was 51 (range $5{\sim}121$) months. $\underline{Results}$: Five-year overall survival was 89.6%. In univariate analysis, statistically significant factors to overall survival were FIGO stage, lymph node metastasis and histologic grade. In disease free survival, FIGO stage, lymph node metastasis and lymphovascular invasion were significant prognostic factors. Recurrence was seen in 11 patients. Of these, systemic failure was in 10 patients. There were no moderate to severe complications after radiation therapy. $\underline{Conclusion}$: The outcome of postoperative adjuvant radiotherapy in endometrial carcinoma was good. Main pattern of failure after postoperative radiotherapy was distant metastasis. So, adjuvant chemotherapy may help in improving outcome. Further study on chemotherapy in combined with postoperative radiotherapy will be needed, especially for patients with high risk factors such as high FIGO stage, lymphovascular invasion, and high histologic grade.

$^{99m}Tc$-Glucarate Uptake in Ischemic Tissue of Experimental Models of Cerebral Ischemia (실험적 뇌허혈증 모델에서 허혈 조직의 $^{99m}Tc$-glucarate 섭취)

  • Jeong, Jae-Min;Kim, Young-Ju;Choi, Seok-Rye;Kim, Chae-Kyun;Mar, Woong-Chun;Chung, June-Key;Lee, Myung-Chul;Koh, Chang-Soon;Lee, Dong-Soo
    • The Korean Journal of Nuclear Medicine
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    • v.30 no.4
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    • pp.484-492
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    • 1996
  • To detect ischemic tissue in experimental model of cerebral ischemia made by middle cerebral artery(MCA)-occlusion, we acquired triple image of $^{99m}Tc$-glucarate, [$^{18}F$]fluoro-deoxyglucose (FDG), and 2,3,5- triphenyltetrazolium (TTC) staining. We made cerebral infarction either with reperfusion (after occlusion of 2 hours) or without reperfusion in 10 Sprague-Dawley rats by inserting thread to MCA through internal carotid artery. After 22 hours, we injected 740 MBq of $^{99m}Tc$-glucarate and 55.5 MBq of [$^{18}F$]FDG through tail vein. Each 1 mm slice of rat brains was frozen and exposed to imaging plate for 20 minutes in freezer to get an [$^{18}F$]FDG image. After 20 hours enough to fade radioactivity of [$^{18}F$]FDG, the slices were again imaged by BAS1500 for $^{99m}Tc$-glucarate uptake. Finally, these brain tissues were stained with TTC. Semi-quantitative visual analysis was done by grading 0 to 3 points according to the degree of uptakes($^{99m}Tc$-glucarate) and decreased uptakes([$^{18}F$]FDG and TTC). Ten rats survived with neurologic symptoms. TTC staining confirmed the development of infarction. The size of the infarction was relatively larger in the group without reperfusion. [$^{18}F$]FDG images were similar to TTC-stained images. However, we found regions with intermediate uptake which were not stained with TTC. We found regions with intermediate [$^{18}F$]FDG uptake where TTC staining was normal. $^{99m}Tc$-glucarate uptake was round only in TTC non-stained region. In the TTC stained regions, there were no uptake of $^{99m}Tc$-glucarate. We could not find clear relation between $^{99m}Tc$-glucarate uptake with [$^{18}F$]FDG uptake. This was partly because percent uptake of $^{99m}Tc$-glucarate was so small (less than 1 percent of injected dose) and because there were quite heterogeneity of patterns of [$^{18}F$]FDG uptake and TTC. With these findings, we could conclude that $^{99m}Tc$-glucarate were taken up only in part of ischemic tissues which were proven to be nonviable. The establishment of MCA-occluded rat model with or without reperfusion and triple imaging for $^{99m}Tc,\;^{18}F$ and TTC helped the characterization of $^{99m}Tc$-glucarate uptakes. Further work is needed to clarify the meaning or diversities or [$^{18}F$]FDG and TTC and their relation with $^{99m}Tc$-glucarate.

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Value of the Serum Thyroglobulin Level Alteration at the First High Dose Radioiodine Treatment in Patients with Differentiated Thyroid Carcinoma (분화성갑상선암에서 최초 고용량 방사성요오드 치료시 혈청 갑상선글로불린 수치 변화의 의의)

  • Nam, Hyun-Yeol;Kim, In-Joo;Kim, Yong-Ki;Kim, Seong-Jang;Jun, Sung-Min;Kim, Bum-Soo
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.4
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    • pp.294-300
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    • 2009
  • Purpose: The purpose of this study was to evaluate if short-term serum thyroglobulin (Tg) elevation after radioiodine administration can predict successful radioiodine remnant ablation (RRA) and whether comparable RRA effectiveness is exhibited between a group administered with recombinant human thyrotropin (rhTSH) and a group experiencing thyroid hormone withdrawal (THW), in preparation for RRA. Materials and Methods: A retrospective chart review was performed on 39 patients in the rhTSH group and 46 patients in the THW group. They were treated for differentiated thyroid carcinoma by total or near total thyroidectomy, and referred for RRA between 2003 and 2006 (the rhTSH group) and between January and June of 2006 (the THW group). They were assessed for serum Tg levels just before I-131 administration (TgD0), reassessed 9 days later (TgD9), and again 6-12 months later. Results: RRA was successful in 64 (37 from the THW group and 27 from the rhTSH group) of the total 85 patients. The success rates of RRA had no statistically significant differences between the two groups. In both groups, TgD9/TgD0 values were significantly higher in the RRA success group (the rhTSH group; P = 0.03, the THW group; P = 0.04). By combining cutoff values of TgD0 and TgD9/TgD0, the successful RRA value was determined to be 96.7% (29/30) with TgD0$\leq$5.28 ng/mL and TgD9/TgD0>4.37 in both groups (the rhTSH group; 100% (16/16), the THW group; 92.9% (13/14)). Using logistic multivariate analysis, only TgD0 was independently associated with successful RRA. Conclusion: We may predict successful ablation by evaluating short-term serum Tg elevation after I-131 administration for RRA, in both rhTSH and THW patients.

Detection of Campylobacter jejuni in food and poultry visors using immunomagnetic separation and microtitre hybridization

  • Simard, Ronald-E.
    • Proceedings of the Korean Society of Fisheries Technology Conference
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    • 2000.05a
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    • pp.71-73
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    • 2000
  • Campylobacter jejuni is most frequently identified cause of cause of acute diarrhoeal infections in developeed countries, exceeding rates of illness caused by both salmonella and shigilla(Skirrow, 1990 ; Lior 1994). Previous studies on campylobacter jejuni contamination of commercial broiler carcasses in u.s.(Stern, 1992). Most cases of the disease result from indirect transmission of Campylobactor from animals via milk, water and meat. In addition to Campylobactor jejuni. the closely relates species Campylobactor coli and Campylobactor lari have also been implicated as agents of gastroenteritis in humans. Campylobactor coli represented only approximately 3% of the Campylobactor isolates from patients with Campylobactor enteritis(Griffiths and Park, 1990) whereas Campylobactor coli is mainly isolated from pork(Lmmerding et al., 1988). Campylobactor jejuni has also been isolated from cases of bacteremia, appendicitis and, recently, has been associated with Guillai-Barre syndrome(Allos and Blaser, 1994; von Wulffen et al., 1994; Phillips, 1995). Studies in volunteers indicated that the infectious dose for Campylobactor jejuni is low(about 500 organisms)(Robinson, 1981). The methods traditionally used to detect Campylobactor ssp. in food require at least two days of incubation in an enrichment broth followed by plating and two days of incubation on complex culture media containing many antibiotics(Goossens and Butzler, 1992). Finnaly, several biochemical tests must be done to confirm the indentification at the species level. Therfore, sensitive and specific methods for the detection of small numbers of Campylobactor cells in food are needed. Polymerase chain reaction(PCR) assays targeting specific DNA sequences have been developed for the detection of Campylobactor(Giesendorf and Quint, 1995; Hemandex et al., 1995; Winter and Slavidk, 1995). In most cases, a short enrichment step is needed to enhance the sensitivity of the assay prior to detection by PCR as the number of bacteria in the food products is low in comparison with those found in dinical samples, and because the complex composition of food matrices can hinder the PCR and lower its sensitivity. However, these PCR systems are technically demanding to carry out and cumbersome when processing a large number of samples simutaneously. In this paper, an immunomagnetic method to concentrate Campylobactor cells present in food or clinical samples after an enrichment step is described. To detect specifically the thermophilic Campylobactor. a monoclonal antibody was adsorbed on the surface of the magnetic beads which react against a major porin of 45kDa present on the surface of the cells(Huyer et al., 1986). After this partial purification and concentration step, detection of bound cells was achieved using a simple, inexpensive microtitre plate-based hybridization system. We examined two alternative detection systems, one specific for thermophilic Campylobactor based on the detection of 23S rRNA using an immobilized DNA probe. The second system is less specific but more sensitive because of the high copy number of the rRNA present in bacterial cell($10^3-10^4$). By using specific immunomagnetic beads against thermophilic Campylobactor, it was possible to concentrate these cells from a heterogeneous media and obtain highly specific hybridization reactions with good sensitivity. There are several advantages in using microtitre plates instead of filter membranes or other matrices for hybridization techniques. Microtitre plates are much easier to handle than filter membranes during the adsorption, washing, hybridization and detection steps, and their use faciilitates the simultanuous analysis of multiple sample. Here we report on the use of a very simple detection procedure based on a monoclonal anti-RNA-DNA hybrid antibody(Fliss et al., 1999) for detection of the RNA-DNA hybrids formed in the wells.

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