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The Role of Poly(ADP-ribose) Polymerase-1 in Ventilator-Induced Lung Injury (기계환기로 인한 급성 폐손상에서 poly(ADP-ribose) polymerase-1의 역할)

  • Kim, Je-Hyeong;Yoon, Dae Wui;Hur, Gyu Young;Jung, Ki Hwan;Lee, Sung Yong;Lee, Sang Yeub;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Yoo, Se Hwa;Kang, Kyung Ho
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.4
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    • pp.451-463
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    • 2006
  • Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through ${\beta}$ -nicotinamide adenine dinucleotide ($NAD^+$) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was $PIP\;15cmH_2O$ + $PEEP\;3cmH_2O$ + RR 90/min + 2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of $PIP\;40cmH_2O$ + $PEEP\;0cmH_2O$ + RR 90/min + 2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines.

A Clinical Study on Transpulmonary Leukostasis and Prophylactic Effects of Steroid in Cardiac Surgery (심장수술시 백혈구의 폐내정체와 스테로이드의 예방적 효과에 관한 연구)

  • 최석철
    • Biomedical Science Letters
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    • v.2 no.2
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    • pp.133-151
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    • 1996
  • After cardiac surgery, it has been recognized that various complications were associated with injured humoral and cellular immunity by cardiopulmonary bypass(CPB). Especially, in postoperative pulmonary dysfunction, transpulmonary leukostasis followed complement activation and inflammatory responses are major pathogen. Some studies have showed that pretreated-corticosteroids before CPB protected postoperative pulmonary dysfunction. Corticosteroids may inhibit complement and leukocyte activation. On based previous studies, present investigator determined changes of leukocyte counts and transpulmonary leukostasis during cardiac surgery and postoperative periods. For the evaluation of postoperative pulmonary function and edema, $PaO_2$ and chest X-ray were compared between pre-CPB and post-CPB. Fever and other parameters were also observed postoperatively. The aim of this study was to define for the prophylactic effects of corticosteroid(Solu-Medrol: 30mg/kg) on all the researched parameters. This study was prospectively designed with randomized-blind fashion for 50 patients undergoing cardiac surgery. According to the purpose of study, all patients were divided into placebo and steroid group. : Placebo group was 25 patients received normal saline(not corticosteroid), and steroid group was 25patients received corticosteroid(Solu-Medrol: 30mg/kg) before initiation of CPB. The results of study were summarized as follows. 1. Total peripheral leukocyte counts decreased significantly at 5 minutes of CPB in all patients(P<0.01), and began to increase progressively at later periods of CPB with neutrophilia. The significant rise remained at postoperative 7th day(P<0.05). 2. During partial CPB, transpulmonary leukostasis occurred in placebo group(P<0.001), whereas it was prevented in steroid group. 3. In both groups, peripheral lymphocyte counts were stable during CPB, but began to reduce at time of intensive care unit(ICU) and the lymphocytopenia remained until postoperative 3rd day. The lymphocyte counts recovered on postoperative 7th day. 4. In both groups, peripheral counts of monocyte were relatively stable in the early peroid of CPB, and increased gradually in the later periods of CPB. This significant monocytosis remained throughout postoperlative periods(P<0.05). 5. The mean value of postoperative $paO)_2$ was lower than that of pre-CPB in placebo group(P=0.01) but didn't significant in steroid group(P=0.90). In the incidence of pulmonary edema signs and fever, placebo group was higher than steroid group(P=0.001, p=0.01, respectively). However mechanical respiratory supporting and care periods at intensive care unit were not significant difference between two groups(P>.0.05).With the above results, the investigator concluded that leukocyte activation and pulmonary sequestration were caused by cardiac surgery with CPB and demonstrated that high dose corticosteroid will provide prophylactic effect for pulmonary leukostasis and higher neutrophilia. These effects may ameliorate postoperative pulmonary dysfunction and contribute to postoperative less morbidity. However, further study should be performed because postoperative lymphocytopenia continued for 3 days in both groups, which may suspected damage or suppression of cell-mediated immunity with used corticosteroid.

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Evaluation of the Fruit Quality Indices during Maturation and Ripening and the Influence of Short-term Temperature Management on Shelf-life during Simulated Exportation in 'Changjo' Pears (Pyrus pyrifolia Nakai) (배 신품종 '창조'의 성숙 중 품질 요인 변화 및 수송온도 환경에 따른 반응성)

  • Lee, Ug-Yong;Choi, Jin-Ho;Ahn, Young-Jik;Chun, Jong-Pil
    • Journal of Bio-Environment Control
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    • v.26 no.4
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    • pp.378-385
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    • 2017
  • In this study, we evaluated the changes of fruit quality indices during fruit development and ripening in Korean new pear cultivar 'Changjo', developed from a cross between 'Tama' and '81-1-27' ('Danbae' ${\times}$ 'Okusankichi') in 1995 and named in 2009, to determine appropriate harvest time and to enhance the market quality and broaden the cultivation area. The fruits of 'Changjo' pears harvested from 132 days after full bloom (DAFB) to 160 DAFB. Fruit growth and quality indices were monitored at 1 week interval by measuring fruit weight, length, diameter, firmness, and taste related quality indices. The calculated fruit fresh weight increased continuously with fruit development and reached to an average of 594g on Sep. 20 (160 DAFB). The ratio of length to diameter declines as fruit maturation progress, resulting in 0.898 for ripe fruit stage as a round oblate shape. Flesh firmness of 'Changjo' pears showed over 30N until 153 DAFB and then decreased abruptly with fruit ripening, reaching a final level of about 26.44N on 160 DAFB. Starch content of fruit sap was also decreased abruptly after 146 DAFB which decreased almost half of the fruits harvested at 139 DAFB. In parallel with the decrease of flesh firmness, ethanol insoluble solids (EIS) content decreased sharply with fruit ripens, only 50% of EIS was detected on the fruits harvested on 160 DAFB when compared to that of the fruits harvested on 139 DAFB (Aug. 30). The maximum value of soluble solids contents was observed in the fruits harvested on 153 DAFB, resulting in $14.2^{\circ}Brix$. The changes of skin color difference $a^*$ which means loss of green color occurred only after 139 DAFB, coincide with the decrease of SPAD value of the fruit skin. The sugars of the 80% ethanol soluble fraction consisted mainly of fructose, sorbitol, glucose and sucrose, also increased during maturation and ripening. Fructose and sucrose contents were larger than those of glucose and sorbitol in flesh tissues. These results were explained that stored starch is converted to soluble sugars during fruit maturation, mainly in fructose and sucrose increasing the sweetness of this cultivar. Total polyphenols were increased up to middle of fruit maturation (146 DAFB) and then decreased continuously until the end of fruit maturation. Consequently, our results suggested that the commercial harvest time of 'Changjo' pears should not be passed 153 DAFB and late harvest of this cultivar would not good for quality maintenance during shelf-life. As a result of the post-harvest low-temperature acclimation experiment during the short-term transportation period, fruits harvested at 146 DAFB tended to maintain higher firmness after 14 days of simulated marketing at $25^{\circ}C$ compared to fruits harvested at 153 DAFB regardless of temperature set. And, the slower the rate of decrease to the final transport temperature of $5^{\circ}C$, the higher the incidence of internal browning and ethylene production. Therefore, in order to suppress the physiological disorder and to maintain the fruit quality when exporting to Southeast Asia in the 'Chanjo' pears, it is desirable to lower the temperature of the fruits within a short time after harvest and to set the harvest time before 146 days after full bloom.

A Study on Preparation of 3'-$[^{18}F]$Fluoro-3'-deoxythymidine and Its Biodistribution in 9L Glioma Bearing Rats (3'-$[^{18}F]$Fluoro-3'-deoxythymidine의 합성과 9L glioma 세포를 이식한 래트에서의 체내동태에 관한 연구)

  • Shim, Ah-Young;Moon, Byung-Seok;Lee, Tae-Sup;Lee, Kyo-Chul;An, Gwang-Il;Yang, Seung-Dae;Yu, Kook-Hyun;Cheon, Gi-Jeong;Choi, Chang-Woon;Lim, Sang-Moo;Chun, Kwon-Soo
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.5
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    • pp.263-270
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    • 2006
  • Purpose: Several radioisotope-labeled thymidine derivatives such as $[^{11}C]$thymidine was developed to demonstrate cell proliferation in tumor. But it is difficult to track metabolism with $[^{11}C]$thymidine due to rapid in vivo degradation and its short physical half-life. 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT) was reported to have the longer half life of fluorine-18 and the lack of metabolic degradation in vivo. Here, we described the synthesis of the 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT) and compared with $([^{18}F]FET)\;and\;([^{18}F]FDG)$ in cultured 9L cell and obtained the biodistribution and PET image in 9L tumor hearing rats. Material and Methods: For the synthesis of $[^{18}F]$FLT, 3-N-tert-butoxycarbonyl-(5'-O-(4,4'-dimet hoxytriphenylmethyl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl)-${\beta}$-D-threopentofuranosyl)thymine was used as a FLT precursor, on which the tert-butyloxycarbonyl group was introduced to protect N3-position and nitrobenzenesulfonyl group. Radiolabeling of nosyl substitued precursor with $^{18}F$ was performed in acetonitrile at $120^{\circ}C$ and deproteced with 0.5 N HCI. The cell uptake was measured in cultured 9L glioma cell. The biodistribution was evaluated in 9L tumor bearing rats after intravenous injection at 10 min, 30 min, 60 min and 120 min and obtained PET image 60 minutes after injection. Results: The radiochemical yield was about 20-30% and radiochemical purity was more than 95% after HPLC purification. Cellular uptake of $[^{18}F]$FLT was increased as time elapsed. At 120 min post-injection, the ratios of tumor/blood, tumor/muscle and tumor/brain were $1.61{\pm}0.34,\;1.70{\pm}0.30\;and\;9.33{\pm}2.22$, respectively. The 9L tumor was well visualized at 60 min post injection in PET image. Conclusion: The uptake of $[^{18}F]$FLT in tumor was higher than in normal brain and PET image of $[^{18}F]$FLT was acceptable. These results suggest the possibility of $[^{18}F]$FLT at an imaging agent for brain tumor.

Clinical Findings of Mycoplasma pneumoniae pneumonia under 3 Year-Old Children (3세 이하 Mycoplasma pneumoniae 폐렴환자의 임상적 고찰)

  • Lee, Sung-Soo;Youn, Kyung-Lim;Kang, Hyeon-Ho;Cho, Byoung-Soo;Cha, Sung-Ho
    • Pediatric Infection and Vaccine
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    • v.6 no.1
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    • pp.78-85
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    • 1999
  • Purpose : Mycoplasma pneumoniae pneumonia has been to be developed frequently in school age children and adolescence and hard to see under 3 year-old children. But it seems to be increased in number of patients with Mycoplasma pneumoniae pneumonia under 3-year old in clinical practice in these days. We have aimed to examine the characteristics of clinical findings of Mycoplasma pneumonia under 3 year-old children. Methods : We had performed retrospective review of medical records of 30 patients with Mycoplasmal pneumonia under 3-year old children who admitted to Department of Pediatrics, Kyunghee University Hospital from Jan. 1994 to Dec. 1997. The diagnostic criteriae was Cold agglutinin titer>1:64 or Mycoplasma antibody titer>1:80. Results : Mycoplasmal pneumonia was 30 out of 235 cases(12.7%) of total pneumonia under 3 year old children. Male female ratio was 1.3 : 1 and age distributions were 0~1y : 0, 1~2y : 8, 2~3y : 22 cases. Clinical symptoms and signs were cough(100.0%), sputum(83.3%), fever(80.0%) rhinorrhea(33.3%), vomiting(33.3%), moist rale(86.7%), decreased breathing sound(26.7%), wheezing(20.0%), and pharyngeal injection(30.0%). Thirteen out of 30 cases(43.3%) had unilateral infiltration, 10 cases(33.4%) had bilateral infiltration, 1 case(3.3%) had pleural effusion, and 6 cases(20.0%) had negative findings on chest radiography and there was no cases of atelectasis. On laboratory findings, 6 out of 30 cases(20.0%) had leukocytosis, 1 case(3.3%) had neutrophilia, 10 cases(30.0%) had eosinophilia, 17 cases(56.7%) had increased ESR, and 18 cases(60.6%) had positive CRP. Positive cold agglutinin titers(>1 : 64) were 19 cases(63.3%), and positive mycoplasma antibody(M-ab) titers(>1 : 80) were 27 cases(93.3%). Mycoplasma antibody test was more valuable than cold agglutinin test for the diagnosis of Mycoplasmal pneumonia and there was no correlation between cold agglutinin titer and mycoplasma antibody titer. Mycoplasma-polymerase chain reaction(M-PCR) was done with 13 cases, 12 out of 13 cases(92.3%) were positive. M-PCR test was valuable to the diagnosis of Mycoplasmal pneumonia but it will be needed to further study for their clinical application. Among 30 cases, 5 cases(16.7%) had complications, 3 cases(10.0%) had skin rash, 1 case(3.3%) had pleural effusion, 1 case(3.3%) had arthralgia, but all complications were mild and recovered without residual sequelae. Conclusion : The occurrence of Mycoplasmal pneumonia under 3 year-old children was not rare from this study. Clinical characteristics of Mycoplasmal pneumonia under 3-year old were normal radiologic findings in many cases, low complication rate, mild clinical course, and tend to rapid recovery compared with general manifestations of Mycoplasmal infectionsin children and adolescence. There were likely to be missed patients with Mycoplasmal pneumonia which did not diagnose by conventional serologic tests that had low sensitivity and specificity. We have to pay attention to the Mycoplasmal infection of the young children with pneumonia during epidemic periods of Mycoplasmal infection.

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Cellular activities of osteoblast-like cells on alkali-treated titanium surface (알칼리 처리된 타이타늄 표면에 대한 골아 유사세포의 세포 활성도)

  • Park, Jin-Woo;Lee, Deog-Hye;Yeo, Shin-Il;Park, Kwang-Bum;Choi, Seok-Kyu;Suh, Jo-Young
    • Journal of Periodontal and Implant Science
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    • v.37 no.sup2
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    • pp.427-445
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    • 2007
  • To improve osseointegration at the boneto-implant interface, several studies have been carried out to modify titanium surface. Variations in surface texture or microtopography may affect the cellular response to an implant. Osteoblast-like cells attach more readily to a rougher titanium surface, and synthesis of extracellular matrix and subsequent mineralization were found to be enhanced on rough or porous coated titanium. However, regarding the effect of roughened surface by physical and mechanical methods, most studies carried out on the reactions of cells to micrometric topography, little work has been performed on the reaction of cells to nanotopography. The purpose of this study was to examme the response of osteoblast-like cell cultured on blasted surfaces and alkali treated surfaces, and to evaluate the influence of surface texture or submicro-scaled surface topography on the cell attachment, cell proliferation and the gene expression of osteoblastic phenotype using ROS 17/2.8 cell lines. In scanning electron micrographs, the blasted, alkali treated and machined surfaces demonstrated microscopic differences in the surface topography. The specimens of alkali treatment had a submicro-scaled porous sur-face with pore size about 200 nm. The blasted surfaces showed irregularities in morphology with small(<10 ${\mu}m$) depression and indentation among flatter-appearing areas of various sizes. Based on profilometry, the blasted surfaces was significantly rougher than the machined and the alkali treated surfaces (p$TiO_2$) were observed on alkali treated surfaces, whereas not observed on machined and blasted surfaces. The attachment morphology of cells according to time was observed by the scanning electron microscope. After 1 hour incubation, the cells were in the process of adhesion and spreading on the prepared surfaces. After 3 hours, the cells on all prepared surfaces were further spreaded and flattened, however on the blasted and alkali treated surfaces, the cells exhibited slightly irregular shapes and some gaps or spaces were seen. After 24 hours incubation, most cells of the all groups had a flattened and polygonal shape, but the cells were more spreaded on the machined surfaces than the blasted and alkali treated surfaces. The MTT assay indicated the increase on machined, alkali treated and blasted surfaces according to time, and the alkali treated and blasted surfaces showed significantly increased in optical density comparing with machined surfaces at 1 day (p<0.01). Gene expression study showed that mRNA expression level of ${\alpha}\;1(I)$ collagen, alkaline phosphatase and osteopontin of the osteoblast-like cells showed a tendency to be higher on blasted and alkali treated surfaces than on the machined surfaces, although no siginificant difference in the mRNA expression level of ${\alpha}\;1(I)$ collagen, alkaline phosphatase and osteopontin was observed among all groups. In conclusion, we suggest that submicroscaled surfaces on osteoblast-like cell response do not over-ride the one of the surface with micro-scaled topography produced by blasting method, although the microscaled and submicro-scaled surfaces can accelerate osteogenic cell attachment and function compared with the machined surfaces.

Categorizing Quality Features of Franchisees: In the case of Korean Food Service Industry (프랜차이즈 매장 품질요인의 속성분류: 국내 외식업을 중심으로)

  • Byun, Sook-Eun;Cho, Eun-Seong
    • Journal of Distribution Research
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    • v.16 no.1
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    • pp.95-115
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    • 2011
  • Food service is the major part of franchise business in Korea, accounting for 69.9% of the brands in the market. As the food service industry becomes mature, many franchisees have struggled to survive in the market. In general, consumers have higher levels of expectation toward service quality of franchised outlets compared that of (non-franchised) independent ones. They also tend to believe that franchisees deliver standardized service at the uniform food price, regardless of their locations. Such beliefs seem to be important reasons that consumers prefer franchised outlets to independent ones. Nevertheless, few studies examined the impact of qualify features of franchisees on customer satisfaction so far. To this end, this study examined the characteristics of various quality features of franchisees in the food service industry, regarding their relationship with customer satisfaction and dissatisfaction. The quality perception of heavy-users was also compared with that of light-users in order to find insights for developing differentiated marketing strategy for the two segments. Customer satisfaction has been understood as a one-dimensional construct while there are recent studies that insist two-dimensional nature of the construct. In this regard, Kano et al. (1984) suggested to categorize quality features of a product or service into five types, based on their relation to customer satisfaction and dissatisfaction: Must-be quality, Attractive quality, One-dimensional quality, Indifferent quality, and Reverse quality. According to the Kano model, customers are more dissatisfied when Must-be quality(M) are not fulfilled, but their satisfaction does not arise above neutral no matter how fully the quality fulfilled. In comparison, customers are more satisfied with a full provision of Attactive quality(A) but manage to accept its dysfunction. One-dimensional quality(O) results in satisfaction when fulfilled and dissatisfaction when not fulfilled. For Indifferent quality(I), its presence or absence influences neither customer satisfaction nor dissatisfaction. Lastly, Reverse quality(R) refers to the features whose high degree of achievement results in customer dissatisfaction rather than satisfaction. Meanwhile, the basic guidelines of the Kano model have a limitation in that the quality type of each feature is simply determined by calculating the mode statistics. In order to overcome such limitation, the relative importance of each feature on customer satisfaction (Better value; b) and dissatisfaction (Worse value; w) were calculated following the formulas below (Timko, 1993). The Better value indicates how much customer satisfaction is increased by providing the quality feature in question. In contrast, the Worse value indicates how much customer dissatisfaction is decreased by providing the quality feature. Better = (A + O)/(A+O+M+I) Worse = (O+M)/(A+O+M+I)(-1) An on-line survey was performed in order to understand the nature of quality features of franchisees in the food service industry by applying the Kano Model. A total of twenty quality features (refer to the Table 2) were identified as the result of literature review in franchise business and a pre-test with fifty college students in Seoul. The potential respondents of our main survey was limited to the customers who have visited more than two restaurants/stores of the same franchise brand. Survey invitation e-mails were sent out to the panels of a market research company and a total of 257 responses were used for analysis. Following the guidelines of Kano model, each of the twenty quality features was classified into one of the five types based on customers' responses to a set of questions: "(1) how do you feel if the following quality feature is fulfilled in the franchise restaurant that you visit," and "(2) how do you feel if the following quality feature is not fulfilled in the franchise restaurant that you visit." The analyses revealed that customers' dissatisfaction with franchisees is commonly associated with the poor level of cleanliness of the store (w=-0.872), kindness of the staffs(w=-0.890), conveniences such as parking lot and restroom(w=-0.669), and expertise of the staffs(w=-0.492). Such quality features were categorized as Must-be quality in this study. While standardization or uniformity across franchisees has been emphasized in franchise business, this study found that consumers are interested only in uniformity of price across franchisees(w=-0.608), but not interested in standardizations of menu items, interior designs, customer service procedures, and food tastes. Customers appeared to be more satisfied when the franchise brand has promotional events such as giveaways(b=0.767), good accessibility(b=0.699), customer loyalty programs(b=0.659), award winning history(b=0.641), and outlets in the overseas market(b=0.506). The results are summarized in a matrix form in Table 1. Better(b) and Worse(w) index indicate relative importance of each quality feature on customer satisfaction and dissatisfaction, respectively. Meanwhile, there were differences in perceiving the quality features between light users and heavy users of any specific franchise brand in the food service industry. Expertise of the staffs was labeled as Must-be quality for heavy users but Indifferent quality for light users. Light users seemed indifferent to overseas expansion of the brand and offering new menu items on a regular basis, while heavy users appeared to perceive them as Attractive quality. Such difference may come from their different levels of involvement when they eat out. The results are shown in Table 2. The findings of this study help practitioners understand the quality features they need to focus on to strengthen the competitive power in the food service market. Above all, removing the factors that cause customer dissatisfaction seems to be the most critical for franchisees. To retain loyal customers of the franchise brand, it is also recommended for franchisor to invest resources in the development of new menu items as well as training programs for the staffs. Lastly, if resources allow, promotional events, loyalty programs, overseas expansion, award-winning history can be considered as tools for attracting more customers to the business.

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Effect of 6-Hydroxydopamine (6-OHDA) on the Expression of Hypothalamus-Pituitary Axis Hormone Genes in Male Rats (수컷 흰쥐의 시상하부-뇌하수체 축 호르몬 유전자 발현에 미치는 6-Hydroxydopamine(6-OHDA)의 영향)

  • Heo, Hyun-Jin;Ahn, Ryun-Sup;Lee, Sung-Ho
    • Development and Reproduction
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    • v.13 no.4
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    • pp.257-264
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    • 2009
  • A neurotoxin, 6-hydroxydopamine (6-OHDA) has been widely used to create animal model for Parkinson's disease (PD) due to its specific toxicity against dopaminergic (DA) neurons. Since DA signals modulate a broad spectrum of CNS physiology, one can expect profound alterations in neuroendocrine activities of both PD patients and 6-OHDA treated animals. Limited applications of 6-OHDA injection model, however, have been made on the studies of hypothalamuspituitary neuroendocrine circuits. The present study was performed to examine whether blockade of brain catecholamine (CA) biosynthesis with 6-OHDA can make any alteration in the transcriptional activities of hypothalamus-pituitary hormone genes in adult male rats. Three-month-old male rats (SD strain) were received 6-OHDA ($200{\mu}g$ in $10{\mu}\ell$ of saline/animal) by intracerebroventricular (icv) injection, and sacrificed after two weeks. To determine the mRNA levels of hypothalamuspituitary hormone genes, total RNAs were extracted and applied to the semi-quantitative RT-PCRs. The mRNA levels of tyrosine hydroxylase (TH), the rate-limiting enzyme for the catecholamine biosynthesis, were significantly lower than those from the control group (control:6-OHDA=1:0.72${\pm}$0.02AU, p<0.001), confirming the efficacy of 6-OHDA injection. The mRNA levels of gonadotropin-releasing hormone (GnRH) and corticotropin releasing hormone (CRH) in the hypothalami from 6-OHDA group were significantly lower than those from the control group (GnRH, control:6-OHDA=1:0.39${\pm}$0.03AU, p<0.001; CRH, control:6-OHDA=1:0.76${\pm}$0.07AU, p<0.01). There were significant decreases in the mRNA levels of common alpha subunit of glycoprotein homones (Cg$\alpha$), LH beta subunit (LH-$\beta$), and FSH beta subunit (FSH-$\beta$) in pituitaries from 6-OHDA group compared to control values (Cg$\alpha$, control:6-OHDA=1:0.81${\pm}$0.02AU, p<0.001; LH-$\beta$, control:6-OHDA=1:0.68${\pm}$0.04AU, p<0.001; FSH-$\beta$, control:6-OHDA=1:0.84${\pm}$0.05AU, p<0.001). Similarly, the level of adrenocorticotrophic hormone (ACTH) transcripts from 6-OHDA group was significantly lower than that from the control group (control: 6-OHDA=1:0.86${\pm}$0.04AU, p<0.01). The present study demonstrated that centrally injected DA neurotoxin could downregulate the transcriptional activities of the two hypothalamus-pituitary neuroendocrine circuits, i.e., GnRH-gonadotropins and CRH-ACTH systems. These results suggested that hypothalamic CA input might affect on the activities of gonad and adrenal through modulation of hypothalamus-pituitary function, providing plausible explanation for frequent occurrence of sexual dysfunction and poor stress-response in PD patients.

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Radiation Therapy Alone for Early Stage Non-small Cell Carcinoma of the Lung (초기 비소세포폐암의 방사선 단독치료)

  • Chun, Ha-Chung;Lee, Myung-Za
    • Radiation Oncology Journal
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    • v.20 no.4
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    • pp.323-327
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    • 2002
  • Purpose : To evaluate the outcome of early stage non-small cell lung cancer patients who were treated with radiation therapy alone and define the optimal radiotherapeutic regimen for these patients. Materials and Methods : A retrospective review was peformed on patients with sage I or II non-small cell carcinoma of the lung that were treated at our institution between June, 1987 and May, 2000. A total of 21 patients treated definitively with radiation therapy alone were included in this study. The age of the patients ranged from 53 to 81 years with a median of 66 years. All the patients were male. The medical reasons for inoperability were lack of pulmonary reserve, cardiovascular disease, poor performance status, old age, and patient refusal in the decreasing order. Pathological evidence was not adequate to characterize the non-small cell subtype in two patients. Of the remaining 19 patients, 16 had squamous cell carcinoma and 3 had adenocarcinoma. Treatment was given with conventional fractionation, once a day, five times a week. The doses to the primary site ranged from 56 Gy to 59 Gy. No patients were lost to follow-up. Results : The overall survival rates for the entire group at 2, 3 and 5 years were 41, 30 and $21\%$, respectively. The cause specific survivals at 2, 3 and 5 years were 55, 36 and $25\%$, respectively. An intercurrent disease was the cause of death in two patients. The cumulative local failure rate at 5 years was $43\%$. Nine of the 21 patients had treatment failures after the curative radiotherapy was attempted. Local recurrences as the first site of failure were documented in 7 patients. Therefore, local failure alone represented $78\%$ of the total failures. Those patients whose tumor sizes were less than 4 cm had a significantly better 5 year disease free survival than those with tumors greater than 4 cm $(0\%\;vs\;36\%)$. Those patients with a Karnofsky performance status less than 70 did not differ significantly with respect to actuarial survival when compared to those with a status greater than 70 $(25\%\;vs\;26\%,\;p>0.05)$. Conclusion : Radiation therapy 리one is an effective and safe treatment for early stage non-small ceil lung cancer patients who are medically inoperable or refuse surgery. Also we believe that a higher radiation dose to the primary site could improve the local control rate, and ultimately the overall survival rate.

The Clinical Significance of Follow Up SCC Levels in Patients with Recurrent Squamous Cell Carcinoma of the Cervix (재발성 자궁경부 편평상피암 환자들에서 Squamous Cell Carcinoma 항원의 유용성)

  • Choi Young Min;Park Sung Kwang;Cho Heung Lae;Lee Kyoung Bok;Kim Ki Tae;Kim Juree;Sohn Seung Chang
    • Radiation Oncology Journal
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    • v.20 no.4
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    • pp.353-358
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    • 2002
  • Purpose : To investigate the clinical usefulness of a follow-up examination using serum squamous cell carcinoma antigen (SCC) for the early detection of recurrence in patients treated for conical squamous cell carcinoma. Materials and Methods : 20 patients who were treated for recurrent cervical squamous cell carcinoma between 1997 and 1998, who had experienced a complete remission after radiotherapy and who underwent an SCC test around the time when recurrence was detected, were included in this study. The levels of SCC were measured from the serum of the patients by immunoassay and values less than 2 ng/mL were regarded as normal. The sensitivity of the SCC test for use in the detection of recurrence, the association between the SCC values and the recurrence patterns and the tumor size and stage, and the temporal relation between the SCC increment and recurrence detection were evaluated. Results : The SCC values were above normal in 17 out of 20 patients, so the sensitivity of the SCC test for the detection of recurrence was $85\%$, and the mean and median of the SCC values were 15.2 and 9.5 ng/mL, respectively. No differences were observed in the SCC values according to the recurrence sites. For 11 patients, the SCC values were measured over a period of 6 months before recurrence was detected, and the mean and median values were 13.6 and 3.6 ng/mL, respectively. The SCC values of 7 patients were higher than the normal range, and the SCC values of the other 4 patients were normal but 3 among them were above 1.5 ng/mL. At the time of diagnosis, the SCC valuess were measured for 16 of the 20 recurrent patients, and the SCC values of the patients with a bulky tumor $(\geq4\;cm)$ or who were in stage IIb or III were higher than those of the patients with a non-bulky tumor or who were in stage Ib or IIa. Conclusion : The SCC test is thought to be useful for the early detection of recurrence during the follow up period in patients treated for cervical squamous cell carcinoma. When an effective salvage treatment is developed in the future, the benefit of this follow-up SCC test will be increased.