• Title/Summary/Keyword: BL-21

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Study on the Characteristics of Heart Rate Variability, Body component analysis and accompanying symptoms in 175 Insomnia Patients (불면환자 175명의 심박변이도, 체성분 분석 및 동반증상의 특징에 관한 연구)

  • Ha, Ji-Won;Kim, Bo-Kyung
    • Journal of Oriental Neuropsychiatry
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    • v.21 no.4
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    • pp.21-39
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    • 2010
  • Objectives : This study was to investigate the characteristics of the heart rate variability(HRV), types of insomnia and accompanying symptoms of 175 insomnia patients. Methods : For this study we carried out HRV, Inbody of 175 patients with insomnia who have come to Dongeui oriental hospital of Dongeui university from the period of Janaury 2008 to September 2010. We studied the association of the insomnia patients' age and gender with HRV, accompanying symptoms and the types of insomnia. The information of the accompanying symptoms and types of insomnia was based on each patients' progress note. Results : l. There was no significant differences in the characteristics of HRV between male and female. 2. The most frequent symptom shown among the insmonia patents' was headache(41.14%). 3. Comparing the symptoms between the gender, female patients had more dry mouth, alternative periodic chill and fever, and hot flush symptoms than the male patients. 4. Comparing the symptoms between the age groups(divided in two), the lower age group (20~59) had more dizziness and constipation symptoms than the higher age group (over 60). 5. Comparing the types of insomma between the age group, the higher age group (over 60) had more termination insomnia. 6. The types of insomnia of the entire insomnia patients were onset insomnia (73.1%), maintenance insomnia(20.6%), termination insomma(l7.1 %), shallow sleep (52.6%), listed by order of frequency. 7. The patients who takes hypnotics had more anorexia symptoms than the patients who doesn't take hypnotics. 8. There was no visible differences of the average fractal portrait between male and female. The age group of 20~30yrs. had the highest average fractal portrait, and the age group of 30~59yrs. the second highest, and the age group over 60yrs. the lowest. 9. The average of the regulation reserves of the autonomic nervous system(B2) - was lower than the regulation level of the ANS at the present (Bl). 10. When compared the priority of the function of the ANS, it showed that the proportion of HF($38.61{\pm}29.19%$)was the most, and than VLF($30.65{\pm}23.36%$), LF($20.04{\pm}19.13%$) the least. 11. The average of the compensation level of the central nervous system at present(Cl) - was lower than the compensation reserves of the CNS(C2). 12. The average of the control reserves of the cerebrum(D2) - was lower than the control level of the cerebrum at the present (Dl). 13. There was no visible differences between different sexes and ages in pulse rate. 14. The abdomen fat ratio above the line of the insomnia patients was 77.97% in male and 93.1% in female. Both sexes showed that insomnia patients had more abdomen fat that the standard, and female patients had more abd. fat than male patients. Conclusions : This study shows that the HRV of insomnia patients had no significant differences between gender. Fractal portrait, HF, LF and VLF of the insomnia patients are in inverse proportion to the age. The study of the Body Component Analysis showed that female had more abdomen fat than male, and both gender showed more abdomen fat than the standard. When looked into the accompanying symptoms of the insomnia patients, the symptoms show differences according to gender, age and hypnotics taking, as shown as below. In the entire patients, Headache was the most accompanying symptom. Female had more dry mouth, alternative periodic chill and fever, and hot flush symptoms than male. Higher age groups had more dizziness and constipation as accompanying symptoms than lower age groups. Patients who takes hypnotics had more anorexia than those who dont.

Vitamin B12 Deficiency after a Total Gastrectomy in Patients with Gastric Cancer (위암으로 위 전절제술 후 비타민 Bl2 결핍과 치료)

  • Chae, Hyun-Dong;Park, Ki-Ho
    • Journal of Gastric Cancer
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    • v.6 no.1
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    • pp.6-10
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    • 2006
  • Purpose: The most common metabolic defect appearing following a gastrectomy is anemia. Two types have been identified: One is related to a deficiency in iron and the other is related to an impairment in vitamin B12 metabolism. The purpose of this study is to evaluate the incidence and treatment of vitamin B12 deficiency after a total gastrectomy. Materials and Methods: Serum vitamin B12 concentrations were measured in 128 patients who had undergone a total gastrectomy. The group with a serum concentration under 200 pg/ml was supplemented at one-month intervals with Actinamide and five-six months later, serum concentrations of the vitamin B12 were rechecked. Results: The group with vitamin B12 under 200 pg/ml was 61 (47.6%) of the 128 patients who had undergone a total gastrectomy. In this group, the cumulative incidences of vitamin B12 deficiency were 7.0, 23.4, 33.6, 39.1, 41.4, and 47.7% at 6 months, 1, 2, 3, 4, and 5 or more years, respectively. The treated group with vitamin B12 under 200 pg/ml had 36 (28.17%) of the 128 patients. The 16 of those cases with vitamin B12 levels of $100{\sim}150\;pg/ml$ were supplemented 5.21 times and the vitamine B12 was elevated to above 650 pg/ml. The other 20 cases with an average of vitamin B12 levels of $150{\sim}200pg/ml$ were supplemented an average of 4.75 times, and the vitamin B12 was elevated to above 780 pg/ml. Conclusion: It is necessary to supplement vitamin B12 even 1 year later after a total gastrectomy. The group with vitamin B12 under 200 pg/ml was supplemented $5{\sim}6$ times at one-month intervals with Actinamide $1,000\;{\mu}g$ IM injections and reached normal levels. (J Korean Gastric Cancer Assoc 2006;1:6-10)

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Analysis of Changes in Tree Height-Diameter Allometry for Major Tree Species in South Korea (우리나라 주요 수종의 수고-직경 상대생장 변화 분석)

  • Moonil Kim;Taejin Park;Youngjin Ko;Go-Mi Choi;Soonchul Son;Yejun Kang;Jaehee Yoo;Minkyeong Kim;Hyeonji Park;Woo-Kyun Lee
    • Journal of Korean Society of Forest Science
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    • v.112 no.1
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    • pp.71-82
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    • 2023
  • Forest biomass is used as a representative indicator of forest size, maturity, and productivity. Therefore, quantitative evaluation is important for management and harvest as well as the evaluation of ecosystem functions and services including CO2 absorption. The allometric equation is a widely used method for estimating the value of each component through the relative growth rate of plants. Recently, studies indicated that the relative growth of trees is changing because of the increased CO2 concentration in the atmosphere and the resulting climate change, raising the need to review the previously developed relative growth models and coefficients. In this study, the height-diameter at breast height (DBH) relationships of four major tree species in Korea [(Pinus densiflora (PD), Larix kaempferi (LK), Quercus variabilis (QV), and Quercus mongolica (QM)] were analyzed using the 5th-7th National Forest Inventory (NFI) data. Furthermore, these results were compared with the present yield table from the National Institute for Forest Science. This analysis revealed that the expected height for the same DBH increased as the NFI progressed. For example, in model analysis, the expected heights for PD, LK, QV, and QM for DBH of 25 cm were 12.48, 19.17, 14.47, and 13.19 m, respectively, in the 5th NFI data. In the 7th NFI data, these values were estimated as 13.61 (+9.1%), 21.58 (+12.7%), 15.76 (+8.9%), and 13.93 m (+5.6%), respectively. These results indicate that the major tree species in South Korean forests currently are more vigorous in height growth than in diameter growth when compared to the height-DBH development trends by tree species identified through past survey data.

The Effect of Physical Therapy on Functional Change and Related Factors in Stroke Patients (뇌졸중환자의 물리치료경과에 따른 기능변화와 관련요인)

  • Lee Seung-Ju;Yeh Min-Hae;Chun Byung-Yeol
    • The Journal of Korean Physical Therapy
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    • v.10 no.1
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    • pp.7-21
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    • 1998
  • An analysis of 101 stroke patients who were enrolled in 10 hospitals of Cities of Pusan, Taegu, and Andong from November 1, 1996 to April 31. 3997 was conducted using the modified Barthel Index(BI) and the adapted PULSES profile index(PS) to evaluate their function. Patients were examined at the following intervals: Initial assessment, one month after initial. at discharge, and one month after discharge. The mean BI score of patients initial assessment was 27.18, and that of PS was 17.54. There were statistically significant between initial score and one month after initial (21.39: p<0.001), at discharge(37.47: p<0.001), one month after discharge(46.49: p<0.001). PS scores were also improved .significantly(-2.62, -4.52. and -6.26(p<0.001). And the score between dischange and one month after discharge was significant (9.01: p<0.001) and in PS score(-1.73: p<0.001). Age and BE score were significantly associated with the improved in BI score between initial and discharge(T3-T1)(p<0.05). Below age forty the Bower initial BI score showed significantly higher improvement(T3-T1) after physical therapy(p<0.05). Initial Bl score, patients' attitude for physical therapy after discharge, age, and surgical operation were significantly associated with the improvement of BI score between initial and one month after discharge(T4-T1)(p<0.05). The lower initial BI score, patients' positive attitude for physical therapy after discharge, below age forty. and no surgical operation showed significantly higher improvement(p<0.05). BI score at discharge, side of hemiparesis and religion were significantly associated with the improvement of BI score between at discharge and one month after discharge(T4-T3) (p<0.05). The lower BI score at discharge. left aide of hemiparesis, with religion showed significantly higher improvement (p<0.05). Age, initial PS score were significantly associated with the improved in PS score between initial and discharge(T3-T1)(p<0.05). The higher initial PS score and below age forty showed significantly higher improvement(T3-T1)(p<0.05). Initial PS score, patient' attitude for physical therapy after discharge, age, educational level, physical therapy hour after discharge, and surgical operation were significantly associated with the improvement of PS score between initial and one month after discharge(T4-T1)(p<0.05). The higher initial PS score, patients' positive attitude for physical therapy after discharge, below age forty, higher education, the shorter physical therapy hour, and no surgical operation showed significantly higher improvement(T4-T1)(p<0.05). PS score at discharge, educational level, patient' attitude far physical therapy after discharge, physical therapy hour after discharge, and gender were significantly associated with the improvement of PS score between discharge and une month after discharge(T4-T3) (p<0.05), The higher PS non at discharge, higher education, patients' positive attitude for Physical therapy after discharge, the shorter physical therapy hour, and male showed significantly higher improvement (T4-T3)(p<0.05). In conclusion, initial BI score and age were significantly associated with BI score improvement and initial PS score, age, and educational level were also significantly associated with PS score improvement in stoke patients.

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Characterization of a Psychrophilic Metagenome Esterase EM2L8 and Production of a Chiral Intermediate for Hyperlipemia Drug (메타게놈유래의 저온성 에스터라제 EM2L8의 효소적 특성과 이를 활용한 고지혈증 치료제 키랄소재의 생산)

  • Jung, Ji-Hye;Choi, Yun-Hee;Lee, Jung-Hyun;Kim, Hyung-Kwoun
    • Microbiology and Biotechnology Letters
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    • v.37 no.2
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    • pp.118-124
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    • 2009
  • Esterase EM2L8 gene isolated from deep sea sediment was expressed in Escherichia coli BL21 (DE3) and the esterase activity of the cell-free extract was assayed using p-nitrophenyl butyrate-spectrophotometric method. Its optimum temperature was $40-45^{\circ}C$ and 45% activity of the maximum activity was retained at $15^{\circ}C$. The activation energy at $15-45^{\circ}C$ was calculated to be 4.9 kcal/mol showing that esterase EM2L8 was a typical cold-adapted enzyme. Enzyme activity was maintained for 6 h and 4 weeks at $30^{\circ}C$ and $4^{\circ}C$, respectively. When each ethanol, methanol, and acetone was added to the reaction mixture to 15% concentration, enzyme activity was maintained. In the case of DMSO, enzyme activity was kept up to 40% concentration. (S)-4-Chloro-3-hydroxy butyric acid is a chiral intermediate for the synthesis of Atorvastatin, a hyperlipemia drug. When esterase EM2L8 (40 U) was added to buffer solution (1.2 mL, pH 9.0) containing ethyl-(R,S)-4-chloro-3-hydroxybutyrate (38 mM), it was hydrolyzed into 4-chloro-3-hydroxy butyric acid with a rate of $6.8\;{\mu}mole/h$. The enzyme hydrolyzed (S)-substrate more rapidly than (R)-substrate. When conversion yield was 80%, e.e.s value was 40%. When DMSO was added, hydrolysis rate increased to $10.4\;{\mu}mole/h$. The plots of conversion yield vs e.e.s in the presence or absence of DMSO were almost same, implying that the reaction enantioselectivity was not changed by the addition of DMSO. Taken together, esterase EM2L8 had high activity and stability at low temperatures as well as in various organic solvents/aqueous solutions. These properties suggested that it could be used as a biocatalyst in the synthesis of useful pharmaceuticals.

Neurochemical Profile Quantification of Regional Adult Mice Brain Using: ex vivo $^1H$ High-Resolution Magic Angle Spinning NMR Spectroscopy (생체 외 조직 고 분해능 Magic Angle Spinning을 이용한 정상 Adult Mice에서의 뇌 부위별 뇌 신경화학 대사물질 정량분석)

  • Lee, Do-Wan;Woo, Dong-Cheol;Lee, Sung-Ho;Kim, Sang-Young;Kim, Goo-Young;Rhim, Hyang-Shuk;Choi, Chi-Bong;Kim, Hwi-Yool;Lee, Chang-Wook;Choe, Bo-Young
    • Progress in Medical Physics
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    • v.21 no.1
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    • pp.35-41
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    • 2010
  • The purpose of this study is to quantitate regional neurochemical profile of regional normal adult mice brain and assess regional metabolic differences by using ex vivo $^1H$ high-resolution magic angle spinning nuclear magnetic resonance spectroscopy ($^1H$ HR-MAS NMRS). The animals were matched in sex and age. The collected brain tissue included frontal cortex, temporal cortex, thalamus, and hippocampus. Quantitative 1D spectra were acquired on 40 samples with the CPMG pulse sequence (8 kHz spectral window, TR/TE = 5500/2.2 ms, NEX = 128, scan time: 17 min 20 sec). The mass of brain tissue and $D_2O$+TSP solvent were 8~14 mg and 7~13 mg. A total of 16 metabolites were quantified as follow: Acet, NAA, NAAG, tCr, Cr, tCho, Cho, GPC + PC, mIns, Lac, GABA, Glu, Gln, Tau and Ala. As a results, Acet, Cho, NAA, NAAG and mIns were showed significantly different aspects on frontal cortex, hippocampus, temporal cortex and thalamus respectively. The present study demonstrated that absolute metabolite concentrations were significantly different among four brain regions of adult mice. Our finding might be helpful to investigate brain metabolism of neuro-disease in animal model.

Improvement of Reproductive Disturbances by In Vitro Fertilization and Spermatozoa Cryopreservation in a Mouse Strain Showing Behavior Abnormality Derived from Korean Wild Mouse (Mus musculus molossinus) (한국야생유래 행동이상 Mouse 에 있어서 체외수정에 의한 번식장애 개선과 정자의 동결보존)

  • 남윤이;김상근;김명수;이철호;최양규;현병화
    • Korean Journal of Animal Reproduction
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    • v.23 no.3
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    • pp.247-256
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    • 1999
  • The present study was performed to improve the reproductive disturbance as well as the elimination of microbiological contamination for animals bred under conventional conditions followed by in vitro fertilization and embryo transfer techniques including embryo and sperm freezing, using a mouse strain(M. m. molossinus-tt@Kist) showing the abnormal behavior disorder derived from Korean wild mice (Mus musculus molossinus). Moreover, hematological and serum biochemical analyses were also carried out to obtain the basic data of this mouse strain The results are summarized as follows: 1. In comparison with hematological data, the numbers of RBC and platelet of this mouse strain were appeared as the higher value those that of the same aged inbred strains such as BALB/c, DBA/2, C57BL/6 and C3H /Hen. However, no differences were found in values of WBC, Hb and Ht. Moreover, total cholesterol of this strain showed a low value but triglyceride, total protein and albumin values were similar as in inbred strains. 2. The average numbers of superovulated oocytes treated with 2.5/2.5 IU and 5.0/5.0 IU of PMSG/hCG were 11.6 and 12.7, respectively. The fertilization rates of 2.5/2.5 IU PMSG /hCG treatment(87.9%) was higher than 5.0/5.0 IU treatment(52.0%) (p<0.05) and the developmental rate of 2 cell stage embryos were 외 so appeared as higher value 99.0% and 90.6%, respectively. 3. The rates of in vitro fertilization treated with frozen sperm(24.8%) was significantly lower than of that fresh sperm(87.9%), (p<0.05). 4. The five, six and ten heads of offspring were obtained from frozen-thawed 2 cell embryos by in vitro fertilized, 2 cell embryos from in vitro fertilized by frozen-thawed spermatozoa. and 2 cell embryos by in vitro fertilization, respectively. These offspring developed the expected disease about 2 weeks after birth, which was confirmed that the disease character of this mutant mouse strain was reliably reproduced. 5. MHV(Mouse hepatitis virus) and Staphylococcus aureus were successfully eliminated from conventional animals by in vitro fertilization-embryo transfer and the use of SPF recipient animals.

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Removal of Chromium (VI) by Escherichia coli Cells Expressing Cytoplasmic or Surface-Displayed ChrB: a Comparative Study

  • Zhou, Xiaofeng;Li, Jianghui;Wang, Weilong;Yang, Fan;Fan, Bingqian;Zhang, Chenlu;Ren, Xiaojun;Liang, Feng;Cheng, Rong;Jiang, Fengying;Zhou, Huaibin;Yang, Juanjuan;Tan, Guoqiang;Lyu, Jianxin;Wang, Wu
    • Journal of Microbiology and Biotechnology
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    • v.30 no.7
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    • pp.996-1004
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    • 2020
  • Various genetically engineered microorganisms have been developed for the removal of heavy metal contaminants. Metal biosorption by whole-cell biosorbents can be enhanced by overproduction of metal-binding proteins/peptides in the cytoplasm or on the cell surface. However, few studies have compared the biosorption capacity of whole cells expressing intracellular or surface-displayed metal-adsorbing proteins. In this study, several constructs were prepared for expressing intracellular and surface-displayed Ochrobactrum tritici 5bvl1 ChrB in Escherichia coli BL21(DE3) cells. E. coli cells expressing surface-displayed ChrB removed more Cr(VI) from aqueous solutions than cells with cytoplasmic ChrB under the same conditions. However, intracellular ChrB was less susceptible to variation in extracellular conditions (pH and ionic strength), and more effectively removed Cr(VI) from industrial wastewater than the surface-displayed ChrB at low pH (<3). An adsorption-desorption experiment demonstrated that compared with intracellular accumulation, cell-surface adsorption is reversible, which allows easy desorption of the adsorbed metal ions and regeneration of the bioadsorbent. In addition, an intrinsic ChrB protein fluorescence assay suggested that pH and salinity may influence the Cr(VI) adsorption capacity of ChrB-expressing E. coli cells by modulating the ChrB protein conformation. Although the characteristics of ChrB may not be universal for all metal-binding proteins, our study provides new insights into different engineering strategies for whole-cell biosorbents for removing heavy metals from industrial effluents.

A Study on Food Service for School Children -Provided by Dong Duck Elementary School in Daegu- (학교급식(學校給食)에 관(關)한 조사연구(調査硏究) -대구 동덕국민학교를 중심(中心)으로-)

  • Song, Wha-Sop
    • Journal of Nutrition and Health
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    • v.6 no.3
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    • pp.47-63
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    • 1973
  • This study concerns the nutritional status of food in a lunch-box and the school lunch program provided for Dong Duck Elementary School Pupils in Daegu. Two hundred andsix pupils were randomly selected as a sample. The nutrients contained in a lunch-box and school lunch menu were analyzed according to the Food Composition Table. Nutrients and cost of the Dong Duck Elementary School Lunch were compared to the average nutrient contents of food in a lunch-box of o pupil. In addition, comparisons between the Recommended Daily Allowances of nutrients for Korean children aged from 9 to 11 (4th, 5th, and 6th grade) and that of the contained nutrients in the average lunch-box were conducted. The average nutrients contained in the lunch-box compared with the Recommended Daily Allowances are: Calorie 77.41% (542.60ca1), Protein 73.60% (16.93gr), Fat 33.95% (3.95gr), Calcium 27.85% (111.39mg), Ferret 80.30% (2.65mg), Vitamin A 10.09% (100.93 I.U.), Vitamin Bl 70.27% (0.27mg), Vitamin B2 88.37% (0.38mg), Vitamin C 15.40% (3.45mg). All of the nutrients in the lunch-box fall far below the Recommended Daily Allowances for the 9-11 age group. The average nutrients of staple food in the lunch-box compared with the side-dishes were found to contain Calorie 90.80%, Protein 50.32%, Fat 58.27%, Calcium 37.07 %, Ferret 53.96%, Vitamin A 0.0028%, Vitamin B1 78.11%, Vitamin B2 21.09%. The nutrients of food contained in the Dong Duck Elementary School Lunch Program compared with the Recommended Daily Allowances were: 1. The Protein, Fat, Ferret, Vitamin B1 and Vitamin B2 content was generally satisfactory. 2. Calcuim, Vitamin A and Vitamin C were lower than the Recommended Daily Allowances. 3. The Calorie content was generally lower for the 9-11 age group. The per pupil cost of the lunch-box was 41.87 won which includes the cost of staple food 16.92 won and side-dishes 24.95 won, whereas the school lune Provided by Dong Duck Elementary School Costs 35 won per pupil. Questionnaires were sent to four hundred parents (through their children) to find out their attitude toward the school lunch program. 390(97.50%) of them were returned and 7 of them dia not answer at all. Therefore, these were eliminated from the samlpe. Among 185 parents whose children were eating the school lunch; 172 parents (92.97% ) would pay 40 won for the proposed new school lunch program whereas only 13 parents (7.03%) did not want it. Among 198 parents whose children were not having the school lunch, 58 parents (29.29%) would agree to have the lunch for their children at the cost of 35 won with the proposed new school lunch program equivalent to 40 won. 126 parents (63.63%) could not agree to have their children being the school lunch because of their financial difficulty (74 parents 58.72%). The rest of parents (52 parents 41.28%) raised other reasons which were minor problems. Among the tatal of 383 parents, 309 parents (80.68%) would agree to gave school lunch for their children if the cost of the proposed new school lunch program would be 35 won to 40 won and if minor problems concerning the school lunch program are solved. Sixty parents (15.66% ) raised questions about the school lunch program concerning sanitary problems, taste of bread, and the quantity of lunch. Among 383 parents, 358 parents answered and 25 parents did not. When school officer asked if the parents would help during the school lunch hour, 101 parents indicated they could not help at all, but 177 parents, replied they could help. Among 177 parents, 40 parents of them could share their time from one or two hours everyday except Saturday and 107 parents could serve 1 to 3 days per week. Through this study, it is evident that further investigation should be done of the school lunch program which can be provided 35 won with the proposed new school lunch program. The parents participation in the school lunch program would be improved the understanding between school and parents as well as insure better nutrition and sanitation for the children.

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Cloning and Characterization of Phosphoinositide 3-Kinase γ cDNA from Flounder (Paralichthys olivaceus) (넙치에서 분리된 phosphoinositide 3-kinase γ 유전자의 클로닝 및 특성 연구)

  • Jeong, Tae Hyug;Youn, Joo Yeon;Ji, Keunho;Seo, Yong Bae;Kim, Young Tae
    • Journal of Life Science
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    • v.24 no.4
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    • pp.343-351
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    • 2014
  • Phosphoinositide 3-kinase (PI3K) plays a central role in cell signaling and leads to cell proliferation, survival, motility, exocytosis, and cytoskeletal rearrangements, as well as specialized cell responses, superoxide production, and cardiac myocyte growth. PI3K is divided into three classes; type I PI3K is preferentially expressed in leukocytes and activated by ${\beta}{\gamma}$ subunits of heterotrimeric G-proteins. In this study, the cDNAs encoding the $PI3K{\gamma}$ gene were isolated from a brain cDNA library constructed using the flounder (Paralichthys olivaceus). The sequence of the isolated $PI3K{\gamma}$ was 1341 bp, encoding 447 amino acids. The nucleotide sequence of the $PI3K{\gamma}$ gene was analyzed with that of other species, including Oreochromis niloticus and Danio rerio, and it turned out to be well conserved during evolution. The $PI3K{\gamma}$ gene was subcloned into the expression vector pET-44a(+), and expressed in the E. coli BL21 (DE3) codon plus cell. The resulting protein was expressed as a fusion protein of approximately 49 kDa containing a C-terminal six-histidine extension that was derived from the expression vector. The expressed protein was purified to homogeneity by His-tag affinity chromatography and showed enzymatic activity corresponding to $PI3K{\gamma}$. The binding of wortmannin to $PI3K{\gamma}$, as detected by anti-wortmannin antisera, closely followed the inhibition of the kinase activities. The results obtained from this study will provide a wider base of knowledge on the primary structure and characterization of the $PI3K{\gamma}$ at the molecular level.