• Title/Summary/Keyword: Disease control

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

  • Yun, Sung-Seob
    • 한국유가공학회:학술대회논문집
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    • 2007.09a
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    • pp.49-58
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    • 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.

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Preliminary Results of Concurrent Chemotherapy and Radiation Therapy using High-dose-rate Brachytherapy for Cervical Cancer (자궁경부암에 항암화학요법과 동시 병용요법으로 외부 방사선조사와 고선량률 강내조사의 예비적 치료 결과)

  • Lee, Kyung-Ja;Lee, Ji-Hye;Lee, Re-Na;Suh, Hyun-Suk
    • Radiation Oncology Journal
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    • v.24 no.3
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    • pp.171-178
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    • 2006
  • [ $\underline{Purpose}$ ]: To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. $\underline{Materials\;and\;Methods}$: From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range $34{\sim}74$) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follows: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of $45{\sim}50.4\;Gy$ (median: 50.4 Gy) over $5{\sim}5.5$ weeks. Ir-192 HDR intracavitary brachytherapy (ICBT) was given after a total dose of 41.4 Gy. HDR-ICBT was performed twice a week, with a fraction point A dose of 4 Gy and median dose to point A was 28 Gy (range: $16{\sim}32\;Gy$) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT+ICBT) was $88\;Gy_{10}$ (range: $77{\sim}94\;Gy_{10}$). The median cumulative BED at ICRU 38 reference point (EBRT+ICBT) was $131\;Gy_3$ (range: $122{\sim}140\;Gy_3$) at point A, $109\;Gy_3$ (range: $88{\sim}125\;Gy_3$) at the rectum and $111\;Gy_3$ (range: $91{\sim}123\;Gy_3$) at the urinary bladder. Cisplatin ($60\;mg/m^2$) and 5-FU ($1,000\;mg/m^2$) was administered intravenously at 3 weeks interval from the first day of radiation for median 5 (range: $2{\sim}6$) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range: $8{\sim}50$ months). $\underline{: The complete response rate after concurrent chemoradiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure rate was 13% and distant metastatic rate was 3.3%. The crude rate of minor hematologic complications (RTOG grade 1-2) occurred in 3 patients (10%) and one patient had suffered from severe leukopenia (RTOG grade 4) during concurrent treatment. Acute minor enterocolitis (RTOG grade 1-2) occurred in 11 patients (37%) and one patient (3%) was suffered from colon perforation during radiation therapy. Late colitis of RTOG grade 1 occurred in 5 patients (15%). Acute cystitis of RTOG grade 1 occurred in 12 patients (40%) and late cystitis of RTOG grade 2 occurred in one patient (3%). No treatment related death was seen. $\underline{Conclusion}$: The results of this study suggest that the concurrent chemoradiation therapy with HDR brachytherapy could be accepted as an effective and safe treatment for cervical cancer.

Effect of Nasal Continuous Positive Airway Pressure after Early Surfactant Therapy in Moderate Respiratory Distress Syndrome (중등도 신생아 호흡 곤란 증후군에서 폐 표면 활성제 조기 투여 후 Nasal CPAP의 치료 효과)

  • Kim, Eun Ji;Kim, Hae Sook;Hur, Man Hoe;Lee, Sang Geel
    • Clinical and Experimental Pediatrics
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    • v.45 no.10
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    • pp.1204-1212
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    • 2002
  • Purpose : Early surfactant therapy with either gentle ventilation, high-frequency ventilation or aggressive weaning of mechanical ventilation are principles for the treatment of respiratory distress syndrome(RDS). We studied to determine the accessibility of noninvasive nasal continuous positive airway pressure(CPAP) rather than mechanical ventilation by invasive intubation after early surfactant therapy. Methods : The study group consisted of 14 infants who were born and diagnosed with moderate respiratory distress syndrome and received early surfactant therapy with nasal CPAP of PEEP 5-6 cm $H_2O$ within two hours after birth in the Fatima neonatal intensive care unit for two years from January 1999 to August 2001. The control group consisted of 15 infants who were diagnosed with the disease and could be weaned from mechanical ventilator within five days after birth during the same period. Results : The characteristics, the severity of clinical symptoms and laboratory findings in the two groups at birth showed no significant difference. Neither did the interim analysis of laboratory data in two groups. Of 14 infants in the study group who received nasal CPAP after early surfactant therapy, only two infants showed weaning failure with this therapy. In the response cases, duration of CPAP was five days and mean airway pressure was $5.4{\pm}0.5cm$ $H_2O$. Two had the complication of CPAP with abdominal distension. Final complications and outcomes in the two groups showed no signifcant difference(P>0.05). Conclusion : The clinical courses in the two groups showed no significant difference. Therefore, we suggest that early surfactant therapy with noninvasive nasal CPAP is a simple and safe method rather than aggressive weaning after invasive mechanical ventilation in moderate respiratory distress syndrome.

A Study on improvement of curriculum in Nursing (간호학 교과과정 개선을 위한 조사 연구)

  • 김애실
    • Journal of Korean Academy of Nursing
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    • v.4 no.2
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    • pp.1-16
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    • 1974
  • This Study involved the development of a survey form and the collection of data in an effort-to provide information which can be used in the improvement of nursing curricula. The data examined were the kinds courses currently being taught in the curricula of nursing education institutions throughout Korea, credits required for course completion, and year in-which courses are taken. For the purposes of this study, curricula were classified into college, nursing school and vocational school categories. Courses were directed into the 3 major categories of general education courses, supporting science courses and professional education course, and further subdirector as. follows: 1) General education (following the classification of Philip H. phoenix): a) Symbolics, b) Empirics, c) Aesthetics. 4) Synthetics, e) Ethics, f) Synoptic. 2) Supporting science: a) physical science, b) biological science, c) social science, d) behavioral science, e) Health science, f) Educations 3) Professional Education; a) basic courses, b) courses in each of the respective fields of nursing. Ⅰ. General Education aimed at developing the individual as a person and as a member of society is relatively strong in college curricula compared with the other two. a) Courses included in the category of symbolics included Korean language, English, German. Chines. Mathematics. Statics: Economics and Computer most college curricula included 20 credits. of courses in this sub-category, while nursing schools required 12 credits and vocational school 10 units. English ordinarily receives particularly heavy emphasis. b) Research methodology, Domestic affair and women & courtney was included under the category of empirics in the college curricula, nursing and vocational school do not offer this at all. c) Courses classified under aesthetics were physical education, drill, music, recreation and fine arts. Most college curricula had 4 credits in these areas, nursing school provided for 2 credits, and most vocational schools offered 10 units. d) Synoptic included leadership, interpersonal relationship, and communications, Most schools did not offer courses of this nature. e) The category of ethics included citizenship. 2 credits are provided in college curricula, while vocational schools require 4 units. Nursing schools do not offer these courses. f) Courses included under synoptic were Korean history, cultural history, philosophy, Logics, and religion. Most college curricular 5 credits in these areas, nursing schools 4 credits. and vocational schools 2 units. g) Only physical education was given every Year in college curricula and only English was given in nursing schools and vocational schools in every of the curriculum. Most of the other courses were given during the first year of the curriculum. Ⅱ. Supporting science courses are fundamental to the practice and application of nursing theory. a) Physical science course include physics, chemistry and natural science. most colleges and nursing schools provided for 2 credits of physical science courses in their curricula, while most vocational schools did not offer t me. b) Courses included under biological science were anatomy, physiologic, biology and biochemistry. Most college curricula provided for 15 credits of biological science, nursing schools for the most part provided for 11 credits, and most vocational schools provided for 8 units. c) Courses included under social science were sociology and anthropology. Most colleges provided for 1 credit in courses of this category, which most nursing schools provided for 2 creates Most vocational school did not provide courses of this type. d) Courses included under behavioral science were general and clinical psychology, developmental psychology. mental hygiene and guidance. Most schools did not provide for these courses. e) Courses included under health science included pharmacy and pharmacology, microbiology, pathology, nutrition and dietetics, parasitology, and Chinese medicine. Most college curricula provided for 11 credits, while most nursing schools provide for 12 credits, most part provided 20 units of medical courses. f) Courses included under education included educational psychology, principles of education, philosophy of education, history of education, social education, educational evaluation, educational curricula, class management, guidance techniques and school & community. Host college softer 3 credits in courses in this category, while nursing schools provide 8 credits and vocational schools provide for 6 units, 50% of the colleges prepare these students to qualify as regular teachers of the second level, while 91% of the nursing schools and 60% of the vocational schools prepare their of the vocational schools prepare their students to qualify as school nurse. g) The majority of colleges start supporting science courses in the first year and complete them by the second year. Nursing schools and vocational schools usually complete them in the first year. Ⅲ. Professional Education courses are designed to develop professional nursing knowledge, attitudes and skills in the students. a) Basic courses include social nursing, nursing ethics, history of nursing professional control, nursing administration, social medicine, social welfare, introductory nursing, advanced nursing, medical regulations, efficient nursing, nursing english and basic nursing, College curricula devoted 13 credits to these subjects, nursing schools 14 credits, and vocational schools 26 units indicating a severe difference in the scope of education provided. b) There was noticeable tendency for the colleges to take a unified approach to the branches of nursing. 60% of the schools had courses in public health nursing, 80% in pediatric nursing, 60% in obstetric nursing, 90% in psychiatric nursing and 80% in medical-surgical nursing. The greatest number of schools provided 48 crudites in all of these fields combined. in most of the nursing schools, 52 credits were provided for courses divided according to disease. in the vocational schools, unified courses are provided in public health nursing, child nursing, maternal nursing, psychiatric nursing and adult nursing. In addition, one unit is provided for one hour a week of practice. The total number of units provided in the greatest number of vocational schools is thus Ⅲ units double the number provided in nursing schools and colleges. c) In th leges, the second year is devoted mainly to basic nursing courses, while the third and fourth years are used for advanced nursing courses. In nursing schools and vocational schools, the first year deals primarily with basic nursing and the second and third years are used to cover advanced nursing courses. The study yielded the following conclusions. 1. Instructional goals should be established for each courses in line with the idea of nursing, and curriculum improvements should be made accordingly. 2. Course that fall under the synthetics category should be strengthened and ways should be sought to develop the ability to cooperate with those who work for human welfare and health. 3. The ability to solve problems on the basis of scientific principles and knowledge and understanding of man society should be fostered through a strengthening of courses dealing with physical sciences, social sciences and behavioral sciences and redistribution of courses emphasizing biological and health sciences. 4. There should be more balanced curricula with less emphasis on courses in the major There is a need to establish courses necessary for the individual nurse by doing away with courses centered around specific diseases and combining them in unified courses. In addition it is possible to develop skill in dealing with people by using the social setting in comprehensive training. The most efficient ratio of the study experience should be studied to provide more effective, interesting education Elective course should be initiated to insure a man flexible, responsive educational program. 5. The curriculum stipulated in the education law should be examined.

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Analysis of Korean Dietary Patterns using Food Intake Data - Focusing on Kimchi and Alcoholic Beverages (식품섭취량을 활용한 우리나라 식이 패턴 분석 - 김치류 및 주류 중심으로)

  • Kim, Soo-Hwaun;Choi, Jang-Duck;Kim, Sheen-Hee;Lee, Joon-Goo;Kwon, Yu-Jihn;Shin, Choonshik;Shin, Min-Su;Chun, So-Young;Kang, Gil-Jin
    • Journal of Food Hygiene and Safety
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    • v.34 no.3
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    • pp.251-262
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    • 2019
  • In this study, we analyzed Korean dietary habits with food intake data from the Korea National Health and Nutrition Examination Survey (KNHANES) and the Korea Centers for Disease Control and Prevention and we proposed a set of management guidelines for future Korean dietary habits. A total of 839 food items (1,419 foods) were analyzed according to the food catagories in "Food Code", which is the representative food classification system in Korea. The average total daily food intake was 1,585.77 g/day, with raw and processed foods accounting for 858.96 g/day and 726.81 g/day, respectively. Cereal grains contributed to the highest proportion of the food intake. Over 90% of subjects consumed cereal grains (99.09%) and root and tuber vegetables (95.80%) among the top 15 consumed food groups. According to the analysis by item, rice, Korean cabbage kimchi, apple, radish, egg, chili pepper, onion, wheat, soybean curds, potato, cucumber and pork were major (at least 1% of the average daily intake, 158.6 g/day) and frequently (eaten by more than 25% of subjects, 5,168 persons) consumed food items, and Korean spices were at the top of this list. In the case of kimchi, the proportion of intake of Korean cabbage kimchi (64.89 g/day) was the highest. In the case of alcoholic beverages, intake was highest by order of beer (63.53 g/day), soju (39.11 g/day) and makgeolli (19.70 g/day), and intake frequency was high in order of soju (11.3%), beer (7.2%), and sake (6.6%). Analysis results by seasonal intake trends showed that cereal grains have steadily decreased and beverages have slightly risen. In the case of alcoholic beverage consumption frequency, some kinds of makgeolli, wine, sake, and black raspberry wine have decreased gradually year by year. The consumption trend for kimchi has been gradually decreasing as well.

Radiation Therapy and Chemotherapy after Breast Conserving Surgery for Invasive Breast Cancer: An Intermediate Result (침윤성 유방암에서 유방보존수술 후 방사선치료 및 항암화학 병용치료의 성적 및 위험인자 분석)

  • Lee, Seok-Ho;Choi, Jin-Ho;Lee, Young-Don;Park, Heoung-Kyu;Kim, Hyun-Young;Park, Se-Hoon;Lee, Kyu-Chan
    • Radiation Oncology Journal
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    • v.25 no.1
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    • pp.16-25
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    • 2007
  • [ $\underline{Purpose}$ ]: Breast conserving surgery (BCS) followed by chemotherapy (CTx.) and radiation therapy (RT) is widely performed for the treatment of early breast cancer. This retrospective study was undertaken to evaluate our interim results in terms of failure patterns, survival and relative risk factors. $\underline{Materials\;and\;Methods}$: From January 1999 through December 2003, 129 patients diagnosed with invasive breast cancer and treated with BCS followed by RT were subject to retrospective review. The median age of the patients was 45 years (age distribution, $27{\sim}76$ years). The proportions of patients according to their tumor, nodes, and metastases (TNM) stage were 65 (50.4%) in stage I, 41 (31.7%) in stage IIa, 13 (10.1%) in stage IIb, 9 (7.0%) in stage III, and 1 patient (0.8%) in stage IIIc. For 32 patients (24.8%), axillary node metastasis was found after dissection. BCS consisted of quadrantectomy in 115 patients (89.1%) and lumpectomy in 14 patients (10.6%). Axillary node dissection at axillary level I and II was performed for 120 patients (93%). For 7 patients (5.4%), only sentinel node dissection was performed with BCS. For 2 patients (1.6%) axillary dissection of any type was not performed. Postoperative RT was given with 6 MV X-rays. A tumor dose of 50.4 Gy was delivered to the entire breast area using a tangential field with a wedge compensator. An aditional dose of $9{\sim}16\;Gy$ was given to the primary tumor bed areas with electron beams. In 30 patients (23.3%), RT was delivered to the supraclavicular node. Most patients had adjuvant CTx. with $4{\sim}6$ cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimens. The median follow-up period was 50 months (range: $17{\sim}93$ months). $\underline{Results}$: The actuarial 5 year survival rate (5Y-OSR) was 96.9%, and the 5 year disease free survival rate (5Y-DFSR) was 93.7%. Local recurrences were noted in 2 patients (true: 2, regional node: 1) as the first sign of recurrence at a mean time of 29.3 months after surgery. Five patients developed distant metastases as the first sign of recurrence at $6{\sim}33$ months (mean 21 months). Sites of distant metastatic sites were bone in 3 patients, liver in 1 patient and systemic lesions in 1 patient. Among the patients with distant metastatic sites, two patients died at 17 and 25 months during the follow-up period. According to stage, the 5Y-OSR was 95.5%, 100%, 84.6%, and 100% for stage I, IIa, IIb, and III respectively. The 5Y-DFSR was 96.8%, 92.7%, 76.9%, and 100% for stage I, IIa, IIb, and III respectively. Stage was the only risk factor for local recurrence based on univariate analysis. Ten stage III patients included in this analysis had a primary tumor size of less than 3 cm and had more than 4 axillary lymph node metastases. The 10 stage III patients received not only breast RT but also received posterior axillary boost RT to the supraclavicular node. During the median 53.3 months follow-up period, no any local or distant failure was found. Complications were asymptomatic radiation pneumonitis in 10 patients, symptomatic pneumonitis in 1 patient and lymphedema in 8 patients. $\underline{Conclusion}$: Although our follow up period is short, we had excellent local control and survival results and reaffirmed that BCS followed by RT and CTx. appears to be an adequate treatment method. These results also provide evidence that distant failure occurs earlier and more frequent as compared with local failure. Further studies and a longer follow-up period are needed to assess the effectiveness of BCS followed by RT for the patients with less than a 3 cm primary tumor and more than 4 axillary node metastases.

Cultural Practices for Reducing Cold Wind Damage of Rice Plant in Eastern Coastal Area of Korea (동해안지대 도작의 냉조풍피해와 피해경감대책)

  • 이승필;김칠용
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.36 no.5
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    • pp.407-428
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    • 1991
  • The eastern coastal area having variability of climate is located within Taebaek mountain range and the east coast of Korea. It is therefore ease to cause the wind damages in paddy field during rice growing season. The wind damages to rice plant in this area were mainly caused by the Fohn wind (dry and hot wind) blowing over the Taebaek mountain range and the cold humid wind from the coast. The dry wind cause such as the white head, broken leaves, cut-leaves, dried leaves, shattering of grain, glume discolouration and lodging, On the other hand the cold humid wind derived from Ootsuku air mass in summer cause such symptom as the poor rice growth, degeneration of rachis brenches and poor ripening. To minimize the wind damages and utilize as a preparatory data for wind injury of rice in future, several experiments such as the selection of wind resistant variety to wind damage, determination of optimum transplanting date, improvement of fertilizer application methods, improvement of soils and effect of wind break net were carried out for 8 years from 1982 to 1989 in the eastern coastal area. The results obtained are summarized as follows. 1. According to available statisical data from Korean meteorological services (1954-1989) it is apperent that cold humid winds frequently cause damage to rice fields from August 10th to September 10th, it is therefore advisable to plan rice cultivation in such a way that the heading date should not be later than August 10th. 2. During the rice production season, two winds cause severe damage to the rice fields in eastern coastal area of Korea. One is the Fohn winds blowing over the Taebaek mountain range and the other is the cold humid wind form the coast. The frequency of occurrence of each wind was 25%. 3. To avoid damage caused by typhoon winds three different varieties of rice were planted at various areas. 4. In the eastern coastal area of Korea, the optimum ripening temperature for rice was about 22.2$^{\circ}C$ and the optimum heading date wad August 10th. The optimum transplanting time for the earily maturity variety was June 10th., medium maturity variety was May 20th and that of late maturity was May 10th by means of growing days degree (GDD) from transplanting date to heading date. 5.38% of this coastal area is sandy loamy soil while 28% is high humus soil. These soil types are very poor for rice cultivation. In this coastal area, the water table is high, the drainage is poor and the water temperature is low. The low water temperature makes it difficult for urea to dissolve, as a result rice growth was delayed, and the rice plant became sterile. But over application of urea resulted in blast disease in rice plants. It is therefore advise that Ammonium sulphate is used in this area instead of urea. 6. The low temperature of the soil inhibits activities of microorganism for phosphorus utilization so the rice plant could not easily absorb the phosphorus in the soil. Therefore phosphorus should be applied in splits from transplanting to panicle initiation rather than based application. 7. Wind damage was severe in the sandy loamy soil as compared to clay soils. With the application of silicate. compost and soil from mointain area. the sand loamy soil was improved for rice grain colour and ripening. 8. The use of wind break nets created a mocro-climate such as increased air. soil and water temperature as well as the reduction of wind velocity by 30%. This hastened rice growth, reduced white head and glume discolouration. improved rice quality and increased yield. 9. Two meter high wind break net was used around the rice experimental fields and the top of it. The material was polyethylene sheets. The optimum spacing was 0.5Cm x 0.5Cm. and that of setting up the wind break net was before panicle initiation. With this set up, the field was avoided off th cold humid wind and the Fohn. The yield in the treatment was 20% higher than the control. 10. After typhoon, paddy field was irrigated deeply and water was sprayed to reduce white head, glume discolouration, so rice yield was increased because of increasing ripening ratio and 1, 000 grain weight.

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Anti-inflammatory Effects of Pentoxifylline and Neutrophil Elastase Inhibitor on Lipopolysaccharide-Induced Acute Lung Injury In Vitro (In Vitro 내독소 유도성 급성 폐손상에서 Pentoxifylline과 Neutrophil Elastase Inhibitor의 항염효과)

  • Kim, Young-Kyoon;Kim, Seung-Joon;Park, Yong-Keun;Kim, Seok-Chan;Kim, Kwan-Hyoung;Moon, Hwa-Sik;Song, Jeong-Sup;Park, Sung-Hak;Kim, Sang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.6
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    • pp.691-702
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    • 2000
  • Background : Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. Methods : To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1, 1:1, 1:5, 0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)-$\alpha$ interleukin (IL)-$1{\beta}$, monocyte chemotactic protein(MCP)-1, IL-6, and IL-10 as well as mRNA expressions of TNF-$\alpha$ inducible nitric oxide synthetase(iNOS), and MCP-1 from LPS-stimulated primary rat alveolar macrophages between groups. Results : (1) PF and ONO-5046 in each or both showed a trend to suppress LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils regardless of their ratio, except for the LPS+PF+ONO group with the 1:5 ratio, although statistical significance was limited to a few selected experimental conditions. (2) PF and ONO-5046 in each or both showed a trend to prevent IP2-E4 cells from LPS-induced cytotoxicity by primary rat alveolar macrophages and peripheral neutrophils regardless their ratio, although statistical significance was limited to a few selected experimental conditions. the effects of PF and/or ONO-5046 on LPS-induced L2 cell cytotoxicity varied according to experimental conditions. (3) PF showed a trend to inhibit LPS-induced productions of INF-$\alpha$ MCP-1, and IL-10 from primary rat alveolar macrophages. ONO-5046 alone didnot affect the LPS-induced productions of proinflammatory cytokines from primary rat alveolar macrophages but the combination of PF and ONO-5046 showed a trend to suppress LPS-induced productions of INF-$\alpha$ and IL-10 PF and ONO-5046 in each or both showed a trend to increase LPS-induced IL-$\beta$ and IL-6 productions from primary rat alveolar macrophages. (4) PF and ONO-5046 in each or both showed a trend to attenuate LPS-induced mRNA expressions of TNF-$\alpha$ and MCP-1 from primary rat alveolar macrophages but at the same time showed a trend increase iNOS mRNA expression. Conclusion : These results suggest that PF and ONO-5046 may play a role in attenuating inflammation in LPS-induced ALI and that further study is needed to use these drugs as a new supportive therapeutic strategy for ALI.

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Studies on Sclerotium rolfsii Sacc. isolated from Magnolia kobus DC. in Korea (목련(Magnolia kobus DC.)에서 분리한 흰비단병균(Sclerotium rolfsii Sacc.)에 관한 연구)

  • Kim Kichung
    • Korean journal of applied entomology
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    • v.13 no.3 s.20
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    • pp.105-133
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    • 1974
  • The present study is an attempt to solve the basic problems involved in the control of the Sclerotium disease. The biologic stranis of Sclerotium rolfsii Sacc., pathogen of Sclerotium disease of Magnolia kobus, were differentiated, and the effects of vitamins, various nitrogen and carbon sources on its mycelial growth and sclerotial production have been investigated. In addition the relationship between the cultural filtrate of Penicillium sp. and the growth of Sclerotium rolfsii, the tolerance of its mycelia or sclerotia to moist heat or drought and to Benlate (methyl-(butylcarbamoy 1)-2-benzimidazole carbamate), Tachigaren (3-hydroxy-5-methylisoxazole) and other chemicals were also clarified. The results are summarizee as follows: 1. There were two biologic strains, Type-l and Type-2 among isolates. They differed from each other in the mode of growth and colonial appearance on the media, aversion phenomenon and in their pathogenicity. These two types had similar pathogenicity to the Magnolia kobus and Robinia pseudoacasia, but behaved somewhat differently to the soybaen and cucumber, the Type-l being more virulent. 2. Except potassium nitrite, sodium nitrite and glycine, all of the 12 nitrogen sources tested were utilized for the mycelial growth and sclerotial production of this fungus when 10r/l of thiamine hydrochloride was added in the culture solution. Considering the forms of nitrogen, ammonium nitrogen was more available than nitrate nitrogen for the growth of mycelia, but nitrate nitrogen was better for sclerotia formation. Organic nitrogen showed different availabilities according to compounds used. While nitrite nitrogen was unavailable for both mycelial growth and sclerotial formation whether thiamine hydrochlioride was added or not. 3. Seven kinds of carbon sources examined were not effective in general, as long as thiamine hydrochloride was not added. When thiamine hydrochloride was added, glucose and saccharose exhibited mycelial growth, while rnaltose and soluble starch gave lesser, and xylose, lactose, and glycine showed no effect at all,. In the sclerotial production, all the tested carbon sources, except lactose, were effective, and glucose, maltose, saccharose, and soluble starch gave better results. 4. At the same level of nitrogen, the amount of mycelial growth increased as more carbon Sources were applied but decreased with the increase of nitrogen above 0.5g/1. The amount of sclerotial production decreased wi th the increase of carbon sources. 5. Sclerotium rolfsii was thiamine-defficient and required thiamine 20r/l for maximun growth of mycelia. At a higher concentration of more than 20r/l, however, mycelial growth decreased as the concentration increased, and was inhibited at l50r/l to such a degree of thiamine-free. 6. The effect of the nitrogen sources on the mycelial growth under the presence of thiamine were recognized in the decreasing order of $NH_4NO_3,\;(NH_4)_2SO_4,\;asparagine,\;KNO_3$, and their effects on the sclerotial production in the order of $KNO_3,\;NH_4NO_3,\;asparagine,\;(NH_4)_2SO_4$. The optimum concentration of thiamine was about 12r/l in $KNO_3$ and about 16r/l in asparagine for the growth of mycelia; about 8r/l in $KNO_3$ and $NH_4NO_3$, and 16r/l in asparagine for the production of sclerotia. 7. After the fungus started to grow, the pH value of cultural filtrate rapidly dropped to about 3.5. Hereafter, its rate slowed down as the growth amount increased and did not depreciated below pH2.2. 8. The role of thiamine in the growth of the organism was vital. If thiamine was not added, the combination of biotin, pyridoxine, and inositol did not show any effects on the growth of the organism at all. Equivalent or better mycelial growth was recognized in the combination of thiamine+pyridoxine, thiamine+inositol, thiamine+biotin+pyridoxine, and thiamine+biotin+pyridoxine+inositol, as compared with thiamine alone. In the combinations of thiamine+biotin and thiamine+biotin+inositol, mycelial growth was inhibited. Sclerotial production in dry weight increased more in these combinations than in the medium of thiamine alone. 9. The stimulating effects of the Penicillium cultural filtrate on the mycelial growth was noticed. It increased linearly with the increase of filtrate concentration up to 6-15 ml/50ml basal medium solution. 10. $NH_4NO_3$. as a nitrogen source for mycelial growth was more effective than asparasine regardless of the concentration of cultural filtrate. 11. In the series of fractionations of the cultural filtrate, mycelial growth occured in unvolatile, ether insoluble cation-adsorbed or anion-unadsorbed substance fractions among the fractions of volatile, unvolatile acids, ether soluble organic acids, ether insoluble, cation-adsorbed, cation-unadsorbed, anion-adsorbed and anion-unadsorbed. and anion-un-adsorbed substance tested. Sclerotia were produced only in cation-adsorbed fraction. 12. According to the above results, it was assumed that substances for the mycelial growth and sclerotial formation and inhibitor of sclerotial formation were include::! in cultural filtrate and they were quite different from each other. I was further assumed that the former two substances are un volatile, ether insotuble, and adsorbed to cation-exchange resin, but not adsorbed to anion, whereas the latter is unvolatile, ether insoluble, and not adsorbed to cation or anion-exchange resin. 13. Seven amino acids-aspartic acid, cystine, glysine, histidine, Iycine, tyrosine and dinitroaniline-were detected in the fractions adsorbed to cation-exchange resin by applying the paper chromatography improved with DNP-amino acids. 14. Mycelial growth or sclerotial production was not stimulated significantly by separate or combined application of glutamic acid, aspartic acid, cystine, histidine, and glysine. Tyrosine gave the stimulating effect when applied .alone and when combined with other amino acids in some cases. 15. The tolerance of sclerotia to moist heat varied according to their water content, that was, the dried sclerotia are more tolerant than wet ones. The sclerotia harvested directly from the media, both Type-1 and Type-2, lost viability within 5 minutes at $52^{\circ}C$. Sclerotia dried for 155 days at$26^{\circ}C$ had more tolerance: sclerotia of Type-l were killed in 15 mins. at $52^{\circ}C$ and in 5 mins. at $57^{\circ}C$, and sclerotia of Type-2 were killed in 10 mins. both at $52^{\circ}C$ or $57^{\circ}C$. 16. Cultural sclerotia of both strains maintained good germinability for 132 days at$26^{\circ}C$. Natural sclerotia of them stored for 283 days under air dry condition still had good germinability, even for 443 days: type-l and type-2 maintained $20\%$ and $26.9\%$ germinability, respectively. 17. The tolerance to low temperature increased in the order of mycelia, felts and sclerotia. Mycelia completely lost the ability to grow within 1 week at $7-8^{\circ}C$> below zero, while mycelial felts still maintained the viability after .3 weeks at $7-20^{\circ}C$ below zero, and sclerotia were even more tolerant. 18. Sclerotia of type-l and type-2 were killed when dipped into the $0.05\%$ solution of mercury chloride for 180 mins. and 240 mins. respectively: and in the $0.1\%$ solution, Type-l for 60 mins. and Type-2 for 30 mins. In the $0.125\%$ uspulun solution, Type-l sclerotia were killed in 180 mins., and those of Type-2 were killed for 90 mins. in the$0.125\%$solution. Dipping into the $5\%$ copper sulphate solution or $0.2\%$ solution of Ceresan lime or Mercron for 240 mins. failed to kill sclerotia of either Type-l or Type-2. 19. Inhibitory effect on mycelial growth of Benlate or Tachi-garen in the liquid culture increased as the concentration increased. 6 days after application, obvious inhibitory effects were found in all treatments except Benlate 0.5ppm; but after 12 days, distingushed diflerences were shown among the different concentrations. As compared with the control, mycelial growth was inhibited by $66\%$ at 0.5ppm and by $92\%$ at 2.0ppm of Benlate, and by$54\%$ at 1ppm and about $77\%$ at 1.5ppm or 2.0ppm of Tachigaren. The mycelial growth was inhibited completely at 500ppm of both fungicides, and the formation of sclerotia was checked at 1,000ppm of Benlate ant at 500ppm or 1,000ppm of Tachigaren. 20. Consumptions of glucose or ammonium nitrogen in the culture solution usually increased with the increment of mycelial growth, but when Benlate or Tachigaren were applied, consumptions of glucose or ammonium nitrogen were inhibited with the increment of concentration of the fungicides. At the low concentrations of Benlate (0.5ppm or 1ppm), however, ammonium nitrogen consumption was higher than that of the ontrol. 21. The amount of mycelia produced by consuming 1mg of glucose or ammonium nitrogen in the culture solution was lowered markedly by Benlate or Tachigaren. Such effects were the severest on the third day after their treatment in all concentrations, and then gradually recovered with the progress of time. 22. In the sand culture, mycelial growth was not inhibited. It was indirectly estimated by the amount of $CO_2$ evolved at any concentrations, except in the Tachigaren 100mg/g sand in which mycelial growth was inhibited significantly. Sclerotial production was completely depressed in the 10mg/g sand of Benlate or Tachigaren. 23. There was no visible inhibitory effect on the germination of sclerotia when the sclerotia were dipped in the solution 0.1, 1.0, 100, 1.000ppm of Benlate or Tachigaren for 10 minutes or even 20 minutes.

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