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Effects of Dietary Protein on the Progression of Early Chronic Renal Failure in Subtotally Nephrectomizid Rats (저단백식이의 투여가 만성신부전증의 진행에 미치는 영향에 관한 실험적 연구)

  • Kim, Kyo-Sun;Kim, Kee-Hyuk;Kim, Sang-Yun;Kang, Yong-Joo;Maeng, Won-Jae
    • Childhood Kidney Diseases
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    • v.3 no.1
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    • pp.64-71
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    • 1999
  • Purpose : The protective effects of dietary protein on the progression of renal failure were studied in subtotally nephrectomized rats. Methods : Treatment groups were as follows; 5/6 nephrectomy and a normal protein ($18.5\%$) diet (NP); 5/6 nephrectomy and a low protein ($6\%$) diet (LP): 5/6 nephrectomy, a normal protein diet and converting enzyme inhibitor, enalapril (NPE): 5/6 nephrectomy, a low protein diet and enalapril (LPE). Both diets were isocaloric and had the same phosphorus content. Proteinuria, remnant kidney weight, mesangial matrix expansion score and glomerular volume were assessed at 4, 12 and 16 weeks after renal ablation. Results : LP and NP developed progressive hypertension. Eight weeks after surgery, LPE and NPE controlled hypertension. LP, LPE, and NPE had significantly less proteinuria than NP at 16 weeks (P<0.05). Kidney weight in LP were markedly less enlarged than NP (P<0.05). There was no difference in kidney weight between LPE and NPE. At 12 and 16 weeks the mesangial matrix expansion score was significantly less in LP, LPE, and NPE compared to NP (P<0.05). At 12 and 16 weeks mean glomerular volume was significantly less in LP compared to NP (P<0.05). At 12 and 16 weeks mean glomerular volume in LPE was significantly less compared to NPE. Conclusion : Dietary protein restriction afforded considerable protection from renal injury in the rat remnant kidney model. During the enalapril treatment, there was no additional protective effect of dietary protein restriction against the development of renal lesions.

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Chest CT Finding and Its Comparison with Bronchoscopic Finding in Endobronchial Tuberculosis (기관지결핵의 흉부전산화단층촬영소견 및 기관지경소견과의 비교)

  • Lee, Jae-Ho;Yoon, Hye-Kyung;Song, Jae-Woo;Yoo, Chul-Gyu;Chung, Hee-Soon;Kim, Young-Hwan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.742-755
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    • 1997
  • Background : Endobronchial tuberculosis(ET) is still relatively common disease in Korea. We intended to evaluate the length of endobronchial lesion, peribronchial thickness, luminal irregularity and associated mediastinal lymph node enlargement with Chest CT to get information for such aggressive treatment as electrocautery, laser therapy and so on of bronchial stricture in ET, and also to compare the change of Chest CT finding with that of bronchoscopic finding after one month of anti-tuberculosis treatment. Method : We performed CT in 26 patients who were diagnosed as ET by bronchoscopy at Boramae Hospital from November 1991 to March 1996. After classifying ET into seven subtypes according to bronchoscopic finding, we analyzed the CT finding of each subtype. And we followed up the bronchoscopy, CT, and PIT after one month of anti-tuberculosis treatment, and compared the change of CT findings with those of bronchoscopic findings in nine patients. Results : Age of the patients was from 17 to 73 years old, and the ratio of male to female was 1 : 25 with absolute female predominance. The site(s) of bronchial involvement by tuberculosis is one in 14 cases, two in nine cases and three in one case, respectively, and the left main bronchus was the most frequently involved site (13 cases for multiple involvements and 7 cases for single involvement among 26 cases). The length of bronchial involvement by tuberculosis which was measured by CT was from 10 to 55 mm, and there was a tendency that the length of involved lesion in fibrostenotic type was shorter than that of actively caseating type. Bronchial stricture on CT was noticed in 25 (96%) cases and the range of severity was from total occlusion to near-normal and also showed wide variation even though the subtype of ET was same. The increase of peribronchial thickness which was measured by CT, was noticed in 21 cases (91%) among 23 cases (in which the measurement was possible), and there was no improvement of peribronchial thickness in those cases which showed little improvement in bronchial stricture despite anti-tuberculosis treatment. There was no difference in the luminal irregularity of involved bronchi on CT in relation to bronchoscopic subtypes. The mediastinal lymph node enlargement, defined as the diameter of lymph node was larger than 1cm on CT, was detected in 20 cases (77%), and right side was more frequently involved (L : R = 1 : 5.2). The CT finding usually showed extrinsic bronchial compression but showed direct invasion in two cases which were bronchoscopically classified as tumorous type. When follow-up bronchoscopy and CT was performed after one month of anti-tuberculosis treatment in nine patients, CT showed significant improvement in peribronchial thickness and mediastinal lymph node enlargement. Bronchial stricture was also improved in 6 cases but aggravated in 3 cases despite anti-tuberculosis therapy. In two cases which were classified as fibrostenotic type by bronchoscopy, CT showed significant improvement in bronchial stricture, interestingly. Conclusion : We concluded that the role of Chest CT was complimentary to bronchoscopy in ET, since CT was useful in evaluating the length of bronchial involvement, peribronchial thickness, and mediastinal lymph node enlargement.

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Studies on the Propagation of the Freshwater Prawn, Macrobrachium nipponense (De Haan) Reared in the Laboratory 2. Life History and Seedling Production (담수산 새우, Macrobrachium nipponense (De Haan)의 증${\cdot}$양식에 관한 생물학적 기초연구 2. 생활사 및 종묘생산에 관한 연구)

  • KWON Chin-Soo;LEE Bok-Kyu
    • Journal of Aquaculture
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    • v.5 no.1
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    • pp.29-67
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    • 1992
  • Life cycle and seed production of the freshwater prawn, Macrobrachium nipponense, were studied and the results are as follows : 1. Larval development : Embryos hatched out as zoea larvae of 2.06 mm in mean body length. The larvae passed through 9 zoea stages in $15{\~}20$ days and then metamorphosed into postlarvae measuring 5.68 mm in mean body length. Each zoea stage can be identified based on the shapes of the first and second antennae, exo- and endopodites of the first and second pereiopods, telson and maxillae. 2. Environmental requirements of zoea larvae : Zoea larvae grew healthy when fed with Artemia nauplii. Metamorphosing rate was $65{\~}72{\%}$ at $26{\~}28\%$ and $7.85{\~}8.28\%_{\circ}Cl.$. The relationship between the zoeal period (Y in days) and water temperature (X in $^{\circ}C$) is expressed as Y=46.0900-0.9673X. Zoeas showed best survival in a water temperature range of $26{\~}32^{\circ}C$ (optimum temperature $28^{\circ}C$), at which the metamorphosing rate into postlarvae was $54{\~}72\%$ The zoeas survived more successfully in chlorinity range of $4.12{\~}14.08{\%_{\circ}}Cl.$, (optimum chlorinity $7.6{\~}11.6\;{\%_{\circ}}Cl.$.), at which the metamorphosing rate was $42{\~}76{\%}$. The whole zoeal stages tended to be longer in proportion as the chlorinity deviated from the optimum range and particularly toward high chlorinity. Zoeas at all stages could not tolerate in the freshwater. 3. Environmental requirements of postlarvae and juveniles : Postlarvae showed normal growth at water temperatures between $24{\~}32^{\circ}C$ (optimun temperature $26{\~}28^{\circ}$. The survival rate up to the juvenile stage was $41{\~}63{\%}$. Water temperatures below $24^{\circ}C$ and above $32^{\circ}$ resulted in lower growth, and postlarvae scarcely grew at below $17^{\circ}C$. Cannibalism tended to occur more frequently under optimum range of temperatures. The range of chlorinity for normal growth of postlarvae and juveniles was from 0.00 (freshwater) to $11.24{\%_{\circ}}Cl.$, at which the survival rate was $32{\~}35\%$. The postlarvae grew more successfully in low chlorinities, and the best growth was found at $0.00\~2.21{\%_{\circ}}Cl.$. The postlarvae and juveniles showed better growth in freshwater but did not survive in normal sea water. 4. Feeding effect of diet on zoea Ilarvae : Zoea larvae were successfully survived and metamorposed into postlarvae when fed commercial artificial plankton, rotifers, and Artemia nauplii in the aquaria. However, the zoea larvae that were fed Artemia nauplii and reared in Chlorella mixed green water showed better results. The rate of metamorphosis was $68\~{\%}75$. The larvae fed cow live powder, egg powder, and Chlorella alone did not survive. 5. Diets of postlarvae, juveniles and adults : Artemia nauplii and/or copepods were good food for postlarvae. Juveniles and adults were successfully fed fish or shellfish flesh, annelids, corn grain, pelleted feed along with viscera of domestic animals or fruits. 6. Growth of postlarvae, juveniles and adults : Under favorable conditions, postlarvae molted every five or six days and attained to the juvenile stage within two months and they reached 1.78 cm in body length and 0.17 g in body weight. The juveniles grew to 3.52 cm in body length and 1.07 g in body weight in about four months. Their sexes became determinable based on the appearance of male's rudimental processes (a secondary sex character) on the endopodites of second pereiopods of males. The males commonly reached sexual maturity in seven months after attaining the postlarvae stage and they grew to 5.65 cm in body length and 3.41 g in body weight. Whereas the females attained sexual maturity within six to seven months, when they measured 4.93 cm in body length and 2.43 g in body weight. Nine or ten months after hatching, the males grew $6.62{\~}7.14$ cm in body length and $6.68{\~}8.36$ g in body weight, while females became $5.58{\~}6.08$ cm and $4.04{\~}5.54$ g. 7. Stocking density : The maximum stocking density in aquaria for successful survival and growth was $60{\~}100$ individuals/$\ell$ for zoeas in 30-days rearing (survival rate to postlarvae, $73{\~}80{\%}$) ; $100{\~}300$ individuals/$m^2$ for postlarvae of 0.57 cm in body length (survival rate for 120 days, $78{\~}85{\%}$) ; $40{\~}60$ individuals/$m^2$ for juveniles of 2.72 cm in body length (survival rate for 120 days, $63{\~}90{\%}$) : $20{\~}40$ individuals/$m^2$ for young prawns of 5.2 cm in body length (survival rate for 120 days, $62\~90{\%}$) ; and $10\~30$ individuals/$m^2$ for adults of 6.1 cm in body length (survival rate for 60 days, $73\~100{\%}$). The stocking density of juveniles, youngs and adults could be increased up to twice by providing shelters.

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Comparison of Nutrient Intakes of Korean Elderly People Living in Rural Area Between 24-hour Recall and Food Frequency Method (24시간회상법과 식품섭취빈도조사법을 이용한 농촌지역 노인의 영양소 섭취수준 비교)

  • Cho, Young-Eun;Lee, Soo-Lim;Cho, Eun-Hyun;Lomeda, Ria-Ann L;Kwak, Eun-Hee;Kim, Yang-Ha;Kwun, In-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.6
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    • pp.698-707
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    • 2006
  • Precise and correct assessment of nutrient intake using appropriate dietary intake method is necessary to improve the nutritional status of the target people group. It is more likely so in elderly people since their dietary habits and inadequate nutrient intakes are of special concern even worse in rural areas. Two popular methods of gathering dietary intake are 24-hour recall and food frequency method (or food frequency questionnaire). In the present study, we conducted both 24-hour recall and food frequency method on 120 rural elderly people $(aged\;65{\sim}74\;years)$, 62 male and 58 female. The dietary intakes were analyzed and the correlation of the dietary intake between 24-hour recall and food frequency method to determine the reliability between two methods. Also each nutrient intake was compared to recommended dietary allowance (RDA) or nutrient reference value (NRV) as appropriate. Even correlation did not show significance between the two methods except for dietary fiber intake (0.65 at p<0.01) and energy-yielding nutrients which mostly showed similar results with nutrient intake level. These support the possible reliability between 24-hours record and food frequency method that is also shown on the cases of most mineral and vitamin intakes. Thus, the food frequency method used in this study for the assessment of nutrient intakes of the elderly people would be reliable for the assessment of the nutrient intake along with the 24-hour recall. Also, the present study results suggested that rural female elderly people would be under optimal nutriture status due to the lower food intake measured by 24-hour recall. The optimal food frequency method would be considered to be developed for the precise nutrient assessment.

The Results of Hvperfractionated Radiation Therapy Combined with Taxol for Paraaortic Node Recurrence in Cervix Cancer (대동맥주위 림프절에 재발된 자궁경부암에서 Taxol을 병행한 과분할 방사선치료의 결과)

  • Kim, Jun-Sang;Jang, Ji-Young;Kim, Jae-Sung;Kim, Sam-Yong;Cho, Moon-June
    • Radiation Oncology Journal
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    • v.18 no.1
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    • pp.27-31
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    • 2000
  • Purpose : The aim of this study was to investigate treatment results, toxicity and efficacy of hypefractionated radiation therapy combined with paclitaxel for paraaortic node recurrence in cervix cancer. Materials and Methods: Between September 1997 to March 1999, 12 patients with paraaortic node recurrence in cervix cancer who previously received radical or postoperative radiotherapy were treated with hypefractionated radiation therapy combined with paclitaxel. Of these, 2 patients who irradiated less than 30 Gy were excluded, 10 patients were eligible for this study. Median age was 51 years. Initial FIGO stage was 1 stage IBI, 2 stage IIA, 7 stage IIB. For initial treatment, 7 patients received radical radiotherapy and 3 received postoperative radiotherapy. The paraaortic field encompassed the gross recurrent disease with superior margin at T12, and inferior margin was between L5 and S1 with gap for previously pelvic radiation field. The radiation field was initially anterior and posterior opposed field followed by both lateral field. The daily dose was 1.2 Gy, twice daily fractions, and total radiotherapy dose was between 50.4 and 60 Gy(median, 58.8 Gy). Concurrent chemotherapy was done with paclitaxel as a radiosensitizer. Dose range was from 20 mg/m$^{3}$ to 30 mg/m$^{3}$ (median, 25 mg/m$^{3}$), and cycle of chemotherapy was from 3 to 6 (median, 4.5 cycle). Follow-up period ranged from 3 to 21 months. Results : Interval between initial diagnosis and paraaortic node recurrence was range from 2 to 63 months (median, 8 months). The 1 year overall survival rate and median survival were 75$\%$ and 9.5 months, respectively. The 1 year disease free survival rate and median disease free survival were 30$\%$ and 7 months, respectively. At 1 month after treatment, 4 (40$\%$) achieved a complete response and 6 (60$\%$) experienced a partial response and all patients showed response above the partial response. There was distant metastasis in 6 patients and pelvic node recurrence In 2 patients after paraaortic node irradiation. There was 2 patients with grade 3 to 4 leukopenla and 8 patients with grade 1 to 2 nausea/ vomiting which was usually tolerable with antlemetic drug. There was no chronic complication in abdomen and pelvis during follow up period. Conclusion : hypefractionated radiation therapy combined with paclitaxel chemotherapy diosensitizer showed high response rate and few complication rate in paraaortic node recurrence in cervix cancer Therefore, present results suggest that hypefractionated radiation therapy combined with paclitaxel chemotherapy can be used as optimal treatment modality in this patients.

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Nutritional Studies for Improvement of Feeding on Korean Native Goat - Absorption of Nutrients in Rumen - (한국재래산양(韓國在來山羊)의 사양개선(飼養改善)에 관(關)한 연구(硏究) - 제일위((第一胃)에서의 영양소(營養素) 흡수(吸收)에 대(對)하여 -)

  • Kwon, Soon Ki
    • Korean Journal of Agricultural Science
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    • v.9 no.1
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    • pp.284-302
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    • 1982
  • Development of protein resources as food has been a big issue especially in Southeast Asia region, and intake of protein is also insufficient in Korea. To cope with this shortage of protein resources and its improvement together with increased production of high nutritive animal protein, studies were carried out on feeding of Korean native goats. In the experiments were made absorption of carbohydrate and volatile fatty acid in miniature rumen, and absorption of amino acid in rumen as in vivo were conducted as part of studies on nutritional absorption in rumen. Those nutritional for improvement of feeding and management as described above are summarized as following. 1. According to the result of test on the nutritional absorption of native goat by means of miniature rumen method, absorption ratio of VFA measured at 0.5, 1 and 2 hours after injection of nutrition showed propionic acid 70-86%, acetic acid 74-87%, and lactic acid 76-89%. In the absorption of organic substances, ethyl alcohol of 0.5% showed 29-87% and lactic acid of 0.1M showed 12-27% of absorption ratio. 2. Result of absorption measurement in rumen from L-type free amino acid injection in the content of rumen vein showed lower rate at menthionine-free group compared to whole-egg amino acid injection in the content of rumen vein showed lower rate at methioine-free group compared to whole-egg amino acid group, and high absorption ratio was observed at methionine 3 times group and urea added group. Deficiency of methionine caused no change of the content in mucous membranes. 3. Absorption of amino acid in rumen muscular layer showed equal tendency as in the mucous membrane without exerting any influence of methionine deficiency. At the methionine3-times group, content of methionine and glutamine were increased by 14.7 and 4.4 times as compared to whole-egg amino acid group, an absorption ratio of glutamine, proline and valine were increased at urea added group. 4. In general, concentration of amino acid in rumen vein plasma was lower than in rumen mucous membrane and muscular layer. Absorption ratio of amino acid is decreased due to methionine deficiency, and tripling of methionine or urea adding caused increment of amino acid. Absorption pattern is thus varied depending on the composition of amino acid. 5. At the urea added group, content of ammonia-N, amino-N and urea were increased in rumen muscular layer. As the inside of goat's rumen was unable to clean thoroughly, investigation was made on remaining bacteria, however, variation of ammonia-N was affected by these bacterial content. 6. Variation in rumen structure by differential absorption of amino acid was observed by general microscope and fluorescent microscope. According to the result of observation in the methionine 3 times group, single cylinder epithelium of mucous membrane showed rather thin, and it was thick at urea added group though no significant differences existed among test groups in submucous membrane and muscular layer.

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Prevalence of Enteyobius vermiculuris infection and preventive effects of masts treatment among children in rural and urban areas, and children in orphanages (농촌, 도시 및 집단생활 아동의 요충 감염과 집단 구충에 의한 예방 효과)

  • Kim, Jong-Su;Lee, Hae-Yong;An, Yeong-Gyeom
    • Parasites, Hosts and Diseases
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    • v.29 no.3
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    • pp.235-244
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    • 1991
  • An epidemiological study and mass treatments of Enterobius vermicularis infection among children near Wonju area of Kangwon province were carried out. The children were divided into 4 groups according to their residing localities; children in the mountainous area, rural area, urban area and in orphanage. They were examined by adhesive cellotape anal swab technique, and egg positive rates were obtained. The rates of egg reduction and re-infection rates after repeated mass treatments were also observed. The results obtained were as follows: 1. The overall egg Positive rate of E. vermicularis in the first screening was 19.9% (251 out of 1, 262 examinees; 19.7% in males and 20.1% in females). The positive rates were 13.0% in the mountainous area, 11 9% in the rural area, 15.1% in the urban (medium-sized) area and 61.9% in orphanages. 2. The highest positive rates were observed in the kindergarten children, and 1st and 2nd grade children of primary schools (26.2~32.2%), and the lowest rate (13.6%) in 6-year grade children of primary schools. 3. Cumulative detection rates from 3 repeated anal swabs at 4~5 days interval were higher (70.8%) than those from single anal swabs (50.0~59.2%). 4. Out of the examinees who showed the highest cumulative positive rate (70.8%), about 39.2% were consecutively positive in 3 anal swabs. Among different groups of children, the higher the total egg detection rates (87.5%), the higher the consecutive positive rates (71.9%) . 5. A total of 2, 609 (male : female=1 : 12.4) worms were collected from 17 egg-positive cases treated with anthelinintics. The mean number of worms per child was 153 (range: 4-824) . 6. The egg-positive cases in several studied groups (180 children) were treated with anthelmintics 6 times at 3-week intervals. In this case, the overall positive rate was decreased from 54.8% to 2.2% at 15 weeks after the treatments, but no complete negative conversion was experienced. However, in a group of children (154 children) including egg Positive and negative cases who were both treated with anthelmintics at 3-week interval, a complete egg-negative conversion was observed in the 9th week after treatments. 7. The egg-detection rate in the brothers or sisters of egg Positive children was 70.0% (28 out of 40 examined), and the egg-positive rate according to the family unit was 69.7%. In summarizing the above results, it is concluded that Enterobius vermicularis infection is still highly prevalent among children in Korea, and that repeated mass treatments of more than 3 times will be effective for control of this infection.

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The Clinical Features of Endobronchial Tuberculosis - A Retrospective Study on 201 Patients for 6 years (기관지결핵의 임상상-201예에 대한 후향적 고찰)

  • Lee, Jae Young;Kim, Chung Mi;Moon, Doo Seop;Lee, Chang Wha;Lee, Kyung Sang;Yang, Suck Chul;Yoon, Ho Joo;Shin, Dong Ho;Park, Sung Soo;Lee, Jung Hee
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.5
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    • pp.671-682
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    • 1996
  • Background : Endobronchial tuberculosis is definded as tuberculous infection of the tracheobronchial tree with microbiological and histopathological evidence. Endobronchial tuberculosis has clinical significance due to its sequela of cicatrical stenosis which causes atelectasis, dyspnea and secondary pneumonia and may mimic bronchial asthma and pulmanary malignancy. Method : The authors carried out, retrospectively, a clinical study on 201 patients confirmed with endobronchial tuberculosis who visited the Department of Pulmonary Medicine at Hangyang University Hospital from January 1990 10 April 1996. The following results were obtained. Results: 1) Total 201 parients(l9.5%) were confirmed as endobronchial tuberculosis among 1031 patients who had been undergone flexible bronchofiberscopic examination. The number of male patients were 55 and that of female patients were 146. and the male to female ratio was 1 : 2.7. 2) The age distribution were as follows: there were 61(30.3%) cases in the third decade, 40 cases(19.9%) in the fourth decade, 27 cases(13.4%) in the sixth decade, 21 cases(10.4%) in the fifth decade, 19 cases(9.5%) in the age group between 15 and 19 years, 19 cases(9.5%) in the seventh decade, and 14 cases(7.0%) over 70 years, in decreasing order. 3) The most common symptom, in 192 cases, was cough 74.5%, followed by sputum 55.2%, dyspnea 28.6%, chest discomfort 19.8%, fever 17.2%, hemoptysis 11.5%, in decreasing order, and localized wheezing was heard in 15.6%. 4) In chest X-ray of 189 cases, consolidation was the most frequent finding in 67.7%, followed by collapse 43.9%. cavitary lesion 11.6%, pleural effusion 7.4%, in decreasing order, and there was no abnormal findings in 3.2%. 5) In the 76 pulmanary function tests, a normal pattern was found in 44.7%, restrictive pattern in 39.5 %, obstructive pattern in 11.8%, and combined pattern in 3.9%. 6) Among total 201 patients, bronchoscopy showed caseous pseudomembrane in 70 cases(34.8%), mucosal erythema and edema in 54 cases(26.9%), hyperplastic lesion in 52 cases(25.9%), fibrous s.enosis in 22 cases(10.9%), and erosion or ulcer in 3 cases(1.5%). 7) In total 201 cases, bronchial washing AFB stain was positive in 103 cases(51.2%), bronchial washing culture for tuberculous bacilli in 55 cases(27.4%). In the 99 bronchoscopic biopsies, AFB slain positive in 36.4%. granuloma without AFB stain positive in 13.1%, chronic inflammation only in 36.4%. and non diagnostic biopsy finding in 14.1%. Conclusions : Young female patients, whose cough resistant to genenal antitussive agents, should be evaluated for endobronchial tuberculosis, even with clear chest roentgenogram and negative sputum AFB stain. Furthermore, we would like to emphasize that the bronchoscopic approach is a substantially useful means of making a differential diagnosis of atelectasis in older patients of cancer age. At this time we have to make a standard endoscopic classification of endobronchial tuberculosis, and well designed prospective studies are required to elucidate the effect of combination therapy using antituberculous chemotherapy with steroids on bronchial stenosis in patients with endobronchial tuberculosis.

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The Production and Correlation of Silica Induced Proinflammatory Cytokines and TGF-$\beta$ from Monocytes of Balb/C Mice (Balb/C mouse의 폐장대식세포에서 유리규산 자극에 의한 Proinflammatory Cytokine과 TGF-$\beta$의 생성 및 상관관계)

  • Ki, Shin-Young;Kim, Eun-Young;Kim, Mi-Ho;Uh, Soo-Taek;Kim, Yong-Hoon;Park, Choon-Sik;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.823-834
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    • 1998
  • Background: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica; they liberate the pro-inflammatory cytokines such as IL-1$\beta$, IL-6, TNF-$\alpha$ and fibrogenic cytokines, TGF-$\beta$ and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGF-$\beta$, a fibrogenic cytokine, have not been defined, yet. In this study, we investigated silica induced IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ production and the effect of IL-1$\beta$, IL-6, TNF-$\alpha$ on the production of TGF-$\beta$ from lung macrophages of Balb/C mice. Method: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica ($SiO_2$) in the various concentration for 2, 4, 8, 12, and 24 hours. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. Results: The production of IL-6 was not observed till 4 hours, and reached the peak levels at 8 hours after stimulation of silica. The production of TNF-$\alpha$ increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-$\beta$ production reached the peak levels at 24 hours. TNF-$\alpha$ upregulated the silica induced TGF-$\beta$ production. Silica induced TGF-$\beta$ production was blocked by pretreated anti-TNF-$\alpha$ antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours TNF-$\alpha$ and 12 hours in TGF-$\beta$. Conclusion: The results above suggest that silica induced the sequential production of IL-6, 1NF-$\alpha$ and TGF-$\beta$ from macrophages and TNF-$\alpha$ upregultaes the production of TGF-$\beta$ from silica-induced macrophages.

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The Effect of Nonspecific Endothelin-1 Receptor Blocker ($Bosentan^{(R)}$) on Paraquat Induced Pulmonary Fibrosis in Rat (Paraquat에 의한 백서의 폐섬유화증에서 비선택적 Endothelin-1 receptor blocker($Bosentan^{(R)}$)의 치료효과)

  • Jeong, Hye-Cheol;Jung, Ki-Hwan;Kim, Byung-Gyu;Lee, Seung-Heon;Kim, Min-Kyung;Kim, Chung-Yeul;Park, Sang-Myun;Lee, Sin-Hyung;Shin, Chol;Cho, Jae-Youn;Shim, Jae-Jeong;In, Kwang-Ho;Kim, Han-Gyum;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.2
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    • pp.182-195
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    • 2001
  • Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$l_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$1_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.

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