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Synthesis and Preliminary Evaluation of $9-(4-[^{18}F]Fluoro-3-hydroxymethylbutyl)$ Guanine $([^{18}F]FHBG)$ in HSV1-tk Gene Transduced Hepatoma Cell (9-(4-$[^{18}F]Fluoro-3-hydroxymethylbutyl)$guanine $([^{18}F]FHBG)$의 합성과 헤르페스 단순 바이러스 티미딘 키나아제 이입 간암 세포주에서의 기초 연구)

  • Moon, Byung-Seok;Lee, Tae-Sup;Lee, Myoung-Keun;Lee, Kyo-Chul;An, Gwang-Il;Chun, Kwon-Soo;Awh, Ok-Doo;Chi, Dae-Yoon;Choi, Chang-Woon;Lim, Sang-Moo;Cheon, Gi-Jeong
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.4
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    • pp.218-227
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    • 2006
  • Purpose: The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), $9-(4-[^{18}F]Fluoro-3-hydroxymethylbutyl)$guanine ($[^{18}F]FHBG$) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. Materials and Methods: Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with $K[^{18}F]/K2.2.2.$ in acetonitrile using N2-monomethoxytrityl-9-14-(tosyl)-3-monomethoxytritylmethylbutyl]guanine as a precursor, followed by deprotection with 1 N HCl. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of $[^{18}F]FHBG$ were performed, and was analyzed correlation between $[^{18}F]FHBG$ uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor bearing Balb/c-nude mouse model. Results: $[^{18}F]FHBG$ was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiothemical yield was about 20-25%) (corrected for decay), radiochemical purity was >95% and specific activity was around >55.5 $GBq/{\mu}\;mol$. Specific accumulation of $[^{18}F]FHBG$ was observed in HSV1-tk gene transduced MCA-tk cells but not in MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked $[^{18}F]FHBG$ was retained inside of cells. The uptake of $[^{18}F]FHBG$ was showed a highly significant linear correlation ($R^2=0.995$) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. Conclusion: $[^{18}F]FHBG$ appears to be a useful as non-invasive PET imaging substrate in HSV1-tk expressing hepatoma model.

Heavy metal concentration of plants in Baekdong serpentine area, western part of chungnam (충남 서부 백동 사문암지역 식물체의 중금속 함량)

  • 송석환;김명희;민일식;장인수
    • Journal of Korea Soil Environment Society
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    • v.4 no.2
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    • pp.113-125
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    • 1999
  • Heavy metal elements were analysed to assess degrees of heavy metal contents for the plants, M. sinensis, A. vulgaris and G. oldhamiana, from the Baekdong serpentine area within the western part of Chungnam. The area was divided into two sites ; serpentine area (SP, consisting of serpentinite, SP) and non-serpentine area (NSP, containing amphibole schist, AS and gneiss, GN). Their host rocks(R) and top soils(S) were also collected from the each site. As the results of the study, the plants contain high concentration of Ni Cr, Co in the SP and Fe, Zn in the AS and GN. Plants from the AS of the NSP contain mainly high content in the most of elements. Averages of Ni, Co and Cr for the plants decreased in the order of SP, AS and GN. In the total element contents, M. sinensis and A. vulgaris decreased in the order of Fe > Ni or Cr > Zn > Co > As > Sc within the SP and in the order of Fe > Zn > Cr > Ni, within the GN. Comparing among the parts of plants, root parts were higher in the most of elements than the above grounds. In the relative element ratios of plants collected from the SP and GN (SP/GN) M. sinensis was lower than A. vulgaris in the most of elements, suggesting that the M. sinenis shows low absorption within the infertile serpentine soil and high absorption within the fertile gneiss soil. In the element contents of the top soils and their host rocks, the SP shows higher Ni, Co and Cr contents than the others. Their total contents decreased from SP to AS and GN, suggesting that the soils reflect the composition of their host rocks. Total element contents of the SP decreased in the order of Fe> Cr or Ni> Co> Zn> As> Sc and, for the GN, in the order of Fe> Zn> Cr> Ni> Co or Sc, respectively. In the relative element ratios, R/S of the SP decreased in the order of Cr> As> Fe> Sc> Co> Ni> Zn and for the GN, in the order of Sc> Fe> Ni> Zn> Cr> Co. Comparing with plants within the each site, their top soils were higher than the plants in the most of elements. and their increase and decrease trends for each element are similar. Differences of element contents between the top soils and plants decreased in the order of SP, AS and GN. Plants of the GN were moi-e similar to their soils than those of the others, suggesting that each plant species show different absorptions within the different soils. Comparing with the plants of GN, higher Ni, Co, Cr contents within those of the SP and their survival within the infertile serpentine soil suggest that the M. sinensis, A vulgaris and G. oldhamiana may be the tolerance species in the serpentine soil. Comparisons with the upper crust show that M. sinensis, and A. vulgaris within the SP show high Hi and Cr contents. suggestive of hyperaccumulation. Upper results with the previous studies for the contaminated soils developed as parent materials with the serpentinites suggest additional studies for ecological behaviors for the plant and degrees of accumulations for the elements need to know phytoextraction of the heavy metal elements within the soils.

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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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Characteristics of Spatio-temporal Variation of the Water Quality in the Lower Keum River (금강 하류역에서 수질의 시공간적 변화특성)

  • YANG Han-Soeb;KIM Seong-Soo
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.23 no.3
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    • pp.225-237
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    • 1990
  • Various chemical constituents were measured from April to August 1988 at the down-ward 20 stations of Keum River, which is located in the Midwest of Korea, to understand the characteristics of water quality with respect to spatio-temporal variations of each constituent. The 24-hrs continuous measurements with 2-hrs interval were made simultaneously at station 2 near the estuary weir and station 9(Ganggyeong) of 35 km upstream from the weir in April. By the results observed for one day in April at station 2, salinity has a range of $7.88\~22.14\%_{\circ}$ and its temporal variability is identical to the pattern of tidal cycle in the neigh-bouring Kunsan Harbor. However, turbidity shows relatively high values only at an interval of 4~5 hours after the lowest salinity time, though hourly fluctuation of pH is very small. Silicate and dissolved inorganic nitrogen have inversively linear correlationships with salinity, implying the concentration of the two nutrients strongly regulated by estuarine mixing of sea and river waters. In contrast, phosphate sustains roughly a constant level over a wide salinity range and distinctly lower values than those corresponding to nitrate in the oceans. Such distributions of phosphate have been observed in some estuaries, and interpreted as driven by removal of dissolved phosphate into bottom sediments and the bufforing of phosphate by particulate matter. COD values at station 2 are relatively high in day-time(particularly afternoon) and in high-salinity periods. At station 9, saltwater intrusion was never found but water level changed to the extent of 2.5 m for one day. Although each parameter at this station exhibits very slight variations in their abundance for 24 hours compared with station 2, the contents of COD, silicate and ammonia are significantly higher than at station 2. Concentration of suspended matter is relatively high in the brackish water region up to $\~20$ km above the river mouth, probably due to strong tidal stirring of the bottom de-posits. Also, relatively high pH, COD and $O_2$ saturation at the upward stations of $40\~50$ km from the weir are presumably attributable to active photosynthesis of plants in the region. In general, COD and nutrients except phosphate are higher values at the upper stations than in the estuary zone, and show the highest abundances in July nearly at all stations. Finally, in the estuarine region tidal mixing of sea-river waters seems to be an important factor controlling the distributions of turbidity, COD, silicate and nitrate as well as salinity. However, water quality in the upward fresh-water zone is remarkably variable according to months or seasons.

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Bronchial Brushing and Bronchial Washing for Diagnosis of Central Lung Cancer (중심형 폐암 진단을 위한 기관지찰과술과 기관지세척술)

  • Park, Ki-Su;Park, Jae-Yong;Cha, Seung-Ick;Son, Ji-Woong;Kim, Kwan-Young;Kim, Jeong-Seok;Chae, Sang-Cheol;Kang, Tae-Kyong;Park, Tae-In;Kim, Chang-Ho;Jung, Tae-Hoon
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.6
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    • pp.817-825
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    • 1999
  • Background : Forceps biopsy, bronchial brushing, and bronchial washing are used in conjunction with bronchoscopy to provide specimens for histologic and cytologic analysis in patients with suspected lung cancer. This study was performed to evaluate how many times brushing should be done and how much fluid should be used during bronchial washing for increasing diagnostic yield, and to evaluate which combination of these procedures gives the highest diagnostic yield. Methods : Forty patients, with suspected lung cancer, who had bronchoscopically visible lesions were enrolled in this prospective study. During one bronchoscopic examination four forceps biopsies, four bronchial brushings, and bronchial washing were done in all patients. The patients were divided into four groups by the amount of normal saline used for bronchial washing; group I, 10 ml ; group II, 20ml ; group III 30ml, and group IV, 40ml. We analyzed the results in 36 patients confirmed as lung cancer. Results : The diagnostic sensitivity of bronchial washing before and after forceps biopsy and bronchial brushing were 36% and 28%, respectively. The cumulative diagnostic sensitivity of bronchial washing was 47% and significantly higher than that of bronchial washing before or after forceps biopsy and bronchial brushing (p<0.05). The diagnostic sensitivity of bronchial washing with saline of 30ml was significantly higher than that of bronchial washing with saline of 10ml or 20ml (p<0.05). The diagnostic sensitivity of the first brushing was 75%, the second brushing 78%, the third brushing 83%, and the fourth brushing 67%. With repeated brushing up to three times, the diagnostic sensitivity increased to 92% (p<0.05). However, inclusion of the fourth brushing did not give a further increase of the diagnostic sensitivity. The diagnostic sensitivity of forceps biopsy was 86%. The diagnostic sensitivities of forceps biopsy by the type of bronchial lesion were as follows: tumor, 88%; infiltration, 67%; infiltration with nodularity, 80%; and collapse, 100%. The combination of forceps biopsy and bronchial washing gave a diagnostic sensitivity of 89%. The diagnostic sensitivity of combining forceps biopsy with bronchial brushing was 97%. Addition of bronchial washing did not increase the diagnostic yield over forceps biopsy and bronchial brushing. Conclusion : In patients with central lung cancer, forceps biopsies and repeated brushings up to three times should be done for maximal diagnostic yield.

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Balloon dilatation for bronchial stenosis in Endobronchial Tuberculosis (협착성 기관지 결핵의 풍선카테타요법(II))

  • Ohn, Joon-Sang;Lee, Young-Sil;Yoon, Sang-Won;Son, Hyung-Dae;Kim, Chang-Seon;Seo, Jee-Young;Park, Mi-Ran;Rheu, Nam-Soo;Cho, Dong-Ill;Kwak, Byung-Kook
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.5
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    • pp.701-708
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    • 1996
  • Background : To evaluate the effect of the balloon dilatation in tuberculous bronchial stenosis, we performed balloon dilatation in 13 cases which had airway obstruction in main bronchus with the impairment of pulmonary function. Material and Methods: Thirteen women with tuberculous bronchial stenosis(9cases : left main bronchus, 4 cases: right main bronchus) underwent fluoroscopically guided balloon dilatation under the local anesthesia. Among the these patient, 9 cases were active endobronchial tuberculosis, and 4 cases were inactive. Immediate and long term follow-up(average 15.6months) assessments were done focused on change on PIT. The increase of FVC or FEV1 more than 15% after the procedure was considered effective. Complications after dilatation were evaluated in all patients. Result : 1) There were an decrease of self-audible wheezing in 75%(6/8), improvement of dyspnea in 62.5%(5/8), improvement of cough and expectoration in 50%(3/6), and improvement of chest discomfort in 50%(1/2). 2) Significant improvement of PFT was noted in 42.9%(3/7) of which respiratory symptoms duration was below 6 months. 8m, significant improvement of PFT was noted in only 25%(1/4) of which respiratory symptoms duration was above 12 months. 3) Active stage was 69.2%(9/13) and inactive was 30.8%(4/13). There was an significant improvement of PFT in 44.4%(4/9) of active stage, but, only 25%(1/4) of inactive stage was improved. 4) In 61.5%(8/13), FVC and FEV1 were increased to 35.5%, and 22.2% at post-dilatation 7 days. After 1 month later, FVC and FEV1 were increased to 54.7%, and 31.8% in 5 cases(38.5%). 4 cases in which long-term follow-up(average 19.8months) was possible the improvement of FVC, and FEV1 were 30.5%, and 10.1%. 5) Just after balloon dilatation therapy, transient leukocytosis or fever was noted in 30.8%(4/13), and blood-tinged sputum was noted in 30.8%(4/13). However, serious complication, such as pneumothorax, pneumomediastinum or mediastinitis, was not noted. Conclusion : We conclude that tuberculous bronchial stenosis, which is on active stage, and short dulation of respiratory symptoms was more effective on balloon dilatation than inactive stage or long duration of respiratory symptoms. Furthermore, balloon dilatation is easier, much less invasive and expensive than open surgery. and cryotherapy or photoresection. Because of these advantage, we think that balloon dilatation could be the first choice for treating bronchial stenosis and could be done at first in early stage if unresponsiveness with steroid therapy is observed.

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THE EFFECTS OF THE PLATELET-DERIVED GROWTH FACTOR-BB ON THE PERIODONTAL TISSUE REGENERATION OF THE FURCATION INVOLVEMENT OF DOGS (혈소판유래성장인자-BB가 성견 치근이개부병변의 조직재생에 미치는 효과)

  • Cho, Moo-Hyun;Park, Kwang-Beom;Park, Joon-Bong
    • Journal of Periodontal and Implant Science
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    • v.23 no.3
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    • pp.535-563
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    • 1993
  • New techniques for regenerating the destructed periodontal tissue have been studied for many years. Current acceptable methods of promoting periodontal regeneration alre basis of removal of diseased soft tissue, root treatment, guided tissue regeneration, graft materials, biological mediators. Platelet-derived growth factor (PDGF) is one of polypeptide growth factor. PDGF have been reported as a biological mediator which regulate activities of wound healing progress including cell proliferation, migration, and metabolism. The purposes of this study is to evaluate the possibility of using the PDGF as a regeneration promoting agent for furcation involvement defect. Eight adult mongrel dogs were used in this experiment. The dogs were anesthetized with Pentobarbital Sodium (25-30 mg/kg of body weight, Tokyo chemical Co., Japan) and conventional periodontal prophylaxis were performed with ultrasonic scaler. With intrasulcular and crestal incision, mucoperiosteal flap was elevated. Following decortication with 1/2 high speed round bur, degree III furcation defect was made on mandibular second(P2) and fourth(P4) premolar. For the basic treatment of root surface, fully saturated citric acid was applied on the exposed root surface for 3 minutes. On the right P4 20ug of human recombinant PDGF-BB dissolved in acetic acid was applied with polypropylene autopipette. On the left P2 and right P2 PDGF-BB was applied after insertion of ${\beta}-Tricalcium$ phosphate(TCP) and collagen (Collatape) respectively. Left mandibular P4 was used as control. Systemic antibiotics (Penicillin-G benzathine and penicillin-G procaine, 1 ml per 10-25 1bs body weight) were administrated intramuscular for 2 weeks after surgery. Irrigation with 0.1% Chlorhexidine Gluconate around operated sites was performed during the whole experimental period except one day immediate after surgery. Soft diets were fed through the whole experiment period. After 2, 4, 8, 12 weeks, the animals were sacrificed by perfusion technique. Tissue block was excised including the tooth and prepared for light microscope with H-E staining. At 2 weeks after surgery, therer were rapid osteogenesis phenomenon on the defected area of the PDGF only treated group and early trabeculation pattern was made with new osteoid tissue produced by activated osteoblast. Bone formation was almost completed to the fornix of furcation by 8 weeks after surgery. New cementum fromation was observed from 2 weeks after surgery, and the thickness was increased until 8 weeks with typical Sharpey’s fibers reembedded into new bone and cementum. In both PDGF-BB with TCP group and PDGF-BB with Collagen group, regeneration process including new bone and new cementum formation and the group especially in the early weeks. It might be thought that the migration of actively proliferating cells was prohibited by the graft materials. In conclusion, platelet-derived growth factor can promote rapid osteogenesis during early stage of periodontal tissue regeneration.

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A Study of Endothelium-dependent Pulmonary Arterial Relaxation and the Role of Nitric oxide on Acute Hypoxic Pulmonary Vasoconstriction in Rats (흰쥐 폐동맥의 내피세포의존성 혈관이완과 급성 저산소성 폐동맥수축에서 산화질소의 역할)

  • In, Kwang-Ho;Lee, Jin-Goo;Cho, Jae-Youn;Shim, Jae-Jung;Kang, Kyung-Ho;Yoo, Se-Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.3
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    • pp.231-238
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    • 1994
  • Backgroud: Since the demonstration of the fact that vascular relaxation by acetylcholine(Ach) results from the release of relaxing factor from the endothelium, the identity and physiology of this endothelium-derived relaxing factor(EDRF) has been the target for many researches. EDRF has been identified as nitric oxide(NO). With the recent evidences that EDRF is an important mediator of vascular tone, there have been increasing interests in defining the role of the EDRF as a potential mediator of hypoxic pulmonary vasoconstriction. But the role of EDRF in modulating the pulmonary circulation is not compeletely clarified. To investigate the endothelium-dependent pulmonary vasodilation and the role of EDRF during hypoxic pulmonary vasoconstriction, we studied the effects of $N^G$-monomethyl-L-arginine(L-NMMA) and L-arginine on the precontracted pulmonary arterial rings of the rat in normoxia and hypoxia. Mothods: The pulmonary arteries of male Sprague Dawley(300~350g) were dissected free of surrounding tissue, and cut into rings. Rings were mounted over fine rigid wires, in organ chambers filled with 20ml of Krebs solution bubbled with 95 percent oxygen and 5 percent carbon dioxide and maintained at $37^{\circ}C$. Changes in isometric tension were recorded with a force transducer(FT.03 Grass, Quincy, USA) Results: 1) Precontraction of rat pulmonry artery with intact endothelium by phenylephrine(PE, $10^{-6}M$) was relaxed completely by acetylcholine(Ach, $10^{-9}-10^{-5}M$) and sodium nitroprusside(SN, $10^{-9}-10^{-5}M$), but relaxing response by Ach in rat pulmonary artery with denuded endothelium was significantly decreased. 2) L-NMMA($10^{-4}M$) pretreatment inhibited Ach($10^{-9}-10^{-5}M$)-induced relaxation, but L-NMMA ($10^{-4}M$) had no effect on relaxation induced by SN($10^{-9}-10^{-5}M$). 3) Pretreatment of the L-arginine($10^{-4}M$) significantly reversed the inhibition of the Ach ($10^{-9}-10^{-5}M$)-induced relaxation caused by L-NMMA($10^{-4}M$) 4) Pulmonary arterial contraction by PE($10^{-6}M$) was stronger in hypoxia than normoxia but relaxing response by Ach($10^{-9}-10^{-5}M$) was decreased, 5) With pretreatment of L-arginine($10^{-4}M$), pulmonary arterial relaxation by Ach($10^{-9}-10^{-5}M$) in hypoxia was reversed to the level of relaxation in normoxia. Conclusion: It is concluded that rat pulmonary arterial relaxation by Ach is dependent on the intact endothelium and is largely mediated by NO. Acute hypoxic pulmonary vasoconstriction is related to the suppression on NO formation in the vascular endothelium.

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An Appreciation of Functional Role of Macrophage in the Acute Lung Injury in the Neutropenic Rat. (호중구 감소증을 보이는 백서의 급성폐손상에서 대식세포의 기능적 역할)

  • Kim, Yong-Hoon;Ki, Sin-Young;Im, Keon-Il;Moon, Seung-Hyug;Cheong, Seung-Whan;Kim, Hyeon-Tae;Uh, Soo-Taek;Park, Choon-Sik;Jin, Byung-Won
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.2
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    • pp.379-390
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    • 1997
  • Background : It has long been suggested that neutrophils and their products are implicated as the central mediators of the acute lung injuries. Contrary to the dominant role of neutrophils in ARDS, many cases of ARDS has occurred in the setting of severe neutropenia without pulmonary neutrophil infiltration. Therefore it is certain that effector cell(s) other than neutrophil play an important role in the pathogenesis of ARDS. This experiment was performed to define the mechanism of ARDS in the setting of neutropenia, 1) by comparing the severity of endotoxin-induced lung injury, 2) by measurement of hydrogen peroxide production and cytokine concentration in the bronchoalveolar lavage cells and fluids obtained from different rats with and without cyclophosphamide-pretreatment. Method : The male Sprague-Dawleys were divided into the normal control (NC)-, endotoxin (ETX)-, and cyclophosphamide (CPA)-group in which neutropenia was induced by injecting cyclophosphamide intraperitoneally. Acute lung injury was evoked by injecting lipopolysaccharide (LPS) into a tail vein. The bronchoalveolar lavage (BAL) was performed at 3 and 6 hour after administration of LPS to measure the change of cell counts and concentrations of protein and cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Hydrogen peroxide (HPO) production from BAL cells was measured at 6 hour after LPS administration by phenol red microassay with and without zymosan stimulation. Results : The results were as follows. A change of leukocyte counts in the peripheral blood after treatment with CPA : More than 95% of total leukocytes and neutrophils were reduced after CPA administration, resulting in severe neutropenia. A change of BAL cells : In the ETX-group, the number of total cells (p < 0.01) and of macrophage and neutrophil (p < 0.05) were increased at 3 and 6 hour after LPS administration compared to those of NC-group. In the CPA-group, the number of total leukocyte and macrophage were not changed after LPS administration, but neutrophil counts were significantly reduced and it took part in less than 0.1% of total BAL cells (p < 0.01 vs NC-group). BAL cells in this group were almost all macrophages (99.7%). A change of protein concentration in the BALF : In the ETX-group, protein concentration was increased at 3 hour and was more increased at 6 hour after LPS administration (p < 0.05 and < 0.01 vs NC-group, respectively). In the CPA-group, it was also significantly elevated at 3 hour after LPS administration (p < 0.05 vs NC-group), but the value was statistically not different from that of ETX-group. The value measured at 6 hour after LPS administration in the CPA-group became lower than that of ETX-group (p < 0.05), but showed still a higher value compared to that of NC-group (p < 0.05). A change of cytokine concentration in the BALF : TNF -alpha and IL-6 were elevated in the ETX - and CPA-group compared to those of NC-group at both time intervals. There was no statistical difference in the values of both cytokines between the ETX- and CPA-groups. Measurement of hydrogen peroxide production from BAL cells : There was no intergroup difference of HPO production from resting cells. HPO production after incubation with opsonized zymosan was significantly elevated in all groups. The percent increment of HPO production was highest in the ETX-group (89.0%, p < 0.0008 vs NC-group), and was 42.85 in the CPA-group (p = 0.003 vs NC-group ). Conclusion : Acute lung injury in the setting of neutropenia might be caused by functional activation of resident alveolar macrophages.

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Efficacy and Safety of Early Bronchoscopy in Patients with Hemoptysis (객혈환자에서 조기기관지경의 유용성 몇 안정성)

  • Kim, Ho-Cheol;Cheon, Eun-Mee;Chung, Man-Pyo;Kim, Ho-Joong;Choi, Dong-Chull;Kwon, O-Jung;Rhee, Chong-H.;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.2
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    • pp.391-400
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    • 1997
  • Background : Bronchoscopy is an essential procedure for identifying the bleeding site and evaluating cause of hemoptysis. However, it is controversial regarding to the timing of bronchoscopy in patients with hemoptysis. Early bronchoscopy, which was performed during hemoptysis or with 48hour after cessation of bleeding, was better for identifying the site of bleeding compared with delayed bronchoscopy, which was performed 48 hours after cessation of bleeding. The diagnostic yield of identifying the bleeding site by bronchoscopy was variable in reported literature and the safety of early bronchoscopy was not mentioned in previous literature. Therefore, we evaluated the efficacy and safety of early bronchoscopy in patients with hemoptysis. Method : From October 1994 to August 1996 in Samsung Medical Center, bronchoscopy was performed in patients with hemoptysis. Early bronchoscopy was performed prospectively during hemoptysis or within 48 hours after cessation of bleeding from May 1995 to August 1996. Delayed bronchoscopy group included patients who did not received early bronchoscopy at the same period or in whom bronchoscopy was performed 48 hour after cessation of bleeding from October 1994 to May 1995. Results : Early bronchoscopy group was performed 73 times in 71 patients. Delayed bronchoscopy was performed in 57 times in 55 patients. There was no difference as to amount and underlying cause of hemoptysis between both groups. Indentification of bleeding site by visualizing active bleeding was significantly higher in early bronchoscopy (38.3%) than delayed bronchoscopy group (8.7%)(p < 0.05). Indentification of bleeding site by bleeding after clot removal was 8 in early and 10 in delayed bronchoscopy. Indentification of bleeding site by visualizing active bleeding and bleeding after clot removal was 36 in early and 15 patients in delayed bronchoscopy(p > 0.05). Causes of hemoptysis was found in 18 patients in early and 16 patients in delayed bronchoscopy group. patients who had early bronchoscopy underwent surgery. We diagnosed the site of bleeding in 4 patients preoperatively. In 3 patients we made a treatment plan promptly right after bronchoscopy. Among early bronchoscopy group, bleeding over 100cc during bronchoscopy occurred in 2 patients. In early bronchoscopy group there was no other major complication during bronchoscopy. Conclusion : In patients with hemoptysis, early bronchoscopy which performed within 48 hours after cessation of bleeding was more effective procedure for identifying the bleeding site than delayed bronchoscopy which was performed after 48 hour cessation of bleeding.

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