• Radiation Oncology Journal
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• v.27 no.4
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• pp.210-217
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• 2009

Purpose: To assess the influence of cyclooxygenase-2 (COX-2) expression on the survival of patients with a combination of rectal cancer and lymph node metastasis. Materials and Methods: The study included rectal cancer patients treated by radical surgery and postoperative radiotherapy at the Dong-A university hospital from 1998 to 2004. A retrospective analysis was performed on a subset of patients that also had lymph node metastasis. After excluding eight of 86 patients, due to missing tissue samples in three, malignant melanoma in one, treatment of gastric cancer around one year before diagnosis in one, detection of lung cancer after one year of diagnosis in one, liver metastasis in one, and refusal of radiotherapy after 720 cGy in one, 78 patients were analyzed. The immunohistochemistry for COX-2 was conducted with an autostainer (BenchMark; Ventana, Tucson, AZ, USA). An image analyzer (TissueMine; Bioimagene, Cupertino, CA, USA) was used for analysis after scanning (ScanScope; Aperio, Vista, CA, USA). A survival analysis was performed using the Kaplan Meier method and significance was evaluated using the log rank test. Results: COX-2 was stained positively in 62 patients (79.5%) and negatively in 16 (20.5%). A total of 6 (7.7%), 15 (19.2%), and 41 (52.6%) patients were of grades 1, 2, and 3, respectively for COX-2 expression. No correlation was found between being positive of COX-2 patient characteristics, which include age (<60-year old vs. $\geq$60), sex, operation methods (abdominoperineal resection vs. lower anterior resection), degrees of differentiation, tumor size (<5 cm vs. $\geq$5 cm), T stages, N stages, and stages (IIIa, IIIb, IIIc). The 5-year overall and 5-year disease free survival rates for the entire patient population were 57.0% and 51.6%, respectively. The 5-year overall survival rates for the COX-2 positive and negative patients were 53.0% and 72.9%, respectively (p=0.146). Further, the 5-year disease free survival rates for the COX-2 positive and negative patients were 46.3% and 72.7%, respectively (p=0.118). The 5-year overall survival rates were significantly different (p<0.05) for the degree of differentiation, N stage, and stage, whereas the 5-year disease free survival rates were significant for N stage and stage. Conclusion: Being positive for and the degree of COX-2 expression did not have a significant influence on the survival of rectal cancer patients with lymph node metastasis. However, N stage and stage did significantly influence the rateof survival. Further analysis of a greater sample size is necessary for the verification of the effect of COX-2 expression on the survival of rectal cancer patients with lymph node involvement.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.916-924
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• 1996

Bacground : Percutaneous needle aspiration biopsy (PCNA) is one of the most frequently used diagnostic methcxJs for intrathoracic lesions. Previous studies have reponed wide range of diagnostic yield from 28 to 98%. However, diagnostic yield has been increased by accumulation of experience, improvement of needle and the image guiding systems. We analysed the results of PCNA performed for one year to evaluate the diagnostic yield, the rate and severity of complications and factors affecting the diagnostic yield. Method : 287 PCNAs undergone in 236 patients from January, 1994 to December, 1994 were analysed retrospectively. The intrathoracic lesions was targeted and aspirated with 21 - 23 G Chiba needle under fluoroscopic guiding system. Occasionally, 19 - 20 G Biopsy gun was used for core tissue specimen. The specimen was requested for microbiologic, cytologic and histopathologic examination in the case of obtained core tissue. Diagnostic yields and complication rate of benign and malignant lesions were ca1culaled based on patients' chans. The comparison for the diagnostic yields according to size and shape of the lesions was analysed with chi square test (p<0.05). Results : There are 19.9% of consolidative lesion and 80.1% of nodular or mass lesion, and the lesion is located at the right upper lobe in 26.3% of cases, the right middle lobe in 6.4%, the right lower lobe 21.2%, the left upper lobe in 16.8%, the left lower lobe in 10.6%, and mediastinum in 1.3%. The lesion distributed over 2 lobes is as many as 17.4% of cases. There are 74 patients with benign lesions, 142 patients with malignant lesions in final diagnosis and confirmative diagnosis was not made in 22 patients despite of all available diagnostic methods. 2 patients have lung cancer and pulmonary tuberculosis concomittantly. Experience with 236 patients showed that PCNA can diagnose benign lesions in 62.2% (42 patients) of patients with such lesions and malignant lesions in 82.4% (117 patients) of patients. For the patients in whom the first PCNA failed to make diagnosis, the procedure was repeated and the cumulative diagnostic yield was increased as 44.6%, 60.8%, 62.2% in benign lesions and as 73.4%, 81.7%, 82.4% in malignant lesions through serial PCNA. Thoracotomy was performed in 9 patients with benign lesions and in 43 patients with malignant lesions. PCNA and thoracotomy showed the same pathologic result in 44.4% (4 patients) of benign lesions and 58.1% (25 patients) of malignant lesions. Thoracotomy confirmed 4 patients with malignat lesions against benign result of PCNA and 2 patients with benign lesions against malignant result of PCNA. There are 1.0% (3 cases) of hemoptysis, 19.2% (55 cases) of blood tinged sputum, 12.5% (36 cases) of pneumothorax and 1.0% (3 cases) of fever through 287 times of PCNA. Hemoptysis and blood tinged sputum didn't need therapy. 8 cases of pneumothorax needed insertion of classical chest tube or pig-tail catheter. Fever subsided within 48 hours in all cases. There was no difference between size and shape of lesion with diagnostic yield. Conclusion: PCNA shows relatively high diagnostic yield and mild degree complications but the accuracy of histologic diagnosis has to be improved.

• The Journal of Korean Society for Radiation Therapy
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• v.26 no.2
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• pp.225-232
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• 2014

Purpose : The purpose of this study was to evaluate the surface and superficial dose for patients requiring postmastectomy radiation therapy(PMRT) with different treatment techniques. Materials and Methods : Computed tomography images were acquired for the phantom(I'mRT, IBA) consisting of tissue equivalent material. Hypothetical chestwall and lung were outlined and modified. Five treatment techniques(Wedged Tangential; WT, 4-field IMRT, 7-field IMRT, TOMO DIRECT, TOMO HELICAL) were evaluated using only 6MV photon beam. GafChromic EBT3 film was used for dose measurements at the surface and superficial dose. Surface dose profiles around the phantom were obtained for each treatment technique. For superficial dose measurements, film were used inside the phantom and analyzed superficial region for depth from 1-6mm. Results : TOMO DIRECT showed the highest surface dose by 47~70% of prescribed dose, while 7-field IMRT showed the lowest by 35~46% of prescribed dose. For the WT, 4-field IMRT and 7-field IMRT, superficial dose were measured over 60%, 70%, and 80% for 1mm, 2mm, and 5mm depth, respectively. In case of TOMO DIRECT and TOMO HELICAL, over 75%, 80%, and 90% of prescribed dose was measured, respectively. Surface and superficial dose range were uniform in overall chestwall for the 7-field IMRT and TOMO HELICAL. In contrast, Because of the dose enhancement effect with oblique incidence, The dose was gradually increased toward the obliquely tangential angle for the WT and TOMO DIRECT. Conclusion : For PMRT, TOMO DIRECT and TOMO HELICAL deliver the higher surface and superficial doses than treatment techniques based linear accelerator. It showed adequate dose(over 75% of prescribed dose) at 1mm depth in skin region.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.191-202
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• 2000

Background: Bronchial asthma is characterized by airway hyperresponsiveness(BHR) and inflammation. The cyclooxygenase(COX) is believed to be one of the important enzymes in these inflammatory reactions. Recently, the COX was divided into two isoforms, COX1 and COX2. COX2 is induced by lipopolysaccharide and some cytokines at the inflammation site. Prostaglandin E2(PGE2), produced from COX2, may affect airway inflammation. The purpose of this study is to evaluate the effect of COX2 inhibitor on COX2 expression, plasma PGE2, airway resistance and histologic finding in an animal asthma model. Methods : Sprague-Dawley rats were divided into 3 groups. The normal control group did not receive any treatment, but the asthma control group was sensitized by ovalbumin but not treated with the COX2 inhibitor(nimesulide, Mesulid$^{(R)}$). The treatment group was sensitized and treated with nimesulide. Specific airway resistance(sRaw) before and after nimesulide ingestion was investigated. The PGE2 level in the plasma was examined and COX2 immunogold-silver stain on lung tissue was performed. Results: sRaw and eosionophilic infiltration on airway, which increased in the asthma control group, was compared to normal control(p=0.014). However, there was no difference in eosinophilic infiltration between asthma control and treatment groups(p=0.408) and no difference in COX2 expression on bronchiolar epithelium among the three groups. Plasma PGE2 levels were not statically different among the three groups. Conclusion: The role of COX2 in the allergen-induced BHR was not significant The effect of nimesulide was not observed on BHR, COX2 expression, and plasma PGE2 level. Therefore, COX2 may not be a major substance of allergic asthma.

• Journal of Life Science
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• v.24 no.2
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• pp.105-111
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• 2014

The purpose of this study was to characterize equine heat-shock protein (Hsp) genes and analyze their expression pattern in various horse tissues and blood leukocytes after exercise. In a previous study, RNA sequencing of blood and skeletal muscles of thoroughbreds before and after exercise was performed using differently expressed gene (DEG) analysis. Three Hsp genes (HspH1, Hsp90${\alpha}$ and Hsp70) were selected by DEG analysis and were found to be differentially expressed in either blood or muscle. To validate and extend previous observations on these genes, we performed RT-PCR analyses of horse tissue as well as real-time qPCR analyses of blood leukocytes after exercise. mRNA expression of these Hsp genes was found to be ubiquitous in the analyzed tissues (including thyroid, colon, skeletal muscle, cecum, kidney, spinal cord, heart, and lung). In addition, Hsp mRNA expression of these genes in extracted whole blood increased after 120 minutes of exercise compared to the baseline condition. These results are in agreement with the results of human and other experimental animals, suggesting that regulatory mechanisms that are responsible for upregulation of Hsp gene transcription may be conserved among species. Further investigations to correlate Hsp gene expression patterns with athletic performance or recovery processes after exercise are warranted.

• Journal of Preventive Medicine and Public Health
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• v.27 no.4 s.48
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• pp.711-734
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• 1994

Among chemical agents in herbicides, dioxin (2, 3, 7, 8-tetrachloro dibenzo-$\rho$-dioxin : TCDD), a chemical contaminant in herbicides sprayed during the Vietnam War has been known to be the major agent causing toxic effects. Approximately 320,000 korean soldiers participated the Vietnam War from 1964 to 1974. Although the potential hazards of the herbicides among Korean veterans exposed were implicated, the problem had not been a public issue until 1991 when Korean veterans were informed U.S. companies, the herbicides manufacturer payed fund, from which a trust fund for New Zealand and Australian Class members were established in 1985. After a series of appeals and demonstration by the Korean Veterans demanding medical care and compensation for their serious health damages, a bill of medical care and compensation for herbicides victims was promulgated in March 1993 and become effective from May 1993, This study was carried out with two major objectives : the first to understand the health problems caused from the herbicides by reviewing literatures published, and the second to examine the nature and extent of health impacts among Korean veterans exposed and to develop valid study methods for the major study by interviewing and reviewing records on a part of veterans (638 persons) registered and completed medical examination in Seoul Veterans Administration Hospital from June to October 1993. The results obtained are as followings: 1. The literature review of 107 papers revealed that 1) Dioxin is teratogenic, carcinogenic and affects almost all organs including nervous, endocrine, and reproductive systems in animal experiments. 2) The diseases showing evidence of causal association were Hodgkin's disease, non-Hodgkin's disease, lung cancer, lymphoma, soft tissue sarcoma, chloroacne and polyneuropathy when judged on the basis of consistency in study results and biological plausibility. 2. Interview and medical record review study on 638 veterans, though limited validity owing to lack of control group, crude estimates of dioxin exposure levels (no biomarkers measurable), and uncertainty of diagnosis, showed that: 1) Most of the study subject's were in their 40's of age and had been dispatched to Vietnam during the period from $1965{\sim}1970$ around one year. 2) Most frequently complained symptoms in medical examination were motor weakness (32%), sensory abnormalities in extremities (23%), skin diseases (22%), and pain in extremities (20%) whereas in Interview they were more frequent in order of skin problem (44%), motor weakness (38%), sensory abnormalities and pain in extremities(17% and 19% each). Kappa indices on the same category of complaints between two sources of information were variable and relatively low. 3) On medical examination, only a part of the 638 subjects had initial impression (442 pts) and final diagnosis (218 pts) suggesting decision making on diagnosis appeared to be difficult even with all available modern medical technologies: in initial impression disorders from peripheral and central neuropathy were predominant whereas in final diagnosis various types of skin disorder were most frequent 4) When dose-response relationship between several conditions (from questionnaire) and arbitrary exposure scores were examined by CMH linear trend test, spontaneous abortion, sexual problems and health problem of offsprings showed statistically significant linear trends. However, pregnancy, accident and suicidal attempts did not show any relationship in this study capacity. 5) Among complaints, psychosis and neurosis (anxiety, phobia) in interview study, and memory disorder and psychosis in medical record study revealed linear trend. 6) Skin disorder was the only condition showing linear trend in initial impression and none in final diagnosis on medical examination. Even though objective to select out dioxin-related disease or group of diseases from this study was not achieved the research experiences provided firm basis for developing various methodological approaches. 3. From this preliminary study we concluded that a larger scale major epidemiologic study on health impacts of herbicides among Korean veterans exposed is not only Indispensible but also well designed study with more valid exposure information and diagnosis may be able to establish causal relationship between certain groups of diseases and exposure to the herbicides among Korean veterans.

• The Journal of Korean Society for Radiation Therapy
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• v.24 no.2
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• pp.85-93
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• 2012

Purpose: It is essential to minimize the respiratory-induced motion of involved organs in the Tomotherapy for tumor located in the chest and abdominal region. However, the application of breathing control system to Tomotherapy is limited. This study was aimed to investigate the possible application of the ABCHES system and its efficacy as a means of breathing control in the tomotherapy treatment. Materials and Methods: Five subjects who were treated with a Hi-Art Tomotherapy system for lung, liver, gallbladder and pancreatic tumors. All patients undertook trained on two breathing methodes using an ABCHES, free breathing methode and shallow breathing methode. When the patients could carry out the breathing control, 4D-CT scan was a total of 10 4D tomographic images were acquired. A radiologist resident manually drew the tumor region, including surrounding nomal organs, on each of CT images at the inhalation phase, the exhalation phase and the 40% phase (mid-inhalation) and average CT image. Those CT images were then exported to the Tomotherapy planning station. Data exported from the Tomotherapy planning station was analyzed to quantify characteristics of dose-volume histograms and motion of tumors. Organ motions under free breathing and shallow breathing were examined six directions, respectively. Radiation exposure to the surrounding organs were also measured and compared. Results: Organ motion is in the six directions with more than a 5 mm displacement. A total of 12 Organ motions occurred during free breathing while organ motions decreased to 2 times during shallow breathing under the use of Abches. Based on the quantitative analysis of the dose-volume histograms shallow breathing showed lower resulting values, compared to free breathing, in every measure. That is, treatment volume, the dose of radiation to the tumor and two surrounding normal organs (mean doses), the volume of healthy tissue exposed to radiation were lower at the shallow breathing state. Conclusion: This study proposes that the use of ABCHES is effective for the Tomotherapy treatment as it makes shortness of breathing easy for patients. Respiratory-induced tumor motion is minimized, and radiation exposure to surrounding normal tissues is also reduced as a result.

• The Journal of Korean Society for Radiation Therapy
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• v.19 no.2
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• pp.107-112
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• 2007

Purpose: The pelvic phantom was fabricated in the following purposes: (1) Dose verification of IMRT plan using Eclipse planning computer, (2) to study the interface effect at the interface between rectal wall and air. The TLD can be inserted in the pelvic phantom to confirm the dose distribution as well as uncertainty at the interface. Materials and Methods: A pelvic phantom with the dimension of 30 cm diameter, 20 cm height and 20 cm thickness was fabricated to investigate the dose at the rectal wall. The phantom was filled with water and has many features like bladder, rectum, and prostate and seminal vesicle (SV). The rectum is made of 3 cm-dimater plastic pipe, and it cab be blocked by using a plug, and film can be inserted around the rectal wall. The phantom was scanned with Philips Brillance scanner and various organs such as prostate, SV, and rectal wall, and bladder wall were delineated. The treatment parameters used in this study are the same as those used in the protocols in the SNUH. TLD chips are inserted to the phantom to evaluate the dose distribution to the rectal wall (to simulate high dose gradient region), bladder wall and SV (to simulate the high dose region) and 2 spots in anterior surface (to simulate the low dose region). The TLD readings are compared with those of the planning computer (ECLIPSE, Varian, USA). Results: The target TLD doses represented as the prostate and SV show excellent agreements with the doses from the RTP within +/-3%. The rectal wall doses measured at the rectal wall are different from the those of the RTP by -11%. This is in literatures called as an interface effect. The underdosages at the rectal wall is independent of 3 heterogeneity correction algorithm in the Eclipse RTP. Also the low dose regions s represented as surface in this study were within +/-1%. Conclusion: The RTP estimate the dosage very accurately withihn +/-3% in the high dose (SV, or prostate) and low dose region (surface). However, the dosage at the rectal wall differed by as much as 11% (In literatures, the underdosage of 9$\sim$15% were reported). This range of errors occurs at the interface, for example, at the interface between lung and chest wall, or vocal cord. This interface effect is very important in clinical situations, for example, to estimate the NTCP (normal tissue complication probability) and to estimate the limitations of the current RTP system. Monte-carlo-based RTP will handle this issue correctly.

• Tuberculosis and Respiratory Diseases
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• v.47 no.2
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• pp.172-183
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• 1999

Background: Nitric oxide is a short-lived effector molecule derived from L-arginine by the nitric oxide synthase(NOS). Nitric oxide plays a role in a number of physiologic and pathophysiologic functions including host defense, edema formation, and regulation of smooth muscle tone. Some kinds of cells including macrophage are known to produce large quantities of nitric oxide in response to inflammatory stimuli such as interleukin-$1\beta$(IL-$1\beta$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), interferon-$\gamma$(IFN-$\gamma$) and lipopolysaccharide(LPS). Reactive oxygen species are also known to be important in the pathogenesis of acute cell and tissue injury such as acute lung injury model Methods: Using the RA W264.7 cells, we have examined the ability of oxidant hydrogen peroxide($H_2O_2$) to stimulate nitric oxide production and inducible NOS mRNA expression. Also, we have examined the effects of NOS inhibitors and antioxidants on $H_2O_2$ induced nitric oxide production. Results: Stimulation of RAW264.7 cells with combinations of 100 ng/ml IL-$1\beta$, 100 ng/ml TNF-$\alpha$, and 100 U/ml IFN-$\gamma$ or 100 U/ml IFN-$\gamma$ and $1{\mu}g/ml$ LPS induced the synthesis of nitric oxide as measured by the oxidation products nitrite($NO_2^-$) and nitrate($NO_3^-$). Addition of $250 {\mu}M-2$ mM $H_2O_2$ to the cytokines significantly augmented the synthesis of $NO_2^-$ and $NO_3^-$(p<0.05). When cells were incubated with increasing concentrations of $H_2O_2$ in the presence of IL-$1\beta$, TNF-$\alpha$ and IFN-$\gamma$ at constant level, the synthesis of $NO_2^-$ and $NO_3^-$ was dose-dependently increased(p<0.05). $N^G$-nitro-L-arginine methyl ester(L-NAME), dose dependently, significantly inhibited the formation of $NO_2^-$ and $NO_3^-$ in cells stimulated with LPS, IFN-$\gamma$ and $H_2O_2$ at constant level(p<0.05). Catalase significantly inhibited the $H_2O_2$-induced augmentation of cytokine-induced $NO_2^-$ and $NO_3^-$ formation(p<0.05). But, boiled catalase did not produce a significant inhibition in comparison with the native enzyme. Another antioxidant 2-mercaptoethanol and orthophenanthroline dose-dependently suppressed $NO_2^-$ and $NO_3^-$ synthesis(p<0.05). Northern blotting demonstrated that H:02 synergistically stimulated the cytokine-induced iNOS mRNA expression in RA W264.7. Conclusion: These results suggest that $H_2O_2$ contributes to inflammatory process by augmenting the iNOS expression and nitric oxide synthesis induced by cytokines.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.184-205
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• 1995

Background: Pulmonary toxicity by bleomycin has multiple mechanisms including direct tissue toxicity due to oxygen-derived free radicals and indirect toxicity through amplification of pulmonary inflammation. To evaluate the effect of chelators or free radical scavenger to lung damage induced by bleomycin, penicillamine as a copper chelator, deferoxamine as an iron chelator and vitamin E as a free radical scavenger were administered. Methods: Two hundred Wistar rats were divided into five groups: Control, bleomycin treated, bleomycin-penicillamine treated, bleomycin-deferoxamine treated, and bleomycin-vitamin E treated groups. Rats sacrificed on day 1, day 3, day 4, day 7, day 14, and day 28 after treatment. Bronchoalveolar lavage, light microscopic and immunohistologic studies for type I, III, IV collagens, fibronectin, laminin and NBD phallicidin were evaluated. Results: There was a significant increase in the total cell counts of bronchoalveolar lavage on day 1 from all treated animals and vitamin treated group showed an abrupt decrease in total cell counts with decrease of neutrophils on day 3. Bleomycin-vitamin E treated group had the least histologic changes such as pulmonary fibrosis. The alveolar basement membranes were positive for type IV collegen and laminin. Basement membranes of bleomycin, bleomycin-penicillamine, or bleomycin-deferoxamine treated groups were disrupted and fragmented on day 4 or 7. The bleomycin-vitamin E treated group had intact basement membranes until day 28. Conclusion: Bleomycin-induced pulmonary fibrosis was related to the severity of acute injury to oxygen radicals or activation of neutrophils and disruption of basement membrane. Vitamin E seemed to be the most effective antioxidant in the inhibition of bleomycin-induced pulmonary injury and fibrosis.