• Radiation Oncology Journal
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• v.20 no.3
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• pp.246-252
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• 2002

Purpose : It has been recognized that interaction of the Fas : Fas ligand plays an important role in radiation-induced apoptosis. The purpose of this study was to investigate the role of Fas mutation in radiation-induced apoptosis in vivo. Materials and Method : Mice with mutations in Fas, $MRL/Mpj-Fas^{Ipr}$, and its normal control, MRL/Mpj, were used in this study. Eight-week old male mice were given whole body radiation. After irradiation, the mice were killed and their spleens were collected at different time intervals. Tissue samples were stained with hematoxylin-eosin and the numbers of apoptotic cells were scored. Regulating molecules of apoptosis including p53, Bcl-2, Bax, $Bcl-X_L,\;and\;Bcl-X_S$ were also analyzed by Western blotting. Results : At 25 Gy irradiation, the level of apoptosis reached the peak value at 8 hr after radiation and recovered to the normal value at 24 hr after radiation in MRL/Mpj mice. In contrast, the peak apoptosis level appeared at 4 hr after radiation in $MRL/Mpj-Fas^{Ipr}$. At 8 hr after radiation, the levels of apoptosis in MRL/Mpj mice and $MRL/Mpj-Fas^{Ipr}$ mice were $52.3{\pm}7.8\%\;and\;8.0{\pm}8.6\%$, respectively (p<0.05). The expression of apoptosis regulating molecules, p53, $Bcl-X_L\;and\;Bcl-X_S$, increased in MRL/Mpj mice in response to radiation; p53 with a peak level of 3-fold at 8 h, $Bcl-X_L$ with a peak level of 3.3-fold at 12 h, and $Bcl-X_S$ with a peak level of 3-fold at 12 h after 25 Gy radiation. Bcl-2 and Bax did not show significant change in MRL/Mpj mice. However in $MRL/Mpj-Fas^{Ipr}$ mice, the expression levels of p53, Bcl-2, Bax, $BCl-X_L\;and\;BCl-X_S$ showed no significant change. Conclusion : The level of radiation-induced apoptosis was lower in Fas mutated mice, Ipr, than in control mice. This seemed to be related to the lack of radiation-induced p53 activation in the Ipr mice. This result suggests that Fas plays an important role in radiation-induced apoptosis in vivo.

• Journal of the Korean Orthopaedic Association
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• v.54 no.1
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• pp.1-8
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• 2019

Globally, the elderly population is increasing rapidly, which means that the number of deformity correction operations for elderly spine deformity patient has increased. On the other hand, for aged patients with deformity correction operation, preoperative considerations to reduce the complications and predict a good clinical outcome are not completely understood. First, medical comorbidity needs to be evaluated preoperatively with the Cumulative Illness Rating Scale for Geriatrics or the Charlson Comorbidity Index scores. Medical comorbidities are associated with the postoperative complication rate. Managing these comorbidities preoperatively decreases the complications after a spine deformity correction operation. Second, bone densitometry need to be checked for osteoporosis. Many surgical techniques have been introduced to prevent the complications associated with posterior instrumentation for osteoporosis patients. The preoperative use of an osteogenesis inducing agent - teriparatide was also reported to reduce the complication rate. Third, total body sagittal alignment need to be considered. Many elderly spine deformity patients accompanied degenerative changes and deformities at their lower extremities. In addition, a compensation mechanism induces the deformed posture of the lower extremities. Recently, some authors introduced a parameter including total body sagittal alignment, which can predict the clinical outcome better than previous parameters limited to the spine or pelvis. As a result, total body sagittal alignment needs to be considered for elderly spine deformity patients after a deformity correction operation. In conclusion, for elderly spine deformity patients, medical comorbidities and osteoporosis need to be evaluated and managed preoperatively to reduce the complication rate. In addition, total body sagittal alignment needs to be considered, which is associated with better clinical outcomes than the previous parameters limited to the spine or pelvis.

• Korean Journal of Radiology
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• v.21 no.7
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• pp.880-890
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• 2020

Objective: Patients with chronic obstructive pulmonary disease (COPD) are known to be at risk of osteoporosis. The purpose of this study was to evaluate the association between thoracic vertebral bone density measured on chest CT (D_Thorax) and clinical variables, including survival, in patients with COPD. Materials and Methods: A total of 322 patients with COPD were selected from the Korean Obstructive Lung Disease (KOLD) cohort. D_Thorax was measured by averaging the CT values of three consecutive vertebral bodies at the level of the left main coronary artery with a round region of interest as large as possible within the anterior column of each vertebral body using an in-house software. Associations between D_Thorax and clinical variables, including survival, pulmonary function test (PFT) results, and CT densitometry, were evaluated. Results: The median follow-up time was 7.3 years (range: 0.1-12.4 years). Fifty-six patients (17.4%) died. D_Thorax differed significantly between the different Global Initiative for Chronic Obstructive Lung Disease stages. D_Thorax correlated positively with body mass index (BMI), some PFT results, and the six-minute walk distance, and correlated negatively with the emphysema index (EI) (all p < 0.05). In the univariate Cox analysis, older age (hazard ratio [HR], 3.617; 95% confidence interval [CI], 2.119-6.173, p < 0.001), lower BMI (HR, 3.589; 95% CI, 2.122-6.071, p < 0.001), lower forced expiratory volume in one second (FEV₁) (HR, 2.975; 95% CI, 1.682-5.262, p < 0.001), lower diffusing capacity of the lung for carbon monoxide corrected with hemoglobin (DL_CO) (HR, 4.595; 95% CI, 2.665-7.924, p < 0.001), higher EI (HR, 3.722; 95% CI, 2.192-6.319, p < 0.001), presence of vertebral fractures (HR, 2.062; 95% CI, 1.154-3.683, p = 0.015), and lower D_Thorax (HR, 2.773; 95% CI, 1.620-4.746, p < 0.001) were significantly associated with all-cause mortality and lung-related mortality. In the multivariate Cox analysis, lower D_Thorax (HR, 1.957; 95% CI, 1.075-3.563, p = 0.028) along with older age, lower BMI, lower FEV₁, and lower DL_CO were independent predictors of all-cause mortality. Conclusion: The thoracic vertebral bone density measured on chest CT demonstrated significant associations with the patients' mortality and clinical variables of disease severity in the COPD patients included in KOLD cohort.

• Tuberculosis and Respiratory Diseases
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• v.51 no.4
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• pp.303-314
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• 2001

Background : Matrix metalioproteinase(MMP)-2 and MMP-9 have been known to play an important role in cell migration and the tissue remodeling process by type IV collagen lysis, a major component of the basement membrane. Intra-alveolar fibrosis, secondary to an injury to the basement membrane of the alveolar epithelial lining, is a major process in the pathogenesis of idiopathic pulmonary fibrosis(IPF). Therefore, MMP-2 and MMP-9 was hypothesized to play an important role in IPF pathogenesis. As a result, their level may reflect the activity or prognosis. Method : Forty one progressive IPF patients(age $59.82{\pm}1.73$ years, M:F=23:18), 16 patients with stable IPF for more than one year without therapy(age : $63.6{\pm}2.8$ years, M:F=13:3), and 7 normal controls were enrolled in this study. The MMP-2 and MMP-9 levels in the BAL fluid and alveolar macrophage conditioned media(AM-CM) were measured by zymography and the TIMP-1 level was measured by ELISA. Results : 1) The MMP-2 level in BALF was highest in the progressive IPF group ($1.36{\pm}0.28$) followed by the stable group ($0.46{\pm}0.13$) and the controls ($0.08{\pm}0.09$), which was statistically significant. The MMP-9 level of the IPF ($0.31{\pm}0.058$) and the stable group ($0.22{\pm}0.078$) were higher than that of the control group ($0.002{\pm}0.004$). In the AM-CM, only MMP-9 was detected, which was significantly higher in IPF group ($0.80{\pm}0.1O$) than in the control group($0.23{\pm}0.081$). The TIMP-1 level was also higher in both the IPF ($36.34{\pm}8.62\;{\mu}g/ml$) and stable group ($20.83{\pm}8.53\;{\mu}g/ml$) compared to the control group ($2.80{\pm}1.05\;{\mu}g/ml$) (p<0.05). 3) There was a correlation between the MMP-2 level in the BALF with the total cell number(r=0.298) and neutrophils(r=0.357) (p<0.05), and the MMP-9 level with the number of neutrophils (r=0.407) and lymphocytes (r=0.574)(p<0.05). The TIMP-1 level correlated with the total number of cell (r=0.338, p<0.05) and neutrophils(r=0.449, p=0.059). Conclusion : Both MMP and TIMP appear to play an important role in IPF pathogenesis, and their level may reflect the disease activity.