• Tuberculosis and Respiratory Diseases
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• v.46 no.5
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• pp.697-708
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• 1999

Background : Leukotriene (LT) $C_4$, $D_4$, and $E_4$, the main components of slow-reacting substance of anaphylaxis (SRS-A), have been suggested to play an important role in bronchial asthma such as antigen-induced bronchoconstriction, airway hyperreactivity, and pulmonary eosinophil accumulation. The purpose of this study was to evaluate the effects of treatment with the cysteinyl-LTs (cys-LTs) antagonist, pranlukast on allergen-induced guinea pig asthma model. Methods : Guinea pigs of treatment and placebo groups were sensitized by subcutaneous injection of ovalbumin(OVA) and challenged by inhalation of aerosolized OVA (1% weight/volume OVA). Normal control group did not sensitize with OVA. Oral ingestion of pranlukast and normal saline to the treatment and placebo groups was performed. In the treatment and placebo groups, airway resistance was measured before and after oral ingestion. Serum $LTC_4$ and eosinophilic infiltration of the bronchiolar and peribronchiolar tissues were measured after ingestion in the treatment and placebo groups. Results : Allergen-induced airway constriction developed in 20 (8 in treatment group, 12 in placebo group) among 35 guinea pigs. Airway resistance was significantly decreased at 3 and 6 minutes after OVA challenge in the pranlukast treatment group. In the placebo group, there was no difference of airway resistance between before and after saline ingestion. Serum $LTC_4$ levels showed 348.4 pg/ml in the treatment group, 373.9 pg/ml in the placebo group, and 364.4 pg/ml in the control group. There were no statistically significant difference between treatment and placebo group (p=0.232), and treatment and control group (p=0.501). Eosinophilic infiltrations in the peribronchiolar region per one-microscopic field ($\times$400 high power fields) demonstrated 7.06 in the treatment group, 19.2 in the placebo group, and 4.50 in the control group. There was significant decrement of eosinophilic infiltration in the treatment group which was compared with placebo group (p=0.001). Conclusion : These results demonstrate that pranlukast, a cys-LTs receptor antagonist, can attenuate allergen induced early-phase bronchoconstriction and eosinophilic infiltration in the bronchiolar tissues.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.241-250
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• 1999

Background: Persistent nonproductive cough is a major adverse effect encountered with ACE inhibitor treatment and the most frequent reason for withdrawal of the drug. The mechanism of cough was postulated to be associated with accumulation of bronchial irritants which are substrates of ACE. It has been speculated that occurrence of this adverse effect is genetically predetermined ; in particular, variants of the genes encoding ACE. To investigate this relationship, we determined ACE gene Insertion/Deletion polymorphism in subjects with and without a history of ACE inhibitor-induced cough. Methods: Among the 339 patients with ACE inhibitor treatment, subjects who developed cough that resolved when not taking medication were designated to cough group and other subjects who did not complain cough were designated to non-cough group. Clinical characteristics of the patients were collected by review of medical records. ACE genotypes were determined by PCR amplification of DNA from peripheral blood and agarose gel electrophoresis. Results: 37 patients complained of dry cough(cough group) and 302 patients did not complained of cough(non-cough group). The incidence of ACE inhibitor induced dry cough was 10.9%. There was a preponderance of females in the cough group (M : F=24.3% : 75.7%) compared to the non-cough group (M : F=49.7% : 50.3%, p=0.004). There was no significant difference in mean age, underlying diseases, and kinds and frequencies of ACE inhibitors and their mean dosage between the both groups. ACE genotypic frequencies were I/I : I/D : D/D=16.2% : 18.9% : 64.9% in the cough group and 18.9% : 18.2% : 62.9% in the non-cough group which showed no significant difference between the both groups(p=0.926). Allelic frequencies were I : D = 25.7% : 74.3% and 28.0% : 72.0% in the cough and non-cough group respectively and the difference was not significant(p = 0.676). Conclusion: The incidence of ACE inhibitor-induced cough are 10.9%, and women are more susceptible to ACE inhibitor-induced cough. ACE inhibitor-induced dry cough is not associated with ACE gene Insertion/Deletion polymorphism.

• Tuberculosis and Respiratory Diseases
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• v.60 no.4
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• pp.451-463
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• 2006

Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through ${\beta}$ -nicotinamide adenine dinucleotide ($NAD^+$) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was $PIP\;15cmH_2O$ + $PEEP\;3cmH_2O$ + RR 90/min + 2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of $PIP\;40cmH_2O$ + $PEEP\;0cmH_2O$ + RR 90/min + 2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines.

• Journal of Preventive Medicine and Public Health
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• v.25 no.2 s.38
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• pp.127-140
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• 1992

This study was done to identify the association between serum copper and zinc levels and the cirrhosis and hepatocellular carcinoma(HCC), and to evaluate its diagnostic value on liver diseases. Sixty-three healthy persons, 60 patients with cirrhosis and 33 patients with hepatocellular carcinoma were rendomly selected and investigated for their general characteristics from October 1990 to August 1991. For analysis of the biochemical markers in liver function test and the serum copper and zinc levels, their fasting venous blood were sampled at 9:00 to 11:00 in the morning and centrifuged to separate the serum within one hour. All the samples were immediately analysed for biochemical markers and stored at $-20^{\circ}C$ in polypropylene tubes further copper and zinc analysis. Mean of serum coppper levels was $91.97{\pm}4.76{\mu}g/dl$ in control, $106.21{\pm}2.73{\mu}g/dl$ in cirrhosis and $127.05{\pm}0.77{\mu}g/dl$ in HCC. The value of HCC was statistically significantly higher than that of the control and cirrhosis(p<0.05). Serum zinc levels were $110.82{\pm}7.24{\mu}g/dl$ in control, $68.10{\pm}5.43{\mu}g/dl$ in cirrhosis and $63.78{\pm}2.20{\mu}g/dl$ in HCC. The values of cirrhosis and HCC were statistically significantly lower than that of control(p<0.05). The Cu/Zn ratio was statiatically significantly different among three groups(p<0.05). Test total protein, albumin, ALP and total bilirubin of biochemical markers of liver function were statistically significantly different among three groups(p<0.05). Differences between cirrhosis and HCC for ALT and AST, and between the control and HCC for direct bilirubin were not statistically significant. Biochemical markers statistically significantly correlated with serum copper and zinc levels and Cu/Zn ratio(p<0.05), were variable in three groups. In multiple logistic regression, odds ratio of serum copper level and Cu/Zn ratio had no statistical significance on the cirrhosis and the HCC, but that of serum sinc was statistically significant as 0.951 and 0.952(p<0.05). Serum copper and zinc levels and Cu/Zn ratio were not statistically significantly different between the cirrhosis and HCC. H\Albumin, ALP, zinc, total bilirubin and age among all variables were selected as main variables for three-group discriminant analysis. Percentage of 'grouped' cases correctly classified by these five variables was 98.4 for control, 73.4 for cirrhosis, 75.7 for HCC and 84.0 for all subjects. This study suggests that zinc level is considered to play a role as diagnostic marker on the hepatic disorders and be more useful than serum copper level and Cu/Zn ratio in diagnosis of the liver diseases.

• Childhood Kidney Diseases
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• v.1 no.1
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• pp.24-30
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• 1997

Purpose: To evaluate the diagnositc value of the absolute and relative renal uptake rates on $^{99m}Tc-DMSA$ renal scan of children with febrile UTI. Method: The absolute and relative renal uptake rates of $^{99m}Tc-DMSA$ were checked in 68 children with febrile urinary tract infection (35 with unilateral focal defect; 13 with bilateral focal defect; and 20 with diffuse bilateral defect) and 49 children with afebrile UTI and normal $^{99m}Tc-DMSA$ renal scan as control. Results: The renal absolute uptake rate in the control group were $21.8{\pm}3.9%(right),\;22.2{\pm}3.9%(left),\;and\;44.2{\pm}7.8%(total)$. The absolute uptake rate gradually increased until the age 12 months and then was stationary. In febrile UTI with unilateral focal defect on the $^{99m}Tc-DMSA$ renal scan, both relative and absolute uptake rates were similarly diagnostic ($41.2{\pm}9.7%,\;16.5{\pm}5.4%$ vs $50.0{\pm}2.6%,\;22.0{\pm}3.9%$, p<0.01). In acute pyelonephritis with bilateral focal defect on the $^{99m}Tc-DMSA$ renal scan, the absolute uptake rate was significantly more diagnostic than the relative uptake rate[$17.3{\pm}5.3%$ (right), $17.4{\pm}5.3%\;(left),\;vs\;21.8{\pm}3.9%,\;(right)\;22.2{\pm}3.9%$, (left)% p<0.01]. In febrile UTI with bilateral diffuse defects on the $^{99m}Tc-DMSA$ renal scan, the absolute uptake rate was significantly diagnostic than the relative uptake rate [$18.1{\pm}3.9%\;(right),\;18.4{\pm}3.8%\;(left),\;vs\;21.8{\pm}3.9%,\;(right)\;22.2{\pm}3.9%$(left), p<0.01]. Conclusion: In the $^{99m}Tc-DMSA$ renal scan, the absolute uptake rate was more useful than the relative uptake rate to evaluate bilateral acute pyelonephritis.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.1
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• pp.115-121
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• 2010

Purpose: The purpose of this study is to measure F-18 FDG with two different types of dose calibrator measuring radionuclide and radioactivity and investigate the effect of F-18 FDG on SUV (Standard Uptake Value) in human body. Materials and Methods: Two different dose calibrators used in this study are CRC-15 Dual PET (Capintec) and CRC-15R (Capintec). Inject 1 mL, 2 mL, 3 mL of F-18 FDG into three 2 mL syringes, respectively, and measure initial radioactivity from each dose calibrator. Then measure and record radioactivity at 30 minute interval for 270 minutes. According to the initial radioactivity, linearity between decay factor driven from radioactive decay formula and the values measured by dose calibrator have been analyzed by simple linear regression. Fine linear regression line optimizing values measured with CRC-15 through regression analysis on the basis of the volume of which the measured value is close to the most ideal one in CRC-15 Dual PET. Create ROI on lung, liver, and region part of 50 persons who has taken PET/CT test, applying values from linear regression equation, and find SUV. We have also performed paired t-test to examine statistically significant difference in the radioactivity measured with CRC-15 Dual PET, CRC-15R and its SUV. Results: Regression analysis of radioactivity measured with CRC-15 Dual PET and CRC-15R shows results as follows: in the case 1 mL, the r statistic representing correlation was 0.9999 and linear regression equation was y=1.0345x+0.2601; in 2 mL case, r=0.9999, linear regression equation y=1.0226x+0.1669; in 3 mL case, r=0.9999, linear regression equation y=1.0094x+0.1577. Based on the linear regression equation from each volume, t-test results show significant difference in SUV of ROI in lung, liver, region part in all three case. P-values in each case are as follows: in 1 mL case, lung, liver and region (p<0.0001); in 2 mL case, lung (p<0.002), liver and region (p<0.0001); in 3 mL case, lung (p<0.044), liver and region (p<0.0001). Conclusion: Radioactivity measured with CRC-15 Dual PET, CRC-15R, dose calibrator for F-18 FDG test, do not show difference correlation, while these values infer that SUV has significant differences in the aspect of uptake in human body. Therefore, it is necessary to consider the difference of SUV in human body when using these dose calibrator.

• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.1
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• pp.77-81
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• 2009

Purpose: The PET of the PET/CT (Positron Emission Tomography/Computed Tomography) quantitatively shows the biological and chemical information of the body, but has limitation of presenting the clear anatomic structure. Thus combining the PET with CT, it is not only possible to offer the higher resolution but also effectively shorten the scanning time and reduce the noises by using CT data in attenuation correction. And because, at the CT scanning, the contrast media makes it easy to determine a exact range of the lesion and distinguish the normal organs, there is a certain increase in the use of it. However, in the case of using the contrast media, it affects semi-quantitative measures of the PET/CT images. In this study, therefore, we will be to establish the reliability of the SUV (Standardized Uptake Value) with CT data correction so that it can help more accurate diagnosis. Materials and Methods: In this experiment, a total of 30 people are targeted - age range: from 27 to 72, average age : 49.6 - and DSTe (General Electric Healthcare, Milwaukee, MI, USA) is used for equipment. $^{18}F$- FDG 370~555 MBq is injected into the subjects depending on their weight and, after about 60 minutes of their stable position, a whole-body scan is taken. The CT scan is set to 140 kV and 210 mA, and the injected amount of the contrast media is 2 cc per 1 kg of the patients' weight. With the raw data from the scan, we obtain a image showing the effect of the contrast media through the attenuation correction by both of the corrected and uncorrected CT data. Then we mark out ROI (Region of Interest) in each area to measure SUV and analyze the difference. Results: According to the analysis, the SUV is decreased in the liver and heart which have more bloodstream than the others, because of the contrast media correction. On the other hand, there is no difference in the lungs. Conclusions: Whereas the CT scan images with the contrast media from the PET/CT increase the contrast of the targeted region for the test so that it can improve efficiency of diagnosis, there occurred an increase of SUV, a semi-quantitative analytical method. In this research, we measure the variation of SUV through the correction of the influence of contrast media and compare the differences. As we revise the SUV which is increasing in the image with attenuation correction by using contrast media, we can expect anatomical images of high-resolution. Furthermore, it is considered that through this trusted semi-quantitative method, it will definitely enhance the diagnostic value.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.332-342
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• 2000

Background : The importance of pro-inflammatory cytokines, especially tumor necrosis factor $\alpha$ (INF-$\alpha$) and interleukin-1$\beta$ (IL-1$\beta$), have been extensively documented in the generation of inflammatory lung disease. Lung epithelial cells are also actively involved in initiating and maintaining inflammation by producing pro-inflammatory mediators. Understanding the mechanism of pro-inflammatory cytokine expression in lung epithelial cells is crucial to the development of new therapeutic modalities for inflammatory lung disease. Transcription of most pro-inflammatory cytokines is dependent on the activation of NF-${\kappa}B$. However, the relationship between pro-inflammatory cytokine expression and NF-${\kappa}B/I{\kappa}B$ pathway in lung epithelial cells is not clear. Methods : BEAS-2B, A549, Na-H157, NCI-H719 cells were stimulated with IL-$1{\beta}$ or TNF-$\alpha$ at various times, and then IL-8 and TNF-$\alpha$mRNA expressions were assayed by Northern blot analysis. IL-$1{\beta}$ or TNF-$\alpha$-induced NF-${\kappa}B$ activation was assessed by the nuclear translocation of p65 NF-${\kappa}B$ subunit. The degradation of $I{\kappa}B{\alpha}$ and $I{\kappa}B{\beta}$ by IL-$1{\beta}$ or TNF-$\alpha$stimulation was assayed by Western blot analysis. The phosphorylation of $I{\kappa}B{\alpha}$ was evaluated by Western blot analysis after pre-treating cells with proteasome inhibitor followed by IL-$1{\beta}$ or TNF-$\alpha$ stimulation. The basal level of IKK $\alpha$ expression was evaluated by Western blot analysis. Results: $I{\kappa}B{\alpha}$ and $I{\kappa}B{\alpha}$ was rapidly degraded after 5 minutes of incubation with IL-$1{\beta}$ or TNF-$\alpha$ in BEAS-2B, A549, and NCI-H157 cells. The activation of NF-${\kappa}B{\alpha}$ and the induction of IL-8 and TNF-$\alpha$ mRNA expression were observed by IL-$1{\beta}$ or TNF-$\alpha$ stimulation in these cells. In contrast, neither the changes in NF-${\kappa}B/I{\kappa}B$ pathway nor IL-8 and TNF-$\alpha$mRNA expression was induced by IL-$1{\beta}$ or TNF-$\alpha$ stimulation in NCI-H719 cells. IL-$1{\beta}$ and TNF-$\alpha$-induced $I{\kappa}B$ phosphorylation was observed in BEAS-2B, A549, and NCI-H157 cells, but not in NCI-H719 cells. The basal level of IKK$\alpha$ expression was not different between cell. Conclusion : NF-${\kappa}B/I{\kappa}B$ pathway plays an important role in the expression of pro-inflammatory cytokine in most lung epithelial cells. The absence of the effect on NF-${\kappa}B/I{\kappa}B$ pathway in NCI-H719 cells sæms to be due to the defect in the intracellular signal transduction pathway upstream to IKK.

• Tuberculosis and Respiratory Diseases
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• v.66 no.3
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• pp.192-197
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• 2009

Background: Despite the benefits of home oxygen therapy in patients suffering chronic respiratory failure, previous reports in Korea revealed lower compliance to oxygen therapy and a shorter time for oxygen use than expected. However, these papers were published before oxygen therapy was covered by the national insurance system. Therefore, this study examined whether there were some changes in compliance, using time and other clinical features of home oxygen therapy after insurance coverage. Methods: This study reviewed the medical records of patients prescribed home oxygen therapy in our hospital from November 1, 2006 to September 31, 2008. The patients were interviewed either in person or by telephone to obtain information related to oxygen therapy. Results: During study period, a total 105 patients started home oxygen therapy. The mean age was 69 and 60 (57%) were male. The mean oxygen partial pressure in the arterial blood was 54.5 mmHg and oxygen saturation was 86.3%. Primary diseases that caused hypoxemia were COPD (n=64), lung cancer (n=14), Tb destroyed lung (n=12) and others. After oxygen therapy, more than 50% of patients experienced relief of their subjective dyspnea. The mean daily use of oxygen was 9.8${\pm}$7.3 hours and oxygen was not used during activity outside of their home (mean time, 5.4${\pm}$3.7 hours). Twenty four patients (36%) stopped using oxygen voluntarily 7${\pm}$4.7 months after being prescribed oxygen and showed a less severe pulmonary and right heart function. The causes of stopping were subjective symptom relief (n=11), inconvenience (n=6) and others (7). Conclusion: The prescription of home oxygen has increased since national insurance started to cover home oxygen therapy. However, the mean time for using oxygen is still shorter than expected. During activity of outside their home, patients could not use oxygen due to the absence of portable oxygen. Overall, continuous education to change the misunderstandings about oxygen therapy, more economic support from national insurance and coverage for portable oxygen are needed to extend the oxygen use time and maintain oxygen usage.

• The Journal of the Korean bone and joint tumor society
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• v.11 no.1
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• pp.54-61
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• 2005

Purpose: The granulocytic sarcoma which developed in leukemic patients are quite rare and it will have bad prognosis, but it's tumor pathogenesis and also their treatment are not yet established. Through this study we have tried to know their clinical course, prognosis and their end result of recent treatment. Material and Methods: Total 20 patients of granulocytic sarcoma which were developed in total 2,197 leukemic patients from April, 1998 to September, 2004 were treated at the leukemic center and the orthopaedic department of St. Mary's hospital, Catholic University of Korea, and followed them for 1~78 months(average 18 months). Results: Total 20 cases of granulocytic sarcoma was found in 14 cases of total 1,331 acute myelocytic leukemic patients(AML), 4 cases of total 744 of chronic myelocytic leukemic patients(CML), and only one case in total 122 of acute biphenotype of leukemia. And so their occurrence rate in leukmic patients are actually 0.91%, total 20 cases of granulocytic sarcoma in total 2,197 leukemic patients at same period. Their ages are average 28.3 years(4~52 years), and male are predominant(13 cases) than female(7 cases). Single involvement was found in 11 cases but multiple lesions are in 9 cases, and spine, brain, extremities, chest, and pelvic bone are involved in frequency. The granulocytic sarcoma was developed in various stages of the leukemia, ie, 8 cases in complete remission of leukemia, and 12 cases in the treatment process of AML. The pathohistologic evaluation of granulocytic sarcoma was done in 6 cases which was developed in their extremities, and confirmed numerous immature myeloblasts and lymphocytes mixed. The treatment of these granulocytic sarcoma was mainly limited for the treatment of leukemia by Glivac and massive steroid therapy(19cases) and also combined with the bone marrow transplantation(13 cases), but radiation therapy with average 3,500 rads in 15 cases out of total 20 sarcomas was also done, and followed them for average 17.5 months after development of granulocytic sarcomas. Finally their prognosis was so bad that 12 patients(60%) out of total 20 granulocytic sarcoma were dead in 6.5 months after sarcoma developed and we found the granulocytic sarcoma was more fatal if they are developed during the process of CML(mortality: 100%(4/4cases). Conclusion: The prognosis of granulocytic sarcomas in leukemic patients are quite fatal, and much more studies for their pathogenesis and ways of treatment should be performed continuously.