• Tuberculosis and Respiratory Diseases
• /
• v.47 no.2
• /
• pp.150-160
• /
• 1999

Background: The CREST syndrome is an indolent form of progressive systemic sclerosis. Although its clinical progress is indolent, pulmonary hypertension(PH) associated with CREST syndrome have grave prognosis with over 40 percent mortality rate at 2 year follow-up. But the pathogenesis of pulmonary hypertension in this disease is not known, and classified as either primary or secondary PH. Clonality of endothelial cell proliferation in plexiform lesion is a molecular marker which allows distinction between primary and secondary PH. We performed this study to know whether the PH associated with CREST syndrome is a variant of primary PH or is a secondary PH. Methods: We assessed the X-chromosome inactivation based on the methylation pattern of the human androgen-receptor gene by PCR(HUMARA). Endothelial cells in plexiform lesions from female patients(n=3) with PH associated with CREST syndrome were microdissected from paraffin blocks. Vascular smooth muscle cells and lung parenchyma were also microdissected for clonality studies. Results: The proliferating endothelial cells in 14 plexiform lesions were all polyclonal. Similarly proliferated smooth muscle cells from 5 vessels with medial hypertrophy were also polyclonal. Conclusion: These results suggest that the pulmonary hypertension associated with CREST syndrome has different pathogenesis from primary PH and to be classified as secondary PH.

• Tuberculosis and Respiratory Diseases
• /
• v.57 no.3
• /
• pp.242-249
• /
• 2004

Background : Because of the low sensitivity of sputum smear and culture, diagnosis of nontuberculous mycobacterium (NTM) pulmonary disease, especially in patients with bronchiectasis, is often difficult. We investigated the usefulness of bronchoscopy for the diagnosis of NTM pulmonary disease including M. avium complex (MAC) and M. abscessus in patients with bronchiectasis and multiple pulmonary nodules on chest computed tomography (CT). Methods : We reviewed 48 cases of patients who were performed bronchoscopic bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) under suspect of NTM pulmonary disease based on CT findings of bronchiectasis and multiple nodules from April 2002 to June 2003. Results : Twenty five of the 48 patients (54%; 12 MAC, 14 M. abscessus) were diagnosed as NTM pulmonary disease on the basis of the American Thoracic Society diagnostic criteria for NTM pulmonary disease. Sixteen of the 21 patients (76%; 5 MAC, 11 M. abscessus) with 3 or more positive sputum cultures of NTM were confirmed tissue invasion by TBLB. Five of the 24 patients (21%; 4 MAC, 1 M. abscessus) who could not be diagnosed with sputum cultures were diagnosed by bronchoscopic BAL and TBLB. Conclusion : Bronchoscopy is helpful for the diagnosis of NTM pulmonary disease and confirmation of tissue invasion by NTM, not only MAC but also M. abscessus, in patients with bronchiectasis and multiple nodules on chest CT scan.

• Journal of Chest Surgery
• /
• v.35 no.7
• /
• pp.535-541
• /
• 2002

Background: The prevalence of pulmonary tuberculosis remains high in several areas of the world, and pneumonectomy is often necessary to treat the sequelae of the disease. We retrospectively analyzed the morbidities, mortalities, and long-term outcomes after pneumonectomy for the treatment of tuberculous sequelae. Material and Method: Between 1981 and 2001, 94 patients underwent either pneumonectomy or extrapleural pneumonectomy for the treatment of tuberculous sequelae. There were 44 males and 50 females. The mean age was 40(16~68) years. The pathology included destroyed lung in 80, main bronchus stenosis in 10, and both lesions in 4. Surgical procedures were pneumonectomy in 47, extrapleural pneumonectomy in 43, and completion pneumonectomy in 4. Results: One patient died postoperatively due to empyema. Twenty-three complications occurred in 20 patients; empyema in 15(including 7 bronchopleural fistulas), wound infection in 5, and others in 3. Univariate analysis revealed presence of empyema, extrapleural pneumonectomy, prolonged operation time, and old age as risk factors of postpneumonectomy empyema. In multivariate analysis, old age and low preoperative FEV1 were risk factors of empyema. Low preoperative FEV1 was the risk factor of bronchopleural fistula(BPF) in univariate analysis. Low preoperative FEV1, positive sputum AFB, and presence of aspergilloma were risk factors of BPF in multivariate analysis. There were twelve late deaths. Actuarial 5-and 10-year survival rates were 94$\pm$3% and 87$\pm$4%, respectively. Conclusion: Pneumonectomy could be performed with acceptable mortality and morbidity, and could achieve good long-term survival for the treatment of tuberculous sequelae. In patients with risk factors, special care is recommended to prevent postoperative empyema or bronchopleural fistula.

• Tuberculosis and Respiratory Diseases
• /
• v.52 no.5
• /
• pp.506-518
• /
• 2002

Background : There have been several studies showing that angiotensin II and the angiotensin converting enzyme (ACE) contribute to the activation of fibroblast including the pulmonary fibrosis, and apoptosis of the alveolar epithelium in idiopathic intersititial pneumonia. This study was performed to identify the relationship between the serum angiotensin II, ACE and the pulmonary function test (PFT), the dyspnea score, and the cell fraction of the bronchoalveolar lavage fluid(BALF). Materials and Methods : Twenty three patients with idiopathic interstitial pneumonia from March, 1999 to October, 2001 at Gachon medical school were enrolled in this study. They were divided into IPF(UIP) (16) and NSIP (7) groups. Twelve of the idiopathic interstitial pneumonia patients (UIP : 5, NSIP : 7) were diagnosed by an open lung biopsy, 11 of IPF patients were diagnosed by the American Thoracic Society (ATS) diagnostic criteria. The PFT values, dyspnea score, serum ACE and angiotensin II were measured, and a bronchoscopy was performed to obtain the BALF. Results : Of all the patients, 7 were in the normal range and 14 showed an increase in the serum level of angiotensin II. In terms of the serum ACE level, 14 patients had an increased level. The DLCO% of the angiotensin II in increased group was significantly lower than the not-increased group (p=0.021). Other factors did not correlate with the serum ACE or the angiotensin II increased group and not-increased group. Conclusion : These results suggest that an increased angiotensin II serum level may be associated with increase in the of alveolar capillary block in the progression of pulmonary fibrosis in idiopathic interstitial pneumonia.

• Clinical and Experimental Pediatrics
• /
• v.46 no.1
• /
• pp.42-50
• /
• 2003

Purpose : The acute respiratory distress syndrome(ARDS), an acute form of severe alveolar-capillary injury evolving after a direct or indirect lung insult is thought to be a common cause of respiratory failure though not many clinical studies on the subject have been made yet. Methods : Between January 1992 and December 2001, we conducted a retrospective study on 33 children who fulfilled the definition of the ARDS recommended by the American-European Consensus Conference in 1994. Results : A total of 33 patients(20 boys and 13 girls) were selected. Their age ranged from 4 months to 12 years with seven children younger than 1 year. The overall mortality rate was 78.8% and no significant difference was noted based on age or sex. Concerning seasonal variation, incidence of the ARDS increased in spring, especially in May(21.2%). Pneumonia(66.7%) was found to be the most common risk factor of the ARDS followed by sepsis(24.2%) and aspiration(3.0%). In immune compromised children(six cases), including a recipient of bone marrow transplantation, the mortality rate was 100%. Compared with children with multiple organ failure recording a 83.3% mortality rate, those with isolated respiratory failure, showed a lower mortality rate of 33.3%, although stastistically insignificant. Between survivor and non-survivor groups, significant differences were shown in hematocrit, $PaO_2$, $PaCO_2$, PEEP, and $PaO_2/FiO_2$ on the seventh day after the onset of the ARDS. Conclusion : According to our study, respiratory failure proved to have a great effect on mortality rate in the ARDS. More aggressive intervention and further studies on this subject should be done to improve the survival rate.

• Clinical and Experimental Pediatrics
• /
• v.46 no.10
• /
• pp.989-995
• /
• 2003

Purpose : Dexamethasone is frequently administered to prevent or treat chronic lung disease in human neonates who are also prone to hypoxic-ischemic(HI) insults. Recently, meta-analysis of the follow-up studies reveals a significantly increased odd ratio for the occurrence of cerebral palsy or an abnormal neurologic outcome, and there is conflicting evidence regarding the impact of dexamethasone exposure on HI brain injury. This study was conducted to explore the effect of post-HI dexamethasone administration on neuronal injury in neonatal rats. Methods : HI was produced in seven-day-old rats by right carotid artery ligation followed by two hours of 8% oxygen exposure. At the end of HI, the animals were injected intraperitoneally either with dexamethasone(0.5 mg/kg) or saline. Neuronal injury was assessed seven days after the HI by the area of infarction, TUNEL reactivity, Bcl-2 and Bax expression in brain. Results : Post-insult dexamethasone administration resulted in reduction of weight gain and a higher mortality rate during seven days after HI. Dexamethasone treatment revealed no effect on the size of brain infarction induced by HI. Bax protein expression increased in dexamethasone treated brain but Bcl-2 protein expression and TUNEL reactivity revealed no significant differences between dexamethasone treated and non treated brain. Increased Bax protein expression suggest upregulation of the apoptosis by dexamethasone. Conclusion : The result suggests the adverse role of Post-HI administration of dexamethasone in neonatal HI.

• Pediatric Infection and Vaccine
• /
• v.8 no.1
• /
• pp.94-100
• /
• 2001

Purpose : Enterovirus is a common cause of aseptic meningitis and nonspecific febrile illness in young children. During the summer and fall months, enterovirus-infected young children are frequently admitted and evaluated to rule out bacterial sepsis and/or meningitis. The purpose of this study was to evaluate the relationship between nonpolio enterovirus infection and febrile illness in infants under 3 months of age during the summer, fall months by using a stool culture to identify the presence of enterovirus. Methods : Patients included febrile infants under 3 months of age admitted to Masan Fatima Hospital for sepsis evaluation from May 1999 to September 1999. Cultures were performed from stool and Cerebrospinal fluid samples and then were tested for enterovirus infection. Viral isolation and serotype identification were performed by cell culture and immunofluorescent testing. Enteroviruses not typed by immunofluorescent testing were confirmed by reverse transcription-polymerase chain reaction. Results : A total of 44 febrile infants were enrolled; of those, 20(45%) were positive for enterovirus. Two enterovirus culture-positive infants had concomitant urinary tract infection and one had Kawasaki disease. All infants infected with an enterovirus recovered without complications. Serotype of 20 enteroviruses were isolated from stool, 3 of echovirus type 9, 1 of echovirus type 11, 1 Coxsachievirus type B4, 15 of untyped enteroviruses. One untyped enterovirus was isolated in the CSF. Conclusion : Nonpolio enterovirus infections are associated with nonspecific febrile illnesses in infants under 3 months of age.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.27 no.5
• /
• pp.373-384
• /
• 2001

Cellular proliferation is an intricately regulated process mediated by the coordinated interactions of critical growth control genes. Two of these factors in mammalian cells are the p53 and mdm-2 genes. A protein product of the mem-2 oncogene has been recently shown to associate with the protein encoded by the tumor suppressor gene p53. The p53 tumor suppressor protein is stabilized in response to DNA damage and other stress signals and causes the cell to undergo growth arrest or apoptosis, thus preventing the establishment of mutations in future cellular generations. Mutation or loss of p53 is a very common event in tumor progression. It occurs in about 50% of all tumors analysed including of colon, lung, breast and liver. The cellular mdm-2 gene, which has potential transforming activity that can be activated by overexpression, is amplified in a significant percentage of human sarcoma and in other mammalian tumors. Proteins encoded by the mdm-2 gene are able to bind to the p53 protein and, when overexpressed, can inhibit p53's transcriptional activation function, thus mdm-2 can act as a negative regulator of p53 function. Experimental study was performed to observe the relationship between p53 gene mutation and mdm-2 protein expression and apply the results to the clinical activity. 36 golden syrian hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek(control side) was treated with mineral oil as the same manner to the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were examined for histology and immunohistochemistry observation, and were completely dissected by microdissection and DNA from both tissue were isolated by proteins K/phenol/chloroform extraction. Segments of the hamster p53 exons 5, 6, 7 and 8 were amplified by PCR using the oligonucleotide primers, and then confirmational change was observed by SSCP respectively. The results were as follows : 1. Dysplasia at 6 weeks, carcinoma in situ at 8 weeks and invasive carcinoma from 10 weeks could be observed in experimental groups. 2. p53 mutations were detected in 10 of the 36(28%) and the exons 6(6 of the 10 : 60%) was the most hot spot area among the highy conserved region(exons 5, 6, 7 & 8). 3. Immunohistochemical study confirmed 22 of the 36(61%) of p53 expression involving 10 of p53 mutations. 4. mdm-2 expression of was showed in 3 of the 36(8%) involving 1 of the 22 of p53 expression and 2 of the 14 of p53 non-expression. From the above results, mutation of p53 gene or expression of p53 protein may have the influence of the DMBA induced carcinoma of hamster buccal pouch but the expression of mdm-2 protein may not have relationship with tumorigenesis.

• Tuberculosis and Respiratory Diseases
• /
• v.50 no.2
• /
• pp.213-221
• /
• 2001

Background : There is a well recognized interlaboratory variation in the results using the polymerase chain reaction(PCR) to detect the IS6110 sequence. The clinical utility of a commercially developed PCR test(Amplicor) in bronchial washings for detecting pulmonary tuberculosis in smear negative patients was evaluated. The sensitivity and specificity of Amplicor was compared with that of an in-house PCR test used for detecting the IS6110 sequence of Mycobacterium tuberculosis(M.tbc) in the bronchial washing fluid. Methods : 66 patients whose sputum smear for M. tbc were negative or who could not produce any sputum were recruited from January 1999 to July 1999. They all had a bronchoscopy performed to determine if there were signs of hemoptysis, patients who could not cough up sputum, lung lesion that exclude pulmonary tuberculosis. Pulmonary tuberculosis was diagnosed on the basis of a positive culture or a response to anti-tuberculosis therapy. Results : 19 patients with tuberculosis were identified and samples from 16 patients were later confirmed by culture. Bronchial washing for Amplicor PCR revealed a sensitivity, specificity, positive and negative predictive values of 94.7%, 97.9%, 94.7%, 97.9%, respectively. Using IS6110 based PCR, the sensitivity, specificity, positive and negative predictive values were of 73.7%, 87.2%, 70%, 89.1% respectively. Conclusion : Bronchial washing for Amplicor PCR proved to be more useful than IS6110 based PCR in rapidly diagnosing smear negative pulmonary pulmoary tuberculosis in patients where tuberculosis was likely to be differential and rapid diagnosis was essential for optimal treatment.

• Tuberculosis and Respiratory Diseases
• /
• v.41 no.3
• /
• pp.248-261
• /
• 1994

Background: Lectins are proteins or glycoproteins of non-immune origin that recognize a specific sequence of sugar residues. The availability of a large number of lectins has provided the capacity to identify selectively glycoconjugates possessing distinctive chemical structure in diverse sites of highly specialized biological activity. The purpose of the present study was to investigate the lectin binding patterns of various components in human pulmonary tubercles. Method: Biopsy specimens of tuberculous lung were obtained from male adult patients who underwent a surgical resection for severe pulmonary tuberculosis. The specimens were processed and stained with 13 kinds of biotinylated lectins according to some modification of Hsu and Raine's methods. Results: 1) In the caseous necrotic lesions, BS $I-B_4$ showed negative reaction and BS I were also negative except some irregularly-shaped cells located in the marginal zone. All other lectins, however, showed a positive reaction with various binding patterns. 2) The epithelioid cells were broadly divided into three groups according to the reaction patterns in the cytoplasms and cell membranes. 3) WGA, ECL, PHA-L, PHA-E and LCA showed strong staining in the lymphocytes. 4) SBA showed a different binding patterns between the endothelial layers located in the region beyond the fibrous layers and those located within the fibrous layers. 5) PNA showed a positive reaction in the outer 1/3 to 1/2 of the fibrous layer, but showed no staining in the inner 1/2 to 2/3 of the fibrous layers. Conclusion: The present lectin histochemical study provided a useful information to assess the characterization and distribution of various glycoconjugates in each constituent of human pulmonary tubercles. The results demonstrate structural differences in the glycoconjugate composition of various components of the tubercles and reveal changes in glycosylation in the components during soft tubercle formation. This study provides a new data useful for the studies on the pathogenesis and pathology of human pulmonary tubercles.