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Aim Memantine is known to be effective in the treatment of the behavioral symptoms of dementia, especially agitation in moderate to severe Alzheimer's disease (AD). However, memantine and rivastigmine patch combination therapy has not been well studied in determining treatment effectiveness with mild to moderate AD patients. Methods This was a multicenter, 24-week, prospective, randomized, open-label study design. A total 147 AD patients with Mini-Mental State Examination scores from 10 to 20 were randomly assigned to rivastigmine patch monotherapy and combination therapy with memantine groups. Agitation symptoms, using the Korean Version of the Cohen Mansfield Agitation Inventory were evaluated at baseline and at study end. Suppression and emergence of agitation symptoms were also evaluated. We carried out factor analyses to evaluate the interrelationship of agitation symptoms and to investigate treatment response in these symptoms. Results Factor analyses showed two symptom clusters: factor A – aggressive agitated behaviors – versus factor B – non-aggressive agitated behaviors. The rivastigmine patch monotherapy group showed significantly decreased factor B scores and had a tendency of decreased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor A scores. Conversely, the combination therapy group showed significantly increased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor B scores. Neither monotherapy nor combination therapy reduced the emergence of new agitation symptoms. Conclusions In this trial of mild to moderate AD patients, the rivastigmine patch monotherapy group experienced a reduction of non-aggressive agitated behaviors. However, combination therapy with memantine did not show any benefit on the agitation associated with mild to moderate AD. Geriatr Gerontol Int 2017; 17: 494–499.

Today companies are struggling to secure a sustainable competitive advantage in a market that is relentlessly more and more competitive. Traditional strategies, like cutting costs and expanding market share, have produced only minimal results. And ominously, these approaches are criticized for being guided by nonrelevant information produced by a firm's information technology (IT) system. But the authors of this article believe there is still a business empowerment role for the chief information officer (CIO)—by expanding IT services. And the authors give a step-by-step plan to make a company more competitive in this tough market by using a more advanced approach to IT management. © 2013 Wiley Periodicals, Inc.

Objective: The aim of this study is to develop an ergonomic office chair that has an alarm function for the unbalanced sitting postures. Background: Contrary to expectation, it is reported that office workers sit on their chairs much more in unbalanced postures during daily work. Even though an office worker uses an ergonomically good-designed chair and begins their work in a good sitting posture, his/her posture is likely to shift to the unbalanced bad posture. Therefore, a posture alarm system would be very helpful in keeping office workers' good postures. Method: We developed a prototype chair with four load cells under a seat pan and one load cell beneath a backrest. Through some experiments, we set the criteria for unbalanced bad postures then implemented the criteria into the alarm system of the prototype chair. The chair called e-BASE chair could detect unbalance postures and show alarms for chair users. We also enhanced back support by developing a step-wised folding backrest. Results: The e-BASE chair showed better performance in interface pressure distributions and balanced posture ratio in VDT work. Conclusion: The ergonomic chair with posture alarm function(e-BASE chair) was developed. It showed better performance in seat pressure distribution and in keeping good posture during office work. Application: The posture alarm system and folding backrest can be applied to the new models of office chair.

PURPOSE Platinum-based chemotherapy has conferred a modest but significant survival benefit and the introduction of newer drugs has led to achieve higher response rate in patients with advanced non-small cell lung cancer (NSCLC). We performed a phase II trial in order to evaluate the efficacy and toxicity of combination chemotherapy with vinorelbine (Navelbine) and cisplatin in advanced NSCLC. MATERIALS AND METHODS Patients with previously untreated, unresectable stage IIIB or IV NSCLC with measurable lesion (s) were eligible for entry into the study. NP chemotherapy consisted of intravenous vinorelbine 25 mg/m2, on day 1 and 8, and intravenous cisplatin 80 mg/m2 on day 1; this cycle was repeated every three weeks. RESULTS A total of 33 patients were enrolled in the study between July 1999 and Feb 2000. Of the 30 patients deemed eligible for analysis, thirteen patients achieved a partial response and thirteen showed a stable disease. The overall response rate was 43.3%. The median duration of response was 5.7 months (95% CI: 2.8~8.5 months). The median time to progression was 7.6 months (95% CI: 5.5~9.7 months) and the overall median survival time was 15.1 months (95% CI: 9.8~20.4 months) in the intent-to-treat analysis. Chemotherapy-related grade 3 or 4 toxicities were anemia in 1.5%, leukopenia in 4.5%, nausea/vomiting in 2.3%, alopecia in 13.3%, and neurotoxicity in 3.3%. CONCLUSION The combination of vinorelbine and cisplatin chemotherapy seems to be active and fairly tolerable in patients with advanced NSCLC.

Given that anti-tuberculosis medication itself has antibacterial activity and that broad-spectrum antibiotics are frequently used, the emergence of multidrug-resistant (MDR) bacteria among patients being treated for tuberculosis (TB) is likely. We used a case-control design to study the clinical predictors of MDR bacterial infection among TB patients. Both cases and controls were selected from among patients who were diagnosed and treated as having TB between 1 January 1996 and 31 August 2006. TB patients with MDR bacterial infection were included as cases and those with non-MDR bacterial infection were included as controls. Multiple logistic regression analysis was performed to elucidate the risk factors for MDR bacterial infection. During the study period 3667 patients were diagnosed with, and treated for, TB. A total of 123 experienced episodes of bacterial infection, of whom 59 (48.0%) were infected by an MDR strain at least once. The presence of chronic renal failure [adjusted odds ratio (OR): 4.96; 95% confidence interval (CI): 1.37-18.01] and the use of antimicrobials other than typical anti-TB drugs within three months (adjusted OR: 4.37; 95% CI: 1.74-10.95) were independent risk factors for MDR bacterial infection. Bacterial infection in TB patients is commonly multidrug resistant. Clinicians should be aware of the possibility of MDR bacterial infection among TB patients with chronic renal failure or recent use of other antimicrobials.

Background and objective: Accurate staging at the time of diagnosis is very important in deciding on the appropriate treatment for cancer patients. FDG PET indicates metabolic changes in cancer cells, enabling the early detection of lesions. This has the advantage of allowing more accurate staging than is possible with conventional staging tools, and has led to the incorporation of FDG PET in the initial work-up protocols for lung cancer patients. In this study, we evaluated the clinical impact of FDG PET as an initial staging tool, on the therapeutic management of patients with non-small cell lung cancer (NSCLC). Methods: Patients diagnosed with NSCLC by histopathology were retrospectively identified and both chest CT and FDG PET were performed for initial staging. Information was collected regarding the results of conventional versus FDG PET staging, and any resulting modifications of treatment were evaluated. Results: Among the 537 patients who were evaluated FDG PET resulted in upstaging of the tumour in 91 (17%) and downstaging of the tumour in 68 (13%). Consequently, therapeutic management was modified in 118 patients (22%). Furthermore, use of FDG PET resulted in the detection of a second primary cancer in six patients. Conclusions: This study confirms that FDG PET has a considerable impact on the initial staging and therapeutic management of patients with NSCLC.

Introduction: As the population of patients with lung cancer increases, the expenditure on lung cancer treatment will become a huge economic burden in many countries. To support public health services for the treatment of lung cancer, the calculation of lung cancer-specific costs is important. Methods: This study included newly diagnosed 76 lung cancer patients who had survived for at least 5 years after the diagnosis in a tertiary care hospital in South Korea. Direct medical costs were calculated from health care claims obtained from Seoul National University Hospital, which included out-of-pocket expenditures. Direct non-medical and indirect costs were calculated from national statistics. Results: Mean direct medical costs, direct non-medical costs, and indirect costs amounted to $21,321, $6444 and $4943 respectively, based on an exchange rate of Korean Won 1200 = US $1. The average cost for treatment of one lung cancer patient for all 5 years was $32,708. This constituted 44.7% of the per capita income during the same 5-year period. Conclusion: The economic burden of lung cancer treatment is significant in Korea.

The aim of the present study was to confirm the association between the CD14-159C/T polymorphism and tuberculosis in the Korean population and to elucidate the functional basis for this putative association. CD14-159C/T genotypes were determined by PCR - restriction fragment length polymorphism analysis in 274 tuberculosis patients and 422 healthy controls. Recombinant CD14 promoter-luciferase reporter constructs, including the -159T or -159C allele, were transfected into K562 and BEAS-2B cells, and luciferase activities were measured and compared. Levels of serum sCD14 and interferon-gamma secreted by peripheral blood mononuclear cells (PBMCs) were measured using enzyme-linked immunosorbent assay.The frequency of -159TT genotypes was higher in tuberculosis patients than in healthy controls. The promoter activity of the -159T allele was higher than that of the -159C allele. Serum sCD14 levels were higher among tuberculosis patients with -159TT genotypes than among those with -159CC genotypes and interferon-gamma release by PBMCs was decreased in subjects with -159TT genotypes. In conclusion, the -159TT CD14 genotypes were associated with tuberculosis development in Koreans. This association might be a result of the higher promoter activity of the -159T allele, the higher level of sCD14, and the decreased interferon-gamma secretion in subjects with -159TT genotypes.

Mycobacterium abscessus (M. abscessus) is the second most common nontuberculous mycobacteria (NTM) in South Korea. Nevertheless, the diagnosis and treatment of M. abscessus lung disease can be problematic. Surgical resection has been tried for patients with localized M. abscessus lung disease refractory to medical treatment. Here, we report on a 25-year-old woman with M. abscessus lung disease who had been diagnosed and treated three times for pulmonary tuberculosis. She was initially diagnosed as having M. intracellulare lung disease; however, M. abscessus was isolated after several months of medication. She had multiple bronchiectatic and cavitary lesions bilaterally, and M. abscessus was repeatedly isolated from her sputa despite prolonged treatment with clarithromycin, ethambutol, moxifloxacin, and amikacin. She improved only after sequential bilateral lung resection. Based on the experience with this patient, we suggest that, if medical treatment fails, surgical resection of a diseased lung should be considered even in patients with bilateral lesions.

Summary Objectives The aim of this study was to analyze changes in the extent of radiographic lesions with treatment in patients with pulmonary tuberculosis (TB) and, further, to identify clinical and radiographic factors related to radiographic response. Methods A prospective cohort study including patients with culture-proven pulmonary TB was performed. The posterior-anterior view films of the chest that had been taken at the time of diagnosis and at 6 months after the initiation of treatment were compared. We expressed the extents of the lesions as percentages involving the parenchyma compared with the remaining normal parenchyma. Results Among 135 patients enrolled, three failed to achieve smear conversion of sputa after 6 months of treatment. The extent of radiographic lesions decreased from 22.8% at the time of diagnosis to 10.5% after 6 months of treatment. Through the multiple regression model, we found that increasing age ( p =0.034), previous history of TB ( p =0.016), presence of cavity ( p =0.016) or fibrotic lesion ( p =0.009), and multidrug-resistant TB ( p =0.002) were significantly associated with a poor radiographic response. Conclusion Patients with less-prominent radiographic improvement and sustained negative tuberculous cultures of the sputa could be closely observed without ordering unnecessary chest radiographs or mycobacterial cultures as well as prolonging treatment.

Connective tissue diseases are the most common disorders causing diffuse alveolar haemorrhage (DAH) confirmed by open lung biopsy. However, it is not known whether these diseases are also the most common causes of DAH in patients presenting with the features of ARDS/acute lung injury (ALI). This study evaluated the frequency of concomitant disease in patients with ARDS/ALI and DAH.The sampling frame comprised all patients in a tertiary referral hospital diagnosed with ARDS/ALI and who underwent BAL between January 2000 and July 2006. The medical records of those patients who had BAL fluid findings compatible with DAH were reviewed.Of the 97 patients diagnosed with ARDS/ALI and who underwent BAL, 27 had BAL fluid findings compatible with DAH. Sixteen of the 27 patients did not have connective tissue diseases (59%); of these 12 patients had concomitant haematological malignancies or solid tumours. Of the seven patients who presented with DAH and no known underlying disease, only two were subsequently diagnosed with a connective tissue disorder. The in-hospital mortality rate was 55% and 63% for patients with DAH with and without connective tissue diseases, respectively (P = 0.710).The majority of patients with DAH presenting with the features of ARDS/ALI did not have underlying connective tissue diseases. Concomitant malignancies were found frequently in these patients. The outcome did not differ between patients with DAH with or without connective tissue diseases.

Good's syndrome is extremely rare. This adult-onset condition is characterized by a thymoma with immunodeficiency, low B- and T-cell counts, and hypo-gammaglobulinemia. The initial clinical presentation is either a mass-lesion thymoma or a recurrent infection. Patients with Good's syndrome are very susceptible to infections; common respiratory and opportunistic infections can be life-threatening. There are no reports of granulomatous lung disease in patients with Good's syndrome, although it has been observed in patients with common variable immunodeficiency, of which Good's syndrome is a subset. We describe a 53-year-old male thymoma patient who presented with respiratory symptoms caused by granulomatous lung disease and an opportunistic infection. He died of uncontrolled fungal infection despite repeated intravenous immunoglobulin and supportive care. Clinicians should look for evidence of immunologic dysfunction in thymoma patients presenting with severe recurrent infections, especially opportunistic infections.

The effective control of tuberculosis (TB) requires that people at high risk for the reactivation of TB are identified. Haematological malignancy has been shown to be a risk factor for the development of TB, either through immune suppression by the tumour or through the effects of chemotherapy. This study assessed the hypothesis that solid-organ malignancy is a risk factor for the development of TB.A retrospective cohort study was performed to determine the incidence of TB in patients with solid-organ malignancy and in control subjects without malignancy. Risk factors for the development of TB among patients with cancer were also assessed.The study recruited 1809 cases with cancer and 1809 control subjects and followed them for 3 years. The incidence of active TB per 1000 person-years was 3.07 in patients with cancer and 0.77 in controls (P = 0.009). Compared with the control group, patients with cancer had an increased risk of developing TB (incidence rate ratio (IRR) 4.69, 95% CI: 1.52-14.46). Proportional hazards regression analysis showed that the risk factors for development of TB were chronic renal failure (IRR 9.91, 95% CI: 1.17-83.60), old healed TB on CXR (IRR 45.05, 95% CI: 5.74-353.88), and anticancer chemotherapy (IRR 4.32, 95% CI: 1.10-16.89). An interaction between old healed TB and anticancer chemotherapy was observed.These findings indicate that immune suppression by cancer or by anticancer chemotherapy increases vulnerability to reactivation of TB, especially in cancer patients with old healed TB.

Background and objectives: Rapid and accurate diagnosis of latent tuberculosis infection (LTBI) is crucial in military settings. This study aimed to detect the prevalence of LTBI using a whole-blood interferon-γ assay based on Mycobacterium tuberculosis-specific antigens, and to identify risk factors for LTBI among military personnel in contact with patients with active pulmonary TB. Methods: This prospective study investigated contacts in military camps in South Korea of soldiers with active pulmonary TB. The whole-blood interferon-γ assay was performed using QuantiFERON TB-Gold. Results: Among the 175 contacts, 25 (14.3%) showed positive results to the assay. Long duration of exposure (OR 2.83; 95% CI: 1.63–4.91), laryngeal TB (OR 6.04; 95% CI: 1.54–23.67) and intensive exposure (OR 5.13; 95% CI: 1.63–16.12) were associated with a positive result. Conclusions: A relatively small number of TB contacts in a military setting had LTBI.

Summary RNA interference is a phenomenon whereby small double-stranded RNA knocks down the expression of a sequence-specific gene. Double-stranded siRNA transfection, as currently used, is considered to have transient and low transfection efficiency. We constructed an adenoviral vector-based short hair-pin(sh)RNA system to overcome the limitations of the genetic blockade of IGF-1R, one of most important cancer therapy targets. We constructed three different IGF-1R specific shRNAs (612, 801, and 3425) and generated three ad-shIGF-1Rs using BD Adeno-X™ expression system. We assessed the effect of ad-shIGF-1R on signal transduction, induction of apoptosis, and in vitro tumorigenicity of lung cancer cell lines. Western blot and FACS assays demonstrated that endogenous IGF-1R expression was efficiently suppressed after transduction of lung cancer cell lines with the three different ad-shIGF-1Rs. IGF-1R blockade by ad-shIGF-1R inhibited ligand induced phosphorylation of pAkt and pErk, and ad-shIGF-1R effectively blocked the in vitro tumorigenicity of lung cancer cell lines. Moreover, the transduction of a human lung cancer cell line with ad-IGF-1R(3425) enhanced chemosensitivity to anticancer drugs. We conclude that the adenoviral vector-based approach to the RNA interference of IGF-1R induced effective IGF-1R silencing in lung cancer cell lines as manifested by effective blocking of the downstream pathway of IGF-1R and by an antitumor effect. We believe that this system can be usefully applied to other cancer targets.

Although mycobacterial culture and the subsequent drug-susceptibility test (DST) for anti-tuberculosis (TB) drugs take several months to complete using solid media, there are no reports on the turnaround times of these tests under clinical conditions. The aim of this study was to determine the interval between initiation of anti-TB treatment and receipt of DST requested at an outpatient clinic. We prospectively enrolled patients with culture-positive pulmonary TB at Seoul National University Hospital from September 2002 to December 2004. Patients were followed up monthly. Mycobacterial cultures were done using Ogawa media at Seoul National University Hospital. DST were performed at the Korean Institute of Tuberculosis. Of the 104 patients enrolled, 54 were male. The median age was 41 yr. The median interval from initiation of anti-TB treatment to receipt of mycobacterial culture results by clinicians was 37 days (range, 0-89 days). The median interval from initiation of treatment to confirmation of DST by requesting clinicians was 80.5 days (range, 28-145 days). Clinicians only received the results of DST more than two months after initiation of treatment when they followed up patients monthly and mycobacterial culture was performed using solid media.

Ground-glass opacity (GGO) attracts attention because of the possibility of early lung cancer. However, some lesions are reduced in size or disappear at follow-up. This study was designed to explore the natural history of solitary GGO, to determine the prevalence of malignancy and to identify factors predictive of benignity or malignancy. Solitary and focal GGO lesions [pGGO (p=pure) and mGGO (m=mixed) based on the presence of a solid component] of less than 3 cm were included. Lesions of less than 1cm were followed up by chest HRCT 3 months later and lesions over 1cm were investigated by percutaneous needle biopsy (PCNB). One hundred and eighty-six patients (69 pGGO and 117 mGGO) were enrolled. Of the 69 pGGO lesions, 7 were diagnosed as pre-malignant or malignant lesions, 3 as benign lesions and 26 pGGO lesions (37.6%) were reduced or disappeared (transient lesions) at follow-up chest HRCT. The other 33 lesions showed no significant change during follow-up. Thus, the probability of malignancy in pGGO was 7/36 (19.4%). On the other hand, of the 117 mGGO lesions, 26 were found to be malignant, 3 were diagnosed as benign and 57 lesions (48.7%) were reduced or had disappeared at follow-up chest HRCT. The other 31 lesions showed no change during follow-up, and thus the probability of malignancy in mGGO was 26/86 (30.2%). A female sex and a spiculated mGGO border were found to be related with malignancy. However, a high blood eosinophil count was strongly associated with regressing or transient mGGO, suggesting that pulmonary infiltrate with eosinophilia (PIE) might have been responsible. We recommend short-term follow-up by chest HRCT be conducted for mGGO lesions in the presence of high eosinophilia--regardless of lesion size.

Hypoxia confers protection against apoptosis in cancer cells, and this hypoxia-induced resistance to apoptosis has been suggested to be associated with genetic and adaptive changes. However, it is not clear whether survival signals, such as the PI3K/Akt and ERK pathways are involved. We investigated the roles of these pathways in hypoxia-induced protection against apoptosis in lung cancer cells. Treatment of cells with either ultraviolet (UV) or etoposide induced apoptosis time-dependently in A549 and NCI-H157 cells. However, though hypoxia alone neither induced apoptosis nor reduced cell survival, it suppressed the apoptosis induced by UV or etoposide. Moreover, hypoxia activated the PI3K/Akt and ERK pathways, and blocking the activation of either pathway reversed resistance to UV- and etoposide-induced apoptosis in response to hypoxia. These results suggest that hypoxia confers resistance to UV- or etoposide-mediated apoptosis in lung cancer cells via the activations of the PI3K/Akt and the ERK pathways.

Study objective To examine the prevalence and characteristics of parenchymal tuberculous pleuritis in adult patients. Design Prospective cohort study. Setting Three hospitals affiliated with Seoul National University in South Korea. Patients All patients > 15 years old with a diagnosis of tuberculous pleuritis were enrolled prospectively between January 1, 2004, and October 31, 2004. Interventions Diagnostic thoracocentesis and CT of the chest were done for each patient. Acid-fast bacilli (AFB) smears and cultures for Mycobacterium tuberculosis were requested if patients produced any sputum. A board-certified radiologist reviewed the chest radiographs for the presence and characteristics of any lesions. Measurements and results One hundred six patients with tuberculous pleuritis were enrolled (median age, 53 years; range 16 to 89 years). Among them, 33 patients (31%) had sputum or bronchial washing findings positive for AFB smears or for M tuberculosis by culture. Lung parenchymal lesions were observed in 91 of the patients (86%) using chest CT; 39 patients (37%) with parenchymal lesions had radiographic characteristics of active pulmonary tuberculosis. In total, 62 patients (59%) had bacteriologically or radiographically active pulmonary tuberculosis. In addition, 78 patients (74%) had features of reactivated pulmonary tuberculosis. Conclusions Lung parenchymal lesions were more common in this series of patients with tuberculous pleuritis than has been reported in previous studies. The patients mostly had radiographic features of reactivated, rather than primary, tuberculosis.

The frequency of resistance genotypes among Beijing and non-Beijing strains was compared using a reverse blot hybridization assay to detect mutations within genes associated with rifampicin (rpoB) and isoniazid (katG, inhA, and ahpC) resistance. Of the 743 Mycobacterium tuberculosis isolates, 569 (77%) belonged to Beijing family. The proportion of Beijing strains was significantly higher among MDR-TB isolates than among drug-susceptible strains (82% vs. 72%, p0.01). Genotype analysis of the rpoB gene revealed significantly lower rates of the Ser531Leu mutation rate among Beijing vs. non-Beijing MDR-TB strains (41% vs. 66%, p0.005). While the mutation for Ser315Thr in the katG gene was more common among Beijing vs. non-Beijing family strains (65% vs. 50%, p0.01), the mutation rate of promoter region of the inhA gene was lower among Beijing strains compared with non-Beijing strains (14% vs. 25%, p0.05). Reverse hybridization successfully detected over 80% of isoniazid-resistant strains and over 92% of rifampicin-resistant strains among Korean isolates. Significant differences in mutation rates in the rpoB, katG, and inhA genes between Beijing strains and non-Beijing strains could explain discrepancies in mutation rates of genotypes in different countries. Reverse hybridization was useful for rapid detection of isoniazid and rifampicin resistant strains.

Heat shock (HS) activates mitogen-activated protein (MAP) kinases. Although prior exposure to nonlethal HS makes cells refractory to the lethal effect of a subsequent HS, it is unclear whether this also occurs in MAP kinase activation. This study was undertaken to evaluate the effect of a heat pretreatment on MAP kinase activation by a subsequent HS and to elucidate its possible mechanism. Preheating did not make BEAS-2B cells refractory to extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) activation by a second HS but accelerated their inactivation after HS. The rapid inactivation of ERK and JNK was dependent on de novo protein synthesis and associated with the up-regulation of heat shock protein 70 (HSP70). Moreover, the inhibition of phosphatase activity reversed this rapid inactivation. MAP kinase phosphatase-1 (MKP-1) expression was increased by HS, and the presence of its phosphorylated form (p-MKP-1) correlated with the observed rapid ERK and JNK inactivation. Blocking induction of p-MKP-1 with antisense MKP-1 oligonucleotides suppressed the rapid inactivation of ERK and JNK in preheated cells. HSP70 overexpression caused the early phosphorylation of MKP-1. Moreover, MKP-1 phosphorylation and the rapid inactivation of ERK were inhibited by blocking HSP70 induction in preheated cells. In addition, MKP-1 was insolubilized by HS, and HSP70 associated physically with MKP-1, suggesting that a chaperone effect of HSP70 might have caused the early phosphorylation of MKP-1. These results indicate that preheating accelerated MAP kinase inactivation after a second HS and that this is related to a HSP70-mediated increase in p-MKP-1.

OBJECTIVE Alpha1-antitrypsin (AAT) deficiency is a recognized susceptible factor for chronic obstructive pulmonary disease (COPD) in Western countries, but its importance in Korea is unclear. To date, no definitive case of alpha1-antitrypsin deficiency has been reported in Korea. This study aimed to clarify whether alpha1-antitrypsin deficiency exists and to determine the distribution of alpha1-antitrypsin alleles in the Korean population. METHODOLOGY The serum concentrations of alpha1-antitrypsin were determined and polymorphisms of the alpha1-antitrypsin gene in 114 COPD patients and in 196 healthy controls were examined. Phenotyping by isoelectric focusing and the genotyping of alpha1-antitrypsin gene by polymerase chain reaction and restriction fragment length polymorphism were performed. RESULTS No alpha1-antitrypsin level abnormality was found in the patients. M1(Val)/M1(Val) was found to be the most frequent genotype in both groups (69.2% and 66.8%, respectively), and M1(Val) the most frequent allele. The distributions of alpha1-antitrypsin alleles were similar in the patient and control groups, and no S or Z allele was found. CONCLUSION Alpha1-antitrypsin deficiency is unlikely to be an important cause of chronic obstructive pulmonary disease in the Korean population.

Chronic obstructive pulmonary disease (COPD) is a major public health problem and its prevalence and mortality are increasing throughout the world, including the Asia–Pacific region. To arrest these worldwide trends, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Expert Panel's global strategy for the diagnosis, management, and prevention of COPD was published in 2001. Based on recently published clinical trials, the GOLD statement was updated in 2003. The Asia–Pacific COPD Roundtable Group, a taskforce of expert respirologists from the Asia–Pacific region, has recently formulated a consensus statement on implementation of the GOLD strategy for COPD in the Asia–Pacific region. The key issues identified by the COPD Roundtable Group for comment are: (i) where there is no access to spirometry, diagnosis of COPD could be suspected on the basis of history, symptoms and physical signs; (ii) inhaled bronchodilators are the preferred regular treatment for COPD in the region, but oral bronchodilators may be considered if the cost of inhaled bronchodilators is a barrier to treatment; (iii) the use of an Metered Dose Inhaler with spacer in place of a nebulizer is recommended in the treatment of acute airflow obstruction in patients with COPD; (iv) influenza vaccination is recommended for all patients with COPD in communities where there is a high likelihood of Severe Acute Respitory Syndrome; and (v) simplified pulmonary rehabilitation programmes should be established in areas where comprehensive programmes are unavailable. Physical exercise training and education on smoking cessation should be core elements of any rehabilitation program. In summary, the COPD Roundtable Group supports implementation of the GOLD strategy for the diagnosis, management and prevention of COPD in the Asia–Pacific region, subject to the additions and modifications to the guidelines suggested above.

To evaluate the incidence and clinical significance of delayed pneumothorax, and to analyze the influence of multiple variables on the rate of delayed pneumothorax associated with transthoracic needle biopsy (TTNB) of the lung.Prospective study.Tertiary care university hospital.Adult patients underwent TTNB from June 2001 to June 2002.Among the 458 patients included in this study, 280 fluoroscopic-guided, 21 CT-guided, and 157 ultrasonography-guided lung biopsies were performed. A follow-up chest radiograph was obtained immediately, and 3 h, 8 h, and 24 h after the biopsy procedure. Pneumothorax that had not developed up to 3 h but developed later was defined as a delayed pneumothorax. Patients with a symptomatic or enlarged pneumothorax were treated using a pigtail catheter or chest tube. Variables such as age, gender, lesion size, location, presence of an emphysematous change, biopsy guidance methods, and biopsy devices were analyzed. Pneumothorax developed in 100 of the 458 patients (21.8%), and delayed pneumothorax developed in 15 patients (3.3%). Seventeen patients, including 3 patients with delayed pneumothorax, required a pigtail catheter or a chest tube insertion. The pigtail catheter or chest tube insertion rate in delayed pneumothorax was 20% (3 of 15 patients). Female gender and the absence of an emphysematous change correlated with an increased rate of delayed pneumothorax (p0.05). Lesion size, location, biopsy guidance methods, devices, and underlying diseases were not correlated with the delayed pneumothorax rate.The incidence of delayed pneumothorax was 3.3% of all TTNBs. Female gender and the absence of an emphysematous change were identified as risk factors for delayed pneumothorax. Delayed pneumothorax is clinically important because of its considerable incidence and the necessity for pigtail catheterization or chest tube insertion in these patients.

Heat shock (HS) was found to suppress the IkappaB/NF-kappaB cascade via the inhibition of IkappaB kinase (IKK) activity; however, the mechanism has not been clear. This study was undertaken to elucidate the detail of the mechanism involved. TNF-alpha-induced activation of IKK was suppressed by HS in human bronchial epithelial cells, and this was associated with the absence of IKK in the immunoprecipitates. It was not due to a degradation of IKK, but due to a conversion of IKK from a soluble to an insoluble form. IKK lost its activity rapidly upon exposure to HS in vitro. The time course of the insolubilization of IKK coincided with the decrease in IKK activity. However, inhibition of IKK insolubilization by the induction of thermotolerance did not reverse the HS-induced suppression of IKK activation and IkappaBalpha degradation. Upstream activators of IKK, such as NF-kappaB-inducing kinase (NIK) and IL-1R-associated kinase (IRAK) were also insolubilized by HS. The HS-induced insolubilization of NIK was not blocked by the induction of thermotolerance. Overexpression of NIK resumed TNF-alpha-induced activation of IKK in thermotolerant cells. These results indicate that the loss of activity of NIK, IRAK, and IKK through insolubilization is responsible for the HS-induced suppression of IkappaB/NF-kappaB pathway.

Object. Malignant glioma could be an ideal candidate for local gene therapy because its invasion is local and it has little metastatic potential. A low expression level and high degradation activity of p27 are known to constitute an independent poor prognostic factor in patients with malignant glioma. In this study, the authors investigated the roles of wild-type p27 and mutant p27 on the treatment of malignant glioma. Methods. The authors used two adenoviruses: one expressed wild-type p27 (ad-p27wt) and the other, containing a mutation at the major metabolic site, expressed mutant p27 (ad-p27mt). The antitumor effects of the two adenoviruses were compared with respect to cell growth arrest, cell cycle alteration, apoptosis induction, and in vitro tumorigenicity in three glioblastoma mutiforme (GBM) cell lines and in a primary GBM cell line. Transduction with ad-p27wt or ad-p27mt induced the production of p27 and the dephosphorylation of pRB. The protein level of mutant p27 was significantly higher than that of wild-type p27. The ad-p27wt induced cell cycle arrest at the G1—S transition point, whereas the ad-p27mt induced arrest at the G2—M point. Both ad-p27wt and ad-p27mt induced a growth-inhibiting effect, apoptosis, and suppression of in vitro tumorigenicity; however, ad-p27mt displayed a stronger antitumor effect than ad-p27wt in brain tumor cell lines. Conclusions. Gene therapy involving p27, especially mutant p27, has the potential to become a novel and powerful therapy for malignant glioma.

The human Toll-like receptor 2 (TLR2) mediates responses of both innate and adaptive immunity to Gram-positive bacteria, including mycobacteria. We sought functional polymorphisms in the 5'-untranslated region (UTR) of TLR2. We found a highly polymorphic (GT)n dinucleotide repeat 100 bp upstream of the TLR2 translational start site in intron 2. The numbers of GT repeats varied from 12 to 28. There were significant differences in allele distribution between African Americans and Caucasians (P=0.008) and between African Americans and Koreans (P=0.0003). The promoter activities of recombinant promoter-intron2/reporter constructs including the shortest [GT)n=12] or longest [(GT)n=28] alleles were significantly more stimulated when exposed to 200 IU ml(-1) of interferon-gamma than when exposed to 100 IU ml(-1) of GM-CSF (P==0.03). Since TLR2 plays a critical role in the human innate immune response, this functional microsatellite polymorphism may be important in the pathogenesis of infectious and inflammatory diseases.

Background: Caveolin-1, as a major component of caveolae, is involved in the regulation of cell cycle by impacting various signaling pathways. Previous studies of caveolin-1 in cancer showed two contrary results. In most in vitro studies, caveolin-1 played a role as a tumor suppressor. On the other hand, the elevated expression of caveolin-1 was often reported to be associated with poor clinical outcome in human studies. These results indicate differential biological functions of caveolin-1 depending on the development and progression stage of cancer in vivo. Methods: To clarify the correlation between the clinicopathologic profiles of pulmonary squamous cell carcinomas and the expression of caveolin-1, 107 cases of formalin-fixed and paraffin-embedded tissues of pulmonary squamous cell carcinomas were immunohistochemically evaluated for the expression of caveolin-1 by the tissue-array method. Results: Caveolin-1 was expressed in 34 cases (31.7%) among 107 cases of pulmonary squamous cell carcinoma. The expression of caveolin-1 was statistically correlated with pathologic stage (stage I and II vs. III; P

Neutrophils are now considered central to the pathogenesis of most forms of acute lung injury. Neutrophils do not cause damage while suspended in the bloodstream; however, a release of cytotoxic agents occurs when neutrophils are adherent to endothelium, epithelium, or extracellular matrix proteins in the interstitium. Such neutrophil adherence is mediated predominantly through beta(2) integrins (CD11/CD18) on its surface. This study was undertaken to investigate whether the IkappaB/nuclear factor (NF)-kappaB cascade is involved in this beta(2) integrin-mediated activation of human neutrophils. beta(2) Integrin Mac-1 (CD11b/CD18) aggregation was induced by antibody cross-linking of the integrins on the cell surface. beta(2) Integrin aggregation induced interleukin-1beta and tumor necrosis factor-alpha production, which suggests the activation of neutrophils by beta(2) integrin. IkappaBalpha was markedly degraded at 1 h, and NF-kappaB-DNA-binding activity markedly increased 2 h after beta(2) integrin aggregation, which activated IkappaB kinase activity at 1 h. beta(2) Integrin-induced cytokine production was suppressed by MG132 or SN50 pretreatment, which blocked the activation of NF-kappaB. These findings suggest that the activation of human neutrophils by beta(2) integrin aggregation is mediated through the activation of the IkappaB/NF-kappaB pathway.

Resistance to chemotherapeutic agents is the major reason for treatment failure of cancer chemotherapy. Some chemotherapeutic drugs induce the activation of NF-kappaB in cancer cells that results in their resistance to anticancer drugs. But the role of NF-kappaB in acquired resistance has not been well investigated. In this study, we transferred the "super-repressor" form of the NF-kappaB inhibitor by adenoviral vector (ad-IkappaBalpha) to human lung cancer cell lines with resistant to cisplatin (PC-14-DDP) and adriamycin (PC-14-ADR), and observed the sensitivity change. Electrophoretic mobility shift assay showed that ad-IkappaBalpha blocked the activation of NF-kappaB induced by cisplatin and adriamycin. Transduction with ad-IkappaBalpha restored the sensitivity of cisplatin and adriamycin resistant lung cancer cell lines (PC-14-DDP and PC-14-ADR) to a level compatible to the parental cell lines. Annexin-V analysis suggested that the enhancement of chemosensitivity was probably a result of the induction of apoptosis. These data demonstrated that ad-IkappaBalpha blockade of chemotherapeutic induced NF-kappaB activation increased apoptosis induction and the chemosensitivity of lung cancer cell lines with acquired resistance to cisplatin and adriamycin. Therefore, gene transfer of IkappaBalpha-SR seems to represent a new therapeutic strategy for the solution of low sensitivity and lung cancer resistance to anticancer drugs.

TRAIL is a cytokine with a unique ability to induce apoptosis selectively in many transformed cell lines. The instability of TRAIL and the resistance of some cancer cells to TRAIL present the main obstacles for clinical experimentation. We generated an adenovirus expressing full-length TRAIL and tested its efficacy in several cancer cell lines. Ad-TRAIL-infected cancer cells localized full-length TRAIL protein to the cytoplasm and released same-sized TRAIL in the media. Ad-TRAIL was found to induce apoptotic cell death in several cancer cell lines resistant to soluble TRAIL (A549, SKOV3, HT-29 and LNCap) and in TRAIL-sensitive cell lines. Ad-TRAIL, but not soluble TRAIL, induced apoptotic cell death in TRAIL-resistant cell lines, manifested by an increased sub-G1 proportion, caspase-3 activation and PARP cleavage. Ad-TRAIL also induced a media-transferable bystander effect, but only in soluble TRAIL-sensitive cell lines. In conclusion, two novel characteristics of ad-TRAIL were found during this study. First, that ad-TRAIL can induce apoptotic cell death in several cancer cell lines resistant to sTRAIL. Second, that ad-TRAIL induces a media-transferable bystander effect, which is expected to increase its therapeutic value by allowing TRAIL to overcome the locally acting nature and low transduction rate commonly encountered in clinical situation.

COPD is a leading cause of mortality and morbidity worldwide. Despite the high rates of cigarette smoking, and the wide use of biomass fuels, there is very little objective data on the prevalence of COPD in Asia.We used a COPD prevalence model to estimate the prevalence of COPD in 12 Asian countries. This model is a validated, computerized tool that uses epidemiological relationships and risk factor prevalence to project the prevalence of COPD within a given population aged 30 years and older.The total number of moderate to severe COPD cases in the 12 countries of this region, as projected by the model, is 56.6 million with an overall prevalence rate of 6.3%. The COPD prevalence rates for the individual countries range from 3.5% (Hong Kong and Singapore) to 6.7% (Vietnam).The COPD prevalence rates projected by the model reflect the high prevalence of the risk factors for the disease in Asia. The combined prevalence of 6.3% for these countries is considerably higher than the overall rate of 3.8% as extrapolated from WHO data for this region. These estimates highlight the need for further epidemiological studies to support appropriate allocation of resources for the prevention and management of COPD.

Uteroglobin is a secretory protein synthesized by most epithelia, including the respiratory tract. It has strong anti-inflammatory properties that appear to be related to the inhibition of phospholipase A2. Recent experimental evidence indicates that uteroglobin has an inhibitory effect on the proliferation and invasion of cancer cells. We investigated the effects of the adenovirus-uteroglobin (ad-UG) transduction on the growth of lung cancer cell lines, which did not express the uteroglobin gene. Upon transduction of ad-UG, the rate of cell growth and the ability to produce colonies in soft agar were evaluated. Cell cycle analysis, Western blot for cell cycle-related proteins and annexin V staining for apoptosis were carried out to see if they were associated with the changes in cell growth. All the tested lung cancer cell lines did not express the uteroglobin gene. The growth rates, and colony-forming ability of transformed cells, were significantly inhibited by the induction of uteroglobin gene expression. The DNA histogram showed that the cell fraction of the G2/M phase was increased, and this G2/M phase arrest was related to a decrease of cdk1 and cyclin A. However, a fraction of apoptotic cells were same as the control. From these results, uteroglobin is thought to have an inhibitory effect on the growth of lung cancer cells. This suggests a potential role for uteroglobin in gene therapy for lung cancer.

The continuous growth of tumors depends on the altered regulation of the cell cycle, which is in turn modulated by signals from growth factors and their receptors. Blockade of insulin-like growth factor (IGF)-I and IGF-IR by antisense or dominant negative plasmid transfection can suppress tumorigenicity and induce regression of established tumors. We have constructed two recombinant adenoviruses: an adenovirus expressing truncated IGF-IR (ad-IGF-IR/950) with an engineered stop codon at amino acid residue 950, and an adenovirus expressing the soluble extracellular domain of IGF-IR (ad-IGF-IR/482) with an engineered stop codon at amino acid residue 482. Ad-IGF-IR/950 produces a defective receptor with an intact alpha subunit and a defective beta subunit lacking the tyrosine kinase domain. Dominant negative inhibition results from competition of the defective receptor with normal IGF-IR subunits, or the competition with normal IGF-IR for ligand by the soluble receptor. We were able to show here that ad-IGF-IR/950 induced the increased expression of IGF-IR on the cell surface and ad-IGF-IR/482 induced the secretion of the soluble fragment of IGF-IR. The transduction of both ad-IGF-IR/950 and ad-IGF-IR/482 could blunt the growth-stimulatory effect of IGF-I on human lung cancer cell lines. Both ad-IGF-IR/950 and ad-IGF-IR/482 effectively blocked IGF-I-induced Akt kinase activation. Intratumoral injection of ad-IGF-IR/482 virus showed significant growth suppression in established lung cancer xenografts. These findings suggest that these ad-IGF-IR/dn (950, 482) have the potential to be effective and practical cancer gene therapy strategies.

p27 Kip1 (p27) is a member of the universal cyclin-dependent kinase inhibitor (CDKI) family and a putative tumor suppressor gene. In several tumors including lung cancer, decreased expression of p27 is associated with poor prognosis. These observations suggest a potential role for p27 as a new gene therapy target. In this study, we constructed adenovirus expressing human p27 (ad-p27) and investigated its antitumor effects on human lung cancer cell lines. Upon transduction of several human lung cancer cells with ad-p27, a high level of p27 expression, with a decrease in cdk2 and an increase in cyclin E were observed. These changes resulted in G1/S arrest. Transduction of human lung cancer cell lines with ad-p27 showed in vitro growth inhibition and a marked suppression of colony formation upon soft agar clonogenic assay. Direct intratumoral injection of ad-p27 induced the growth suppression of established lung tumors in nude mice. From these observations, gene therapy using ad-p27 seems to offer a potential basis for the development of new cancer gene therapy modality and a useful tool to investigate the mechanisms of cell cycle control.

The anti-inflammatory effect of acetylsalicylic acid (ASA) has been thought to be secondary to the inhibition of prostaglandin synthesis. Because doses of ASA necessary to treat chronic inflammatory diseases are much higher than those needed to inhibit prostaglandin synthesis, a prostaglandin-independent pathway has been emerging as the new anti-inflammatory mechanism of ASA. Here, we examined the effect of ASA on the interleukin (IL)-1 beta- and tumor necrosis factor (TNF)-alpha-induced proinflammatory cytokine expression and evaluated whether this effect is closely linked to the nuclear factor (NF)-kappa B/I kappa B-alpha pathway. A high dose of ASA blocked IL-1 beta- and TNF-alpha-induced TNF-alpha and IL-8 expression, respectively. ASA inhibited TNF-alpha-induced activation of NF-kappa B by preventing phosphorylation and subsequent degradation of I kappa B-alpha in a prostanoid-independent manner. TNF-alpha-induced activation of I kappa B kinase was also suppressed by ASA pretreatment. These observations suggest that the anti-inflammatory effect of ASA in lung epithelial cells may be due to suppression of I kappa B kinase activity, which thereby inhibits subsequent phosphorylation and degradation of I kappa B-alpha, activation of NF-kappa B, and proinflammatory cytokine expression in lung epithelial cells.

The Asian Pacific Society of Respirology (APSR) held its 14th Congress and 3rd Joint Congress of the APSR/American College of Chest Physicians (ACCP) in Seoul, Korea, between 14 and 18 November 2009. It was attended by 1906 delegates from around the world and was particularly well represented by people from the Asia-Pacific Rim. The Congress was highlighted by an excellent scientific program, preceded by an educational course on manuscript preparation and several postgraduate courses. Office Bearers representing the American Thoracic Society, European Respiratory Society and ACCP, amongst others, made significant contributions, further enhancing the high-quality faculty. © 2010 Expert Reviews Ltd.

Heat shock protein (HSP) induction confers protection against diverse forms of cellular and tissue injury. However, the mechanism by which HSP exerts cytoprotective effects is unclear. Because HSP induction inhibits genetic expression of pro-inflammatory cytokines, the transcription of which is dependent on NF-kappa B activation, we explored the relationship between the anti-inflammatory effect of HSP induction and the NF-kappa B/I kappa B alpha pathway. Both HS and sodium arsenite treatment increased HSP70 expression time dependently at mRNA and protein levels. Prior induction of HSP suppressed cytokine-induced IL-8 and TNF-alpha expression at both mRNA and protein levels. Although HSP induction did not affect total cellular expression of NF-kappa B, TNF-alpha-induced increase in NF-kappa B-DNA binding activity and nuclear translocation of the p65 subunit of NF-kappa B were inhibited by prior HSP induction, suggesting that activation of NF-kappa B was blocked. Cytokine-induced I kappa B alpha phosphorylation and its degradation were blocked in HSP-induced cells. Immune complex kinase assays demonstrated that TNF-alpha induced increase in I kappa B kinase activity was suppressed by prior HSP induction. These results suggest that the anti-inflammatory effect of HSP induction in respiratory epithelial cells is related to stabilization of I kappa B alpha, possibly through the prevention of I kappa B kinase activation, which thereby inhibits activation of NF-kappa B.

Summary Increased levels of matrix metalloproteinase-9 (MMP-9) in patients with tuberculous meningitis, tuberculous pleuritis, and advanced pulmonary tuberculosis (TB) suggest a pivotal role for MMP-9 in the development of pulmonary TB and its clinical manifestations. The present study was performed to evaluate the role of the −1562C/T single nucleotide polymorphism (SNP) in the promoter region of the human MMP-9 gene in development of pulmonary TB and its radiographic characteristics. A case–control study was performed with a study population of 205 patients with pulmonary TB and 223 healthy controls. Differences were explored in the allele and genotype distributions of the −1562C/T polymorphism between patients with pulmonary TB and healthy controls, between patients with single- and multi-lobe involvement, and between patients with and without cavities. The −1562C/C genotype was more common in patients with multi-lobe involvement than in those with single-lobe involvement (81.8 vs . 67.6%, P = 0.03). However, there were no significant differences in the distribution between patients with pulmonary TB and healthy controls ( P = 0.40) or between patients with and without cavities ( P = 0.18). These results suggest that the −1562C/C genotype is associated with the intrapulmonary spread of TB rather than its development.

Diffuse panbronchiolitis (DPB) is a chronic obstructive pulmonary disease of unknown etiology. Observations of significantly increased frequency of human leukocyte antigen (HLA)-B54 in Japanese patients and occurrence of familial cases suggest possible genetic predisposition to the disease susceptibility. To evaluate the possible association of HLA with the disease in Koreans, we have analyzed 30 patients for HLA class I (A, B, C) and class II (DR) antigens by the serologic and DNA typing methods, respectively. The most significant change in the patients compared to the control subjects was increased frequency of HLA-A11 (53.3% versus 17.5%, corrected p [pc] = 1.2 x 10(-)4, odds ratio [OR] = 5.4). In addition, B55 showed significant positive association (16.7% versus 3.5%, pc = 0.05, OR = 5.5), and B62 and Cw4 showed rather weak association with the disease. Certain A11-associated haplotypes showed much stronger positive association with the disease, compared to A11 antigen itself. Observations of a strong association of HLA-A11 in Koreans and B54 in Japanese with DPB suggest that the candidate gene(s) responsible for the disease susceptibility is located within the HLA class I region, most probably between HLA-A and HLA-B loci.

Objectives : p16 is known to be an important tumor suppressor gene and is also called MTS1(multiple tumor suppressive gene 1). Especially in the case of non-small cell lung cancer, it was not expressed in more than 70% of cell lines examined. To determine changes in cell-cycle related proteins and the tumorigenic effect, we, therefore, transfected p16INK4A gene into lung cancer cell lines. Methods : We transfected p16INK4A gene into lung cancer cell lines which do not express p16 protein. We evaluated the effect by clonogenic assay and observed the changes of cell-cycle related proteins. Results : The newly-expressed p16 formed a complex with cdk4, and phosphorylated pRB was decreased, although cyclin D1 and pRB:cyclin D1 complex were unchanged. Clonogenic assay after selection with G418 showed that, in the cell lines transfected with p16, tumorigenicity was significantly less than in the control. Conclusion : These results suggest that the p16INK4A gene can be a candidate for gene therapy in cases of NSCLC in which p16INK4A gene is inactivated.

It has long been known that almost all isoniazid (INH) resistant mycobacteria lose the catalase and peroxidase activities along with reduced or no virulence for guinea pigs. Recently resistance to INH has become known to be associated with mutations of katG gene encoding the HPI (Hydroperoxidase I) type catalase and peroxidase. Among these mutations, the point mutation of codon 463 of katG gene is found frequently, and is suggested as being associated with INH resistance. Therefore we performed this study in order to confirm the correlation between the point mutation of codon 463 of the katG gene and INH resistance of M. tuberculosis in Korea. Fifty isolates, 32 of which were resistant to INH, and 18 of which were sensitive to INH, were selected for this study. We used PCR-SSCP and RFLP analysis to detect the point mutation of the codon 463 of katG gene and confirmed the CGG (arginine) to CTG (leucine) mutation by direct sequencing analysis. Among 32 resistant isolates, 7 isolates (22%) had the same restriction pattern compared with that of the reference strain (H37Rv), and 25 isolates (78%) showed a different restriction pattern. Among 18 sensitive isolates, 7 isolates (39%) had the same restriction pattern compared with that of H37Rv, and 11 isolates (61%) showed a different restriction pattern. These results suggest that the CGG to CTG change of codon 463 of katG gene of M. tuberculosis may be a polymorphism not related with INH resistance.

Endobronchial tuberculosis (EBTB) is a highly infectious disease that remains a diagnostic challenge in the developed countries. It also presents as a troublesome therapeutic problem due to its sequelae of cicatrical stenosis. Due to the worldwide decrease of tuberculosis, diagnosis of EBTB is frequently delayed until the onset of serious bronchial stenosis with resultant atelectasis and bronchiectasis. The exact pathogenesis of EBTB is not yet completely understood and the course of EBTB differs according to the type. The prognosis of actively caseating type and edematous-hyperemic type EBTB is grave, resulting fibrostenosis in two thirds of patients. Fibrostenotic type EBTB shows no change or worsening of stenosis. The prognosis is good for granular and non-specific bronchitic type EBTB; however, the prognosis of tumorous type is poor, frequently resulting in bronchial stenosis despite adequate treatment. Antituberculous chemotherapy is effective in controlling the infection, but does not prevent residual bronchostenosis. Early treatment with steroid therapy is effective in certain groups of EBTB. Balloon dilatation and stent insertion is an effective treatment of bronchial stenosis id obstruction of the stent by granulation tissue overgrowth can be prevented. Future research should focus on the pathogenesis of bronchial inflammatory reaction and resulting fibrosis to prevent bronchial stenosis at the early stage.

A case of an unusual pulmonary epithelioid hemangioendothelioma is described in which two distinctive types of histologic lesion were combined. The patient was a 54-year-old man with persistent hemoptysis. The main lesion was an endobronchial tumor that had classic features of epithelioid hemangioendothelioma of soft tissue. Multiple peripheral parenchymal nodules resembled features of intravascular bronchioloalveolar tumor of the lung. The endothelial origin of the tumor cells was evident on both ultrastructural and immunohistochemical findings, including the presence of Weibel-Palade bodies and positive immunostaining to Ulex lectin and factor VIII-related antigen. This case seems to be an example with mixture of endobronchial epitheloid hemangioendothelioma of soft tissue type and peripheral intravascular bronchioloalveolar tumor histology, an association that has not been reported as yet. Int J Surg Pathol 3(1):59-64, 1995