Sung Koo Han

Anti-Inflammatory Effect of Heat Shock Protein Induction Is Related to Stabilization of IκBα Through Preventing IκB Kinase Activation in Respiratory Epithelial Cells

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-κB activation, we explored the relationship between the anti-inflammatory effect of HSP induction and the NF-κB/IκBα 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-α expression at both mRNA and protein levels. Although HSP induction did not affect total cellular expression of NF-κB, TNF-α-induced increase in NF-κB-DNA binding activity and nuclear translocation of the p65 subunit of NF-κB were inhibited by prior HSP induction, suggesting that activation of NF-κB was blocked. Cytokine-induced IκBα phosphorylation and its degradation were blocked in HSP-induced cells. Immune complex kinase assays demonstrated that TNF-α induced increase in IκB 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 IκBα, possibly through the prevention of IκB kinase activation, which thereby inhibits activation of NF-κB.

Impact of Extensive Drug Resistance on Treatment Outcomes in Non-HIV-Infected Patients with Multidrug-Resistant Tuberculosis

BACKGROUND Recently, serious concerns about extensively drug-resistant tuberculosis (XDR-TB), which shows resistance to second-line anti-TB drugs in addition to isoniazid and rifampicin, have been raised. The aim of this study was to elucidate the impact of extensive drug resistance on treatment outcomes in non-human immunodeficiency virus (HIV)-infected patients with multidrug-resistant tuberculosis (MDR-TB). METHODS Patients who received the diagnosis of and treatment as having MDR-TB at Seoul National University Hospital (Seoul, Republic of Korea) between January 1996 and December 2005 were included. The definition of XDR-TB was TB caused by bacilli showing resistance to both isoniazid and rifampicin and also showing resistance to any fluoroquinolone and to at least 1 of the following 3 injectable anti-TB drugs: capreomycin, kanamycin, and amikacin. To identify the impact of extensive drug resistance on treatment outcomes, univariate comparison and multiple logistic regression were performed. RESULTS A total of 211 non-HIV-infected patients with MDR-TB were included in the final analysis. Among them, 43 patients (20.4%) had XDR-TB. Treatment failure was observed in 19 patients (44.2%) with XDR-TB, whereas treatment of 46 patients (27.4%) with non-XDR-TB failed (P=.057). The presence of extensive drug resistance (adjusted odds ratio [OR], 4.46; 95% confidence interval [CI], 1.35-14.74) and underlying comorbidity (adjusted OR, 2.62; 95% CI, 1.00-6.87) were independent risk factors for treatment failure. However, a higher level of albumin was inversely associated with treatment failure (adjusted OR, 0.87; 95% CI, 0.77-0.97). CONCLUSION The presence of extensive drug resistance, the presence of comorbidity, and hypoalbuminemia were independent poor prognostic factors in non-HIV-infected patients with MDR-TB.

Genetic susceptibility to chronic obstructive pulmonary disease in Koreans : combined analysis of polymorphic genotypes for microsomal epoxide hydrolase and glutathione S-transferase M1 and T1

BACKGROUND Although smoking is the major causal factor in the development of chronic obstructive pulmonary disease (COPD), only 10–20% of chronic heavy cigarette smokers develop symptomatic COPD which suggests the presence of genetic susceptibility. This genetic susceptibility to COPD might depend on variations in enzyme activities that detoxify cigarette smoke products such as microsomal epoxide hydrolase (mEPHX) and glutathione-S transferase (GST). As there is increasing evidence that several genes influence the development of COPD, multiple gene polymorphisms should be investigated to find out the genetic susceptibility to COPD. METHODS The genotypes of 83 patients with COPD and 76 healthy smoking control subjects were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (PCR-RFLP) for the mEPHX gene, and multiplex PCR for GST M1 and GST T1 genes. The frequencies of polymorphic genotypes of mEPHX, GST M1, and GST T1 genes were compared both individually and in combination in patients with COPD and healthy smokers. RESULTS No differences were observed in the frequency of polymorphic genotypes in exons 3 and 4 of mEPHX, GST M1, and GST T1 genes between patients with COPD and healthy smokers. The frequencies of any combination of these genotypes also showed no differences between the COPD group and the control group. CONCLUSIONS Genetic polymorphisms in mEPHX, GST M1, and GST T1 genes are not associated with the development of COPD in Koreans.

Surgery increased the chance of cure in multi-drug resistant pulmonary tuberculosis

BACKGROUND Medical treatment of multiple drug resistant (MDR) pulmonary tuberculosis is generally quite unsuccessful. Recently, surgical management is increasing and shows promise. We analyzed our experience to identify the benefits and complications of pulmonary resection in MDR pulmonary tuberculosis. METHODS A retrospective review was performed in 27 patients undergoing pulmonary resection for MDR pulmonary tuberculosis between January 1994 and March 1998. Their average ages were 40 years and were diagnosed a median of 15 months before surgery. All patients had resistance to an average of 4.4 drugs including isoniazid and rifampin, and had received second line drugs selected according to drug sensitivity test preoperatively. Most patients (92.6%) had cavitary lesions. Bilateral lesions were also identified in 19 patients (70.4%), but the main focus was recognized in one side of the lung. Most patients were indicated to operation for those who could not achieve negative sputum despite adequate medical treatment (n = 16, 59.3%); or for negative patients who had significant pulmonary parenchymal lesion (n = 11, 40.7%) which would have had a high probability of recurrence. Pneumonectomy was done in nine patients, lobectomy in 16 and segmentectomy in two. RESULTS There was no operative mortality. Morbidity occurred in seven patients (25.9%); prolonged air leakage in three patients, reoperation due to bleeding in two, bronchopleural fistula in one, and reversible blindness in one. The median follow up period was 15 months (range 3-45). Sputum negative conversion was achieved in 22 patients (81.5%) initially. However, continued postoperative chemotherapy could convert to negative in another four patients (14.8%). Only one pneumonectomy patient (3.7%) failed because of considerable contralateral cavity. CONCLUSION For patients with MDR pulmonary tuberculosis which is localized, and with adequate pulmonary reserve function, surgical pulmonary resection combined with appropriate pre and postoperative anti-tuberculosis chemotherapy can achieve high success rate with acceptable morbidity.

Recombinant adenoviruses expressing dominant negative insulin-like growth factor-I receptor demonstrate antitumor effects on 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 α subunit and a defective β 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.

The Prevalence and Impact of Depression Among Medical Students: A Nationwide Cross-sectional Study in South Korea

Purpose This nationwide cross-sectional study assessed the prevalence, possible risk factors, and impact of depression among Korean medical students. Method Of all medical students (14,095) registered in 41 medical schools in 2006 in South Korea, 7,357 (52.2%) completed the survey. Depression was measured using the patient-rated version of the Mini International Neuropsychiatric Interview (MINI-PR). Data on academic functioning, and sociodemographic characteristics were also obtained. Results Current, one-year, and lifetime prevalence of major depressive disorder (MDD) were 2.9%, 6.5%, and 10.3%, respectively. Possible risk factors for one-year MDD were female gender, lower class years, admission track with exemption from entrance exam, living alone at a lodging house or a rented room, and financial difficulty (P < .05). The grade point averages (GPAs) of students with MDD were significantly lower than those of nondepressed students for both semesters (t = 3.8, P < .001; t = 4.8, P < .001). The odds ratio of students with MDD of receiving a GPA below 2.0 was 1.8 (CI 1.4–2.4) as compared with nondepressed students. Conclusions This study demonstrated that Korean medical students experience depression frequently. It also highlighted the possible risk factors of MDD among medical students and pervasive association of depression with poor functioning.

Prognostic factors for surgical resection in patients with multidrug-resistant tuberculosis

Although surgical lung resection could improve prognosis in some patients with multidrug-resistant tuberculosis (MDR-TB), there are no reports on the optimal candidates for this surgery. The aim of the present study was to elucidate the prognostic factors for surgery in patients with MDR-TB. Patients who underwent lung resection for the treatment of MDR-TB between March 1993 and December 2004 were included in the present study. Treatment failure was defined as greater than or equal to two of the five cultures recorded in the final 12 months of treatment being positive, any one of the final three cultures being positive, or the patient having died during treatment. The variables that affected treatment outcomes were identified through univariate and multivariate logistic regression analysis. In total, 79 patients with MDR-TB were included in the present study. The treatment outcomes of 22 (27.8%) patients were classified as failure. A body mass index <18.5 kg·m-2, primary resistance, resistance to ofloxacin and the presence of a cavitary lesion beyond the range of the surgical resection were associated with treatment failure. Low body mass index, primary resistance, resistance to ofloxacin and cavitary lesions beyond the range of resection are possible poor prognostic factors for surgical lung resection in multidrug-resistant tuberculosis patients.

Giant lymph node hyperplasia (Castleman's disease) in the chest

We have experienced 7 cases of giant lymph node hyperplasia in the chest from 1981 to 1992. The ages of the 1 male and 6 female patients ranged from 9.9 to 40.4 years (mean age, 29.2 +/- 10.4 years). In 4 patients, a mass was discovered in routine radiographs. Focal calcification suggesting continual enlargement over a long time was noted in 1 patient. The sites of lesions were unusual in 2 patients (intercostal space and intrapulmonary fissure). All patients underwent surgical removal of the mass. Five cases had typical features of the hyaline-vascular type, and 2 cases revealed a mixture of the hyaline-vascular type and the plasma-cell type. Follow-up was available in all patients (mean follow-up, 31.9 months). In 1 patient, recurrence was observed 9 years after surgical removal. In general, giant lymph node hyperplasia can occur anywhere in the chest, grow without symptoms, and recur in spite of complete resection. Surgical resection and close follow-up are advised.

Solid-organ malignancy as a risk factor for tuberculosis.

Background and objective:  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.

Clinical characteristics of tuberculosis in patients with liver cirrhosis.

Background and objectives:  Patients with liver cirrhosis are likely to be susceptible to tuberculosis (TB) because of immune system dysfunction. The aim of this study was to elucidate the clinical characteristics and treatment responses in TB patients with cirrhosis.