Ju Ock Na

Association of IL-17RB Gene Polymorphism With Asthma

BACKGROUND Interleukin (IL)-17E is a member of the IL-17 family, which induces IL-4, IL-5, IL-13, and eotaxin in experimental animals via IL-17 receptor B (IL-17RB). The activation of IL-17RB amplifies allergic-type inflammatory responses by inducing Jun kinase (or JNK), p38 mitogen-activated protein kinase (or MAPK), and nuclear factor-kappaB. OBJECTIVES We examined the association of polymorphisms in the IL-17RB gene with asthma susceptibility and investigated the effects of those polymorphisms on the transcription of various IL-17RB isoforms. METHODS In total, 954 asthmatic patients or 265 healthy control subjects were screened for polymorphisms in IL-17RB by single-base extension. The messenger RNA expression IL-17RB in B-cell lines derived from patients was also measured by reverse transcription-polymerase chain reaction. RESULTS Direct sequencing of 24 unrelated Korean DNA samples revealed 18 genetic variants, including four insertion/deletions and 14 single-nucleotide polymorphisms (SNPs). Six of the SNPs (-1465G>A, +5661G>A, +6297T>C [Y123Y], +13797C>T, +18661C>T, and +18965G>A) were used to screen a larger group of subjects. Intronic polymorphism +5661G>A was significantly associated with the development of asthma (p = 0.001); moreover, a minor allele of IL-17RB +5661G>A appeared at a lower frequency in the asthmatic patients than in the healthy control subjects (0.13 vs 0.19, respectively). The IL-17RB messenger RNA expression in B cells homozygous for IL-17RB+ 5661GG was significantly higher than that in B cells homozygous for IL-17RB+5661AA (p = 0.002). CONCLUSIONS A rare allele of IL-17RB +5661G>A may have a protective role against the development of asthma via regulation at the level of transcription. The SNPs identified in this study may be used to develop markers to assess the risk of asthma.

The Effect of Post-Treatment N-Acetylcysteine in LPS-Induced Acute Lung Injury of Rats

Background Oxidation plays an important role in acute lung injury. This study was conducted in order to elucidate the effect of repetitive post-treatment of N-acetylcysteine (NAC) in lipopolysaccaride (LPS)-induced acute lung injury (ALI) of rats. Methods Six-week-old male Sprague-Dawley rats were divided into 4 groups. LPS (Escherichia coli 5 mg/kg) was administered intravenously via the tail vein. NAC (20 mg/kg) was injected intraperitoneally 3, 6, and 12 hours after LPS injection. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the ALI at 24 hours after LPS injection. The concentration of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were measured in BALF. Nuclear factor κB (NF-κB), lipid peroxidation (LPO), and myeloperoxidase (MPO) were measured using lung tissues. Micro-computed tomography (micro-CT) images were examined in each group at 72 hours apart from the main experiments in order to observe the delayed effects of NAC. Results TNF-α and IL-1β concentration in BALF were not different between LPS and NAC treatment groups. The concentration of LPO in NAC treatment group was significantly lower than that of LPS group (5.5±2.8 nmol/mL vs. 16.5±1.6 nmol/mL) (p=0.001). The activity of MPO in NAC treatment group was significantly lower than that of LPS group (6.4±1.8 unit/g vs. 11.2±6.3 unit/g, tissue) (p<0.048). The concentration of NF-κB in NAC treatment group was significantly lower than that of LPS group (0.3±0.1 ng/µL vs. 0.4±0.2 ng/µL) (p=0.0001). Micro-CT showed less extent of lung injury in NAC treatment than LPS group. Conclusion After induction of ALI with lipopolysaccharide, the therapeutic administration of NAC partially attenuated the extent of ALI through the inhibition of NF-κB activation.

Remarkable Effect of Gefitinib Retreatment in a Lung Cancer Patient With Lepidic Predominat Adenocarcinoma who had Experienced Favorable Results From Initial Treatment With Gefitinib: A Case Report

Gefitnib is an oral agent of epidermal growth factor receptor tyrosine kinase inhibitor, and it has a certain efficacy against non-small cell lung cancer. There are some reports that the non-small cell lung cancer patients who experienced disease progression after responding to gefitinib were again sensitive to re-administration of gefitinib following temporary cessation of gefitinib. This is the case report showing a remarkable effect of gefitinib re-treatment in a patient with metastatic invasive adenocarinoma who had experienced favorable results from the initial treatment with gefitinib.

Association of IKBA gene polymorphisms with the development of asthma.

Nuclear factor-κB (NF-κB) orchestrates the expression of genes responsible for airway inflammation and remodeling in asthma. The activity of NF-κB is tightly regulated by IKBA, which may be modulated by genetic polymorphisms of the IKBA gene. We investigated the association between asthma susceptibility and IKBA gene polymorphisms in a Korean population. Genotyping was performed in BA (bronchial asthma) and NC (normal control). We measured reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, and luciferase reporter assays, respectively. A -673A>T (rs2233407) was associated with asthma development in subjects with atopic asthma (odds ratio = 0.56, p = 0.004). The IKBA mRNA level was higher in B-cell lines with the rs2233407 TT genotype compared with those with the AA genotype (p = 0.024). The luciferase activity of the rs2233407 T genotype was higher than that of the A (p = 0.002). The cytoplasmic levels of total IKBA and IKBA [p-S32] were higher in B cell lines of the rs2233407 TT genotype than those of the AA (p = 0.016 and p = 0.036, respectively), whereas nuclear NF-κB activity in cells with the IKBA rs2233407 AA genotype was higher than in cells with the AA (p = 0.038). The IKBA rs2233407 A>T polymorphism may predispose individuals to the development of atopic asthma via regulation of IKBA gene expression at the transcriptional level.

Indolent Metastatic Squamous Cell Carcinoma of Unknown Primary in the Intrathoracic Lymph Node: A Case Report and Review of the Literatures

Metastatic squamous cell carcinoma from a cancer of unknown primary (CUP) affecting the intrathoracic lymph node is very rare. We reported a case of metastatic squamous cell carcinoma in the hilar and interlobar lymph node from a patient with CUP and reviewed the associated literature. Abnormal mass in the right hilar area was incidentally detected. A chest computed tomography scan showed a 2.5-cm diameter mass in the right hilum that had changed little in size for 3 years. The patient underwent a right pneumonectomy and mediastinal lymph node dissection. A metastatic squamous cell carcinoma in the hilar and interlobar lymph nodes without a primary lung or other lesion was diagnosed. The patient received adjuvant chemotherapy for a diagnosis of T0N1M0 lung cancer.

A Case of Adult Congenital Cystic Adenomatoid Malformation of the Lung with Atypical Adenomatous Hyperplasia

Congenital cystic adenomatoid malformation of the lung is a rare disease that shows multiple cystic lesions in pulmonary tissues in the development process. It was first described by Chin et al.1 in 1949 and its incidence is known to be 1:25,000 to 1:35,0002. With the development of prenatal diagnosis, this disease can be diagnosed in 60% and detected within 2 years because of such symptoms as respiratory distress by compression of surrounding lung tissues immediately after birth and repeated respiratory infections in infancy. Among adults, it is detected accidentally on X-ray or by such symptoms as pneumonia, pneumothorax, and hemoptysis. In Korea, the first case in a 28 year-old woman was reported by Geun-Heung Ki et al.3 in 1989. Since then, about 25 adult cases were reported until 2006.