p16(INK4a) Promoter Hypermethylation in Sputum, Blood, and Tissue from Non-Small Cell Lung Cancer and Pulmonary Inflammation / 결핵및호흡기질환

BACKGROUND: The aberrant promoter hypermethylation of p16(INK4a), as a tumor suppressor gene, is contributory factor to non-small cell lung cancer(NSCLC). However, its potential diagnostic impact of lung cancer is unclear. This study measured the level of p16(INK4a) promoter hypermethylation in the sputum and blood, and compared this with the level measured in the tissue obtained from NSCLC and pulmonary inflammation. METHODS: Of the patients who visited the Our Lady of Mercy Hospital in Incheon, Korea for an evaluation of a lung mass and underwent blood, sputum, and tissue tests, 23patients (18 NSCLC, 5 pulmonary inflammation) were enrolled in this study. DNA was extracted from each sample and the level of p16(INK4a) methylation was determined using methylation-specific polymerase chain reaction. RESULTS: p16(INK4a) methylation of the blood was observed in 88.9% (16 of 18) and 20.0% (1 of 5) of NSCLC and from pulmonary inflammation samples, respectively (P=0.008). Methylation of the sputum was observed in 83.3% (10 of 12) 80.0% (4 of 5) of NSCLC and pulmonary inflammation samples, respectively (P=1.00). Among the 8 NSCLC tissue samples, methylation changes were detected in 75.0% of samples (6 cases). Four out of seven tissue samples (57.1%) showed concordance, being methylated in both the blood and sputum. CONCLUSIONS: There was a higher level of p16(INK4a) methylation of the blood from NSCLC patients than from pulmonary inflammation. The tissue showed a high concordance with the blood in the NSCLC samples. These findings suggest that p16(INK4a) promoter hypermethylation of the blood can used to discriminate between NSCLC and pulmonary inflammation.

A Case of Acromegaly Associated with Lung and Gastric Cancer / 결핵및호흡기질환

Patients with acromegaly have high incidence of benign or malignant neoplasia than general population. Around fifteen percent of the deaths reported in acromegaly are attributable to malignancy of cancer. On the whole, mortality in acromegaly has been shown to be correlated with the degree of growth hormone (GH) control. Especially, the levels of insulin like growth factor-1 (IGF-1) may be higher in neoplasm, but there is no clear evidence to prove that tumor development is triggered by IGF-1 in acromegaly. Henceforth, we report a case of acromegaly associated with lung and gastric cancer in a 58-year-old man, suggesting the possible carcinogenic role of IGF-1.

Influence of Obstructive Sleep Apnea on Soluble Intercellular Adhesion Molecule-1 and Vascular Endothelial Growth Factor / 결핵

BACKGROUND: Obstructive sleep apnea is a contributory factor of hypertension, arrhythmia, ischemic heart disease and other cardiovascular diseases. However, the pathophysiology underlying this relationship is unclear. Recent reports have shown that the soluble intercellular adhesion molecule-1(sICAM-1) and vascular endothelial growth factor(VEGF) are involved in the initiation and progression of atherosclerosis, and some reports state that increased levels of these cytokines are found in patients with obstructive sleep apnea. In this study, the levels of sICAM-1 and VEGF were measured in patients with obstructive sleep apnea in order to determine if obstructive sleep apnea is involved in the pathophysiology of cardiovascular diseases. METHODS: Thirty-seven patients were chosen amongst a population who visited the Sleep Disorders Clinic of St. Paul's Hospital in Seoul, Korea for a diagnosis of obstructive sleep apnea and who had subsequently undergone an overnight polysomnography at the clinic. The sera from these patients were retrieved after an overnight polysomnography session and the samples were kept at -70degrees C. The cytokine levels were determined with ELISA and the relationships between the serum levels of sICAM-1 and VEGF along with polysomnography parameters were analyzed. RESULTS: No statistically significant correlation was observed between the sICAM-1 levels and the apnea-hypopnea index(r=0.27, P>0.05). Positive correlations were found between the apnea-hypopnea index and serum VEGF levels (r=0.50, P<0.01), the apnea index and the serum sICAM-1 levels (r=0.31, P<0.01), and the apnea index and the serum VEGF levels (r=0.45, P<0.01). CONCLUSIONS: Obstructive apnea or hypopnea leads to an increase in the sICAM-1 and VEGF levels. Such an increase in the cytokine levels most likely leads to the higher incidence of cardiovascular diseases observed in patients with obstructive sleep apnea.

A Case of Ischemic Colitis Following Colonoscopy / 대한소화기내시경학회지

Ischemic colitis can be caused either by vascular or colonic wall factor or by both. Shunting of blood away from the mucosa may contribute to ischemia of the colon, but the mechanism of ischemia is not known. Ischemic colitis precipitated by colonoscopy has rarely been reported. Potentially air insufflation or mechanical effect during colonoscopic examination can cause ischemic colitis as a colonic wall factor. Recently, we experienced a case of ischemic colitic, which had been developed several hours after colonoscopic polypectomy. So we report this case with brief review of literature.

Feedback Control of Cyclooxygenase-2 Expression by Prostaglandin E2 in Rheumatoid Synoviocytes

Objective: The role of prostaglandin E2 (PGE2) in the etiopathogenesis of immune and inflammatory diseases has become the subject of recent debate. To determine the role of PGE2 in rheumatoid arthritis (RA), we tested the effect of exogenous PGE2 on the production of cyclooxygenase-2 (COX-2) by rheumatoid synoviocytes. METHODS: Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of RA patients, and cultured in the presence of PGE2. The COX-2 mRNA and protein expression levels were determined by RT-PCR and Western blot analysis, respectively. The PGE2 receptor subtypes in the FLS were analyzed by RT-PCR. Electrophoretic mobility shift assay (EMSA) was used to measure the NF-kappaB binding activity for COX-2 transcription. The in vivoeffect of PGE2 on the development of arthritis was also tested in collagen induced arthritis (CIA) animals. RESULTS: PGE2 (10(-11) to 10(-5) M) dose-dependently inhibited the expression of COX-2 mRNA and the COX-2 protein stimulated with IL-1beta, but not COX-1 mRNA. NS-398, a selective COX-2 inhibitor, displayed an additive effect on PGE2-induced COX-2 downregulation. The FLS predominantly expressed the PGE2 receptor (EP) 2 and EP4, which mediated the COX-2 suppression by PGE2. Treatment with anti-IL-10 monoclonal antibodies partially reversed the PGE2-induced suppression of COX-2 mRNA, suggesting that IL-10 may be involved in modulating COX-2 by PGE2. Experiments using an inducer and an inhibitor of cyclic AMP (cAMP) suggest that cAMP is the major intracellular signal that mediates the regulatory effect of PGE2 on COX-2 expression. EMSA revealed that PGE2 inhibited the binding of NF-kappaB in the COX-2 promoter via a cAMP dependent pathway. In addition, a subcutaneous injection of PGE2 twice daily for 2 weeks significantly reduced the incidence and severity of CIA as well as the production of IgG antibodies to type II collagen. CONCLUSION: Our data suggest that overproduced PGE2 in the RA joints may function as an autocrine regulator of its own synthesis by inhibiting COX-2 production and may, in part, play an anti-inflammatory role in the arthritic joints.

Fate of Atrial Myocardium in Severe Mitral Regurgitation in the Aspect of Programmed Cell Death

BACKGROUND AND OBJECTIVES: From the view point of the molecular aspects, the fate of long standing pressure and volume overloaded atrium in severe MR has not been evaluated. This study was performed to elucidate whether apoptosis of right atrial myocytes is related to atrial changes. SUBJECTS AND METHODS: The medical records of 16 patients (M: F=8: 8, mean age=52+/-12), with severe MR having undergone valve replacement surgery, were retrospectively reviewed. The subjects were divided into 2 groups according to the duration of their symptoms (group I, symptom duration less than 12 months, n=10 and group II, more than 12 months, n=6). Using the atrial myocardium specimens obtained during surgery, TUNEL assays and immunohistochemical staining were performed for the expressions of Fas, Bax and the Bcl family. RESULTS: Apoptotic indices of TUNEL assay were 31.1+/-12.6 and 4.9+/-4.3% in groups I and II, respectively (p<0.01). The Fas expressions were 42.1+/-14.4 and 27.8+/-10.5% in groups I and II, respectively (p<0.05), but in group I, with atrial fibrillation (AF), was 49.3+/-6.9%, which was higher than the 29.2+/-12.5% in group I without AF and group II (p<0.001). The Bax expression in group I patients with a left atrial size less than 4 cm was 19.2+/-10.7%, which was higher than the 7.2+/-6.2% in group I with a left atrial size more than 4 cm and group II (p<0.05). CONCLUSION: Programmed cell death of the atrial myocardium, in severe MR, might be an early molecular pathological change rather than the late sequelae. The causality between programmed cell death and electrical and structural changes of the atrium should be further investigated.

Muscle Mass in the Calf as a Presenting Symptom of Sarcoidosis / 대한류마티스학회지

Sarcoidosis is a multisystemic granulomatous disease of unknown cause. Lung, skin, eye, liver and lymph nodes are commonly affected. But the nodular type of muscular sarcoidosis is rare. The nodular type can be presented with a soft tissue mass that may be confused with a tumor. Magnetic resonance imaging and muscle biopsy are useful methods for early diagnosis. Optimal management of nodular sarcoidosis is not well known, but surgical excision or corticosteroid may be considered as an initial management. We report a case of nodular muscular sarcoidosis as an initial manifestation of sarcoidosis in a 56-year-old woman who was treated with corticosteroid therapy after surgical excision.