SCI 발표논문

2006년 77편

772006

제1저자 박병래 · 교신저자 이효석

, , , , , ,
Association of common promoter polymorphisms of MCP1 with hepatitis B virus clearance.
Exp Mol Med. 2006;38(6):694-702.

Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant cancers closely associated with chronic infection by the hepatitis B virus (HBV) or the hepatitis C virus (HCV) throughout the world. In this study, the genetic associations of 20 known polymorphisms in eight candidate genes, including angiotensinogen (AGT), cadherin 1 (CDH1), cyclooxygenase 2 (COX2), monocyte chemotactic protein-1 (MCP1), multidrug resistance 1 (MDR1), chemokine ligand 5 (RANTES), thrombospondin 2 (THBS2), and thrombospondin 4 (THBS4), were analyzed in a large chronic hepatitis B cohort (n=1,095) recruited from the Korean population. In addition, three polymorphisms in chemokine receptor 4 (CXCR4) and vimentin (VIM) identified in this study were also genotyped. Using logistic regression analysis controlling possible confounding factors, one common (freq.=0.367) promoter polymorphism of MCP1 (MCP1-2518G>A) among analyzed polymorphisms was significantly associated with clearance of HBV infection. The frequency of homozygotes for the MCP1-2518A allele (MCP1-2518A/A) among chronic hepatitis B virus (HBV) carrier patients was significantly higher than that among spontaneously recovered (SR) subjects (17.7% vs. 10.4%)(OR=1.78, P=0.004). Our findings imply a plausible explanation for the contribution of host genetic determinants to the variable outcome of HBV infection, which might provide valuable information for future genetic study in this area.
PubMed IF 17.5 소화기내과
762006

제1저자 최창민 · 교신저자 임재준

, , , , , ,
The role of TST in the diagnosis of latent tuberculosis infection among military personnel in South Korea.
Int J Tuberc Lung Dis. 2006;10(12):1342-6.

Abstract
BACKGROUND The rapid and accurate diagnosis of latent tuberculosis infection (LTBI) is crucial in military settings because military personnel live in crowded circumstances and are of an age group with a high incidence of tuberculosis (TB). We tried to elucidate whether the tuberculin skin test (TST) accurately reflects the risk of TB infection among military personnel, in a setting of intermediate TB prevalence and where bacille Calmette-Guérin (BCG) vaccination is mandatory.
METHODS A multi-stage cluster survey was conducted among military personnel in South Korea. Participants were grouped according to their risk of TB infection: Group 1, no identifiable risk of TB; Groups 2 and 3, recent casual (Group 2) or close (Group 3) contact with smear-positive TB patients.
RESULTS Of 1045 participants, 857 (82.0%) had been BCG-vaccinated. The odds ratio (OR) of a positive TST (10 mm cut-off) for Group 2 (n = 184) and Group 3 (n = 83) compared with Group 1 (n = 778) were 0.95 (95%CI 0.67-1.38) and 1.7 (95%CI 1.06-2.70), respectively (P value for trend 0.16).
CONCLUSIONS The TST does not accurately reflect the risk of LTBI among young military personnel in a setting where there is intermediate TB prevalence and extensive BCG coverage.
PubMed IF 3.6 호흡기내과
752006

제1저자 천재희 · 교신저자 김주성

, , , , ,
Plant sterol guggulsterone inhibits nuclear factor-kappaB signaling in intestinal epithelial cells by blocking IkappaB kinase and ameliorates acute murine colitis.
Inflamm Bowel Dis. 2006;12(12):1152-61.

Abstract
BACKGROUND/AIMS The plant sterol guggulsterone has been shown to have anti-inflammatory properties. It remains unknown, however, whether guggulsterone is effective for the treatment of inflammatory bowel disease (IBD). Therefore, we investigated anti-inflammatory effects of guggulsterone on intestinal epithelial cells (IEC) and on experimental murine colitis models and elucidated its molecular mechanisms.
METHODS Human Caco-2 cells and rat non-transformed IEC-18 cells were stimulated with interleukin (IL)-1beta or lipopolysaccharide (LPS) with or without guggulsterone. The effects of guggulsterone on nuclear factor (NF)-kappaB signaling in IEC were examined by intercellular adhesion molecule (ICAM)-1 real-time reverse-transcription polymerase chain reaction, NF-kappaB transcriptional activity assay, Western blotting for IkappaB phosphorylation/degradation, electrophoretic mobility shift assay, and in vitro IkappaB kinase (IKK) assay. For in vivo study, dextran sulfate sodium (DSS)-treated mice were fed with or without guggulsterone. Colitis was quantified by disease activity index and evaluation of macroscopic and microscopic findings. Phosphorylation of IkappaB and IKK in colon mucosa was assessed by Western blotting and immunohistochemistry.
RESULTS Guggulsterone significantly inhibited LPS- or IL-1beta-induced ICAM-1 gene expression, NF-kappaB transcriptional activity, IkappaB phosphorylation/degradation, and NF-kappaB DNA binding activity in IEC. Moreover, guggulsterone strongly blocked IKK activity. Administration of guggulsterone significantly reduced the severity of DSS-induced murine colitis as assessed by clinical disease activity score, colon length, and histology. Furthermore, tissue upregulation of IkappaB and IKK phosphorylation induced by DSS was attenuated in guggulsterone-treated mice.
CONCLUSION Guggulsterone blocks NF-kappaB signaling pathway by targeting IKK complex in IEC and attenuates DSS-induced acute murine colitis, which suggests that guggulsterone could be an attractive therapeutic option in the treatment of IBD.
PubMed IF 5.5 소화기내과
742006

제1저자 곽금연 · 교신저자 윤정환

, , , , ,
Lysophosphatidylcholine suppresses apoptotic cell death by inducing cyclooxygenase-2 expression via a Raf-1 dependent mechanism in human cholangiocytes.
J Cancer Res Clin Oncol. 2006;132(12):771-9.

Abstract
PURPOSE The high incidence of biliary tract carcinoma in patients with anomalous pancreaticobiliary ductal junction (APBDJ) implicates that a compositional alteration in bile may contribute to the genesis of this cancer. Lysophosphatidylcholine (LPC) is generated in the bile of these patients. Given the role of cyclooxygenase-2 (COX-2) in biliary tract carcinogenesis, we postulated that LPC induces COX-2 in cholangiocytes.
METHODS The effect of LPC on COX-2 expression in cholangiocytes was evaluated by immunoblot analysis, real-time PCR and reporter gene assay. Apoptosis was induced by TRAIL treatment, and quantified using DAPI staining.
RESULTS Lysophosphatidylcholine increased COX-2 protein expression in cholangiocytes in a concentration- and time-dependent manner. LPC-induced Raf-1 activation was responsible for this COX-2 induction. Accordingly, LPC increased COX-2 mRNA levels in a Raf-1 dependent manner by stabilizing COX-2 mRNA. Finally, LPC attenuated TRAIL-mediated apoptosis through a COX-2/PgE2 dependent mechanism.
CONCLUSIONS Collectively, these results implicate that LPC inhibits cholangiocyte apoptosis by inducing COX-2 expression via a Raf-1 dependent mechanism. This anti-apoptotic signaling may participate in biliary tract carcinogenesis in APBDJ patients, and therefore, its interruption may be a viable chemopreventative strategy.
PubMed IF 3.3 소화기내과
732006

제1저자 김연수 · 교신저자 김연수

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Distinctive role of donor strain immature dendritic cells in the creation of allograft tolerance.
Int Immunol. 2006;18(12):1771-7.

Abstract
Dendritic cells (DCs) are pivotal antigen-presenting cells and serve a unique role in initiating immunity. To test the hypothesis that pre-immunization of recipient with certain DC subsets of donor origin can influence graft outcome, we have studied the effects of immunization with allogeneic CD4(+)CD8(-)CD11c(+) dendritic cell (CD4(+)DC) and CD4(-)CD8(+)CD11c(+) dendritic cell (CD8(+)DC) on the allograft response. Although both immature CD4(+)DC and CD8(+)DC subsets from DBA/2 were able to prime naive allogeneic C57BL/6 (B6) T cells in mixed lymphocyte reaction (MLR), CD8(+)DC exerted more vigorous alloimmune responses than CD4(+)DC did. Also, CD4(+)DC-driven allogeneic T cell response was attenuated more significantly by anti-CD154 mAb than CD8(+)DC-driven response. Consistent with the MLR results, combined pre-treatment with CD4(+)DC, but not CD8(+)DC, plus anti-CD154 mAb produced donor strain-specific long-term graft survival and induced tolerance while treatment with CD8(+)DC plus anti-CD154 mAb created minimal prolongation of allograft survival in a pancreas islet transplant model (DBA/2-->B6). The beneficial effects exerted by CD4(+)DC and anti-CD154 mAb pre-treatment were correlated with T(h)1 to T(h)2 immune deviation and with the amplified donor-specific suppressive capacity by recipient CD4(+)CD25(+) T cells. These findings highlight the capacity of CD4(+)DC to modulate alloimmune responses, and suggest therapeutic approaches for the induction of donor-specific tolerance.
PubMed IF 3.4 신장내과
722006

제1저자 이세원 · 교신저자 임재준

, , , , , , , , ,
The prevalence and evolution of anemia associated with tuberculosis.
J Korean Med Sci. 2006;21(6):1028-32.

Abstract
Tuberculosis (TB) may produce abnormalities in the peripheral blood, including anemia. However, the evolution of TB-associated anemia with short-term combination anti-TB chemotherapy has not been well elucidated. The aim of this study was to characterize TB-associated anemia by clarifying its prevalence, characteristics, and evolution, through involving large numbers of patients with TB. The medical records of adult patients with TB diagnosed between June 2000 and May 2001 were reviewed. Among 880 patients with TB, 281 (31.9%) had anemia on diagnosis of TB, however, the hemoglobin concentration was less than 10 g/dL in only 45 patients (5.0%). Anemia was more frequently associated with the female and old age. Good treatment response, young age (< or =65 yr-old) and initial high hemoglobin were the predictive factor for resolution of anemia. In 202 patients with anemia (71.9%), anemia was normocytic and normochromic. During or after anti-TB treatment, anemia was resolved in 175 (64.6%) out of 271 patients without iron intake. The mean duration of resolution from the initiation of anti-TB treatment was 118.8+/-113.2 days. In conclusion, anemia is a common hematological abnormality in patients with TB and close observation is sufficient for patients with TB-associated anemia, because TB-associated anemia is usually mild and resolves with anti-TB treatment.
PubMed IF 3.2 호흡기내과
712006

제1저자 이은영 · 교신저자 송영욱

, , , , , , , , , , ,
Tramadol 37.5-mg/acetaminophen 325-mg combination tablets added to regular therapy for rheumatoid arthritis pain: a 1-week, randomized, double-blind, placebo-controlled trial.
Clin Ther. 2006;28(12):2052-60.

Abstract
OBJECTIVE This study evaluated the efficacy and tolerability of tramadol 37.5-mg/acetaminophen 325-mg combination tablets (tramadoUAPAP) as add-on therapy in subjects with rheumatoid arthritis (RA) pain that was inadequately controlled by NSAIDs and disease-modifying antirheumatic drugs alone.
METHODS Subjects in this multicenter, double-blind trial were randomized in a 3:1 ratio to receive 1 tramadol/ APAP tablet TID or a matching placebo for 1 week. Stable doses of previous medications were continued during the study. The primary efficacy variable was the mean daily pain relief score over 1 week, measured on a 6-point scale (4 = complete; ' = a lot; 2 = some; 1 = a little; 0 = none; -1 = worse). Secondary outcomes included the mean daily pain intensity score, measured on a 100-mm visual analog scale (VAS) (from 0 mm = no pain to 100 mm = extreme pain); pain intensity and pain relief at day 7; subjects' and investigators' mean overall assessments of study drug, measured on a Likert scale (from 2 = very good to -2 = very poor); and subjects' assessments of 8 aspects of physical function (measured on the Health Assessment Questionnaire).
RESULTS Of 277 subjects randomized to treatment, 267 (201 tramadol/APAP, 66 placebo) were included in the intent-to-treat population. Mean (SD) daily pain relief scores at the end of 1 week were significantly greater in the tramadol/APAP group compared with the placebo group (1.04 [0.89] vs 0.78 [0.80], respectively; P = 0.037), and mean daily pain intensity scores at the end of 1 week were significantly lower (47.23 [19.96] vs 53.81 [16.59]; P = 0.018). Physical function at the end of 1 week did not differ significantly between tramadol/APAP and placebo. Two hundred seventy-two subjects (205 tramadol/APAP, 67 placebo) were evaluable for tolerability. One hundred thirty-three of these subjects had at least 1 adverse event. The incidence of adverse events was significantly higher in the tramadol/APAP group than in the placebo group (57.6% vs 22.4%; P < 0.001). Discontinuations due to adverse events occurred in 19.0% of the tramadol/APAP group and 3.0% of the placebo group (P = 0.001). Of 213 treatment-related adverse events in tramadol/APAP subjects, nausea (34.1%) was the most frequent, followed by dizziness (20.0%) and vomiting (15.6%). One serious adverse event--chest discomfort, nausea, and vomiting after taking study medication-occurred in a subject receiving tramadol/APAP The symptoms resolved 1 day after discontinuing tramadol/APAP.
CONCLUSIONS In this study, tramadol/APAP used as add-on therapy in subjects with symptomatic RA was associated with a significant improvement in pain relief and a significant reduction in pain intensity compared with placebo, with no improvement in physical function. Use of tramadol/APAP may be considered when analgesics are needed in addition to conventional NSAIDs and disease-modifying antirheumatic drugs in subjects with RA.
PubMed IF 3.7 류마티스내과
702006

제1저자 이주희 · 교신저자 김태유

, , , , , ,
Histone deacetylase inhibitor enhances 5-fluorouracil cytotoxicity by down-regulating thymidylate synthase in human cancer cells.
Mol Cancer Ther. 2006;5(12):3085-95.

Abstract
Thymidylate synthase (TS) overexpression is a key determinant of 5-fluorouracil (5-FU) resistance in human cancer cells. TS is also acutely up-regulated with 5-FU treatment, and, thus, novel strategies targeting TS down-regulation seem to be promising in terms of modulating 5-FU resistance. Here, we report that histone deacetylase inhibitors can reverse 5-FU resistance by down-regulating TS. By using cDNA microarrays and validation experiments, we found that trichostatin A reduced the expression of both TS mRNA and TS protein. Cotreatment with trichostatin A and cycloheximide restored TS mRNA expression, suggesting that TS mRNA is repressed through new protein synthesis. On the other hand, TS protein expression was significantly reduced by lower doses of trichostatin A (50 nmol/L). Mechanistically, TS protein was found to interact with heat shock protein (Hsp) complex, and trichostatin A treatment induced chaperonic Hsp90 acetylation and subsequently enhanced Hsp70 binding to TS, which led to the proteasomal degradation of TS protein. Of note, combined treatment with low-dose trichostatin A and 5-FU enhanced 5-FU-mediated cytotoxicity in 5-FU-resistant cancer cells in accordance with TS protein down-regulation. We conclude that a combinatorial approach using histone deacetylase inhibitors may be useful at overcoming 5-FU resistance.
PubMed IF 6.9 혈액종양내과
692006

제1저자 강해연 · 교신저자 김나영

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Progression of atrophic gastritis and intestinal metaplasia drives Helicobacter pylori out of the gastric mucosa.
Dig Dis Sci. 2006;51(12):2310-5.

Abstract
This study was performed to evaluate the implication of anti-H. pylori IgG positivity when CLOtest, histological test, and culture in the antrum and body are all negative, and to find out the specific disease category that is more affected by the hostile relationship of atrophic gastritis and intestinal metaplasia (IM) with H. pylori. Four hundred thirty-six patients (84 controls, 69 with duodenal ulcer, 96 with benign gastric ulcer, 43 with dysplasia, 144 with gastric cancer), who had not received any eradication therapy, were divided into three groups according to H. pylori test: CLOtest or histological H. pylori-positive group (group A; 294 cases), only anti-H. pylori IgG-positive group (group B; 62 cases), and anti-H. pylori IgG-negative group (group C; 80 cases). The grade of neutrophil and monocyte infiltration, atrophic gastritis, and IM was compared according to the updated Sydney system classification. Neutrophil and monocyte infiltrations were significantly severe in the group A. In contrast, the grade of atrophic gastritis and IM in the antrum was significantly higher in group B than the other two groups, A or C. When patients were divided according to the disease outcome in each group, the grade of IM in the body was statistically higher only in the patients with cancer or dysplasia in group B. These results suggest that anti-H. pylori IgG positivity with all negative invasive H. pylori tests represents past infection with H. pylori rather than a false negative, especially in the case of dysplasia and gastric cancer.
PubMed IF 2.8 소화기내과
682006

제1저자 이재정 · 교신저자 허대석

, , ,
Enhanced specificity of the p53 family proteins-based adenoviral gene therapy in uterine cervical cancer cells with E2F1-responsive promoters.
Cancer Biol Ther. 2006;5(11):1502-10.

Abstract
p63 and p73, the p53 family proteins, are similar to p53 in many aspects: structural homology, transactivation of p53-downstream genes, and induction of apoptosis. Interestingly, they also differ from p53; in particular, they are not inhibited by viral oncoproteins such as HPV E6. This feature would be an advantage over p53 in HPV-associated cancers and therefore, we evaluated the therapeutic potentials of various p53 family proteins (p73alpha, p73beta, p63alpha and p63gamma) against HPV-infected cervical cancers. In clonogenic assay, exogenous expression of p73alpha, p73beta and p63gamma inhibited the colony formation of HPV-positive cervical cancer cells under G418- selection while p53 could not. Recombinant adenoviruses Ad/CMVp73alpha, Ad/CMVp73beta and Ad/CMVp63gamma induced potent apoptosis in all infected cervical cancers (CasKi, SiHa, HeLa, C33A, SNU682, SNU17, SNU1005, SNU703), irrespective of their HPV-infection status. Unfortunately however, Ad/CMVp73alpha, Ad/CMVp73beta, and Ad/CMVp63gamma inhibited also normal cells such as endothelial cells, fibroblasts, and keratinocytes thus, tumorspecific promoter was indispensable to the p53 family proteins-based therapy. Here we report a stringent tumor killing by p73beta in combination with ESM6, a synthetic promoter targeting the DNA tumor virusassociated cancers. Recombinant adenoviruses encoding p73beta by ESM6 (Ad/ESM6p73beta and Ad/ESM6p73bENH) expressed p73beta and induced apoptosis only in the cancer cells but not in normal cells. Collectively, we suggest that the p53 family proteins are potent therapeutic agents for HPV-associated uterine cervical cancers and ESM6 mediated expression of the p53 family proteins would be a safe and strong tumor targeting strategy.
PubMed IF 5.7 혈액종양내과
672006

제1저자 강영애 · 교신저자 임재준

, , , , , , , ,
Cost of treatment for multidrug-resistant tuberculosis in South Korea.
Respirology. 2006;11(6):793-8.

Abstract
OBJECTIVE AND BACKGROUND Costs associated with multidrug-resistant tuberculosis (MDR-TB) are higher than those associated with drug-susceptible TB because of the higher prices of second-line anti-TB drugs, the prolonged duration of treatment, greater productivity loss and higher mortality. The aim of this study was to estimate the cost of treatment for MDR-TB according to the treatment strategy and prognosis in South Korea.
METHODS We estimated the direct (medical and non-medical) and indirect cost for the treatment of MDR-TB according to the treatment strategies and prognosis: in medically treated, surgically treated and deceased patients groups. The same analyses were undertaken for drug-susceptible TB for comparison. The patients with MDR-TB or drug-susceptible TB were randomly selected from the TB cohort of Seoul National University Hospital, Seoul, South Korea.
RESULTS Direct costs per person were US$4000 (US$2527-4841) in the medically treated group, US$17,457 (US$10,133-26,418) in the surgically treated group and US$33,362 (US$25 386-40 338) in the deceased group. Total costs per person were US$15,856 (US$10,752-38,421), US$47,159 (US$20,587-77,622) and US$478,357 (US$257,377-777,778), respectively. For the patients with drug-susceptible TB, the total cost ranged from US$1680 to US$7637 (median US$2166).
CONCLUSIONS The cost for the treatment of MDR-TB is seven to 22 times that of managing the drug-susceptible TB in South Korea. Considering the high cost, transmissibility and considerable fatality of MDR-TB, there is a need to provide specific separate funding for multidrug-resistant tuberculosis.
PubMed IF 7.2 호흡기내과
662006

제1저자 조영민 · 교신저자 박경수

, , , , , , ,
Plasma retinol-binding protein-4 concentrations are elevated in human subjects with impaired glucose tolerance and type 2 diabetes.
Diabetes Care. 2006;29(11):2457-61.

Abstract
OBJECTIVE The dysregulation of adipokines is closely associated with the pathogenesis of insulin resistance and type 2 diabetes. Retinol-binding protein-4 (RBP4), a new adipokine, was recently reported to provide a link between obesity and insulin resistance. Here, we examined the relation between plasma RBP4 concentrations and various metabolic parameters in humans.
RESEARCH DESIGN AND METHODS An enzyme-linked immunosorbent assay was developed to measure human RBP4 plasma concentrations, which were then compared with various parameters related to insulin resistance in subjects with normal glucose tolerance (NGT; n = 57), impaired glucose tolerance (IGT; n = 48), and type 2 diabetes (n = 49).
RESULTS Plasma RBP4 concentrations were higher in the IGT and type 2 diabetic groups than in the NGT group (median 18.9 [range 11.2-45.8], 20.9 [9.9-48.5], and 18.1 microg/ml [9.3-30.5], respectively). However, no difference was found between plasma RBP4 concentrations in the IGT and type 2 diabetic groups. Plasma RBP4 concentrations were found to be associated with sex, waist circumference, fasting plasma glucose, and insulin resistance. Of these, sex and fasting plasma glucose levels were found to be independent determinants of plasma RBP4 concentration.
CONCLUSIONS Plasma RBP4 concentrations were found to be elevated in subjects with IGT or type 2 diabetes and to be related to various clinical parameters known to be associated with insulin resistance.
PubMed IF 22.6 내분비대사내과
652006

제1저자 박주경 · 교신저자 류지곤

, , , , , ,
Gemcitabine chemotherapy versus 5-fluorouracil-based concurrent chemoradiotherapy in locally advanced unresectable pancreatic cancer.
Pancreas. 2006;33(4):397-402.

Abstract
OBJECTIVES The aim of this study was to compare the survival benefits associated with gemcitabine chemotherapy and 5-fluorouracil (5-FU)-based concurrent chemoradiotherapy (CCRT) in locally advanced unresectable pancreatic cancer.
METHODS One hundred and thirty-eight locally advanced unresectable pancreatic cancer patients were retrospectively enrolled from January 1995 to January 2005. All cases were histologically proven, and patients received gemcitabine chemotherapy, 5-FU-based CCRT, or supportive care at Seoul National University Hospital.
RESULTS Median overall survival was 8.2 months. Twenty-six patients received gemcitabine chemotherapy, 56 patients 5-FU-based CCRT, and 56 patients supportive care. Weight loss and treatment modality were identified as independent prognostic factors by multivariate analysis. Patients in the 5-FU-based CCRT (overall survival, 10.4 months) and gemcitabine chemotherapy (11.3 months) groups showed survival benefit over those received supportive care (6.1 months, P < 0.0001). No grades 3 to 4 toxic adverse effects occurred in either treatment group and no statistical significant survival difference was found between gemcitabine chemotherapy and 5-FU-based CCRT (P = 0.5).
CONCLUSIONS Patients with locally advanced pancreatic cancer who received gemcitabine chemotherapy or 5-FU-based CCRT showed better survival than those who received supportive care only. Gemcitabine chemotherapy and 5-FU-based CCRT showed similar survival advantages.
PubMed IF 2.2 소화기내과
642006

제1저자 한세원 · 교신저자 김태유

, , , , , , , , , , ,
Clinical predictors versus epidermal growth factor receptor mutation in gefitinib-treated non-small-cell lung cancer patients.
Lung Cancer. 2006;54(2):201-7.

Abstract
BACKGROUND Clinical predictors including Asian, female, adenocarcinoma and never-smoker and epidermal growth factor mutation are associated with gefitinib responsiveness in non-small-cell lung cancer. Direct comparison between clinical predictors and EGFR mutation for their predictive power has not been reported.
PATIENTS AND METHODS For 120 Korean NSCLC patients treated with gefitinib, we have analyzed EGFR mutational status in exons 18, 19 and 21. Patients were grouped according to the number of clinical predictors (female, adenocarcinoma and never-smoker). Response rate (RR), time-to-progression (TTP) and overall survival (OS) were analyzed. Multivariate analysis was performed to investigate which approach yielded better prediction.
RESULTS RRs according to number of clinical predictors were 0: 3.4%, 1: 17.1%, 2: 29.4% and 3: 33.3% (p=0.002). Patients with gefitinib-sensitive EGFR mutation showed 61.9% RR compared with 12.1% in the remaining patients (p<0.001). RRs were higher in patients with the EGFR mutations regardless of the number of clinical predictors. In multivariate analysis, gefitinib-sensitive EGFR mutation showed higher odds ratio of response (9.6, 95% confidence interval [CI] 3.2-28.7) compared with number of clinical predictors (1.7, 95% CI 1.1-2.7). Hazard ratio (HR) of TTP was also better in gefitinib-sensitive EGFR mutation (0.24, 95% CI 0.12-0.47) than number of clinical predictors (0.83, 95% CI 0.69-0.99). Only gefitinib-sensitive EGFR mutation was associated with improved OS (HR 0.25, 95% CI 0.12-0.52).
CONCLUSION EGFR mutation should be analyzed whenever possible for effective prediction of objective benefit from gefitinib in NSCLC patients with one or more clinical predictors.
PubMed IF 5.3 혈액종양내과
632006

제1저자 최형진 · 교신저자 박경수

, , , , , , , ,
Polymorphisms in the ghrelin gene are associated with serum high-density lipoprotein cholesterol level and not with type 2 diabetes mellitus in Koreans.
J Clin Endocrinol Metab. 2006;91(11):4657-63.

Abstract
CONTEXT Ghrelin is known to play a role in glucose metabolism and in beta-cell function. There are controversies regarding the role of ghrelin polymorphisms in diabetes and diabetes-related phenotypes.
OBJECTIVE The objective of this study was to examine polymorphisms of the ghrelin gene in a Korean cohort and investigate associations between them and susceptibility to type 2 diabetes and its related phenotypes.
DESIGN AND PATIENTS The ghrelin gene was sequenced to identify polymorphisms in 24 DNA samples. Common variants were then genotyped in 760 type 2 diabetic patients and 641 nondiabetic subjects. Genetic associations with diabetes-related phenotypes were also analyzed.
RESULTS Nine polymorphisms were identified, and four common polymorphisms [g.-1500C>G, g.-1062G > C, g.-994C > T, g.+408C > A (Leu72Met)] were genotyped in a larger study. The genotype distributions of these four common polymorphisms in type 2 diabetes patients were similar to those of normal nondiabetic controls. However, these four common polymorphisms were variably associated with several diabetes-related phenotypes, such as high-density lipoprotein (HDL) cholesterol, fasting plasma glucose, and homeostasis model assessment of insulin resistance. In particular, subjects harboring g.-1062C were associated with a lower serum HDL cholesterol level after adjusting for other variables (P = 0.0004 or 0.01 after Bonferroni correction for 24 tests).
CONCLUSION The aforementioned four common polymorphisms in the ghrelin gene were not found to be significantly associated with susceptibility to type 2 diabetes mellitus in the Korean population. However, the common polymorphism g.-1062G > C in the promoter region of the ghrelin gene was found to be significantly associated with serum HDL cholesterol levels.
PubMed IF 5.4 내분비대사내과
622006

제1저자 이상민 · 교신저자 유철규

, , , , ,
Hypoxia confers protection against apoptosis via PI3K/Akt and ERK pathways in lung cancer cells.
Cancer Lett. 2006;242(2):231-8.

Abstract
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.
PubMed IF 11.8 호흡기내과
612006

제1저자 한주용 · 교신저자 김효수

, , , , , , , , , , , ,
Beta-catenin overexpression reduces myocardial infarct size through differential effects on cardiomyocytes and cardiac fibroblasts.
J Biol Chem. 2006;281(41):30979-89.

Abstract
Beta-catenin is a transcriptional regulator of several genes involved in survival and proliferation. Although previous studies suggest that beta-catenin may be involved in the process of preconditioning and healing after myocardial infarction (MI), little is known regarding the role of beta-catenin in cardiomyocytes and cardiac fibroblasts. We investigated the role of beta-catenin in cardiomyocytes and cardiac fibroblasts and whether beta-catenin overexpression could reduce MI size. Adenovirus-mediated gene transfer of nonphosphorylatable constitutively active beta-catenin (Ad-catenin) decreased apoptosis in cardiomyocytes and cardiac fibroblasts with increased expression of survivin and Bcl-2. Although Ad-catenin increased the percentage of cells in the S phase with enhanced expression of cyclin D1 and E2 in both cell types, the increase in cell number was only evident in cardiac fibroblasts, whereas hypertrophy and binuclear cells were more prominent in cardiomyocytes. All of these effects of beta-catenin gene transfer were blocked by inhibition of its nuclear translocation. Furthermore, Ad-catenin enhanced the expression of vascular endothelial growth factor in both cells and induced differentiation of cardiac fibroblasts into myofibroblasts. In a rat MI model, injection of Ad-catenin into the infarct border zone resulted in a significantly decreased MI size with anti-apoptotic effect and cell cycle activation in both cardiomyocytes and myofibroblasts. beta-Catenin may play an important role in the healing process after MI by promoting survival and cell cycle not only in cardiomyocytes but also in cardiac fibroblasts with its differentiation into myofibroblasts.
PubMed IF 4.1 순환기내과
602006

제1저자 조영민 · 교신저자 조영민

, , , , , , ,
Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells.
Biochem Biophys Res Commun. 2006;348(4):1472-8.

Abstract
Embryonic cells before implantation are exposed to a hypoxic condition and dependent on anaerobic metabolism. Human embryonic stem cells (HESCs) derived from pre-implantation blastocyst also grow well in hypoxic conditions. Expecting that the differentiating HESCs might mimic anaerobic-to-aerobic metabolic transition of the early human life, we examined the mitochondria-related changes in these cells. We observed that mitochondrial mass and mitochondrial DNA content were increased with differentiation, which was accompanied by the increase of the amount of ATP (4-fold) and its by-product reactive oxygen species (2.5-fold). The expression of various antioxidant enzymes including mitochondrial and cytoplasmic superoxide dismutases, catalase, and peroxiredoxins showed a dramatic change during the early differentiation. In conclusion, HESC differentiation was followed by dynamic changes in mitochondrial mass, ATP and ROS production, and antioxidant enzyme expressions. Therefore, the HESCs would serve as a good model to examine the mitochondrial biology during the early human differentiation.
PubMed IF 2.5 내분비대사내과
592006

제1저자 김성한 · 교신저자 지영미

, , , , , , , ,
Cell-mediated immune responses to smallpox vaccination.
Clin Vaccine Immunol. 2006;13(10):1172-4.

Abstract
We report that vaccine dilution (1:1 or 1:10) and previous vaccinia virus vaccination status had no significant effect on cell-mediated immune responses (i.e., the immediate vaccinia virus-specific gamma interferon-producing T-cell response measured by enzyme-linked immunospot assay) 1 month after smallpox vaccination (Lancy-Vaxina; Berna Biotech, Switzerland).
PubMed IF 2.06 감염내과
582006

제1저자 천재희 · 교신저자 정현채

, , , , , , ,
Combinations containing amoxicillin-clavulanate and tetracycline are inappropriate for Helicobacter pylori eradication despite high in vitro susceptibility.
J Gastroenterol Hepatol. 2006;21(10):1590-5.

Abstract
BACKGROUND The purpose of the present paper was to evaluate the efficacy and tolerability of amoxicillin-clavulanate and tetracycline-based quadruple therapy as an alternative second-line treatment for H. pylori infection.
METHODS The study subjects consisted of 54 patients infected with H. pylori, in whom initial triple therapy had failed. Subjects were randomized to receive the following 7-day therapies: (i) pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., amoxicillin-clavulanate 1000 mg b.i.d., and tetracycline 500 mg q.i.d. (PBAT); or (ii) pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. (PBMT). Eradication rates based on antibiotic susceptibility, drug compliance and side-effect rates were evaluated and compared.
RESULTS The H. pylori eradication rates were 16.0%/17.4% with PBAT and 65.5%/70.4% with PBMT by intention-to-treat (P<0.001) and per-protocol analyses (P<0.001), respectively. In patients who received PBAT, the eradication rates were only 16.7% (2/12) for both amoxicillin and tetracycline-susceptible H. pylori strains. Drug compliance and side-effect rates were similar in the two groups.
CONCLUSIONS Despite high individual in vitro antimicrobial activity, amoxicillin-clavulanate and tetracycline-based quadruple therapy showed low eradication rates, which strongly suggests that it should not be considered as a therapeutic option for H. pylori eradication.
PubMed IF 3.5 소화기내과
572006

제1저자 이윤종 · 교신저자 송영욱

, , , , , ,
Interleukin-18 promoter polymorphisms in patients with Behçet's disease.
Hum Immunol. 2006;67(10):812-8.

Abstract
Behçet's disease (BD) is an idiopathic systemic inflammatory disease and is considered to be a T helper 1 (Th1) type cytokine driven disorder. Moreover, levels of interleukin-18 (IL-18), a pivotal mediator of Th1 cytokine response, have been reported to be upregulated in BD. Therefore, we investigated the distribution of IL-18 promoter -607 C/A and -137 G/C polymorphisms in 103 BD patients (mean age 41.0 years; 48 male, 55 female) using allele-specific-polymerase chain reaction. As compared with healthy control subjects, BD patients had a significantly higher frequency of the -607 CC genotype (42.7% vs 23.3%, odds ratio [OR] = 2.455, 95% confidence interval [CI] = 1.350-4.461, p(c) = 0.021) and a higher frequency of the -607 C allele (60.7% vs 48.1%, OR = 1.668, 95% CI = 1.129-2.464, p = 0.0101). Haplotype analysis showed that BD patients had significantly less -607A/-137G haplotype (27.3% vs 44.2%, OR = 0.469, 95% CI = 0.268-0.820, p(c) = 0.032) and -607A/-137G haplotype homozygote (5.8% vs 20.4%, OR = 0.242, 95% CI = 0.096-0.612, p(c) = 0.014) than control subjects. In addition, the frequency of -607C/-137G haplotype homozygote was significantly higher in BD patients than control subjects (48.5% vs 20.4%, OR = 3.684, 95% CI = 1.997-6.791, p(c) = 0.0014). Although there were no associations between the polymorphisms and clinical manifestations or severity, patients with the -607 CC genotype or -607C/-137G haplotype homozygote showed significantly earlier symptom development (p = 0.034 by ANOVA; p = 0.009 by t-test, respectively) than those with other genotypes or diplotypes. These results suggest that the IL-18 promoter gene is a candidate susceptibility gene in BD patients.
PubMed IF 2.1 류마티스내과
562006

제1저자 진호준 · 교신저자 채동완

, , , ,
The clinical significances of simple renal cyst: Is it related to hypertension or renal dysfunction?
Kidney Int. 2006;70(8):1468-73.

Abstract
Simple renal cyst has controversy related to hypertension and renal dysfunction. We analyzed the impacts of cyst on hypertension and renal dysfunction, focusing on elimination of the confounding factors. We grouped 436 patients and 436 controls by characteristics of cyst and stratified with clinical parameters among 6603 patients who had routine health check-up in Seoul National University Bundang Hospital, Seongnam, Korea. The presence of cyst was related to hypertension but not to renal dysfunction. The number and the size of cyst were independent risk factors to the prevalence of hypertension. The presence of multiple renal cysts was related to hypertension in males, in persons over the age of 60 years, in persons with glomerular filtration rate (GFR) more than 60 ml/min/1.73 m2, or in persons without proteinuria. The effect of the large cyst and the peripheral cyst on the prevalence of hypertension was similar to that of the multiple cyst. The blood pressure of the multiple-cyst group, the large-cyst group, or the peripheral-cyst group was higher than that of the single-cyst group, the small-cyst group, or the perihilar-cyst group, respectively, regardless of antihypertensive medications. In conclusion, the presence of cysts or characteristics of cyst were not related to the decreased GFR. In conclusion, the presence of simple renal cyst was related to hypertension but not to renal dysfunction. The effect of simple cyst on hypertension was evident in males, aged persons, and persons without the evidence of renal disease. The number, size, and location were important characteristics of cyst related to hypertension.
PubMed IF 21.8 신장내과
552006

제1저자 정성수 · 교신저자 박경수

, , , ,
Sp1 mediates repression of the resistin gene by PPARgamma agonists in 3T3-L1 adipocytes.
Biochem Biophys Res Commun. 2006;348(1):253-8.

Abstract
Resistin is an adipokine related to obesity and insulin resistance. Expression of the resistin gene is repressed by the treatment of peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, thiazolidinediones (TZDs). In this study, we investigated the mechanism by which TZDs inhibit the resistin gene expression. Resistin gene expression was decreased by TZD in fully differentiated 3T3-L1 adipocytes, which was abolished after treatment of cycloheximide (a protein synthesis inhibitor). TZD could not repress the expression of the resistin gene in the presence of mithramycin A (an Sp1 binding inhibitor). Sp1 binding site of the resistin promoter (-122/-114bp) was necessary for the repression. Further investigation of the effect of TZDs on the modification of Sp1 showed that the level of O-glycosylation of Sp1 was decreased in this process. These results suggest that PPARgamma activation represses the expression of the resistin gene by modulating Sp1 activity.
PubMed IF 2.5 내분비대사내과
542006

제1저자 조상호,연태진 · 교신저자 김효수

, , , , , , , , , , , , ,
Renal toxicity evaluation and comparison between visipaque (iodixanol) and hexabrix (ioxaglate) in patients with renal insufficiency undergoing coronary angiography: the RECOVER study: a randomized controlled trial.
J Am Coll Cardiol. 2006;48(5):924-30.

Abstract
OBJECTIVES This study sought to compare the nephrotoxicity of iodixanol and ioxaglate in patients with renal impairment undergoing coronary angiography.
BACKGROUND Iodixanol, a nonionic, dimeric, iso-osmolar contrast medium (IOCM), may be less nephrotoxic than low-osmolar contrast media (LOCM) in high-risk patients.
METHODS In a prospective, randomized trial in 300 adults with creatinine clearance (CrCl) < or =60 ml/min, patients received either iodixanol or ioxaglate and underwent coronary angiography with or without percutaneous coronary intervention. The primary end point was the incidence of contrast-induced nephropathy (CIN) (an increase in serum creatinine [SCr] > or =25% or > or =0.5 mg/dl [> or =44.2 mumol/l]). The incidence of CIN in patients with severe renal impairment at baseline (CrCl <30 ml/min) or diabetes and in those receiving large doses (> or =140 ml) of contrast medium was also determined.
RESULTS The incidence of CIN was significantly lower with iodixanol (7.9%) than with ioxaglate (17.0%; p = 0.021), corresponding to an odds ratio (OR) of CIN of 0.415 (95% confidence interval [CI] 0.194 to 0.889) for iodixanol. The incidence of CIN was also significantly lower with iodixanol in patients with severe renal impairment (p = 0.023) or concomitant diabetes (p = 0.041), or in patients given > or =140 ml of contrast media (p = 0.038). Multivariate analysis identified use of ioxaglate (OR 2.65, 95% CI 1.11 to 6.33, p = 0.028), baseline SCr, mg/dl (OR 2.0, 95% CI 1.04 to 3.85, p = 0.038), and left ventricular ejection fraction, % (OR 0.97, 95% CI 0.94 to 0.99, p = 0.019) as independent risk factors for CIN.
CONCLUSIONS The IOCM iodixanol was significantly less nephrotoxic than ioxaglate, an ionic, dimeric LOCM. (The RECOVER Trial; http://clinicaltrials.gov; NCT00247325).
PubMed IF 22.3 순환기내과
532006

제1저자 김진 · 교신저자 정숙향

, , , , , , , , , , , ,
Elevated plasma osteopontin levels in patients with hepatocellular carcinoma.
Am J Gastroenterol. 2006;101(9):2051-9.

Abstract
OBJECTIVES Osteopontin (OPN) is a secreted glycoprotein, frequently associated with various tumors. We investigated the usefulness of plasma OPN level as a biomarker for hepatocellular carcinoma (HCC).
METHODS We determined plasma levels of OPN, alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence II (PIVKA II) in a group of 62 HCC patients, in 60 patients with chronic liver diseases, and in 60 healthy control individuals using a standardized ELISA kit. To determine the source of elevated plasma level of OPN, immunohistochemical analysis of 285 HCC samples on tissue microarray was performed.
RESULTS Plasma OPN levels in the HCC patients (median 954 ng/mL, range 168-5,742) were significantly higher (p-value < 0.001) than those patients with chronic liver diseases (381 ng/mL, 29-1,688) or of a healthy control group (155 ng/mL, 10-766). Within the HCC patient group, plasma OPN level increased significantly with advancing degree of Child-Pugh class and of tumor stage. Diagnostic sensitivity and specificity of OPN for HCC was 87% and 82%, respectively (cut-off value: 617.6 ng/mL). OPN had a greater area under curve value (0.898) than AFP (0.745) or PIVKA II (0.578), suggesting superior diagnostic accuracy of OPN. Immunohistochemistry of 285 samples of HCC showed that OPN was expressed in 92 of 285 tumors (32.3%). OPN expression was found in the malignant hepatocytes and cancer-infiltrating macrophages, not in the noncancerous hepatocytes or Kupffer cells.
CONCLUSIONS These data propose elevated plasma OPN levels as a potential biomarker for HCC.
PubMed IF 7.6 소화기내과
522006

제1저자 김덕겸 · 교신저자 임재준

, , , , , ,
Microarray analysis of gene expression associated with extrapulmonary dissemination of tuberculosis.
Respirology. 2006;11(5):557-65.

Abstract
OBJECTIVE Although extrapulmonary organs are involved in 20% of patients with tuberculosis, the host genetic factors associated with the extrapulmonary dissemination of tuberculosis are not yet known. The aim of this study was to identify the host genetic factors associated with the extrapulmonary dissemination of tuberculosis by comparing gene expression profiles of patients who had recovered from extrapulmonary tuberculosis and those who had recovered from pulmonary tuberculosis.
METHODS Five patients from each group were enrolled. Total RNA was extracted from peripheral blood mononuclear cells that had been incubated for 48 h with whole lysate of Mycobacterium tuberculosis (H37Rv, 0.5 microg/mL). Gene expression profiles were acquired using the GeneChip array and its applied systems. Gene expression profiles from five patients with previous extrapulmonary tuberculosis and one pooled control sample from five patients with previous pulmonary tuberculosis were analysed and compared. Genes that were expressed concordantly in more than 80% of arrays and that showed more than twofold changes in at least one array among samples from patients who had recovered from extrapulmonary tuberculosis were identified.
RESULTS Compared with the control sample, the expression of 16 genes, including those for tumour necrosis factor (TNF)-alpha and cathepsin W, was increased, and the expression of 45 genes including that for TNF-receptor superfamily member 7 (TNFRSF7), was decreased in the extrapulmonary tuberculosis patients. The altered expression of the TNF-alpha, cathepsin W and TNFRSF7 genes was confirmed by quantitative RT-PCR.
CONCLUSIONS Altered expression of the genes for TNF-alpha, cathepsin W and TNFRSF7 may be risk factors for the extrapulmonary dissemination of tuberculosis in humans.
PubMed IF 7.2 호흡기내과
512006

제1저자 예병덕 · 교신저자 정현채

, , , , , ,
Omeprazole may be superior to famotidine in the management of iatrogenic ulcer after endoscopic mucosal resection: a prospective randomized controlled trial.
Aliment Pharmacol Ther. 2006;24(5):837-43.

Abstract
BACKGROUND Acid suppressing agents are widely used to treat the iatrogenic ulcers following endoscopic mucosal resection for gastric neoplasms. However, the relative merits of proton pump inhibitor or histamine(2)-receptor antagonist for endoscopic mucosal resection-induced ulcers are not known.
AIM To prospectively compare omeprazole and famotidine for the healing of endoscopic mucosal resection-induced ulcers and for bleeding control.
METHODS After endoscopic mucosal resection, patients were randomly assigned to omeprazole (20 mg/day) or to famotidine (40 mg/day) group for a 28-day treatment period. The ulcer sizes and stages, bleeding rates and ulcer-related symptoms were compared.
RESULTS A total of 100 patients were randomized equally to each group. Forty-one patients in each group were finally compared. The two groups were comparable in terms of baseline characteristics. Twenty-eight days after treatment, the two groups were not different with respect to ulcer stage (P = 0.137) or ulcer reduction ratio (P = 0.380). No difference was observed with respect to ulcer-related symptoms (P = 0.437) and no bleeding episode occurred in any of the 82 patients. In subgroup that underwent endoscopic submucosal dissection, fewer patients in the omeprazole group showed active ulcers than those in the famotidine group (P = 0.035).
CONCLUSION Our results demonstrate that omeprazole may be superior to famotidine for iatrogenic ulcers following endoscopic mucosal resection, especially for large ulcers.
PubMed IF 6.8 소화기내과
502006

제1저자 김현지 · 교신저자 임재준

, , , , , , , , , , ,
Prognostic factors for surgical resection in patients with multidrug-resistant tuberculosis.
Eur Respir J. 2006;28(3):576-80.

Abstract
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 x 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.
PubMed IF 23.8 호흡기내과
492006

제1저자 김나영 · 교신저자 정현채

, , , , , , ,
Institutional difference of antibiotic resistance of Helicobacter pylori strains in Korea.
J Clin Gastroenterol. 2006;40(8):683-7.

Abstract
GOALS This study was performed to evaluate whether the prevalence rates of primary antibiotic resistance in Helicobacter pylori isolates could be different between 2 institutions, which are located in the different areas in Korea, and to evaluate the effect of antibiotic resistance on the eradication rate of H. pylori.
STUDY H. pylori were isolated from gastric mucosal biopsy specimens obtained from 113 Koreans, who did not have any eradication history. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin were examined according to the agar dilution method by 1 technician.
RESULTS All of these patients were treated with the same regimen, proton pump inhibitor-amoxicillin-clarithromycin triple therapy. There was a statistical difference in resistance to metronidazole, levofloxacin, and moxifloxacin among 6 antibiotics between 2 institutions located in Seoul and Gyeonggi province. The rates of eradication were 94.2% for the clarithromycin and amoxicillin-susceptible strains, and 42.8% for the amoxicillin-susceptible and clarithromycin-resistant strains. In contrast, eradication rate was 100% for the amoxicillin-resistant strains.
CONCLUSIONS These results show that there is institutional difference of antibiotic resistance of H. pylori, explaining the institutional difference of eradication rate of H. pylori. The resistance to clarithromycin seems to be an important determinant for the eradication by proton pump inhibitor triple therapy but resistance to amoxicillin does not have any effect.
PubMed IF 2.7 소화기내과
482006

제1저자 임재준 · 교신저자 Steven M Holland

, , ,
Evolution of an intronic microsatellite polymorphism in Toll-like receptor 2 among primates.
Immunogenetics. 2006;58(9):740-5.

Abstract
Nonhuman primates express varying responses to Mycobacterium tuberculosis: New World monkeys appear to be resistant to tuberculosis (TB) while Old World monkeys seem to be particularly susceptible. The aim of this study was to elucidate the presence of the regulatory guanine-thymine (GT) repeat polymorphisms in intron 2 of Toll-like receptor 2 (TLR2) associated with the development of TB in humans and to determine any variations in these microsatellite polymorphisms in primates. We sequenced the region encompassing the regulatory GT repeat microsatellites in intron 2 of TLR2 in 12 different nonhuman primates using polymerase chain reaction amplification, TA cloning, and automatic sequencing. The nonhuman primates included for this study were as follows: chimpanzee (Pan troglodytes), bonobo (Pan paniscus), gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), Celebes ape (Macaca nigra), rhesus monkey (Macaca mulatta), pigtail macaque (Macaca nemestrina), patas monkey (Erythrocebus patas), spider monkey (Ateles geoffroyi), Woolly monkey (Lagothrix lagotricha), tamarin (Saguinus labiatus), and ring-tailed lemur (Lemur catta). Nucleotide sequences encompassing the regulatory GT repeat region are similar across species and are completely conserved in great apes. However, Old World monkeys lack GT repeats altogether, while New World monkeys and ring-tailed lemurs have much more complex structures around the position of the repeats. In conclusion, the genetic structures encompassing the regulatory GT repeats in intron 2 of human TLR2 are similar among nonhuman primates. The sequence is most conserved in New World monkeys and less in Old World monkeys.
PubMed IF 2.1 호흡기내과

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