AIM: To determine whether gastrointestinal (GI) symptoms are more frequent in type 2 diabetic patients and to examine which diabetic factors are associated with the symptoms.
METHODS: Consecutive subjects with diabetes and age-/gender-matched normal controls were recruited for this study. GI symptoms were assessed using a structured questionnaire divided into two GI symptom categories (upper and lower GI symptoms), and consisting of 11 individual symptoms. In the diabetic patient group, diabetic complications including peripheral neuropathy, nephropathy and retinopathy, glycosylated hemoglobin (HbA1c) level and diabetes duration were evaluated.
RESULTS: Among the total 190 diabetic patients and 190 controls enrolled, 137 (72%) of the diabetic patients and 116 (62%) of the controls had GI symptoms. In the diabetic patient group, 83 (43%) had upper GI symptoms and 110 (58%) lower GI symptoms; in the control group, 59 (31%) had upper GI symptoms and 104 (55%) lower GI symptoms. This difference between the two groups was significant for only the upper GI symptoms (P = 0.02). Among the diabetic factors, the HbA1c level was the only independent risk factor for upper GI symptoms in the multiple logistic regression analysis (odds ratio = 2.01, 95% confidence interval: 1.02-3.95).
CONCLUSION: Type 2 diabetes was associated with an increased prevalence of upper GI symptoms and these symptoms appeared to be independently linked to poor glycemic control, as measured by the HbA1c levels.
Diabetes; HbA1c; Upper gastrointestinal symptoms
AIM: To elucidate the efficacy and safety of a split dose of midazolam in combination with meperidine for colonoscopy.
METHODS: Eighty subjects undergoing outpatient colonoscopy were randomly assigned to group A or B. Group A (n = 40) received a split dose of midazolam in combination with meperidine. Group B (n = 40) received a single dose of midazolam in combination with meperidine. Outcome measurements were level of sedation, duration of sedation and recovery, degree of pain and satisfaction, procedure-related memory, controllability, and adverse events.
RESULTS: Group A had a lower frequency of significant hypoxemia (P = 0.043) and a higher sedation score on withdrawal of the endoscope from the descending colon than group B (P = 0.043). Group B recovered from sedation slightly sooner than group A (P < 0.002). Scores for pain and memory, except insertion-related memory, were lower in group A one week after colonoscopic examination (P = 0.018 and P < 0.030, respectively). Poor patient controllability was noted by the endoscopist and nurse in group B (P = 0.038 and P = 0.032, respectively).
CONCLUSION: Split dose midazolam in combination with meperidine resulted in a safer, more equable sedation status during colonoscopic examination and a reduction in procedure-related pain and memory, but resulted in longer recovery time.
Amnesia; Colonoscopy; Conscious sedation; Midazolam
AIM: To examine the characteristics of colonic polyps, where it is difficult to distinguish adenomatous polyps from hyperplastic polyps, with the aid of acetic acid chromoendoscopy.
METHODS: Acetic acid spray was applied to colonic polyps smaller than 10 mm before complete excision. Endoscopic images were taken before and 15-30 s after the acetic acid spray. Both pre- and post-sprayed images were shown to 16 examiners, who were asked to interpret the lesions as either hyperplastic or adenomatous polyps. Regression analysis was performed to determine which factors were most likely related to diagnostic accuracy.
RESULTS: In 50 cases tested by the 16 examiners, the overall accuracy was 62.4% (499/800). Regression analysis demonstrated that surrounding colonic mucosa was the only factor that was significantly related to accuracy in discriminating adenomatous from hyperplastic polyps (P < 0.001). Accuracy was higher for polyps with linear surrounding colonic mucosa than for those with nodular surrounding colonic mucosa (P < 0.001), but was not related to the shape, location, or size of the polyp.
CONCLUSION: The accuracy of predicting histology is significantly related to the pattern of colonic mucosa surrounding the polyp. Making a histological diagnosis of colon polyps merely by acetic acid spray is helpful for colon polyps with linear, regularly patterned surrounding colonic mucosa, and less so for those with nodular, irregularly patterned surrounding colonic mucosa.
Colon polyp; Chromoendoscopy; Acetic acid
RNA analysis has become a reliable method of body fluid identification for forensic use. Previously, we developed a combination of four multiplex quantitative PCR (qRT-PCR) probes to discriminate four different body fluids (blood, semen, saliva, and vaginal secretion). While those makers successfully identified most body fluid samples, there were some cases of false positive and negative identification. To improve the accuracy of the identification further, we tried to use multiple markers per body fluid and adopted the NanoString nCounter system instead of a multiplex qRT-PCR system. After measuring tens of RNA markers, we evaluated the accuracy of each marker for body fluid identification. For body fluids, such as blood and semen, each body fluid-specific marker was accurate enough for perfect identification. However, for saliva and vaginal secretion, no single marker was perfect. Thus, we designed a logistic regression model with multiple markers for saliva and vaginal secretion and achieved almost perfect identification. In conclusion, the NanoString nCounter is an efficient platform for measuring multiple RNA markers per body fluid and will be useful for forensic RNA analysis.
body fluids; forensic; RNA
The management of asymptomatic erosive esophagitis is controversial. We surveyed physicians' opinions on asymptomatic erosive esophagitis using e-mail.
All members of the Korean Society of Neurogastro-enterology and Motility were invited to answer the questionnaire on the treatment and follow-up of patients with asymptomatic erosive esophagitis by e-mail.
A total of 73 members answered the questionnaire (response rate, 18%). As initial management, 41% of respondents chose pharmacologic treatment, whereas 59% chose nonpharmacologic treatment. In the case of pharmacologic treatment, proton pump inhibitors were the preferred medication. The most common treatment duration was 4 weeks (43%), followed by 8 weeks (38%), and 6 months (11%). Sixty-two percent of the respondents recommended follow-up endoscopy annually, whereas 29% chose no endoscopic follow-up. Thirty-four percent of the respondents answered that they would talk about reflux-related sleep disturbances. Only 25% of the respondents explained the possibility of Barrett's esophagus or esophageal adenocarcinoma to their patients.
There are substantial practice variations in the management of asymptomatic erosive esophagitis in Korea.
Esophagitis; Endoscopy; Asymptomatic diseases; Therapeutics
Improvements in the endoscopic evaluation and management of gastric cancer have made it possible to determine the depth of invasion during endoscopic examination. The aim of this study was to elucidate the differences between early gastric cancer (EGC) that resembles advanced gastric cancer (AGC) and AGC that resembles EGC.
We retrieved cases of EGC-like AGC and AGC-like EGC from consecutive gastric cancers that had been completely resected. The endoscopic diagnoses and clinicopathological findings were analyzed.
AGC-like EGCs were located mainly in the distal part of the stomach, whereas EGC-like AGCs were located mainly in the proximal part of the stomach (p<0.001). Sixty percent of AGC-like EGCs were moderately differentiated adenocarcinomas, while 64% of EGC-like AGCs were poorly differentiated adenocarcinomas (p=0.015). According to Lauren's classification, 68% of AGC-like EGCs were intestinal type, whereas 71% of EGC-like AGCs were diffuse type (p=0.020).
AGC-like EGCs predominate in the distal part of the stomach, while EGC-like AGCs predominate in the proximal part. When evaluating the depth of a gastric cancer, care should be taken not to underestimate measurements in proximal gastric cancers since they tend to be poorly-differentiated adenocarcinomas, in Lauren's diffuse type, and invade deeper than their endoscopic appearance might suggest.
Early gastric cancer; Advanced gastric cancer; Gastrointestinal endoscopy
The Wnt signaling pathway plays an important role not only in embryonic development but also in the maintenance and differentiation of the stem cells in adulthood. In particular, Wnt signaling has been shown as an important regulatory pathway in the osteogenic differentiation of mesenchymal stem cells. Induction of the Wnt signaling pathway promotes bone formation while inactivation of the pathway leads to osteopenic states. Our current understanding of Wnt signaling in osteogenesis elucidates the molecular mechanisms of classic osteogenic pathologies. Activating and inactivating aberrations of the canonical Wnt signaling pathway in osteogenesis results in sclerosteosis and osteoporosis respectively. Recent studies have sought to target the Wnt signaling pathway to treat osteogenic disorders. Potential therapeutic approaches attempt to stimulate the Wnt signaling pathway by upregulating the intracellular mediators of the Wnt signaling cascade and inhibiting the endogenous antagonists of the pathway. Antibodies against endogenous antagonists, such as sclerostin and dickkopf-1, have demonstrated promising results in promoting bone formation and fracture healing. Lithium, an inhibitor of glycogen synthase kinase 3β, has also been reported to stimulate osteogenesis by stabilizing β catenin. Although manipulating the Wnt signaling pathway has abundant therapeutic potential, it requires cautious approach due to risks of tumorigenesis. The present review discusses the role of the Wnt signaling pathway in osteogenesis and examines its targeted therapeutic potential.
Wnt signaling; bone formation; osteoporosis; fracture healing; bone tumors
Although a small amount of fecal material can obscure significant colorectal lesions, it has not been well documented whether bowel preparation status affects the missing risk of colorectal polyps and adenomas during a colonoscopy.
We prospectively enrolled patients with one to nine colorectal polyps and at least one adenoma of >5 mm in size at the screening colonoscopy. Tandem colonoscopy with polypectomy was carried out within 3 months.
A total of 277 patients with 942 polyps and 714 adenomas completed index and tandem examinations. At the index colonoscopy, 187 polyps (19.9%) and 127 adenomas (17.8%) were missed. The per-patient miss rate of polyps and adenomas increased significantly as the bowel cleansing rate declined from excellent to poor/inadequate on the Aronchick scale (polyps, p=0.024; adenomas, p=0.040). The patients with poor/inadequate bowel preparation were independently associated with an increased risk of having missed polyps (odds ratio [OR], 3.21; 95% confidence interval [CI], 1.13 to 9.15) or missed adenomas (OR, 3.04; 95% CI, 1.04 to 8.88) compared to the patients with excellent bowel preparation.
The risk of missing polyps and adenomas during screening colonoscopy is significantly affected by bowel preparation status. It seems appropriate to shorten the colonoscopy follow-up interval for patients with suboptimal bowel preparation.
Bowel preparation; Polyp miss rate; Adenoma miss rate; Colonoscopy; Surveillance
Homocysteine is involved in a one-carbon transfer reaction, which is important for DNA synthesis and methylation. High level of plasma homocysteine, biochemical marker of folate status, is known to be a risk factor for cancer. However, it is inconclusive as to whether plasma homocysteine concentration can predict colorectal adenoma. We conducted a case-control study to determine whether hyperhomocysteinemia is a risk factor for adenoma. Data from 1,039 subjects who underwent a colonoscopy and plasma homocysteine concentration determination during health examinations at single center over a two-year period were analyzed. The subjects were classified into two groups (422 adenoma and 617 controls). Subjects defined as having advanced adenomas were those with more than three adenomas, over 1 cm in size, high grade dysplasia, or villous components. Male, old age, high body mass index, low high-density lipoprotein-cholesterol, smoking, fasting glucose, and past history of colon polyps were significantly associated with adenoma according to multiple logistic regression. According to subgroup analysis by gender, plasma homocysteine concentration was not associated with adenoma in males; however, a high plasma homocysteine concentration significantly increased the risk of adenoma as well as advanced adenoma in females. Hyperhomocysteinemia is a risk factor for colorectal adenoma in women.
risk factors; homocysteine; adenoma
Phlorotannins (marine algal polyphenols) have been reported to exhibit beneficial biological activities, serving as both antioxidants and anti-inflammatory agents. Among marine algae, Ecklonia cava, a member of the Laminariaceae, is a very popular food regarded as healthy in Korea and Japan. Recently, benefits afforded by phlorotannins in the treatment of various clinical conditions have been reported, but any therapeutic effects of such materials in the treatment of neurodegenerative diseases such as stroke remain unclear. Also, the mechanisms of action of the algal components remain poorly understood. In the present in vivo study, administration of Ecklonia cava polyphenols (ECP) at 10 mg/kg and 50 mg/kg intraperitoneally (i.p.) significantly decreased infarct size and the extent of brain edema in the rat after induction of transient focal ischemia via middle cerebral artery occlusion (MCAO). Further, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay revealed dose-dependent blockage of neuronal apoptosis upon intravenous ECP treatment. Neurobehavioral tests performed over the 6 days after MCAO revealed a reduction in neurological motor performance in control animals, but administration of ECP (50 mg/kg i.p.) prevented this decline. In vitro, a significant neuroprotective effect of ECP was evident when cell viability was assayed after induction of H2O2-mediated oxidative stress, upon retinoic acid treatment, in the differentiated neuroblastoma cell line SH-SY5Y. Interestingly, ECP blocked the rise in cytosolic calcium, in a dose-dependent manner, in differentiated SH-SY5Y cells exposed to H2O2. Together, the results suggest that ECP exerts neuroprotective effects in the focally ischemic brain by reducing Ca2+-mediated neurotoxicity.
Ecklonia cava; Middle cerebral artery infarction; Neurodegenerative diseases; SH-SY5Y cells
Bacilli with fibrinolytic activities were isolated from traditionally-prepared Meju and some of these strains showed strong antifungal activities. One isolate, MJ1-4, showed the strongest antifungal activity. MJ1-4 and other isolates were identified as B. amyloliquefaciens strains by recA gene sequencing and RAPD-PCR results. B. amyloliqufaciens MJ1-4 efficiently inhibited an Aspergillus spp.-producing aflatoxin B1 (AFB1) and a Penicillium spp.-producing ochratoxin (OTA) in addition to other fungi. Antifungal activity of B. amyloliquefaciens MJ1-4 culture reached its maximum (40 AU/mg protein) in LB or TSB medium around 48 hr at 37°C. Antifungal activity of the concentrated culture supernatant was not decreased significantly by protease treatments, implying that the antifungal substance might not be a simple peptide or protein. Considering its antifungal and fibrinolytic activities together, B. amyloliquefaciens MJ1-4 can serve as a starter for fermented soyfoods such as Cheonggukjang and Doenjang.
antifungal agents; Meju; Bacillus amyloliquefaciens; food preservatives
Gastroesophageal reflux disease (GERD) is the most common cause of noncardiac chest pain (NCCP) and is present in up to 60% of patients with NCCP in Western countries. In Korea, after a reasonable cardiac evaluation, GERD is reported to underlie 41% of NCCP cases. Typical reflux symptoms are frequent in Korean patients suffering from NCCP. Therefore, a careful history of the predominant symptoms, including heartburn and acid regurgitation, is relatively indicative of the GERD diagnosis in Korea. In Korea, in contrast to Western countries, patients aged 40 years and over who have been diagnosed with NCCP but who are without alarming features should undergo endoscopy to exclude gastric cancer or peptic ulcers because of the higher prevalence of peptic ulcer disease and gastric cancers in the region. In a primary care setting, in the absence of any alarming symptoms, a symptomatic response to a trial of a proton pump inhibitor (PPI) is sufficient for the presumptive diagnosis of GERD. In addition, the optimal duration of a PPI test may be at least 2 weeks, as GERD symptoms tend to be less frequent or atypical in Korean patients than in patients from Western countries. In patients diagnosed with GERD-related NCCP, long-term therapy (more than 2 months) with double the standard dose of a PPI is required to alleviate symptoms. Esophageal dysmotility is relatively uncommon, and pain modulators seem to offer significant improvement of chest pain control in non-GERD-related NCCP. Most traditionally available tricyclics or heterocyclics have many undesirable effects. Therefore, newer drugs with fewer side effects (for example, the serotonin - norepinephrine reuptake inhibitors) may be needed.
Noncardiac chest pain; Gastroesophageal reflux disease; Upper endoscopy; Proton pump inhibitor; Serotonin-norepinephrine reuptake inhibitor
In the present study, we examined the gastroprotective effect of selenium against ethanol-induced gastric mucosal lesions in rats. The gastric mucosal lesions were produced by oral administration with various concentrations of ethanol for three days, and 80% ethanol treatment was determined to be the optimal condition for induction of gastric damage. To identify the protective effect of selenium on ethanol-induced gastric damage, various doses of selenium were given as pretreatment for three days, and then gastric damage was induced by 80% ethanol treatment. Selenium showed a protective effect against ethanol-induced gastric mucosal lesions in a dose dependent manner. Specifically, 100 μg/kg selenium showed the highest level of gastroprotection. In addition, selenium markedly attenuated ethanol-induced lipid peroxidation in gastric mucosa and increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Histological data showed that 100 μg/kg selenium distinctly reduced the depth and severity of the ethanol induced gastric lesion. These results clearly demonstrate that selenium inhibits the formation of ethanol-induced gastric mucosal lesions through prevention of lipid peroxidation and activation of enzymatic radical scavenging.
selenium; ethanol; gastric mucosal lesions; radical scavenging enzymes
A large-scale, genome-wide association study was performed to identify genetic variations influencing serum bilirubin levels using 8841 Korean individuals. Significant associations were observed at UGT1A1 (rs11891311, P = 4.78 × 10−148) and SLCO1B3 (rs2417940, P = 1.03 × 10−17), which are two previously identified loci. The two single-nucleotide polymorphisms (SNPs) were replicated (rs11891311, P = 3.18 × 10−15) or marginally significant (rs2417940, P = 8.56 × 10−4) in an independent cohort of 1096 individuals. In a conditional analysis adjusted for the top UGT1A1 variant (rs11891311), another variant in UGT1A1 (rs4148323, P = 1.22 × 10−121) remained significant; this suggests that in UGT1A1 at least two independent genetic variations influence the bilirubin levels in the Korean population. The protein coding variant rs4148323, which is monomorphic in European-derived populations, may be specifically associated with serum bilirubin levels in Asians (P = 2.56 × 10−70). The SLCO1B3 variant (rs2417940, P = 1.67 × 10−18) remained significant in a conditional analysis for the top UGT1A1 variant. Interestingly, there were significant differences in the associated variations of SLCO1B3 between Koreans and European-derived populations. While the variant rs2417940 at intron 7 of SLCO1B3 was more significantly associated in Koreans, variants rs17680137 (P = 0.584) and rs2117032 (P = 2.76 × 10−5), two of the top-ranked SNPs in European-derived populations, did not reach the genome-wide significance level. Also, variants in SLCO1B1 did not reach genome-wide significance in Koreans. Our result supports the idea that there are considerable ethnic differences in genetic association of bilirubin levels between Koreans and European-derived populations.
Cardiac amyloidosis describes a clinical disorder caused by infiltration of abnormal insoluble fibrils in the heart, characterized by progressive heart failure and a grave prognosis. Pleural effusion in cardiac amyloidosis may represent a sign of heart failure, but it can also result from pleural infiltration of amyloid, manifested by recurrent large fluid accumulations. Recently, the role of vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of refractory pleural effusion. We report a case of a 53 year-old female patient with cardiac amyloidosis who presented with recurrent accumulation of large pleural effusions. She was initially treated with high dose loop diuretics, but the pleural effusion persisted, with the daily amount of drainage averaging 1 L/day. Accumulation of pleural fluid did not subside after 3 cycles of melphalan/prednisolone therapy. After the introduction of bevacizumab, an anti-VEGF antibody, the amount of pleural effusion decreased significantly. Efficacy of anti-VEGF therapy for refractory pleural effusions needs to be defined through further studies.
Heart disease; Amyloidosis; Pleural effusion; Bevacizumab
AIM: To investigate the changes in renal function at 12-24 mo in patients following sodium phosphate (NaP) preparation for screening colonoscopy.
METHODS: We carried out a retrospective study on the results from patients who received health check-up services as part of an employer-provided wellness program performed between August 2006 and May 2008 and who were followed up for 12-24 mo. Prior to screening colonoscopy, 224 patients underwent bowel cleansing with NaP (NaP group) and 113 patients with polyethylene glycol (PEG group). The control group comprised 672 age-matched patients. We compared the changes in the creatinine levels and the glomerular filtration rates (GFRs) from baseline to 12-24 mo between the NaP, PEG, and control groups using two-way repeated measured analysis of variance. In addition, multivariate linear regression analysis was performed to assess the risk factors for a decreased GFR.
RESULTS: The baseline mean serum creatinine level in the NaP, PEG, and control groups was 1.12 ± 0.15, 1.12 ± 0.16, and 1.12 ± 0.15 mg/dL, which increased to 1.15 ± 0.15, 1.15 ± 0.18, and 1.15 ± 0.15 mg/dL, respectively, after 12-24 mo. The baseline mean GFR in the NaP, PEG, and control groups was 69.0 ± 7.7, 68.9 ± 8.0, and 69.6 ± 6.7 mL/min per 1.73 m2, which decreased to 66.5 ± 7.8, 66.5 ± 8.3, and 67.4 ± 6.4 mL/min per 1.73 m2, respectively, after 12-24 mo. The changes in serum creatinine levels and GFRs were not significantly between the NaP, PEG, and control groups (P = 0.992 and P = 0.233, respectively). Using multivariate linear regression analysis, only the baseline GFR was associated with the change in GFR (P < 0.001). Indeed, the bowel preparations were not associated with the change in GFR (P = 0.297).
CONCLUSION: NaP bowel preparation in subjects with normal renal function was not associated with renal injury, and NaP can thus be used safely for screening colonoscopy.
Sodium phosphate; Polyethylene glycol; Purgatives; Colonoscopy; Creatinine; Glomerular filtration rate
Noncardiac chest pain (NCCP) is a very common disorder world-wide and gastroesophageal reflux disease (GERD) is known to be the most common cause. The prevalence of NCCP may tend to decrease with increasing age. However, there is little report about young aged NCCP. The aim of this study was to examine the prevalence of GERD and to evaluate the efficacy of proton pump inhibitor (PPI) test in the young NCCP patients.
Thirty patients with at least weekly NCCP less than 40 years were enrolled. The baseline symptoms were assessed using a daily symptom diary for 14 days. Esophago-gastro-duodenoscopy (EGD) and 24 hr esophageal pH monitoring were performed for the diagnosis of GERD and esophageal manometry was done. Then, patients were tried with lansoprazole 30 mg twice daily for 14 days, considering positive if a symptom score improved ≥ 50% compared to the baseline.
Nine (30%) of the patients were diagnosed with GERD at EGD and/or 24 hr esophageal pH monitoring, also, 3 (10%) were diagnosed with GERD-associated esophageal motility disorder and 3 (10%) were non GERD-associated. Concerning PPI test, GERD-related NCCP had a higher positive PPI test (n = 8, 89%) than non GERD-related NCCP (n = 5, 24%) (p = 0.002).
In young patients with NCCP, a prevalence of GERD diagnosed using EGD and/or 24 hr esophageal pH monitoring was 30%. PPI test was very predictable on diagnosis of GERD-related NCCP, thus, PPI test in young NCCP patients may assist to the physician's clinical judgment of NCCP.
Gastroesophageal reflux disease; Noncardiac chest pain; Proton pump inhibitor; Young adult
The present study was designed to investigate the question of whether or not astaxanthin improves stem cell potency via an increase in proliferation of neural progenitor cells (NPCs). Treatment with astaxanthin significantly increased proliferation and colony formation of NPCs. For identification of possible activated signaling molecules involved in active cell proliferation occurring after astaxanthin treatment, total protein levels of several proliferation-related proteins, and expression levels of proliferation-related transcription factors, were assessed in NPCs. In Western blot analysis, astaxanthin induced significant activation of phosphatidylinositol 3-kinase (PI3K) and its downstream mediators in a time-dependent manner. Results of RT-PCR analysis showed upregulation of proliferation-related transcription factors and stemness genes. To estimate the relevance of PI3K and mitogen-activated protein, or extracellular signal-regulated kinase kinase (MEK) signaling pathways in cell growth of astaxanthin-treated NPCs, inhibition assays were performed with LY294002, a specific inhibitor of PI3K, and PD98059, a specific inhibitor of MEK, respectively. These results clearly showed that astaxanthin induces proliferation of NPCs via activation of the PI3K and MEK signaling pathways and improves stem cell potency via stemness acting signals.
astaxanthin; neural progenitor cells; PI3K; proliferation; stem cell
Ambulatory 24-hr esophageal pH monitoring is considered the gold standard for diagnosing gastroesophageal reflux disease. The aim of this study was to establish normal values for gastroesophageal acid exposure in healthy Koreans. Fifty healthy volunteers (24 males and 26 females; mean age, 45 yr) without reflux symptoms and without reflux esophagitis or hiatal hernia on upper endoscopy underwent ambulatory 24-hr esophageal pH monitoring after esophageal manometry. The 95th percentiles for the reflux parameters were: the percent total time pH <4, 3.7%; the percent upright time pH <4, 5.7%; the percent supine time pH <4, 1.0%; the number of reflux episodes with pH <4, 76.5; the number of reflux episodes with pH <4 for >5 min, 1.5; the duration of the longest episode, 12.5 min; and the composite score, 14.2. Age and gender were not associated with any of the pH parameters. In conclusion, physiological gastroesophageal reflux occurs in healthy Koreans. These normal esophageal pH values will provide reference data for clinical and research studies in Korea.
Gastroesophageal Reflux; Ambulatory 24-hr Esophageal pH Monitoring; Reference Values
Copy number variations (CNVs) are deletions, insertions, duplications, and more complex variations ranging from 1 kb to sub-microscopic sizes. Recent advances in array technologies have enabled researchers to identify a number of CNVs from normal individuals. However, the identification of new CNVs has not yet reached saturation, and more CNVs from diverse populations remain to be discovered.
We identified 65 copy number variation regions (CNVRs) in 116 normal Korean individuals by analyzing Affymetrix 250 K Nsp whole-genome SNP data. Ten of these CNVRs were novel and not present in the Database of Genomic Variants (DGV). To increase the specificity of CNV detection, three algorithms, CNAG, dChip and GEMCA, were applied to the data set, and only those regions recognized at least by two algorithms were identified as CNVs. Most CNVRs identified in the Korean population were rare (<1%), occurring just once among the 116 individuals. When CNVs from the Korean population were compared with CNVs from the three HapMap ethnic groups, African, European, and Asian; our Korean population showed the highest degree of overlap with the Asian population, as expected. However, the overlap was less than 40%, implying that more CNVs remain to be discovered from the Asian population as well as from other populations. Genes in the novel CNVRs from the Korean population were enriched for genes involved in regulation and development processes.
CNVs are recently-recognized structural variations among individuals, and more CNVs need to be identified from diverse populations. Until now, CNVs from Asian populations have been studied less than those from European or American populations. In this regard, our study of CNVs from the Korean population will contribute to the full cataloguing of structural variation among diverse human populations.
Transcriptional factor 4 (TCF4), encoding a basic helix-loop-helix transcriptional factor, has recently been demonstrated as a causative gene for Pitt-Hopkins syndrome, a neurodevelopmental disease. Examination of gastric cancers using the restriction landmark genomic scanning technique revealed methylation at a NotI enzyme site in TCF4 intron 8 and further identified CpG dinucleotide hypermethylation in TCF4 exon 1, strongly associated with gene silencing in gastric cancer cell lines. Treatment with 5-aza-2′-deoxycytidine and/or trichostatin A restored TCF4 expression in TCF4-silenced gastric cancer cell lines. Real-time reverse transcription–polymerase chain reaction analysis of 77 paired primary gastric tumor samples revealed that 38% of analyzed tumors had a >2-fold decrease in TCF4 expression compared with adjacent normal-appearing tissue, and the decrease significantly correlated with increased CpG methylation in TCF4 exon 1. Clinicopathologic data showed that decreased TCF4 expression occurred significantly more frequently in intestinal-type (22/37, 59%) than in diffuse-type (7/37, 19%) gastric cancers (P = 0.0004) and likewise more frequently in early (12/18, 67%) than in advanced (17/59, 29%) gastric cancers (P = 0.004). CpG methylation markedly increased with patient age among normal-appearing tissues, suggesting that CpG methylation in gastric mucosa may be one of the earliest events in carcinogenesis of intestinal-type gastric cancers. Furthermore, ectopic expression of TCF4 decreased cell growth in a gastric cancer cell line, and the knock down of TCF4 using small interfering RNA increased cell migration. Based on these results, we propose that the observed frequent epigenetic-mediated TCF4 silencing plays a role in tumor formation and progression.