Serum PG Research Articles

Eradication Therapy for Helicobacter pylori Improves Nutrition Status Depended on Severity of Gastric Mucosal Atrophy and Plasma Ghrelin Level in Japanese Hemodialysis Patients

Introduction: The state of metabolic and nutritional derangement, called protein—energy wasting (PEW), has a major impact on mortality in hemodialysis (HD) patients. Ghrelin has multiple favorable functions and associates with the pathogenesis of PEW in HD patients. Plasma and gastric ghrelin levels are affected in H pylori status. Here, we investigated relationships among nutrition status, ghrelin level, H. pylori and severity of atrophy in HD patients and investigated the efficacy of H. pylori eradication therapy for improvement of nutrition status related with ghrelin in H. pylori—positive HD patients. Methods: H. pylori&#x2014;IgG and pepsinogen levels of 500 HD patients at 8 dialysis centers were measured. We classified H. pylori infectionstatus into three groups: present infection, past infection and non—infection. Plasma ghrelin levels were measured and we investigated above relationship among three groups. H. pylori—positives underwent endoscopy for evaluation of the severity of atrophy, and eradicated by PPI, amoxocollin and clarithromycin for 7days. We evaluated nutrition markers and ghrelin levels before and 1 year after eradication. Results: Acyl— and desacyl—ghrelin levels were 29.7±21.3 fmol/mland 279.2±168.5 fmol/ml, respectively. Acyl—ghrelin in the non—infection group was significantly higher than in the present and past infection groups. Acyl—ghrelin level was positively correlated with serum PG I level and PG I/II ratio and was significantly lower in patients with severe atrophy than in those with no atrophy (20.9±14.6and 40.4±21.9, p<0.001). Cholinesterase level was significantly increased after eradication compared with before eradication (303.2±76.0 vs. 287.3±68.1, p=0.029). In particular, cholesterol(before, 196.6±23.2; after, 206.1±25.9, p=0.042) and cholinesterase levels(before, 296.9±70.8; after, 316.4±73.8, p=0.049) increased more strongly in patients with mild-moderate atrophy than those with severe atrophy. Conclusion: Plasma ghrelin level was associated with endoscopic and serological severity of atrophy related with H. pylori infection in HD patients. Eradication improved nutrition status by increasing serum cholinesterase and cholesterol levels, especially those with mild and moderate gastric mucosal atrophy. In HD patients, eradication therapy may contribute to an improvement in prognosis associated with PEW.

Nitric oxide/Asymmetric Dimethylarginine Axis may Interplay With Some Sex Hormones for Pathogenesis and Severity of Pre-eclampsia: Study controlled by Uterine Arterial Doppler.

Objectives: To evaluate relations of asymmetric dimethylarginine (ADMA) and nitric oxide (NO) with estrogen (E2) and progesterone (Pg) and its role in pathogenesis and severity of pre-eclampsia (PE). Patients & Methods: At 12th week gestational age (GA) constitutional data, systolic and diastolic blood pressures (SBP and DBP), uterine artery pulsatility index (UAPI) and serum NO, ADMA, E2 and Pg levels were determined for primigravida attending the antenatal care unit. During pregnancy, women who developed PE were categorized as early or late and mild or severe according to ACOG Practice Bulletin of PE guidelines. Studied parameters were evaluated statistically as early predictors for development and severity of PE. Results: Ninety pregnant women developed PE; 39 early and 51 late. Only 13 women had severe and 77 women had mild PE. At 12th week GA, UAPI and serum ADMA levels were significantly higher with significantly lower E2 and NO levels in PE women than women free of PE and in early than in late PE. High SBP at time of PE diagnosis showed positive significant correlation with body mass index (BMI) and serum ADMA levels but showed negative significant correlation with serum NO and E2 levels. Serum ADMA levels showed positive significant correlation with BMI, but negative significant correlation with serum E2 levels. High UAPI, serum ADMA and high BMI were significant early predictors for PE development and severity. Conclusion: Disturbed maternal serum ADMA/NO axis and low E2 serum levels may underlie PE development. High BMI and low E2 level may have a role in PE pathogenesis through induction of high serum ADMA levels. High UAPI and serum ADMA at 12th week GA could be used as early predictors of PE especially early-onset and severe PE.

Evaluation of Pepsinogen I as a Biomarker of Drug-induced Gastric Mucosal Injury in Cynomolgus Monkeys.

Gastric mucosal injury is frequently observed in nonclinical studies of nonhuman primates. Because microscopic evaluation of stomach is generally a terminal procedure, our objective was to determine whether serum pepsinogen I (PG I) could serve as a noninvasive biomarker for detection of gastric mucosal injury in monkey. Serum PG I was measured using a commercial human immunoassay in cynomolgus monkeys ( n = 166) prior to dosing and/or terminally in 11 studies of up to 1 month duration. Mean ( SD) PG I values (ug/L) for monkeys with ( n = 59) and without ( n = 100) gastric mucosal degeneration were 101 (215) and 28 (12.6), respectively. For monkeys with baseline and terminal PG I data, mean ( SD) fold change (ratio of terminal to baseline PG I) for monkeys with ( n = 57) and without ( n = 76) glandular degeneration were 4.1 (11.3) and 1 (0.28). Receiver operating characteristic area under the curve (AUC) data demonstrated moderate diagnostic accuracy for serum PG I for glandular degeneration, AUC ( SE) 0.789 (0.04), with improved diagnostic accuracy as a fold change of baseline, AUC ( SE) 0.816 (0.04), consistent with the large interindividual but low intraindividual variability of serum PG I values in control monkeys. These data demonstrate that serum PG I is a useful biomarker of drug-induced gastric mucosal injury in the cynomolgus monkey.

Impact of Helicobacter pylori Immunoglobulin G Levels and Atrophic Gastritis Status on Risk of Metabolic Syndrome.

BackgroundHelicobacter pylori (HP) infection is implicated in gastric and extra-gastric diseases. While gastritis-related chronic inflammation represents a known trigger of metabolic disturbances, whether metabolic syndrome (MetS) is affected by gastritis status remains unclear. We aimed to clarify the effect of HP-related gastritis on the risk of MetS.Materials and MethodsWe retrospectively enrolled patients undergoing screening for MetS between 2014 and 2015. Investigations included HP-specific immunoglobulin G (IgG) antibody assays to detect HP infection, and serum pepsinogen assays to evaluate atrophic gastritis status. The risk of MetS was evaluated via multiple logistic regression analyses with two covariates: serum HP infection status (IgG levels) and atrophic gastritis status (two criteria were applied; pepsinogen I/II ratio < 3 or both pepsinogen I levels ≤ 70 μg/L and pepsinogen I/II ratio < 3).ResultsOf 1,044 participants, 247 (23.7%) were HP seropositive, and 62 (6.0%) had MetS. HP seronegative and seropositive patients had similar risks of MetS. On the other hand, AG (defined in terms of serum PG I/II <3) was significant risk of MetS (OR of 2.52 [95% CI 1.05–7.52]). After stratification according to HP IgG concentration, patients with low HP infection status had the lowest MetS risk (defined as an odds ratio [OR] adjusted for age, sex, smoking, drinking and physical activity status). Taking this result as a reference, patients with negative, moderate, and high HP infection status had ORs (with 95% confidence intervals [CI]) of 2.15 (1.06–4.16), 3.69 (1.12–16.7), and 4.05 (1.05–26.8).ConclusionsHP-associated gastritis represents a risk factor for MetS. Research should determine why low and not negative HP infection status is associated with the lowest MetS risk.

Assessment of ADMA, estradiol, and progesterone in severe preeclampsia

ABSTRACTBackground: Decreased nitrous oxide (NO) levels are crucial factors in severe preeclampsia (sPE), and asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthetase. Steroid hormones are closely related to the vascular endothelium. This study determined the levels of and correlations between ADMA, estradiol (E2), and progesterone (Pg) in sPE to investigate the roles of these factors in this disease. Methods: Sixty-two sPE patients (sPE group) were divided into the sPE1 subgroup (28+1–32+0 weeks of pregnancy), the sPE2 subgroup (32+1–36+0 weeks), and the sPE3 subgroup (36+1–40+0 weeks) and 75 normal pregnant women (NC group) were divided into the NC1 subgroup (28+1–32+0 weeks of gestation), the NC2 subgroup (32+1–36+0 weeks), and the NC3 subgroup (36+1–40+0 weeks). Serum and placental ADMA levels were measured by enzyme-linked immunosorbent assay (ELISA), and serum E2 and Pg concentrations were determined by the chemilumineseent immunoassay (CLIA). Results: ADMA concentrations in both the placenta and the maternal serum were significantly higher in the sPE group (p < 0.05). Higher ADMA contents were observed in the placenta relative to the maternal serum (p < 0.05). Serum E2 levels were significantly lower in the sPE group (p < 0.05). For Pg, the only significant difference was observed between the sPE1 and NC1 subgroups (p < 0.05). The Pg/E2 ratios in the sPE groups were significantly higher, with a significant high positive correlation between Pg/E2 ratios and serum ADMA levels. Conclusion: Increased serum levels of ADMA in sPE may result from increased secretion from the placenta, and the increased Pg/E2 ratio may play a role in the development of sPE by aggravating ADMA.

Paper] Classification of Gastric Cancer Risk From X-ray Images Based on Efficient Image Features Related to Serum Hp Antibody Level and Serum PG Levels

In this paper, a fully automatic gastric cancer risk classification method with the aim of constructing a computer-aided diagnosis (CAD) system is presented. Two-stage classification is used in the proposed method for determining gastric cancer risk. In the first stage, the proposed method detects H. pylori-infected patients, i.e., detection of patients who have gastric cancer risk, and the proposed method classifies the level of gastric cancer risk, i.e., high or low, from H. pylori-infected patients in the second stage. In each stage, we derive new image features that are closely related to values of blood examination via kernel canonical correlation analysis. The introduction of these new image features provides classification improvement in each stage, and it is the main contribution of this paper. Consequently, accurate classification becomes feasible by the proposed method. Experimental results obtained by applying the proposed method to real X-ray images show that our method outperforms several comparative methods.

Serum Indicators Reflecting Gastric Function May Also Correlate with Other Extragastric Diseases.

Aim. Serological indicators of organ function can reveal intrinsic links between different organs. The present study aimed to determine the correlations of serum indicators for gastric and extragastric function. Methods. A total of 823 individuals were enrolled. Data on indicators reflecting blood lipids, blood glucose, indexes of stomach, kidney, liver, and thyroid function, and H. pylori IgG antibody level were collected. Results. As creatine (Cr) levels increased, PGI (pepsinogen I), PGII concentrations, and PGI/II ratio increased monotonically from 79.7 to 105.15 µg/L, 6.5 to 8.4 µg/L, and 11.97 to 12.27, respectively (P < 0.05). As thyroid peroxidase antibody (TPOAb) levels increased, PGI level decreased from 100.85 to 84 µg/L (P < 0.05) and as thyroid stimulating hormone (TSH) increased, PGI/II ratio increased monotonically from 11.54 to 12.68 (P < 0.05). As triglyceride (TG) levels increased, gastrin 17 (G17) concentrations increased monotonically from 1.73 to 2.7 pmol/L (P < 0.05). As serum glucose and glycated hemoglobin (HbA1C) increased, PGI/II concentrations increased monotonically from 11.98 to 12.67 and 9.7 to 13.54 (P < 0.05), respectively. Conclusions. Serum PG and G17 levels were associated with blood glucose and lipids, kidney function, and thyroid function but not with liver function. Serum indicators reflecting gastric function may correlate not only with primary diseases, but also with other extragastric diseases.

Population-based gastric cancer screening in Zhuanghe, Liaoning, from 1997 to 2011

To investigate the feasibility of gastric cancer screening for the susceptible population in the high-risk areas of China and to optimize the screening programme. By using the two-round screening method i.e. serum pepsinogen test combined with gastric mucosa biopsy, large-scale population screening programs were carried out in Zhuanghe, Liaoning province. All adults or residents above 35 years old with a positive family history of gastric cancer or gastrointestinal symptoms were targeted. Three large-scale population screenings were developed over the past 15 years. All together, 13078 participants accepted the two-round screening, and 108 gastric cancer cases were detected. Among them, the detection rate of early gastric cancer was 56.82%, 51.22% and 82.61%, respectively. The pathologically confirmed gastric cancer cases were immediately arranged to have early surgical treatment, and meanwhile, the follow-up files for the patients were established. With a consecutive and regular 10-year postoperative follow-up, the 5-year survival rate for these early gastric cancer patients reached 90.48%. Effectiveness and health economic evaluation confirmed that there are good specificity and sensitivity for the two round screening programs. It is cost-effective. As the primary screening method serum PG test can improve the screening examination rate and concentrate the gastric cancer risk populations. It is feasible to develop the gastric cancer screening program among the susceptible population in high-risk areas in our country, and the two-round screening method is of practical value. Research for early detection of gastric cancer should be further enhanced, and multidisciplinary and multicenter cooperation should be organized. It is necessary to extend the implementation the gastric cancer screening and to further improve the early detection programme, in order to make a breakthrough based on the present practice.

Low serum pepsinogen I and pepsinogen I/II ratio and Helicobacter pylori infection are associated with increased risk of gastric cancer: 14‐year follow up result in a rural Chinese community

The correlation between low serum PG level and H. pylori infection with the development of gastric cancer has caused considerable concerns all over the world. Some authors exclaimed that gastric cancer developed only in patients infected with H. pylori, whereas the other had different findings. In this study, 1,501 adult local residents with determined serum PG levels and anti H. pylori IgG status were followed for 14 years for the development of gastric cancer in a rural community with high risk of gastric cancer in Hebei Province, China. The results showed the accumulated gastric cancer incidence in the subjects with abnormal PG level and those with H. pylori infection were all significantly higher than that in the corresponding normal controls (53.9‰ vs. 12.7‰, p < 0.05 and 23.1‰ vs. 5.93‰, p < 0.05). The highest gastric cancer incidence was seen in the subjects with both abnormal serum PG and positive H. pylori (56.0‰), and followed by the subjects with abnormal PG and negative H. pylori (47.6‰) and those with normal serum PG and positive H. pylori (18.4‰). The abnormal serum PG level (OR 3.029) and H. pylori infection (OR 4.345) were all risk factors for the development of gastric cancer. The results suggested that the subjects with abnormal serum PG level and/or positive H. pylori infection in the rural area of China were all high risk population for gastric carcinoma and the subjects with both abnormal serum PG and positive H. pylori infection were at especially high risk for the development of gastric carcinoma.

Health economic assessment for screening of gastric cancer in a high risk population in northeastern China

To assess economic cost-effects for the screening programs of gastric cancer in a high risk population in northeastern China. The data were collected from November 2001 to December 2003. The multi-stage sampling to define the screening group and the control group was applied in this study. Two stage screening programs were used in the study. An epidemiological survey and serum PG test were carried out in the first stage. The endoscopy and pathological examination were performed in the second stage screening. Effectiveness was assessed by the increased quality adjusted life-year (QALY) because of reduced gastric cancer deaths in screening. A total of 27,970 participants (n=7,128 screening group, n=20,842 control group) were enrolled in the survey. Twenty nine gastric cancer cases were detected in the screening group with 20 cases in the early stage and 9 cases in the advanced stage, respectively. Eighty six gastric cancer cases were detected in the control group, all of whom were in the advanced stage and had died before the study finished. The screening and treatment of 29 cases cost $152,227 and $5,249 per each case, respectively. The costs were $459 to gain per QALY. The screening program of gastric cancer used in our study is an economic and society-beneficial measure to detect gastric cancer in high risk area. The methods fit China's present economic development level.

Low Serum Levels of Pepsinogen and Gastrin 17 Are Predictive of Extensive Gastric Atrophy with High-Risk of Early Gastric Cancer

Atrophic gastritis (AG) is a well-recognized high-risk condition for developing gastric cancer (GC). Gastrin 17 (G17), a hormone secreted from antral G cells, regulates gastric acid secretion, and its serum level is a possible indicator of antral atrophy. Serum pepsinogen is well established as the indicator of AG involving the corpus. Here we investigated whether serum PG and G17 levels would be useful for determining the topographic pattern of AG and estimating the risk of GC. Enrolled were 122 Japanese patients with early GC (114 well- to moderate-differentiated cancers and 8 poorly-differentiated cancers). In addition, 178 subjects without GC were recruited as control from those undergoing endoscopic examination (non-GC group). All subjects were histologically assigned to the following four groups: non-AG, antrum-predominant AG, corpus-predominant AG, and multifocal AG, affecting the antrum and corpus. Serum concentrations of pepsinogen and G17 were determined using ELISA. Multifocal AG was more frequent in the GC group than in the adjusted non-GC group, and had the highest risk of GC (OR 25.1). Serum G17 was significantly decreased with the exacerbation of antral atrophy in the coexistence of corpus atrophy. Serum biomarker profiles showed that the low levels of pepsinogen and G17 could discriminate between multifocal AG and other types of AG, but not with pepsinogen level alone. Serologically defined multifocal AG had the highest cancer risk among other serologically defined AG groups (OR 26.9). In conclusion, the low serum levels of pepsinogen and G17 are predictive of extensive gastric atrophy with high-risk of early GC.

Usefulness of a New Gastric Cancer Screening Program Using the Combination Assay of Serum Anti-Helicobacter pylori IgG Antibody and the Serum Pepsinogen Levels

Purpose: This study was performed to evaluate a new gastric cancer screening program using this combination assay of the serum Hp and PG test method. Methods: Serum Hp and PG levels were measured in the total number of 48073 asymptomatic individuals (about 16000 per year; majority participants checked every year) at a work place in Tokyo as a primary screening between April 2007 and March 2010 (a ratio of man to woman=3.6, a mean age of 47.4 years). We classified into 1 of 4 groups based on the results of the serum Hp and PG levels; group A [Hp (-) PG (-)] (73.2%), group B [Hp (+) PG (-)] (16.4%), group C [Hp (+) PG (+)] (9.3%), and group D [Hp (-) PG (+)] (1.1%), respectively. Group A, B, C, and D were recommended to undergo endoscopic examination every 5 years, 3 years, 2 years, and every year, respectively, and we examined the detection rate of gastric cancers and details of detected cancers. Simultaneously, we estimated the annual increasing or decreasing ratio of each group, comparing the ratio of each group in 2007, 2008, and 2009. Results: In a total of 48073 participating individuals, 6965 planned to undergo endoscopic examination (4202 in group B, 2346 in group C, and 417 in group D). For the total of planned examination, 3921 individuals underwent endoscopic examination (2244 in group B, 1436 in group C, and 241 in group D). Gastric cancer was detected in 23 patients (12 patients in 2007, 8 patients in 2008, and 3 patients in 2009), and 16 and 7 of them were detected from group B and C, respectively. 18 of them were early gastric cancers and 12 of them could be resected endoscopically. Although 5 advanced cancers were detected in this screening program, it was the first time for all of them to have this program for reasons such as mid-career hiring. Histopathologically, 47.8% of the detected cancers were diffuse type, and the ratio of diffuse type was increasing gradually (25.0% in 2007, 62.5% in 2008, and 100% in 2009). The ratio of group A in 2007, 2008, and 2009 was 70.7%, 72.7%, and 75.8%, and the ratio of group B was 19.4%, 16.7%, and 13.5%, respectively. Consequently, the annual increasing ratio of group A per year was estimated about 3% and the decreasing rate of group B was about 3% per year. Conclusion: A mass screening for gastric cancer using the combination assay of the serum Hp and PG test method was useful to select a high-risk and low-risk population of developing gastric cancers and to detect not only intestinal type but also diffuse type cancers in early stage. The number of individuals in group A will continue to increase at a rate of about 3%, which is expected to contribute to a further reduction in the number of individuals who are advised to undergo a mass screening method for gastric cancer in the future.

Inhibitory effects of Japanese apricot (Prunus mume Siebold et Zucc.; Ume) on Helicobacter pylori-related chronic gastritis

We investigated the correlation between Japanese apricot (JA) intake and Helicobacter pylori-related chronic atrophic gastritis (CAG). A questionnaire was administered and serum anti-H. pylori IgG antibodies measured in 1358 asymptomatic adults. The subjects were divided into high-intake and low-intake groups. Histological and serological evaluation of H. pylori-related CAG was performed in 68 non-elderly volunteers. The H. pylori-negative rate did not differ significantly between the high-intake and low-intake groups. Mean antibody titers were lower in the high-intake group, but the difference was not significant. There was no significant difference in the rate of H. pylori infection on the basis of JA intake when subjects were stratified by age. Among H. pylori-positive non-elderly subjects, antibody titers were significantly lower in the high-intake group (P=0.041). Endoscopic tissue biopsy from the 68 volunteers showed less H. pylori bacterial load and mononuclear infiltration irrespective of gastric site in the high-intake group. In the high-intake group, antral neutrophil infiltration was significantly less pronounced and corporal atrophy was less extensive. Serological evaluation using serum PG levels also confirmed these histopathological data. Our findings strongly indicate a preventive effect of JA intake on CAG by inhibiting H. pylori infection and reducing active mucosal inflammation.

Hunting down a double gap metabolic acidosis

Double gap metabolic acidosis occurs in the setting of unmeasured active osmoles in the serum (osmolal gap) and anion gap (AG) metabolic acidosis. We describe a 67-year-old woman with acute respiratory failure on mechanical ventilator from pneumonia and anuric acute on chronic renal failure (urea nitrogen 21.4 mmol/L, creatinine 530.4 micromol/L) requiring haemodialysis (HD). On hospital day 5, she was found to have progressive metabolic acidosis (serum pH 7.16, PCO(2) 4.38 kPa, HCO(3)(-) 12.1 mmol/L and AG 21 mmol/L). There was no evidence of hypoxaemia, hypoperfusion or haemodynamic instability. Normal serum ketone and L-lactate but high serum osmolal gap (89.4 mmol/kg) was detected. A search for toxic alcohols revealed a high serum propylene glycol (PG 32.9 mmol/L), a stabilizing solvent for intravenous formulations of lorazepam, which was being used as sedation for mechanical ventilation. Unexpectedly, serum L- and D-lactate as metabolites of PG were not elevated. Although extended HD for eight hours completely removed serum PG and the osmolal gap, the predialysis high AG metabolic acidosis persisted, potentially related to hypercatabolism and anuric renal failure. PG should be in the differential diagnosis of the disorders with high osmolar gap and may not always be associated with L- or D-lactic acidosis.

Usefulness of serum pepsinogen levels as a screening test for atrophic gastritis and gastric cancer.

The purpose of our study was to research the applicability of measuring serum pepsinogen I (PG I) and PG I/pepsinogen II (PG II) ratios as screening tests for atrophic gastritis, which is the most important predisposition for stomach cancer. We measured serum pepsinogen levels in non-specific gastritis, atrophic gastritis and gastric cancer using a radioimmunoassay method. We included in this study 30 healthy control, 30 nonspecific gastritis, 30 atrophic gastritis and 50 gastric cancer cases. The serum PG I level was statistically higher in the control group and in the patient group with chronic nonspecific gastritis compared to the patient groups with chronic atrophic gastritis and stomach cancer (p<0.05). The best cutoff values for diagnosing stomach cancer using serum PG I and PG I / PG II ratios were found to be <25 ng/ml for PG I and <3.0 for PG I / PG II. The same cut-off values were also most effective for the patients with atrophic gastritis. Serum pepsinogen screening was shown to be a practical predictor of stomach cancer and atrophic gastritis, the most important predisposing lesion for stomach cancer. Although the diagnosis of stomach cancers localized in the pylorus and cardia via this method is difficult, we believe that the detection of early-stage cancers that develop following chronic atrophic gastritis in particular will be possible, and therefore the morbidity and mortality of stomach cancer will be decreased.

A Significant Increase of Pepsinogen I/II Ratio is a Reliable Biomarker for the Successful Helicobacter pylori Eradication in Patients without Peptic Ulcer or Gastric Cancer

Purpose: Serum pepsinogen I (PG I) and pepsinogen II (PG II) levels reflect the inflammation and atrophy of gastric mucosa. They were shown to reflect the severity of atrophic gastritis and thus to be useful for detecting an individual who has a tendency to develop gastric cancer. (Miki K, et al. Am J Gastroenterol 2003, 98:735-739). PG I and PG II change after Helicobacter pylori (H. pylori) eradication as the result of the improvement of gastric mucosal inflammation, and the PG I/PG II ratio (PGR) has been shown to be a reliable indicator for the success of H. pylori eradication in peptic ulcer patients.(Furuta T, et al. Am J Gastroenterol, 1997, 92:84-87). An aim of this study was to investigate the usefulness of PGR as an indicator of successful H. pylori eradication in patients without peptic ulcers or gastric cancer. Methods: We enrolled in this study, between June 2008 and May 2009, 44 patients (16 males and 28 females, average age: 61.5 years, range: 34-73 years). None of them had peptic ulcer or gastric cancer endoscopically. They were confirmed to have H. pylori infection by 13C-urea breath test (UBT). All of them had fasting serum PGR ≤3. They were given with lansoprazole 30 mg, clarithromycin 400 mg, and amoxicillin 750 mg b.i.d. for one week in order to eradicate H. pylori at first therapy. For the judgment of the success of H. pylori eradication, serum PG I and PG II were analyzed and UBT were performed 3 months after eradication. UBT value less than 0.5% was regarded as the golden standard for the eradication success. H. pylori eradication was judged as successful when the fasting serum PGR increased more than 40% of the pre-eradication value. Statistical analysis of the results was calculated by means of paired t test. Results:H. pylori eradication was successful in 29 patients and failed in 15 patients. Serum PG I, PG II, PGR (mean±SE) before and after H. pylori eradication was 46.9±4.4, 28.8±2.2, 1.64 ± 0.12 and 24.6±1.6, 7.13±0.34, 3.52 ± 0.21 (p <0.0001) in patients H. pylori eradication was successful. On the other hand, they were 52.5±7.4, 26.6±4.0, 1.97± 0.17 and 50.3±8.0, 25.0±3.1, 1.96 ± 0.19 (n.s.) in patients H. pylori eradication was unsuccessful. Conclusion: A significant (>40%) increase of fasting serum PGR after H. pylori eradication is a reliable biomarker for the successful H. pylori eradication (PGR change method) in patients without peptic ulcer or gastric cancer. Serum PGR has the comparable efficacy to UBT in determining the success of H. pylori eradication.Figure: Symptoms across 4 days - GCSI.

Serum biomarker tests are useful in delineating between patients with gastric atrophy and normal, healthy stomach.

To study the value of serum biomarker tests to differentiate between patients with healthy or diseased stomach mucosa: i.e. those with Helicobacter pylori (H pylori) gastritis or atrophic gastritis, who have a high risk of gastric cancer or peptic ulcer diseases. Among 162 Japanese outpatients, pepsinogen I (Pg I) and II (Pg II) were measured using a conventional Japanese technique, and the European GastroPanel examination (Pg I and Pg II, gastrin-17 and H pylori antibodies). Gastroscopy with gastric biopsies was performed to classify the patients into those with healthy stomach mucosa, H pylori non-atrophic gastritis or atrophic gastritis. Pg I and Pg II assays with the GastroPanel and the Japanese method showed a highly significant correlation. For methodological reasons, however, serum Pg I, but not Pg II, was twice as high with the GastroPanel test as with the Japanese test. The biomarker assays revealed that 5% of subjects had advanced atrophic corpus gastritis which was also verified by endoscopic biopsies. GastroPanel examination revealed an additional seven patients who had either advanced atrophic gastritis limited to the antrum or antrum-predominant H pylori gastritis. When compared to the endoscopic biopsy findings, the GastroPanel examination classified the patients into groups with "healthy" or "diseased" stomach mucosa with 94% accuracy, 95% sensitivity and 93% specificity. Serum biomarker tests can be used to differentiate between subjects with healthy and diseased gastric mucosa with high accuracy.

Combined Determination of Serum PG and CEA and its Clinical Application in Distinctive Diagnosis of Benign and Malignant Gastric Ulcer

Objective The aim of this study was to evaluate the clinical value and the possibilities of measuring the serum levels of pepsinogen I (PG I ) and careineembryonic antigen (CEA) in 402 patients with gastric ulcer.Methods The patients with gastric ulcer were all confirmed by either operation or gastrofiberscope,and divided into two groups,benign and malignant gastric ulcer.After comparing the relationship between the patients'clinical appearance and the Radioimmunoaasay(RIA) results,(CEA and PG I ).Results There were 73 patients were onfirmed malignant gastric ulee in 402 patients.The positive rate of PG was 52.05% (38/73).The positive rate of CEA was 64.38% (47/73).Both were 30.14% (22/73).Then there were 63(63/73) patients who was positive in the combined determination.Solo determination's positive rate of CEA and PG were significantly different from the combined determination.(P＜0.05 and 0.01) Conclusions Feasibility and the necessity of combined determination were evaluated.Compared with solo determination,for patients with malignant gastric ulcer,it was more sensitive to determine and analysis the serum levels of PG I and CEA sYnthetically.So it is recommended to popularize the combined determination of serum PG I and CEA in clinical distinctive diagnosis of benign and malignant gastric ulcer. Key words: Pepsinogon; Careinoembryonic antigen ; Immunoradiometric assay; Stomach ulcer

Risk Prediction of Gastric Cancer by Analysis of Aberrant DNA Methylation in Non-Neoplastic Gastric Epithelium

Background: Aberrant DNA methylation is one of the major events in carcinogenesis. Promoter DNA methylation is also present in various non-neoplastic tissues including gastric epithelium as age-related phenomenon, suggesting that it occurs early in the process of tumorigenesis. Aim: We aimed to clarify the relationship of aberrant DNA methylation in non-neoplastic gastric epithelia with the risk of gastric cancer, Helicobactor pylori infection, and the degree of H. pylori-induced gastritis. Methods: 89 patients enrolled in this study. The status of aberrant DNA methylation was compared in two groups of patients: 43 cases with gastric cancer (mean age 65.9 years [29–91], F:M = 0.30, intestinal type [n = 25], diffuse type [n = 18]) and 46 age- and sex-matched patients without gastric cancer (peptic ulcer diseases [n = 11], gastritis [n = 35]) as a control group. Genomic DNA was extracted directly from non-neoplastic epithelia of antral biopsies obtained by endoscopy. The promoter methylation status of the p14 and p21 genes was determined by methylation-specific-polymerase chain reaction (MSP). The promoter methylation status of the p16 gene was quantified by digital densitographic analysis following MSP. The degree of gastritis in the antrum was assessed according to the updated Sydney system. The PG I/II ratio was calculated based on the data of serum PG I and PG II levels measured by radioimmunoassay. Results: In all 89 subjects, CpG island methylation was found in 25.8% for p14, 52.8% for p16, 1.1% for p21. Among non-cancer patients, the methylation frequency of the p14 gene was significantly higher in H. pylori-positive than in H. pylori-negative patients (38.5 vs. 10.0%, p = 0.03). The mean (± SD) methylation levels of the p16 gene in non-neoplastic gastric epithelium was significantly higher in gastric cancer cases both in all patients and in H. pylori-positive patients (0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.019, 0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.016, respectively). The methylation level of the p16 gene was also associated with the presence of intestinal-type gastric cancer (p = 0.017). The methylation level of the p16 gene was significantly higher in patients with intestinal metaplasia (IM) than those without (p = 0.04). Furthermore, the methylation level of the p16 gene was correlated with lower PG l/ll ratio (p = 0.04). The methylation of the p21gene was found in only 1 patient with gastric cancer. Conclusions: Our data suggest that promoter of the p14 gene may be one of the specific regions whose methylation is closely associated with H. pylori infection. Methylation levels of the p16 gene seem to be accumulated in the progression of gastric mucosal atrophy and IM, and thus may be associated with the presence of gastric cancer especially for intestinal-type histopathology.

Erratum: Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages

Nature 443, 998–1002 (2006) In this Letter, the units of the y-axis for Fig. 3d should be picograms, not micrograms. The label should read ‘TNF-α in serum (pg ml-1)’.