Introduction
It is suggested that minimal change (grade M) esophagitis is a spectrum of gastric acid reflux disease. We evaluated the clinical significance of grade M esophagitis, including its ...subtypes (reddish change: MR and whitish change: MW), especially with attempt to pathological conditions in the stomach that relates to gastric acid secretion.
Materials and Methods
Using 241 subjects undergoing esophagogastroduodenoscopy for various indications, we investigated the association between grade M esophagitis with histological and serological severity of gastritis and endoscopic degree of atrophy. We also examined its association with ulcer diseases and various symptoms.
Results
When grade M cases were divided into MR and MW, all MR cases had MW in considerable degrees. Dyspeptic symptoms were more likely to be associated with
H. pylori
negative grade M cases, while presence of duodenal ulcer and its scar were associated with
Helicobacter pylori
-positive grade M cases. In all subjects, histological parameters, especially in the corpus, were lower in grade M cases compared to normal appearance. In grade M cases, degree of acute and chronic inflammation, and atrophy in corpus were lowest in cases that have grade MR. Grade M cases were also associated with higher pepsinogen I/II ratio and lower endoscopic atrophy.
Conclusions
Pathological conditions of the stomach relate to higher gastric acid secretion correlates with grade M esophagitis. In grade M cases, appearance of MR may reflect higher gastric acid secretion or severe acid reflux than cases that have grade MW only.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Combining the magnifying endoscopy and the narrow-band imaging (NBI) system is an endoscopic imaging technique for the enhanced visualization of mucosal microscopic structure and capillaries of the ...superficial mucosal layer. Light blue crest (LBC) and, ridge/villous pattern have been thought to be suggestive signs for gastric intestinal metaplasia (IM) of magnifying NBI endoscopy. Since the IM is related to gastric cancer risk (GC), the prevalence of LBC and ridge/villous pattern in the nonneoplastic gastric antrum was examined in relation to gastric cancer (GC) risk and serological severity of gastritis.
In 100 subjects including 13 GC patients, gastric mucosal pattern were examined using magnifying NBI. The mucosal patterns in the antrum were classified according to the presence of LBC or ridge/villous pattern. Serum pepsinogen (PG) levels were also examined.
The sensitivity and specificity for predicting IM was the best when LBC and ridge/villous patterns were combined (sensitivity 95.2%, specificity 98.7%). Both LBC and ridge/villous pattern showed lower serum PGI and PGI/II ratio than those without (P = 0.046, 0.0005, respectively.) In particular, PGI/II ratio was lowest in ridge/villous pattern. The LBC and ridge/villous pattern showed higher incidence of all GC and diffuse GC compared to those without (P = 0.002, 0.002, respectively).
LBC and ridge/villous pattern in uninvolved gastric antrum by magnifying NBI endoscopy are useful signs for predicting gastric atrophy in the entire stomach and GC risk.
Inflammatory changes in the gastric mucosa are commonly observed in Japanese
patients with functional dyspepsia (FD). However, detailed data regarding the
relationship between the genetic regulatory ...factors of inflammation and FD are
not available. We investigated the associations between FD and genetic polymorphisms
of molecules associated with inflammation or immune response (IL-17A, -17F and
MIF). The study was performed with 278 subjects (188 with no upper abdominal symptoms
and 90 with FD according to the Roma III criteria). We employed the PCR-SSCP (multiplex
PCR for IL-17A and -17F) method to detect the gene polymorphisms. Overall, the
polymorphisms of the IL-17A, -17F and MIF genes were not correlated with the susceptibility
to FD. However, the MIF -173C allele carrier had a significantly increased risk
for the development of epigastric pain syndrome (EPS) of FD (OR, 2.12; 95% CI,
1.00-4.49; p=0.0497). In Helicobacter pylori (H. pylori)-infected cases, the number
of IL-17F 7488T alleles was positively correlated with the development of EPS
(OR, 11.3; 95% CI, 1.23-103.2; p=0.032), while the IL-17F T/T homozygote and the
MIF -173C carrier had an increased risk for EPS (OR, 10.4; 95% CI, 1.17-92.3;
p=0.036 and OR, 3.66; 95% CI, 1.19-11.3; p=0.024, respectively). In addition,
a significant interaction between the IL-17F 7488 polymorphism and H. pylori infection
was shown to increase the activity and inflammation scores (p=0.043 and 0.042,
respectively). There were no significant associations between the IL-17A polymorphism
and FD. Our results provide the first evidence that the IL-17F and MIF gene polymorphisms
are significantly associated with the development of FD, particularly EPS, a subgroup
of FD, in H. pylori-infected subjects. The genetic polymorphisms of inflammation
or immune response-related molecules are involved in the development of one of
the FD subgroups via H. pylori-induced gastric inflammation.
Transcription factor Nrf2 regulates the expression of detoxifying and antioxidant genes. Three promoter polymorphisms of this gene have been identified. This study attempted to clarify the ...relationship between Nrf2 gene polymorphism and ulcerative colitis in a Japanese population.
The study was performed in 89 patients with ulcerative colitis (mean age: 40.2 years, M:F = 47:42) and 141 healthy volunteers (mean age: 38.7 years, M:F = 75:66). The PCR-SSCP method was employed to detect Nrf2 polymorphisms using DNA extracted from peripheral blood cells.
Comparison of genotype frequency, -686*-684 A* G/A*G genotype was significantly lower in the UC group than those in the HC group (OR = 0.45, 95% CI:0.22-0.93, p = 0.029) and G*G carrier was higher in the UC group, especially in female subjects. Furthermore, -686*-684 G*G carrier was more closely associated with chronic continuous phenotype (OR = 2.57, 95% CI:1.01-6.60, p = 0.043). On the other hand, no association between -650 genotype and ulcerative colitis was found.
The -686*-684 genotype of Nrf2 gene may be associated with the development of ulcerative colitis.
A number of association studies have focused on the effect of polymorphisms related to DNA repair or the xenobiotic pathway, on the susceptibility to gastric cancer (GC). Here, the possible ...association between common polymorphisms in the X-ray repair cross-complementing groups (XRCC) 1, and glutathione-S-transferase (GST) genes and various clinicopathological characteristics, including overall survival, in GC patients were evaluated.
XRCC1 Arg399Gln, and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were determined in 130 GC patients.
XRCC1 codon 194 Trp carriers (Trp/Trp + Arg/Trp) held a significantly higher risk of venous invasion (OR = 3.76, 95%CI = 1.05-13.51, p = 0.043). A similar trend was also found for the XRCC1 codon 194 Trp/Trp genotype (OR = 2.15, 95% CI = 0.87-5.34, p = 0.099). The frequencies of the XRCC1 codon 399 Gln/Gln and Arg/Gln genotypes tended to be lower in lymphatic invasion-positive GC (XRCC1 codon 399 Gln/Gln: OR = 0.27, 95% CI = 0.06-1.15, p = 0.075, Gln/Gln + Arg/Gln: OR = 0.46, 95% CI = 0.20-1.06, p = 0.069), while the frequencies of the XRCC1 codon 194 Trp/Trp genotype tended to be higher in lymphatic invasion-positive GC (XRCC1 codon 194 Trp/Trp: OR = 7.70, 95% CI = 0.95-62.60, p = 0.056). The patients with the GSTT1 null genotype showed significantly better overall survival than the patients with the GSTT1 present genotype (p = 0.019).
XRCC1 codon 194 Trp carrier status is correlated with more aggressive biological behavior of GC, such as venous invasion, and the GSTT1 null genotype is associated with better survival in GC patients.
There have been reports showing a protective role of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) against gastrointestinal cancers. E-cadherin (CDH1) is an adhesion molecule ...involved in tumour invasion/metastasis. Silencing of CDH1 by promoter CpG island methylation was shown in gastric cancer, precancerous lesion, and Helicobacter pylori-infected chronic gastritis. We investigated the methylation status of CDH1 in noncancerous gastric mucosa in chronic aspirin user, and assessed its effect on methylation-associated carcinogenesis. Gastric mucosa samples from antrum were obtained from 217 cancer-free subjects, including 37 chronic aspirin users and 180 subjects with no history of chronic or occasional intake of aspirin. Methylation-specific polymerase chain reaction (PCR), i.e., MSP, was performed for CDH1 gene promoter. In all 217 subjects, CDH1 methylation was detected for 69 subjects (31.7%). CDH1 methylation more frequently occurred in H. pylori-infection-positive subjects (P < 0.0001), while chronic aspirin users had a significantly lower risk of CDH1 methylation nonuser versus user 36.1% versus 10.8%; odds ratio (OR) = 0.21, 95% confidence interval (CI) = 0.07-0.63, P = 0.005. Logistic regression analysis showed that chronic aspirin use was the independent factor for lower risk of CDH1 methylation (adjusted OR = 0.21, 95%CI = 0.07-0.66, P = 0.008). Chronic aspirin use was associated with lower risk of CDH1 methylation in H. pylori-positive subjects (nonuser versus user 49.5% versus 19.0%; OR = 0.24, 95%CI = 0.08-0.76, P = 0.01). Similar trend was also found in H. pylori-negative subjects (P = 0.07). No association was found between CDH1 methylation status, and duration and dose of aspirin. Our data suggest that chronic aspirin use is associated with reduced risk of CDH1 methylation in human gastric mucosa. Aspirin may have suppressive role against methylation-related gastric carcinogenesis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The oxidation of human and rat erythrocyte ghost membranes by molecular oxygen has been performed in an aqueous suspension at 37°C. A constant rate of oxygen uptake was observed in the presence of ...radical initiator. α-Tocopherol in the membrane suppressed the oxidation and the induction period was clearly observed. α-Tocopherol decreased linearly during the induction period and when it was depleted the induction period was over and a rapid oxidation started. The rate of oxidation was proportional to the square root of the rate of initial radical generation. The kinetic chain length, the ratio of the rate of propagation to that of initiation, was long, ranging from 7 to 100. These results indicate that the erythrocyte ghost membranes are oxidized by a free radical chain mechanism by molecular oxygen. Among the fatty acids of membrane lipids, polyunsaturated fatty acids were oxidized exclusively. Proteins as well as polyunsaturated fatty acids were oxidized and the formation of the high- and low-molecular-weight proteins and the decrease of protein bands were observed on gel electrophoresis.
BACKGROUNDPromoter hypermethylation of tumor suppressor genes is one of the major events in gastric carcinogenesis. Promoter hypermethylation is also present in non-neoplastic gastric epithelium as ...age-related phenomenon and some reports suggest the potential association between promoter hypermethylation and Helicobacter pylori infection. Here, we examined whether methylation of multiple promoter CpG islands would occur by H. pylori infection and correlate with histological or serological severity of chronic gastritis.
METHODSOne hundred and ninety-one gastric mucosa samples were obtained by endoscopy. The promoter methylation status of the p14, p16, DAP-kinase and CDH1 genes were determined by methylation-specific-polymerase chain reaction. The degree of gastritis in the antrum was assessed according to the updated Sydney system in 150 participants. The pepsinogen (PG) I/II ratio was calculated based on the data of serum PG I and PG II levels measured by radioimmunoassay in 54 selected cases.
RESULTSCpG island methylation was found in 32.5% for p14, 35.1% for p16, 43.5% for DAP-kinase and 36.1% for CDH1, whereas non, 1, 2, 3, and all methylation of four promoter CpG sites were present in 46 (24.1%), 59 (30.9%), 46 (24.1%), 30 (15.7%), and 10 (5.2%) participants, respectively. A strong association between the increased number of methylated CpG islands and H. pylori infection was observed (P<0.0001). An increased number of methylated CpG islands was also associated with severity of neutrophil infiltration (P<0.0001), mononuclear cell infiltration (P<0.0001) and atrophy (P=0.0021) in all, and severity of neutrophil infiltration (P=0.0177) and mononuclear cell infiltration (P=0.0004) in H. pylori-positive participants. An increased number of methylated CpG islands correlated with lower PG I/II ratio in all (P=0.0105) and H. pylori-infected participants (P=0.074).
CONCLUSIONMultiple promoter CpG islands would be methylated by H. pylori infection, and an increased number of methylated CpG sites correlate with histological and serological severity of chronic gastritis.
CpG island hyper-methylation (CIHM) is one of the major events in the gastric
carcinogenesis. IL-17A, -17F and MIF have a crucial role in the gastric inflammation
and carcinogenesis. Recently, we ...showed that the genetic polymorphisms of MIF-794-CATT
repeat are associated with CIHM status in the non-neoplastic gastric mucosa. Consequently,
the CIHM status in the gastric cancer tissue, in relation to IL-17A (-197G>A),
-17F (7488T>C), and MIF (-173G>C and -794 tetranucleotide repeats) polymorphisms
was investigated. Gastric cancer tissues were obtained from 102 patients. CIHM
of p14, p16, DAP-kinase and CDH1 genes were determined by methylation-specific
polymerase chain reaction (MSP). CIHM high was defined as three or all CpG islands
methylated. We employed the PCR-SSCP (multiplex PCR for IL-17A and -17F) method
to detect the gene polymorphisms. We did not find significant association between
CIHM status and IL-17F (7488T>C) and MIF (-173G>C) polymorphisms. However,
concerning the IL-17A (-197G>A) polymorphism, we found that IL-17A G carrier
(GG+GA) held a significantly higher risk of CIHM of p16 (OR=11.22, 95% CI=1.38-91.17,
p=0.024) and CIHM high (OR=3.51, 95% CI=1.15-10.68, p=0.027). An association was
also found between the 7-CATT repeat carrier (5/7 + 6/7 + 7/7) of the MIF polymorphism
(-794-CATT) and reduced risk of CIHM of CDH1 (OR=0.36, 95% CI=0.14-0.92, p=0.032).
No association was found between CHIM status and homozygote genotypes of each
repeat (-794-CATT 5/5, 6/6, and 7/7). The present results provided evidence that
the genetic polymorphisms of IL-17A, and MIF-794-CATT repeat are associated with
CIHM status in the gastric cancer. Genetic polymorphisms of IL-17A, and MIF-794-CATT
repeat may be involved in methylation-related carcinogenesis in the stomach.
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