1.Relevance of vacA Genotypes of Helicobacter pylori to cagA Status and Its Clinical Outcome.
Sill Moo PARK ; Joongwon PARK ; Jae Gyu KIM ; Byung Chul YOO
The Korean Journal of Internal Medicine 2001;16(1):8-13
BACKGROUND: Determination of vacA mosaicism may be important because specific Helicobacter pylori vacA genotype can be used to predict different clinical outcome. The aim of this study was to assess the relationship of vacA genotypes of Helicobacter pylori to cagA status and its development of peptic ulcer diseases in Korean patients. METHODS: Gastric biopsy specimens were obtained from 53 patients with gastric ulcer(GU), 57 with duodenal ulcer (DU) and 26 with chronic gastritis(CG) patients; all patients were infected with Helicobacter pylori. Bacterial mRNAs in the gastric mucosa were amplified by RT-PCR, using synthetic oligonucleotide primers specific for the vacA and the cagA gene. Patients with vacA s1 subtype were further examined to determine whether they had s1a or s1b subtype. RESULTS: There was no correlation in frequency of vacA s1 and/or s1a genotype between CG and either GU or DU, as the vacA s1 and s1a/m1 were present in the majority of strains independent of clinical status(s1 ; 100.0% versus 94.3 % or 93.0 % and s1a/m1 ; 76.9% versus 62.3% or 64.9%, res pectively). Likewise, there was no difference in the prevalence of the cagA gene between CG and either GU or DU patients (92.3% versus 90.6% or 98.2%, respectively). In addition, the cagA-negative status did not predict the presence of vacA s2 genotype. CONCLUSION: These results strongly suggest that either cagA or vacA s1 and/or s1a is not proved to be a useful marker to distinguish disease-specific Helicobacter pylori strains for the development of peptic ulcer diseases in Korean patients.
Adolescence
;
Adult
;
Aged
;
Aged, 80 and over
;
Bacterial Proteins/analysis*
;
Base Sequence
;
Biopsy, Needle
;
Chi-Square Distribution
;
Chronic Disease
;
Duodenal Ulcer/pathology
;
Duodenal Ulcer/genetics
;
Female
;
Gastritis/pathology
;
Gastritis/genetics
;
Genotype
;
Helicobacter Infections/pathology
;
Helicobacter Infections/genetics*
;
Helicobacter pylori/genetics*
;
Human
;
Korea
;
Male
;
Middle Age
;
Molecular Sequence Data
;
Peptic Ulcer/pathology
;
Peptic Ulcer/genetics*
;
Polymerase Chain Reaction
;
Probability
;
Prognosis
;
Sensitivity and Specificity
;
Stomach Ulcer/pathology
;
Stomach Ulcer/genetics
;
Support, Non-U.S. Gov't
;
Tissue Culture
2.DNA Methylation Patterns of Ulcer-Healing Genes Associated with the Normal Gastric Mucosa of Gastric Cancers.
Seung Jin HONG ; Jung Hwan OH ; Yu Chae JUNG ; Young Ho KIM ; Sung Ja KIM ; Seok Jin KANG ; Eun Joo SEO ; Sang Wook CHOI ; Moo Il KANG ; Mun Gan RHYU
Journal of Korean Medical Science 2010;25(3):405-417
Recent evidence suggests that gastric mucosal injury induces adaptive changes in DNA methylation. In this study, the methylation status of the key tissue-specific genes in normal gastric mucosa of healthy individuals and cancer patients was evaluated. The methylation-variable sites of 14 genes, including ulcer-healing genes (TFF1, TFF2, CDH1, and PPARG), were chosen from the CpG-island margins or non-island CpGs near the transcription start sites. The healthy individuals as well as the normal gastric mucosa of 23 ulcer, 21 non-invasive cancer, and 53 cancer patients were examined by semiquantitative methylation-specific polymerase chain reaction (PCR) analysis. The ulcer-healing genes were concurrently methylated with other genes depending on the presence or absence of CpG-islands in the normal mucosa of healthy individuals. Both the TFF2 and PPARG genes were frequently undermethylated in ulcer patients. The over- or intermediate-methylated TFF2 and undermethylated PPARG genes was more common in stage-1 cancer patients (71%) than in healthy individuals (10%; odds ratio [OR], 21.9) and non-invasive cancer patients (21%; OR, 8.9). The TFF2-PPARG methylation pattern of cancer patients was stronger in the older-age group (> or =55 yr; OR, 43.6). These results suggest that the combined methylation pattern of ulcer-healing genes serves as a sensitive marker for predicting cancer-prone gastric mucosa.
Biological Markers/metabolism
;
Cadherins/genetics
;
CpG Islands
;
*DNA Methylation
;
Female
;
*Gastric Mucosa/pathology/physiology
;
Gene Expression Regulation, Neoplastic
;
Growth Substances/genetics
;
Humans
;
Male
;
Middle Aged
;
Neoplasm Invasiveness
;
PPAR gamma/genetics
;
Peptides/genetics
;
*Stomach Neoplasms/genetics/pathology
;
*Stomach Ulcer/genetics/pathology
;
Tumor Suppressor Proteins/genetics
;
Wound Healing/*genetics
3.Effects of jianwei yuyang granule on inflammatory reaction and NF-kappaB expression in rat gastric mucosa of ulcer healing and recurrence.
Jiang-Hong LING ; Ye-Qiang CHEN ; Jia-Bang LI ; Yu-Zheng PAN ; Yang CAO ; Ding-Zhu SHEN
China Journal of Chinese Materia Medica 2006;31(17):1454-1457
OBJECTIVETo observe the effects of Jianwei Yuyang granule (JWYY) on inflammatory reaction and NF-kappaB expression in rat gastric mucosa of ulcer healing and recurrence.
METHODGastric ulcer was induced in rat by acetic acid according Okeba's method with some modification and the recurrence model was induced by IL-1beta. Pathohistology of ulcer healing and recurrence was observed. Density of inflammatory cell infiltrating regenerative mucosa, NF-kappaB protein and mRNA expression were measured.
RESULTJWYY had effects on improving the quality of ulcer healing, reducing the rate of ulcer recurrence, decreasing the density of inflammatory cell infiltrating regenerative mucosa and suppressing the activation and expression quantity of NF-kappaB protein and mRNA.
CONCLUSIONJWYY may promote the ulcer healing and prevent the recurrence of the gastric ulcer by suppressing the activation of NF-kappaB and the following inflammatory reaction.
Acetic Acid ; Animals ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Gastric Mucosa ; metabolism ; pathology ; Male ; NF-kappa B ; biosynthesis ; genetics ; Plants, Medicinal ; chemistry ; RNA, Messenger ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Recurrence ; Stomach Ulcer ; chemically induced ; metabolism ; pathology
4.MG7 expression in helicobacter pylori-related gastric diseases.
Dongli GUO ; Ming DONG ; Yuan YUAN
Chinese Journal of Oncology 2002;24(2):151-153
OBJECTIVETo determine the influence of Helicobacter pylori (H. pylori) on gastric cancer-related antigen MG7 expression.
METHODSThe H. pylori infection and the expression level of antigen MG7 in gastric mucosa were determined by HE stain, PCR, ELISA and immunohistochemistry in 291 patients with H. pylori-related conditions, among whom 34 were followed-up.
RESULTSNo significant difference was found between H. pylori-negative and H. pylori-positive intestinal metaplasia, atrophic gastritis and dysplasia of gastric epithelium in positive rate of antigen MG7 expression. There was significant difference between H. pylori-negative and H. pylori-positive superficial gastritis in the positive rate of MG7 expression (P < 0.05). During follow-up, one of 3 H. pylori-negative cases turned to be H. pylori-positive, and its MG7 expression turned to be higher at the same time. Three of 31 H. pylori-positive patients were discovered as having early gastric cancer, among whom one with antigen MG7 expression (+ + +) was found to have a reduced Mg7 expression accompanied with H. pylori eliminutied after operation.
CONCLUSIONThere is correlationship between H. pylori infection and MG7 expression in superficial gastritis. Although the MG7-positive lesions with H. pylori infection shows a benign nature in morphology, they also have the potential risk of developing into gastric cancer. Therefore, they should be followed up, during which special attention should be paid to patients with increased MG7 expression.
Antibodies, Bacterial ; blood ; Antigens, Neoplasm ; biosynthesis ; DNA, Bacterial ; genetics ; Enzyme-Linked Immunosorbent Assay ; Gastric Mucosa ; metabolism ; microbiology ; pathology ; Gastritis ; metabolism ; microbiology ; Helicobacter Infections ; metabolism ; microbiology ; Helicobacter pylori ; genetics ; growth & development ; immunology ; Humans ; Immunohistochemistry ; Polymerase Chain Reaction ; Stomach Diseases ; metabolism ; microbiology ; Stomach Ulcer ; metabolism ; microbiology
5.Selective COX-2 inhibitor delays experimental gastric ulcer healing by stimulating gastric acid secretion in rats.
Mei-rong HE ; Jin-qiu LIN ; Yu-gang SONG
Journal of Southern Medical University 2007;27(7):1015-1017
OBJECTIVETo observe the effect of selective cyclooxygenase-2 (COX-2) inhibitor on the healing of experimental gastric ulcer in rats and explore its mechanisms in light of gastric acid secretion.
METHODSGastric ulcers were induced in rats by an application of acetic acid to the serosal surface of the anterior gastric body. The effects of selective COX-2 inhibitor, celecoxib, on the healing of gastric ulcer, the total acidity of gastric juice, the expressions of H+, K+-ATPase mRNA and protein, and the ultrastructure of the parietal cell were observed in comparison with the effects of normal saline.
RESULTSNine days after ulcer induction, the ulcer area was 11.9-/+3.1 mm square and 19.7-/+3.8 mm square in rats with normal saline and celecoxib treatments, respectively (P<0.01). The total acidity of gastric juice and the expressions of H+, K+-ATPase mRNA and protein in celecoxib group were significantly higher than that in normal saline group at both 6 and 9 days after ulcer induction, but no significant difference was found between the two groups in the amount of secretary canaliculus and microvillus.
CONCLUSIONSelective COX-2 inhibitor can significantly delay the healing of experimental gastric ulcer in rats, the mechanism of which might be associated with enhanced digestive action of gastric acid on the new granulation tissue at the ulcer base as a result of celecoxib-stimulated gastric acid secretion of the parietal cells.
Animals ; Celecoxib ; Cyclooxygenase 2 Inhibitors ; pharmacology ; therapeutic use ; Gastric Acid ; secretion ; Gene Expression Regulation, Enzymologic ; drug effects ; H(+)-K(+)-Exchanging ATPase ; genetics ; metabolism ; Hydrogen-Ion Concentration ; Male ; Microvilli ; drug effects ; pathology ; Parietal Cells, Gastric ; drug effects ; ultrastructure ; Pyrazoles ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Stomach Ulcer ; drug therapy ; metabolism ; pathology ; Sulfonamides ; pharmacology ; therapeutic use
6.Clinical study on effect of Jianwei Yuyang Granule in treating patients with gastric ulcer.
Yuan LIN ; Shu-sheng LIAO ; Yong-jie ZHOU
Chinese Journal of Integrated Traditional and Western Medicine 2007;27(7):606-609
OBJECTIVETo observe the clinical effects of Jianwei Yuyang Granule (JYG) in treating patients with gastric ulcer and its influence on interleukin-1beta (IL-1beta) and basic fibroblast growth factor (bFGF) mRNA expression in gastric mucosa for exploring the therapeutic mechanism.
METHODSFifty-six patients with confirmed gastric ulcer unader gastroscope and differentiated as Gan-stagnant Pi-deficient syndrome were randomly assigned to two groups, the treated group (26 cases) treated with JYG and the control group (30 cases) treated with famotidine and sucralfate, 4 weeks as one therapeutic course. The changes before and after treatment in clinical compliance, symptom integral, ulcer-healing rate, clinical effective rate, and HP-clearance rate were observed. And the gastric mucosa biopsy was fetched for morphological examination and IL-1beta and bFGF mRNA expression detection by RT-PCR as well.
RESULTSThe clinical compliance rate in the treated group was 100 %, which was obviously better than that in the control group (86.7 %, P< 0.01); the improvement on symptom integral in the former was also better (P < 0.01); no statistical significance was shown in ulcer-healing rate, clinical effective rate and HP-clearance rate between the two groups. Morphological observation showed markedly decreased inflammatory cell infiltration, epithelial cell regeneration and rather regular glandular arrangement in both groups. The IL-1beta mRNA expression level decreased and that of bFGF increased in both groups after treatment significantly ( P < 0.01), but showed insignificant difference between the two groups.
CONCLUSIONJYG, with its good clinical compliance, has favorable effects in relieving clinical symptoms, promoting endoscopic ulcer healing and HP clearance, decreasing the expression of IL-1beta mRNA and increasing the expression of bFGF, therefore, it could promote the recovering of gastric ulcer.
Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Fibroblast Growth Factor 2 ; genetics ; Gastric Mucosa ; drug effects ; metabolism ; pathology ; Humans ; Interleukin-1beta ; genetics ; Male ; Middle Aged ; Phytotherapy ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Ulcer ; drug therapy ; Young Adult
7.Grifola frondosa water extract alleviates intestinal inflammation by suppressing TNF-alpha production and its signaling.
Jong Suk LEE ; Su Young PARK ; Dinesh THAPA ; Mi Kyoung CHOI ; Ill Min CHUNG ; Young Joon PARK ; Chul Soon YONG ; Han Gon CHOI ; Jung Ae KIM
Experimental & Molecular Medicine 2010;42(2):143-154
TNF-alpha is a major cytokine involved in inflammatory bowel disease (IBD). In this study, water extract of Grifola frondosa (GFW) was evaluated for its protective effects against colon inflammation through the modulation of TNF-alpha action. In coculture of HT-29 human colon cancer cells with U937 human monocytic cells, TNF-alpha-induced monocyte adhesion to HT-29 cells was significantly suppressed by GFW (10, 50, 100 microg/ml). The reduced adhesion by GFW correlated with the suppressed expression of MCP-1 and IL-8, the major IBD-associated chemokines. In addition, treatment with GFW significantly suppressed TNF-alpha-induced reactive oxygen species production and NF-kappaB transcriptional activity in HT-29 cells. In differentiated U937 monocytic cells, LPS-induced TNF-alpha production, which is known to be mediated through NF-kappaB activation, was significantly suppressed by GFW. In an in vivo rat model of IBD, oral administration of GFW for 5 days (1 g/kg per day) significantly inhibited the trinitrobenzene sulfonic acid (TNBS)-induced weight loss, colon ulceration, myeloperoxidase activity, and TNF-alpha expression in the colon tissue. Moreover, the effect of GFW was similar to that of intra-peritoneal injection of 5-aminosalicylic acid (5-ASA), an active metabolite of sulfasalazine, commonly used drug for the treatment of IBD. The results suggest that GFW ameliorates colon inflammation by suppressing production of TNF-alpha as well as its signaling through NF-kappaB leading to the expression of inflammatory chemokines, MCP-1 and IL-8. Taken together, the results strongly suggest GFW is a valuable medicinal food for IBD treatment, and thus may be used as an alternative medicine for IBD.
Animals
;
Cell Adhesion/drug effects/immunology
;
Cell Extracts/administration & dosage/*pharmacology
;
Chemokine CCL2/biosynthesis/genetics
;
Coculture Techniques
;
Colon/drug effects/*metabolism/pathology
;
Grifola
;
HT29 Cells
;
Humans
;
Inflammatory Bowel Diseases/chemically induced/*drug therapy/pathology/physiopathology
;
Interleukin-8/biosynthesis/genetics
;
Intestinal Mucosa/*drug effects/metabolism/pathology
;
Monocytes/*drug effects/metabolism/pathology
;
NF-kappa B/genetics/metabolism
;
Peroxidase/metabolism
;
Rats
;
Rats, Sprague-Dawley
;
Reactive Oxygen Species/metabolism
;
Stomach Ulcer
;
Transcription, Genetic/drug effects
;
Trinitrobenzenesulfonic Acid/administration & dosage
;
Tumor Necrosis Factor-alpha/*biosynthesis/genetics
;
U937 Cells
;
Weight Loss