AIM To evaluate the frequency of Helicobacter pylori(H. pylori) Cag A antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori Cag A-immune respo...AIM To evaluate the frequency of Helicobacter pylori(H. pylori) Cag A antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori Cag A-immune response.METHODS Systematic data to H. pylori isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile(anti-H. pylori, anti-Cag A) was correlated with H. pylori isolates(cag A, EPIYA, vac A s/m genotype), histology(Sydney classification) and mucosal interleukin-8(IL-8) m RNA and protein expression. Selected H. pylori strains were assessed for H. pylori Cag A protein expression and IL-8 induction in co-cultivation model with AGS cells.RESULTS Thirty point three percent of microbiologically confirmed H. pylori infected patients were seropositive for Cag A. Majority of H. pylori isolates were cag A gene positive(93.9%) with following vac A polymorphisms: 42.4% vac A s1m1, 23.2% s1m2 and 34.3% s2m2. Anti-Cag AIg G seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and cag A m RNA expression. V a c A s a n d m p o l y m o r p h i s m s w e r e t h e m a j o r determinants for positive(vac A s1m1) or negative(vac A s2m2) anti-Cag A serological immune response, which also correlated with the in vitro inflammatory potential in AGS cells. In vitro co-cultivation of representative H. pylori strains with AGS cells confirmed functional Cag A translocation, which showed only partial correlation with Cag A seropositivity in patients, supporting vac A as major co-determinant of the immune response.CONCLUSION Serological immune response to H. pylori cag A + strain in H. pylori infected patients is strongly associated with vac A polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.展开更多
AIM:To assess whether antibiotic resistance varies between the antrum and corpus of the stomach of patients that are either Helicobacter pylori(H.pylori)therapy-naive or pre-treated.METHODS:H.pylori strains were isola...AIM:To assess whether antibiotic resistance varies between the antrum and corpus of the stomach of patients that are either Helicobacter pylori(H.pylori)therapy-naive or pre-treated.METHODS:H.pylori strains were isolated from antrum and corpus biopsies from 66 patients that received a diagnostic gastroduodenoscopy for variant clinical indications.Antimicrobial susceptibility to amoxicillin,clarithromycin,tetracycline,metronidazole,levofloxacin and rifabutin was tested with the E-test method on IsoSensitest agar with 10 vol%defibrinated horse blood.In patients with a different antibiotic susceptibility pattern between the isolates from the antrum and corpus,DNA fingerprinting via random amplified polymorphic DNA analysis was performed to detect differences among DNA patterns of H.pylori isolates.RESULTS:Primary,secondary and tertiary resistance to clarithromycin was 6.9%,53.8%and 83.3%,retrospectively.Metronidazole and levofloxacin resistance also increased according to the number of previous treatments(17.2%,69.2%,83.3%;13.8%,23.1%,33.3%).Tertiary resistance to rifabutin was detected in12.5%of patients.In none of the 66 patients a resistance against amoxicillin or tetracycline was detectable.Discordant antibiotic susceptibility between antrum and corpus isolates for different antibiotics was seen in 15.2%(10/66)of the patients.Two out of those ten patients were naive to any H.pylori antibiotic treatment.The remaining eight patients previously received at least one eradication therapy.DNA fingerprinting analysis revealed no substantial differences among DNA patterns between antrum and corpus isolates in the majority of patients suggesting an infection with a single H.pylori strain.CONCLUSION:Different antibiotic susceptibility between antrum and corpus biopsies is a common phenomenon and a possible explanation for treatment failure.Resistant H.pylori strains may be missed if just one biopsy from one anatomic site of the stomach is taken for H.pylori susceptibility testing.展开更多
AIM To evaluate associations between mi RNA target genes IL12B,INSR,CCND1 and IL10 polymorphisms and gastric cancer(GC)in European population.METHODS Gene polymorphisms were analyzed in 508 controls and474 GC patients...AIM To evaluate associations between mi RNA target genes IL12B,INSR,CCND1 and IL10 polymorphisms and gastric cancer(GC)in European population.METHODS Gene polymorphisms were analyzed in 508 controls and474 GC patients from 3 tertiary centers in Germany,Lithuania and Latvia.Controls were patients from the out-patient departments,who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy.Gastric cancer(GC)patients had histopathological verification of gastric adenocarcinoma.Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells.IL12B T>G(rs1368439),INSR T>C(rs1051690),CCND1 A>C(rs7177)and IL10 T>C(rs3024498)SNPs were genotyped by the real-time polymerase chain reaction.Associations between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex,age and country of birth.RESULTS We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR rs1051690.The frequency of the T allele of INSR gene was significantly higher in GC patients than in controls(23.26%and 19.19%respectively,P=0.028).CT genotype was also more prevalent in patients compared to control group(38.48%and 30.12%respectively,P<0.021).Logistic regression analysis revealed that only one polymorphism(rs1051690 in INSR gene)was associated with increased risk of GC.Carriers of CT genotype had higher odds of GC when compared to CC genotype(OR=1.45,95%PI:1.08-1.95,P=0.01).Similar association was observed in a dominant model for INSR gene,where comparison of TT+CT vs CC genotypes showed an increased risk of GC(OR=1.44,95%PI:1.08-1.90,P=0.01).Other analyzed SNPs were not associated with the presence of GC.CONCLUSION INSR rs1051690 SNP is associated with increased risk of GC,while polymorphisms in IL12B,CCND1 and IL10genes are not linked with the presence of GC.展开更多
AIM:To study the impact of an endoscopy-based long-term study on the quality of life in healthy volunteers(HV).METHODS:Ten HV were included into a long-term prospective endoscopy-based placebo-controlled trial with 15...AIM:To study the impact of an endoscopy-based long-term study on the quality of life in healthy volunteers(HV).METHODS:Ten HV were included into a long-term prospective endoscopy-based placebo-controlled trial with 15 endoscopic examinations per person in 5 different drug phases.Participants completed short form-36(SF-36) and visual analog scale-based questionnaires(VAS) for different abdominal symptoms at days 0,7 and 14 of each drug phase.Analyses wereperformed according to short-and long-term changes and compared to the control group.RESULTS:All HV completed the study with duration of more than 6 mo.Initial quality of life score was comparable to a general population.Analyses of the SF-36 questionnaires showed no significant changes in physical,mental and total scores,either in a short-term perspective due to different medications,or to potentially endoscopic procedure-associated long-term cumulative changes.Analogous to SF-36,VAS revealed no significant changes in total scores for pathological abdominal symptoms and remained unchanged over the time course and when compared to the control population.CONCLUSION:This study demonstrates that quality of life in HV is not significantly affected by a longterm endoscopy-based study with multiple endoscopic procedures.展开更多
AIM: To investigate a pathophysiological role of cathepsin W (CatW), a putative thiol-dependent cysteine protease,which is specifically expressed in cytotoxic lymphocytes,in different types of chronic inflammation of ...AIM: To investigate a pathophysiological role of cathepsin W (CatW), a putative thiol-dependent cysteine protease,which is specifically expressed in cytotoxic lymphocytes,in different types of chronic inflammation of the gastric mucosa.METHODS: Gastric and duodenal biopsies of patients with Helicobacter pylori ( H pylori)-associated active gastritis ( Hp,n = 19), chemically induced reactive gastritis (CG, n = 17),autoimmune atrophic gastritis (AIG, n = 20), lymphocytic corpus gastritis (LG, n = 29), celiac disease (CD, n = 10),and corresponding controls (n = 24) were analyzed by immunohistochemistry for the expression of CatW and CD45. Furthermore, immunohistochemical double staining with anti-CD3 and anti-cathepsin was performed for the samples of AIG.RESULTS: Median values of CatW-expressing cells among CD45-positive immune cells were between 2% and 6% for normal gastric mucosa, CG, and LG, whereas the corresponding value was significantly increased for AIG (24.7%, P＜0.001) and significantly decreased for HP (0.7%, P＜0.05). Double staining with anti-CD3 and antiCatW antibodies revealed that ＞90% of CatW-expressing cells in gastric mucosa of AIG were T cells. Duodenal mucosa had significantly more CatW/CD45-positive cells than normal gastric mucosa (median: 17.8% vs 2%, P＜0.01).The corresponding proportion of CatW/CD45-positive cells was decreased in CD compared to duodenal mucosa (median: 2.1% vs 17.8%, P＜0.05).CONCLUSION: The opposite findings regarding the presence of CatW-positive cells in AIG (increase) and CD (decrease) reflects the different cellular composition of immune cells involved in the pathogenesis of these diseases.展开更多
基金Supported by the BMBF No.BMBF-0315905D in the frame of ERA-NET Patho Geno Mics to Malfertheiner P
文摘AIM To evaluate the frequency of Helicobacter pylori(H. pylori) Cag A antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori Cag A-immune response.METHODS Systematic data to H. pylori isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile(anti-H. pylori, anti-Cag A) was correlated with H. pylori isolates(cag A, EPIYA, vac A s/m genotype), histology(Sydney classification) and mucosal interleukin-8(IL-8) m RNA and protein expression. Selected H. pylori strains were assessed for H. pylori Cag A protein expression and IL-8 induction in co-cultivation model with AGS cells.RESULTS Thirty point three percent of microbiologically confirmed H. pylori infected patients were seropositive for Cag A. Majority of H. pylori isolates were cag A gene positive(93.9%) with following vac A polymorphisms: 42.4% vac A s1m1, 23.2% s1m2 and 34.3% s2m2. Anti-Cag AIg G seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and cag A m RNA expression. V a c A s a n d m p o l y m o r p h i s m s w e r e t h e m a j o r determinants for positive(vac A s1m1) or negative(vac A s2m2) anti-Cag A serological immune response, which also correlated with the in vitro inflammatory potential in AGS cells. In vitro co-cultivation of representative H. pylori strains with AGS cells confirmed functional Cag A translocation, which showed only partial correlation with Cag A seropositivity in patients, supporting vac A as major co-determinant of the immune response.CONCLUSION Serological immune response to H. pylori cag A + strain in H. pylori infected patients is strongly associated with vac A polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.
基金Supported by In part supported by a grant from the BMBF,BMBF-0315905D in the frame of ERA-NET Patho Geno Mics
文摘AIM:To assess whether antibiotic resistance varies between the antrum and corpus of the stomach of patients that are either Helicobacter pylori(H.pylori)therapy-naive or pre-treated.METHODS:H.pylori strains were isolated from antrum and corpus biopsies from 66 patients that received a diagnostic gastroduodenoscopy for variant clinical indications.Antimicrobial susceptibility to amoxicillin,clarithromycin,tetracycline,metronidazole,levofloxacin and rifabutin was tested with the E-test method on IsoSensitest agar with 10 vol%defibrinated horse blood.In patients with a different antibiotic susceptibility pattern between the isolates from the antrum and corpus,DNA fingerprinting via random amplified polymorphic DNA analysis was performed to detect differences among DNA patterns of H.pylori isolates.RESULTS:Primary,secondary and tertiary resistance to clarithromycin was 6.9%,53.8%and 83.3%,retrospectively.Metronidazole and levofloxacin resistance also increased according to the number of previous treatments(17.2%,69.2%,83.3%;13.8%,23.1%,33.3%).Tertiary resistance to rifabutin was detected in12.5%of patients.In none of the 66 patients a resistance against amoxicillin or tetracycline was detectable.Discordant antibiotic susceptibility between antrum and corpus isolates for different antibiotics was seen in 15.2%(10/66)of the patients.Two out of those ten patients were naive to any H.pylori antibiotic treatment.The remaining eight patients previously received at least one eradication therapy.DNA fingerprinting analysis revealed no substantial differences among DNA patterns between antrum and corpus isolates in the majority of patients suggesting an infection with a single H.pylori strain.CONCLUSION:Different antibiotic susceptibility between antrum and corpus biopsies is a common phenomenon and a possible explanation for treatment failure.Resistant H.pylori strains may be missed if just one biopsy from one anatomic site of the stomach is taken for H.pylori susceptibility testing.
基金Supported by Lithuanian Research Council Grant,No.MIP-14418
文摘AIM To evaluate associations between mi RNA target genes IL12B,INSR,CCND1 and IL10 polymorphisms and gastric cancer(GC)in European population.METHODS Gene polymorphisms were analyzed in 508 controls and474 GC patients from 3 tertiary centers in Germany,Lithuania and Latvia.Controls were patients from the out-patient departments,who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy.Gastric cancer(GC)patients had histopathological verification of gastric adenocarcinoma.Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells.IL12B T>G(rs1368439),INSR T>C(rs1051690),CCND1 A>C(rs7177)and IL10 T>C(rs3024498)SNPs were genotyped by the real-time polymerase chain reaction.Associations between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex,age and country of birth.RESULTS We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR rs1051690.The frequency of the T allele of INSR gene was significantly higher in GC patients than in controls(23.26%and 19.19%respectively,P=0.028).CT genotype was also more prevalent in patients compared to control group(38.48%and 30.12%respectively,P<0.021).Logistic regression analysis revealed that only one polymorphism(rs1051690 in INSR gene)was associated with increased risk of GC.Carriers of CT genotype had higher odds of GC when compared to CC genotype(OR=1.45,95%PI:1.08-1.95,P=0.01).Similar association was observed in a dominant model for INSR gene,where comparison of TT+CT vs CC genotypes showed an increased risk of GC(OR=1.44,95%PI:1.08-1.90,P=0.01).Other analyzed SNPs were not associated with the presence of GC.CONCLUSION INSR rs1051690 SNP is associated with increased risk of GC,while polymorphisms in IL12B,CCND1 and IL10genes are not linked with the presence of GC.
基金Supported by A Research Grant of Astra-Zeneca (Wedel,Germany)
文摘AIM:To study the impact of an endoscopy-based long-term study on the quality of life in healthy volunteers(HV).METHODS:Ten HV were included into a long-term prospective endoscopy-based placebo-controlled trial with 15 endoscopic examinations per person in 5 different drug phases.Participants completed short form-36(SF-36) and visual analog scale-based questionnaires(VAS) for different abdominal symptoms at days 0,7 and 14 of each drug phase.Analyses wereperformed according to short-and long-term changes and compared to the control group.RESULTS:All HV completed the study with duration of more than 6 mo.Initial quality of life score was comparable to a general population.Analyses of the SF-36 questionnaires showed no significant changes in physical,mental and total scores,either in a short-term perspective due to different medications,or to potentially endoscopic procedure-associated long-term cumulative changes.Analogous to SF-36,VAS revealed no significant changes in total scores for pathological abdominal symptoms and remained unchanged over the time course and when compared to the control population.CONCLUSION:This study demonstrates that quality of life in HV is not significantly affected by a longterm endoscopy-based study with multiple endoscopic procedures.
基金Supported by the "Deutsche Forschungsgemeinschaft", Germany (We2170/3-1)the NBL-3 program of the "Bundesministerium für Forschung und Technik" (NBL3/01ZZ0407/PFG1)
文摘AIM: To investigate a pathophysiological role of cathepsin W (CatW), a putative thiol-dependent cysteine protease,which is specifically expressed in cytotoxic lymphocytes,in different types of chronic inflammation of the gastric mucosa.METHODS: Gastric and duodenal biopsies of patients with Helicobacter pylori ( H pylori)-associated active gastritis ( Hp,n = 19), chemically induced reactive gastritis (CG, n = 17),autoimmune atrophic gastritis (AIG, n = 20), lymphocytic corpus gastritis (LG, n = 29), celiac disease (CD, n = 10),and corresponding controls (n = 24) were analyzed by immunohistochemistry for the expression of CatW and CD45. Furthermore, immunohistochemical double staining with anti-CD3 and anti-cathepsin was performed for the samples of AIG.RESULTS: Median values of CatW-expressing cells among CD45-positive immune cells were between 2% and 6% for normal gastric mucosa, CG, and LG, whereas the corresponding value was significantly increased for AIG (24.7%, P＜0.001) and significantly decreased for HP (0.7%, P＜0.05). Double staining with anti-CD3 and antiCatW antibodies revealed that ＞90% of CatW-expressing cells in gastric mucosa of AIG were T cells. Duodenal mucosa had significantly more CatW/CD45-positive cells than normal gastric mucosa (median: 17.8% vs 2%, P＜0.01).The corresponding proportion of CatW/CD45-positive cells was decreased in CD compared to duodenal mucosa (median: 2.1% vs 17.8%, P＜0.05).CONCLUSION: The opposite findings regarding the presence of CatW-positive cells in AIG (increase) and CD (decrease) reflects the different cellular composition of immune cells involved in the pathogenesis of these diseases.
