AIM： To evaluate several risk factors for gastric cancer （GC） in Costa Rican regions with contrasting GC incidence rate （GCIR）. METHODS： According to GCIR, 191 Helicobacter pylori （H pylori）-positive patients ...AIM： To evaluate several risk factors for gastric cancer （GC） in Costa Rican regions with contrasting GC incidence rate （GCIR）. METHODS： According to GCIR, 191 Helicobacter pylori （H pylori）-positive patients were classified into groups A （high GCIR, n = 101） and B （low GCIR, n = 90）. Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin （IL）-1β and IL-10 by PCRRFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS： Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach （mixed strain infection） were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR （P = 0.026 and 0.041, respectively）. IL- 1β＋3954_T/C （OR 2.1, 1.0-4.3）, IL-1RN^＊2/L （OR 3.5, 1.7-7.3） and IL-10-592_C/A （OR 3.2, 1.5-6.8） were individually associated with GC, and a combination of these cytokine polymorphisms with Hpylori vacA slb and ml further increased the risk （OR 7.2, 1.4-36.4）. CONCLUSION： Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of Hpylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica.展开更多
The bacterial pathogen Helicobacter pylori (H. pylori) colonizes in over half of the world’s population. H. pylori that establishes life-long infection in the stomach is definitely associated with gastro-d...The bacterial pathogen Helicobacter pylori (H. pylori) colonizes in over half of the world’s population. H. pylori that establishes life-long infection in the stomach is definitely associated with gastro-duodenal diseases and a wide variety of non-gastrointestinal tract conditions such as immune thrombocytopenia. Triple therapy which consists of a proton pump inhibitor and combinations of two antibiotics (amoxicillin, clarithromycin or amoxicillin, metronidazol) is commonly used for H. pylori eradication. Recently, the occurrence of drug-resistant H. pylori and the adverse effect of antibiotics have severely weakened eradication therapy. Generally antibiotics induce the disturbance of human gastrointestinal microflora. Furthermore, there are inappropriate cases of triple therapy such as allergy to antibiotics, severe complications (liver and/or kidney dysfunction), the aged and people who reject the triple therapy. These prompt us to seek alterative agents instead of antibiotics and to develop more effective and safe therapy with these agents. The combination of these agents actually may result in lower a dose of antibiotics. There are many reports world-wide that non-antibiotic substances from natural products potentially have an anti-H. pylori agent. We briefly review the constituents derived from nature that fight against H. pylori in the literature with our studies.展开更多
AIM： To investigate genetic diversity of Helicobacter pylori （H. pylorl） cell division-related gene A （cdrA） and its effect on the host response.METHODS： Inactivation of H. py/ori cdrA, which is involved in ceil...AIM： To investigate genetic diversity of Helicobacter pylori （H. pylorl） cell division-related gene A （cdrA） and its effect on the host response.METHODS： Inactivation of H. py/ori cdrA, which is involved in ceil division and morphological elonga- tion, has a role in chronic persistent infections. Ge- netic property of H. pylori cdrA was evaluated using polymerase chain reaction and sequencing in 128 （77 American and 51 Japanese） clinical isolates obtained from 48 and 51 patients, respectively. Enzyme-linked immunosorbent assay was performed to measure in- terleukin-8 （IL-8） secretion with gastric biopsy speci- mens obtained from American patients colonized with cdrA-positive or -negative strains and AGS cells co- cultured with wild-type HPK5 （cdrA-positive） or its de- rivative HPKT510 （cdrA-disruptant）. Furthermore, the cytotoxin-associated gene A （cagA） status （transloca- tion and phosphorylation） and kinetics of transcription factors [nuclear factor-kappa B （NF-~：B） and inhibition kappa B] were investigated in AGS cells co-cultured with HPK5, HPKT510 and its derivative HPKSCA （cagA- disruptant） by western blotting analysis with immuno- precipitation. RESULTS： Genetic diversity of the H. pylori cdrA gene demonstrated that the cdrA status segregated into two categories including four allele types, cdrA-positive （al- lele types, I and 11 ） and cdrA-negative （allele types; 111 and IV） categories, respectively. Almost all Japanese isolates were cdrA-positive （ 1 ： 7.8% and 11 ： 90.2%）, whereas 16.9% of American isolates were cdrA-positive （11） and 83.1% were cdrA-negative （nl： 37.7% and IV： 45.5%）, indicating extended diversity of cdrA in individual American isolates. Comparison of each isolate from different regions （antrum and corpus） in the stomach of 29 Americans revealed that cdrA status was identical in both isolates from different regions in 17 cases. However, 12 cases had a different cdrA al- lele and 6 of them exhibited a different cdrA category between two regions in the stomach. Furthermore, in 5 of the 6 cases possessing a different cdrA category, cdrA-negative isolate existed in the corpus, suggesting that cdrA-negative strain is more adaptable to coloni- zation in the corpus. IL-8 secretions from AGS revealed that IL-8 levels induced by a cdrA-disrupted HPKT510 was significantly lower （P 〈 0.01） compared to wild- type HPK5： corresponding to 50%-60% of those of wild-type HPK5. These data coincided with in vivo data that an average value of IL-8 in biopsy specimens from cdrA-positive and cdrA-negative groups was 215.6 and 135.9 pg/mL, respectively. Western blotting analysis documented that HPKT510 had no effect on CagA translocation and phosphorylation, however, nuclear accumulation of NF-κB was lower by HPKT510 com- pared to HPK5. CONCLUSION： Colonization by a cdrA-negative or cdrA-dysfunctional strain resulted in decreased IL-8 production and repression of NF-κB, and hence, atten- uate the host immunity leading to persistent infection.展开更多
AIM:To evaluate the prevalence of Helicobacter pylori(H.pylori ) babA2 ,babB and a recombinant gene between babA2 and babB(babA2/B ),and their role in the development of atrophic gastritis in Costa Rican and Japanese ...AIM:To evaluate the prevalence of Helicobacter pylori(H.pylori ) babA2 ,babB and a recombinant gene between babA2 and babB(babA2/B ),and their role in the development of atrophic gastritis in Costa Rican and Japanese clinical isolates.METHODS:A total of 95 continuous H.pylori-positive Costa Rican(41 males and 54 females;mean age,50.65 years;SD,± 13.04 years) and 95 continuous H.pylori-positive Japanese(50 males and 45 females;mean age,63.43;SD,± 13.21 years) patients underwent upper endoscopy from October 2005 to July 2006.They were enrolled for the polymerase chain reaction(PCR)-based genotyping of the H.pylori babA2 ,babB and babA2/B genes.Statistical analysis was performed using the χ2 test and the Fisher's exact probability test and multivariate analysis was performed by logistic regression adjusting for gender and age.P < 0.05 was regarded as statistically significant.RESULTS:The PCR-based genotyping of 95 Costa Rican and 95 Japanese isolates showed a higher prevalence of babA2 in Japan(96.8%) than in Costa Rica(73.7%),while that of babA2/B was higher in Costa Rica(11.6%) than in Japan(1.1%).In Costa Rican isolates only,babA2 was significantly associated with atrophic gastritis(P = 0.01).CONCLUSION:These results suggest that the status of babA2 and babA2/B shows geographic differences,and that babA2 has clinical relevance in Costa Rica.展开更多
文摘AIM： To evaluate several risk factors for gastric cancer （GC） in Costa Rican regions with contrasting GC incidence rate （GCIR）. METHODS： According to GCIR, 191 Helicobacter pylori （H pylori）-positive patients were classified into groups A （high GCIR, n = 101） and B （low GCIR, n = 90）. Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin （IL）-1β and IL-10 by PCRRFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS： Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach （mixed strain infection） were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR （P = 0.026 and 0.041, respectively）. IL- 1β＋3954_T/C （OR 2.1, 1.0-4.3）, IL-1RN^＊2/L （OR 3.5, 1.7-7.3） and IL-10-592_C/A （OR 3.2, 1.5-6.8） were individually associated with GC, and a combination of these cytokine polymorphisms with Hpylori vacA slb and ml further increased the risk （OR 7.2, 1.4-36.4）. CONCLUSION： Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of Hpylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica.
基金Supported by JSPS KAKENHI Grant,No.24590697 and No.24590698the Vietnam National Foundation for Science and Technology Development(NAFOSTED,106.99-2011.22)
文摘The bacterial pathogen Helicobacter pylori (H. pylori) colonizes in over half of the world’s population. H. pylori that establishes life-long infection in the stomach is definitely associated with gastro-duodenal diseases and a wide variety of non-gastrointestinal tract conditions such as immune thrombocytopenia. Triple therapy which consists of a proton pump inhibitor and combinations of two antibiotics (amoxicillin, clarithromycin or amoxicillin, metronidazol) is commonly used for H. pylori eradication. Recently, the occurrence of drug-resistant H. pylori and the adverse effect of antibiotics have severely weakened eradication therapy. Generally antibiotics induce the disturbance of human gastrointestinal microflora. Furthermore, there are inappropriate cases of triple therapy such as allergy to antibiotics, severe complications (liver and/or kidney dysfunction), the aged and people who reject the triple therapy. These prompt us to seek alterative agents instead of antibiotics and to develop more effective and safe therapy with these agents. The combination of these agents actually may result in lower a dose of antibiotics. There are many reports world-wide that non-antibiotic substances from natural products potentially have an anti-H. pylori agent. We briefly review the constituents derived from nature that fight against H. pylori in the literature with our studies.
基金Supported by The Project Research Fund from Kochi University,to Takeuchi Ha Grant-in-Aid for Scientific Research from the Ministry of Education,Science and Culture of Japan,No. 21590631 and 21590629,in part
文摘AIM： To investigate genetic diversity of Helicobacter pylori （H. pylorl） cell division-related gene A （cdrA） and its effect on the host response.METHODS： Inactivation of H. py/ori cdrA, which is involved in ceil division and morphological elonga- tion, has a role in chronic persistent infections. Ge- netic property of H. pylori cdrA was evaluated using polymerase chain reaction and sequencing in 128 （77 American and 51 Japanese） clinical isolates obtained from 48 and 51 patients, respectively. Enzyme-linked immunosorbent assay was performed to measure in- terleukin-8 （IL-8） secretion with gastric biopsy speci- mens obtained from American patients colonized with cdrA-positive or -negative strains and AGS cells co- cultured with wild-type HPK5 （cdrA-positive） or its de- rivative HPKT510 （cdrA-disruptant）. Furthermore, the cytotoxin-associated gene A （cagA） status （transloca- tion and phosphorylation） and kinetics of transcription factors [nuclear factor-kappa B （NF-~：B） and inhibition kappa B] were investigated in AGS cells co-cultured with HPK5, HPKT510 and its derivative HPKSCA （cagA- disruptant） by western blotting analysis with immuno- precipitation. RESULTS： Genetic diversity of the H. pylori cdrA gene demonstrated that the cdrA status segregated into two categories including four allele types, cdrA-positive （al- lele types, I and 11 ） and cdrA-negative （allele types; 111 and IV） categories, respectively. Almost all Japanese isolates were cdrA-positive （ 1 ： 7.8% and 11 ： 90.2%）, whereas 16.9% of American isolates were cdrA-positive （11） and 83.1% were cdrA-negative （nl： 37.7% and IV： 45.5%）, indicating extended diversity of cdrA in individual American isolates. Comparison of each isolate from different regions （antrum and corpus） in the stomach of 29 Americans revealed that cdrA status was identical in both isolates from different regions in 17 cases. However, 12 cases had a different cdrA al- lele and 6 of them exhibited a different cdrA category between two regions in the stomach. Furthermore, in 5 of the 6 cases possessing a different cdrA category, cdrA-negative isolate existed in the corpus, suggesting that cdrA-negative strain is more adaptable to coloni- zation in the corpus. IL-8 secretions from AGS revealed that IL-8 levels induced by a cdrA-disrupted HPKT510 was significantly lower （P 〈 0.01） compared to wild- type HPK5： corresponding to 50%-60% of those of wild-type HPK5. These data coincided with in vivo data that an average value of IL-8 in biopsy specimens from cdrA-positive and cdrA-negative groups was 215.6 and 135.9 pg/mL, respectively. Western blotting analysis documented that HPKT510 had no effect on CagA translocation and phosphorylation, however, nuclear accumulation of NF-κB was lower by HPKT510 com- pared to HPK5. CONCLUSION： Colonization by a cdrA-negative or cdrA-dysfunctional strain resulted in decreased IL-8 production and repression of NF-κB, and hence, atten- uate the host immunity leading to persistent infection.
基金Supported by (in part) A Grant-in-Aid for Scientific Research from the Ministry of Education,Science and Culture of Japan(21590631)the Project Research Fund from the Kochi University
文摘AIM:To evaluate the prevalence of Helicobacter pylori(H.pylori ) babA2 ,babB and a recombinant gene between babA2 and babB(babA2/B ),and their role in the development of atrophic gastritis in Costa Rican and Japanese clinical isolates.METHODS:A total of 95 continuous H.pylori-positive Costa Rican(41 males and 54 females;mean age,50.65 years;SD,± 13.04 years) and 95 continuous H.pylori-positive Japanese(50 males and 45 females;mean age,63.43;SD,± 13.21 years) patients underwent upper endoscopy from October 2005 to July 2006.They were enrolled for the polymerase chain reaction(PCR)-based genotyping of the H.pylori babA2 ,babB and babA2/B genes.Statistical analysis was performed using the χ2 test and the Fisher's exact probability test and multivariate analysis was performed by logistic regression adjusting for gender and age.P < 0.05 was regarded as statistically significant.RESULTS:The PCR-based genotyping of 95 Costa Rican and 95 Japanese isolates showed a higher prevalence of babA2 in Japan(96.8%) than in Costa Rica(73.7%),while that of babA2/B was higher in Costa Rica(11.6%) than in Japan(1.1%).In Costa Rican isolates only,babA2 was significantly associated with atrophic gastritis(P = 0.01).CONCLUSION:These results suggest that the status of babA2 and babA2/B shows geographic differences,and that babA2 has clinical relevance in Costa Rica.
