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Anti-parietal cell antibody is induced by Helicobacter pylori infection followed by atrophic gastritis
April 2000
AGAA1251
5724 SEQUENCE DIVERSITY OF HELICOBACTER PYLORI ICEAl GENES FROM SIX GEOGRAPHICAL REGIONS. Yoshiyuki Ito, Asish K. Mukhopadhyay, Takeshi Azuma, Douglas E. Berg, WASHINGTON Univ, St. Louis, MO; FUKUI Med Univ, Fukui, Japan. Background and Aims: Differences in types of virulence associated genes from Helicobacter pylori (Hp) in various human populations may help us define factors important in the evolution of this gastric pathogen. Recent analyses have shown that sequence motifs in vacA and cagA genes of East Asian strains differ from those in the West. Here we demonstrate regional differences in iceA 1, a homolog of restriction endonuclease NlaIII. Materials and Methods: We sequenced iceAI genes of H. pylori strains from four regions: Japan (14), Hong Kong (18), India (16) and South Africa (8). Two deletion motifs were investigated by PCR with strains from Japan (27), Hong Kong (13), India (28), Spain (25), and Alaska (27). Results: Twenty one (51.2%) of 41 Japanese and 20 (64.5%) of 31 Hong Kong iceAI genes contained a specific deletion of 24 bp, whereas only 3 (6.8%) of 44 Indian, I (4%) of 25 Spanish, 4 (14.8%) of 27 Alaskan, or none of 8 South African strains carried this deletion. In contrast, ten (22.7%) of 44 Indian strains contained a specific 94bp deletion, which in tum was not in any of 132 iceA I genes from other regions of the world. Conclusions: Regional differences in DNA sequence motifs in iceAI genes help distinguish three distinct Hp gene pools: East Asian, South Asian, and the West. These results bring to focus a need to learn whether Asian Hp strains carry genes important in colonization or disease that could not have been found in the two ethnic European strains whose genomes have been fully sequenced.
5725 ANTI-PARIETAL CELL ANTIBODY IS INDUCED BY HELICOBACTER PYLORI INFECTION FOLLOWED BY ATROPHIC GASTRITIS. Masanori Ito, Ken Harurna, Tomoari Kamada, Yasuhiko Kitadai, Mitsuhiro Mihara, Shinji Tanaka, Masaharu Yoshihara, Koji Surnii, Soichiro Kido, Masahiro Ota, Toru Hiyama, Goro Kajiyama, JR Hiroshima Hosp, Hiroshima, Japan; First Dept of Internal Medicine, Hiroshima Univ, Hiroshima, Japan; First Dept Internal Medicine, Hiroshima Univ, Hiroshima, Japan; First Dept of Internal Medicine, Hiroshima, Japan. AIM; Although, Helicobacter pylori infection induces chronic gastritis, the pathogenic mechanism of Hipylori infection is still unknown. Claeys et al. indicated a relation between Hipylori infection and anti-H+ -K+ ATPase antibody. In the present study, we aimed to clarify the relation between Hpylori infection, corpus atrophic gastritis (CAG) and anti-parietal cell antibody (APCA) induction. METHODS; We studied 24 patients (mean age 58.5 years old; male/female 16/8) consisted of 6 gastric ulcers, 2 duodenal ulcers and 16 gastritis patients. Endoscopic biopsies were obtained from the greater curvature of the gastric corpus. The presence of Il.pylori infection was judged by Giemsa staining. Immunohistochemical analysis was performed using paraffin-embedded sections as described previously (Claeys et al. Gastroenterology, 1999). RESULTS; Seventeen out of 24 patients were Hipylori positive. Among 17 Il.pylori positive patients, 14 patients showed CAG. Seven patients were Il.pylori negative and did not showed atrophic changes. Out of all 24 patients, II (46%) showed positive immunohistochemical signals in the parietal cells especially in near by the pseudo-pyloric gland. APCA was detected more frequently in Hpylori-positive patients (65%,11/17) than in Hipylorinegative ones (017; p<0.05). In addition, this immunohistochemical signals were observed more frequently in patients with CAG (71%, 10/14) than in patients without CAG (10%,1110; p<0.05). CONCLUSIONS; The induction of APCA is correlated tightly with Htpylori infection and CAG in Japanese patients. H.pylor;
Corpus Atrophy
Anti-parietal cellantibody
Negative Positive Positive
Negative (7patients) Negative (3patients) Positive (14 patients)
0%(0/7) 33% (1/3) 71%(10/14)
5726 COMPARATIVE ANALYSIS OF LASER BASED 13C-UBT AND HISTOLOGY DATA IN H.PYLORI-ASSOCIATED GASTRITIS. Vladimir T. Ivashkin, Elena 1. Nicitina, Evgenii V. Stepanov, Moscow Sechenov Med Acad, Moscow, Russia; Gen Physics Institute of RAS, Moscow, Russia. Various diagnostics approaches based on different methodologies are in use for the evaluation of pathology processes in Hpylori-associated diseases. Every of these diagnostic methods has it s own advantages and disadvantages and are preferable in different cases. Comparative analysis of data obtained with the different techniques revealing their correlation are desirable to solve the problem of their adequate usage and interchangability in clinical applications. Aim: Correlations of the data of non invasive laser based i3C-UBT with the histology changes evaluated semi-quantitatively including stomach mucous Hipylori bacterial loading, gastritis activity and inflammatory changes (mononuclear infiltration) and atrophy in Hipyloriassociated chronic gastritis (CG) were studied. Methods: For 53 patients with Hpylori-associated CG (MIF 33/20, age range 17-76. mean 41 years)
endoscopy was performed for CG evaluation and 2 antral biopsies were taken for histology studies. Laser based i3C-UBT using molecular spectroscopy technique for i3CO/2C02 rate analysis and standard i3C-UBT protocol was applied for non invasive Hipylori infection detection. Results: The i3C-UBT data averaged over the subjects with the same semi-quantitative grade of histology changes were under consideration. Distinct linear dependence of the averaged 13C-UBT data on the grade of mucous Hcpylori colonization as well as on the grade of gastritis activity were observed. The 13C-UBT data were found to be less sensitive to the grade of mononuclear infiltration. No any reliable correlation was demonstrated for the atrophy data. Conclusion: The laser based 13C-UBT could be used not only for reliable and quantitative evaluation of the Htpylori mucous colonization but also for non invasive and quantitative analysis of the gastritis activity.
5727 EFFECT OF ERADICATION QUADROTHERAPY WITH PANTOPRAZOLE ON THE ATPASE ACTIVITY OF MICROSOMAL FRACTION OBTAINED FROM BIOPTATES OF GASTRIC MUCOSA OF PATIENTS WITH DUODENAL ULCER. Vladimir T. Ivashkin, Ella S. Podkolzina, Alexandr M. Rubtsov, Olga D. Lopina, Moscow Sechenov Med Acad, Moscow, Russia; Lomonosov Moscow State Univ, Moscow, Russia. Aim: To determine the effect of eradication quadrotherapy on the activity of ion-translocating ATPases in gastric mucosa of patients with duodenal ulcer associated with infection of Helicobacter pylori. Methods: Bioptates of gastric mucosa were obtained from patients (volontiers) during the procedure of gastroscopy before and one week after the therapy and were stored in liquid nitrogen. The infection with H pylori was confirmed using morphology and CLO-tests. Total ATPase activity of crude microsomal fraction obtained from bioptates of gastric mucosa of patients before treatment and measured in the presence of 10 mM KCI, 0.1 roM EGT A, 3 mM MgCl 2 and 3 mM ATP was equal to 6.62 + 1.14 [.Lmiol/mg h. Sodium azide (1 mM), ouabain (0.5 mM) and SCH 28080 (100 [.LM) inhibited ATPase activity by about 25, 14 and 10%, respectively. Eradication quadrotherapy (Pantoprazole, metronidazol, amoxicilin and ventrizol for 2 weeks) resulted in the recovery of the ulcer and in the eradication of H pylori. After treatment of patients the total ATPase activity of crude microsomal fraction fells to 3.76+0.85 [.Lmol/mg h without the significant change of the yield of of microsomal protein and the ratio between different ATPases (mitochondrial, Na,K-, and H,K-ATPases). Conclusion: Eradication quadrotherapy with Pantoprazole results in the decrease H, K - ATPase activity and other membrane A'TPases activities of crude microsomal fraction from human gastric mucosa. The proposed mechanisms involved in the decrease of the activities of ion-translocating ATPases after antihelicobacter therapy are discussed. Supported by RFBR grant No. 98-04-49184 and Byk-Gulden company.
5728 TECHNICAL FEASIBILITY OF AMBULATORY PH MONITORING TO ESOPHAGOPHARYNGEAL AND GASTROESOPHAGEAL ACID REFLUX. Abdul Jabbar, Zarina Mohiuddin, Brian Hawkins, Welby Winstead, Mark A. Wilson, Debbie Huff, John M. Wo, Univ of Louisville, Louisville, KY; Louisvile, KY. Ambulatory pH testing is considerd very reliable for distal esophageal reflux (DR), but technical aspects of detecting esophagopharyngeal reflux (EPR) is unclear. AIM:To compare technical feasibility between pharyngeal and esophageal pH testing. Methods: 101 consective 24-hr dual-sensor pH tracings (46 EPR/55 DR) were evaluated. Dual-sensors were placed in the pharynx & proximal esophagus for EPR and proximal & distal esophagus for DR. Tracings were read randomly with the interpretor blinded to pt's name, symptoms and type of monitoring. Proximal reflux episode was defined when: l)nadir pH<4, 2)abrupt drop in pH (onset to nadir in <30 sees, and 3)pH drop during distal sensor pH<4. The following artifacts were defined prospectively; type I:out of range (pH=O or >9), type 2:pH drift (onset of pH drop to nadir in >30 sees) and type 3:isolated pH drop (proximal sensor pH<4 without distal sensor pH<4). Overall results were calculated before and after exclusion of artifacts. Results: No signifacnt differences in artifacts were detected between EPR and DR (see table). Conclusions: 1) Types and durations of pH artifacts were similar between EPR and DR pH testing. 2) Results after excluding artifacts are minimal. 3) Dual-sensor pH testing in the pharynx is as technically feasible as in the esophagus.
Study duration (median) Total # of artifacts # of type1 artifacts # of type2 artifacts # of type3 artifacts # of artifacts/stUdy' Total timeof artifacts/study' # of studies withno artifacts Total %timepH<4 before adjustment' Total % timepH<4 afteradjustment'
EPR pHtesling
DR pHtesting
22hrs 55mins 119 28(24%) 31 (26%) 61 (50%) 1(0-17) 3mins (0-423) 14(30%) 0.6% (0-28) 0.5% (0-8.5)
22hrs 43mins 141 35(25%) 31 (22%) 75(53%) 1(0-15) 2 mins (0-159) 23" (42%) 5.4% (0-34) 5.1% (0-34)
'presented asmedian (range), "no difference bychi-square test
AGAA1251
5724 SEQUENCE DIVERSITY OF HELICOBACTER PYLORI ICEAl GENES FROM SIX GEOGRAPHICAL REGIONS. Yoshiyuki Ito, Asish K. Mukhopadhyay, Takeshi Azuma, Douglas E. Berg, WASHINGTON Univ, St. Louis, MO; FUKUI Med Univ, Fukui, Japan. Background and Aims: Differences in types of virulence associated genes from Helicobacter pylori (Hp) in various human populations may help us define factors important in the evolution of this gastric pathogen. Recent analyses have shown that sequence motifs in vacA and cagA genes of East Asian strains differ from those in the West. Here we demonstrate regional differences in iceA 1, a homolog of restriction endonuclease NlaIII. Materials and Methods: We sequenced iceAI genes of H. pylori strains from four regions: Japan (14), Hong Kong (18), India (16) and South Africa (8). Two deletion motifs were investigated by PCR with strains from Japan (27), Hong Kong (13), India (28), Spain (25), and Alaska (27). Results: Twenty one (51.2%) of 41 Japanese and 20 (64.5%) of 31 Hong Kong iceAI genes contained a specific deletion of 24 bp, whereas only 3 (6.8%) of 44 Indian, I (4%) of 25 Spanish, 4 (14.8%) of 27 Alaskan, or none of 8 South African strains carried this deletion. In contrast, ten (22.7%) of 44 Indian strains contained a specific 94bp deletion, which in tum was not in any of 132 iceA I genes from other regions of the world. Conclusions: Regional differences in DNA sequence motifs in iceAI genes help distinguish three distinct Hp gene pools: East Asian, South Asian, and the West. These results bring to focus a need to learn whether Asian Hp strains carry genes important in colonization or disease that could not have been found in the two ethnic European strains whose genomes have been fully sequenced.
5725 ANTI-PARIETAL CELL ANTIBODY IS INDUCED BY HELICOBACTER PYLORI INFECTION FOLLOWED BY ATROPHIC GASTRITIS. Masanori Ito, Ken Harurna, Tomoari Kamada, Yasuhiko Kitadai, Mitsuhiro Mihara, Shinji Tanaka, Masaharu Yoshihara, Koji Surnii, Soichiro Kido, Masahiro Ota, Toru Hiyama, Goro Kajiyama, JR Hiroshima Hosp, Hiroshima, Japan; First Dept of Internal Medicine, Hiroshima Univ, Hiroshima, Japan; First Dept Internal Medicine, Hiroshima Univ, Hiroshima, Japan; First Dept of Internal Medicine, Hiroshima, Japan. AIM; Although, Helicobacter pylori infection induces chronic gastritis, the pathogenic mechanism of Hipylori infection is still unknown. Claeys et al. indicated a relation between Hipylori infection and anti-H+ -K+ ATPase antibody. In the present study, we aimed to clarify the relation between Hpylori infection, corpus atrophic gastritis (CAG) and anti-parietal cell antibody (APCA) induction. METHODS; We studied 24 patients (mean age 58.5 years old; male/female 16/8) consisted of 6 gastric ulcers, 2 duodenal ulcers and 16 gastritis patients. Endoscopic biopsies were obtained from the greater curvature of the gastric corpus. The presence of Il.pylori infection was judged by Giemsa staining. Immunohistochemical analysis was performed using paraffin-embedded sections as described previously (Claeys et al. Gastroenterology, 1999). RESULTS; Seventeen out of 24 patients were Hipylori positive. Among 17 Il.pylori positive patients, 14 patients showed CAG. Seven patients were Il.pylori negative and did not showed atrophic changes. Out of all 24 patients, II (46%) showed positive immunohistochemical signals in the parietal cells especially in near by the pseudo-pyloric gland. APCA was detected more frequently in Hpylori-positive patients (65%,11/17) than in Hipylorinegative ones (017; p<0.05). In addition, this immunohistochemical signals were observed more frequently in patients with CAG (71%, 10/14) than in patients without CAG (10%,1110; p<0.05). CONCLUSIONS; The induction of APCA is correlated tightly with Htpylori infection and CAG in Japanese patients. H.pylor;
Corpus Atrophy
Anti-parietal cellantibody
Negative Positive Positive
Negative (7patients) Negative (3patients) Positive (14 patients)
0%(0/7) 33% (1/3) 71%(10/14)
5726 COMPARATIVE ANALYSIS OF LASER BASED 13C-UBT AND HISTOLOGY DATA IN H.PYLORI-ASSOCIATED GASTRITIS. Vladimir T. Ivashkin, Elena 1. Nicitina, Evgenii V. Stepanov, Moscow Sechenov Med Acad, Moscow, Russia; Gen Physics Institute of RAS, Moscow, Russia. Various diagnostics approaches based on different methodologies are in use for the evaluation of pathology processes in Hpylori-associated diseases. Every of these diagnostic methods has it s own advantages and disadvantages and are preferable in different cases. Comparative analysis of data obtained with the different techniques revealing their correlation are desirable to solve the problem of their adequate usage and interchangability in clinical applications. Aim: Correlations of the data of non invasive laser based i3C-UBT with the histology changes evaluated semi-quantitatively including stomach mucous Hipylori bacterial loading, gastritis activity and inflammatory changes (mononuclear infiltration) and atrophy in Hipyloriassociated chronic gastritis (CG) were studied. Methods: For 53 patients with Hpylori-associated CG (MIF 33/20, age range 17-76. mean 41 years)
endoscopy was performed for CG evaluation and 2 antral biopsies were taken for histology studies. Laser based i3C-UBT using molecular spectroscopy technique for i3CO/2C02 rate analysis and standard i3C-UBT protocol was applied for non invasive Hipylori infection detection. Results: The i3C-UBT data averaged over the subjects with the same semi-quantitative grade of histology changes were under consideration. Distinct linear dependence of the averaged 13C-UBT data on the grade of mucous Hcpylori colonization as well as on the grade of gastritis activity were observed. The 13C-UBT data were found to be less sensitive to the grade of mononuclear infiltration. No any reliable correlation was demonstrated for the atrophy data. Conclusion: The laser based 13C-UBT could be used not only for reliable and quantitative evaluation of the Htpylori mucous colonization but also for non invasive and quantitative analysis of the gastritis activity.
5727 EFFECT OF ERADICATION QUADROTHERAPY WITH PANTOPRAZOLE ON THE ATPASE ACTIVITY OF MICROSOMAL FRACTION OBTAINED FROM BIOPTATES OF GASTRIC MUCOSA OF PATIENTS WITH DUODENAL ULCER. Vladimir T. Ivashkin, Ella S. Podkolzina, Alexandr M. Rubtsov, Olga D. Lopina, Moscow Sechenov Med Acad, Moscow, Russia; Lomonosov Moscow State Univ, Moscow, Russia. Aim: To determine the effect of eradication quadrotherapy on the activity of ion-translocating ATPases in gastric mucosa of patients with duodenal ulcer associated with infection of Helicobacter pylori. Methods: Bioptates of gastric mucosa were obtained from patients (volontiers) during the procedure of gastroscopy before and one week after the therapy and were stored in liquid nitrogen. The infection with H pylori was confirmed using morphology and CLO-tests. Total ATPase activity of crude microsomal fraction obtained from bioptates of gastric mucosa of patients before treatment and measured in the presence of 10 mM KCI, 0.1 roM EGT A, 3 mM MgCl 2 and 3 mM ATP was equal to 6.62 + 1.14 [.Lmiol/mg h. Sodium azide (1 mM), ouabain (0.5 mM) and SCH 28080 (100 [.LM) inhibited ATPase activity by about 25, 14 and 10%, respectively. Eradication quadrotherapy (Pantoprazole, metronidazol, amoxicilin and ventrizol for 2 weeks) resulted in the recovery of the ulcer and in the eradication of H pylori. After treatment of patients the total ATPase activity of crude microsomal fraction fells to 3.76+0.85 [.Lmol/mg h without the significant change of the yield of of microsomal protein and the ratio between different ATPases (mitochondrial, Na,K-, and H,K-ATPases). Conclusion: Eradication quadrotherapy with Pantoprazole results in the decrease H, K - ATPase activity and other membrane A'TPases activities of crude microsomal fraction from human gastric mucosa. The proposed mechanisms involved in the decrease of the activities of ion-translocating ATPases after antihelicobacter therapy are discussed. Supported by RFBR grant No. 98-04-49184 and Byk-Gulden company.
5728 TECHNICAL FEASIBILITY OF AMBULATORY PH MONITORING TO ESOPHAGOPHARYNGEAL AND GASTROESOPHAGEAL ACID REFLUX. Abdul Jabbar, Zarina Mohiuddin, Brian Hawkins, Welby Winstead, Mark A. Wilson, Debbie Huff, John M. Wo, Univ of Louisville, Louisville, KY; Louisvile, KY. Ambulatory pH testing is considerd very reliable for distal esophageal reflux (DR), but technical aspects of detecting esophagopharyngeal reflux (EPR) is unclear. AIM:To compare technical feasibility between pharyngeal and esophageal pH testing. Methods: 101 consective 24-hr dual-sensor pH tracings (46 EPR/55 DR) were evaluated. Dual-sensors were placed in the pharynx & proximal esophagus for EPR and proximal & distal esophagus for DR. Tracings were read randomly with the interpretor blinded to pt's name, symptoms and type of monitoring. Proximal reflux episode was defined when: l)nadir pH<4, 2)abrupt drop in pH (onset to nadir in <30 sees, and 3)pH drop during distal sensor pH<4. The following artifacts were defined prospectively; type I:out of range (pH=O or >9), type 2:pH drift (onset of pH drop to nadir in >30 sees) and type 3:isolated pH drop (proximal sensor pH<4 without distal sensor pH<4). Overall results were calculated before and after exclusion of artifacts. Results: No signifacnt differences in artifacts were detected between EPR and DR (see table). Conclusions: 1) Types and durations of pH artifacts were similar between EPR and DR pH testing. 2) Results after excluding artifacts are minimal. 3) Dual-sensor pH testing in the pharynx is as technically feasible as in the esophagus.
Study duration (median) Total # of artifacts # of type1 artifacts # of type2 artifacts # of type3 artifacts # of artifacts/stUdy' Total timeof artifacts/study' # of studies withno artifacts Total %timepH<4 before adjustment' Total % timepH<4 afteradjustment'
EPR pHtesling
DR pHtesting
22hrs 55mins 119 28(24%) 31 (26%) 61 (50%) 1(0-17) 3mins (0-423) 14(30%) 0.6% (0-28) 0.5% (0-8.5)
22hrs 43mins 141 35(25%) 31 (22%) 75(53%) 1(0-15) 2 mins (0-159) 23" (42%) 5.4% (0-34) 5.1% (0-34)
'presented asmedian (range), "no difference bychi-square test