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Prevalence of Two Homologous Genes Encoding Glycosyltransferases of Helicobacter pylori in the United States and Japan
with GI symptom severity per se, and it does not seem to have a major impact on change in GI symptom severity over time. Further studies assessing the effect of sense of coherence on health care seeking behavior and coping with symptoms is desirable.
monitor the intensity (scale 0-6) of various GI and extra GI symptoms were considered for this retrospective analysis. Of these patients, we kept those having completed 2 questionnaires in at least 1 yr interval (49F,13M; mean age: 43.7). To assess the variation between the 2 questionnaires in a same patient, we analysed the change in score on a 0 to 6 scale for each symptom as well as the apparition or resolution of symptoms. RESULTS: 44 patients with initial diagnosis of IBS, 11 with functional dyspepsia (FD) and 7 patients with non-specific FGID were included. At the second evaluation( mean interval: 44 months ), the main GI symptom had changed (from IBS to NUD or vice-versa) in 16% pts, and IBS subtype changed (from IBS-D or C to IBS-M) in 14% IBS pts. Variation ( 2 points or more on the 6 points symptom scale) in the intensity of extra GI symptoms was seen for sleep disorders (45.2% pts), sexual difficulties (35.5%), low tolerance to activity (33.9%), fatigue (33.9%), back pain (30.6%), urinary symptoms (25.8%), tiredness upon awakening (27.4%), joint pain (27.4%) and headache (24.2%). One or more extra GI symptoms resolved in 21% pts. New symptoms appeared in 29% pts. CONCLUSION: As for GI symptoms, a significant variation in intensity and nature of extra GI symptoms was observed over time in patients with FGID.
AGA Abstracts
Su1364 Personality of Patients With Upper Gastrointestinal Symptoms: Alexithymia, Anxiety, Depression and Coping Style Investigation in a Preliminary Study Stefano Pontone, Massimo Marianetti, Concetta Mina, Paolo Pontone INTRODUCTION/OBJECTIVES: Psychological disorders are often associated with diseases of the upper digestive tract, especially functional dyspepsia, but this association with other upper gastrointestinal disorders is debatable. Despite the increasing number of studies regarding psychological factors, the impact of coping style on outcome of gastroenterological patients has not yet been rated. AIMS & METHODS: The aim of our study was to assess the personality of outpatients with upper gastroenterological symptoms by using standardized questionnaires. A total of 86 patients with a mean age of 55±18.3 years (55 female), who attended our Department, over the period May 2009 - September 2010, in order to perform an upper gastrointestinal endoscopy for upper gastrointestinal symptoms, were enrolled. No exclusion criteria were formulated. Subjects were asked to complete several validated questionnaires before endoscopic examination. Alexithymia, anxiety, depression and coping style were assessed using the Toronto Alexithymia Scale (TAS-20), Spielberger Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI-II) and Coping Inventory for Stressful Situations (CISS), respectively. RESULTS: seven patients were excluded (6/incomplete and 1/refused questionnaires). Intestinal biopsies were performed in 51 (64%) patients, due to the mucosal appearance. Alexithymia, anxiety, depression and coping alterations were found in 46%, 33%, 34% and 76%, respectively, often in association(Table 1). In our study, these personality changes are not significantly related to functional pathology (Figure 1). Three styles of coping were evaluated by CISS: task-oriented, emotion-oriented and avoidanceoriented. Task-oriented, emotion-oriented and avoidance-oriented alterations were found in 53%, 38% and 60%, respectively, frequently in association. CONCLUSION: Our study demonstrates that among patients with gastrointestinal symptoms personality alterations could be found. The high prevalence of alexithymia, anxiety, depression and coping alterations, that is even higher than what expected, it does not seem to be reserved for the functional pathology, but most commonly affects patients who have an organic disease. Thus, personality alterations should always be taken into account in upper gastrointestinal patients management. Further studies on correlation with diagnosis, endoscopical and histological findings, personality disorders and long term follow-up will clarify an eventual role of these factors for patients prognosis and therapeutical response. Correlation between endoscopical/histological findings and personality disorders
Su1662 Iron-Uptake System for the Antioxidant Ability of Helicobacter pylori Regulated by Ferric Uptake Regulator (FUR) Hitoshi Tsugawa, Hidekazu Suzuki, Kenro Hirata, Juntaro Matsuzaki, Sawako Okada, Seiichiro Fukuhara, Yoshimasa Saito, Toshifumi Hibi Although the gastric pathogen, Helicobacter pylori (H. pylori) induces a strong inflammatory host response, it maintains long-term colonization in the host gastric mucosa. H. pylori combats oxidative stress using an iron-cofactored superoxide dismutase (SodB), which is essential for protection against superoxide challenge. In addition, metronidazole (Mtz) is a prodrug, which is converted to its active form when its nitro group is reduced and superoxide radicals are generated. Recently, we reported that a number of Mtz-resistant strains carried amino acid mutations of Ferric uptake regulator (Fur) (C78Y, P114S; mutant-type Fur) which is a direct repressor of sodB (Antioxid. Redox Signal.,14:15,2011). These Mtz-resistant strains showed overexpression of SodB by mutant-type Fur, resulting in the development of Mtz resistance. Since iron ions are necessary for the expression of SodB, SodB activity might be prevented by avoiding iron-uptake. The present study was designed to examine the ironuptake mechanisms associated with SodB activity. Methods: H. pylori strains ATCC700392 and KS0189 were used as the Mtz-susceptible strains with wild-type Fur (WT-Fur) and strains KS0048 and KS0145 were used as the Mtz-resistant strains with mutant-type Fur (MT-Fur). The expression of the iron transporter genes (fecA1-A2, frpB1-B2, feoB) which are repressed by Fur was measured by quantitative RT-PCR. The binding affinity (Kd value) of Fur to the promoter region of fecA1 was measured using BIAcore2000. The fecA1-deletion mutant strains (ΔfecA1 strain) were also constructed by homologous recombination. The SodB-overexpressing strain (ATCC700392 pHel3::sodB) was constructed using a pHel3 vector. Results: The MICs of Mtz for KS0048, KS0145 and ATCC700392 pHel3::sodB were 32, 128 and 32 μg/mL, respectively. Under the iron-restricted condition, the MICs for the same strains were 16, 32 and 4 μg/mL, respectively; only the MIC for ATCC700392 pHel3::sodB decreased to the Mtz-susceptible level (MIC<8 μg/mL). Similarly only the H2O2 resistance for ATCC700392 pHel3::sodB was significantly decreased under the iron-restricted condition. The expression of fecA1 mRNA was significantly increased by 1.4, 1.5-fold, respectively, in the KS0048 and KS0145 strains under Mtz exposure. The binding affinity of MT-Fur to the fecA1 promoter was significantly decreased as compared with that of WTFur. The SodB activity of the ΔfecA1 strains was significantly decreased by 20-80%. In addition, the H2O2 resistance and Mtz-resistance of the ΔfecA1 strains were no longer seen. Conclusion: The antioxidant ability of H. pylori associated with H2O2 resistance and Mtzresistance is supported by effective iron-uptake by FecA1 regulated by Fur. Su1663 Prevalence of Two Homologous Genes Encoding Glycosyltransferases of Helicobacter pylori in the United States and Japan Miyuki Matsuda, Seiji Shiota, Ayaka Takahashi, Osamu Matsunari, Masahide Watada, Rumiko Suzuki, Katsuhiro Hanada, Kazunari Murakami, Toshio Fujioka, Yoshio Yamaoka Background and aims: Helicobacter pylori jhp0562 and β-(1,3)galT (jhp0563) has been suggested as novel virulent factors in Portuguese children population. However, there is no previous study investigating the association between the two genes and H. pylori-related diseases in other countries. This study investigated whether there was an association between the genes and clinical outcomes in population from another Western country (i.e., the Unites States [U.S.]) and from Asian country (Japan). Methods: A total of 308 patients were included in this study; 171 from the U.S. (82 with gastritis, 46 with duodenal ulcer [DU], 28 with gastric ulcer [GU], and 15 with gastric cancer [GC]) and 137 from Japan (37 with gastritis, 45 with DU, 39 with GU, and 16 with GC). The status of the jhp0562, β-(1,3)galT and the cagA genes were examined by polymerase chain reaction. Results: There were significant differences in the cagA, jhp0562 and β-(1,3)galT status between the U.S. and Japan (P < 0.001). In the U.S. strains, the prevalence of the β-(1,3)galT gene was significantly lower in strains isolated from patients with DU and GU than those with gastritis (45.7, 28.6 and 69.5%, respectively). Multivariate analysis showed that the absence of the β-(1,3)galT gene was an independent discriminating factor for DU and GU from gastritis (adjusted odds ratio; 4.21 and 8.52, 95% confidence interval; 1.75-10.12 and 2.76-26.33, respectively). With regard to the jhp0562 and β-(1,3)galT genes, five different patterns by the combinations of these two genes were observed; single copy of jhp0562 (jhp0562-positive/β-(1,3)galT-negative), single copy of β-(1,3)galT (jhp0562-negative/β-(1,3)galT-positive), double positive for jhp0562 and β-(1,3)galT, double negative for jhp0562 and β-(1,3)galT, and two copies of β-(1,3)galT. The prevalence of the jhp0562-positive/β-(1,3)galT-negative status was significantly higher in strains from DU and GU patients than those from gastritis patients in the U.S. (50.0, 64.3, and 23.2%, respectively). The cagA status was significantly correlated with jhp0562 status and inversely correlated with β-(1,3)galT. In contrast, the prevalence of three genes was not significantly different in Japan. Conclusions: The jhp0562 or β-(1,3)galT gene is used as discriminating factor of peptic ulcer from gastritis in the U.S. but not in Japan.
Not organic pathologies incidence in personality alterations Su1365 Long Term Evolution of Extra Gastrointestinal (GI) Symptoms in Patients With Functional GI Disorders (FGID) Frédéric Mongeau, Alexandre Gougeon, Mickael Bouin, Pierre Poitras INTRODUCTION: Patients suffering of irritable bowel syndrome (IBS) often present extra GI symptoms (fibromyalgia, migraine, etc). Changes over time of GI symptoms (diarrhea, constipation, etc.) in IBS patients are well documented. However we know little on the evolution of extra GI symptoms. OBJECTIVE: Assess the evolution of extra GI symptoms in terms of frequency and intensity in patients with FGID. METHODS: patients with FGID followed in a tertiary care center with a standardized self-adminstered questionnaire to
AGA Abstracts
S-468
monitor the intensity (scale 0-6) of various GI and extra GI symptoms were considered for this retrospective analysis. Of these patients, we kept those having completed 2 questionnaires in at least 1 yr interval (49F,13M; mean age: 43.7). To assess the variation between the 2 questionnaires in a same patient, we analysed the change in score on a 0 to 6 scale for each symptom as well as the apparition or resolution of symptoms. RESULTS: 44 patients with initial diagnosis of IBS, 11 with functional dyspepsia (FD) and 7 patients with non-specific FGID were included. At the second evaluation( mean interval: 44 months ), the main GI symptom had changed (from IBS to NUD or vice-versa) in 16% pts, and IBS subtype changed (from IBS-D or C to IBS-M) in 14% IBS pts. Variation ( 2 points or more on the 6 points symptom scale) in the intensity of extra GI symptoms was seen for sleep disorders (45.2% pts), sexual difficulties (35.5%), low tolerance to activity (33.9%), fatigue (33.9%), back pain (30.6%), urinary symptoms (25.8%), tiredness upon awakening (27.4%), joint pain (27.4%) and headache (24.2%). One or more extra GI symptoms resolved in 21% pts. New symptoms appeared in 29% pts. CONCLUSION: As for GI symptoms, a significant variation in intensity and nature of extra GI symptoms was observed over time in patients with FGID.
AGA Abstracts
Su1364 Personality of Patients With Upper Gastrointestinal Symptoms: Alexithymia, Anxiety, Depression and Coping Style Investigation in a Preliminary Study Stefano Pontone, Massimo Marianetti, Concetta Mina, Paolo Pontone INTRODUCTION/OBJECTIVES: Psychological disorders are often associated with diseases of the upper digestive tract, especially functional dyspepsia, but this association with other upper gastrointestinal disorders is debatable. Despite the increasing number of studies regarding psychological factors, the impact of coping style on outcome of gastroenterological patients has not yet been rated. AIMS & METHODS: The aim of our study was to assess the personality of outpatients with upper gastroenterological symptoms by using standardized questionnaires. A total of 86 patients with a mean age of 55±18.3 years (55 female), who attended our Department, over the period May 2009 - September 2010, in order to perform an upper gastrointestinal endoscopy for upper gastrointestinal symptoms, were enrolled. No exclusion criteria were formulated. Subjects were asked to complete several validated questionnaires before endoscopic examination. Alexithymia, anxiety, depression and coping style were assessed using the Toronto Alexithymia Scale (TAS-20), Spielberger Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI-II) and Coping Inventory for Stressful Situations (CISS), respectively. RESULTS: seven patients were excluded (6/incomplete and 1/refused questionnaires). Intestinal biopsies were performed in 51 (64%) patients, due to the mucosal appearance. Alexithymia, anxiety, depression and coping alterations were found in 46%, 33%, 34% and 76%, respectively, often in association(Table 1). In our study, these personality changes are not significantly related to functional pathology (Figure 1). Three styles of coping were evaluated by CISS: task-oriented, emotion-oriented and avoidanceoriented. Task-oriented, emotion-oriented and avoidance-oriented alterations were found in 53%, 38% and 60%, respectively, frequently in association. CONCLUSION: Our study demonstrates that among patients with gastrointestinal symptoms personality alterations could be found. The high prevalence of alexithymia, anxiety, depression and coping alterations, that is even higher than what expected, it does not seem to be reserved for the functional pathology, but most commonly affects patients who have an organic disease. Thus, personality alterations should always be taken into account in upper gastrointestinal patients management. Further studies on correlation with diagnosis, endoscopical and histological findings, personality disorders and long term follow-up will clarify an eventual role of these factors for patients prognosis and therapeutical response. Correlation between endoscopical/histological findings and personality disorders
Su1662 Iron-Uptake System for the Antioxidant Ability of Helicobacter pylori Regulated by Ferric Uptake Regulator (FUR) Hitoshi Tsugawa, Hidekazu Suzuki, Kenro Hirata, Juntaro Matsuzaki, Sawako Okada, Seiichiro Fukuhara, Yoshimasa Saito, Toshifumi Hibi Although the gastric pathogen, Helicobacter pylori (H. pylori) induces a strong inflammatory host response, it maintains long-term colonization in the host gastric mucosa. H. pylori combats oxidative stress using an iron-cofactored superoxide dismutase (SodB), which is essential for protection against superoxide challenge. In addition, metronidazole (Mtz) is a prodrug, which is converted to its active form when its nitro group is reduced and superoxide radicals are generated. Recently, we reported that a number of Mtz-resistant strains carried amino acid mutations of Ferric uptake regulator (Fur) (C78Y, P114S; mutant-type Fur) which is a direct repressor of sodB (Antioxid. Redox Signal.,14:15,2011). These Mtz-resistant strains showed overexpression of SodB by mutant-type Fur, resulting in the development of Mtz resistance. Since iron ions are necessary for the expression of SodB, SodB activity might be prevented by avoiding iron-uptake. The present study was designed to examine the ironuptake mechanisms associated with SodB activity. Methods: H. pylori strains ATCC700392 and KS0189 were used as the Mtz-susceptible strains with wild-type Fur (WT-Fur) and strains KS0048 and KS0145 were used as the Mtz-resistant strains with mutant-type Fur (MT-Fur). The expression of the iron transporter genes (fecA1-A2, frpB1-B2, feoB) which are repressed by Fur was measured by quantitative RT-PCR. The binding affinity (Kd value) of Fur to the promoter region of fecA1 was measured using BIAcore2000. The fecA1-deletion mutant strains (ΔfecA1 strain) were also constructed by homologous recombination. The SodB-overexpressing strain (ATCC700392 pHel3::sodB) was constructed using a pHel3 vector. Results: The MICs of Mtz for KS0048, KS0145 and ATCC700392 pHel3::sodB were 32, 128 and 32 μg/mL, respectively. Under the iron-restricted condition, the MICs for the same strains were 16, 32 and 4 μg/mL, respectively; only the MIC for ATCC700392 pHel3::sodB decreased to the Mtz-susceptible level (MIC<8 μg/mL). Similarly only the H2O2 resistance for ATCC700392 pHel3::sodB was significantly decreased under the iron-restricted condition. The expression of fecA1 mRNA was significantly increased by 1.4, 1.5-fold, respectively, in the KS0048 and KS0145 strains under Mtz exposure. The binding affinity of MT-Fur to the fecA1 promoter was significantly decreased as compared with that of WTFur. The SodB activity of the ΔfecA1 strains was significantly decreased by 20-80%. In addition, the H2O2 resistance and Mtz-resistance of the ΔfecA1 strains were no longer seen. Conclusion: The antioxidant ability of H. pylori associated with H2O2 resistance and Mtzresistance is supported by effective iron-uptake by FecA1 regulated by Fur. Su1663 Prevalence of Two Homologous Genes Encoding Glycosyltransferases of Helicobacter pylori in the United States and Japan Miyuki Matsuda, Seiji Shiota, Ayaka Takahashi, Osamu Matsunari, Masahide Watada, Rumiko Suzuki, Katsuhiro Hanada, Kazunari Murakami, Toshio Fujioka, Yoshio Yamaoka Background and aims: Helicobacter pylori jhp0562 and β-(1,3)galT (jhp0563) has been suggested as novel virulent factors in Portuguese children population. However, there is no previous study investigating the association between the two genes and H. pylori-related diseases in other countries. This study investigated whether there was an association between the genes and clinical outcomes in population from another Western country (i.e., the Unites States [U.S.]) and from Asian country (Japan). Methods: A total of 308 patients were included in this study; 171 from the U.S. (82 with gastritis, 46 with duodenal ulcer [DU], 28 with gastric ulcer [GU], and 15 with gastric cancer [GC]) and 137 from Japan (37 with gastritis, 45 with DU, 39 with GU, and 16 with GC). The status of the jhp0562, β-(1,3)galT and the cagA genes were examined by polymerase chain reaction. Results: There were significant differences in the cagA, jhp0562 and β-(1,3)galT status between the U.S. and Japan (P < 0.001). In the U.S. strains, the prevalence of the β-(1,3)galT gene was significantly lower in strains isolated from patients with DU and GU than those with gastritis (45.7, 28.6 and 69.5%, respectively). Multivariate analysis showed that the absence of the β-(1,3)galT gene was an independent discriminating factor for DU and GU from gastritis (adjusted odds ratio; 4.21 and 8.52, 95% confidence interval; 1.75-10.12 and 2.76-26.33, respectively). With regard to the jhp0562 and β-(1,3)galT genes, five different patterns by the combinations of these two genes were observed; single copy of jhp0562 (jhp0562-positive/β-(1,3)galT-negative), single copy of β-(1,3)galT (jhp0562-negative/β-(1,3)galT-positive), double positive for jhp0562 and β-(1,3)galT, double negative for jhp0562 and β-(1,3)galT, and two copies of β-(1,3)galT. The prevalence of the jhp0562-positive/β-(1,3)galT-negative status was significantly higher in strains from DU and GU patients than those from gastritis patients in the U.S. (50.0, 64.3, and 23.2%, respectively). The cagA status was significantly correlated with jhp0562 status and inversely correlated with β-(1,3)galT. In contrast, the prevalence of three genes was not significantly different in Japan. Conclusions: The jhp0562 or β-(1,3)galT gene is used as discriminating factor of peptic ulcer from gastritis in the U.S. but not in Japan.
Not organic pathologies incidence in personality alterations Su1365 Long Term Evolution of Extra Gastrointestinal (GI) Symptoms in Patients With Functional GI Disorders (FGID) Frédéric Mongeau, Alexandre Gougeon, Mickael Bouin, Pierre Poitras INTRODUCTION: Patients suffering of irritable bowel syndrome (IBS) often present extra GI symptoms (fibromyalgia, migraine, etc). Changes over time of GI symptoms (diarrhea, constipation, etc.) in IBS patients are well documented. However we know little on the evolution of extra GI symptoms. OBJECTIVE: Assess the evolution of extra GI symptoms in terms of frequency and intensity in patients with FGID. METHODS: patients with FGID followed in a tertiary care center with a standardized self-adminstered questionnaire to
AGA Abstracts
S-468