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Atrophic corpus gastritis raises the serum levels of homocysteine
1253 Cyclooxygenase-2 Expression in Gastric Intestinal Mntaplaoia John H. Sun, Koushik K. Das, Peter S. Amenta, UMDNJ-RobertWood Johnson Medical Sch, New Brunswick, NJ; Kinichi Yokota, Jiro Watari, Tomonobu Sato, Yutaka Kohgo, Asahikawa Medical Coil, AsahikawaJapan; Kiron M. Das, UMDNJ-RobertWood Johnson Medical Sch, New Brunswick, NJ Expression of Cyclooxygenase-2,or COX-2, in gastric cancer is well documented. Gastric intestinal metaplasia,or GIM, has beenconsidereda pre-cancerouslesion in the development of an intestinal-type of gastric adenocarsinoma.However, the expression of COX-2 protein in GIM is unknown. Objectives: 1. To examine the expression of COX-2 in the metaplastic epithelium in GIM. 2. To examine the difference in expression of COXo2in GIM associated with and without cancer. Methods: We examinedCOX-2 protein expression in histologically confirmed GIM tissues from Japanesepatients (biopsy and surgical) by immunoperoxidase assay using a polysional anti-COX-2 antibody. Group A included 34 patients with gastric carcinoma, and in group B there were 31 patients with no history of gastric carcinoma. In group A, we examined both cancer tissues as well as GIM tissues away from the tumor. Results: Table 1 shows the results. COX-2 expression was localized in cancer cells and in metaplastic glandular epithelial cells of GIM along the luminal surface and in the cytoplasm. in 2 of 34 cancer specimensthat were negativefor COX-2 expression,GIM away from those cancer tissues was also negative,suggesting a non-COX-2associatedgastric carcinogenesis in a smaller number of these patients. In the non-cancer patients, only 7 of 31 (23%) GIM tissues were positivefor COX-2expression.Normal gastric epitheliumfrom any of the patients with and without malignancydid not react with anti-COX-2. Conclusion: We found that COX2 protein is detected in most of the patients with gastric cancer and in the GIM away from the cancer. Furthermore,the expressionof COX-2in GIM was significantly (p
expression was confined to goblet cells in the normal epithelium, but was absent from GM TFF3was co-expressedwith MUC2 in goblet cells, but was absent in 87% of GM. Metaplastic cells were characterizedby ubiquitous expression of MUC5AC,while expressionof MUC5AC in adjacentgoblet cells (MUC5ACco-localizedin these cells with MUC2) was closely correlated with the extent of GM. TFF1 and TFF2 were found in 84% and 92% of GM, respectively,and their extent of expression correlated positively to the size of the GM. Expression of MUC6 was observed in 65% of GM, but did not correlate with the size of the GM. MUC5B was not found in the epithelium or in GM. SI was expressed by villus enterocytes, but was never found in GM Brunner's glands always expressed MUC58, MUC6, TFF1 and TFF3, and their expression was not affected by presence of GM, age, H. pylod infection, or villus atrophy. Conclusions:Gastric metaplasticcells were characterizedby the expressionof gastric secretory proteins MUC5AC, MUC6, TFF1 and TFF2, and the absence of the intestinal markers MUC2, TFF3 and Sl. As proliferation was deemed absent in GM [1], the location of the metaplastic cells on the villi suggeststhat epithelialcells migrating towards the villus tips switch to gastric type cacretory calls. The positive correlation with H. pyloriinfection may suggest a inductive role of the bacterium in the developmentof GM. Giventhe very different expression patterns of the secretory proteins, it is highly unlikely that GM originate as an outgrowth of the Brunner's glands. 1. Warren, Gastroenterol Clin North Am 2000, 29: 705-51.
1256 Combined Histological and Functional Evaluation in Hp + Atrophic Body Gastritis (ABG) Patients Discriminates Atrophy from "indefinite for Atrophy" Bruno Annibale, Univ La Sapienza,Roma Italy; Cesare Bordi, Univ, Parma Italy; Edith Lahner, Univ La Sapienza,Roma Italy; Pietro Caruana, Univ, Parma Italy; Gabdele Capurso, Cristina Grossi, Giancarlo D'Ambra, Emilio Di Giulio, Gianfranco Delle Fave, Univ La Sapienza, Roma Italy Background:ABGmay be induced by Hp infection but discrepancies still exist on the ability of Hp eradicationto reversebody atrophy.There is no completeagreementamong pathologists on body atrophy criteria. Furthermore,the denseinflammatory infiltrate, causedby Hp infection, may simulate the glandular loss and give the impression of atrophy. In these cases delay of diagnosis after Hp cure and the term of "indefinite for atrophy" have been suggested.Aim: to investigate in ABG patients the prevalenceof not confirmed atrophy after Hp cure and if these patients have different gastric morpho-functional features. Patients: 59 consecutive Hp + ABG patients aged 22-73 yr were treated between '94-'98. Methods: Gastroscopywith antral(n =3)and body(n=3)biopsies evaluatedaccording to Sydney System was performed at entry,6 and 24 rags after Hp cure. Fasting gastdn, Pepsinogen I and BAO and PAO were evaluatedbefore and after cure. Results are expressedas mean-+SEMor as median (range). Results: 40 pts (78.4%)were successfully cured. At 6 mos in 8/40 (20%,Group A) body atrophy was not confirmed,in 32 pts (Group B) body atrophy was confirmed. The same respective histological data were confirmed at 24 mos. In Group A, gastrin (pg/ml) was lower 6 mos after than before cure [220 (135-650) vs 55(25-70)p<0.001] and PAO (mEq/h) values normalized in all but one patient [1.65 (O-6.9)vs 13.5 (5.4-41.9)].1n Group B, gastrin and PAO were not significantly modified by the cure. In order to ascertain if group A pts had different morphofunctional features before Hp cure compared to group B pts, baselinedata were analysed.Acute and chronic body inflammation before curs were higher in Group A than group B, respectively:1.12+0.22 vs 0.66_+0.12 (p
Table I GroupCOX-2ExpressionStatisties A-Cancertissues (n=34) A.GIMtissues (n=34) B-GIMwithout cancer (n=31)
32/34 (94%) 28/34 (82%) 7/31 (23%)
GroupA GIM vs. GroupB p=
1254 Atrophic Corpus Gastritis Raises The Serum Levels Of Homocystelne Matti Harkonen, Helsinki Univ Hosp, Helsinki Finland; Marjo Nikulin, Biohit PIc, Helsioki Finland; Frank Laxen, Turku Univ Cent Hosp, Turku Finland; Osmo Suovaniemi, Biohit PIc, Helsinki Finland; Pentti Sipponen, Jorvi Hosp, Espoo Finland Background: Advancedatrophic gastritis of the gastric corpus mucoca, both in autoimmune and H.pyloriforms,results in reduction of secretion of intrinsic factor and leads,thereby, into a low intestinal absorption of vitamin 612.Vitamin B12is an essentialcofactor in the metabolism of methionine, and its absence results in an increase in homocysteinein tissues and blood. High serum levelsof homocysteineare linkedto increasedrisk of atherosclerosisand thromboembolic disease. Objectives: The aim was to investigate the prevalence of high levels of homocysteine (>15 p.mol/I)in subjects with advanced(moderate or severe) atrophic corpus gastritis. Methods: The study population consisted of 12,252 frae-living males aged 51-65 from two cities in Southern Finland. They were screened by serum pepsinogen I (PGI) for atrophic corpus gastritis, and those with PGI <25 p.g/I (cut-off value for advancedatrophic corpus gastritis) were invited to gastroscopy, and their serum levels of vitamin B12,folate and homocysteine were assayed. Results: Low PGI was found in 566 men (4.5%), and moderate or severe atrophic corpus gastritis could be confirmed by endoscopic biopsies in 80% of these men. Among these subjects, vitamin B12deficiency (<170 pmol/I) was found in 30.6% (168 of 549 subjects tested). Of these men, 56.3% (90 of 160) had a high serum level of homocysteine (>15 p.mol/I), and in 25% of them the homocysteine level was 40160 p.mol/I. All had normal level of serum folate. Normal but low serum B1~level (170-230 pmol/I) was found in 25% of the men with low PGI. Among these subjects, a high serum homocysteine level (>15/~mol/I) was found in 30% (range 16-40 pmol/I). Conclusions: Advancedatrophic corpus gastritis is an important and common cause of low serum vitamin B~2and increased serum homocysteine.Consequently, it is possible that advancedatrophic corpus gastritis is a common risk factor for high homocysteine-relatedextragastdcdiseases, such as atherosclerosis,tromboembolic disease,stroke, anemias,and degenerativeneurological diseases.
1257 Effects Of Sumntriptan On Antroduodenal Motility In Patients With Gastrointestinal Dysmotility Carnie Mathis, Virginia A. Schettler-Duncan, Michael D. Crowell, Brian E. Lacy, Johns Hopkins Univ, Baltimore, MO Background: Sumatriptan (SUM) is a 5HTlp-receptor agonist that modifies interdigestive gastrointestinal(GI) motility in healthyvolunteersby inducing prematuresmall intestinal phase lit activity while suppressing gastric phase III activity. The effects of SUM in patients with dysmotility of the GI tract are not known. Aims: To assess the effects of SUM on motility in patients with altered upper GI motility and/or transit and compare with changes in motility induced by erythromycin (EM). Methods: Studies were conducted in 13 patients (M/F; 1564 yr; 67-+5 kg) with complaints of nausea,vomiting and early satiety. 8 patients had delayed gastxicemptying with antral hypomotility, while 4 patients had either delayedgastric emptying (2) or antrsl hypomotility (2). Gastric and duodenal motility after EM (50 mg IV) and SUM (6 mg sc) were monitored with a 6 port solid state manometrycatheter. Results: In all patients, EM stimulated the appearanceof antral phase III activity by inducing greater amplitude (84.9 -+ 11.53 vs 27.3 -+ 8.24 mmHg) and more frequent contractions (2.1 -+ 0.23 vs 0.6 _+ 0.21 / min). The activity front propagatednormally into the duodenum in 10/13 patients.After SUM, antrsl activity was completely suppressed (8/13), inhibited (3/13, 19.5 -+ 3.30 mmHg, 0.2 __. 0.01/min), or stimulated (2/13, 54.8 ___13.6 mmHg, 3 -+ 1.2/min). In the duodenum, SUM induced a normally propagated phase III activity front with contractions of similar amplitude and frequencyas the EM induced phase III in 13/13 patients. Side effects of nausea, vomiting, bloating and cramping were reported by 5 patients after EM, and by 7 patients after SUM. Conclusions: SUM inhibits antral activity while inducing a duodenal phase III activity front in patients with abnormal upper GI motility. These results suggest that SUM might prove an effective drug for the managementof intestinal dysmotility.
1255 The Expression nt Gastric-Type Protective Molecules MUCBAC, MUCG, TFF1 and TFF2 in Metaplasiu in the Duodenum Is Correlated with Gastric H. pylori Infection Jeroen H B Van de Bovenkamp,Anita M. Korteland-Vanmale, Lab Pediatric, Erasmus Univ, Rotterdam Netherlands; Hans A. Bueller, Sophia Children's Hosp, Rotterdam Netherlands; Aiexandra W C Einerhand, Jan Dekker, Lab Pediatric, Erasmus Univ, Rotterdam Netherlands Background/Aims:Gastric H. pyloriinfection was found to be correlatedwith gastric metaplasia (GM) in the duodenum, yet the origin of the metaplastic cells remains an enigma [1]. We studied the expression of secretory mocins (MUC) and treloit peptides (TFF) in metaptasia in order to better understand the phenotype and the origin of these cells. Methods: We examined Bulbus duodeni biopsies of 95 patients (0-83 yrs old, 27 with gastric H. py/ofi). Expression patterns were examined by immunohistochemistry: MUC2, MUC5AC, MUC5B, MUC6, TFF1,TFF2,TFF3,and sucrase-isomaltase(SI). Villus atrophy and expressionof each protein was quantified morphometdcally. Results: GM, defined by alcian blue/PAS-staining, was found on duodenal villi in 37 patients, and the presence and extent of the GM was positively correlated to H. pylori infection in the stomach, age, and villus atrophy. MUC2
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expression was confined to goblet cells in the normal epithelium, but was absent from GM TFF3was co-expressedwith MUC2 in goblet cells, but was absent in 87% of GM. Metaplastic cells were characterizedby ubiquitous expression of MUC5AC,while expressionof MUC5AC in adjacentgoblet cells (MUC5ACco-localizedin these cells with MUC2) was closely correlated with the extent of GM. TFF1 and TFF2 were found in 84% and 92% of GM, respectively,and their extent of expression correlated positively to the size of the GM. Expression of MUC6 was observed in 65% of GM, but did not correlate with the size of the GM. MUC5B was not found in the epithelium or in GM. SI was expressed by villus enterocytes, but was never found in GM Brunner's glands always expressed MUC58, MUC6, TFF1 and TFF3, and their expression was not affected by presence of GM, age, H. pylod infection, or villus atrophy. Conclusions:Gastric metaplasticcells were characterizedby the expressionof gastric secretory proteins MUC5AC, MUC6, TFF1 and TFF2, and the absence of the intestinal markers MUC2, TFF3 and Sl. As proliferation was deemed absent in GM [1], the location of the metaplastic cells on the villi suggeststhat epithelialcells migrating towards the villus tips switch to gastric type cacretory calls. The positive correlation with H. pyloriinfection may suggest a inductive role of the bacterium in the developmentof GM. Giventhe very different expression patterns of the secretory proteins, it is highly unlikely that GM originate as an outgrowth of the Brunner's glands. 1. Warren, Gastroenterol Clin North Am 2000, 29: 705-51.
1256 Combined Histological and Functional Evaluation in Hp + Atrophic Body Gastritis (ABG) Patients Discriminates Atrophy from "indefinite for Atrophy" Bruno Annibale, Univ La Sapienza,Roma Italy; Cesare Bordi, Univ, Parma Italy; Edith Lahner, Univ La Sapienza,Roma Italy; Pietro Caruana, Univ, Parma Italy; Gabdele Capurso, Cristina Grossi, Giancarlo D'Ambra, Emilio Di Giulio, Gianfranco Delle Fave, Univ La Sapienza, Roma Italy Background:ABGmay be induced by Hp infection but discrepancies still exist on the ability of Hp eradicationto reversebody atrophy.There is no completeagreementamong pathologists on body atrophy criteria. Furthermore,the denseinflammatory infiltrate, causedby Hp infection, may simulate the glandular loss and give the impression of atrophy. In these cases delay of diagnosis after Hp cure and the term of "indefinite for atrophy" have been suggested.Aim: to investigate in ABG patients the prevalenceof not confirmed atrophy after Hp cure and if these patients have different gastric morpho-functional features. Patients: 59 consecutive Hp + ABG patients aged 22-73 yr were treated between '94-'98. Methods: Gastroscopywith antral(n =3)and body(n=3)biopsies evaluatedaccording to Sydney System was performed at entry,6 and 24 rags after Hp cure. Fasting gastdn, Pepsinogen I and BAO and PAO were evaluatedbefore and after cure. Results are expressedas mean-+SEMor as median (range). Results: 40 pts (78.4%)were successfully cured. At 6 mos in 8/40 (20%,Group A) body atrophy was not confirmed,in 32 pts (Group B) body atrophy was confirmed. The same respective histological data were confirmed at 24 mos. In Group A, gastrin (pg/ml) was lower 6 mos after than before cure [220 (135-650) vs 55(25-70)p<0.001] and PAO (mEq/h) values normalized in all but one patient [1.65 (O-6.9)vs 13.5 (5.4-41.9)].1n Group B, gastrin and PAO were not significantly modified by the cure. In order to ascertain if group A pts had different morphofunctional features before Hp cure compared to group B pts, baselinedata were analysed.Acute and chronic body inflammation before curs were higher in Group A than group B, respectively:1.12+0.22 vs 0.66_+0.12 (p
Table I GroupCOX-2ExpressionStatisties A-Cancertissues (n=34) A.GIMtissues (n=34) B-GIMwithout cancer (n=31)
32/34 (94%) 28/34 (82%) 7/31 (23%)
GroupA GIM vs. GroupB p=
1254 Atrophic Corpus Gastritis Raises The Serum Levels Of Homocystelne Matti Harkonen, Helsinki Univ Hosp, Helsinki Finland; Marjo Nikulin, Biohit PIc, Helsioki Finland; Frank Laxen, Turku Univ Cent Hosp, Turku Finland; Osmo Suovaniemi, Biohit PIc, Helsinki Finland; Pentti Sipponen, Jorvi Hosp, Espoo Finland Background: Advancedatrophic gastritis of the gastric corpus mucoca, both in autoimmune and H.pyloriforms,results in reduction of secretion of intrinsic factor and leads,thereby, into a low intestinal absorption of vitamin 612.Vitamin B12is an essentialcofactor in the metabolism of methionine, and its absence results in an increase in homocysteinein tissues and blood. High serum levelsof homocysteineare linkedto increasedrisk of atherosclerosisand thromboembolic disease. Objectives: The aim was to investigate the prevalence of high levels of homocysteine (>15 p.mol/I)in subjects with advanced(moderate or severe) atrophic corpus gastritis. Methods: The study population consisted of 12,252 frae-living males aged 51-65 from two cities in Southern Finland. They were screened by serum pepsinogen I (PGI) for atrophic corpus gastritis, and those with PGI <25 p.g/I (cut-off value for advancedatrophic corpus gastritis) were invited to gastroscopy, and their serum levels of vitamin B12,folate and homocysteine were assayed. Results: Low PGI was found in 566 men (4.5%), and moderate or severe atrophic corpus gastritis could be confirmed by endoscopic biopsies in 80% of these men. Among these subjects, vitamin B12deficiency (<170 pmol/I) was found in 30.6% (168 of 549 subjects tested). Of these men, 56.3% (90 of 160) had a high serum level of homocysteine (>15 p.mol/I), and in 25% of them the homocysteine level was 40160 p.mol/I. All had normal level of serum folate. Normal but low serum B1~level (170-230 pmol/I) was found in 25% of the men with low PGI. Among these subjects, a high serum homocysteine level (>15/~mol/I) was found in 30% (range 16-40 pmol/I). Conclusions: Advancedatrophic corpus gastritis is an important and common cause of low serum vitamin B~2and increased serum homocysteine.Consequently, it is possible that advancedatrophic corpus gastritis is a common risk factor for high homocysteine-relatedextragastdcdiseases, such as atherosclerosis,tromboembolic disease,stroke, anemias,and degenerativeneurological diseases.
1257 Effects Of Sumntriptan On Antroduodenal Motility In Patients With Gastrointestinal Dysmotility Carnie Mathis, Virginia A. Schettler-Duncan, Michael D. Crowell, Brian E. Lacy, Johns Hopkins Univ, Baltimore, MO Background: Sumatriptan (SUM) is a 5HTlp-receptor agonist that modifies interdigestive gastrointestinal(GI) motility in healthyvolunteersby inducing prematuresmall intestinal phase lit activity while suppressing gastric phase III activity. The effects of SUM in patients with dysmotility of the GI tract are not known. Aims: To assess the effects of SUM on motility in patients with altered upper GI motility and/or transit and compare with changes in motility induced by erythromycin (EM). Methods: Studies were conducted in 13 patients (M/F; 1564 yr; 67-+5 kg) with complaints of nausea,vomiting and early satiety. 8 patients had delayed gastxicemptying with antral hypomotility, while 4 patients had either delayedgastric emptying (2) or antrsl hypomotility (2). Gastric and duodenal motility after EM (50 mg IV) and SUM (6 mg sc) were monitored with a 6 port solid state manometrycatheter. Results: In all patients, EM stimulated the appearanceof antral phase III activity by inducing greater amplitude (84.9 -+ 11.53 vs 27.3 -+ 8.24 mmHg) and more frequent contractions (2.1 -+ 0.23 vs 0.6 _+ 0.21 / min). The activity front propagatednormally into the duodenum in 10/13 patients.After SUM, antrsl activity was completely suppressed (8/13), inhibited (3/13, 19.5 -+ 3.30 mmHg, 0.2 __. 0.01/min), or stimulated (2/13, 54.8 ___13.6 mmHg, 3 -+ 1.2/min). In the duodenum, SUM induced a normally propagated phase III activity front with contractions of similar amplitude and frequencyas the EM induced phase III in 13/13 patients. Side effects of nausea, vomiting, bloating and cramping were reported by 5 patients after EM, and by 7 patients after SUM. Conclusions: SUM inhibits antral activity while inducing a duodenal phase III activity front in patients with abnormal upper GI motility. These results suggest that SUM might prove an effective drug for the managementof intestinal dysmotility.
1255 The Expression nt Gastric-Type Protective Molecules MUCBAC, MUCG, TFF1 and TFF2 in Metaplasiu in the Duodenum Is Correlated with Gastric H. pylori Infection Jeroen H B Van de Bovenkamp,Anita M. Korteland-Vanmale, Lab Pediatric, Erasmus Univ, Rotterdam Netherlands; Hans A. Bueller, Sophia Children's Hosp, Rotterdam Netherlands; Aiexandra W C Einerhand, Jan Dekker, Lab Pediatric, Erasmus Univ, Rotterdam Netherlands Background/Aims:Gastric H. pyloriinfection was found to be correlatedwith gastric metaplasia (GM) in the duodenum, yet the origin of the metaplastic cells remains an enigma [1]. We studied the expression of secretory mocins (MUC) and treloit peptides (TFF) in metaptasia in order to better understand the phenotype and the origin of these cells. Methods: We examined Bulbus duodeni biopsies of 95 patients (0-83 yrs old, 27 with gastric H. py/ofi). Expression patterns were examined by immunohistochemistry: MUC2, MUC5AC, MUC5B, MUC6, TFF1,TFF2,TFF3,and sucrase-isomaltase(SI). Villus atrophy and expressionof each protein was quantified morphometdcally. Results: GM, defined by alcian blue/PAS-staining, was found on duodenal villi in 37 patients, and the presence and extent of the GM was positively correlated to H. pylori infection in the stomach, age, and villus atrophy. MUC2
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