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Background Helicobacter pylori infection produces progressive mucosal damage that may eventually result in gastric cancer. We studied the changes that occurred in the presence and severity of atrophic gastritis and the prevalence of H. pylori infection that occurred coincident with improvements in economic and hygienic conditions in Japan since World War II. Materials and Methods The prevalence of H. pylori infection and histologic grades of gastric damage were retrospectively evaluated using gastric biopsy specimens obtained over a 40-year period. Gastric atrophy and intestinal metaplasia were scored using the updated Sydney classification system. Results The prevalence of H. pylori and severity of atrophy were examined in 1381 patients including 289 patients examined in the 1970s (158 men; mean age, 44.9 years), 787 in the 1990s (430 men; 44.2 years), and 305 in the 2010s (163 men; 53.2 years). Overall, the prevalence of H. pylori infection decreased significantly from 74.7% (1970s) to 53% (1990s) and 35.1% (2010s) ( p < .01). The prevalence of atrophy in the antrum and corpus was significantly lower in the 2010s (33, 19%, respectively) compared to those evaluated in either the 1970s (98, 82%) ( p < .001) or 1990s (80, 67%) ( p < .001). The severity of atrophy and intestinal metaplasia also declined remarkably among those with H. pylori infection. Conclusions There has been a progressive and rapid decline in the prevalence of H. pylori infection as well a fall in the rate of progression of gastric atrophy among H. pylori-infected Japanese coincident with the westernization and improvements in economic and hygienic conditions in Japan since World War II. [ABSTRACT FROM AUTHOR]

Established risk factors for gastric cancer include a diet high in nitrate or nitrite and low in vitamin C and the presence of achlorhydria or hypochlorhydria. The aim of this study was to investigate the relationship between intragastric nitrite concentration and atrophic change of the stomach or gastric carcinogenesis in Japanese Helicobacter pylori-infected patients. Gastric juice pH, nitrite, and total vitamin C concentrations in gastric juice, serum pepsinogen I and II concentrations, and specific Helicobacter pylori antibody were analyzed. Intragastric total vitamin C concentration was decreased by Helicobacter pylori infection of the gastric mucosa and with progression of the atrophic grade. There was a significant positive correlation between atrophic grade and intragastric nitrite concentration. In conclusion, the levels of nitrite in gastric juice play a causal role in the development of cancer in Helicobacter pylori-associated atrophic gastric mucosa. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim: Helicobacter pylori infection in gastric mucosa is a form of chronic active gastritis that leads to expression of inducible nitric oxide synthase in host macrophages and polymorphonuclear leukocytes. Nitric oxide produced by these cells infiltrating the gastric mucosa could damage DNA. We correlated apoptosis in H. pylori -infected antral tissue from peptic ulcer patients with serum nitrate-plus-nitrite. Methods: Biopsy specimens were obtained endoscopically from antrum and fundus in 17 peptic ulcer patients before and after H. pylori eradication. Tissue samples were subjected to rapid urease testing and histopathological scoring (updated Sydney system), as well as immunohistochemical detection of single-stranded DNA indicating apoptotic cells. Fasting serum samples were analyzed for combined nitrate and nitrite content. Results: In all cases atrophy was absent to mild in antral mucosa and H. pylori was eradicated successfully. A strong positive correlation was present between apoptosis and both inflammation and activity scores in infected antral mucosa. A significant positive correlation also was noted between apoptosis and H. pylori density. Serum nitrite concentrations were decreased significantly by successful eradication of H. pylori , and showed a strong positive correlation with H. pylori density. Serum nitrite concentrations showed a significant positive correlation with numbers of single-stranded DNA-positive cells. Conclusions: High H. pylori density was associated with elevated serum nitrate-plus-nitrite (a marker of nitric oxide production in gastric mucosa). Increased apoptosis and abnormal gastric cell turnover are likely results. © 2003 Blackwell Publishing Asia Pty Ltd. [ABSTRACT FROM AUTHOR]

Background: We investigated the effects of rabeprazole compared with those of omeprazole on enterochromaffin-like cells and parietal cells in rats.Methods: Rabeprazole or omeprazole was administered for 7 days by intraperitoneal injection (100 mg/kg or 20mg/kg once a day) and the serum gastrin concentration, the antral density of G cells and D cells, fundic histamine content, fundic H+, K+-ATPase mRNA level, and parietal cell morphology were determined.Results: Both rabeprazole and omeprazole inhibited gastric acid secretion and increased the intragastric pH to over 6.5, as well as causing a marked increase in the serum gastrin concentration. The serum gastrin level was lower with rabeprazole treatment than with omeprazole treatment at both doses. Also, the antral G-cell density was higher with omeprazole than with rabeprazole, while the increase in both the histamine content and the H+, K-ATPase mRNA level in the fundic mucosa was higher with omeprazole treatment at both doses, with the difference being significant at 100 mg/kg. Ultrastructural examination indicated that the stimulation of parietal cells by omeprazole was stronger than that by rabeprazole.Conclusions: Rabeprazole treatment does not drive enterochromaffin-like cells and parietal cells as strongly as omeprazole treatment despite its potent acid suppressive effect, suggesting that it represents a new generation of proton pump inhibitors. [ABSTRACT FROM AUTHOR]

Abstract Background. Helicobacter pylori infection causes chronic gastritis and results in increased serum concentrations of pepsinogens I and II as well as gastrin, while the ratio of pepsinogen I to II (I: II) is decreased. Inducible nitric oxide synthase (iNOS) is induced in H. pylori -associated gastritis and may modulate inflammation. However serum nitrate and nitrite (NOx) concentrations in patients with H. pylori -induced chronic gastritis have not been reported. We examined differences in serum NOx between H. pylori -negative and positive volunteers relative to differences in pepsinogens and gastrin. Materials and methods. Sera from 80 healthy asymptomatic volunteers younger than 36 years were analyzed for anti-H. pylori antibody, NOx, gastrin and pepsinogens. Results. In H. pylori antibody-positive subjects serum NOx concentrations were higher than in negative subjects (p < .005). In H. pylori -negative subjects, NOx correlated with pepsinogen II (r = .405, p < .05). In subjects with low pepsinogen I or II, NOx was higher in H. pylori -positive than negative subjects (p < .001). In subjects with high pepsinogen I: II (6 or higher), serum NOx was higher in H. pylori -positive than in negative subjects. Conclusions. H. pylori -induced gastritis increases serum NOx concentrations more prominently than those of pepsinogen. In H. pylori -negative subjects, serum correlates with serum pepsinogen II. [ABSTRACT FROM AUTHOR]

This study investigated whether the serum nitrite concentration reflects Helicobacter pylori-induced inflammation and atrophic changes of gastric mucosa. Ninety-seven patients underwent biopsy of both antrum and fundus. Samples were analyzed by the rapid urease test and histopathological examination according to the updated Sydney system. Fasting serum samples from each subject were analyzed for specific IgG Helicobacter pylori antibodies, pepsinogen I and II concentrations, and NO2-/NO3- content. Eleven patients had H. pylori eradicated with proton pump-based triple therapy. There was a strong positive correlation between the Helicobacter pylori density in the gastric mucosa and the serum nitrite concentration, but a negative correlation existed between the atrophic grade of the gastric mucosa and both serum nitrite concentration and Helicobacter pylori density in the gastric mucosa. Serum nitrite concentrations decreased significantly after successful eradication of Helicobacter pylori. Therefore, serum nitrite concentration may be a useful marker for oxidative DNA damage and apoptosis associated with Helicobacter pylori infection. [ABSTRACT FROM AUTHOR]

Purpose. The [sup 13] C-urea breath test (UBT) is considered to be the most accurate way of diagnosing Helicobacter pylori infection. Values are affected by H. pylori infection and by the severity of atrophic gastritis. Our objective was to determine the association of UBT values with gastric cancer, and to evaluate the risk of gastric cancer in terms of UBT values. Methods. Our study involved 413 consecutive patients who had undergone esophagogastroduodenal examination and the UBT test. Results. Of the 398 patients with positive UBT results, atrophy and intestinal metaplasia scores in both antrum and corpus were significantly higher in patients with gastric cancer than in those with gastritis, duodenal ulcer, and gastric ulcer. The UBT value related to gastric cancer (22.01 ± 1.89‰) was significantly lower than that for gastritis (35.19 ± 1.53‰; P < 0.01), duodenal ulcer (29.01 ± 1.97‰; P < 0.05), or gastric ulcer (30.79 ± 2.83‰; P < 0.05). When the UBT values were less than 20‰, increases in the risk of gastric cancer correlated with decreasing UBT values. Conclusions. These findings indicate that the UBT value related to gastric cancer is significantly lower than that for gastritis, duodenal ulcer, or gastric ulcer in H. pylori-positive patients. Low UBT values were associated with the risk of gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract Background and Aims: The aim of this study was to clinicopathologically distinguish the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma without a MALT lymphoma component (DLL). Methods: We investigated clinicopathological features of these gastric lymphomas including age, sex ratio, tumor location and depth, macroscopic appearance, and infection with Helicobacter pylori of these gastric lymphomas and hepatitis viruses in 24 patients with gastric low-grade MALT lymphoma, 10 patients with high-grade MALT lymphoma, and 19 patients with DLL. The frequency of H. pylori infection in lymphoma patients was compared with that in age- and sex-matched control subjects. Results: There was a predominance of females with MALT lymphoma (male to female ratio, 8/16 for low-grade MALT lymphomas and 1/9 for high-grade MALT lymphomas), and there was a predominance of males with DLL (male to female ratio, 13/6); the ratios differed significantly (P < 0.05). Ninety-two percent of low-grade MALT lymphomas and 80% of high-grade MALT lymphomas were confined to the mucosal and submucosal layers, but lymphoma cells invaded the muscular layer or more deeply in 74% of DLL. Helicobacter pylori infection occurred significantly more often in patients with low-grade MALT lymphoma than in age- and sex-matched controls (96 vs 67%, P < 0.01). Conversely, the frequency of H. pylori infection in DLL patients did not differ from that in controls. Conclusions: These data suggest that H. pylori infection may be associated with the development of gastric MALT lymphoma, but not DLL, and that MALT lymphoma and DLL may have a different pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the mechanism of the regulation of histamine synthesis in enterochromaffin-like cells, chemically and structurally, by treatment with omeprazole and pirenzepine.Methods: The ultrastructures of enterochromaffin-like cells and parietal cells were examined in rats treated with oral omeprazole (20 mg/kg) or intraperitoneal pirenzepine (1 mg/kg) administration. Serum gastrin concentrations, mRNA levels of H+-K+-ATPase and histidine decarboxylase, and the fundic concentrations of somatostatin and histamine were determined.Results: Pirenzepine treatment suppressed omeprazole-induced increases in serum gastrin levels and mRNA levels of H+-K+-ATPase and histidine decarboxylase. Pirenzepine also decreased omeprazole-induced increases of histamine concentration in fundic mucosa. Pirenzepine elevated somatostatin mRNA level, previously decreased by omeprazole treatment, in fundic mucosa. In the cytoplasm of enterochromaffin-like cells, omeprazole markedly reduced the numbers of vesicles and granules, but significantly increased their diameters, whereas pirenzepine treatment changed neither of these features. The densities and diameters of both vesicles and granules produced by treatment with omeprazole and pirenzepine were between those produced by treatment with omeprazole alone and pirenzepine alone.Conclusions: Omeprazole-induced hypergastrinemia and pirenzepine-induced somatostatin synthesis play important roles not only in histamine synthesis but also in ultrastructural changes in enterochromaffin-like cells. [ABSTRACT FROM AUTHOR]

Although several recent studies have reported that curing Helicobacter pylori (H. pylori) may result in the development of reflux esophagitis (RE), the mechanisms leading to this complication are unknown. One by product of H. pylori infection is ammonia, which serves as an acid neutralizer. The aim of this study was to clarify whether ammonia, which is produced during H. pylori infection, has a protective effect on the esophagus. Eight-week-old male Sprague-Dawley rats were fasted for 24 hrs. Under anesthesia, both the pylorus and limiting ridge were simultaneously ligated. One hour postligation, 0.3 ml of saline or ammonia at various concentrations was administered intragastrically by gastric intubation. Three hours after ligation, the animals were killed, the esophagus and stomach were removed, and the length of esophageal hemorrhagic erosions was measured. The incidence of RE was 100% (7/7) in the control group, 71% (5/7) in the low-ammonia group, 29% (2/7) in the middle-ammonia group, and 14% (1/7) in the high-ammonia group. The severity of lesions decreased in correspondence to increases in ammonia concentration. The development of RE was significantly inhibited by ammonia in a dose-dependent manner. This study indicates that ammonia protects against development of RE. A decreased amount of ammonia in the stomach might be related to the development of RE after H. pylori eradication therapy. [ABSTRACT FROM AUTHOR]

B-cell monoclonality has been reported not only in gastric lymphoma, but also in 1.3–21% of Helicobacter pylori-associated chronic gastritis ( Hp-CG) cases. The aim of this study was to determine the significance of B-cell monoclonality in Hp-CG. We examined 134 gastric biopsy specimens from 99 patients with Hp-CG. The density of Hp, polymorphonuclear neutrophil activity, chronic inflammation, glandular atrophy, and intestinal metaplasia (IM) were scored according to the updated Sydney System. B-cell monoclonality was analyzed for immunoglobulin heavy chain gene rearrangement using polymerase chain reaction amplification. B-cell monoclonality was detected in 6% of informative samples. B-cell monoclonality was found in 18% of the samples from Hp-CG patients with marked glandular atrophy but in none of the samples from Hp-CG patients with none to moderate glandular atrophy. Monoclonality was also detected in 20% of the samples from Hp-CG patients with marked IM, in 11% of the samples from Hp-CG patients with moderate IM, and in none of the samples from Hp-CG patients without IM. Therefore, B-cell monoclonality was significantly more frequent in Hp-CG patients with marked glandular atrophy than in Hp-CG patients with none to moderate atrophy. It was also more significantly frequent in Hp-CG patients with moderate or marked IM than in Hp-CG patients without IM ( P<0.05). Of 35 Hp-CG patients, 26 (74%) had identical B-cell populations in the antrum and the corpus, and all were polyclonal. The remaining nine (26%) Hp-CG patients had B-cell populations that differed in the antrum and the corpus. Four of the nine (44%) showed monoclonal B-cell populations in at least one gastric biopsy specimen. There were no patients with monoclonal B-cell populations in both the antrum and the corpus. These data suggest that glandular atrophy and IM in gastric biopsy specimens may be markers for gastric mucosa-associated lymphoid tissue (MALT) lymphomagenesis and that multiple gastric biopsy specimens from both the antrum and the corpus may be needed to assess the risk of gastric MALT lymphoma. [ABSTRACT FROM AUTHOR]

Objective: Malignant cells exhibit increased glucose uptake and utilization in vitro and in vivo. This process is thought to be mediated by the glucose transporter (Glut) family. The aim of this study was to elucidate the clinical significance of Glut1 expression at the site of deepest invasion as a predictor of the invasive/metastatic potential and prognosis of advanced colorectal carcinoma (CRC). Methods: One hundred and fifty-two patients who had undergone surgical resection for advanced CRC were entered in this study. Histologic subclassifications at the deepest invasive site included well-differentiated (W), moderately to well-differentiated (Mw), moderately to poorly differentiated (Mp), poorly differentiated (Por) and mucinous (Muc) adenocarcinomas. Glut1 expression was examined immunohistochemically with a labeled streptavidin-biotin kit using anti-Glut1 polyclonal antibody MYM. As a marker of cell proliferation, Ki-67 expression was also examined. All immunoreactivity was analyzed at the deepest invasive site, central portion and superficial part. The immunohistochemical expression of Glut1 was defined as positive if distinct staining of the membrane or cytoplasm was observed in at least 30% of tumor cells. Results: Glut1 expression was detected in 56 of 152 lesions (36.8%) at the deepest invasive site. The incidence of Glut1 expression at the deepest invasive site correlated significantly with histologic grade (W/Mw grade, 28% vs. Mp/Por/Muc grade, 48%), depth of invasion (invasion of muscularis propria/invasion of subserosa or subadventitia, 29% vs. invasion of serosa or adventitia/invasion of adjacent structures, 52%), lymphatic invasion (absence of lymphatic invasion, 19% vs. presence of lymphatic invasion, 40%), lymph node metastasis (absence of lymph node metastasis, 25% vs. presence of lymph node metastasis, 41%) and Duke’s stage (Duke’s

Early superficial colorectal carcinoma (CRC) has been commonly detected by routine colonoscopic examination in Japan. A series of 769 early CRCs and 4821 adenomas were diagnosed by colonoscopy at Hiroshima University Medical Hospital between 1991 and 1998. Of early CRCs, macroscopically superficial early CRCs accounted for 209 lesions (28%). Among 5590 lesions of adenomas and carcinomas, depressed-type lesions showed a significantly higher malignant potential for cancerous and submucosal invasion than elevated lesions (polypoid, IIa-type lesions, and G-LST). As one of the quantitative examinations for early CRC, pit pattern observed by magnifying videocolonoscopy was useful. We performed magnifying observations for 265 lesions of colorectal neoplasias using Kudo's pit pattern classification for 2 years. Depressed-type lesions characterized the Ills and V pit patterns, and elevated lesions characterized the IIIL pit pattern. The incidence of cancer was significantly higher in lesions with Ills and V pit patterns. Furthermore, the VN pit pattern was considered a significant indicator of submucosal invasion. These results indicated that superficial early CRC could be considered to constitute about one-third of all early CRCs. Of them, the depressed-type lesions showed a significantly higher malignant potential than elevated lesions. Pit pattern observation by magnifying videocolonoscopy is useful for predicting the histology/invasion depth of early CRC. [ABSTRACT FROM AUTHOR]

Purpose: Tissue growth depends on both cell proliferation and cell death. This study was designed to examine the growth characteristics of rectal carcinoid tumors. Methods: Fifty rectal carcinoid tumors were studied clinicopathologically and experimentally. Expression of Ki-67, TGF-α, p53, and bcl-2 was examined immunohistochemically, and apoptotic cells were identified by the in situ DNA nick end labeling method. EGF receptor expression was examined by a colorimetric in situ mRNA hybridization technique. Results: The median Ki-67 labeling index (LI) in all lesions was 0.62 ± 0.59%. Ki-67 LI was significantly (p < 0.01) higher in lesions larger than 5 mm than in lesions smaller than 5 mm. TGF-α was expressed more frequently (p < 0.01) in lesions larger than 5 mm (100%) than in lesions smaller than 5 mm (65.2%). Ki-67 LI was significantly (p < 0.05) higher in lesions with TGF-α expression than in lesions without TGF-α expression. The in situ hybridization revealed EGF receptor expression in all 46 lesions with intact mRNA (100%), and coexpression of TGF-α and EGF receptor was found in 39 of the 46 (84.8%) lesions. The median apoptotic index (AI) in all lesions was 0.15 ± 0.12%. AI has increased with tumor size and was significantly (p < 0.05) higher in lesions with a higher Ki-67 LI than in lesions with a lower Ki-67 LI. p53 protein was detected in only 1 patient who had liver metastases, and the gene mutation was confirmed by polymerase chain reaction and single-strand conformation polymorphism analysis. bcl-2 expression was absent in all lesions. Conclusions: The Ki-67 LI indicated a low cellular proliferative activity in rectal carcinoid tumors. AI was very low, and was significantly correlated with proliferative rate. Inhibition of apoptosis by mutated p53 or bcl-2 may not have occurred in most of these tumors. TGF-α/EGF receptor autocrine mechanisms may play a possible role in tumor growth, and the cellular proliferative activity may increase as tumors grow larger.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

AbstractBackground and Aims: Although antroduodenal motility has usually been studied by using manometric or scintigraphic methods, ultrasonography is an established, non-invasive method to evaluate duodenogastric motility. We used ultrasonography to evaluate gastric motility in patients with functional dyspepsia. Methods: Sixty-four patients with functional dyspepsia and 36 asymptomatic healthy subjects were given liquid and solid test meals. We investigated the gastric emptying rate, motility index, and duodenogastric reflux for the liquid meal and gastric emptying time, half-emptying time, and motility index for the solid meal. Results: After the liquid meal, the gastric emptying rate and motility index were significantly lower and the duodenogastric reflux was significantly higher in functional dyspepsia patients than in healthy subjects. After the solid meal, gastric emptying time, half-emptying time and the motility index were significantly lower in the patients than in the healthy subjects. Delayed gastric emptying of both meals occurred in only 20.3% of patients. Delayed emptying of the liquid or solid meal occurred in 62.5% of patients. In both groups, gastric emptying time of the solid meal was positively correlated with the motility index at 15 min post-ingestion. Conclusion: In functional dyspepsia patients, delayed gastric emptying of a solid meal was related to antral hypomotility during the early postprandial phase. Ultrasonographic assessment of gastric motility in both liquid and solid meals may provide a better understanding of the pathogenesis of functional dyspepsia. [ABSTRACT FROM AUTHOR]

PURPOSE: Recently, endoscopic mucosal resection has been performed commonly for colorectal tumors. However, incomplete endoscopic mucosal resection produces a residual tumor that grows rapidly. The aim of this study was to clarify the characteristics of the residual tumor using the nude mouse model. METHODS: Human colon cancer cells (colo201 or colo32ODM) were implanted subcutaneous into nude mice. We then removed more than one-half of the tumor with an electrocautery snare or a surgical knife, and compared the tumor growth rate with that of control tumors. Before and after resection, we examined the Ki-67 labeling index of the tumors with an immunohistochemical assay and mRNA expression for epidermal growth factor receptor, vascular endothelial growth factor, and transforming growth factor alpha. RESULTS: Residual tumors showed a higher growth rate in tumor volume than control tumors using both methods (electrocautery snare and surgical knife). Colo201 groups showed a higher total volume change per day than colo320DM groups after resection. Furthermore, these tumors also showed a higher Ki-67 labeling index, and a stronger epidermal growth factor receptor and transforming growth factor alpha mRNA expression than primary and control tumors in the colo201 implanted groups. There was no significant difference in vascular endothelial growth factor mRNA expression between groups implanted with colo201 or colo320DM. CONCLUSION: Our results suggest that residual tumors caused by incomplete endoscopic mucosal resection may have a higher growth potential than the tumors before resection. [ABSTRACT FROM AUTHOR]

Abstract Background and Aims: There has been no suitable animal model for human insulinoma because incidence of pancreatic tumours induced by whole-body irradiation or chemicals has been very low. The purpose of this study was to establish an experimental model with a high incidence of insulinoma. The induction of islet cell tumour by X-irradiation was investigated. Methods: Forty Sprague–Dawley male rats were used in this study. Twenty-eight rats were irradiated with two 10-Gy doses to the gastric region at a 3-day interval, and 12 rats not subjected to X-irradiation served as a control group. The rats were killed 16 months after the first irradiation. Expression of insulin mRNA and protein was examined by northern blot analysis and immunohistochemistry, respectively. Rat serum insulin and glucose levels were measured using enzyme-linked immunosorbent assay. Results: Tumour incidence was 89.3% (25/28) in X-ray group and 8.3% (1/12) in the control group (P < 0.05). Pancreatic tumours, which appeared in all 25 rats with tumours, showed the highest incidence of all neoplasms detected. Tumour cells showed strong immunoreactivity for insulin in 20 of 25 pancreatic tumours (80%). Expression of insulin mRNA was confirmed by northern blot analysis. Furthermore, rats with pancreatic tumours had lower serum glucose levels and higher insulin levels than the control rats. Conclusion: X-irradiated SD rats may be considered a suitable model for insulinoma because of their high tumorigenicity. [ABSTRACT FROM AUTHOR]

We examined the role of capsaicin-sensitive afferent neurons in pH-dependent gastrin secretion in the rat stomach. The change in serum gastrin levels relative to changes in luminal pH (using omeprazole for luminal alkalization or 0.1 N HCl for luminal acidification) was studied after oral administration of 4% lidocaine or capsaicin-induced ablation of afferent neurons. The increase of serum gastrin levels by luminal alkalization was significantly inhibited (50%) after administration of 4% lidocaine. Capsaicin pretreatment (125 mg/kg subcutaneously over two days) inhibited the change in serum gastrin levels both the luminal alkalization (38%) and acidification (66%). Antral gastrin contents, somatostatin contents, gastrin mRNA expression, and somatostatin mRNA expression were not significantly affected by capsaicin pretreatment. Our results indicate that capsaicin-sensitive afferent neurons participate in the secretion of gastrin by luminal alkalization and inhibition of gastrin by luminal acidification. [ABSTRACT FROM AUTHOR]

Background. The 13C urea breath test (UBT) is considered to be the most accurate way of diagnosing Helicobacter pylori infection. Our objective was to investigate the accuracy of the UBT in Japanese patients and the association of UBT values with histological findings. Materials and Methods. A total of 169 consecutive patients were studied by endoscopy with histology, by serology with IgG antibody and test serum pepsinogen (PG), and by UBT. The association between UBT values and histological findings and the PG I / II ratio were analyzed in H. pylori–positive patients. Results. Of 169 Japanese patients, 135 were H. pylori–positive on both histology and serology analysis, 27 were H. pylori–negative on both histology and serology analysis, and 7 patients showed differing results. Using a cutoff value of 2.5‰, test sensitivity was 100%, while specificity was 96%. Among the 135 H. pylori–positive patients, a significant relation was observed between UBT value and H. pylori colonization density of the corpus and antrum, neutrophil activity of the antrum, atrophy, and intestinal metaplasia of the corpus in the H. pylori–positive patients. Also, UBT values correlated with the PG I /II ratio. In multivariate analysis, the PG I /II ratio was the most important factor related to UBT values (odds ration [OR], 4.99; 95% confidence interval, 1.60–15.55). Conclusions. The UBT is an accurate method for detecting H. pylori infection in the Japanese population, which shows a high prevalence of atrophic gastritis. Values are affected by H. pylori infection and by the severity of atrophic gastritis. [ABSTRACT FROM AUTHOR]

Background. Recent studies have clarified a close association between H. pylori infection and gastritis, peptic ulcer disease, and gastric cancer, but there is little information concerning the relationship between H. pylori infection and reflux esophagitis (RE). We investigated the relationship between H. pylori, RE, and corpus gastritis. Subjects and Methods. Ninety-five patients with RE and 190 sex- and age-matched asymptomatic healthy controls demonstrating no localized lesions in the upper GI tract were studied and evaluated for H. pylori infection, histologic gastritis, serum gastrin, and pepsinogens (PGs). Results. H. pylori infection was significantly lower in RE patients than in asymptomatic controls (41% vs. 76%, p < .01). Histologic gastritis of both the antrum and corpus was significantly less frequent (antrum; p < .01, corpus; p < .01), and serum levels of PGI and the PG I/II ratio were significantly higher in RE patients than in controls (PGI; p < .05, PG I/II ratio; p < .01). When the subjects were divided into two age groups (59 years of age and younger and 60 years of age and older), a significant difference was found only among patients over 60 years of age (29% vs. 85%, p < .01). Among subjects in this age group, gastritis in both the antrum and corpus were significantly milder in RE patients than in controls. Although the prevalence of H. pylori infection was similar between the two groups of patients under 59 years of age, corpus gastritis was significantly milder in patients than in controls (p < .05). Conclusions. A significantly low prevalence of H. pylori infection was found in RE patients over 60 years of age but not in those under 59 in comparison with sex- and age-matched controls. The relative lack of corpus gastritis might play a role in the pathogenesis of RE in our population through preservation of the acid secretion area. [ABSTRACT FROM AUTHOR]

AbstractBackground: Whether gastric acid secretion decreases with age is still controversial. With the discovery of Helicobacter pylori, the association of this bacterium with gastric acid secretion has also been discussed. The aim of this study was to investigate the relationship between gastric acid secretion, age and H. pylori infection. Methods: The presence of H. pylori infection, the grade of fundic atrophic gastritis (FAG), and gastric acid secretion were investigated in 280 subjects without localized lesions in the upper gastrointestinal tract. Helicobacter pylori infection was confirmed by Giemsa and immunohistochemical staining, and FAG of biopsy specimens was graded on a scale of 0–4. Results: Both basal and maximal acid output decreased with age in H. pylori-positive subjects, while they did not change with age in H. pylori-negative subjects. Gastric acid secretion decreased with the progression of FAG. An age-correlated decrease in gastric acid secretion in H. pylori-positive subjects depended on an increasing prevalence of FAG with age. Conclusions: In the population studied, advancing age had no influence on gastric acid secretion in H. pylori-negative subjects. Gastric acid secretion decreases with age in H. pylori-positive subjects because of the increasing prevalence of FAG with age. © 2000 Blackwell Science Asia Pty Ltd. [ABSTRACT FROM AUTHOR]

AbstractBackground: The purpose of this study was to establish a method to determine lower oesophageal sphincter (LOS) pressure using an endoscopic manometric sleeve assembly. Methods: We used a 250-cm, three-lumen, 2.2-mm external diameter silicon catheter with a 3-cm sleeve sensor that was passed easily through the biopsy channel (2.8 mm diameter) of the gastroscope. Each lumen was perfused with distilled water using a low-compliance, pneumohydraulic capillary infusion system. Forty-seven healthy subjects and 35 patients with oesophageal disorders underwent study during routine diagnostic endoscopy. In 27 of the subjects, standard transnasal manometry with a three-lumen, 4.5-mm diameter polyvinyl catheter with a 5-cm sleeve sensor was also performed. Results: Lower oesophageal sphincter pressure (LOS) was evaluated in all subjects (median pressure 16 mmHg, range 0–55 mmHg) for 6 min during routine endoscopic examination. The LOS pressure readings between standard and endoscopic manometry correlated well. The LOS pressure was significantly lower in healthy subjects with hiatal hernia than in those without hernia and was also significantly lower in patients with reflux oesophagitis than in healthy subjects. Conclusions: Endoscopic manometric sleeve assembly was used during routine endoscopic examination and was useful for easily determining LOS pressure. It could be used for evaluation of oesophageal motility disorders, thus avoiding the use of a more invasive and time-consuming method. [ABSTRACT FROM AUTHOR]

Purpose: The mucin core peptide MUC1 often is detectable in colorectal carcinoma (CRC) tissue and cell lines. However, whether MUC1 in CRC correlates with tumor histogenesis and progression is unclear. We studied the relationship between MUC1 expression in intramucosal CRC and clinicopathologic features, expression of Ki-67, and p53 protein, and apoptosis. Methods: The intramucosal CRC we studied included 140 endoscopically or surgically resected lesions, including 106 low-grade carcinomas and 34 high-grade carcinomas. De novo carcinoma, defined as carcinoma with no adenomatous component, represented 9 of 140 tumors. Three macroscopic types were identified: 57 lesions were polypoid, 55 were superficial and flat, and 28 were granular-type laterally spreading tumors (G-LST). MUC1, Ki-67, and p53 expression were examined immunohistochemically. Apoptotic cells were identified by in situ DNA nick end labeling. Results: MUC1 expression in high-grade carcinomas was significantly more frequent (p < 0.01) than in low-grade carcinomas; expression in adenomas was almost nil. MUC1 expression in polypoid carcinomas was significantly more frequent (p < 0.05) than in superficial carcinomas or G-LST. MUC1 expression in carcinomas with p53 expression was significantly more frequent (p < 0.01) than in carcinomas not expressing p53. No significant correlation was found between expression of MUC1 and Ki-67 labeling index. MUC1 was expressed more frequently in carcinomas with relatively high apoptotic index (p < 0.01). MUC1 expression did not differ between de novo carcinomas and those developing from adenomas. Conclusions: The results suggest that MUC1 is likely to be expressed in the course of colorectal carcinoma development when p53 protein is overexpressed and apoptosis is prominent. [ABSTRACT FROM AUTHOR]

Background. Duodenal ulcer (DU) patients exhibit raised postprandial gastrin release as compared to that in healthy controls. It is believed that serum pepsinogen I (PG I) concentration reflects the chief cell mass and that hyperpepsinogenemia I plays an important role in the pathogenesis of DU. Currently, strong evidence suggests that Helicobacter pylori (H. pylori) infection plays an important role in the pathogenesis of DU. Materials and Methods. Subjects consisted of 15 patients with H. pylori–positive DU, 10 H. pylori–positive volunteers, and 35 H. pylori–negative volunteers. Blood samples were taken before and at 15, 30, and 60 minutes after eating the test meal, which consisted of 100 gm rice, 130 gm chicken, and 1 egg. The 1-hour integrated gastrin response (IGR) was taken as the area under the serum gastrin time curve, calculated by the trapezoid method. Serum gastrin (SG) and fasting serum PG I concentrations were measured by radioimmunoassay. Results. Meal-stimulated SG response and fasting PG I concentration were significantly higher in DU patients than in H. pylori–positive and –negative volunteers. The DU patients were divided into two groups in accordance with their IGR levels as follows: hyper-IGR and normo-IGR. Serum PG I concentration was significantly higher in the hyper-IGR than in the normo-IGR group. Conclusions. The DU patients differed in some way (other than H. pylori infection) from the H. pylori–positive healthy volunteers. The fact that hyper-IGR DU patients had higher serum PG I concentrations suggests that patients in this group may be acid hypersecretors. [ABSTRACT FROM AUTHOR]

Background. The combination of omeprazole, amoxicillin, and clarithromycin is a common regimen against Helicobacter pylori. Several recent studies have shown that smoking, high intragastric acidity, and the degree of histological gastritis are associated with H. pylori eradication failure. Materials and Methods. One hundred and thirty-seven H. pylori–positive patients were treated with a 1-week regimen composed of omeprazole, 20 mg once daily; amoxicillin, 500 mg; and clarithromycin, 200 mg thrice daily. Success of the treatment was evaluated by histology and the 13C-urea breath test at least 4 weeks after completion of therapy. Data about age, gender, alcohol intake, smoking habits, and previous proton pump inhibitor intake were collected in patient interviews. We evaluated fasting gastric pH and the degree of histological gastritis before eradication of H. pylori. Results. The overall eradication of H. pylori at 4 weeks was successful in 98 of 137 patients (72%). On the multivariate analysis, a low grade of inflammation in the antrum (p ≤ .01; 95% confidence interval [CI], 2.34–16.75), low grade of activity in the fundus (p ≤ .05; 95% CI, 1.31–9.65), and smoking (p ≤ .05; 95% CI, 1.27–6.82) were the significant independent factors predicting treatment failure. Conclusions. These findings indicate that H. pylori eradication therapy with omeprazole, amoxicillin, and clarithromycin is less effective in patients who smoke and more effective in patients with high scores of antral inflammation and fundal activity at baseline biopsy. [ABSTRACT FROM AUTHOR]

Background. This study examines endoscopic findings in the diagnosis of Helicobacter pylori (H. pylori) in the Japanese population. Materials and Methods. The endoscopic findings (including gastric fold findings and degree of atrophy by the Kimura-Takemoto classification system), histologic severity of inflammation, and glandular atrophy were assessed according to the Sydney system in 642 patients (419 men; 223 women; mean age 43.5 years, range 13–86). H. pylori infection was evaluated by Giemsa staining and serum IgG antibodies. Results. 391 of 642 patients (60.9%) were diagnosed as having endoscopic gastritis. Of the 391 patients with endoscopic gastritis, 318 (82.6%) had histologic gastritis and 310 (79.3%) had H. pylori infection. Of the 251 patients with endoscopically normal stomachs, 43 (17.1%) had histologic gastritis and 32 (12.7%) had H. pylori infection. Atrophic gastritis was the most prevalent finding (56.3%) among those with endoscopic gastritis. The prevalence of H. pylori infection in patients with atrophic gastritis (92.7%) and rugal hyperplastic gastritis (92.3%) was significantly higher than in those with other types of gastritis or with a normal stomach (12.7%). A markedly high prevalence of H. pylori infection was found in subjects with tortuosity, hyperrugosity, and/or hyporugosity of the gastric folds. Conclusions. The accurate endoscopic assessment of gastritis according to the Sydney system along with gastric fold findings and the endoscopically identified extent of gastric atrophy are valuable indicators for determining H. pylori infection and histologic gastritis in the Japanese population. [ABSTRACT FROM AUTHOR]

Association of breast tumor susceptibility gene products BRCA1 and BRCA2 with the RAD51 recombination protein suggested that cancer could arise through defects in recombination. The identification of NBS1, responsible for Nijmegen breakage syndrome, from the MRE11/RAD50 recombination protein complex also supports this hypothesis. However, our mutation analysis revealed that known members of the RAD52 epistasis group are rarely mutated in human primary cancer. Here we describe the isolation of a novel member of the SNF2 superfamily, characterized with sequence motifs similar to those in DNA and RNA helicases. The gene, designated RAD54B, is significantly homologous to the RAD54 recombination gene. The expression of RAD54B was high in testis and spleen, which are active in meiotic and mitotic recombination. These findings suggest that RAD54B may play an active role in recombination processes in concert with other members of the RAD52 epistasis group. RAD54B maps to human chromosome 8q21.3-q22 in a region associated with cancer-related chromosomal abnormalities. Homozygous mutations at highly conserved positions of RAD54B were observed in human primary lymphoma and colon cancer. These findings suggest that some cancers arise through alterations of the RAD54B function. [ABSTRACT FROM AUTHOR]

Apoptotic cell death and cell proliferation play important roles in the histogenesis and development of colorectal carcinoma. The aim of this study was to examine the relationship between apoptosis and cell proliferation in various macroscopic types of intramucosal colorectal carcinoma in relation to the expression of p53 and bcl-2.One hundred forty cases with endoscopically or surgically resected intramucosal colorectal carcinoma were studied. There were 57 cases of polypoid-type carcinomas, 55 cases of superficial-type carcinomas, and 28 cases of granular-type, laterally spreading tumors. Polypoid-type carcinomas were pedunculated, subpedunculated, or sessile polyps. Superficial-type carcinomas were flat lesions with a smooth, even surface. Granular-type, laterally spreading tumors were superficially spreading lesions with aggregates of nodules and a granular surface. Apoptotic cells were identified by the in situ DNA nick end labeling method. Ki-67, p53, and bcl-2 expression were examined immunohistochemically.The superficial-type carcinoma apoptotic index (30.9 percent) was significantly lower than that of polypoid-type carcinoma (54.4 percent) and granular-type, laterally spreading tumor (60.7 percent). The superficial-type carcinoma proliferative index (67.3 percent) was significantly higher than that of polypoid-type carcinoma (42.1 percent) and granular-type, laterally spreading tumor (28.6 percent). In superficial-type carcinomas the proliferative index in p53-positive carcinomas was significantly higher, and the apoptotic index was higher in carcinomas with a lower proliferative index. There was no significant difference in apoptotic index, proliferative index, or p53 protein overexpression between de novo carcinomas and those that had arisen in precursor adenomas.The pattern of cell death and proliferation may vary with different macroscopic types of intramucosal colorectal carcinoma. Superficial-type colorectal carcinomas especially demonstrate diminished apoptosis and increased cell proliferation. This may be useful in understanding their biologic behavior. [ABSTRACT FROM AUTHOR]

The growth rates of elevated-type early gastric carcinoma in 12 patients were determined chronologically using serial radiographs. Eight progressed from an early to an advanced stage during periods of observation ranging from 4-82 months (mean 31.7 months), while four patients were still in an early stage at final examination, despite an increase in tumor size. The tumor volume doubling time ranged from 2.2-23.4 months (mean 10.1 months) but varied considerably among patients. Aggressive endoscopy should be performed for all elevated lesions of the stomach because they can harbor malignancy; some can grow rapidly as reported here. [ABSTRACT FROM AUTHOR]

Omeprazole effectively suppresses acid secretion, resulting in the long-term elevation of intragastric pH and serum gastrin level. Pirenzepine has been reported to inhibit gastrin secretion. This study was carried out to examine the effects of additional pirenzepine treatment on the hypergastrinemia and gastric acid suppression induced by omeprazole. Concentrations of serum gastrin and plasma somatostatin were measured in 28 peptic ulcer patients before treatment, after omeprazole treatment (20 mg/day) for 2 weeks, and after omeprazole and pirenzepine (100 mg/day) treatment for 2 weeks. The acid inhibitory effect of pirenzepine treatment in addition to omeprazole was evaluated by 24-h intragastric pH measurement in six healthy volunteers. Serum gastrin level was increased significantly, to 2.4-fold the pretreatment level, by omeprazole treatment. Additional treatment with pirenzepine suppressed serum gastrin level to 0.6-fold the omeprazole-treatment level. The serum somatostatin level was not altered significantly either by omeprazole treatment or by omeprazole and pirenzepine treatment. In healthy volunteers whose pH 3 holding time on 24-h intragastric pH monitoring was 70% by omeprazole treatment, omeprazole and pirenzepine treatment markedly increased the pH 3 holding time, to 89%. These findings suggest that pirenzepine is useful in reducing the undesirable effects of omeprazole-induced hypergastrinemia, i.e., the excessive trophic effect of omeprazole on the acid-secreting part of the stomach and the overstimulation of acid secretion. The additional pirenzepine treatment is also effective in suppressing acid secretion. [ABSTRACT FROM AUTHOR]

A clinicopathological analysis of the risk factors for lymph node metastasis was performed in 177 patients with submucosal invasive colorectal carcinoma (CRC). The submucosal deepest invasive portion was histologically subclassified as well (W), moderately (M), or poorly (Por) differentiated. M type was further subdivided into moderately-well (Mw) and moderately-poorly (Mp) differentiated. The pattern of tumor growth was classified as polypoid growth (PG) and non-polypoid growth (NPG). Lymph node metastasis was detected in 21 (12%) of the 177 patients. Macroscopically, type IIc and IIa + IIc lesions showed a significantly higher incidence of lymph node metastasis (44% and 30%) than type IIa and I (4% and 8%). Regarding the histologic subclassification, Por and Mp lesions showed a significantly higher incidence of lymph node metastasis (67% and 37%) than W and Mw lesions (4% and 14%). NPG tumors showed a significantly higher incidence of lymph node metastasis (29%) than PG tumors (7%). The depth of submucosal invasion and lymphatic invasion (ly) were also significantly correlated with the incidence of lymph node metastasis (submucosal scanty (sm-s) invasion 4%, massive invasion 20%; ly(+) 23%, ly(-) 5%). None of the lesions with both sm-s invasion and of W or Mw type showed lymph node metastasis. These results indicate that submucosal invasive CRC with both sm-s invasion and of W or Mw type, which shows no ly, is the appropriate indication for endoscopic curative treatment. [ABSTRACT FROM AUTHOR]

To establish a sensitive and efficient screening method for gastric cancer using serum pepsinogen, we investigated the characteristics of serum pepsinogen I and II levels and the I/II ratio and their cut-off points. We found that the pepsinogen I level and the I/II ratio were significantly lower in patients with gastric cancer than in control subjects, especially in patients with cancers of the differentiated type, the elevated type, and the depressed type without ulceration. However, sex, depth of invasion, and location of tumor did not correlate with the pepsinogen levels. A suitable cut-off point in screening for gastric cancer was a pepsinogen I level of less than 50 ng/ml and a I/II ratio of less than 3.0, as determined by receiver operator characteristics curves. The sensitivity, the specificity, and the accuracy of detection for all types of gastric cancer were approximately 55%, 75%, and 72%, respectively. If restricted to cancers of the elevated and the depressed type without ulceration, the sensitivity was approximately 85%, and the specificity and accuracy were approximately 76% and 77%, respectively. These results suggest that, in screening for gastric cancer when using pepsinogen levels and morphological examinations, the suitable cut-off point in regard to specificity is as stated above. However, regarding sensitivity, when the pepsinogen method is used alone, a pepsinogen I level of less than 70 ng/ml and a I/II ratio of less than 3.0 is acceptable. [ABSTRACT FROM AUTHOR]

A solitary pedunculated gastric polyp in the gastric fundus was removed from an asymptomatic 36-year-old woman with normal gastric acid secretion and a normal serum gastrin level. This lesion exhibited distinctive histological features including prominent proliferation of pseudopyloric glands, fundic glands, foveolar epithelium and a fibromuscular stroma. Moreover, its surface was entirely covered by a layer of normal gastric epithelium. Biopsies of the background mucosa taken from the gastric fundus revealed only mild superficial gastritis. A gastric gland heterotopia was diagnosed because of its unique morphology. [ABSTRACT FROM AUTHOR]

In a search for genetic markers of duodenal ulcer, serum pepsinogen I level, ABO blood groups and secretor status were determined in 89 siblings of 34 duodenal ulcer families. Duodenal ulcer patients were likely either to have hyperpepsinogenemia I or to be non-secretors on a familial basis, but not to have an increased frequency of blood group O. The frequency of duodenal ulcer in the siblings was highest in hyperpepsinogenemia I/non-secretor and lowest in normopepsinogenemia I/secretor. Therefore, the influence of two genes, hyperpepsinogenemia I and non-secretor, on the risk of duodenal ulcer is multiplicative. These results provide evidence on the hypothesis of polygenic inheritance of duodenal ulcer. [ABSTRACT FROM AUTHOR]

The specific binding ofI-labeled gastrin-17 was studied in samples of human gastric mucosa, duodenal mucosa, colonic mucosa or pancreatic tissue obtained surgically. With regard to gastric fundic mucosa, the criteria for receptor binding were studied, and saturability, high affinity, tissue specificity and hormone specificity were demonstrated. The dissociation constant for gastric fundic mucosa was 1.6 x 10M, and the binding capacity was 15 fmol/mg protein. Tissue specificity studies revealed a high degree of gastrin receptor binding in human gastric fundic mucosa, duodenal mucosa and pancreas, whereas antral mucosa and colonic mucosa demonstrated a low degree of binding. [ABSTRACT FROM AUTHOR]

Investigates the physiological role of endogenous gastrin-releasing peptide in regulating the release of gastrin by evaluating the response of intragastric pH, gastrin and GRP after omeprazole treatment in rats. Tissue extraction and blood samples for GRP radioimmunoassay; Gel chromatography; Preparation and blotting of RNA.

This study sought to examine the relationship between MUC1 expression at the deepest invasive portion, invasive/metastatic potential, and prognosis of colorectal cancer in relation to cellular proliferation. MUC1 expression was detected immunohistochemically using KL-6 antibody (anti-MUC1 monoclonal antibody) in 100 surgically resected specimens of advanced colorectal cancer. Distinct staining of the luminal surfaces, defined as positive immunoreactive (IR)-MUC1 expression, was seen in more than 30% of the tumor cells at the deepest invasive portion. The proliferating cell nuclear antigen labeling index (PCNA-LI) was also examined in the same areas. IR-MUC1 expression was detected in 71 (71%) of 100 lesions. Lesions with lymphatic or venous invasion showed a significantly higher incidence of IR-MUC1 expression than those without lymphatic or venous invasion (80 vs. 42% and 82 vs. 61%, respectively). Lesions with lymph node metastasis showed a significantly higher incidence of IR-MUC1 expression than those without lymph node metastasis (88 vs. 53%). Lesions with liver metastasis showed a significantly higher incidence of IR-MUC1 expression than those without liver metastasis (92 vs. 59%). Dukes’ stage was also significantly correlated with IR-MUC1 expression. The incidence of IR-MUC1 expression did not significantly differ with regard to histologic subclassification and depth of invasion. There was no significant correlation between IR-MUC1 expression and the PCNA-LI. IR-MUC1 expression at the deepest invasive portion revealed a significant correlation with prognosis; furthermore, in patients with better differentiated lesions, in those with lesions confined to muscularis propria or subserosa (subadventitial) invasion, in those with Dukes’ B and C, or in those undergoing curative resection, IR-MUC1 expression significantly correlated with prognosis. Patients with high PCNA-LI lesions showed a significantly poorer prognosis than those with low PCNA-LI lesions. Only in patients undergoing curative resection, patients with IR-MUC1-positive and high PCNA-LI lesions showed a significantly poorer prognosis than those with IR-MUC1-negative and low PCNA-LI lesions. The significant risk factors in the order of poorer prognosis in patients undergoing curative resection by the multivariate analysis were the histologic grade (moderately–poorly, poorly or mucinous adenocarcinomas), IR-MUC1 expression, and lymph node metastasis. These results indicate that IR-MUC1 expression is an important predictor of the metastatic potential and the prognosis of colorectal cancer, independent of histologic grade, depth of invasion or cellular proliferative activity. Combined analysis of IR-MUC1 and histologic grade, and combined expression of IR-MUC1 and PCNA at the deepest invasive portion are especially useful in predicting colorectal cancer prognosis. [ABSTRACT FROM AUTHOR]

HLA-DR antigen expression and the proliferating cell nuclear antigen labeling index (PCNA-LI) were examined immmunohistochemically in 59 surgically resected advanced colorectal cancers to clarify the clinicopathologic significance of the HLA-DR antigen. HLA-DR antigen expression was detected in 33 (56%) of the 59 lesions, which showed less frequent liver metastasis than lesions without HLA-DR antigen expression (40 vs. 68%; p < 0.05). Five-year survival rates of patients with and without HLA-DR antigen expression were 50 and 19%, respectively. Lesions combining HLA-DR antigen expression and a relatively low PCNA-LI had the best prognosis. These results indicate that HLA-DR antigen expression, particularly combined with a low PCNA-LI, is an important outcome predictor in colorectal cancer. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether gastrin regulates morphological changes and alpha-subunit gene expression in parietal cells through the gastrin/CCK-B receptor on enterochromaffin-like cells by histamine release. Treatment with 100 mg/kg of YM022, a potent and selective gastrin/CCK-B receptor antagonist, for one week in rats did not alter mRNA levels of histidine decarboxylase or H+, K+-ATPase. However, parietal cell morphology predominantly changed to the resting form, although the serum gastrin concentration was significantly increased. Additional treatment with YM022 and oral omeprazole, 100 mg/kg, for one week markedly suppressed the increases of mRNA levels of histidine decarboxylase and H+, K+-ATPase and completely blocked the morphological transformation of the parietal cells to a stimulated form induced by treatment with omeprazole alone. This indicates that the morphological transformation of parietal cells to an activated form with a subsequent increase in H+, K+-ATPase synthesis caused by hypergastrinemia is mediated by increased histidine decarboxylase gene expression in enterochromaffin-like cells via gastrin/CCK-B receptors. [ABSTRACT FROM AUTHOR]

This study was performed to examine the effects of additional enprostil administration on hypergastrinemia and gastric acid suppression induced by omeprazole. Serum gastrin concentrations were measured in 10 peptic ulcer patients (six Helicobacter pylori-positive and four Helicobacter pylori-negative patients) before treatment, after two weeks of omeprazole (20 mg/day), and after two weeks of omeprazole and enprostil (50 micrograms/day). The additional acid inhibitory effect of enprostil was evaluated by 24-hr intragastric pH measurements in five healthy Helicobacter pylori-negative volunteers. After omeprazole treatment, the serum gastrin level of Helicobacter pylori-positive patients (3.5-fold of control) was markedly higher than that of Helicobacter pylori-negative patients (1.7-fold of control). Additional treatment with enprostil suppressed serum gastrin levels to 0.4-fold and 0.7-fold of omeprazole treatment levels in Helicobacter pylori-positive and Helicobacter pylori-negative patients, respectively. In healthy volunteers, median pH recorded during the nonmeal daytime interval increased significantly with additional enprostil. Thus, enprostil reduces undesirable omeprazole-induced hypergastrinemia, especially in Helicobacter pylori-positive patients, and effectively suppresses acid secretion. [ABSTRACT FROM AUTHOR]