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Chronic gastritis in a sample of the general population: Helicobacter pylori infection, metaplastic transformation, epithelial proliferation, p53- and p21 expression and antral mucosal gastrin content with reference to gastric carcinoma development
Linköping University, Department of Neuroscience and Locomotion. Linköping University, Faculty of Health Sciences.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Infection with H. pylori is the main cause of chronic inflammation in the stomach. lt is strongly associated with benign ulcer disease and a risk factor for gastric carcinoma (GC). Different tophographical types of gastritis bear different risks for future development of GC. Mucosal changes, atrophy and intestinal metaplasia (IM) are known precancerous conditions.

The aims of this thesis were to map out the prevalence of chronic gastritis, including different tophographical types, carditis and H. pylori infection in an adult Swedish general population sample. To determine the prevalence of atrophy and different types of IM and measure the mucosal proliferative activity (Ki-67), expression of p53 and p21 with immunohistochemistry. Furthermore, to determine plasma levels of gastrin and the content of G-cells in the antrum with immunohistochemistry measured with three different morphometrical methods.

The prevalence of chronic gastritis was 50%. lt was associated with H. pylori infection in 87%. The prevalence of carditis was 55% and it was associated with local H. pylori infection in 70%. The most common type of gastritis was antrum predominant (44%) followed by pangastritis (37%) and corpus predominant (19%). The prevalence of atrophy (antrum and/or corpus) was 55% and it increased with age, as did the prevalence of IM, which was present in the antrum or corpus in 23% and in the cardia in 10%. Corresponding figures for the prevalence of type III IM was 4% and 1%, repspectively. In all locations there was a strong correlation between the occurrence of IM and both H. pylori infection and chronic inflammation. Chronic inflammation and H. pylori infection were associated with increased mucosal proliferation and expression of p53. Atrophy as well as IM were associated with increased expression of p53 in both the corpus and antrum. IM was associated with increased proliferation in the mucosa, as was atrophy in the corpus. The expression of p21 was low and not affected by infection or inflammation. Plasma levels of gastrin were increased in subjects with H. pylori infection and showed no correlation with the amount of antral G-cells. The three different methods for G-cell quantification correlated poorly.

In conclusion,chronic gastritis and carditis in this sample of an adult Swedish general population were frequent and strongly associated with H. pylori infection. The prevalences of different gastritis types and mucosal changes associated with increased cancer risk were determined and the relationships between chronic gastritis/carditis and both increased mucosal proliferation and expression of p53 in all parts of the stomach were established. Increased plasma levels of gastrin among subejects with H. pylori infection were established, as was the lack of a correlation between circulating gastrin levels and the amount of G-cells in the antrum. Poor correlations between three different methods for G-cell quantification highlight a methodological problem.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2004. , 85 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 855
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-23315Local ID: 2744ISBN: 91-7373-831-X (print)OAI: oai:DiVA.org:liu-23315DiVA: diva2:243629
Public defence
2004-09-24, Aulan, Länssjukhuset, Ryhov, Jönköping, 10:00 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-31Bibliographically approved
List of papers
1. Prevalence of gastroduodenitis and Helicobacter priori infection in a general population sample: relations to symptomatology and life-style
Open this publication in new window or tab >>Prevalence of gastroduodenitis and Helicobacter priori infection in a general population sample: relations to symptomatology and life-style
Show others...
2000 (English)In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 45, no 7, 1322-1329 p.Article in journal (Refereed) Published
Abstract [en]

Some benign and malignant diseases develop on the background of chronic gastritis or duodenitis. The present study was performed in order to determine the magnitude of these background changes with relations to symptomatology and life style in the general population. Examinations were performed in 501 volunteers (age 35–85 years). Fifty percent had gastritis; this was associated with H. pylori in 87%. H. pylori-negative gastritis was associated with regular use of NSAIDs [odds ratio 3.8 (1.6–9.9)]. Duodenitis, observed in 32%, was associated with H. pylori infection [odds ratio 2.3 (1.3–4.6)], previous cholecystectomy [odds ratio 3.6 (1.1–16.1)], and regular use of NSAIDs [odds ratio 3.0 (1.4–7.1)]. Neither gastritis nor duodenitis was associated with smoking or alcohol consumption. The rate of digestive symptoms did not differ between subjects with and without uncomplicated gastritis or duodenitis. In conclusion, half of this adult population had gastritis strongly associated with H. pylori infection. Gastritis without H. pylori infection was frequently associated with regular NSAID intake. One third had duodenitis, which was associated with H. pylori infection as well as with regular use of NSAIDs and previous cholecystectomy. Digestive symptoms were not overrepresented in uncomplicated gastritis or duodenitis.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24959 (URN)10.1023/A:1005547802121 (DOI)9370 (Local ID)9370 (Archive number)9370 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-31
2. Prevalence of subtypes of intestinal metaplasia in the general population and in patients with autoimmune chronic atrophic gastritis
Open this publication in new window or tab >>Prevalence of subtypes of intestinal metaplasia in the general population and in patients with autoimmune chronic atrophic gastritis
2002 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 37, no 3, 262-266 p.Article in journal (Refereed) Published
Abstract [en]

Background: Gastric intestinal metaplasia (IM) is seen mostly in association with chronic gastritis, induced either by Helicobacter pylori infection or autoimmune mechanisms. IM can be categorized into three subtypes, where type III is associated with gastric carcinoma of intestinal type.

Methods: Gastric biopsies from 475 subjects randomly selected from the general population and from 27 patients with autoimmune gastritis associated with pernicious anaemia were used. The criteria of Filipe & Jass were applied using different histochemical techniques in combination with haematoxylin and eosin stained material.

Results: Twenty-three percent (109/475) of the subjects from the general population and 88% (24/27) in the group with autoimmune gastritis had IM. Type III IM occurred in 4% in both populations. Type III IM was located in the antrum in 90% in the general population. In the group with autoimmune gastritis, only one patient had type III IM, which was located in the corpus.

Conclusions: This study reveals for the first time the prevalence and distribution of subtypes of IM in a general population from the Western world. The comparatively high prevalence of type III IM in the general population (4%) indicates that its role as a precursor of gastric carcinoma may have been overemphasized. A similar prevalence of type III IM in patients with autoimmune gastritis may be considered low and suggests that mechanisms for gastric carcinogenesis other than the atrophy - metaplasia-dysplasia sequence could also operate in this condition.

Keyword
Chronic Gastritis, Epidemiology, Helicobacter, Pylori, Intestinal Metaplasia
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24963 (URN)10.1080/003655202317284156 (DOI)9374 (Local ID)9374 (Archive number)9374 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-31
3. Gastric epithelial proliferation and p53 and p21 expression in a general population sample: relations to age, sex, and mucosal changes associated with H. pylori infection
Open this publication in new window or tab >>Gastric epithelial proliferation and p53 and p21 expression in a general population sample: relations to age, sex, and mucosal changes associated with H. pylori infection
2002 (English)In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 47, no 7, 1558-1566 p.Article in journal (Refereed) Published
Abstract [en]

Helicobacter pylori infection is the main cause of chronic gastritis. The infection has been linked to altered proliferative activity and changes in various cell cycle regulating proteins. To determine, in a general population sample, the proliferative activity and expression of p53 and p21 in males and females of different age groups with and without H. pylori-associated chronic gastritis, gastric biopsies from 273 subjects (188 with and 85 without H. pylori infection) randomly selected from a general population were examined immunohistochemically for Ki-67, p53, and p21. One thousand epithelial cells, including the surface, neck, and glandular areas, were counted in both the corpus and the antrum. Results are expressed as the percentage of positive cells. Subjects with H. pylori infection showed significantly increased proliferative activity and expression of p53 compared to uninfected individuals. Regarding the expression of p21, no difference was detected. Multiple linear regression analysis showed significant associations between chronic inflammation or inflammatory activity, on the one hand, and the degree of proliferation in both the corpus and the antrum, on the other hand. In the antrum, the degree of H. pylori colonization was related to the expression of p53. H. pylori seems to cause increased proliferation and increased expression of p53 (but not p21) in the gastric mucosa, neither of which is age or sex dependent. The proliferative activity is related mainly to events associated with inflammation, while the expression of p53 in the antrum is associated with the degree of H. pylori infection. The action of p53 appears to be independent of p21 activity.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24964 (URN)10.1023/A:1015938303993 (DOI)9375 (Local ID)9375 (Archive number)9375 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-31
4. Characterization of the gastric cardia in volunteers from the general population: type of mucosa, helicobacter pylori infection, inflammation, mucosal proliferative activity, p53 and p21 expression, and relations to gastritis
Open this publication in new window or tab >>Characterization of the gastric cardia in volunteers from the general population: type of mucosa, helicobacter pylori infection, inflammation, mucosal proliferative activity, p53 and p21 expression, and relations to gastritis
2010 (English)In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 55, no 1, 46-53 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this research was to characterize the mucosa of the gastric cardia in relation to infection with Helicobacter pylori and the occurrence of chronic gastritis in other parts of the stomach in a sample of the general population. In this study, 80 adult volunteers underwent esophagogastroscopy with biopsies from the gastric cardia, corpus, and antrum. Gastritis was classified according to the Sydney system. Chronic gastritis (cardia excepted) was diagnosed in 35 subjects, 30 with Hpylori infection. Epithelial proliferative activity (Ki-67), p53- and p21 expression were examined quantitatively with cell counting after immunohistochemical stainings. Esophagitis was diagnosed macroscopically. Fourty eight subjects had cardia-type and 32 corpus-type mucosa in the anatomical cardia. The prevalence of esophagitis (nine cases) did not differ between these groups. Carditis was more prevalent among subjects with cardia-type mucosa (73 vs. 28%, P < 0.0001). Hpylori was present in 48% of those with cardia-type and 25% of those with corpus-type mucosa (P = 0.06). Of the 44 subjects with carditis, 31 had Hpylori in this location. The group with Hpylori infection had significantly higher mucosal proliferative activity when compared to uninfected subjects. Among the subjects with H. pylori-associated carditis, more p53-positive epithelial cells were detected compared to both the non-infected group (P = 0.0004) and to subjects with non-Hpylori-associated carditis (P = 0.03). In subjects with cardia-type mucosa, and both carditis and gastritis, the degree of chronic inflammation was higher in the cardia compared to the corpus and antrum and the p53 expression was significantly higher in the cardia compared to the corpus, but similar to that in the antrum. The proliferative activity was significantly higher in the antrum compared to the cardia and corpus, respectively. In conclusion, H. pylori infection, carditis, and increased p53 expression are more common in subjects with cardia- than corpus-type mucosa in the gastric cardia. Carditis is mainly related to Hpylori infection. There are some differences regarding inflammation, proliferative activity, and p53 expression between the cardia and other regions of the stomach, yet the significance of these differences remains to be clarified.

Keyword
Cardia, Carditis, Gastritis, Helicobacter pylori, Proliferation, Ki-67, p53, p21
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-53693 (URN)10.1007/s10620-008-0705-0 (DOI)
Available from: 2010-02-01 Created: 2010-02-01 Last updated: 2012-10-31
5. A morphometric study of antral G-cell density in a sample of adult general population: comparison of three different methods and correlation with patient demography, helicobacter pylori infection, histomorphology and circulating gastrin levels
Open this publication in new window or tab >>A morphometric study of antral G-cell density in a sample of adult general population: comparison of three different methods and correlation with patient demography, helicobacter pylori infection, histomorphology and circulating gastrin levels
2009 (English)In: International Journal of Clinical and Experimental Pathology, ISSN 1936-2625, Vol. 2, no 3, 239-248 p.Article in journal (Refereed) Published
Abstract [en]

Helicobacter pylori infection has been linked to hypergastrinemia and either decreased or normal G-cell content in the antral mucosa. To clarify this controversial issue, we quantitatively determined antral G-cell content on the same biopsy specimens with three different methods and examined whether these methods are intercorrelated and the relation of these methods to plasma gastrin concentrations, demography, the occurrence of H. pylori infection and chronic gastritis. Gastric antral mucosal biopsy sections from 273 adults (188 with and 85 without H pylori infection) from a general population sample were examined immunohistochemically for G-cells using cell counting, stereology (point counting) and computerized image analysis. Gastritis was scored according to the updated Sydney system. Basal plasma gastrin concentrations were measured by radioimmunoassay. The three methods for G-cell quantification were poorly correlated and the results showed no correlation with basal plasma gastrin concentrations. The antral G-cell density and scores for H. pylori colonization were positively related to age. Neither the scores for chronic inflammation, nor the scores for inflammatory activity, atrophy or intestinal metaplasia were consistently related to the antral G-cell content. In conclusion, the results of three techniques for G-cell quantification in the gastric antral mucosa were poorly intercorrelated and none of the methods correlated with plasma gastrin concentrations. Age and scores for H pylori colonization seem to be determinants of the G-cell density. That common morphometric techniques correlate poorly is of utmost importance to bear in mind when quantitative morphological studies are planned, compared or interpreted.

Keyword
Gastrin, cell counting, computerized image analysis, gastritis, inflammation, morphometry, point counting, stereology, stomach
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-21318 (URN)19079618 (PubMedID)
Note

Published article from the manuscript entitled "Antral G-cell content in a sample of the adult general population. A Quantitative Study comparing three methods with reference to demography, H pylori infection, histomorphology and circulating gastrin levels"

Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2012-10-31

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