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  • 1.
    Azerkan, Leila
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bengtsson, Per
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Tømmerås, Karin
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Li, Zhao-Qi
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Mårdh, Sven
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Characterization of oxyntic glands isolated from the rat gastric mucosa2001In: Comparative Biochemistry and Physiology A, ISSN 1095-6433, E-ISSN 1531-4332, Vol. 128, no 2, p. 349-357Article in journal (Refereed)
    Abstract [en]

    A simple and reproducible method for isolating oxyntic glands from the rat gastric mucosa was developed. The mucosa was incubated with pronase and EGTA, and then treated mechanically to release glands that were separated from single cells by sedimentation. Parietal cells were identified by immunostaining using a monoclonal antibody against H,K-ATPase. The glandular cells appeared morphologically intact. By careful control of the conditions of gland isolation, long glandular structures comprising hundreds of cells surrounding the lumen were obtained. Intraperitoneal injection of Br-deoxyuridine in the rat 1.5 h before the isolation procedure resulted in glands with a labeling of cells in their neck region. The glands were viable, as demonstrated by their ability to respond to various hormones. Histamine dose-dependently stimulated the acid formation which was measured as the accumulation of [14C]aminopyrine. At 100 microM histamine the accumulation was increased 5-10-fold. At 100 nM, pentagastrin potentiated the histamine stimulated accumulation by approximately 40% but pentagastrin alone did not stimulate. The oxyntic glands obtained by the present procedure appear useful for studies on cell physiology, including regulation of acid secretion, cellular interactions, and possibly also differentiation and proliferation mechanisms since long glandular fragments that contained the proliferative zone could be isolated.

  • 2.
    Bengtsson, Per
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Azerkan, Leila
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Lundqvist, Gudmar
    Department of Clinical Chemistry, Academic Hospital, Uppsala, Sweden.
    Nilsson, Göran
    Department of Physiology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Mårdh, Sven
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Effects of cholecystokinin on acid formation in glands and cells isolated from rabbit and rat gastric mucosa2000In: Comparative Biochemistry and Physiology A, ISSN 1095-6433, E-ISSN 1531-4332, Vol. 126, no 1, p. 77-84Article in journal (Refereed)
    Abstract [en]

    Isolated gastric glands and isolated cells prepared from rabbit and rat were studied to analyse the influence of cholecystokinin octapeptide (CCK 8) on histamine stimulated parietal cell acid formation as assessed by [14C]aminopyrine sequestered in acid tissue compartments. In rabbit gastric glands, CCK 8 evoked 32±6% (P<0.01) inhibition of histamine stimulated acid formation, whereas in glands prepared from rat no inhibition was recorded. Instead, CCK 8 seemed to induce a variable increase of the histamine stimulation in rat gastric glands as the aminopyrine accumulation was increased by 110±46% (P<0.1). Further studies on cell preparations derived from rabbit gastric mucosa revealed dual properties of CCK 8, eliciting either inhibition or stimulation of the parietal cell depending on the presence of endocrine cells. The results show that paracrine communication may be effective in glandular preparations, but seems to vary depending on species.

  • 3.
    Borch, Kurt
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Grodzinsky, Ewa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Petersson, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery.
    Jönsson, Kjell-Åke
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Valdimarsson, Trausti
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    Prevalence of coeliac disease and relations to Helicobacter pylori infection and duodenitis in a Swedish adult population sample: A histomorphological and serological survey2000In: InflammoPharmacology, ISSN 0925-4692, E-ISSN 1568-5608, Vol. 8, no 4, p. 341-350Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to determine the prevalence of coeliac disease and its relation to duodenitis, H. pylori infection and gastritis in a sample of the adult general population. Methods: A Swedish population sample of 482 subjects (aged 35 to 85 years) were examined with gastro-duodenoscopy with multiple biopsies taken. Circulating antibodies to endomycium, gliadin, and H. pylori were also determined. Results: Based on histomorphological findings, coeliac disease was evident in 9 of 482 subjects giving a prevalence of 1.9 [1.0-4.0, 95% confidence interval] percent. The prevalence of gastritis with or without H. pylori infection did not differ between subjects with and without coeliac disease. Considering subjects without coeliac disease, there was no difference in the serum levels of gliadin antibodies between those with and without duodenitis. However, subjects with positive H. pylori status had significantly higher levels of gliadin antibodies than those with negative H. pylori status. Conclusions: This study confirms that there is a relatively high prevalence of undiagnosed coeliac disease in Swedish adults. There was no association between coeliac disease and H. pylori infection or gastritis, although serum gliadin antibody levels were slightly increased in subjects with positive H. pylori status.

  • 4.
    Borch, Kurt
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Jönsson, Kjell-Åke
    Petersson, Fredrik
    Redéen, Stefan
    Mårdh, Sven
    Franzén, Lennart
    Prevalence of gastroduodenitis and Helicobacter priori infection in a general population sample: relations to symptomatology and life-style2000In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 45, no 7, p. 1322-1329Article in journal (Refereed)
    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.

  • 5.
    Borch, Kurt
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Skarsgard, J
    Franzén, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Rehfeld, JF
    Benign gastric polyps - Morphological and functional origin2003In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 48, no 7, p. 1292-1297Article in journal (Refereed)
    Abstract [en]

    The most common types of benign gastric polyps are fundic gland polyps, hyperplastic polyps, and adenomas. The aim of this study was to determine on which morphological and functional background benign gastric polyps develop. The study includes 85 consecutive patients with gastric polyps and sex and age-matched controls without polyps selected at random from a general population sample. The type of polyp was hyperplastic in 52 (61%), fundic gland in 18 (21%), adenoma in 10 (12%), carcinoid in 2 (2%), hamartoma in 2 ( 2%), and inflammatory fibroid in 1 (1%) of the cases. Routine biopsies from the gastric corpus and antrum were examined for presence of gastritis and H. pylori. Blood samples were analyzed for H. pylori antibodies, H+, K+-ATPase antibodies, gastrin, and pepsinogen I. Patients with hyperplastic polyps had increased P-gastrin concentrations and S-H+, K+-ATPase antibody titers and decreased S-pepsinogen I concentrations with a high prevalence of atrophic corpus gastritis or pangastritis. A similar pattern was observed among patients with adenomas, whereas patients with fundic gland polyps had normal serology and a lower prevalence of gastritis and H. pylori infection than controls. In conclusion, hyperplastic polyps and adenomas are generally associated with atrophic gastritis. Patients with fundic gland polyps seem to have a sounder mucosa than controls. Whereas the risk of malignant gastric neoplasia is increased in patients with hyperplastic polyps or adenomas, this does not seem to be the case in patients with fundic gland polyps.

  • 6.
    Cao, Jun
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Sun, Yi-Qian
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Berglindh, Thomas
    Mellgård, Björn
    Li, Zhao-qi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Mårdh, Bibbi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Helicobacter pylori-antigen-binding fragments expressed on the filamentous M13 phage prevent bacterial growth2000In: Biochimica et Biophysica Acta - General Subjects, ISSN 0304-4165, E-ISSN 1872-8006, Vol. 1474, no 1, p. 107-113Article in journal (Refereed)
    Abstract [en]

    Colonization of the human stomach by Helicobacter pylori is associated with the development of gastritis, duodenal ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. H. pylori-antigen-binding single-chain variable fragments (ScFv) were derived from murine hybridomas producing monoclonal antibodies and expressed as a g3p-fusion protein on a filamentous M13 phage. The recombinant ScFv-phage reacted specifically with a 30-kDa monomeric protein of a H. pylori surface antigen preparation and by means of immunofluorescence microscopy the phage was shown to bind to both the spiral and coccoid forms of the bacterium. In vitro, the recombinant phage exhibited a bacteriocidal effect and inhibited specifically the growth of all the six strains of H. pylori tested. When H. pylori was pretreated with the phage 10 min before oral inoculation of mice, the colonization of the mouse stomachs by the bacterium was significantly reduced (P<0.01). The results suggest that genetic engineering may be used to generate therapy-effective phages.

  • 7. Kanagawa, M
    et al.
    Kaya, S
    Umezu, H
    Watanabe, S
    Togawa, K
    Shimada, A
    Imagawa, T
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Taniguchi, K
    Direct evidence for in vivo reversible tyrosine phosphorylation of the N-terminal domain of the H/K-ATPase alpha-subunit in mammalian stomach cells.1999In: Journal of Biochemistry (Tokyo), ISSN 0021-924X, E-ISSN 1756-2651, Vol. 126, p. 266-270Article in journal (Refereed)
  • 8.
    Kuroda, Tsuyoshi
    et al.
    Hiroshima University.
    Ito, Masanori
    Hiroshima University.
    Wada, Yoshihiro
    Hiroshima University.
    Kitadai, Yasuhiko
    Hiroshima University.
    Tanaka, Shinji
    Hiroshima University.
    Yoshida, Kazuhiro
    Hiroshima University.
    Yoshihara, Masaharu
    Hiroshima University.
    Haruma, Ken
    Kawasaki Medical University.
    Mårdh, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Cellbiology. Linköping University, Faculty of Health Sciences.
    Chayama , Kazuaki
    Hiroshima University.
    Presence of Poorly Differentiated Component Correlated with Submucosal Invasion in the Early Diffuse-type Gastric Cancer2008In: HEPATO-GASTROENTEROLOGY, ISSN 0172-6390 , Vol. 55, no 88, p. 2264-2268Article in journal (Refereed)
    Abstract [en]

    Background/Aims. Diffuse-type gastric carcinoma is associated with a poor prognosis. However, the clinical behavior of diffuse-type gastric cancer is not fully understood. The aim of this study is to distinguish the behaviors of early diffuse-type gastric carcinomas by sub classifying tumors according to their histologic features.

    Methodology. A total of 114 cases of diffuse-type early gastric cancer were studied retrospectively. We analyzed and compared the resected cancer specimens according to the histologic components: as poorly differentiated adenocarcinoma component-present (poor+) versus poorly differentiated adenocarcinoma component-absent (poor-). Helicobacter pylori status was evaluated by Giemsa staining and IgG serology. We assessed the degree of cancer invasion and compared back-ground status of gastritis in accordance with the updated Sydney System criteria and serologic markers.

    Results. In comparison to the poor+ cancers, the poor- cancers had a significantly larger portion of cells confined to the mucosa (p=0.002). Only 8 of the 114 cases were regarded as H. pylori-negative. Although we could not detect any serologic markers specific for gastritis with poor+ cancer, but the serum levels of gastrin was slightly higher in patients with poor+ cancers than in those with poor- cancers.

    Conclusions. The biologic behavior of poor+ gastric carcinoma is worse than that of poor- carcinoma. There is a close relation between H. pylori infection and carcinogenesis of poorly differentiated adenocarcinoma.

  • 9.
    Mårdh, Erik
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Mårdh, Bibbi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Borch, Kurt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Diagnosis of gastritis by means of a combination of serological analyses2002In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 320, no 1-2, p. 17-27Article in journal (Refereed)
    Abstract [en]

    Background: Gastroscopy and examination of biopsy is normally required for diagnosis of gastritis. This is costly and inconvenient for the patient, and there is a need for a simple pregastroscopic screening method to reduce the endoscopy workload. Our aim was to develop a serological screening test for gastritis. Methods: Sera from subjects examined with gastroscopy and biopsy were analyzed for H,K-ATPase antibodies, Helicobacter pylori antibodies and pepsinogen I. The diagnoses were normal gastric mucosa (n=50), duodenal ulcer (n=53) and atrophic corpus gastritis, with (n=50) or without pernicious anemia (n=46). Results: An evaluation scheme was constructed to optimize the diagnostic agreement between serology and gastric mucosal morphology. The sensitivity to detect gastritis was 98% (146/149) (95% CI 94-100%) and the specificity 84% (42/50) (95% CI 71-93%). Additional sera from 483 subjects from the general population were analyzed. There was a good agreement between serology and gastric mucosal morphology. Conclusions: Assays of multiple serum analytes are useful for the initial screening of gastritis. They are complementary to upper gastroscopy by identification of subjects with a normal gastric mucosa, those who qualify for eradication of H. pylori, and those who have developed atrophy and are at risk of developing malignancy and, therefore, require gastroscopic examination.

  • 10.
    Nägga, Katarina
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Rajani, Rupesh
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Mårdh, Erik
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Borch, Kurt
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Mårdh, Sven
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Cobalamin, folate, methylmalonic acid, homocysteine, and gastritis markers in dementia2003In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 16, no 4, p. 269-275Article in journal (Refereed)
    Abstract [en]

    The prevalence of dementia disorders, cobalamin and/or folate deficiency as well as gastritis increases with age. To investigate whether there is an association between these conditions, plasma homocysteine (Hcy), serum methylmalonic acid, serum cobalamin and blood folate concentrations were measured. Gastritis was indirectly diagnosed by measuring serum antibodies against H,K-ATPase, Helicobacter pylori and intrinsic factor, using enzyme-linked immunosorbent assays. The studied groups consisted of 47 patients with Alzheimer’s disease (AD), 9 with AD pathology in combination with additive vascular lesions, 59 with vascular dementia, 8 who were cognitively impaired, and 101 control cases. Plasma Hcy concentrations were significantly elevated in the dementia groups, with the highest levels in patients with vascular pathology. We conclude that hyperhomocysteinemia is a common finding in patients with dementia disorders of different etiologies. The markers for gastritis did not contribute to an elucidation of a possible connection between this condition, dementia disorders, or cobalamin/folate deficiency.

  • 11. Sagar, M
    et al.
    Bertilsson, L
    Stridsberg, M
    Kjellin, A
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Seensalu, R
    Omeprazole and CYP2C19 polymorphism: Effects of long-term treatment on gastrin, pepsinogen I, and chromogranin A in patients with acid related disorders2000In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 14, no 11, p. 1495-1502Article in journal (Refereed)
    Abstract [en]

    Background: The polymorphic enzyme CYP2C19 is of importance for the metabolism and effects of omeprazole during short-term treatment. Aim: To investigate the relationship between CYP2C19 genotype and the effects of long-term omeprazole treatment. Material and methods: A total of 180 patients with acid related disorders were genotyped for wild type and mutated CYP2C19 alleles by allele-specific PCR amplification. Gastrin and chromogranin A were assessed by radioimmunoassays, and pepsinogen I and H. pylori serology were assessed by ELISA methods. Results: In 108 of the patients, who received a single dose of 20 mg omeprazole, there was no difference in gastrin and chromogranin A concentrations between the three CYP2C19 genotypes. In 72 patients on long-term treatment (> 1 year) with 20 mg omeprazole daily, serum gastrin as well as plasma chromogranin A concentrations (mean ▒ s.e.) were both about threefold higher in the wild type/mutated (52.1 ▒ 7.6 pM and 7.3 ▒ 1.3 nM (n = 19), respectively) compared to wild type/wild type (14.7 ▒ 0.9 pM and 2.5 ▒ 0.1 nM (n = 52), respectively, both comparisons P = 0.0001). In a single mutated/mutated patient on long-term treatment, both gastrin and chromogranin A were high (88 pM and 13.7 nM, respectively). Serum pepsinogen I concentration was significantly lower in wild type/mutated (n = 19) patients on long-term treatment, compared with the corresponding wild type/wild type (n = 49) group (147 ▒ 19 ╡g/L vs. 193 ▒ 12 ╡g/L, P = 0.04). Conclusion: Patients with one (and probably also with two) mutated CYP2C19 allele(s) on long-term treatment with omeprazole had significantly affected serum gastrin and pepsinogen I and plasma chromogranin A concentrations compared with patients with two normal alleles. This indicates that changes in gastric mucosal morphology during omeprazole treatment might be dependent upon the degree of the individual's capacity to metabolize omeprazole.

  • 12.
    Sundbom, M.
    et al.
    Department of Surgery, University Hospital, Uppsala, Sweden, Department of Surgery, University Hospital, S-751 85 Uppsala, Sweden.
    Mårdh, Erik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Ohrvall, M.
    Öhrvall, M., Dept. of Pub. Hlth./Caring Sciences, University Hospital, Uppsala, Sweden.
    Gustavsson, S.
    Department of Surgery, University Hospital, Uppsala, Sweden.
    Reduction in serum pepsinogen I after Roux-en-Y gastric bypass2003In: Journal of Gastrointestinal Surgery, ISSN 1091-255X, E-ISSN 1873-4626, Vol. 7, no 4, p. 529-535Article in journal (Refereed)
    Abstract [en]

    The excluded stomach after Roux-en-Y gastric bypass (RYGBP) cannot be readily examined by endoscopy for obvious anatomic reasons. Thus it is difficult to monitor possible changes in the gastric mucosa. However, the type and severity of gastritis can now be assessed by a combination of serologic tests: pepsinogen I and antibodies to Helicobacter pylori and H,K-ATPase. Morbidly obese patients were examined before and 1 to 4 years after surgery. A group of 34 patients (mean age 39 years, BMI 44 kg/m2) underwent RYGBP, another group of 30 patients (mean age 42 years, BMI 44 kg/m2) had simple gastric restriction and served as control subjects. All patients, except one in the control group, had normal titers of pepsinogen I before surgery. One year after RYGBP, pepsinogen I levels were significantly reduced, as compared to the control group (P<0.0001), and remained low throughout the study. The control group had stable pepsinogen I levels. In both groups, few patients had increased titers of H. pylori or H,K-ATPase antibodies, but these abnormalities remained unchanged. Low pepsinogen I levels, similar to those we observed in our RYGBP patients, have been linked to chronic atrophic gastritis. However, the absence of food stimulation in the excluded stomach could also be a reason for the low pepsinogen I levels. © 2003 The Society for Surgery of the Alimentary Tract, Inc.

  • 13. Taniguchi, K
    et al.
    Kaya, S
    Yokoyama, T
    Abe, K
    Katoh, T
    Yazawa, M
    Hayashi, Y
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    New aspects of Na/K-ATPase, Acid labile ATP and/or ADP/Pi binding to the tetraprotomer2000In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 78, no 1, p. 447Pos-Conference paper (Other academic)
  • 14. Taniguchi, Kazuya
    et al.
    Kaya, Shunji
    Abe, Kazuhiro
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    The oligomeric nature of Na/K-transport ATPase2001In: Journal of Biochemistry (Tokyo), ISSN 0021-924X, E-ISSN 1756-2651, Vol. 129, no 3, p. 335-342Article in journal (Refereed)
    Abstract [en]

    Since the discovery of Na/K-ATPase, evidence has accumulated to suggest that 1 mol of ATP hydrolysis occurs via the Na+-occluded ADP-sensitive phosphoenzyme, the K+-sensitive phosphoenzyme and the K+-occluded enzyme accompanying active transport of 3Na+ and 2K+ according the Post-Albers scheme. However, some controversial issues have arisen concerning whether the functional unit of the enzyme is an a▀-protomer or a much higher oligomer, which would be related to the mechanism of transport, either sequential or simultaneous. Detailed studies of oligomer interaction and the reactivity of the enzyme and a comparison of the extent of phosphorylation with ligand-binding capacities in the presence or absence of ATP hydrolysis and others strongly suggest that the functional unit of the enzyme in the membrane is a tetraprotomer, (a▀)4. They also suggest that each reaction intermediate of the Post-Albers scheme, respectively, reflects half of the site property of the intermediate and that another half binds ATP. These data may be useful not only to answer the long-standing question of whether the mechanism functions in the presence of both Na+ and K+ but also contribute to a better understanding of the mechanism of P-type pump ATPase in general.

  • 15.
    Tiveljung, Annika
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Borch, Kurt
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Jonasson, Jon
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Mårdh, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Petersson, Fredrik
    Ryhov Hospital, Jönköping.
    Monstein, Hans-Jürg
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Identification of Helicobacter in gastric biopsies by PCR based on 16S rDNA sequences: a matter of little significance for the prediction of H. pylori-associated gastritis?1998In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 47, no 8, p. 695-704Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to correlate molecular evidence of the presence of Helicobacter pylori in gastric biopsy samples, based on analysis of 16S rDNA, vacuolating toxin (vacA), urease A (ureA) and cagA genes, with the clinical, histological and serological findings in patients with H. pylori-associated gastritis. Fresh biopsy samples were collected from the gastric antrum and corpus of 22 asymptomatic volunteers with or without H. pylori-associated gastritis. Total DNA was extracted from the biopsy material and subjected to 16S rDNA PCR amplification, Southern blotting and 16S rDNA sequence analysis of the PCR products. The vacA, ureA and cagA genes were characterised by PCR amplification and Southern blot analysis. Based on partial 16S rDNA sequence analysis, DNA belonging to the genus Helicobacter was detected in gastric biopsy samples from 20 of 22 subjects, including seven of nine histologically and serologically normal controls. Six of 20 partial 16S rDNA sequences revealed variations within variable regions V3 and V4 that deviated from those of the H. pylori type strain ATCC 4350T and, therefore, possibly represented other species of Helicobacter. VacA genes identical with those of the type strain were found predominantly in the subjects with H. pylori gastritis, and all the patients except one were found to be cagA-positive. There was no evidence of false positive PCR reactions. In conclusion, the PCR-based molecular typing methods used here were apparently too sensitive when applied to the detection of H. pylori in human gastric tissues. The lack of quantitative analysis makes them inappropriate as clinical tools for the diagnosis of H. pylori-associated gastritis, despite the fact that they provide a qualitative and sensitive tool for the detection and characterisation of H. pylori in the gastrointestinal tract.

  • 16.
    Tømmerås, Karin
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Ay, Juliyana
    Discovery, Research Area CV & GI, AstraZeneca R&D Mölndal, Mölndal, Sweden.
    Cabero, José Luis
    Discovery, Research Area CV & GI, AstraZeneca R&D Mölndal, Mölndal, Sweden.
    Sundler, Frank
    Department of Physiological Sciences, Section for Neuroendocrine Cell Biology, Lund University, Lund, Sweden.
    Mårdh, Sven
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Effects of Extracellular Matrix Proteins on Development of Fetal Rat Gastric Epithelial Cells in CultureManuscript (preprint) (Other academic)
    Abstract [en]

    Undifferentiated fetal gastric epithelial cells and stem cells of adult gastric glands give rise to surface mucous, parietal, mucous neck, zymogenic, caveolated, and endocrine cells by yet-unknown mechanisms. Our aim was to establish an in vitro model for investigating the effects of extracellular matrix proteins on development of gastric epithelial cells, and to determine whether collagen type I affects growth and maturation of undifferentiated epithelial cells. Fetal rat gastric cells were isolated and then cultured for 15 days on uncoated glass coverslips or on collagen types I or IV, fibronectin, or laminin. The appearance of epithelial cells was investigated by means of Alcian blue-periodic acid Schiff (AB-PAS) staining, inununostaining for cytokeratin, H,K-ATPase and chromogranin A, acridine orange accumulation, and by transmission and scamting electron microscopy. AB-PAS-positive cells containing mucous-type granules were detected. These mucoid cells were abundant on uncoated coverslips and collagen, but scarce on fibronectin and laminin. No cytokeratin, H,K-ATPase or chromogranin A, or increased acridine orange accumulation in response to secretagogues were observed. Rarely, endocrine cells were observed by electron microscopy. In conclusion, undifferentiated epithelial cells did proliferate and differentiate, and mucoid and endocrine cells matured in the established in vitro system. Moreover, development of mucoid cells from undifferentiated gastric epithelial cells was stimulated by collagen matrices but inhibited by fibronectin and laminin.

  • 17.
    Tømmerås, Karin
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Cabero, José Luis
    Department of Cell Biology and Biochemistry, AstraZeneca R&D, Mölndal, Sweden.
    Mårdh, Sven
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Expression of extracellular matrix proteins in the fetal rat gastric mucosa2000In: Anatomy and Embryology, ISSN 0340-2061, E-ISSN 1432-0568, Vol. 201, no 3, p. 149-156Article in journal (Refereed)
    Abstract [en]

    At gestational day 16 the epithelium of the rat stomach consists of a stratified layer of undifferentiated cells, and two days later glandular structures appear. The present study was carried out to identify extracellular matrix proteins that could be involved in the epithelial cell proliferation and differentiation processes that occur in the fetal rat stomach during this period. For comparative purposes the expression of the same components in the adult gastric mucosa was examined. Pregnant Sprague-Dawley rats received an intraperitoneal injection of 5-bromo-2’-deoxyuridine to label proliferating cells. One, 3.5, or 6 h post-injection the stomachs were excised and immediately frozen. The specimens were sectioned and stained with hematoxylin and eosin or for 5-bromo-2’-deoxyuridine, cytokeratin no. 8, H,K-ATPase, and the extracellular matrix proteins fibronectin, laminin, and collagens type I and IV. A stratified layer of proliferating cells was observed in the epithelium of the fetal stomachs, while in adult stomachs proliferating cells were detected in the isthmus/neck region of the glands. Cytokeratin, an epithelial cell marker, was sparse at gestational day 16 but abundant both at gestational day 18 and in the isthmus/neck region of gastric glands of the adult stomach. The parietal cell marker H,K-ATPase could not be detected in the fetal stomachs during this period. Fibronectin was observed in the stroma of both fetal and adult stomachs. Collagen type I could only be detected in the stroma close to the oesophagus at gestational day 16. Two days later, collagen type I was abundant in the lamina propria, the submucosa and in the serosa of the fetal stomachs. In adult tissue collagen type I was detected in the surface epithelium, the submucosa and in the serosa of the stomach. Collagen type IV and laminin were expressed in the lamina propria, the basement membranes around blood vessels, muscle cells, and nerve bundles, as well as in the serosa of both 16- and 18-day-old fetal and adult rat stomachs. In conclusion, a high cell proliferation rate was observed in the epithelium at both gestational days 16 and 18. The increased expression of cytokeratin observed during this period indicates that the epithelial character of the embryonic cells becomes more distinct, while the remarkable change in the expression of collagen type I might reflect an important role of collagen type I in the development of the gastric epithelium.

  • 18.
    Tømmerås, Karin
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Chen, Y.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Rhedin, M.
    Department of Cell Biology, Astra Hässle AB, Mölndal, Sweden.
    Cabero, J. L.
    Department of Cell Biology, Astra Hässle AB, Mölndal, Sweden.
    Mårdh, Sven
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Proliferation and differentiation of cells from explants of fetal rat stomach1997In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 159, no 2, p. 155-161Article in journal (Refereed)
    Abstract [en]

    The current understanding of the mechanisms controlling the proliferation and differentiation of the stem cells of the gastric oxyntic glands is limited. The aim of the present study was to develop a method for investigating proliferation and differentiation of undifferentiated cells from fetal rat stomach. Outgrowth of cells was initiated from explants of 16-day-old fetal rat stomachs. At this stage of the fetal development the gastric epithelial cells are undifferentiated. The explants were cultured in DMEM/F-12 medium supplemented with fetal calf serum only, or fetal calf serum combined with either hydrocortisone or pentagastrin. Morphological characterization by means of light microscopy, dye staining and immunostaining was used to identify the growing cells. Both hydrocortisone and pentagastrin accelerated the differentiation towards H,K-ATPase-positive cells, mucus-producing cells and other epithelial cells. H,K-ATPase-positive cells, which were identified by immunostaining with a monoclonal antibody reacting with the α-subunit of the H,K-ATPase, grew on top of the confluent layer of epithelioid and fibroblastoid cells. With this method in vitro investigations of the mechanisms of proliferation and differentiation of gastric mucosal cells are possible. Although by different mechanisms, both hydrocortisone and pentagastrin appear to play a regulatory role in these processes.

  • 19.
    Tømmerås, Karin
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Hammer, Pål
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Sundler, Frank
    Department of Physiological Sciences, Section of Neuroendocrine Cell Biology, Lund University, Lund, Sweden.
    Borch, Kurt
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Mårdh, Sven
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Cabero, José Lius
    Discovery, Research Area CV & GI, AstraZeneca R&D Mölndal, Mölndal, Sweden.
    Immunolocalization of Cholecystokinin-2 Receptors in Rat Gastric Mucosa2002In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, no 9, p. 1017-1024Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Gastrin exerts trophic effects on the gastric mucosa by mechanisms not yet completely elucidated. Our aim was to localize the cholecystokinin-2 (CCK2) receptor in epithelial cells of foetal and adult rat stomachs in order to determine the cell types that are directly affected by gastrin.

    METHODS: Gastric tissue was subjected to indirect double immunofluorescence staining with antiserum against the C-terminal decapeptide of the CCK2 receptor and antibodies against 5' bromo-2-deoxyuridine, which had been injected into the rats I h before they were killed, the acid pump H,K-ATPase, the membrane-cytoskeletal linker ezrin, pepsin/pepsinogen or histidine decarboxylase.

    RESULTS: Undifferentiated foetal gastric epithelial cells expressed CCK2 receptors, whereas stem cells of adult gastric glands did not exhibit immunoreactivity. However, other epithelial cells in the progenitor zone of adult gastric glands did express CCK2 receptors. Some of these cells were faintly stained for H,K-ATPase; pepsin/pepsinogen was also detected in this region. Parietal cells in the isthmus/pit region of the glands contained ezrin, and some showed weak immunoreactivity for the CCK2 receptor. As expected, enterochromaffin-like cells also expressed CCK2 receptors.

    CONCLUSION: Our findings are consistent with the hypothesis that a CCK2 receptor mediates direct effects of gastrin on gastric epithelial cells during both stomach organogenesis and adult life.

  • 20. Yokohama, T
    et al.
    Kaya, S
    Abe, K
    Taniguchi, K
    Katoh, T
    Yazawa, M
    Hayashi, Y
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Acid-labile ATP and/or ADP/Pi binding to the tetraprotomeric form ofNa/K-ATPase accompanying catalytic phosphorylation-dephosphorylation cycle.1999In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 274, p. 31792-31794Article in journal (Refereed)
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