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  • 1.
    Andersson, Peter
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Kullman, Eric
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Halldestam, Ingvar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Einarsson, Curt
    Borch, Kurt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Bouveret's syndrome followed by gallstone entrapment in the stomach: An uncommon cause of upper gastrointestinal bleeding and gastric retention2000Ingår i: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 166, nr 2, s. 183-185Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    [No abstract available]

  • 2.
    Borch, Kurt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Ventrikelcancer - förändringar mot en bättre prognos.2000Ingår i: Incitament, ISSN 1103-503X, Vol. 7, s. 569-573Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 3.
    Borch, Kurt
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Ahrén, Bo
    Ahlman, Håkan
    Falkmer, Sture
    Granérus, Göran
    Grimelius, Lars
    Gastric carcinoids: Biologic behavior and prognosis after differentiated treatment in relation to type2005Ingår i: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 242, nr 1, s. 64-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To analyze tumor biology and the outcome of differentiated treatment in relation to tumor subtype in patients with gastric carcinoid. Background: Gastric carcinoids may be subdivided into ECL cell carcinoids (type 1 associated with atrophic gastritis, type 2 associated with gastrinoma, type 3 without predisposing conditions) and miscellaneous types (type 4). The biologic behavior and prognosis vary considerably in relation to type. Methods: A total of 65 patients from 24 hospitals (51 type 1, 1 type 2, 4 type 3, and 9 type 4) were included. Management recommendations were issued for newly diagnosed cases, that is, endoscopic or surgical treatment of type 1 and 2 carcinoids (including antrectomy to abolish hypergastrinemia) and radical resection for type 3 and 4 carcinoids. Results: Infiltration beyond the submucosa occurred in 9 of 51 type 1, 4 of 4 type 3, and 7 of 9 type 4 carcinoids. Metastases occurred in 4 of 51 type 1 (3 regional lymph nodes, 1 liver), the single type 2 (regional lymph nodes), 3 of 4 type 3 (all liver), and 7 of 9 type 4 carcinoids (all liver). Of the patients with type 1 carcinoid, 3 had no specific treatment, 40 were treated with endoscopic or surgical excision (in 10 cases combined with antrectomy), 7 underwent total gastrectomy, and 1 underwent proximal gastric resection. Radical tumor removal was not possible in 2 of 4 patients with type 3 and 7 of 9 patients with type 4 carcinoid. Five- and 10-year crude survival rates were 96.1% and 73.9% for type 1 (not different from the general population), but only 33.3% and 22.2% for type 4 carcinoids. Conclusion: Subtyping of gastric carcinoids is helpful in the prediction of malignant potential and long-term survival and is a guide to management. Long-term survival did not differ from that of the general population regarding type 1 carcinoids but was poor regarding type 4 carcinoids. Copyright © 2005 by Lippincott Williams & Wilkins.

  • 4.
    Borch, Kurt
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Grodzinsky, Ewa
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Petersson, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi.
    Jönsson, Kjell-Åke
    Mårdh, Sven
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi.
    Valdimarsson, Trausti
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi.
    Prevalence of coeliac disease and relations to Helicobacter pylori infection and duodenitis in a Swedish adult population sample: A histomorphological and serological survey2000Ingår i: InflammoPharmacology, ISSN 0925-4692, E-ISSN 1568-5608, Vol. 8, nr 4, s. 341-350Artikel i tidskrift (Refereegranskat)
    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.

  • 5.
    Borch, Kurt
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Jönsson, Björn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kärlkirurgi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Tarpila, Erkki
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Hand och plastikkirurgi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Franzén, Thomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Berglund, J
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kärlkirurgi. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Kullman, Eric
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Franzén, L
    Changing pattern of histological type, location, stage and outcome of surgical treatment of gastric carcinoma2000Ingår i: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 87, nr 5, s. 618-626Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There are indications that some features of gastric carcinoma are changing, with a possible impact on prognosis. The aim of this study was to examine any changes in type, location, stage, resection rate, postoperative mortality rate or prognosis for patients with gastric carcinoma in a well defined population. Methods: During 1974-1991, 1161 new cases of gastric adenocarcinoma were diagnosed in Ostergotland County, Sweden. Tumour location, Lauren histological type, tumour node metastasis (TNM) stage, radicality of tumour resection and postoperative complications were recorded after histological re-evaluation of tissue specimens and examination of all patient records. Dates of death were obtained from the Swedish Central Bureau of Statistics. Time trends were studied by comparing the intervals 1974-1982 (period 1) and 1983-1991 (period 2). Results: The proportion of diffuse type of adenocarcinoma increased (from 27 to 35 per cent), while that of mixed type decreased (from 16 to 9 per cent) and that of intestinal type was unchanged. The proportion of tumours located in the proximal two-thirds of the stomach increased (from 32 to 42 per cent) and the proportion of patients with tumours in TNM stage IV decreased (from 32 to 25 per cent). Overall tumour resection rates were unchanged, although the proportion of radical total gastrectomies increased (from 36 to 50 per cent). Excluding tumours of the cardia or gastric remnant after previous ulcer surgery, the 5-year relative survival rate after radical resection increased from 25 to 36 per cent and the postoperative mortality rate decreased for both radical (from 11 to 4 per cent) and palliative (from 18 to 6 per cent) resection. Conclusion: The patterns of tumour histology, location and stage of gastric carcinoma have changed in the authors' region. These changes were paralleled by a significant improvement in survival and postoperative mortality rates.

  • 6.
    Borch, Kurt
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, K.-A.
    Zdolzek, J.
    Halldestam, Ingvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi.
    Kullman, Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Prevalence of gallstone disease in a Swedish population sample: Relations to occuption, childbirth, health status, life style, medications and blood lipids1998Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 33, nr 11, s. 1219-1225Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There are only a few Swedish studies on the prevalence of gallstone disease in selected age groups, and none including possible risk factors. Methods: Of a population sample of 1200 individuals (age, 35-85 years), 857 participated in the study. The study subjects were asked to answer a questionnaire about potential risk factors (occupation, childbirth, life style, and so forth), symptoms, and quality of life. Cholecystectomy had previously been done in 115 subjects, leaving 742 for ultrasound examination of the gallbladder. Results: The prevalence of gallstone disease increased with age, and at 75 years or more, 53% of the women and 32% of the men either had gallstones or had previously undergone cholecystectomy (32% and 13%, respectively). When comparing subjects with and without gallstones, there were no differences with regard to any variable, including blood lipid levels. The odds ratio of previous cholecystectomy was increased in subjects with an occupation requiring no specific education and reduced in subjects using wine or spirits every week. The odds ratio of abdominal pain was increased after previous cholecystectomy. Women in this group also experienced a lower quality of life. Conclusions: The age and sex distribution of gallstone disease was in the order of the magnitude seen in other Scandinavian countries. None of the studied variables differed between subjects with and without gallstones. Subjects previously operated on with cholecystectomy did worse with regard to symptoms and quality of life.

  • 7.
    Borch, Kurt
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    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-style2000Ingår i: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 45, nr 7, s. 1322-1329Artikel i tidskrift (Refereegranskat)
    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.

  • 8.
    Borch, Kurt
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Petersson, Fredrik
    Kronisk gastrit - en asymptomatisk folksjukdom.2000Ingår i: Incitament, ISSN 1103-503X, Vol. 7, s. 558-562Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 9.
    Borch, Kurt
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Skarsgard, J
    Franzén, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    Mårdh, Sven
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi.
    Rehfeld, JF
    Benign gastric polyps - Morphological and functional origin2003Ingår i: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 48, nr 7, s. 1292-1297Artikel i tidskrift (Refereegranskat)
    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.

  • 10.
    Escobar Kvitting, John-Peder
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Sandström, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Thorelius, Lars
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Medicinsk radiologi.
    Kullman, Eric
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Borch, Kurt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Radiofrequency ablation of a liver metastasis complicated by extensive liver necrosis and sepsis caused by gas gangrene2006Ingår i: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 139, nr 1, s. 123-125Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    [No abstract available]

  • 11.
    Halldestam, Ingvar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Enell, E.-L.
    Kullman, Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Development of symptoms and complications in individuals with asymptomatic gallstones2004Ingår i: British Journal of Surgery, ISSN 0007-1323, Vol. 91, nr 6, s. 734-738Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Gallbladder stones are common in the developed world. Complications of gallstones contribute substantially to healthcare costs and may be life threatening. The identification of individuals likely to develop complications would be of benefit in clinical practice as elective cholecystectomy could then be performed.

    Methods: Seven hundred and thirty-nine subjects aged 35-85 years from the general population were screened for gallbladder problems by ultrasonography and questionnaire assessment of putative risk factors and digestive symptoms. Gallstones, cholesterolosis or sludge in the gallbladder were diagnosed in 123 (16·3 per cent) of 739 subjects, 120 of whom were followed for a median of 87 (range 3-146) months to May 2003 or until treatment was required.

    Results: Fourteen patients were admitted to hospital and treated for gallstone-related complications or symptoms. The cumulative risk of being treated during the first 5 years after detection of asymptomatic gallstones was 7·6 per cent and there was no indication of this risk levelling off. There were no significant differences between treated and untreated subjects with regard to digestive symptoms or any of the risk factors monitored at the initial screening, although treated subjects were significantly younger than those who were not treated.

    Conclusion: Nearly one in ten individuals with asymptomatic gallbladder stones in the general population may be expected to develop symptoms or complications that require treatment within 5 years. Age may be inversely related to the incidence of complications.

  • 12.
    Halldestam, Ingvar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Kullman, Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Incidence of and potential risk factors for gallstone disease in a general population sample2009Ingår i: BRITISH JOURNAL OF SURGERY, ISSN 0007-1323, Vol. 96, nr 11, s. 1315-1322Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Several epidemiological studies have been published, but there are few reports on relations between gallstone incidence, symptomatology and risk factors. Methods: Of 621 randomly selected individuals aged 35-85 years in a general population who been screened previously, with ultrasonography and found to have no gallbladder stones, 503 (81.0 per cent) were re-examined after a minimum interval of 5 years. At baseline and re-examination, heredity for gallstone disease was explored and body mass index, digestive symptoms including abdominal pain, quality of life, alcohol and smoking habits, use of non-steroidal anti-inflammatory drugs and oestrogen, parity and blood lipid levels were recorded. Results: Forty-two (8.3 per cent) of the 503 subjects developed stones. Subjects were followed for a total of 3025.8 person-years, yielding an incidence for newly developed gallstones of 1.39 per 100 person-years. A positive association for gallstone development,was found only for length of follow-up and plasma low-density lipoprotein-cholesterol levels at baseline. Weekly alcohol consumption was inversely related to gallstone development. Conclusion: The incidence of gallstones in this population was 1.39 per 100 person-years. Gallstone development was related to length of follow-up and LDL-cholesterol levels, and inversely related to alcohol consumption.

  • 13.
    Halldestam, Ingvar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Kullman, Eric
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Incidence of gallstone disease in a general population sample: relations to symptomatology and potential risk factors2008Artikel i tidskrift (Refereegranskat)
  • 14.
    Halldestam, Ingvar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Kullman, Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Defined indications for elective cholcystectomy for gallstone disease2008Ingår i: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 95, nr 5, s. 620-626Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: This study examined symptomatology and quality of life following elective cholecystectomy for symptomatic gallstone disease with defined indications for surgery.

    Methods: In this prospective study of 200 consecutive patients (161 women; median age 46·5 (range 24-79) years), strict indications for elective cholecystectomy were stipulated. Digestive symptoms and quality of life were recorded with a self-administered questionnaire before and at 3 and 12 months after surgery.

    Results: Of 149 patients who experienced abdominal pain with typical location before surgery, 136 (91·3 per cent) reported total remission or reduced frequency of that type of pain 12 months later. Of 35 patients who reported atypical or multiple pain location before operation, 27 (77 per cent) experienced reduced frequency or disappearance of that type of pain. Frequency of pain episodes, atypical or multiple pain location, specific food intolerance and frequency of disturbing abdominal gas at baseline correlated positively with the frequency of abdominal pain episodes at 12 months after surgery. There was a tendency towards an inverse relation to age.

    Conclusion: The frequency of persistent abdominal pain after elective cholecystectomy was low among patients with typical pain location before surgery. Atypical pain location, and frequent pain episodes before operation significantly reduced the chance of becoming pain-free.

  • 15.
    Hellqvist, Eva
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Morad, Vivian
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    IGHV3-21 stereotyped subset-2 chronic lymphocytic leukemia cells make autoantibodies that bind to an 11.5kDa gastric mucosal antigenManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background: The immunoglobulin heavy chain variable region (IGHV) gene mutational status is an important prognostic factor in chronic lymphocytic leukemia (CLL). Patients with mutated IGHV genes show significantly longer survival than unmutated cases. CLL patients with mutated IGHV3-21 genes, however, have a shorter survival compared to other mutated CLL cases. Recently, we showed that CLL cells react with oxidized epitopes exposed on apoptotic cells and bacteria. The gastric mucosal reactivity was of special interest to further characterize in detail.

    Methods: We collected corpus biopsies from seven Helicobacter pylori (H.p.)+ study subjects withnon-atrophic gastritis, six subjects with H.p.- atrophic gastritis, eight subjects with H.p.+ atrophicgastric and from eight controls without gastritis. The binding pattern of CLL subset-2 IGHV3-21antibodies was analyzed by immunohistochemistry and the antigen was biochemically purified byaffinity chromatography.

    Results: The subset-2 IGHV3-21 Abs bound to mucosal glands in 18 of 29 cases regardless of H.p.status or diagnosis. It also showed staining of connective tissue in all of the biopsies. The antigen waspurified and a protein of 11.5 kDa MW was isolated.

    Conclusion: The results from this study indicate that IGHV3-21 subset-2 CLL Abs bind an 11.5kDaprotein present in gastric mucosal glands or connective tissue. This autoantigen has no associationwith H.p. since it is present in normal, non-atrophic H.p.+ and atrophic H.p.+/H.p.- gastric mucosafrom corpus. The exact nature of the 11.5 kDa protein is currently under detailed structure massspectrometry analysis in order to reveal whether bacterial mimicry is the mechanism behind theinduction of this particular autoantibody.

  • 16.
    Karlsson, Anneli
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Ryberg, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk mikrobiologi.
    Dehnoei, Marjan Nosouhi
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk mikrobiologi.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Monstein, Hans-Jürg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk mikrobiologi.
    Association between cagA and vacA genotypes and pathogenesis in a Helicobacter pylori infected population from South-eastern Sweden2012Ingår i: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 12, nr 129Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    UNLABELLED: ABSTRACT:

    BACKGROUND: Chronic gastritis, peptic ulcer disease, and gastric cancer have been shown to be related to infection with Helicobacter pylori (H. pylori). Two major virulence factors of H. pylori, CagA and VacA, have been associated with these sequelae of the infection. In this study, total DNA was isolated from gastric biopsy specimens to assess the cagA and vacA genotypes.

    RESULTS: Variations in H. pylori cagA EPIYA motifs and the mosaic structure of vacA s/m/i/d regions were analysed in 155 H. pylori-positive gastric biopsies from 71 individuals using PCR and sequencing. Analysis of a possible association between cagA and vacA genotypes and gastroduodenal pathogenesis was made by logistic regression analysis. We found that H. pylori strains with variation in the number of cagA EPIYA motif variants present in the same biopsy correlated with peptic ulcer, while occurrence of two or more EPIYA-C motifs was associated with atrophy in the gastric mucosa. No statistically significant relation between vacA genotypes and gastroduodenal pathogenesis was observed.

    CONCLUSIONS: The results of this study indicate that cagA genotypes may be important determinants in the development of gastroduodenal sequelae of H. pylori infection. In contrast to other studies, vacA genotypes were not related to disease progression or outcome. In order to fully understand the relations between cagA, vacA and gastroduodenal pathogenesis, the mechanisms by which CagA and VacA act and interact need to be further investigated.

  • 17.
    Karlsson, Anneli
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Ryberg, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Nosouhi Dehnoei, Marjan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Monstein, Hans-Jürg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk mikrobiologi.
    Variation in number of cagA EPIYA-C phosphorylation motifs between cultured Helicobacter pylori and biopsy strain DNA2012Ingår i: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 12, nr 1, s. 175-179Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Helicobacter pylori cagA gene encodes a cytotoxin which is activated by phosphorylation after entering the host epithelial cell. Phosphorylation occurs on specific tyrosine residues within EPIYA motifs in the variable 3'-region. Four different cagA EPIYA motifs have been defined according to the surrounding amino acid sequence; EPIYA-A, -B, -C and -D. Commonly, EPIYA-A and -B are followed by one or more EPIYA-C or -D motif. Due to observed discrepancies in cagA genotypes in cultured H. pylori and the corresponding DNA extracts it has been suggested that genotyping assays preferentially should be performed directly on DNA isolated from biopsy specimens. Gastric biopsies randomly selected from a Swedish cohort were homogenised and used for both direct DNA isolation and for H. pylori specific culturing and subsequent DNA isolation. In 123 of 153 biopsy specimens, the cagA EPIYA genotypes were in agreement with the corresponding cultured H. pylori strains. A higher proportion of mixed cagA EPIYA genotypes were found in the remaining 30 biopsy specimens. Cloning and sequencing of selected cagA EPIYA amplicons revealed variations in number of cagA EPIYA-C motifs in the mixed amplicons. The study demonstrates that culturing of H. pylori introduces a bias in the number of EPIYA-C motif. Consistent with other H. pylori virulence genotyping studies, we suggest that cagA EPIYA analysis should be performed using total DNA isolated from biopsy specimens.

  • 18.
    Kechagias, Stergios
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Akutkliniken.
    Botella, Sofia
    Petersson, Fredrik
    Borch, Kurt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Ericson, Ann-Charlott
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi.
    Expression of vanilloid receptor-1 in epithelial cells of human antral gastric mucosa2005Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 40, nr 7, s. 775-782Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. Capsaicin, which acts by binding to the vanilloid receptor-1 (VR1), has been shown to give protection against gastric mucosal injury and to enhance healing of gastric ulcers. Although VR1 has recently been reported to be present in non-neural tissues, it is primarily considered to be expressed in nociceptor sensory neurons of small diameter. The aim of the present study was to evaluate the distribution of VR1 immunoreactivity in the normal human gastric mucosa. Material and methods. Ten volunteers underwent gastroscopy and biopsies were obtained from the corpus and the antrum. The specimens were labelled immunohistochemically using polyclonal goat anti-VR1 and evaluated at the light- and electronmicroscopic level. Moreover, post-embedding immunogold labelling was performed and subsequently analysed at the electronmicroscopic level. Results. In the antrum, VR1 immunoreactivity was located in epithelial cells that fulfilled the criteria of endocrine cells of the "open type". These cells were located primarily in the neck region of the antral glands and the labelling was concentrated on the microvilli of these cells. At the ultrastructural level, round granulae with differences in electron density were identified in the basal compartment of the labelled cells. VR1 immunoreactivity was also identified in axon-like structures that were located in the lamina propria, often in close vicinity of vessels, in the corpus as well as in the antrum. Conclusions. VR1-immunoreactivity was evident in antral epithelial cells exhibiting characteristics of endocrine-like cells. This may indicate that the gastroprotective effects of capsaicin, which hitherto have been attributed to primary afferent neurons, at least partly may be explained by an action on specific epithelial cells in the antrum. © 2005 Taylor & Francis.

  • 19.
    Kechagias, Stergios
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, Kjell-Åke
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Borch, Kurt
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Jones, A. Wayne
    Linköpings universitet, Institutionen för medicin och hälsa, Rättskemi. Linköpings universitet, Hälsouniversitetet.
    Influence of Age, Sex, and Helicobacter pylori Infection Before and After Eradication on Gastric Alcohol Dehydrogenase Activity2001Ingår i: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 25, nr 4, s. 508-512Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Gastric alcohol dehydrogenase may contribute to the metabolism of orally ingested ethanol and decrease the bioavailability of the drug. The aims of this study were to assess the impact of Helicobacter pylori infection and its eradication on gastric alcohol dehydrogenase activity and to relate the findings to gastric histology. Furthermore, the role of age- and sex-related differences in gastric alcohol dehydrogenase activity were studied.

    Methods: A total of 76 subjects (39 women and 37 men) underwent upper gastrointestinal endoscopy, and biopsies were obtained from the corpus and antrum. The specimens were used for determining gastric alcohol dehydrogenase activity, histological examination, and urease testing. Subjects with H. pylori infection (n= 36) received medication to eradicate the infection, and repeat biopsies were taken 2 and 12 months later.

    Results: No significant difference in gastric alcohol dehydrogenase activity was found between men and women (p > 0.05). Gastric alcohol dehydrogenase activity did not differ significantly between the subjects older than 50 years (n= 39) and those 50 years or younger (n= 37). In subjects with H. pylori infection, gastric alcohol dehydrogenase activity was significantly reduced in the antrum (p < 0.05). After eradication of H. pylori, alcohol dehydrogenase activity in the antrum increased significantly within 2 months (p < 0.01). Antral biopsies with the most pronounced inflammation and histological changes had significantly decreased alcohol dehydrogenase activity (p < 0.05). In contrast, no significant differences were found in corpus.

    Conclusions: H. pylori infection is associated with decreased antral alcohol dehydrogenase activity, which seems to be related to the severity of the inflammatory changes in the mucosa. Eradication of H. pylori normalizes antral alcohol dehydrogenase activity within 2 months.

  • 20. Lindell, Gert
    et al.
    Borch, Kurt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Tingstedt, Bobby
    Enell, Eva-Lena
    Ihse, Ingemar
    Management of cancer of the ampulla of Vater: Does local resection play a role?2003Ingår i: Digestive Surgery, ISSN 0253-4886, E-ISSN 1421-9883, Vol. 20, nr 6, s. 511-515Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The clinical outcome of patients with ampullary carcinoma is significantly more favorable than for patients with pancreatic head carcinoma. The Whipple procedure is the operation of choice for both diagnoses. Still local resection is recommended in selected cases. The aim of this study was to assess the outcome of local resection of cancer of the ampulla of Vater by comparison with pancreaticoduodenectomy. Method: 92 patients with cancer of the ampulla of Vater treated between 1975 and 1999 with local resection (n = 10), pancreatic resection (n = 49) or laparotomy and no resection (n = 33) were studied retrospectively. The main outcome measures were postoperative morbidity and mortality, surgical radicality and long-term survival. Results: The postoperative complication rate was significantly lower after local resection (p = 0.036) whereas mortality did not differ between the 2 resection groups. UICC stages were less advanced in the local resection group (p < 0.04). Still, the frequency of positive resection margins and RO resections was the same in both groups, as was long-term survival. Local recurrence was diagnosed in 8/10 (80%) patients after local and in 11/49 (22%) patients after pancreatic resection (p = 0.001). Conclusion: Pancreaticoduodenectomy is the preferred operation for cancer of the ampulla of Vater in patients who are fit for the procedure. Local resection plays a limited role in carefully selected patients.

  • 21.
    Mjönes, Anna-Britta
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Tibbling, Lita
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland. Östergötlands Läns Landsting.
    Ledin, Torbjörn
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Hultcrantz, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Öronkliniken US.
    Hoarseness and misdirected swallowing in patients with hiatal hernia2007Ingår i: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 264, nr 12, s. 1437-1439Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The purpose of this study was to elucidate whether misdirected swallowing is an extra-laryngeal cause of hoarseness and investigate whether the prevalence of misdirected swallowing and hoarseness in patients with hiatal hernias differ from those with and without pathological gastroesophageal reflux (GER). One hundred and ninety eight patients with hiatal hernias diagnosed via esophageal manometry and pH-reflux test and 262 subjects in the general population who did not have a hiatal hernia at endoscopy, filled in a questionnaire about symptoms on hoarseness, misdirected swallowing, and heartburn. Hoarseness (35%), misdirected swallowing to the larynx (MSL; 35%), misdirected swallowing to the nose (MSN; 22%) and heartburn (85%) were significantly more common in patients with hiatal hernia than in controls (13, 5, 1, and 6%, respectively, P<0.001). MSL and MSN in the patient group were significantly interrelated (P<0.0001). Hoarseness and MSL were not significantly associated (P<0.076). Hoarseness and MSL were as common in the hernia group with normal GER, as in the group with pathological GER. There is a predisposition for hoarseness and MSL in patients with hiatal hernias, but the cause-and-effect relationship is unclear. Hoarseness does not seem to be caused by pathological GER.

  • 22.
    Monstein, Hans-Jurg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk mikrobiologi.
    Karlsson, Anneli
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Ryberg, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk mikrobiologi.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Application of PCR amplicon sequencing using a single primer pair in PCR amplification to assess variations in Helicobacter pylori CagA EPIYA tyrosine phosphorylation motifs2010Ingår i: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 3, nr 35Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    The presence of various EPIYA tyrosine phosphorylation motifs in the CagA protein of Helicobacter pylori has been suggested to contribute to pathogenesis in adults. In this study, a unique PCR assay and sequencing strategy was developed to establish the number and variation of cagA EPIYA motifs.

    Findings

    MDA-DNA derived from gastric biopsy specimens from eleven subjects with gastritis was used with M13- and T7- sequence-tagged primers for amplification of the cagA EPIYA motif region. Automated capillary electrophoresis using a high resolution kit and amplicon sequencing confirmed variations in the cagA EPIYA motif region. In nine cases, sequencing revealed the presence of AB, ABC, or ABCC (Western type) cagA EPIYA motif, respectively. In two cases, double cagA EPIYA motifs were detected (ABC/ABCC or ABC/AB), indicating the presence of two H. pylori strains in the same biopsy.

    Conclusion

    Automated capillary electrophoresis and amplicon sequencing using a single, M13- and T7-sequence-tagged primer pair in PCR amplification enabled a rapid molecular typing of cagA EPIYA motifs. Moreover, the techniques described allowed for a rapid detection of mixed H. pylori strains present in the same biopsy specimen.

  • 23.
    Monstein, Hans-Jurg
    et al.
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Tiveljung, Annika
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Kraft, C. H.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Borch, Kurt
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Jon
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Profiling of bacterial flora in gastric biopsies from patients with Helicobacter pylori-associated gastritis and histologically normal control individuals by temperature gradient gel electrophoresis and 16S rDNA sequence analysis2000Ingår i: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 49, nr 9, s. 817-822Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to establish bacterial profiles in gastric biopsy specimens from patients with Helicobacter pylori-associated gastritis by means of temporal temperature gradient gel electrophoresis (TTGE) of PCR-amplified 16S rDNA fragments. Specimens from eight patients with asymptomatic gastritis and five histologically normal controls revealed a Helicobacter-specific band in the TTGE profile with increased amounts of Helicobacter-specific DNA in the biopsies from most of the gastritis patients. DNA from other genera including Enterococcus, Pseudomonas, Streptococcus, Staphylococcus and Stomatococcus was also found in the stomach. In the absence of gastric inflammation, Helicobacter spp. appeared to be part of a complex, presumably indigenous microbial flora found in the biopsy specimens from the stomach.

  • 24.
    Mårdh, Erik
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi.
    Mårdh, Sven
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi.
    Mårdh, Bibbi
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi.
    Borch, Kurt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Diagnosis of gastritis by means of a combination of serological analyses2002Ingår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 320, nr 1-2, s. 17-27Artikel i tidskrift (Refereegranskat)
    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.

  • 25.
    Nägga, Katarina
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Geriatrik. Linköpings universitet, Hälsouniversitetet.
    Rajani, Rupesh
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Mårdh, Erik
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Borch, Kurt
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Mårdh, Sven
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Marcusson, Jan
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Geriatrik. Linköpings universitet, Hälsouniversitetet.
    Cobalamin, folate, methylmalonic acid, homocysteine, and gastritis markers in dementia2003Ingår i: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 16, nr 4, s. 269-275Artikel i tidskrift (Refereegranskat)
    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.

  • 26. Petersson, Fredrik
    et al.
    Borch, Kurt
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Franzén, L. E.
    Prevalence of subtypes of intestinal metaplasia in the general population and in patients with autoimmune chronic atrophic gastritis2002Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, nr 3, s. 262-266Artikel i tidskrift (Refereegranskat)
    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.

  • 27.
    Petersson, Fredrik
    et al.
    Pathology Research Department, Ryhov Hospital, Jönköping.
    Borch, Kurt
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Franzén, Lennart
    Department of Pathology, Medical Centre Hospital, Örebro, Sweden.
    Gastric epithelial proliferation and p53 and p21 expression in a general population sample: relations to age, sex, and mucosal changes associated with H. pylori infection2002Ingår i: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 47, nr 7, s. 1558-1566Artikel i tidskrift (Refereegranskat)
    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.

  • 28.
    Petersson, Fredrik
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Rehfeld, J.F.
    Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Denmark.
    Franzén, Lennart E.
    Department of Pathology, University Hospital, Örebro, Sweden.
    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 levels2009Ingår i: International Journal of Clinical and Experimental Pathology, ISSN 1936-2625, E-ISSN 1936-2625, Vol. 2, nr 3, s. 239-248Artikel i tidskrift (Refereegranskat)
    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.

  • 29.
    Petersson, Fredrik
    et al.
    Pathology Research Department, Ryhov Hospital, Jönköping, Sweden and Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
    Franzén, Lennart E
    Department of Pathology, Medical Centre Hospital, Örebro, Sweden.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    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 gastritis2010Ingår i: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 55, nr 1, s. 46-53Artikel i tidskrift (Refereegranskat)
    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.

  • 30.
    Redéen, Stefan
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Petersson, F
    Jönsson, K-Å
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Borch, Kurt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Relationship of gastroscopic features to histological findings in gastritis and Helicobacter pylori infection in a general population sample2003Ingår i: Endoscopy, ISSN 0013-726X, E-ISSN 1438-8812, Vol. 35, nr 11, s. 946-950Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and study aim: Various gastroscopic features may be interpreted as signs of gastritis, but the significance of such features in relation to histomorphology is uncertain. The aim of this study was to determine how macroscopic findings were related to histomorphological changes and the presence of Helicobacter pylori in the gastric mucosa, in a sample of the general population. Subjects and methods: 488 adult individuals, randomly selected from a general population, were screened with gastroscopy and biopsy. The macroscopic features recorded were erythema (diffuse, spotty, linear), erosions, absence of rugae in the gastric corpus, and presence of visible vessels. Gastritis was classified microscopically according to the Sydney system. The presence of H. pylori was determined histologically and using the urease test on fresh biopsy specimens. Results: The sensitivity and specificity of absence of rugae for moderate to severe atrophic gastritis in the gastric corpus were 67% and 85%, respectively. Corresponding valuers for severe atrophy were 90% and 84%. The sensitivity and specificity of the presence of visible vessels for moderate to severe atrophy in the corpus were 48% and 87%, and for severe atrophy the values were 80% and 87%, respectively. Considering the antrum, the sensitivity and specificity of the presence of visible vessels for moderate to severe atrophy was 14% and 91%, respectively. With regard to chronic inflammation (moderate to severe in the corpus or antrum), none of the features, alone or in combination, showed a sensitivity of more than 56%. No endoscopic features (alone or in combination) showed a sensitivity of more than 57 % for H. pylori infection. Conclusions: Except for the absence of rugae and visible vessels in the gastric corpus, macroscopic features as observed during gastroscopy are of very limited value in the evaluation of whether or not gastritis or H. pylori infection are present. This is in accordance with most previous studies in patient populations, and it must be emphasized that the diagnosis of gastritis should be based on histological examination of the gastric mucosa.

  • 31.
    Redéen, Stefan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Petersson, Fredrik
    National University Health System, Singapore.
    Kechagias, Stergios
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Mårdh, Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Natural history of chronic gastritis in a population-based cohort2010Ingår i: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, ISSN 0036-5521, Vol. 45, nr 5, s. 540-549Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To describe and explore the natural history of Helicobacter pylori infection and chronic gastritis in terms of gastric mucosal atrophy and ulcer development over time in a population-based cohort. Material and methods. A population-based cohort of 314 volunteers was re-screened (median follow-up interval of 8.4 years) with gastroduodenoscopy with biopsy, assessment of H. pylori status, analysis of pepsinogens, and monitoring of a nonsteroidal anti-inflammatory drug (NSAID) use and alcohol and smoking habits. Results. The incidence of duodenal or prepyloric ulcer was 0.45 per 100 person years and was associated with weekly NSAID use (odds ratios, OR 27.8), weekly alcohol consumption (OR 19.4) and smoking (OR 31.0), but not with H. pylori status. De novo infection with H. pylori was not observed, and the infection had disappeared in 11 of 113 subjects. Among subjects with chronic gastritis, the incidence of atrophy of the corpus mucosa was 1.4 per 100 person years. Atrophy development was related to age (OR 1.23) and to the severity of chronic inflammation in the corpus mucosa at baseline (OR 8.98). Substituting atrophy for subnormal S-pepsinogen I/S-pepsingen II gave similar results. Conclusions. In this cohort, the minimum incidence of ulcer was 0.45 per 100 person years. Smoking, alcohol, and NSAIDs, but not H. pylori infection were significant risk factors. The incidence of atrophy of the corpus mucosa was 1.4 per 100 person years with a positive relation to age and to the degree of chronic inflammation at baseline. Atrophy was stationary in advanced stages.

  • 32.
    Redéen, Stefan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Petersson, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Rättsmedicin. Linköpings universitet, Hälsouniversitetet.
    Törnkrantz, E.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi.
    Levander, H.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi.
    Mårdh, Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Reliability of diagnostic tests for Helicobacter pylori infection2011Ingår i: Gastroenterology Research and Practice, ISSN 1687-6121, E-ISSN 1687-630X, Vol. 2011, nr 940650Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Helicobacter pylori (H.pylori) infection is very common worldwide. A reliable diagnosis is crucial for patients with H.pylori related diseases. At follow-up it is important to confirm that eradication therapy has been successful. There is no established gold standard for the diagnosis of H.pylori infection.

    Material and Methods: A sample of 304 volunteers from the general population was screened for H.pylori infection with serology, 13C-urea breath test (UBT), rapid urease test (RUT) on fresh biopsy, culture from biopsy and histological examination. Each method was tested against the other methods (except serology) taken together as gold standard.

    Result: The sensitivity was 0.99 for serology 0.92 for UBT, 0.96 for RUT, 0.99 for culture and 0.95 for histological examination. Corresponding specificities were 0.82, 0.94, 0.93, 0.90 and 0.92, respectively. The accuracy was 0.86 for serology, 0.94 for UBT, 0.94 for RUT, 0.93 for culture and 0.93 for histology. There was a strong correlation between the results of UBT and histological scores for H.pylori colonization as well as between the results of UBT and the scores of RUT.

    Conclusion: There were only minor differences in accuracy between three invasive tests for H.pylori infection in this population. RUT may be recommended as first choice since a result is obtained within hours. The accuracy of UBT was comparable to the invasive tests and it is recommended for situations when endoscopy is not needed.

  • 33.
    Redéen, Stefan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Ryberg, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Petersson, Fredrik
    Ryhov Hospital.
    Eriksson, Olle
    Linköpings universitet, Institutionen för datavetenskap, Statistik. Linköpings universitet, Filosofiska fakulteten.
    Nägga, Katarina
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Geriatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Geriatriska kliniken.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Homocysteine Levels in Chronic Gastritis and Other Conditions: Relations to Incident Cardiovascular Disease and Dementia2010Ingår i: DIGESTIVE DISEASES AND SCIENCES, ISSN 0163-2116, Vol. 55, nr 2, s. 351-358Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Homocysteine levels in circulation are determined by several factors and hyperhomocysteinemia is reportedly associated with cardiovascular diseases and dementia. The aim of this study is to determine the relation of chronic gastritis and other conditions to homocysteine levels and their relation to incident cardiovascular diseases and dementia. Methods An adult population-based cohort (N = 488) was screened for H. pylori infection, gastro-duodenitis ( endoscopic biopsies), disease history, and lifestyle factors. Blood samples were analyzed for pepsinogen I and II ( gastric function), vitamin B12, folate, homocysteine, and cystatin C ( renal function). The methylenetetrahydrofolate reductase C677T polymorphism reportedly associated with hyperhomocysteinemia was analyzed by pyrosequencing. Incident cardiovascular diseases and dementia were monitored during a median follow-up interval of 10 years. Results At baseline, there was a positive relation of S-homocysteine to male gender, age, S-cystatin C, methylenetetrahydrofolate reductase 677TT genotype and atrophic gastritis. During follow-up, cardiovascular diseases occurred in 101/438 and dementia in 25/488 participants, respectively. Logistic regression analysis ( adjusting for gender, age at baseline, follow-up interval, BMI, smoking, alcohol consumption, NSAID use, P-cholesterol, and P-triglycerides) showed an association of S-homocysteine higher than 14.5 mu mol/l to cardiovascular diseases (OR 2.05 [95% c.i. 1.14-3.70]), but not to dementia overall. Conclusions Gender, age, vitamin B12, folate, renal function, atrophic gastritis and the methylenetetrahydrofolate 677TT genotype were significant determinants of homocysteine levels, which were positively related to incident cardiovascular diseases.

  • 34.
    Ryberg, Anna
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Monstein, Hans-Jürg
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk mikrobiologi.
    Expression of multiple forms of 3'-end variant CCK2 receptor mRNAs in human pancreatic adenocarcinoma2011Ingår i: BMC research notes, ISSN 1756-0500, Vol. 4, s. 131-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Two main types of receptors for gastrin and cholecystokinin (CCK) have been cloned and identified. CCK1 (CCK-A) receptors are expressed in the pancreas, the gallbladder, and parts of the brain, while CCK2 (CCK-B/gastrin) receptors (CCK2R) are expressed in gastric glands and in most of the brain. A splice variant of the CCK2R designated CCKRi4sv (CCK-C), which is constitutively expressed in human pancreatic cancer cells, has also been described. The purpose of the present investigation was to study CCK2R, CCK2i4svR, and gastrin mRNA expression in human pancreatic adenocarcinoma on the assumption that co-expression of CCK2R and gastrin or constitutive CCK2i4svR mRNA expression plays a pivotal role in the progression of pancreatic cancer.

    FINDINGS: PCR amplification using CCK2R specific primer-pairs, followed by ethidium-bromide stained agarose gel electrophoresis revealed the expression of wild-type CCK2R mRNA in 12 of 17 biopsy specimens. A CCK2R intron 4 specific nested PCR assay revealed that CCK2i4svR mRNA was expressed in only one of the biopsy specimen. The authenticity of PCR amplicons was confirmed by cloning of selected amplicons and DNA sequence analysis. Moreover, we found that hitherto undescribed multiple forms of 3'-end variant CCK2R mRNAs with various deletions in the retained intron 4 and exon 5, tentatively generating truncated proteins, were expressed in the pancreatic adenocarcinomas.

    CONCLUSION: Cloning and DNA sequencing of selected amplicons revealed that CCK2R and multiple CCK2i4svR-like mRNAs are expressed in human pancreatic adenocarcinoma. The originally described CCK2i4svR mRNA was only expressed in one of 17 tumours and appears to be rarely expressed in pancreatic adenocarcinoma. We report that CCK2R- and gastrin mRNA co-expression may play a role in a portion, but not in all of these tumours, and that aberrant splicing takes places in these tissues generating multiple forms of 3'-end variant CCK2R mRNAs.

  • 35.
    Ryberg, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Borch, Kurt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Sun, Yi-Qian
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Monstein, Hans-Jürg
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk mikrobiologi.
    Concurrent genotyping of Helicobacter pylori virulence genes and human cytokine SNP sites using whole genome amplified DNA derived from minute amounts of gastric biopsy specimen DNA2008Ingår i: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 8, s. 175-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Bacterial and cellular genotyping is becoming increasingly important in the diagnosis of infectious diseases. However, difficulties in obtaining sufficient amount of bacterial and cellular DNA extracted from the same human biopsy specimens is often a limiting factor. In this study, total DNA (host and bacterial DNA) was isolated from minute amounts of gastric biopsy specimens and amplified by means of whole genome amplification using the multiple displacement amplification (MDA) technique. Subsequently, MDA-DNA was used for concurrent Helicobacter pylori and human host cellular DNA genotyping analysis using PCR-based methods.

    Results: Total DNA was isolated from gastric biopsy specimens of 12 subjects with gastritis and 16 control subjects having a normal mucosa. The DNA was amplified using a multiple displacement amplification (MDA) kit. Next, concurrent genotyping was performed using H. pylori-specific virulence gene PCR amplification assays, pyrosequencing of bacterial 16S rDNA and PCR characterisation of various host genes. This includes Interleukin 1-beta (IL1B) and Interferon-gamma receptor (IFNGR1) SNP analysis, and Interleukin-1 receptor antagonist (IL1RN) variable tandem repeats (VNTR) in intron 2. Finally, regions of the vacA-gene were PCR amplified using M13-sequence tagged primers which allowed for direct DNA sequencing, omitting cloning of PCR amplicons. H. pylori specific multiplex PCR assays revealed the presence of H. pylori cagA and vacA genotypic variations in 11 of 12 gastritis biopsy specimens. Using pyrosequencing, 16S rDNA variable V3 region signatures of H. pylori were found in 11 of 12 individuals with gastritis, but in none of the control subjects. Similarly, IL1B and IFNGR1-SNP and IL1RN-VNTR patterns could be established in all individuals. Furthermore, sequencing of M13-sequence tagged vacA-PCR amplicons revealed the presence of highly diverse H. pylori vacA-s/i/m regions.

    Conclusion: The PCR-based molecular typing methods applied, using MDA-amplified DNA derived from small amounts of gastric biopsy specimens, enabled a rapid and concurrent molecular analysis of bacterial and host genes in the same biopsy specimen. The principles and technologies used in this study could also be applied to any situation in which human host and microbial genes of interest in microbial-host interactions would need to be sequenced.

  • 36.
    Sjöstedt, Camilla
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Hannestad, Ulf
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi.
    Franzén, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    Söderholm, Johan D
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Borch, Kurt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Atrophic gastritis is associated with increased sucrose permeability related to chronic inflammation2005Ingår i: Digestion, ISSN 0012-2823, E-ISSN 1421-9867, Vol. 72, nr 4, s. 201-206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Different theories have been presented to explain how atrophic gastritis may lead to gastric cancer development. One contributing factor could be impaired function of the gastric mucosal barrier. The aim of this study was to investigate if there are changes in gastric mucosal permeability to sucrose in atrophic gastritis. Methods: The study comprised 22 patients with atrophic gastritis and 21 normal controls. Gastritis was classified according to the Sydney system from endoscopic biopsies of the gastric corpus and antrum. All subjects were exposed to oral sucrose load (100 g), and the fraction of sucrose excreted in urine was measured by gas chromatography-mass spectrometry. Results: The fraction of sucrose excreted in urine after oral load was significantly increased in atrophic gastritis compared with controls (median 0.08 vs. 0.04%, p = 0.003). Sucrose excretion was positively related to the degree of chronic inflammation (median fraction excreted: mild inflammation 0.06%, moderate inflammation 0.08%, severe inflammation 0.18%, p = 0.04) rather than to the degree of atrophy in the gastric mucosa. Occurrence of intestinal metaplasia was also associated with significantly higher sucrose excretion. However, in multivariate analysis, including intestinal metaplasia, only the degree of inflammation was positively related to sucrose excretion. Conclusion: Atrophic gastritis is associated with increased sucrose permeability, suggesting paracellular leakage of the gastric mucosa. This leakage seems to be related to the degree of inflammation rather than the degree of atrophy. The findings may have implications for the diseases and complications associated with atrophic gastritis. Copyright © 2005 S. Karger AG.

  • 37.
    Sun, Yi-Qian
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Girgensone, Ilze
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Leanderson, Per
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Petersson, Fredrik
    Pathology Research Department, Ryhov Hospital, Jönköping, Sweden.
    Borch, Kurt
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Effects of antioxidant vitamin supplements on Helicobacter pylori-induced gastritis in Mongolian gerbils2005Ingår i: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 10, nr 1, s. 33-42Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background.  Epidemiological studies show that high intake of food-bound vitamin C and E reduces the risk of gastric cancer. Whether dietary supplementation with antioxidant micronutrients interferes with Helicobacter pylori infection and associated diseases is unclear. The aim of this study was to investigate if dietary vitamin C or E supplementation influences the progression of gastritis, gastric mucosal nitrosative and oxidative protein damage, gastric mucosal lipid peroxidation, or gastric mucosal oxidative DNA damage in H. pylori-infected Mongolian gerbils.

    Materials and methods.  Gerbils were divided into four groups: H. pylori-infected animals fed with vitamin C- or vitamin E-supplemented food, and infected and uninfected animals given standard rodent food. Subgroups of animals were killed at different time-points until 52 weeks postinfection. Concentrations of 3-nitrotyrosine and thiobarbituric acid-reactive substances (TBARS) in the gastric mucosa were determined with an immunodot blot and a fluorometric method, respectively. Mucosal concentrations of carbonyl carbons on proteins and 8-hydroxydeoxyguanosine were determined by enzyme-linked immunosorbent assay. Gastritis was scored semiquantitatively.

    Results.  Vitamin supplements had no effect on the colonization with H. pylori. Vitamin C as well as vitamin E supplements reduced mucosal 3-nitrotyrosine concentrations to normal levels in infected animals. Vitamin E supplements decreased mucosal protein carbonyls and TBARS in short-term gastritis. In addition, vitamin C supplements caused attenuated mucosal oxidative DNA damage and milder mucosal inflammation in short-term gastritis.

    Conclusion.  Vitamin C or vitamin E supplementation leads to some short-term protective effects on H. pylori-induced gastritis in Mongolian gerbils. These effects seem to subside over time when the infection persists.

  • 38.
    Sun, Yi-Qian
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi.
    Monstein, Hans-Jurg
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Molekylärbiologiska tekniklaboratoriet.
    Ryberg, Anna
    Borch, Kurt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Multiple strand displacement amplification of DNA isolated from human archival plasma/serum: Identification of cytokine polymorphism by pyrosequencing analysis2007Ingår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 377, nr 1-2, s. 108-113Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: DNA isolation from formalin-fixed paraffin-embedded tissue appears to be problematic due to degradation caused by fixative. Our aim was to investigate if the isolated genomic DNA from archival plasma/serum, combined with multiple strand displacement amplification (MDA) can be used for genotyping. Methods: Nine archival plasma/serum samples and freshly frozen gastric biopsies from the same nine H. pylori-infected subjects were used for DNA isolation. Subsequently, MDA-DNA derived from the plasma/serum samples and DNA isolated from the antrum biopsies were analyzed by PCR amplification and pyrosequencing for the presence of interleukin-1beta gene (IL-1B) single nucleotide polymorphism (SNP). In addition, Southern blot and pyrosequencing analysis of H. pylori-specific PCR amplicons were performed. Results: IL-1B SNP profiles obtained from the plasma/serum MDA-DNA and antrum biopsy DNA were identical. A C/C genotype was observed in 7 of 9 samples, and 2 of 9 revealed a C/T genotype for IL-1B - 511. Similarly, 7 of 9 had a T/T, and 2 of 9 had a C/T genotype for IL-1B - 31, 4 of 9 had a C/C, 4 of 9 had a C/T, and 1 of 9 had a T/T genotype, respectively, for IL-1B + 3954. Moreover, pyrosequencing analysis revealed the presence of H. pylori 26695 and J99-like 16S rDNA variable V3 region sequence motifs in the antrum biopsies but not in the plasma/serum samples. Conclusions: We conclude that MDA combined with pyrosequencing enables a rapid and accurate molecular typing of cytokine single nucleotide polymorphisms from archival plasma/serum samples. © 2006 Elsevier B.V. All rights reserved.

  • 39.
    Sun, Yi-Qian
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Monstein, Hans-Jürg
    Östergötlands Läns Landsting, LMÖ - Laboratoriemedicin i Östergötland.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Petersson, Fredrik
    Pathology Research Department, Ryhov Hospital, Jönköping, Sweden.
    Borch, Kurt
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Profiling and identification of eubacteria in the stomach of Mongolian gerbils with and without Helicobacter pylori infection2003Ingår i: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 8, nr 2, s. 149-157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Mongolian gerbils are frequently used to study Helicobacter pylori-induced gastritis and its consequences. The presence of an indigenous bacterial flora with suppressive effect on H. pylori may cause difficulties with establishing this experimental model.

    Aim. The aim of the present study was to determine bacterial profiles in the stomach of Mongolian gerbils with and without (controls) H. pylori infection.

    Methods. Gastric tissue from H. pylori ATCC 43504 and CCUG 17874 infected and control animals were subjected to microbial culturing and histology. In addition, gastric mucosal samples from H. pylori ATCC 43504 infected and control animals were analyzed for bacterial profiling by temporal temperature gradient gel electrophoresis (TTGE), cloning and pyrosequencing of 16S rDNA variable V3 region derived PCR amplicons.

    Results. Oral administration of H. pylori ATCC 43504, but not CCUG 17874, induced colonization and gastric inflammation in the stomach of Mongolian gerbils. Temporal temperature gradient gel electrophoresis (TTGE) and partial 16S rDNA pyrosequencing revealed the presence of DNA representing a mixed bacterial flora in the stomach of both H. pylori ATCC 43504 infected and control animals. In both cases, lactobacilli appeared to be dominant.

    Conclusion. These findings suggest that indigenous bacteria, particularly lactobacilli, may have an impact on the colonization and growth of H. pylori strains in the stomach of Mongolian gerbils.

  • 40.
    Sun, Yi-Qian
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Petersson, Fredrik
    Pathology Research Department, Ryhov Hospital, Jönköping.
    Monstein, Hans-Jürg
    Östergötlands Läns Landsting, LMÖ - Laboratoriemedicin i Östergötland.
    Söderholm, Johan D
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Rehfeld, Jens F
    Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen.
    Borch, Kurt
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Long-term morpho-functional development of Helicobacter pylori-induced gastritis in Mongolian gerbils2005Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 40, nr 10, s. 1157-1167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    Epidemiological studies have shown that Helicobacter pylori infection with associated chronic gastritis is the main risk factor for development of gastric cancer. The aim of this study was to investigate the long-term development of H. pylori-induced gastritis in Mongolian gerbils in terms of morphology, gastrin secretion, epithelial proliferation and gene expression of pro-inflammatory cytokines.

    MATERIAL AND METHODS:

    A total of 133 gerbils were inoculated with H. pylori and 62 served as controls. The gerbils were killed at different time-points between 6 and 94 weeks after inoculation. Serum concentrations of anti-H. pylori IgG and gastrin were determined by enzyme-linked immunoabsorbent assay (ELISA) and radioimmunoassay (RIA), respectively. Epithelial proliferation was evaluated immunohistochemically after labeling with 5-bromo-2'-deoxy-uridine. Gene expression of beta-actin, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Histological parameters of gastritis were assessed semiquantitatively and expressed as a "gastritis score".

    RESULTS:

    Serum concentrations of anti-H. pylori IgG and gastrin increased over time. Epithelial proliferation in the antrum was increased 6 weeks after inoculation, followed by increased proliferation in the corpus 32 weeks after inoculation. Gene expression of IL-1beta and TNF-alpha were increased in H. pylori-infected gerbils. Beta-actin was not a reliable endogenous control for RT-PCR. With time, gastritis expanded from the antrum to the corpus and the gastritis score increased to reach a peak 32 weeks after inoculation. Pseudopyloric metaplasia (loss of specialized cells) was a characteristic feature in the corpus mucosa. Gastric ulcers, but neither dysplasia nor carcinoma, were observed during 94 weeks of infection.

    CONCLUSIONS:

    Long-term H. pylori infection in Mongolian gerbils led to progressive gastritis, glandular atrophy, hypergastrinemia, increased epithelial proliferation and elevated gene expression of pro-inflammatory cytokines.

  • 41.
    Sun, Yi-Qian
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Söderholm, Johan D
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Petersson, Fredrik
    Pathology Research Department, Ryhov Hospital, Jönköping, Sweden.
    Borch, Kurt
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Long-standing gastric mucosal barrier dysfunction in Helicobacter pylori-induced gastritis in Mongolian gerbils2004Ingår i: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 9, nr 3, s. 217-227Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Aims. Helicobacter pylori infection causes chronic gastritis and leads to peptic ulcer and gastric adenocarcinoma. An impaired gastric mucosal barrier could be involved in these processes. Our aim was to investigate gastric barrier function in H. pylori-induced gastritis.

    Methods.  Stripped gastric mucosal tissues of H. pylori-infected Mongolian gerbils (4 weeks and 70 weeks after inoculation, respectively) and controls were mounted in Ussing chambers. 51Cr-EDTA (paracellular probe) and horseradish peroxidase (HRP, protein antigen) were used to assess mucosal barrier function. The electrophysiological parameters of the mucosa (transepithelial potential, short circuit current, and transepithelial resistance) were monitored as measurements of barrier integrity and viability. Tissue histology was performed to assess inflammation.

    Results.  In the antrum, both short-term gastritis [4.68 (3.88–5.74) × 10−6 vs. control 2.86 (2.34–3.77) × 10−6 cm/s, p < .001] and gastritis of long-standing [5.72 (3.88–10.94) × 10−6 cm/s, p < .001 vs. control] showed increased permeability to 51Cr-EDTA. In long-standing antral gastritis there was also an increased HRP flux [9.01 (2.98–45.02) vs. control 0.52 (0.06–1.20) pmol/h/cm2, p < .001]. In the corpus, permeability to 51Cr-EDTA was increased only in long-standing gastritis [4.63 (3.64–7.45) × 10−6 vs. control 2.86 (2.12–3.98) × 10−6 cm/s, p < .01]. Gastric mucosal permeability to 51Cr-EDTA was correlated to histological inflammation and inflammatory activity. The levels of serum anti-H. pylori immunoglobulin G were positively correlated to HRP flux and 51Cr-EDTA permeation.

    Conclusions. Helicobacter pylori-induced gastritis in Mongolian gerbils was associated with a long-standing gastric mucosal barrier dysfunction. The barrier defect extended from the antrum into the corpus over time. This impaired barrier function may contribute to perpetuation of chronic inflammation and may be involved in H. pylori-associated carcinogenesis.

  • 42.
    Tiveljung, Annika
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Jonasson, Jon
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk mikrobiologi.
    Mårdh, Sven
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Petersson, Fredrik
    Ryhov Hospital, Jönköping.
    Monstein, Hans-Jürg
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk mikrobiologi.
    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?1998Ingår i: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 47, nr 8, s. 695-704Artikel i tidskrift (Refereegranskat)
    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.

  • 43.
    Tjomsland, Vegard
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Niklasson, Lina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Sandström, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Druid, Henrik
    Department of Oncology-pathology, Karolinska Institutet, Stockholm, Sweden.
    Bratthall, Charlotte
    Division of Oncology, Kalmar hospital, Kalmar, Sweden.
    Messmer, Davorka
    Cancer Center, University of California San Diego, La Jolla, USA.
    Larsson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Spångeus, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Pancreatic cancer microenvironment has a high degree of inflammation and infiltrating immune cells in its stroma2010Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Tumor microenvironment is composed of tumor cells, fibroblasts, and infiltrating immune cells, and other cellular components, which work together and create an inflammatory environment favoring tumor progression. The present study aimed to characterize the expression and location of immune cells and investigate inflammatory factors that influence pancreatic ductal adenocarcinoma (PDAC).

    Methods: qPCRs and immunohistological stainings were performed for inflammatory factors and immune cells localized in tumor tissues from patients with PDAC (N=30).

    Results: All PDAC tissues had significant increased levels of inflammatory and chemotactic factors such as IL-1α, COX-2, CXCL8, CCL2, and CCL20 as compared to controls. The PDAC stroma, i.e. the fibrosis surrounding the tumor, was the main producer of these factors with the exception of IL-1α, which was expressed by tumor cells and some infiltrating immune cells. The gene expression for immune cell specific markers CD163, CD1c, CD303, and CD8, corresponding to macrophages, myeloid dendritic cells (DCs), plasmacytoid DCs, and cytotoxic T lymphocytes (CTL), respectively, were all significantly increased in PDAC tissues. Immunostaining of the tumor tissue confirmed the elevated levels of infiltrating macrophages, DCs, mature DCs, and cytotoxic T lymphocytes (CTL). The different immune cells were in nearly all cases localized in the fibrotic tissue adjacent to tumor nests. Production of CXCL8 mRNA and protein by the stroma was dependent on the tumor expression of IL-1α. Of importance, we found a correlation in expression of the proinflammatory factor IL-1α and the PDAC patients’ survival time.

    Conclusion: PDAC cells seem to take advantage of IL-1α to create an inflammatory microenvironment with high degree of fibrosis and the ability to both recruit and activate immune cells and the level of inflammation in this environment influenced the clinical outcome for the patients. Therapies targeting the inflammation might be beneficial for the survival of patients with PDAC.

  • 44.
    Tjomsland, Vegard
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Niklasson, Lina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Sandström, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Druid, Henrik
    Karolinska Institute.
    Bratthall, Charlotte
    Kalmar Hospital.
    Messmer, Davorka
    University of Calif San Diego.
    Larsson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Spångeus, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    The Desmoplastic Stroma Plays an Essential Role in the Accumulation and Modulation of Infiltrated Immune Cells in Pancreatic Adenocarcinoma2011Ingår i: Clinical & Developmental Immunology, ISSN 1740-2522, E-ISSN 1740-2530, Vol. 2011, nr 212810Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Tumor microenvironment is composed of tumor cells, fibroblasts, and infiltrating immune cells, which all work together and create an inflammatory environment favoring tumor progression. The present study aimed to investigate the role of the desmoplastic stroma in pancreatic ductal adenocarcinoma (PDAC) regarding expression of inflammatory factors and infiltration of immune cells and their impact on the clinical outcome. The PDAC tissues examined expressed significantly increased levels of immunomodulatory and chemotactic factors (IL-6, TGF beta, IDO, COX-2, CCL2, and CCL20) and immune cell-specific markers corresponding to macrophages, myeloid, and plasmacytoid dendritic cells (DCs) as compared to controls. Furthermore, short-time survivors had the lowest levels of DC markers. Immunostainings indicated that the different immune cells and inflammatory factors are mainly localized to the desmoplastic stroma. Therapies modulating the inflammatory tumor microenvironment to promote the attraction of DCs and differentiation of monocytes into functional DCs might improve the survival of PDAC patients.

  • 45.
    Tjomsland, Vegard
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Sandström, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Spangeus, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Messmer, Davorka
    University of California.
    Emilsson, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Falkmer, Ursula
    Jonköping Hospital.
    Falkmer, Sture
    Jonköping Hospital.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Larsson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity?2010Ingår i: BMC CANCER, ISSN 1471-2407, Vol. 10, nr 87Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Dendritic cells (DCs) isolated from tumor bearing animals or from individuals with solid tumors display functional abnormalities and the DC impairment has emerged as one mechanism for tumor evasion from the control of the immune system. Ductal pancreatic adenocarcinoma (PDAC), the most common pancreatic cancer, is recognized as a very aggressive cancer type with a mortality that almost matches the rate of incidence. Methods: We examined the systemic influence ductal pancreatic adenocarcinoma ( PDAC) exerted on levels of peripheral blood DCs and inflammatory mediators in comparison to the effects exerted by other pancreatic tumors, chronic pancreatitis, and age-matched controls. Results: All groups examined, including PDAC, had decreased levels of myeloid DCs (MDC) and plasmacytoid DCs (PDC) and enhanced apoptosis in these cells as compared to controls. We found elevated levels of PGE2 and CXCL8 in subjects with PDAC, and chronic pancreatitis. Levels of these inflammatory factors were in part restored in PDAC after tumor resection, whereas the levels of DCs were impaired in the majority of these patients similar to 12 weeks after tumor removal. Our results prove that solid pancreatic tumors, including PDAC, systemically affect blood DCs. The impairments do not seem to be tumor-specific, since similar results were obtained in subjects with chronic pancreatitis. Furthermore, we found that PDAC patients with a survival over 2 years had significant higher levels of blood DCs compared to patients with less than one year survival. Conclusions: Our findings points to the involvement of inflammation in the destruction of the blood MDCs and PDCs. Furthermore, the preservation of the blood DCs compartment in PDAC patients seems to benefit their ability to control the disease and survival.

  • 46.
    Tjomsland, Vegard
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Spångeus, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Sandström, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Messmer, Davorka
    University of California San Diego, CA 92093, USA.
    Larsson, Marie
    University of California San Diego, CA 92093, USA.
    Semi Mature Blood Dendritic Cells Exist in Patients with Ductal Pancreatic Adenocarcinoma Owing to Inflammatory Factors Released from the Tumor2010Ingår i: PLOS ONE, ISSN 1932-6203, Vol. 5, nr 10Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Much evidence exists regarding the fact that blood DCs, both myeloid DCs (MDCs) and plasmacytoid DCs (PDCs), are negatively affected in different types of cancer, with both reduced numbers and impaired functionality. Functional impairment of DCs in patients with pancreatic ductal adenocarcinoma (PDAC), may contribute to the poor clinical outcome. The aim of this study was to examine the effects PDAC had on blood DCs and elucidate the underlying mechanism responsible for the DC impairment. Methodology/Principal Findings: We examined the systemic influence PDAC exerted on blood DCs by ex vivo measuring numerous activation and maturation markers expressed on these cells. Furthermore, the effect patient plasma and the inflammatory factors CXCL8 and PGE(2) had on purified MDCs and PDCs from healthy donors was assessed and compared to the DCs existing in PDAC patients. We found a partial maturation of the blood MDCs and PDCs in PDAC patients with significantly enhanced expression of CD83, CD40, B7H3, PDL-1, CCR6, and CCR7 and decreased expression of ICOSL, and DCIR. These changes lead to impairment in their immunostimulatory function. Furthermore, chronic pancreatitis gave rise to DCs with similar semi-mature phenotype as seen in PDAC. Low expression of ICOSL was associated with poor prognosis. We found that the mechanism underlying this semi-maturation of DCs was inflammatory factors existing in the PDAC patients plasma. Of note, PGE2, which is elevated PDAC patient plasma, was one contributing factor to the changes seen in MDCs and PDCs phenotype. Conclusion/Significance: Our findings point to a role for the systemic inflammation in transforming blood MDCs and PDCs into semi-mature cells in PDAC patients and we show a correlation between maturation status and clinical outcome. Thus, means to preserve a functional blood DC compartment in PDAC patients by diminishing the inflammation could facilitate their ability to control the disease and improve survival.

  • 47.
    Tjomsland, Vegard
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Spångeus, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Välilä, Johanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Sandström, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Druid, Henrik
    Department of Oncology-pathology, Karolinska Institutet, Stockholm, Sweden.
    Falkmer, Sture
    Department of Clinical Pathology, County Hospital Ryhov, Jönköping, Sweden.
    Falkmer, Ursula
    Department of Oncology, County Hospital Ryhov, Jönköping, Sweden.
    Messmer, Davorka
    Cancer Center, University of California San Diego, La Jolla, USA.
    Larsson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    IL-1α Sustains the Inflammation in Human Pancreatic Cancer Microenvironment by Targeting Cancer Associated Fibroblasts2010Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is dynamic with an extensive interaction between the stroma and tumor cells. Our aim for this study was to delineate the cross-talk between PDAC and cancer-associated fibroblasts (CAFs) with focus on the mechanism creating the chronic inflammatory tumor milieu. We assessed the effect cross talk between primary PDAC and CAF cell lines propagated from tumors had on the creation and sustenance of an inflammatory environment and what factors that were involved in establishing the inflammation.

    The coculture of PDAC and CAF cell lines, propagated from tumor tissues, enhanced the levels of inflammatory factors including IL-1α, IL-6, CXCL8, VEGFA, CCL20, and COX-2. The production of these factors correlated with the expression detected in vivo in PDAC tissues. The key producers of nearly all inflammatory factors were the CAFs and not the tumor cells.

    IL-1α was produced by the tumor cell lines, whereas almost all IL-1RI was expressed by CAFs thus corresponding to their in vivo expression profile in PDAC tissues, indicating a role for the IL-1 signaling cascade in a tumor favorable microenvironment. Neutralization of the IL-1α pathway efficiently diminished the cross talk induced production of inflammatory factors, both in stroma and tumor cells. These data suggest that the cross-talk between PDAC cells and the main stroma cell type, i.e. CAFs, is one contributing factor in the formation of the inflammatory tumor environment and we propose that the neutralization of IL-1α pathway might be a potential therapy for this cancer.

  • 48.
    Tjomsland, Vegard
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Spångeus, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Välilä, Johanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Sandström, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Borch, Kurt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Druid, Henrik
    Department of Oncology – Pathology, Karolinska Institutet, Stockholm.
    Falkmer, Sture
    Department of Clinical Pathology, County Hospital Ryhov, Jönköping.
    Falkmer, Ursula
    Department of Oncology, Aalborg University Hospital, Aalborg, Denmark.
    Messmer, Davorka
    Moores Cancer Center, University California San Diego, La Jolla, CA, USA.
    Larsson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär virologi. Linköpings universitet, Hälsouniversitetet.
    Interleukin 1α sustains the expression of inflammatory factors in human pancreatic cancer microenvironment by targeting cancer-associated fibroblasts2011Ingår i: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 13, nr 8, s. 664-675Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is dynamic with an extensive interaction between the stroma and tumor cells. The aim for this study was to delineate the cross-talk between PDAC and cancer-associated fibroblasts (CAFs) with focus on the mechanism creating the chronic inflammatory tumor milieu. We assessed the effects of the cross-talk between primary PDAC and CAF cell lines on the creation and sustenance of the inflammatory tumor microenvironment in pancreatic cancer. The coculture of primary PDAC and CAF cell lines enhanced the levels of inflammatory factors including IL-1á, IL-6, CXCL8, VEGFA, CCL20, and COX-2. CAFs were superior to tumor cells regarding the production of most inflammatory factors and tumor cell associated IL-1á was established as the initiator of the enhanced production of inflammatory factors through the binding of IL-1á to the active IL-1 receptor (IL-1R1) expressed predominantly by CAFs. Furthermore, we found a positive correlation between IL-1á and CXCL8 expression levels in PDAC tissues and correlation between IL-1á expression and the clinical outcome of the patients. This confirmed an important role for the IL-1 signaling cascade in the creation and sustenance of a tumor favorable microenvironment. Neutralization of the IL-1á signaling efficiently diminished the cross-talk induced production of inflammatory factors. These data suggest that the cross-talk between PDAC cells and the main stroma cell type, i.e. CAFs, is one essential factor in the formation of the inflammatory tumor environment and we propose that neutralization of the IL-1á signaling might be a potential therapy for this cancer.

  • 49.
    Tømmerås, Karin
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Hammer, Pål
    Linköpings universitet, Institutionen för biomedicin och kirurgi. Linköpings universitet, Hälsouniversitetet.
    Sundler, Frank
    Department of Physiological Sciences, Section of Neuroendocrine Cell Biology, Lund University, Lund, Sweden.
    Borch, Kurt
    Linköpings universitet, Institutionen för biomedicin och kirurgi. Linköpings universitet, Hälsouniversitetet.
    Mårdh, Sven
    Linköpings universitet, Institutionen för biomedicin och kirurgi. Linköpings universitet, Hälsouniversitetet.
    Cabero, José Lius
    Discovery, Research Area CV & GI, AstraZeneca R&D Mölndal, Mölndal, Sweden.
    Immunolocalization of Cholecystokinin-2 Receptors in Rat Gastric Mucosa2002Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, nr 9, s. 1017-1024Artikel i tidskrift (Refereegranskat)
    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.

  • 50. Veress, B
    et al.
    Franzén, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    Bodin, L
    Borch, Kurt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Duodenal intraepithelial lymphocyte-count revisited2004Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 39, nr 2, s. 138-144Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The number of intraepithelial lymphocytes in the duodenum was determined 30 years ago, the suggested normal upper limit being 40 lymphocytes per 100 epithelial cells. Methods: Duodenal mucosa was analysed from 18 healthy individuals and 56 consecutive patients biopsied because of epigastralgia (17 cases), diarrhoea (10 cases), oesophagitis (10 cases), iron-deficiency (9 cases) and B12-deficiency (10 cases) showing normal histology, along with 10 cases of active coeliac disease. The biopsies were fixed in 4% formalin overnight and embedded in paraffin. Three micrometre thick sections were stained with haematoxylin and eosin and CD3. At least 300 epithelial cells were counted, the number of intraepithelial lymphocytes was given as the mean/100 epithelial cells. Extensive statistical analyses were performed. Results: In the healthy individuals the mean number (s) of intraepithelial lymphocytes/100 epithelial cells was 10.8 (2.6) and 13.2 (3.8) in H&E and CD3 stained sections, respectively. The upper limit of the confidence interval for CD3 staining was 29. There was no significant difference between normal individuals and the clinical groups, with the exception of coeliac disease. Conclusion: Two-step analysis of intraepithelial lymphocyte-determination is suggested: (a) semi-quantitative estimate on H&E-stained sections (normal ratio of 1:5 between lymphocytes and enterocytes, upper normal limit 20 lymphocytes) and (b) CD3-staining and counting if intraepithelial lymphocytosis is suspected. The upper normal range of intraepithelial lymphocytes is set at 25 CD3+ lymphocytes/100 epithelial cells. Values between 25 and 29 are regarded as 'borderline' and 30 or more represent pathologic intraepithelial lymphocytosis in the duodenum.

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