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Biomedical subjects

Katri Kaukinen

Publications and source records attributed to Katri Kaukinen.

At least 19 recordsLinked to original sources
PubMed2006

Gene expression in TGFbeta-induced epithelial cell differentiation in a three-dimensional intestinal epithelial cell differentiation model.

BACKGROUND: The TGFbeta1-induced signal transduction processes involved in growth and differentiation are only partly known. The three-dimensional epithelial differentiation model, in which T84 epithelial cells are induced to differentiate either with TGFbeta1 or IMR-90 mesenchymal cell-secreted soluble factors, is previously shown to model epithelial cell differentiation seen in intestine. That model has not been used for large scale gene expression studies, such as microarray method. Therefore the gene expression changes were studied in undifferentiated and differentiated three-dimensional T84 cultures with cDNA microarray method in order to study the molecular changes and find new players in epithelial cell differentiation. RESULTS: The expression of 372 genes out of 5188 arrayed sequences was significantly altered, and 47 of them were altered by both mediators. The data were validated and the altered genes are presented in ontology classes. For the genes tested the expressions in protein level were in accordance with the mRNA results. We also found 194 genes with no known function to be potentially important in epithelial cell differentiation. The mRNA expression changes induced by TGFbeta1 were bigger than changes induced by soluble factors secreted by IMR-90 mesenchymal cells. The gene expression data was depicted in already known signaling pathway routes. CONCLUSION: Our results reveal potential new signaling pathways and several new genes affected by TGFbeta in epithelial cell differentiation. The differentiation induced by TGFbeta1 appears to be more potent than the differentiation induced by mesenchymal cells. This study indicates that our cell culture model is a suitable tool in studying regulatory mechanisms during epithelial cell differentiation in intestine. Furthermore the present results indicate that our model is a good tool for finding new players acting in the differentiation of epithelial cells.

Cell Culture Techniques↗
PubMed2005

Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells.

Claudin proteins comprise a recently described family of tight junction proteins that differentially regulate paracellular permeability. Since other tight junction proteins show alterations in distribution or expression in inflammatory bowel disease (IBD) we assessed expression of claudins (CL) 2, 3 and 4 in IBD. CL 2 was strongly expressed along the inflamed crypt epithelium, whilst absent or barely detectable in normal colon. In contrast, CL 3 and 4 were present throughout normal colonic epithelium and were reduced or redistributed in the diseased surface epithelium. In a T84-cell culture model of the gut barrier, paracellular permeability decreased with time after plating and correlated with a marked decrease in the expression of CL 2. Addition of IFNgamma/TNFalpha led to further decreases in CL 2 and 3, the redistrbution of CL 4 and a marked increase in paracellular permeability. Conversely, IL-13 dramatically increased CL 2, with little effect on CL 3 or 4, but also resulted in increased paracellular permeability. Expression of CL 2 did not correlate with proliferation or junctional reorganisation after calcium ion depletion. Re-expression of CL 2 in response to IL-13 was inhibited by phophatidylinositol 3 kinase inhibitor, LY294002, which also restored the ion permeability to previous levels. CL 2 expression could be stimulated in the absence of IL-13 by activation of phospho-Akt in the phophatidylinositol 3 kinase pathway. These results suggest that INFgamma/TNFalpha and IL-13 have differential effects on CL 2, 3 and 4 in tight junctions, which may lead to increased permeability via different mechanisms.

Base Sequence↗
PubMed2005

Coeliac disease, autoimmune diseases and gluten exposure.

OBJECTIVE: Gluten-free diet treatment has been proposed to prevent the development of autoimmune diseases in coeliac subjects. The aim here was to investigate the occurrence of autoimmune disorders in relation to gluten intake in coeliac patients in a well-defined area. MATERIAL AND METHODS: The frequency of autoimmune disorders was evaluated in 703 adults and children with coeliac disease and in 299 controls with normal duodenal histology. Incidence figures were given per 10,000 person-years. In logistic regression analysis, where the prevalence of autoimmune disorders was a dependent variable, the effect of age at end of follow-up, age at diagnosis of coeliac disease, actual gluten exposure time, gender and diagnostic delay were assessed. RESULTS: The prevalence of autoimmune diseases was significantly higher in coeliac subjects than in controls. In logistic regression analysis, age at end of follow-up, age at diagnosis of coeliac disease and female gender increased the risk of autoimmune disorders, whereas actual gluten exposure time reduced the risk; diagnostic delay had no effect. A similar, though not statistically significant, trend was seen in childhood coeliac disease to that in the whole study group. CONCLUSIONS: Despite that fact that patients with coeliac disease are at increased risk of various autoimmune conditions, the duration of gluten exposure seems not to be of crucial importance in the development of autoimmune diseases.

Adolescent↗
PubMed2005

Small-bowel mucosal transglutaminase 2-specific IgA deposits in coeliac disease without villous atrophy: a prospective and randomized clinical study.

OBJECTIVE: In coeliac disease, autoantibodies directed against transglutaminase 2 are produced in small-bowel mucosa, and they have been found to be deposited extracellularly. The aim of this study was to investigate whether such mucosal IgA deposits are important in the diagnostic work-up of early-stage coeliac disease without small-bowel mucosal villous atrophy. MATERIAL AND METHODS: Forty-one adults suspected of coeliac disease owing to increased density of mucosal gamma(delta)+ intraepithelial lymphocytes but normal villous morphology were randomized to gluten challenge or a gluten-free diet for 6 months. Clinically and histologically verified gluten dependency was compared with existence of small-bowel mucosal transglutaminase 2-specific extracellular IgA deposits and (coeliac disease-type) HLA DQ2 and DQ8; 34 non-coeliac subjects and 18 patients with classical coeliac disease served as controls. RESULTS: Of the 41 patients, 5 in the challenge group and 6 in the gluten-free diet group were clinically gluten sensitive; all 11 had HLA DQ2 or DQ8. Ten of these 11 patients showed transglutaminase 2-targeted mucosal IgA deposits, which were dependent on gluten consumption. Minimal IgA deposits were seen in only 3 out of 30 patients with suspected coeliac disease without any clinically detected gluten dependency. The deposits were found in all classical coeliac patients and in none of the non-coeliac control subjects. CONCLUSIONS: Clinically pertinent coeliac disease exists despite normal small-bowel mucosal villous architecture. Mucosal transglutaminase 2-specific IgA deposits can be utilized in detecting such patients with genetic gluten intolerance.

Adult↗
PubMed2005

Antiendomysial and antihuman recombinant tissue transglutaminase antibodies in the diagnosis of coeliac disease: a biopsy-proven European multicentre study.

OBJECTIVE: To investigate the value of serum antitissue transglutaminase IgA antibodies (IgA-TTG) and IgA antiendomysial antibodies (IgA-EMA) in the diagnosis of coeliac disease in cohorts from different geographical areas in Europe. The setting allowed a further comparison between the antibody results and the conventional small-intestinal histology. METHODS: A total of 144 cases with coeliac disease [median age 19.5 years (range 0.9-81.4)], and 127 disease controls [median age 29.2 years (range 0.5-79.0)], were recruited, on the basis of biopsy, from 13 centres in nine countries. All biopsy specimens were re-evaluated and classified blindly a second time by two investigators. IgA-TTG were determined by ELISA with human recombinant antigen and IgA-EMA by an immunofluorescence test with human umbilical cord as antigen. RESULTS: The quality of the biopsy specimens was not acceptable in 29 (10.7%) of 271 cases and a reliable judgement could not be made, mainly due to poor orientation of the samples. The primary clinical diagnosis and the second classification of the biopsy specimens were divergent in nine cases, and one patient was initially enrolled in the wrong group. Thus, 126 coeliac patients and 106 controls, verified by biopsy, remained for final analysis. The sensitivity of IgA-TTG was 94% and IgA-EMA 89%, the specificity was 99% and 98%, respectively. CONCLUSIONS: Serum IgA-TTG measurement is effective and at least as good as IgA-EMA in the identification of coeliac disease. Due to a high percentage of poor histological specimens, the diagnosis of coeliac disease should not depend only on biopsy, but in addition the clinical picture and serology should be considered.

Adolescent↗
PubMed2005

Celiac disease: from inflammation to atrophy: a long-term follow-up study.

OBJECTIVES: Celiac disease develops gradually from lymphocytosis, crypt hyperplasia and minor villous atrophy to overt villous atrophy. It IS NOT known how such minor mucosal changes predict eventual celiac disease. The aim of this study was to evaluate the role of intraepithelial lymphocytosis and marginally decreased villous height/crypt depth ratio in the development of overt villous atrophy in a long-term follow-up. METHODS: The authors evaluated 980 small bowel biopsies of children who had previously been studied and found to be histologically negative for celiac disease between 1976 and 1992. Villous height/crypt depth ratio and the number of intraepithelial lymphocytes were measured in these initial biopsies. Cases with slight biopsy changes were identified for further study and sex and age matched subjects with normal biopsies from same group were selected as controls. They all were asked to submit serum samples for gliadin, endomysial and tissue transglutaminase antibodies 8 to 28 years after the initial biopsy. Those with positive screening tests were asked to undergo endoscopy and small intestinal biopsy. RESULTS: 236 cases with slight changes were identified, and 236 with normal mucosa served as controls; 76 cases and 68 controls participated in the follow-up study. Ten individuals had positive screening test results. Two new celiac disease patients, one in each group, were found. Four patients in the case group had been diagnosed with celiac disease by routine procedures during the follow-up. Thus, five cases and one control had developed celiac disease. CONCLUSIONS: Small bowel mucosal lymphocytosis or slight reduction in villous height/crypt depth ratio are common findings in patients with suspicion of celiac disease. These findings alone are poor predictors of celiac disease.

Adolescent↗
PubMed2004

Oats can diversify a gluten-free diet in celiac disease and dermatitis herpetiformis.

Finnish celiac disease and dermatitis herpetiformis patients have used oat-containing gluten-free diets since 1997. The aim of this study was to evaluate how the use of oats has been adopted. The use of oats and the effect of oats on symptoms and quality of life were investigated in 1,000 randomly selected members of the Celiac Society. Altogether, 710 patients responded: 423 (73%) with celiac disease and 70 (55%) with dermatitis herpetiformis were currently consuming oats. Patients appreciated the taste, the ease of use, and the low costs; 94% believed that oats diversified the gluten-free diet; 15% of celiac disease and 28% of dermatitis herpetiformis patients had stopped eating oats. The most common reasons for avoiding oats were fear of adverse effects or contamination. There is a market demand for oats, and celiac societies and dietitians should make efforts to promote the development of products free of wheat contamination.

Adolescent↗
PubMed2004

Should we screen reflux oesophagitis patients for coeliac disease?

OBJECTIVES: Oesophagitis and gastro-oesophageal reflux have been implicated recently in the manifestations of coeliac disease. The aim was to investigate this association in a primary-care setting. METHODS: First, the prevalence of coeliac disease was calculated in 1198 adults with oesophagitis, in 2541 adults with reflux symptoms and in 200 adults suffering from dysphagia; 5459 patients with a history consistent with dyspepsia and 709 patients with a suspicion of coeliac disease served as controls. Second, the prevalence of oesophagitis was estimated in 382 untreated and 232 treated coeliac patients; controls here comprised 5404 patients with dyspeptic symptoms and 2525 patients with reflux symptoms. Third, oesophagitis and oesophageal reflux symptoms were investigated before and after a gluten-free diet was followed in 67 adults with coeliac disease. The diagnosis of coeliac disease was based on small-bowel histology; histological exclusion of the disease was unambiguous in all controls. Oesophagitis was identified by endoscopic inspection. RESULTS: Altogether, 0.9% of patients with oesophagitis and 0.6% of those with oesophageal reflux symptoms had coeliac disease. The corresponding percentages were 1.0% in patients with dyspepsia and 12% with suspicion of coeliac disease. The prevalence of oesophagitis was 5.2% in untreated coeliac disease, 5.6% in treated coeliac disease, 7.0% in patients with dyspepsia, and 27% in symptomatic reflux disease. In coeliac patients, the reflux symptoms were mild but nevertheless were alleviated on a gluten-free diet. CONCLUSIONS: This study does not support the conception that patients with reflux oesophagitis should be screened vigorously for coeliac disease. The association between these two conditions is, at most, weak, but a gluten-free diet may still bring symptomatic relief for reflux symptoms in coeliac disease.

Adolescent↗
PubMed2003

Intraepithelial lymphocytes in celiac disease.

OBJECTIVE: The aim of this study was to investigate the value of immunohistochemical characterization of different intraepithelial lymphocytes (IELs) in the diagnostic workup of celiac disease (CD). METHODS: The study involved 928 consecutive adult patients undergoing endoscopy undertaken on suspicion of CD or to ascertain the dietary compliance; the control group consisted of 59 adults who underwent endoscopy because of indigestion. Small bowel mucosal morphology, CD3+, alphabeta+, and gammadelta+ IELs were determined. RESULTS: CD was detected in 138 and excluded in 545 adults. CD3+ and gammadelta+ IELs both showed a sensitivity of 93% for CD; specificity was 73% and 88%, respectively. For alphabeta+ cells, the sensitivity was 83% and specificity, 66%. The mucosal morphology recovered on a gluten-free diet and the densities of different IELs, even gammadelta+ cells, decreased. Only the density of gammadelta+ cells remained elevated compared with controls. CONCLUSIONS: Counting of IELs is recommended in borderline cases where the histology is difficult to interpret. An increase especially in gammadelta+ cells strengthens the probability of CD. However, IELs are not invariably increased in CD.

Adolescent↗
PubMed2002

Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure.

BACKGROUND & AIMS: Mild liver abnormalities are common in patients with celiac disease and usually resolve with a gluten-free diet. We investigated the occurrence of celiac disease in patients with severe liver failure. METHODS: Four patients with untreated celiac disease and severe liver disease are described. Further, the occurrence of celiac disease was studied in 185 adults with previous liver transplantation using serum immunoglobulin A endomysial and tissue transglutaminase antibodies in screening. RESULTS: Of the 4 patients with severe liver disease and celiac disease, 1 had congenital liver fibrosis, 1 had massive hepatic steatosis, and 2 had progressive hepatitis without apparent origin. Three were even remitted for consideration of liver transplantation. Hepatic dysfunction reversed in all cases when a gluten-free diet was adopted. In the transplantation group, 8 patients (4.3%) had celiac disease. Six cases were detected before the operation: 3 had primary biliary cirrhosis, 1 had autoimmune hepatitis, 1 had primary sclerosing cholangitis, and 1 had congenital liver fibrosis. Only 1 patient had maintained a long-term strict gluten-free diet. Screening found 2 cases of celiac disease, 1 with autoimmune hepatitis and 1 with secondary sclerosing cholangitis. CONCLUSIONS: The possible presence of celiac disease should be investigated in patients with severe liver disease. Dietary treatment may prevent progression to hepatic failure, even in cases in which liver transplantation is considered.

Adolescent↗
PubMed2002

IgA-class transglutaminase antibodies in evaluating the efficacy of gluten-free diet in coeliac disease.

OBJECTIVE: Serum IgA-class tissue transglutaminase antibody has proved effective in screening for coeliac disease. The response to a gluten-free diet has been assessed on the basis of small-intestinal morphology. We investigated whether the tissue transglutaminase antibody test could substitute biopsy in this respect, and whether the test is better than the endomysial antibody test in follow-up. DESIGN: Controlled cross sectional, and follow-up study. METHODS: Serum IgA-class tissue transglutaminase antibodies and endomysial antibodies were determined in 87 coeliac adults on a gluten-free diet. All underwent small bowel biopsy, and the mucosal morphology was interpreted along with Marsh's grading 0-3. In 30 patients histological and serological data could be analysed before and after adopting the diet; Marsh 3 was considered inadequate mucosal recovery during the diet. RESULTS: Of the 87 coeliac patients 27 showed Marsh 3 villous atrophy on gluten-free diet; of these 27, tissue transglutaminase antibody was within normal limits in 16 (59%) and endomysial antibody in 20 (74%). Two (7%) out of 29 with normal mucosa (Marsh 0) had positive tissue transglutaminase antibodies. Six (55%) out of 11 admitting regular dietary lapses remained tissue transglutaminase antibody negative. In the follow-up, serum IgA-class tissue transglutaminase antibody was initially positive in 28 (93%) out of 30 untreated patients; even a significant decrease in tissue transglutaminase antibody did not guarantee mucosal recovery. CONCLUSIONS: A substantial number of coeliac patients with negative tissue transglutaminase or endomysial antibodies may still have manifest mucosal villous atrophy. Small bowel biopsy is therefore still necessary to ensure that the gluten-free diet is adequate.

Biopsy↗
PubMed2002

HLA-DQ typing in the diagnosis of celiac disease.

OBJECTIVE: More than 95% of celiac patients share the major histocompatibility complex II class human leukocyte antigen (HLA) DQ2 or DQ8 haplotype; patients negative for both types are unlikely to suffer from celiac disease. Our aim was to investigate whether HLA-DQ2 and -DQ8 typing is helpful when diagnosis is uncertain because of the absence of unequivocal small bowel villous atrophy. METHODS: HLA-DQ2 and -DQ8 typing was carried out in 59 patients evincing nondiagnostic small bowel mucosal lesion or positive celiac serology, and in 17 patients maintaining a gluten-free diet without biopsy-proven celiac disease. HLA findings were compared to small bowel mucosal morphology; intraepithelial lymphocytes; and serum endomysial (EmA), reticulin, tissue transglutaminase (anti-tTG) and gliadin antibodies. RESULTS: Of the 59 patients evincing only minor small bowel mucosal changes or positive celiac disease serology, 22 (37%) were negative for DQ2 and DQ8. All EmA-positive patients had celiac-type HLA, but antireticulin antibody, anti-tTg, and antigliadin antibody were also present in HLA-DQ2- and -DQ8-negative individuals. Eleven of 17 patients (65%) observing a gluten-free diet before small bowel biopsy did not share celiac-type HLA. None of the 17 had apparent villous atrophy. Serum EmA and anti-tTG were negative in all. HLA-DQ typing is less expensive than follow-up biopsy in the exclusion of celiac disease. CONCLUSIONS: HLA-DQ2 and -DQ8 determination is useful in exclusion, probably lifelong, of celiac disease in individuals with an equivocal small bowel histological finding. The low specificity of this test must, however, be borne in mind.

Adolescent↗
PubMed2002

Celiac disease and HLA DQ in patients with IgA nephropathy.

OBJECTIVES: Despite some reports on an association between celiac disease and IgA nephropathy, the evidence is still sparse. Celiac disease is strongly associated with the HLA DQ2 and DQ8 haplotypes, which might explain the potential risk of patients to contract various autoimmune conditions. In this study, we sought to establish how common celiac disease is in patients with IgA nephropathy, and whether the possible association can be explained by similar HLA DQ status. METHODS: A total of 223 consecutive adult patients with IgA nephropathy were studied; 95 cadaver organ transplant donors served as controls for HLA DQ analysis. The diagnosis of celiac disease was based on small bowel mucosal biopsy. All known celiac cases were recorded, and eligible patients (n = 168) underwent serological screening for celiac disease as well as HLA DQ2 and DQ8 analysis. Screening methods were serum endomysium and tissue transglutaminase antibodies; patients who tested positive underwent mucosal biopsy. RESULTS: Eight patients (3.6%, 95% CI = 1.6-7.0%) with IgA nephropathy were found to have celiac disease; three of them were identified by serological screening. All celiac cases had the HLA DQ2 or DQ8 haplotype, but these were not more common in patients with IgA nephropathy than in controls. As many as 14% of HLA DQ2 positive patients with IgA nephropathy had celiac disease. Gluten-free diet had no apparent influence on the course of nephropathy. CONCLUSIONS: Although there is no increase in celiac-type HLA DQ, patients with IgA nephropathy carry a risk of contracting celiac disease. It can be hypothesized that the increased intestinal permeability in IgA nephropathy may predispose genetically susceptible patients to celiac disease.

Adolescent↗