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- Nilsson, Ingrid, et al.
(författare)
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Helicobacter ganmani infection associated with a spontaneous outbreak of inflammatory bowel-like disease in an IL-10-deficient mouse colony
- 2008
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Ingår i: Scandinavian Journal of Laboratory Animal Science. - 0901-3393. ; 35:1, s. 13-24
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Tidskriftsartikel (refereegranskat)abstract
- Background: A breeding colony of IL-10 deficient B6.129P2-Il10(tmICgn/J) mice, kept under conventional conditions, developed an inflammatory bowel-like disease (IBD) with rectal prolapse and blood tinged diarrhoea. No clinical signs of disease were observed at the time of arrival to our animal house. These animals were originally planned to serve as a negative control group in an experimental infection study with Helicobacter species to investigate colonization of the murine gut. Results: A spiral-shaped, Gram-negative bacterium was isolated from the breeding mice colony. In a first group of six animals, tissue specimens from the liver, small and large intestines, faeces and blood, were analysed by culture, PCR-denaturing gradient gel electrophoresis (PCR-DGGE), species-specific PCR assays and DNA-sequencing, histology and serology. Helicobacter ganmani, but no other Helicobacter species, was isolated from the liver, small bowel, caecum, colon and faeces. We found inflammation in caeca, colon and livers, most pronounced in the caecal areas of culture positive mice with a severe typhlitis with cystic dilatation of glandular structures and irregular crypt architecture. Some animals showed a pronounced colitis with mucosal and sub-mucosal inflammatory infiltrates. Other animals displayed large lymphoid infiltrates in the livers and hepatitis. Tissue samples and sera from 18 additional animals from the same breeding colony were analysed by the same methods, except for culture. H. ganmani was identified by PCR in most tissue samples of the 18 additional animals as well. Sero-conversion to H. ganmani correlated well with histopathological changes. Conclusions: Our findings emphasize the importance of using Helicobacter-free animals to develop murine models of chronic hepatitis and colitis.
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- Abu Al-Soud, Waleed, et al.
(författare)
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DNA of Helicobacter spp. and common gut bacteria in primary liver carcinoma.
- 2008
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Ingår i: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658. ; 40:2, s. 126-131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIM: Gastric and enteric Helicobacter species have been associated with the pathogenesis of some extragastric diseases. METHODS: We retrospectively investigated the presence of DNA of Helicobacter species in samples of the cancer and the surrounding tumour-free liver tissues of patients with hepatocellular carcinoma (HCC, n=12) and cholangiocarcinoma (CC, n=13). The patients were from an area with low liver cancer incidence and with low hepatitis B and C prevalence. Patients with a benign liver disease (n=24) were included as controls. Paraffin-embedded liver samples were examined by a Helicobacter genus-specific PCR assay as well as group-specific PCR assays for Enterobacteriaceae, Bacteroides, Lactobacillus and Enterococcus. PCR products of positive samples were characterised by denaturing gradient gel electrophoresis (DGGE) and DNA sequencing. RESULTS: PCR assay detected Helicobacter DNA in seven of 12 (58%) and eight of 13 (62%) normal liver tissue specimens from HCC and CC patients, respectively. Two cancer samples from HCC patients were Helicobacter-positive but none of the CC cancers. In the control group, three of 24 (12.5%) patients with a benign liver condition were positive for Helicobacter species (p<0.01 compared to results of tumour-free liver tissue from the cancer patients). DGGE and DNA sequence analysis showed that 90% of the detected PCR products were "H. pylori-like". DNA of some other enteric bacteria was detected in the liver of one cancer patient and one control (4% of all patients). CONCLUSION: The presence of DNA of Helicobacter species in liver specimens, but not of other common gut bacteria, was associated with human hepatic carcinogenesis.
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- Friis-Hansen, Lennart, et al.
(författare)
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Gastric inflammation, metaplasia, and tumor development in gastrin-deficient mice
- 2006
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Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 131:1, s. 246-258
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Gastrin deficiency and proton pump inhibitor treatment cause achlorhydria, which predisposes to disease. To elucidate the underlying molecular biology, we examined the changes in gastric gene expression in both types of achlorhydria. We also explored the associated changes in the gastric microflora and the long-term consequences of gastrin-deficient achlorhydria. Methods: Expression profiles were generated from gastric RNA from wild-type mice, gastrin knockout (KO) mice, gastrin KO mice after I week of gastrin infusion, and wild-type mice treated for I month with a proton pump inhibitor. The results were confirmed using real-time polymerase chain reaction and immuno-histochemistry. Selective media were used to characterize the gastric microflora. Results: The number of gastric bacteria was increased in both gastrin KO and PPI-treated mice. The expression profiles revealed activation of immune defense genes, interferon-regulated response genes, and intestinal metaplasia of the gastric mucosa. In young gastrin-deficient mice, gastrin infusions reversed the changes. Over time, the changes accumulated, became irreversible, and progressed into metaplasia and polyp development. Finally, the study showed that gastrin regulated the expression of genes encoding extracellular matrix proteins. Conclusions: Independently of gastrin, achlorhydria is associated with gastric bacterial overgrowth and intestinal gene expression patterns and is associated with predisposition to disease. Gastrin is therefore essential for prevention of gastric disease, mainly through control of acid secretion but to a lesser extent also through control of gastric gene expression. The gastrin-deficient mouse serves as a useful new model for gastric metaplasia and neoplasia.
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- Grundberg, Elin, et al.
(författare)
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Vitamin D receptor 3' haplotypes are unequally expressed in primary human bone cells and associated with increased fracture risk: the MrOS Study in Sweden and Hong Kong.
- 2007
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 0884-0431. ; 22:6, s. 832-40
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Tidskriftsartikel (refereegranskat)abstract
- The VDR is a prime candidate gene for osteoporosis. Here, we studied three common VDR haplotypes in relation to bone phenotypes in 5014 participants of the global MrOS Study. We also studied the relative expression of the haplotypes in human bone cells. One haplotype was associated with increased fracture risk and differently expressed in primary human bone cells. INTRODUCTION: Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of BMD is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population. MATERIALS AND METHODS: Here, we reconstructed common haplotypes in the VDR 3' untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in elderly men from Sweden (n = 3014) and Hong Kong (n = 2000), all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, we studied allele-specific expressions of the different VDR 3' UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples. RESULTS: Three major haplotypes were reconstructed and in agreement with the previously well-defined baT, BAt, and bAT haplotypes, herein denoted Hap1, Hap2, and Hap3. The Hap1 haplotype was independently associated with increased risk of vertebral fractures in Swedish men (OR, 1.655; 95% CI, 1.146-2.391; p < 0.01) and with lower lumbar spine BMD in elderly men from Sweden (p < 0.01) and Hong Kong (p < 0.05). The VDR gene was also shown to exhibit a 3' UTR haplotype dependent allelic imbalance, indicating that the VDR Hap1 allele was overexpressed in human trabecular bone samples. CONCLUSIONS: The results indicate that the relatively overexpressed VDR Hap1 haplotype could be considered a risk allele for osteoporosis regardless of ethnicity.
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- Grundberg, Elin, et al.
(författare)
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Vitamin D receptor 3 ' haplotypes are unequally expressed in primary human bone cells and associated with increased fracture risk: The MrOS study in Sweden and Hong kong
- 2007
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 22:6, s. 832-840
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Tidskriftsartikel (refereegranskat)abstract
- The VDR is a prime candidate gene for osteoporosis. Here, we studied three common VDR haplotypes in relation to bone phenotypes in 5014 participants of the global MrOS Study. We also studied the relative expression of the haplotypes in human bone cells. One haplotype was associated with increased fracture risk and differently expressed in primary human bone cells. Introduction: Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of BMD is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population. Materials and Methods: Here, we reconstructed common haplotypes in the VDR 3 ' untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in elderly men from Sweden (n = 3014) and Hong Kong (n = 2000), all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, we studied allele-specific expressions of the different VDR 3 ' UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples. Results: Three major haplotypes were reconstructed and in agreement with the previously well-defined baT, BAt, and bAT haplotypes, herein denoted Hap1, Hap2, and Hap3. The Hap1 haplotype was independently associated with increased risk of vertebral fractures in Swedish men (OR, 1.655; 95% Cl, 1.146-2.391;p < 0.01) and with lower lumbar spine BMD in elderly men from Sweden (p < 0.01) and Hong Kong (P < 0.05). The VDR gene was also shown to exhibit a 3 ' UTR haplotype dependent allelic imbalance, indicating that the VDR Hap1 allele was overexpressed in human trabecular bone samples. Conclusions: The results indicate that the relatively overexpressed VDR Hap1 haplotype could be considered a risk allele for osteoporosis regardless of ethnicity.
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