| 1. |
- Henstrom, M., et al.
(författare)
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Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome
- 2018
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 67:2, s. 263-270
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Tidskriftsartikel (refereegranskat)abstract
- Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucraseisomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p. Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.
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| 2. |
- Knowles, CH, et al.
(författare)
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Deranged smooth muscle alpha-actin as a biomarker of intestinal pseudo-obstruction: a controlled multinational case series
- 2004
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 53:11, s. 1583-1589
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Chronic idiopathic intestinal pseudo-obstruction (CIIP) is a severe motility disorder associated with significant morbidity. Several histopathological ( neuropathic and myopathic) phenotypes have been described but only a single adult with jejunal smooth ( circular) muscle alpha-actin deficiency. We present a prospective multinational case series investigating smooth muscle alpha-actin deficiency as a biomarker of this disease. Methods: A total of 115 fully clinically and physiologically ( including prolonged ( 24 hour) ambulatory jejunal manometry) characterised CIIP patients from three European centres were studied. Immunohistochemical localisation of actins and other cytoskeletal proteins were performed on laparoscopic full thickness jejunal biopsies and compared with adult controls. Distribution of alpha-actin was also characterised in other gut regions and in the developing human alimentary tract. Results: Twenty eight of 115 (24%) CIIP patient biopsies had absent (n = 22) or partial ( n = 6) jejunal smooth muscle alpha-actin immunostaining in the circular muscle layer. In contrast, smooth muscle alpha-actin staining was preserved in the longitudinal muscle and in adult jejunal controls ( n = 20). Comparative study of other adult alimentary tract regions and fetal small intestine, suggested significant spatial and temporal variations in smooth muscle alpha-actin expression. Conclusions: The ability to modulate alpha-smooth muscle actin expression, evident in development, is maintained in adult life and may be influenced by disease, rendering it a valuable biomarker even in the absence of other structural abnormalities.
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| 3. |
- Lindberg, G
(författare)
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Bloating in dyspepsia
- 2014
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 63:3, s. 378-379
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Tidskriftsartikel (refereegranskat)
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| 4. |
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| 5. |
- Lindberg, G., et al.
(författare)
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Full-thickness biopsy findings in chronic intestinal pseudo-obstruction and enteric dysmotility
- 2009
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 58:8, s. 1084-1090
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Small bowel manometry is increasingly used in the clinical investigation of patients with symptoms of intestinal motor dysfunction. Enteric dysmotility (ED) has been suggested as a new diagnostic term for patients with abnormal intestinal motor activity but no radiological signs of chronic intestinal pseudo-obstruction (CIP). Histopathological features of adult patients with ED and CIP have been compared in a large case series to study differences and similarities between the two diagnostic groups. Methods: Routine staining and an extensive panel of immunohistochemical stains on transversal and tangential cuts from full-thickness biopsies of the small bowel were used. Results: 39 females and 11 males with CIP and 58 females and 7 males with ED were investigated. The underlying lesion was more often a visceral myopathy (22% vs 5%) or neuromyopathy (30% vs 12%) in patients with CIP than in those with ED, whereas the predominant lesion in ED was neuropathy with inflammation. Conclusion: CIP in adults is associated with very different underlying pathology, whereas ED is more homogeneously associated with neuropathy in the enteric nervous system. Neuropathy of enteric ganglia with inflammation seems to be the most common cause for measurable disturbances of intestinal motor function.
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