| 1. |
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| 2. |
- Amcoff, Karin, 1975-, et al.
(författare)
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Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition : Results of a European Study of Twins with Crohn's Disease
- 2016
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Ingår i: Journal of Crohn's & Colitis. - Oxford, United Kingdom : Oxford University Press. - 1873-9946 .- 1876-4479. ; 10:6, s. 695-702
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: An adaptive immunological response to microbial antigens has been observed in Crohn's disease (CD). Intriguingly, this serological response precedes the diagnosis in some patients and has also been observed in healthy relatives. We aimed to determine whether genetic factors are implicated in this response in a CD twin cohort.Methods: In total, 82 twin pairs (Leuven n = 13, Maastricht n = 8, Örebro n = 61) took part: 81 pairs with CD (concordant monozygotic n = 16, discordant monozygotic n = 22, concordant dizygotic n = 3, discordant dizygotic n = 40) and 1 monozygotic pair with both CD and ulcerative colitis. Serology for Pseudomonas fluorescens-related protein (anti-I2), Escherichia coli outer membrane porin C (anti-OmpC), CBir1flagellin (anti-CBir1) and antibodies to oligomannan (anti-Saccharomyces cerevisiae antibody [ASCA]) was determined by standardized enzyme-linked immunoassay.Results: All markers were more often present in CD twins than in their healthy twin siblings. Using the intraclass correlation coefficient (ICC), agreements in concentrations of anti-OmpC and anti-I2 were observed in discordant monozygotic but not in discordant dizygotic twin pairs with CD (anti-OmpC, ICC 0.80 and -0.02, respectively) and (anti-I2, ICC 0.56 and 0.05, respectively). In contrast, no agreements were found in anti-CBir, immunoglobulin (Ig) G ASCA and ASCA IgA.Conclusions: We show that anti-I2 and anti-CBir1 statuses have specificity for CD and confirm previous reported specificities for anti-OmpC and ASCA. Based on quantitative analyses and observed ICCs, genetics seems to predispose to the anti-OmpC and anti-I2 response but less to ASCA and anti-CBir1 responses.
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| 3. |
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| 4. |
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| 5. |
- Lundberg, J. O. N., et al.
(författare)
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Increased nitric oxide production in collagenous and lymphocytic colitis
- 1997
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 27:10, s. 869-871
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Tidskriftsartikel (refereegranskat)abstract
- The production of nitric oxide (NO) is increased in active ulcerative colitis and in Crohn's disease. We have studied NO production in collagenous colitis (CC) and lymphocytic colitis (LC), both of which are inflammatory bowel disorders of unknown aetiology. NO levels were measured directly in gas sampled from the colon during colonoscopy. Plasma levels of NO metabolites (nitrate/nitrite) were also measured. Luminal NO levels were more than 100 times higher in patients with CC compared with controls. In addition, plasma levels of nitrate/nitrite were increased in the patients as compared with controls. Measurements of NO directly in the colon or its oxidation products in plasma may be a helpful tool in further understanding the role of NO in the pathophysiology of CC and LC. Moreover, it is tempting to speculate that these measurements could be clinically useful in the diagnosis and therapy monitoring of these two inflammatory bowel diseases.
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| 6. |
- Olesen, Martin, 1967-, et al.
(författare)
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Luminal nitric oxide and epithelial expression of inducible and endothelial nitric oxide synthase in collagenous and lymphocytic colitis
- 2003
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 38:1, s. 66-72
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colonic nitric oxide (NO) production in collagenous colitis (CC) has been studied in a small number of patients and found increased. The cellular source of NO is believed to be the colonic epithelial cells. The aim of this study was to investigate colonic NO levels in patients with CC and lymphocytic colitis (LC), to compare with the histopathological status and with the clinical activity, and to assess the epithelial expression of inducible and endothelial nitric oxide synthase (iNOS and eNOS).Methods: We included 19 patients with CC, 8 patients with LC and 15 controls. During colonoscopy, luminal gas was sampled and NO levels were measured using the chemiluminescence technique. Mucosal biopsies were obtained for routine histopathologic examination and immunohistochemical studies of iNOS and eNOS. Clinical activity, as measured by the mean frequency of daily bowel movements during the week prior to colonoscopy, was assessed.Results: Luminal NO levels, median (25-75 percentiles), in the patients with CC and LC were greatly increased compared to the controls, 1673 (145-8143) parts per billion (ppb) and 1838 (1065-2694) ppb versus 28 (20-46) ppb (P < 0.005, both). A positive association was seen between NO levels and histopathological status as well as clinical activity. Strong expression of iNOS was seen in the surface epithelium in 5 of 6 patients with CC and in 2 of 5 patients with LC.Conclusions: The fact that luminal NO levels are related to histopathological status and correlate with clinical activity indicates that NO is involved in the pathophysiology of CC and LC. The epithelial cells are the most likely source of luminal NO.
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| 7. |
- Travaglini, Gabriele, et al.
(författare)
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The SAGEX review on scattering amplitudes
- 2022
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Ingår i: Journal of Physics A. - : IOP Publishing. - 1751-8113 .- 1751-8121. ; 55:44
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Forskningsöversikt (refereegranskat)abstract
- This is an introduction to, and invitation to read, a series of review articles on scattering amplitudes in gauge theory, gravity, and superstring theory. Our aim is to provide an overview of the field, from basic aspects to a selection of current (2022) research and developments.
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| 8. |
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| 9. |
- Abramson, Alex, et al.
(författare)
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Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors
- 2021
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 40:1, s. 103-109
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Tidskriftsartikel (refereegranskat)abstract
- Oral administration provides a simple and non-invasive approach for drug delivery. However, due to poor absorption and swift enzymatic degradation in the gastrointestinal tract, a wide range of molecules must be parenterally injected to attain required doses and pharmacokinetics. Here we present an orally dosed liquid auto-injector capable of delivering up to 4-mg doses of a bioavailable drug with the rapid pharmacokinetics of an injection, reaching an absolute bioavailability of up to 80% and a maximum plasma drug concentration within 30 min after dosing. This approach improves dosing efficiencies and pharmacokinetics an order of magnitude over our previously designed injector capsules and up to two orders of magnitude over clinically available and preclinical chemical permeation enhancement technologies. We administered the capsules to swine for delivery of clinically relevant doses of four commonly injected medications, including adalimumab, a GLP-1 analog, recombinant human insulin and epinephrine. These multi-day dosing experiments and oral administration in awake animal models support the translational potential of the system.
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| 10. |
- Bjerrum-Bohr, N. E. J., et al.
(författare)
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General Relativity from Scattering Amplitudes
- 2018
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Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 121:17
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Tidskriftsartikel (refereegranskat)abstract
- Weoutline the program to apply modern quantum field theory methods to calculate observables in classical general relativity through a truncation to classical terms of the multigraviton, two-body, on-shell scattering amplitudes between massive fields. Since only long-distance interactions corresponding to nonanalytic pieces need to be included, unitarity cuts provide substantial simplifications for both post-Newtonian and post-Minkowskian expansions. We illustrate this quantum field theoretic approach to classical general relativity by computing the interaction potentials to second order in the post-Newtonian expansion, as well as the scattering functions for two massive objects to second order in the post-Minkowskian expansion. We also derive an all-order exact result for gravitational light-by-light scattering.
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| 11. |
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| 12. |
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| 13. |
- Bohr, J, et al.
(författare)
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Yersinia species in collagenous colitis.
- 2002
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Ingår i: Scandinavian Journal of Gastroenterology. - 0036-5521 .- 1502-7708. ; 37, s. 711-714
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Tidskriftsartikel (refereegranskat)
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| 14. |
- Bohr, Tomas, et al.
(författare)
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The glymphatic system : Current understanding and modeling
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:9
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Forskningsöversikt (refereegranskat)abstract
- We review theoretical and numerical models of the glymphatic system, which circulates cerebrospinal fluid and interstitial fluid around the brain, facilitating solute transport. Models enable hypothesis development and predictions of transport, with clinical applications including drug delivery, stroke, cardiac arrest, and neurodegenerative disorders like Alzheimer's disease. We sort existing models into broad categories by anatomical function: Perivascular flow, transport in brain parenchyma, interfaces to perivascular spaces, efflux routes, and links to neuronal activity. Needs and opportunities for future work are highlighted wherever possible; new models, expanded models, and novel experiments to inform models could all have tremendous value for advancing the field.
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| 15. |
- Carstens, Adam, 1975-, et al.
(författare)
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The Gut Microbiota in Collagenous Colitis Shares Characteristics With Inflammatory Bowel Disease-Associated Dysbiosis
- 2019
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Ingår i: Clinical and Translational Gastroenterology. - : Nature Publishing Group. - 2155-384X. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: In inflammatory bowel disease (IBD), an aberrant immune response to gut microbiota is important, but the role of the microbiota in collagenous colitis (CC) is largely unknown. We aimed to characterize the microbiota of patients with CC compared with that of healthy control and patients with IBD.METHODS: Fecal samples were collected from patients with CC (n = 29), age- and sex-matched healthy controls (n = 29), patients with Crohn's disease (n = 32), and patients with ulcerative colitis (n = 32). Sequence data were obtained by 454 sequencing of 16S rRNA gene amplicons, and the obtained sequences were subsequently taxonomically classified.RESULTS: Analysis of similarity statistics showed a segregation between patients with CC and healthy controls with increasing taxonomic resolution, becoming significant comparing operational taxonomic unit data (P = 0.006). CC had a lower abundance of 10 different taxa. Taxa-specific analyses revealed a consistent lower abundance of several operational taxonomic units belonging to the Ruminococcaceae family in patients with CC, q < 0.05 after false discovery rate correction. Loss of these taxa was seen in patients with CC with active disease and/or corticosteroid treatment only and resembled the findings in patients with IBD.DISCUSSION: CC is associated with a specific fecal microbiome seen primarily in patients with active disease or ongoing corticosteroid treatment, whereas the microbiome of CC patients in remission resembled that of healthy controls. Notably, the shift in key taxa, including the Ruminococcaceae family, was also observed in IBD. There may be common mechanisms in the pathogenesis of CC and IBD.
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| 16. |
- Järnerot, G, et al.
(författare)
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Familial occurrence of microscopic colitis: a report on five families
- 2001
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 36:9, s. 959-962
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The etiology and pathogenesis of microscopic colitis is unknown. Whether genetic predisposition is of importance, as in many other gastrointestinal diseases, is unknown. Familial occurrence of collagenous colitis has earlier been reported only in two families. METHODS: Familial occurrence of microscopic colitis was searched for in a Swedish national microscopic colitis register. RESULTS: Familial occurrence of microscopic colitis was identified in five families. In all families a sister-sister relationship was found. Two sisters with collagenous colitis had been living apart in different Nordic countries for many years before developing the disease. In one pair, the smoking sister had collagenous colitis and the never smoking sister had lymphocytic colitis. CONCLUSIONS: Considering the relative rarity of microscopic colitis, these findings indicate that a genetic predisposition may be of importance.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Larsson, Johanna K, et al.
(författare)
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Cancer Risk in Collagenous Colitis
- 2019
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- Data on malignancy in patients with collagenous colitis (CC) is scarce. We aimed to determine the incidence of cancers in patients with CC. In a two-stages, observational study, data on cancers in patients diagnosed with CC during 2000-2015, were collected from two cohorts. The risk was calculated according to the age-standardized rate for the first cohort and according to the standardized incidence ratio for the second cohort. The first cohort comprised 738 patients (394 from Scotland and 344 from Sweden; mean age 71 +/- 11 and 66 +/- 13 years, respectively). The incidence rates for lung cancer (RR 3.9, p = 0.001), bladder cancer (RR 9.2, p = 0.019), and non-melanoma skin cancer (NMSC) (RR 15, p = 0.001) were increased. As the majority of NMSC cases (15/16) came from Sweden, a second Swedish cohort, comprising 1141 patients (863 women, mean age 65 years, range 20-95 years) was collected. There were 93 cancer cases (besides NMSC). The risk for colon cancer was decreased (SIR 0.23, p= 0.0087). The risk for cutaneous squamous cell carcinoma was instead markedly increased (SIR 3.27, p = 0.001).
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| 21. |
- Maynard, S, et al.
(författare)
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Lamin A/C promotes DNA base excision repair
- 2019
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 47:22, s. 11709-11728
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Tidskriftsartikel (refereegranskat)abstract
- The A-type lamins (lamin A/C), encoded by the LMNA gene, are important structural components of the nuclear lamina. LMNA mutations lead to degenerative disorders known as laminopathies, including the premature aging disease Hutchinson-Gilford progeria syndrome. In addition, altered lamin A/C expression is found in various cancers. Reports indicate that lamin A/C plays a role in DNA double strand break repair, but a role in DNA base excision repair (BER) has not been described. We provide evidence for reduced BER efficiency in lamin A/C-depleted cells (Lmna null MEFs and lamin A/C-knockdown U2OS). The mechanism involves impairment of the APE1 and POLβ BER activities, partly effectuated by associated reduction in poly-ADP-ribose chain formation. Also, Lmna null MEFs displayed reduced expression of several core BER enzymes (PARP1, LIG3 and POLβ). Absence of Lmna led to accumulation of 8-oxoguanine (8-oxoG) lesions, and to an increased frequency of substitution mutations induced by chronic oxidative stress including GC>TA transversions (a fingerprint of 8-oxoG:A mismatches). Collectively, our results provide novel insights into the functional interplay between the nuclear lamina and cellular defenses against oxidative DNA damage, with implications for cancer and aging.
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| 22. |
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| 23. |
- Münch, A., et al.
(författare)
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Metotrexat vid budesonid refraktär kollagen kolit
- 2012
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Ingår i: Gastrokuriren. - Stockholm : Svensk Gastroenterologisk Förening. - 1651-0453. ; 17:34, s. PO-15-PO-15
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 24. |
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| 25. |
- Nyhlin, N., et al.
(författare)
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Systematic review : microscopic colitis
- 2006
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 23:11, s. 1525-1534
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Collagenous and lymphocytic colitis are fairly common causes of chronic non-bloody diarrhoea, especially in elderly female. AIM: To present a systematic review of microscopic colitis. METHODS: A PubMed search using the MeSH terms microscopic colitis, collagenous colitis, lymphocytic colitis and chronic diarrhoea was performed. RESULTS: Annual incidence of each disorder is 4-6/100,000 inhabitants. The aetiology is unknown. Clinical characteristics are well described and there is an association with autoimmune diseases. Budesonide is the best-documented short-term treatment of collagenous colitis. In meta-analysis pooled odds ratio for clinical response after 6-8 weeks of treatment was 12.3 (95% CI: 5.5-27.5) in comparison with placebo. The evidence for bismuth subsalicylate is weaker and the effectiveness of other alternatives such as loperamide, cholestyramine, aminosalicylates, probiotics, or Boswellia serrata extract is unknown. Although unproven, in unresponsive severe disease azathioprine or methotrexate may be tried. No controlled trials have been carried out in lymphocytic colitis. The long-term prognosis of microscopic colitis is good, serious complications are rare and there is no increased mortality. CONCLUSIONS: Clinical and epidemiological aspects of microscopic colitis are well described. Budesonide is the best-documented short-term therapy in collagenous colitis, but the optimal long-term strategy needs further study. Controlled treatment data of lymphocytic colitis are awaited for.
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| 26. |
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| 27. |
- Olesen, Martin, 1967-, et al.
(författare)
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Lymphocytic colitis : a retrospective clinical study of 199 Swedish patients
- 2004
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 53:4, s. 536-541
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lymphocytic colitis is characterised by chronic diarrhoea and specific microscopic changes in a macroscopically normal colonic mucosa. We report clinical features and treatment outcome in a large patient cohort.Methods: Patients were searched for in 24 Swedish gastroenterology clinics. The biopsy material was reassessed using strict histopathological criteria. Clinical data were obtained from medical notes.Results: Lymphocytic colitis was diagnosed in 199 cases. The female:male ratio was 2.4:1. Median age at diagnosis was 59 (48–70) years. The most frequent symptoms were diarrhoea (96%), abdominal pain (47%), and weight loss (41%). The course was chronic intermittent in 30% of patients, chronic continuous in 7%, and a single attack in 63%, and in these cases the disease duration was 6 (4–11) months. Seventy nine (40%) patients reported associated diseases, of which thyroid disorders, coeliac disease, and diabetes mellitus were the most common. In 34 first or second degree relatives of 24 (12%) patients, a family history of ulcerative colitis, Crohn’s disease, collagenous colitis, or coeliac disease was reported. Drug induced disease was suspected in 19 (10%) patients. A non-significant peak of disease onset was seen in December-January. More than 80% of treated patients improved on corticosteroids, including budesonide.Conclusions: A family history of other bowel disorders is a new finding. The sudden onset and single attack of limited duration may support a possible infectious cause in some cases. Drugs may cause lymphocytic colitis.
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| 28. |
- Olesen, Martin, 1967-, et al.
(författare)
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Microscopic colitis: a common diarrhoeal disease : an epidemiological study in Örebro, Sweden, 1993–1998
- 2004
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 53:3, s. 346-350
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Tidskriftsartikel (refereegranskat)abstract
- Background: Microscopic colitis, including collagenous colitis and lymphocytic colitis, mainly affects middle aged and older subjects, with a female predominance in collagenous colitis. The diseases have previously been regarded as rare. We present an epidemiological study of microscopic colitis in a well defined Swedish population.Methods: Patients were retrospectively searched for in colonoscopy reports of those who had a colonoscopy in the period 1993–1998 for non-bloody diarrhoea. All colonic mucosal biopsies were reassessed using strict diagnostic criteria.Results: Biopsies from 1018 patients were reassessed. Fifty one (45 female) collagenous colitis patients and 46 (31 female) lymphocytic colitis patients were diagnosed. Median age at diagnosis was 64 years in collagenous colitis and 59 years in lymphocytic colitis. The mean annual incidence of collagenous colitis was 4.9/105 inhabitants (95% confidence interval (CI) 3.6–6.2/105) and of lymphocytic colitis 4.4/105 inhabitants (95% CI 3.1–5.7/105). The annual incidence of collagenous colitis increased from 3.7/105 in 1993–1995 to 6.1/105 in 1996–1998 (difference 2.4/105 (95% CI −0.3–5.1/105)) whereas the incidence of lymphocytic colitis increased from 3.1/105 to 5.7/105 (difference 2.6/105 (95% CI 0.1–5.2/105)).Conclusions: The annual incidences of collagenous colitis and lymphocytic colitis are higher than considered previously and are now equal to the incidence of Crohn’s disease in Sweden, and combined rates approach the incidence of ulcerative colitis. Microscopic colitis was diagnosed in 10% of all patients with non-bloody diarrhoea referred for colonoscopy and in almost 20% of those older than 70 years.
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| 29. |
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| 30. |
- Verhaegh, Bas P. M., et al.
(författare)
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Course of disease in patients with microscopic colitis : a European prospective incident cohort study
- 2021
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 15:7, s. 1174-1183
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The disease course of microscopic colitis (MC) is considered chronic but benign. However, this assumption is based on mainly retrospective studies, reporting on incomplete follow-up of selective cohorts. Systematic, prospective and unbiased data to inform patients and health care professionals on the expected course of the disease and real-life response to therapy are warranted.METHODS: A prospective, pan-European, multi-center, web-based registry was established. Incident cases of MC were included. Data on patient characteristics, symptoms, treatment and quality of life were systematically registered at baseline and during real-time follow-up. Four disease course phenotypes were discriminated and described.RESULTS: Among 381 cases with complete 1-year follow-up, 49% had a chronic active or relapsing disease course, 40% achieved sustained remission after treatment and 11% had a quiescent course. In general, symptoms and quality of life improved after 3 months of follow-up. A relapsing or chronic active disease course was associated with significantly more symptoms and impaired quality of life after 1 year.CONCLUSIONS: A minority of MC patients follow a quiescent disease course with spontaneous clinical improvement, whereas the majority suffers a chronic active or relapsing disease course during the first year after diagnosis, with persisting symptoms accompanied by a significantly impaired quality of life.
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| 31. |
- Vigren, L., et al.
(författare)
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Rökning och kollagen kolit
- 2011
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Ingår i: Gastrokuriren. - : Svensk Gastroenterologisk Förening. - 1651-0453. ; 16:29, s. PO-17-PO-17
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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