| 1. |
- Andersson, C, et al.
(författare)
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The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes
- 2011
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Ingår i: Autoimmunity. - : Taylor & Francis. - 0891-6934 .- 1607-842X. ; 44:5, s. 394-405
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We tested whether autoantibodies to all three ZnT8RWQ variants, GAD65, insulinoma-associated protein 2 (IA-2), insulin and autoantibodies to islet cell cytoplasm (ICA) in combination with human leukocyte antigen (HLA) would improve the diagnostic sensitivity of childhood type 1 diabetes by detecting the children who otherwise would have been autoantibody-negative.Methods: A total of 686 patients diagnosed in 1996–2005 in Skåne were analyzed for all the seven autoantibodies [arginin 325 zinc transporter 8 autoantibody (ZnT8RA), tryptophan 325 zinc transporter 8 autoantibody (ZnT8WA), glutamine 325 Zinc transporter 8 autoantibody (ZnT8QA), autoantibodies to glutamic acid decarboxylase (GADA), Autoantibodies to islet-antigen-2 (IA-2A), insulin autoantibodies (IAA) and ICA] in addition to HLA-DQ genotypes.Results: Zinc transporter 8 autoantibody to either one or all three amino acid variants at position 325 (ZnT8RWQA) was found in 65% (449/686) of the patients. The frequency was independent of age at diagnosis. The ZnT8RWQA reduced the frequency of autoantibody-negative patients from 7.5 to 5.4%—a reduction by 28%. Only 2 of 108 (2%) patients who are below 5 years of age had no autoantibody at diagnosis. Diagnosis without any islet autoantibody increased with increasing age at onset. DQA1-B1*X-0604 was associated with both ZnT8RA (p = 0.002) and ZnT8WA (p = 0.01) but not with ZnT8QA (p = 0.07). Kappa agreement analysis showed moderate (>0.40) to fair (>0.20) agreement between pairs of autoantibodies for all combinations of GADA, IA-2A, ZnT8RWQA and ICA but only slight ( < 0.19) agreement for any combination with IAA.Conclusions: This study revealed that (1) the ZnT8RWQA was common, independent of age; (2) multiple autoantibodies were common among the young; (3) DQA1-B1*X-0604 increased the risk for ZnT8RA and ZnT8WA; (4) agreement between autoantibody pairs was common for all combinations except IAA. These results suggest that ZnT8RWQA is a necessary complement to the classification and prediction of childhood type 1 diabetes as well as to randomize the subjects in the prevention and intervention of clinical trials.
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| 2. |
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| 3. |
- Kanatsuna, N, et al.
(författare)
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Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes
- 2015
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Ingår i: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 0300-9475 .- 1365-3083. ; 82:4, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P < 0.001). Irrespective of age at diagnosis, 19% (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (P < 0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.
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| 4. |
- Nilsson, Johan L.Å., et al.
(författare)
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N,N'-Bis(2-mercaptoethyl)isophthalamide Binds Electrophilic Paracetamol Metabolites and Prevents Paracetamol-Induced Liver Toxicity
- 2018
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Ingår i: Basic and Clinical Pharmacology and Toxicology. - : Wiley. - 1742-7835. ; 123:5, s. 589-593
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Tidskriftsartikel (refereegranskat)abstract
- Paracetamol overdosing may cause liver injury including fulminant liver failure due to generation of the toxic metabolites, N-acetyl-p-benzoquinone imine (NAPQI) and p-benzoquinone (p-BQ). Herein, the chelating agent, N,N'-Bis(2-mercaptoethyl)isophthalamide (NBMI), was examined for its potential ability to entrap NAPQI and p-BQ and to prevent paracetamol-induced liver injury. Both NBMI and the conventional paracetamol antidote N-acetylcysteine (NAC) were investigated with regard to their abilities to scavenge the NAPQI and p-BQ in a Transient Receptor Potential Ankyrin 1-dependent screening assay. Stoichiometric evaluations indicated that NBMI was able to entrap these metabolites more efficiently than NAC. Furthermore, oral administration of either NBMI (680 mg/kg) or NAC (680 mg/kg) prevented the development of the characteristic liver necrosis and elevation of serum alanine aminotransferase in a mouse model for paracetamol-induced liver injury. In summary, these results show that NBMI is able to entrap the toxic metabolites NAPQI and p-BQ and to prevent paracetamol-induced liver injury in mice.
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| 5. |
- Nilsson, P M, et al.
(författare)
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Fetal growth predicts stress susceptibility independent of parental education in 161 991 adolescent Swedish male conscripts.
- 2004
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 1470-2738 .- 0143-005X. ; 58:7, s. 571-573
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Tidskriftsartikel (refereegranskat)abstract
- Psychosocial stress could lead to a wide range of possible physiological reactions, due to both the total burden of stress as well as individual susceptibility. Two useful Swedish registers to investigate early life influences on stress susceptibility are the Swedish Medical Birth Register (MBR) and the Military Service Conscription Register (MSCR). In a previous study we showed a positive relation between fetal growth and psychological functioning (PF) including an assessment of stress susceptibility.1 However, in that study we did not adjust for family social class—nor did another related study.2 We have therefore now carried out such an analysis in an expanded cohort study, by adding parental educational level as a marker of family social class. The aim was to investigate independent associations between fetal growth and stress susceptibility in young men.
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| 6. |
- Nilsson, Ulf, et al.
(författare)
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Dietary supplementation with β-glucan enriched oat bran increases faecal concentration of carboxylic acids in healthy subjects
- 2008
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 62:8, s. 978-984
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Tidskriftsartikel (refereegranskat)abstract
- Background/Objective: Carboxylic acids (CAs), especially butyric acid, have been suggested to counteract colonic diseases, such as ulcerative colitis and colon cancer. Colonic formation of CAs can be influenced by the diet, but the concentrations and pattern formed need to be evaluated for different food products in humans. To elucidate how the colonic concentration of CAs in healthy subjects is influenced by dietary supplementation with oat bran, and whether the concentration varies over time and during consecutive days. Subjects/Methods: Twenty-five healthy subjects ( age 24 +/- 1.3) were recruited to the study. The subjects were given 40 g beta-glucan enriched oat bran per day, corresponding to 20 g dietary fibre, in 4 slices of bread. CAs were analysed in faeces during three consecutive days after 0, 4, 8 and 12 weeks on this diet. Results: The concentration of acetic, propionic, butyric, isobutyric and isovaleric acid was higher (P<0.05-0.001) after 8 weeks on the oat bran diet as compared with values at entry, whereas that of lactic acid was lower (P<0.05).After 12 weeks, the concentrations of acetic, propionic and isobutyric acid were still higher and that of lactic acid lower. The variation between individuals was considerable, whereas in the same individuals there was little variation. Conclusions: Oat bran increased the faecal concentration of CAs after 8 weeks, indicating an increased concentration also in the distal colon. The concentration of all main acids increased, except for lactic acid, which decreased. Oat bran may therefore have a preventive potential adjunct to colonic diseases.
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| 7. |
- Nilsson, Å., et al.
(författare)
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Olsalazine versus sulphasalazine for relapse prevention in ulcerative colitis : A multicenter study
- 1995
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Ingår i: American Journal of Gastroenterology. - 0002-9270 .- 1572-0241. ; 90:3, s. 381-387
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare the relapse-preventing effect and the frequency of adverse events of olsalazine and sulphasalazine in sulphasalazine-tolerant patients with ulcerative colitis. METHODS: Patients in remission, with at least two episodes of active disease during the last 5 yr, were randomized to 2 g of sulphasalazine or 1 g of olsalazine daily and were followed for 6-18 months. Relapse rates in the two groups were compared using frequency and life-table analysis. Sixty-nine patients with proctitis, 140 with left-sided colitis, and 113 with subtotal or total colitis were evaluated. RESULTS: In the intention-to-treat analysis, the failure rate (relapses plus withdrawals) was 54.7% in the olsalazine and 47.2% in the sulphasalazine group. In the per-protocol analysis excluding withdrawals, 44.7% relapsed in the olsalazine and 39.3% in the sulphasalazine group. Remission curves did not differ significantly, although at all time intervals the frequency of remission was slightly higher in the sulphasalazine group (p = 0.19 in the intention-to-treat analysis and p = 0.42 in the per-protocol analysis estimated by the log-rank test). Twelve patients (of whom five had diarrhea) in the olsalazine group versus eight patients in the sulphasalazine group discontinued the study because of side effects. CONCLUSION: The relapse-preventing effect of olsalazine and sulphasalazine in sulphasalazine-tolerant patients did not differ. Furthermore, the tolerability of olsalazine, particularly concerning diarrhea, appears to be better than previously reported.
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| 8. |
- Andersson, C., et al.
(författare)
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Immunocytochemical demonstration of oestrogen receptor beta in blood vessels of the female rat
- 2001
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Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 169:2, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- The role of oestrogen receptor (ER) beta in vascular function remains unclear. With the use of a specific ERbeta antibody we have now, using immunocytochemistry, visualized ERbeta in different parts of the vascular tree. In about 70% of medial smooth muscle cells of female rat aorta, tail artery and uterine artery, nuclear immunoreactivity to ERbeta was observed. In these vessels endothelial cells also expressed ERbeta. Vascular expression of the ERalpha subtype was lower than that of ERbeta. In aorta and tail artery, no immunoreactivity towards ERalpha was observed, while in uterine vessels occasional medial smooth muscle and endothelial cells expressed this ER subtype. ERbeta and alpha expression in uterine vessels was independent of the stage of the oestrous cycle, suggesting that variations in uterine blood flow occurring during the cycle are independent of ER density. The regional distribution of ERalpha, as determined by immunocytochemistry, was supported by measurements of ERalpha levels by enzyme immunoassay. In the uterine artery, the level of ERalpha was several times higher (P<0.001) than that of aorta and tail artery (10.1+/-1.7 fmol/mg protein in the uterine artery vs 3.3+/-1.0 and 0.5+/-0.5 fmol/mg protein in aorta and tail artery respectively). Thus, a prominent nuclear expression of ERbeta was observed in the vascular wall of several parts of the vascular tree, while ERalpha predominantly was expressed in uterine vessels, suggesting that ERbeta and alpha may have different roles in vascular function.
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| 9. |
- Antonov, D, et al.
(författare)
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HCV inhibiting macrocyclic phenylcarbamates
- 2008
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Patent (populärvet., debatt m.m.)abstract
- Compounds of the formula I: including a stereoisomer thereof, or an N-oxide, a pharmaceutically acceptable addition salt, or a pharmaceutically acceptable addition solvate thereof; useful as HCV inhibitors; processes for preparing these compounds as well as pharmaceutical compositions comprising these compounds as active ingredient.
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| 10. |
- Berggren, Å, et al.
(författare)
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Evaluating reflexive methodologies at Çatalhöyük
- 2014
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Ingår i: Integrating Çatalhöyük: themes from the 2000-2008 seasons : Çatal Research Project vol. 10 - Çatal Research Project vol. 10. - 9781898249320 ; 49, s. 55-68
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Bokkapitel (refereegranskat)
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