| 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. |
- 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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| 3. |
- 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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| 4. |
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| 5. |
- Hagmar, L., et al.
(författare)
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Intra-individual variations and time trends 1991-2001 in human serum levels of PCB, DDE and hexachlorobenzene
- 2006
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 64:9, s. 1507-1513
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Tidskriftsartikel (refereegranskat)abstract
- Background: An important question is whether human serum levels of persistent organic pollutants has continued to decrease during the last decades. The aim of this study was to assess intra-individual variations over time of serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethene (p,p'-DDE) and hexachlorobenzene (HCB), considering the impact of a number of possible determinants. Methods: Blood samples were drawn for the same 39 subjects in 1991 and 2001. Interviews were made at both occasions. Lipid adjusted serum concentrations of CB-153, p,p'-DDE and HCB were determined in both sets of blood samples using gas chromatography-mass spectrometry. The fatty acid composition of the serum lipids was analyzed by means of gas-liquid chromatography. Result: The CB-153 concentrations in serum had averagely decreased with 34% in between 1991 and 2001 (p < 0.001). Of individual determinants only increasing BMI was associated with decreasing CB-153 levels (beta = -1.0, 95% CI -1.8, -0.2, p = 0.01), explaining 13% of the variation. The average decrease of p,p'-DDE was 55%, and could only weakly be associated with a relative increase of BMI (beta = - 1.0, 95% CI-2.3, 0.2, p=0.09), explaining only 5% of the variation. The average decrease of HCB was 53%, and was associated only with high fish consumption in 1991, explaining 12% of the variation. Conclusions: The results support a continuing decrease in human body burdens of PCBs, DDE and HCB during the 1990s. The explanatory factors relative change of BMI and fish consumption explained only a minor part of the time-related variations in serum levels.
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| 6. |
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| 7. |
- Jones, A. Wayne, et al.
(författare)
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Effect of high-fat, high-protein, and high-carbohydrate meals on the pharmacokinetics of a small dose of ethanol
- 1997
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Ingår i: British Journal of Clinical Pharmacology. - : Blackwell Publishing Ltd. - 0306-5251 .- 1365-2125. ; 44:6, s. 521-526
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Tidskriftsartikel (refereegranskat)abstract
- Aims To investigate whether the relative amounts of fat, carbohydrate (CHO), or protein in a meal influence the pharmacokinetics of a small dose of ethanol. Methods Nine healthy men received ethanol (0.30 g kg−1 body weight) on five occasions in a randomized cross-over fashion. On three occasions the dose of ethanol was consumed within 15 min of eating a standardized breakfast of similar volume and calorific value but containing different amounts of fat, CHO, and protein. On two other occasions the same dose of ethanol was ingested on an empty stomach (overnight fast) or administered by intravenous (i.v.) infusion over 30 min. Results The blood-ethanol profiles showed large inter and intraindividual variations, especially when ethanol was ingested after eating food. The peak blood-alcohol concentrations (BAC) were 16.6±4.0, 17.7±7.1, and 13.3±4.0 mg dl−1 (mean±s.d.) after fat, CHO, and protein-rich meals and 30.8±4.3 and 54.3±6.4 mg dl−1 after fasting and i.v. infusion, respectively. The corresponding areas under the concentration-time profiles (AUC) were 1767±549, 1619±760, 1270±406 mg dl−1 min after fat, CHO, and protein-rich meals compared with 3210±527 and 4786±446 mg dl−1 min after fasting and i.v. infusion, respectively. The time required to eliminate ethanol from the blood was shortened by 1–2 h in the fed-state. Conclusions Drinking ethanol after eating a meal, regardless of the nutritional composition, decreases the systemic availability of ethanol. Because gastric emptying is slow and more prolonged with food in the stomach, the delivery of ethanol to the duodenum and the liver will be highly variable as will the hepatic clearance of ethanol. Provided that portal venous BAC remains fairly low and ethanol metabolizing enzymes are not fully saturated then part of the dose of ethanol can be cleared by hepatic first-pass metabolism (FPM), as one consequence of Michaelis-Menten elimination kinetics.
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| 8. |
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| 9. |
- Kechagias, Stergios, 1969-, et al.
(författare)
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Impact of gastric emptying on the pharmacokinetics of ethanol as influenced by cisapride
- 1999
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 48:5, s. 728-732
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Tidskriftsartikel (refereegranskat)abstract
- Aims To examine the influence of cisapride on the pharmacokinetics of ethanol and the impact of gastric emptying monitored by the paracetamol absorption test. Methods Ten healthy male volunteers took part in a cross-over design experiment. They drank a moderate dose of ethanol 0.30 g kg−1 body weight exactly 1 h after eating breakfast either without any prior drug treatment or after taking cisapride (10 mg three times daily) for 4 consecutive days. In a separate study, the same dose of ethanol was ingested on an empty stomach (overnight fast). Paracetamol (1.5 g) was administered before consumption of ethanol to monitor gastric emptying. Venous blood was obtained at 5–10 min intervals for determination of ethanol by headspace gas chromatography and paracetamol was analysed in serum by high performance liquid chromatography (h.p.l.c.). Results The maximum blood-ethanol concentration (Cmax ) increased from 3.8±1.7 to 5.6±2.3 mmol l−1 (±s.d.) after treatment with cisapride (95% confidence interval CI on mean difference 0.28–3.28 mmol l−1 ). The area under the blood-ethanol curve (AUC) increased from 6.3±3.5 to 7.9±2.6 mmol l−1 h after cisapride (95% CI −0.74–3.9 mmol l−1 h). The mean blood ethanol curves in the cisapride and no-drug sessions converged at ≈2 h after the start of drinking. Both Cmax and AUC were highest when the ethanol was ingested on an empty stomach (Cmax 9.5±1.7 mmol l−1 and AUC 14.6±1.9 mmol l−1 h), compared with drinking 1 h after a meal and regardless of pretreatment with cisapride. Conclusions A small but statistically significant increase in Cmax occurred after treatment with cisapride owing to faster gastric emptying rate as shown by the paracetamol absorption test. However, the rate of absorption of ethanol, as reflected in Cmax and AUC, was greatest after drinking the alcohol on an empty stomach. The cisapride–ethanol interaction probably lacks any clinical or forensic significance.
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| 10. |
- Kechagias, Stergios, et al.
(författare)
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Low-dose aspirin decreases blood alcohol concentrations by delaying gastric emptying
- 1997
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science Business Media. - 0031-6970 .- 1432-1041. ; 53:04-Mar, s. 241-246
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine if treatment with low-dose aspirin (ASA) influences the bioavailability of orally administered alcohol and to assess whether this is caused by altered gastric emptying as measured by the paracetamol absorption test.Methods: In a single-center controlled crossover trial, ten healthy male medical students, aged 20–27 years, participated in two experiments in random order. Both times they took paracetamol (1.5 g together with a standardized breakfast) and drank ethanol (0.3 g/kg) 1 h after eating breakfast. On one drinking occasion, no previous medication was given. The other alcohol session was performed after the subjects had taken 75 mg ASA once daily for 7 days. On both occasions, venous blood samples were obtained at exactly timed intervals for a period of 3.5 h.Results: The blood-ethanol profiles showed large interindividual variations for both experiments. After treatment with ASA, the maximum blood-ethanol concentration was distinctly lower in seven subjects, almost unchanged in two subjects and increased in one subject. Overall, a statistically significant decrease in the peak blood-ethanol concentration was observed. The time required to reach peak blood-ethanol levels was somewhat longer after treatment with ASA. Although the areas under the concentration–time profiles were smaller after ASA treatment, these differences were not statistically significant. The concentrations of paracetamol in plasma were lower when ethanol was ingested after treatment with ASA and the areas under the concentration–time curves (0–170 min) were smaller.Conclusions: Intake of low-dose ASA (75 mg daily) tends to delay the absorption of a moderate dose of ethanol, which results in lower peak blood-ethanol concentrations and smaller areas under the concentration–time curves. The underlying mechanism seems to be delayed gastric emptying as indicated by the paracetamol absorption test.
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| 11. |
- Kechagias, Stergios, 1969-, et al.
(författare)
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Reliability of breath-alcohol analysis in individuals with gastroesophageal reflux disease
- 1999
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Ingår i: Journal of Forensic Sciences. - 0022-1198 .- 1556-4029. ; 44:4, s. 814-818
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Tidskriftsartikel (refereegranskat)abstract
- Gastroesophageal reflux disease (GERD) is widespread in the population among all age groups and in both sexes. The reliability of breath alcohol analysis in subjects suffering from GERD is unknown. We investigated the relationship between breath-alcohol concentration (BrAC) and blood-alcohol concentration (BAC) in 5 male and 5 female subjects all suffering from severe gastroesophageal reflux disease and scheduled for antireflux surgery. Each subject served in two experiments in random order about 1-2 weeks apart. Both times they drank the same dose of ethanol (~0.3 g/kg) as either beer, white wine, or vodka mixed with orange juice before venous blood and end-expired breath samples were obtained at 5-10 min intervals for 4 h. Ah attempt was made to provoke gastroesophageal reflux in one of the drinking experiments by applying an abdominal compression belt, Blood-ethanol concentration was determined by headspace gas chromatography and breath-ethanol was measured with an electrochemical instrument (Alcolmeter SD-400) of a quantitative infrared analyzer (Data-Master). During the absorption of alcohol, which occurred during the first 90 min after the start of drinking, BrAC (mg/210 L) tended to be the same of higher than venous BAC (mg/dL). In the post-peak phase, the BAC al ways exceeded BrAC. Four of the 10 subjects definitely experienced gastric reflux during the study although this did not result in widely deviant BrAC readings compared with BAC when sampling occurred at 5- min intervals. We conclude that the risk of alcohol erupting from the stomach into the mouth owing to gastric reflux and falsely increasing the result of an evidential breath-alcohol test is highly improbable.
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| 12. |
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| 13. |
- Nelson, K, et al.
(författare)
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Separation of rat leukocytes by countercurrent distribution in aqueous two-phase systems. II. Subpopulations which mediate selective and nonselective lysis of normal and colon carcinoma target cells in vitro
- 1978
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Ingår i: Cellular Immunology. - : Elsevier BV. - 0008-8749. ; 37:2, s. 422-431
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Tidskriftsartikel (refereegranskat)abstract
- Spleen cells from WF rats immunized to allogeneic lymphoid cells or to syngeneic colon carcinomas and from unimmunized controls were separated by countercurrent distribution in aqueous two-phase systems. The cells were assayed for cytotoxicity to allogeneic fibroblasts or syngeneic colon carcinoma cells and to syngeneic fibroblasts in a 24-hr 51Cr-release assay. Cells from immunized rats which selectively lysed the specific target cells were repeatedly found in one area of the distribution separate from the majority of cells, which nonselectively lysed syngeneic fibroblasts as well. A similar subpopulation which nonselectively lysed all target cells assayed was recovered from the spleens of unimmunized rats. The cells were also assayed for the ability to lyse antibody-coated thymocytes in a 4-hr 51Cr-release assay. The peak of K cells was found to overlap partially that of cells with nonselective cytotoxicity.
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| 14. |
- Redéen, Stefan, 1961-, et al.
(författare)
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Relationship of gastroscopic features to histological findings in gastritis and Helicobacter pylori infection in a general population sample
- 2003
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Ingår i: Endoscopy. - : Georg Thieme Verlag KG. - 0013-726X .- 1438-8812. ; 35:11, s. 946-950
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Tidskriftsartikel (refereegranskat)abstract
- Background and study aim: Various gastroscopic features may be interpreted as signs of gastritis, but the significance of such features in relation to histomorphology is uncertain. The aim of this study was to determine how macroscopic findings were related to histomorphological changes and the presence of Helicobacter pylori in the gastric mucosa, in a sample of the general population. Subjects and methods: 488 adult individuals, randomly selected from a general population, were screened with gastroscopy and biopsy. The macroscopic features recorded were erythema (diffuse, spotty, linear), erosions, absence of rugae in the gastric corpus, and presence of visible vessels. Gastritis was classified microscopically according to the Sydney system. The presence of H. pylori was determined histologically and using the urease test on fresh biopsy specimens. Results: The sensitivity and specificity of absence of rugae for moderate to severe atrophic gastritis in the gastric corpus were 67% and 85%, respectively. Corresponding valuers for severe atrophy were 90% and 84%. The sensitivity and specificity of the presence of visible vessels for moderate to severe atrophy in the corpus were 48% and 87%, and for severe atrophy the values were 80% and 87%, respectively. Considering the antrum, the sensitivity and specificity of the presence of visible vessels for moderate to severe atrophy was 14% and 91%, respectively. With regard to chronic inflammation (moderate to severe in the corpus or antrum), none of the features, alone or in combination, showed a sensitivity of more than 56%. No endoscopic features (alone or in combination) showed a sensitivity of more than 57 % for H. pylori infection. Conclusions: Except for the absence of rugae and visible vessels in the gastric corpus, macroscopic features as observed during gastroscopy are of very limited value in the evaluation of whether or not gastritis or H. pylori infection are present. This is in accordance with most previous studies in patient populations, and it must be emphasized that the diagnosis of gastritis should be based on histological examination of the gastric mucosa.
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| 15. |
- Steneholm, K., et al.
(författare)
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The role of process control on the steel cleanliness
- 2018
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Ingår i: Ironmaking & steelmaking. - : Taylor & Francis. - 0301-9233 .- 1743-2812. ; 45:2, s. 114-124
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Tidskriftsartikel (refereegranskat)abstract
- The possibilities of obtaining a good process control in order to reach a good cleanliness of the steel were studied based on plant trials. Steel and slag samples were taken from two steel grades with a slightly different composition, but with similar processing conditions. Thereafter, the chemical compositions of the steel and slag samples were determined. The results show that the sum of the FeO and MnO was found to be a clear indicator for when reoxidation had taken place. No conclusive indicator was found to predict the extent of slag carry-over from the electric arc furnace. However, most of the variation in deoxidation seem to originate from the accuracy of the slag raking. Steel grades with low amounts of deoxidisers such as C and Si naturally were found to result in higher oxygen contents at the start of deoxidation. Furthermore, calculations of oxygen activities in the steel melt were made and the results were compared to measurements with varying results. Overall, the results indicate that calculation of oxygen activities with multivalence slag species such as Fe and Cr requires additional measurements to obtain accurate results.
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| 16. |
- Winter, C, et al.
(författare)
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Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic
- 2016
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 27:8, s. 8-1532
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A mutation found in the BRCA1 or BRCA2 gene of a breast tumor could be either germline or somatically acquired. The prevalence of somatic BRCA1/2 mutations and the ratio between somatic and germline BRCA1/2 mutations in unselected breast cancer patients are currently unclear.PATIENTS AND METHODS: Paired normal and tumor DNA was analyzed for BRCA1/2 mutations by massively parallel sequencing in an unselected cohort of 273 breast cancer patients from south Sweden.RESULTS: Deleterious germline mutations in BRCA1 (n = 10) or BRCA2 (n = 10) were detected in 20 patients (7%). Deleterious somatic mutations in BRCA1 (n = 4) or BRCA2 (n = 5) were detected in 9 patients (3%). Accordingly, about 1 in 9 breast carcinomas (11%) in our cohort harbor a BRCA1/2 mutation. For each gene, the tumor phenotypes were very similar regardless of the mutation being germline or somatically acquired, whereas the tumor phenotypes differed significantly between wild-type and mutated cases. For age at diagnosis, the patients with somatic BRCA1/2 mutations resembled the wild-type patients (median age at diagnosis, germline BRCA1: 41.5 years; germline BRCA2: 49.5 years; somatic BRCA1/2: 65 years; wild-type BRCA1/2: 62.5 years).CONCLUSIONS: In a population without strong germline founder mutations, the likelihood of a BRCA1/2 mutation found in a breast carcinoma being somatic was ∼1/3 and germline 2/3. This may have implications for treatment and genetic counseling.
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