| 1. |
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| 2. |
- Nilsson, Å., et al.
(author)
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Olsalazine versus sulphasalazine for relapse prevention in ulcerative colitis : A multicenter study
- 1995
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In: American Journal of Gastroenterology. - 0002-9270 .- 1572-0241. ; 90:3, s. 381-387
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Journal article (peer-reviewed)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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| 3. |
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| 4. |
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| 5. |
- Ekdahl, K N, et al.
(author)
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Defective Fc receptor-mediated clearance in patients with primary biliary cirrhosis.
- 1991
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In: Gastroenterology. - 0016-5085 .- 1528-0012. ; 101:4, s. 1076-1082
-
Journal article (peer-reviewed)abstract
- Fc receptor-mediated clearance of immunoglobulin G-coated autologous erythrocytes was studied in patients with primary biliary cirrhosis (n = 14), alcoholic liver cirrhosis (n = 5) and healthy reference individuals (n = 14). The mean half-life of the sensitized erythrocytes was significantly prolonged in patients with primary biliary cirrhosis (85 +/- 25 minutes; P less than 0.001) compared with the corresponding value in patients with alcoholic cirrhosis (16 +/- 2 minutes) and healthy reference individuals (20 +/- 5 minutes), respectively. No correlation between clearance rate and age, liver histopathology, or serum levels of bilirubin, aminotransferases, immunoglobulin G, immunoglobulin A, and Clq binding or C3-containing immune complexes was found. The results presented here indicate a profound disturbance of Fc receptor-mediated immune clearance function in patients with primary biliary cirrhosis.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Landahl, Jonas, 1986, et al.
(author)
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Towards Adopting Digital Twins to Support Design Reuse during Platform Concept Development
- 2018
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In: Proceedings of NordDesign: Design in the Era of Digitalization, NordDesign 2018.
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Conference paper (peer-reviewed)abstract
- To gain a first-mover advantage on the marketplace, manufacturers are striving to develop innovative products that meet the needs of a wide range of customers. Traditionally to support innovative design, the fuzzy concept stage has long been supported by heuristic design philosophies. In recent years, new supportive technologies have enabled concept generation based on the collection and reuse of existing data. Existing data can be collected from various sources; for example, customer reviews, historical data, or by studying existing products or other industrial assets such as production machines and tooling. Lately, the concept of Digital Twin (DT) has gained a wealth of attention as a means to construct a high-fidelity digital copy of a physical asset and to study its shape, position, gesture, status and motion. The common aim of the DT is to support the realistic model of system behavior that can support performance prediction and optimization. However, in providing sufficient support during the conceptual stages the realistic models become heavy and costly to adapt. While the emerging data-driven design approaches can be used to generate designs with alterations, there is a lack of support to generate and evaluate solutions during the conceptual stages. In this paper, a framework of a Digital Platform Twin (DPT) is proposed to fill this gap. In contrast to a sole high-fidelity digital representation, the DPT builds on abstracting multiple high-fidelity Digital Twins into a low- fidelity platform model, represented as a function model. The DPT framework proclaims the vision of supporting design engineers in the process of abstracting functionalities of existing assets, inserting new functionalities and technologies in the function structure to ultimately support the generation and evaluation of new functional concepts. To demonstrate the DPT framework, an automotive example is presented. We believe that reuse during platform concept development can be supported with the use of multiple DTs. To achieve this, a challenge is to practically realize the transcending in abstraction levels of the models: from Digital Twins to function model and from function model to geometry models. The transcending in abstraction levels is therefore a matter of future work.
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| 10. |
- Larsson, D. G. Joakim, 1969, et al.
(author)
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Läkemedel i miljön
- 2014
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In: Läkemedelsboken 2014. ; , s. 1267-1279
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Research review (peer-reviewed)
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| 11. |
- Lavö, B, et al.
(author)
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Fc receptor function and circulating immune complexes in gluten sensitive enteropathy - possible significance of serum IgA
- 1991
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 32, s. 876-880
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Journal article (peer-reviewed)abstract
- The capacity to clear IgG containing immune complexes from the circulation was studied in patients with coeliac disease (n = 13), dermatitis herpetiformis (n = 8), and coeliac disease with concomitant serum IgA deficiency (n = 4). A small group of patients with active ulcerative colitis (n = 4) was included as a bowel disease control group. Clearance was estimated by measuring the disappearance rate of a bolus dose of intravenously injected IgG coated autologous erythrocytes. The mean T1/2 of clearance was prolonged in both coeliac disease (86 (24) minutes) and dermatitis herpetiformis (111 (35) minutes), compared with healthy subjects (20 (5) minutes) and coeliac patients with concomitant serum IgA deficiency (T1/2 = 17 (6) minutes). Patients with ulcerative colitis had a prolonged clearance, with a T1/2 of 195 (63) minutes. Values of circulating immune complexes were measured by four assays; C1q binding and C3, IgG, and IgA containing immune complexes. C1q binding immune complexes were detected only in IgA deficient gluten sensitive enteropathy. Patients with coeliac disease and dermatitis herpetiformis had higher values of C3, IgG, and IgA containing immune complexes than control subjects and serum IgA deficient patients with coeliac disease. The clearance rate was inversely correlated to the amount of immune complexes for the subgroups of gluten sensitive enteropathy.
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| 12. |
- Lindqvist, Ulla, et al.
(author)
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A hyaluronan-loading test applied to patients with liver and joint diseases
- 1992
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In: Clinica Chimica Acta. - 0009-8981 .- 1873-3492. ; 210:1-2, s. 119-132
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Journal article (peer-reviewed)abstract
- The serum hyaluronan disappearance data, after an intravenous bolus injection of hyaluronan, were evaluated in terms of model-based parameters. The loading test was performed in 10 healthy persons (basal serum hyaluronan concentration, C0, 24.9 +/- 8.9 micrograms/l [mean +/- S.D.]), 6 patients with joint disease (62.3 +/- 41.1 micrograms/l) and 19 patients with liver disease (206 +/- 214 micrograms/l). The highest maximum Michaelis-Menten elimination rate (Vmax = 287 +/- 86 micrograms/min) was found in patients with joint disease, significantly higher than in healthy persons (Vmax = 179 +/- 16, P = 0.0015) and in patients with liver disease (Vmax = 149 +/- 59, P = 0.0002). C0 and Vmax were evaluated as discriminants for assessment of residual liver function. In patients with liver disease C0 correlated with liver function score (r = 0.875, P < 0.0001) and serum albumin concentration (r = -0.813, P < 0.0001). The Vmax parameter did not correlate with conventional liver function tests or with the liver score but a significantly negative correlation of Vmax with C0 was found in patients with liver disease. A combination of the C0 level and the Vmax parameter was found to discriminate between healthy persons, patients with joint disease and patients with liver disease and should be of benefit in separating patients, with or without elevated serum hyaluronan levels, into groups having increased influx or reduced elimination, respectively, of circulating hyaluronan.
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| 13. |
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| 14. |
- Madrid, Julia, 1988, et al.
(author)
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Mitigating Risk of Producibility Failures in Platform Concept Development
- 2018
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In: 31st Congress of the International Council of the Aeronautical Sciences, ICAS 2018.
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Conference paper (peer-reviewed)abstract
- Late detection of producibility problems once a product is in production implies several risks. In aerospace applications, high manufacturing variation rates on a product can imply design modifications with subsequent increase of lead time and detriment of product performance, decreasing customer satisfaction. In the context of platform development, in which a wide range of customer needs are met by designing a variety of product variants, these risks can multiply to an unmanageable sum. To mitigate the risk of late modifications of a variety of designs, producibility aspects needs to become an imperative part of the early platform development stages. This paper presents a two- stage producibility assessment method employed to systematically narrow down a set of product- manufacturing variants based on information generated using various types of rule-based and simulation-based models. The assessments are used to mitigate the risk of producibility failures, classified in this study as operational failures and quality failures. The two-stage producibility assessment method is demonstrated in an aerospace case wherein a variety of aero engine sub-systems and welding resources are modeled and assessed. The results show that the risk of producibility failures can be mitigated by means of rapid and precise assessments during platform concept development. By mitigating these risks early on, the negative effects on manufacturing variation and lead time may be reduced.
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| 15. |
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| 16. |
- Michaëlsson, Gerd, et al.
(author)
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Increased lymphocyte infiltration in duodenal mucosa from patients with psoriasis and serum IgA antibodies to gliadin
- 1995
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In: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 133:6, s. 896-904
-
Journal article (peer-reviewed)abstract
- In a screening study concerning IgA and IgG antibodies to gliadin (IgA AGA and IgG AGA, respectively) in psoriasis, raised levels of IgA and AGA were found to be more common than in a reference group. To determine whether elevated AGA levels were associated with an increased number of intraepithelial lymphocytes, 33 patients with IgA AGA (n = 28) or IgG AGA (n = 5) values above 90% of the reference values (> 50 units/ml IgA AGA and < 12 units/ml IgG AGA) underwent gastroduodenoscopy and duodenal biopsy in a prospective study. For comparison, six patients with low levels of both IgA AGA and IgG AGA were included. Five biopsy specimens were taken in each patient. Paraffin-embedded specimens were examined with regard to the degree of intraepithelial lymphocyte infiltration, and scored from 0 to 3. Biopsy specimens with a score of 0 had one mononuclear cell or less per four epithelial cells. The specimens were also examined with regard to the presence of intraepithelial CD3+ T lymphocytes and gamma/delta+ T lymphocytes. In the six patients with low IgA AGA and low IgG AGA, the biopsy score was 0. Fourteen of the 33 patients with raised AGA had a score of > or = 1; of these, 12 had raised IgA AGA and two had slightly raised IgG AGA. Two of the patients with raised IgA AGA had partial villous atrophy, but the majority had normal villous architecture. There was a significant correlation both between the biopsy score and the number of intraepithelial CD3+ cells and between the score and the number of intraepithelial gamma/delta+ positive T lymphocytes. The serum IgA AGA levels were significantly correlated with the duodenal biopsy score, the number of intraepithelial gamma/delta+ T lymphocytes, and the number of CD3+ intraepithelial T lymphocytes. Most patients had no, or only mild, gastrointestinal symptoms. Of the 14 patients with biopsy scores > or = 1, seven had severe psoriasis and five moderately severe psoriasis, whereas only two had mild psoriasis. There was no relationship between the duodenal score and haemoglobin, folate, whole blood selenium or serum zinc levels. Some of these patients improve on a gluten-free diet, but it is still too early to draw any definite conclusions concerning the type of relationship between the skin lesions, the increased number of intraepithelial lymphocytes in the duodenal mucosa and gluten hypersensitivity.
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| 17. |
- Michaëlsson, Gerd, et al.
(author)
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Patients with psoriasis have elevated levels of serum eosinophil cationic protein and increased numbers of EG2 positive eosinophils in the duodenal stroma
- 1996
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In: British Journal of Dermatology. - 0007-0963 .- 1365-2133. ; 135:3, s. 371-378
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Journal article (peer-reviewed)abstract
- The occurrence of EG2-positive (EG2+) eosinophils and IgE in biopsy specimens of duodenal mucosa and skin from 39 psoriasis patients was studied, with emphasis on the relation to serum eosinophil cationic protein (ECP), serum IgE and the presence or absence of serum IgA and IgG antigliadin antibodies. Psoriasis patients had significantly elevated serum levels of ECP even after exclusion of five of 37 sera which were Phadiatop positive. The elevated serum ECP was not associated with the presence of IgA or IgG antibodies to gliadin. After exclusion of Phadiatop positive sera the serum IgE values did not differ from those of a group of healthy blood donors. Patients with psoriasis had a pronounced increase of EG2+ cells in their duodenal stroma. Patients without antibodies to gliadin tended to have even more EG2+ cells than those with such antibodies and those with increased duodenal intraepithelial lymphocytes. IgE+ cells were present in most duodenal specimens, and in some specimens there were > 100 IgE+ cells/section. The number of EG2+ cells was increased in lesional skin and, in some patients, also in non-involved skin, but there was a more pronounced increase in EG2 reactivity in the duodenal than in the skin specimens. IgE reactivity was increased both in non-involved and involved skin and was significantly related to the number of IgE-positive cells in the duodenal stroma. The results of this study indicate that the gastrointestinal tract and the eosinophil granulocyte might be involved in psoriasis in a hitherto unknown way.
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| 18. |
- Michaëlsson, Gerd, et al.
(author)
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Psoriasis patients have highly increased numbers of tryptase-positive mast cell in the duodenal stroma
- 1997
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In: British Journal of Dermatology. - 0007-0963 .- 1365-2133. ; 136:6, s. 866-870
-
Journal article (peer-reviewed)abstract
- We have shown that the number of tryptase-positive mast cells in the duodenal mucosa in psoriasis is increased and that a subgroup of psoriasis patients showed elevated levels of antibodies to gliadin (some of whom also had increased lymphocytes in the duodenal epithelium). Duodenal biopsy specimens from 37 patients with psoriasis (eight mild, 13 moderate and 16 severe) and 22 patients with irritable bowel syndrome (IBS) were examined regarding the presence of tryptase + mast cells. Intraepithelial infiltration by lymphocytes was evaluated and scored from 0 to 3. Patients with psoriasis had 131 +/- 58 mast cells/mm2 (mean +/- SD) and those with IBS 28 +/- 18. Only in four of the 37 psoriasis patients was the number within the range of that in the IBS group. There were no signs of stromal inflammation except in one psoriasis patient. No relationship was found between degree of severity of psoriasis and number of mast cells. In 25 of the 37 specimens from psoriasis patients there was no increase in intraepithelial lymphocytes, whereas seven showed a slight increase (score 1-2) and five a moderate increase (score > or = 2-3). The number of tryptase + mast cells was similar in patients with or without increased intraepithelial lymphocytes. The number of mast cells showed no relation to the presence or absence of antibodies to gliadin. We hypothesize that there are at least two types of abnormalities in the duodenal mucosa in psoriasis, one type that is present in most psoriasis patients and characterized by an increase in mast cells and eosinophils, and another that is present in a subgroup of patients with antibodies to gliadin and an increased number of duodenal intraepithelial lymphocytes. The mechanisms underlying the increase in the number of mast cells and its relevance are not yet known.
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| 19. |
- Michaëlsson, Gerd, et al.
(author)
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Psoriasis patients with antibodies to gliadin can be improved by a gluten-free diet
- 2000
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In: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 142:1, s. 44-51
-
Journal article (peer-reviewed)abstract
- In a previous screening study, 16% of patients with psoriasis had IgA and/or IgG antibodies to gliadin (AGA). The aim of the present study was to evaluate the effect of a gluten-free diet (GFD) in 33 AGA-positive and six AGA-negative psoriasis patients. Of the 33 AGA-positive patients, two had IgA antibodies to endomysium (EmA) and 15 an increased number of lymphocytes in the duodenal epithelium, but in some this increase was slight. Two patients had villous atrophy. A 3-month period on a GFD was followed by 3 months on the patient's ordinary diet. The severity of psoriasis was evaluated with the psoriasis area and severity index (PASI). The examining dermatologists were unaware of the EmA and duodenal biopsy results throughout the study. Thirty of the 33 patients with AGA completed the GFD period, after which they showed a highly significant decrease in mean PASI. This included a significant decrease in the 16 AGA-positive patients with normal routine histology in duodenal biopsy specimens. The AGA-negative patients were not improved. After GFD, the AGA values were lower in 82% of those who improved. There was a highly significant decrease in serum eosinophil cationic protein in patients with elevated AGA. When the ordinary diet was resumed, the psoriasis deteriorated in 18 of the 30 patients with AGA who had completed the GFD period. In conclusion, psoriasis patients with raised AGA might improve on a GFD even if they have no EmA or if the increase in duodenal intraepithelial lymphocytes is slight or seemingly absent.
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| 20. |
- Michaëlsson, Gerd, et al.
(author)
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The skin and the gut in psoriasis : the number of mast cells and CD3+ lymphocytes is increased in non-involved skin and correlated to the number of intraepithelial lymphocytes and mast cells in the duodenum
- 1997
-
In: Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 77:5, s. 343-346
-
Journal article (peer-reviewed)abstract
- The aim of this work was to study tryptase+ mast cells and CD3+ T lymphocytes in non-involved skin in psoriasis and their possible relation to mast cells and lymphocytes in the duodenal mucosa. Skin biopsy specimens were obtained from 43 patients with psoriasis of variable severity and from 10 healthy subjects. Compared with the reference subjects, the number of mast cells in non-involved skin was clearly increased, most markedly in the papillary dermis. The increase was present both in mild, moderate and severe psoriasis. CD3+ lymphocytes were increased in non-involved skin in moderate and severe psoriasis. Patients with an increased number of duodenal intraepithelial lymphocytes had significantly more mast cells in non-involved skin than those without such an increase, and there was a significant correlation between the number of mast cells in non-involved skin and score for intraepithelial lymphocytes. However, when the 14 patients with increased intraepithelial duodenal lymphocytes were excluded-as they may represent a separate type of psoriasis-another type of correlation between the skin and the duodenal mucosa was found, namely a highly significant inverse correlation between the number of CD3+ lymphocytes in non-involved skin and the number of duodenal mast cells, which is highly elevated in psoriasis. The results might indicate an interplay between skin and intestinal mast cells and lymphocytes in a hitherto unknown way.
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| 21. |
- Nilsson, B, et al.
(author)
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Identification of a nonproteolytically activated C3 with CR 1-binding properties in sera from subjects with primary biliary cirrhosis.
- 1986
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In: International archives of allergy and applied immunology. - 0020-5915. ; 80:3, s. 312-319
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Journal article (peer-reviewed)abstract
- Complement factor C3 associated with immune complex-like material was precipitated by 2.7% (w/v) polyethylene glycol (PEG) in sera from patients with primary biliary cirrhosis. Radioimmunoassay analysis demonstrated that this C3 expressed antigens which are specific for bound and denatured C3 but absent in native C3. Gelfiltration of the PEG precipitate revealed a C3 peak which corresponded to a molecular weight of more than 2 X 10(7) daltons but sucrose-gradient centrifugation of the same material showed that the C3 had a sedimentation coefficient of 4-7 S. SDS-PAGE followed by immunoblotting presented intact C3 alpha and C3 beta chains, and immune electrophoresis showed that the PEG-precipitated C3 was slower than native C3. The biological properties of the PEG-precipitable C3 were demonstrated by the inhibitory effect on the binding of immune complexes containing C3b to complement receptor 1. These data are not compatible with coprecipitation of native C3, nor with immune complex-bound C3b.
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| 22. |
- Nilsson, B, et al.
(author)
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Quantitation and antigenic characterization of bound C3 of circulating immune complexes in systemic lupus erythematosus, rheumatoid arthritis, and primary biliary cirrhosis.
- 1987
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In: Journal of Clinical Immunology. - 0271-9142 .- 1573-2592. ; 7:5, s. 420-426
-
Journal article (peer-reviewed)abstract
- In recent years defective function of the complement-mediated clearance of immune complexes (IC) has been reported in patients with immune complex disease. The defect has been found at different levels in the clearance system. An important event in this sequential system is the binding of C3-coated particles to C3 receptors on erythrocytes and phagocytes. This study focuses on immunochemical properties of IC-bound C3 that reflect the functional state of the molecule. Sera from patients with primary biliary cirrhosis (PBC), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) and from normal subjects were analyzed for their level of C3 precipitable in 2.7% (w/v) polyethylene glycol (PEG). The mean levels for the patient categories were significantly higher than that for the normal subjects. The immunochemical study revealed several differences among the different forms of PEG-precipitable C3. All forms expressed C3(D) antigens which are expressed by immune complex-associated and denatured forms but not by soluble physiological forms of C3. The expression of these antigens was proportionately lower for the complex-associated C3 of PBC compared to that of RA and SLE. Furthermore, employing monoclonal anti-C3(D) antibodies against the C3c and the C3d domain, distinct differences could be detected among all forms of PEG-precipitable C3. Sera from RA and SLE, in particular, contained PEG-precipitable C3 that exhibited distinctive immunochemical features with respect to these epitopes.
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| 23. |
- Nilsson Ekdahl, Kristina, et al.
(author)
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An improved method to study complement receptor-mediated function of the fixed macrophage system in vivo
- 1991
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In: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 61:1, s. 47-52
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Journal article (peer-reviewed)abstract
- A method to coat unsensitized erythrocytes with fragments of C3 and C4 using autologous serum, in order to study complement receptor-dependent function of the fixed macrophage system, is presented. After incubation with serum under optimal conditions, at least 90% of the cells had C3b/iC3b deposited on the surface, with an average of 20 × 103 molecules per cell. Elimination of the coated cells by the fixed macrophage system was studied in 12 normal subjects. With a dose of 4.5 × 108 red cells injected, 75% of the cells were eliminated with a half-life of approximately 2.4 ± 0.3 min (n = 7). In subjects receiving ten times more cells, there was a rapid decrease in the amount of C3-coated cells, reaching a nadir with 85% remaining for 4–6 min, after which there was a gradual release of cells for another 20 min (n = 5). In absolute numbers, 3 × 108 of labeled cells were eliminated regardless of the dose injected. The coating procedure presented here is simple, does not introduce heterologous blood components and makes it possible to control the amount and the degree of fragmentation of the C3 and C4 deposited on the erythrocyte surface.
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| 24. |
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| 25. |
- Nilsson Ekdahl, Kristina, et al.
(author)
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Defective Fc receptor-mediated clearance in patients with primary biliary cirrhosis
- 1991
-
In: Gastroenterology. - 0016-5085 .- 1528-0012. ; 101:4, s. 1076-1082
-
Journal article (peer-reviewed)abstract
- Fc receptor-mediated clearance of immunoglobulin G-coated autologous erythrocytes was studied in patients with primary biliary cirrhosis (n = 14), alcoholic liver cirrhosis (n = 5) and healthy reference individuals (n = 14). The mean half-life of the sensitized erythrocytes was significantly prolonged in patients with primary biliary cirrhosis (85 +/- 25 minutes; P less than 0.001) compared with the corresponding value in patients with alcoholic cirrhosis (16 +/- 2 minutes) and healthy reference individuals (20 +/- 5 minutes), respectively. No correlation between clearance rate and age, liver histopathology, or serum levels of bilirubin, aminotransferases, immunoglobulin G, immunoglobulin A, and Clq binding or C3-containing immune complexes was found. The results presented here indicate a profound disturbance of Fc receptor-mediated immune clearance function in patients with primary biliary cirrhosis.
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