| 1. |
- Widell, Anders, et al.
(author)
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Relation between donor transaminase and recipient hepatitis non-A, non-B in Sweden
- 1988
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In: Vox Sanguinis. - 1423-0410. ; 54:3, s. 154-159
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Journal article (peer-reviewed)abstract
- The relation between donor alanine aminotransferase (ALT) and recipient post-transfusion hepatitis (PTH) non-A, non-B was studied in patients tested before and 6 and 12 weeks after transfusion. The minimum ALT criterion for PTH was 105 IU/l (greater than 2.5 times the upper normal of 42 IU/l). In 8.8% of donors, ALT was greater than 42 IU/l, and in 2.3% ALT was greater than 63 IU/l, i.e., 1.5 times elevated. PTH non-A, non-B occurred in 14 of 742 recipients. The PTH incidence increased when donor ALT was above 63 IU/l (1.5 vs. 5.6%; p less than 0.05). However, if the confounding factor of volume variations was compensated for, elevated donor ALT and PTH were only statistically linked among recipients less than 70 years (p less than 0.02; Mantel-Haenszel test).
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| 2. |
- Axelsson, Annika, et al.
(author)
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Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca 2+-influx and β-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key β-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of β-cell phenotype and function.
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| 3. |
- Berggren Söderlund, Maria, et al.
(author)
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Biological variation of retinoids in man.
- 2002
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 62:7, s. 511-519
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Journal article (peer-reviewed)abstract
- This investigation was undertaken to assess biological variation, especially the within-subject variations of all- trans retinoic acid, 13- cis retinoic acid and retinol in human serum. Diurnal variation and variation over a week, a month and a year were studied in 11 males (aged 21 - 54 years) and 17 females (aged 22 - 63 years), all subjectively healthy. We found no diurnal variation with the exception of all- trans retinoic acid, which had maximal concentrations at noon irrespective of food intake. Seasonal variations were marginal. Both all- trans and 13- cis retinoic acids had fairly high within-subject (13.1% and 12.6%, respectively) and between-subject coefficients of variation (15.9% and 21.0%, respectively), while the within-subject CV of retinol was less (5.6%, with a between-subject CV of 21.1%). Thus, the indices of individuality were <1 for all retinoids. The critical differences between two consecutive samples were <40% for the retinoic acids and <20% for retinol. Women had higher all- trans retinoic acid concentrations in serum (5.1 nmol/L vs. 4.5 nmol/L), lower 13- cis retinoic acid concentrations (4.5 nmol/L vs. 5.5 nmol/L) and lower retinol concentrations in serum (2.1 µmol/L vs. 2.5 µmol/L) than men. Thus, samples for retinoid determinations should be drawn in the morning and evaluated using separate gender reference intervals.
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| 4. |
- Eksmyr, R, et al.
(author)
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Low molecular weight proteinuria and slight hyperlipoproteinemia in three mentally retarded brothers.
- 1976
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In: Acta paediatrica Scandinavica. - 0001-656X. ; 65:4, s. 521-5
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Journal article (peer-reviewed)abstract
- Mental retardation in combination with proteinuria and a slight hyperlipoproteinemia was found in three brothers. The increased urinary protein excretion was dominated by albumin and the low molecular weight proteins retinol-binding protein (RBP) and beta2-microglobulin, indicating the presence of proximal tubular dysfunction. However, there was no glucosuria, phosphaturia or amino aciduria and the renal concentrating and acidification capacities were normal. A kidney biopsy in one of the patients revealed morphologic evidence of glomerular damage but a normal tubular structure. A mild hyper-beta-lipoproteinemia was found in the patients but not in their healthy siblings. The cause of this syndrome, hitherto not described, is unknown.
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| 5. |
- Abels, Mia, et al.
(author)
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CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion
- 2016
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:9, s. 1928-1937
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Journal article (peer-reviewed)abstract
- Aims/hypothesis Insufficient insulin release and hyperglucagonaemia are culprits in type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART, encoded by Cartpt) affects islet hormone secretion and beta cell survival in vitro in rats, and Cart(-/-) mice have diminished insulin secretion. We aimed to test if CART is differentially regulated in human type 2 diabetic islets and if CART affects insulin and glucagon secretion in vitro in humans and in vivo in mice. Methods CART expression was assessed in human type 2 diabetic and non-diabetic control pancreases and rodent models of diabetes. Insulin and glucagon secretion was examined in isolated islets and in vivo in mice. Ca2+ oscillation patterns and exocytosis were studied in mouse islets. Results We report an important role of CART in human islet function and glucose homeostasis in mice. CART was found to be expressed in human alpha and beta cells and in a subpopulation of mouse beta cells. Notably, CART expression was several fold higher in islets of type 2 diabetic humans and rodents. CART increased insulin secretion in vivo in mice and in human and mouse islets. Furthermore, CART increased beta cell exocytosis, altered the glucose-induced Ca2+ signalling pattern in mouse islets from fast to slow oscillations and improved synchronisation of the oscillations between different islet regions. Finally, CART reduced glucagon secretion in human and mouse islets, as well as in vivo in mice via diminished alpha cell exocytosis. Conclusions/interpretation We conclude that CART is a regulator of glucose homeostasis and could play an important role in the pathophysiology of type 2 diabetes. Based on the ability of CART to increase insulin secretion and reduce glucagon secretion, CART-based agents could be a therapeutic modality in type 2 diabetes.
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| 6. |
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| 7. |
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| 8. |
- Berggren Söderlund, Maria, et al.
(author)
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Expression of human all-trans-retinoic acid receptor beta and its ligand-binding domain in Escherichia coli
- 1995
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In: Biochemical Journal. - 0264-6021. ; 308:Pt 1, s. 353-359
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Journal article (peer-reviewed)abstract
- all-trans-Retinoic acid, one of the hormonally active derivatives of vitamin A, occurs physiologically in plasma at a concentration below 10 nmol/l. The methods currently used for its quantification are based on HPLC, need about 1 ml of serum, are relatively laborious and thus not well suited for mass analysis. The affinity and specificity of retinoic acid receptors for all-trans-retinoic acid encouraged us to express both the entire human retinoic acid receptor beta (RAR-beta) and two versions of its retinoic acid-binding domain in Escherichia coli in the hope that these recombinant proteins might be used as binders in a ligand-binding assay for all-trans-retinoic acid. The recombinant receptors, the whole receptor [RAR-beta-(V7-Q448)], corresponding to domains A-F, and the ligand-binding domain [RAR-beta-(E149-Q448)], corresponding to domains D-F, were expressed in the vector pET 3d/BL21 (DE3) as inclusion bodies, solubilized with guanidinium chloride, renatured and purified by ion-exchange chromatography. RAR-beta-(P193-Q448), corresponding to domains E-F, was expressed in the vector pET 3d/BL21(DE3)pLysS, and purified by reversed-phase chromatography. Under non-denaturing conditions, the expressed whole receptor [RAR-beta-(V7-Q448)] and the D-F construct (RAR-beta-(E149-Q448)] behaved chromatographically as monomeric proteins whereas the E-F construct [RAR-beta-(P193-Q448)] had a strong tendency to aggregate. RAR-beta-(V7-Q448) and RAR-beta-(E149-Q448) had similar Kd values for all-trans-retinoic acid (1.4 and 0.6 nmol/l respectively) whereas RAR-beta-(P193-Q448) bound all-trans-retinoic acid less avidly (Kd 9.6 nmol/l). 9-cis-Retinoic acid bound to RAR-beta-(E149-Q448) and RAR-beta-(V7-Q448) as avidly as all-trans-retinoic acid. Competition experiments showed weak or no binding of 4-oxo-all-trans-retinoic acid, 4-oxo-13-cis-retinoic acid, 13-cis-retinoic acid, acitretin and retinol by RAR-beta-(E149-Q448).
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| 9. |
- Bitzén, Ulrika, et al.
(author)
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Retinyl palmitate is a reproducible marker for chylomicron elimination from blood
- 1994
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 54:8, s. 611-613
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Journal article (peer-reviewed)abstract
- To study the individual variation in chylomicron clearance rate, young healthy volunteers were given a p.o. dose of 50,000 IU retinyl palmitate in the morning to label their chylomicrons. Serial blood samples were then obtained in the time interval 4-8 h after retinyl palmitate intake, to closely monitor the clearance of retinyl ester from the blood. The procedure was repeated in an identical way two days later. The calculated individual halflives for retinyl palmitate clearance ranged from 1.54 to 9.90 h, i.e. a more than five-fold variation. The intraindividual variation was much less (relative SD 11%). Retinyl palmitate clearance (and probably chylomicron clearance) is, thus, relatively constant within the same individual on different occasions but varies considerably between individuals.
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| 10. |
- Fex, G, et al.
(author)
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Isolation and partial characterization of a low molecular weight trypsin inhibitor from human urine
- 1981
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In: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 0005-2795. ; 667:2, s. 8-303
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Journal article (peer-reviewed)abstract
- A low molecular weight glycoprotein which completely inhibited trypsin at a 1 : 1 molar ratio was isolated from human urine. It was generated from a precursor molecule which in turn derived from plasma inter-alpha-trypsin inhibitor. It had one polypeptide chain with a molecular weight of about 20 000 and a high content of half-cystine residues. Its amino-terminal amino-acid sequence was Val-Thr-Glu-Val-Thr-X-Leu-Glu-Asp-.
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