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- Graham, Jinko, et al.
(författare)
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Negative association between type 1 diabetes and HLA DQB1*0602-DQA1*0102 is attenuated with age at onset
- 1999
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Ingår i: European Journal of Immunogenetics. - : Wiley. - 0960-7420 .- 1365-2370. ; 26, s. 117-
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Tidskriftsartikel (refereegranskat)abstract
- HLA-associated relative risks of type 1 (insulin-dependent) diabetes mellitus were analysed in population-based Swedish patients and controls aged 0-34 years. The age dependence of HLA-associated relative risks was assessed by likelihood ratio tests of regression parameters in separate logistic regression models for each HLA category. The analyses demonstrated an attenuation with increasing age at onset in the relative risk for the positively associated DQB1*0201-A1*0502/B1*0302-A1*0301 (DQ2/8) genotype (P = 0.02) and the negatively associated DQB1*0602-A1*0102 (DQ6.2) haplotype (P = 0.004). At birth, DQ6.2-positive individuals had an estimated relative risk of 0.03, but this increased to 1.1 at age 35 years. Relative risks for individuals with DQ genotype 8/8 or 8/X or DQ genotype 2/2 or 2/X, where X is any DQ haplotype ether than 2, 8 or 6.2, were not significantly age-dependent. An exploratory analysis of DQ haplotypes other than 2, 8 and 6.2 suggested that the risk of type 1 diabetes increases with age for DQB1*0604-A1*0102 (DQ6.4) and that the peak risk for the negatively associated DQB1*0301-A1*0501 haplotype is at age 18 years. There was also weak evidence that the risk for DQB1*0303-A1*0301 (DQ9), which has a positive association in the Japanese population, may decrease with age. We speculate that HLA-DQ alleles have a significant effect on the rate of beta cell destruction, which is accelerated in DQ2/8-positive individuals and inhibited, but not completely blocked, in DQ6.2-positive individuals.
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- Haq, I., et al.
(författare)
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Interaction of Delta- and Lambda-[Ru(phen)2DPPZ]2+ with DNA: A Calorimetric and Equilibrium Binding Study
- 1995
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 117:17, s. 4788-4796
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescence and absorption spectroscopy, isothermal titration calorimetry, and viscosity measurements have been used to characterize the interaction of Delta and Lambda [Ru(phen)(2)DPPZ](2+) with calf thymus DNA. The method of continuous variations revealed two distinct binding stoichiometries for both Delta- and Lambda-DPPZ, corresponding to 0.7 and 3 mol of base pair/mol of ligand. Binding isotherms were obtained for the two enantiomers, both of which show strong binding to DNA, with K = 3.2 x 10(6) M(-1) bp and 1.7 x 10(6) M(-1) bp for the Delta and Lambda isomers, respectively, at 25 degrees C in solutions containing 50 mM NaCl. Titration calorimetry gave Delta H values of +0.3 kcal mol(-1) for Delta-DPPZ and +2.9 kcal mol(-1) for Lambda-DPPZ for their interaction with DNA. These small positive enthalpies, which were confirmed using thermal difference spectroscopy, indicated that the binding of these compounds to DNA is entropically driven. An enthalpy of +2.5 kcal mol(-1) was obtained for the binding of the parent compound, tris(phenanthroline)-Ru(II), to DNA. Titration of all three compounds into buffer gave a nonnegligible heat of dilution. The salt dependence of the binding constant was examined for both isomers. The slope SK = (delta logK/delta log[Na+]) was found to be 1.9 and 2.1 for the Delta and Lambda isomers, respectively. By using polyelectrolyte theory to interpret the observed salt dependence of the equilibrium constant, it can be shown that there is a significant nonelectrostatic contribution to the binding constant. Relative viscosity experiments showed that both Delta- and Lambda-DPPZ increase the length of rod-like DNA, in a manner consistent with binding by classical intercalation. Fluorescence energy transfer experiments provided additional evidence for the intercalation of Delta- and Lambda-[Ru(phen)(2)DPPZ](2+) into DNA.
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- Hedberg, U., et al.
(författare)
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Miniaturized thermal biosensors
- 1996
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Ingår i: Biochemical Technology. - 1569-2558. - 0762301147 - 9780762301140 ; 15, s. 499-505
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Bokkapitel (refereegranskat)abstract
- A summary of our efforts to develop miniaturized biosensors based on the enzyme thermistor is presented. Three constructions are described. The work focuses on the measurement of glucose in whole blood.The first biosensor was used to analyze concentrated and tenfold diluted blood samples. The glucose concentration obtained using this construction correlated well with the reference method.Using the second biosensor, the response time could be reduced from 3 minutes down to 30 seconds using a sample volume of 1 μl. The relative standard deviation for 100 blood samples (3.8 tnM) was 3.7%.Micromachining technology was used to construct the third thermal biosensor on a silicon chip. Enzymes were immobilized directly onto the 30 parallel flow channels. Injection of 200 samples containing 10 mM hydrogen peroxide gave a relative standard deviation of 3%.
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- Karlsson, B R, et al.
(författare)
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Effect of cerebral ischemia on hypotension-induced increase in plasma vasopressin and hepatic glycogen concentration in the rat.
- 1991
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Ingår i: Circulatory shock. - 0092-6213. ; 34:4, s. 371-8
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Tidskriftsartikel (refereegranskat)abstract
- The effect of cerebral ischemia on the vasopressin response to hemorrhagic hypotension and on the hepatic and muscular glycogen mobilization was studied in rats. The addition of cerebral ischemia to the hemorrhage required withdrawal of significantly more blood to lower mean arterial pressure (MAP) to 50 mmHg but not if combined with ganglionic blockade. The increase in plasma vasopressin concentration during hypotension was not significantly different in rats with and without concurrent cerebral ischemia. Ganglionic blockade blunted the vasopressin response. Thus cerebral ischemia in fact attenuated the vasopressin response to hemorrhage. One hour after the insult, the hormone concentration in rats exposed to combined cerebral ischemia and hemorrhagic hypotension without ganglionic blockade was still above control levels and higher than in all other groups. Concomitantly the hepatic but not the muscular glycogen concentration in these rats was significantly lower than in the other groups.
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- Karlsson, B R, et al.
(författare)
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The severity of postischemic hypoperfusion increases with duration of cerebral ischemia in rats.
- 1994
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172 .- 1399-6576. ; 38:3, s. 248-53
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Tidskriftsartikel (refereegranskat)abstract
- Regional cerebral blood flow was studied after a period of hypotensive bilateral carotid occlusion in rats. As other studies have found, we confirm that 15 min of ischemia caused an initial brief hyperemic episode followed by severe hypoperfusion in all areas. With varying duration of ischemia from 5 to 10, 15 and 20 min, the median cerebral blood flow 60 min postischemia was 79%, 46%, 48% and 34% of control, respectively. Thus the degree of postischemic hypoperfusion increased significantly with the duration of ischemia.
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