| 1. |
- Abdul-Rahman, A, et al.
(författare)
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Local cerebral blood flow in the rat during severe hypoglycemia, and in the recovery period following glucose injection
- 1980
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 109:3, s. 307-314
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Tidskriftsartikel (refereegranskat)abstract
- In order to assess the influence of severe hypoglycemia on local cerebral blood flow (1-CBF) artificially ventilated rats, maintained on 70% N2O, were injected with insulin to provide either an EEG pattern of slow-wave polyspikes, or cessation of spontaneous EEG activity for 5, 15 or 30 min ("coma"). In other animals, glucose was injected at the end of a 30 min period of "coma" and 1-CBF was measured after recovery periods of 5, 30, 90, or 180 min. Local CBF was measured autoradiographically with 14C-iodoantipyrine as the diffusible tracer. In the slow-wave polyspike period 1-CBF was increased in most of the structures studied, and reached values that were 1.4 to 3.2 times greater than control. In many structures, cessation of EEG activity was accompanied by a further increase in 1-CBF, with some structures (thalamus, hypothalamus, pontine gray, and cerebellar cortex) showing flow rates of 400--500% of control. The increase in 1-CBF was unrelated to arterial hypertension, hypercapnia, or hypoxia. 5 min after glucose injection the hyperemia persisted in only some of the structures studied; in others, the 1-CBF were close to, or below, control values. During the subsequent recovery period 1-CBF was markedly reduced with some structures (cerebral cortical areas, hippocampus, and caudate-putamen) showing flow rates of only 20--35% of control. In others, notably pontine gray and cerebellar cortex, secondary hypoperfusion was never observed. The hypoperfusion was unrelated to arterial hypertension, hypocapnia, or increase in intracranial pressure. It is concluded that, like hypoxia and ischemia, substrate deficiency due to hypoglycemia is accompanied by vasodilatation in the brain. Furthermore, like long-lasting ischemia, severe hypoglycemia is followed by a delayed hypoperfusion syndrome that, by restricting oxygen supply, may well contribute to the final cell damage incurred.
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| 2. |
- Aberg, T, et al.
(författare)
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Cerebral function monitoring in rats with a critical hepatic injury treated with pneumatic antishock garment and infusion
- 1989
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Ingår i: Journal of Trauma. - 0022-5282. ; 29:2, s. 168-174
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Tidskriftsartikel (refereegranskat)abstract
- Twenty-nine rats were subjected to a severe standardized hepatic injury and divided into four groups. In addition to controls, the animals were treated with PASG inflated to 40 mm Hg, PASG and infusion of Ringer's acetate, or PASG and infusion of Ringer's acetate and Dextran 70 in combination. The aim of the infusion therapy was to stabilize the mean aortic blood pressure at 60 mm Hg. PASG significantly prolonged the survival time and the time during which a sensory evoked response could be observed. The PASG also prolonged the time before the EEG amplitude began to decrease or a burst-suppression pattern appeared in the EEG. Intravenous infusion of Ringer's acetate did not prolong these times compared to when PASG was used alone; when Dextran 70 was added to the infusion therapy these times were reduced. Changes in the EEG were recorded at a mean aortic pressure of 60 mm Hg when infusions were given, whereas the aortic pressure had to fall to 40 mm Hg before any changes could be observed when no infusions were used.
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| 3. |
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| 4. |
- Abrahamson, Magnus
(författare)
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Cystatins
- 1994
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Ingår i: Methods in Enzymology. - : Elsevier. - 0076-6879. ; 244, s. 685-700
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Tidskriftsartikel (refereegranskat)
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| 5. |
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| 6. |
- Abrahamson, Magnus, et al.
(författare)
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Efficient production of native, biologically active human cystatin C by Escherichia coli
- 1988
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Ingår i: FEBS Letters. - 1873-3468. ; 236:1, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- A cDNA encoding the mature human cysteine proteinase inhibitor cystatin C was fused to the coding sequence for the Escherichia coli outer membrane protein A signal peptide, and the recombinant gene was expressed in E. coli under the control of the λ PR promoter, an optimized Shine-Dalgarno sequence and the λ cI 857 repressor. When induced at 42°C, such cells expressed large amounts of recombinant cystatin C. The recombinant protein was isolated in high yield and characterized. All physicochemical properties investigated, including the positions of disulfide bonds, indicated that the E. coli derived cystatin C was identical to cystatin C isolated from human biological fluids, except that the proline residue in position three was not hydroxylated. The recombinant protein displayed full biological activity against papain, cathepsin B and dipeptidyl peptidase I.
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| 7. |
- Abrahamson, Magnus, et al.
(författare)
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Hereditary cystatin C amyloid angiopathy: Identification of the disease causing mutation and specific diagnosis by polymerase chain reaction based analysis
- 1992
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Ingår i: Human Genetics. - 1432-1203. ; 89:4, s. 377-380
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary cystatin C amyloid angiopathy (HCCAA) is a dominantly inherited disease characterized by amyloidosis, dementia and fatal cerebral hemorrhage of young adults. A method for rapid and simple diagnosis of HCCAA is described. It is based upon oligonucleotide-directed enzymatic amplification of a 275-bp genomic DNA segment containing exon 2 of the cystatin C gene from a blood sample, followed by digestion of the amplification product with AluI. Loss of an AluI recognition site in the amplified DNA segment from HCCAA patients results in a deviating band-pattern at agarose gel electrophoresis, compared with that obtained from normal subjects or unaffected HCCAA family members. In a population of 9 patients with manifest HCCAA, 14 patients with other causes of brain hemorrhage and 16 healthy individuals, the diagnostic procedure displayed a sensitivity and specificity for HCCAA of 100%. Amplified DNA segments from 4 HCCAA patients of four different families were analyzed by nucleotide sequencing; the HCCAA-causing mutation in all families was found to be a single TrarrA substitution in the codon for amino acid residue 68 of cystatin C.
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| 8. |
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| 9. |
- Abrahamson, Magnus, et al.
(författare)
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Human cystatin C: Role of the N-terminal segment in the inhibition of human cysteine proteinases and in its inactivation by leucocyte elastase
- 1991
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Ingår i: Biochemical Journal. - 0264-6021. ; 273:3, s. 621-626
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Tidskriftsartikel (refereegranskat)abstract
- Leucocyte elastase in catalytic amounts was observed to rapidly cleave the Val-10-Gly-11 bond of the human cysteine-proteinase inhibitor cystatin C at neutral pH. The resulting modified inhibitor had size and amino acid composition consistent with a cystatin C molecule devoid of the N-terminal Ser-1-Val-10 decapeptide. Leucocyte-elastase-modified cystatin C had more than 240-fold lower affinity than native cystatin C for papain. Removal of the N-terminal decapeptide of human cystatin C also decreased inhibition of human cathepsins B and L by three orders of magnitude, but decreased inhibition of cathepsin H by only 5-fold. A tripeptidyldiazomethane analogue of of the N-terminal portion of cystatin C was a good inhibitor of cathepsins B and L but a poor inhibitor of cathepsin H. It therefore appears that amino acid side chains of the N-terminal segment of cystatin C bind in the substrate-binding pockets of cathepsins B and L but not in those of cathepsin H. It is argued that the N-terminal cystatin C interaction with cathepsin B is physiologically important and hence that leucocyte elastase could have a function as a regulator of extracellular cysteine-proteinase inhibitory activity at sites of inflammation.
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| 10. |
- Abrahamson, Magnus
(författare)
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Human cysteine proteinase inhibitors. Isolation, physiological importance, inhibitory mechanism, gene structure and relation to hereditary cerebral hemorrhage
- 1988
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Ingår i: Scandinavian journal of clinical and laboratory investigation. Supplementum. - 0085-591X. ; 48, s. 21-31
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Tidskriftsartikel (refereegranskat)abstract
- The isolation and characterization of six human cysteine proteinase inhibitors is reported. Their distribution in human biological fluids is also described and discussed with respect to physiological function. Studies on kininogen and cystatin C with respect to structure-function relationships and, as a result of the cystatin C studies, a general model for the mechanism of cysteine proteinase inhibition by cystatins are presented. The model was used for the construction of synthetic inhibitors which showed good inhibitory properties against papain and the streptococcal cysteine proteinase. Structures of cDNA and gene for normal human cystatin C are accounted for, as well as studies on the cystatin C gene in patients suffering from hereditary cystatin C amyloid angiopathy (HCCAA). As a result of this an RFLP that showed total co-segregation with the disease was found. It was concluded that the disease is caused by a point mutation in the cystatin C structural gene and that the RFLP will be a most useful tool for diagnosis of HCCAA. The production of recombinant cystatin C in E. coli is also reported and its possible use for treatment of HCCAA is discussed.
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