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| 2. |
- 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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| 3. |
- 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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| 5. |
- 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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| 6. |
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| 7. |
- 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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| 8. |
- Abrahamson, Magnus, et al.
(författare)
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Identification of the probable inhibitory reactive sites of the cysteine proteinase inhibitors human cystatin C and chicken cystatin
- 1987
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 262:20, s. 9688-9694
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Tidskriftsartikel (refereegranskat)abstract
- When an excess of human cystatin C or chicken cystatin was mixed with papain, an enzyme-inhibitor complex was formed immediately. The residual free cystatin was then progressively converted to a form with different electrophoretic mobility and chromatographic properties. The modified cystatins were isolated and sequenced, showing that there had been cleavage of a single peptide bond in each molecule: Gly11-Gly12 in cystatin C, and Gly9-Ala10 in chicken cystatin. The residues Gly11 (cystatin C) and Gly9 (chicken cystatin) are among only three residues conserved in all known sequences of inhibitory cystatins. The modified cystatins were at least 1000-fold weaker inhibitors of papain than the native cystatins. An 18-residue synthetic peptide corresponding to residues 4-21 of cystatin C did not inhibit papain but was cleaved at the same Gly-Gly bond as cystatin C. When iodoacetate or L-3-carboxy- trans-2,3-epoxypropionyl-leucylamido-(4-guanidin o)butane was added to the mixtures of either cystatin with papain, modification of the excess cystatin was blocked. Papain-cystatin complexes were stable to prolonged incubation, even in the presence of excess papain. We conclude that the peptidyl bond of the conserved glycine residue in human cystatin C and chicken cystatin probably is part of a substrate- like inhibitory reactive site of these cysteine proteinase inhibitors of the cystatin superfamily and that this may be true also for other inhibitors of this superfamily. We also propose that human cystatin C and chicken cystatin, and probably other cystatins as well, inhibit cysteine proteinases by the simultaneous interactions with such proteinases of the inhibitory reactive sites and other, so far not identified, areas of the cystatins. The cleavage of the inhibitory reactive site glycyl bond in mixtures of papain with excess quantities of cystatins is apparently due to the activity of a small percentage of atypical cysteine proteinase molecules in the papain preparation that form only very loose complexes with cystatins under the conditions employed and degrade the free cystatin molecules.
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| 9. |
- Abrahamson, Magnus, et al.
(författare)
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Isolation of six cysteine proteinase inhibitors from human urine. Their physicochemical and enzyme kinetic properties and concentrations in biological fluids
- 1986
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 261:24, s. 11282-11289
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Tidskriftsartikel (refereegranskat)abstract
- Six cysteine proteinase inhibitors were isolated from human urine by affinity chromatography on insolubilized carboxymethylpapain followed by ion-exchange chromatography and immunosorption. Physicochemical and immunochemical measurements identified one as cystatin A, one as cystatin B, one as cystatin C, one as cystatin S, and one as low molecular weight kininogen. The sixth inhibitor displayed immunochemical cross-reactivity with salivary cystatin S but had a different pI (6.85 versus 4.68) and a different (blocked) N-terminal amino acid. This inhibitor was tentatively designated cystatin SU. The isolated inhibitors accounted for nearly all of the cysteine proteinase inhibitory activity of the urinary pool used as starting material. The enzyme inhibitory properties of the inhibitors were investigated by measuring inhibition and rate constants for their interactions with papain and human cathepsin B. Antisera raised against the inhibitors were used in immunochemical determinations of their concentrations in several biological fluids. The combined enzyme kinetic and concentration data showed that several of the inhibitors have the capacity to play physiologically important roles as cysteine proteinase inhibitors in many biological fluids. Cystatin C had the highest molar concentration of the inhibitors in seminal plasma, cerebrospinal fluid, and milk; cystatin S in saliva and tears; and kininogen in blood plasma, synovial fluid, and amniotic fluid.
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| 10. |
- Abrahamson, Magnus, et al.
(författare)
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Molecular cloning and sequence analysis of cDNA coding for the precursor of the human cysteine proteinase inhibitor cystatin C
- 1987
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Ingår i: FEBS Letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 216:2, s. 229-233
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant cystatin C producing clones were isolated from a human placenta λgt11 cDNA library. The cDNA insert of one of the clones, containing 777 base pairs, encodes the complete mature cystatin C (120 amino acids) and a hydrophobic leader sequence of 26 amino acids, indicating an extracellular function of the inhibitor. The deduced protein sequence confirms the protein sequence of cystatin C isolated from human urine, but differs in one position from the sequence of the cystatin C fragment deposited as amyloid in hereditary cerebral hemorrhage with amyloidosis.
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