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| 2. |
- Eng, H, et al.
(författare)
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Beta 2-adrenergic receptor antibodies in myasthenia gravis.
- 1992
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Ingår i: Journal of autoimmunity. - 0896-8411. ; 5:2, s. 213-27
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Tidskriftsartikel (refereegranskat)abstract
- Although autoantibodies against the nicotinic acetylcholine receptor are the characteristic feature of the autoimmune disease myasthenia gravis (MG), no strong correlation is found between the autoantibody titer and the degree of clinical severity. Numerous studies have attempted to detect the presence of other autoantibody populations that might have a role in the pathology of the disease. We report, for the first time, that 18% of the MG patients we screened have antibodies in their serum to a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor (residues 172-197). Affinity purified antibodies to the beta 2-adrenergic receptor peptide 172-197 reacted with the human beta 2-adrenergic receptor protein obtained from transfected E. coli cell membrane extracts, but did not cross-react with the human AChR. Sufficient material was obtained from nine MG patients and it was found that the gamma globulin fraction from these patients immunoprecipitated the receptor, and that affinity purified IgG to peptide 172-197 competed for receptor binding with the beta-antagonist iodo-cyanopindolol. Using truncated peptides or amino acid modification procedures, no immunodominant B-cell epitope could be detected within region 172-197. Thus, a subpopulation of MG patients possesses anti-beta 2-adrenergic receptor antibodies which are a distinct set of autoantibodies with possible pharmacological activity.
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| 3. |
- Fu, Michael, 1963, et al.
(författare)
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Gi-mediated muscarinic adenylyl cyclase inhibition in timolol-treated stunned porcine myocardium.
- 1994
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Ingår i: Acta physiologica Scandinavica. - 0001-6772. ; 151:3, s. 291-9
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Tidskriftsartikel (refereegranskat)abstract
- The Gi-mediated muscarinic receptor-adenylyl cyclase system was examined in stunned myocardium induced by either three or five brief ischaemic periods after beta-adrenoceptor blockade by timolol (0.1 mg kg-1). The mid-left anterior descending coronary artery was occluded for 2, 10 and 2 min in four pigs, and for 2, 2, 5, 10 and 2 min in four other pigs. All the ischaemic periods were separated by 30 min of reperfusion and the biopsies were obtained 60 min after the last ischaemic period. Segment length function was measured in the ischaemic region and in the control region supplied by the left circumflex artery. In the two groups, the percentage systolic shortening was reduced equally, to 59 +/- 9 and 58 +/- 10% of control in the region subjected to ischaemia and only minimally in the control region. The biopsies from the stunned region from both groups showed: (1) no change in either the affinity for carbachol or the number of binding sites of the muscarinic receptors; (2) no alterations in messenger RNA encoding for the alpha subunit-2 of the inhibitory guanine nucleotide binding protein, as demonstrated by northern blot and solution hybridization; (3) no change in membrane-bound inhibitory guanine nucleotide binding protein, as shown by enzyme immunoassay utilizing a specific anti-peptide antibody, and (4) unchanged inhibition of stimulated adenylyl cyclase activity. These results suggest that there is an intact inhibitory guanine nucleotide binding protein-mediated muscarinic receptor adenylyl cyclase system in the stunned porcine myocardium.
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| 4. |
- Fu, Michael, 1963, et al.
(författare)
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Oxygen free radical injury and Gs mediated signal transduction in the stunned porcine myocardium.
- 1992
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Ingår i: Cardiovascular research. - 0008-6363. ; 26:5, s. 449-55
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim was to investigate involvement of oxygen free radicals and any changes in the Gs mediated beta adrenergic signalling system of stunned porcine myocardium. METHODS: Myocardial stunning was induced in eight pentobarbitone anaesthetised pigs by brief occlusions of the distal left anterior descending coronary artery for periods of up to 10 min. Segment length function was measured in the ischaemic region and in a control region supplied by the circumflex artery. Left ventricular biopsies were obtained from the two regions 1 h after the last occlusion for ultrastructural and biochemical studies. Timolol has been used to prevent arrhythmia during ischaemia. RESULTS: At the time when biopsies were obtained, percent systolic shortening was reduced to 58% in the region subjected to ischaemia and was only minimally reduced in the control region. In the biopsies from the stunned region: (1) electron microscopy showed mild and reversible intracellular changes in the stunned myocardium; (2) the activities of superoxide dismutase and glutathione peroxidase were decreased by 66% and 52%, respectively; (3) the content of malondialdehyde was increased by 49%; (4) neither density nor affinity of beta adrenoceptors showed any changes; (5) there were no alterations in messenger RNA encoding for the alpha subunit of the stimulatory guanine nucleotide binding protein (Gs), demonstrated by northern and dot-blot hybridisations; (6) ELISA technique utilising a specific antipeptide antibody showed no quantitative change in Gs; (7) the activity of adenyl cyclase was unchanged. CONCLUSIONS: Even though the stunned porcine myocardium showed substantial evidence of free radical injury, the beta adrenergic signalling system was intact.
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| 5. |
- Guillet, J G, et al.
(författare)
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Induction of a pharmacologically active clonotypic B cell response directed to an immunogenic region of the human beta 2-adrenergic receptor.
- 1992
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Ingår i: Clinical and experimental immunology. - 0009-9104. ; 89:3, s. 461-7
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Tidskriftsartikel (refereegranskat)abstract
- It has been reported that autoantibodies against the beta 2-adrenergic receptors are involved in the pathology of allergic disorders and of Chagas' disease. Therefore, the immune response against a peptide (H26Q) corresponding to the putative second extracellular loop of the human beta 2-adrenergic receptor, which could be a target for autoantibody attack, was analysed in view of its possible immunogenicity. The free peptide induced a T cell-mediated humoral response in the context of three different murine MHC haplotypes. The T cell epitope was found to be localized in the N-terminal region of the peptide. Highly specific T helper cells were capable of stimulating B cells with the potential to generate a large antibody repertoire reactive with the loop peptide. MoAbs were screened to analyse this B cell response for antibodies potentially interfering with receptor function and a MoAb was found that impaired ligand binding to the receptor.
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| 6. |
- Hofgren, K, et al.
(författare)
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Word descriptors in suspected acute myocardial infarction. A comparison between patients with and without confirmed acute myocardial infarction
- 1994
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Ingår i: Heart & Lung. - : Elsevier. - 0147-9563 .- 1527-3288. ; 23:5, s. 397-403
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acute myocardial infarction (AMI) will not develop in a large proportion of patients admitted to the coronary care unit because of suspected AMI. OBJECTIVE: To evaluate whether patients with confirmed AMI use different words to describe their pain than patients in whom AMI was not confirmed. DESIGN: A retrospective descriptive design. METHODS: The Pain-O-Meter, a verbal pain scale composed of 12 sensory and 10 emotional word descriptors, was used to assess pain. SETTING: Coronary care unit in Sahlgrenska Hospital in Goteborg, Sweden. SUBJECTS: A convenience sample of 889 consecutive patients admitted to the coronary care unit because of suspected AMI. RESULTS: SENSORY COMPONENT--patients with confirmed AMI differed from those without AMI in the use of the words "pricking" (12% vs 17%; p < 0.05) and "tearing" (11% vs 6%; p < 0.05). No difference was found in the remaining 10 words. Affective components--Patients with confirmed AMI differed from those without AMI in the use of "terrifying" (29% vs 18%; p < 0.001), "intolerable" (16% vs 10%; p < 0.01), and "worrying" (48% vs 59%; p < 0.01). Women used stronger word descriptors more frequently than men. CONCLUSION: The use of specific or more word descriptors to separate patients with AMI from those without AMI was not supported by the study data. Although patients with AMI more frequently used the sensory word tearing as well as the affective words terrifying and intolerable and less frequently used the sensory word pricking and the affective word worrying than patients without AMI, the differences do not suggest a clinical profile that can be used to differentiate these clinical entities.
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| 7. |
- Johan, Zdenek, et al.
(författare)
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A Data Parallel Finite Element Method for Computational Fluid Dynamics on the Connection Machine Systems
- 1992
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Ingår i: Computer Methods in Applied Mechanics and Engineering. - : Elsevier BV. - 0045-7825 .- 1879-2138. ; 99:1, s. 113-134
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Tidskriftsartikel (refereegranskat)abstract
- A finite element method for computational fluid dynamics has been implemented on the Connection Machine systems CM-2 and CM-200. An implicit iterative solution strategy, based on the pre-conditioned matrix-free GMRES algorithm, is employed. Parallel data structures built on both nodal and elemental sets are used to achieve maximum parallelization. Communication primitives provided through the Connection Machine Scientific Software Library substantially improved the overall performance of the program. Computations of three-dimensional compressible flows using unstructured meshes having close to one million elements, such as a complete airplane, demonstrate that the Connection Machine systems are suitable for these applications. Performance comparisons are also carried out with the vector computers Cray Y-MP and Convex C-1.
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| 8. |
- Johan, Zdenek, et al.
(författare)
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An Efficient Communication Strategy for Finite Element Methods on the Connection Machine CM-5 System
- 1994
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Ingår i: Computer Methods in Applied Mechanics and Engineering. - 0045-7825 .- 1879-2138. ; 113:3-4, s. 363-387
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this paper is to propose communication procedures suitable for unstructured finite element solvers implemented on distributed-memory parallel computers such as the Connection Machine CM-5 system. First, a data-parallel implementation of the recursive spectral bisection (RSB) algorithm proposed by Pothen et al. is presented. The RSB algorithm is associated with a node renumbering scheme which improves data locality of reference. Two-step gather and scatter operations taking advantage of this data locality are then designed. These communication primitives make use of the indirect addressing capability of the CM-5 vector units to achieve high gather and scatter bandwidths. The performance of the proposed communication strategy is illustrated on large-scale three-dimensional fluid dynamics problems
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| 9. |
- Johan, Zdenek, et al.
(författare)
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Scalability of Finite Element Applications on Distributed–Memory Parallel Computers
- 1994
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Ingår i: Computer Methods in Applied Mechanics and Engineering. - 0045-7825 .- 1879-2138. ; 119:1-2, s. 61-72
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Tidskriftsartikel (refereegranskat)abstract
- This paper demonstrates that scalability and competitive efficiency can be achieved for unstructured grid finite element applications on distributed memory machines, such as the Connection Machine CM-5 system. The efficiency of finite element solvers is analyzed through two applications: an implicit computational aerodynamics application and an explicit solid mechanics application. Scalability of mesh decomposition and of data mapping strategies is also discussed. Numerical examples that support the claims for problems with an excess of fourteen million variables are presented.
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| 10. |
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