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- Abrahamson, Magnus, 1972-
(författare)
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Jesu uppståndelse som historiskt problem : En studie av Rudolf Bultmanns och Wolfhart Pannenbergs tolkningar
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main purpose of this study is to make a critical examination of Rudolf Bultmann´s (1884–1976) and Wolfhart Pannenberg´s (b. 1928) interpretations of the resurrection of Jesus. Bultmann is best known for seeking to demythologize the miracles of the New Testament. Pannenberg has gained much attention for arguing that the resurrection of Jesus is an event in chronological history. In this thesis I first present Bultmann´s and Pannenberg´s interpretations of the resurrection of Jesus. In order to help the reader understand the context in which these interpretations were made, I give a brief sketch of the German theological setting. Second, I compare the theologies of Bultmann and Pannenberg from the concept of background theory, principles of interpretation, exegetical reasoning, the meaning of the resurrection and what it means to accept the resurrection. Third, I categorize different ways that the resurrection could be interpreted today. Fourth, I critically discuss the way that Bultmann and Pannenberg argue and give some proposals for how their theologies can be developed. Developing the theology of Bultmann I give more attention to chronological history than he does. I also make alterations in the way he understands God´s action. Concerning Pannenberg I discuss the importance of rational arguments in his theology. I argue that the resurrection should be interpreted from the perspective of a faith or an interpretation which seeks understanding.
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| 2. |
- Eksandh, Louise, et al.
(författare)
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Different clinical expressions in two families with Stargardt's macular dystrophy (STGD1)
- 2001
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 79:5, s. 524-530
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe the clinical expressions, with emphasis on electrophysiological examinations, in two Swedish families with Stargardt's macular dystrophy (STGD1). Methods. Two pairs of siblings with STGD1, for whom diagnosis had been confirmed by genetic linkage to the ABCA4 gene region, were examined regarding visual acuity, kinetic perimetry, fundus photography, full-field ERG and multifocal ERG (MERG). Possible disease-causing mutations were screened for by DNA sequencing of selected regions of the ABCA4 gene. Results. All STGD1 patients, had visual acuity 0.07-0.1. The two families presented different fundus appearances, MERGs and implicit times on. 30 Hz flicker white light full-field ERGs. Genetic analysis revealed one unique sequence variation in exon 19 of the ABCA4 gene, in one allele from the patients of one of the families. This point mutation causes the amino acid substitution T972N in the ABCR protein. Conclusion. Two pairs of siblings with STGD1 presented two different expressions of the disease regarding the distribution of the retinal dysfunction. One possible molecular explanation to the different clinical expressions may be the T972N substitution present in the ABCR protein in one of the STGD1 families investigated.
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| 3. |
- Gränse, Lotta, et al.
(författare)
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Electrophysiologic findings in two young patients with Bothnia dystrophy and a mutation in the RLBP1 gene
- 2001
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Ingår i: Ophthalmic Genetics. - : Swets & Zeitlinger Publishers. - 1744-5094 .- 1381-6810. ; 22:2, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To characterize the clinical phenotype, with emphasis on electrophysiology, of two children with suspected Bothnia dystrophy. Methods: Two unrelated affected patients, 10 and 11 years old, were studied. Ophthalmological examination included testing of visual acuity, fundus inspection and fundus photography, kinetic perimetry, full-field electroretinogram (ERG), and multifocal ERG. The presence of a mutation in exon 7 of the RLBP1 gene was investigated by DNA sequencing. Results: Both patients were homozygous for the Arg234Trp-causing mutation in the RLBP1 gene, but the resulting disease phenotype appeared to vary somewhat between them. Visual acuity was moderately reduced in one patient and normal in the other. Fundus inspection at this age revealed no pathology in either patient and there were no signs of retinitis punctata albescens, which has been described previously as a frequent clinical feature of Bothnia dystrophy. The result of kinetic perimetry was normal. The final rod threshold was moderately elevated. Full-field ERG demonstrated the uncommon combination of absent rod response and normal cone response after 40 minutes of dark adaptation. However, after prolonged dark adaptation (20-24 h), both the rod response and the dark adaptation threshold became normal. Multifocal ERG was performed in one of the patients (the one with normal visual acuity and normal fundus appearance) and showed a reduced cone response in the central region of the tested area. There was no improvement of the multifocal ERG result after 20-24 h of dark adaptation. Conclusion: Patients with mutations in the RLBP1 gene (Arg234Trp) may have a normal fundus appearance early in the disease course. Multifocal ERG can be used for the objective documentation of the disturbed macular function, especially when the patient's visual acuity and fundus appearance are normal. The rod response is absent in the electroretinogram; however, after prolonged dark adaptation (20-24 hours), the rods recover completely. The central cones do not seem to recover.
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| 4. |
- Janowski, Robert, et al.
(författare)
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Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping
- 2001
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Ingår i: Nature Structural Biology. - : Springer Science and Business Media LLC. - 1072-8368. ; 8:4, s. 316-320
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Tidskriftsartikel (refereegranskat)abstract
- The crystal structure of human cystatin C, a protein with amyloidogenic properties and a potent inhibitor of cysteine proteases, reveals how the protein refolds to produce very tight two-fold symmetric dimers while retaining the secondary structure of the monomeric form. The dimerization occurs through three-dimensional domain swapping, a mechanism for forming oligomeric proteins. The reconstituted monomer-like domains are similar to chicken cystatin except for one inhibitory loop that unfolds to form the open interface of the dimer. The structure explains the tendency of human cystatin C to dimerize and suggests a mechanism for its aggregation in the brain arteries of elderly people with amyloid angiopathy. A more severe conformational disease is associated with the L68Q mutant of human cystatin C, which causes massive amyloidosis, cerebral hemorrhage and death in young adults. The structure of the three-dimensional domain-swapped dimers shows how the L68Q mutation destabilizes the monomers and makes the partially unfolded intermediate less unstable. Higher aggregates may arise through the three-dimensional domain-swapping mechanism occurring in an open-ended fashion in which partially unfolded molecules are linked into infinite chains.
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| 6. |
- Kasprzykowski, F., et al.
(författare)
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Peptidyl diazomethylketones as cysteine protease inhibitors structurally based upon the inhibitory centers of cystatins
- 2001
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Ingår i: Polish Journal of Chemistry. - 0137-5083. ; 75:6, s. 831-837
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Tidskriftsartikel (refereegranskat)abstract
- Six new putative cysteine protease inhibitors based upon sequences of the N-terminal binding fragments of rat cystatin A, bovine cystatin C and human cystatins D and S were synthesized, inhibitory activities of these compounds against papain and bovine cathepsin B were tested. Additionally, agar well diffusion test of their antibacterial activity against Streptococcus pyogenes was performed.
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| 7. |
- Monteiro, Ana C. S., et al.
(författare)
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Identification, characterization and localization of chagasin, a tight-binding cysteine protease inhibitor in Trypanosoma cruzi
- 2001
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Ingår i: Journal of Cell Science. - 0021-9533. ; 114:21, s. 3933-3942
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Tidskriftsartikel (refereegranskat)abstract
- Lysosomal cysteine proteases from mammalian cells and plants are regulated by endogenous tight-binding inhibitors from the cystatin superfamily. The presence of cystatin-like inhibitors in lower eukaryotes such as protozoan parasites has not yet been demonstrated, although these cells express large quantities of cysteine proteases and may also count on endogenous inhibitors to regulate cellular proteolysis. Trypanosoma cruzi, the causative agent of Chagas heart disease, is a relevant model to explore this possibility because these intracellular parasites rely on their major lysosomal cysteine protease (cruzipain) to invade and multiply in mammalian host cells. Here we report the isolation, biochemical characterization, developmental stage distribution and subcellular localization of chagasin, an endogenous cysteine protease inhibitor in T. cruzi. We used high temperature induced denaturation to isolate a heat-stable cruzipain-binding protein (apparent molecular mass, 12 kDa) from epimastigote lysates. This protein was subsequently characterized as a tight-binding and reversible inhibitor of papain-like cysteine proteases. Immunoblotting indicated that the expression of chagasin is developmentally regulated and inversely correlated with that of cruzipain. Gold-labeled antibodies localized chagasin to the flagellar pocket and cytoplasmic vesicles of trypomastigotes and to the cell surface of amastigotes. Binding assays performed by probing living parasites with fluorescein (FITC)-cruzipain or FITC-chagasin revealed the presence of both inhibitor and protease at the cell surface of amastigotes. The intersection of chagasin and cruzipain trafficking pathways may represent a checkpoint for downstream regulation of proteolysis in trypanosomatid protozoa.
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| 8. |
- Stoka, Veronika, et al.
(författare)
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Lysosomal protease pathways to apoptosis - Cleavage of Bid, not pro-caspases, is the most likely route
- 2001
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 276:5, s. 3149-3157
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the mechanism of lysosome-mediated cell death using purified recombinant pro-apoptotic proteins, and cell-free extracts from the human neuronal progenitor cell line NT2, Potential effectors were either isolated lysosomes or purified lysosomal proteases. Purified lysosomal cathepsins B, H, K, L, S, and X or an extract of mouse lysosomes did not directly activate either recombinant caspase zymogens or caspase zymogens present in an NT2 cytosolic extract to any significant extent. In contrast, a cathepsin L-related protease from the protozoan parasite Trypanosana cruzi, cruzipain, showed a measurable caspase activation rate. This demonstrated that members of the papain family can directly activate caspases but that mammalian lysosomal members of this family may have been negatively selected for caspase activation to prevent inappropriate induction of apoptosis, Given the lack of evidence for a direct role in caspase activation by lysosomal proteases, we hypothesized that an indirect mode of caspase activation may involve the Bcl-2 family member Bid. In support of this, Bid was cleaved in the presence of lysosomal extracts, at a site six residues downstream from that seen for pathways involving capase 8, Incubation of mitochondria with Bid that had been cleaved by lysosomal extracts resulted in cytochrome c release. Thus, cleavage of Bid may represent a mechanism by which proteases that have leaked from the lysosomes can precipitate cytochrome c release and subsequent caspase activation. This is supported by the finding that cytosolic extracts from mice ablated in the bid gene are impaired in the ability to release cytochrome c in response to lysosome extracts, Together these data suggest that Bid represents a sensor that allows cells to initiate apoptosis in response to widespread adventitious proteolysis.
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| 9. |
- Wasselius, Johan, et al.
(författare)
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Identification and localization of retinal cystatin C
- 2001
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Ingår i: Investigative Ophthalmology & Visual Science. - 1552-5783. ; 42:8, s. 1901-1906
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Cystatin C is a mammalian cysteine protease inhibitor, synthesized in various amounts by many kinds of cells and appearing in most body fluids. There are reports that it may be synthesized in the mammalian retina and that a cysteine protease inhibitor may influence the degradation of photoreceptor outer segment proteins. In the current study cystatin C was identified, quantitated, and localized in mouse, rat, and human retinas. METHODS. Enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), DNA sequencing, Western blot analysis, and immunohistochemistry have been used on mouse, rat, and human retinas (pigment epithelium included). RESULTS. Cystatin C is present in high concentrations in the normal adult rat retina, as it is throughout its postnatal development. Its concentration increases to a peak at the time when rat pups open their eyes and then remains at a high level. It is mainly localized to the pigment epithelium, but also to some few neurons of varying types in the inner retina. Cystatin C is similarly expressed in normal mouse and human retinas. CONCLUSIONS. Cystatin C was identified and the localization described in the retinas of rat, mouse, and human using several techniques. Cystatin C is known to efficiently inactivate certain cysteine proteases. One of them, cathepsin S, is present in the retinal pigment epithelium and affects the proteolytic processing by cathepsin D of diurnally shed photoreceptor outer segments. Hypothetically, it appears possible that retinal cystatin C, given its localization to the pigment epithelium and its ability to inhibit cathepsin S, could be involved in the regulation of photoreceptor degradation.
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