| 1. |
- Bao, Lei
(författare)
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Immunomodulation and immunopathogenesis in autoimmune disease with emphasis on autoimmune neuritis and arthritis
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Experimental autoimmune neuritis (EAN) and arthritis are CD4+ T cell mediated autoimmune animal models for the study of immunomodulation and immunopathogenesis of human Guillain-Barré syndrome (GBS) and rheumatoid arthritis (RA). Inflammatory cell infiltration and cytokine production in the target organs are characteristic features of both diseases, suggesting a role of cytokine production in the pathogenesis. A significant reduction in the incidence and severity of EAN and a delayed time of onset of EAN were found in IL-12 deficient (IL-12-/-), as compared to wild type mice. The clinical symptoms were associated with a reduced IFN-gamma and TNF-alpha, while enhanced IL-4 production in the sciatic nerve as well as significantly suppressed levels of anti-PO peptide IgG2b antibody in serum suggested that IL-12 has a major role in the initiation, enhancement and perpetuation of pathogenic events in EAN by promoting a Th1 cell-mediated immune response and suppressing the Th2 response. These results demonstrate that IIL-12 may play a critical role in the pathogenesis of EAN. Tumor necrosis factor receptor I (TNFR I) is thought to mediate the majority of TNF activities. When administered soluble TNFR I (sTNFR I) to mice immunized with PO peptide the severity and the duration of EAN were decreased. This was accompanied in vitro by a marked reduction in antigen-specific T cell proliferation and IFN-gamma synthesis by spleen cells in sTNFR I treated mice. Immunohistochemical analysis revealed a strong decrease in the number of infiltrating macrophages, CD4+ T cells and CD8+ T cells in the sciatic nerve. These data directly demonstrate a pivotal role for TNF in the development of EAN and also suggest that sTNFR I may have a therapeutic potential in human GBS. CC chemokine receptor 5 deficient (CCR5-/-) mice showed a significant reduction in the incidence of collagen-induced arthritis in comparison to wild-type (CCR5+/+) mice. However, the severity score once they developed arthritis showed clinical features similar to wild-type mice. There were significantly lower levels of antibodies against CH in CCR5-/- mice compared to wild- type mice, especially IgG2a and IgG2b, and obviously higher levels of EL10 in CCR5-/- mice. There was overproduction of MIP-1beta in serum and culture supernatant of spleen cells in CCR5 deficient mice after CH-immunization that might partly have contributed to the severity of arthritis. Our results indicate that CCR5 plays a role in the pathogenesis of arthritis, but its role can probably be substituted by other factors. Changes of glia and cytokine expression were found in the spinal cord of adjuvantinduced arthritic (AIA) rats. Macroglia and MHC class 11 immunostaining were enhanced, and the numbers and immunostaining intensity of astrocytes expressing GFAP were increased. Using in situ hybridization and immunohistochemical methods, both mRNA and protein levels of IL-1beta, IL-6 and TNF-alpha were significantly increased in the spinal cord of arthritic rats. Higher levels of cytokine expression were noted in reactive astrocytes and microglia.
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| 2. |
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| 3. |
- Brüggemann, Oliver, et al.
(författare)
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New configurations and applications of molecularly imprinted polymers
- 2000
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Ingår i: Journal of Chromatography A. - 0021-9673. ; 889:1-2, s. 15-24
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Tidskriftsartikel (refereegranskat)abstract
- Molecularly imprinted polymers (MIPs) are applicable in a variety of different configurations. For example, bulk polymers imprinted with β-lactam antibiotics are presented to be used as stationary phases for the chromatographic separation of β-lactam antibiotics with both aqueous and organic mobile phases. However, in some analytical applications, monosized spherical beads are preferred over the currently used ground bulk polymers. A precipitation polymerization technique allows preparation of monosized spherical imprinted beads with diameters down to 200 nm having excellent recognition properties for different target molecules. Nevertheless, with current imprinting protocols a substantial amount of template has to be used to prepare the polymer. This can be problematic if the template is poorly soluble, expensive or difficult to obtain. It is shown that for analytical applications, the functional monomer:template ratio can be drastically increased without jeopardizing the polymer's recognition properties. Furthermore, a substantial reduction of the degree of crosslinking is demonstrated, resulting in much more flexible polymers that are useful for example the preparation of thin imprinted films and membranes for sensors. Apart from analysis, MIPs also are applicable in chemical or enzymatic synthesis. For example, MIPs using the product of an enzyme reaction as template are utilized for assisting the synthetic reaction by continuously removing the product from the bulk solution by complexation. This results in an equilibrium shift towards product formation. Copyright (C) 2000 Elsevier Science B.V.
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| 4. |
- Chen, Li, et al.
(författare)
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Internet-Enabled Real-Time Collaborative Assembly Modeling via An e-Assembly System: Status and Promise
- 2004
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Ingår i: Computer-Aided Design. - : Elsevier BV. - 0010-4485 .- 1879-2685. ; 36:9, s. 835-847
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Tidskriftsartikel (refereegranskat)abstract
- Collaborative CAD systems enabling collaboration in computer-aided design processes among distributed designers are gaining more and more attention. Yet, such systems, especially in support of collaborative assembly modeling, are hardly achievable. Targeting this gap, this paper addresses an Internet-enabled real-time collaborative assembly modeling system, named e-Assembly. This emerging system allows a group of geographically dispersed designers to jointly build an assembly model in real time over the Internet. In particular, this paper proposes a new assembly representation, called Collaborative Assembly Representation, for Internet-based collaborative assembly modeling. Also, collaborative assembly constraint satisfaction is addressed based on three coordination rules embedded in e-Assembly. Furthermore, the system architecture and realization of e-Assembly are provided. Finally, a prototypic implementation of e-Assembly is presented for demonstration and discussion.
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| 5. |
- Hong, X, et al.
(författare)
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Tumors acquire inhibitor of apoptosis protein (IAP)-mediated apoptosis resistance through altered specificity of cytosolic proteolysis
- 2003
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 197:12, s. 1731-1743
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Tidskriftsartikel (refereegranskat)abstract
- Many tumors overexpress members of the inhibitor of apoptosis protein (IAP) family. IAPs contribute to tumor cell apoptosis resistance by the inhibition of caspases, and are degraded by the proteasome to allow further progression of apoptosis. Here we show that tumor cells can alter the specificity of cytosolic proteolysis in order to acquire apoptosis resistance, which promotes formation of rapidly growing tumors. Survival of tumor cells with low proteasomal activity can occur in the presence of high expression of Tri-peptidyl-peptidase II (TPP II), a large subtilisin-like peptidase that complements proteasomal activity. We find that this state leaves tumor cells unable of effectively degrading IAPs, and that cells in this state form rapidly growing tumors in vivo. We also find, in studies of apoptosis resistant cells derived from large in vivo tumors, that these have acquired an altered peptidase activity, with up-regulation of TPP II activity and decreased proteasomal activity. Importantly, we find that growth of subcutaneous tumors is limited by maintenance of the apoptosis resistant phenotype. The apoptosis resistant phenotype was reversed by increased expression of Smac/DIABLO, an antagonist of IAP molecules. Our data suggest a reversible mechanism in regulation of apoptosis resistance that drives tumor progression in vivo. These data are relevant in relation to the multitude of therapy-resistant clinical tumors that have increased levels of IAP molecules.
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| 6. |
- Hu, Xiao-Lei
(författare)
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Apoptotic and necrotic cell death after photothrombotic ring stroke : characterization of a stroke model and its morphological and molecular consequences
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cerebral ischemic cell death is a major cause of disability and death among stroke patients. The brain cell demise can occur through apoptosis or necrosis or as a continuum of both. This study aimed at establishing a dual setup of a photothrombotic ring stroke model and exploring its morphological and molecular consequences. Photothrombotic ring stroke was induced in adult male Wistar rats by a ring shaped laser irradiation beam (514.5nm, outer diameter 5mm, thickness 0.35 mm) for 120 seconds focused on the exposed intact skull bone with simultaneous intravenous infusion of the photosensitizer erythrosin B (17 mg/kg). By using otherwise identical experimental conditions, high intensity irradiation (1.94 W/cm2) resulted in consistent lack of reperfusion in the region at risk whereas low intensity irradiation (0.90 W/cm2) induced late spontaneous reperfusion. The morphological appearance of apoptotic and necrotic cells was demonstrated by H&E, TUNEL and Hoechst stainings under light microscopy, immunohistochemistry and electron microscopy. This was further confirmed by gel electrophoresis showing DNA laddering that coexisted with DNA smear. Cell counts revealed that apoptotic cells appeared earlier (at 24 h) and remained as long as the necrotic cells, that is up to 72 hours after ischemic onset in regions with severe CBF reduction. After low intensity irradiation, we observed early and widespread increased expression of the anti-apoptotic protein bcl-w and a prolonged elevation of Bcl-2 with unchanged pro-apoptotic Bax in mitochondria. In contrast, decreased bcl-w and Bcl-2 with scattered Bax remained after high intensity irradiation. Correspondingly, the release of the pro-apoptotic factor Smac/DIABLO from the mitochondria to the cytosol was more persistent in high- compared with low-intensity irradiation. Apoptotic and necrotic cell death coexisted in the same regions at the same time after photothrombotic ring stroke induced by low- or high-intensity irradiation, where spontaneous morphological recovery or pannecrosis were evident in the region at risk. The ratios between Bcl-w, Bcl-2 and Bax may direct the translocation of Smac/DIABLO from the mitochondria to the cytosol and thereby influence cell death or survival after focal cerebral ischemia.
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| 7. |
- Hu, Xiao-Lei, et al.
(författare)
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Dynamic changes of the anti- and pro-apoptotic proteins Bcl-w, Bcl-2, and Bax with Smac/Diablo mitochondrial release after photothrombotic ring stroke in rats
- 2004
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Ingår i: European Journal of Neuroscience. - : Wiley-Blackwell. - 0953-816X .- 1460-9568. ; 20:5, s. 1177-1188
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Tidskriftsartikel (refereegranskat)abstract
- The anti‐apoptotic proteins Bcl‐w and Bcl‐2 and the pro‐apoptotic protein Bax may mediate cell death or survival via regulation of the mitochondria including second mitochondria‐derived activator of caspase (Smac)/direct inhibitor of apoptosis protein (IAP)‐binding protein with low pI (DIABLO) release. This study aimed to explore alterations in Bcl‐w, Bcl‐2, and Bax and the relationship between these proteins and Smac/DIABLO by means of in situ hybridization, immunohistochemical (IHC) staining, and Western blots after low‐ and high‐intensity photothrombotic ring stroke. At 4 h after low‐intensity irradiation, we found widespread bcl‐w overexpression on both the mRNA and protein levels in the bilateral cortex except the ring lesion region and in subcortical regions. A prolonged elevation of Bcl‐2 with relatively unchanged Bax in the mitochondrial fraction was demonstrated from 4 to 72 h. These upregulated anti‐apoptotic proteins combined with little Smac/DIABLO release might be associated with increased cell survival and thereby remarkable morphological recovery after low‐intensity irradiation. After high‐intensity irradiation, we observed decreased bcl‐w and bcl‐2 mRNA with increased Bcl‐2 protein in the cytosolic fraction, whereas the Bax protein remained in scattered ischaemic cells in the ring lesion and the region at risk that corresponded with release of Smac/DIABLO from mitochondria to the cytosol at 1–24 h. These changes might be related to the massive cell death observed after high‐intensity irradiation. Taken together, the balance and the location of anti‐apoptotic proteins vs. pro‐apoptotic proteins could be associated with the translocation of Smac/DIABLO from the mitochondria to the cytosol and therefore closely related to cell death or survival after focal cerebral ischaemia.
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| 8. |
- Huang, Z. L., et al.
(författare)
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Novel heterocycle-based organic molecules with two-photon induced blue fluorescent emission
- 2003
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Ingår i: Journal of Materials Chemistry. - : Royal Society of Chemistry (RSC). - 0959-9428 .- 1364-5501. ; 13:4, s. 708-711
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Tidskriftsartikel (refereegranskat)abstract
- Two-photon absorption and two-photon induced blue emission characteristics of a series of heterocycle-based organic molecules are investigated experimentally and by quantum-chemical computations. The molecules consist of a typical A-pi-A' structure, where heterocycle, styryl and formyl groups are employed as A, pi-conjugated and A' moieties, respectively. Experimental results indicate that significant enhancements in the blue emission efficiency and two-photon absorption cross-sections can be achieved by replacing S and O atoms with an N atom in the heterocycle acceptor moiety, which is also supported by the quantum-chemical computations. Additionally, larger two-photon absorption cross-sections can be obtained by choosing appropriate solvents, as indicated by the computations.
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| 9. |
- James, Helen F, et al.
(författare)
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Pseudopodoces humilis, a misclassified terrestrial tit (Paridae) of the Tibetan Plateau: evolutionary consequences of shifting adaptive zones
- 2003
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Ingår i: Ibis. - 0019-1019 .- 1474-919X. ; 145:2, s. 185-202
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Tidskriftsartikel (refereegranskat)abstract
- Pseudopodoces humilis (Hume's Ground-Jay) is a small passerine bird that inhabits the high rocky steppes of the Tibetan (Qinghai–Xizang) Plateau. Although it was long classified as a small species of ground jay (Podoces), two previous anatomical studies cast doubt on its assignment to the Corvidae (crows and jays). We studied the evolutionary relationships of Pseudopodoces using three independent datasets drawn from comparative osteology, the nuclear c-myc gene, and the mitochondrial cytochrome b gene. All three datasets agree on the placement of Pseudopodoces in the family Paridae (tits and chickadees). The cytochrome b data further suggest that Pseudopodoces may be closest to the Great Tit Parus major species group. Pseudopodoces is the only species of parid whose distribution is limited to treeless terrain. Its evolutionary relationships were long obscured by adaptations to open habitat, including pale, cryptic plumage; a long, decurved bill for probing in crevices among rocks or in the ground; and long legs for terrestrial locomotion. Despite these accommodations to a novel adaptive zone, its evolutionary affinity with the Paridae is clearly expressed in comparative osteology and genetics, and is supported by its habit of nesting in cavities.
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| 10. |
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| 11. |
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| 12. |
- Lei, Haixin
(författare)
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Functional analysis of genetic variants in putative low penetrate breast cancer genes
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Paper I & II: CDH1 germline mutations predispose individuals to diffuse gastric cancer, but its role in breast cancer is less clear. Somatic CDH1 mutations were reported to be frequent in lobular tumours (ILC), but they have not been found in ductal carcinomas (IDC). To define the role of CDH1 in breast cancer, we used denaturing high performance liquid chromatography to screen a series of breast cancer samples for mutations. Somatic mutations were detected in 4 of 83 IDC (5%) and 3 of 25 ILC (12%). No germline mutation was found in 19 familial breast cancer patients that showed loss of heterozygosity (LOH) at 16q24, in 12 cases from 10 families with breast, gastric and colon cancer and in 13 familial lobular breast tumours. Another somatic mutation was detected in one of the familial breast cancer patient with both ductal and lobular foci. Putative breast cancer risk conferred by the promoter polymorphism -161C-A of CDH1 or 1774G-A (Ala592Thr) was also analyzed in case-control studies. No significant difference in allelic frequency was found between the breast cancer patients and controls for either polymorphism. A novel promoter polymorphism was identified at position -152 with a similar frequency of the rare C allele in both breast cancer patients and controls. Transient transfection assay using constructs containing -16IC/-152C or -161A/-152T showed only a slight decrease of the transcription activity as compared to the wild type constructs carrying -161C/152T. We conclude that CDH1 is not a prominent lowpenetrance gene in breast cancer, but CDH1 mutations contribute to the progression of both lobular and ductal tumours. Paper III: BACH1, a gene located in 17q22 and encoding a protein directly interacting with BRCA1, was suggested to be a candidate gene for breast cancer susceptibility. Using PCR-SSCP, we screened for germline BACH] mutations with 29 breast cancer families linked to 17q22 and additional 95 familial breast cancer cases, which were all without detectable BRCA112 mutations. No mutation was found. A C/T polymorphism at position 517 was detected, which leads to Arg173Cys substitution in the putative nuclear localization sequence. This alteration may contribute to the development of breast cancer, but BACH1 is not a major breast cancer gene. Paper IV: ATM has been suggested to act as a tumour suppression gene that requires the inactivation of both alleles in the development of a malignancy. Two mutations designated as T7271G and IVS1O+6 T-G were reported to increase breast cancer risk in multiple-case families in a dominant negative manner. We evaluated the population frequency of these two mutations in Sweden and Czech populations using PCR-RFLP. The mutation T7271G was not detected, mutation IVS 10+6 T-G was found in 2 of 768 cases and I in 557 controls, giving the allelic frequency of 0. 1%. We also tested the hypothesis that ATM mutations would be enriched in breast cancer patients with LOH at 11q22-23 if ATM acted as TSG. Forty-two selected DNA samples from breast cancer cases were screened for mutations in ATM from exons 50 to 66 using PCR-SSCP, but no mutation was detected. Paper V: (manuscript) LST1 is a gene located in the TNFalpha region and producing many isoforms with a possible role in immune response. In an attempt to understand the mechanism of the 3' splicing site selection in LST1, we found that removal of a nearby AG dinucleotide repeat TNFd led to a serine-arginine protein-dependent activation of a cryptic 3' splice site. The highest yield of the novel isoform named LST1/n was induced by ASF and SRp40. This effect was dose-dependent, it was also dependent on the length of TNFd. Deletion of RNA recognition motif 2 (RRM2) of ASF/SF2 abolished the usage of the cryptic splice site, indicating that the activation is mediated by RNA binding. In addition, we showed that hnRNP Al but not hnRNP K could effectively antagonize SR-protein induced activation. Replacement of TNFd with AC or AT repeat indicated a AG-AC>AT repressing hierarchy on the SR protein induced activation. Further removal of a putative splicing silencer A3 alleviated the requirement for exogenous SR proteins in LST/n activation. We also showed that lack of this event in the wild type construct was not due to the differential efficiency in RTPCR for TNFd+ or TNFd-isoform. Insertion of TNFd in a heterologous context showed no evidence of splicing inhibition in in vitro splicing analysis. Insertion of A3 into a middle exon of a heterologousACE Alu + 136/3'ss minigene led to almost full exon skipping, suggesting that A3 contains splicing inhibitory sequences. All these data are consistent with the existence of multiple mechanisms in the repression of pseudo splice sites and with the concept that dinucleotide repeats could act as splicing regulatory elements in the vicinity of splice sites.
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| 13. |
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| 14. |
- Lei, H, et al.
(författare)
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Olfactory protocerebral pathways processing sex pheromone and plant odor information in the male moth Agrotis segetum
- 2001
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Ingår i: Journal of Comparative Neurology. - : Wiley. - 1096-9861 .- 0021-9967. ; 432:3, s. 356-370
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Tidskriftsartikel (refereegranskat)abstract
- We investigated protocerebral processing of behaviorally relevant signals in the turnip moth, Agrotis segetum. Single neurons were studied both physiologically and morphologically using intracellular recording techniques. In moth pheromone communication systems, the presence of the complete, female-produced pheromone blend is necessary for male attraction. We predicted that more protocerebral neurons, compared with AL, would display blend interactions. However, only a few protocerebral neurons responded differently to the blend than could be deduced from the response to single components. The majority of the pheromone-sensitive protocerebral neurons identified in this study responded to the major pheromone component. In coding time, most AL neurons can follow a 5-Hz odor stimulus, whereas most protocerebral neurons failed at higher frequencies than 1 Hz. The majority of neurons that responded to the odorants tested innervated one or both of the protocerebral lateral accessory lobes. If only one of these was innervated, then the innervation always displayed a varicose appearance, suggesting a presynaptic function. Thus, information seems to be transferred from other protocerebral areas to the lateral accessory lobes. Into these, descending neurons sent smooth, postsynaptic branches. A majority of the neurons innervating the superior medial protocerebrum were found to display single-component specificity. Few additional correlations between odor specificity and structural characteristics were apparent.
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| 15. |
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| 16. |
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| 17. |
- Lei, Zhu, et al.
(författare)
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A multicarrier allocation (MCA) scheme for variable-rate 3Gwireless systems
- 2000
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Ingår i: IEEE Communications Magazine. - New York : IEEE. - 0163-6804 .- 1558-1896. ; 38:10, s. 86-91
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Tidskriftsartikel (refereegranskat)abstract
- High spectral efficiency and flexible data rate access are the main focus of future wireless networks. Multiple channel allocation schemes have the potential of achieving this goal. By assigning multiple slots and/or multiple carriers to one user, it is possible to provide a flexible data rate with quite low complexity. In this article we propose a simple allocation scheme where each user is assigned a fixed group of carriers. These carriers are adaptively used depending on the interference situation within the system. The system performance in terms of average throughput is investigated for two different types of allocation schemes: a fully centralized scheme and a distributed one that uses frequency diversity as a mean of improving the user link quality. The obtained results show that both schemes improve the system throughput over single carrier allocation without affecting the capacity of the system in terms of number of users per cell.
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| 18. |
- Lei, Zhu
(författare)
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On the Downlink Performance of Multicarrier Allocation (MCA)-based System for Wireless IP Networks
- 2001
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Konferensbidrag (refereegranskat)abstract
- Wireless IP is becoming a cutting-edge technology to accomplish Internet truly wireless. Aiming at transmitting IP packets over wireless bearer efficiently, Multicarrier is believed to be a good candidate by offering flexible and high peak rate to each user, as well as reducing buffer size at a receiver. In this article, we take a glimpse at current wireless access technologies for wireless IP, and then from the aspect of radio resource management (RRM), introduce a multicarrier allocation (MCA) approach. Focusing on impacts of frequency diversity, power control, and so-called carrier-grouping techniques, we discuss and investigate the downlink performance enhancement of multicarrier based systems, in terms of spectral efficiency (data throughput) and system fairness. As a brief investigation, simulations are conducted on network level. Finally, conclusions are drawn that frequency diversity in combine with maximal ratio combining obtains significant improvement on both spectral efficiency and system fairness. Dealing with co-channel interference, power control and carrier-grouping enhance system fairness. We also caution that study radio resource management for multicarrier based systems is interested and important.
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| 19. |
- Lei, Zhu
(författare)
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RRM in Multicarrier Allocation-Based Systems
- 2002. - 1
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Ingår i: WIRELESS IP AND BUILDING THE MOBILE INTERNET. - Norwood : Artech House Publishers. - 158053354X ; , s. 255-276
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Konferensbidrag (refereegranskat)
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| 20. |
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| 21. |
- Lin, Lei, et al.
(författare)
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Comparison of chopstick using skills between 3-7-year-old children and adults
- 2001
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Ingår i: Acta Psychologica Sinica. - 0439-755X. ; 33:3, s. 40-46
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Tidskriftsartikel (refereegranskat)abstract
- The acquisition and development of motor skill is an important aspect in human development. Children's motor skills have been investigated for many decades as the developmental milestones and have been used as a scale to describe children's developmental level by researchers. However,studies on the characteristics and the development of culturally related motor skill are very limited.Investigating culturally related motor skill will be very helpful to understand the nature and developmental course of human motor skill. Chopstick using is not only a necessary operation in the daily lives in eastern countries, but also one of the typical fine motor skills which are very important for the functional activities in early child development. In the present study,the characteristics and the development of chopstick using skills were investigated by comparing the types and frequencies of chopstick using gestures in 3-7 year old children and adults.181 participants were included in this study. 91 children aged from 3-5 and 60 pupils aged from 6-7 were selected from one kindergarten and one primary school as the children group. 30 undergraduates were selected as the adult group. Wooden objects in different sizes were used in this study. Participants were asked to hold and move the objects from one testing board to another with a pair of chopsticks. Their gestures and actions were photographed.Results indicated that 8 kinds of chopstick using gestures were found in both children and adults and they differed in the relative position of each finger,the interplay between fingers and chopsticks, the space of the palm and the agility in dealing with different tasks etc. The frequencies of Gesture Two, Five and Six were very low both in children and adults, which showed that similarity existed between children and adults,and the gestures used during early ages may have some effect later. With age increase,more and more people tended to use the more efficient gesture. In children, frequencies of the more efficient gesture (Gesture Type One) changed from 3.7% in 3 year olds to 23.1% in 7 year olds,while frequency of the lower efficient gesture (Gesture Type Four) changed from 59.3% to 23.1% accordingly. In adults, frequency of Gesture Type One was 50%,which was significantly higher than the ones in children, while frequency of Gesture Type Four was 10%, which was significantly lower than the ones in children.
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| 22. |
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| 23. |
- Martin-Sanchez, F., et al.
(författare)
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Synergy between medical informatics and bioinformatics : Facilitating genomic medicine for future health care
- 2004
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Ingår i: Journal of Biomedical Informatics. - : Elsevier BV. - 1532-0464 .- 1532-0480. ; 37:1, s. 30-42
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we review the results of BIOINFOMED, a study funded by the European Commission (EC) with the purpose to analyse the different issues and challenges in the area where Medical Informatics and Bioinformatics meet. Traditionally, Medical Informatics has been focused on the intersection between computer science and clinical medicine, whereas Bioinformatics have been predominantly centered on the intersection between computer science and biological research. Although researchers from both areas have occasionally collaborated, their training, objectives and interests have been quite different. The results of the Human Genome and related projects have attracted the interest of many professionals, and introduced new challenges that will transform biomedical research and health care. A characteristic of the 'post genomic' era will be to correlate essential genotypic information with expressed phenotypic information. In this context, Biomedical Informatics (BMI) has emerged to describe the technology that brings both disciplines (BI and MI) together to support genomic medicine. In recognition of the dynamic nature of BMI, institutions such as the EC have launched several initiatives in support of a research agenda, including the BIOINFOMED study.
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| 24. |
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| 25. |
- Pei, Lei
(författare)
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A fibrinogen-binding protein from Staphylococcus epidermidis
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Staphylococcus epidermidis, a coagulase negative staphylococci (CoNS), is a major component of human flora. It is one of the leading pathogens of nosocomial infections, particularly associated with foreign body infections. The increasing rate of nosocomial epidemics caused by multi-resistant staphylococci requires a better understanding of the pathogenesis of staphylococcal infections. Two steps are involved in bacterial infections on the implants: initial colonization and cell accumulation. Adherence of S.epidermidis to fibrinogen deposited on the surfaces of implants is important for the development of foreign body infections. We here report our studies on a fibrinogen-binding protein from S.epidermidis. A gene (fbe) encoding a fibrinogen-binding protein from S.epidermidis (Fbe) is identified by shotgun phage display. As a member of the SD-multigene family in staphylococci, Fbe shares some similar constructions with other surface proteins of staphylococci. Although most strains of S.epidermidis contain part of fbe, the binding of S.epidermidis to immobilized Fg in vitro shows a heterogeneous pattern, suggesting that other factors may influence the surface exposure of Fbe. The interactions between rFbe and Fg have been extensively studied. The Fg binding responding domain is located on a 331-amino-acid sequence of the A- region of Fbe. rFbe binds to the P chains of Fg and this interaction can be accelerated by calcium. Such an interaction between Fbe and Fg may promote the binding of S.epidermidis to Fg in physiological environments. In the inhibition study, the binding between Fg and S.epidermidis can be blocked by rFbe and its antibodies. The antibodies against rFbe efficiently block the binding between S.epidermidis and surface-bound Fg. The inhibition of adherence to subcutaneously implanted catheters from rats and peripheral venous catheters from patients is less efficient than to Fg-coated ones. This suggests that other components adsorbed on the implant surfaces may also be involved. In the study on the isogenic mutant lacking fbe, lower adherence to Fg exposed surfaces is found fbeisogenic mutant in comparison to its wild type. Thus, Fbe may be a major adhesin to Fg in S.epidermidis. The remained adherence of the mutant to explants suggests that adhesins to other host components may strengthen the interaction between bacteria and the implants. Furthermore, the strategies to prevent and treat S.epidermidis-associated foreign body infections are discussed, including infection controls, new antibiotics, new biomaterials, and immunoglobulin therapy. With more knowledge of the pathogenesis, opsonophagocytic properties of antibodies, and the role of cytokines in S.epidermidis-associated infections, an immunoglobulin therapy targeting Fbe may become a promising strategy in prophylaxis and therapy.
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