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- Breccia, J., et al.
(författare)
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The search for a peptide ligand targeting the lipolytic enzyme cutinase
- 2003
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Ingår i: Enzyme and Microbial Technology. - 0141-0229. ; 33:2-3, s. 244-249
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Tidskriftsartikel (refereegranskat)abstract
- A constrained nonapeptide phage display library was evaluated as a potential source of affinity ligand(s) for purification of cutinase, a lipolytic enzyme. After seven cycles of biopanning, 500 clones were isolated and individually tested for their capability to interact with cutinase. Three out of six sequenced clones carrying a cutinase-specific constrained peptide showed the same insert sequence (CRLHHWRYC). Sequences of two of the other clones highlighted a LXXW motif as a critical determinant in the make-up of a cutinase-specific sequence. Although the affinity of the most commonly found peptide for cutinase is low, we suggest that LXXW motif may be a suitable starting point in the development of affinity peptides suitable for use in the study and purification of cutinase.
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- Fritzell, Peter, et al.
(författare)
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Cost-effectiveness of lumbar fusion and nonsurgical treatment for chronic low back pain in the Swedish lumbar spine study : A multicenter, randomized, controlled trial from the Swedish Lumbar Spine Study Group
- 2004
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Ingår i: Spine. - : Lippincott Williams & Wilkins. - 0362-2436 .- 1528-1159. ; 29:4, s. 421-434
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Tidskriftsartikel (refereegranskat)abstract
- Study Design. A cost-effectiveness study was performed from the societal and health care perspectives. Objective. To evaluate the costs-effectiveness of lumbar fusion for chronic low back pain (CLBP) during a 2-year follow-up. Summary of Background Data. A full economic evaluation comparing costs related to treatment effects in patients with CLBP is lacking. Patients and Methods. A total of 284 of 294 patients with CLBP for at least 2 years were randomized to either lumbar fusion or a nonsurgical control group. Costs for the health care sector ( direct costs), and costs associated with production losses ( indirect costs) were calculated. Societal total costs were identified as the sum of direct and indirect costs. Treatment effects were measured using patient global assessment of improvement, back pain ( VAS), functional disability (Owestry), and return to work. Results. The societal total cost per patient ( standard deviations) in the surgical group was significantly higher than in the nonsurgical group: Swedish kroner (SEK) 704,000 ( 254,000) vs. SEK 636,000 ( 208,000). The cost per patient for the health care sector was significantly higher for the surgical group, SEK 123,000 ( 60,100) vs. 65,200 ( 38,400) for the control group. All treatment effects were significantly better after surgery. The incremental cost-effectiveness ratio ( ICER), illustrating the extra cost per extra effect unit gained by using fusion instead of nonsurgical treatment, were for improvement: SEK 2,600 ( 600 - 5,900), for back pain: SEK 5,200 ( 1,100 - 11,500), for Oswestry: SEK 11,300 ( 1,200 - 48,000), and for return to work: SEK 4,100 ( 100 21,400). Conclusion. For both the society and the health care sectors, the 2-year costs for lumbar fusion was significantly higher compared with nonsurgical treatment but all treatment effects were significantly in favor of surgery. The probability of lumbar fusion being cost-effective increased with the value put on extra effect units gained by using surgery.
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- Gunnarsson, Lavinia Cicortas, 1977-, et al.
(författare)
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A carbohydrate binding module as a diversity-carrying scaffold
- 2004
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Ingår i: Protein Engineering Design & Selection. - : Oxford University Press. - 1741-0126 .- 1741-0134. ; 17:3, s. 213-221
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Tidskriftsartikel (refereegranskat)abstract
- The growing field of biotechnology is in constant need of binding proteins with novel properties. Not just binding specificities and affinities but also structural stability and productivity are important characteristics for the purpose of large-scale applications. In order to find such molecules, libraries are created by diversifying naturally occurring binding proteins, which in those cases serve as scaffolds. In this study, we investigated the use of a thermostable carbohydrate binding module, CBM4-2, from a xylanase found in Rhodothermus marinus, as a diversity-carrying scaffold. A combinatorial library was created by introducing restricted variation at 12 positions in the carbohydrate binding site of the CBM4-2. Despite the small size of the library (1.6 x 10(6) clones), variants specific towards different carbohydrate polymers (birchwood xylan, Avicel and ivory nut mannan) as well as a glycoprotein (human IgG4) were successfully selected for, using the phage display method. Investigated clones showed a high productivity (on average 69 mg of purified protein/l shake flask culture) when produced in Escherichia coli and they were all stable molecules displaying a high melting transition temperature (75.7 +/- 5.3 degrees C). All our results demonstrate that the CBM4-2 molecule is a suitable scaffold for creating variants useful in different biotechnological applications.
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- Lantto, Johan, et al.
(författare)
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A divalent antibody format is required for neutralization of human cytomegalovirus via antigenic domain 2 on glycoprotein B
- 2002
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Ingår i: Journal of General Virology. - 1465-2099. ; 83:Pt 8, s. 2001-2005
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Tidskriftsartikel (refereegranskat)abstract
- Glycoprotein B (gB) of human cytomegalovirus (HCMV) is the dominating protein in the envelope of this virus and gives rise to virus-neutralizing antibodies in most infected individuals. We have previously isolated a neutralizing human antibody specific for antigenic domain 2 (AD-2) on gB, a poorly immunogenic epitope, which nevertheless is capable of eliciting potent neutralizing antibodies. In order to define parameters important for the neutralization of HCMV via gB, we have investigated the virus-neutralizing capacity and the kinetics of the interaction with AD-2 of the monomeric and dimeric forms of a single chain variable fragment (scFv) corresponding to this antibody. We demonstrate here that neutralization of HCMV via AD-2 on gB can be mediated by dimeric scFv, while monomeric fragments cannot mediate neutralization of the virus, despite a slow dissociation from the intact glycoprotein. This finding is discussed in the context of possible mechanisms for antibody-mediated virus neutralization.
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