| 1. |
- Gonzalez, Henrik, et al.
(författare)
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Identification of novel candidate protein biomarkers for the post-polio syndrome — Implications for diagnosis, neurodegeneration and neuroinflammation
- 2009
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 71:6, s. 670-681
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Tidskriftsartikel (refereegranskat)abstract
- Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, a condition known as post-polio syndrome (PPS). The condition affects 20-60% of previous polio patients, making it one of the most common causes of neurological deficits worldwide. The underlying pathogenesis is not fully understood and accurate diagnosis is not feasible. Herein we investigated whether it was possible to identify proteomic profile aberrations in the cerebrospinal fluid (CSF) of PPS patients. CSF from 15 patients with well-defined PPS were analyzed for protein expression profiles. The results were compared to data obtained from nine healthy controls and 34 patients with other non-inflammatory diseases which served as negative controls. In addition, 17 samples from persons with secondary progressive multiple sclerosis (SPMS) were added as relevant age-matched references for the PPS samples. The CSF of persons with PPS displayed a disease-specific and highly predictive (p=0.0017) differential expression of five distinct proteins: gelsolin, hemopexin, peptidylglycine alpha-amidating monooxygenase, glutathione synthetase and kallikrein 6, respectively, in comparison with the control groups. An independent ELISA confirmed the increase of kallikrein 6. We suggest that these five proteins should be further evaluated as candidate biomarkers for the diagnosis and development of new therapies for PPS patients.
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| 2. |
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| 3. |
- Ottervald, Jan, et al.
(författare)
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Multiple sclerosis : Identification and clinical evaluation of novel CSF biomarkers
- 2010
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1876-7737 .- 1874-3919. ; 73:6, s. 1117-1132
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that results in damage to myelin sheaths and axons in the central nervous system and which preferentially affects young adults. We performed a proteomics-based biomarker discovery study in which cerebrospinal fluid (CSF) from MS and control individuals was analyzed (n=112). Ten candidate biomarkers were selected for evaluation by quantitative immunoassay using an independent cohort of MS and control subjects (n=209). In relapsing remitting MS (ARMS) patients there were significant increases in the CSF levels of alpha-1 antichymotrypsin (A1AC), alpha-1 macroglobulin (A2MG) and fibulin 1 as compared to control subjects. In secondary progressive MS (SPMS) four additional proteins (contactin 1, fetuin A, vitamin D binding protein and angiotensinogen (ANGT)) were increased as compared to control subjects. In particular, ANGT was increased 3-fold in SPMS, indicating a potential as biomarker of disease progression in MS. In PPMS, A1AC and A2MG exhibit significantly higher CSF levels than controls, with a trend of increase for ANGT. Classification models based on the biomarker panel could identify 70% of the RRMS and 80% of the SPMS patients correctly. Further evaluation was conducted in a pilot study of CSF from RRMS patients (n=36), before and after treatment with natalizumab.
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| 4. |
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| 5. |
- Ottervald, Jan
(författare)
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Proteomics in neurological disease
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neurodegenerative and neuroinflammatory diseases are conditions affecting the central nervous system that in the end have dramatic impacts on the affected individuals and their families. Today, large efforts are made to understand the disease origin and progression. This thesis focuses on Multiple Sclerosis (MS), which is the most common neurological disease among young adults. The diagnosis of MS is based on a series of clinical and neuroimaging criteria, and at present no reliable prognostic tools are available. We have aimed at developing a solid technical platform for investigation of potential biomarkers in MS. New purification methods to remove abundant proteins from the cerebrospinal fluid and tissue from individuals with MS and controls were developed. The samples were further analyzed using proteomic techniques, two-dimensional gel electrophoresis, mass spectrometry and bioinformatics. We demonstrated that proteins in MS plaques, adjacent tissue and non-affected brain tissue were differentially expressed. Cerebrospinal fluid samples of individuals affected with MS encompassing its different disease phases and control individuals were analyzed. A reference disease, Post-Polio Syndrome (PPS), was included and regarded as a non-inflammatory condition. Prediction models were constructed and univarate analysis of the protein expression was performed. The results revealed that there was a large heterogeneity in protein profiles between the MS subgroups. In PPS individuals, a protein profile based on three proteins could predict the disease with a high sensitivity and specificity. Interestingly, in contrast to the prevailing assumption, the identification of these proteins indicated that there is an ongoing neuroinflammation and neurodegeneration in PPS. To further evaluate the MS results we developed a multiplex quantitative immunoassay based on the expression pattern of ten proteins. A new cohort comprising individuals affected with MS and control individuals was assembled, and the expression of the proteins was analyzed. Classification models based on the biomarker panel could identify 70% of the relapsing-remitting MS and 80% of the secondary progressive MS individuals and controls correctly. Thus, protein expression profiles differ between the different forms of MS. In conclusion, we have developed a proteomic platform that has enabled the discovery of potential biochemical biomarkers of diagnostic and prognostic value in MS and the PPS. Further analysis of the protein expression patterns has also added biological information, which may prove useful for the understanding of etiology and disease course
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| 6. |
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| 7. |
- Rezeli, Melinda, et al.
(författare)
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MRM assay for quantitation of complement components in human blood plasma - a feasibility study on multiple sclerosis.
- 2011
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 75:1, s. 211-220
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Tidskriftsartikel (refereegranskat)abstract
- As a proof-of-principle study, a multiple reaction monitoring (MRM) assay was developed for quantitation of proteotypic peptides, representing seven plasma proteins associated with inflammation (complement components and C-reactive protein). The assay development and the sample analysis were performed on a linear ion trap mass spectrometer. We were able to quantify 5 of the 7 target proteins in depleted plasma digests with reasonable reproducibility over a 2 orders of magnitude linear range (RSD < 25%). The assay panel was utilized for the analysis of a small multiple sclerosis sample cohort with 10 diseased and 8 control patients.
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| 8. |
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| 9. |
- Végvári, Akos, et al.
(författare)
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Implementation of a protein profiling platform developed as an academic-pharmaceutical industry collaborative effort
- 2008
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Ingår i: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 29:12, s. 705-2696
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Tidskriftsartikel (refereegranskat)abstract
- As much attention has devoted to the proteome research during the last few years, biomarker discovery has become an increasingly hot area, potentially enabling the development of new assays for diagnosis and prognosis of severe diseases. This is the field of research interest where efforts originating from both academic and industrial groups should jointly work on solutions. In this paper, we would like to demonstrate the fruitful combination of both research domains where the scientific crossroads sprout fresh ideas from the basic research domain and how these are refined and tethered to industrial standards. We will present an approach that is based on novel microfluidic devices, utilizing their benefits in processing small-volume samples. Our biomarker discovery strategy, built around this platform, involves optimized samples processing (based on SPE and sample enrichment) and fast MALDI-MS readout. The identification of novel biomarkers at low-abundance level has been achieved by the utilization of a miniaturized sample handling platform, which offers clean-up and enrichment of proteins in one step. Complete automation has been realized in the form of a unique robotic instrumentation that is able to extract and transfer 96 samples onto standard MALDI target plates with high throughput. The developed platform was operated with a 60 sample turnaround per hour allowing sensitivities in femtomol regions of medium- and low-abundant target proteins from clinical studies on samples of multiple sclerosis and gastroesophageal reflux disease. Several proteins have been identified as new biomarkers from cerebrospinal fluid and esophagus epithelial cells.
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