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Screening for biomarkers in plasma from patients with gangrenous phlegmonous appendicitis using CE and CEC in combination with MS
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
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2007 (English)In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 28, no 9, 1435-1443 p.Article in journal (Refereed) Published
Abstract [en]

Today a high degree of "false" appendicitis diagnoses are occurring. In this study, a screening experiment of biomarkers of two different kinds of appendicitis, gangrenous and phlegmonous, were conducted with CE and CEC coupled to MS. Plasma samples were obtained from patients pre- and post-surgery. A large amount of data was generated to be able to compare them, and chemometrics tools were utilized to visualize the differences. Indicative patterns were found for both pre- and post-surgery of the two types of inflammation as well as between them. The divergences were traced back to the MS peaks obtained in the CE- and CEC-MS setups as possible biomarkers for the two forms of appendicitis.

Place, publisher, year, edition, pages
2007. Vol. 28, no 9, 1435-1443 p.
Keyword [en]
Appendicitis, Biomarker, Fourier transform ion cyclotron resonance-MS, Open tubular CEC, TOF-MS
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96249DOI: 10.1002/elps.200600606ISI: 000246557400018PubMedID: 17372941OAI: oai:DiVA.org:uu-96249DiVA: diva2:170758
Available from: 2007-09-21 Created: 2007-09-21 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Managing and Exploring Large Data Sets Generated by Liquid Separation - Mass Spectrometry
Open this publication in new window or tab >>Managing and Exploring Large Data Sets Generated by Liquid Separation - Mass Spectrometry
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A trend in natural science and especially in analytical chemistry is the increasing need for analysis of a large number of complex samples with low analyte concentrations. Biological samples (urine, blood, plasma, cerebral spinal fluid, tissue etc.) are often suitable for analysis with liquid separation mass spectrometry (LS-MS), resulting in two-way data tables (time vs. m/z). Such biological 'fingerprints' taken for all samples in a study correspond to a large amount of data. Detailed characterization requires a high sampling rate in combination with high mass resolution and wide mass range, which presents a challenge in data handling and exploration. This thesis describes methods for managing and exploring large data sets made up of such detailed 'fingerprints' (represented as data matrices).

The methods were implemented as scripts and functions in Matlab, a wide-spread environment for matrix manipulations. A single-file structure to hold the imported data facilitated both easy access and fast manipulation. Routines for baseline removal and noise reduction were intended to reduce the amount of data without loosing relevant information. A tool for visualizing and exploring single runs was also included. When comparing two or more 'fingerprints' they usually have to be aligned due to unintended shifts in analyte positions in time and m/z. A PCA-like multivariate method proved to be less sensitive to such shifts, and an ANOVA implementation made it easier to find systematic differences within the data sets.

The above strategies and methods were applied to complex samples such as plasma, protein digests, and urine. The field of application included urine profiling (paracetamole intake; beverage effects), peptide mapping (different digestion protocols) and search for potential biomarkers (appendicitis diagnosis) . The influence of the experimental factors was visualized by PCA score plots as well as clustering diagrams (dendrograms).

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 61 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 346
Keyword
Analytical chemistry, liquid chromatography, capillary electrophoresis, capillary electrochromatography, mass spectrometry, electro spray ionization, chemometrics, multivariate data analysis, peptide, biomarkers, fingerprints, PCA, alignment, data compression, ANOVA, target correlation, data management, Analytisk kemi
Identifiers
urn:nbn:se:uu:diva-8223 (URN)978-91-554-6976-4 (ISBN)
Public defence
2007-10-12, B21, BMC, Box 599, 751 24 Uppsala, 10:15
Opponent
Supervisors
Available from: 2007-09-21 Created: 2007-09-21 Last updated: 2011-05-10Bibliographically approved
2. Column Development in Capillary Electrophoresis and Electrochromatography for Bioanalytical Applications
Open this publication in new window or tab >>Column Development in Capillary Electrophoresis and Electrochromatography for Bioanalytical Applications
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Analysis of biological samples can be a difficult task. This thesis covers a broad aspect of the analytical areas of capillary electrophoresis (CE) and capillary electrochromatography (CEC) in combination with mass spectrometry (MS) that are of great importance for achieving fast, accurate and sensitive bioanalyses. A significantly time reduced and automated system for sample cleanup was developed to greatly simplify the pretreatment process of biological samples with a complex matrix. Desalting and preconcentration of species in urine was conducted and the limit of detection for the antidepressant escitalopram was lowered 10 times. This extraction devise was also successfully incorporated in a chip based platform for the possibility to be a part of multidimensional separation systems. The reduced risk of sample loss leads to improved detection limits, which are usually one the most challenging parts when working with bioanalyses.

In the area of separation, a monomer surface with tailored hydrophobicity was developed to achieve rapid, high efficient separations of complex mixtures. Within five minutes a tryptic digest of a protein could be separated and then identified by a Mascot search.

The applications addressed have been focused on medical conditions which are of highest interest for both physicians and patients. A high throughput analysis of the kynurenine metabolites with CE-MS offers a new method to rapidly examine samples from patients with neurological disorders.

A screening study of possible biomarkers for the two different types of appendicitis, gangraenous and phlegmonous was conducted. Indicative patterns were found for both pre and post surgery of the two types of inflammation as well as between them. The divergences were traced back to the MS peaks obtained in the CE- and CEC-MS setups as possible biomarkers for the two forms of appendicitis. A preliminary study of polycystic ovary syndrome also offered some valuable results for future biomarker identification.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 54 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 216
Keyword
Analytical chemistry, Capillary electrophoresis (CE), Capillary electrochromatography (CEC), Mass spectrometry (MS), Bioanalysis, Sample pretreatment, Sol-gel, Analytisk kemi
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-7124 (URN)91-554-6644-3 (ISBN)
Public defence
2006-10-06, B22, BMC, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2006-09-15 Created: 2006-09-15 Last updated: 2012-02-08Bibliographically approved

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Bäckström, DanielWetterhall, MagnusDanielsson, RolfBergquist, Jonas

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