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Article ; Online: Plasma Protein Profiling of Incident Cardiovascular Diseases: A Multisample Evaluation.

Lind, Lars / Titova, Olga / Zeng, Rui / Zanetti, Daniela / Ingelsson, Martin / Gustafsson, Stefan / Sundström, Johan / Ärnlöv, Johan / Elmståhl, Sölve / Assimes, Themistocles / Michaëlsson, Karl

Circulation. Genomic and precision medicine

2023 Volume 16, Issue 6, Page(s) e004233

Abstract: Background: Proteomic profiling could potentially disclose new pathophysiological pathways for cardiovascular diseases (CVD) and improve prediction at the individual level. We therefore aimed to study the plasma protein profile associated with the ... ...

Abstract	Background: Proteomic profiling could potentially disclose new pathophysiological pathways for cardiovascular diseases (CVD) and improve prediction at the individual level. We therefore aimed to study the plasma protein profile associated with the incidence of different CVDs. Methods: Plasma levels of 245 proteins suspected to be linked to CVD or metabolism were measured in 4 Swedish prospective population-based cohorts (SIMPLER [Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research], ULSAM (Uppsala Longitudinal Study of Adult Men), EpiHealth, and POEM [Prospective Investigation of Obesity, Energy Production, and Metabolism]) comprising 11 869 individuals, free of CVD diagnoses at baseline. Our primary CVD outcome was defined by a combined end point that included either incident myocardial infarction, stroke, or heart failure. Results: Using a discovery/validation approach, 42 proteins were associated with our primary composite end point occurring in 1163 subjects. In separate meta-analyses for each of the 3 CVD outcomes, 49 proteins were related to myocardial infarction, 34 to ischemic stroke, and 109 to heart failure. Thirteen proteins were related to all 3 outcomes. Of those, urokinase plasminogen activator surface receptor, adrenomedullin, and KIM-1 (kidney injury molecule 1) were also related to several markers of subclinical CVD in Prospective Investigation of Obesity, Energy production and Metabolism, reflecting myocardial or arterial pathologies. In prediction analysis, a lasso selection of 11 proteins in ULSAM improved the discrimination of CVD by 3.3% ( Conclusions: Protein profiling in multiple samples disclosed several new proteins to be associated with subsequent myocardial infarction, stroke, and heart failure, suggesting common pathophysiological pathways for these diseases. KIM-1, urokinase plasminogen activator surface receptor, and adrenomedullin were novel early markers of CVD. A selection of 11 proteins improved the discrimination of CVD.
MeSH term(s)	Male ; Adult ; Humans ; Cardiovascular Diseases/diagnosis ; Longitudinal Studies ; Prospective Studies ; Proteomics ; Urokinase-Type Plasminogen Activator ; Myocardial Infarction/epidemiology ; Myocardial Infarction/genetics ; Heart Failure ; Stroke/diagnosis ; Obesity
Chemical Substances	Urokinase-Type Plasminogen Activator (EC 3.4.21.73)
Language	English
Publishing date	2023-11-28
Publishing country	United States
Document type	Journal Article
ISSN	2574-8300
ISSN (online)	2574-8300
DOI	10.1161/CIRCGEN.123.004233
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Article ; Online: Nowcasting (Short-Term Forecasting) of COVID-19 Hospitalizations Using Syndromic Healthcare Data, Sweden, 2020.

Spreco, Armin / Jöud, Anna / Eriksson, Olle / Soltesz, Kristian / Källström, Reidar / Dahlström, Örjan / Eriksson, Henrik / Ekberg, Joakim / Jonson, Carl-Oscar / Fraenkel, Carl-Johan / Lundh, Torbjörn / Gerlee, Philip / Gustafsson, Fredrik / Timpka, Toomas

Emerging infectious diseases

2022 Volume 28, Issue 3, Page(s) 564–571

Abstract: ... The complaint cough by adult showed satisfactory performance (Pearson correlation coefficient r>0.80; mean ...

Abstract	We report on local nowcasting (short-term forecasting) of coronavirus disease (COVID-19) hospitalizations based on syndromic (symptom) data recorded in regular healthcare routines in Östergötland County (population ≈465,000), Sweden, early in the pandemic, when broad laboratory testing was unavailable. Daily nowcasts were supplied to the local healthcare management based on analyses of the time lag between telenursing calls with the chief complaints (cough by adult or fever by adult) and COVID-19 hospitalization. The complaint cough by adult showed satisfactory performance (Pearson correlation coefficient r>0.80; mean absolute percentage error <20%) in nowcasting the incidence of daily COVID-19 hospitalizations 14 days in advance until the incidence decreased to <1.5/100,000 population, whereas the corresponding performance for fever by adult was unsatisfactory. Our results support local nowcasting of hospitalizations on the basis of symptom data recorded in routine healthcare during the initial stage of a pandemic.
MeSH term(s)	Adult ; COVID-19/epidemiology ; Delivery of Health Care ; Forecasting ; Hospitalization ; Humans ; SARS-CoV-2 ; Sweden/epidemiology
Language	English
Publishing date	2022-02-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2803.210267
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Article ; Online: Visualisation in imaging mass spectrometry using the minimum noise fraction transform.

Stone, Glenn / Clifford, David / Gustafsson, Johan O R / McColl, Shaun R / Hoffmann, Peter

BMC research notes

2012 Volume 5, Page(s) 419

Abstract: ... information from IMS data. The MNF transform is implemented through an R-package which is available together ...

Abstract	Background: Imaging Mass Spectrometry (IMS) provides a means to measure the spatial distribution of biochemical features on the surface of a sectioned tissue sample. IMS datasets are typically huge and visualisation and subsequent analysis can be challenging. Principal component analysis (PCA) is one popular data reduction technique that has been used and we propose another; the minimum noise fraction (MNF) transform which is popular in remote sensing. Findings: The MNF transform is able to extract spatially coherent information from IMS data. The MNF transform is implemented through an R-package which is available together with example data from http://staﬀ.scm.uws.edu.au/~glenn/∖#Software. Conclusions: In our example, the MNF transform was able to find additional images of interest. The extracted information forms a useful basis for subsequent analyses.
MeSH term(s)	Animals ; Cluster Analysis ; Image Processing, Computer-Assisted/methods ; Mesencephalon/metabolism ; Mice ; Models, Statistical ; Principal Component Analysis ; Signal-To-Noise Ratio ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods
Language	English
Publishing date	2012-08-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2413336-X
ISSN	1756-0500 ; 1756-0500
ISSN (online)	1756-0500
ISSN	1756-0500
DOI	10.1186/1756-0500-5-419
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Article ; Online: MALDI Imaging Mass Spectrometry (MALDI-IMS)-application of spatial proteomics for ovarian cancer classification and diagnosis.

Gustafsson, Johan O R / Oehler, Martin K / Ruszkiewicz, Andrew / McColl, Shaun R / Hoffmann, Peter

International journal of molecular sciences

2011 Volume 12, Issue 1, Page(s) 773–794

Abstract: MALDI imaging mass spectrometry (MALDI-IMS) allows acquisition of mass data for metabolites, lipids, peptides and proteins directly from tissue sections. IMS is typically performed either as a multiple spot profiling experiment to generate tissue ... ...

Abstract	MALDI imaging mass spectrometry (MALDI-IMS) allows acquisition of mass data for metabolites, lipids, peptides and proteins directly from tissue sections. IMS is typically performed either as a multiple spot profiling experiment to generate tissue specific mass profiles, or a high resolution imaging experiment where relative spatial abundance for potentially hundreds of analytes across virtually any tissue section can be measured. Crucially, imaging can be achieved without prior knowledge of tissue composition and without the use of antibodies. In effect MALDI-IMS allows generation of molecular data which complement and expand upon the information provided by histology including immuno-histochemistry, making its application valuable to both cancer biomarker research and diagnostics. The current state of MALDI-IMS, key biological applications to ovarian cancer research and practical considerations for analysis of peptides and proteins on ovarian tissue are presented in this review.
MeSH term(s)	Female ; Humans ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/metabolism ; Proteomics/methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods
Language	English
Publishing date	2011-01-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms12010773
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Article ; Online: Citric acid antigen retrieval (CAAR) for tryptic peptide imaging directly on archived formalin-fixed paraffin-embedded tissue.

Gustafsson, Johan O R / Oehler, Martin K / McColl, Shaun R / Hoffmann, Peter

Journal of proteome research

2010 Volume 9, Issue 9, Page(s) 4315–4328

Abstract: Imaging mass spectrometry (IMS) is a powerful technology for mapping distributions of biological molecules like proteins and peptides within tissue sections. It is therefore potentially extremely useful for the analysis of pathological conditions such as ...

Abstract	Imaging mass spectrometry (IMS) is a powerful technology for mapping distributions of biological molecules like proteins and peptides within tissue sections. It is therefore potentially extremely useful for the analysis of pathological conditions such as neoplastic diseases. The use of IMS is typically limited to fresh frozen tissue specimens. However, there is a high interest in the possibility of being able to analyze the tissue proteome of formalin-fixed paraffin-embedded (FFPE) specimens that have been stored together with the clinicopathological information of patients in huge archives over many decades. We have therefore developed an antigen-retrieval protocol using a high temperature citric acid buffer to allow partial reversal of FFPE protein cross-linking. Coupled with automated deposition of trypsin and matrix, our method allows the generation of meaningful peptide ion distribution images. In situ peptide fragmentation provided identification of high abundance proteins such as Actin and Collagen. Furthermore, downstream application of three different HPLC-MS strategies allowed identification of a maximum of 106 proteins, 67 of which were mass correlated to ions from IMS analysis of archived FFPE ovarian tissue. The CAAR method presented here complements previously described antigen-retrieval protocols and is an important step in being able to fully analyze the proteome of archived FFPE tissue.
MeSH term(s)	Antigens, Neoplasm/chemistry ; Antigens, Neoplasm/metabolism ; Biomarkers, Tumor/chemistry ; Citric Acid/chemistry ; Citric Acid/metabolism ; Collagen Type I/chemistry ; Female ; Formaldehyde/chemistry ; Hot Temperature ; Humans ; Image Processing, Computer-Assisted/methods ; Immunohistochemistry/methods ; Nebulizers and Vaporizers ; Ovarian Neoplasms/metabolism ; Ovary/chemistry ; Ovary/pathology ; Paraffin Embedding ; Peptide Fragments/chemistry ; Peptide Fragments/metabolism ; Proteomics/methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Tandem Mass Spectrometry ; Trypsin/chemistry ; Trypsin/metabolism
Chemical Substances	Antigens, Neoplasm ; Biomarkers, Tumor ; Collagen Type I ; Peptide Fragments ; Formaldehyde (1HG84L3525) ; Citric Acid (2968PHW8QP) ; Trypsin (EC 3.4.21.4)
Language	English
Publishing date	2010-09-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/pr9011766
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Article: RNA-sequencing and mass-spectrometry proteomic time-series analysis of T-cell differentiation identified multiple splice variants models that predicted validated protein biomarkers in inflammatory diseases.

Magnusson, Rasmus / Rundquist, Olof / Kim, Min Jung / Hellberg, Sandra / Na, Chan Hyun / Benson, Mikael / Gomez-Cabrero, David / Kockum, Ingrid / Tegnér, Jesper N / Piehl, Fredrik / Jagodic, Maja / Mellergård, Johan / Altafini, Claudio / Ernerudh, Jan / Jenmalm, Maria C / Nestor, Colm E / Kim, Min-Sik / Gustafsson, Mika

Frontiers in molecular biosciences

2022 Volume 9, Page(s) 916128

Abstract: Profiling of mRNA expression is an important method to identify biomarkers but complicated by limited correlations between mRNA expression and protein abundance. We hypothesised that these correlations could be improved by mathematical models based on ... ...

Abstract	Profiling of mRNA expression is an important method to identify biomarkers but complicated by limited correlations between mRNA expression and protein abundance. We hypothesised that these correlations could be improved by mathematical models based on measuring splice variants and time delay in protein translation. We characterised time-series of primary human naïve CD4
Language	English
Publishing date	2022-08-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2022.916128
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Article ; Online: Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake.

Williamson, Alice / Norris, Dougall M / Yin, Xianyong / Broadaway, K Alaine / Moxley, Anne H / Vadlamudi, Swarooparani / Wilson, Emma P / Jackson, Anne U / Ahuja, Vasudha / Andersen, Mette K / Arzumanyan, Zorayr / Bonnycastle, Lori L / Bornstein, Stefan R / Bretschneider, Maxi P / Buchanan, Thomas A / Chang, Yi-Cheng / Chuang, Lee-Ming / Chung, Ren-Hua / Clausen, Tine D /

Damm, Peter / Delgado, Graciela E / de Mello, Vanessa D / Dupuis, Josée / Dwivedi, Om P / Erdos, Michael R / Fernandes Silva, Lilian / Frayling, Timothy M / Gieger, Christian / Goodarzi, Mark O / Guo, Xiuqing / Gustafsson, Stefan / Hakaste, Liisa / Hammar, Ulf / Hatem, Gad / Herrmann, Sandra / Højlund, Kurt / Horn, Katrin / Hsueh, Willa A / Hung, Yi-Jen / Hwu, Chii-Min / Jonsson, Anna / Kårhus, Line L / Kleber, Marcus E / Kovacs, Peter / Lakka, Timo A / Lauzon, Marie / Lee, I-Te / Lindgren, Cecilia M / Lindström, Jaana / Linneberg, Allan / Liu, Ching-Ti / Luan, Jian'an / Aly, Dina Mansour / Mathiesen, Elisabeth / Moissl, Angela P / Morris, Andrew P / Narisu, Narisu / Perakakis, Nikolaos / Peters, Annette / Prasad, Rashmi B / Rodionov, Roman N / Roll, Kathryn / Rundsten, Carsten F / Sarnowski, Chloé / Savonen, Kai / Scholz, Markus / Sharma, Sapna / Stinson, Sara E / Suleman, Sufyan / Tan, Jingyi / Taylor, Kent D / Uusitupa, Matti / Vistisen, Dorte / Witte, Daniel R / Walther, Romy / Wu, Peitao / Xiang, Anny H / Zethelius, Björn / Ahlqvist, Emma / Bergman, Richard N / Chen, Yii-Der Ida / Collins, Francis S / Fall, Tove / Florez, Jose C / Fritsche, Andreas / Grallert, Harald / Groop, Leif / Hansen, Torben / Koistinen, Heikki A / Komulainen, Pirjo / Laakso, Markku / Lind, Lars / Loeffler, Markus / März, Winfried / Meigs, James B / Raffel, Leslie J / Rauramaa, Rainer / Rotter, Jerome I / Schwarz, Peter E H / Stumvoll, Michael / Sundström, Johan / Tönjes, Anke / Tuomi, Tiinamaija / Tuomilehto, Jaakko / Wagner, Robert / Barroso, Inês / Walker, Mark / Grarup, Niels / Boehnke, Michael / Wareham, Nicholas J / Mohlke, Karen L / Wheeler, Eleanor / O'Rahilly, Stephen / Fazakerley, Daniel J / Langenberg, Claudia

Nature genetics

2023 Volume 55, Issue 6, Page(s) 973–983

Abstract: Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic ... ...

Abstract	Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10
MeSH term(s)	Humans ; Insulin/genetics ; Genome-Wide Association Study ; Insulin Resistance/genetics ; Diabetes Mellitus, Type 2/genetics ; Glucose/metabolism ; Blood Glucose/genetics
Chemical Substances	Insulin ; Glucose (IY9XDZ35W2) ; Blood Glucose
Language	English
Publishing date	2023-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-023-01408-9
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Article ; Online: Internal calibrants allow high accuracy peptide matching between MALDI imaging MS and LC-MS/MS.

Gustafsson, Johan O R / Eddes, James S / Meding, Stephan / Koudelka, Tomas / Oehler, Martin K / McColl, Shaun R / Hoffmann, Peter

Journal of proteomics

2012 Volume 75, Issue 16, Page(s) 5093–5105

Abstract: One of the important challenges for MALDI imaging mass spectrometry (MALDI-IMS) is the unambiguous identification of measured analytes. One way to do this is to match tryptic peptide MALDI-IMS m/z values with LC-MS/MS identified m/z values. Matching ... ...

Abstract	One of the important challenges for MALDI imaging mass spectrometry (MALDI-IMS) is the unambiguous identification of measured analytes. One way to do this is to match tryptic peptide MALDI-IMS m/z values with LC-MS/MS identified m/z values. Matching using current MALDI-TOF/TOF MS instruments is difficult due to the variability of in situ time-of-flight (TOF) m/z measurements. This variability is currently addressed using external calibration, which limits achievable mass accuracy for MALDI-IMS and makes it difficult to match these data to downstream LC-MS/MS results. To overcome this challenge, the work presented here details a method for internally calibrating data sets generated from tryptic peptide MALDI-IMS on formalin-fixed paraffin-embedded sections of ovarian cancer. By calibrating all spectra to internal peak features the m/z error for matches made between MALDI-IMS m/z values and LC-MS/MS identified peptide m/z values was significantly reduced. This improvement was confirmed by follow up matching of LC-MS/MS spectra to in situ MS/MS spectra from the same m/z peak features. The sum of the data presented here indicates that internal calibrants should be a standard component of tryptic peptide MALDI-IMS experiments.
MeSH term(s)	Amino Acid Sequence ; Calibration ; Carcinoma/chemistry ; Carcinoma/metabolism ; Chromatography, Liquid/methods ; Chromatography, Liquid/standards ; Diagnostic Imaging/methods ; Diagnostic Imaging/standards ; Female ; Humans ; Microtomy/methods ; Microtomy/standards ; Observer Variation ; Ovarian Neoplasms/chemistry ; Ovarian Neoplasms/metabolism ; Peptide Mapping/methods ; Peptide Mapping/standards ; Peptides/analysis ; Peptides/chemistry ; Reproducibility of Results ; Sequence Analysis, Protein/methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Tandem Mass Spectrometry/methods ; Tandem Mass Spectrometry/standards
Chemical Substances	Peptides
Language	English
Publishing date	2012-05-23
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Validation Studies
ZDB-ID	2400835-7
ISSN	1876-7737 ; 1874-3919
ISSN (online)	1876-7737
ISSN	1874-3919
DOI	10.1016/j.jprot.2012.04.054
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Article: Internal calibrants allow high accuracy peptide matching between MALDI imaging MS and LC-MS/MS

Gustafsson, Johan O.R / Eddes, James S / Meding, Stephan / Koudelka, Tomas / Oehler, Martin K / McColl, Shaun R / Hoffmann, Peter

Journal of proteomics. 2012 Aug. 30, v. 75, no. 16

2012

Abstract	One of the important challenges for MALDI imaging mass spectrometry (MALDI-IMS) is the unambiguous identification of measured analytes. One way to do this is to match tryptic peptide MALDI-IMS m/z values with LC-MS/MS identified m/z values. Matching using current MALDI-TOF/TOF MS instruments is difficult due to the variability of in situ time-of-flight (TOF) m/z measurements. This variability is currently addressed using external calibration, which limits achievable mass accuracy for MALDI-IMS and makes it difficult to match these data to downstream LC-MS/MS results. To overcome this challenge, the work presented here details a method for internally calibrating data sets generated from tryptic peptide MALDI-IMS on formalin-fixed paraffin-embedded sections of ovarian cancer. By calibrating all spectra to internal peak features the m/z error for matches made between MALDI-IMS m/z values and LC-MS/MS identified peptide m/z values was significantly reduced. This improvement was confirmed by follow up matching of LC-MS/MS spectra to in situ MS/MS spectra from the same m/z peak features. The sum of the data presented here indicates that internal calibrants should be a standard component of tryptic peptide MALDI-IMS experiments. This article is part of a Special Issue entitled: Imaging Mass Spectrometry: A User’s Guide to a New Technique for Biological and Biomedical Research.
Keywords	animal ovaries ; biomedical research ; data collection ; equipment ; image analysis ; mass spectrometry ; new methods ; ovarian neoplasms
Language	English
Dates of publication	2012-0830
Size	p. 5093-5105.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2400835-7
ISSN	1876-7737 ; 1874-3919
ISSN (online)	1876-7737
ISSN	1874-3919
DOI	10.1016/j.jprot.2012.04.054
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Article ; Online: MALDI Imaging Mass Spectrometry (MALDI-IMS)―Application of Spatial Proteomics for Ovarian Cancer Classification and Diagnosis

Johan O. R. Gustafsson / Martin K. Oehler / Andrew Ruszkiewicz / Shaun R. McColl / Peter Hoffmann

International Journal of Molecular Sciences, Vol 12, Iss 1, Pp 773-

2011 Volume 794

Abstract	MALDI imaging mass spectrometry (MALDI-IMS) allows acquisition of mass data for metabolites, lipids, peptides and proteins directly from tissue sections. IMS is typically performed either as a multiple spot profiling experiment to generate tissue specific mass profiles, or a high resolution imaging experiment where relative spatial abundance for potentially hundreds of analytes across virtually any tissue section can be measured. Crucially, imaging can be achieved without prior knowledge of tissue composition and without the use of antibodies. In effect MALDI-IMS allows generation of molecular data which complement and expand upon the information provided by histology including immuno-histochemistry, making its application valuable to both cancer biomarker research and diagnostics. The current state of MALDI-IMS, key biological applications to ovarian cancer research and practical considerations for analysis of peptides and proteins on ovarian tissue are presented in this review.
Keywords	MALDI ; imaging ; mass spectrometry ; ovarian cancer ; grading ; biomarker ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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