Disease Markers - Volume 17, issue 4

Authors: Srivastava, Sudhir | Hanash, Sam

Article Type: Research Article

Citation: Disease Markers, vol. 17, no. 4, pp. 203-204, 2001

Authors: Karlsen, Allan E. | Sparre, Thomas | Nielsen, Karin | Nerup, Jørn | Pociot, Flemming

Article Type: Research Article

Abstract: Type 1 (insulin-dependent) diabetes mellitus (T1DM) is associated with a specific destruction of the insulin-producing beta-cells in the islets of Langerhans. Several factors, e.g. genetic, environmental and immunologial, may be involved in the etiology and pathogenesis of T1DM. Autoreactive T- and B-lymphocytes, together with macrophages infiltrate the islets during the pathogenesis, releasing a mixture of cytokines, demonstrated to be specifically toxic to the beta-cells within the islets. Our goal is to understand the …molecular mechanisms responsible for the beta-cell specific toxicity enabling us to design novel intervention strategies in T1DM. The proteome approach allows us to get a detailed picture of the beta-cell proteins, which change expression level or are post-translationally modified in different {\it in vitro} and {\it in vivo} models of T1DM-associated beta-cell destruction. Combining the information obtained from this extended proteome approach, with that of genetic-, transcriptome- and candidate-gene approaches, we believe that it is possible to reach this goal. Show more

Citation: Disease Markers, vol. 17, no. 4, pp. 205-216, 2001

Authors: Shalhoub, Philip | Kern, Sarah | Girard, Sophie | Beretta, Laura

Article Type: Research Article

Abstract: There is increasing evidence for an immune response to cancer in humans, demonstrated in part by the identification of autoantibodies to tumor antigens. The identification of panels of tumor antigens that elicit a humoral response may have utility in cancer screening, diagnosis or in establishing prognosis. Several approaches are currently available for the identification of tumor antigens. We have used a proteomic-based approach for the identification of tumor antigens that induce an antibody response which we …have applied to hepatocellular carcinoma, a major type of cancer worldwide. Two-dimensional gel electrophoresis allows simultaneous separation of several thousand individual proteins from tumor tissue or tumor cell lines. Proteins eliciting a humoral response in HCC were identified by 2-D Western blotting using sera from patients with hepatocellular carcinoma, followed by mass spectrometry analysis and database search. The common occurrence of autoantibodies to specific proteins may have utility for HCC screening and diagnosis. Show more

Citation: Disease Markers, vol. 17, no. 4, pp. 217-223, 2001

Authors: Miller, Jeremy C. | Butler, E. Brian | Teh, Bin Sing | Haab, Brian B.

Article Type: Research Article

Citation: Disease Markers, vol. 17, no. 4, pp. 225-234, 2001

Authors: James, Peter

Article Type: Research Article

Abstract: In this review I will describe the advances that have recently been made in `traditional' two-dimensional gel based protein expression analysis. A major jump has been made toward the automation of gel image analysis and comparison, one of the major bottlenecks in the analysis chain as well as the automation of spot excision and preparation for mass spectrometric analysis. Currently the gel-based `proteome mapping' approach is highly effective and 300 gels and over 10,000 spots a …week can be analysed. Very recently, viable alternatives to the use of two-dimensional gel electrophoresis have emerged and these approaches are discussed here. In combination with the recently developed stable isotopic tagging methods for peptide quantitation and new mass spectrometers, this emerging technology will be a rapid and highly effective alternative to gel-based methods with few of the latter's shortcomings. Show more

Citation: Disease Markers, vol. 17, no. 4, pp. 235-246, 2001

Authors: Tsuji, T. | Shimohama, S.

Article Type: Research Article

Abstract: In proteome analysis, it is necessary to separate proteins as a first step prior to characterization. Thus, the overall performance of the analysis depends strongly on the separation tool, which is usually two-dimensional electrophoresis (2DE). We have utilized 2DE to begin characterization of the complex pathologic processes in Alzheimer's disease (AD). In the present study, we show how a reliable 2-DE database of brain proteins in Alzheimer's disease was created, improving reproducibility by using …an immobilized pH gradient (IPG) for the first dimension gel electrophoresis. The recent progress in this field, and future prospects in this area are also discussed. Preparation of brain proteins into a suitable solubilized state enabled us to separate over 1000 well-defined protein spots in each 2-DE. A comparison of the density of the spots identified on the reference map between the AD and control group, showed that 5 protein spots were significantly increased, 28 spots were significantly decreased and 7 spots were specifically detected in AD. Two spots among those significantly increased and one spot among those significantly decreased were identified as GFAP related. It is hoped that comparative studies to identify, quantitate, and characterize the proteins differentially expressed in normal brain versus diseased brain will give insight into the mechanisms of pathogenesis and allow the development of a strategy to control both the etiology and course of the diseases. Show more

Keywords: two-dimensional gel electrophoresis, Alzheimer's disease, database, Internet

Citation: Disease Markers, vol. 17, no. 4, pp. 247-257, 2001

Authors: Thalmann, Isolde

Article Type: Research Article

Abstract: The inner ear, one of the most complex organs, contains within its bony shell three sensory systems, the evolutionary oldest gravity receptor system, the three semicircular canals for the detection of angular acceleration, and the auditory system -- unrivaled in sensitivity and frequency discrimination. All three systems are susceptible to a host of afflictions affecting the quality of life for all of us. In the first part of this review we present an introduction to the …milestones of inner ear research to pave the way for understanding the complexities of a proteomics approach to the ear. Minute sensory structures, surrounded by large fluid spaces and a hard bony shell, pose extreme challenges to the ear researcher. In spite of these obstacles, a powerful preparatory technique was developed, whereby precisely defined microscopic tissue elements can be isolated and analyzed, while maintaining the biochemical state representative of the {\it in vivo} conditions. The second part consists of a discussion of proteomics as a tool in the elucidation of basic and pathologic mechanisms, diagnosis of disease, as well as treatment. Examples are the organ of Corti proteins OCP1 and OCP2, oncomodulin, a highly specific calcium-binding protein, and several disease entities, Meniere's disease, benign paroxysmal positional vertigo, and perilymphatic fistula. Show more

Keywords: cochlea, organ of Corti, gap junctions, proteomics, oncomodulin, Meniere's disease, benign paroxysmal positional vertigo, otoconia, perilymphatic fistula

Citation: Disease Markers, vol. 17, no. 4, pp. 259-270, 2001

Authors: Noël-Georis, Isabelle | Bernard, A. | Falmagne, Paul | Wattiez, Ruddy

Article Type: Research Article

Abstract: Most lung disorders are known to be associated to considerable modifications of surfactant composition. Numerous of these abnormalities have been exploited in the past to diagnose lung diseases, allowing proper treatment and follow-up. Diagnosis was then based on phospholipid content, surface tension and cytological features of the epithelial lining fluid (ELF), sampled by bronchoalveolar lavage (BAL) during fiberoscopic bronchoscopy. Today, it appears that the protein content of ELF displays a remarkably high complexity, …not only due to the wide variety of the proteins it contains but also because of the great diversity of their cellular origins. The significance of the use of proteome analysis of BAL fluid for the search for new lung disease marker proteins and for their simultaneous display and analysis in patients suffering from lung disorders has been examined. Show more

Citation: Disease Markers, vol. 17, no. 4, pp. 271-284, 2001

Authors: Sherman, Nicholas E. | Stefansson, Bjarki | Fox, Jay W. | Goldberg, Joanna B.

Article Type: Research Article

Abstract: {\it Pseudomonas aeruginosa} is a Gram-negative bacterium that is ubiquitous in the environment and can cause a variety of diseases in compromised patients. The genome of {\it P. aeruginosa} strain PAO1 has been reported to contain 5570 potential proteins. The value of this genomic database is that new proteins can be recognized to use as diagnostic markers, novel drug targets, and to better understand the physiology of this organism. However, similar to what has been observed …in other sequenced bacterial genomes, approximately one third of the potential proteins have no known function. This is somewhat surprising given the long-standing interest in {\it P. aeruginosa} as an opportunistic pathogen. Obviously new tools, in addition to sequence similarity analysis, are needed to determine the role of these proteins. Proteomics using two-dimensional gel electrophoresis followed by mass spectrometry to detect and identify {\it P. aeruginosa} proteins represents a novel approach to address this gap. Show more

Citation: Disease Markers, vol. 17, no. 4, pp. 285-293, 2001

Authors: Hanash, Samir | Brichory, Franck | Beer, David

Article Type: Research Article

Abstract: We have developed a comprehensive approach to the identification of protein markers in lung cancer that includes profiling of tumor tissue and cell lines as well as the analysis of serum for autoantibodies to lung tumor antigens. A large number of proteins that are differentially expressed in the major subtypes of lung cancer have been identified by mass spectrometry. A database of protein expression in lung cancer and other types of cancer has been constructed that …integrates two-dimensional gel profiles, mass spectrometry data, quantitative protein data and gene expression data at the RNA level, that serves as a resource for biomarker identification. Analysis of the serological response in lung cancer has led to the identification of novel markers detectable in serum of lung cancer patients at the time of diagnosis. The proteomic approach is likely to yield novel classification schemes and novel markers for early diagnosis of lung cancer. Show more

Keywords: lung, cancer, proteomics, markers

Citation: Disease Markers, vol. 17, no. 4, pp. 295-300, 2001