Publications (4)16.46 Total impact
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Article: Caged fluorescent haptens reveal the generation of cryptic epitopes in allergic contact dermatitis.
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ABSTRACT: Allergic contact dermatitis (ACD) is the most prevalent form of human immunotoxicity. It is caused by skin exposure to haptens, i.e., protein-reactive, low-molecular-weight chemical compounds, which form hapten-protein complexes (HPCs) in the skin, triggering the immune system. These immunogenic HPCs are elusive. In this study a series of thiol-reactive caged fluorescent haptens, i.e., bromobimanes, were deployed in combination with two-photon fluorescence microscopy, immunohistochemistry, and proteomics to identify possible hapten targets in proteins in human skin. Key targets found were the basal keratinocytes and the keratins K5 and K14. Particularly, cysteine 54 of K5 was found to be haptenated by the bromobimanes. In addition, elevated levels of anti-keratin antibodies were found in the sera of mice exposed to bromobimanes in vivo. The results indicate a general mechanism in which thiol-reactive haptens generate cryptic epitopes normally concealed from the immune system. In addition, keratinocytes and keratin seem to have an important role in the mechanism behind ACD, which is a subject for further investigations.Journal of Investigative Dermatology 01/2011; 131(7):1486-93. · 6.31 Impact Factor -
Article: A study of the expression of Cyclin E and its isoforms in tumor and adjacent mucosa, correlated to patient outcome in early colon cancer.
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ABSTRACT: Cyclin E, a key regulator in the cell cycle, is often over-expressed in malignant disease. It can present as full length (FL) and low-molecular-weight (LMW) isoforms. The purpose of this study was to characterize the expression pattern of cyclin E in colon cancer, both in tumor and in macroscopically normal adjacent mucosa. A secondary aim was to study the possible correlation to clinical factors and patient outcome. Tumor and mucosa tissue from 114 patients with radically operated, non-metastatic colon tumors were analyzed. The cyclin E expression was measured by Western Blot in the tumor and adjacent mucosa using the antibody targeting C-terminal. The cyclin E expression was correlated to both pathology factors as differentiation grade and to the patient outcome. Cyclin E was detected in both tumor and adjacent mucosa and in both FL and LMW-forms. FL was present in 29 (25.4%) tumors and only in three (2.6%) mucosa samples, the corresponding figures for the LMW-isoforms were 80 (70.2%) and 67 (58.8%). There was no correlation between the cyclin E expression and gender, age, tumor location or tumor pathology. Patients with a high expression of LMW isoforms (p < 0.03) or a high total expression (FL+LMW) (p < 0.006) had higher risks of recurrence and thus a worse survival. Cyclin E is expressed in FL- and LMW-forms in both colon tumors and the macroscopically normal adjacent mucosa. A high expression of cyclin E in tumor was associated with an increased risk of tumor recurrence and a worse outcome. It could be a possible prognostic marker in non-metastatic colon cancer.Acta oncologica (Stockholm, Sweden) 12/2009; 49(1):63-9. · 2.27 Impact Factor -
Article: Proteomic study of non-typable Haemophilus influenzae.
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ABSTRACT: Non-typable Haemophilus influenzae (NTHi) are small, gram-negative bacteria and are strictly human pathogens, causing acute otitis media, sinusitis and community-acquired pneumonia. There is no vaccine available for NTHi, as there is for H. influenzae type b. Recent advances in proteomic techniques are finding novel applications in the field of vaccinology. There are several protein separation techniques available today, each with inherent advantages and disadvantages. We employed a combined proteomics approach, including sequential extraction and analytical two-dimensional polyacrylamide electrophoresis (2D PAGE), and two-dimensional semi-preparative electrophoresis (2D PE), in order to study protein expression in the A4 NTHi strain. Although putative vaccine candidates were identified with both techniques, 11 of 15 proteins identified using the 2D PE approach were not identified by 2D PAGE, demonstrating the complementarily of the two methods.Journal of Chromatography B 01/2003; 782(1-2):219-26. · 2.89 Impact Factor -
Article: The presence of stomatin in detergent-insoluble domains of neutrophil granule membranes.
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ABSTRACT: Neutrophil azurophil granules, traditionally regarded as the neutrophil counterpart to lysosomes, lack the lysosomal marker lysosome-associated membrane glycoprotein and have recently been suggested to be nonlysosomal secretory organelles. The membrane of the azurophil granules is poorly characterized-CD63 and CD68 are the only membrane proteins identified so far. Here, azurophil granule membranes were isolated by Percoll gradient subcellular fractionation. Using matrix-assisted laser desorption ionization time of flight mass spectrometry of tryptic peptides from an isolated protein, stomatin was identified in these membranes. Using immunoelectron microscopy and immunoblot analysis of isolated organelles, stomatin was found to be subcellularly localized, not only to the azurophil granules but also by a major part to the specific granules and by a minor part to the secretory vesicles/plasma membrane. We also show the presence of detergent-insoluble, low-density membrane domains in the plasma membrane and the granule membranes and found stomatin to be localized to these domains.Journal of Leukocyte Biology 12/2002; 72(5):970-7. · 4.99 Impact Factor
