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153 results on '"Bauer, J.W."'

8. Cytokeratin 8 interacts with clumping factor B: a new possible virulence factor target

Author

Haim, M., Trost, A., Maier, C.J., Achatz, G., Feichtner, S., Hintner, H., Bauer, J.W., and Onder, K.

Subjects
Staphylococcus aureus -- Physiological aspects, Keratin -- Properties, Virulence (Microbiology) -- Research, Biological sciences
Abstract

Staphylococcus aureus is a human pathogen of growing clinical significance, owing to its increasing levels of resistance to most antibiotics. Infections range from mild wound infections to severe infections such as endocarditis, osteomyelitis and septic shock. Adherence of S. aureus to human host cells is an important step, leading to colonization and infection. Adherence is mediated by a multiplicity of proteins expressed on the bacterial surface, including clumping factor B. In this study, we aimed to identify new targets of clumping factor B in human keratinocytes by undertaking a genome-wide yeast two-hybrid screen of a human keratinocyte cDNA library. We show that clumping factor B is capable of binding cytokeratin 8 (CK8), a type II cytokeratin. Using a domain-mapping strategy we identified amino acids 437-464 as necessary for this interaction. Recombinantly expressed fragments of both proteins were used in pull-down experiments and confirmed the yeast two-hybrid studies. Analysis with S. aureus strain Newman deficient in clumping factor B showed the clumping factor B-dependence of the interaction with CK8. We postulate that the clumping factor B-CK8 interaction is a novel factor in S. aureus infections. DOI 10.1099/mic.0.034413-0

Published
2010

13. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility

Author

Has, C., primary, Bauer, J.W., additional, Bodemer, C., additional, Bolling, M.C., additional, Bruckner‐Tuderman, L., additional, Diem, A., additional, Fine, J.‐D., additional, Heagerty, A., additional, Hovnanian, A., additional, Marinkovich, M.P., additional, Martinez, A.E., additional, McGrath, J.A., additional, Moss, C., additional, Murrell, D.F., additional, Palisson, F., additional, Schwieger‐Briel, A., additional, Sprecher, E., additional, Tamai, K., additional, Uitto, J., additional, Woodley, D.T., additional, Zambruno, G., additional, and Mellerio, J.E., additional

Published
2020
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20. 185 CRISPR/Cas9 mediated gene correction of COL7A1

Author

Hainzl, S., primary, Peking, P., additional, Kocher, T., additional, Murauer, E.M., additional, Larcher, F., additional, Río, M del, additional, Duarte, B.G., additional, Steiner, M., additional, Klausegger, A., additional, Bauer, J.W., additional, Reichelt, J., additional, and Koller, U., additional

Published
2017
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33. Increased tumour cell PD‐L1 expression, macrophage and dendritic cell infiltration characterise the tumour microenvironment of ulcerated primary melanomas.

Author

Koelblinger, P., Emberger, M., Drach, M., Cheng, P.F., Lang, R., Levesque, M.P., Bauer, J.W., and Dummer, R.

Subjects
DENDRITIC cells, TUMORS, MELANOMA, NEURAL development, ANTIGEN processing
Abstract

Background: Primary melanoma ulceration is an unfavourable prognostic factor included in current staging systems. Yet, the immunological and molecular alterations responsible for this adverse outcome have not been fully elucidated. Objectives: We aimed to identify immunological differences between ulcerated and non‐ulcerated primary melanomas concerning both innate and adaptive immunity and to correlate these with clinical outcome. Methods: Formalin‐fixed paraffin‐embedded primary melanomas from 112 patients (pts) were analysed by immunohistochemistry. The expression of various markers identifying tumour‐infiltrating lymphocytes, macrophages and dendritic cells was evaluated semi‐quantitatively by three independent investigators. Tumour cell expression of programmed death‐ligand 1 (PD‐L1), transporter of antigen processing 1 and the MxA protein was also analysed. Results: Recurrence occurred in 21/56 pts (37.5%) with ulcerated vs. 14/56 pts (25.0%) with non‐ulcerated tumours (P = 0.15). Tumour ulceration was associated with more frequent development of brain metastasis (17.6 vs. 3.6% of pts, P = 0.015). Immunohistochemistry showed an association of ulceration with the presence of intratumoural CD68+ macrophages (P = 0.028) as well as with increased numbers of intratumoural CD11c+ dendritic cells (P = 0.014) and CD163+ macrophages (P = 0.001). PD‐L1 positivity (expression in >1% of tumour cells) was more frequent in ulcerated than non‐ulcerated tumours [40 (72.7%) vs. 25 (44.6%), P = 0.003]. A positive correlation between intratumoural CD11c+ (Spearman's correlation coefficient ρ: 0.42) and CD163+ (ρ: 0.31) cell count and frequency of tumour cell PD‐L1 expression was detected. Conclusions: Our results confirm the adverse clinical outcome associated with primary melanoma ulceration, particularly concerning the risk of recurrence and subsequent development of brain metastases. The observed immunological differences suggest a conceivable role of increased intratumoural macrophage and dendritic cell counts associated with enhanced tumour cell PD‐L1 expression potentially contributing to the immunosuppressive, growth‐promoting microenvironment of ulcerated primary melanomas. [ABSTRACT FROM AUTHOR]

Published
2019
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41. An ex vivo RNA trans‐splicing strategy to correct human generalized severe epidermolysis bullosa simplex.

Author

Breitenbach, J.S., Ablinger, M., Poetschke, F.J., Kocher, T., Koller, U., Hainzl, S., Kitzmueller, S., Reichelt, J., Lettner, T., Wally, V., Peking, P., Muss, W.H., and Bauer, J.W.

Abstract

Summary: Background: Generalized severe epidermolysis bullosa simplex (EBS‐gen sev) is a genetic blistering skin disease in which autosomal dominant mutations in either the keratin KRT5 or KRT14 genes lead to impaired function of the intermediate filament cytoskeleton in the basal epidermis. Here we present an ex vivo RNA trans‐splicing‐based therapeutic approach to correct the phenotype. Objectives: To correct a mutation within exon 1 of the KRT14 gene, using a 5′‐trans‐splicing approach, where any mutation within the first seven exons could be replaced by a single therapeutic molecule. Methods: A therapeutic RNA trans‐splicing molecule containing wild‐type exons 1–7 was stably transduced into an EBS patient‐derived keratinocyte line. Trans‐splicing was confirmed via reverse‐transcriptase polymerase chain reaction, Western blotting and immunofluorescence microscopy. Skin equivalents generated from corrected keratinocytes were grafted onto nude mice and analysed about 8 weeks post‐transplantation for regular epidermal stratification, trans‐splicing‐induced green fluorescent protein expression and blistering. Results: Transplanted skin equivalents generated from trans‐splicing‐corrected patient keratinocytes showed a stable and blister‐free epidermis. KRT14 correction disrupted EBS‐gen sev‐associated proinflammatory signalling, as shown at the mRNA and protein levels. Disruption of the pathogenic feedback loop in addition to overall downregulation of KRT14 expression highlighted the effect of KRT14 correction on the EBS pathomechanism. Conclusions: Our data demonstrate that trans‐splicing‐mediated mRNA therapy is an effective method for the correction of dominantly inherited KRT14 mutations at the transcriptional level. This results in the rescue of the EBS‐gen sev phenotype and stabilization of the epidermis in a xenograft mouse model. What's already known about this topic? RTM163, described in this study, was previously used in a transient in vitro transfection system, where the ability to correct KRT14 at the mRNA level was demonstrated. What does this study add? In this study, we stably transduced RTM163 in a second patient‐derived keratinocyte line.Successful trans‐splicing was confirmed in this cell line.The expression of disease‐related marker genes, which are characteristically deregulated in epidermolysis bullosa simplex, were analysed.For the first time this study showed that RNA trans‐splicing molecule‐transduced patient keratinocytes can differentiate into a phenotypically normal and blister‐free epidermis in a xenograft mouse model. What is the translational message? This study shows the feasibility of using spliceosome‐mediated RNA trans‐splicing to generate a stable and blister‐free epidermis in vivo.Combined with pre‐existing ex vivo gene therapeutic methods, this might be a valid option for future treatments of dominantly inherited genodermatoses. Linked Comment: Bremer and van den Akker. Br J Dermatol 2019; 180:17–19. [ABSTRACT FROM AUTHOR]

Published
2019
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44. miR-17, miR-19b, miR-20a and miR-106a are down-regulated in human aging

Author

Strasser, A., Trost, A., Grubeck-Loebenstein, B., Mück, C., Papak, C., Schreiner, C., Herndler-Brandstetter, D., Tschachler, E., Laschober, G., Lepperdinger, G., Kühnel, H., Grillari, J., Bauer, J.W., Fortschegger, K., Eckhard, L., Micutkova, L., Breitenbach, M., Hackl, M., Mildner, M., Rinnerthaler, M., Scheideler, M., Wieser, M., Sampson, N., Berger, P., Jansen-Dürr, P., Grillari-Voglauer, R., Brunner, S., and Trajanoski, Z.

Subjects
Biological Sciences
Abstract

Aging is a multifactorial process where deterioration of body functions is driven by stochastic damage while counteracted by distinct genetically encoded repair systems. In order to better understand the genetic component of aging, many studies have addressed the gene and protein expression profiles of various aging model systems engaging different organisms from yeast to human. The recently identified small non-coding miRNAs are potent post-transcriptional regulators that can modify the expression of up to several hundred target genes per single miRNA, similar to transcription factors. Increasing evidence shows that miRNAs contribute to the regulation of most if not all important physiological processes, including aging. However, so far the contribution of miRNAs to age-related and senescence-related changes in gene expression remains elusive. To address this question, we have selected 4 replicative cell aging models including endothelial cells, replicated CD8+ 13 T cells, renal proximal tubular epithelial cells, and skin fibroblasts. Further included were three organismal aging models including foreskin, mesenchymal stem cells and CD8+ 16 T cell populations from old and young donors. Using LNA-based miRNA microarrays we identified four commonly regulated miRNAs, miR-17 down-regulated in all 7, miR-19b and miR-20a, down-regulated in 6 models and miR-106a down19 regulated in 5 models. Decrease in these miRNAs correlated with increased transcript levels of some established target genes, especially the cdk inhibitor p21/CDKN1A. These results establish miRNAs as novel markers of cell aging in humans.

Published
2009

48. Autoimmune Bullous Diseases in Austria

Author

Laimer, Martin, primary, Pohla-Gubo, Gabriela, additional, Kraus, Lukas, additional, Nischler, Elke, additional, Bauer, J.W., additional, Ahlgrimm-Siess, V., additional, and Hintner, Helmut, additional

Published
2011
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