Biomedical subjects

Martin Eisenacher

Publications and source records attributed to Martin Eisenacher.

10 recordsLinked to original sources

PubMed2026

AI-Supported, Integrative Prediction of Postoperative Delirium: Protocol for the CONFUSED Study.

BACKGROUND: Postoperative delirium (POD) is a frequent and serious complication in older surgical patients, characterized by acute cognitive dysfunction and fluctuating levels of consciousness. POD is associated with prolonged hospitalization, long-term cognitive decline, reduced quality of life, and increased mortality. Despite its clinical relevance, the underlying pathophysiological mechanisms remain poorly understood, and reliable biomarkers for early prediction and prevention are lacking. OBJECTIVE: The CONFUSED study aims to identify molecular and clinical predictors of POD by integrating clinical data with proteomic, transcriptomic, and epigenetic analyses. The primary objective is to develop predictive models for POD using multimodal data. Secondary objectives include the identification of delirium-associated genes, proteins, and epigenetic signatures, as well as the exploration of patient subgroups at increased risk for POD. METHODS: CONFUSED is a prospective observational cohort study conducted at a German university hospital. Adult patients undergoing major surgery under general anesthesia will be enrolled until 100 cases of POD have been observed, which is expected to require a total sample size of approximately 200 to 300 patients. Blood samples are collected at 4 predefined time points: before premedication, immediately after surgery, and on postoperative days 2 and 5. Samples undergo comprehensive proteomic profiling, transcriptomic analysis using RNA microarrays, DNA methylation analysis, and genotyping of selected polymorphisms. Clinical data, including demographics, comorbidities, perioperative variables, medications, and delirium assessments using the Confusion Assessment Method (CAM) and CAM for the intensive care unit, are systematically recorded. Statistical analyses include univariate and multivariate methods, as well as machine learning approaches such as random forests and support vector machines, to identify relevant biomarkers and develop predictive models. The study protocol follows STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guidelines and was approved by the responsible ethics committees. RESULTS: The study was registered in the German Clinical Trials Register (DRKS00033854) on March 18, 2024. Recruitment started in January 2024 and is ongoing at the time of manuscript submission. As of now, 135 patients have been enrolled. Sample collection and laboratory analyses are ongoing. Data analysis began in January 2026, with first results anticipated in July 2026. Final data lock is anticipated after the completion of recruitment. CONCLUSIONS: By integrating multimodal molecular data with clinical parameters and applying advanced machine learning techniques, the CONFUSED study aims to improve the prediction and understanding of POD. The results are expected to support the development of personalized preventive strategies and contribute to improved perioperative care for patients at risk of POD.

Humans↗

PubMed2025

Proteomics of Duchenne Muscular Dystrophy Patient iPSC-Derived Skeletal Muscle Cells Reveal Differential Expression of Cytoskeletal and Extracellular Matrix Proteins.

Proteomics of dystrophic muscle samples is limited by the amount of protein that can be extracted from patient biopsies. Cells and tissues derived from patient-derived induced pluripotent stem cells (iPSCs) can be an expandable alternative source. We have patterned iPSCs from three Duchenne muscular dystrophy (DMD) patient lines into skeletal muscle cells using a two-dimensional as well as our three-dimensional organoid differentiation system. Probes with sufficient protein amounts could be extracted and prepared for mass spectrometry. In total, 3007 proteins in 2D and 2709 proteins in 3D were detected in DMD patient probes. A total of 83 proteins in 2D and 338 proteins in 3D can be described as differentially expressed between DMD and control patient probes in a post hoc test. We have identified and we propose Myosin-9, Collagen 18A, Tropomyosin 1, BASP1, RUVBL1, and NCAM1 as proteins specifically altered in their expression in DMD for further investigation. Proteomics of skeletal muscle organoids resulted in greater consistency of results between cell lines in comparison to the two-dimensional myogenic differentiation protocol.

Humans↗

PubMed2007

Transformation of adult retina from the regenerative to the axonogenesis state activates specific genes in various subsets of neurons and glial cells.

The purpose of this study was to identify the gene expression profile of the regenerating retina in vitro. To achieve this goal, three experimental groups were studied: (1) an injury control group (OC-LI group) that underwent open crush (OC) of the optic nerve and lens injury (LI) in vivo; (2) an experimental group (OC-LI-R group) that comprised animals treated like those in the OC-LI group except that retinal axons were allowed to regenerate (R) in vitro; and (3) an experimental group (OC-LI-NR group) that comprised animals treated as those in the OC-LI group, except that the retinas were cultured in vitro with the retinal ganglion cell (RGC) layer facing upwards to prevent axonal regeneration (NR). Gene expression in each treatment group was compared to that of untreated controls. Immunohistochemistry was used to examine whether expression of differentially regulated genes also occurred at the protein level and to localize these proteins to the respective retinal cells. Genes that were regulated belonged to different functional categories such as antioxidants, antiapoptotic molecules, transcription factors, secreted signaling molecules, inflammation-related genes, and others. Comparison of changes in gene expression among the various treatment groups revealed a relatively small cohort of genes that was expressed in different subsets of cells only in the OC-LI-R group; these genes can be considered to be regeneration-specific. Our findings demonstrate that axonal regeneration of RGC involves an orchestrated response of all retinal neurons and glia, and could provide a platform for the development of therapeutic strategies for the regeneration of injured ganglion cells.

Animals↗

PubMed2007

Expression analysis of pancreatic cancer cell lines reveals association of enhanced gene transcription and genomic amplifications at the 8q22.1 and 8q24.22 loci.

Despite tremendous effort and progress in the diagnostics of pancreatic cancer with respect to imaging techniques and molecular genetics, only very few patients can be cured by surgery leading to a 5-year survival rate of only 3%. Especially the lack of chemotherapeutical options in this entity requires a better understanding of the molecular mechanisms leading to pancreatic carcinoma growth and progression in order to develop novel treatment regimens. To identify signaling pathways that are critical for this tumor entity, we compared six well-established pancreatic cancer cell lines (Capan-1, Capan-2, HUP-T3, HUP-T4, KCL-MOH, PaTu-8903) with colon cancer cell lines and tumor cell lines of non-epithelial origin by expression profiling. For this purpose we employed Human Genome Focus Arrays representing about 8500 well annotated human genes. We identified 353 genes with significantly high expression in the group of pancreatic carcinomas. Based on Gene Ontology annotations these genes are especially involved in Rho protein signal transduction, proteasome activator activity, cell motility, apoptotic program, and cell-cell adhesion processes indicating these pathways to be interesting candidates for the design of targeted therapies. Most pancreatic carcinomas are characterized by mutations in the TP53 and the KRAS genes and the absence of microsatellite instability, which could also be confirmed for our panel of pancreatic carcinoma cell lines. Looking for individual differences within this group that may be responsible for more or less aggressive behavior, we identified genomic amplifications at the 8q22.1 and the 8q24.22 loci to be associated with enhanced gene transcription. Because we have previously shown that gains of genomic material from the long arm of chromosome 8 have an adverse effect on the outcome of pancreatic carcinoma patients, we conclude that functional analysis of amplified genes at 8q22 and/or 8q24 may lead to an improved understanding of pancreatic carcinoma progression.

Apoptosis↗

PubMed2006

Glucocorticoids induce differentiation of a specifically activated, anti-inflammatory subtype of human monocytes.

Monocytes and macrophages may either promote or down-regulate inflammatory reactions depending on their state of activation. The effects of glucocorticoids (GCs), the most widely used immunosuppressive drugs, on monocytes are currently not well defined. By analyzing the GC-induced expression pattern in human monocytes by microarray technology, we identified for the first time GC-dependent regulation of 133 genes, including anti-inflammatory molecules such as adenosine A3 receptor, CD1d, and IL-1 receptor II. The results were independently confirmed by real-time polymerase chain reaction (PCR) and flow cytometry. Functional clustering of GC-regulated genes indicated induction of monocytic properties such as phagocytosis and motility as well as repression of adhesion, apoptosis, and oxidative burst. These predictions were confirmed by independent functional assays. GCs up-regulate fMLP receptors and specifically promote chemotaxis to this chemoattractant. Furthermore, GCs promote survival of an anti-inflammatory monocytic phenotype in inflammatory reactions, probably by inhibition of apoptosis because of oxidative stress. GCs limit tissue damage because of induction of antioxidative properties and high capacity for phagocytosis of proinflammatory agents. Thus, GC treatment did not cause a global suppression of monocytic effector functions but results in differentiation of a specific anti-inflammatory phenotype which seems to be actively involved in resolution of inflammatory reactions.

Apoptosis↗

PubMed2006

Reporter metabolite analysis of transcriptional profiles of a Staphylococcus aureus strain with normal phenotype and its isogenic hemB mutant displaying the small-colony-variant phenotype.

In this study, full-genome DNA microarrays based on the sequence of Staphylococcus aureus N315 were used to compare the transcriptome of a clinical S. aureus strain with a normal phenotype to that of its isogenic mutant with a stable small-colony-variant (SCV) phenotype (hemB::ermB). In addition to standard statistical analyses, systems biology advances were applied to identify reporter metabolites and to achieve a more detailed survey of genome-wide expression differences between the hemB mutant and its parental strain. Genes of enzymes involved in glycolytic and fermentative pathways were found to be up-regulated in the hemB mutant. Furthermore, our analyses allowed identification of additional differences between the normal-phenotype S. aureus and the SCV, most of which were related to metabolism. Profound differences were identified especially in purine biosynthesis as well as in arginine and proline metabolism. Of particular interest, a hypothetical gene of the Crp/Fnr family (SA2424) that is part of the arginine-deiminase (AD) pathway, whose homologue in Streptococcus suis is assumed to be involved in intracellular persistence, showed significantly increased transcription in the hemB mutant. The hemB mutant potentially uses the up-regulated AD pathway to produce ATP or (through ammonia production) to counteract the acidic environment that prevails intracellularly. Moreover, genes involved in capsular polysaccharide and cell wall synthesis were found to be significantly up-regulated in the hemB mutant and therefore potentially responsible for the changed cell morphology of SCVs. In conclusion, the identified differences may be responsible for the SCV phenotype and its association with chronic and persistent infections.

Arginine↗

PubMed2006

Mass analysis peptide sequence prediction (MAPSP).

UNLABELLED: The software tool MAPSP allows the combinatorial prediction of novel short peptides such as hormones with common sequence features. In addition, it assists in de novo sequencing in general. The tool was designed for use in conjunction with the analytical identification method of mass spectrometry (MS) and it can considerably speed-up the analysis of unknowns. AVAILABILITY: The web interface is freely available at http://mapsp.ifg.uni-muenster.de/

Algorithms↗

PubMed2006

Sampling strategy for intraoral detection of periodontal pathogens before and following periodontal therapy.

BACKGROUND: The aim of this study was to identify a sampling strategy with high probability for detecting oral colonization by Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Eikenella corrodens, Tannerella forsythensis, Prevotella intermedia, Prevotella nigrescens, and Treponema denticola before and following mechanical periodontal therapy. METHODS: Samples were taken from the following intraoral sites in 35 patients with untreated chronic periodontitis before and 1.5, 3, and 6 months after non-surgical periodontal therapy: supra- and subgingival plaque from the deepest pockets in each sextant; pooled supra- and subgingival plaque from another six randomly selected, less affected teeth; mucosal swab samples from the tongue, tonsils, throat, and buccal mucosa; and stimulated and unstimulated saliva. Microbial species were identified by polymerase chain reaction (PCR). RESULTS: Of the sampling of all assessed sites, the highest probability for simultaneously detecting the tested pathogens was found in respect to the combination of supra- and subgingival plaque samples taken from the most affected tooth in each sextant in untreated patients (probability: 83% to 95% for the assessed bacteria). These results were consistently observed throughout the study period. CONCLUSIONS: For determining the intraoral carrier state of patients with periodontitis, a combined sample of supra- and subgingival plaque taken from the deepest periodontal pocket in each sextant may yield the most reliable result. This sampling strategy may be used in routine microbial testing and clinical research.

Bacteria, Anaerobic↗

PubMed2004

Expression profiling of t(12;22) positive clear cell sarcoma of soft tissue cell lines reveals characteristic up-regulation of potential new marker genes including ERBB3.

Clear cell sarcoma of soft tissue (CCSST), also known as malignant melanoma of soft parts, represents a rare lesion of the musculoskeletal system usually affecting adolescents and young adults. CCSST is typified by a chromosomal t(12;22)(q13;q12) translocation resulting in a fusion between the Ewing sarcoma gene (EWSR1) and activating transcription factor 1 (ATF1), of which the activity in nontransformed cells is regulated by cyclic AMP. Our aim was to identify critical differentially expressed genes in CCSST tumor cells in comparison with other solid tumors affecting children and young adults to better understand signaling pathways regulating specific features of the development and progression of this tumor entity. We applied Affymetrix Human Genome U95Av2 oligonucleotide microarrays representing approximately 12,000 genes to generate the expression profiles of the CCSST cell lines GG-62, DTC-1, KAO, MST2, MST3, and Su-CC-S1 in comparison with 8 neuroblastoma, 7 Ewing tumor, and 6 osteosarcoma cell lines. Subsequent hierarchical clustering of microarray data clearly separated all four of the tumor types from each other and identified differentially expressed transcripts, which are characteristically up-regulated in CCSST. Statistical analysis revealed a group of 331 probe sets, representing approximately 300 significant (P < 0.001) differentially regulated genes, which clearly discriminated between the CCSST and other tumor samples. Besides genes that were already known to be highly expressed in CCSST, like S100A11 (S100 protein) or MITF (microphthalmia-associated transcription factor), this group shows an obvious portion of genes that are involved in cyclic AMP response or regulation, in pigmentation processes, or in neuronal structure and signaling. Comparison with other expression profile analyses on neuroectodermal childhood tumors confirms the high robustness of this strategy to characterize tumor entities based on their gene expression. We found the avian erythroblastic leukemia viral oncogene homologue 3 (ERBB3) to be one of the most dramatically up-regulated genes in CCSST. Quantitative real-time PCR and Northern blot analysis verified the mRNA abundance and confirmed the absence of the inhibitory transcript variant of this gene. The protein product of the member of the epidermal growth factor receptor family ERBB3 could be shown to be highly present in all of the CCSST cell lines investigated, as well as in 18 of 20 primary tumor biopsies. In conclusion, our data demonstrate new aspects of the phenotype and the biological behavior of CCSST and reveal ERBB3 to be a useful diagnostic marker.

Blotting, Northern↗

PubMed2002

Cytogenetic alterations and cytokeratin expression patterns in breast cancer: integrating a new model of breast differentiation into cytogenetic pathways of breast carcinogenesis.

The introduction of a concept proposing multiple cellular subgroups in the normal female breast, including cytokeratin 5/6 (Ck 5/6)-positive progenitor cells, offers a new explanation for the existence of highly aggressive breast cancers with and without Ck 5/6 expression. Using the tissue microarray technique, 166 breast cancer cases, all characterized by comparative genomic hybridization, were evaluated by immunohistochemistry, using 15 different antibodies (estrogen receptor, progesterone receptor, p53, Ki-67, c-erbB2, epidermal growth factor receptor, cyclins A, D1, and E, bcl-2, p21, p27, Ck 5/6, Ck 8/18, and smooth muscle actin) and chromogenic in situ hybridization for c-erbB2. Biomathematical cluster analysis was applied to confirm the conventional interpretation of the results by an independent approach. Ck 5/6-positive breast carcinomas were in general negative for estrogen receptor and progesterone receptor, were highly proliferating (as reflected by Ki67 and cyclin A), and were associated with specific protein expression patterns, such as expression of p53 and epithelial growth factor receptor (all related to more aggressive tumor behavior), which could further be demonstrated by biomathematical cluster analysis. In contrast Ck 5/6-negative breast carcinomas revealed a lower tumor proliferation rate, an increased expression of p21, p27, c-erbB2, and bcl-2, and a significantly lower number of genetic alterations, with losses of chromosomal material of 16q as the most common genetic alteration. Our data give the first hints to the hypothesis that different cellular subgroups in the female breast give rise to subgroups of breast carcinomas with differing protein expression and cytogenetic alteration patterns that may be related to clinical behavior.

Breast Neoplasms↗