Gernot Zissel | Albert-Ludwigs-University of Freiburg (original) (raw)

Papers by Gernot Zissel

Applied Nanoscience, Jun 22, 2021

The current frontiers in Biology thus in Medicine and Pharmacy are at the nanoscale. Indeed, this... more The current frontiers in Biology thus in Medicine and Pharmacy are at the nanoscale. Indeed, this is the relevant scale for extracting or synthetizing, visualizing, counting, characterizing and/or modifying nanoparticles. Nanoparticles are highly diverse including: extracellular vesicles (e.g.: exosomes), proteins, viruses and nanovectors or drug delivery systems for instance. To quantify the concentration of nano-sized objects, a growing number of size-tracking instruments is being developed. However, to date, the generated data is only used to provide a concentration measurement. The objective of this study was to determine which sizes of nanoparticles are statistically significant between 2 groups of samples. Using different samples (in silico data; calibrated beads; various biological samples), an approach that statistically compares 2 groups of samples was developed and validated. The proof of concept of the proposed approach was illustrated with applications in the field of Biology, Medicine and Pharmacy using liposomes and extracellular vesicles. For the first time to our knowledge, our results suggest that the presented approach enables comparing different groups of biological samples. It may be extended to situations such as batch 1 versus batch 2; healthy versus disease or non-treated versus treated.

Zentralblatt Fur Chirurgie, Sep 1, 2017

Respiratory Research, Jul 24, 2018

Background: The origin of collagen-producing cells in lung fibrosis is unclear. The involvement o... more Background: The origin of collagen-producing cells in lung fibrosis is unclear. The involvement of embryonic signaling pathways has been acknowledged and trans-differentiation of epithelial cells is discussed critically. The work presented here investigates the role of TGFB in cytoskeleton remodeling and the expression of Epithelial-Mesenchymal-Transition markers by Alveolar Epithelial Cells Type II and tests the hypothesis if human alveolar epithelial cells are capable of trans-differentiation and production of pro-fibrotic collagen. Methods: Primary human alveolar epithelial cells type II were extracted from donor tissues and stimulated with TGFβ and a TGFβ-inhibitor. Transcriptome and pathway analyses as well as validation of results on protein level were conducted. Results: A TGFβ-responsive fingerprint was found and investigated for mutual interactions. Interaction modules exhibited enrichment of genes that favor actin cytoskeleton remodeling, differentiation processes and collagen metabolism. Cross-validation of the TGFβ-responsive fingerprint in an independent IPF dataset revealed overlap of genes and supported the direction of regulated genes and TGFβ-specificity. Conclusions: Primary human alveolar epithelial cells type II seem undergo a TGFβ-dependent phenotypic change, exhibit differential expression of EMT markers in vitro and acquire the potential to produce collagen.

Annals of the Rheumatic Diseases, Jun 1, 2013

Background: Both MRI and ultrasonography (US) detect subclinical disease activity in most remissi... more Background: Both MRI and ultrasonography (US) detect subclinical disease activity in most remission and low disease activity patients with rheumatoid arthritis (RA) (1, 2). Fluorescence optical imaging (FOI) has been shown to be not only a sensitive detector of synovitis (3), but also a useful tool in assessing treatment response in patients with RA and psoriatic arthritis (PsA) (4). Objectives: This is the first data on FOI in RA and PsA patients in clinical remission. The objective was to evaluate FOI as a method to detect subclinical disease activity in these patients. Methods: Admission criteria of this prospective study was patient or physician global assessment of disease activity of 10% or less on a visual analogue scale (VAS 0-10), thus resulting in the inclusion of 113 consecutive patients into the inception cohort. Admitted patients received a clinical examination by an independent investigator, and blood samples were taken for measurement of systemic inflammation (ESR, CRP). With these data, patients in DAS28 remission (DAS28 <2.6), SDAI remission (SDAI ≤3.3), CDAI remission (CDAI ≤2.8) and 2011 ACR/EULAR remission (Boolean based definition) were determined. Inflammatory activity in FOI was assessed by an experienced reader using the semiquantitative fluorescent optical imaging activity score (FOIAS) (3), which comprises of the measurement of joint-related fluorescent signal in an automatically generated composite image (Prima Vista Mode, PVM) and in three predefined phases of FOI (P1, P2, P3). Results: 78-87% of patients in remission showed remaining inflammatory activity in the PVM (table).

Anticancer Research, Jun 1, 2020

Frontiers in Immunology, Feb 5, 2021

Background: About 20% of patients with common variable immunodeficiency (CVID) suffer from inters... more Background: About 20% of patients with common variable immunodeficiency (CVID) suffer from interstitial lung disease (ILD) as part of a systemic immune dysregulation. Current understanding suggests a role of B cells in the pathogenesis based on histology and increased levels of BAFF and IgM associated with active disease corroborated by several reports which demonstrate the successful use of rituximab in CVID-ILD. It is debated whether histological confirmation by biopsy or even video-assisted thoracoscopy is required and currently not investigated whether less invasive methods like a bronchoalveolar lavage (BAL) might provide an informative diagnostic tool. Objective: To gain insight into potential immune mechanisms underlying granulomatous and lymphocytic interstitial lung disease (GLILD) and to define biomarkers for progressive ILD by characterizing the phenotype of B-and T-cell populations and cytokine profiles in BAL fluid (BALF) of CVID-ILD compared to sarcoidosis patients and healthy donors (HD).

Airway cell biology and immunopathology, 2021

Data in Brief, 2021

Based on the classification of the Union for International Cancer Control 8th Edition. * * Median... more Based on the classification of the Union for International Cancer Control 8th Edition. * * Median SUV max of the primary tumor. * * * Median FEV 1 percent predicted. * * * * Median serum CCL18 level in ng/mL.

Pneumologie, Feb 19, 2019

PLOS ONE, Jul 25, 2012

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PubMed, Jun 17, 1998

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in inflammatory diseases. It i... more Intercellular adhesion molecule-1 (ICAM-1) plays an important role in inflammatory diseases. It is believed that its soluble form (sICAM-1) might be a serum parameter of inflammatory activity with possible relevance in granulomatous disorders. To evaluate this role we measured sICAM-1 by ELISA in serum and shedding of this molecule by BAL cells in patients with granulomatous lung diseases (pulmonary tuberculosis (TB), hypersensitivity pneumonitis (HSP), pulmonary sarcoidosis (PS), and controls). Serum concentrations of sICAM-1 in patients with TB (496.9 +/- 49.7 ng/ml), with HSP (636.5 +/- 85.9.8 ng/ml), and with PS (588.3 +/- 72.2 ng/ml) were significantly increased compared to controls (275.7 +/- 33.1 ng/ml). Spontaneous release of sICAM-1 by BAL cells differed among patient groups (TB: 9.3 +/- 1.7; HSP: 17.5 +/- 1.4; PS: 9.7 +/- 1.5 ng/ml), however, exceeding that of controls significantly (3.8 +/- 0.6 ng/ml). No correlations between the circulating level and the shedding of this molecule by BAL cells were observed within the groups. Significant correlations between serum sICAM-1 and serum tumor necrosis factor alpha (TNFalpha) level were observed in patients with HSP and TB. Kinetic cell culture experiments with BAL cells revealed a dissociation in sICAM-1 shedding and TNFalpha release. After stimulation rapid upregulation of both molecules (5 h) was followed by a cessation of TNFalpha production at 28 h. sICAM-1 shedding, however, was maintained over 2 days. Our results evidence that the circulating pool of sICAM-1, as well as the shedding of this molecule by BAL cells reflect the activity of cells in the inflammatory processes of granulomatous diseases.

Journal of Internal Medicine, Oct 15, 2019

Background. Bronchoalveolar lavage (BAL) is standard diagnostic procedure. Procedural recommendat... more Background. Bronchoalveolar lavage (BAL) is standard diagnostic procedure. Procedural recommendations have been made by pneumological societies including normal values for interpretation of BAL cytology. These normal values derive from small studies in healthy volunteers and have never been analysed for their sensitivity and specificity. Objectives. This study aims to analyse sensitivity and specificity of these normal values by assessing lavage cell composition in healthy and diseased individuals. Methods. More than 6000 BAL were retrospectively analysed for their cellular distribution including BALs of 250 healthy individuals. All BALs were obtained under similar conditions. Results. Bronchoalveolar lavage cytology of healthy individuals mirrors data from previous studies with smoking being the most important manipula-tor of BAL cytology. Analyses of proposed normal values demonstrate specificity between 80% and 95%, whereas sensitivity ranges between 35% and 65%. Using different mathematical models, a value summing up the differences to ATS-proposed normal values of the cytological pattern was found to best discriminate between healthy and diseased individuals with a sensitivity of nearly 60% with a predefined specificity of 95%. Conclusion. In summary, our analysis confirmed prior results for healthy volunteers and enlarged these findings by analysing sensitivity and specificity of lavage results in an independent validation cohort of diseased individuals. Thereby, the study may influence the acceptance of BAL in the diagnostic workup of individuals with pulmonary diseases. Additionally, the study proposes a novel value that facilitates lavage interpretation and may therefore be useful in further studies.

Oxford University Press eBooks, Oct 1, 2013

Sarcoidosis is a systemic disease characterized by non-necrotizing granulomata and manifestations... more Sarcoidosis is a systemic disease characterized by non-necrotizing granulomata and manifestations in almost any organ. Diagnosis relies on the exclusion of other granulomatous disorders and a compatible pattern of symptoms and clinical findings. Inflammatory lesions and granulomata may undergo spontaneous resolution or persist in chronic disease with eventual fibrosis and permanent organ damage. Immunological disease mechanisms are linked to severe derangements of the cytokine network. In systemic resolution or under prednisolone therapy of symptomatic disease proinflammatory cytokines are downregulated and histological lesions may completely vanish. Corticosteroid-resistant disease, however, requires treatment with an immunosuppressive regimen consisting of prednisolone and an immunosuppressive agent or anti-tumour necrosis factor (TNF) monoclonal antibodies.

Pneumologie, Nov 13, 2012

Lung cancer is one of the leading causes of cancer related death worldwide with more than a milli... more Lung cancer is one of the leading causes of cancer related death worldwide with more than a million deaths per year. The poor prognosis is due to its high aggressiveness and its early metastasis. Although the exact mechanisms are still unknown, the process of epithelial to mesenchymal transition (EMT) seems to be involved in these neoplastic processes. We already demonstrated that serum levels of CCL18, a primate specific chemokine, are highly elevated in patients with lung cancer and correlate with their survival time of patients with adenocarcinoma of the lung. Therefore, we hypothesized that CCL18 may be directly involved in pathological processes of lung cancer, e.g. EMT. We investigated the effect of CCL18 on A549, an adenocarcinoma cell line of the lung, on EMT and other cell functions like proliferation, chemotaxis, invasion, chemoresistance and proliferation. Exposure of A549 lung cancer cells to CCL18 in various concentrations decreases the epithelial marker E-cadherin, whereas FSP-1, a marker of the mesenchymal phenotype increases. Accordingly, CCL18 induced the transcriptional EMT regulator SNAIL1 in a dose dependent fashion. In contrast, an increasing CCL18 concentration was associated with a decline of cell proliferation rate. In addition, CCL18 induced chemotaxis of these cells and increased their chemoresistance. Therefore, CCL18 may be an interesting therapeutic target for NSCLC.

American Journal of Respiratory and Critical Care Medicine, Nov 1, 1997

The TCR repertoire and the CD4/CD8 ratio of clones from peripheral blood (PB), transbronchial bio... more The TCR repertoire and the CD4/CD8 ratio of clones from peripheral blood (PB), transbronchial biopsies (TBB), and bronchoalveolar lavage (BAL) of 16 sarcoid patients was analyzed by staining the clones with monoclonal antibodies against nine V ␤-families. We observed a striking increase in the CD4/ CD8 ratio of the clones from BAL; whereas the CD4/CD8 ratio of the clones from PB was in the normal range. The CD4/CD8 ratio of the TBB-clones had also increased, but this increase did not reach the level of that of the BAL clones. The most prominent changes in the V ␤ percentages could be detected in the CD4 ϩ subpopulation of the BAL-clones. The most abundant V ␤ families were V ␤ 5 in PB and BAL (11.8 and 28.6%, respectively) and V ␤ 6 in the TBB (12.4%). A similar compartmentalized V ␤ usage could be demonstrated in one patient with tuberculosis and one patient with HP. The increase in V ␤ 5, V ␤ 8, V ␤ 12, V ␤ 13.3, and V ␤ 19 in the BAL and the increase of V ␤ 5, V ␤ 6, V ␤ 13.3, and V ␤ 19 in the TBB suggest an antigen-driven activation of the T cells in both compartments. Differences in the V ␤ percentages between BAL and TBB and the lower CD4/CD8 ratio in the TBB, however, demonstrate a relative independence of the two compartments. Zissel G, Bäumer I, Fleischer B, Schlaak M, Müller-Quernheim J. TCR V ␤ families in T cell clones from sarcoid lung parenchyma, BAL, and blood.

American Journal of Respiratory Cell and Molecular Biology, Nov 1, 2016

Sarcoidosis is a granulomatous disease characterized by a T-helper type 1 (Th1) cell-dominated al... more Sarcoidosis is a granulomatous disease characterized by a T-helper type 1 (Th1) cell-dominated alveolitis. As a role of bacteria in the pathogenesis of sarcoidosis has been discussed, Toll-like receptors (TLRs) may be involved in the initiation of a first immune reaction. We analyzed expression and functional relevance of several TLRs in bronchoalveolar lavage (BAL) cells from patients with pulmonary sarcoidosis. In parallel, we determined the release of C-X-C motif chemokine 9 (CXCL9), CXCL10, and CXCL11 by BAL cells from patients with pulmonary sarcoidosis. Nucleotide-binding oligomerization domain-containing protein (NOD) 1 and 2, TLR2, TLR6, and TLR9 expression by BAL cells was analyzed by real-time RT-PCR and cell surface expression by flow cytometry. Chemokine release was measured in BAL cell culture supernatants by ELISA. We found increased TLR9 mRNA expression in patients with sarcoidosis with chest X-ray type I and II and TLR9 protein expression in BAL cells from patients with chest X-ray type II and III. Stimulation with CpG nucleotides increased CXCL10 release by BAL cells from patients with sarcoidosis type II significantly compared with control subjects or other patients with sarcoidosis. In contrast, no increase in TNF, IL-12p40, or CXCL8 was detected. Spontaneous release of CXCL10, but not CXCL9 or CXCL11, by cultured BAL cells was also highest in cells from patients with chest X-ray type II. We found a significant association between TLR9 expression and CD4 1 lymphocytes in BAL. Our data demonstrate that TLR9 ligands may contribute to the immunopathogenesis of sarcoidosis via induction of CXCL10 release in the alveolar macrophages.