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  1. Book ; Thesis: Die Rolle des angeborenen Immunsystems bei chronischen Entzündungsprozessen und Autoimmunität

    Bossaller, Lukas Friedrich Magnus

    2018  

    Author's details vorgelegt von Lukas Friedrich Magnus Bossaller
    Language German ; English
    Size 177 Seiten, Illustrationen, 31 cm
    Publishing place Greifswald
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Habilitationsschrift, Universität Greifswald, 2018
    HBZ-ID HT020128147
    Database Catalogue ZB MED Medicine, Health

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  2. Article ; Online: CMV Retinitis in Undetected Immune Deficiency Syndrome.

    Stahl, Andreas / Bossaller, Lukas

    Deutsches Arzteblatt international

    2022  Volume 119, Issue 27-28, Page(s) 494

    MeSH term(s) Humans ; Cytomegalovirus Retinitis/complications ; Cytomegalovirus Retinitis/diagnosis ; Cytomegalovirus Retinitis/drug therapy ; Antiviral Agents/therapeutic use
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2022-10-29
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2406159-1
    ISSN 1866-0452 ; 1866-0452
    ISSN (online) 1866-0452
    ISSN 1866-0452
    DOI 10.3238/arztebl.m2022.0126
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Inflammasome activation and formation of ASC specks in patients with juvenile idiopathic arthritis.

    Wittmann, Nico / Mishra, Neha / Gramenz, Jana / Kuthning, Daniela / Behrendt, Ann-Kathrin / Bossaller, Lukas / Meyer-Bahlburg, Almut

    Frontiers in medicine

    2023  Volume 10, Page(s) 1063772

    Abstract: Objective: The formation of large intracellular protein aggregates of the inflammasome adaptor ASC is a hallmark of inflammasome activation and characteristic of autoinflammation. Inflammasome activated cells release the highly proinflammatory cytokine ... ...

    Abstract Objective: The formation of large intracellular protein aggregates of the inflammasome adaptor ASC is a hallmark of inflammasome activation and characteristic of autoinflammation. Inflammasome activated cells release the highly proinflammatory cytokine IL-1β in addition to ASC specks into the extracellular space. Autoinflammatory activity has been demonstrated in systemic JIA, however minimal data exist on the role of inflammasomes in other JIA subtypes. We therefore investigated, if pyroptotic cells are present in the circulation of oligo- and poly-articular JIA.
    Methods: Peripheral blood of JIA patients (
    Results: Oligo-articular JIA patients showed a significantly increased proportion of ASC speck
    Conclusion: For the first time, we detect
    Language English
    Publishing date 2023-03-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2023.1063772
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Streifenmeniskometrie und Schirmer-Test : Vergleichende Betrachtung in der Diagnostik des trockenen Auges.

    Schulze, Konrad / Großjohann, Rico / Paul, Sebastian / Bossaller, Lukas / Tost, Frank

    Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft

    2020  Volume 118, Issue 6, Page(s) 561–568

    Abstract: Background: As one alternative to the Schirmer test, strip meniscometry has been presented as a methodology which also seems to be suitable for quantifying a lack of tear volume.: Methods: In a randomized prospective clinical study 391 eyes from 201 ... ...

    Title translation Schirmer's test and strip meniscometry : Comparative consideration in the diagnostics of dry eye.
    Abstract Background: As one alternative to the Schirmer test, strip meniscometry has been presented as a methodology which also seems to be suitable for quantifying a lack of tear volume.
    Methods: In a randomized prospective clinical study 391 eyes from 201 subjects were assigned to 3 groups according to the severity of eye surface deficiency (group 0: 225 healthy eyes, f/m = 1.25, mean age = 50.1 ± 17.6 years; group 1: 112 eyes with mild keratoconjunctivitis sicca (KCS), f/m = 1.38, mean age = 58.7 ± 13.9 years; group 2: 54 eyes with manifest KCS, f/m = 2.375, mean age = 52.6 ± 14.1 years). Objective test parameters used were strip meniscometry, Schirmer's 1 test and the Jones-test. In order to determine the condition of the ocular surface and tear film more precisely, slit-lamp examination, the detection of lid-parallel conjunctival folds (LIPCOF) and optical coherence tomography (OCT) meniscometry were also performed. Subjective discomfort was objectified by using the Ocular Surface Disease Index questionnaire (OSDI).
    Results: The results of strip meniscometry, Schirmer's 1 test, the Jones test and OCT meniscometry were significantly lower in KCS subjects than in healthy subjects (p < 0.001), whereas the OSDI score was significantly higher (p < 0.001). The parameters strip meniscometry, Schirmer's 1 test, the Jones test and OCT meniscometry scores correlated with each other. Sensitivity and specificity of strip meniscometry ranged from 0.79 to 0.89 and from 0.42 to 0.5.
    Conclusion: Strip meniscometry is suitable to detect a lack of tear volume. Advantageous is the rapid performance of the procedure (5 s per eye) and a good agreement with established tests (e.g. Schirmer's test). To improve the specificity, strip meniscometry must be combined with other examination methods.
    MeSH term(s) Adult ; Aged ; Dry Eye Syndromes/diagnosis ; Humans ; Middle Aged ; Prospective Studies ; Reproducibility of Results ; Sensitivity and Specificity ; Tears
    Language German
    Publishing date 2020-11-04
    Publishing country Germany
    Document type Journal Article ; Randomized Controlled Trial
    ZDB-ID 1105167-x
    ISSN 1433-0423 ; 0941-293X
    ISSN (online) 1433-0423
    ISSN 0941-293X
    DOI 10.1007/s00347-020-01208-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Instructions for Flow Cytometric Detection of ASC Specks as a Readout of Inflammasome Activation in Human Blood.

    Wittmann, Nico / Behrendt, Ann-Kathrin / Mishra, Neha / Bossaller, Lukas / Meyer-Bahlburg, Almut

    Cells

    2021  Volume 10, Issue 11

    Abstract: Inflammasome activation is linked to the aggregation of the adaptor protein ASC into a multiprotein complex, known as the ASC speck. Redistribution of cytosolic ASC to this complex has been widely used as a readout for inflammasome activation and ... ...

    Abstract Inflammasome activation is linked to the aggregation of the adaptor protein ASC into a multiprotein complex, known as the ASC speck. Redistribution of cytosolic ASC to this complex has been widely used as a readout for inflammasome activation and precedes the downstream proteolytic release of the proinflammatory cytokines, IL-1β and IL-18. Although inflammasomes are important for many diseases such as periodic fever syndromes, COVID-19, gout, sepsis, atherosclerosis and Alzheimer's disease, only a little knowledge exists on the precise and cell type specific occurrence of inflammasome activation in patient samples ex vivo. In this report, we provide detailed information about the optimal conditions to reliably identify inflammasome activated monocytes by ASC speck formation using a modified flow cytometric method introduced by Sester et al. in 2015. Since no protocol for optimal sample processing exists, we tested human blood samples for various conditions including anticoagulant, time and temperature, the effect of one freeze-thaw cycle for PBMC storage, and the fast generation of a positive control. We believe that this flow cytometric protocol will help researchers to perform high quality translational research in multicenter studies, and therefore provide a basis for investigating the role of the inflammasome in the pathogenesis of various diseases.
    MeSH term(s) Anticoagulants ; CARD Signaling Adaptor Proteins/metabolism ; Flow Cytometry/methods ; Flow Cytometry/standards ; Humans ; Inflammasomes/immunology ; Inflammasomes/metabolism ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Monocytes/cytology ; Monocytes/immunology ; Monocytes/metabolism ; Specimen Handling ; Temperature ; Time Factors
    Chemical Substances Anticoagulants ; CARD Signaling Adaptor Proteins ; Inflammasomes ; PYCARD protein, human
    Language English
    Publishing date 2021-10-26
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10112880
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Conference proceedings: Inflammasom-Aktivierung und Bildung von ASC-Specks bei Patienten mit juveniler idiopathischer Arthritis

    Wittmann, Nico / Mishra, Neha / Gramenz, Jana / Kuthning, Daniela / Behrendt, Ann-Kathrin / Bossaller, Lukas / Meyer-Bahlburg, Almut

    2023  , Page(s) KI.20

    Event/congress Deutscher Rheumatologiekongress 2023, 51. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 37. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 33. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR); Leipzig; ; Gesellschaft für Kinder- und Jugendrheumatologie; 2023
    Keywords Medizin, Gesundheit
    Publishing date 2023-08-30
    Publisher German Medical Science GMS Publishing House; Düsseldorf
    Document type Conference proceedings
    DOI 10.3205/23dgrh142
    Database German Medical Science

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  7. Article ; Online: Proteasome inhibition potentiates Kv1.3 potassium channel expression as therapeutic target in drug-sensitive and -resistant human melanoma cells.

    Cammann, Clemens / Kulla, Jonas / Wiebusch, Lüder / Walz, Christian / Zhao, Fang / Lowinus, Theresa / Topfstedt, Eylin / Mishra, Neha / Henklein, Petra / Bommhardt, Ursula / Bossaller, Lukas / Hagemeier, Christian / Schadendorf, Dirk / Schmidt, Boris / Paschen, Annette / Seifert, Ulrike

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2023  Volume 168, Page(s) 115635

    Abstract: Primary and acquired therapy resistance is a major problem in patients with BRAF-mutant melanomas being treated with BRAF and MEK inhibitors (BRAFI, MEKi). Therefore, development of alternative therapy regimes is still required. In this regard, new drug ... ...

    Abstract Primary and acquired therapy resistance is a major problem in patients with BRAF-mutant melanomas being treated with BRAF and MEK inhibitors (BRAFI, MEKi). Therefore, development of alternative therapy regimes is still required. In this regard, new drug combinations targeting different pathways to induce apoptosis could offer promising alternative approaches. Here, we investigated the combination of proteasome and Kv1.3 potassium channel inhibition on chemo-resistant, BRAF inhibitor-resistant as well as sensitive human melanoma cells. Our experiments demonstrated that all analyzed melanoma cell lines were sensitive to proteasome inhibitor treatment at concentrations that are not toxic to primary human fibroblasts. To further reduce proteasome inhibitor-associated side effects, and to foster apoptosis, potassium channels, which are other targets to induce pro-apoptotic effects in cancer cells, were blocked. In support, combined exposure of melanoma cells to proteasome and Kv1.3 channel inhibitor resulted in synergistic effects and significantly reduced cell viability. On the molecular level, enhanced apoptosis correlated with an increase of intracellular Kv1.3 channels and pro-apoptotic proteins such as Noxa and Bak and a reduction of anti-apoptotic proteins. Thus, use of combined therapeutic strategies triggering different apoptotic pathways may efficiently prevent the outgrowth of drug-resistant and -sensitive BRAF-mutant melanoma cells. In addition, this could be the basis for an alternative approach to treat other tumors expressing mutated BRAF such as non-small-cell lung cancer.
    MeSH term(s) Humans ; Proteasome Endopeptidase Complex/metabolism ; Kv1.3 Potassium Channel/genetics ; Proteasome Inhibitors/pharmacology ; Proteasome Inhibitors/therapeutic use ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins B-raf/metabolism ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Lung Neoplasms/drug therapy ; Melanoma/pathology ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Apoptosis Regulatory Proteins/metabolism ; Mutation
    Chemical Substances Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Kv1.3 Potassium Channel ; Proteasome Inhibitors ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Protein Kinase Inhibitors ; Apoptosis Regulatory Proteins
    Language English
    Publishing date 2023-10-08
    Publishing country France
    Document type Journal Article
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2023.115635
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Monoclonal antibody treatments for rheumatoid arthritis.

    Bossaller, Lukas / Rothe, Achim

    Expert opinion on biological therapy

    2013  Volume 13, Issue 9, Page(s) 1257–1272

    Abstract: Introduction: Rheumatoid arthritis (RA) is a systemic disease and the most prevalent of all autoimmune disorders. Here we review recent advances in the development and availability of biologic agents with a focus on monoclonal antibody or smaller ... ...

    Abstract Introduction: Rheumatoid arthritis (RA) is a systemic disease and the most prevalent of all autoimmune disorders. Here we review recent advances in the development and availability of biologic agents with a focus on monoclonal antibody or smaller formats of targeted engineered therapeutics including novel, non-antibody-based therapeutics.
    Areas covered: Today an array of biologics blocking either proinflammatory cytokines or lymphocyte activation/survival are available that enable a substantial improvement over conventional disease-modifying antirheumatic drugs (DMARDs). We review the engineering process of antibody-based biologics, their preclinical and clinical application, and current efforts to treat RA by interfering with B-cell function (notable targets covered are CD20, CD38, B-cell activating factor, transmembrane activator and calcium-modulating and cyclophilin interactor), with T-cell function (CD3, CD4, CD28), with bone erosion (RANKL), and with cytokines or growth factors (tumor necrosis factor, interleukin-1 [IL-1], IL-6, IL-17, VEGF). Future treatment choices might encompass the blockade or modulation of danger-associated molecular patterns such as HMGB1, pattern recognition receptors, messenger RNAs or noncoding RNAs, histone acetylation, and inflammasome components.
    Expert opinion: Although current therapies can reduce the signs and symptoms of RA for many patients, the quest for a cure (or a more complete blockade of the structural damage) in RA is still ongoing and will need treatment approaches, which are not exclusively confined to blocking a particular cytokine, receptor, or autoreactive B or T cell involved in disease progression. To this end exciting treatment alternatives and drug targets are on the horizon that may become available to patients in the future.
    MeSH term(s) Antibodies, Monoclonal/therapeutic use ; Arthritis, Rheumatoid/therapy ; Biological Products/therapeutic use ; Clinical Trials as Topic ; Drug Evaluation, Preclinical ; Humans ; Protein Engineering
    Chemical Substances Antibodies, Monoclonal ; Biological Products
    Language English
    Publishing date 2013-09
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2052501-1
    ISSN 1744-7682 ; 1471-2598
    ISSN (online) 1744-7682
    ISSN 1471-2598
    DOI 10.1517/14712598.2013.811230
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Book ; Online ; Thesis: Investigations on the role of SLP-65 and other B cell signaling proteins in human leukemia

    Bossaller, Lukas Friedrich Magnus

    2003  

    Author's details vorgelegt von Lukas Friedrich Magnus Bossaller
    Language English
    Size Online-Ressource
    Document type Book ; Online ; Thesis
    Thesis / German Habilitation thesis Univ., Diss--Freiburg (Breisgau), 2003
    Database Former special subject collection: coastal and deep sea fishing

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  10. Article ; Online: Evidence of inflammasome activation and formation of monocyte-derived ASC specks in HIV-1 positive patients.

    Ahmad, Fareed / Mishra, Neha / Ahrenstorf, Gerrit / Franklin, Bernardo S / Latz, Eicke / Schmidt, Reinhold E / Bossaller, Lukas

    AIDS (London, England)

    2017  Volume 32, Issue 3, Page(s) 299–307

    Abstract: Objective: The formation of large intracellular protein aggregates of the inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a caspase-recruitment domain; also know as PYCARD) is a hallmark of inflammasome activation. ... ...

    Abstract Objective: The formation of large intracellular protein aggregates of the inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a caspase-recruitment domain; also know as PYCARD) is a hallmark of inflammasome activation. ASC speck-forming cells release the highly proinflammatory cytokine IL-1β in addition to ASC specks into the extracellular space during pyroptotic cell death. There ASC specks can propagate inflammation to other nonactivated cells or tissues. HIV-1 retroviral infection triggers inflammasome activation of abortively infected CD4⁺ T cells in secondary lymphatic tissues. However, if pyroptosis occurs in other peripheral blood mononuclear cells (PBMCs) of HIV-1-infected patients is currently unknown. We investigated if ASC speck positive cells are present in the circulation of HIV-1-infected patients.
    Design and methods: PBMCs or plasma of HIV-1 infected, antiretroviral therapy-naive patients were analyzed for the presence of ASC speck⁺ cells or extracellular ASC and compared with healthy controls. Intracellular staining for ASC was employed to detect ASC speck⁺ cells within PBMCs by flow cytometry, and ELISA to detect free ASC in the plasma. ASC multimerization was confirmed by immunoblot.
    Results: Peripheral blood CD14⁺⁺CD16⁻ monocytes were ASC speck⁺ in HIV patients, but not in healthy controls. In the subgroup analysis, HIV patients with lower CD4⁺ T-cell counts and higher viral load had significantly more ASC speck⁺ monocytes. ASC speck formation did not correlate with Gag expression, coinfection, lactate dehydrogenase or C-reactive protein.
    Conclusion: Our findings suggest that pyroptotic CD14⁺⁺CD16⁻ classical monocytes of HIV-1-infected patients release ASC specks into the blood stream, a phenomenon that may contribute to HIV-1 induced inflammation and immune activation.
    MeSH term(s) Adult ; CARD Signaling Adaptor Proteins/analysis ; CD4 Lymphocyte Count ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; GPI-Linked Proteins/analysis ; HIV Infections/pathology ; Humans ; Immunoblotting ; Inflammasomes/metabolism ; Lipopolysaccharide Receptors/analysis ; Male ; Middle Aged ; Monocytes/chemistry ; Receptors, IgG/analysis ; Staining and Labeling ; Viral Load
    Chemical Substances CARD Signaling Adaptor Proteins ; FCGR3B protein, human ; GPI-Linked Proteins ; Inflammasomes ; Lipopolysaccharide Receptors ; PYCARD protein, human ; Receptors, IgG
    Language English
    Publishing date 2017-11-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639076-6
    ISSN 1473-5571 ; 0269-9370 ; 1350-2840
    ISSN (online) 1473-5571
    ISSN 0269-9370 ; 1350-2840
    DOI 10.1097/QAD.0000000000001693
    Database MEDical Literature Analysis and Retrieval System OnLINE

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