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  • 1
    Language: English
    In: Journal of the Science of Food and Agriculture, September 2011, Vol.91(12), pp.2234-2240
    Description: Food allergies are increasing in the European population. At present the onset of symptoms can be avoided only by elimination of a particular fruit or vegetable from the diet. A new approach is to develop hypoallergenic food products. This study characterises the allergenic potential of tomatoes, considering cultivation conditions, developmental stages and genotypes, in order to identify hypoallergenic fruits. Patients with a history of tomato allergy were recruited for skin allergy tests. Tomatoes carrying distinct genotypes were grown under various cultivation conditions and harvested at different maturation stages. Cultivation conditions (nitrogen fertilisation, light exposure and plant nutrition) did not affect the skin reactivity in tomato‐allergic patients. However, skin reactivity was significantly lower when using green‐unripe compared with red‐ripe tomatoes and when using landrace cultivars compared with cultivars bred for use in organic horticulture. Depending on their genetic background and maturity level, some tomato cultivars elicit positive reactions in tomato‐allergic patients in the skin allergy test. This novel finding should pave the way for the development of tomatoes with reduced allergenicity to relieve sufferers of tomato allergy. Copyright © 2011 Society of Chemical Industry
    Keywords: Food Allergy ; Tomato ; Cultivars ; Environmental Cultivation Conditions
    ISSN: 0022-5142
    E-ISSN: 1097-0010
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  • 2
    Language: English
    In: Mycorrhiza, 2011, Vol.21(5), pp.341-349
    Description: Arbuscular mycorrhizal (AM) fungi influence the expression of defence-related genes in roots and can cause systemic resistance in plants probably due to the induced expression of specific defence proteins. Among the different groups of defence proteins, plant food allergens were identified. We hypothesized that tomato-allergic patients differently react to tomatoes derived from plants inoculated or not by mycorrhizal fungi. To test this, two tomato genotypes, wild-type 76R and a nearly isogenic mycorrhizal mutant RMC, were inoculated with the AM fungus Glomus mosseae or not under conditions similar to horticultural practice. Under such conditions, the AM fungus showed only a very low colonisation rate, but still was able to increase shoot growth of the wild-type 76R. Nearly no colonisation was observed in the mutant RMC, and shoot development was also not affected. Root fresh weights were diminished in AM-inoculated plants of both genotypes compared to the corresponding controls. No mycorrhizal effects were observed on the biomass and the concentration of phosphate and nitrogen in fruits. Real-time quantitative polymerase chain reaction analysis revealed that six among eight genes encoding for putative allergens showed a significant induced RNA accumulation in fruits of AM-colonised plants. However, human skin reactivity tests using mixed samples of tomato fruits from the AM-inoculated and control plants showed no differences. Our data indicate that AM colonisation under conditions close to horticultural practice can induce the expression of allergen-encoding genes in fruits, but this does not lead necessarily to a higher allergenic potential.
    Keywords: Allergy ; Defence proteins ; Glomus mosseae ; RNA accumulation ; Skin prick test
    ISSN: 0940-6360
    E-ISSN: 1432-1890
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  • 3
    Language: English
    In: Journal of proteome research, March 2009, Vol.8(3), pp.1111-22
    Description: Tomato fruit and seed allergens were detected by IgE-immunoblotting using sera from 18 adult tomato-sensitized patients selected based on a positive history skin prick test (SPT) and specific Immunglobulin (Ig) E-levels. Isolated tomato seed total protein showed high SPT activity comparable or even higher than tomato fruit protein. For the molecular characterization of tomato seed allergens, a multidimensional protein fractionation strategy and LC-MS/MS was used. Two legumin- and vicilin-proteins were purified and showed strong IgE-reactivity in immunoblots. Individual patient sera exhibited varying IgE-sensitivity against the purified proteins. In silico structural modeling indicates high homology between epitopes of known walnut allergens and the detected IgE-crossreactive tomato proteins.
    Keywords: Allergens -- Immunology ; Immunoglobulin E -- Immunology ; Lycopersicon Esculentum -- Immunology ; Plant Proteins -- Immunology ; Seed Storage Proteins -- Immunology ; Seeds -- Immunology
    ISSN: 1535-3893
    E-ISSN: 15353907
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  • 4
    Language: English
    In: PLoS ONE, 01 January 2016, Vol.11(3), p.e0152580
    Description: Glycosylated hemoglobin A1c (HbA1c) has been proposed as an independent predictor of long-term prognosis in pulmonary arterial hypertension. However, the clinical relevance of HbA1c in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) remains unknown. The aim of the...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 5
    Language: English
    In: eLife, 29 September 2015, Vol.4
    Description: Perforin-2 (MPEG1) is an effector of the innate immune system that limits the proliferation and spread of medically relevant Gram-negative, -positive, and acid fast bacteria. We show here that a cullin-RING E3 ubiquitin ligase (CRL) complex containing cullin-1 and βTrCP monoubiquitylates Perforin-2 in response to pathogen associated molecular patterns such as LPS. Ubiquitylation triggers a rapid redistribution of Perforin-2 and is essential for its bactericidal activity. Enteric pathogens such as Yersinia pseudotuberculosis and enteropathogenic Escherichia coli disarm host cells by injecting cell cycle inhibiting factors (Cifs) into mammalian cells to deamidate the ubiquitin-like protein NEDD8. Because CRL activity is dependent upon NEDD8, Cif blocks ubiquitin dependent trafficking of Perforin-2 and thus, its bactericidal activity. Collectively, these studies further underscore the biological significance of Perforin-2 and elucidate critical molecular events that culminate in Perforin-2-dependent killing of both intracellular and extracellular, cell-adherent bacteria.
    Keywords: Cif ; E. Coli ; Epec ; Mpeg1 ; Nedd8 ; Perforin-2 ; Yersinia Pseudotuberculosis ; Human ; Immunology ; Infectious Disease ; Microbiology ; Mouse ; Host-Pathogen Interactions ; Microbial Viability ; Cell Cycle -- Drug Effects ; Enteropathogenic Escherichia Coli -- Immunology ; Pore Forming Cytotoxic Proteins -- Toxicity ; Virulence Factors -- Metabolism ; Yersinia Pseudotuberculosis -- Immunology
    E-ISSN: 2050-084X
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  • 6
    In: Journal of Immunotherapy, 2015, Vol.38(7), pp.259-266
    Description: The classical model for identification and clinical development of anticancer agents was based on small molecules, which were often quite toxic. Early studies in small groups of patients would seek to identify a maximum tolerated dose and major dose-limiting toxicities. Tumor response (shrinkage) would be assessed after a minimum number of doses in phase II testing. The decision to take the drug into the randomized phase III clinical setting was usually based on the proportion and duration of objective tumor responses, along with overall survival compared with historical controls. Immune-oncologics that are designed to fight cancer by direct CD8 T-cell priming and activation or by blocking a negative regulatory molecule have a number of sharp distinctions from cytotoxic drugs. These include cytoreductive effects that may be very different in timing of onset from traditional chemotherapy and the potential for inducing long-term durable remissions even in heavily pretreated patients with metastatic disease. In this paper we review the different classes of immune-oncologic drugs in clinical development with particular attention to the biostatistical challenges associated with evaluating efficacy in clinical trials. Confronting these issues upfront is particularly important given the rapidly expanding number of clinical trials with both monotherapy and combination trials in immunooncology.
    Keywords: Molecular Modelling ; Statistics ; Chemotherapy ; Immunotherapy ; Remission ; Drug Development ; Tumors ; Toxicity ; Cd8 Antigen ; Clinical Trials ; Antitumor Agents ; Cancer ; Metastases ; Cytotoxicity ; Lymphocytes T ; Atrophy ; Cancer Immunology;
    ISSN: 1524-9557
    E-ISSN: 15374513
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  • 7
    Language: English
    In: Hellenic Journal of Cardiology, January 2018, Vol.59(1), pp.16-23
    Description: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease, and therefore, there is a lack of data regarding its clinical presentation, diagnosis, and management at a national basis. We aimed to describe the demographics and management of patients with CTEPH in Northern Greece. We conducted a retrospective, observational study by a joint collaboration between two pulmonary hypertension expert centers in Greece, and the study included patients diagnosed with CTEPH. The patient population was divided into two groups depending on their operability. Overall, 27 consecutive patients were included (59% female, mean age 59.3±15.1 years). Dyspnea and fatigue were the most common presenting symptoms. History of pulmonary embolism was present in 82%. Of patients, 18 (67%) were assessed as operable, of whom 10 (55%) finally underwent pulmonary endarterectomy (PEA). There were no differences in symptoms, WHO functional class, 6-min walking test distance, and hemodynamics between the operable and nonoperable groups. At the end of follow-up, all non-operable and operable patients who did not receive surgical treatment were treated with at least one pulmonary hypertension-specific drug. This is the first report that presents data of patients diagnosed with CTEPH in Greece. The percentage of patients who underwent surgical treatment is lower but approaches the reported rates in large registries. Considering that PEA is a relatively safe and potentially curative surgical procedure, we emphasize the need for establishing a designated PEA center in Greece.
    Keywords: Chronic Thromboembolic Pulmonary Hypertension ; Pulmonary Endarterectomy ; Registry ; Riociguat ; Medicine
    ISSN: 1109-9666
    E-ISSN: 22415955
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  • 8
    Language: English
    In: Current Alzheimer Research, 2015, Vol.12(9), p.814-828
    Description: A potential strategy to alleviate the aggregation of intrinsically disordered proteins (IDPs) is to maintain the native functional state of the protein by small molecule binding. However, the targeting of the native state of IDPs by small molecules has been challenging due to their heterogeneous conformational ensembles. To tackle this challenge, we applied a high-throughput chemical microarray surface plasmon resonance imaging screen to detect the binding between small molecules and monomeric full-length Tau, a protein linked with the onset of a range of Tauopathies. The screen identified a novel set of drug-like fragment and lead-like compounds that bound to Tau. We verified that the majority of these hit compounds reduced the aggregation of different Tau constructs in vitro and in N2a cells. These results demonstrate that Tau is a viable receptor of drug-like small molecules. The drug discovery approach that we present can be applied to other IDPs linked to other misfolding diseases such as Alzheimer's and Parkinson's diseases.
    Keywords: Alzheimer'S Disease Drug Discovery High Throughput Screening Inhibitor Protein Aggregation Tau Taupathies Therapeutic.
    ISSN: 1567-2050
    E-ISSN: 1875-5828
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  • 9
    Language: English
    In: The Journal of biological chemistry, 10 January 2014, Vol.289(2), pp.956-67
    Description: Understanding the formation and propagation of aggregates of the Alzheimer disease-associated Tau protein in vivo is vital for the development of therapeutics for this devastating disorder. Using our recently developed live-cell aggregation sensor in neuron-like cells, we demonstrate that different variants of exogenous monomeric Tau, namely full-length Tau (hTau40) and the Tau-derived construct K18 comprising the repeat domain, initially accumulate in endosomal compartments, where they form fibrillar seeds that subsequently induce the aggregation of endogenous Tau. Using superresolution imaging, we confirm that fibrils consisting of endogenous and exogenous Tau are released from cells and demonstrate their potential to spread Tau pathology. Our data indicate a greater pathological risk and potential toxicity than hitherto suspected for extracellular soluble Tau.
    Keywords: Alzheimer Disease ; Amyloid ; Endocytosis ; Fluorescence Lifetime Imaging Microscopy ; Propagation ; Protein Aggregation ; Superresolution Microscopy ; Tau ; Endocytosis ; Neurofibrillary Tangles -- Metabolism ; Neurons -- Metabolism ; Tau Proteins -- Metabolism
    ISSN: 00219258
    E-ISSN: 1083-351X
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  • 10
    Language: English
    In: Thrombosis and haemostasis, April 2016, Vol.115(4), pp.781-8
    Description: Platelet-monocyte interactions are strongly implicated in thrombo-inflammatory injury by actively contributing to intravascular inflammation, leukocyte recruitment to inflamed sites, and the amplification of the procoagulant response. Instant blood-mediated inflammatory reaction (IBMIR) represents thrombo-inflammatory injury elicited upon pancreatic islet transplantation (islet-Tx), thereby dramatically affecting transplant survival and function. Developmental endothelial locus-1 (Del-1) is a functionally versatile endothelial cell-derived homeostatic factor with anti-inflammatory properties, but its potential role in IBMIR has not been previously addressed. Here, we establish Del-1 as a novel inhibitor of IBMIR using a whole blood-islet model and a syngeneic murine transplantation model. Indeed, Del-1 pre-treatment of blood before addition of islets diminished coagulation activation and islet damage as assessed by C-peptide release. Consistently, intraportal islet-Tx in transgenic mice with endothelial cell-specific overexpression of Del-1 resulted in a marked decrease of monocytes and platelet-monocyte aggregates in the transplanted tissues, relative to those in wild-type recipients. Mechanistically, Del-1 decreased platelet-monocyte aggregate formation, by specifically blocking the interaction between monocyte Mac-1-integrin and platelet GPIb. Our findings reveal a hitherto unknown role of Del-1 in the regulation of platelet-monocyte interplay and the subsequent heterotypic aggregate formation in the context of IBMIR. Therefore, Del-1 may represent a novel approach to prevent or mitigate the adverse reactions mediated through thrombo-inflammatory pathways in islet-Tx and perhaps other inflammatory disorders involving platelet-leukocyte aggregate formation.
    Keywords: Developmental Endothelial Locus 1 (Del-1) ; Gpib ; Instant Blood-Mediated Inflammatory Reaction (Ibmir) ; Mac-1 Integrin ; Coagulation ; Islet Transplantation ; Platelet-Monocyte Aggregates ; Islets of Langerhans Transplantation ; Blood Platelets -- Physiology ; Carrier Proteins -- Metabolism ; Inflammation -- Genetics ; Islets of Langerhans -- Metabolism ; Monocytes -- Physiology ; Thrombosis -- Genetics
    ISSN: 03406245
    E-ISSN: 2567-689X
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