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  1. Article ; Online: Question 1: Is a low-bacterial diet helpful in preventing infection in immunosuppressed children?

    Friend, Amanda J / Maltby, Sarah

    Archives of disease in childhood

    2017  Volume 102, Issue 4, Page(s) 380–382

    Language English
    Publishing date 2017-03-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 524-1
    ISSN 1468-2044 ; 0003-9888 ; 1359-2998
    ISSN (online) 1468-2044
    ISSN 0003-9888 ; 1359-2998
    DOI 10.1136/archdischild-2016-312125
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  2. Article ; Online: Assessing the Response of Biomarkers to Anti-Inflammatory Medications in PIMS-TS by Longitudinal Multilevel Modeling: Real-World Data from a UK Tertiary Center.

    Tonge, Joseph J / Stevens, Olivia / Dawson, Jeremy / Hawley, Daniel / Kerrison, Caroline / Krone, Nils / Maltby, Sarah L / McMahon, Anne-Marie / Shackley, Fiona / Talekar, Rupa / Gonzalez-Martinez, Carmen / Lawrence, Neil

    Pediatric allergy, immunology, and pulmonology

    2023  Volume 36, Issue 3, Page(s) 94–103

    Abstract: Background: ...

    Abstract Background:
    MeSH term(s) Female ; Humans ; Male ; Child ; Adolescent ; Child, Preschool ; COVID-19 ; Glucocorticoids ; Immunoglobulins, Intravenous ; Retrospective Studies ; SARS-CoV-2 ; Anti-Inflammatory Agents ; Biomarkers ; Ferritins ; Hospitals, Pediatric
    Chemical Substances Glucocorticoids ; Immunoglobulins, Intravenous ; Anti-Inflammatory Agents ; Biomarkers ; Ferritins (9007-73-2)
    Language English
    Publishing date 2023-07-11
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 2566338-0
    ISSN 2151-3228 ; 2151-321X
    ISSN (online) 2151-3228
    ISSN 2151-321X
    DOI 10.1089/ped.2023.0024
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  3. Article ; Online: An Evaluation of Matrix-Containing and Humanised Matrix-Free 3-Dimensional Cell Culture Systems for Studying Breast Cancer.

    Roberts, Grace C / Morris, Paul G / Moss, Marcus A / Maltby, Sarah L / Palmer, Chelsea A / Nash, Claire E / Smart, Emily / Holliday, Deborah L / Speirs, Valerie

    PloS one

    2016  Volume 11, Issue 6, Page(s) e0157004

    Abstract: Background: 3D cell cultures are emerging as more physiologically meaningful alternatives to monolayer cultures for many biological applications. They are attractive because they more closely mimic in vivo morphology, especially when co-cultured with ... ...

    Abstract Background: 3D cell cultures are emerging as more physiologically meaningful alternatives to monolayer cultures for many biological applications. They are attractive because they more closely mimic in vivo morphology, especially when co-cultured with stromal fibroblasts.
    Methodology/principal findings: We compared the efficacy of 3 different 3D cell culture systems; collagen I, low attachment culture vessels and a modification of Fibrolife®, a specialised humanised cell culture medium devoid of animal-derived components, using breast cancer cell lines representative of the different molecular subtypes of breast cancer, cultured alone or with human mammary fibroblasts with a view to developing matrix-free humanised systems. 3D collagen I culture supported the growth of a range of breast cancer cell lines. By modifying the composition of Fibrolife® to epiFL, matrix-free cell culture was possible. During sequential transfer to epiFL breast cancer cells gradually detached from the flask, growing progressively as spheroids. Phenotype was stable and reversible with cells remaining actively proliferating and easily accessible throughout culture. They could also be revived from frozen stocks. To achieve co-culture with fibroblasts in epiFL required use of low attachment culture vessels instead of standard plastic as fibroblasts remained adherent in epiFL. Here, cancer cell spheroids were allowed to form before adding fibroblasts. Immunohistochemical examination showed fibroblasts scattered throughout the epithelial spheroid, not dissimilar to the relationship of tumour stroma in human breast cancer.
    Conclusions: Because of its ease of handling, matrix-free 3D cell culture may be a useful model to study the influence of fibroblasts on breast cancer epithelial cells with use of epiFL culture medium taking this a step further towards a fully humanised 3D model. This methodology could be applied to other types of cancer cell lines, making this a versatile technique for cancer researchers wishing to use in vitro systems that better reflect cancer in vivo.
    MeSH term(s) Biocompatible Materials/chemistry ; Breast/cytology ; Breast/pathology ; Breast Neoplasms/pathology ; Cell Adhesion ; Cell Line, Tumor ; Cell Survival ; Coculture Techniques/methods ; Collagen Type I/analysis ; Female ; Fibroblasts/cytology ; Fibroblasts/pathology ; Humans ; Spheroids, Cellular ; Tumor Cells, Cultured
    Chemical Substances Biocompatible Materials ; Collagen Type I
    Language English
    Publishing date 2016-06-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0157004
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  4. Article ; Online: Epithelium-dependent modulation of responsiveness of airways from caveolin-1 knockout mice is mediated through cyclooxygenase-2 and 5-lipoxygenase.

    Sharma, Pawan / Ryu, Min H / Basu, Sujata / Maltby, Sarah A / Yeganeh, Behzad / Mutawe, Mark M / Mitchell, Richard W / Halayko, Andrew J

    British journal of pharmacology

    2012  Volume 167, Issue 3, Page(s) 548–560

    Abstract: Background and purpose: Acute silencing of caveolin-1 (Cav-1) modulates receptor-mediated contraction of airway smooth muscle. Moreover, COX-2- and 5-lipoxygenase (5-LO)-derived prostaglandin and leukotriene biosynthesis can influence smooth muscle ... ...

    Abstract Background and purpose: Acute silencing of caveolin-1 (Cav-1) modulates receptor-mediated contraction of airway smooth muscle. Moreover, COX-2- and 5-lipoxygenase (5-LO)-derived prostaglandin and leukotriene biosynthesis can influence smooth muscle reactivity. COX-2 half-life can be prolonged through association with Cav-1. We suggested that lack of Cav-1 modulated levels of COX-2 which in turn modulated tracheal contraction, when arachidonic acid signalling was disturbed by inhibition of COX-2.
    Experimental approach: Using tracheal rings from Cav-1 knockout (KO) and wild-type mice (B6129SF2/J), we measured isometric contractions to methacholine and used PCR, immunoblotting and immunohistology to monitor expression of relevant proteins.
    Key results: Tracheal rings from Cav-1 KO and wild-type mice exhibited similar responses, but the COX-2 inhibitor, indomethacin, increased responses of tracheal rings from Cav-1 KO mice to methacholine. The phospholipase A₂ inhibitor, eicosatetraynoic acid, which inhibits formation of both COX-2 and 5-LO metabolites, had no effect on wild-type or Cav-1 KO tissues. Indomethacin-mediated hyperreactivity was ablated by the LTD₄ receptor antagonist (montelukast) and 5-LO inhibitor (zileuton). The potentiating effect of indomethacin on Cav-1 KO responses to methacholine was blocked by epithelial denudation. Immunoprecipitation showed that COX-2 binds Cav-1 in wild-type lungs. Immunoblotting and qPCR revealed elevated levels of COX-2 and 5-LO protein, but not COX-1, in Cav-1 KO tracheas, a feature that was prevented by removal of the epithelium.
    Conclusion and implications: The indomethacin-induced hypercontractility observed in Cav-1 KO tracheas was linked to increased expression of COX-2 and 5-LO, which probably enhanced arachidonic acid shunting and generation of pro-contractile leukotrienes when COX-2 was inhibited.
    MeSH term(s) Animals ; Arachidonate 5-Lipoxygenase/drug effects ; Arachidonate 5-Lipoxygenase/genetics ; Arachidonate 5-Lipoxygenase/metabolism ; Arachidonic Acid/metabolism ; Bronchial Hyperreactivity/pathology ; Bronchoconstriction/drug effects ; Caveolin 1/genetics ; Cyclooxygenase 2/drug effects ; Cyclooxygenase 2/genetics ; Cyclooxygenase 2/metabolism ; Cyclooxygenase Inhibitors/pharmacology ; Epithelial Cells/metabolism ; Female ; Gene Expression Regulation ; Immunoprecipitation ; Indomethacin/pharmacology ; Methacholine Chloride/pharmacology ; Mice ; Mice, Knockout ; Muscle, Smooth/drug effects ; Muscle, Smooth/metabolism ; Trachea/drug effects ; Trachea/metabolism
    Chemical Substances Caveolin 1 ; Cyclooxygenase Inhibitors ; Methacholine Chloride (0W5ETF9M2K) ; Arachidonic Acid (27YG812J1I) ; Arachidonate 5-Lipoxygenase (EC 1.13.11.34) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Indomethacin (XXE1CET956)
    Language English
    Publishing date 2012-05-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/j.1476-5381.2012.02014.x
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  5. Article ; Online: Multi-centre national audit of juvenile localised scleroderma: describing current UK practice in disease assessment and management.

    Lythgoe, Hanna / Almeida, Beverley / Bennett, Joshua / Bhat, Chandrika / Bilkhu, Amarpal / Brennan, Mary / Deepak, Samundeeswari / Dawson, Pamela / Eleftheriou, Despina / Harrison, Kathryn / Hawley, Daniel / Heaf, Eleanor / Leone, Valentina / Long, Ema / Maltby, Sarah / McErlane, Flora / Rafiq, Nadia / Ramanan, Athimalaipet V / Riley, Phil /
    Rangaraj, Satyapal / Varnier, Giulia / Wilkinson, Nick / Pain, Clare E

    Pediatric rheumatology online journal

    2018  Volume 16, Issue 1, Page(s) 80

    Abstract: Objective: To describe current United Kingdom practice in assessment and management of patients with juvenile localised scleroderma (JLS) compared to Paediatric Rheumatology European Society (PRES) scleroderma working party recommendations.: Methods: ...

    Abstract Objective: To describe current United Kingdom practice in assessment and management of patients with juvenile localised scleroderma (JLS) compared to Paediatric Rheumatology European Society (PRES) scleroderma working party recommendations.
    Methods: Patients were included if they were diagnosed with JLS and were under the care of paediatric rheumatology between 04/2015-04/2016. Retrospective data was collected in eleven UK centres using a standardised proforma and collated centrally.
    Results: 149 patients were included with a median age of 12.5 years. The outcome measures recommended by the PRES scleroderma working party were not utilised widely. The localised scleroderma cutaneous assessment tool was only used in 37.6% of patients. Screening for extracutaneous manifestations did not meet recommendations that patients with head involvement have regular screening for uveitis and baseline magnetic resonance imaging (MRI) brain: only 38.5% of these patients were ever screened for uveitis; 71.2% had a MRI brain. Systemic treatment with disease-modifying anti-rheumatic drugs (DMARDs) or biologics was widely used (96.0%). In keeping with the recommendations, 95.5% of patients were treated with methotrexate as first-line therapy. 82.6% received systemic corticosteroids and 34.2% of patients required two or more DMARDs/biologics, highlighting the significant treatment burden. Second-line treatment was mycophenolate mofetil in 89.5%.
    Conclusion: There is wide variation in assessment and screening of patients with JLS but a consistent approach to systemic treatment within UK paediatric rheumatology. Improved awareness of PRES recommendations is required to ensure standardised care. As recommendations are based on low level evidence and consensus opinion, further studies are needed to better define outcome measures and treatment regimens for JLS.
    MeSH term(s) Adolescent ; Antirheumatic Agents/therapeutic use ; Child ; Clinical Audit ; Female ; Glucocorticoids/therapeutic use ; Humans ; Male ; Mass Screening/statistics & numerical data ; Practice Guidelines as Topic ; Practice Patterns, Physicians'/statistics & numerical data ; Retrospective Studies ; Scleroderma, Localized/diagnosis ; Scleroderma, Localized/drug therapy ; Societies, Medical ; United Kingdom
    Chemical Substances Antirheumatic Agents ; Glucocorticoids
    Language English
    Publishing date 2018-12-18
    Publishing country England
    Document type Journal Article ; Multicenter Study
    ZDB-ID 2279468-2
    ISSN 1546-0096 ; 1546-0096
    ISSN (online) 1546-0096
    ISSN 1546-0096
    DOI 10.1186/s12969-018-0295-0
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  6. Article ; Online: Aquaporin 1 is an independent prognostic factor in pleural malignant mesothelioma.

    Kao, Steven Chuan-Hao / Armstrong, Nicola / Condon, Bridget / Griggs, Kim / McCaughan, Brian / Maltby, Sarah / Wilson, Alan / Henderson, Douglas W / Klebe, Sonja

    Cancer

    2012  Volume 118, Issue 11, Page(s) 2952–2961

    Abstract: Background: Malignant mesothelioma (MM) is an aggressive cancer of serosal membranes, mostly pleura. It is related to asbestos exposure and its incidence in most industrialized countries is projected to remain stable or to increase until 2020. Prognosis ...

    Abstract Background: Malignant mesothelioma (MM) is an aggressive cancer of serosal membranes, mostly pleura. It is related to asbestos exposure and its incidence in most industrialized countries is projected to remain stable or to increase until 2020. Prognosis remains poor. Clinical prognostic scoring systems lack precision. No prognostic tissue markers are available. Aquaporin 1 (AQP1) is a cell membrane channel involved in water transport, cell motility, and proliferation. A blocker and an agonist are available.
    Methods: Two independent cohorts of MM were studied. Cohort 1 consisted of 80 consecutive patients who underwent radical surgery (extrapleural pneumonectomy [EPP]). Cohort 2 included 56 conservatively managed patients from another institution. Clinical information was obtained from files. Diagnoses were histologically verified. Immunohistochemical labeling for AQP1 was performed on tumor tissue and the percentage of positive cells was scored.
    Results: We demonstrated expression of AQP1 in normal and neoplastic mesothelium at the apical aspect of the cell, in keeping with a role in water transport. For both cohorts, expression of AQP1 by ≥50% of tumor cells was associated with significantly enhanced survival (9.4 months vs 30.4 months in EPP patients and 5 months vs 15 months in conservatively treated patients). This was independent of established prognostic factors, including histologic subtype, pathologic stage, sex, and age at time of diagnosis.
    Conclusion: Expression of AQP1 correlated significantly with prognosis in MM, irrespective of treatment or established prognostic factors. Immunohistochemical labeling for AQP1 should be included in the routine histopathologic workup. An agonist or blocker may become useful for treatment.
    MeSH term(s) Adult ; Aged ; Aquaporin 1/metabolism ; Biomarkers, Tumor/metabolism ; Female ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/diagnosis ; Microscopy, Immunoelectron ; Middle Aged ; Pleural Neoplasms/diagnosis ; Prognosis
    Chemical Substances Biomarkers, Tumor ; Aquaporin 1 (146410-94-8)
    Language English
    Publishing date 2012-06-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1429-1
    ISSN 1097-0142 ; 0008-543X ; 1934-662X
    ISSN (online) 1097-0142
    ISSN 0008-543X ; 1934-662X
    DOI 10.1002/cncr.26497
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  7. Article ; Online: Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia.

    Ponchel, Frederique / Verburg, Robert J / Bingham, Sarah J / Brown, Andrew K / Moore, John / Protheroe, Andrew / Short, Kath / Lawson, Catherine A / Morgan, Ann W / Quinn, Mark / Buch, Maya / Field, Sarah L / Maltby, Sarah L / Masurel, Aurelie / Douglas, Susan H / Straszynski, Liz / Fearon, Ursula / Veale, Douglas J / Patel, Poulam /
    McGonagle, Dennis / Snowden, John / Markham, Alexander F / Ma, David / van Laar, Jacob M / Papadaki, Helen A / Emery, Paul / Isaacs, John D

    Arthritis research & therapy

    2005  Volume 7, Issue 1, Page(s) R80–92

    Abstract: We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor ...

    Abstract We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis. In the present study we demonstrated reduced levels of circulating IL-7 in a cross-section of RA patients. IL-7 production by bone marrow stromal cell cultures was also compromised in RA. To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue. Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3-4 months. Both cohorts produced naive T-cells containing T-cell receptor excision circles. The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment. Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia. Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion. Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4+ T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort.
    MeSH term(s) Alemtuzumab ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm/adverse effects ; Antibodies, Neoplasm/therapeutic use ; Arthritis, Rheumatoid/blood ; Arthritis, Rheumatoid/drug therapy ; Autoimmune Diseases/blood ; Autoimmune Diseases/drug therapy ; Blood Specimen Collection/instrumentation ; Bone Marrow/metabolism ; CD4-Positive T-Lymphocytes/pathology ; Cells, Cultured/metabolism ; Cohort Studies ; Combined Modality Therapy ; Cytokines/blood ; Gene Rearrangement, T-Lymphocyte ; Humans ; Interleukin-6/blood ; Interleukin-7/biosynthesis ; Interleukin-7/blood ; Interleukin-7/deficiency ; Lymphocyte Depletion ; Lymphopenia/chemically induced ; Lymphopoiesis ; Neoplasms/drug therapy ; Neoplasms/therapy ; Oncostatin M ; Peripheral Blood Stem Cell Transplantation ; Stromal Cells/metabolism ; Thymus Gland/pathology ; Transforming Growth Factor beta/blood ; Tumor Necrosis Factor-alpha/analysis ; Tumor Necrosis Factor-alpha/antagonists & inhibitors
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm ; Cytokines ; Interleukin-6 ; Interleukin-7 ; OSM protein, human ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha ; Oncostatin M (106956-32-5) ; Alemtuzumab (3A189DH42V)
    Language English
    Publishing date 2005
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2107602-9
    ISSN 1478-6362 ; 1478-6354
    ISSN (online) 1478-6362
    ISSN 1478-6354
    DOI 10.1186/ar1452
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