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  1. Article ; Online: Real-world routine diagnostic molecular analysis for TP53 mutational status is recommended over p53 immunohistochemistry in B-cell lymphomas.

    de Haan, Lorraine M / de Groen, Ruben A L / de Groot, Fleur A / Noordenbos, Troy / van Wezel, Tom / van Eijk, Ronald / Ruano, Dina / Diepstra, Arjan / Koens, Lianne / Nicolae-Cristea, Alina / Hartog, Wietske C E den / Terpstra, Valeska / Ahsmann, Els / Dekker, Tim J A / Sijs-Szabo, Aniko / Veelken, Hendrik / Cleven, Arjen H G / Jansen, Patty M / Vermaat, Joost S P

    Virchows Archiv : an international journal of pathology

    2023  

    Abstract: Previous studies in patients with mature B-cell lymphomas (MBCL) have shown that pathogenic TP53 aberrations are associated with inferior chemotherapeutic efficacy and survival outcomes. In solid malignancies, p53 immunohistochemistry is commonly used as ...

    Abstract Previous studies in patients with mature B-cell lymphomas (MBCL) have shown that pathogenic TP53 aberrations are associated with inferior chemotherapeutic efficacy and survival outcomes. In solid malignancies, p53 immunohistochemistry is commonly used as a surrogate marker to assess TP53 mutations, but this correlation is not yet well-established in lymphomas. This study evaluated the accuracy of p53 immunohistochemistry as a surrogate marker for TP53 mutational analysis in a large real-world patient cohort of 354 MBCL patients within routine diagnostic practice. For each case, p53 IHC was assigned to one of three categories: wild type (staining 1-50% of tumor cells with variable nuclear staining), abnormal complete absence or abnormal overexpression (strong and diffuse staining > 50% of tumor cells). Pathogenic variants of TP53 were identified with a targeted next generation sequencing (tNGS) panel. Wild type p53 expression was observed in 267 cases (75.4%), complete absence in twenty cases (5.7%) and the overexpression pattern in 67 cases (18.9%). tNGS identified a pathogenic TP53 mutation in 102 patients (29%). The overall accuracy of p53 IHC was 84.5% (95% CI 80.3-88.1), with a robust specificity of 92.1% (95% CI 88.0- 95.1), but a low sensitivity of 65.7% (95% CI 55.7-74.8). These results suggest that the performance of p53 IHC is insufficient as a surrogate marker for TP53 mutations in our real-world routine diagnostic workup of MBCL patients. By using p53 immunohistochemistry alone, there is a significant risk a TP53 mutation will be missed, resulting in misevaluation of a high-risk patient. Therefore, molecular analysis is recommended in all MBCL patients, especially for further development of risk-directed therapies based on TP53 mutation status.
    Language English
    Publishing date 2023-10-18
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1184867-4
    ISSN 1432-2307 ; 0945-6317
    ISSN (online) 1432-2307
    ISSN 0945-6317
    DOI 10.1007/s00428-023-03676-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Comparison of Prehospital Assessment by Paramedics and In-Hospital Assessment by Physicians in Suspected Stroke Patients: Results From 2 Prospective Cohort Studies.

    Dekker, Luuk / Daems, Jasper D / Duvekot, Martijne H C / Nguyen, T Truc My / Venema, Esmee / van Es, Adriaan C G M / Rozeman, Anouk D / Moudrous, Walid / Dorresteijn, Kirsten R I S / Hensen, Jan-Hein J / Bosch, Jan / van Zwet, Erik W / de Schryver, Els L L M / Kloos, Loet M H / de Laat, Karlijn F / Aerden, Leo A M / van den Wijngaard, Ido R / Dippel, Diederik W J / Kerkhoff, Henk /
    Wermer, Marieke J H / Roozenbeek, Bob / Kruyt, Nyika D

    Stroke

    2023  Volume 54, Issue 9, Page(s) 2279–2285

    Abstract: Background: It is unknown if ambulance paramedics adequately assess neurological deficits used for prehospital stroke scales to detect anterior large-vessel occlusions. We aimed to compare prehospital assessment of these stroke-related deficits by ... ...

    Abstract Background: It is unknown if ambulance paramedics adequately assess neurological deficits used for prehospital stroke scales to detect anterior large-vessel occlusions. We aimed to compare prehospital assessment of these stroke-related deficits by paramedics with in-hospital assessment by physicians.
    Methods: We used data from 2 prospective cohort studies: the LPSS (Leiden Prehospital Stroke Study) and PRESTO study (Prehospital Triage of Patients With Suspected Stroke). In both studies, paramedics scored 9 neurological deficits in stroke code patients in the field. Trained physicians scored the National Institutes of Health Stroke Scale (NIHSS) at hospital presentation. Patients with transient ischemic attack were excluded because of the transient nature of symptoms. Spearman rank correlation coefficient (r
    Results: We included 2850 stroke code patients. Of these, 1528 had ischemic stroke, 243 intracranial hemorrhage, and 1079 stroke mimics. Correlation between the total prehospital assessment score and NIHSS score was strong (r
    Conclusions: The overall prehospital assessment of stroke code patients correlates strongly with in-hospital assessment. Prehospital assessment of neglect, abnormal speech, and gaze deviation differed most from in-hospital assessment. Focused training on these deficits may improve prehospital triage.
    MeSH term(s) Humans ; Emergency Medical Services/methods ; Paramedics ; Prospective Studies ; Stroke ; Triage/methods ; Hospitals ; Physicians
    Language English
    Publishing date 2023-07-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80381-9
    ISSN 1524-4628 ; 0039-2499 ; 0749-7954
    ISSN (online) 1524-4628
    ISSN 0039-2499 ; 0749-7954
    DOI 10.1161/STROKEAHA.123.042644
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Prehospital Stroke Triage: A Modeling Study on the Impact of Triage Tools in Different Regions.

    Duvekot, Martijne H C / Garcia, Bjarty L / Dekker, Luuk / Nguyen, Truc My / van den Wijngaard, Ido R / de Laat, Karlijn F / de Schryver, Els L L M / Kloos, Loet M H / Aerden, Leo A M / Zylicz, Stas A / Bosch, Jan / van Belle, Eduard / van Zwet, Erik W / Rozeman, Anouk D / Moudrous, Walid / Vermeij, Frédérique H / Lingsma, Hester F / Bakker, Jeannette / van Doormaal, Pieter Jan /
    van Es, Adriaan C G M / van der Lugt, Aad / Wermer, Marieke J H / Dippel, Diederik W J / Kerkhoff, Henk / Roozenbeek, Bob / Kruyt, Nyika D / Venema, Esmee

    Prehospital emergency care

    2023  Volume 27, Issue 5, Page(s) 630–638

    Abstract: Background and purpose: Direct transportation to a thrombectomy-capable intervention center is beneficial for patients with ischemic stroke due to large vessel occlusion (LVO), but can delay intravenous thrombolytics (IVT). The aim of this modeling ... ...

    Abstract Background and purpose: Direct transportation to a thrombectomy-capable intervention center is beneficial for patients with ischemic stroke due to large vessel occlusion (LVO), but can delay intravenous thrombolytics (IVT). The aim of this modeling study was to estimate the effect of prehospital triage strategies on treatment delays and overtriage in different regions.
    Methods: We used data from two prospective cohort studies in the Netherlands: the Leiden Prehospital Stroke Study and the PRESTO study. We included stroke code patients within 6 h from symptom onset. We modeled outcomes of Rapid Arterial oCclusion Evaluation (RACE) scale triage and triage with a personalized decision tool, using drip-and-ship as reference. Main outcomes were overtriage (stroke code patients incorrectly triaged to an intervention center), reduced delay to endovascular thrombectomy (EVT), and delay to IVT.
    Results: We included 1798 stroke code patients from four ambulance regions. Per region, overtriage ranged from 1-13% (RACE triage) and 3-15% (personalized tool). Reduction of delay to EVT varied by region between 24 ± 5 min (
    Conclusions: In this modeling study, we showed that prehospital triage reduced time to EVT without disproportionate IVT delay, compared to a drip-and-ship strategy. The effect of triage strategies and the associated overtriage varied between regions. Implementation of prehospital triage should therefore be considered on a regional level.
    MeSH term(s) Humans ; Triage ; Brain Ischemia/diagnosis ; Emergency Medical Services ; Prospective Studies ; Stroke/therapy ; Stroke/drug therapy ; Fibrinolytic Agents/therapeutic use ; Thrombolytic Therapy ; Treatment Outcome
    Chemical Substances Fibrinolytic Agents
    Language English
    Publishing date 2023-06-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1461751-1
    ISSN 1545-0066 ; 1090-3127
    ISSN (online) 1545-0066
    ISSN 1090-3127
    DOI 10.1080/10903127.2023.2215859
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Active encouragement of older women with urinary incontinence in primary care to undergo diagnosis and treatment: a matched-pair cluster randomized controlled trial.

    Visser, Els / de Bock, Geertruida H / Messelink, Embert J / Schram, Aaltje J / Kollen, Boudewijn J / la Bastide-van Gemert, Sacha / van den Heuvel, Edwin R / Berger, Marjolein Y / Dekker, Janny H

    Maturitas

    2015  Volume 80, Issue 2, Page(s) 212–219

    Abstract: Objectives: The URINO trial investigated the effect of offering treatment to older women with urinary incontinence in the general population, who had not sought help on their own initiative.: Study design: In a cluster randomized trial, 14 general ... ...

    Abstract Objectives: The URINO trial investigated the effect of offering treatment to older women with urinary incontinence in the general population, who had not sought help on their own initiative.
    Study design: In a cluster randomized trial, 14 general practitioners were matched into pairs and randomly allocated to an intervention or a control group. Women aged ≥ 55 years registered in the participating practices were asked about urinary incontinence via a postal questionnaire. Patients in the intervention group were assessed and treated whereas patients in the control group received standard care.
    Main outcome measures: Primary outcome was improvement (yes or no) of the severity of symptoms at 12-month follow-up measured with the Incontinence Severity Index. Secondary outcomes were the number of incontinence episodes per day and quality of life. The primary analysis was on an intention-to-treat basis with multiple imputation of missing data. A logistic regression model with correction for cluster randomization was fitted to estimate odds ratios (ORs).
    Results: At 12 months, the severity of symptoms had improved in more patients in the intervention group (n166) than in the controls (n184) (OR 1.9; 95% CI 1.1-3.3). Also, the number of patients with fewer episodes of incontinence had increased (OR 2.5; 95% CI 1.5-4.1). No between-group differences in changes in quality of life were apparent (p0.14).
    Conclusions: It is recommended to encourage women in the general population aged ≥ 55 years with urinary incontinence to undergo diagnosis and treatment.
    MeSH term(s) Aged ; Directive Counseling ; Female ; Humans ; Logistic Models ; Mass Screening ; Middle Aged ; Odds Ratio ; Patient Acceptance of Health Care ; Primary Health Care ; Quality of Life ; Surveys and Questionnaires ; Urinary Bladder, Overactive/diagnosis ; Urinary Bladder, Overactive/therapy ; Urinary Incontinence/diagnosis ; Urinary Incontinence/therapy
    Language English
    Publishing date 2015-02
    Publishing country Ireland
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 80460-5
    ISSN 1873-4111 ; 0378-5122
    ISSN (online) 1873-4111
    ISSN 0378-5122
    DOI 10.1016/j.maturitas.2014.11.015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: How baseline, new-onset, and persistent depressive symptoms are associated with cardiovascular and non-cardiovascular mortality in incident patients on chronic dialysis.

    van Dijk, Sandra / van den Beukel, Tessa O / Kaptein, Adrian A / Honig, Adriaan / le Cessie, Saskia / Siegert, Carl E / Boeschoten, Els W / Krediet, Ray T / Dekker, Friedo W

    Journal of psychosomatic research

    2013  Volume 74, Issue 6, Page(s) 511–517

    Abstract: Objective: Depressive symptoms are associated with mortality among patients on chronic dialysis therapy. It is currently unknown how different courses of depressive symptoms are associated with both cardiovascular and non-cardiovascular mortality.: ... ...

    Abstract Objective: Depressive symptoms are associated with mortality among patients on chronic dialysis therapy. It is currently unknown how different courses of depressive symptoms are associated with both cardiovascular and non-cardiovascular mortality.
    Methods: In a Dutch prospective nation-wide cohort study among incident patients on chronic dialysis, 1077 patients completed the Mental Health Inventory, both at 3 and 12months after starting dialysis. Cox regression models were used to calculate crude and adjusted hazard ratios (HRs) for mortality for patients with depressive symptoms at 3months only (baseline only), at 12months only (new-onset), and both at 3 and 12months (persistent), using patients without depressive symptoms at 3 and 12months as reference group.
    Results: Depressive symptoms at baseline only seemed to be a strong marker for non-cardiovascular mortality (HRadj 1.91, 95% CI 1.26-2.90), whereas cardiovascular mortality was only moderately increased (HRadj 1.41, 95% CI 0.85-2.33). In contrast, new-onset depressive symptoms were moderately associated with both cardiovascular (HRadj 1.66, 95% CI 1.06-2.58) and non-cardiovascular mortality (HRadj 1.46, 95% CI 0.97-2.20). Among patients with persistent depressive symptoms, a poor survival was observed due to both cardiovascular (HRadj 2.14, 95% CI 1.42-3.24) and non-cardiovascular related mortality (HRadj 1.76, 95% CI 1.20-2.59).
    Conclusion: This study showed that different courses of depressive symptoms were associated with a poor survival after the start of dialysis. In particular, temporary depressive symptoms at the start of dialysis may be a strong marker for non-cardiovascular mortality, whereas persistent depressive symptoms were associated with both cardiovascular and non-cardiovascular mortality.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Cardiovascular Diseases/mortality ; Cardiovascular Diseases/psychology ; Cause of Death ; Depression/mortality ; Depression/psychology ; Female ; Humans ; Incidence ; Kidney Failure, Chronic/mortality ; Kidney Failure, Chronic/psychology ; Kidney Failure, Chronic/therapy ; Male ; Middle Aged ; Prognosis ; Renal Dialysis/mortality ; Renal Dialysis/psychology ; Surveys and Questionnaires
    Language English
    Publishing date 2013-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80166-5
    ISSN 1879-1360 ; 0022-3999
    ISSN (online) 1879-1360
    ISSN 0022-3999
    DOI 10.1016/j.jpsychores.2013.03.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: The epithelial calcium channels, TRPV5 & TRPV6: from identification towards regulation.

    den Dekker, Els / Hoenderop, Joost G J / Nilius, Bernd / Bindels, René J M

    Cell calcium

    2003  Volume 33, Issue 5-6, Page(s) 497–507

    Abstract: The epithelial calcium channels, TRPV5 and TRPV6, have been extensively studied in epithelial tissues controlling the Ca(2+) homeostasis and exhibit a range of distinctive properties that distinguish them from other TRP channels. This review focuses on ... ...

    Abstract The epithelial calcium channels, TRPV5 and TRPV6, have been extensively studied in epithelial tissues controlling the Ca(2+) homeostasis and exhibit a range of distinctive properties that distinguish them from other TRP channels. This review focuses on the tissue distribution, the functional properties, the architecture and the regulation of the expression and activity of the TRPV5 and TRPV6 channel.
    MeSH term(s) Animals ; Calcium/metabolism ; Calcium Channels/chemistry ; Calcium Channels/physiology ; Epithelium/chemistry ; Epithelium/metabolism ; Humans ; Ion Channel Gating ; Protein Structure, Tertiary ; Signal Transduction ; TRPV Cation Channels
    Chemical Substances Calcium Channels ; TRPV Cation Channels ; TRPV5 protein, human ; TRPV6 channel ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2003-07-04
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 757687-0
    ISSN 1532-1991 ; 0143-4160
    ISSN (online) 1532-1991
    ISSN 0143-4160
    DOI 10.1016/s0143-4160(03)00065-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Development of platelet inhibition by cAMP during megakaryocytopoiesis.

    den Dekker, Els / Gorter, Gertie / Heemskerk, Johan W M / Akkerman, Jan-Willem N

    The Journal of biological chemistry

    2002  Volume 277, Issue 32, Page(s) 29321–29329

    Abstract: Prostacyclin is a potent inhibitor of agonist-induced Ca2+ increases in platelets, but in the megakaryocytic cell line MEG-01 this inhibition is absent. Using human megakaryocytic cell lines representing different stages in megakaryocyte (Mk) maturation ... ...

    Abstract Prostacyclin is a potent inhibitor of agonist-induced Ca2+ increases in platelets, but in the megakaryocytic cell line MEG-01 this inhibition is absent. Using human megakaryocytic cell lines representing different stages in megakaryocyte (Mk) maturation as well as stem cells and immature and mature megakaryocytes, we show that the inhibition by prostacyclin develops at a late maturation stage shortly before platelets are formed. This late appearance is not caused by insufficient cAMP formation or absent protein kinase A (PKA) activity in immature cells. Instead, the appearance of Ca2+ inhibition by prostacyclin is accompanied by a sharp increase in the expression of the catalytic subunit of PKA (PKA-C) but not by changes in the expression of the PKA-regulatory subunits Ialpha/beta, IIalpha, and IIbeta. Overexpression of PKA-C in the megakaryocytic cell line CHRF-288-11 potentiates the Ca2+ inhibition by prostacyclin. Thus, up-regulation of PKA-C appears to be a key step in the development of Ca2+ inhibition by prostacyclin in platelets.
    MeSH term(s) Antigens, CD34/biosynthesis ; Blood Platelets/metabolism ; Blotting, Western ; Calcium/metabolism ; Cell Line ; Cell Separation ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Epoprostenol/metabolism ; Flow Cytometry ; Humans ; Megakaryocytes/cytology ; Megakaryocytes/pathology ; Plasmids/metabolism ; Protein Binding ; Protein Kinase C/metabolism ; Signal Transduction ; Time Factors ; Transfection ; Tumor Cells, Cultured
    Chemical Substances Antigens, CD34 ; Epoprostenol (DCR9Z582X0) ; Cyclic AMP (E0399OZS9N) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11) ; Protein Kinase C (EC 2.7.11.13) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2002-05-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M111390200
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Characterization of a Madin-Darby canine kidney cell line stably expressing TRPV5.

    den Dekker, Els / Schoeber, Joost / Topala, Catalin N / van de Graaf, Stan F J / Hoenderop, Joost G J / Bindels, René J M

    Pflugers Archiv : European journal of physiology

    2005  Volume 450, Issue 4, Page(s) 236–244

    Abstract: To provide a cell model for studying specifically the regulation of Ca2+ entry by the epithelial calcium channel transient receptor potential-vanilloid-5 (TRPV5), green fluorescent protein (GFP)-tagged TRPV5 was expressed stably in Madin-Darby canine ... ...

    Abstract To provide a cell model for studying specifically the regulation of Ca2+ entry by the epithelial calcium channel transient receptor potential-vanilloid-5 (TRPV5), green fluorescent protein (GFP)-tagged TRPV5 was expressed stably in Madin-Darby canine kidney type I (MDCK) cells. The localization of GFP-TRPV5 in this cell line showed an intracellular granular distribution. Ca2+ uptake in GFP-TRPV5-MDCK cells cultured on plastic supports was threefold higher than in non-transfected cells. Moreover, apical Ca2+ uptake in GFP-TRPV5-MDCK cells cultured on permeable supports was eightfold higher than basolateral Ca2+ uptake, indicating that GFP-TRPV5 is expressed predominantly in the apical membrane. Patch-clamp analysis showed the presence of typical electrophysiological features of GFP-TRPV5, such as inwardly rectifying currents, inhibition by divalent cations and Ca2+-dependent inactivation. Moreover, the TRPV5 inhibitor ruthenium red completely inhibited Ca2+ uptake in GFP-TRPV5-MDCK cells, whereas Ca2+ uptake in non-transfected cells was not inhibited. The characterized GFP-TRPV5-MDCK cell line was used to assess the regulation of TRPV5. The protein kinase C activator phorbol 12-myristate 13-acetate and the cAMP-elevating compounds forskolin/3-isobutyl-1-methylxanthine, 8-Br-cAMP and PGE2 stimulated TRPV5 activity in GFP-TRPV5-MDCK cells by 121+/-7, 79+/-5, 55+/-4 and 61+/-7%, respectively. These compounds did not affect Ca2+ uptake in non-transfected cells. In conclusion, the GFP-TRPV5-MDCK cell line provides a model to specifically study the regulation of TRPV5 activity.
    MeSH term(s) Animals ; Calcium/metabolism ; Calcium Channels/biosynthesis ; Calcium Channels/genetics ; Cell Line ; Dogs ; Green Fluorescent Proteins/metabolism ; Humans ; Kidney ; Rabbits ; Recombinant Fusion Proteins ; Transfection
    Chemical Substances Calcium Channels ; Recombinant Fusion Proteins ; Green Fluorescent Proteins (147336-22-9) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2005-07
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 6380-0
    ISSN 1432-2013 ; 0031-6768
    ISSN (online) 1432-2013
    ISSN 0031-6768
    DOI 10.1007/s00424-005-1409-3
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  9. Article: Monocyte cell surface glycosaminoglycans positively modulate IL-4-induced differentiation toward dendritic cells.

    den Dekker, Els / Grefte, Sander / Huijs, Tonnie / ten Dam, Gerdy B / Versteeg, Elly M M / van den Berk, Lieke C J / Bladergroen, Bellinda A / van Kuppevelt, Toin H / Figdor, Carl G / Torensma, Ruurd

    Journal of immunology (Baltimore, Md. : 1950)

    2008  Volume 180, Issue 6, Page(s) 3680–3688

    Abstract: IL-4 induces the differentiation of monocytes toward dendritic cells (DCs). The activity of many cytokines is modulated by glycosaminoglycans (GAGs). In this study, we explored the effect of GAGs on the IL-4-induced differentiation of monocytes toward ... ...

    Abstract IL-4 induces the differentiation of monocytes toward dendritic cells (DCs). The activity of many cytokines is modulated by glycosaminoglycans (GAGs). In this study, we explored the effect of GAGs on the IL-4-induced differentiation of monocytes toward DCs. IL-4 dose-dependently up-regulated the expression of DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), CD80, CD206, and CD1a. Monocytes stained positive with Abs against heparan sulfate (HS) and chondroitin sulfate (CS) B (CSB; dermatan sulfate), but not with Abs that recognize CSA, CSC, and CSE. Inhibition of sulfation of monocyte/DC cell surface GAGs by sodium chlorate reduced the reactivity of sulfate-recognizing single-chain Abs. This correlated with hampered IL-4-induced DC differentiation as evidenced by lower expression of DC-SIGN and CD1a and a decreased DC-induced PBL proliferation, suggesting that sulfated monocyte cell surface GAGs support IL-4 activity. Furthermore, removal of cell surface chondroitin sulfates by chondroitinase ABC strongly impaired IL-4-induced STAT6 phosphorylation, whereas removal of HS by heparinase III had only a weak inhibitory effect. IL-4 bound to heparin and CSB, but not to HS, CSA, CSC, CSD, and CSE. Binding of IL-4 required iduronic acid, an N-sulfate group (heparin) and specific O sulfates (CSB and heparin). Together, these data demonstrate that monocyte cell surface chondroitin sulfates play an important role in the IL-4-driven differentiation of monocytes into DCs.
    MeSH term(s) Antigens, CD1/biosynthesis ; B7-1 Antigen/biosynthesis ; Cell Adhesion Molecules/biosynthesis ; Cell Differentiation/immunology ; Cell Membrane/immunology ; Cell Membrane/metabolism ; Cells, Cultured ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Dose-Response Relationship, Immunologic ; Glycosaminoglycans/metabolism ; Glycosaminoglycans/physiology ; Humans ; Interleukin-4/metabolism ; Interleukin-4/physiology ; Lectins, C-Type/biosynthesis ; Mannose-Binding Lectins/biosynthesis ; Monocytes/cytology ; Monocytes/immunology ; Monocytes/metabolism ; Protein Binding/immunology ; Receptors, Cell Surface/biosynthesis ; Up-Regulation/immunology
    Chemical Substances Antigens, CD1 ; B7-1 Antigen ; CD1a antigen ; Cell Adhesion Molecules ; DC-specific ICAM-3 grabbing nonintegrin ; Glycosaminoglycans ; Lectins, C-Type ; Mannose-Binding Lectins ; Receptors, Cell Surface ; mannose receptor ; Interleukin-4 (207137-56-2)
    Language English
    Publishing date 2008-02-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.180.6.3680
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Characterization of a murine renal distal convoluted tubule cell line for the study of transcellular calcium transport.

    Diepens, Robin J W / den Dekker, Els / Bens, Marcelle / Weidema, A Freek / Vandewalle, Alain / Bindels, René J M / Hoenderop, Joost G J

    American journal of physiology. Renal physiology

    2004  Volume 286, Issue 3, Page(s) F483–9

    Abstract: To unravel the molecular regulation of renal transcellular Ca(2+) transport, a murine distal convoluted tubule (mpkDCT) cell line derived from distal convoluted tubules (DCT) microdissected from a SV-PK/Tag transgenic mouse was characterized. This cell ... ...

    Abstract To unravel the molecular regulation of renal transcellular Ca(2+) transport, a murine distal convoluted tubule (mpkDCT) cell line derived from distal convoluted tubules (DCT) microdissected from a SV-PK/Tag transgenic mouse was characterized. This cell line originated from DCT only, as mRNA encoding for the DCT marker thiazide-sensitive Na(+)/Cl(-) cotransporter was expressed, whereas mRNA encoding for the connecting tubule and collecting duct marker aquaporin-2 was not detected, as determined by reverse-transcriptase PCR. mpkDCT cells expressed mRNA encoding the Ca(2+) channels TRPV5 and TRPV6 and other key players necessary for transcellular Ca(2+) transport, i.e., calbindin-D(9k), calbindin-D(28k), plasma membrane Ca(2+)-ATPase isoform 1b, and Na(+)/Ca(2+) exchanger 1. Primary cultures of DCT cells exhibited net transcellular Ca(2+) transport of 0.4 +/- 0.1 nmol.h(-1).cm(-2), whereas net transcellular Ca(2+) transport across mpkDCT cells was significantly higher at 2.4 +/- 0.4 nmol.h(-1).cm(-2). Transcellular Ca(2+) transport across mpkDCT cells was completely inhibited by ruthenium red, an inhibitor of TRPV5 and TRPV6, but not by the voltage-operated Ca(2+) channel inhibitors felodipine and verapamil. With the use of patch-clamp analysis, the IC(50) of ruthenium red on Na(+) currents was between the values measured for TRPV5- and TRPV6-expressing HEK 293 cells, suggesting that TRPV5 and/or TRPV6 is possibly active in mpkDCT cells. Forskolin in combination with IBMX, 1,25-dihydroxyvitamin D(3), and 1-deamino-8-d-arginine vasopressin increased transcellular Ca(2+) transport, whereas PMA and parathyroid hormone had no significant effect. In conclusion, the murine mpkDCT cell line provides a unique cell model in which to study the molecular regulation of transcellular Ca(2+) transport in the kidney in vitro.
    MeSH term(s) Animals ; Calcitriol/pharmacology ; Calcium/metabolism ; Cell Line ; Cyclic AMP/metabolism ; Electric Conductivity ; Female ; Ion Transport ; Kidney Tubules, Distal/cytology ; Kidney Tubules, Distal/drug effects ; Kidney Tubules, Distal/metabolism ; Mice ; Mice, Inbred C57BL ; RNA, Messenger/metabolism ; Ruthenium Red/pharmacology
    Chemical Substances RNA, Messenger ; Ruthenium Red (11103-72-3) ; Cyclic AMP (E0399OZS9N) ; Calcitriol (FXC9231JVH) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2004-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 1931-857X ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 1931-857X ; 0363-6127
    DOI 10.1152/ajprenal.00231.2003
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