Shwachman's Syndrome: Pathomorphosis and Long-term Outcome

Cipolli, Marco; D'Orazio, Ciro; Delmarco, Antonella; Marchesini, Cristina; Miano, A.; Mastella, G

doi:10.1097/00005176-199909000-00006

Cited by 71 publications

(81 citation statements)

References 25 publications

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“…16 In one patient, the indication for BMT was not given. 15 Collectively, among these previously reported cases of HSCT for SDS, eight of 15 (53%) patients died between 23 days and 1 year following transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8][9][10][11][12][13][14][15][16] Donors were HLA-matched siblings in five cases, unrelated individuals in eight cases, and a mismatched relative in one case. The stem cell source was bone marrow in each of these cases.…”

Section: Discussionmentioning

confidence: 99%

“…The longest follow-up period reported in surviving patients was 20 months post HSCT with the range of follow-up being 3 to 20 months. 6,8,9,12,[14][15][16] Long-term survival data were not available for the majority of cases reported. When listed, the causes of death were congestive heart failure (1), infection (3), multi-organ failure (1), respiratory failure (1) and pulmonary hemorrhage (2).…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4] Allogeneic hematopoietic stem cell transplantation (HSCT) can be curative for the hematologic disturbances of SDS; however, our review of the literature reveals limited survival with transplant, with only seven of 15 reported cases alive post HSCT. [5][6][7][8][9][10][11][12][13][14][15][16] Poor outcome with HSCT is frequently related to excessive cardiac and other organ toxicity from the preparative therapy. We describe two young children with SDS who underwent successful allografting using a non-cardiotoxic conditioning regimen.…”

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confidence: 99%

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Successful allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman–Diamond syndrome

Fleitz

Rumelhart

Goldman

et al. 2002

Bone Marrow Transplant

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Successful allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman–Diamond syndrome

Fleitz

Rumelhart

Goldman

et al. 2002

Bone Marrow Transplant

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“…[3][4][5][6] Also patients suffering from Shwachman-Diamond syndrome (SDS) display neutrophil chemotaxis defects. [7][8][9][10][11] SDS is characterized by exocrine pancreas defects and neutropenia, often accompanied by thrombocytopenia and anemia. 8,12,13 Most SDS patients have mutations in the SBDS gene located at chromosome 7, which is currently the only known affected gene in SDS.…”

Section: Introductionmentioning

confidence: 99%

Shwachman-Diamond syndrome neutrophils have altered chemoattractant-induced F-actin polymerization and polarization characteristics

Orelio

Kuijpers

2009

Haematologica

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delayed in SDS neutrophils. This is the first study revealing a molecular defect, namely defective F-actin cytoskeletal remodeling, which may contribute to impaired chemotaxis in SDS patients. Design and Methods Neutrophil isolation and cell cultureBlood was obtained after informed consent of healthy volunteers (26-43 years) and SDS patients (2-29 years; all with mutations 183-184 A>CT [K62X]/IVS2 258+2T>C [C84fs]). The study was approved by the Medical Ethics Committees of the AMC Hospital and the institutional review board and was in accordance with the Declaration of Helsinki. Neutrophils were isolated as described. 8 PLB-985 and GFP-Rac2 PLB-985 17 cells were cultured in RPMI/10% FCS/penicillin (200 µg/mL)/streptomycin (200 µg/mL)/ L-glutamine (4 mM). PLB-985 cells were differentiated with 0.5% dimethylformamide (DMF; Sigma-Aldrich) for 5-7 days. Cellular spreading and immunofluorescenceNeutrophils or PLB-985 cells in Hepes medium (132 mM NaCl, 20 mM Hepes, 6mM KCL, 1 mM MgSO4, 1.2 mM K2HPO4, 1 mM CaCl2, 5 mM Glucose, 2.5% human albumin (Cealb; Sanquin reagents)) were seeded on fibronectin-coated coverslips and allowed to adhere for 30 min. Cells were stimulated with 20nM fMLP, fixed with 4% paraformaldehyde/PBS and processed for immunofluorescence staining as described. 18 Antibodies used: SBDS (rabbit polyclonal), Phalloidin-Alexa488 or BODIPY conjugated. Pictures were taken with a Zeiss LSM510 microscope with a Zeiss 65x oil lens and processed with LSM 510 software. Neutrophils (2×10 6 /mL) in Hepes medium were stimulated with 100nM fMLP or 40nM C5a. At indicated time points 2×10 5 cells were harvested and fixed with buffer 1 (Intraprep Permeabilization Reagent Kit; Immunotech), permeabilized with buffer 2 and stained with Phalloidin-Alexa488 (Molecular Probes, Invitrogen). Cells were analyzed on LSRII (BD Biosciences) flow cytometer for F-actin content. F-actin polymerization and cellular polarizationTo determine F-actin polarization, neutrophils were embedded with Mowiol 4-88 and analyzed by confocal microscopy. For each experiment at least 50 cells per time-point were analyzed in a blind fashion. Results and Discussion SBDS co-localizes with F-actin and Rac2 in human neutrophilsTo investigate a possible link between SBDS and the actin cytoskeleton, we performed immunofluorescence stainings in neutrophils and PLB-985 cells, with an anti-SBDS antibody that we have generated and which specifically recognized SBDS (Online Supplementary Figure S1A/B). In resting human neutrophils we observed that SBDS is localized prominently to the nucleus and to a lesser extent to the cytoplasm (Online Supplementary Figure 1C). However, in these resting cells there is not much polymerized F-actin cytoskeleton detectable (data not shown) and therefore we set out to investigate SBDS in relation to the F-actin cytoskeleton in activated neutrophilic cells. Human peripheral blood neutrophils were allowed to adhere to fibronectin and were subsequently stimulated with fMLP. These activated cells displayed Factin enriched c...

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Approach to the Patient with Diarrhea

Powell¹

2008

Principles of Clinical Gastroenterology

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Shwachman's Syndrome: Pathomorphosis and Long-term Outcome

Cited by 71 publications

References 25 publications

Successful allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman–Diamond syndrome

Successful allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman–Diamond syndrome

Shwachman-Diamond syndrome neutrophils have altered chemoattractant-induced F-actin polymerization and polarization characteristics

Approach to the Patient with Diarrhea

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