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Biomedical subjects

A A van de Loosdrecht

Publications and source records attributed to A A van de Loosdrecht.

At least 19 recordsLinked to original sources
PubMed2006

MHC class II molecules in tumour immunology: prognostic marker and target for immune modulation.

MHC class II molecules presenting MHC class II restricted antigens play an important role in the activation of CD4+ T cells, which are the central orchestrating cells of an immune response. This review focuses on the particular role of MHC class II molecules in tumour immunology. The MHC class II antigen presentation pathway and the expression of MHC class II molecules on tumour cells related to clinical outcome is discussed. Improving the MHC class II tumour antigen presentation pathway, for instance by downregulation of the invariant chain or modulation of HLA-DO expression, offers many opportunities for developing new modalities of immunotherapy.

Animals↗
PubMed2006

Mucormycosis in a patient with low risk myelodysplasia treated with anti-TNF-alpha.

Accelerated programmed cell death or apoptosis appears to play an important role in the pathogenesis of myelodysplasia. As overexpression of TNF-alpha has been described to induce cell death in myelodysplasia, treatment with anti-TNF-alpha is currently being explored. Caution is needed because of an increased risk of opportunistic infection during anti-TNF-alpha treatment. We here describe a patient who was treated with anti-TNF-alpha for low risk myelodysplasia and died of invasive mucormycosis.

Anemia, Refractory↗
PubMed2004

Limited numbers of apoptotic cells in fresh paraffin embedded bone marrow samples of patients with myelodysplastic syndrome.

In myelodysplasia (MDS) the precise mechanism of ineffective erythropoiesis is not fully elucidated, but it is suggested that apoptosis may contribute to this process. We performed TdT-mediated dUTP-nick end labelling (TUNEL) staining of paraffin embedded bone marrow specimens to assess the amount of apoptotic cells in 21 MDS patients (7 RA, 3 RARS, 5 RAEB, 3 RAEB-T, 3 CMML) and five normal controls. In 10 MDS patients the TUNEL assay was performed in combination with immunostaining for Glycophorin-A (GpA) to determine apoptosis in the maturing erythroid compartment. To assess the proliferation of the bone marrow cells the expression of Ki-67 antigen was used as a marker. The mean apoptotic index (AI) in MDS patients was not increased (2.3 +/- 3.0% in MDS versus 4.8 +/- 1.2% in normal controls (P < 0.05)). Moreover, no significant difference in mean AI was observed in the GpA+ compartment between MDS and normal controls (0.8 +/- 0.2% versus 0.6 +/- 0.1%). In addition the different FAB-classifications and the different International Prognostic Scoring System (IPSS)-risk groups showed no significant differences between the subgroups. The expression of Ki-67, as marker for proliferative activity, in the GpA+ compartment from MDS did not differ significantly from normal controls (84.0 +/- 12.2% versus 79.9 +/- 20.2%). Our findings suggest that the observed increased apoptosis in in vitro culture assays is related to the detachment of the cells from the microenvironment leading to an increased susceptibility to apoptosis.

Adult↗
PubMed2003

CD40-targeted adenoviral GM-CSF gene transfer enhances and prolongs the maturation of human CML-derived dendritic cells upon cytokine deprivation.

Vaccination with autologous leukaemia-derived dendritic cells (DC) presents an adjuvant treatment option for chronic myeloid leukaemia (CML). Here, we show that high-efficiency CD40-targeted adenoviral gene transfer of GM-CSF to CML-derived DC induces long-lived maturation in the absence of exogenous cytokines and may thus ensure protracted stimulation of CML-specific T cells upon vaccination.

Adenoviridae↗
PubMed2002

Intraspinal extramedullary haematopoiesis in a patient with myelofibrosis.

A 54-year-old patient with myelofibrosis developed paresis of the legs, and bladder dysfunction due to extramedullary haematopoiesis in the spinal channel. He was given palliative radiotherapy but died shortly afterwards. Although rare, the possibility of extramedullary haematopoiesis in the central nervous system should be considered when neurological symptoms appear in a patient with myelofibrosis, because good palliation is possible with timely radiotherapy.

Hematopoiesis, Extramedullary↗
PubMed2001

Mitochondrial disruption and limited apoptosis of erythroblasts are associated with high risk myelodysplasia. An ultrastructural analysis.

AIMS: To investigate the ultrastructural characteristics of erythroblasts in myelodysplasia (MDS) which might be of additional importance in understanding its pathogenesis. METHODS AND RESULTS: 22 patients were classified according to FAB (French-American-British classification), IPSS (international prognostic score system), cytogenetic risk factors and transfusion dependency. Using electron microscopy, in 77% of the cases, nuclear abnormalities consisting of disrupted membranes and cystic/dilated perinuclear spaces were noted. In a limited number of patients (n=7), a low percentage of apoptosis in the erythroid lineage (mean 3.1+/-1.6%; median 3%: range 1-6) (normal controls: <0.5%) could be noted, primarily in mature erythroblasts and significantly associated with spongiform nuclear features. In all patients extensive cytoplasmic vacuolization and myelin figures in erythroblasts were demonstrated. In 55% of the cases, enlarged and abnormal mitochondria were observed, significantly associated with iron-accumulation. A significant inverse relation existed between the absence of apoptosis and more advanced, or high risk disease and cytogenetic risk factors. Mitochondrial abnormalities were significantly correlated with high risk disease as well with an increase in transfusion dependency. CONCLUSIONS: These data indicate that in MDS apoptosis may play a role in early stages of disease. The overall prominent defects in mitochondria might be an additional defect that is involved in ineffective erythropoiesis.

Adult↗
PubMed2000

Central diabetes insipidus preceding acute myeloid leukemia with t(3;12)(q26;p12).

A 52-year-old woman presented with polyuria and polydipsia. A diagnosis of central diabetes insipidus (DI) was made, which turned out to be the first sign of acute myeloid leukemia (AML). Cytogenetic analysis revealed a balanced translocation between chromosome 3 and 12 t(3;12)(q26;p12). The patient was treated with standard induction chemotherapy and vasopressin. Before consolidation chemotherapy could be administered, deep venous thrombosis was diagnosed and leukemia relapsed. Rescue chemotherapy was started. This is the first report of an association between AML with t(3;12) and DI. Its possible pathogenesis is discussed with a review of the literature.

Acute Disease↗