PubMed Health⌕ Search

Biomedical subjects

H De Raeve

Publications and source records attributed to H De Raeve.

At least 19 recordsLinked to original sources
PubMed2006

Current diagnostic criteria for the chronic myeloproliferative disorders (MPD) essential thrombocythemia (ET), polycythemia vera (PV) and chronic idiopathic myelofibrosis (CIMF).

The clinical criteria for the diagnosis of essential thrombocythemia (ET) according to the polycythemia vera study group (PVSG) do not distinguish between ET and thrombocythemia associated with early stage PV and prefibrotic chronic idiopathic myelofibrosis (CIMF). The clinical criteria of the PVSG for the diagnosis of polycythemia vera (PV) only detects advanced stage of PV with increased red cell mass. The bone marrow criteria of the World Health Organization (WHO) are defined by pathologists to explicitly define the pathological criteria for the diagnostic differentiation of ET, PV, and prefibrotic and fibrotic CIMF. As the clinical PVSG and the pathological WHO criteria show significant shortcomings, an updated set of European Clinical and Pathological (ECP) criteria combined with currently available biological and molecular markers are proposed to much better distinct true ET from early PV mimicking ET, to distinguish ET from thrombocythemia associated with prefibrotic CIMF, and to define the various clinical and pathological stages of PV and CIMF that has important therapeutic and prognostic implications. Comparing the finding of clustered giant abnormal megakaryocytes in a representative bone marrow as a diagnostic clue to MPD, the sensitivity for the diagnosis of MPD associated with splanchnic vein thrombosis was 63% for increased red cell mass, 52% for low serum EPO level, 72% for EEC, and 74% for splenomegaly indicating the superiority of bone marrow histopathology to detect masked early and overt MPD in this setting. The majority of PV and about half of the ET patients have spontaneous EEC, low serum EPO levels and PRV-1 over-expression and are JAK2 V617F positive. The positive predictive value for the diagnosis of PV of spontaneous growth of endogenous erythroid colonies (EEC) of peripheral blood (PB) and bone marrow (BM) cells is about 80-85% when either PB or BM EEC assays, and up to 94% when BM and PB EEC assays were performed. The diagnostic impact of low serum EPO levels (ELISA assay) in a large study of 186 patients below the normal range (<3.3 IU/l) had a sensitivity specificity and positive predictive value of 87%, 97% and 97.8%, respectively, for the diagnosis of PV. There is a significant overlap of serum EPO levels in PV versus control and controls versus SE. The specificity of a JAK2 V617F PCR test for the diagnosis of MPD is high (near 100%), but only half of ET and MF (50%) and the majority of PV (up to 97%) are JAK2 V617F positive. The use of biological markers including JAK2 V617 PCR test, serum EPO, PRV-1, EEC, leukocyte alkaline phosphatase score and peripheral blood parameters combined with bone marrow histopathology has a high sensitivity and specificity (almost 100%) to diagnose the early and overt stages of ET, PV and CIMF in JAK2 V617F positive and negative MPDs.

Amino Acid Substitution↗
PubMed2006

Endothelial cell-driven regulation of CD9 or motility-related protein-1 expression in multiple myeloma cells within the murine 5T33MM model and myeloma patients.

The cell surface expression of CD9, a glycoprotein of the tetraspanin family influencing several processes including cell motility and metastasis, inversely correlates with progression in several solid tumors. In the present work, we studied the expression and role of CD9 in multiple myeloma (MM) biology using the 5T33MM mouse model. The 5T33MMvitro cells were found to be CD9 negative. Injection of these cells in mice caused upregulation of CD9 expression, while reculturing them resulted in downregulation of CD9. Coculturing of CD9-negative 5T33MMvitro cells with BM endothelial cells (BMECs) resulted in a partial retrieval of CD9. Laser microdissection followed by real-time polymerase chain reaction and immunohistochemistry performed on bone sections of 5T33MMvivo diseased mice demonstrated strong local expression of CD9 on MM cells in contact with BMEC compared to MM cells further away. These findings were also confirmed by immunohistochemistry in MM patients. Neutralizing anti-CD9 antibodies inhibited transendothelial invasion of CD9-expressing human MM5.1 and murine 5T33MMvivo cells. In conclusion, we provide evidence that CD9 expression by the MM cells is upregulated in vivo by close interaction of the cells with BMEC and that CD9 is involved in transendothelial invasion, thus possibly mediating homing and/or spreading of the MM cells.

Animals↗
PubMed2006

Immunomodulatory drugs as a therapy for multiple myeloma.

Thalidomide and the analogues lenalidomide (CC-5013, Revlimid) and CC-4047 (Actimid) belong to the family of immunomodulatory drugs (IMiDs). These agents have anti-angiogenic properties, modulate TNFalpha and IL-12 secretion, co-stimulate T cells, increase NK cell toxicity and have direct anti-tumour effects. These characteristics have made of them promising drugs for treatment of relapsed, refractory and newly diagnosed MM. It seems that lenalidomide and CC-4047 are more powerful in inhibiting TNFalpha and have, except for myelosuppression, less side effects than Thal. Combination of IMiDs with dexamethasone, bortezomib and with chemotherapeutic agents are tested in numerous trials, which will help in determining the optimal combination and administration schedule of different molecules to take advantage of non-overlapping toxicities and synergisms between those agents.

Animals↗
PubMed2005

Bortezomib-induced Sweet's syndrome.

Sweet's syndrome is an uncommon acute skin disease, associated with a variety of medical problems. The drug-induced variant is even rarer. We describe two cases of this syndrome associated with the administration of the proteasome inhibitor bortezomib. The diagnostic criteria for drug-induced Sweet's syndrome as proposed by Walker and Cohen were fulfilled. Vasculitis and neutrophilic eccrine hidradenitis were excluded.

Aged↗
PubMed2004

Angiogenesis and the role of bone marrow endothelial cells in haematological malignancies.

Increased microvessel density (MVD) has been observed in the bone marrow (BM) of patients with multiple myeloma (MM), acute lymphoblastic leukaemia, acute myeloid leukaemia, and myelodysplastic and myeloproliferative syndrome. The MVD is the net result of cumulative phases of angiogenesis and angio-regression and is as such not an indicator of the ongoing angiogenesis at the time of biopsy. There is, therefore, a need for additional methods that allow the estimation of ongoing angiogenesis. Double immunostainings for CD34 and Ki-67 can be used on paraffin-embedded tissue to determine the endothelial proliferation fraction. The BM endothelial cells, as a component of the BM stroma, have a close interaction with the malignant cells. In MM, for example, they are involved in the specific homing and are a source of paracrine growth factors. Targeting the BM microvessels will not only influence the nutrient and oxygen supply, but will in addition reduce the growth stimuli provided by the EC.

Angiogenesis Inhibitors↗
PubMed2004

Primary ovarian small cell carcinoma of the pulmonary type: a case report and review of the literature.

Small cell carcinoma of the ovary is a rare type of ovarian carcinoma with a poor prognosis. Two types should be distinguished: the hypercalcemic type and the pulmonary type. We report the case history of a 54-year-old woman with both a Stage IIIC small cell carcinoma, pulmonary type and a well-differentiated endometrioid adenocarcinoma of the left ovary in combination with a Brenner tumor in the right ovary. A review of the literature on small cell carcinoma of the ovary is given and the findings of our patient are brought into perspective in terms of both histopathogenesis and treatment outcome.

Brenner Tumor↗
PubMed2003

Malignant large cell calcifying Sertoli cell tumor of the testis.

A 45-year old man presented with a slow-growing, unilateral beige testicular mass, with a diameter of 4 cm. The testosterone, FSH, LH, estradiol and betahCG serum levels were within normal limits, and there were no associated hormonal syndromes. The patient was treated with inguinal orchidectomy. Microscopically, the tumor was composed of nests of cells with large eosinophilic, slightly granular cytoplasm. There was only a mild degree of atypia and no mitotic activity. The tumor extended into the rete testis. There were intratumoral calcifications, and in the vicinity of the tumor, there was intratubular growth. Although this case is histologically similar to the three previously reported cases of clinically benign large cell calcifying Sertoli cell tumor of the testis with rete testis involvement, the current patient developed right sided para-aortic lymph node metastases 18 months after the initial diagnosis.

Calcinosis↗
PubMed2002

Murine 5T multiple myeloma cells induce angiogenesis in vitro and in vivo.

Multiple myeloma is a B cell malignancy. Recently, it has been demonstrated that bone marrow samples of patients with multiple myeloma display an enhanced angiogenesis. The mechanisms involved seem to be multiple and complex. We here demonstrate that the murine 5T multiple myeloma models are able to induce angiogenesis in vitro by using a rat aortic ring assay and in vivo by determining the microvessel density. The rat aortic rings cultured in 5T multiple myeloma conditioned medium exhibit a higher number of longer and more branched microvessels than the rings cultured in control medium. In bone marrow samples from 5T multiple myeloma diseased mice, a statistically significant increase of the microvessel density was observed when compared to bone marrow samples from age-matched controls. The angiogenic phenotype of both 5T multiple myeloma cells could be related, at least in part, to their capacity to produce vascular endothelial growth factor. These data clearly demonstrate that the 5T multiple myeloma models are good models to study angiogenesis in multiple myeloma and will allow to unravel the mechanisms of neovascularisation, as well as to test new putative inhibitors of angiogenesis.

Animals↗
PubMed2002

Nodular fasciitis: correlation of MRI findings and histopathology.

OBJECTIVE: To compare the histopathology of nodular fasciitis (NF) with the magnetic resonance imaging (MRI) findings in order to evaluate the basis of the MR signal characteristics. DESIGN AND PATIENTS: Ten patients with NF, nine females and 1 male, with an age ranging from 13 to 58 years (mean 26.8 years) were studied. MRI findings, available in all 10 patients, were compared with the histopathology in nine patients, and an area-to-area comparative study of the whole specimen section histopathology and MRI was performed in two patients. RESULTS: On the basis of an excisional biopsy or resection specimen, the nine lesions were classified into myxoid ( n=4), cellular ( n=3) and fibrous ( n=2) subtypes. Four myxoid lesions with a subcutaneous location showed a homogeneous SI comparable with muscle on T1-weighted images, high SI on T2-weighted images, and had homogeneous enhancement. One cellular lesion presented with homogeneous, slightly higher SI than muscle on T1-weighted images and inhomogeneous, high SI on T2-weighted images. Alcian blue stain of the whole specimen section revealed the lesion had two parts corresponding to different enhancement patterns on MRI. The blue-stained myxoid part showed markedly diffuse enhancement, while the non-stained cystic space had only peripheral enhancement. Two other cellular lesions had the same appearance on both T1- and T2-weighted images and showed inhomogeneous, diffuse enhancement. One fibrous subtype lesion presented with inhomogeneous, overall slightly higher SI than muscle on T1-weighted images, lower SI at the periphery and high SI in the center on STIR images and only peripheral enhancement. Microscopy and CD-31 staining of the lesion showed more extracellular matrix, with poor vascularity in the center and more collagenous matrix with higher vascularity at the periphery. CONCLUSION: Although similar findings were found in some lesions, the large histologic variability of NF hampers the definition of a prototype of NF on MRI. However, the MRI appearance of the myxoid subtype is rather characteristic. Histologic findings reflect the different SI characteristics and enhancement pattern on MRI.

Adolescent↗
PubMed2001

A unique pathway in the homing of murine multiple myeloma cells: CD44v10 mediates binding to bone marrow endothelium.

Our group recently reported that multiple myeloma (MM) cells preferentially adhere to bone marrow (BM) endothelial cells and selectively home to the BM, suggesting the involvement of specific adhesive interactions in this process. The highly regulated expression of CD44 variant isoforms (CD44v) on the MM cells makes them good candidate adhesion molecules involved in this homing. We addressed this in the 5T experimental mouse model of myeloma. Fluorescence-activated cell sorting analysis demonstrated expression of CD44v6, CD44v7, and CD44v10 on the in vivo growing 5T2MM and 5T33MM myeloma lines. Antibody blocking experiments revealed the involvement of CD44v10 in the adhesion of 5T2MM and 5T33MM cells to BM endothelial cells. Coinjection of anti-CD44v10 antibodies with the myeloma cells into syngeneic mice demonstrated a selective blocking of their BM homing which resulted in a decreased BM tumor load and serum paraprotein at the end stage of the disease. The highly restricted expression of CD44v10 on MM cells, the blocking of MM adhesion to BM endothelial cells and of homing to BM by anti-CD44v10, and the decreased BM tumor load suggest that myeloma cells home to the BM via interactions mediated by this specific region of the adhesion molecule CD44.

Animals↗
PubMed2001

In vivo homing and differentiation characteristics of mature (CD45-) and immature (CD45+) 5T multiple myeloma cells.

Multiple myeloma, a plasma cell malignancy, is predominantly localized in the bone marrow. These tumoral cells display a heterogeneous expression of CD45. It is, however, unclear which subpopulation is responsible for the homing and outgrowth of the myeloma cells. In this work, we investigated the in vivo homing, proliferation, and differentiation of both CD45+ and CD45- cells in two murine myeloma models.5T2MM and 5T33MM in vivo lines of murine multiple myeloma were used. CD45 and IGF-I receptor expression was analyzed by FACS. Proliferative capacity was assessed by in vivo bromodeoxyuridine incorporation. 5TMM cells were separated into CD45+ and CD45- fractions by MACS. Initial homing was investigated in vivo by tracing of radioactively labeled cells. Myeloma cells were detected by FACS and histology. Osteolytic lesions were analyzed by radiography. Both CD45+ and CD45- 5TMM cells were able to home to the bone marrow, although the migration of the latter subset was lower, which was related to a low IGF-I receptor expression. Recipients of both fractions developed myeloma as evidenced by the presence of serum paraprotein, osteolytic lesions, and bone marrow infiltration by myeloma cells. The tumor load in the recipients of CD45- cells was higher than the CD45+ cells, which could be explained by a lower proliferation rate of the latter population. While the separated cells before injection had a homogenous expression of CD45, cells isolated from the bone marrow of these terminally diseased mice had a heterogeneous expression pattern, indicating an in vivo differentiation pattern of CD45- to CD45+ cells and vice versa. We conclude that both CD45+ and CD45- 5TMM subpopulations contain clonogenic myeloma cells with bone marrow homing and proliferative capacity.

Animals↗
PubMed2001

Myeloma isotype-switch variants in the murine 5T myeloma model: evidence that myeloma IgM and IgA expressing subclones can originate from the IgG expressing tumour.

Isotype-switch variants can easily be detected in a significant proportion of multiple myeloma (MM) patients. The biological significance of these isotype-switch variants remains obscure. Therefore, we studied the appearance of these isotype-switch variants in two murine MM models, 5T2MM and 5T33MM, both of IgG isotype. With a MM-specific PCR assay we could detect isotype-switch variants in the bone marrow of both the 5T2MM and the 5T33MM bearing mice, reflecting again the close resemblance of this mouse model to the human MM. These isotype-switch variants were not found in an in vitro stroma-independent variant of the 5T33MM line. However, when this 5T33MMvitro line was injected into young syngeneic mice, isotype-switch variants appeared thereafter in the isolated tumour cells. These isotype-switch variants could only originate from the MM-IgG expressing cell since IgG subclones from the 5T33MMvitro line again gave rise to isotype-switch variants. The appearance of IgA cells can be explained by down-stream switching of IgG to IgA, while the emergence of IgM cells have to occur via trans-switching to the sister chromatid as the Cmu region is deleted from the CIS-chromosome. This study demonstrates that isotype-switch variants originate from the major tumour clone suggesting no role for the MM-IgM expressing cell as a pre-switch precursor MM cell. The appearance of isotype-switch variants should be considered as a rare but normal event now becoming visible due to the high number of clonal cells present in MM.

Amino Acid Sequence↗
PubMed2001

Cystosarcoma phyllodes of the prostate with rhabdomyoblastic differentiation.

A 36-year-old man presented with recurrent urinary obstruction and an enlarged, partially cystic prostate tumour on ultrasonography. Microscopically, the tumour was composed of cystically dilated ducts with leaf-like stromal projections in the lumen. A portion of the stroma was very cellular with atypia and a high mitotic rate. In addition, there was a small focus with well differentiated rhabdomyoblasts. This case is the second description of a cystosarcoma phyllodes of the prostate with rhabdomyoblasts differentiation. With radical surgery and chemotherapy only partial remission could be obtained.

Adult↗
PubMed2001

Surface of localized pleural plaques quantitated by computed tomography scanning: no relation with cumulative asbestos exposure and no effect on lung function.

To evaluate if there is a relation between the size of asbestos plaques and the level of past exposure and pulmonary function, we measured the surface of localized pleural plaques found on high-resolution (HR) CT scan, using a computerized video display unit-imaging system, in 73 workers (mean age, 43.5 yr) who had worked from 23 to 27 yr in an asbestos-cement factory. Their estimated cumulative exposure to asbestos ranged from 16.4 to 98.7 fiber-years/ ml (mean, 26.3 fiber-years/ml). Lung function measurements included lung volumes, maximal expiratory flows, and diffusing capacity. A control group of 21 workers was examined by the same procedures. Plaques were detected by CT in 51 (70%) asbestos-exposed subjects and in none of the control subjects. The average calculated plaque surface was 47.9 +/- 61.7 cm2 (median, 22.1 cm2; range, 0 to 278.4 cm2). There was no relation between plaque surface and cumulative asbestos exposure (p = 0.24). In the 51 subjects with pleural plaques, the surface of the pleural lesions was not related to cumulative asbestos exposure, or to smoking history or time since first exposure. Neither the presence nor the extent of the plaques was correlated with lung function parameters.

Asbestosis↗
PubMed2001

Observer variation in computed tomography of pleural lesions in subjects exposed to indoor asbestos.

To assess the reliability of computed tomography (CT) in detecting discrete pleural lesions, the interobserver and intra-observer variability in reading the conventional and high-resolution CT (HRCT) scans of 100 volunteers, who had worked for > or = 10 yrs in a building with known asbestos contamination, was evaluated. In the first session, pleural abnormalities were detected by a single radiologist (A1) in 13 subjects. In the second session, the scans were read again independently by the same radiologist (A2) and two other experienced radiologists (B, C). The final decision for the presence of pleural lesions was made in a final consensus reading. This gave a diagnosis of pleural abnormalities in 18 subjects, of whom eight (44%) had been detected by all three readers, five (28%) by two readers and four (22%) by only one reader; one scan, rated normal by all readers during the second session, was reconsidered because pleural abnormalities had been noted at the first reading (A1). The intra-observer agreement for reader A was good (kappa (kappa) 0.68) but the interobserver agreement between the readers was only fair to moderate (weighted kappa: A2-B=0.43, A2-C = 0.45, B-C = 0.26) in the second reading session. In conclusion, when looking for the prevalence of pleural lesions in indoor asbestos exposed subjects, the potential lack of consistency in reporting the presence of small pleural abnormalities must be borne in mind and strict precautions must be taken.

Adult↗
PubMed2001

Airborne polyvinyl alcohol (PVA) and cellulose fibre levels in fibre-cement factories in seven European countries.

Because of their relatively high diameter, polyvinyl alcohol (PVA) fibres, as used in fibre-cement, are not fibres as defined by WHO (or other) regulations. Nevertheless, as with all particulate raw materials, it can be questioned if and to what extent particles with critical fibrous dimensions might be generated by the handling or machining of this material. In order to investigate any tendency of PVA fibres to release airborne particles with critical fibrous dimensions (WHO fibres), static and/or personal samples were taken in eight fibre-cement factories at locations where potential exposures to PVA fibres were expected to be the highest. The following locations were surveyed: the PVA fibre weighing station, where PVA bales are opened mechanically and the PVA fibres are dispersed and weighed in a dry state; the fibre-cement slate punching machine; the slate 'riven edge' cutting machine or sheet sawing machine, whichever was present in the respective factories. Since cellulose fibres are an important constituent of fibre-cement, the organic fibre concentrations observed at the machining operations include cellulose. At each factory a control sample was taken in open air. Sampling, sample preparation and sample analysis by scanning electron microscopy (SEM) were performed according to standard German procedures. Only very low number concentrations of organic WHO fibres, ranging from below detection limit to 0.006 f/ml, were found. These levels are lower than the typical levels of organic fibres commonly found in the normal personal environment (0.009-0.02 f/ml), stemming from the release of particles by a person's activities and from clothing and other textiles (bed sheets, blankets, pillow,.). We conclude that the handling of PVA fibres as well as the machining of PVA and cellulose fibre containing cement products in the fibre-cement factories surveyed have a low potential to release fibres with critical fibrous (WHO) dimensions.

Air Pollutants↗