Biomedical subjects

M Van Driel

Publications and source records attributed to M Van Driel.

3 recordsLinked to original sources

PubMed2002

CD44 variant isoforms are involved in plasma cell adhesion to bone marrow stromal cells.

Expression of CD44v9-containing isoforms (CD44v9) on myeloma plasma cells correlates with unfavorable prognosis, suggesting that CD44 variant molecules are involved in the disease process. In this study, the presence of CD44v on B cell lines from different stages of development was analyzed by flow cytometry and a role in adhesion to stromal cells from different tissues was evaluated in in vitro binding assays. CD44v3, v6 and v9 isoforms were exclusively expressed on plasma cell lines and CD44v9 expression correlated with IL-6-dependent plasma cell growth. Binding studies using CD44 isoform- specific reagents showed that CD44v6 and CD44v9 were involved in binding to bone marrow stromal cells, but not to in vitro synthesized ECM or hyaluronic acid. CD44v9-mediated plasma cell binding resulted in a significant induction of IL-6 secretion by bone marrow stromal cells. Large differences in quantitative plasma cell binding to stromal cells from different tissues were observed. These, however, could not be related to a differential use of CD44v in these binding processes. The role of CD44v9 in adhesion induced IL-6 secretion and its preferential expression on IL-6-dependent plasma cell lines may explain the previously observed correlation between CD44v9 expression and adverse prognosis in multiple myeloma.

Adult↗

PubMed2000

Response to flumazenil in women with premenstrual dysphoric disorder.

OBJECTIVE: The authors sought to determine whether the administration of flumazenil would induce marked panic symptoms in women suffering from premenstrual dysphoric disorder. METHOD: Ten women with premenstrual dysphoric disorder and 11 comparison subjects were injected with flumazenil or placebo in a double-blind, randomized, balanced crossover design in a single session in the luteal phase of their menstrual cycles. RESULTS: Flumazenil induced a much greater panic response in the women with premenstrual dysphoric disorder than in the comparison subjects. CONCLUSIONS: These preliminary results are consistent with a dysregulation of the g-aminobutyric acid A/benzodiazepine receptor complex during the premenstruum of women suffering from premenstrual dysphoric disorder.

Cross-Over Studies↗

PubMed1996

Different CD44 splicing patterns define prognostic subgroups in multiple myeloma.

CD44 variant isoforms (CD44v) are generated by alternative splicing of the nuclear RNA resulting in the expression of additional protein domains in the extracellular region of the CD44 standard molecule (CD44s). In multiple myeloma (MM), CD44 mediates binding of tumor cells to stroma and regulates interleukin-6 production. To evaluate the role of CD44v isoforms in MM, CD44v expression was analyzed by immunohistochemical staining of 64 bone marrow biopsies from 38 MM patients. Expression of variant isoforms containing the 9v domain was observed in 36% of cases and was associated with an advanced stage (P < .02; n = 61), a progressive disease (P < .001; n = 61), and a shorter overall survival (P < .02; n = 36). In contrast, 3v, 4v, 6v, or 10v isoforms were detected only in a small percentage of the patients. To analyze the exon composition in RNA-transcripts, reverse transcriptase polymerase chain reaction analyses followed by Southern hybridization with exon-specific probes were performed in fluorescence-activated cell sorted myeloma plasma cells. Tumors expressing the 9v domain showed complex, 9v-containing transcripts in combinations with the 3v, 7v, 8v, and 10v exons. Identical transcripts were detected in several myeloma cell lines and in a Ki-1 B-immunoblastic lymphoma. Similar to high-grade non-Hodgkin's lymphoma and gastric and renal cell carcinoma, overexpression of 9v-containing isoforms in MM is related to an unfavorable clinical presentation and represents a new prognostic parameter.

Adult↗