Els Rhijnsburger | Maastrichtuniversity, Faculty Of Health, Medicine And Life Sciences (original) (raw)

Uploads

Papers by Els Rhijnsburger

International Journal of Cancer, 1983

DBNZ mice which are neonatally infected with Rauscher helper virus (R-MuLV) develop predominantly... more DBNZ mice which are neonatally infected with Rauscher helper virus (R-MuLV) develop predominantly lymphatic leukemias. From one of these lymphatic leukemias we established a permanent cell line which we named RLD (Rauscher Lymphoid DBAD). Phenotyping of this cell line with a panel of monoclonal antibodies directed to cell-surface determinants shows that RLD cells have T-cell characteristics: they bind monoclonal antibodies directed to the antigens Thy-I, T-200 and Lyt-I ; they do not react with anti-Lyt-2 antibodies, nor do they react with antibodies directed to determinants on B cells or myelomonocytic cells. RLD cells show a high activity of the nuclear enzyme terminal deoxyribonucleotidyl transferase (TdT).

International Journal of Cancer, 1988

Hybridomas producing syngeneic monoclonal antibodies (MAbs) were prepared by fusion of spleen cel... more Hybridomas producing syngeneic monoclonal antibodies (MAbs) were prepared by fusion of spleen cells of BALB/c mice, which were immunized with sublethal doses of RMB-1 cells. This cell line originates from a Rauscher virus (R-MuLV)-induced myeloid leukemia and forms tumors when re-inoculated into mice. MAbs were characterized as regards their reactivity against virally and non-virally induced cell lines. Two selected MAbs, ICSF5 and 4D2B4, were analyzed further. Their binding to subcellular structures was determined, and so were the properties of the antigens to which they are directed. MAb IC5F5 is of the IgG2A and 4D2B4 of the IgG2b subclass. Both bind to R-MuLV-infected or -transformed cell lines and are not mutually competitive. The antibodies do not react with other murine and human myeloid leukemic cells. As shown by immuno-electron microscopy, these MAbs have affinity to the cell membrane of non-virus producing RMB-1 cells. When lysates of purified virus were analyzed, the MAbs were found to be directed to the gag precursor protein Pr65, and one of them (IC5F5) also to be directed to the core protein p12. In RMB-1 cells, binding occurs to a 50-kDa glycoprotein and 2 proteins of 26 and 29 kDa. Since RMB-1 cells do not produce virus, but express aberrant viral proteins, these MAbs are tumor-specific and useful for immunotherapy.

Archives of Virology, 1989

After transfection of NIH 3T3 cells with DNA from molecularly cloned Rauscher MuLV, virus was iso... more After transfection of NIH 3T3 cells with DNA from molecularly cloned Rauscher MuLV, virus was isolated which showed a disease spectrum comparable to that of R-MuLV cloned biologically by endpoint dilution. In both cases sites of proviral integration vary from 2–5 per leukemic tissue and occur apparently at random.

Cell Differentiation, 1981

Cancer Immunology Immunotherapy, 1988

The binding of the syngeneic monoclonal antibodies IC5F5 and 4D2B4 to Rauscher virus-induced myel... more The binding of the syngeneic monoclonal antibodies IC5F5 and 4D2B4 to Rauscher virus-induced myeloid leukemic (RMB-1) cells was analyzed in vivo in tumor-bearing BALB/c mice. To verify it these antibodies bind specifically to RMB-1 cells, purified antibodies were iodinated with the isotopes 125I and 131I. Mice previously inoculated with tumor cells were injected with these labeled monoclonal antibodies and the plasma clearance and the tissue distribution were determined. The clearance in tumor-bearing animals was faster than in control mice. The tissue distribution was corrected for nonspecific accumulation by scoring for an unrelated antibody. Calculation of a localization index showed that IC5F5 binds at least 4.5 times more specifically to tumor cells than to other tissues. A preferential localization of radioactivity in s.c. tumor tissue was seen in the scanning of animals injected with 131I-labeled antibodies. The most direct proof of specific binding was observed in autoradiograms of animals treated with 125I-labeled antibodies. Small islands of tumor cells in the livers of mice inoculated i.v. had a high density of grains compared to other tissues and also compared to tumor cells in mice treated with unrelated monoclonal antibodies. These results show efficient targeting of these monoclonal antibodies and make immunotherapy of these myeloid leukemic cells possible.

Nutrition and Cancer-an International Journal, 1997

A water extract of raw garlic (RGE) and two organosulfur compounds, diallyl sulfide and S‐allylcy... more A water extract of raw garlic (RGE) and two organosulfur compounds, diallyl sulfide and S‐allylcysteine (SAC), were evaluated for their relative effectiveness in reducing benzo[a]pyrene (BaP)‐DNA adduct formation in stimulated human peripheral blood lymphocytes in vitro. In replicate experiments, RGE significantly inhibited BaP‐DNA adduct formation at concentrations of 0.001, 0.01, and 0.1 mg/ml. SAC also significantly decreased BaP‐DNA adduct formation at concentrations of 0.01 and 0.1 mg/ml. For diallyl sulfide, no significant reduction in BaP‐DNA adduct formation was found. BaP‐DNA adduct formation was not associated with cell viability or proliferation of peripheral blood lymphocytes after the various treatments. No clear scavenging activity was detected for the garlic constituents. Aryl hydrocarbon hydroxylase activity was not decreased, nor was formation of sulfate and glucuronide conjugates of 3‐hydroxy‐BaP increased in the presence of RGE and SAC, indicating that increased glutathione S‐transferase activity or a more efficient repair of BaP‐DNA adducts may explain the observed effects. In addition, reactive oxygen species‐induced 8‐oxodeoxyguanosine in DNA was reduced in the presence of SAC. It is concluded that raw garlic and SAC may be useful in the prevention of BaP‐associated tu‐morigenesis and that further evaluation of their preventive potential in humans at risk appears feasible.

Carcinogenesis, 1995

The food additive butylated hydroxyanisole (BHA) has been shown to induce gastrointestinal hyperp... more The food additive butylated hydroxyanisole (BHA) has been shown to induce gastrointestinal hyperplasia in rodents by an unknown mechanism. The relevance of this observation for human risk assessment is not clear. We therefore analysed the effect of BHA and its primary metabolites tert-butylhydroquinone (TBHQ) and tert-butylquinone (TBQ) on 8-oxo-deoxyguanosine formation and labelling induces in human lymphocytes in vitro. Analysis of culture medium and cell lysate fractions after administration of BHA or metabolites of BHA revealed that BHA and TBHQ undergo biotransformation in whole blood cultures. Moreover, TBQ can be reduced to TBHQ. While in cultures treated with BHA 50-60% of the dose administered was recovered, a much lower dose recovery was found in cultures treated with either TBHQ or TBQ. This indicates a considerable binding of these compounds to macromolecules. BHA and TBHQ, as well as TBQ, induced a dose-dependent increase in cell proliferation of phytohaemagglutinin-stimulated lymphocytes, 50 microM being the optimal dose. Since BHA is metabolized to TBHQ, it is not clear which compound is responsible for the proliferation enhancing effects observed in culture. Inhibition of IBHQ metabolism to its semiquinone radical by acetylsalicylic acid (ASA) reduced the increase in labelling indices induced by TBHQ. This indicates that this metabolic pathway is involved in the enhancement of cell proliferation induced by the hydroquinone. HPLC-ECD analysis of oxidative DNA damage in lymphocytes exposed to 10, 50 and 100 microM BHA, TBHQ or TBQ respectively showed that BHA was not capable of inducing oxidative DNA damage to a significant degree. TBQ and, in particular, TBHQ at a dose of 50 microM (the optimal dose for induction of cell proliferation), however, increased lymphocyte 7-hydroxy-8-oxo-2'-deoxyguanosine formation by 320 and 680% respectively. Inhibition of prostaglandin H synthase by ASA in cultures treated with TBHQ decreased the oxidation ratio significantly, confirming the significance of this enzyme system in the mechanism of toxicity of BHA.

Lancet, 1994

Horizontal lines indicate median values. Data were tested with Wilcoxon rank sum test (paired dat... more Horizontal lines indicate median values. Data were tested with Wilcoxon rank sum test (paired data). bronchopulmonary P aeruginosa infections, and whether any changes in eosinophil activity (ie, sputum ECP) could be detected before, during, and after antipseudomonal treatment.