Search Results - (Author, Cooperation:M. Jules)

Pieters, Jules M.; Breuer, Klaus; Simons, P.Robert-Jan

Unknown

364 S.

3540529039

Recent Research in Psychology

2012-03-03

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Adaptation, Physiological ; Algorithms ; Bacillus subtilis/*genetics/*physiology ; Binding Sites ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; Gene Regulatory Networks ; Oligonucleotide Array Sequence Analysis ; *Promoter Regions, Genetic ; RNA, Antisense/genetics/metabolism ; RNA, Bacterial/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Regulon ; Sigma Factor/metabolism ; Terminator Regions, Genetic ; *Transcription, Genetic ; *Transcriptome

2012-03-03

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

*Adaptation, Physiological ; Algorithms ; Bacillus subtilis/*genetics/*metabolism ; Bacterial Proteins/metabolism ; Computer Simulation ; Data Interpretation, Statistical ; Gene Expression Regulation, Bacterial ; *Gene Regulatory Networks ; Genome, Bacterial ; Glucose/*metabolism ; Malates/*metabolism ; Metabolic Networks and Pathways/*genetics ; Metabolome ; Metabolomics ; Models, Biological ; Operon ; Promoter Regions, Genetic ; Transcription Factors/metabolism ; Transcription, Genetic

1746-8361

Blackwell Publishing Journal Backfiles 1879-2005

Philosophy

A general definition is given of what is comicality. Molière's Misanthrope then appears as a comedy on comedy. It is because of his universal and indignant censure of laugh that Alceste is ridiculous.

Electronic Resource

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] A pool of frog HMW plasma proteins, containing both the HMW Ig and the non-Ig cross-reactive component, was subjected either to periodate oxidation (to degrade carbohydrate determinants) or to reduction and alkylation in guanidine (to degrade protein determinants). After periodate treatment, the ...

Electronic Resource

0010-7565

General, Interdisciplinary

1432-0851

Key words: Doxorubicin immunoconjugate – Carcinoembryonic antigen conjugate – Internalization

Springer Online Journal Archives 1860-2000

Medicine

Abstract. An immunoconjugate between doxorubicin and anti-(carcinoembryonic antigen) (CEA) was prepared by using aminodextran (M r = 40 000) as the intermediate carrier, and the carbohydrate moiety of the antibody as the linking site. The resulting immunoconjugate was subjected to an in vitro evaluation for the internalization on the target cells (LoVo), and compared to that of unconjugated antibody, as well as the cellular uptake of unconjugated doxorubicin. The internalization was evaluated microscopically by following the translocation of the red fluorescence of doxorubicin and the green fluorescence of the fluorescein-isothiocyanate-labeled goat anti-(mouse Ig) antibody, which visualizes the location of the primary mouse antibody. Anti-CEA monoclonal antibody (NP-4) was found to internalize into LoVo cells. The immunoconjugate made with this antibody was similarly internalized, and the doxorubicin was found to distribute with the primary antibody. The cell surface and cytoplasm were the major compartments of their distribution. These results indicate that the drug molecules were indeed delivered into the cells by the antibody as an intact conjugate. Unconjugated doxorubicin, on the contrary, was quickly absorbed by the cells and concentrated in the nucleus within 30 min, and never showed a distribution in the cytoplasm or cell membrane as in the nucleus by this procedure. The intermediate drug conjugate, doxorubicin-dextran, did not show internalization. The internalization of NP-4 antibody (or the doxorubicin conjugate) was also confirmed by studying the intracellular catabolism of the cell-bound antibody (or conjugate). The release of the degraded antibody by the cells, as differentiated by trichloroacetic acid precipitation techniques, was considered an indication of internalization. Lysosomes were involved in the degradation, since the process was markedly inhibited in the presence of the lysosomal enzyme inhibitor, ammonium chloride.

Electronic Resource

1432-0851

Doxorubicin immunoconjugate ; Carcinoembryonic antigen conjugate ; Internalization

Springer Online Journal Archives 1860-2000

Medicine

Abstract An immunoconjugate between doxorubicin and anti-(carcinoembryonic antigen) (CEA) was prepared by using aminodextran (M r=40 000) as the intermediate carrier, and the carbohydrate moiety of the antibody as the linking site. The resulting immunoconjugate was subjected to an in vitro evaluation for the internalization on the target cells (LoVo), and compared to that of unconjugated antibody, as well as the cellular uptake of unconjugated doxorubicin. The internalization was evaluated microscopically by following the translocation of the red fluorescence of doxorubicin and the green fluorescence of the fluorescein-isothiocyanate-labeled goat anti-(mouse Ig) antibody, which visualizes the location of the primary mouse antibody. Anti-CEA monoclonal antibody (NP-4) was found to internalize into LoVo cells. The immunoconjugate made with this antibody was similarly internalized, and the doxorubicin was found to distribute with the primary antibody. The cell surface and cytoplasm were the major compartments of their distribution. These results indicate that the drug molecules were indeed delivered into the cells by the antibody as an intact conjugate. Unconjugated doxorubicin, on the contrary, was quickly absorbed by the cells and concentrated in the nucleus within 30 min, and never showed a distribution in the cytoplasm or cell membrane as in the nucleus by this procedure. The intermediate drug conjugate, doxorubicin-dextran, did not show internalization. The internalization of NP-4 antibody (or the doxorubicin conjugate) was also confirmed by studying the intracellular catabolism of the cell-bound antibody (or conjugate). The release of the degraded antibody by the cells, as differentiated by trichloroacetic acid precipitation techniques, was considered an indication of internalization. Lysosomes were involved in the degradation, since the process was markedly inhibited in the presence of the lysosomal enzyme inhibitor, ammonium chloride.

Electronic Resource

1432-0851

Key words: Antibody immunotherapy  –  Antibody internalization

Springer Online Journal Archives 1860-2000

Medicine

Summary. In order to obtain rapid blood clearance of circulating antibodies (Ab) at a desired time, cross-linking reagents such as second Ab are often employed. Such reagents will generally bind to Ab located at the tumor site as well as free Ab, and we therefore investigated whether the cross-linking of Ab bound to the surface of tumor cells affects the processing of those Ab. Cross-linking was induced in various ways: a polyclonal second Ab [rabbit anti-(mouse IgG)], a monoclonal rat anti-(mouse IgG constant region) Ab, and streptavidin used in conjunction with a biotinylated first Ab. Processing was followed for 3 days, to allow nearly all of the bound Ab to reach its ultimate fate. Results depended strongly on the particular first Ab used. Two basic effects were observed. First, the second Ab efficiently prevented the early dissociation of intact Ab from the cell; once the second Ab bound, there was virtually no dissociation of the primary Ab bound to the cells. For most Ab, where only a small proportion of bound Ab dissociated intact, this effect was relatively small. However, for an unusual Ab, where the majority dissociated intact (L6) the effect of a second Ab in prolonging Ab retention by the cell was dramatic. Second, cross-linking sometimes resulted in markedly accelerated internalization and degradation of the bound Ab, coupled with the release of degradation products into the medium. This process resulted in much shorter retention of the radioisotope by the cell. If a “residualizing” radiolabel was used, 125I-dilactitoltyramine, which is probably trapped within lysosomes after Ab catabolism, the effect of the second Ab in accelerating loss from the cell was largely prevented. We also tested anti-idiotype Ab as cross-linking reagents. In addition to testing anti-idiotype Ab known to react with the cell-bound primary Ab, we also tested anti-idiotype Ab not expected to bind to cell-bound Ab, initially as a negative control. Unexpectedly, all anti-idiotype Ab tested induced rapid release of the primary Ab from the cell. This effect was similar to the effect of a large excess of unlabeled Ab, and we attribute it to the blocking of the free binding site of a “wobbling” Ab, which prevents its re-binding to a second antigen molecule. We conclude that the use of selected anti-idiotype Ab to clear circulating Ab, while not reacting with cell-bound Ab, must be done cautiously. These effects must be taken into consideration in developing procedures that utilize second Ab or other cross-linking agents.

Electronic Resource

1432-0851

Antibody immunotherapy ; Antibody internalization

Springer Online Journal Archives 1860-2000

Medicine

Summary In order to obtain rapid blood clearance of circulating antibodies (Ab) at a desired time, cross-linking reagents such as second Ab are often employed. Such reagents will generally bind to Ab located at the tumor site as well as free Ab, and we therefore investigated whether the cross-linking of Ab bound to the surface of tumor cells affects the processing of those Ab. Cross-linking was induced in various ways: a polyclonal second Ab [rabbit anti-(mouse IgG)], a monoclonal rat anti-(mouse IgG constant region) Ab, and streptavidin used in conjunction with a biotinylated first Ab. Processing was followed for 3 days, to allow nearly all of the bound Ab to reach its ultimate fate. Results depended strongly on the particular first Ab used. Two basic effects were observed. First, the second Ab efficiently prevented the early dissociation of intact Ab from the cell; once the second Ab bound, there was virtually no dissociation of the primary Ab bound to the cells. For most Ab, where only a small proportion of bound Ab dissociated intact, this effect was relatively small. However, for an unusual Ab, where the majority dissociated intact (L6) the effect of a second Ab in prolonging Ab retention by the cell was dramatic. Second, cross-linking sometimes resulted in markedly accelerated internalization and degradation of the bound Ab, coupled with the release of degradation products into the medium. This process resulted in much shorter retention of the radioisotope by the cell. If a “residualizing” radiolabel was used,125I-dilactitoltyramine, which is probably trapped within lysosomes after Ab catabolism, the effect of the second Ab in accelerating loss from the cell was largely prevented. We also tested anti-idiotype Ab as cross-linking reagents. In addition to testing anti-idiotype Ab known to react with the cell-bound primary Ab, we also tested antiidiotype Ab not expected to bind to cell-bound Ab, initially as a negative control. Unexpectedly, all anti-indiotype Ab tested induced rapid release of the primary Ab from the cell. This effect was similar to the effect of a large excess of unlabeled Ab, and we attribute it to the blocking of the free binding site of a “wobbling” Ab, which prevents its rebinding to a second antigen molecule. We conclude that the use of selected anti-idiotype Ab to clear circulating Ab, while not reacting with cell-bound Ab, must be done cautiously. These effects must be taken into consideration in developing procedures that utilize second Ab or other crosslinking agents.

Electronic Resource

1432-0851

Springer Online Journal Archives 1860-2000

Medicine

Summary Binding parameters were determined for four mouse monoclonal antibodies reacting with three antigens on the surface of fresh human ovarian carcinoma ascites cells, under nearly physiological conditions. The object of these experiments was to aid in the selection of the optimal monoclonal antibodies for intraperitoneal immunotherapy. The number of antigenic sites per cell, the effective equilibrium association constant (affinity) and the half-life for dissociation were: for Ab MH99, 1.2×106 sites/cell, (1.9−4.1)×108M−1, and 4 h; for Ab MX35, (3.2−4.1)×105 sites/cell, (3.4−4.8)×108M−1, and 〉10 h; and for Ab MW207, 1.3×105 sites/cell, (3.6−4.1)×109M−1, and 3.1 h, respectively. One of the antigens, MH99, is recognized by five different monoclonal antibodies, and competitive inhibition experiments demonstrated that two distinct determinants are present; this antigen is also recognized by the previously described Ab 17-1A. These binding data will aid the rational design of immunotherapy strategies.

Electronic Resource

1432-0851

Key words B-cell non-Hodgkin’s lymphoma ; Radioimmunodetection ; Radioimmunotherapy ; Anti-CD22 monoclonal antibody ; Internalization ; Radioactive metals ; Residualizing iodine label

Springer Online Journal Archives 1860-2000

Medicine

Abstract  LL2 is an anti-CD22 pan-B-cell monoclonal antibody which, when radiolabeled, has a high sensitivity for detecting B-cell, non-Hodgkin’s lymphoma (NHL), as well as an antitumor efficacy in therapeutic applications. The aim of this study was to determine whether intracellularly retained radiolabels have an advantage in the diagnosis and therapy of lymphoma with LL2. In vitro studies showed that iodinated LL2 is intracellularly catabolized, with a rapid release of the radioiodine from the cell. In contrast, residualizing radiolabels, such as radioactive metals, are retained intracellularly for substantially longer. In vivo studies were performed using LL2-labeled with radioiodine by a non-residualizing (chloramine-T) or a residualizing method (dilactitol-tyramine, DLT), or with a radioactive metal (111In). The biodistribution of a mixture of 125I (non-residualizing chloramine-T compared to residualizing DLT), 111In-labeled LL2 murine IgG2a or its fragments [F(ab′)2, Fab′], as well as its humanized, CDR-grafted form, was studied in nude mice bearing the RL human B-cell NHL cell line. Radiation doses were calculated from the biodistribution data according to the Medical International Radiation Dose scheme to assess the potential advantage for therapeutic applications. At all assay times, tumor uptake was higher with the residualizing labels (i.e., 111In and DLT-125I) than with the non-residualizing iodine label. For example, tumor/blood ratios of 111In-labeled IgG were 3.2-, 3.5- and 2.8-fold higher than for non-residualizing iodinated IgG on days 3, 7 and 14, respectively. Similar results were obtained for DLT-labeled IgG and fragments with residualized radiolabels. Tumor/organ ratios also were higher with residualizing labels. No significant differences in tumor, blood and organ uptake were observed between murine and humanized LL2. The conventionally iodinated anti-CD20 antibody, 1F5, had tumor uptake values comparable to those of iodinated LL2, the uptake of both antibodies being strongly dependent on tumor size. These data suggest that, with internalizing antibodies such as LL2, labeling with intracellularly retained isotopes has an advantage over released ones, which justifies further clinical trials with residualizing 111In-labeled LL2 for diagnosis, and residualizing 131I and 90Y labels for therapy.

Electronic Resource

1432-0851

Key words CD74 ; Radiolabeled Ab ; Radioimmunotherapy ; B cell lymphoma ; Major histocompatibility complex class II invariant chain

Springer Online Journal Archives 1860-2000

Medicine

Abstract The tumor-specific localization of an anti-CD74 Ab, LL1, was demonstrated in nude mice bearing xenografts of human B-cell lymphoma. This Ab, conjugated to radionuclides emitting Auger electrons, including 125I and 111In, was previously reported to kill tumor cells in vitro effectively and specifically. The cytotoxic potency of this Ab is due to its uptake and catabolism at a very high level, which also affected the Ab biodistribution experiments. Thus, Ab localization to the tumor was only detected if a “residualizing” radiolabel was used, meaning a label that is trapped within cells, usually within lysosomes, after catabolism of the Ab to which it was conjugated. Similar results were obtained with three different residualizing labels: 111In conjugated via the chelators benzyl diethylenetriaminepentaacetic acid (DTPA) or 1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA), or 131I-dilactitol-tyramine, a residualizing form of iodine. The Ab protein dose could be high, 0.5 mg/mouse, without causing a decrease in specific tumor uptake, probably reflecting the high capacity for uptake. Moreover, tumors of moderate size were found to cause rapid, specific removal of the Ab from the blood, also a result of catabolic processes. This induced blood clearance naturally affected the Ab localization experiments, but this factor could be circumvented by increasing the Ab protein dose. Using a different Ab, anti-(mature MHC class II), the ability of Ab to penetrate relatively large solid tumors was investigated. Complete saturation of antigenic sites was observed in tumors up to 0.3 g in size, but quite high Ab protein doses were required, 5.0 mg/mouse. These results provide a rationale for attempting therapy with radiolabeled LL1.

Electronic Resource

book

1999

Unterrichtsforschung ; Geschichte (Histor) ; Aufsatzsammlung ; Twente

Dutch

Online

2004

Kognitionspsychologie ; Entdeckendes Lernen ; Lernen ; Lernprozess ; Lernumgebung ; Wissenserwerb ; Unterrichtsgestaltung ; Computerunterstützter Unterricht ; Selbst gesteuertes Lernen ; Gestaltung

European educational research journal, Bd. 3 (2004) H. 1, S. 77-100, 1474-9041

German

Literaturangaben 69

book

1988

Dutch

book

1989

Dutch

book

1990

Computerunterstützter Unterricht

Dutch

book

1990

Computerunterstützter Unterricht ; Erwachsenenbildung

Dutch

book

1990

Kognitive Entwicklung ; Lernpsychologie ; Lehrer ; Lehrerverhalten ; Schüler ; Unterrichtsplanung ; Unterrichtsmaterial ; Unterrichtstechnologie

English