Dutch agriculture and horticulture with a glance at South Korea : policies and results in the past, present en future

Dit rapport geeft inzicht in de huidige verschillen en overeenkomsten tussen Zuid-Korea en Nederland. Meer specifiek is ingegaan op de ontwikkelingen van de Nederlandse land- en tuinbouw in verleden, heden en toekomst en wat de voorwaarden zijn geweest voor de sterke internationale positie van de Neder landse land- en tuinbouw. Ook de ontwikkelingen in het beleid van de Europese Unie en de Nederlandse Overheid, het gehele agro!complex en het landelijk gebied zijn in deze studie beschouwd. In het rapport is ook een bijlage opgeno men met adressen van de meest belangrijke instanties, instituties en bedrijven rondom de land- en tuinbouwsecto

Synthesis and biodistribution of immunoconjugates of a human IgM and polymeric drug carriers

The synthesis and purification of radiolabelled immunoconjugates, composed of a human IgM monoclonal antibody directed against an intracellular tumour-associated antigen and either poly (alpha-L-glutamic acid) (PGA) or poly[N5-(2-hydroxyethyl)-L-glutamine] (PHEG) is described. Coupling of polymers to the antibody was performed through disulfide bond formation involving a single thiol group at the C-terminus of the polymer chain and 2-pyridyldisulfide groups introduced onto the antibody. The antibody was iodinated with 131I before conjugation. The polymers contained tyrosinamide in a low degree of substitution and were radiolabelled with 125I. 125I-labelled PGA and PHEG were found to be stable for at least 3 days in murine and human plasma. The biodistribution in mice of the doubly labelled immunoconjugates was studied and was compared with the pharmacokinetics of the individual components.\ud \ud PHEG showed a relatively slow blood clearance, the half-life being approximately 10 h with low uptake in liver, kidneys and spleen. PGA was rapidly cleared from the circulation and was significantly taken up in liver, kidneys and spleen. The biodistribution of both immunoconjugates was indistinguishable from that of the IgM proper, with plasma half-lives of approximately 6 h, indicating that the pharmacokinetic properties of the immunoconjugates are largely determined by the antibody part

Differential fMet-Leu-Phe- and Platelet-activating Factor-induced Signaling Toward Ral Activation in Primary Human Neutrophils

We have measured the activation of the small GTPase Ral in human neutrophils after stimulation with fMet- Leu-Phe (fMLP), platelet activating factor (PAF), and granulocyte macrophage-colony stimulating factor and compared it with the activation of two other small GTPases, Ras and Rap1. We found that fMLP and PAF, but not granulocyte macrophage-colony stimulating factor, induce Ral activation. All three stimuli induce the activation of both Ras and Rap1. Utilizing specific inhibitors we demonstrate that fMLP-induced Ral activation is mediated by pertussis toxin-sensitive G-proteins and partially by Src-like kinases, whereas fMLP-induced Ras activation is independent of Src-like kinases. PAFinduced Ral activation is mediated by pertussis toxininsensitive proteins, Src-like kinases and phosphatidylinositol 3-kinase. Phosphatidylinositol 3-kinase is not involved in PAF-induced Ras activation. The calcium ionophore ionomycin activates Ral, but calcium depletion partially inhibits fMLP- and PAF-induced Ral activation, whereas Ras activation was not affected. In addition, 12-O-tetradecanoylphorbol-13-acetate-induced activation of Ral is completely abolished by inhibitors of protein kinase C, whereas 12-O-tetradecanoylphorbol- 13-acetate-induced Ras activation is largely insensitive. We conclude that in neutrophils Ral activation is mediated by multiple pathways, and that fMLP and PAF induce Ral activation differently

Effecten prioriteitsverlegging natuurbeleid van de Rijksoverheid : achtergronddocument bij Natuurbalans 2003

Studie t.b.v. Natuurplanburea

Assessing the feasibility of stationary-phase-assisted modulation for two-dimensional liquid-chromatography separations

Two-dimensional liquid chromatography (2DLC) offers great separation power for complex mixtures. The frequently encountered incompatibility of two orthogonal separation systems, however, makes its application complicated. Active-modulation strategies can reduce such incompatibility issues considerably. Stationary-phase-assisted modulation (SPAM) is the most-common of these techniques, but also the least robust due to the major disadvantage that analytes may elute prematurely. The range of liquid chromatography (LC) applications continues to expand towards ever more complex mixtures. Retention modelling is increasingly indispensable to comprehend and develop LC separations. In this research, a tool was designed to assess the feasibility of applying SPAM in 2DLC. Several parameters were investigated to accurately predict isocratic retention of analytes on trap columns under dilution-flow conditions. Model parameters were derived from scanning-gradient experiments performed on analytical columns. The trap-to-trap repeatability was found to be similar to the prediction error. Dead volumes for the trap columns could not be accurately determined through direct experimentation. Instead, they were extrapolated from dead-volume measurements on analytical columns. Several known retention models were evaluated. Better predictions were found using the quadratic model than with the log-linear (“linear-solvent-strength”) model. Steep scanning gradients were found to result in inaccurate predictions. The impact of the dilution flow on the retention of analytes proved less straightforward than anticipated. Under certain conditions dilution with a weaker eluent was found to be counter productive. A tool was developed to quantify the effect of the dilution flow and to predict whether SPAM could be applied in specific situations. For nine different analytes under 36 different sets of conditions and with three different modulation times, the SPAM tool yielded a correct assessment in more than 95% of all cases (less than 5% false positives plus false negatives)

Synthesis and biological evaluation of immunoconjugates of adriamycin and a human IgM linked by poly[N5-(2-hydroxyethyl)-l-glutamine

The synthesis and purification of radiolabelled immunoconjugates, composed of a human IgM monoclonal antibody (IgM 16.88) directed against an intracellular tumour-associated antigen, the drug carrier poly[N5-(2-hydroxyethyl)--glutamine] (PHEG) and the cytostatic drug adriamycin (ADR) are described. The immunoconjugates were constructed to allow selective release of ADR in the putatively acidic environment of the tumour through a novel acid-labile maleamic acid linker. The conjugate of PHEG and the acid-labile ADR derivative effectively released ADR in cytotoxic amounts at a pH of 6.0 as judged from incubation in buffer and from inhibition of the growth of HT-29 colon tumour cells in vitro. Immunoconjugates were prepared by coupling of PHEG-ADR having a hydrolytically stable amide bond with 131I-labelled antibody through thioether bond formation involving a single thiol group at the C-terminus of the polymer chain and maleimido groups introduced onto th

Cardiovascular events in type 2 diabetes: comparison with nondiabetic individuals without and with prior cardiovascular disease - 10-year follow-up of the Hoorn Study

Aims: We questioned whether prior cardiovascular disease has the same impact on risk of cardiovascular events as type 2 diabetes, and whether this differed between men and women. Methods and results: To address these issues we compared the 10-year risk of cardiovascular events among 208 Caucasian individuals with diabetes to that of 2253 Caucasian individuals without diabetes, in a population-based cohort study. Gender significantly modified the association between type 2 diabetes and cardiovascular events (p=0.01). The hazard ratio of cardiovascular events associated with the presence of diabetes was higher in women (adjusted hazard ratio, 1.8; 95% CI, 1.2 to 2.7) than in men (adjusted hazard ratio, 1.3; 0.9 to 2). As compared to men without diabetes but with prior cardiovascular disease, risk of cardiovascular events was significantly lower in men with diabetes but without prior cardiovascular disease (adjusted hazard ratio, 0.5; 0.3 to 0.9). In contrast, this risk was equal in women with diabetes but without prior cardiovascular disease and women without diabetes but with prior cardiovascular disease (adjusted hazard ratio, 1.0; 0.6 to 1.7; P for interaction between gender and diabetes=0.05). Conclusions: Women with diabetes but without prior cardiovascular disease have a risk of cardiovascular events that is similar to that of women without diabetes but with prior cardiovascular disease, whereas in men the presence of prior cardiovascular disease conferred a higher risk. These data emphasise the necessity of aggressive treatment of cardiovascular risk factors in women with type 2 diabetes. © 2003 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved