PubMed Health⌕ Search

Biomedical subjects

J Van Dijk

Publications and source records attributed to J Van Dijk.

At least 19 recordsLinked to original sources
PubMed2004

Quality control and reliability of reported doses.

Results of performance tests verifying the dosimetric properties of dosimetric systems are published in various reports (e.g. IAEA and EURADOS). However, there is hardly any information in the open literature relating to the uncertainty in a dose measurement or in the annual dose, which is increased by failure of the evaluation or data management system, damage of the dosemeter itself or by the loss of dosemeter. In this article, an attempt is made to estimate the importance of the above-mentioned conditions. This is achieved by sending questionnaires to about 200 approved dosimetric services in Europe. In total 88 questionnaires were returned and analysed. In the questionnaires, the frequency of occurrence of the various error conditions were investigated. Participants were also asked to evaluate the impact of the error condition from a dosimetric point of view and what countermeasures are taken. The article summarises all responses and compares different sources of errors according to their impact on the uncertainty of the resulting dose and gives a comprehensive overview on quality control actions and reliability on reported doses from European dosimetric services.

Body Burden↗
PubMed2000

Interaction of myosin with F-actin: time-dependent changes at the interface are not slow.

The kinetics of formation of the actin-myosin complex have been reinvestigated on the minute and second time scales in sedimentation and chemical cross-linking experiments. With the sedimentation method, we found that the binding of the skeletal muscle myosin motor domain (S1) to actin filament always saturates at one S1 bound to one actin monomer (or two S1 per actin dimer), whether S1 was added slowly (17 min between additions) or rapidly (10 s between additions) to an excess of F-actin. The carbodiimide (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, EDC)-induced cross-linking of the actin-S1 complex was performed on the subsecond time scale by a new approach that combines a two-step cross-linking protocol with the rapid flow-quench technique. The results showed that the time courses of S1 cross-linking to either of the two actin monomers are identical: they are not dependent on the actin/S1 ratio in the 0.3-20-s time range. The overall data rule out a mechanism by which myosin rolls from one to the other actin monomer on the second or minute time scales. Rather, they suggest that more subtle changes occur at the actomyosin interface during the ATP cycle.

Actins↗
PubMed2000

Comparison of conformal radiation therapy techniques within the dynamic radiotherapy project 'Dynarad'.

The objective of the dynamic radiotherapy project 'Dynarad' within the European Community has been to compare and grade treatment techniques that are currently applied or being developed at the participating institutions. Cervical cancer was selected as the tumour site on the grounds that the involved organs at risk, mainly the rectum and the bladder, are very close to the tumour and partly located inside the internal target volume. In this work, a solid phantom simulating the pelvic anatomy was used by institutions in Belgium, France, Greece, Holland, Italy, Sweden and the United Kingdom. The results were evaluated using both biological and physical criteria. The main purpose of this parallel evaluation is to test the value of biological and physical evaluations in comparing treatment techniques. It is demonstrated that the biological objective functions allow a much higher conformality and a more clinically relevant scoring of the outcome. Often external beam treatment techniques have to be combined with intracavitary therapy to give clinically acceptable results. However, recent developments can reduce or even eliminate this need by delivering more conformal dose distributions using intensity modulated external dose delivery. In these cases the reliability of the patient set-up procedure becomes critical for the effectiveness of the treatment.

European Union↗
PubMed1999

Functional characterization of the secondary actin binding site of myosin II.

The role of the interaction between actin and the secondary actin binding site of myosin (segment 565-579 of rabbit skeletal muscle myosin, referred to as loop 3 in this work) has been studied with proteolytically generated smooth and skeletal muscle myosin subfragment 1 and recombinant Dictyostelium discoideum myosin II motor domain constructs. Carbodiimide-induced cross-linking between filamentous actin and myosin loop 3 took place only with the motor domain of skeletal muscle myosin and not with those of smooth muscle or D. discoideum myosin II. Chimeric constructs of the D. discoideum myosin motor domain containing loop 3 of either human skeletal muscle or nonmuscle myosin were generated. Significant actin cross-linking to the loop 3 region was obtained only with the skeletal muscle chimera both in the rigor and in the weak binding states, i.e., in the absence and in the presence of ATP analogues. Thrombin degradation of the cross-linked products was used to confirm the cross-linking site of myosin loop 3 within the actin segment 1-28. The skeletal muscle and nonmuscle myosin chimera showed a 4-6-fold increase in their actin dissociation constant, due to a significant increase in the rate for actin dissociation (k(-)(A)) with no significant change in the rate for actin binding (k(+A)). The actin-activated ATPase activity was not affected by the substitutions in the chimeric constructs. These results suggest that actin interaction with the secondary actin binding site of myosin is specific for the loop 3 sequence of striated muscle myosin isoforms but is apparently not essential either for the formation of a high affinity actin-myosin interface or for the modulation of actomyosin ATPase activity.

Actins↗
PubMed1999

Differences in the ionic interaction of actin with the motor domains of nonmuscle and muscle myosin II.

Changes in the actin-myosin interface are thought to play an important role in microfilament-linked cellular movements. In this study, we compared the actin binding properties of the motor domain of Dictyostelium discoideum (M765) and rabbit skeletal muscle myosin subfragment-1 (S1). The Dictyostelium motor domain resembles S1(A2) (S1 carrying the A2 light chain) in its interaction with G-actin. Similar to S1(A2), none of the Dictyostelium motor domain constructs induced G-actin polymerization. The affinity of monomeric actin (G-actin) was 20-fold lower for M765 than for S1(A2) but increasing the number of positive charges in the loop 2 region of the D. discoideum motor domain (residues 613-623) resulted in equivalent affinities of G-actin for M765 and for S1. Proteolytic cleavage and cross-linking approaches were used to show that M765, like S1, interacts via the loop 2 region with filamentous actin (F-actin). For both types of myosin, F-actin prevents trypsin cleavage in the loop 2 region and F-actin segment 1-28 can be cross-linked to loop 2 residues by a carbodiimide-induced reaction. In contrast with the S1, loop residues 559-565 of D. discoideum myosin was not cross-linked to F-actin, probably due to the lower number of positive charges. These results confirm the importance of the loop 2 region of myosin for the interaction with both G-actin and F-actin, regardless of the source of myosin. The differences observed in the way in which M765 and S1 interact with actin may be linked to more general differences in the structure of the actomyosin interface of muscle and nonmuscle myosins.

Actins↗
PubMed1998

Effect of ATP analogues on the actin-myosin interface.

The interaction between skeletal myosin subfragment 1 (S1) and filamentous actin was examined at various intermediate states of the actomyosin ATPase cycle by chemical cross-linking experiments. Reaction of the actin-S1 complex with 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide and N-hydroxysuccinimide generated products with molecular masses of 165 and 175 kDa, in which S1 loops of residues 626-647 and 567-578 were cross-linked independently to the N-terminal segment of residues 1-12 of one actin monomer, and of 265 kDa, in which the two loops were bound to the N termini of two adjacent monomers. In strong-binding complexes, i.e., without nucleotide or with ADP, S1 was sequentially cross-linked to one and then to two actin monomers. In the weak-binding complexes, two types of cross-linking pattern were observed. First, during steady-state hydrolysis of ATP or ATPgammaS at 20 degreesC, the cross-linking reaction gave rise to a small amount of unknown 200 kDa product. Second, in the presence of AMPPNP, ADP.BeFx, ADP.AlF4-, or ADP.VO43- or with S1 internally cross-linked by N,N'-p-phenylenedimaleimide, only the 265 kDa product was obtained. The presence of 200 mM salt inhibited cross-linking reactions in both weak- and strong-binding states, while it dissociated only weak-binding complexes. These results indicate that, in the weak-binding state populated with the ADP.Pi analogues, skeletal S1 interacts predominantly and with an apparent equal affinity with the N termini of two adjacent actin monomers, while these ionic contacts are much less significant in stabilizing the rigor actin-S1 complexes. They also suggest that the electrostatic actin-S1 interface is not influenced by the type of ADP.Pi analogue bound to the active site.

Actins↗
PubMed1998

[Mechanisms of action and cellular functions of molecular motors].

Cytoskeleton based molecular motors support most of the cellular movements and by consequence they are associated with a variety of human disorders. The wide functional diversity of these molecular motors is now explained by the presence of three different families: the myosin, kinesin and dynein families. Although they are functionally distinct, these motors present unexpected structural homologies at the ATP and actin or microtubule binding sites. However, these homologies do not seem sufficient to design a common molecular mechanism which allows these proteins to move along the cytoskeleton.

Actins↗
PubMed1997

Quality assurance in conformal radiotherapy: DYNARAD consensus report on practice guidelines.

BACKGROUND AND PURPOSE: Conformal radiotherapy has only recently been widely implemented. Although not all aspects have yet been adequately proven, it is generally recognized that maintaining a high degree of precision throughout the process is critical to the treatment outcome while the focus for quality assurance and quality improvement will need to concentrate more on human factors, procedures, communication, organization and training. A general consensus document on quality assurance guidelines for institutions that deliver conformal radiotherapy treatments to patients has been elaborated within the framework of the DYNARAD/BIOMED concerted action on conformal radiotherapy. The present paper aims to highlight those issues that were identified as of specific importance to conformal radiotherapy. The work reported here further details this guidance by direct correlation with the issues involved in the special case of conformal radiotherapy. METHODS: The DYNARAD document has been drafted in the form of a desktop guide comprising six sets of guidelines and is based on the ESTRO advisory report on 'Quality Assurance in Radiotherapy'. RESULTS AND CONCLUSIONS: The document has been endorsed by the DYNARAD group of institutions. As such it can form the basis for further discussions and enter into the subsequent phase of expanding its consensus basis.

Consensus Statements as Topic↗
PubMed1992

Interleukin-1 alpha-stimulated fibroblast eicosanoid synthesis is not mediated by interleukin-6.

Adherent human dermal fibroblasts secreted interleukin-6, prostaglandin E2, prostaglandin I2 and 15-hydroxyeicosatetraenoic acid (assayed by radioimmunoassay) during a 3 h incubation period. Although human dermal fibroblasts did not secrete interleukin-1 alpha or interleukin-1 beta, human recombinant interleukin-1 alpha stimulated arachidonic acid metabolism and interleukin-6 synthesis. This effect was, at least partly, dependent on de novo protein synthesis. In contrast, human recombinant interleukin-6 had no effect on the synthesis and release of the eicosanoids measured. Human recombinant interleukin-1 alpha also stimulated the metabolism of [14C]arachidonic acid, but only if fibroblast were pre-incubated with the cytokine for three hours. Our data indicate that (a) fibroblasts secrete interleukin-6 but not interleukin-1, (b) interleukin-1 alpha, but not interleukin-6, stimulates fibroblast arachidonic acid metabolism and (c) the mechanisms involved in the metabolism of endogenous arachidonic acid are more sensitive to human recombinant interleukin-1 alpha than those involved in metabolism of the exogenous substrate.

Arachidonic Acid↗
PubMed1990

Effect of acidosis on skeletal muscle metabolism with and without propranolol.

Does the stimulatory effect of circulating catecholamines counteract the inhibitory effect of acidosis on skeletal muscle metabolism? To investigate this possibility, we studied gastrocnemii in dogs breathing either air (n = 10) or 4% carbon dioxide in air (n = 10) at rest and during contractions. In five dogs from each group, we infused propranolol into the arterial supply of the right and left muscles for 40 min. After 30 min of infusion, the left muscle was stimulated at 3 Hz for 10 min. During the 10th min of contractions, we removed and froze both muscles in liquid nitrogen. Oxygen uptake and blood flow to the left muscle prior to or during stimulation was not affected by acidosis either with or without propranolol. Glycogen concentration in resting muscle was unaffected by acidosis with or without propranolol. There was an acidosis related decrease of approximately 50% in the glycolytic intermediates (glucose 6-phosphate, fructose 1,6-diphosphate, alpha-glycerol phosphate, and dihydroxyacetone phosphate) in unstimulated muscles without beta-blockade. At rest, acidosis decreased muscle lactate by 50% with and 64% without propranolol, but lactate release was decreased only with acidosis without propranolol (1.4-0.1 mumols/kg.s). Acidosis without propranolol had no effect on the changes in glycogen concentration or the change in the concentration of glycolytic intermediates resulting from contractions. In beta-blocked muscle, the difference between stimulated and unstimulated concentrations of glycogen and glycolytic intermediates including lactate was 20-50% smaller with acidosis. Thus, with beta-blockade, the acidotic effects at rest disappeared and an inhibition of the metabolic adjustment to contractions appeared, indicating that circulating catecholamines do modify some metabolic effects of acidosis.

Acidosis↗
PubMed1989

Bispecific antibodies reactive with the multidrug-resistance-related glycoprotein and CD3 induce lysis of multidrug-resistant tumor cells.

We describe the lysis of multidrug-resistant (MDR) tumor cells by various lymphocytic effector cells, retargeted with bispecific antibodies (heteroconjugates). The Ab-heteroconjugate used was prepared by chemically cross-linking the OKT3 monoclonal antibody (MAb) reactive with CD3 antigen on T lymphocytes, with the MRK16 MAb, which recognizes the MDR-associated P-glycoprotein. Cloned TCR alpha beta/CD3+ T lymphocytes, OKT3-activated peripheral-blood mononuclear cells and peripheral-blood mononuclear blood lymphocytes, stimulated with allogeneic irradiated cells in a mixed lymphocyte culture, could be induced to lyse MDR ovarian tumor cells in the presence of Ab-heteroconjugate CD3/MRK16, whereas the drug-sensitive parental tumor cells lacking the P-glycoprotein were not lysed by these retargeted effector cells. Cloned TCR gamma delta/CD3+ T lymphocytes showed a high MHC-unrestricted lysis of MDR tumor cells. Addition of Ab-heteroconjugate CD3/MRK16 could therefore not enhance target-cell lysis. Melanoma tumor cells transfected with the mdr-I gene which codes for the P-glycoprotein were also efficiently lysed by Ab-heteroconjugate retargeted cloned TCR alpha beta/CD3+ T cells. Tumor cell lines derived from organs known to express the P-glycoprotein also were lysable by the retargeted effector cells.

Animals↗
PubMed1989

Actin cytoskeletal lesions in differentiated human colon carcinoma Caco-2 cells after exposure to soybean agglutinin.

We have investigated the effects of soybean agglutinin on the cytoskeletal element actin in differentiated Caco-2 cells. The actin cytoskeleton of the cells was visualized by fluorescence microscopy using 7-nitrobenz-2-oxa-1, 3-diazole phallacidin as a specific marker for F-actin. Compared with control Caco-2 cells no changes in the fluorescence pattern were observed after incubation with soybean agglutinin. However, using the deoxyribonuclease-I inhibition assay a dose-related response was noted in the increase of intracellular G-actin after a 2-hour incubation period with soybean agglutinin. Already after exposure for 15 min to soybean agglutinin a decrease in intracellular F-actin was demonstrable. This apparent depolymerization could be prevented by incubating the Caco-2 cells with soybean agglutinin and the appropriate monosaccharide simultaneously. The increase in the amount of G-actin appeared to be correlated with a shortening of microvilli on the Caco-2 cells.

Actins↗
PubMed1985

Asymmetry in the recognition of HLA-A3 molecules by virus-specific cytotoxic T cells.

Cytotoxic T cells specific for influenza virus A/HK or Epstein-Barr virus were used to study the heterogeneity of the HLA-A3 molecule. Variability of the recognition of HLA-A3 in both systems was observed. The hierarchy was both effector cell and target cell specific. An extreme example of the hierarchy of HLA-A3 recognition is the following. Virus-specific cytotoxic T lymphocytes of a given donor were found to recognize all HLA-A3-matched target cells, including target cells of a donor from whom the virus-specific effector cells did not recognize target cells of that given donor: Donor A recognizes target B but donor B does not recognize target A. Both will recognize a third HLA-A3-matched target cell C. Cold target inhibition studies confirmed that the recognition of target cell B by effector cell A involved the recognition of only HLA-A3. Examples of such asymmetric recognition were found in both influenza A and Epstein-Barr virus-specific cytotoxic T-lymphocyte responses but not one combination was asymmetric in both systems. This suggests that influenza virus A/HK-specific cytotoxic T lymphocytes recognize other HLA-A3 histotopes than do Epstein-Barr virus-specific cytotoxic T lymphocytes.

HLA Antigens↗
PubMed1982

The effects of hypercapnia on the metabolic response to steady-state exercise.

Studies on isolated muscle and resting man have demonstrated that altering CO2 stores influences intracellular lactate production and/or tissue lactate release. In the present project, subjects (N = 6) performed steady-state exercise for 30 min while inspiring 0, 2, 4, or 6% CO2 and 21% O2. They were tested on eight occasions, four at 50% and four at 65% VO2max. Arterialized venous blood PCO2 increased in proportion to FICO2 (P less than 0.05). Blood pH had a similar but inverse relationship, decreasing from 7.371 to 7.233 (P less than 0.05). The VI increased directly with PCO2 (P less than 0.05), but no differences were found for VO2 or VO2. The R decreased in proportion to PCO2 (P less than 0.05) at both exercise intensities. Blood lactate was reduced (P less than 0.05) with CO2. At 65% VO2max lactate had an inverse linear relationship with blood PCO2 (P less than 0.05). The mean lactate decreased 43% from 3.88 mM . l-1 with 0% CO2 to 2.22 mM . l-1 with 6% CO2. The R shift suggest that carbohydrate metabolism may have been inhibited and lipid metabolism enhanced.

Acidosis, Respiratory↗
PubMed1980

The effects of hypercapnia on metabolic responses to progressive exhaustive work.

Altering CO2 storage has been shown to influence lactate metabolism. However, the metabolic effects on man during physical activity have not been well documented. Subjects (n = 8) performed a progressive bicycle test (beginning at 0 and increasing 30 W every 4 min to exhaustion) on two occasions (once inspiring compressed air and once 4% CO2 and 21% O2). The work time, peak Vo2, VCO2, and HR achieved were the same in the two trials for each subject. The VI was significantly (p less than or equal to 0.05) elevated throughout the CO2 work and the recovery. The O2 debt increased from a mean of 5.87 to 7.761 with CO2, although the difference was not significant. Blood lactate was lower (p less than or equal to 0.05) from the onset of the work and throughout both the exercise and the 30 min. recovery period. Peak lactate was decreased from a mean of 9.59 to 6.99mM.1(-1). The oxygen cost of the work was not altered but the blood lactate response to the activity was significantly depressed. The reduction in lactate could be due to glycolytic inhibition and enhanced fat metabolism. The data support, but do not prove, this hypothesis.

Adult↗