Search PubMed⌕ Search

Biomedical subjects

J A Mulder

Publications and source records attributed to J A Mulder.

At least 19 recordsLinked to original sources

Violations and errors during simulation-based driver training.

The effectiveness of virtual driving instruction can increase when techniques that automatically distinguish between violations and errors are available, two behaviours requiring different types of remediation. This study reports the analysis of the objectively measured performance of 520 participants completing a simulation-based training programme. Factor analysis of failure reasons showed that violations and errors were the primary underlying factors. Men committed more violations and women made more errors; the magnitude of sex differences corresponded to the factor loadings. Factor analysis of the mean task completion times yielded a factor that can be described as the extent to which motivation for speed resulted in quicker task execution. Quicker participants completed more tasks, committed more violations, but made fewer errors. Participants reduced errors during forced-paced driving and increased speed during self-paced driving. The authors would recommend exploiting the distinction between violations and errors by developing interfaces and feedback for both types of aberration.

Accidents, Traffic↗

The first regioselective alpha-deprotonation and functionalization of allenamides. An application in intramolecular Pauson-Khand-type cycloadditions.

[rection: see text] The first regioselective alpha-deprotonation and functionalization of electron-deficient allenamines are described here. The acidities of alpha- and gamma-allenic protons of these allenamides are readily differentiated using strong bases, thereby allowing regioselective substitutions at either the alpha- or gamma-allenic position. A specific synthetic application of the novel alpha-substituted allenamides in intramolecular Pauson-Khand-type cycloadditions is also described here.

Journal Article↗

Synthesis of dihydroxanthone derivatives and evaluation of their inhibitory activity against acetylcholinesterase: unique structural analogs of tacrine based on the BCD-ring of arisugacin.

A general approach to synthesis of dihydroxanthone derivatives is described here. In vitro evaluation of these dihydroxanthones demonstrated that some derivatives possess moderate anti-cholinesterase activities and better selectivities than tacrine for acetylcholinesterase over butyrylcholinesterase. Structural effects on anti-cholinesterase activities were also examined, and docking experiments were carried out to provide preliminary understandings of these experimental observations.

Acetylcholinesterase↗

Inflammatory mediators in children with protein-energy malnutrition.

Edema is a typical sign in kwashiorkor, which is present in a subset of patients with protein-energy-malnutrition (PEM). The pathophysiology of this edema is not well established. One of the abnormalities found in kwashiorkor is reduced concentrations of antioxidants, suggesting a compromised capacity to neutralize free radicals, which are known to induce tissue damage. We have studied plasma concentrations of several mediators of the inflammatory cascade. Concentrations of interleukin 6 (IL-6), C-reactive protein, and the soluble receptors of tumor necrosis factor alpha (sTNFR-p55 and sTNFR-p75) are greater in children with PEM, particularly in those with kwashiorkor, whereas soluble receptors of IL-6 (sIL6R-gp80) and IL-1 receptor antagonist concentrations are not significantly different from those of healthy children. In addition, concentrations of IL-6, sTNFR-p55, and sTNFR-p75 are greater in kwashiorkor patients irrespective of the presence of infection. Antioxidant status, as determined by plasma concentrations of glutathione and vitamin E, is significantly reduced in kwashiorkor patients. These data support the notion that children with edematous malnutrition show increased inflammatory reactivity that may contribute to edema formation.

Antioxidants↗

Differential induction of pro- and anti-inflammatory cytokines in whole blood by bacteria: effects of antibiotic treatment.

The in vitro production of interleukin-1beta (IL-1beta), IL-6, and the IL-1 receptor antagonist (IL-1ra) in whole blood upon stimulation with different bacterial strains was measured to study the possible relationship between disease severity and the cytokine-inducing capacities of these strains. Escherichia coli, Neisseria meningitidis, Neisseria gonorrhoeae, Bacteroides fragilis, Capnocytophaga canimorsus, Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Streptococcus pyogenes induced the cytokines IL-1beta, IL-6, and IL-1ra. Gram-negative bacteria induced significantly higher levels of proinflammatory cytokine production than gram-positive bacteria. These differences were less pronounced for the anti-inflammatory cytokine IL-1ra. In addition, blood was stimulated with E. coli killed by different antibiotics to study the effect of the antibiotics on the cytokine-inducing capacity of the bacterial culture. E. coli treated with cefuroxime and gentamicin induced higher levels of IL-1beta and IL-6 production but levels of IL-1ra production similar to that of heat-killed E. coli. In contrast, ciprofloxacin- and imipenem-cilastatin-mediated killing showed a decreased or similar level of induction of cytokine production as compared to that by heat-killed E. coli; polymyxin B decreased the level of production of the cytokines.

Anti-Bacterial Agents↗

Persistent Yersinia enterocolitica infection in three rat strains.

Yersinia enterocolitica may persist for prolonged periods of time in humans sometimes resulting in the development of reactive arthritis. To elucidate factors predisposing for persistence we developed animal models. In Lewis and Fischer rats, viable bacteria could be demonstrated for prolonged time and abscesses could be found in the liver, spleen and lungs. Splenic abscesses were observed for more than 20 weeks. Yersinia enterocolitica persisted in Lewis and Fischer rats, but only Lewis rats developed reactive arthritis. In Brown Norway rats abscesses developed early during infection but in contrast to the other strains disappeared after 3 weeks. Culture of homogenized abscess-containing tissue of all three rat strains yielded Yersiniae. Immunofluorescence studies of the abscesses showed diffuse staining inside the abscesses only, indicating the presence of Yersinia enterocolitica antigen. Brown Norway rats, in contrast to Lewis and Fischer rats, developed a different serological reaction pattern against Yersinia enterocolitica antigens and this correlated with the disappearance of the abscesses.

Animals↗

In-vitro antimicrobial susceptibility of Yersinia enterocolitica isolates from stools of patients in The Netherlands from 1982-1991.

The MICs of 24 antimicrobial agents were determined for 335 strains of Yersinia enterocolitica isolated from faeces in the Netherlands during 1982-1991. The isolates belonged to biotypes 1A, 1B, 2, 3, 4 and to serotypes O3, O5.27, O6.3, O7.8, O8, O9. Almost all strains were susceptible to piperacillin, piperacillin/tazobactam, imipenem, all cephalosporins except cefazolin, the aminoglycosides, quinolones, co-trimoxazole, doxycycline and chloramphenicol but resistant to amoxycillin, co-amoxiclav and macrolides. No association was observed between susceptibility patterns, biotype or serotype nor were there marked changes in the susceptibility during the last decade. The agents traditionally used to treat human infection, including co-trimoxazole, doxycycline and chloramphenicol may remain drugs of first choice.

Anti-Bacterial Agents↗

Breath alcohol legislation in The Netherlands.

In October 1987 the legislation on driving under the influence of alcohol has been changed thoroughly in The Netherlands. From that date breath analysis was introduced to obtain legal evidence for prosecuting drunken drivers. For financial and logistic reasons a transitional period of two years was allowed which means that from October 1989 breath analysis was completely introduced. One of the features of this legislation is that the suspect has no choice between breath--or blood analyses. The blood test will only be used if there is a technical or medical reason which prevents that a breath sample is collected. The legal limit is set at 220 micrograms/litre, which is equivalent to the Dutch blood alcohol limit of 0.5 mg/ml at a assumed blood/breath ratio of 2300. The features of the legislation are described; the technical requirements are stressed.

Accidents, Traffic↗

New method for the analysis of flow cytometric data.

A numerical method for deriving the fractions of cells in different phases of the cell cycle from a single observed DNA histogram is presented. The observed histogram is regarded as a polluted version (containing allocation errors) of the true histogram. A mathematical model is used to describe the pollution process. A theoretical histogram, representing the true histogram, is constructed so that G1 cells are put into one channel and G2M cells into another; the distribution of S cells in between is approximated with a set of harmonic functions. This theoretical histogram is subsequently disturbed with Gaussian dispersion functions to stimulate the pollution, yielding a predicted histogram. Using a maximum likelihood estimation technique, the model parameters are adjusted iteratively, matching the predicted histogram to the actually observed one. With the final parameter values substituted, the corresponding final theoretical histogram is regarded as a reliable reconstruction of the true histogram. From the latter, the required percentages can be read directly. The advantage of this approach over other mathematical analysis methods is that it allows a wide range of different, continuous distributions for relatively few model parameters (thus featuring flexibility and realism and a diminished risk of encountering computational problems). In addition, estimation errors providing a measure of accuracy can be obtained. To test the method, it was used to analyze various observed histograms from the literature that have been obtained by either simulation or actual flow cytometric measurements. The method appeared to perform well, as compared to the reported results of several other methods of analysis applied to the same data.

Cell Separation↗

The laboratory testing of evidential breath-testing (EBT) machines.

Six types of evidential breath testing (EBT) machines were tested in a laboratory. The testing experiments are classified into three paragraphs: analytical performance, sampling and operating conditions. In order to characterize the analytical performance a set of parameters (repeatability, reproducibility, linearity, accuracy, specificity) was established. The results were, in general, good, although an underestimation of the actual vapour concentration was observed. Different types of EBT machines showed significant differences measuring the same vapour.

Alcoholic Intoxication↗

Isolation and partial characterization of Bacillus subtilis mutants impaired in DNA entry.

Transformation-deficient mutants of Bacillus subtilis have been identified either by screening for a nuclease-deficient phenotype on methyl green-DNA agar or for nontransformability on transforming DNA-containing agar. After purification of the mutations causing a reduction in the entry of DNA, a set of isogenic entry-deficient strains was obtained. In addition to being entry deficient to various extents, the strains usually were less capable of association with DNA than the entry-proficient parent. Likewise, the specific transforming activity in the purified mutant strains continued to be less than that in the wild type. With the possible exception of one strain, no evidence was obtained that the mutant strains were impaired in recombination. Since the breakdown of transforming DNA to acid-soluble products correlated fairly well with the residual capacity of the strains to take up DNA, nucleolytic activity is likely to be involved in the entry of DNA in B. subtilis.

Bacillus subtilis↗

Transformation-deficient mutants of Bacillus subtilis impaired in competence-specific nuclease activities.

A comparison of the nucleolytic activities in competent and physiologically low-competent wild-type cultures of Bacillus subtilis in DNA-containing sodium dodecyl sulfate-polyacrylamide gels revealed the existence of three competence-associated nuclease activities with apparent molecular weights of 13,000, 15,000, and 26,000. The three activities, which were dependent on manganese or magnesium ions, were specifically present in the competent fraction of a competent culture. The competence-associated nucleolytic activities of eight transformation-defective mutant strains were assayed, resulting in the following three classes of mutants: (i) four strains which, according to this assay, were not impaired in any of the nucleolytic activities mentioned above; (ii) one strain which was strongly impaired in the 13,000- and 26,000-molecular-weight activities, but showed a considerable level of the 15,000-molecular-weight activity; and (iii) three strains which were severely impaired in all three activities. The results indicated that the 26,000-molecular-weight activity was a dimer of the 13,000-molecular-weight activity and that this nuclease was involved in the entry of DNA.

Bacillus subtilis↗

Development and identification of a multicompartment model for the distribution of adriamycin in the rat.

The distribution kinetics of adriamycin in the rat were analyzed by using a multicompartment mathematical model. The set of a priori unknown model parameters, the drug rate constants, were estimated from 48 hr multicompartment drug distribution data by applying multivariate system identification techniques. Simultaneously, the information in all the measurements is exploited for the calculation of drug concentration time curves of each compartment of the model. No quantitative a priori information is required in the form of blood flow or membrane transport limitations. This approach requires only qualitative a priori biological information in the form of a mathematical model structure and successfully analyzes complex multidimensional pharmacokinetics. It results in a compact and realistic representation of physiologic drug transport processes.

Animals↗

Prescription of home exercise therapy for cardiovascular fitness.

The importance of regular exercise activity in health maintenance has been continually emphasized. Family physicians, as the primary health care providers to many individuals, need a protocol for exercise prescription that is both practical for the physician to administer and reasonable for the patient to understand and follow. A practical protocol applicable to individuals of varying cardiac states is presented.

Angina Pectoris↗

Patient compliance to individualized home exercise programs.

Of individuals prescribed individualized home exercise programs, 55.2 percent continued to achieve greater than 75 percent of thier exercising goal after 32 weeks of participation. A method of predicting compliance early in the course of an exercise program is presented. The parameters as outlined were successful in correctly predicting by four weeks of participation the level of compliance in 89.6 percent of the individuals in this program. Family physicians should therefore be encouraged to prescribe exercise for their patients with the expectation of a significant compliant response. Early predictability also provides the physician the opportunity of intervention and modification of the program to further enhance compliance.

Adult↗

Arachidonic acid distribution in lipids of mammary glands and DMBA-induced tumors of rats.

In the phospholipid fractions, arachidonic acid represented a several fold higher percentage of fatty acids from DMBA-induced tumors and in mammary glands from midpregnant rats when compared to mammary glands from virgin rats. Arachidonic acid was not present in measurable quantities in the neutral lipid fractions of mammary glands from virgin rats. The arachidonic acid in the neutral lipid fraction of mammary glands from midpregnant rats was only detectable in the triglyceride-sterol ester fraction, but in that fraction less than 1% of the fatty acids were arachidonic acid. In the neutral lipids of the DMBA-induced tumors, it was of particular interest that a high proportion (19%) of the fatty acids in the diglyceride fraction consisted of arachidonic acid; no arachidonic acid was detected in the diglycerides of the normal tissues.

9,10-Dimethyl-1,2-benzanthracene↗