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Biomedical subjects

J van Pelt

Publications and source records attributed to J van Pelt.

At least 37 records · Page 2Linked to original sources

Natural variability in the number of dendritic segments: model-based inferences about branching during neurite outgrowth.

A study was made of the possible basis for naturally occurring variations in the number of segments in individual dendritic trees. Distributions of the number of terminal segments have been studied in dendrites from rat, cat, and frog motoneurons, basal dendrites from rat visual cortex pyramidal and non-pyramidal neurons, in rat cerebellar Purkinje cell dendritic trees, and in human hippocampal dentate granule cells. By means of a mathematical model for dendritic branching, it was shown that the variation in the number of dendritic segments can be accounted for by assuming that new branches during neurite outgrowth are formed randomly at terminal segments. The observed terminal segment number distributions could be closely approximated by additionally assuming that branching probabilities decline with increasing number of terminal segments in growing dendrites. The pyramidal neuron group differed significantly from the other neuron groups in such a way as to suggest that this decline is stronger than in the dendrites of other types of neurons. By using literature data on the mean number of terminal segments in rat cerebellar Purkinje cells, measured at different times during early development, an estimate could be obtained of the time-course of the branching probabilities. The branching probability of a terminal segment was found to be in the order of 0.002 per hour in the first 4 weeks postnatal with a 5-fold transient increase in the second week.

Animals↗

Effect of pruning on dendritic tree topology.

The variability in topological shapes of observed neuronal branching patterns can accurately be described by a simple model for random sequential growth. This finding is remarkable in view of the fact that the actual neuritic growth process can vary, and includes phases of regression and removal of branches which were not considered in the model. The aim of the present study is to investigate the influence of removal of branches on the topological structure of branching patterns as well as the effect of variable growth rules. A tree asymmetry index is used for the characterization of the topological structure of a tree. The mean value of the asymmetry index for a set of dendritic trees is sensitive to the mode of growth. The effect of removal of branches ("pruning") on the topological structure of dendritic trees has been studied for several random pruning schemes, namely (i) removal of uniform randomly chosen subtrees, (ii) removal of uniform randomly chosen terminal segments, (iii) uniform random pruning during the growth process itself, and (iv) non-uniform random pruning schemes. It was found that the effect of pruning depends on both the mode of pruning and the mode of growth. Uniform random (terminal) pruning had no effect on the mean and standard deviation of the asymmetry index of trees grown with an order-independent mode of branching. Changes in the mean of the asymmetry index could occur either with non-uniform random pruning or when trees are grown according to an order-dependent mode of branching. The effect of variable growth rules was studied for several specific schemes, and it could be shown that they all result in a substantial increase in the variation in the asymmetry index of the trees.

Animals↗

[Carbohydrate-deficient transferrin: a new biochemical marker for chronic excessive alcohol consumption].

OBJECTIVE: To assess the usefulness of the biochemical marker 'carbohydrate deficient transferrin' (CDT) in relation to conventional markers for chronic excessive alcohol use. DESIGN: Prospective. SETTING: Addiction clinic Paschalis, Wanssum, the Netherlands. METHOD: Addicts for weaning (n = 125) were questioned at admission about their drinking habits in the last two weeks. Based on the criterion more or less than 60 g alcohol per day, the group was divided into excessive and nonexcessive alcohol users (men: 52 abusers, 51 non-abusers; women: 12 abusers, 10 non-abusers). Mean cell volume (MCV), gamma-glutamyl transpeptidase (gamma GT) and total transferrin were measured in blood collected 2 days after admission, as well as CDT by two methods (CDTect and % CDTriTIA). RESULTS: In men the CDTect test was the most sensitive: sensitivity 82% with specificity 88%. The sensitivity and specificity were 62% and 86% for gamma GT, 50% and 95% for % CDTriTIA, and 34% and 98% for MCV. The combination of a positive CDTect result and a positive gamma GT result gave a predictive value of use of alcohol > 60 g/day of 100%. The results of CDT and gamma GT were also used for a logistic regression model, giving a statistical prediction for excessive alcohol use. The subgroups of women were too small to detect statistical significant differences between tests. CONCLUSION: The CDTect test was more sensitive for the detection of chronic excessive alcohol use than the conventional markers. The combination of gamma GT and CDTect results increased the positive predictive value.

Alcoholism↗

Organ and species specificity of hepatitis B virus (HBV) infection: a review of literature with a special reference to preferential attachment of HBV to human hepatocytes.

Hepatitis B virus (HBV) infection is still a major public health problem worldwide. Although much information about the molecular biology of HBV has been gained in the last decades, little is known about the mechanism of attachment and penetration of the HBV particle into human hepatocytes. The HBV envelope proteins are important for the interaction between the HBV particle and the hepatocyte plasma membrane. Although initially it was suggested that the preS2 domain could act, via polymerized human serum albumin, as an attachment site to human hepatocytes, in recent years other observations showed that the preS1 domain is probably the most important attachment site to human hepatocytes. However, controversial findings on cellular proteins for binding to the preS1 domain has been described, namely the IgA-, the IL6-, the asialoglycoprotein receptor and GAPD. Although the preS1 attachment site may be important, apo H has been shown to bind specifically to small HBsAg. Recently, we have identified human liver Annexin V as a specific small HBsAg-binding protein. In a preliminary report, the direct involvement of human Annexin V in the initial step of HBV infection has been demonstrated. A rat hepatoma cell line, which does not express human Annexin V and which is not infectable by HBV, gained the ability to become infected by HBV after transfection with human Annexin V. This result may facilitate the progress of HBV receptor research and elucidate the molecular mechanism of the initial step of HBV infection.

Animals↗

Hepatitis G viral RNA in serum and in peripheral blood mononuclear cells and its relation to HCV-RNA in patients with clotting disorders.

The hepatitis G virus (HGV) has recently been identified as a new member of the Flaviviridae family. Infection by this virus is thought to be associated with blood borne hepatitis. In this study, the presence of HCV- and HGV-RNAs in serum or plasma (175 patients) and in peripheral blood mononuclear cells (PBMC) (133 patients) was investigated in patients with clotting disorders using a sensitive reverse transcriptase polymerase chain reaction (RT-PCR). HGV-RNA was detected in serum of 26 patients (14.8%). In apparently healthy blood donors, serum HGV-RNA was detected in 4 of 358 individuals investigated (1.12%). Ninety two percent of the 26 serum HGV-RNA positive patients had coinfection with the hepatitis C virus (HCV), especially with HCV genotype 1b, the most common genotype in Belgium. Of these coinfected patients, 15 (62.5%) showed elevated serum ALT levels. Two patients who were solely infected with HGV had normal serum ALT.HGV-RNA in PBMC was found in 18 patients, of whom 3 were negative for serum HGV-RNA. As in case of HCV, HGV-RNA in PBMC is preferentially sensitive to interferon treatment. Nevertheless, rapid reappearance of HGV-RNA in PBMC was observed after cessation of treatment. In one patient, persistent serum ALT elevation seems to be associated with continued HGV viremia, despite the disappearance of serum HCV-RNA.

Adolescent↗

Complex periodic behaviour in a neural network model with activity-dependent neurite outgrowth.

Empirical studies have demonstrated that electrical activity of the neuron can directly affect neurite outgrowth. High levels of activity cause neurites to retract, whereas low levels allow further outgrowth. Previously we studied networks in which all the cells reacted in the same way on electrical activity. Since experiments have shown that neurons may in fact react differentially, we study in this paper networks in which the range of activity where outgrowth takes place varies among cells. We show that this can lead to complex periodic behaviour in electrical activity and connectivity of individual cells. The precise behaviour depends on the spatial distribution of the cells and the distribution of the outgrowth properties over the cells. Any other cellular property that adapts slowly to electrical activity such that neuronal activity is attempted to be maintained at a given level, can lead to similar results.

Animals↗

[Quality improvement project 'laboratory diagnosis by family physicians' leads to considerable decrease in number of laboratory tests].

OBJECTIVE: Quality improvement of laboratory diagnostics by general practitioners (GPs) through introduction of a simplified, problem-oriented application form, supported by information and feedback. DESIGN: Prospective descriptive study. SETTING: Laboratory of Clinical Chemistry and Haematology of St. Maartens Gasthuis, Venlo, the Netherlands and the GPs in the region. METHODS: The effects of the intervention were measured by counting the analyses requested by all GPs in the region in 1992, 1993 and 1994. Furthermore requests by every GP for fifteen selected analyses in the first 6 months of 1992, 1993 and 1994 were counted and reported together with the anonymous data of all colleagues. RESULTS: After the intervention a 23% reduction of the total number of analyses request by GPs was noticed. Blood sampling increased by 8% and the mean number of laboratory test requests per patient decreased from 5.9 to 4.2. The largest request reductions were noticed for analyses not listed on the application form. Measurements in the first 6 months of 1992, 1993 and 1994 showed continuation of the trend and a fadeaway of 'redundant' analyses. CONCLUSION: The introduction of a simplified problem-oriented application form for GPs supported by feedback caused a marked decrease of the number of (redundant) laboratory requests.

Clinical Laboratory Techniques↗

Growth cone dynamics and activity-dependent processes in neuronal network development.

Many structural and functional properties of neuronal networks find their origin in the dynamic behavior of growth cones during development. The variation in dendritic morphologies can be traced back to random branching of growth cones. Segment length characteristics arise under random branching and steady growth cone propagation. Delayed outgrowth, as a result of competition between growth cones after splitting, is hypothesized to explain different lengths of paired terminal segments in Purkinje cells. The implications of activity-dependent neurite outgrowth were studied using an outgrowth function based on the theory of Kater et al. (1988, 1990). This theory embodies a homeostatic principle, according to which a neuron adapts its neuritic field so as to maintain a certain level bioelectric activity. It is shown that such homeostasis has many implications for neuromorphogenesis and network formation, as it may underlie phenomena such as overshoot during development, size differences among cells, differentiation between excitatory and inhibitory cells and compensatory sprouting. Finally, function-dependent regulation of development involves physiological as well as morphological variables. For instance, activity dependent regulation of ionic conductances such as to stabilize functional activity can result in a differentiation of certain neurons into, respectively, bursting and regular firing sub-types (Abbot et al., 1993; LeMasson et al., 1993). Similarly, the GABAergic phenotype comes fully to expression in hindbrain (cerebellar) and forebrain (neocortical) networks only if the level of ongoing excitatory activity during development is sufficiently high, whereas chronically intensified activity leads to a compensatory hypertrophy of inhibitory mechanisms (for review, see Corner 1994). Many of these results could only have been obtained by the use of mathematical models which allow rigorous analysis of the consequences of basic assumptions in the dynamics of neurite outgrowth. All in all, the findings further emphasize the role of spontaneous bioelectric activity during early development in neuronal network formation, the importance of which was first established in cultures of developing neural tissue.

Animals↗

The transferability of a candidate reference method for determination of creatinine in serum.

We developed a candidate reference method for the determination of creatinine in serum. For the acceptance of a reference method it is important that it be rigorously validated against a definitive method and that the method can be transferred from one laboratory to another. This study focussed on the transferability and consisted of two parts: introduction and familiarization with the method in four clinical chemistry laboratories in the Netherlands, followed by independent measurements of Standard Reference Material 909a2 and several commercial quality control materials provided with reference method values according to the protocol of the German Quality Assessment Organisation. The criterion for judging transferability was the mean total error (%) of the five sera used in the accuracy experiment. For creatinine we used a total error of < 2.2%. For Standard Reference Material 909a2 all four laboratories were able to comply with this demand, while only two laboratories met this requirement for the other four sera. The results for the Standard Reference Material 909a2 from the collaborating laboratories demonstrate that this candidate reference method can be successfully transferred without loss of precision and accuracy.

Chromatography, High Pressure Liquid↗

Pitfalls in the differentiation of N-glycosylation variants of prostate-specific antigen using concanavalin A.

We determined the optimal conditions for the separation of N-glycosylation variants of prostate-specific antigen using concanavalin A. Concanavalin A is a lectin that binds to the terminal sugar residues of glycoproteins. We demonstrated that differences in the percentage of prostate-specific antigen bound to concanavalin A-Sepharose in patients with benign prostatic hyperplasia compared with patients with prostatic carcinoma, as described in the literature, arise when insufficient concanavalin A binding sites are added for complete binding of the glycosylation variants of prostate-specific antigen. We observed similar percentages of prostate-specific antigen bound to concanavalin A-Sepharose for benign prostatic hyperplasia (86.3% +/- 7.5, mean +/- SD) and carcinoma patients (81.8% +/- 12.0, mean +/- SD), when sufficient concanavalin A-Sepharose was added to allow optimal binding, and when samples with high prostate-specific antigen concentrations were not pre-diluted before incubation with concanavalin A-Sepharose. We conclude that differentiation of patients with benign prostatic hyperplasia or carcinoma of the prostate on the basis of differences in percentages of prostate-specific antigen bound to concanavalin A-Sepharose, i.e. separation of N-glycosylation variants, is not possible.

Binding Sites↗