PubMed Health⌕ Search

Biomedical subjects

J M Ruijter

Publications and source records attributed to J M Ruijter.

At least 19 recordsLinked to original sources
PubMed2006

The 3'-UTR of the glutamine-synthetase gene interacts specifically with upstream regulatory elements, contains mRNA-instability elements and is involved in glutamine sensing.

Glutamine synthetase (GS) is expressed at various levels in a wide range of tissues, suggesting that a complex network of modules regulates its expression. We explored the interactions between the upstream enhancer, regulatory regions in the first intron, and the 3'-untranslated region and immediate downstream genomic sequences of the GS gene (the GS "tail"), and compared the results with those obtained previously in conjunction with the bovine growth hormone (bGH) tail. The statistical analysis of these interactions revealed that the GS tail was required for full enhancer activity of the combination of the upstream enhancer and either the middle or the 3'-intron element. The GS tail also prevented a productive interaction between the upstream enhancer and the 5'-intron element, whereas the bGH tail did not, suggesting that the 5'-intron element is a regulatory element that needs to be silenced for full GS expression. Using the CMV promoter/enhancer and transfection experiments, we established that the 2.8 kb GS mRNA polyadenylation signal is approximately 10-fold more efficient than the 1.4 kb mRNA signal. Because the steady-state levels of both mRNAs are similar, the intervening conserved elements destabilize the long mRNA. Indeed, one but not all constructs containing these elements had a shorter half life in FTO-2B cells. A construct containing only 300 bases before and 100 bases after the 2.8 kb mRNA polyadenylation site sufficed for maximal expression. A stretch of 21 adenines inside this fragment conferred, in conjunction with the upstream enhancer and the 3'-part of the first intron, sensitivity of GS expression to ambient glutamine.

3' Untranslated Regions↗
PubMed2003

Image processing and analysis program for measurement of bone density changes in reference and follow-up standardized extraoral oblique lateral cephalometric radiographs of the mandible.

OBJECTIVES: The aim of this study was to develop an image processing and analysis program for peri-implant bone density measurements of the mandible using extraoral radiographs, which includes a correction for the variable projection of the soft tissues of the face. METHODS: The measurement procedure is based on pairs of reference and follow-up extraoral oblique lateral cephalometric radiographs (OLCRs) of patients with endosseous implants in the anterior part of the atrophic edentulous mandible. The procedure consists of image acquisition, correction for radiographic variation using an aluminium wedge (i.e. film exposure and development) and transformation of the grey values into aluminium-equivalent values. After correction for variation in the projection of the soft tissues of the face using internal calibration fields, the actual peri-implant bone density measurements are performed. RESULTS: The soft tissue projection correction significantly reduces the variation between radiographs owing to the position of the soft tissues. CONCLUSIONS: It is concluded that the described image processing and analysis program, in combination with extraorally made OLCRs, is a valuable technique for measurement of peri-implant bone density changes of the mandible. With minor adaptations, the program can be used for other semi-edentulous patients.

Absorptiometry, Photon↗
PubMed2002

[Onlay grafts in combination with endosseous implants in severe mandibular atrophy. A prospective radiological study].

The placement of endosseous implants in combination with iliac crest onlay grafting of the anterior mandible is one of the treatment modalities for extreme atrophy of the mandible. The remodelling of these onlay grafts was studied using standardized extraoral oblique lateral cephalometric radiographs (OLCRs). A group of 8 patients was used in this prospective study. The measurements obtained from the OLCRs indicated the existence of the following stages in the process of remodelling of the bone grafts: 1. decrease in thickness and radiographic density of the (upper) cortex of the graft, predominantly during the first half year after grafting; 2. no significant changes in the radiographic density of the upper spongeous part of the graft; 3. a mean decrease of approximately 25% in the overall thickness of the graft, particularly during the first half year; and 4. an increase in the radiographic density of the lower part of the spongeous bone in the second half year after grafting. It is concluded that the remodelling of the graft has a predictable pattern in time. Densitometric measurement using standardized OLCRs can be a useful tool to evaluate quantitative changes of bone grafts to the mandible. The treatment described can be used on very strict indications only.

Absorptiometry, Photon↗
PubMed2001

Increased tumour risk for BWS patients correlates with aberrant H19 and not KCNQ1OT1 methylation: occurrence of KCNQ1OT1 hypomethylation in familial cases of BWS.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth malformation syndrome that maps to human chromosome 11p15.5, a region that harbours a number of imprinted genes. We studied the methylation status of H19 and KCNQ1OT1 (LIT1/KvDMR1) in a large series of BWS patients. Different patient groups were identified: group I patients (20%) with uniparental disomy and hence aberrant methylation of H19 and KCNQ1OT1; group II patients (7%) with a BWS imprinting centre 1 (BWSIC1) defect causing aberrant methylation of H19 only; group III patients (55%) with a BWS imprinting centre 2 (BWSIC2) defect causing aberrant methylation of KCNQ1OT1 only; and group IV patients (18%) with normal methylation patterns for both H19 and KCNQ1OT1. BWS patients have an increased risk of developing childhood tumours. In our patient group, out of 31 patients (group III) with KCNQ1OT1 demethylation only, none developed a tumour. However, tumours were found in 33% of patients with H19 hypermethylation (group I and II) and in 20% of patients with no detectable genetic defect (group IV). All four familial cases of BWS showed reduced methylation of KCNQ1OT1, suggesting that in these cases the imprinting switch mechanism is disturbed.

Alleles↗
PubMed2001

Melatonin generates an outward potassium current in rat suprachiasmatic nucleus neurones in vitro independent of their circadian rhythm.

The present study investigated the membrane mechanisms underlying the inhibitory influence of melatonin on suprachiasmatic nucleus (SCN) neurones in a hypothalamic slice preparation. Perforated-patch recordings were performed to prevent the rapid rundown of spontaneous firing rate as observed during whole cell recordings and to preserve circadian rhythmicity in SCN neurones. In current-clamp mode melatonin (1 microM or 1 nM) application, in the presence of agents that block action potential generation and fast synaptic transmission, resulted in a membrane hyperpolarisation accompanied with a decrease in input resistance in the majority of SCN neurones (71-86%). The amplitude of the hyperpolarisation was not found to be significantly different between circadian time 5-12 and 14-21. In voltage-clamp mode melatonin (1 microM or 1 nM) induced an outward current accompanied with an increase in membrane conductance. The current was found to be mainly potassium driven with voltage kinetics resembling those of an open rectifying potassium conductance. Investigations into the signal transduction mechanism revealed melatonin-induced inhibition of SCN neurones to be sensitive to pertussis toxin but independent of intracellular cAMP levels and phospholipase C activity. The present study shows that melatonin, at night-time physiological concentrations, reduces the neuronal excitability of the majority of SCN neurones independent of the time of application in the circadian cycle. Thus in vivo melatonin may be important for circadian time-keeping by amplifying the circadian rhythm in SCN neurones, by lowering their sensitivity to phase-shifting stimuli occurring at night.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Preliminary report: prescription of prism-glasses by the Measurement and Correction Method of H.-J. Haase or by conventional orthoptic examination: a multicenter, randomized, double-blind, cross-over study.

In a multicenter, randomized, double-blind, cross-over study in the Netherlands, the effectiveness of (prism-)glasses prescribed by the Measurement and Correction Method of H.-J. Haase (MKH) was compared to that of glasses prescribed by conventional orthoptic examination. Nine pairs of MKH-optometrists and orthoptists recruited patients who primarily presented with asthenopia, and each prescribed the patient (prism-)glasses. A questionnaire for asthenopia was developed that rated headache and tired eyes as 0-7 days per week and none-light-medium-severe, respectively. Light sensitivity, problems with focusing, near-work problems and burning eyes were each rated as: never-occasionally-often-always. A patient was eligible if he scored 'medium', 'often' or '5 days a week' twice; or 'medium' (etc.) once and 'light' (etc.) twice. Controls, in contrast to the patients, typically answered 'none' or 'never' to half of the complaints, but 37% of them would have passed the admission criteria. Among other criteria were: 18 to 40 years of age, horizontal angle < 4 degrees, vertical < 1.7 degrees, acuity > or = 0.8, stereopsis threshold disparity < 120". Seventy-two patients fulfilled all criteria and returned sufficient questionnaires. They wore the first glasses for six weeks, were without glasses for two weeks, and then wore the second glasses for six weeks. At the start, halfway and at the end of each 6-week period, questionnaires were filled out; 97% were returned. Only 19 of the orthoptists' glasses contained prisms (14 horizontal, 5 vertical; horizontal average of all glasses 0.49 PD, vertical 0.05 PD). Five of the orthoptists' glasses were plano. All MKH glasses contained prisms, 53 of 72 both horizontal and vertical, 18 only horizontal and one only vertical (horizontal average of all glasses 2.83 PD, vertical 0.79 PD). The starting levels of complaints were high and both glasses improved complaints dramatically. The starting levels were lower, but not significantly, in the second 6-week period and improvement was less outspoken. Because of these differences, the two periods had to be evaluated separately. The primary outcome of the study was defined as the difference between the effect of the MKH glasses and that of the orthoptists' glasses in the first and second 6-week periods. For problems with focusing, in the first 6-week period, and for tired eyes, in the second 6-week period, the difference exceeded the difference that had been defined as clinically significant (one day per week less headache or half the distance light-medium or half the distance occasionally-often), but it did not reach statistical significance. The statistical power was approximately 0.7 for demonstrating this clinically significant difference. Statistical significance was not reached in multivariate repeated measure ANOVA either. Forty-four patients preferred to keep the MKH glasses, 25 the orthoptists' glasses, including one plano. It is striking that 25% of the patients did not prefer the glasses that, according to the questionnaire, improved their complaints the most. A year after the study, the questionnaire was sent again to all patients: The levels of complaints after a year were similar to those at the end of the second 6-week period, whether they had preferred the MKH or the orthoptists' glasses, and were similar to the levels in controls. The most conspicuous finding was that both glasses improved the complaints dramatically. Apart from the prisms, other reasons could be: spherical and cylindrical correction, improved wearing comfort of the frame, placebo effect, Hawthorne effect and regression to the mean.

Adolescent↗
PubMed2001

Overexpression of arginase alters circulating and tissue amino acids and guanidino compounds and affects neuromotor behavior in mice.

Arginine is an intermediate of the ornithine cycle and serves as a precursor for the synthesis of nitric oxide, creatine, agmatine and proteins. It is considered to be a conditionally essential amino acid because endogenous synthesis only barely meets daily requirements. In rapidly growing suckling neonates, endogenous arginine biosynthesis is crucial to compensate for the insufficient supply of arginine via the milk. Evidence is accumulating that the intestine rather than the kidney plays a major role in arginine synthesis in this period. Accordingly, ectopic expression of hepatic arginase in murine enterocytes by genetic modification induces a selective arginine deficiency. The ensuing phenotype, whose severity correlates with the level of transgene expression in the enterocytes, could be reversed with arginine supplementation. We analyzed the effect of arginine deficiency on guanidine metabolism and neuromotor behavior. Arginine-deficient transgenic mice continued to suffer from an arginine deficiency after the arginine biosynthetic enzymes had disappeared from the enterocytes. Postweaning catch-up growth in arginine-deficient mice was characterized by increased levels of all measured amino acids except arginine. Furthermore, plasma total amino acid concentration, including arginine, was significantly lower in adult male than in adult female transgenic mice. Decreases in the concentration of plasma and tissue arginine led to significant decreases in most metabolites of arginine. However, the accumulation of the toxic guanidino compounds, guanidinosuccinic acid and methylguanidine, corresponded inversely with circulating arginine concentration, possibly reflecting a higher oxidative stress under hypoargininemic conditions. In addition, hypoargininemia was associated with disturbed neuromotor behavior, although brain levels of toxic guanidino compounds and ammonia were normal.

Amino Acids↗
PubMed2000

USAGE: a web-based approach towards the analysis of SAGE data. Serial Analysis of Gene Expression.

MOTIVATION: SAGE enables the determination of genome-wide mRNA expression profiles. A comprehensive analysis of SAGE data requires software, which integrates (statistical) data analysis methods with a database system. Furthermore, to facilitate data sharing between users, the application should reside on a central server and be accessed via the internet. Since such an application was not available we developed the USAGE package. RESULTS: USAGE is a web-based application that comprises an integrated set of tools, which offers many functions for analysing and comparing SAGE data. Additionally, USAGE includes a statistical method for the planning of new SAGE experiments. USAGE is available in a multi-user environment giving users the option of sharing data. USAGE is interfaced to a relational database to store data and analysis results. The USAGE query editor allows the composition of queries for searching this database. Several database functions have been included which enable the selection and combination of data. USAGE provides the biologist increased functionality and flexibility for analysing SAGE data. AVAILABILITY: USAGE is freely accessible for academic institutions at http://www.cmbi.kun.nl/usage/. The source code of USAGE is freely available for academic institutions on request from the first author.

Databases, Factual↗
PubMed2000

Vasopressin increases GABAergic inhibition of rat hypothalamic paraventricular nucleus neurons in vitro.

This investigation used an in vitro hypothalamic brain slice preparation and whole cell and perforated-patch recording to examine the response of magnocellular neurons in hypothalamic paraventricular nucleus (PVN) to bath applications of vasopressin (VP; 100-500 nM). In 22/38 cells, responses were characterized by an increase in the frequency of bicuculline-sensitive inhibitory postsynaptic potentials or currents with no detectable influence on excitatory postsynaptic events. Perforated-patch recordings confirmed that VP did not have an effect on intrinsic membrane properties of magnocellular PVN neurons (n = 17). Analysis of intrinsic membrane properties obtained with perforated-patch recording (n = 23) demonstrated that all of nine VP-sensitive neurons showed a rebound depolarization after transient membrane hyperpolarization from rest. By contrast, 12/14 nonresponding neurons displayed a delayed return to resting membrane potentials. Recordings of reversed inhibitory postsynaptic currents with chloride-loaded electrodes showed that responses to VP persisted in media containing glutamate receptor antagonists but were abolished in the presence of tetrodotoxin. In addition, responses were mimicked by vasotocin [Phe(2), Orn(8)], a selective V(1a) receptor agonist, and blocked by [beta-Mercapto-beta, beta-cyclopentamethylenepropionyl(1),O-Me-Tyr(2), Arg(8)]-VP (Manning compound), a V(1a)/OT receptor antagonist. Neither [deamino-Cys(1),Val(4),D-Arg(8)]-VP, a selective V(2) receptor agonist, nor oxytocin were effective. Collectively, the results imply that VP acts at V(1a) receptors to excite GABAergic neurons that are presynaptic to a population of magnocellular PVN neurons the identity of which features a unique rebound depolarization. Endogenous sources of VP may be VP-synthesizing neurons in suprachiasmatic nucleus, known to project toward the perinuclear regions of PVN, and/or the magnocellular neurons within PVN.

Action Potentials↗
PubMed1999

Myocardialization of the cardiac outflow tract.

During development, the single-circuited cardiac tube transforms into a double-circuited four-chambered heart by a complex process of remodeling, differential growth, and septation. In this process the endocardial cushion tissues of the atrioventricular junction and outflow tract (OFT) play a crucial role as they contribute to the mesenchymal components of the developing septa and valves in the developing heart. After fusion, the endocardial ridges in the proximal portion of the OFT initially form a mesenchymal outlet septum. In the adult heart, however, this outlet septum is basically a muscular structure. Hence, the mesenchyme of the proximal outlet septum has to be replaced by cardiomyocytes. We have dubbed this process "myocardialization." Our immunohistochemical analysis of staged chicken hearts demonstrates that myocardialization takes place by ingrowth of existing myocardium into the mesenchymal outlet septum. Compared to other events in cardiac septation, it is a relatively late process, being initialized around stage H/H28 and being basically completed around stage H/H38. To unravel the molecular mechanisms that are responsible for the induction and regulation of myocardialization, an in vitro culture system in which myocardialization could be mimicked and manipulated was developed. Using this in vitro myocardialization assay it was observed that under the standard culture conditions (i) whole OFT explants from stage H/H20 and younger did not spontaneously myocardialize the collagen matrix, (ii) explants from stage H/H21 and older spontaneously formed extensive myocardial networks, (iii) the myocardium of the OFT could be induced to myocardialize and was therefore "myocardialization-competent" at all stages tested (H/H16-30), (iv) myocardialization was induced by factors produced by, most likely, the nonmyocardial component of the outflow tract, (v) at none of the embryonic stages analyzed was ventricular myocardium myocardialization-competent, and finally, (vi) ventricular myocardium did not produce factors capable of supporting myocardialization.

Animals↗
PubMed1999

A mechanistic model for the development and maintenance of portocentral gradients in gene expression in the liver.

In the liver, genes are expressed along a portocentral gradient. Based on their adaptive behavior, a gradient versus compartment type, and a dynamic versus stable type of gradient have been recognized. To understand at least in principle the development and maintenance of these gradients in gene expression in relation to the limited number of signal gradients, we propose a simple and testable model. The model uses portocentral gradients of signal molecules as input, while the output depends on two gene-specific variables, viz., the affinity of the gene for its regulatory factors and the degree of cooperativity that determines the response in the signal-transduction pathways. As a preliminary validity test for its performance, the model was tested on control and hormonally induced expression patterns of phosphoenolpyruvate carboxykinase (PCK), carbamoylphosphate synthetase I (CPS), and glutamine synthetase (GS). Affinity was found to determine the overall steepness of the gradient, whereas cooperativity causes these gradients to steepen locally, as is necessary for a compartment-like expression pattern. Interaction between two or more different signal gradients is necessary to ensure a stable expression pattern under different conditions. The diversity in sequence and arrangement of related DNA-response elements of genes appears to account for the gene-specific shape of the portocentral gradients in expression. The feasibility of testing the function of hepatocyte-specific DNA-response units in vivo is demonstrated by integrating such units into a ubiquitously active promoter/enhancer and analyzing the pattern of expression of these constructs in transgenic mice.

Animals↗
PubMed1999

Glutamine synthetase expression in perinatal spiny mouse liver.

The pronounced increase in the protein/mRNA ratio of ammonia-metabolising enzymes in rat liver in the last prenatal week represents a clear example of a post-transcriptional level of control of gene expression. Both the underlying mechanism, namely an increase in translational efficiency of the mRNA and/or enhanced stability of the protein, and its importance for perinatal adaptation are unknown. We investigated this process in spiny mouse liver, because the comparison of rat and spiny mouse can discriminate adaptively from developmentally regulated processes in the perinatal period. We focused on glutamine synthetase (GS) because of the conveniently small size of its mRNA. Prenatally, GS enzyme activity slowly accumulated to approximately 1.3 U x g-1 liver at birth and postnatally more rapidly to 5.5 U x g-1 at 2 weeks. Both phases of enzyme accumulation obeyed exponential functions. Western-blot analysis showed that changes in GS activity reflected changes in GS protein content. GS mRNA content of the liver was 45 fmol x g-1 at 2 weeks before birth and slowly declined to approximately 25 fmol x g-1 at 2 weeks after birth. The GS protein/mRNA ratio increased 2.5-fold prenatally and sixfold postnatally. Analysis of prenatal and postnatal polysome profiles revealed no evidence of GS mRNA-containing ribonucleoprotein particles. Instead, GS mRNAs were (fully) occupied by 12 ribosomes, indicating regulation at the level of elongation. The kinetics of GS protein accumulation, in conjunction with GS mRNA content, are consistent with an approximately sixfold increase in its rate of synthesis at birth as the result of a corresponding stimulation of the rate of elongation.

Animals↗
PubMed1999

Dynamics of gene expression revealed by comparison of serial analysis of gene expression transcript profiles from yeast grown on two different carbon sources.

We describe a genome-wide characterization of mRNA transcript levels in yeast grown on the fatty acid oleate, determined using Serial Analysis of Gene Expression (SAGE). Comparison of this SAGE library with that reported for glucose grown cells revealed the dramatic adaptive response of yeast to a change in carbon source. A major fraction (>20%) of the 15,000 mRNA molecules in a yeast cell comprised differentially expressed transcripts, which were derived from only 2% of the total number of approximately 6300 yeast genes. Most of the mRNAs that were differentially expressed code for enzymes or for other proteins participating in metabolism (e.g., metabolite transporters). In oleate-grown cells, this was exemplified by the huge increase of mRNAs encoding the peroxisomal beta-oxidation enzymes required for degradation of fatty acids. The data provide evidence for the existence of redox shuttles across organellar membranes that involve peroxisomal, cytoplasmic, and mitochondrial enzymes. We also analyzed the mRNA profile of a mutant strain with deletions of the PIP2 and OAF1 genes, encoding transcription factors required for induction of genes encoding peroxisomal proteins. Induction of genes under the immediate control of these factors was abolished; other genes were up-regulated, indicating an adaptive response to the changed metabolism imposed by the genetic impairment. We describe a statistical method for analysis of data obtained by SAGE.

Carbon↗
PubMed1999

RNA content differs in slow and fast muscle fibers: implications for interpretation of changes in muscle gene expression.

Quantification of a specific muscle mRNA per total RNA (e.g., by Northern blot analysis) plays a crucial role in assessment of developmental, experimental, or pathological changes in gene expression. However, total RNA content per gram of a particular fiber type may differ as well. We have tested this possibility in the distinct fiber types of adult rat skeletal muscle. Sections of single fibers were hybridized against 28S rRNA as a marker for RNA content. Quantification of the hybridization showed that the 28S rRNA content decreases in the order I>IIA>IIX>IIB, where Type I fibers show a five- to sixfold higher expression level compared to Type IIB fibers. Results were verified with an independent biochemical determination of total RNA content performed on pools of histochemically defined freeze-dried single fibers. In addition, the proportion of myosin heavy chain (MHC) mRNA per microgram of total RNA was similar in slow and fast fibers, as demonstrated by Northern blot analysis. Consequently, Type I fibers contain five- to sixfold more MHC mRNA per microgram of tissue than IIB fibers. These differences are not reflected in the total fiber protein content. This study implies that proper assessment of mRNA levels in skeletal muscle requires evaluation of total RNA levels according to fiber type composition.

Animals↗
PubMed1998

Visual half-field development in children: detection of motion-defined forms.

It is widely accepted that the maturation of the extrastriate cortex is not completed before late puberty. To gain insight into the functionality of the extrastriate cortex during normal development, we tested a group of 21 children (age 6-16 years) on their ability to detect motion-defined forms. With a two-alternative forced-choice procedures we determined thresholds and visual half-field asymmetries (i.e., left vs right) for detection of relative motion. It was found that children had higher thresholds than adults. Furthermore, children had more difficulty with the detection of motion in the left than right half-field, whereas the control group of 33 adults (age 21-55 years) performed similarly in both visual half-fields. These results are discussed in the light of a hemispheric asymmetry in the maturation of the extrastriate cortex.

Adolescent↗
PubMed1998

Visual half-field development in children: detection of colour-contrast-defined forms.

Recently we have shown that children's ability to perceive motion-defined forms shows an asymmetry in the left and right visual half-fields which disappears in adulthood. The present study is focused on the visual half-field development of colour contrast vision in the same group of subjects. It was found that colour contrast thresholds for the detection of colour-contrast-defined forms decrease with age to reach adult values around puberty. This improvement of colour contrast vision with age is attributed to the maturation of cortical mechanisms. However, in contrast to a visual half-field asymmetry for motion detection during childhood, no visual half-field differences were observed for colour contrast detection in children.

Adolescent↗
PubMed1998

Development of macronutrient composition of very preterm human milk.

The effects of gestational age at delivery (GA), postnatal age (PNA) and post-menstrual age (PMA = PNA + GA, an indicator of autonomous developmental processes not affected by the moment of birth) on macronutrient composition of very preterm milk were studied. Total N, fat, lactose and carbohydrate concentrations, energy density and 24 h volume were determined in 282 24 h milk samples collected at weekly intervals (days 7-55 of lactation) from seventy-nine women delivering their babies between 25 and 29 weeks of gestation. GA related differences were found for carbohydrate concentration only: carbohydrate concentration was lower with increasing GA. PNA was related to a decrease in total N and an increase in lactose concentration. PMA was not related to milk composition. Our data indicate that PNA strongly influences the development of the composition of very preterm human milk, while GA affects carbohydrate content with a negligible effect on the nutritional value of the milk. We conclude that in accordance with current opinion in paediatrics, human milk is the best source of nutrients even for very preterm (< 30 weeks GA) infants.

Analysis of Variance↗