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Biomedical subjects

A Wenzel

Publications and source records attributed to A Wenzel.

At least 127 records · Page 7Linked to original sources

Distribution of NMDA receptor subunit proteins NR2A, 2B, 2C and 2D in rat brain.

The regional distribution of the NMDA receptor subunits NR2A, 2B, 2C and 2D was visualized in adult rat brain using the histo-blot technique with newly developed subunit-specific antisera. NR2A immunoreactivity was found in almost all regions of the brain, whereas NR2B staining was restricted to forebrain, and NR2D immunoreactivity to diencephalic, mesencephalic and brain stem structures. NR2C staining was confined to cerebellum, thalamus and olfactory bulb. Thus, NMDA receptors containing the NR2A subunit are likely to represent a receptor subtype predominant throughout the brain, while those containing the NR2B, NR2C or NR2D subunit represent more region-specific receptor subtypes. The regionally overlapping distribution of certain NR2 subunits points to the existence of NMDA receptors containing more than one NR2 subunit variant.

Animals↗

Individual identification by means of conventional bitewing film and subtraction radiography.

An analysis of simulated post- and antemortem (p.m. and a.m.) victim radiographs was performed. Existing pairs of bitewing radiographs randomly sampled from a large population of adolescents were used. Two categories of individuals were included based on dental therapy conditions (none or few simple fillings). Subtraction images were performed of pairs of bitewings originating from the same individual (identical images) and different individuals (non-identical images) within each group. Four observers were asked to match the bitewings and to assess the subtraction images with respect to identity based on the score system: 1 = 'eliminated', 2 = 'possible', 3 = 'likely', or 4 = 'certain'. Three observers each mismatched the film radiographs among two out of 12 individuals without fillings. True positive identification (identified by scores 2 + 3 + 4) of subtraction images were made in 10-12 individuals out of a possible 12. The range of false positive (FP) and false negative (FN) scorings was 3-15 and 0-2, respectively. All observers were capable of correctly matching bitewings originating in the 12 individuals with amalgam fillings. By use of subtraction radiography, 12-14 identical images out of a possible 15 were assessed correctly. The range of FP and FN scorings of subtraction images in this group was 1-4 and 1, respectively. Defining only score 4 as positive identification, the sensitivity of the subtraction technique decreased from approximately 0.90 to 0.70 in both categories of individuals, while specificity increased to almost 1.00 from 0.82 vs. 0.96 in the categories with and without dental restorations. Bitewing radiographs from single individuals within a group of individuals were sufficiently identical to allow for valid identification by a strict criterion. The subtraction technique may add to the subjective matching of radiographs as a screening test in victim identification.

Adolescent↗

Non-syntenic amplification of MDM2 and MYCN in human neuroblastoma.

Amplification of the MYCN gene is a well documented genetic alteration of aggressively growing human neuroblastomas. Through cytogenetic studies we have identified neuroblastoma cell lines which, in addition to amplified MYCN, carry amplified DNA not harbouring MYCN. In situ hybridization of biotinylated total genomic DNA to metaphase chromosomes of normal human lymphocytes by reverse genomic hybridization revealed the amplified DNA to be derived from chromosome 12 band q13-14. Subsequent filter analyses showed a 20- to 40-fold amplification of the MDM2 gene, located at 12q13-14, both in three cell lines and in an original tumor, in addition to amplified MYCN. As the apparent consequence of amplification abundant MDM2 protein was present, a part of which was complexed with p53.

Chromosomes, Human, Pair 12↗

The mycN/max protein complex in neuroblastoma. Short review.

The oncogenic activation by amplification of the MYCN gene is frequently observed in human neuroblastomas and occasionally in other tumours with neuronal qualities. As a consequence of amplification, elevated levels of the mycN protein are expressed. mycN contains a C-terminal basic region (BR) that can bind to DNA, and a helix-loop-helix (HLH)-leucine zipper (Zip) domain, which is responsible for the physical interaction with another HLH-Zip protein, max. This principle structure is conserved among all members of the MYC gene family. The resulting dimers can bind to the DNA sequence CACGTG. The mycN protein, but not max, contains, near the N-terminus, a region conferring the ability to activate the transcription of genes. mycN/max heterodimers probably activate and max/max homodimers repress transcription of, as yet, unidentified target genes. In neuroblastoma cells, where mycN is deregulated, the balanced interaction of BR-HLH-Zip proteins is probably perturbed, and, therefore, genes controlled by mycN might be abnormally expressed and thereby alter normal cell growth with the consequence of tumorigenesis.

Base Sequence↗

Classification of contaminants by mode of action based on in vitro assays.

A concept for toxicity assessments based on in vitro assays of variant levels (i.e., from whole cells to isolated enzymes) is presented. Due to the complexity of organisms of different species, it is evident that no single in vitro test can represent the entire spectrum of toxic potency of chemicals, rather a carefully designed battery of tests has to be employed to account for the various targets attacked in organisms yielding the different modes of action. Cytotoxicity tests like the Neutral-Red Assay predominantly reflect non-specific toxicity, which can be modelled according to a log Pow dependent baseline QSAR. Specific toxicants (e.g., decouplers, acetylcholinesterase inhibitors or photosystem II inhibitors) may be identified based on according in vitro tests and eventually modelled by the respective mode of action related QSARs employing also, e.g., steric or polarizability descriptors to account for specific interactions. The complementation and partial replacement of in vivo (eco)toxicological testing by in vitro assays depends on two criteria: (a) the sensitivity of the tests to reliably detect environmentally relevant concentrations of toxicants and (b) the specificity of the assays to provide an unambiguous classification of toxicants by modes of action: the pattern of interaction with the various targets allows to recognize those compounds of specific effects that frequently occur as outliers in QSAR analyses.

Acetylcholine↗

Clinical and radiographical split-mouth-study on resorbable versus non-resorbable GTR-membranes.

The aim of this prospective split-mouth-study was to compare the 5-months-healing results after implantation of resorbable (Polyglactin-910) and non-resorbable (e-PTFE) GTR-membranes. 12 healthy patients with 41 periodontal defects were treated. Radiographical and clinical examinations (papillary bleeding index, gingival recession, probing pocket depth, probing attachment level, and furcation depth) were carried out under standardized conditions immediately before and 5 months after surgery. The vertical relative attachment gain (V-rAG) was calculated as a % of the bony defect depth (intra-operatively measured) at baseline, and the horizontal relative attachment gain (H-rAG) as a % of the furcation depth at baseline. The standardized radiographs were evaluated blind by 4 experienced examiners for changes of the alveolar bone. Furthermore, digital subtraction radiography was carried out using the standard deviation of the grey level histograms in the experimental region and in a control region as a test parameter for bone changes. Both types of membranes achieved an attachment gain. Using the split-mouth-design, no statistically significant (< or = 0.05) difference between the two membranes could be detected (number of defects/median) with regard to V-rAG (Polyglactin: 12/77.5%, e-PTFE: 12/73.2%) or to H-rAG of class-II-furcations (Polyglactin: 5/66.7%, e-PTFE: 5/66.7%), or to bone changes using conventional and subtraction radiographic evaluation. In conclusion based on this 5-months-study, the resorbable membranes provided attachment gain comparable to the e-PTFE-membranes.

Adult↗

Stereomicroscopy, film radiography, microradiography and naked-eye inspection of tooth sections as validation for occlusal caries diagnosis.

In establishing a trustworthy validation for occlusal caries lesions, various methods have been used after sectioning teeth. The aim of the present study was to compare the accuracy of four such methods: stereomicroscopy (SM), film radiography (FR), microradiography (MR) and naked-eye inspection (NEI) for the detection of caries in occlusal tooth surfaces. Further, the interobserver agreement between three observers' registrations of occlusal caries by these methods was evaluated. The material consisted of 18 unerupted third molars known to be sound with respect to caries, as they were embedded in bone prior to removal, and 20 erupted third molars with an unknown 'true state of disease'. The teeth were serially sectioned, coded and examined blindly for occlusal caries by three independent observers by the four validation methods under study. SM was demonstrated to be the only method by which all observers correctly identified all 18 unerupted teeth as sound, resulting in a specificity of 1.00. By the other three methods, 1 or more of the unerupted teeth were falsely classified as carious. In the erupted teeth, 73, 58, 52 and 32%, respectively, of the teeth were determined carious by SM, MR, NEI and FR. As it was possible by SM to detect caries in nearly three quarters of the erupted teeth and at the same time to identify all unerupted teeth as sound, this method seemed to be the most trustworthy of the validation methods under study.

Dental Caries↗

Accuracy of caries diagnosis in digital images from charge-coupled device and storage phosphor systems: an in vitro study.

OBJECTIVES: To evaluate the diagnostic accuracy of carries detection with four intra-oral digital radiographic systems in vitro and to investigate the impact of image compression. METHODS: 116 extracted human premolars and molars mounted three in a line with approximal contacts were radiographed with four digital systems (Digora, RVG, Sens-A-Ray, and Visualix) and imported into a Windows-based program. Sixteen images from each system were compressed (JPEG, irreversible compression). The total of 528 images was assessed by six radiologists using a 5-point confidence scale for the detection of approximal and occlusal caries. Caries was validated histologically. The disease threshold was caries in enamel for approximal surfaces and in dentine for occlusal surfaces. RESULTS: Mean ROC curve areas for approximal surfaces were 0.611 (DIG), 0.572 (RVG), 0.594 (SAR), and 0.596 (VIX), and for occlusal surfaces 0.794 (DIG), 0.819 (RVG), 0.751 (SAR), and 0.761 (VIX). There were no significant differences between the areas under the ROC curves (p > 0.05); nor were there any significant differences between the compressed and uncompressed images (p > 0.05). CONCLUSIONS: The four digital systems performed almost equally well for detection of caries in vitro, and compressed images were as accurate as uncompressed.

Bicuspid↗

Direct digital radiography in the dental office.

With rapidly developing technology, conventional dental radiography is being overtaken by a revolution in digital radiography. In recent years the emphasis has been on indirect digital radiography involving the conversion of conventional film radiographs into digital images. This stage has been useful in helping the research and development of direct digital radiography which is now coming to the fore. Using this technique, direct images are acquired in the dental practice. These images can be manipulated, enhanced, stored and exchanged for referral and other purposes, making them of great potential use. In addition to the direct clinical and diagnostic benefits, the techniques also have distinct environmental advantages including less use of resources and reduced radiation dosages.

Humans↗

Involvement of metabotropic and ionotropic glutamate receptors in inositol polyphosphate formation in carp retinal slices.

The contribution of ionotropic and metabotropic glutamate receptors to inositol polyphosphate accumulation in carp retinal slices was investigated using myo-[2-3H]inositol prelabelling. In the presence of the glutamate agonists quisqualate, (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and trans-(+/-)-1-amino-1,3-cyclopentane-dicarboxylic acid (t-ACPD), formation of [3H]inositol phosphate was significantly increased in a dose-dependent manner, with EC50 values of 350 nM, 1.5 microM and 10 microM respectively. The complete AMPA-induced response and a large component of the quisqualate-induced response were inhibited in a competitive manner when the ionotropic antagonist 6-cyano-7-nitroquinoxalin- 2,3-dione (CNQX) was present. Furthermore, the remaining level of quisqualate-induced [3H]inositol phosphate formation closely matched that produced by ACPD alone, and coincubation of AMPA and ACPD showed additive effects, suggesting that the quisqualate-induced response resulted from coactivation of metabotropic and ionotropic glutamate receptors. The ionotropic component was partially reduced in the presence of cobalt, suggesting indirect effects resulting from synaptic interactions. We could exclude indirect effects through depolarization-induced release of other neurotransmitters. Only serotonin (EC50 1 microM) and carbachol (at a concentration of 1 mM) stimulated [3H]inositol phosphate formation, but their antagonists did not affect the quisqualate response and coactivation with quisqualate and serotonin or carbachol resulted in additive effects. The ionotropic component was completely suppressed when Ca2+ was omitted from the medium and cobalt was present. This makes it likely that the ionotropic component resulted from Ca2+ entry through AMPA-gated channels and subsequent Ca(2+)-dependent activation of phospholipase C.

Animals↗

Biotests using unicellular algae and ciliates for predicting long-term effects of toxicants.

Test systems for predicting long-term effects with the freshwater algae Chlamydomonas reinhardi and Scenedesmus subspicatus and the ciliate Tetrahymena pyriformis were evaluated with respect to the following reference chemicals: atrazine, bromacil, diuron, methyl parathion, lindane, 3,4-dichloroaniline, pentachlorophenol, cadmium, copper, and the volatile 1,2-dichloropropane. In growth-inhibition tests under static conditions the algae revealed a higher sensitivity to the toxicants than the ciliate except for lindane and methyl parathion. Comparison of the impairment of photosynthetic efficiency (EPR, NOEC 24 hr) with the inhibition of growth (NOEC 72 hr) of S. subspicatus revealed a higher sensitivity of the EPR parameter for inhibitors of the photosynthesis. A flowthrough system was developed for long-term tests and testing of volatile and instable substances. Under flowthrough conditions C. reinhardi was more susceptible to the chemicals than under static test conditions, except for pentachlorophenol. Due to the high volatility, 1,2-dichloropropane was only tested in the flowthrough system. The data obtained from these toxicity tests provide information about effects on organisms representing different levels of the aquatic food web, possessing differences in sensitivity against toxicants. The presented flowthrough system allows the testing of volatile and instable chemicals, problematic in static test systems, and the EPR parameter is suitable for the early characterization of chemicals acting as specific inhibitors of the photosynthetic electron transport chain.

Animals↗

Sensor noise in direct digital imaging (the RadioVisioGraphy, Sens-a-Ray, and Visualix/Vixa systems) evaluated by subtraction radiography.

The aim of this study was to evaluate sensor noise with the use of the subtraction method in radiographs captured with three direct digital intraoral systems. Ten radiographs were taken of the lower left molar region of a phantom head at each of three exposure times: 0.20 seconds, 0.46 seconds, and 0.60 seconds with the use of the RadioVisioGraphy (Trophy Radiologie, Vincennes, France), Sens-a-Ray (Regam Medical Systems, AB, Sundsvall, Sweden), and Visualix (Gendex, Philips Medical Systems, Inc., Monza, Italy) systems. Neither the x-ray tube nor the phantom were moved between exposures, and the three sensors were identically positioned. The images were stored in the tagged image file format provided by the systems in 8-bit depth and imported by a subtraction program. Subtractions were performed between identical images taken with the three systems. The standard deviation for the distribution of the shades of grey in the subtraction image histogram served as an expression for image noise. Paired t tests evaluated differences between the standard deviations of the subtraction images from the three systems. The standard deviation increased with increasing exposure time for all three systems (p < 0.00001). The standard deviation for the images performed with Visualix were 6.47, 10.34, and 11.16 at exposure times 0.20, 0.46, and 0.60, respectively. For the RadioVisioGraphy, these values were 1.61, 2.03, and 2.18, and for Sens-a-Ray 2.90, 3.98, and 3.96, respectively. The differences between the systems were highly statistically significant (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Artifacts↗

In vitro comparison of D- and E-speed film radiography, RVG, and visualix digital radiography for the detection of enamel approximal and dentinal occlusal caries lesions.

The aims of this study were (1) to compare the accuracy of conventional D- and E-speed film radiography and direct digital radiography using the RadioVisioGraphy and Visualix systems for the detection of enamel approximal caries lesions and (2) to compare the accuracy of D- and E-speed films and the Visualix system for the detection of dentinal occlusal caries lesions. In total, 122 approximal surfaces were examined in vitro by 3 observers and 65 occlusal surfaces by 2 observers. The true caries diagnosis was based on histological assessment of the surfaces after sectioning the teeth. Approximal surfaces were deemed diseased by the presence of a demineralization in enamel, while occlusal surfaces were deemed diseased by the presence of a demineralization into dentine. The diagnostic accuracy for each radiographic method was expressed as a receiver operating characteristic (ROC) curve area. For the approximal surfaces, the areas under the ROC curves ranged from 0.53 (Visualix) to 0.70 (E-speed film). For the occlusal surfaces, the areas ranged from 0.62 (Visualix) to 0.79 (D- and E-speed films). No statistically significant differences between mean ROC curve areas for the radiographic methods were found either for the approximal or for the occlusal surfaces. It was concluded that radiography was of almost no value in the detection of enamel approximal caries lesions, but of some value in the detection of dentinal lesions in occlusal surfaces.

Bicuspid↗

Impact of the validator and the validation method on the outcome of occlusal caries diagnosis.

In studies evaluating the performance of caries-diagnostic methods, a validation of the true state of disease is needed. The aim of this study was to evaluate the impact of the validator and the validation system (stereomicroscopy or radiography of tooth sections) on the outcome of diagnostic tests for occlusal caries. The material consisted of 60 extracted third molars which were serially sectioned (500-600 microns thick). Four observers examined the sections by two caries validation methods: stereomicroscopy and film radiography. The presence of caries in the occlusal surfaces of these teeth had previously been recorded by visual inspection and conventional film radiography. The kappa values for interobserver agreement within one validation method ranged from 0.44 to 0.76 for radiography and from 0.47 to 0.60 for microscopy. The intraobserver agreement with the two methods was low (range 0.31-0.49), and by cross-tabulating the data, it was found that the disagreements originated in a consistently deeper lesion score with stereomicroscopy than with radiography by all observers except 1. By use of receiver operating characteristic curve areas, little impact of the validation method was seen when visual inspection was validated (against microscopy mean area = 0.75, against radiography mean area = 0.74). The mean receiver operating characteristic area was higher when diagnostic film radiographs were validated against radiography (0.68) than against microscopy (0.63). The differences between observers within a validation method were larger with microscopy than with radiography. In conclusion, caries validation methods are subject to variability. The outcome of caries--diagnostic tests may be influenced both by the validator and the validation method.

Dental Caries↗

Clinically undetected dental caries assessed by bitewing screening in children with little caries experience.

Following the decline in caries prevalence, it has been questioned whether it is still justifiable to continue the practice of radiographic bitewing screening. This study was undertaken to compare the value of a clinical examination with screening bitewing radiograph in children who had little previous caries experience. One hundred and sixty-eight 14-year-old children participated in the investigation. The children were examined clinically by one of three pedodontists for the presence of 'sound', 'suspect caries', and 'carious' occlusal and approximal tooth surfaces. Bitewing screening radiographs were obtained of all the children prior to the clinical examination. The radiographs were assessed for the presence and extent of occlusal and approximal caries. Radiography detected more than 94% of the total number of reported (clinically and radiographically) caries lesions. 1.2% of the occlusal and 10.2% of the approximal surfaces clinically designated sound were scored as carious by radiography. Of these clinically undetected lesions, 15% were assessed to have penetrated into dentine on the radiographs. Although the number of false-positive radiographic scores could not be ascertained in this study, it is likely that, as the caries prevalence was low, the probability of a false-positive diagnosis would be high. It was therefore concluded that there was no convincing evidence that 14-year-old children with little previous caries experience benefit from a screening bitewing examination.

Adolescent↗