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Biomedical subjects

M Muller

Publications and source records attributed to M Muller.

At least 253 records · Page 14Linked to original sources
PubMed1988

A new quantitative model of total endolymph flow in the system of semicircular ducts.

1. A new concept of endolymph flow in the vertebrate vestibular system is presented. This approach describes quantitatively the flow in the entire system of three semicircular ducts interconnected by the utriculus and the crus commune. This approach is quite distinct from the classical theory in which the labyrinth is generally conceived to consist of three separate duct circuits. 2. The present approach shows the following set of distinct differences to the classical view: (a) In a labyrinth composed of three ducts perpendicular to each other the flow is non-zero in the other ducts when the labyrinth is rotated in the plane of a particular duct. (b) In a labyrinth with two equal ducts and with the duct planes under approximately 73 degrees the flow in one duct is zero when the rotation takes place in the plane of the other duct. Previous measurements of duct angles reflect this value surprisingly well. An obtuse or sharp angle between duct planes can lead to better performance of a particular labyrinth because the "external impulses" in the different ducts may amplify or compensate each other. (c) The behaviour of the flow in the entire labyrinth is a non-linear function of direction or rotation (cf. points (d), (e]. (d) Six time constants for the entire labyrinth can be distinguished (three long, three short); the flow in a particular duct is composed of six terms with these time constants. The composition of this flow and thus the relative importance of the terms depends on the positioning of the labyrinth with respect to the rotation vector. (e) The time constants also depend, for different labyrinths, on a shared influence of the dimensions of the ducts and the elastic properties of all three cupulae. (f) The forces in a particular duct depend also on the amount of motion the fluid will acquire in the other ducts. (g) The sensitivity of a particular duct depends also on the dimensions of the other parts in the vestibular system. 3. Equations for a system consisting of two ducts and for the classical single duct system are also given. Both systems are special cases of the three-duct system. The single duct equations are equivalent with equations given by Oman (1980) and Oman et al. (1987) which include the contribution of a wide utriculus. 4. The present theory of endolymph flow is mainly supported by the outcome of previously performed experiments concerning time constants and rotation of human subjects in different planes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

A mathematical approach enabling the calculation of the total endolymph flow in the semicircular ducts.

1. A mathematical treatment of the flow inside the vertebrate labyrinth is given. The main difference to former theories (e.g. the "torsion pendulum" theory) is that the entire system formed by the three semicircular ducts, interconnected by the crus commune and the utriculus, is considered, instead of a single duct circuit. 2. The theory consists of a geometrical description of a labyrinth rotating in space, the solution of the continuity equation, determination of the initial velocities in all the ducts in a "cupulometry" experiment and derivation of the equation of motion (e.o.m.). 3. Equations for a system consisting of two ducts and for the classical single-duct system are special cases of the three-duct system. 4. Three different methods for the solution of the e.o.m. are described: an analytical one, a Runge-Kutta simulation and an "asymptotic" method. The last method includes approximations of the solution of the e.o.m. on a long and a short time scale. Its advantage is that it gives an insight based on rather manageable formulae. 5. The physiological basis of the presented theory, biological applications and verification are given in a separate paper (Muller & Verhagen, 1988).

Animals↗
PubMed1988

Pairing properties of bromouracil and repair of bromouracil-containing DNA. Possible utilization of bromodeoxyuridine triphosphate for site-directed mutagenesis.

5-Bromo-2'-deoxyuridine triphosphate (Br-dUTP) and dTTP are used interchangeably for DNA synthesis in vitro by the Klenow fragment of Escherichia coli DNA polymerase I. When DNA containing Br-dUMP instead of dTMP at a few preselected sites is transfected into competent bacteria, no mutation occurs, indicating that in vivo E. coli DNA polymerase always places a dAMP residue in front of any unrepaired Br-dUMP residue. On the other hand, in vitro Br-dUTP can also replace dCTP, but only with difficulty: when dCTP is absent, Br-dUMP can be forced in front of a dGMP residue, but the Klenow polymerase pauses before and after addition of Br-dUMP. Transfection into E. coli of the substituted DNA leads to the expected G----A transitions. These mutations can easily be targeted by using a suitable primer and the correctly chosen mix of deoxynucleoside triphosphates containing Br-dUTP. When Br-dUMP has been placed in front of a dGMP residue, the mutation yield is not 100%, showing a partial repair of the transfected DNA before it is replicated. Advantage can be taken of this partial repair to prepare a set of different mutations within a target region in a single experiment.

Base Composition↗
PubMed1988

Cooperativity of the glucocorticoid receptor and the CACCC-box binding factor.

Glucocorticoid receptor binding sites (GRE) are often tightly clustered with other transcription factor binding sequences. Examples of this occur upstream of the genes for chicken lysozyme and human metallothionein IIA (ref. 3), in several retroviral LTRs and upstream of the rat tryptophan oxygenase (TO) gene. In the TO gene, sequences immediately upstream of a glucocorticoid receptor binding site are required for steroid induction and contain a CACCC-box identical to that found in the beta globin gene. Here we demonstrate specific binding to this TO-CACCC element and show that it will also act cooperatively with a MMTV glucocorticoid receptor binding site. The response to dexamethasone is independent of the order and relative orientation of these elements but does depend on their precise spacing. Optimal induction occurs at a periodicity of approximately 10 base pairs (bp) indicating a requirement for stereospecific alignment. Binding to the CACCC box, however, is not affected by its distance from the glucocorticoid receptor site. We conclude that the observed cooperativity is mediated by protein:protein interactions and does not depend on cooperative DNA binding.

Acetyltransferases↗
PubMed1988

Determination of U in human tissues by delayed neutron activation analysis.

A rapid, sensitive and highly selective technique using Delayed Neutron Activation Analysis (DNAA) has been used to determine U concentrations in human tissues. Two different sample preparation techniques were compared: one involves total matrix destruction to a dry ash while the other is a nondestructive preparation of the wet sample. The data obtained from the analyses of the same sample by DNAA of wet tissues, DNAA of ashed tissues and from radiochemical analyses using alpha spectroscopy (a standard method of U determination) were statistically equivalent on the basis of variance analysis at the p = 0.05 level.

Activation Analysis↗
PubMed1988

[The oro-dental status of a population of school children in the southeast of France].

This cross-sectional investigation, part of a national epidemiological survey, studied the oral conditions of schoolchildren, aged 6 to 15 years, of the South East of France. This region is mainly urban and the drinking water has a low fluoride content. The highest dft and dfs indices were observed respectively at 6 and 8 years from when they decreased. The DMFT and DMFS indices increased progressively from 6 years on. This study confirmed a North-South difference in caries prevalence since the observed values of the caries indices were similar to those of other mediterranean countries like Greece and Italy. The observed caries indices were higher than the mean indices of France and the rest of Europe. This South East region of France therefore needs special care from the dental profession and the french authorities.

Adolescent↗
PubMed1987

Lysozyme gene activity in chicken macrophages is controlled by positive and negative regulatory elements.

The chicken lysozyme gene is constitutively active in macrophages and under the control of steroid hormones in the oviduct. To investigate which DNA elements are involved in the control of its expression in macrophages we performed transient DNA transfer experiments with two different types of plasmids: 5'-deletion mutants of the upstream region of the chicken lysozyme gene and different fragments from this area in front of the thymidine kinase promoter (herpes simplex virus), each placed in front of the CAT (chloramphenicol acetyl transferase) coding sequence. Two enhancers (E-2.7 kb and E-0.2 kb) were characterized. They are active in macrophages, but not in chicken fibroblasts. Furthermore a negative element (N-2.4 kb) was identified, which is active in fibroblasts and promyelocytes, but not in mature macrophages. The combined action of all three elements contributes to the observed lysozyme gene activities: no activity in fibroblasts, moderate activity in promyelocytes and high activity in mature macrophages.

Animals↗
PubMed1987

Activity of two different silencer elements of the chicken lysozyme gene can be compensated by enhancer elements.

The chicken lysozyme gene is constitutively expressed in macrophages. Transfection of recombinant genes containing different portions of the lysozyme 5' upstream region revealed the existence of two negative transcriptional elements within 1 kb upstream of the start sites. Both elements placed upstream or downstream of a heterologous promoter-gene unit repress transcription independent of their orientation and are therefore called silencer elements, although their repressing activities 3' of the gene are reduced. One silencer (N-1.0 kb) at position -1 kb consists of the central region of the chicken middle repetitive sequence element CR1 and can be divided into two functional domains. N-1.0 kb is active in all cell types tested. The other silencer (N-0.25 kb) at position -0.25 kb shows reduced activity in primary macrophages. Despite their different specificities, the activity of both silencer elements can be influenced similarly. An inverse linear relationship between the transcriptional activity of the tested constructs and the potential inhibition by the silencer elements was found: weak transcription units can be strongly repressed, whereas strong transcription units can be only weakly repressed. Such a mechanism may help to turn off completely a particular gene in situations or tissues where strong positive regulators are inactive.

Animals↗
PubMed1987

Importance of the hour of sampling in the lymphoblastic transformation assay of sheep peripheral blood lymphocytes.

This paper describes the effect of the nycthemeral cycle on the lymphocyte response of sheep to different mitogens (PHA, Con A and PWM). A considerable decline in the lymphocyte response was evident in the afternoon and early in the morning in all 6 animals tested. Three peak responses were identified during a 24 hour study period, at 14.00 h, 24.00 h and 08.00 h. The results presented here suggest that this variation in lymphocyte response is a meaningful difference in the response ability of individual lymphocytes. Factors affecting the number of leukocytes and the proportion of different types of lymphocytes in peripheral blood might be the essential causes of variation. To obtain an accurate indication of an individual's immunocompetence, it is important to make a preliminary determination of the optimal hour for sampling. If this is not possible, all the samples must be taken at the same hour on each test day, in order to make significant comparisons.

Animals↗
PubMed1987

Wanted: entrepreneurial parasitologists.

At the recent World Water '86 conference in London, the Director of Water Supply and Urban Development in the Operations Policy Department of the World Bank chastised the assembled engineers for behaving like religious fanatics, convinced that their work is good and righteous but not willing (or able) to demonstrate this. There must be an opening here for an entrepreneurial parasitologist.

Journal Article↗
PubMed1986

Differential implication of deoxyribonucleic acid methylation in rat prolactin and rat growth hormone gene expressions: a comparison between rat pituitary cell strains.

In order to assess the potential role of DNA methylation in the expression of rat PRL (rPRL) as compared to rat GH (rGH) gene, the cleavage patterns generated by the isoschizomeric restriction enzymes HpaII and MspI were examined in DNA isolated from rat pituitary cell lines producing either high levels of rPRL (GH3B6) or of rGH (GC) and in a stable variant cell strain which produces minute amounts of both hormones (GH3CDL cells). The rPRL and the rGH genes were found hypomethylated in GH3B6 and GC cells, respectively, whereas in GH3CDL cells both genes were methylated, indicating a correlation between the extent of gene methylation and the level of expression. However the use of 5-azacytidine (5-azaC), which decreases DNA methylation, suggested a variable importance of gene methylation in the control of rPRL and rGH gene expression. 5-AzaC was unable to increase rPRL production to a detectable level in GC cells, whereas the cytidine analog markedly increased rPRL production and rGH production in GH3CDL cells. Further analysis using GH3CDL cells showed that the extent of the 5-azaC-induced rPRL and rGH gene demethylation was consistent with the 5-azaC-induced increase of gene expressions. However, in these cells, the stimulation of rPRL and rGH production unexpectedly increased as a function of time elapsed after drug withdrawal. The maximal stimulation, 30-fold and 7-fold, respectively, was observed 3 weeks after a 60-h exposure to 5-azaC. This pattern suggests that other events are required for the full expression of rPRL and rGH genes in addition to their own demethylation.

Animals↗