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Biomedical subjects

M Muller

Publications and source records attributed to M Muller.

At least 19 recordsLinked to original sources

Herpes simplex virus type 1 polypeptide ICP4 bends DNA.

ICP4, the major regulatory polypeptide of herpes simplex virus type 1, is expressed at the earliest stages of virus infection and is required for the activation of transcription from the majority of viral promoters. It is a DNA binding protein which specifically recognises bipartite sites related to the sequence ATCGTnnnnnCGG. In this report we show that both partially purified ICP4, and its isolated DNA binding domain, bend DNA at occupied binding sites. The apparent angles of bend at two different binding sites were very similar and in both cases the centre of the bend was very close to the binding site sequence.

Binding Sites

The infant mortality rate at Cherbourg aboriginal community: an update.

The infant mortality rate (IMR) at Cherbourg Aboriginal Community in south-eastern Queensland remained high from 1906 to about 1955-60, but since then has dropped from over 200/1000 live births in 1956-60 to 16/1000 live births in 1986-90, compared with the 1987 rate for Queensland (9.2/1000) and Australia (8.6/1000). The rapid improvement in the IMR was associated with the installation of a piped and chlorinated water supply, sewerage and an intensive campaign to eradicate intestinal worms. There has also been a change in community attitudes towards routine health practices and it is likely that this has been a major factor in the changes.

Humans

Bacterial metabolism of human polymorphonuclear leukocyte-derived arachidonic acid.

Evidence for transcellular bacterial metabolism of phagocyte-derived arachidonic acid was sought by exposing human blood polymorphonuclear leukocytes, prelabelled with [3H]arachidonic acid, to opsonized, stationary-phase Pseudomonas aeruginosa (bacteria-to-phagocyte ratio of 50:1) for 90 min at 37 degrees C. Control leukocytes were stimulated with the calcium ionophore A23187 (5 microM) for 5 min. Radiochromatograms of arachidonic acid metabolites, extracted from A23187-stimulated cultures and then separated by reverse-phase high-performance liquid chromatography, revealed leukotriene B4, its omega-oxidation products, and 5-hydroxy-eicosatetraenoic acid. In contrast, two major metabolite peaks, distinct from known polymorphonuclear leukocyte arachidonic acid products by high-performance liquid chromatography or by thin-layer chromatography, were identified in cultures of P. aeruginosa with [3H]arachidonic acid-labelled polymorphonuclear leukocytes. Respective chromatographic characteristics of these novel products were identical to those of two major metabolite peaks produced by incubation of stationary-phase P. aeruginosa with [3H]arachidonic acid. Production of the metabolites was dependent upon pseudomonal viability. UV spectral data were consistent with a conjugated diene structure. Metabolism of arachidonic acid by P. aeruginosa was not influenced by the presence of catalase, superoxide dismutase, nordihydroguaiaretic acid, ethanol, dimethyl sulfoxide, or ferrous ions but was inhibited by carbon monoxide, ketoconazole, and 1,2-epoxy-3,3,3-trichloropropane. Our data suggest that pseudomonal metabolism of polymorphonuclear leukocyte-derived arachidonic acid occurs during phagocytosis, probably by enzymatic epoxidation and hydroxylation via an oxygenase. By this means, potential proinflammatory effects of arachidonic acid or its metabolites may be modulated by P. aeruginosa at sites of infection in vivo.

Arachidonic Acid

Leukotriene B4 omega-oxidation by human polymorphonuclear leukocytes is inhibited by pyocyanin, a phenazine derivative produced by Pseudomonas aeruginosa.

Human polymorphonuclear leukocytes (PMNL) metabolize the potent chemotaxin leukotriene B4 (LTB4) by omega-oxidation to 20-hydroxyl-LTB4 and 20-carboxy-LTB4. The ability of unstimulated human PMNL to metabolize exogenous LTB4 was found to be inhibited by pyocyanin, a phenazine derivative produced by Pseudomonas aeruginosa, in a dose-dependent manner. 1-Hydroxyphenazine (1-OHP), a metabolite of pyocyanin, was not inhibitory under identical conditions. The initial enzymic step in the conversion of LTB4 is catalyzed by an NADPH-dependent cytochrome, P-450. Reduction of the phenazine derivatives by NADPH was measured spectrophotometrically. Pyocyanin was reduced by NADPH in vitro in a pH-dependent manner, while 1-OHP was poorly or negligibly reduced under similar conditions. Formation of NADP+ was 20.3 +/- 1.8 nmol min-1 for pyocyanin (10 microM) at pH 5.5, compared with 0.6 +/- 0.2 nmol min-1 for 1-OHP (10 microM), while at pH 7.5 a value of 2.2 +/- 1.3 nmol min-1 was obtained for pyocyanin, with no detectable activity for 1-OHP. This indicates that inhibition of LTB4 omega-hydroxylase activity by pyocyanin might be achieved by competition for NADPH. Incorporation of exogenous 5-hydroxyeicosatetraenoic acid by PMNL into lipid pools was not affected by either phenazine derivative. The ability of bacterial pyocyanin to limit the omega-oxidation of LTB4 may have important implications for PMNL LTB4 receptor status and chemotaxis in vivo.

Humans

[The contribution of unit managers in the education of student nurses].

The contribution of a group of unit managers towards student education, as well as the problems related thereto, has been investigated contextually by means of an explorative descriptive study, utilising structured interviews. The results indicate that, although unit managers have a positive attitude towards student education, they lack insight regarding the programme content, as well as their own informal educational function in the clinical situation. Lack of time and inadequate liaison between the college and unit managers seem to aggravate this problem. The recommendations include the design and implementation of inservice programmes for unit managers, improved liaison between educational and unit staff, as well as role clarification concerning their informal education responsibilities.

Curriculum

Plasma polymerization and grafting of ethylene oxide on polysiloxane surfaces.

Polysiloxane films were prepared by plasma polymerization and dip coating. Upon these films PEG was grafted by conventional methods, and ethylene oxide by plasma activation. Before and after grafting the films were analyzed by contact angle and ESCA measurements as well as by FTIR-ATR-spectroscopy and TOF-SIMS. Furthermore results of protein adsorption measurements are reported. The polysiloxane structures obtained by the plasma polymerization of HMDSO are rather similar to those ones yielded by dip coating. The two types of grafting applied on the polysiloxane substrates led to different structures of the grafted layers as was revealed by TOF-SIMS spectra.

Adsorption

Co-operative binding of the glucocorticoid receptor DNA binding domain is one of at least two mechanisms for synergism.

Steroid induction of responsive genes functions through the synergistic activity of steroid receptor binding sequences with adjacent binding sites either for other transcription factors or for further steroid receptors. Analysis of the human glucocorticoid receptor revealed that the DNA-binding domain of the receptor is sufficient to mediate co-operative binding to adjacent receptor binding sites. This is a novel feature of the domain in addition to its DNA-binding, trans-activating and trans-repressing properties. Chimaeric proteins containing the N- or C-terminal receptor halves fused to the GAL4 DNA-binding domain do not co-operate in DNA-binding, however they do functionally synergize. Thus, at least two mechanisms contribute to the synergism of the human glucocorticoid receptor bound to two adjacent receptor binding sites.

Base Sequence

Embryology of the hair follicle.

A study of hair follicle development has enabled us to differentiate four stages by relating them to corresponding gestation ages. Stage I of the hair bud is characterized by an epiblastic proliferation penetrating the subjacent mesenchyma at the extremity of which mesenchymal cells accumulate. This appears, at the level of the lower lip, before the 11th week of intrauterine life. Stage II of the hair bulb is reached on the 12th-13th week of intrauterine life, as soon as the distal extremity of the hair bud, which has extended, becomes depressed at the mesenchymal papilla level. Stage III is defined by the observation of hair cone and rough sebaceous glands on the 15th week of intrauterine life. Finally, stage IV shows a differentiated sebaceous gland with a hair which comes through the skin surface on the 18th week of intrauterine life.

Fetus

Production of leukotriene B4 and 5-hydroxyeicosatetraenoic acid by human neutrophils is inhibited by Pseudomonas aeruginosa phenazine derivatives.

Pyocyanin, a phenazine pigment produced by Pseudomonas aeruginosa, and its metabolite 1-hydroxyphenazine inhibited leukotriene B4 and 5-hydroxyeicosatetraenoic acid production by up to 70% in human neutrophils stimulated with the calcium ionophore A23187 (5 microM). This potential anti-inflammatory effect was dose dependent and occurred at low concentrations (10 to 50 microM) that did not inhibit neutrophil viability.

Calcimycin

Multiple domains of the glucocorticoid receptor involved in synergism with the CACCC box factor(s).

Steroid induction of responsive genes functions through the synergistic activity of steroid receptor-binding sequences with adjacent transcription factor-binding sites. To analyze the mechanism of synergy we tested different human glucocorticoid receptor mutants for synergistic function with another transcription factor in comparison with intrinsic trans-activation obtained with a single receptor binding site (glucocorticoid response element). Multiple domains were found to be involved in synergistic activity of the glucocorticoid receptor with the CACCC box factor. Deletions within the N-terminal receptor half affected simultaneously intrinsic trans-activation and synergism. However, deletion of the hormone-binding domain mainly impaired synergism rather than intrinsic trans-activation, clearly showing that this domain synergizes by a mechanism independent of intrinsic activation. A chimeric protein where the DNA-binding domain of the glucocorticoid receptor was replaced by that of the yeast GAL4 protein also showed functional synergism. These data suggest that some of the receptor domains outside the DNA-binding domain synergize by their intrinsic trans-activating property, but the hormone-binding domain contributes to synergism by a different mechanism.

Animals

Embryology and secretory activity of labial salivary glands.

This study was carried out on the heads of 20 foetuses aged between 11 and 26 weeks. Four stages were distinguished in the development of labial salivary glands, each stage corresponding to gestational age. Stage I is characterized by a localized, rounded thickening of the stomodial epiblast into the mesenchyma of the mucosal side of the lower lip. This occurs at the 9th-10th week of gestation. Stage II is reached when the epiblastic thickening assumes the form of a single cord. It is oval when sectioned transversally and is the result of the proliferation of epiblastic cells into the underlying mesenchyma during the 11th-12th week. Stage III corresponds to a branching process which takes place at the 13th week. The single cord branches to form the future secretory lobes, which rapidly assume a grape-like appearance. The number of rudimentary glands increases during the first three stages of development, i.e. as long as the first formed glands have not developed ducts. Stage IV corresponds to the process of duct formation at the 18th week. Simultaneous differentiation of acinal and duct cells is observed and this procedes the onset of secretory activity.

Basement Membrane

The Dandy-Walker syndrome.

Ten cases of the Dandy-Walker syndrome are presented. The clinical manifestations are analyzed. Almost 80 percent of these children had associated anomalies. The characteristic findings are based on the magnetic resonance image scan. Satisfactory treatment of our patients had mostly consisted in shunting the lateral ventricular system to the peritoneum. The incidence of the complications was high.

Abnormalities, Multiple

[Research methodology for the formulation of nursing standards].

The purpose of this article is to describe the research methodology to be utilised when formulating nursing standards. Standards guide the practice and should be formulated within the context of the culture of a country, its philosophical and ethical values, and its social, economic and political development. Two approaches of standard formulation were identified, namely a national generic approach and a decentralised, specific approach. A structured two-phase model is recommended, consisting of a developmental and a quantification phase. In the case of national standards, statistical determination of the content validity of the standards is recommended by means of a content validity index determination of each standard.

Humans