Biomedical subjects

M Muller

Publications and source records attributed to M Muller.

At least 55 records · Page 3Linked to original sources

PubMed2001

The ornithine decarboxylase gene is essential for cell survival during early murine development.

Overexpression and inhibitor studies have suggested that the c-Myc target gene for ornithine decarboxylase (ODC), the enzyme which converts ornithine to putrescine, plays an important role in diverse biological processes, including cell growth, differentiation, transformation, and apoptosis. To explore the physiological function of ODC in mammalian development, we generated mice harboring a disrupted ODC gene. ODC-heterozygous mice were viable, normal, and fertile. Although zygotic ODC is expressed throughout the embryo prior to implantation, loss of ODC did not block normal development to the blastocyst stage. Embryonic day E3.5 ODC-deficient embryos were capable of uterine implantation and induced maternal decidualization yet failed to develop substantially thereafter. Surprisingly, analysis of ODC-deficient blastocysts suggests that loss of ODC does not affect cell growth per se but rather is required for survival of the pluripotent cells of the inner cell mass. Therefore, ODC plays an essential role in murine development, and proper homeostasis of polyamine pools appears to be required for cell survival prior to gastrulation.

Animals↗

PubMed2001

Exposure to violence and its relationship to psychopathology in adolescents.

OBJECTIVES: This study aimed to establish prevalence of adolescents' exposure to violence and related symptoms in the South African context and to explore relationships between exposure and symptoms. SETTING: Four high schools in Cape Town, South Africa. METHODS: Self report questionnaires were administered to 104 students. Types of violence explored included: witnessing or being a victim of violence perpetrated by someone known to the child or in the home and witnessing or being a victim of violence perpetrated by a stranger. The Harvard Trauma Scale, Beck Depression Inventory, and Zung Self-Rating Anxiety Scale were used to assess potentially related symptoms. RESULTS: The majority of children had been exposed to at least one type of violence, and exposure to the one type of violence was related to the other type. Symptoms of post-traumatic stress disorder and depression appear to be related to most types of exposure to violence, but anxiety symptoms only to exposure to violence perpetrated by someone known to the child or in the home. CONCLUSIONS: Rates of exposure to violence, and related symptoms, were unacceptably high. Symptoms were associated with exposure to violence.

Adolescent↗

PubMed2001

Protein adsorption on preadsorbed polyampholytic monolayers.

The adsorption behaviour of five different globular proteins on pure silicon substrates and on preadsorbed polyampholytic monolayers has been investigated as a function of protein concentration. The prelayers were prepared by adsorption of the ampholytic diblock copolymerpoly(methacrylic acid)-block-poly((dimethylamino)ethyl methacrylate) (PMAA-b-PDMAEMA). This polyampholyte adsorbs in densely packed micelles directly from aqueous solution. Ellipsometry was used to determine the amount of adsorbed polyampholyte and protein. While ATR-IR spectroscopy gives information about the adsorption and desorption behaviour of the preadsorbed polyampholytic layer, the lateral structures of the dried films were investigated by scanning force microscopy (SFM). The amount of protein adsorbed was found to be strongly influenced by the preadsorbed polyampholyte compared to the adsorption on the pure silicon substrates. No displacement of the polyampholyte by the proteins was detected. In most cases the protein adsorption was reduced by the preadsorbed polyampholytic layer. The observed trends are explained by the change in electrostatic and hydrophilic characteristics of the substrates. Furthermore, the entropy of adsorption has to be taken into account.

Adsorption↗

PubMed2001

Cardiovascular autonomic dysregulation and fatigue in multiple sclerosis.

Both cardiovascular disturbances and fatigue are frequent in multiple sclerosis (MS). We investigated their relationship in 84 MS patients (mean age 39.9 +/- 8.9 years) using five established autonomic tests and three different fatigue questionnaires. 64.2% of the patients were categorised as being fatigued Fatigue perception was weakly related to EDSS. Moderate cardiovascular disturbances were found in 16.6% of the patients, and 10.7% had severe cardiovascular autonomic abnormalities. Cardiovascular dysfunction was slightly related to age and to EDSS. In 19.4% of all patients signs of autonomic failure and fatigue were co-existent Using correlation analysis, we found only weakly significant correlation coefficients between some single autonomic test parameters and fatigue scores, which were confounded by age effects. The analysis of dichotomised data revealed slightly significant differences in fatigue experience between patients with and without abnormalities regarding the handgrip test and the Valsalva reaction. Thus, autonomic disturbances might contribute to fatigue symptoms in a MS subgroup, but the overall influence of the autonomic cardiovascular regulation towards fatigue experience seems to be of minor relevance.

Adult↗

PubMed2001

Inhibition of protein phosphatase PP1 in GH3B6, but not in GH3 cells, activates the MEK/ERK/c-fos pathway and the human prolactin promoter, involving the coactivator CPB/p300.

The human (hPRL) PRL gene proximal promoter (-164/+15) is the target for numerous signal transduction pathways involving protein kinases. The inhibitor of Ser/Thr-protein phosphatases okadaic acid (OA) was shown to induce this promoter in rat pituitary GH3B6 through a synergism between increased amounts of the ubiquitous factor AP-1 and the pituitary-specific factor Pit-1. Here we show that this activation results mainly from transcriptional stimulation of the c-fos promoter leading to increased AP-1 activity. We report the surprising absence of the hPRL and c-fos promoter stimulation by OA in GH3 cells, closely related to GH3B6 cells, and we use this discrepancy to dissect the precise mechanism of action. c-fos gene activation involves the mitogen-activated kinase (MAPK)-ternary complex factor (TCF) pathway and can be obtained by expressing active V12ras in both cell lines. We show that OA acts by inhibiting protein phosphatase PP1, thereby protecting MAPK kinase (MEK)1/2 and/or a MEK1/2-kinase from dephosphorylation. PP1 inhibition of MEK activation by V12ras does not occur in GH3 cells, indicating that a distinct, PP1-sensitive phosphorylation site is used in GH3B6 cells to activate the TCF pathway in GH3B6 cells. Finally, we show that the synergistic OA activation of the hPRL promoter by Pit-1 and AP-1 is independent of the Pit-1 transactivation domain and is mediated by the general coactivator (CRE-binding protein)-binding protein (CBP)/p300.

Animals↗

PubMed2001

Strike action by nurses in South Africa: a value clarification.

The Labour Relations Act (South Africa, 1991) made provision for protected strike action by employees, subject to certain conditions, procedures and negotiated agreements. This led to the removal of the strike clause in the Nursing Act (South Africa, 1992). The labour rights of all citizens are entrenched in the Constitution of the country (South Africa, 1996). Participation in strike action by the nurse/midwife, regardless of the legal requirements and specifications, does, however, pose an ethical question. It is therefore necessary to conduct a value clarification on strike action by nurses in South Africa. The purpose of this research is to explore and describe the perceived values of participants from an accessible population on this phenomenon. A qualitative, exploratory and descriptive research design was deployed. The perceived values of nurses on strike action were collected by means of an open-ended questionnaire/sketch. Over a period of three years a purposive and convenient sampling method was used, involving all the enrolled post basic nursing/midwifery students/learners at a particular Nursing Education Institution. The justification of the sample was further enhanced by also collecting data on the participants' age and provincial distribution location. Although a 63% sample realisation (of the accessible population) was achieved, this represents only 1.5% of the registered nursing/midwifery population in the country. A descriptive analysis of the participants' age and provincial distribution was undertaken, as well as a content analysis of their perceived values on strike action. The mean age of the participants was 48 years, which could be attributed to the fact that most of them were enrolled for a post-basic Diploma in Community Nursing Science. Most of the responses (52.7%) were against strike action and 32.5% supported strike action by nurses as a constitutional and legal right. A fairly substantial number of participants (14.8%) expressed mixed views as to whether strike action by nurses is right or wrong. Some respondents (15.7%) also reflected confusion regarding the enactment of strike action and the removal of the strike clause from the nursing legislation. Although this study does not claim external validity due to inappropriate representation of the nursing profession, the nurse of today opposes strike action. It is recommended that the study be replicated at national level and that the values be entrenched and published in position papers of and by the regulatory and organised nursing profession.

Adult↗

PubMed2001

Cooking and oxygen. An explosive recipe.

BACKGROUND: Home oxygen therapy is commonly prescribed for the treatment of chronic obstructive pulmonary disease (COPD). The risks of smoking while using this therapy have been well described. OBJECTIVE: To discuss the Royal Brisbane Hospital Burns Unit's experience and present case studies which illustrate the danger of alternative ignition sources while using home oxygen. DISCUSSION: The dangers of home oxygen therapy can be minimised by careful patient selection, education and ongoing monitoring.

Accidents, Home↗

PubMed2001

[Value of sonography in the diagnosis and follow-up of patients with cryptogenic inflammatory bowel diseases in current practice: review of a 10-year experience in a community hospital].

Inflammatory bowel diseases (IBD) are chronic inflammatory diseases of the bowel that are of unknown etiology. These diseases either progress with intermittent flare-ups interrupted by periods of remission or on a chronic active progressive mode. IBDs include Crohn disease (CD) and ulcerative colitis (UC). Clinical and imaging diagnosis often is challenging, hence explaining the frequent time delay between onset of disease and initiation of therapy. Clinical evaluation is characterized by three consecutive steps: consider a diagnosis of IBD; exclude other causes of inflammatory bowel disease; differentiate CD from UC since a definitive curative surgical treatment is available for UC. US is non-invasive, widely available, easy to perform, and relatively inexpensive and thus represents a significant advance in the evaluation of these three steps. The role of US in the evaluation of patients with suspected IBD will be reviewed.

Colitis, Ulcerative↗

PubMed2000

[Splenic thrombosis and celiac disease: a fortuitous association?].

BACKGROUND: Rare cases of venous thrombosis associated with celiac disease have been reported. CASE REPORT: We report a case of 40-year-old woman with splenic infarction and splenic venous thrombosis associated with celiac disease. This patient was homozygous for the C677T mutation of the methyltetrahydrofolate reductase (MTHFR) gene and had moderately elevated homocysteinemia. DISCUSSION: We discuss the link between celiac disease and thrombosis as well as the interest and appropriate duration of anticoagulation and hypothesize a mechanism of thrombotic disease in this setting with hyperhomocyseinemia.

Abdominal Pain↗

PubMed2000

How are you feeling? Who wants to know? Patients' and oncologists' preferences for discussing health-related quality-of-life issues.

PURPOSE: This study investigated (1) the attitudes of cancer patients toward discussing health-related quality-of-life (HRQL) issues; (2) the association between such attitudes and patients' characteristics; and (3) oncologists' attitudes and self-reported behavior regarding these same issues. PATIENTS AND METHODS: Two hundred seventy-three patients receiving palliative chemotherapy and ten physicians were asked to complete a series of questionnaires. RESULTS: Almost all patients wanted to discuss their physical symptoms and physical functioning and were also willing to address their emotional functioning and daily activities. However, 25% of the patients were only willing to discuss these latter two issues at the initiative of their physician. Patients varied most in their willingness to discuss their family and social life, with 20% reporting no interest in discussing these issues at all. Female patients were more reluctant to discuss various HRQL issues than male patients. Older and less well-educated patients were more likely to prefer that their physician initiate discussion of HRQL issues. All physicians considered it to be primarily their task to discuss the physical aspects of their patients' health, whereas four physicians indicated that discussion of psychosocial issues was a task to be shared with other health care providers. All physicians indicated that they generally defer to their patients in initiating discussion of psychosocial issues. CONCLUSION: Although both patients and oncologists seem willing to discuss a wide range of HRQL issues, communication regarding psychosocial issues may be hampered by competing expectations as to who should take the lead in initiating such discussions.

Adult↗

PubMed2000

Molecular determinants of Ca2+-dependent K+ channel function in rat dorsal vagal neurones.

Using in situ hybridisation histochemistry in combination with patch-clamp recordings and specific pharmacological tools, the molecular nature of the channels underlying Ca2+-dependent K+ currents was determined in dorsal vagal neurones (DVNs) of rat brainstem slices. In situ hybridisation analysis at cellular resolution revealed the presence of 'big'-conductance Ca2+- and voltage-activated K+ (BK) channel alpha-subunit mRNA, and of only one 'small'-conductance Ca2+-activated K+ (SK) channel subunit transcript, SK3, at very high levels in DVNs. By contrast, SK1 and SK2 mRNAs were below the threshold limit of detection. The SK channel-mediated after-hyperpolarising current (IAHP) was blocked by apamin with a half-maximal inhibitory concentration of approximately 2.2 nM. This is consistent with homomultimeric SK3 channels mediating IAHP in DVNs. IAHP was also blocked by scyllatoxin (20-30 nM) and curare (100-200 microM). Application of apamin (100 nM) or scyllatoxin (20 nM) invariably caused a substantial increase to 146.1 +/- 10.4 and 181.8 +/- 12.9 % of control, respectively, in the spontaneous firing rate of DVNs. Action potential duration was not affected by these SK channel blockers. The selective BK channel blocker iberiotoxin (50 nM) increased action potential duration by 22.5 +/- 7.3 %, as did low concentrations of tetraethylammonium (0.5 mM; 99.3 +/- 16.4 %) and the Ca2+ channel blocker Cd2+ (100 microM; 49.5 +/- 20.9 %). BK channel blockade did not significantly affect the firing rate of DVNs. These results allow us to establish a tight correlation between the properties of cloned and native BK and SK channels, and to achieve an understanding, at the molecular level, of their role in regulating the spontaneous firing frequency and in shaping single action potentials of central neurones.

Action Potentials↗

PubMed2000

Nic1p, a relative of bacterial transition metal permeases in Schizosaccharomyces pombe, provides nickel ion for urease biosynthesis.

The Schizosaccharomyces pombe genome sequencing project identified an open reading frame (O74869 and O74912, named Nic1p in the present study) with significant similarity to members of a family of bacterial transition metal permeases. These uptake systems transport Ni(2+) ion with extremely high affinity across the bacterial cytoplasmic membrane, but they differ in selectivity toward divalent transition metal cations. An S. pombe mutant harboring an interrupted nic1 allele (nic1-1) was strongly impaired in (63)Ni(2+) uptake in the presence of a high molar ratio of Mg(2+) relative to Ni(2+), conditions that reflect the natural situation. Under these conditions, the nic1-1 mutant contained only background activities of the nickel-dependent cytoplasmic enzyme urease and could not catabolize urea. Among a series of divalent transition metal cations tested (Cd(2+), Co(2+), Cu(2+), Mn(2+), and Zn(2+)), only Co(2+) caused considerable inhibition of Nic1p-mediated Ni(2+) uptake. On the other hand, experiments with (57)Co(2+) (at nm concentrations) did not show significant differences in Co(2+) uptake between the nic1-1 mutant and the parental strain. Our data suggest that Nic1p acts as a plasma-membrane nickel transporter in fission yeast, a finding that invites searches for isologous counterparts in higher eukaryotes.

Amino Acid Sequence↗

PubMed2000

Magnetic phase in the near-surface region of an FeBO3 single crystal

An FeBO3 single crystal was studied from 291 K up to the Neel temperature T(N) = 348.35 K by depth selective conversion electron Mossbauer spectroscopy in ultrahigh vacuum (10(-9) mbar). A new magnetic near-surface phase was found. Its thickness D diverges on approaching T(N) and gives a critical exponent for the correlation length of nu = 0.59(4). The phase boundary between the bulk and near-surface phase could be identified.

Journal Article↗

PubMed2000

Cloning and expression analysis of an inducible HSP70 gene from tilapia fish.

We isolated and characterized the tilapia (Oreochromis mossambicus) HSP70 gene, highly homologous to other HSP70 genes. A dramatic increase of tilapia HSP70 mRNA levels was observed after heat shock of whole animals in all organs tested. Reporter constructs were tested for transient expression in carp cells and in microinjected zebrafish embryos. The entire isolated regulatory region (-851/+157) was able to mediate heat shock inducible expression of the reporter gene, with no preference for a particular tissue. Our studies represent the first transcriptional analysis of a HSP70 promoter from fish, revealing a powerful tool to direct controlled, tissue-independent gene expression in fish.

Amino Acid Sequence↗

PubMed2000

Physical constraints on body size in teleost embryos.

All members of the subphylum "Vertebrata" display the characteristics of the vertebrate body plan. These characteristics become apparent during the phylotypic period, in which all vertebrate embryos have a similar body shape and internal organization. Phylogenetic constraints probably limit the morphological variation during the phylotypic period. Physical laws, however, also limit growth and morphogenesis in embryos. We investigated to what extent oxygen availability-as a physical constraint-might limit morphological variation during embryonic development. This paper gives an analysis of time-dependent diffusion into spherical embryos without a circulatory system. Equilibrium appeared to settle in about 1.5 min in running water and in about 10min in stagnant water. Hence, steady-state conditions were assumed and expressions for maximum body size were obtained for spherical, cylindrical and sheet-like embryos in running water and spherical embyros in stagnant water. Predictions of the model based on literature data suggest that in running water-both for spherical, cylindrical and sheet-like embryos-diffusion alone suffices to cover the oxygen needs of a teleost embryo in its phylotypic period. The size of carp (Cyprinus carpio) and African catfish (Clarias gariepinus) embryos is very close to the predicted maximum. This suggests that in these species the development of a functional circulatory system is correlated with the onset of oxygen shortage. Oxygen availability is therefore a potentially important physical constraint on embryonic morphology, though in most species the circulatory system becomes functional well in advance of the onset of oxygen shortage and other demands than oxygen delivery (e.g. nutrient distribution, waste disposal, osmoregulation) might require the development of a circulatory system.

Animals↗

PubMed2000

Non-destructive determination of local strain with 100-nanometre spatial resolution

Structure sizes of approximately 180 nm are now standard in microelectronics, and state-of-the-art fabrication techniques can reduce these to just a few tens of nanometres. But at these length scales, the strain induced at interfaces can locally distort the crystal lattice, which may in turn affect device performance in an unpredictable way. A means of non-destructively characterizing such strain fields with high spatial resolution and sensitivity is therefore highly desirable. One approach is to use Raman spectroscopy, but this is limited by the intrinsic approximately 0.5-microm resolution limit of visible light probes. Techniques based on electron-beam diffraction can achieve the desired nanometre-scale resolution. But either they require complex sample preparation procedures (which may alter the original strain field) or they are sensitive to distortional (but not dilational) strain within only the top few tens of nanometres of the sample surface. X-rays, on the other hand, have a much greater penetration depth, but have not hitherto achieved strain analysis with sub-micrometre resolution. Here we describe a magnifying diffraction imaging procedure for X-rays which achieves a spatial resolution of 100nm in one dimension and a sensitivity of 10(-4) for relative lattice variations. We demonstrate the suitability of this procedure for strain analysis by measuring the strain depth profiles beneath oxidized lines on silicon crystals.

Journal Article↗

PubMed2000

Effect of surface penetrating sealant on surface texture and microhardness of composite resins.

The application of Fortify (Bisco, Lombard, IL), an unfilled resin, to the surface of composite resin restorations is intended to fill in defects in the surface that persist despite polishing, improve marginal integrity, and increase these materials' resistance to abrasion. The aim of this study was to observe the surface texture by scanning electron microscopy and measure the microhardness of the surface. For each sample of composite resin covered with glaze, 40 measurements were made of the thickness of the resin. Measurements of the Vickers microhardness included three samples of composite resin, three samples of glaze, and six samples of composite resin covered with glaze. A relationship was established between microhardness and thickness. Scanning electron microscopy showed a noticeable improvement in the surface texture. Nevertheless, areas were seen in which glaze seemed very thin or even completely absent. Measurements of the thickness ranged from 0-70 microm. The mean microhardness of composite resin was 65.8 +/- 0.7, while the mean hardness of glaze was 7.3 +/- 0.7. The microhardness of the double layer was reduced, depending on the thickness of the glazing resin. The capacity of glaze to mask surface defects of composite resin was shown, but it was difficult to obtain a regular surface with liquid resin. The application of this product caused a decrease of the microhardness of the composite resin's surface.

Composite Resins↗

PubMed2000

Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1,25-dihydroxyvitamin D(3).

1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] inhibits production of IL-12, a cytokine involved in the development of Th1 cells and in the pathogenesis of Th1-mediated autoimmune diseases. Here, we show that 1,25(OH)(2)D(3) and a non-hypercalcemic analogue are selective and potent inhibitors of Th1 development in vitro and in vivo without inducing a deviation to the Th2 phenotype. Administration of 1,25(OH)(2)D(3) or its analogue prevents chronic-relapsing experimental allergic encephalomyelitis (CR-EAE) induced by the myelin oligodendrocyte glycoprotein (MOG) peptide 35 - 55 (MOG(35 - 55)) in Biozzi AB / H mice. The inhibition of EAE induction is associated with a profound reduction of MOG(35 - 55)-specific proliferation and Th1 cell development. Importantly, the non-hypercalcemic analogue also provides long-term protection from EAE relapses induced by immunization with spinal cord homogenate when administered for a short time at symptom onset or even after the first peak of disease. Neuropathological analysis shows a reduction of inflammatory infiltrates, demyelinated areas and axonal loss in brains and spinal cords of treated mice. These resuls indicate that inhibition of IL-12-dependent Th1 cell development is associated with effective treatment of CR-EAE and suggest the feasibility of an approach based on low molecular weight inhibitors of IL-12 production in the treatment of multiple sclerosis.

Animals↗