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Biomedical subjects

M Meyer

Publications and source records attributed to M Meyer.

At least 109 records · Page 6Linked to original sources

Employees' perceptions of the implementation of affirmative action in the health sector in the Standerton District in South Africa.

Since the inception of a fully democratic government in South Africa in 1994, government and trade unions have been placing increasing pressure on government departments and public institutions to introduce steps to correct racial discrimination through the implementation of affirmative action (AA). This study, which was carried out in the Standerton Health District, assesses employees' perceptions of and attitudes towards the implementation of AA. A quantitative design was used. Data was gathered from a total population of 360 employees by means of a questionnaire. The study revealed the following major themes: Respondents feel that if AA were effectively implemented, there would be an increase in productivity. There is strong support for the implementation of AA appointments. The implementation of AA will fail if the goals of AA are not properly and effectively communicated to all employees.

Adult↗

Chlamydia pneumoniae in atherosclerotic carotid artery plaques: high prevalence among heavy smokers.

This study was designed to determine the prevalence of Chlamydia pneumoniae in carotid artery plaques. Although there have been numerous studies evaluating coronary plaques for this bacterium fewer studies have assessed noncoronary vasculature. In addition we wished to evaluate whether correlation exists between the presence of C. pneumoniae in carotid plaques and established risk factors for atherosclerosis. Sixty intact carotid artery plaques removed during surgery (carotid endarterectomy) were formalin-fixed and paraffin-embedded according to conventional techniques. These samples were evaluated by polymerase chain reaction analysis to detect presence of C. pneumoniae DNA. Results were tabulated and compared against established risk factors for atherosclerosis: diabetes, hypertension, hyperlipidemia, age, and smoking. Forty-two (70.0%) of the 60 plaques that were evaluated tested positive for the presence of C. pneumoniae DNA by polymerase chain reaction analysis. In the sample defined as being from heavy smokers (greater than 15-pack-year history) 33 (94.3%) of 35 plaques tested positive whereas two (5.7%) tested negative. This correlation demonstrated statistical significance (P = 1.36 x 10(-6), two-tailed Fisher exact test). Presence of C. pneumoniae in carotid plaques demonstrated no statistically significant correlation with diabetes, hypertension, or hyperlipidemia. Age as a risk factor was examined but not statistically evaluated because of the narrow range within our patient sample. Analysis of the data reveals that C. pneumoniae is present in large numbers of atheromatous plaques as is consistent with emerging data. What is interesting though is that 33 (94.3%) of the 35 smokers had plaques that tested positive for the bacterium as opposed to only nine (36.0%) of the 25 nonsmokers. Identification of specific populations exhibiting a high prevalence of C. pneumoniae may serve to focus future studies. Ongoing investigation will seek to determine whether C. pneumoniae plays an active role in the pathogenesis of atherosclerosis.

Age Factors↗

The process and results of departmental specific safety surveys for health care organizations. Successful program.

1. Meeting compliance and accreditation standards can be challenging for any organization, especially in the health care setting. Safety surveys can play a strategic role in proactively preparing for such events. 2. Implementing department specific safety surveys offers a tailored approach to monitoring and addressing the occupational safety issues that occur within each department. 3. Safety surveys are a method for assessing and monitoring the environment and employee training needs, and for driving safety decisions. 4. Safety in the workplace must be a shared and continuous responsibility among employees. A formal safety survey process instilling a culture of responsibility and "buy in" by all employees is necessary.

Accreditation↗

Pim-1: a serine/threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis.

Pim-1 belongs to a family of serine/threonine protein kinases that are highly conserved through evolution in multicellular organisms. Originally identified from moloney murine leukemia virus (MuLV)-induced T-cell lymphomas in mice, Pim-1 kinase is involved in the control of cell growth, differentiation and apoptosis. Expression of Pim-1 kinase can be stimulated by a variety of growth factors and regulated at four different levels: transcriptional, post-transcriptional, translational and post-translational. Several signal transduction pathways may be associated with the regulation of Pim-1's expression; accumulating data support that the expression of Pim-1 protein is mediated through activation of JAK/STATs. Recent studies of Pim family kinases indicate that Pim-1 kinase plays important roles outside of the hematopoietic system as well.

Animals↗

GDNF and neublastin protect against NMDA-induced excitotoxicity in hippocampal slice cultures.

The potential neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) and neublastin (NBN) against NMDA-induced excitotoxicity were examined in hippocampal brain slice cultures. Recombinant human GDNF (25-100 ng/ ml) or NBN, in medium conditioned by growth of transfected, NBN-producing HiB5 cells, were added to slice cultures I h before exposure to 10 microM NMDA for 48h. Neuronal cell death was monitored, before and during the NMDA exposure, by densitometric measurements of propidium iodide (PI) uptake and loss of Nissl staining. Both the addition of rhGDNF and NBN-containing medium significantly reduced the NMDA-induced PI uptake in the CA1 (p < 0.01), suggesting neuroprotective effects of these factors, beyond their well-known trophic effects on dopaminergic neurons.

Animals↗

Out into the open.

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Blood Donors↗

An axotomy model for the induction of death of rat and mouse corticospinal neurons in vivo.

To study trophic dependencies of rat and mouse corticospinal neurons (CSN), we established a lesion model for the induction of death of analogous populations of CSN in these rodent species. Before lesion, CSN were retrogradely labeled with Fast Blue (FB). A stereotaxic cut lesion through the entire internal capsule (ICL) was used to axotomize CSN. The extent of axotomy was determined by application of a control tracer. In both species, FB-labeled CSN were localized in three major areas: (1) the sensory motor cortex; (2) the supplementary motor and medial prefrontal cortex; and (3) the somatosensory cortex. ICL does not lead to complete axotomy of CSN of the rat and mouse somatosensory cortex. In rats, ICL results in complete axotomy of CSN of the sensory motor cortex and incomplete axotomy of the caudal portion of the supplementary motor and medial prefrontal cortex. In mice, the area of axotomized CSN extends significantly further frontally. In both species, axotomy-induced death of CSN is observed in the center of the sensory motor cortex. This lesion model is useful for investigations on the response of CSN of the sensory motor cortex to lesion and therapeutic drugs.

Animals↗

Nonviral glial cell-derived neurotrophic factor gene transfer enhances survival of cultured dopaminergic neurons and improves their function after transplantation in a rat model of Parkinson's disease.

Transplantation of dopaminergic fetal mesencephalic tissue into the striatum is currently being developed for treatment of patients with advanced Parkinson's disease. Ethical concerns regarding the use of human fetal tissue, and the limited availability as well as poor survival and differentiation of dopaminergic neurons after transplantation have reduced the extent and outcome of this approach so far. With the purpose of finding means to increase the yield of dopaminergic neurons in transplants, and to reduce the amount of fetal tissue needed for each transplanted patient, we transfected rat fetal ventral mesencephalic (VM) tissue grown as organotypic free-floating roller tube (FFRT) cultures with a vector encoding human glial cell-derived neurotrophic factor (hGDNF). For transfer of an episomal expression vector (pRep7-GDNF8) a nonviral, nonliposomal cationic transfection technique was applied and optimized. Recombinant hGDNF expression resulted in a higher number of TH-positive neurons in the cultures as measured 6 days after transfection. Ventral mesencephalic cultures expressing hGDNF were then grafted into the striatum of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. Grafting of genetically modified VM cultures resulted in earlier functional recovery compared with grafting nontransfected cultures. We conclude that organotypic free-floating roller tube cultures can be successfully transfected to produce hGDNF with effects on TH-expressing neurons in vitro and functional effects after grafting in a rat Parkinson's disease model.

Animals↗

Genetic susceptibility to tuberculosis in Africans: a genome-wide scan.

Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by clinical tuberculosis. For any chromosomal region containing a major tuberculosis-susceptibility gene, affected sibpairs inherit the same parental alleles more often than expected by chance. In the first round of the screen, 299 highly informative genetic markers, spanning the entire human genome, were typed in 92 sibpairs from The Gambia and South Africa. Seven chromosomal regions that showed provisional evidence of coinheritance with clinical tuberculosis were identified. To identify whether any of these regions contained a potential tuberculosis-susceptibility gene, 22 markers from these regions were genotyped in a second set of 81 sibpairs from the same countries. Markers on chromosomes 15q and Xq showed suggestive evidence of linkage (lod = 2.00 and 1.77, respectively) to tuberculosis. The potential identification of susceptibility loci on both chromosomes 15q and Xq was supported by an independent analysis designated common ancestry using microsatellite mapping. These results indicate that genome-wide linkage analysis can contribute to the mapping and identification of major genes for multifactorial infectious diseases of humans. An X chromosome susceptibility gene may contribute to the excess of males with tuberculosis observed in many different populations.

Adolescent↗

Partial IGF affinity of circulating N- and C-terminal fragments of human insulin-like growth factor binding protein-4 (IGFBP-4) and the disulfide bonding pattern of the C-terminal IGFBP-4 domain.

Within the IGF axis, the insulin-like growth factor-binding proteins (IGFBPs) are known to play a pivotal role in cell proliferation and differentiation. Defined proteolysis of the IGFBPs is proposed to be an essential mechanism for regulating IGF bioavailability. The generated IGFBP fragments in part exhibit different IGF-dependent and -independent biological activities. Characterizing naturally occurring forms of IGFBPs in human plasma, we identified both a N- and a C-terminal fragment of IGFBP-4 by means of immunoreactivity screening. As a source for peptide isolation, we used large amounts of human hemofiltrate obtained from patients with chronic renal failure. Purification of the IGFBP-4 peptides from hemofiltrate was performed by consecutive cation-exchange and reverse-phase chromatographic steps. Mass spectrometric and sequence analysis revealed an M(r) of 13 233 for the purified N-terminal fragment spanning residues Asp(1)-Phe(122) of IGFBP-4 and an M(r) of 11 344 for the C-terminal fragment extending from Lys(136) to Glu(237). Proteolytic digestion and subsequent biochemical analysis showed that the six cysteines of the C-terminal IGFBP-4 fragment are linked between residues 153-183, 194-205, and 207-228 (disulfide bonding pattern, 1-2, 3-4, and 5-6). Plasmon resonance spectroscopy, ligand blot analysis, and saturation and displacement studies demonstrated a very low affinity of the C-terminal IGFBP-4 fragment for the IGFs (IGF-II, K(d) = 690 nM; IGF-I, K(d) > 60 nM), whereas the N-terminal fragment retained significant IGF binding properties (IGF-II, K(d) = 17 nM; IGF-I, K(d) = 5 nM). This study provides the first molecular characterization of circulating human IGFBP-4 fragments formed in vivo exhibiting an at least 5-fold decrease in the affinity of the N-terminal IGFBP-4 fragment for the IGFs and a very low IGF binding capacity of the C-terminal fragment.

Amino Acid Sequence↗

Imaging the rat brain on a 1.5 T clinical MR-scanner.

Magnetic resonance imaging (MRI) offers a noninvasive technique for studying neurodegenerative events in the rat brain, however, most of the studies are performed on small bore purpose dedicated MR scanners of limited availability and at high cost. The present study explored the feasibility of using a clinical whole body MR-scanner to perform imaging in rat brain and specifically in models of Parkinson's (PD) and Huntington's disease (HD). For that purpose rats were placed into a specially designed PVC device equipped with a flexible surface coil-and T2-weighted spin echo sequences were acquired on a Siemens Magnetom Vision at 1.5 T. In the experimental protocols of PD and HD, animals underwent 6-hydroxydopamine (6-OHDA) and quinolinic acid (QA) injections, respectively and were subsequently grafted with fetal tissue. T2-weighted images showed a small hyperintense area at the 6-OHDA lesion site and a diffuse hyperintensity in the striata with QA lesions. Transplants were seen as a hypointense area surrounded by a hyperintense rim on T1-weighted images. Moreover, disturbances of the blood-brain-barrier and its time of restoration could be monitored. In conclusion, high-resolution in vivo imaging of small animals is feasible with clinical MR-scanners and hence allows the study of various experimental protocols.

Animals↗

Novel activity of a phycobiliprotein lyase: both the attachment of phycocyanobilin and the isomerization to phycoviolobilin are catalyzed by the proteins PecE and PecF encoded by the phycoerythrocyanin operon.

The structure of phycoviolobilin, the photoactive chromophore of alpha-phycoerythrocyanin, is incompatible with a chromophore ligation to the apoprotein via SH-addition (cysteine) to a Delta3, 3(1)-double bond of the phycobilin. The two putative phycoerythrocyanin lyase genes of Mastigocladus laminosus, pecE and pecF, were overexpressed in Escherichia coli. Their action has been studied on the addition reaction of phycocyanobilin to apo-alpha-phycoerythrocyanin (PecA). In the absence of the components of alpha-PEC-phycoviolobilin lyase PecE and PecF, or in the presence of only one of them, phycocyanobilin binds covalently to PecA forming a fluorescent chromoprotein with a red-shifted absorption (lambda(max)=641 nm) and low photoactivity (<10%). In the presence of both PecE and PecF, a chromoprotein forms which by its absorption (lambda(max)=565 nm) and high photoreversible photochromism (100% type I) has been identified as integral alpha-phycoerythrocyanin. We conclude that PecE and PecF jointly catalyze not only the addition of phycocyanobilin to PecA, but also its isomerization to the native phycoviolobilin chromophore.

Bacterial Proteins↗

The prothrombin nt20210 A allele as a risk factor for venous thromboembolism: detection of heterozygous and homozygous carriers by alternative methods.

The A allele of a G/A dimorphism at position nt20210 in the 3'-untranslated region of the prothrombin gene has been recently identified as a common risk factor for venous thrombosis. It is detected mostly by PCR amplification using a mutagenic primer and subsequent restriction analysis. We have applied two alternative methods--DGGE and SSCP-to analyse the nt20210 dimorphism in a series of 383 consecutive patients with deep venous thrombosis and in 144 controls. Both screening methods resulted in the unambiguous identification of carriers of the nt20210 A allele not only in heterozygotes but in two cases as well in homozygous state. The frequency of the A allele was 0.7% in the control group but 3.7% in the patient group, demonstrating a substantial increase in risk for venous thrombosis in carriers of the 20210 A allele. Both methods have the potential to detect other DNA sequence variations in the vicinity of the 20210 G/A dimorphism. This was demonstrated by the identification of a new mutation T20122G in the 3'-untranslated region of the prothrombin gene in a single patient.

Alleles↗

SB7: the new bending-magnet double-headed dragon beamline at SuperACO.

A new beamline is now operational at LURE on bending-magnet 7 of the SuperACO storage ring in Orsay. The monochromator is of the ;dragon' type, designed to work in the energy range 150-1500 eV, and is equipped with a double vertical focusing mirror in order to allow for fast switching of light polarization. In this paper the results of photoion-yield experiments performed on N(2), Ar and Ne gases are presented. The observed resonance structures enable us to determine the available energy resolution: a resolving power higher than 8500 is obtained at the Ar 2p, N 1s and Ne K-edges when using all the optical elements at full aperture. The total flux as a function of the measured photon energy resolution and the characterization of the double-head behaviour in delivering circularly polarized light are reported.

Journal Article↗

Characterization of Cre-mediated cassette exchange after plasmid microinjection in fertilized mouse oocytes.

DNA cassette exchange methodologies are powerful tools for rapid modification of defined genomic loci. Until now, most studies have focused on transfected cell lines that were subjected to positive and negative selection to enrich for correctly recombined clones. This is the first report on Cre-mediated cassette exchange (CMCE) in early mouse embryos, a nonselectable biological system. A Cre expression plasmid and a replacement plasmid were introduced into fertilized oocytes by plasmid microinjection and recombination products were investigated. Both, replacement plasmid and oocyte genome carried heterospecific lox sites (lox511 and loxP) to direct CMCE toward integration. Here, we demonstrate the general feasibility of CMCE in early mouse embryos and characterize the system with respect to integration efficiency, competing reactions and parameters affecting recombination rates.

Animals↗

Auditory language comprehension: an event-related fMRI study on the processing of syntactic and lexical information.

The functional specificity of different brain areas recruited in auditory language processing was investigated by means of event-related functional magnetic resonance imaging (fMRI) while subjects listened to speech input varying in the presence or absence of semantic and syntactic information. There were two sentence conditions containing syntactic structure, i.e., normal speech (consisting of function and content words), syntactic speech (consisting of function words and pseudowords), and two word-list conditions, i.e., real words and pseudowords. The processing of auditory language, in general, correlates with significant activation in the primary auditory cortices and in adjacent compartments of the superior temporal gyrus bilaterally. Processing of normal speech appeared to have a special status, as no frontal activation was observed in this case but was seen in the three other conditions. This difference may point toward a certain automaticity of the linguistic processes used during normal speech comprehension. When considering the three other conditions, we found that these were correlated with activation in both left and right frontal cortices. An increase of activation in the planum polare bilaterally and in the deep portion of the left frontal operculum was found exclusively when syntactic processes were in focus. Thus, the present data may be taken to suggest an involvement of the left frontal and bilateral temporal cortex when processing syntactic information during comprehension.

Adult↗