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Biomedical subjects

D Muller

Publications and source records attributed to D Muller.

At least 37 records · Page 2Linked to original sources
PubMed2001

Plasma selenium level before diagnosis and the risk of prostate cancer development.

PURPOSE: Epidemiological studies and a randomized intervention trial suggest that the risk of prostate cancer may be reduced by selenium intake. We investigated whether plasma selenium level before diagnosis correlated with the risk of later developing prostate cancer. MATERIALS AND METHODS: A case control study was performed on men from the Baltimore Longitudinal Study of Aging registry, including 52 with known prostate cancer and 96 age matched controls with no detectable prostatic disease. Plasma selenium was measured at an average time plus or minus standard deviation of 3.83 +/- 1.85 years before the diagnosis of prostate cancer by graphite furnace atomic absorption spectrophotometry. Adjusted odds ratio and 95% confidence interval were computed with logistic regression. RESULTS: After correcting for years before diagnosis, body mass index, and smoking and alcohol use history, higher selenium was associated with a lower risk of prostate cancer. Compared with the lowest quartile of selenium (range 8.2 to 10.7 microg./dl.), the odds ratios of the second (10.8 to 11.8), third (11.9 to 13.2) and fourth (13.3 to 18.2) quartiles were 0.15 (95% confidence interval 0.05 to 0.50), 0.21 (0.07 to 0.68) and 0.24 (0.08 to 0.77, respectively, p =0.01). Furthermore, plasma selenium decreased significantly with patient age (p <0.001). CONCLUSIONS: Low plasma selenium is associated with a 4 to 5-fold increased risk of prostate cancer. These results support the hypothesis that supplemental selenium may reduce the risk of prostate cancer. Because plasma selenium decreases with patient age, supplementation may be particularly beneficial to older men.

Aged↗
PubMed2000

[Evaluation of an educational program on asthma for pharmacists].

OBJECTIVES: The purpose of this work was to assess the impact of an educational program on asthma for dispensing pharmacists and their teams aimed at improving patient awareness and self-care (use of consultations, drug use, inhalation techniques). METHODS: This retrospective study used a before-after design (T0/T1 year). The patients were recruited by their primary care physician in the vicinity of dispensing pharmacies that had participated in the educational program. Data were collected with a self-administered questionnaire. The study population was divided into two groups, patients who were clients at a pharmacy that had participated in the program ("educated patients") or not ("non-educated patients"). RESULTS: After 1 year, there were fewer emergency consultations, more frequent follow-up visits, greater use of chronic inhalation therapy, better control of drug use techniques, and better knowledge of the asthmatic disease in "educated" patients. DISCUSSION: This study demonstrates the importance of educational programs for dispensary teams: better response to the demands of patients and physicians, better management of the disease and its treatment, better observance and consequently better control of asthma.

Asthma↗
PubMed2000

Adsorption of Diblock Copolymers of Poly(ethylene oxide) and Poly(lactide) at Hydrophilic Silica from Aqueous Solution.

The adsorption of a series of amphiphilic poly(ethylene oxide)-poly(DL-lactide) (PEO-PL) diblock copolymers at the water/silica interface was investigated by ellipsometry and reflectometry. For all copolymers, a much higher saturation adsorption is found compared to that of the PEO homopolymers, indicating the importance of the PL block for the adsorption. The copolymers display a saturation adsorption that increases with increasing hydrophobic content of the polymer, and decreases with increasing hydrophilic content of the polymer. Despite this, however, the layer thickness observed is rather similar for all polymers, regardless of the length and composition of the copolymers. Moreover, the layer thicknesses were significantly higher than what would be expected for the unperturbered copolymer dimensions. The initial adsorption kinetics of the different copolymers are comparable. The initial adsorption rate increases cooperatively with concentration and is slower than that expected for diffusion-controlled adsorption. Moreover, the adsorption increases only slightly over a concentration the range from 20 to 50 degrees C. Furthermore, pH titrations show that all polymers exhibit a critical desorption pH of 8-9, which is lower than the corresponding value of pH 10.5 observed for the PEO homopolymer. These results are discussed in terms of the adsorption mechanism and the adsorbed layer structure and formation. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Adsorption of Diblock Copolymers of Poly(ethylene oxide) and Polylactide at Hydrophobized Silica from Aqueous Solution.

The adsorption of a series of amphiphilic diblock copolymers of poly(ethylene oxide) (PEO) and poly(DL-lactide) (PL) at hydrophobized silica from aqueous solution was studied using time-resolved ellipsometry and reflectometry. The adsorbed amounts only display a weak dependence on the copolymer composition in both water and phosphate-buffered solution. For the short copolymers, the layer thickness decreases slightly with increasing length of the hydrophobic block. Furthermore, in comparison with the short copolymers, the layer thickness of the long copolymers is substantially higher. Upon degradation of the PL block, the adsorbed amount is found to decrease and approach that of the corresponding PEO homopolymer. Protein rejection studies indicate that the adsorption of fibrinogen is inhibited by copolymer preadsorption. The protein rejection is enhanced with increasing surface coverage of the preadsorbed copolymer, but largely independent of the length of the PL block and the PEO block. For all polymers investigated, essentially complete protein rejection is obtained above a critical surface coverage that is significantly lower than the saturation coverage of the copolymers. Removing the copolymer from bulk solution after preadsorption causes a partial desorption, resulting in reduced protein rejection. However, the protein rejection capacity with and without copolymer in the bulk solution is found to be similar at a given surface coverage. Contrary to the behavior of the intact copolymers, fibrinogen adsorption is found to be significant at surfaces pretreated with an extensively degraded copolymer and, in fact, quantitatively comparable to that at the hydrophobic surface in the absence of preadsorption. This finding, together with that of the effect of the copolymer composition on protein rejection, suggests that an efficient protein rejection is maintained until only a few L units remain in the copolymer, i.e., until nearly completed degradation. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Epicranial sensory evoked potential recordings for repeated assessment of cortical functions in mice.

In the present study, we describe a simple and minimally invasive method to record sensory evoked potentials (SEP) in the anesthetized mouse. The hardware includes a 16-channel acquisition system with a high signal/noise ratio and high temporal resolution. Under general anesthesia the skull is exposed and stainless steel electrodes are placed directly over the bone. A computer controlled electromechanical stimulation is applied to a single whisker or a group of whiskers unilaterally and cortical responses are recorded bilaterally. Primary SEP are detected over the contralateral barrel cortex, but delayed signals appear over the motor cortex, secondary somatosensory cortex and the ipsilateral hemisphere. The size of evoked SEP correlates with the number of stimulated whiskers and responses are reproducible and consistent over time when recorded repeatedly for up to 6 weeks. We conclude that epicranial multichannel recording of SEP represents an interesting, minimally invasive approach to monitor repeatedly cortical activity and study certain aspects of long-term plasticity of evoked responses in mice.

Anesthesia↗
PubMed2000

Brain-derived neurotrophic factor restores long-term potentiation in polysialic acid-neural cell adhesion molecule-deficient hippocampus.

The neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) contribute to long-term potentiation (LTP) in the CA1 hippocampus. Here we report that the deficient LTP found in slices prepared from NCAM knockout mice and in organotypic slice cultures treated with Endo-N, an enzyme that cleaves the PSA moiety of NCAM, can be rescued by brain-derived neurotrophic factor (BDNF). This effect is not reproduced by nerve growth factor, but can be obtained with high concentrations of NT4/5. The effect of BDNF cannot be accounted for by modifications of N-methyl-D-aspartate receptor-dependent responses or of high-frequency bursts. PSA-NCAM, however, could directly interact with BDNF. Exogenous application of PSA residues or recombinant PSA-NCAM also prevents LTP. Furthermore trkB phosphorylation, and thus BDNF signaling, is reduced in both NCAM knockout mice and Endo-N-treated slice cultures. These results suggest that one action of PSA-NCAM could be to sensitize pyramidal neurons to BDNF, thereby modulating activity-dependent synaptic plasticity.

Animals↗
PubMed2000

Spine changes associated with long-term potentiation.

High-frequency stimulation of excitatory synapses in many regions of the brain triggers a lasting increase in the efficacy of synaptic transmission referred to as long-term potentiation (LTP) and believed to contribute to learning and memory. One hypothesis proposed to account for the stability and properties of this functional plasticity is a structural remodeling of spine synapses. This possibility has recently received support from several studies. It has been found that spines are highly dynamic structures, that they can be formed very rapidly, and that synaptic activity and calcium modulate changes in spine shape and formation of new spines. Ultrastructural analyses bring additional support to these observations and suggest that LTP is associated with a remodeling of the postsynaptic density (PSD) and a process of spine duplication. This new information is reviewed and interpreted in light of other recent advances concerning the mechanisms of LTP and especially the role of postsynaptic glutamate receptor turnover in this form of plasticity. Taken together, a view is emerging that suggests that morphologic changes of spine synapses are associated with LTP and that they not only correlate with, but probably also contribute to the increase in synaptic transmission.

Animals↗
PubMed2000

Monoclonal antibodies to human apolipoproteins: application to the study of high density lipoprotein subpopulations.

We produced, selected and cloned hybridomas that secrete monoclonal antibodies against human apolipoprotein (apo) A-I. All of the antibodies corresponded to the IgG(1) subclass and were named 1C11, 2B4, 2C10, 7C5, 8A4 and 8A5. The antibodies were characterized by their reactivity with whole lipoproteins, apolipoproteins, synthetic peptides and fragments generated by cleavage of the apo A-I. Three of the monoclonal antibodies studied (2B4, 2C10 and 7C5) were similarly inhibited by an amino-terminal peptide (amino acid sequence 1-20) of apo A-I, whereas antibodies 1C11, 8A4 and 8A5 had no reaction. Other results show that monoclonal antibody 1C11 recognizes an epitope located between amino acids 135-148. We evaluated the monoclonal antibody 8A4 against different HDL subpopulations by competitive displacement analysis and it showed a similar reactivity with the HDL particles: LpA-I and LpA-I:A-II. This antibody was used to standardize a sandwich ELISA to quantitate LpA-I in plasma. We conclude that these monoclonal antibodies are relevant for the study of apo A-I epitope expression and for quantitating apo A-I containing lipoparticles.

Animals↗
PubMed2000

Infection of organotypic slice cultures from rat central nervous tissue with Trypanosoma brucei brucei.

We recently described a new procedure to grow nervous tissue as organotypic culture. The main feature of these slice cultures is to maintain a well preserved, three-dimensional organisation of the central nervous tissue. As these cultures can be kept for several weeks (up to three months), we have used this in vitro approach to study the complex interactions between host tissue and parasites during late stages of cerebral African trypanosomiasis. Light and electron microscopical studies, as well as electrophysiological recordings demonstrate that the structure and function of the nervous tissue is not severely affected even after several weeks of trypanosome infection. The presence of a large number of parasites does not seem to be deleterious to neuronal survival. Secondly, most of the trypanosomes are located around the periphery of the nervous tissue, but many of them also penetrate into the nervous parenchyma. Thirdly, trypanosomes with well-conserved morphology are found within the cytoplasm of glial cells, which in some cases were identified as astrocytes. These "intracellular parasites" seem to actively invade the target cells. Our study demonstrates that the presence of proliferating trypanosomes does not per se interfere with the neural activity of CNS tissues. Secondly, it provides, to the best of our knowledge, the first in vitro demonstration of intracellular forms of African trypanosomes.

Animals↗
PubMed2000

Synaptic plasticity and dynamic modulation of the postsynaptic membrane.

The biochemical composition of the postsynaptic membrane and the structure of dendritic spines may be rapidly modulated by synaptic activity. Here we review these findings, discuss their implications for long-term potentiation (LTP) and long-term depression (LTD) and propose a model of sequentially occurring expression mechanisms.

Animals↗
PubMed2000

Decreased protein phosphatase 2A activity in hippocampal long-term potentiation.

Using autophosphorylated Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) as substrate, we now find that long-term potentian (LTP) induction and maintenance are also associated with a significant decrease in calyculin A-sensitive protein phosphatase (protein phosphatase 2A) activity, without changes in Mg2+-dependent protein phosphatase (protein phosphatase 2C) activity. This decrease in protein phosphatase 2A activity was prevented when LTP induction was inhibited by treatment with calmidazolium or D-2-amino-5-phosphonopentanoic acid. In addition, the application of high-frequency stimulation to 32P-labeled hippocampal slices resulted in increases in the phosphorylation of a 55-kDa protein immunoprecipitated with anti-phosphatase 2A antibodies. Use of a specific antibody revealed that the 55-kDa protein is the B'alpha subunit of protein phosphatase 2A. Following purification of brain protein phosphatase 2A, the B'alpha subunit was phosphorylated by CaM kinase II, an event that led to the reduction of protein phosphatase 2A activity. These results suggest that the decreased activity in protein phosphatase 2A following LTP induction contributes to the maintenance of constitutively active CaM kinase II and to the long-lasting increase in phosphorylation of synaptic components implicated in LTP.

Animals↗
PubMed2000

Immunopathologic weight loss in intracranial LCMV infection initiated by the anorexigenic effects of IL-1beta.

Lymphocytic choriomeningitis virus (LCMV) infection of beta2-microglobulin-deficient (beta2m-/-) mice results in a substantial loss of body weight that is not mediated by the virus itself, but rather by CD4+ T cells responding to the viral infection. In this study, we further characterized LCMV-induced weight loss in immunocompetent and beta32m-/- mice. We show that intracranial (i.c.), but not intraperitoneal (i.p.) LCMV infection elicited significant weight loss and that weight loss was preceded by anorexia. Also, uninfected mice fed an equivalent amount as eaten by infected mice had similar weight loss compared to their infected counterparts. Interestingly, both weight loss and anorexia were greater in female than male beta2m-/- mice. LCMV-infected female beta2m-/- mice also had significantly more interleukin (IL)-betag in their cerebrospinal fluid (CSF) than did male beta2m-/- mice. Finally, intracerebroventricular (i.c.v.) administration of anti-IL-1beta antibody, but not control immunoglobulin G (IgG), attenuated the initial weight loss and increased food intake. Taken together, these results suggest that the majority of weight loss after intracranial LCMV infection is the result of anorexia and IL-1beta mediates initial anorexic weight loss.

Animals↗
PubMed2000

Differential neurotoxic effects of propofol on dissociated cortical cells and organotypic hippocampal cultures.

BACKGROUND: Propofol is a widely used anesthetic agent for adults and children. Although extensive clinical use has demonstrated its safety, neurologic dysfunctions have been described after the use of this agent. A recent study on a model of aggregating cell cultures reported that propofol might cause irreversible lesions of gamma-aminobutyric acid-mediated (GABAergic) neurons when administered at a critical phase of brain development. We investigated this issue by comparing the effects of long-term propofol treatment on two models of brain cultures: dissociated neonatal cortical cell cultures and organotypic slice cultures. METHODS: Survival of GABAergic neurons in dissociated cultures of newborn rat cortex (postnatal age, 1 day) treated for 3 days with different concentrations of propofol was assessed using histologic and cytochemical methods. For hippocampal organotypic slice cultures (postnatal age, 1 and 7 days), cell survival was assessed by measuring functional and morphologic parameters: extracellular and intracellular electrophysiology, propidium staining of dying cells, and light and electron microscopy. RESULTS: In dissociated neonatal cell cultures, propofol induced dose-dependent lesions of GABAergic neurons and of glial cells. In contrast, no evidence for neurotoxic effects of propofol were found after long-term treatment of organotypic slice cultures. Excitatory transmission was not affected by propofol, and inhibitory transmission was still functional. Histologic preparations showed no evidence for cell degeneration or death. CONCLUSION: Although long-term applications of propofol to dissociated cortical cell cultures produced degeneration and death of GABAergic neurons and glial cells, no such lesions were found when using a model of postnatal organotypic slice cultures. This conclusion is based on both functional and morphologic tests.

Anesthetics, Intravenous↗
PubMed2000

Trapped rossby waves

The possibility of tidal dynamics at strictly imaginary Lamb parameters has been known for more than three decades. The present paper explores the prevailing physics in this parameter regime. To this end, basic features of the global circulation such as baroclinicity and geostrophy have to be incorporated into tidal dynamics. The tidal equations of the thermal wind are readily obtained in the framework of spherical bishallow water theory. Density surfaces of a circulation with available potential energy alter the spatial inhomogenities of the generic tidal problem. Wave dynamics in an inhomogeneous medium are characterized not only by a dispersion relation but also by a wave guide geography: significant wave amplitudes are trapped in specific regions of frequency-dependent width. As an inherently global issue, evaluation of the Rossby wave guide geography for a given circulation cannot rely on the familiar regional filters of tidal theory. On the global domain, the Rossby wave specification is given by the Margules filter. A thermal wind is stable against nondivergent Rossby wave disturbances. Rossby waves propagating with a geostrophic wind are governed by prolate dynamics (real Lamb parameters) while imaginary Lamb parameters emerge for the oblate dynamics of Rossby waves running against a geostrophic wind. Oblate Rossby wave dynamics include pole-centered wave guides and very low-frequency disturbances propagating eastward against a westward wind.

Journal Article↗
PubMed2000

[Germ-line mutations of the BRCA1 gene in northeastern France].

Thirty-seven breast/ovarian or breast-only cancer families selected on a regional basis have been analyzed for mutations at BRCA1. By combining direct sequence analysis and protein truncation test, mutations were detected in 14 families (38%). We found seven different mutations, two of which have not been described before. Mutations at BRCA1 were present in 60% of breast/ovarian and 32% of breast-only cancer families. Mutations were frequent in families with at least one breast cancer case before age 40 (44%) and/or one bilateral breast cancer case (54%). Two mutations, namely 3600del11 and G1710X, are frequent in the population native from northeastern France. Oriented BRCA1 analysis should facilitate carrier detection in breast and/or ovarian cancer families stemming from this French area.

Adult↗
PubMed1999

LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite.

Structural remodelling of synapses and formation of new synaptic contacts has been postulated as a possible mechanism underlying the late phase of long-term potentiation (LTP), a form of plasticity which is involved in learning and memory. Here we use electron microscopy to analyse the morphology of synapses activated by high-frequency stimulation and identified by accumulated calcium in dendritic spines. LTP induction resulted in a sequence of morphological changes consisting of a transient remodelling of the postsynaptic membrane followed by a marked increase in the proportion of axon terminals contacting two or more dendritic spines. Three-dimensional reconstruction revealed that these spines arose from the same dendrite. As pharmacological blockade of LTP prevented these morphological changes, we conclude that LTP is associated with the formation of new, mature and probably functional synapses contacting the same presynaptic terminal and thereby duplicating activated synapses.

Axons↗