Control of free calcium in plant cell nuclei.
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Calcium↗
Biomedical subjects
M Moreau
Publications and source records attributed to M Moreau.
Stokes formula and density perturbances for driven tracer diffusion in an adsorbed monolayer
We study the intrinsic friction of monolayers adsorbed on solid surfaces from a gas phase or vapor. Within the framework of the Langmuir model of delocalized adsorption, we calculate the resistance offered by the mobile adsorbate's particles to some impure tracer molecule, whose diffusive random motion is biased by a constant external force. We find that for sufficiently small driving forces the force exerted on the tracer shows viscouslike behavior. We derive then the analog of the Stokes formula for two-dimensional adsorbates, calculate the corresponding friction coefficient, and determine the stationary particle distribution in the monolayer as seen from the driven impurity.
Journal Article↗
Meropenem versus ceftazidime as empirical monotherapy for febrile neutropenic cancer patients.
A total of 101 cancer patients with 121 febrile neutropenia episodes were randomised to receive empirical treatment with i.v. meropenem (1g/8 h) or ceftazidime (2 g/8 h). After 3 days, 89% of patients were on unmodified therapy in the meropenem group, compared with 83% in the ceftazidime group. Of the evaluable episodes (n = 106), the success rate with unmodified empirical therapy until the end of the treatment course was slightly higher with meropenem than with ceftazidime (48% vs 38%, P=0.39). Furthermore, initial success with further infections was observed in 22% of episodes treated with meropenem and in 13% of episodes treated with ceftazidime. Glycopeptides were used as first modification in 28% and 39% of meropenem and ceftazidime recipients, respectively. Both treatments were well tolerated and there were no reports of drug-related nausea/vomiting or seizures. No significant differences in response rate or in tolerability were observed when analysing only the first febrile episodes. In conclusion, meropenem seems to be as efficacious and well tolerated as ceftazidime and may be associated with a lesser requirement for the addition of glycopeptides.
Adolescent↗
Role of dihydropyridine-sensitive calcium channels in meiosis and fertilization in the bivalve molluscs Ruditapes philippinarum and Crassostrea gigas.
Prophase-arrested oocytes of Ruditapes philippinarum can not be fertilized or stimulated by a depolarizing agent such as an excess of KCl, in contrast to the situation found in Crassostrea gigas. We have performed a comparative study between the two situations found in these species. In vitro, both of these oocytes can be triggered to reinitiate meiosis following a treatment by serotonin which promotes an intracellular calcium surge. Ruditapes and Crassostrea oocytes further arrest in metaphase I, at which stage they can be either activated by sperm or by excess KCl. These treatments trigger an intracellular calcium increase. This suggests that functional voltage-operated Ca2+ channels are expressed in Ruditapes during the course of maturation between prophase and metaphase I. Results obtained using pharmacological tools and direct binding of specific dihydropyridines, strongly suggest that these channels are dihydropyridine-sensitive calcium channels. In Ruditapes they become functional after 5-HT stimulation, their number increasing before GVBD. In Crassostrea the dihydropyridine-sensitive Ca2+ channels are already present at prophase stage and their density is constant from prophase to metaphase I. Moreover, we have shown for Ruditapes and Crassostrea that: 1) the addition of 10 microM of S(-)BayK8644, an agonist of dihydropyridine-sensitive calcium channels to metaphase-arrested oocytes releases them from metaphase block; and 2) incubating these oocytes with nicardipine, a potent blocker of dihydropyridine-sensitive Ca2+ channels, inhibits both their activation by excess KCl or fertilization. Taken together these data suggest that the absence of dihydropyridine-sensitive Ca2+ channels in the membrane of prophase-arrested oocytes of Ruditapes may account for their inability to be fertilized at this stage, while the presence of dihydropyridine-sensitive Ca2+ channels in prophase-arrested oocytes of Crassostrea may explain their fertilizability at this stage.
Animals↗
Acute pancreatitis associated with severe lactic acidosis in human immunodeficiency virus-infected patients receiving triple therapy.
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Acidosis, Lactic↗
Kinetics of stochastically gated diffusion-limited reactions and geometry of random walk trajectories
In this paper we study the kinetics of diffusion-limited, pseudo-first-order A+B-->B reactions in situations in which the particles' intrinsic reactivities are not constant but vary randomly in time. That is, we suppose that the particles are bearing "gates" which fluctuate in time, randomly and independently of each other, between two states-an active state, when the reaction may take place between A and B particles appearing in close contact; and a blocked state, when the reaction is completely inhibited. We focus here on two customary limiting cases of pseudo-first-order reactions-the so-called target annihilation and the Rosenstock trapping model-and consider four different particular models, such that the A particle can be either mobile or immobile or gated or ungated, and ungated or gated B particles can be fixed at random positions or move randomly. All models are formulated on a d-dimensional regular lattice, and we suppose that the mobile species perform independent, homogeneous, discrete-time lattice random walks. The model involving a single, immobile, ungated target A and a concentration of mobile, gated B particles is solved exactly. For the remaining three models we determine exactly, in the form of rigorous lower and upper bounds showing the same N dependence, the large-N asymptotical behavior of the probability that the A particle survives until the Nth step. We also realize that for all four models studied here the A particle survival probability can be interpreted as the moment generating function of some functionals of random walk trajectories, such as, e. g., the number of self-intersections, the number of sites visited exactly a given number of times, the "residence time" on a random array of lattice sites, etc. Our results thus apply to the asymptotic behavior of corresponding generating functions which are not known as yet.
Journal Article↗
Generalized model for dynamic percolation
We study the dynamics of a carrier, which performs a biased motion under the influence of an external field E-->, in an environment which is modeled by dynamic percolation and created by hard-core particles. The particles move randomly on a simple cubic lattice, constrained by hard-core exclusion, and they spontaneously annihilate and reappear at some prescribed rates. We determine the density profiles of the "environment" particles, as seen from the stationary moving carrier, and calculate its terminal velocity V(c) as the function of the applied field and other system parameters. For sufficiently small driving forces the force exerted on the carrier by the "environment" particles shows a viscouslike behavior. An analog Stokes formula for such dynamic percolative environments and the corresponding friction coefficient are derived. We show that the density profile of the environment particles is strongly inhomogeneous: In front of the stationary moving carrier the density is higher than the average density rho(s), while past the carrier the local density is lower than rho(s).
Journal Article↗
Tat protein of human immunodeficiency virus type 1 induces interleukin-10 in human peripheral blood monocytes: implication of protein kinase C-dependent pathway.
The clinical manifestations observed in human immunodeficiency virus type 1 (HIV-1)-infected patients are primarily due to the capacity of the virus and its components to inactivate the immune system. HIV-1 Tat protein could participate in this immune system disorder. This protein is secreted by infected cells of HIV-infected patients and is free in the plasma, where it can interact and be taken up by both infected and noninfected cells. In asymptomatic patients infected by HIV-1, production of interleukin-10 (IL-10), a highly immunosuppressive cytokine, is associated with disease progression to AIDS. In the present work, we tested the capacity of Tat to induce IL-10 production by peripheral blood monocytes of healthy donors. The results show that Tat causes the production of IL-10 in a dose- and stimulation time-dependent manner. Investigations of the mechanisms involved in signal transduction show that (i) the calcium pathway is not or only slightly involved in Tat-induced IL-10 production, (ii) the protein kinase C pathway plays an essential role, and (iii) monocyte stimulation by Tat results in the intranuclear translocation of transcription factor NF-kappaB and in the induction of phosphorylation of the mitogen-activated protein kinases ERK1 and ERK2; activation of these two potential substrates of protein kinase C is required for the production of IL-10. Finally, our results suggest that the effect of Tat is exerted at the membrane level and that the active domain is located within N-terminal residues 1 to 45. This production of IL-10 induced by Tat could participate in the progression of HIV infection to AIDS.
Calcium↗
Imaging patterns of calcium transients during neural induction in Xenopus laevis embryos.
Through the injection of f-aequorin (a calcium-sensitive bioluminescent reporter) into the dorsal micromeres of 8-cell stage Xenopus laevis embryos, and the use of a Photon Imaging Microscope, distinct patterns of calcium signalling were visualised during the gastrulation period. We present results to show that localised domains of elevated calcium were observed exclusively in the anterior dorsal part of the ectoderm, and that these transients increased in number and amplitude between stages 9 to 11, just prior to the onset of neural induction. During this time, however, no increase in cytosolic free calcium was observed in the ventral ectoderm, mesoderm or endoderm. The origin and role of these dorsal calcium-signalling patterns were also investigated. Calcium transients require the presence of functional L-type voltage-sensitive calcium channels. Inhibition of channel activation from stages 8 to 14 with the specific antagonist R(+)BayK 8644 led to a complete inhibition of the calcium transients during gastrulation and resulted in severe defects in the subsequent formation of the anterior nervous system. BayK treatment also led to a reduction in the expression of Zic3 and geminin in whole embryos, and of NCAM in noggin-treated animal caps. The possible role of calcium transients in regulating developmental gene expression is discussed.
Aequorin↗
Improved methods for the quantification of free and linked spacer in conjugate vaccine process.
In polysaccharide (PS)-protein conjugate vaccine process, indirect coupling via derivatization of the antigenic PS by diamino spacer molecules is widely used. Such a conjugation technology requires the accurate determination of both the degree of PS-amino substitution (linked spacer) and the removal of residual unlinked (free) diamino spacer. We report two methods for the microdetermination of the spacer primary amino groups, based on their fluorescent labelling. In the first developed assay, activated PS is derivatized with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and the free spacer is separated and detected as its AQC derivative by RP-HPLC with fluorescence detection (lambda(Ex,Em) 246/396 nm). In the second assay, activated PS is derivatized with 3-(2-furoyl)quinoline-2-carboxaldehyde (FQ) and its FQ derivative is separated by capillary zone electrophoresis (CZE) with laser-induced-fluorescence (LIF) detection (lambda(Ex/Em) 488/590 nm). Compared to the traditional gel filtration and colorimetric assays, these two methods show major advances in terms of sensitivity, reduced analysis time and small sample requirements.
Chromatography, Gel↗
Quantification of C-polysaccharide in Streptococcus pneumoniae polysaccharides by high-performance anion-exchange chromatography with pulsed amperometric detection.
A sensitive method, using high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) has been developed for measurement of the C-polysaccharide contamination in Streptococcus pneumoniae capsular polysaccharides, which are part of the polysaccharides based vaccines for the prevention of pneumococcal infections. This method, based on the quantification by HPAEC-PAD of the ribitol released by aqueous hydrofluoric acid (HF) followed by trifluoro acid hydrolysis (TFA) of the pneumococcal polysaccharides is simple and provides both a qualitative and quantitative method for control of the polysaccharides.
Chromatography, High Pressure Liquid↗
A radiographic and tomographic imaging system integrated into a medical linear accelerator for localization of bone and soft-tissue targets.
PURPOSE: Dose escalation in conformal radiation therapy requires accurate field placement. Electronic portal imaging devices are used to verify field placement but are limited by the low subject contrast of bony anatomy at megavoltage (MV) energies, the large imaging dose, and the small size of the radiation fields. In this article, we describe the in-house modification of a medical linear accelerator to provide radiographic and tomographic localization of bone and soft-tissue targets in the reference frame of the accelerator. This system separates the verification of beam delivery (machine settings, field shaping) from patient and target localization. MATERIALS AND METHODS: A kilovoltage (kV) x-ray source is mounted on the drum assembly of an Elekta SL-20 medical linear accelerator, maintaining the same isocenter as the treatment beam with the central axis at 90 degrees to the treatment beam axis. The x-ray tube is powered by a high-frequency generator and can be retracted to the drum-face. Two CCD-based fluoroscopic imaging systems are mounted on the accelerator to collect MV and kV radiographic images. The system is also capable of cone-beam tomographic imaging at both MV and kV energies. The gain stages of the two imaging systems have been modeled to assess imaging performance. The contrast-resolution of the kV and MV systems was measured using a contrast-detail (C-D) phantom. The dosimetric advantage of using the kV imaging system over the MV system for the detection of bone-like objects is quantified for a specific imaging geometry using a C-D phantom. Accurate guidance of the treatment beam requires registration of the imaging and treatment coordinate systems. The mechanical characteristics of the treatment and imaging gantries are examined to determine a localizing precision assuming an unambiguous object. MV and kV radiographs of patients receiving radiation therapy are acquired to demonstrate the radiographic performance of the system. The tomographic performance is demonstrated on phantoms using both the MV and the kV imaging system, and the visibility of soft-tissue targets is assessed. RESULTS AND DISCUSSION: Characterization of the gains in the two systems demonstrates that the MV system is x-ray quantum noise-limited at very low spatial frequencies; this is not the case for the kV system. The estimates of gain used in the model are validated by measurements of the total gain in each system. Contrast-detail measurements demonstrate that the MV system is capable of detecting subject contrasts of less than 0.1% (at 6 and 18 MV). A comparison of the kV and MV contrast-detail performance indicates that equivalent bony object detection can be achieved with the kV system at significantly lower doses (factors of 40 and 90 lower than for 6 and 18 MV, respectively). The tomographic performance of the system is promising; soft-tissue visibility is demonstrated at relatively low imaging doses (3 cGy) using four laboratory rats. CONCLUSIONS: We have integrated a kV radiographic and tomographic imaging system with a medical linear accelerator to allow localization of bone and soft-tissue structures in the reference frame of the accelerator. Modeling and experiments have demonstrated the feasibility of acquiring high-quality radiographic and tomographic images at acceptable imaging doses. Full integration of the kV and MV imaging systems with the treatment machine will allow on-line radiographic and tomographic guidance of field placement.
Animals↗
The promoter of human tissue factor pathway inhibitor gene: identification of potential regulatory elements.
Tissue factor pathway inhibitor is the major potent physiologic inhibitor of tissue factor-induced coagulation. Several potential binding sites for transcription factors have been described in the 750 bp of the 5' flanking region of the human tissue factor pathway inhibitor gene reported earlier. To identify elements that regulate the expression of tissue factor pathway inhibitor in endothelial, hepatocyte, and monocyte cells, the sequence of an additional 770 bp of tissue factor pathway inhibitor was determined. Comparison of this new sequence as well as that reported earlier with consensus sequences for transcription factor binding sites provided matches for GATA-2, SP1, and c-Myc sequences. Moreover, plasmids containing deletion mutants of the 5' tissue factor pathway inhibitor promoter region and the luciferase reporter gene were transfected into HepG2, ECV304, and THP1 cells. Three negative regulatory elements were localized between -548 to -390, - 390 to -75, and -1158 to -796 relative to the transcriptional start, respectively, in HepG2, ECV304 and THP-1 cells.
Base Sequence↗
Adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-1 reduces atherosclerotic lesions in apolipoprotein E-deficient mice.
BACKGROUND: To define the role of metalloproteinases (MMPs) in the development of lipid-rich atherosclerotic lesions in relation to the balance between proteolytic and antiproteolytic activities, we investigated the impact of adenovirus-mediated elevation in the circulating levels of human tissue inhibitor of MMP (TIMP-1) in atherosclerosis-susceptible apolipoprotein E-deficient (apoE(-/-)) mice. METHODS AND RESULTS: Infusion of apoE(-/-) mice fed a lipid-rich diet with rAd.RSV.TIMP-1 (1x10(11) viral particles) resulted in high hepatic expression of TIMP-1. At 2 weeks after injection, plasma TIMP-1 levels ranged from 7 to 24 micrograms/mL (mean 14.8+/-6.8). Marked overexpression of TIMP-1 was transient, with levels of TIMP-1 decreasing to 2.5 to 8 micrograms/mL (mean 4.3+/-2.1) at 4 weeks. Plasma lipid and lipoprotein levels in mice treated with rAd.RSV.TIMP-1 were similar to those treated with rAd.RSV.betaGal. However, rAd.RSV.TIMP-1-infused mice displayed a marked reduction (approximately 32%; P<0.05) in mean lesion area per section (512+/-121 micrometers(2)x10(3); n=12 sections from 4 animals) as compared with rAd.RSV.betaGal-infused mice (750+/-182 micrometers(2)x10(3); n=12 sections from 4 animals). Similarly, marked reduction in macrophage deposition as well as MMP-2, MMP-3, and MMP-13 antigens was observed. CONCLUSIONS: Histological and immunohistologic analyses of atherosclerotic lesions revealed increases in collagen, elastin, and smooth muscle alpha-actin content in mice treated with rAd.RSV.TIMP-1. These qualitative and quantitative features were the consequence of TIMP-1 infiltration from plasma to arterial intima, as immunohistochemical analyses revealed an abundance of TIMP-1 specifically in lesions of rAd.RSV. TIMP-1-treated mice.
Adenoviridae↗
Interleukin-8 mediates downregulation of tissue inhibitor of metalloproteinase-1 expression in cholesterol-loaded human macrophages: relevance to stability of atherosclerotic plaque.
BACKGROUND: The accumulation of macrophage-derived foam cells in atherosclerotic lesions correlates with increased local release of matrix-degrading metalloproteinases (MMPs) and a thin fibrous cap. The activity of these enzymes is controlled by specific tissue inhibitors of metalloproteinases (TIMPs). METHODS AND RESULTS: Because oxidized low-density lipoprotein (OxLDL) modulates gene expression, we investigated the effect of these particles on the levels of MMP-1, MMP-3, MMP-9, TIMP-1, and TIMP-2 in the culture media of human monocyte-derived macrophages. OxLDL but not native LDL or high-density lipoprotein reduced the level of TIMP-1 in a dose-dependent manner with maximal effect (60% of control) at approximately 100 microg protein/mL. In addition, Northern blotting revealed marked reduction in the abundance of TIMP-1 mRNA in OxLDL-treated cells. Evaluation of the effect of oxysterol components of OxLDL on TIMP-1 production revealed that 25-hydroxycholesterol (1 microg/mL) was the most potent inhibitor ( approximately 30% of control). Such inhibition was partially mediated by interleukin (IL)-8. Indeed, IL-8 (2.5 ng/mL) induced maximal inhibition of TIMP-1 accumulation (30% of control) in 4 of 6 cell preparations. In addition, the inhibitory effect of OxLDL-treated cells in the presence of an anti-IL-8 neutralizing antibody was partially reversed. CONCLUSIONS: Immunohistochemical analyses of human atherosclerotic plaques revealed the expression of TIMP-1 in some but not all macrophage-rich and IL-8-rich areas. Therefore, IL-8 may play a potential atherogenic role by inhibiting local TIMP-1 expression, thereby leading to an imbalance between MMPs and TIMPs at focal sites in the atherosclerotic plaque.
Antibodies, Monoclonal↗
The production of scoliosis after pinealectomy in young chickens, rats, and hamsters.
STUDY DESIGN: This study involved weekly radiographic examination of pinealectomized rats, hamsters, and chickens to observe the development of scoliosis. OBJECTIVES: To determine whether pinealectomy produces scoliosis in animals more closely related phylogenetically to humans than to chickens, namely rats and hamsters, which are representative of mammals. SUMMARY OF BACKGROUND DATA: Pinealectomy in 3-day-old chickens has consistently resulted in the development of scoliosis with many characteristics similar to those seen in patients with adolescent idiopathic scoliosis. It has not been determined whether this phenomenon is restricted solely to chickens or is applicable to other animals, especially those more closely related to humans. METHODS: The pineal gland was removed from young rats, hamsters, and chickens. All animals underwent radiography weekly to detect the development of any scoliosis. Weight and length measurements were also taken weekly, and serum melatonin levels were determined at the time the animals were killed. RESULTS: Scoliosis was not observed in either the rats or the hamsters. In contrast, scoliosis developed in 10 of 21 chickens. Serum melatonin levels in all pinealectomized animals were zero. CONCLUSIONS: In contrast to the chickens, pinealectomy does not seem to cause scoliosis in either young rats or hamsters. The reasons for this discrepancy may include differences in the physiology and spinal morphology of the rat and hamster in comparison with the chicken. In the pinealectomized chickens, the results also suggest that future scoliosis development might be indicated by a significant increase in size when they are compared with pinealectomized chickens that do not develop scoliosis. Such differences in growth rates also distinguish patients with adolescent idiopathic scoliosis.
Animals↗
Noggin upregulates Fos expression by a calcium-mediated pathway in amphibian embryos.
In amphibia, noggin, one of the neural inducers expressed in the Spemann organizer, acts by neutralizing the effects of bone morphogenetic protein-4 (BMP-4). It is shown that noggin is able to activate L-type calcium channels. The fos proto-oncogene is known to be induced within minutes by calcium signaling. Here it is reported that in animal cap explants of the amphibian Pleurodeles waltl, noggin can induce upregulation of a FOS-related protein in a calcium-dependent manner. Specific inhibition of the dihydropyridine sensitive L-type calcium channels blocked both calcium influx and the induction of FOS-related protein. When animal cap explants were treated with caffeine in order to release calcium from an internal store or with a specific agonist of the L-type calcium channels, FOS-related protein could be detected in cell nuclei by 5 or 15 min, respectively. Additionally, the calcium calmodulin kinase inhibitor. KN62, could block the upregulation of FOS-related protein induced by agents that increased intracellular calcium ([Ca2+]i). The present results suggest that transcription factors from the FOS family are downstream targets of neural inducer noggin.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Cidofovir-induced end-stage renal failure.
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Antiviral Agents↗