Changing managed-care model offers opportunities for nutrition coverage.
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Dietary Services↗
Biomedical subjects
M Mathieu
Publications and source records attributed to M Mathieu.
In vivo evidence for the production of sulfated steroids in the frog brain.
It is well established that sulfated neurosteroids are potent regulators of neuronal activity but the biosynthesis of sulfate esters of steroids in the central nervous system (CNS) has received little attention. In particular, the localization of hydroxysteroid sulfotransferase (HST), the enzyme which is responsible for the formation of sulfated steroids, has never been determined in the brain. We took advantage of the availability of an antiserum raised against rat liver HST to investigate the distribution of this enzyme in the CNS of the frog Rana ridibunda. Two populations of HST-positive neurons were localized in the anterior preoptic area and the magnocellular nucleus of the hypothalamus. Numerous HST-immunoreactive fibers were visualized throughout the telencephalon and the diencephalon. Reversed-phase high performance liquid chromatography (HPLC) analysis of frog telencephalon and hypothalamus extracts combined with radioimmunoasssay (RIA) detection showed the presence of substantial amounts of DHEAS-immunoreactive material which coeluted with synthetic DHEAS. The concentrations of DHEAS detected in the telencephalon and hypothalamus were respectively eight and five times higher than in the serum. The present study demonstrates the occurrence of HST-immunoreactive material in neurons of the frog telencephalon and diencephalon. This report also provides evidence for the presence of HST bioactivity, in vivo, in the frog brain.
Animals↗
Storage metabolism in the Pacific oyster (Crassostrea gigas) in relation to summer mortalities and reproductive cycle (west coast of France).
We describe seasonal changes in the biochemical composition of digestive gland, adductor muscle and gonad and surrounding mantle area in Crassostrea gigas from the Western Atlantic coast of France. Seasonality in histology of storage tissues and glycogen storage capacity in isolated vesicular cells were also studied. Proteins, the main muscle components did not contribute to the gametogenetic effort. Glycogen and lipids were stored in the digestive gland, gonad and surrounding mantle area during the wintering period and the gonad and surrounding mantle area represented the main storage compartment supplying the reproductive effort. Gametogenesis in spring and summer was associated with an increase in lipid and protein contents and took place at the expense of glycogen reserves. Histological study of storage tissue in the gonad led us to define four seasonal stages of storage tissue development. In vitro, glycogen storage capacity in isolated vesicular cells was high from November to March and markedly reduced during gametogenesis, decreasing below detectable levels after spawning. This physiological state should be taken into account with relation to summer mortalities occurring in commercial growing areas.
Animals↗
In vivo studies of upstream regulatory cis-acting elements of the alcR gene encoding the transactivator of the ethanol regulon in Aspergillus nidulans.
The alcR gene of Aspergillus nidulans, which encodes the specific transactivator of the ethanol utilization pathway, is positively autoregulated and carbon catabolite repressed. Regulation by these two circuits occurs at the transcriptional level via the binding of the two regulators, AlcR and CreA, to their cognate targets respectively. We demonstrate here that out of two clustered putative AlcR repeated consensus sequences, only the palindromic target is functional in vivo. Hence, it is solely responsible for the alcR positive autogenous activation loop. Transcript mapping of the alcR gene showed that transcription initiation can occur at 553 bp and at or near 86 bp upstream of the start codon. These transcription start sites yield a transcript of 3.0 kb, which appears only under induced growth conditions, and of 2.6 kb, which is present under both induced and non-induced growth conditions respectively. Nine CreA consensus sites are present in the alcR promoter but only two pairs of two sites are functional in vivo. One of them is located in close proximity to the AlcR functional target. Within this pair, both sites are necessary to mediate a partial repression of alcR transcription. Disruption of either site results in an overexpression of alcR due to the absence of direct competition between AlcR and CreA for the same DNA region. The second functional pair of CreA sites is located between the two transcription initiation sites. Disruption of either of the two sites results in a totally derepressed alcR transcription, showing that they work as a pair constituting the more efficient repression mechanism. Thus, CreA acts by two different mechanisms: by competing with AlcR for the same DNA region and by an efficient direct repression. The latter mechanism presumably interfers with the general transcriptional machinery.
Aspergillus nidulans↗
Structure and expression of mGDF, a new member of the transforming growth factor-beta superfamily in the bivalve mollusc Crassostrea gigas.
To gain insight into the evolution of the structure and functions of transforming growth factor (TGF)-beta superfamily members, a cDNA encoding a new member from the bivalve mollusc Crassostrea gigas named mGDF (molluscan growth and differentiation factor) was identified by PCR using degenerate primers. The mGDF precursor exhibits characteristic features of the TGF-beta superfamily and shows highest homology with human BMP2 and Drosophila DPP. Conversely, the mgdf gene displays a distinct pattern of expression during development. Indeed mgdf transcripts were not detected early in development but increased markedly before metamorphosis. These findings raise the possibility that mGDF could play a central role in the biological processes that allow larvae to become competent to metamorphose.
Amino Acid Sequence↗
Environmental regulation of Bacillus subtilis sigma(D)-dependent gene expression.
The sigma(D) regulon of Bacillus subtilis is composed of genes encoding proteins for flagellar synthesis, motility, and chemotaxis. Concurrent analyses of sigma(D) protein levels and flagellin mRNA demonstrate that sigD expression and sigma(D) activity are tightly coupled during growth in both complex and minimal media, although they exhibit different patterns of expression. We therefore used the sigma(D)-dependent flagellin gene (hag) as a model gene to study the effects of different nutritional environments on sigma(D)-dependent gene expression. In complex medium, the level of expression of a hag-lacZ fusion increased exponentially during the exponential growth phase and peaked early in the transition state. In contrast, the level of expression of this reporter remained constant and high throughout growth in minimal medium. These results suggest the existence of a nutritional signal(s) that affects sigD expression and/or sigma(D) activity. This signal(s) allows for nutritional repression early in growth and, based on reconstitution studies, resides in the complex components of sporulation medium, as well as in a mixture of mono-amino acids. However, the addition of Casamino Acids to minimal medium results in a dose-dependent decrease in hag-lacZ expression throughout growth and the postexponential growth phase. In work by others, CodY has been implicated in the nutritional repression of several genes. Analysis of a codY mutant bearing a hag-lacZ reporter revealed that flagellin expression is released from nutritional repression in this strain, whereas mutations in the transition state preventor genes abrB, hpr, and sinR failed to elicit a similar effect during growth in complex medium. Therefore, the CodY protein appears to be the physiologically relevant regulator of hag nutritional repression in B. subtilis.
Amino Acids↗
Transcriptional potencies of inhaled glucocorticoids.
Glucocorticoids (GC) are the most effective anti-inflammatory drugs used in asthma. By a process called trans-activation, they increase the transcription of genes involved in either beneficial processes or certain side effects. Through trans-repression, they inhibit the transcription factors nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1), thereby decreasing the expression of many genes encoding inflammatory mediators such as the cytokine RANTES. We have measured the trans-activation and trans-repression potencies of the five currently available inhaled GC using reporter gene assays. The rank order of trans-activation potencies in HeLa cells stably transfected with a GC-inducible luciferase gene was fluticasone propionate > budesonide and triamcinolone acetonide > beclomethasone dipropionate and flunisolide. For all GC except beclomethasone dipropionate, there was a highly significant correlation between their potency to trans-activate in HeLa cells and their capacity to induce the gluconeogenic enzyme tyrosine aminotransferase in hepatoma tissue culture (HTC) cells. The rank order of trans-repression potencies in A549 lung cells transiently transfected with an AP-1- or NF-kappaB-dependent luciferase gene was fluticasone propionate > budesonide > beclomethasone dipropionate, triamcinolone acetonide, and flunisolide. The same rank order was found for inhibition of RANTES release. Thus, determination of trans-repression and trans-activation potencies of GC may help to predict their capacity to produce anti-inflammatory and side effects, respectively.
Administration, Inhalation↗
Glucocorticoid receptor alpha and beta in glucocorticoid dependent asthma.
Patients with glucocorticoid (GC)-dependent asthma present an ongoing inflammation of the airways despite chronic long-term treatment with oral GC. Interleukin (IL)-8 and granulocyte/macrophage colony-stimulating factor (GM-CSF) have been implicated in airway inflammation in severe asthma and their synthesis is normally repressed by GC. To further characterize the inflammatory process in GC-dependent asthma, we measured the release of IL-8 and GM-CSF by peripheral blood mononuclear cells (PBMC) of eight normal subjects, six untreated controlled asthmatics, six untreated uncontrolled asthmatics, and nine GC-dependent asthmatics. We show that PBMC from GC-dependent asthmatics released high amounts of these cytokines despite chronic in vivo exposure to GC (p < 0.001 versus normal subjects). In contrast, when untreated uncontrolled asthmatics were given a short course of oral GC, IL-8 and GM-CSF production was inhibited (p = 0.0078). Release of IL-8 and GM-CSF by PBMC of GC-dependent asthmatics was reduced after in vitro GC treatment (p < 0.002). We investigated whether the incapacity of GC to inhibit production of these cytokines in vivo was the result of a dysregulation of the glucocorticoid receptor (GR) in GC-dependent asthma. GRalpha and GRbeta are, respectively, the functional receptor and a putative dominant negative form of the receptor. Western blot and polymerase chain reaction (PCR) analyses indicated that GRalpha was expressed at similar level in all groups and was largely predominant over GRbeta. Thus, persistent release of IL-8 and GM-CSF in GC-dependent asthma is not associated with low expression of GRalpha or overexpression of GRbeta.
Adult↗
The KBG syndrome: an additional sporadic case.
We report the sporadic case of a boy with clinical features of KBG syndrome, including slight mental retardation, characteristic facies, macrodontia, and skeletal anomalies.
Abnormalities, Multiple↗
Distribution of vasoactive intestinal peptide-like immunoreactivity in the brain and pituitary of the frog (Rana esculenta) during development.
The localization of vasoactive intestinal peptide (VIP)-like immunoreactive (ir) elements was investigated in the brain of the anuran amphibian, Rana esculenta, during development. Using an antiserum raised against the porcine VIP, ir cell bodies and fibers were observed in the forebrain of tadpoles a few days after hatching. During early premetamorphosis, ir perikarya were distributed in the ventral infundibular nucleus of the hypothalamus and in the posterocentral nucleus of the thalamus. Labeled fibers were detected in the olfactory bulbs and in the hypothalamus. In these larvae, furthermore, several VIP-ir cells were found in the pars distalis of the pituitary and there were ir fibers in the pars nervosa. In tadpoles at stages VIII-IX, a new group of VIP-labeled neurons was observed in the dorsal part of the infundibular nucleus. In other brain regions, the distribution of the immunoreactivity was similar to that described in the earliest stages, i.e., IV-VII. During mid-premetamorphosis, stages X-XII of development, an additional set of ir perikarya appeared in the ventrolateral area of the thalamus. During late premetamorphosis, stages XIII-XVIII, the organization of VIP-like immunoreactivity was more complex and its distribution more widespread. Two new groups of ir cell bodies appeared, one in the preoptic nucleus and another in the anteroventral area of the thalamus, and for the first time, VIP immunoreactivity was observed in the median eminence. This distribution pattern persisted through to the prometamorphic, four-limb stage. Strikingly, no VIP-ir elements were observed anywhere in the mid- and hindbrain. The present results indicate that a VIP-like ir peptide may be involved in the processing of olfactory information or may act as a neurohormone, hypophysiotropic factor, and neuromodulator in the brain of R. esculenta during development.
Animals↗
Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus.
We report the crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus, a major human pathogen, to 2.8-A resolution. This enzyme is a key target for developing specific antiviral therapy. The structure of the catalytic domain contains 531 residues folded in the characteristic fingers, palm, and thumb subdomains. The fingers subdomain contains a region, the "fingertips," that shares the same fold with reverse transcriptases. Superposition to the available structures of the latter shows that residues from the palm and fingertips are structurally equivalent. In addition, it shows that the hepatitis C virus polymerase was crystallized in a closed fingers conformation, similar to HIV-1 reverse transcriptase in ternary complex with DNA and dTTP [Huang H., Chopra, R., Verdine, G. L. & Harrison, S. C. (1998) Science 282, 1669-1675]. This superposition reveals the majority of the amino acid residues of the hepatitis C virus enzyme that are likely to be implicated in binding to the replicating RNA molecule and to the incoming NTP. It also suggests a rearrangement of the thumb domain as well as a possible concerted movement of thumb and fingertips during translocation of the RNA template-primer in successive polymerization rounds.
Amino Acid Sequence↗
Dystonin-deficient mice exhibit an intrinsic muscle weakness and an instability of skeletal muscle cytoarchitecture.
Dystonia musculorum (dt) was originally described as a hereditary sensory neurodegeneration syndrome of the mouse. The gene defective in dt encodes a cytoskeletal linker protein, dystonin, that is essential for maintaining neuronal cytoskeletal integrity. In addition to the nervous system, dystonin is expressed in a variety of other tissues, including muscle. We now show that dystonin cross-links actin and desmin filaments and that its levels are increased during myogenesis, coinciding with the progressive reorganization of the intermediate filament network. A disorganization of cytoarchitecture in skeletal muscle from dt/dt mice was observed in ultrastructural studies. Myoblasts from dt/dt mice fused to form myotubes in culture; however, terminally differentiated myotubes contained incompletely assembled myofibrils. Another feature observed in dt/dt myotubes in culture and in skeletal muscle in situ was an accumulation and abnormal distribution of mitochondria. The diaphragm muscle from dt/dt mice was weak in isometric contractility measurements in vitro and was susceptible to contraction-induced sarcolemmal damage. Altogether, our data indicate that dystonin is a cross-linker of actin and desmin filaments in muscle and that it is essential for establishing and maintaining proper cytoarchitecture in mature muscle.
Actins↗
[Corticosteroid-resistant asthma: basic aspects].
A CONTROVERSIAL DEFINITION: The current definition of corticosteroid-resistant asthma is a spirometry definition. There is however, no consensus on dose, treatment duration, steroid administration route and the degree of FEV1 non-reversibility allowing the diagnosis of corticosteroid-resistant asthma. Finally, the beneficial effect of steroids in clinical terms (symptom frequency, number of hospitalizations, quality of life) is not taken into consideration, thus nearly one-half al all patients included in studies on corticosteroid resistance are taking long-term oral steroids. This subgroup of patients must be considered individually when examining these studies. COMPLEX PATHOGENESIS: There are a wide range of anomalies described in the literature involving: glucocorticoid pharmacokinetics, cytokine regulation, cell function (monocytes, lymphocytes, eosionophils), and transcription factors (glucocorticoid and AP-1 receptors). DIFFICULT THERAPEUTIC MANAGEMENT: There are several prerequisites before proposing exceptional regimens using cyclosporine, gold salts, methotrexate, or immunoglobulins: i) certain diagnosis of asthma (with CT scan and ultrasonographic explorations if needed, ii) proper control of environmental factors and good compliance, iii) proof of the absence of clinical benefit with long-term corticosteroids. These exceptional therapeutic schemes have their disadvantages and are only warranted by clinically patent corticosteroid resistance (whatever the "biological" cause).
Adrenal Cortex Hormones↗
Effects of five natural gonadotropin-releasing hormones on cell suspensions of marine bivalve gonad: stimulation of gonial DNA synthesis.
Gonadotropin-releasing hormones (GnRH) constitute a family of neuropeptides which are important regulators of reproduction in vertebrates. The effect of mammalian GnRH (mGnRH), salmon GnRH, chicken GnRH-I, chicken GnRH-II, and lamprey GnRH-I on [3H]thymidine incorporation into DNA of dissociated gonadal cells of marine bivalves has been studied. The incorporation of [3H]thymidine is linear between 1.5 and 8 h of incubation. All five GnRHs significantly increased DNA synthesis in gonial cells of Crassostrea gigas. The maximal activation was about of 135-140% above control. The activation is dose dependent, over the range 10(-11) to 10(-6) M, but is modulated by the physiological condition of the cells and the stage of sexual maturity of the gonad. mGnRH has also a mitogenic effect in dissociated mantle cells of Mytilus edulis. The effect of mGnRH is blocked by a GnRH antagonist ([D-pGlu1,D-Phe2, D-Trp3,6]GnRH, 5 x 10(-6)M) in C. gigas as well as in M. edulis, suggesting that the GnRH action in the gonad is mediated by specific receptors for GnRH or GnRH-like peptides. The existence of GnRH-immunoreactive neurons and fibers in the cerebral and pedal ganglia of M. edulis was demonstrated by immunocytochemistry. They are located principally in the anterior internal area of the cerebral ganglia, close to the cerebral commissure and in the posterior part of the pedal ganglia. The presence of GnRH-responsive cells and GnRH-like immunoreactive material suggests that peptides of the GnRH-like family are present and functional in bivalve molluscs.
Animals↗
Etiology of preoperative anemia in patients undergoing scheduled cardiac surgery.
PURPOSE: Ten percent of our cardiac surgical patients have preoperative anemia. Anemia diagnosed before scheduled cardiac surgery is a strong predictor of the need for homologous blood transfusion (RBC) perioperatively but the cause of this preoperative anemia is not known. The purpose of this study was to evaluate the etiology of preoperative anemia. METHODS: Seventy-five consecutive anemic cardiosurgical patients (Hb = < 120 g x L(-1) the day before surgery) were studied prospectively. All had multiple diagnostic blood tests done in the preoperative period to diagnose the cause of the anemia and subsequently underwent non-emergency cardiac surgery. Anesthesia and RBC transfusion were standardized according to the protocol. Data in respect to operation, RBC and other blood product transfusion during operation and hospital stay were recorded. RESULTS: Hospital-acquired anemia was present in 37.3% of anemic patients (hemoglobin decrease during hospitalization before surgery > or =9 g x l(-1)). The second most common diagnosis was iron deficiency anemia (29.3% patients) followed by anemia of chronic renal disease (10.7% patients). When coronary angiography was performed close to operation time, patients had a higher decrease in hemoglobin concentration during hospitalization --suggesting that blood loss during angiography was, in part, responsible for anemia. Seventy-five percent of anemic patients were transfused with RBC perioperatively compared with our overall transfusion rate of 30% of cardiac surgery patients. CONCLUSIONS: In the majority of patients, preoperative anemia is potentially preventable. Investigation and treatment of anemia before cardiac surgery should be a priority in preparing the patient for surgery.
Aged↗
Metaphyseal anadysplasia in two sisters.
Metaphyseal anadysplasia is a rare form of metaphyseal chondrodysplasia with well-defined radiological abnormalities. The prognosis is good as the natural course results in regression of the lesions with normal stature in adulthood. The few reported cases, exclusively in male children, indicated possible X-linked recessive transmission. The documentation of two affected sisters suggests genetic heterogeneity or another mode of inheritance.
Cartilage↗
Identification of an urotensin I-like peptide in the pituitary of the lungfish Protopterus annectens: immunocytochemical localization and biochemical characterization.
In the present study we have investigated the localization and biochemical characteristics of urotensin I (UI)-like and urotensin II (UII)-like immunoreactive peptides in the central nervous system (CNS) and pituitary of the lungfish, Protopterus annectens, by using antisera raised against UI from the white sucker Catostomus commersoni and against UII from the goby Gillichythys mirabilis. UI-like immunoreactive material was found within the melanotrope cells of the intermediate lobe of the pituitary. By contrast, no UI-immunoreactive structures were found in the brain. No UII-like peptides structurally similar to goby UII were found in the brain and pituitary of P. annectens. The UI-immunoreactive material localized in the pituitary was characterized by combining reversed-phase high-performance liquid chromatography (HPLC) analysis and radioimmunological detection. The UI-like immunoreactivity contained in a pituitary extract eluted as a single peak with a retention time intermediate between those of sucker UI and rat corticotropin-releasing factor (CRF). Control tests on adjacent sections of pituitary showed that the UI antiserum cross-reacted with the frog skin peptide sauvagine, but lungfish UI did not co-elute with synthetic sauvagine on HPLC. On the contrary, no cross-reaction was observed between the UI antiserum and CRF or alpha-melanocyte-stimulating hormone (alpha-MSH). The occurrence of an UI-like peptide in the intermediate lobe of the pituitary of P. annectens suggests that, in lungfish, this peptide may act as a classic pituitary hormone or may be involved in the control of melanotrope cell secretion.
Amino Acid Sequence↗
Determination of total fatty acids in plasma: cis-5-tetradecenoic acid (C14:1 omega-9) in the diagnosis of long-chain fatty acid oxidation defects.
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3-Hydroxyacyl CoA Dehydrogenases↗