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1.
Rev Med Interne ; 38(4): 250-255, 2017 Apr.
Article in French | MEDLINE | ID: mdl-27890382

ABSTRACT

The role of biomarkers in clinical research was recently highlighted in the new criteria for the diagnosis of Alzheimer's disease. Cerebro-spinal fluid (CSF) biomarkers (total Tau protein, threonine 181 phosphorylated Tau protein and amyloid Aß1-42 peptide) are associated with cerebral neuropathological lesions observed in Alzheimer's disease (neuronal death, neurofibrillary tangle with abnormal Tau deposits and amyloid plaque). Aß1-40 amyloid peptide dosage helps to interpret Aß1-42 results. As suggested in the latest international criteria and the French HAS (Haute Autorité de santé) recommendations, using theses CSF biomarkers should not be systematic but sometimes could be performed to improve confidence about the diagnostic of Alzheimer's disease in young subjects or in complex clinical situations. Future biomarkers actually in development will additionally help in diagnostic process (differential diagnosis) and in prognostic evaluation of neurodegenerative diseases.


Subject(s)
Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/diagnosis , Biomarkers/cerebrospinal fluid , Dementia/diagnosis , Amyloid beta-Peptides/cerebrospinal fluid , Biomedical Research/methods , Biomedical Research/trends , Dementia/cerebrospinal fluid , Diagnosis, Differential , Humans , Memory/physiology , Practice Patterns, Physicians' , tau Proteins/cerebrospinal fluid
2.
Can Respir J ; 2016: 4592702, 2016.
Article in English | MEDLINE | ID: mdl-27445541

ABSTRACT

Background. Cystic fibrosis-associated liver disease (CFLD) is a major cause of death. The objective of our retrospective study was to describe the relevance of magnetic resonance imaging (MRI) and liver stiffness measurement (LSM) for CFLD evaluation. Methods. All cystic fibrosis adult patients evaluated by MRI and LSM were included. MR signs of portal hypertension (PHT), dysmorphia, or cholangitis were collected and LSM expressed in kPa and Metavir. Results. Of 25 patients, 52% had abnormal MRI. Median LSM was 5.7 kPa (3.4-9.9). Three patients had F2 score and one had F3 score. In patients with PHT, LSM was 7.85 kPa (3.7-9.9) compared to 5 (3.4-7.5) in others, p = 0.02. In patients with abnormal liver function tests, 50% had increased LSM (≥F2), whereas 94% with normal tests had normal LSM (p = 0.04). Seven patients had abnormal MRI despite normal ultrasonography. Conclusions. MRI and LSM provide useful information on CFLD and may help to screen patients with PHT.


Subject(s)
Cholangiography , Cystic Fibrosis/complications , Elasticity Imaging Techniques , Imaging, Three-Dimensional , Liver Diseases/diagnostic imaging , Adolescent , Adult , Female , Humans , Liver Diseases/etiology , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Young Adult
3.
Autoimmun Rev ; 14(6): 547-54, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25661980

ABSTRACT

Fecal calprotectin (FC) is a simple, non-invasive and reproducible test, which has been described to be highly elevated in patients with active inflammatory bowel diseases. Recently, few authors have reported increased levels of FC in SSc patients, although the relationship between FC levels and the degree of gastrointestinal involvement has not yet been determined in patients with SSc. Thus, this prospective study aimed to: 1) determine the prevalence of increased fecal calprotectin (FC) levels in unselected patients with systemic sclerosis (SSc); 2) make prediction about which SSc patients exhibit increased levels of FC; and 3) evaluate the correlation between increased levels of FC and digestive symptoms, and gastrointestinal involvement, including the presence of small intestinal bacterial overgrowth (SIBO) using glucose H2/CH4 breath test. 125 consecutive patients with SSc underwent FC levels and glucose H2/CH4 breath test. All of the patients with SSc also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. 93 (74.4%) patients had abnormal levels of FC (>50 µg/g); 68 patients (54.4%) exhibited highly elevated levels of FC (>200 µg/g). A marked correlation was found between abnormal FC levels and GSS score of digestive symptoms, esophageal involvement and delayed gastric emptying. Moreover, we found a strong association between abnormal levels of FC and the presence of SIBO on glucose H2/CH4 breath test, with the higher correlation between the presence of SIBO and the level of FC ≥275 µg/g with an area under the receiver operating characteristic curve of 0.97 ± 0.001 (CI: 0.93-0.99; p<10(-6)); the sensitivity of FC level ≥275 µg/g for predicting SIBO was as high as 0.93, while the specificity was 0.95. Finally, eradication of SIBO was obtained in 52.4% of the SSc patients with a significant improvement of intestinal symptoms. Finally, after 3 months of rotating courses of alternative antibiotic therapy, eradication of SIBO was associated with significant decrease of FC levels in SSc patients. The current study underscores that abnormal FC levels were correlated with gastrointestinal impairment, especially SIBO. Because FC levels ≥275 µg/g were markedly associated with the presence of SIBO, our findings suggest that FC may be a helpful test in identifying the group of SSc patients at high risk for SIBO requiring glucose breath test to detect SIBO. Finally, we also suggest that FC levels may be helpful in SSc patients to assess SIBO eradication, as long-term antibiotic therapy is costly and carries risks such as the onset of pseudo-membranous colitis and SIBO-related antibiotic resistance.


Subject(s)
Feces/chemistry , Leukocyte L1 Antigen Complex/analysis , Scleroderma, Systemic/diagnosis , Breath Tests , Humans , Scleroderma, Systemic/complications , Surveys and Questionnaires
4.
Rev Neurol (Paris) ; 166(5): 534-7, 2010 May.
Article in English | MEDLINE | ID: mdl-20070997

ABSTRACT

INTRODUCTION: Tangier disease (TD) is a rare autosomal recessive disorder characterized by a deficiency or absence of high-density lipoprotein (HDL) caused by mutations in the adenotriphosphate-binding cassette transporter-1 gene (ABCA1). Mutations of ABCA1 lead to a defect in cellular cholesterol removal and to deposition of cholesterol esters throughout the body. OBSERVATION: We report here on the case of a 53-year-old woman with a severe phenotype of TD. The patient had a dizygous twin sister who had only asymptomatic corneal opacities and thrombopenia. CONCLUSION: This family demonstrates the wide intrafamilial phenotype diversity of TD.


Subject(s)
Tangier Disease/genetics , Tangier Disease/pathology , ATP Binding Cassette Transporter 1 , ATP-Binding Cassette Transporters/genetics , Biopsy , Demyelinating Diseases/pathology , Electrocardiography , Electroencephalography , Electromyography , Female , Hormones/blood , Humans , Lipids/blood , Middle Aged , Nerve Fibers/pathology , Phenotype , Schwann Cells/pathology , Sensory Receptor Cells/pathology , Tangier Disease/cerebrospinal fluid , Twins, Dizygotic
5.
Ann Biol Clin (Paris) ; 67(6): 629-39, 2009.
Article in French | MEDLINE | ID: mdl-19939766

ABSTRACT

Research of new diagnosis or prognosis biomarkers is a major challenge for the management of patients with complex pathologies like cancer. Clinical proteomics is one of the recent approaches to identify these biomarkers in biological fluids. Over the last five years, many problems related to the variability and the quality control of these analyses have been observed. This was notably related to the different preanalytical status of each sample. A strong need for standardization of the critical preanalytical phases (collection, transport, processing, storage...) has been therefore recognized. With this goal in mind, working groups of the "Institut national du cancer" (INCa) and the "Société française de biologie clinique" (SFBC) proposed here preanalytical proteomics guidelines for the most common biological fluids: plasma, serum, urine and cerebrospinal fluid. To goal is to provide the basis for the harmonization of the procedures in clinical laboratories and biobanks to allow an optimal use of biological collections.


Subject(s)
Body Fluids/physiology , Clinical Laboratory Techniques/standards , Diagnostic Techniques and Procedures/standards , Practice Guidelines as Topic , Proteomics/methods , Blood Chemical Analysis/standards , Humans , Prognosis , Proteinuria/diagnosis , Proteomics/standards , Urine/chemistry
6.
Ann Biol Clin (Paris) ; 67(6): 641-9, 2009.
Article in French | MEDLINE | ID: mdl-19939767

ABSTRACT

The SFBC Working Group on << Preanalytics and multiplex analyses in proteomics >> is presenting a protocol which will allow harmonization of biospecimen research studies on the impact of different preanalytical variations on peptidic and protein analytes. This protocol is based upon standardization of preanalytical options corresponding to different preanalytical variations and different types of biospecimens (serum, plasma, cedrebrospinal fluid and urine). Application of this protocol will allow, not only harmonization of Biospecimen research, but also elaboration of standard nomenclature of the preanalytical steps.


Subject(s)
Peptides/analysis , Proteins/analysis , Proteomics/methods , Biological Specimen Banks/standards , Blood Chemical Analysis/standards , Cerebrospinal Fluid , Female , Humans , Male , Proteomics/standards , Specimen Handling/standards , Terminology as Topic , Urine
7.
Rev Neurol (Paris) ; 164(8-9): 728-32, 2008.
Article in French | MEDLINE | ID: mdl-18805305

ABSTRACT

Iridodonesis or tremulous iris is a clinical sign of ectopia lentis which is frequently associated with homocystinuria. We present a forty-two-year-old woman victim of a left middle cerebral artery ischemic stroke. The clinical examination found bilateral iridodonesis and laboratory tests showed an increased level of serum homocysteine and homocystinuria. Homocystinuria was caused by a compound heterozygous I278T and D444N mutation of cystathionine beta-synthase (CBS) gene and also a C667T heterozygous polymorphism of methylene-tetrahydrofolate-reductase gene. This case was atypical because of the incomplete phenotype, development of complications in adulthood and the association of a rare compound heterozygous mutation of the CBS gene.


Subject(s)
Homocystinuria/complications , Homocystinuria/genetics , Iris Diseases/etiology , Iris Diseases/genetics , Stroke/etiology , Adult , Brain/pathology , Brain Ischemia/complications , Brain Ischemia/etiology , Female , Heterozygote , Humans , Iris/pathology , Magnetic Resonance Imaging , Mutation/physiology
8.
J Clin Immunol ; 28(5): 445-55, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18587633

ABSTRACT

OBJECTIVE: The objective of this study was to analyze the effects of 3 anti-TNFalpha agents on markers of autoimmunity in rheumatoid arthritis (RA) and spondylarthropathy (SPA) patients. METHODS: First-time anti-TNFalpha biologics (infliximab, etanercept, or adalimumab) were prescribed to 156 RA and 95 SPA (58 ankylosing spondylarthritides, 37 psoriatic arthritides). During 1-2 years of follow-up, clinical, biological [antinuclear (ANA) and anti-double-stranded (dsDNA) antibodies, rheumatoid factors (RF), and anti-cyclic citrullinated peptide (CCP) for RA], and therapeutic data were collected biannually. RESULTS: ANA appeared or ANA and anti-dsDNA titers increased significantly (P < 0.001) more under infliximab than etanercept in both rheumatisms and than adalimumab in RA patients. During the 2-year follow-up, ANA appeared more in RA patients taking adalimumab than etanercept (P = 0.003), but independently of the anti-TNFalpha used; anti-dsDNA titers rarely became positive. Under etanercept or infliximab, ANA and anti-dsDNA were not influenced by the underlying pathology nor were they affected by infliximab intensification over 18 months. Only one case of cutaneous lupus was observed in a patient having IgG anti-dsDNA. The therapeutic responses were independent of ANA and anti-dsDNA titers for all rheumatisms and biologics. In RA patients, RF titers, but not anti-CCP levels, declined with the therapeutic response for all biologics. CONCLUSION: This is the first study that has evaluated the impact of three TNFalpha blockers on ANA and anti-dsDNA antibodies in RA and SPA patients. Autoimmunity was more induced with infliximab than etanercept and to a lesser degree to adalimumab but, more importantly, this emergent autoimmunity was exceptionally associated to clinical manifestations of lupus.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Arthritis, Rheumatoid/drug therapy , Autoantibodies/immunology , Autoimmunity/drug effects , Immunoglobulin G/administration & dosage , Receptors, Tumor Necrosis Factor/administration & dosage , Spondylarthropathies/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Adrenal Cortex Hormones/administration & dosage , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized , Antibody Formation/drug effects , Antibody Formation/immunology , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/immunology , Autoantibodies/blood , Autoimmunity/immunology , Dose-Response Relationship, Drug , Drug Therapy, Combination , Etanercept , Female , Follow-Up Studies , Humans , Infliximab , Male , Middle Aged , Peptides, Cyclic/blood , Peptides, Cyclic/immunology , Severity of Illness Index , Spondylarthropathies/blood , Spondylarthropathies/immunology , Tumor Necrosis Factor-alpha/immunology
9.
Ann Biol Clin (Paris) ; 65(5): 463-71, 2007.
Article in French | MEDLINE | ID: mdl-17913666

ABSTRACT

This review focuses on "clinical proteomics" which represents an emerging discipline in biomedical research. "Clinical proteomics" relies on the analysis of the proteome, i.e. the entire set of peptides and proteins present in a biological sample, to provide relevant data for diagnosis, prognosis or therapeutic strategies of human pathologies. This new type of approach has tremendous potential for the diagnosis of complex pathologies or for the early detection of cancers. This article reports the conclusions of a workgroup of the French Society for Clinical Biology (SFBC) 2004-2006 which evaluated the status, the impact and the future development of proteomics in the clinical field. It provides therefore a broad view going from the methods already present in the clinical laboratories (multiplex technologies...), to the tools for clinical and basis research including bioinformatics.


Subject(s)
Proteomics/trends , Biomarkers/analysis , Electrophoresis, Gel, Two-Dimensional , Forecasting , Gas Chromatography-Mass Spectrometry , Humans , Microfluidic Analytical Techniques , Protein Array Analysis , Proteomics/instrumentation , Proteomics/methods , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
10.
Ann Biol Clin (Paris) ; 61(6): 699-704, 2003.
Article in French | MEDLINE | ID: mdl-14711612

ABSTRACT

Plasma total homocysteine is a parameter frequently included in the biological investigation of arterious or venous thrombotic diseases. Different techniques, chromatographic, enzymatic, and immunochemical, are used in the measurement of homocysteine. Among immunochemical methods, some are conceived to function on multiparametric automates, leading to a greater accessibility of the test for most of the clinical laboratories. In this study, we have evaluated a new immunoassay proposed by the DPC Company for the Immulite 2000 analyzer (chemiluminescence) and compared its performance against the Abbott's immunoassay on IMx (fluorescence polarization). The results obtained show very good general performance of the DPC's technique. Linearity is also excellent. The within run CVs are 9.9, 7.0 and 5.4% and the between run CVs are 8.2, 3.9 and 4.3% respectively for homocysteine levels of 4.2, 13.9 and 27.7 pmol/L. We found a very good correlation between DPC's and Abbott's methods (regression analysis:y=0.948 x + 0.05; r=0.895). The mean of differences between both methods is -0.55 micromol/L. On the whole, the DPC technique appeared in our experience as easily exchangeable, from the analytical point of view, with Abbott's technique.


Subject(s)
Homocysteine/blood , Blood Chemical Analysis/methods , Fluorescence Polarization Immunoassay , Humans , Immunoassay , Luminescent Measurements
11.
Ann Biol Clin (Paris) ; 60(4): 421-8, 2002.
Article in French | MEDLINE | ID: mdl-12147446

ABSTRACT

A lot of methods are now available for total plasma homocysteine (tHcy) determination. Commercial kits using immunoassay, easier to use, begin to supplant in-house laboratory methods. Our aim is to evaluate the interchangeability of tHcy measurements in 9 French hospital laboratories. Six different method types were used: 2 gas chromatography-mass spectrometry (GC-MS), 2 HPLC with fluorescence detection subdivided in one in-house method and one commercial kit (Bio-Rad ), 3 fluorescence polarization immunoassays (FPIA), 1 enzyme immunoassay, 1 amino acid analyser, 1 capillary electrophoresis coupled with laser-induced fluorescence detection (EC-LIF). Each laboratory analysed 41 patient's plasma samples in which 8 samples contained added homocystine. Results were analysed for imprecision, recovery, and methodological differences. The mean among-laboratory imprecision (CV) ranged from 12.5 to 18% in function of plasma sample type and was identical to the mean among-method variation. In terms of recovery, we obtained underestimated results with immunoassays. The bias relative to the GC-MS method was less than 12.5% except for two laboratories, one using FPIA assay and the other EC-LIF. In conclusion, the interchangeability of tHcy results between laboratories is not satisfactory and does not allow us to evaluate cardiovascular risk linked to moderate increases of tHcy.


Subject(s)
Blood Chemical Analysis/methods , Homocysteine/blood , Laboratories, Hospital , Blood Chemical Analysis/standards , Chromatography, Gas , Chromatography, High Pressure Liquid , Electrophoresis, Capillary , Fluorescence , Fluorescence Polarization Immunoassay , France , Humans , Immunoenzyme Techniques , Laboratories, Hospital/standards , Lasers , Mass Spectrometry , Reagent Kits, Diagnostic
13.
Nephrol Dial Transplant ; 16(12): 2407-11, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11733634

ABSTRACT

BACKGROUND: Dialysis patients with primary hyperoxaluria are exposed to risks and hazards associated with calcium oxalate salt deposition in body tissues, since regular dialysis treatment does not adequately correct hyperoxalaemia. The purpose of this study was to evaluate oxalate mass removal using various dialysis modes in a patient suffering from primary hyperoxaluria type 1 (PH1). METHODS: Oxalate kinetics during daily haemodialysis was compared with that of standard haemodialysis (STD HD) and haemodiafiltration (HDF) using high flux dialysers (FB 170 H and FB 210 U, Transdial, Paris, France). All dialysis sessions lasted for 4 h. Blood was withdrawn and spent dialysate was collected in plastic bags every hour to evaluate mass removal. Oxalate concentration in plasma and in spent dialysate was determined by an enzymatic method. Oxalate generation, distribution volume and tissue deposition were calculated using single-pool models adapted from previous studies. RESULTS: Although no significant difference was found in mass removal per session between dialysis strategies and dialyser types, weekly mass removal with daily HD was about 2 times greater than with STD HD or HDF. Even when daily HD was performed, the oxalate generation rate-mass removal ratio (G/R ratio) remained at a value of approximately 2. CONCLUSION: Although daily HD sessions led to a substantial increase in weekly oxalate removal, all three types of renal replacement therapy were insufficient to compensate for estimated oxalate generation. To eliminate sufficient amounts of oxalate generated in PH1 patients, at least 8 h of daily dialysis with a high-flux membrane would probably be required. Renal replacement therapy for PH1 patients needs be improved further.


Subject(s)
Hyperoxaluria, Primary/blood , Hyperoxaluria, Primary/therapy , Oxalates/blood , Renal Dialysis , Female , Hemodiafiltration , Humans , Kinetics , Middle Aged , Models, Biological , Osmolar Concentration , Oxalates/metabolism
14.
Acta Ophthalmol Scand ; 77(1): 23-6, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10071142

ABSTRACT

PURPOSE: We studied changes in the vision of 16 people after consumption of a small quantity of alcohol, at a blood alcohol level (BAL) of 0.57 g/kg. METHODS: We studied visual contrast sensitivity (VCS) using Vistech VCTS 6500, visual evoked potential (VEP) by checked pattern stimulations and the peripheral visual field (PVF) with a perimetric automatic Humphrey. We first carried out the tests on sober people and then on individuals with a BAL of 0.57 g/kg. RESULTS: Alcohol consumption caused no significant difference in performance for these 3 tests. However, at a BAL of 0.57 g/kg there was a decrease in cerebral function, as shown by an increase in the number of mistakes made in the Wisconsin Card Sorting Test. CONCLUSION: These results suggest that for a low blood alcohol level, visual performance is less affected by the visual changes than by alteration in brain functions.


Subject(s)
Alcohol Drinking/adverse effects , Central Nervous System Depressants/adverse effects , Contrast Sensitivity/drug effects , Ethanol/adverse effects , Evoked Potentials, Visual/drug effects , Visual Fields/drug effects , Adult , Alcohol Drinking/blood , Alcohol Drinking/physiopathology , Central Nervous System Depressants/blood , Chromatography, Gas , Contrast Sensitivity/physiology , Ethanol/blood , Evoked Potentials, Visual/physiology , Female , Humans , Male , Reference Values , Visual Field Tests , Visual Fields/physiology
15.
Ann Biol Clin (Paris) ; 56(5): 557-62, 1998.
Article in French | MEDLINE | ID: mdl-9769503

ABSTRACT

Glutamine is transported into the hepatocyte in a sodium-dependent manner. A consequence of the sodium-dependent entry of glutamine is an osmotic swelling of the cell. In the past, glutamine has been given a number of anabolic properties such as the stimulation of both glycogen and lipid synthesis from glucose. The mechanism through which glutamine activates key enzymes in these metabolic pathways involves the glutamine-induced cell swelling. Moreover, glutamine regulates gene expression of the beta-actin gene at a transcriptional level as well as that of the phosphoenolpyruvate carboxykinase gene by stabilizing its mRNA. Regulation of gene expression by glutamine also involves the cell swelling phenomena. Cell swelling is now regarded as a novel regulatory element of hepatic metabolism.


Subject(s)
Glutamine/metabolism , Liver/cytology , Liver/metabolism , Actins/genetics , Animals , Cell Size/physiology , Gene Expression Regulation , Homeostasis , Humans , Lipid Metabolism , Liver Glycogen/metabolism , Osmolar Concentration , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , Sodium/metabolism
16.
FEBS Lett ; 423(2): 125-8, 1998 Feb 20.
Article in English | MEDLINE | ID: mdl-9512343

ABSTRACT

The mechanism of action of hydration state was studied on phosphoenolpyruvate carboxykinase (PCK) gene expression in isolated rat hepatocytes. Hypoosmolarity decreased the level of the PCK mRNA after a lag period of about 60 min. The decreasing effect of hypoosmolarity was totally blocked by inhibitors of both protein synthesis and gene transcription. Moreover, hypoosmolarity specifically increased the synthesis of a 45000 Mr protein, which decreased in the presence of inhibitors of transcription. A close relationship between the synthesis of the 45000 Mr protein and the decrease in the PCK mRNA level was observed, suggesting that this protein might potentially be involved in the regulation of the level of the PCK mRNA by cell swelling.


Subject(s)
Liver/enzymology , Phosphoenolpyruvate Carboxykinase (GTP)/biosynthesis , RNA, Messenger/metabolism , Amanitins/pharmacology , Animals , Cell Size , Dactinomycin/pharmacology , Liver/cytology , Liver/drug effects , Male , Molecular Weight , Nucleic Acid Synthesis Inhibitors/pharmacology , Osmolar Concentration , Phosphoenolpyruvate Carboxykinase (GTP)/chemistry , Protein Synthesis Inhibitors/pharmacology , Rats , Rats, Wistar
17.
Biochimie ; 80(10): 807-11, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9893939

ABSTRACT

Glutamine is able to regulate the expression of various genes in rat hepatocytes. This includes genes coding for proteins involved in glutamine utilization, such as argininosuccinate synthetase (ureagenesis) or phosphoenolpyruvate carboxykinase (gluconeogenesis). Moreover, glutamine is also able to stimulate the expression of genes involved in the acute-phase response, such as the alpha 2-macroglobulin gene. The effect of glutamine on the regulation of gene expression may be explained, at least in part, by the cell swelling due to its sodium-dependent transport. The physiological significance of the effect of glutamine is discussed.


Subject(s)
Gene Expression Regulation , Glutamine/physiology , Liver/metabolism , Aminoisobutyric Acids/metabolism , Animals , Argininosuccinate Synthase/genetics , Argininosuccinate Synthase/metabolism , Cell Size/physiology , Dose-Response Relationship, Drug , Interleukin-6/metabolism , Models, Biological , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , Phosphoenolpyruvate Carboxykinase (ATP)/metabolism , Rats , Time Factors , alpha-Macroglobulins/genetics , alpha-Macroglobulins/metabolism
18.
Biochimie ; 79(2-3): 125-8, 1997.
Article in English | MEDLINE | ID: mdl-9209708

ABSTRACT

The repertoire of the actions of specific amino acids on gene expression is relatively limited in mammalian cells. Glutamine constitutes the most studied amino acid and recent works intended to demonstrate its mechanism of action on two genes: the beta-actin and the phosphoenolpyruvate carboxykinase genes. From these studies, it appears that glutamine may regulate gene expression by, at least, two different mechanisms: one through the glutamine-induced cell swelling, and another through its intracellular metabolism. The involvement of phosphatidylinositol 3-kinase in the signaling pathway triggered by cell swelling is discussed.


Subject(s)
Glutamine/physiology , Phosphoenolpyruvate Carboxykinase (GTP)/genetics , Actins/genetics , Androstadienes/pharmacology , Animals , CHO Cells , Cell Size , Cricetinae , Gene Expression Regulation, Enzymologic , Humans , Liver/cytology , Liver/enzymology , Phosphatidylinositol 3-Kinases , Phosphotransferases (Alcohol Group Acceptor)/physiology , Polyenes/pharmacology , Rats , Sirolimus , Water-Electrolyte Balance , Wortmannin
19.
Eur J Biochem ; 242(3): 537-43, 1996 Dec 15.
Article in English | MEDLINE | ID: mdl-9022679

ABSTRACT

The expression of phosphoenolpyruvate carboxykinase (P-pyruvate CK) was shown to be decreased by hypoosmolarity and increased by glutamine in perfused liver from fed rats [Newsome, W. P., Warskulat, U., Noe, B., Wettstein, M., Stoll, B., Gerok, W. & Häussinger, D. (1994) Biochem, J. 304, 555-560]. This work was undertaken to specify the mechanisms of glutamine action, using isolated hepatocytes from rats that had been starved for 24 h. At low concentrations (up to 5 mM), glutamine elicited a decrease in the level of P-pyruvate CK mRNA through cell swelling and, at higher concentrations, an increase in the mRNA level was observed. Experiments with combinations of glucose and glutamine or glucose and various amino acids demonstrated that glutamine counteracted the inhibitory effect of glucose on P-pyruvate CK mRNA at a transcriptional, level, and strongly suggested that the amide group of glutamine was involved in this effect. The metabolism of glucose was required for the reinforcement of the apparent stimulatory effect of glutamine, as demonstrated by the use of various sugars. Glucosamine, but not mannosamine, increased the level of P-pyruvate CK mRNA, as did glucose plus glutamine. These results suggest that the pathway leading from glucosamine-6-phosphate production might be responsible, at least partly, for the effect observed on P-pyruvate CK mRNA.


Subject(s)
Gene Expression Regulation, Enzymologic/drug effects , Glucose/metabolism , Glutamine/pharmacology , Liver/enzymology , Phosphoenolpyruvate Carboxykinase (GTP)/genetics , Animals , Cells, Cultured , Cyclic AMP/physiology , Dose-Response Relationship, Drug , Glucosamine/pharmacology , Male , Rats , Rats, Wistar , Structure-Activity Relationship , Time Factors
20.
FEBS Lett ; 394(3): 353-5, 1996 Oct 07.
Article in English | MEDLINE | ID: mdl-8830673

ABSTRACT

The mechanism of action of hydration state was studied on beta-actin gene expression in isolated hepatocytes. Results obtained with Northern blot analysis and run on transcription assays show that hypoosmolarity increased and hyperosmolarity decreased the beta-actin mRNA level through a corresponding modulation of the rate of the gene transcription. Glutamine, which is known to induce cell swelling, also increased the beta-actin mRNA level in a dose-dependent manner and induced a stimulation of the beta-actin gene transcription. Thus, cell hydration state regulates gene expression in the liver through a transcriptional mechanism.


Subject(s)
Actins/biosynthesis , Gene Expression Regulation , Liver/metabolism , Transcription, Genetic , Actins/genetics , Animals , Cell Size , Dactinomycin/pharmacology , Dose-Response Relationship, Drug , Glutamine/pharmacology , Liver/cytology , Liver/drug effects , Male , Nucleic Acid Synthesis Inhibitors , Osmotic Pressure , RNA, Messenger/biosynthesis , Rats , Rats, Wistar , Water/metabolism
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