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1.
Cogn Emot ; 30(8): 1388-1401, 2016 Dec.
Article de Anglais | MEDLINE | ID: mdl-26222227

RÉSUMÉ

We investigated the relationship between self-regulation and two types of boredom proneness (perceived lack of internal stimulation, perceived lack of external stimulation) using a variety of measures of self-regulation. These included a general measure of self-control, measures of both regulatory focus (i.e., promotion or a sensitivity to gains/non-gains vs. prevention or a sensitivity to losses/non-losses) and regulatory mode (i.e., assessment or the tendency to compare means and goals vs. locomotion or the tendency to initiate and maintain commitment to action), and measures of cognitive flexibility (i.e., a perceived sense of control and the tendency to seek alternative solutions). Results identified a unique set of factors related to each boredom proneness component. Trait self-control and prevention focus were associated with lower boredom propensity due to a lack of external stimulation. Locomotion and the tendency to seek alternatives were associated with lower boredom propensity due to a lack of internal stimulation. These findings suggest that effective goal pursuit is associated with reduced likelihood of experiencing boredom.

2.
Eplasty ; 11: e48, 2011.
Article de Anglais | MEDLINE | ID: mdl-22140594

RÉSUMÉ

OBJECTIVE: Early studies of plastic surgery patient triage using telemedicine are descriptive and deal with feasibility rather than accuracy. The inpatient study arm compares on-site wound-evaluation accuracy with remotely viewed digital images. The outpatient arm prospectively compares on-site and remote diagnosis, management, and outcomes in a busy, urban, reconstructive-surgery clinic. The concurrent 6 patient case studies illustrate significant systems improvement by using remote consultation. METHODS: A total of 43 inpatients and 100 consecutive outpatients were evaluated by on-site and remote surgeons as performed in previous arms with digital-camera and store and forward technology. Consent was obtained from all patients participating. Agreements regarding diagnosis (skin lesion, hand injury, wound type, and scar character) and management (healing problem, emergent evaluation, antibiotics, and hospitalization) were calculated. RESULTS: In the first study arm, on-site and remote agreement (46%-86% for wound description and 65%-81% for management) generally matched agreement among on-site surgeons (68%-100% and 84%-89%). Moreover, when on-site agreement was low (68% for edema), agreement between on-site and remote surgeons was also low (57%). Remote evaluation was least sensitive detecting wound drainage (46%). On-site surgeons opted for more treatment, often prescribing antibiotics and admitting the patient. The second teleconsult arm provides further evidence of accuracy, overall agreement of 32%, sensitivity 48.55%, specificity 96.92%, positive predictive value 49.26%, negative predictive value 96.83%, and P < .001 regarding diagnosis (skin lesion, hand injury, wound type, wound problem, and scar character). Patient transfer, postoperative monitoring, and outcomes via electronic image transfer, as well as cost-benefit analysis of this clinic-based study, are presented. CONCLUSIONS: eConsultation renders similar outcomes to standard, on-site examination in a selected group of plastic surgery patients. Remote evaluation may assist triage decisions, thereby decreasing emergency room throughput time and office-visit frequency, supplementing satellite facility consultation by plastic surgeons, and providing real-time postoperative assessments, thereby improving quality and reducing costs.

4.
J Intern Med ; 258(1): 77-85, 2005 Jul.
Article de Anglais | MEDLINE | ID: mdl-15953135

RÉSUMÉ

OBJECTIVES: The aim of this study was to define the impact of B-type natriuretic peptide (BNP) levels on the management of elderly patients presenting with acute dyspnoea. DESIGN: We performed a prospective randomized controlled study in 269 elderly patients at least 70 years of age included in the B-type natriuretic peptide for Acute Shortness of breath Evaluation (BASEL) study. Patients were randomly assigned to a diagnostic strategy with (n = 136, BNP group) or without (n = 133, control group) the use of BNP levels provided by a rapid bedside assay. The time to discharge and the total cost of treatment were the primary end-points. RESULTS: Amongst elderly patients, baseline characteristics were well matched between both groups. The use of BNP levels significantly reduced the time to discharge (median 9.0 in the BNP group versus 11.0 days in the control group; P = 0.029). Total treatment cost was $5381 (95% CI, 4482-6280) in the BNP group when compared with $7411 (95% CI, 6180-8642; P = 0.009) in the control group. In addition, a significant reduction in 30-day mortality was observed (9% in the BNP group versus 17% in the control group; P = 0.039). CONCLUSIONS: Used in conjunction with other clinical information, rapid measurement of BNP in the emergency department improved the management of elderly patients presenting with acute dyspnoea and thereby reduced the time to discharge and the total treatment cost. In addition, BNP testing seemed to reduce 30-day mortality.


Sujet(s)
Dyspnée/sang , Peptide natriurétique cérébral/sang , Maladie aigüe , Sujet âgé , Sujet âgé de 80 ans ou plus , Bas débit cardiaque/sang , Bas débit cardiaque/complications , Bas débit cardiaque/diagnostic , Dyspnée/étiologie , Dyspnée/thérapie , Femelle , Hospitalisation , Humains , Mâle , Pneumopathie infectieuse/sang , Pneumopathie infectieuse/complications , Pneumopathie infectieuse/diagnostic , Études prospectives , Broncho-pneumopathie chronique obstructive/sang , Broncho-pneumopathie chronique obstructive/complications , Broncho-pneumopathie chronique obstructive/diagnostic
5.
Exp Appl Acarol ; 33(1-2): 93-102, 2004.
Article de Anglais | MEDLINE | ID: mdl-15285141

RÉSUMÉ

Larvae of the trombiculid mite Neotrombicula autumnalis were collected at 18 sites in and around Bonn, Germany, to be screened for infection with Borrelia burgdorferi s.l. by means of PCR. Questing larvae numbering 1380 were derived from the vegetation and 634 feeding ones were removed from 100 trapped micromammals including voles, mice, shrews and hedgehogs. In a laboratory infection experiment, a further 305 host-seeking larvae from the field were transferred onto Borrelia-positive mice and gerbils, and examined for spirochete infection at various intervals after repletion. In three cases borrelial DNA could be amplified from the mites: (1) from a larva feeding on a wild-caught greater white-toothed shrew (Crocidura russula), (2) from a pool of four larvae feeding on a B. garinii-positive laboratory mouse, and (3) from a nymph that had fed on a B. afzelii-positive laboratory gerbil as a larva. In the first case, borrelial species determination by DNA hybridization of the PCR product was only possible with a B. burgdorferi complex-specific probe but not with a species-specific one. In the second case, probing showed the same borrelial genospecies (B. garinii) as the laboratory host had been infected with. In the latter case, however, DNA hybridization demonstrated B. valaisiana while the laboratory host had been infected with B. afzelii. Subsequent DNA sequencing confirmed much higher similarity of the PCR product to B. valaisiana than to B. afzelii indicating an infection of the mite prior to feeding on the laboratory host. The negligible percentage of positive mites found in this study suggests that either the uptake of borrelial cells by feeding trombiculids is an extremely rare event or that ingested spirochetes are rapidly digested. On the other hand, the results imply a possible transstadial and transovarial transmission of borreliae once they are established in their trombiculid host. However, unless the transmission of borreliae to a given host is demonstrated, a final statement on the vector competence of trombiculid mites is not possible.


Sujet(s)
Vecteurs arachnides/microbiologie , Borrélioses/transmission , Groupe Borrelia burgdorferi/croissance et développement , Maladies des rongeurs/parasitologie , Trombiculidae/microbiologie , Animaux , Vecteurs arachnides/génétique , Vecteurs arachnides/croissance et développement , Séquence nucléotidique , Groupe Borrelia burgdorferi/génétique , ADN bactérien/composition chimique , ADN bactérien/génétique , Espaceur de l'ADN ribosomique/composition chimique , Espaceur de l'ADN ribosomique/génétique , Données de séquences moléculaires , Réaction de polymérisation en chaîne , Rodentia , Trombiculidae/génétique , Trombiculidae/croissance et développement
7.
Ann Clin Biochem ; 38(Pt 4): 376-85, 2001 Jul.
Article de Anglais | MEDLINE | ID: mdl-11471880

RÉSUMÉ

A group of international experts prepared two lists of drugs with their serum/plasma and urine concentrations, which should be used when evaluating the performance of a new laboratory method. The two lists were verified by running in vitro interference studies in three European laboratories on Hitachi instruments. The study identified the following new interferants: acid phosphatase in serum by ibuprofen and theophylline; non-prostatic acid phosphatase in serum by cefoxitin and doxycycline; creatine kinase MB in serum by doxycycline; total bilirubin in serum (Jendrassik-Grof method) by rifampicin and intralipid; total bilirubin in serum (DPD method) by intralipid; creatinine in serum (Jaffe method) by cefoxitin; fructosamine in serum by levodopa and methyldopa; uric acid in serum by levodopa, methyldopa and tetracycline; carbamazepine in serum by doxycycline, levodopa, methyldopa and metronidazole; digitoxin in serum by rifampicin; phenytoin in serum by doxycycline, ibuprofen, metronidazole and theophylline; theophylline in serum by acetaminophen, cefoxitin, doxycycline, levodopa, phenylbutazone and rifampicin; tobramycin in serum by cefoxitin, doxycycline, levodopa, rifampicin and phenylbutazone; valproic acid in serum by phenylbutazone; C3 in serum by intralipid; C4 in serum by doxycycline; rheumatoid factor in serum by ibuprofen and metronidazole; pancreatic amylase and total amylase in urine by acetylcysteine, ascorbic acid, cefoxitin, gentamicin, levodopa, methyldopa and ofloxacin; magnesium in urine by acetylcysteine, gentamicin and methyldopa; beta2-microglobulin in urine by ascorbic acid; total protein in urine by ascorbic acid, Ca-dobesilate and phenylbutazone. Interference in acid phosphatase, creatine kinase MB and bilirubin methods was observed at very low analyte concentrations, and therefore it may not be evident at higher concentrations. The study confirmed the usefulness of the recommendation.


Sujet(s)
Analyse chimique du sang/méthodes , Analyse chimique du sang/normes , Chimie clinique/méthodes , Chimie clinique/normes , Préparations pharmaceutiques/sang , Analyse chimique du sang/instrumentation , Chimie clinique/instrumentation , Tests enzymatiques en clinique/méthodes , Tests enzymatiques en clinique/normes , Europe , Recommandations comme sujet , Humains , Laboratoires/normes , Contrôle de qualité , Reproductibilité des résultats , Troubles liés à une substance/sang , Troubles liés à une substance/diagnostic
8.
J Anal Toxicol ; 25(4): 258-69, 2001.
Article de Anglais | MEDLINE | ID: mdl-11386639

RÉSUMÉ

The abuse of the designer amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is increasing throughout the world. They have become popular drugs, especially at all-night techno dance parties (Raves), and their detection is becoming an important issue. Presently, there are no MDMA- or MDA-specific immunoassays on the market, and detection of the designer amphetamines is dependent upon the use of commercially available amphetamine assays. The success of this approach has been difficult to assess because of the general unavailability of significant numbers of samples from known drug users. The objectives of the present study are to characterize the drug content of urine samples from admitted Ecstasy users by chromatographic methods and to assess the ability of the available amphetamine/methamphetamine immunoassays to detect methylenedioxyamphetamines. We found that, when analyzed by high-performance liquid chromatography with diode-array detection (HPLC-DAD), 64% of 70 urine samples (by gas chromatography-mass spectrometry [GC-MS]: 88% of 64 urine samples) obtained from Rave attendees contained MDMA and/or 3,4-methylenedioxyamphetamine (MDA) alone or in combination with amphetamine, methamphetamine, or other designer amphetamines such as 3,4-methylenedioxyethylamphetamine (MDEA). This suggests that the majority of the Ravers are multidrug users. At the manufacturer's suggested cutoffs, the Abbott TDx Amphetamine/Methamphetamine II and the new Roche HS Amphetamine/MDMA assays demonstrated greater detection sensitivity for MDMA than the other amphetamine immunoassays tested (Abuscreen OnLine Hitachi AMPS, Abuscreen OnLine Integra AMPS, Abuscreen OnLine Integra AMPSX, CEDIA AMPS, and EMIT II AMPS). There is 100% agreement between each of the two immunoassays with the reference chromatographic methods, HPLC-DAD and GC-MS, for the detection of methylenedioxyamphetamines.


Sujet(s)
Stimulants du système nerveux central/urine , Hallucinogènes/urine , Substances illicites/urine , Dosage immunologique/méthodes , N-Méthyl-3,4-méthylènedioxy-amphétamine/urine , Chromatographie en phase liquide à haute performance/méthodes , Chromatographie gazeuse-spectrométrie de masse/méthodes , Hallucinogènes/composition chimique , Hallucinogènes/toxicité , Humains , Substances illicites/composition chimique , Substances illicites/toxicité , N-Méthyl-3,4-méthylènedioxy-amphétamine/composition chimique , N-Méthyl-3,4-méthylènedioxy-amphétamine/toxicité , Sensibilité et spécificité , Détection d'abus de substances/méthodes
9.
J Invasive Cardiol ; 13(3): 211-6, 2001 Mar.
Article de Anglais | MEDLINE | ID: mdl-11231646

RÉSUMÉ

To investigate the incidence of chest pain early after percutaneous coronary interventions and its correlation with ECG changes, cardiac enzymes, clinical and procedural variables and follow-up events, we prospectively studied 199 patients (84% male; mean age, 60.1 +/- 9.4 years) after primary successful percutaneous coronary interventions (21% PTCA; 79% additional stent implantation). During the first 16 hours following the intervention, the occurrence of chest pain was noted, ECGs were recorded and serial measurements of cardiac enzymes were performed. Seventy-six patients (38%) with elevated enzyme levels at time 0 were excluded. A clinical follow-up was obtained at 6 months. Forty patients (32.5%) experienced chest pain; new ECG changes were detected in 3 (2.5%). The mean levels of all enzymes were significantly higher in patients with chest pain 16 hours after the intervention. In patients with chest pain versus those without, CK-MB mass and troponin I levels higher than twice the upper normal limit were seen in 43.6% versus 11.0% (p < 0.0001) and 45.0% versus 17.3% (p < 0.002), respectively. Elevated troponin I (< 0.004) and CK-MB mass (< 0.04) as well as presumed ischemic chest pain (< 0.03) could be identified as risk factors for recurrent chest pain during follow-up. In conclusion, chest pain was common early after percutaneous coronary interventions and correlated with elevated cardiac enzymes, suggesting peri-interventional myocardial necrosis. Elevated levels of CK-MB mass and troponin I, as well as presumed ischemic chest pain, were associated with recurrent chest pain during follow-up.


Sujet(s)
Angine de poitrine/étiologie , Angioplastie coronaire par ballonnet , Électrocardiographie , Infarctus du myocarde/thérapie , Endoprothèses , Sujet âgé , Coronarographie , Creatine kinase/analyse , Femelle , Humains , Mâle , Adulte d'âge moyen , Infarctus du myocarde/imagerie diagnostique , Infarctus du myocarde/enzymologie , Études prospectives , Récidive , Facteurs de risque , Troponine I/analyse
12.
Clin Chim Acta ; 297(1-2): 261-73, 2000 Jul.
Article de Anglais | MEDLINE | ID: mdl-10841927

RÉSUMÉ

The measurement of urinary marker proteins is not a generally accepted laboratory practice because the results are difficult to interpret. MDI-LABLINK is software for classifying patterns of specific urinary marker proteins. The interpretations are completely user definable thanks to a specific 'pattern definition database'. Our interpretation set is based on Hofmann and Guder's work in measuring and interpreting single urinary proteins. We include additional marker proteins in order to adapt Boesken's SDS-PAGE classification. During the last 3 years, 1905 patterns were fully differentiated and identically interpreted. Firstly, the samples were classified into three patterns: normal (25.8%), predominantly glomerular (27.2%, selective, unselective, mixed, and with additional tubular proteins) and predominantly tubular (36.9%, complete/incomplete form, with additional glomerular proteins); 8.9% showed postrenal proteinuria. Secondly, glomerular selectivity measured by using urinary transferrin/IgG ratio alone correlates well with the established SI index (the ratio between IgG and transferrin clearances). Thirdly, the creatinine concentration substantiates the validity of the sample. The quality of the preanalytical phase can be improved through the ongoing education of the medical staff. Finally, measurement of urinary albumin and alpha-1-microglobulin is mandatory where kidney disease is suspected, has to be ruled out, or requires close monitoring, even when the total protein concentration is normal.


Sujet(s)
Systèmes de gestion de bases de données , Examen des urines , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Enfant , Enfant d'âge préscolaire , Systèmes experts , Femelle , Hématurie/urine , Humains , Mâle , Adulte d'âge moyen , Protéinurie/urine
13.
Eur J Gastroenterol Hepatol ; 12(1): 19-24, 2000 Jan.
Article de Anglais | MEDLINE | ID: mdl-10656205

RÉSUMÉ

BACKGROUND AND AIMS: Low bone density with an increased risk of vertebral fractures is a frequent complication in inflammatory bowel disease. Since the aetiology of osteopathia in these patients is different compared to postmenopausal or steroid-induced osteoporosis, no treatment strategy is established. Supplementation of calcium and vitamin D has been shown to prevent further bone loss, but no data are available showing the anabolic effect of sodium fluoride in Crohn's disease. METHODS: We carried out a one-year prospective clinical trial in 33 patients with chronic active Crohn's disease who were randomly assigned to receive either calcium (500 mg b.i.d.) and 1000 IU vitamin D3 only, or retarded-release sodium fluoride (25 mg t.i.d.) additionally. The diagnosis of Crohn's disease had been made at least two years ago, and all patients had received systemic high-dose steroid therapy during the previous year. Eleven of 15 patients who received calcium/vitamin D and 15 of 18 patients who additionally received sodium fluoride completed the study. The primary endpoint of the study was the increase of bone mineral density, measured by dual energy X-ray absorptiometry (DXA) after one year of treatment. Bone-specific alkaline phosphatase and osteocalcin were used as markers for bone turnover. RESULTS: In the calcium/vitamin D only group, bone density was not significantly changed after one year of treatment, whereas in the calcium/vitamin D/fluoride group, bone density of the lumbar spine increased from -1.39+/-0.3 (Z-score, mean +/- SEM) to -0.65+/-0.3 (P<0.05) after one year of treatment. Increase of bone density was positively correlated to the osteoblastic markers bone-specific alkaline phosphatase (r = 0.53) and osteocalcin (r = 0.43). CONCLUSIONS: Sodium fluoride in combination with vitamin D and calcium is an effective, well-tolerated and inexpensive treatment to increase lumbar bone density in patients with chronic active Crohn's disease and osteoporosis.


Sujet(s)
Densité osseuse/effets des médicaments et des substances chimiques , Maladie de Crohn/complications , Ostéoporose/prévention et contrôle , Fluorure de sodium/pharmacologie , Adulte , Calcium/administration et posologie , Cholécalciférol/administration et posologie , Association de médicaments , Femelle , Humains , Mâle , Ostéoporose/étiologie , Études prospectives , Fluorure de sodium/administration et posologie
14.
Int J Mol Med ; 1(6): 989-93, 1998 Jun.
Article de Anglais | MEDLINE | ID: mdl-9852636

RÉSUMÉ

Evidence for the operation of expanded trinucleotide repeats in the pathogenesis of bipolar affected disorder has recently been found at the molecular genetic level. For the screening of these repeat motifs in genomes of patients with bipolar affective disorder, we established a modified PCR-based fingerprinting technique, called triplet repeat enhanced arbitrarily primed PCR (TREAP-PCR). Using this approach, 40 patients suffering from bipolar affective disorder (ICD10: F31) and 15 healthy controls were investigated. Interindividual polymorphisms generated by TREAP-PCR seemed to depend on the type of triplet. Using CCG triplet primers, polymorphisms could be observed more often in the genomes of patients compared with controls, whereas no significant differences could be found using primers of the CAG or AAT type. These data might indicate the existence of subgroups of manic-depressive patients based on molecular genetic differences.


Sujet(s)
Trouble bipolaire/génétique , Génome humain , Répétitions de trinucléotides/génétique , Adulte , Trouble bipolaire/anatomopathologie , ADN/composition chimique , ADN/génétique , Profilage d'ADN , Amorces ADN , Femelle , Humains , Mâle , Adulte d'âge moyen , Réaction de polymérisation en chaîne/méthodes , Polymorphisme génétique , Analyse de séquence d'ADN
15.
Eur J Clin Chem Clin Biochem ; 35(2): 133-40, 1997 Feb.
Article de Anglais | MEDLINE | ID: mdl-9056758

RÉSUMÉ

In accordance with the guidelines of the European Committee for Clinical Laboratory Standards (ECCLS), the performance of the Abbott AxSYM Abused Drugs assays were evaluated and compared with the results provided by the following systems: Syva Emit d.a.u./Roche Cobas Mira S Plus, Abbott TDx and ADx, Syva Emit d.a.u./Syva ETS Plus, Syva Emit II/Hitachi 717 and Roche Abuscreen OnLine/Roche Cobas Mira S Plus. The test analytes, cannabinoids, cocaine metabolites, opiates, benzodiazepines and barbiturates, were each investigated in three laboratories on different systems. The imprecision of all systems in the series and from day to day was good, with CVs less than 5% or 10%, respectively. The AxSYM calibration curves were stable for 3-4 months and none of the systems displayed any shift in the results of the analyses within one day or any faults caused by sample contamination. Within the framework of this study, a total of 1860 urine samples were investigated; 741 results were positive. All results which remained discrepant between AxSYM and the comparison systems after repeated analysis (n = 17) were subjected to further investigation using a reference method, with the exception of one barbiturate and two benzodiazepine samples. An additional test criterion was the practicability of the systems investigated and the versatility of the software. During this evaluation, the results provided by the Abbott AxSYM were excellent and were fully in line with the manufacturer's claims. The reliability of the FPIA technology that has been the subject of frequent investigation was also convincing during this evaluation. The possibility of semi-quantitative determination, the stability of the calibration curves, the ability to process an emergency sample without delay and its high suitability to routine operations are the convincing benefits offered by this system.


Sujet(s)
Substances illicites/analyse , Trousses de réactifs pour diagnostic , Calibrage , Europe , Études d'évaluation comme sujet , Humains , Substances illicites/urine , Contrôle de qualité , Logiciel
16.
Clin Chem ; 43(1): 92-9, 1997 Jan.
Article de Anglais | MEDLINE | ID: mdl-8990228

RÉSUMÉ

A new turbidimetric inhibition immunoassay for digoxin (Tina-quant [a] Digoxin, Boehringer Mannheim) was evaluated in seven laboratories. It can be performed without sample pretreatment with ready-to-use reagents on nondedicated analyzers in combination with routine clinical chemistry. The studies revealed a good analytical performance: lower limit of detection 0.12 microg/L (3 SD from mean of blank); linearity up to 7.5 microg/L; median between-run CVs 8.1% (0.6 microg/L), 2.8% (1.5 microg/L), 1.9% (3 microg/L); mean analytical recovery in control sera 98-102%; slopes from 0.97 to 1.09 and intercepts from -0.28 to 0.10 microg/L in comparison with four immunoassays; and a high resistance to common interferents. The test was more resistant to digoxin-like immunoreactive factor (DLIF) interference than other methods, showing cross-reactivity only in some intensive care patient samples. Among 192 patients in whom DLIF is expected (e.g., pregnant women, patients with renal failure, newborns), 90% of results were < or =0.26 microg/L digoxin. Cortisol showed no cross-reactivity and digoxigenin had a low reactivity. An interlaboratory survey revealed a good comparability of the Tina-quant [a] test with the median of all methods (slope 0.99, intercept -0.06 microg/L). An HPLC method for digoxin based on isocratic separation of samples on an RP-18 column followed by detection by an immunoassay yielded a reasonable comparability with the immunochemical tests with noncritical samples. Divergent results of immunoassays caused by DLIFs or different cross-reactivities with digoxin metabolites or derivatives can be explained by the use of this HPLC method.


Sujet(s)
Chromatographie en phase liquide à haute performance , Digoxine/sang , Dosage immunologique/méthodes , Néphélométrie et turbidimétrie/méthodes , Anticoagulants , Soins de réanimation , Femelle , Humains , Dosage immunologique/statistiques et données numériques , Indicateurs et réactifs , Nouveau-né , Laboratoires , Grossesse , Contrôle de qualité , Valeurs de référence , Dialyse rénale , Insuffisance rénale/sang , Sensibilité et spécificité
17.
Nucleic Acids Res ; 24(12): 2331-7, 1996 Jun 15.
Article de Anglais | MEDLINE | ID: mdl-8710504

RÉSUMÉ

The CSRE (carbon source-responsive element) is a sequence motif responsible for the transcriptional activation of gluconeogenic structural genes in Saccharomyces cerevisiae. We have isolated a regulatory gene, DIL1 (derepression of isocitrate lyase, = CAT8), which is specifically required for derepression of CSRE-dependent genes. Expression of CAT8 is carbon source regulated and requires a functional Cat1p (Snf1p) protein kinase. The derepression defect of CAT8 in a cat1 mutant could be suppressed by a mutant Mig1p repressor protein. Derepression of CAT8 also requires a functional HAP2 gene, suggesting a regulatory connection between respiratory and gluconeogenic genes. Carbon source-dependent protein-CSRE complexes detected in a gel retardation analysis with wild-type extracts were absent in cat8 mutant extracts. However, similar experiments with an epitope-tagged CAT8 gene product in the presence of tag-specific antibodies gave evidence against a direct binding of Cat8p to the CSRE. A constitutively expressed GAL4-CAT8 fusion gene revealed a carbon source-dependent transcriptional activation of a UAS(GAL)-containing reporter gene. Activation mediated by Cat8p was no longer detectable in a cat1 mutant. Thus, biosynthetic control of CAT8 as well as transcriptional activation by Cat8p requires a functional Cat1p protein kinase. A model proposing CAT8 as a specific activator of a transcription factor(s) binding to the CSRE is discussed.


Sujet(s)
Protéines fongiques/métabolisme , Régulation de l'expression des gènes fongiques , Néoglucogenèse/génétique , Protein-Serine-Threonine Kinases/métabolisme , Protéines de Saccharomyces cerevisiae , Saccharomyces cerevisiae/génétique , Transactivateurs/métabolisme , Séquence d'acides aminés , Séquence nucléotidique , Carbone/métabolisme , ADN fongique , Protéines fongiques/génétique , Dosage génique , Données de séquences moléculaires , Mutation , Protein-Serine-Threonine Kinases/génétique , Saccharomyces cerevisiae/métabolisme , Transactivateurs/génétique , Activation de la transcription
18.
Mol Cell Biol ; 14(6): 3613-22, 1994 Jun.
Article de Anglais | MEDLINE | ID: mdl-8196607

RÉSUMÉ

The expression of yeast genes encoding gluconeogenic enzymes depends strictly on the carbon source available in the growth medium. We have characterized the control region of the isocitrate lyase gene ICL1, which is derepressed more than 200-fold after transfer of cells from fermentative to nonfermentative growth conditions. Deletion analysis of the ICL1 promoter led to the identification of an upstream activating sequence element, UASICL1 (5' CATTCATCCG 3'), necessary and sufficient for conferring carbon source-dependent regulation on a heterologous reporter gene. Similar sequence motifs were also found in the upstream regions of coregulated genes involved in gluconeogenesis. This carbon source-responsive element (CSRE) interacts with a protein factor, designated Ang1 (activator of nonfermentative growth), detectable only in extracts derived from derepressed cells. Gene activation mediated by the CSRE requires the positively acting derepression genes CAT1 (= SNF1 and CCR1) and CAT3 (= SNF4). In the respective mutants, Ang1-CSRE interaction was no longer observed under repressing or derepressing conditions. Since binding of Ang1 factor to the CSRE could be competed for by an upstream sequence derived from the fructose-1,6-bisphosphatase gene FBP1, we propose that the CSRE functions as a UAS element common to genes of the gluconeogenic pathway.


Sujet(s)
Régulation de l'expression des gènes codant pour des enzymes , Néoglucogenèse/génétique , Isocitrate lyase/génétique , Régions promotrices (génétique) , Saccharomyces cerevisiae/enzymologie , Saccharomyces cerevisiae/génétique , Séquence nucléotidique , Métabolisme glucidique , Séquence consensus , Protéines de liaison à l'ADN/métabolisme , Fructose-1,6-diphosphatase/génétique , Délétion de gène , Régulation de l'expression des gènes fongiques , Gènes fongiques , Génotype , Isocitrate lyase/biosynthèse , Données de séquences moléculaires , Mutagenèse par insertion , Mutagenèse dirigée , Sondes oligonucléotidiques , Plasmides , Saccharomyces cerevisiae/métabolisme , Activation de la transcription
19.
J Hepatol ; 19(1): 133-9, 1993 Aug.
Article de Anglais | MEDLINE | ID: mdl-8301033

RÉSUMÉ

In clinical practice, the seriousness of liver disease is assessed based on the combined information from clinical examination, routine biochemical tests, and liver histology. Recently, the assessment of hepatic lidocaine metabolism has been proposed as a quantitative liver function test offering valuable additional information. To evaluate whether this new liver function test reflects the combined clinical assessment, we prospectively measured lidocaine metabolism in 111 patients with well characterized liver disease. In addition, lidocaine test results were compared with the aminopyrine breath test and the galactose elimination capacity. Lidocaine (1 mg/kg) was injected i.v. and serum concentrations of its main metabolite monoethylglycinexylidide were determined after 15 min. The results varied widely and the means (+/- S.D.) were similar among patients with mild liver disease (46 +/- 23 ng/ml), but significantly (P < 0.05) lower among patients with Child class A cirrhosis (19 +/- 11 ng/ml) or Child class B or C cirrhosis (21 +/- 19 ng/ml). The [13C]aminopyrine breath test, however, gave a better discrimination among patients with increasing severity of liver disease than lidocaine metabolite formation. The galactose elimination capacity finally best separated patients with mild liver disease from those with cirrhosis. The correlations between any two of the different quantitative liver function tests were weak (R2 consistently < 0.2). We conclude that lidocaine metabolite formation, like other quantitative liver function tests that are based on the microsomal metabolism of model compounds, quantitates a very particular enzymatic reaction which may not be representative for the functional reserve of the entire organ.


Sujet(s)
Lidocaïne/analogues et dérivés , Lidocaïne/métabolisme , Maladies du foie/sang , Adolescent , Adulte , Aminophénazone/analyse , Tests d'analyse de l'haleine , Enfant , Galactose/urine , Humains , Lidocaïne/sang , Maladies du foie/anatomopathologie , Tests de la fonction hépatique
20.
Curr Genet ; 23(5-6): 375-81, 1993.
Article de Anglais | MEDLINE | ID: mdl-8319292

RÉSUMÉ

The ICL1 gene encoding the isocitrate lyase from Saccharomyces cerevisiae was cloned and sequenced. A reading frame of 557 amino acids showing significant similarity to isocitrate lyases from seven other species could be identified. Construction of icl1 null mutants led to growth defects on C2 carbon sources while utilization of sugars or C3 substrates remained unaffected. Using an ICL1-lacZ fusion integrated at the ICL1 locus, a more than 200-fold induction of beta-galactosidase activity was observed after growth on ethanol when compared with glucose-repressed conditions. A preliminary analysis of the ICL1 upstream region identified a 364-bp fragment necessary and sufficient for this regulatory phenotype. Sequence motifs also present in the upstream regions of co-regulated genes were found within this region.


Sujet(s)
Régulation de l'expression des gènes codant pour des enzymes , Régulation de l'expression des gènes fongiques , Isocitrate lyase/génétique , Saccharomyces cerevisiae/génétique , Séquence d'acides aminés , Séquence nucléotidique , Technique de Northern , Clonage moléculaire , ADN fongique , Isocitrate lyase/métabolisme , Données de séquences moléculaires , Mutation , Séquences d'acides nucléiques régulatrices , Cartographie de restriction , Saccharomyces cerevisiae/enzymologie , Similitude de séquences d'acides aminés , Spécificité du substrat , Transactivateurs/métabolisme
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