RESUMEN
AIM: The elucidation of the structure of the 5' flanking region and the exonic organisation of the human cysteine dioxygenase type I gene. METHODS: Material for sequence studies was generated by polymerase chain reaction (PCR) methods using human genomic DNA, a cosmid clone containing the entire gene, and a commercial gene walking kit. RESULTS AND CONCLUSIONS: The gene was found to be--12 kb in length and made up of five exons (418, 78, 155, 170, and 731 base pairs, respectively). The immediate 5' flanking region did not contain the canonical TATAA box. One DNA source (Clontech promoter finder kit) contained a liver specific nuclear factor response element approximately 550 base pairs from the transcription start site, whereas a second source did not. This and other cis acting factors in the 5' flanking region were identified by computer analysis. The physiological significance of such elements requires detailed experimental evaluation.
Asunto(s)
Dioxigenasas , Exones , Intrones , Oxigenasas/genética , Secuencia de Bases , Cisteína-Dioxigenasa , Humanos , Hígado/enzimología , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa/métodosRESUMEN
The possibility that ethanol regulated the expression of thyroid hormone receptor mRNA levels was explored in a model involving human hepatocyte primary culture. Ethanol (20, 50 and 100 mM for 24 h was found to have no effect on the steady-state levels of either triiodothyronine (T3) receptor alpha 1 or alpha 2 mRNAs. In contrast both T3 (1, 10 and 100 nM) and oestradiol (0.1, 1 and 10 ng/ml) treatments affected either one or both of these mRNA levels in a complex manner, showing that the model was capable of responding to other stimuli. Triiodothyronine receptor beta 1 mRNA was not assayed. The hypermetabolic effects of long-term ethanol consumption in humans appears not to be due to the direct effect of ethanol on the regulation of these receptors.
Asunto(s)
Estradiol/farmacología , Etanol/farmacología , Hígado/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/genética , Receptores de Hormona Tiroidea/genética , Triyodotironina/farmacología , Técnicas de Cultivo , Relación Dosis-Respuesta a Droga , Expresión Génica/efectos de los fármacos , Humanos , ARN Mensajero/genética , Receptores Citoplasmáticos y Nucleares/efectos de los fármacos , Receptores de Hormona Tiroidea/efectos de los fármacosRESUMEN
A single-stranded conformational polymorphism in the monoamine oxidase B gene was shown to be A or G, 36 bases upstream from the intron 13-exon 14 boundary. An allelic association study revealed no statistically significant associations between this single-base polymorphism and Parkinson's disease, unlike the results of a previous study.
Asunto(s)
Monoaminooxidasa/genética , Enfermedad de Parkinson/enzimología , Enfermedad de Parkinson/genética , Polimorfismo Conformacional Retorcido-Simple , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
A portion of the human X-chromosome (> 5 kb) encoding the translated portion of the thyroxine-binding globulin (TBG) gene was sequenced. The primary templates for sequencing were isolated from a human X-chromosome library (two positive plaques from 400,000 screened initially with a TBG cDNA probe) or were produced by PCR amplification using leucocyte genomic DNA as the amplification template. Potential hormone response elements (HREs) were identified at either end of the gene. These HREs have sequences based on the consensus half-site of thyroid hormone response elements, although it is unclear whether the structures are functional HREs. Other potential regulatory elements also were identified towards the 3' end of the gene.
Asunto(s)
Hominidae/genética , Proteínas de Unión a Tiroxina/genética , Cromosoma X , Animales , Secuencia de Bases , Secuencia de Consenso , Sondas de ADN , Exones , Humanos , Datos de Secuencia Molecular , Oligonucleótidos Antisentido , Reacción en Cadena de la Polimerasa , Biosíntesis de Proteínas , Mapeo Restrictivo , Homología de Secuencia de Ácido Nucleico , Moldes GenéticosRESUMEN
The modulatory effect of vitamin C (Vit C) on the mutagenic effect of the antineoplastic drug cyclophosphamide (CP) was assessed in the in vivo micronucleus test in Swiss mice. Simultaneous oral administration of Vit C with i.p. administration of CP was found to decrease the frequency of micronucleated polychromatic erythrocytes elevated by CP. Vit C exhibited a significant antimutagenic effect over a wide dose range (1.56-200 mg/kg). The dose-response relationship was highly significant. These results demonstrated the ability of the in vivo micronucleus test to detect in vivo modulation of CP mutagenicity by Vit C. Our earlier results and those from other laboratories also indicate that this model system is suitable for primary in vivo screening of modulation of mutagenesis.
Asunto(s)
Antimutagênicos/farmacología , Ácido Ascórbico/farmacología , Ciclofosfamida/toxicidad , Animales , Ciclofosfamida/antagonistas & inhibidores , Masculino , Ratones , Pruebas de Micronúcleos , Relación Estructura-ActividadRESUMEN
Bacillus licheniformis produced 2,3-butanediol from glucose with an optimum yield of 47 g/100 g glucose after 72 h of growth on a peptone/beef extract medium containing 2% (w/v) glucose at pH 6.0 and 37°C. This yield of 2,3-butanediol was higher than those previously reported forKlebsiella oxytoca (37 g/100 g glucose) andBacillus polymyxa (24 g/100 glucose).
RESUMEN
Plasma concentrations of 3,5,3'-triiodothyronine (T3) and thyroxine (T4) were measured before, during and for between 2 and 6 hr following a meal, in young growing piglets. T3 increased after a meal and reached a peak at approximately 60 min. The magnitude of the rise was dependent on both the energy content and nutrient composition of the meal. In animals given either a high or low energy intake baseline values of T3 were similar, whereas there was a difference in the response to a meal (P less than 0.01). Average increases in hormone concentration were 120% (P less than 0.001) and 50% (P less than 0.05) on the high and low intakes respectively. Plasma T4 also increased in those on high intake (P less than 0.025), but no change was detected when the intake was low. The response of T3 to a meal high in either glucose, sucrose, fat or protein was statistically significant except for the protein meal. The rise in T4 after each of these four meals was less consistent, although it did increase significantly after meals high in sucrose or fat. Amongst several possibilities, these results suggest that a meal may induce an increase in secretion of T3 and T4 from the thyroid gland.
Asunto(s)
Ingestión de Energía , Tiroxina/sangre , Triyodotironina/sangre , Animales , Carbohidratos de la Dieta/farmacología , Grasas de la Dieta/farmacología , Glucosa/farmacología , Cinética , Sacarosa/farmacología , PorcinosRESUMEN
Non-specific beta-blockade with either propranolol or nadolol was shown not to reduce serum TBG concentration in 20 untreated thyrotoxic patients, but to cause significant reductions in the same subjects once they were rendered euthyroid. Similar reductions were also seen in a group of 10 clinically and biochemically euthyroid subjects, who were under investigation for anxiety or mild angina. Since nadolol does not possess the membrane stabilising properties of propranolol, nor is it metabolized like propranolol, the effect on TBG concentration would appear to be due to beta-blockade.