Asunto(s)
Enfermedades del Esófago/microbiología , Histoplasmosis/diagnóstico , Corticoesteroides/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Enfermedades del Esófago/diagnóstico , Esofagitis/diagnóstico , Esofagitis/microbiología , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana EdadRESUMEN
Symptomatic patients with Type 1 protein C deficiency and venous thrombosis were analysed for defects in this gene using polymerase chain reaction amplification and direct sequencing of all nine exons. Ten different heterozygous point mutations were detected in 19 patients from eleven American families. Seven represent novel mutations. Two of these were found in the TATA box or near the transcription initiation site and presumably lead to loss of transcription, and seven missense mutations were found including G103R, P168L, R169W, I201T, P279L, T298M, and C384Y. These may lead to abnormal folding or thermodynamic instability of the protein C molecule, potentially causing abnormal secretion or rapid clearance from the circulation. Two other protein C mutations, a nonsense mutation at codon Trp-145 and a deletion inducing a frameshift at codon 364 resulting in premature termination at codon 378, likely lead to unstable products. The previously published R169W mutation resulted in a Type 1 deficiency. The data show that diverse molecular defects result in similar phenotypes and emphasize that a wide variety of mutations are responsible for Type 1 protein C deficiency in the American setting of a diverse population.
Asunto(s)
Mutación , Deficiencia de Proteína C , Proteína C/genética , Tromboflebitis/genética , Adulto , Secuencia de Bases , Niño , Codón , ADN/química , Eliminación de Gen , Humanos , Masculino , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , TATA Box , Transcripción GenéticaRESUMEN
Vanadate has been reported to inhibit (Na+ + K+)-ATPase of many cells and in some systems to stimulate adenylate cyclase. Since intestinal transport is influenced by these enzymes, we studied the effects of varying concentrations of orthovanadate (VO-4) on alanine transport in the in vitro rat jejunum. At the higher concentrations tested (10(-3) and 10(-2) M) vanadate had a ouabainlike action on alanine transport. It decreased the mucosal-to-serosal flux and the influx of alanine into the intestinal epithelium and it caused a reduction of (Na+ + K+)-ATPase activity of basolateral membranes. The relatively lower vanadate concentration of 10(-4) M increased the influx and the efflux of alanine across the mucosal border of the jejunum. The increase was associated with elevation of cyclic AMP in the intestinal mucosa. The studies suggest the presence of a dual action of vanadate on amino acid transport, a stimulatory effect at low concentration, due to increased adenylate cyclase activity, and an inhibitory effect at higher concentrations, due to a decreased activity of (Na+ + K+)-ATPase.
Asunto(s)
Alanina/metabolismo , Yeyuno/metabolismo , Microvellosidades/metabolismo , Vanadio/farmacología , Adenosina Trifosfatasas/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , ATPasa de Ca(2+) y Mg(2+)/metabolismo , AMP Cíclico/metabolismo , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Cinética , Masculino , Microvellosidades/efectos de los fármacos , Ratas , Ratas Endogámicas , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , VanadatosRESUMEN
Intestinal obstruction inhibits amino acid absorption. The inhibition, being dependent on the pathological changes of the absorptive epithelium, was considered as an index of injury and measured after varying periods of obstruction and after pretreatment with clindamycin, indomethacin, 16,16-dimethyl-PGE2 or arachidonic acid. A reduction in amino acid uptake was apparent after 2h of obstruction and was increasingly evident after 4, 6 and 18 h. During the late phase (after 6 h), inhibition was partly prevented by pretreatment with clindamycin, but the antibiotic was ineffective during the early phase (within the first 2 h). Bacterial colony counts of luminal contents of rats obstructed for 2 h, were not different from counts obtained in controls, but significantly lower than counts in rats that have been obstructed for 6 h. Pretreatment of rats with 16,16-dimethyl-PGE2 or with arachidonic acid prevented the early inhibitory effects of the obstruction. The findings suggest that the early inhibition in amino acid uptake may be related to metabolic changes that are correctable by the administration of 16,16-dimethyl-PGE2 or of arachidonic acid. The inhibition, during the late phase, is mainly related to an overgrowth of the enteric bacteria.