RESUMEN
Two experiments were conducted exploring on-line processing of filler-gap construction in aphasia. An auditory-auditory lexical decision paradigm was used to investigate whether Broca's and Wernicke's aphasic patients show, as do normals, reactivation of the filler at the gap site. Experiment I investigated the processing of a number of filler-gap constructions including wh-questions, relative clauses as subject, relative clauses as object, and embedded wh-questions. Broca's aphasics showed reactivation of the filler at the gap site, whereas Wernicke's aphasics did not. Experiment II examined object relative clauses and their processing by Broca's aphasics. In addition, we investigated whether the presence (or absence) of the relative pronoun played any role in on-line processing. Broca's aphasics performed as did normals. In addition, their performance was unaffected by the presence or absence of the relative pronoun. The results of these experiments suggest that Broca's aphasics do not have an impairment in processing or representing thematic relationships of NP arguments to predicates or relating traces to their antecedents.
Asunto(s)
Afasia de Broca/diagnóstico , Afasia de Wernicke/diagnóstico , Procesos Mentales , Anciano , Afasia de Broca/patología , Afasia de Wernicke/patología , Encéfalo/patología , Femenino , Humanos , Lenguaje , Masculino , Persona de Mediana Edad , Tiempo de Reacción , SemánticaRESUMEN
The mechanism of inhibition of cholesterol side-chain cleavage by specific antibodies was studied systematically. The antibodies had no effect on substrate binding as determined by optical spectroscopy or on the heme environment of the cytochrome P-450 insofar as was detectable by electron paramagnetic resonance spectroscopy. They did not bind to either iron-sulfur protein or its reductase. The antibodies had no effect on chemical reduction of the P-450 or on P-450-CO complex formation. They did inhibit the NADPH-dependent reduction of P-450 and subsequent formation of the P-450-CO complex. This inhibitory effect was concentration dependent and was correlated with the inhibitory effect of the antibodies on enzymatic cholesterol side-chain cleavage. Similar results were obtained using Fab fragments. These results indicate that the antibodies inhibit side-chain cleavage by binding to a region close to the iron-sulfur protein-binding site, thereby preventing transfer of reducing electrons to the cytochrome P-450.
Asunto(s)
Anticuerpos/inmunología , Colesterol/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Proteínas Hierro-Azufre/metabolismo , Metaloproteínas/metabolismo , Aminoglutetimida/farmacología , Animales , Sitios de Unión , Bovinos , Sistema Enzimático del Citocromo P-450/inmunología , Transporte de Electrón , Técnicas In Vitro , NADP/farmacología , Oxidación-ReducciónRESUMEN
Tamoxifen (TAM), a standard endocrine treatment for advanced breast cancer, probably acts by competing for the estrogen receptor protein in the breast tumor cells. If so, resistance to TAM may be a function of the level of the available endogenous estrogen. Inhibition of estrogen synthesis by aminoglutethimide may therefore facilitate the action of the antiestrogen. To test this hypothesis, the two agents were given concurrently (a) to patients who had become resistant to TAM and (b) to patients who had never received TAM in a randomized cross-over study against TAM alone. Patients with estrogen receptor protein-negative disease were excluded. Estrogen and aminoglutethimide levels were measured serially. In the first study, four of 26 patients experienced partial responses, and four of 26, stabilization of their disease. In the randomized study, four of 11 patients on the combination and three of nine on TAM alone had responses. Two patients on the combination and three on TAM alone had stabilization of disease. In the first group, the low rate of response may be attributed to extensive prior treatment. In the randomized study, there is presently no clear advantage for one treatment, and overall, there was no statistically significant correlation between degree of estrogen suppression, aminoglutethimide level, and response. The findings do not exclude the possibility that these agents may act in breast cancer by mechanisms other than inhibition of estrogen receptor.
Asunto(s)
Aminoglutetimida/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Tamoxifeno/administración & dosificación , Adulto , Anciano , Aminoglutetimida/sangre , Unión Competitiva , Neoplasias de la Mama/patología , Ensayos Clínicos como Asunto , Esquema de Medicación , Quimioterapia Combinada , Estrógenos/biosíntesis , Estrógenos/sangre , Femenino , Humanos , Persona de Mediana Edad , Distribución Aleatoria , Receptores de Estrógenos/metabolismoRESUMEN
Potent inhibitors of cholesterol side chain cleavage were tested for inhibition of 11 beta-hydroxylation of 11-deoxycortisol by bovine adrenal cortex mitochondria. Compounds which inhibited 11 beta-hydroxylation were metyrapone, 4-phenylimidazole, 1-benzylimidazole, 17 beta-ureido - 1, 4- androstadien-3-one. SU-8000, 4-methylaminoglutethimide, and 20 alpha-hydroxycholestrol. Compounds which did not inhibit 11 beta-hydroxylation at concentrations of 0.5 mM were d-aminoglutethimide tartrate, 1-aminoglutethimide tartrate, N-methylaminoglutethimide, 16 alpha-methylpregnenolone, 16 beta-methylpregnenolone, 20-tolylpregnenediol, 16 alpha-chloropregnenolone-3-acetate, 16 alpha-benzyloxpregnenolone-3-acetate and cyanoketone. The results obtained indicate that aminoglutethimide and its congeners, the 16-halogenated and 16-benzoylated derivatives of pregnenolone and cyanoketone are specific inhibitors of cholesterol side chain cleavage enzyme. The two mitochondrial steroid oxyganase systems are linked through their competition for a single electron source.
Asunto(s)
Corteza Suprarrenal/enzimología , Aminoglutetimida/análogos & derivados , Androstenoles/farmacología , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/antagonistas & inhibidores , Cianocetona/farmacología , Mitocondrias/enzimología , Oxidorreductasas/antagonistas & inhibidores , Pregnenolona/análogos & derivados , Esteroide 11-beta-Hidroxilasa/antagonistas & inhibidores , Esteroide Hidroxilasas/antagonistas & inhibidores , Animales , Bovinos , Cortodoxona/metabolismo , Cianocetona/análogos & derivados , Hidrocortisona/biosíntesisRESUMEN
Various techniques have been utilized for antigen solubilization, isolation, and purification. This report is the first to describe the isolation and purification of a type-specific antigen from Chlamydia trachomatis serotype A grown in cell culture. The type-specific antigen was prepared from Chlamydia trachomatis serotype A organisms grown in baby hamster kidney cells (BHK21). The extraction process employed a combination of both pH change and Triton X-100 solubilization. The soluble extract was radioiodinated and subjected to ion exchange and gel filtration chromatography. The fractions eluted were tested for type specificity utilizing the IgG prepared from exhaustively cross-absorbed hyperimmune sera from rabbits immunized with homologous organisms. Molecular shift chromatography was employed for analysis. Small samples of the isolated antigen were later used as markers for preparation of larger quantities necessary for antigenic characterization. The purified type-specific antigen has a m.w. of 30,000 to 32,000.
Asunto(s)
Antígenos Bacterianos/aislamiento & purificación , Chlamydia trachomatis/inmunología , Epítopos , Animales , Reacciones Antígeno-Anticuerpo , Células Cultivadas , Infecciones por Chlamydia/diagnóstico , Cromatografía en Gel , Cricetinae , Peso Molecular , Pruebas de Neutralización , ConejosRESUMEN
The luteolytic potency of D- and L-aminoglutethimide (D- and L-AG) was compared in in vivo assays in the rat and rabbit. By assay of plasma progesterone depletion in the rabbit, the potency of L-AG relative to D-AG was 0.21. By the plasma procedure in the rat, the relative potencies of L-AG and of the racemic mixture to D-AG were 0.04 and 0.37, respectively. By the ovarian progesterone depletion method, the L-form had very little activity and the DL-mixture was half as active as the D-isomer. Thus, in both species, almost all of the activity of the racemic mixture results from the content of D-AG. Interpretation of paradoxical data implies that in the rat, L-AG may inhibit liver degradation of progesterone at levels which do not modify secretion from the corpus luteum.
Asunto(s)
Aminoglutetimida/farmacología , Cuerpo Lúteo/efectos de los fármacos , Luteolíticos/farmacología , Animales , Bioensayo , Femenino , Ovario/efectos de los fármacos , Ovario/metabolismo , Progesterona/sangre , Conejos , Ratas , EstereoisomerismoRESUMEN
Serial endocrine studies were performed during the refeeding of a group of nine young women who presented with amenorrhea associated with injudicious dieting. No significant psychopathology was disclosed by the Lanyon Psychological Screening Inventory in any of the patients, six of whom were single and three married and infertile. The mean weight before refeeding was 81.6% of the normal for height. The mean initial serum follicle-stimulating hormone concentration was within the limits of normal for young women of reproductive age, but the serum luteinizing hormone (LH) concentration and the vaginal maturation score were low. As weight was regained, the serum LH concentration increased (the pooled r for LH versus percent normal weight = 0.85) and the vaginal maturation score rose (the pooled r for vaginal maturation score versus percent normal weight = 0.93). When a mean weight of 96.6% of normal was reached after a mean of 5.3 (range, 2 to 11) months of refeeding, spontaneous menses occurred. The initial cycle was ovulatory in two instances and anovulatory in five, as determined by basal body temperature patterns, plasma progesterone concentrations, and endometrial biopsies. With continued weight gain, menstruation became regular and the three married patients conceived.