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Biomedical subjects

M Dennis

Publications and source records attributed to M Dennis.

At least 163 records · Page 9Linked to original sources
PubMed1987

Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: [3H]chlorpromazine labels homologous residues in the beta and delta chains.

The membrane-bound acetylcholine receptor from Torpedo marmorata was photolabeled by the noncompetitive channel blocker [3H]chlorpromazine under equilibrium conditions in the presence of the agonist carbamoylcholine. The amount of radioactivity incorporated into all subunits was reduced by addition of phencyclidine, a specific ligand for the high-affinity site for noncompetitive blockers. The labeled beta chain was purified and digested with trypsin or CNBr, and the resulting fragments were fractionated by high-performance liquid chromatography. Sequence analysis resulted in the identification of Ser-254 and Leu-257 as residues labeled by [3H]chlorpromazine in a phencyclidine-sensitive manner. These residues are located in the hydrophobic and potentially transmembrane segment M II of the beta chain, a region homologous to that containing the chlorpromazine-labeled Ser-262 in the delta chain [Giraudat, J., Dennis, M., Heidmann, T., Chang, J. Y., & Changeux, J.-P. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 2719-2723]. These results show that homologous regions of different receptor subunits contribute to the unique high-affinity site for noncompetitive blockers, a finding consistent with the location of this site on the axis of symmetry of the receptor molecule.

Amino Acid Sequence↗
PubMed1987

Using language to parse the young damaged brain.

Functional distinctions within the language domain can be used to parse the young damaged brain. Parsing means resolving something into its component parts and describing them; parsing the young damaged brain with language involves selecting and grouping features of early brain damage according to how they sustain or disrupt the language performance of brain-injured children and adolescents. And the nature of neural representation for language can be inferred from such brain parsing. Three language factors concerned with lexical access were identified as discrete, that is, as isolable from other language functions in a brain-damaged population, and also as distinct, that is, as having a characteristic set of brain damage features that sustain or disrupt them. Criteria were also outlined for judging the lexical access factors as autonomous, that is, as able to maintain their boundaries with other language functions in the face of brain damage.

Adolescent↗
PubMed1987

Language of hydrocephalic children and adolescents.

How adequate a substrate for the development of language is the young hydrocephalic brain? To answer this question, the development of five language domains (word finding, fluency and automaticity, immediate sentence memory, understanding of grammar, and metalinguistic awareness) was studied in children and adolescents, 75 with hydrocephalus in the first year of life, and 50 normal controls. The results revealed a limited resilience of language to the effects of early hydrocephalus. Resilience was indicated by the finding that, for several language skills, hydrocephalics scored at comparable levels to normals and improved their test performances as they matured. The limits to resilience were also apparent. Language development was not uniform after early hydrocephalus, and, within particular language domains, hydrocephalics were either less skilled or less able to maintain age-appropriate skill mastery than normal peers. Early hydrocephalus had diverse effects on language development: Of the variables measuring its forms, manifestations, and treatments, some were indicative of preserved language functioning while others were predictive of language deficit. The young hydrocephalic brain mediates language development in a manner that is adequate, but far from ideal.

Adolescent↗
PubMed1986

Making reference: the cohesive use of pronouns in the narrative discourse of hemidecorticate adolescents.

The cohesive use of referential language in narrative production reveals communicative goals as well as specific aspects of language use. A formalism for analyzing pronominal cohesion was developed and applied to the narrative discourse of three hemidecorticate adolescents. The results revealed hemisphere-dependent differences in overall narrative skill as well as distinct individual discourse strategies. Neither left hemidecorticate planned narration in extended discourse units: One demonstrated a linear and highly explicit discourse style with redundant over-statement of referent nouns and the other produced narratives cluttered with pronouns of both correct and ambiguous reference, relying on nonpersonal pronouns at considerable cost to narrative specificity. The right hemidecorticate produced narratives that were more economical in form and richer in content: He was the only subject able to maintain simultaneous story lines with multiple pronouns and referential relationships cohesively embedded. All subjects expressed at least some story content, but only the right hemidecorticate narratives conveyed suggestion and implication as well as explicit statement.

Adolescent↗
PubMed1986

Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: serine-262 of the delta subunit is labeled by [3H]chlorpromazine.

The membrane-bound acetylcholine receptor from Torpedo marmorata was photolabeled by the noncompetitive channel blocker [3H]chlorpromazine under equilibrium conditions in the presence of agonist. Incorporation of radioactivity into all subunits occurred and was reduced by addition of phencyclidine, a specific ligand for the high-affinity site for noncompetitive blockers. The delta subunit was purified and digested with trypsin, and the resulting fragments were fractionated by reversed-phase HPLC. The labeled peptide could not be purified to homogeneity because of its marked hydrophobic character, but a combination of differential CNBr subcleavage and cosequencing of partially purified fragments enabled us to identify Ser-262 as being labeled by [3H]chlorpromazine. The labeling of this particular residue was prevented by phencyclidine and thus took place at the level of, or in proximity to, the high-affinity site for noncompetitive blockers. Ser-262 is located in a hydrophobic and potentially transmembrane segment termed MII.

Affinity Labels↗
PubMed1985

Regional distribution of a novel pituitary protein (7B2) in the rat brain.

The regional distribution of a novel pituitary protein (7B2) in the rat brain was studied using a specific and sensitive radioimmunoassay. Immunoreactive (IR)-7B2 was distributed throughout the brain, with the highest concentrations in the pituitary, hypothalamus and basal ganglia. Immunoreactive 7B2 from the brain and other tissues had an apparent molecular weight of around 20,000 as estimated by SDS-polyacrylamide gel electrophoresis as observed with other tissues. In homozygous Brattleboro rats which do not synthesize vasopressin or its associated neurophysin, IR-7B2 levels in the brain and pituitary gland were shown to be similar to those of control animals. Furthermore, the molecular weight of 7B2 in the brain and pituitary gland of homozygous Brattleboro rats was similar to that of control animals.

Animals↗
PubMed1985

Intelligence after early brain injury. I: Predicting IQ scores from medical variables.

To study how psychometric intelligence is related to early brain damage, the medical histories and Wechsler IQ scores of 407 subjects were analysed by multiple regression techniques. The study separated those medical variables that predicted IQ from those that did not, estimated the relative importance of the predictor variables as modifying influences on intelligence, and established the overall predictive power of significant variable sets. Intelligence varied with some aspects of brain damage but not with others. There was no single predictor of intelligence; instead, there were sets of predictors that operated in contexts of varying width and definition, each set having a different level of predictive power. Intelligence itself was diverse, with different predictive sets for Full Scale, Verbal, and Performance IQ. An analysis of the pattern and magnitude of the nonpredictive and predictive medical variables, and of the predictor variables vis-à-vis each other, reveals some of the principles by which verbal and nonverbal intelligence are represented in the young damaged brain.

Age Factors↗
PubMed1985

Intelligence after early brain injury. II: IQ scores of subjects classified on the basis of medical history variables.

The problem of multivariate classification in early brain-damaged individuals was addressed by generating a typology based on various dimensions of brain damage, and by describing the consequences for intelligence of membership in the typology. More than 100 medical-history variables were expressed as a small set of factors that represented common patterns of medical variables; subjects were clustered on the basis of all these factors considered simultaneously, rather than on any single variable or set of variables; and the IQ scores of the subject clusters were compared. The results provide both a descriptive account of intelligence in most of the frequently occurring forms of early brain insult and allow a set of inferences to be drawn about the neural basis of intelligence in the young damaged brain.

Brain Damage, Chronic↗
PubMed1983

Characterization of beta-endorphin immunoreactive peptides in rat pituitary and brain by coupled gel and reversed-phase high-performance liquid chromatography.

A procedure which combines gel high-performance liquid chromatography (HPLC) and reversed-phase HPLC in two systems with radioimmunoassay was developed for the analysis of beta-endorphin (beta END)-related peptides in rat pituitary and brain. The gel HPLC system allows rapid screening for relative amounts of precursors and products involved in beta END biosynthesis. Reversed-phase HPLC reveals minor post-translational modifications, such as acetylation, which greatly alter the biological activity of beta END. The application of this coupled procedure clearly demonstrates tissue-specific differences in the processing of beta END in pituitary and brain regions and indicates that the system may be generally applicable to the analysis of neuropeptide heterogeneity.

Animals↗
PubMed1983

Enzymatic maturation of pro-opiomelanocortin by anterior pituitary granules. Methodological approach leading to definite characterization of cleavage sites by means of high-performance liquid chromatography and microsequencing.

The coupling of high-performance liquid chromatography, gel-permeation, and reversed-phase chromatography with microsequencing proved to be advantageous for the unambiguous determination of specific sites in pro-opiomelanocortin, cleaved by secretory granule lysates of pig anterior pituitary. This system allows the unambiguous identification of a major chymotrypsin-like enzyme activity, optimal at pH 8.0, in the granule preparation, with a specificity directed towards some Phe decreases X and Tyr decreases X cleavage sites. The approach used emphasizes the necessity to use methodologies leading to the unambiguous determination of conversion activities.

Amino Acid Sequence↗
PubMed1983

Regional heterogeneity in the processing of pro-opiomelanocortin in rat brain.

The occurrence of alpha-N-acetylated forms of beta-endorphin (beta END) and alpha-melanotropin (alpha MSH) in rat pituitary and brain regions was investigated using high-performance liquid chromatography and radioimmunoassay. Acetylated derivatives of both peptides predominated in neurointermediate pituitary but represented minor components in anterior pituitary, in agreement with previous reports. Regional differences in the degree of acetylation were also observed in brain. Arcuate nucleus, the major source of beta END and alpha MSH in brain, contained small amounts of acetylated forms but most of the immunoreactivity chromatographed with the unmodified beta END 1-31 and des-acetyl-alpha MSH. Amygdala and periaquaductal grey contained the non-acetylated forms only, whereas in nucleus accumbens the major immunoreactive species were the acetylated derivatives of beta END 1-31 and beta END 1-27 along with the mono- and di-acetyl forms of alpha MSH. The selective distribution of acetylated beta END and alpha MSH suggests heterogeneity in the processing of POMC in brain and may indicate a role for alpha-N-acetylation in regulating the biological activities of these peptides in specific brain regions.

Animals↗
PubMed1981

The intelligence of hydrocephalic children.

In a group of 78 children with hydrocephalus in the first months of life, the level and pattern of intelligence were considered in relation to various parameters and symptoms of their condition. These included demography (age, sex, handedness); early developmental status; symptoms (visual, motor, and seizure); formative pathology; type of hydrocephalus; site of CSF obstruction; extent and configuration of cortical thinning; and shunt treatment. The common outcome of early hydrocephalus is an uneven growth of intelligence during childhood, with nonverbal intelligence developing less well than verbal intelligence. The origin of this selective cognitive deficit is in neither the hydrocephalic condition itself nor its treatment, but rather in the developmental brain anomalies and symptoms to which the hydrocephalic child is prone: In children with aqueduct blocks and intraventricular hydrocephalus, a selectively thin vertex and occipital lobe; in any hydrocephalic child, ocular abnormalities, motor deficits, and seizures.

Age Factors↗
PubMed1981

Observations on the clinical pharmacology and plasma concentrations of diacetolol, the major human metabolite of acebutolol.

1 The pharmacological effects and plasma levels of diacetolol, the major human metabolite of acebutolol, were measured in a double-blind, balanced study in which five healthy men received single oral doses of diacetolol 100, 200, 400 and 800 mg, or placebo, at weekly intervals. 2 Resting and exercise heart rate (HR), forced expiratory volume in 1 second (FEV1), resting and exercise peak expiratory flow rate (PEFR), and plasma concentrations of diacetolol were determined at 0, 2, 4, 6, 8 and 24 h after each treatment. 3 Diacetolol caused a slight dose-related reduction in resting HR and a substantial dose-related reduction in exercise HR. AT the same time it was found that diacetolol had no significant effects on FEV1 and resting and exercise PEFR. 4 Mean highest observed plasma concentrations (ng/ml) of diacetolol were 177 at a mean of 4.4 h after the 100 mg dose, 243 at 4.0 h after the 200 mg dose, 807 at 5.2 h after the 400 mg dose, and 1,306 at 4.4 h after the 800 mg dose. 5 Using the mean data, there was a strong correlation (r = 0.90) between % reduction in exercise HR and the logarithm of the plasma concentration of diacetolol. 6 Diacetolol exhibits marked cardiac beta-adrenoceptor blocking activity in man which is still evident 24 h after the administration of the higher doses of the drug. No adverse effects on pulmonary function could be detected.

Acebutolol↗