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C M Powell

Publications and source records attributed to C M Powell.

25 records · Page 2Linked to original sources
PubMed1993

X-chromosome effects on female brain: a magnetic resonance imaging study of Turner's syndrome.

Many neuropsychiatric disorders differ between the sexes in incidence, symptoms, and age at onset. To investigate the effects of X-chromosome aneuploidy and of sex steroid deficiency during childhood on brain structure and function, we used neuropsychological tests and quantitative magnetic resonance imaging (MRI) to study the brains of eighteen women with Turner's syndrome (TS) and nineteen healthy control women of similar age. Nine TS subjects had mosaic 45,X karyotypes, and 9 had non-mosaic 45,X. The TS group had significantly lower scores than the controls for all the Wechsler adult intelligence scale tests, except verbal comprehension and reading level. The greatest difference was in visuospatial construction (mean 90 [SD12] vs 118 [13], p < 0.0001). The TS subjects also had a greater discrepancy than controls between verbal and performance intelligence quotients (9 [8] vs -5 [9], p < 0.001). We found that TS subjects had significantly smaller values than controls in MRI-measured volumes of hippocampus, caudate, lenticular, and thalamic nuclei, and parieto-occipital brain matter, on both sides. Women with mosaic TS had values between the full TS and control groups for cerebral hemisphere and lenticular and thalamic nuclei volume and for verbal ability. Within the mosaic TS group, visuospatial ability was significantly correlated with the percentage of lymphocytes that had the 45,X karyotype. Hippocampal volume and memory test scores were significantly lower in mosaic and non-mosaic 45,X TS subjects than in controls. We postulate that in human beings the X chromosome plays an important part in the development and ageing of grey matter in striatum, diencephalon, and cerebral hemispheres.

Adult↗
PubMed1993

PHAVER syndrome: an autosomal recessive syndrome of limb pterygia, congenital heart anomalies, vertebral defects, ear anomalies, and radial defects.

We have studied 2 sibs with vertebral, radial, congenital heart, and ear defects. The second patient also had limb pterygia and meningomyelocele. The abnormalities in these two sibs are seen in the VATER association; however, distinguishing these cases from the VATER association are the findings of pterygia, meningomyelocele, and probable autosomal recessive inheritance. We propose the acronym PHAVER syndrome for limb pterygia, heart defects, autosomal recessive inheritance, vertebral defects, ear anomalies and radial defects. This represents a new autosomal recessive disorder with phenotypic variability.

Abnormalities, Multiple↗
PubMed1993

Mosaic 5p tetrasomy.

We report on a mildly abnormal 5-year-old girl with seizures, psychomotor retardation, and areas of hyperpigmentation who had a supernumerary marker chromosome in fibroblasts which was identified as an i(5p). To our knowledge, this is the first reported case of tetrasomy 5p. She shares in common some, but not all, manifestations of the dup (5p) syndrome. Cytogenetic analysis of relatives showed that the phenotypically apparently normal mother, maternal grandmother, and a brother of the proband also had a marker chromosome in their lymphocytes which was unrelated to the i(5p).

Abnormalities, Multiple↗
PubMed1993

Studies with synthetic peptide substrates derived from the neuronal protein neurogranin reveal structural determinants of potency and selectivity for protein kinase C.

The neuronal protein neurogranin, also known as RC3, is a selective substrate for protein kinase C (PKC). We synthesized a peptide corresponding to the phosphorylation domain of neurogranin (amino acids 28-43) and characterized its properties as a PKC substrate. Neurogranin(28-43) was phosphorylated by purified PKC with a Km of 150 nM. No significant phosphorylation of the peptide by either cAMP-dependent protein kinase or by calcium/calmodulin-dependent protein kinase II could be detected. Thus, neurogranin(28-43) is a potent and selective substrate for PKC. We tested several peptide analogues of neurogranin(28-43) for their substrate potency and specificity as kinase substrates, in order to help elucidate the structural determinants involved in the phosphorylation of substrates by PKC. Substituting Arg36 with Ile caused a significant reduction in the affinity for PKC. Replacing Lys30 with Arg enhanced the catalytic efficiency (Vmax/Km) for PKC but diminished the selectivity of the substrate for PKC. These results support the generally held model that basic amino acids on both sides of the phosphorylated Ser are important structural determinants in PKC substrates. However, the data also suggest that the presence of particular basic amino acids (Arg vs Lys) can contribute to the degree of selectivity of a substrate for PKC. Replacement with Ala of Phe35, the amino acid adjacent to the Ser34 phosphorylation site, resulted in a peptide with greatly diminished potency as a PKC substrate. This finding indicates a critical role of Phe35 in modulating binding and phosphorylation of neurogranin-derived peptides by PKC.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1985

Treatment of strabismus in adults with botulinum toxin A.

Eighty-five adults with horizontal concomitant strabismus were treated with an injection of a low dose of botulinum toxin A (BTXA) into the lateral or medial rectus muscle. The ocular deviation was reduced by an average of 60% independently of its size and whether or not surgery had previously been performed. The change was temporary, however, except in those cases with binocular functions, when fusion was re-established. Repeated low dose injections can maintain the improvement, but at higher doses, although larger reductions are produced, temporary local side effects--ptosis and vertical strabismus--are common. The technique is simple, well tolerated, and has no systemic side effects.

Adolescent↗
PubMedDate not supplied

Ca(2+)-induced persistent protein kinase C activation in rat hippocampal homogenates.

Protein kinase C (PKC) is thought to play an important role in neuronal function by mediating changes in synaptic strength. Specifically, it has been argued that persistent PKC activation underlies the maintenance of long-term potentiation (LTP) of synaptic transmission in the hippocampus, a model widely used to study mammalian learning and memory. Because the induction of LTP is known to be dependent upon Ca2+ influx into the postsynaptic neuron, we investigated Ca(2+)-dependent mechanisms that operate to elicit persistent PKC activation in the hippocampus. Hippocampal homogenates were incubated with Ca2+ for a brief period and subsequently assayed for persistent changes in basal (Ca(2+)-independent) PKC activity, using the selective PKC substrate neurogranin(28-43) (NG(28-43)). After Ca2+ incubation, basal PKC phosphorylation of NG(28-43) was increased and expression of the increased activity could be inhibited by PKC(19-36), a selective peptide inhibitor of PKC. These data indicate the presence of a persistently activated form of PKC in Ca(2+)-pretreated hippocampal homogenates. The persistently activated PKC was localized to the soluble fraction of homogenates. Generation of the soluble, persistently activated form of PKC was blocked by the calpain inhibitor, leupeptin, suggesting a proteolytic activation of PKC. Column chromatography and Western blots indicated the presence of PKM, a proteolytic fragment of PKC that is active in the absence of calcium, diacylglycerols, or phospholipid cofactors. Thus, Ca2+ induces proteolytic activation of PKC in hippocampal homogenates. This suggests that proteolytic activation is a plausible candidate as a mechanism underlying the persistent activation of PKC associated with LTP.

Animals↗