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Biomedical subjects

M A Wallace

Publications and source records attributed to M A Wallace.

At least 19 recordsLinked to original sources
PubMed1992

Semantically-bounded anomia: implications for the neural implementation of naming.

We describe a patient whose anomia is disproportionately severe for fruits and vegetables when familiarity and name frequency are taken into account. His fruit and vegetable naming impairment was evident in a variety of different tasks. In contrast, he retained good general knowledge of fruits and vegetables, and he could access their names when given a phonemic cue. We discuss the phenomenon of semantically-bounded anomia in relation to the issues of local vs distributed representation, the existence of semantic "maps" in the brain, and the implementation of arbitrary associations in neural networks.

Anomia↗
PubMed1992

Concerted CMP-dependent [3H]inositol labeling of phosphoinositides and agonist activation of phospholipase C in rat brain cortical membranes.

[3H]Inositol ([3H]Ins) labeling of phosphoinositides was studied in rat brain cortical membranes. [3H]Ins was incorporated into a common lipid pool through both CMP-dependent and independent mechanisms. These are as follows: (1) a reverse reaction catalyzed by phosphatidyl-inositol (PtdIns) synthase, and (2) the reaction performed by the PtdIns headgroup exchange enzyme, respectively. Membrane phosphoinositides prelabeled in either CMP-dependent or independent fashions were hydrolyzed by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)- and carbachol-stimulated phospholipase C. Unlike CMP-dependent labeling, however, CMP-independent incorporation of [3H]Ins into lipids was inhibited by 1 mM (0.04%) sodium deoxycholate. Thus, when PtdIns labeling and phospholipase C stimulation were studied in a concerted fashion, [3H]Ins was incorporated into lipids primarily through the PtdIns synthase-catalyzed reaction because of the presence of deoxycholate required to observe carbachol-stimulation of phospholipase C. Little direct breakdown of [3H]PtdIns was detected because production of myo-[3H]inositol 1-monophosphate was minimal and myo-[3H]inositol 1,4-bisphosphate was the predominant product. Although PtdIns labeling and 3H-polyphosphoinositide formation were unaffected by GTP gamma S and carbachol and had no or little lag period, GTP gamma S- and carbachol-stimulated appearance of 3H-Ins phosphates exhibited an appreciable lag (10 min). Also, flux of label from [3H]Ins to 3H-Ins phosphates was restricted to a narrow range of free calcium concentrations (10-300 nM). These results show the concerted activities of PtdIns synthase, PtdIns 4-kinase, and phospholipase C, and constitute a simple assay for guanine nucleotide-dependent agonist stimulation of phospholipase C in a brain membrane system using [3H]Ins as labeled precursor.

Animals↗
PubMed1991

Unconscious perception of "extinguished" visual stimuli: reassessing the evidence.

When parietal-damaged patients fail to report a contralesional stimulus because of extinction, is this because the stimulus is not perceived, or because it is perceived but cannot reach conscious awareness? VOLPE et al. [10] reported an intriguing study that seemed to locate the problem at least partly in the transfer of information to conscious awareness. They showed patients with extinction pairs of stimuli, one in each hemifield. Although patients were predictably poor at reporting the identity of the contralesional stimulus, they were able to make accurate same/different judgements comparing the two stimuli. This was interpreted as evidence that both stimuli were perceived. In the present paper, we point out that the dissociation between identification and same/different matching could also be due to the possibility that less visual information about the contralesional stimulus is necessary to make a same/different judgement than to identify the stimulus, and that chance performance is considerably higher in the first than in the second type of task. In Experiment 1, we verified this by degrading one side of a stimulus display and "replicating" the dissociation with normal subjects. We also equated the amount of visual information needed for the two tasks by yoking the stimulus pairs on "different" trials of the same/different matching task with the choice pairs on a forced choice identification task. Under these conditions, the dissociation vanished. In Experiment 2, we administered these tasks to three parietal-damaged patients with extinction. When the original method was used, same/different matching was better than identification of the contralesional stimulus. With the forced choice identification method, the dissociation again vanished.

Aged↗
PubMed1991

Altered phosphoinositide-specific phospholipase C and adenylyl cyclase in brain cortical membranes of cats with GM1 and GM2 gangliosidosis.

Phosphoinositide-specific phospholipase C and adenylyl cyclase were studied in brain cortical membranes from cats with GM1 and GM2 gangliosidosis. In contrast to brain cortical membranes from unaffected control cats, phospholipase C acting against exogenously supplied phosphoinositide substrates did not respond to stimulation by GTP gamma S, carbachol or fluoroaluminate in cortical membranes of cats with gangliosidosis. However, the enzyme was activated by calcium in membranes from affected cats to the same extent as in membranes from control cats. Basal adenylyl cyclase activity was increased 3-fold in cortical membranes of cats with GM1 and GM2 gangliosidosis, compared with unaffected sibling controls. Fluoroaluminate was equally effective in stimulating adenylyl cyclase in controls and in membranes of affected and normal cats. In addition, GppNHp was able to inhibit the forskolin-activated enzyme both in membranes from cats with gangliosidosis and sibling controls. These data suggest that the activation of phosphoinositide-specific phospholipase C in brain membranes by guanine nucleotide binding proteins is markedly impaired in GM1 and GM2 gangliosidoses.

Adenylyl Cyclases↗
PubMed1990

Purification and characterization of PLC-beta m, a muscarinic cholinergic regulated phospholipase C from rabbit brain membrane.

Two isozymes of phosphoinositide-specific phospholipase C were isolated and purified from salt-washed rabbit brain membranes. The membranes were extensively washed with isotonic, hypertonic and hypotonic buffers prior to solubilization with sodium cholate. Two isozymes (PLC-IV and PLC-beta m) were purified by a combination of DEAE-Sephacel, AH-Sepharose, heparin-Sepharose, AcA-34 gel filtration and mono-Q FPLC chromatographies. The major activity (PLC-beta m) was purified to homogeneity and had an estimated molecular weight of 155,000 on sodium-dodecyl sulfate-polyacrylamide gels (SDS-PAGE). This isozyme was immunologically identified as PLC-beta, an isozyme previously characterized in bovine brain cytosol and 2 M KCl membrane extracts. A second isozyme, PLC-IV, was immunologically distinct from PLC-beta and PLC-gamma and was purified to a stage where three protein bands (Mr 66,000, 61,000 and 54,000) on SDS-PAGE correlated with enzyme activity. The catalytic properties of the isozymes were studied and found to be very similar. The specific activities for PIP2 were greater than those obtained when PI was used. Both PLC-IV and PLC-beta m were Ca2(+)-dependent; near maximal stimulation for PI and PIP2 hydrolysis was observed at 0.5 microM free Ca2+. Sodium pyrophosphate and sodium fluoride stimulated phospholipase C activity of both isozymes. Polyclonal antibodies raised against PLC-beta m were able to inhibit carbachol and GTP gamma S stimulated phospholipase C activity in 2 M KCl washed rabbit cortical membranes. This suggests that in rabbit brain muscarinic cholinergic stimulation regulates PLC-beta m.

Animals↗
PubMed1990

Activation of phospholipase C in rabbit brain membranes by carbachol in the presence of GTP gamma S; effects of biological detergents.

Rabbit brain cortical membranes incubated with carbachol in the presence of GTP gamma S show a marked increase in the degradation of exogenous phosphatidylinositol 4,5-bisphosphate. This activation of phospholipase C is dependent on the presence of deoxycholate and maximal at 0.8-1 mM deoxycholate. There is negligible activation by carbachol alone but in the presence of GTP gamma S a carbachol effect can be readily demonstrated. Optimal activation of phospholipase C by carbachol was seen at 10 to 100 nM free Ca2+. Washing cortical membranes with hypertonic buffer extracted 60% of the membrane protein yet the carbachol and GTP gamma S coupling remained intact. Incubation of the membranes with lysophosphatidylcholine, Nonidet P-40, sodium deoxycholate or digitonin at concentrations considerably less than those frequently used to solubilize membrane proteins abolished the carbachol response. Octyl glucoside and sodium cholate also uncoupled receptor regulation of phospholipase C but only at concentrations where solubilization of membrane proteins occurred. Prior exposure of membranes to carbachol did not prevent the uncoupling observed as a result of detergent treatment. Incubation of the membranes with carbachol and GTP gamma S did not appear to be accompanied by specific release of either active phospholipase C or inhibitors of phospholipase C activity.

Animals↗
PubMed1990

Dual effect of fluoride on phosphoinositide metabolism in rat brain cortex. Stimulation of phospholipase C and inhibition of polyphosphoinositide synthesis.

We have studied the effects of fluoride, guanosine 5'-[gamma-thio]triphosphate (GTP[S]) and carbachol on phospholipase C and polyphosphoinositide synthesis. The experimental system consisted of membranes from rat brain cortex, with exogenous [3H]phosphatidylinositol ([3H]PtdIns) as substrate. In such systems, we have not found evidence to support carbachol and/or GTP[S] stimulation of PtdIns phosphorylation. Fluoride inhibited synthesis of PtdIns4P and PtdIns(4,5)P2 from PtdIns. Consequently, under conditions where breakdown of polyphosphoinositides by phospholipase C was dependent on PtdIns kinase activity, fluoride inhibited activation by GTP[S] plus carbachol of phospholipase C. When conditions allowed direct breakdown of PtdIns and precluded PtdIns kinase activity, the stimulatory effects of fluoride and GTP[S] plus carbachol on phospholipase C activity were additive.

1-Phosphatidylinositol 4-Kinase↗
PubMed1990

A novel role for dopamine: inhibition of muscarinic cholinergic-stimulated phosphoinositide hydrolysis in rat brain cortical membranes.

Dopamine inhibited phosphoinositide breakdown as stimulated by carbachol in rat brain cortical membranes. The IC50 value was 14 +/- 2 microM for dopamine's inhibition of phosphatidylinositol hydrolysis as stimulated by 1 mM carbachol. The inhibition was found at low (0.1 microM), but not high (greater than 0.3 microM), concentrations of the non-hydrolyzable guanine nucleotide analog, GTP gamma S. Pharmacological characterization of the response indicated that the dopamine effects were mediated by D1 receptors. The assay conditions precluded any involvement of cyclic-AMP as a mediator of the dopamine response, and thus, a novel role is proposed for dopamine in cortex working through D1 receptors to inhibit phosphoinositide degradation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Frames of reference for allocating attention to space: evidence from the neglect syndrome.

With respect to what frames of reference, or spatial coordinate systems, is attention allocated to locations in space? We posed this question about the spatial attention system that has been damaged in neglect patients, distinguishing among three possible types of spatial reference frame: viewer-centered, according to which locations are coded with respect to the viewer, environment-centered, according to which locations or coded with respect to the environment, and object-centered, according to which locations are coded with respect to an object. The three candidate frames of reference were decoupled from one another by rotating either the viewer or the stimulus object. Visual search performance suggested that the neglected hemifield was defined with respect to both viewer-centered and environment-centered frames of reference, but not with respect to an object-centered frame of reference. The role of objects in the allocation of attention to space, and the relation between our findings and the "two cortical visual systems" hypothesis, are discussed.

Aged↗
PubMed1990

Comparison of serotoninergic to muscarinic cholinergic stimulation of phosphoinositide-specific phospholipase C in rat brain cortical membranes.

Stimulation of phosphoinositide-specific phospholipase C (PLC) by muscarinic cholinergic and serotoninergic agonists was measured in rat brain cortical membranes by using exogenously supplied substrates. Serotonin, tryptamine, 5-fluorotryptamine and 5-methyltryptamine stimulated PLC with EC50 values of 1.7, 11.2, 15.0, and 29.4 microM, respectively. Maximal PLC stimulation by serotoninergic agonists, which were all equally efficacious, was about 30% of that attained by carbachol. Ketanserin blocked serotoninergic but not cholinergic activation of PLC, whereas, conversely, atropine blocked the latter but not the former response. The rank order of potency for muscarinic agonists was oxotremorine-M greater than pilocarpine = arecoline greater than carbachol = bethanecol. Unlike the case with tissue slices, all of these muscarinic agonists exhibited full efficacy in this assay of PLC stimulation. Activation of PLC by the neurotransmitters or their analogs was dependent on the addition of guanosine 3'-O-thiotriphosphate (GTP gamma S). Stimulation of PLC by GTP gamma S alone or in combination with 5-methyltryptamine had an apparent EC50 of about 0.4 microM. However, when carbachol or other muscarinic agonists were used, the EC50 for GTP gamma S was significantly lower. We have previously shown that dopamine working through D1 receptors inhibits the PLC response to carbachol by preventing this shift in the apparent EC50 for GTP gamma S. Dopamine did not have a similar effect on 5-methyltryptamine stimulation of PLC. The results indicate that the postreceptor mechanisms of PLC activation are distinct for muscarinic as opposed to serotoninergic agonists in brain cortex.

Animals↗
PubMed1989

Effects of the wasp venom peptide, mastoparan, on a phosphoinositide-specific phospholipase C purified from rabbit brain membranes.

The wasp venom peptide, mastoparan (Ile-Asn-Leu-Lys-Ala-Leu-Ala-Ala-Leu-Ala-Lys-Lys-Ile-LeuNH2), activated phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis as catalyzed by a phosphoinositide-specific phospholipase C (PLC-Im) purified from rabbit brain membranes. This activation was found when the molar ratio of mastoparan to PIP2 was less than 1 and when the concentration of PIP2 exceeded 10 microM. PIP2 breakdown was inhibited at both high and low substrate concentrations if the molar ratio of mastoparan to PIP2 was greater than 1. The stimulatory effect of mastoparan correlated with its ability to restrict aggregation of PIP2 into higher order structures (liposomes or mixed deoxycholate/phospholipid micelles) as the concentration of PIP2 was increased to 10 microM or greater. Mastoparan stimulation of PIP2 breakdown required the presence of a higher calcium concentration than was necessary for detection of enzyme activity. Both the stimulatory and inhibitory effects of mastoparan on PIP2 hydrolysis were lost if 2.5 mM deoxycholate was present in the assays. Hydrolysis of phosphatidylinositol (PI) by PLC-Im was inhibited at all concentrations of mastoparan tested. These results show that both PIP2 and PI are suitable substrates for PLC-Im, depending on the physical characteristics of their aggregates in aqueous suspension. An amphiphilic alpha-helix-forming peptide such as mastoparan may modulate phospholipase C activity due to the peptide's interaction with phospholipid substrates.

Amino Acid Sequence↗
PubMed1989

Carbachol in the presence of guanosine 5'-O-(3-thiotriphosphate) stimulates the breakdown of exogenous phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 4-phosphate, and phosphatidylinositol by rat brain membranes.

The breakdown of exogenously added [3H]inositol-labeled phosphoinositides by rat brain cortical membranes was stimulated by the muscarinic cholinergic agonist carbachol. The stimulation required the presence of guanine nucleotide. Optimal conditions were similar to those described for guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) + carbachol stimulation of phosphoinositide breakdown in [3H]inositol-prelabeled brain membranes (Claro, E., Garcia, A., and Picatoste, F. (1989) Biochem J. 261, 29-35). Carbachol stimulated [3H]phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown was inhibited by atropine and guanosine 5'-O-(2-thiobisphosphate). The magnitude of the stimulation of exogenous PIP2 breakdown by carbachol and GTP gamma S (2- to 3-fold) was little affected over a PIP2 concentration range of 0.03-100 microM. Phosphatidylinositol 4-phosphate (PIP) was as good a substrate at all concentrations as PIP2 for carbachol stimulation of phospholipase C activity. There was appreciable phosphomonoesterase degradation of PIP to phosphatidylinositol (PI) over 10 min. There was also some conversion of added PIP to PIP2 in the presence of added ATP. The effect of calcium on PIP breakdown was similar to that on PIP2 breakdown, with an apparent EC50 for Ca2+ stimulation of 0.74 and 0.72 microM, respectively, under basal conditions. The stimulation of PIP2 and PIP breakdown by carbachol in the presence of GTP gamma S was greatest on a percentage basis at the lowest free Ca2+ concentrations. Above 1 microM free Ca2+, the stimulatory effect was lost, whereas 10 microM free Ca2+ gave a maximal stimulation of basal phospholipase C activity. Degradation of added PI was also stimulated by carbachol in the absence of ATP. PI breakdown had an EC50 for Ca2+ stimulation of 1.07 microM. The best stimulation of PI breakdown due to carbachol plus GTP gamma S was seen with 0.3 microM free Ca2+ and 100 microM PI. Maximal activation of PI breakdown was seen at 1 mM deoxycholate as was true for PIP2 and PIP breakdown. There was little effect, even of 30 microM GTP gamma S alone or of carbachol alone, on PI breakdown. Half-maximal activation of the carbachol response required only 0.2 microM GTP gamma S. These results indicate that the phospholipase C enzyme(s) activated by carbachol in the presence of GTP gamma S in rat brain cortical membranes can degrade PIP2, PIP, and PI to inositol phosphates and diacylglycerol.

Adenosine Triphosphate↗
PubMed1988

Evidence for involvement of guanine nucleotide-binding regulatory proteins in the activation of phospholipases by hormones.

Guanine nucleotide-binding regulatory proteins similar to Gs and Gi may be involved in the activation of phospholipases C and A2 by hormones and other ligands. The binding of hormones to receptors that activate phospholipase C is decreased by guanine nucleotides and these hormones also stimulate a high-affinity GTPase activity in cell membranes. Effects of hormones on phospholipase C activity in cell-free preparations are dependent on the presence of guanine nucleotides. In addition, fluoride and nonhydrolyzable GTP analogs activate phospholipases in a manner that can be blocked by GDP beta S. The putative guanine nucleotide-binding regulatory protein that appears to be involved in activation of phospholipase C is sensitive to pertussis toxin in some cells but not in others.

Animals↗
PubMed1988

Worldwide experience in newborn screening for classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

The need for a reliable screening test for classical congenital adrenal hyperplasia prompted development of newborn screening programs. Worldwide incidence of classical congenital adrenal hyperplasia in this report was taken from newborn screening programs in France, Italy, Japan, New Zealand, Scotland, and the United States. Two populations in which the occurrence of congenital adrenal hyperplasia among live births has been reported with greater than usual frequency are the Yupik Eskimos of southwestern Alaska (1:282) and the people of La Reunion, France (1:2,141). Aside from these populations, 1,093,310 newborns were screened between 1980 and 1988, of whom 77 had congenital adrenal hyperplasia. Thus, worldwide incidence of this disorder was estimated at 1:14,199 live births for homozygous patients, 1:60 for heterozygous subjects, with a gene frequency of 0.0083. Incidence of congenital adrenal hyperplasia among whites was estimated to be 1:11,909 (41:488,279) for homozygous patients, 1:55 for heterozygous subjects with a gene frequency of 0.0091. Incidence for the salt-wasting form of congenital adrenal hyperplasia was 1:18,850 (58:1,093,310) compared with 1:57,543 (19:1,093,310) for congenital adrenal hyperplasia in the simple virilizing form. Thus, salt-wasting congenital adrenal hyperplasia was three times more common than simple virilizing congenital adrenal hyperplasia. Estimated incidence of congenital adrenal hyperplasia in white populations in Italy and France (1:10,866) was higher than in Scotland (1:17,098), New Zealand (1:14,500). The incidence in an Asian population (Japan) (1:15,800) did not differ significantly from that of the white population. In four of five populations, overall incidence was higher than previously reported, as was the frequency of the salt-wasting form (75% v 50% to 66%), suggesting improved case detection by newborn screening.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1987

Guanine nucleotide and pyrophosphate activate exogenous phosphatidylinositol 4,5-bisphosphate hydrolysis in rat liver plasma membranes.

5'-guanylylimidodiphosphate (GppNHp) in the presence of deoxycholate, stimulated the phospholipase C-mediated hydrolysis of exogenous [3H]phosphatidylinositol 4,5-bisphosphate ([3H]PIP2) to myo-[3H]inositol 1,4,5-trisphosphate in rat liver plasma membranes. Activation was not specific for guanine nucleotides as 5'-adenylylimidodiphosphate, imidodiphosphate and pyrophosphate stimulated the enzyme with similar efficacies and potencies. Enzyme activation by GppNHp was most pronounced when [3H]PIP2 was used as substrate. No added Ca++ was required for [3H]PIP2 breakdown but hydrolysis was inhibited by divalent ion chelators. GppNHp stimulation was apparent in the presence of Ca++ or Mg++ as well as chelator concentrations that partially inhibited the enzyme, indicating that this effect was not attributed to changes in affinity of these divalent cations for the enzyme or substrate. These results suggest that guanine nucleotides can stimulate the hydrolysis of exogenous [3H]PIP2 in rat liver membranes by a non-specific effect probably due to the interaction of the diphosphate moiety with the enzyme or substrate.

Calcium↗
PubMed1987

Analysis of the effects of inhaled diesel exhaust on the alveolar intravascular and interstitial cellular components of rodent lungs.

Transmission electron microscopy (TEM) was used to determine the effect of diesel engine exhaust (DEE) on the intravascular and interstitial cellular population of the lungs of exposed rats and guinea pigs. Animals with matched controls were subjected to environments of either 250, 750, 1500 or 6000 micrograms/m3 for either 2 weeks, 6 weeks, 10 weeks or 18 months. These animals were sacrificed immediately following the exposure periods and their lungs perfused with fixative. Following dissection, random stratified biopsies from the lungs of these animals were made. Ultrathin sections from the alveolar lung were prepared and conventionally processed for TEM and randomly photographed to compose a micrograph database. These micrographs were analyzed by point counting using a Zeiss MOP 3 Digital Image Analyzer. The results indicated no significant intravascular cellular response but a significant increase in the mononuclear population in the interstitium.

Animals↗