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Biomedical subjects

S E Bryson

Publications and source records attributed to S E Bryson.

At least 37 records · Page 2Linked to original sources
PubMed1994

Imitation and action in autism: a critical review.

This article considers the evidence for an imitative deficit in autism and for the possible role of deficiencies in the representation of actions. An argument is developed for the claim that the imitation problem is diagnostic of a basic information-processing rather than a social dysfunction. Reviews are offered of the empirical literature on gestural imitation in autism (and other developmental disorders) and the more anecdotal evidence for problems in the domain of action development in autism. An account that may help to integrate these areas is suggested, as are directions for future research.

Autistic Disorder↗
PubMed1994

Comparative pharmacology of recombinant rat AT1A, AT1B and human AT1 receptors expressed by transfected COS-M6 cells.

1. Currently available antagonists and agonists cannot distinguish between angiotensin AT1 receptor subtypes. 2. We synthesized a series of compounds selected on the basis of having the most diverse structural features with respect to losartan (DuP753), the prototype non-peptide AT1 receptor antagonist. Using a radioligand-receptor binding assay and membranes prepared from COS-M6 cells transfected with individual AT1 receptor subtypes, we determined whether any of these compounds could distinguish between the receptor subtypes. 3. The diversity of the structural features of this series of compounds was reflected by the wide range of affinities (pIC50 values) displayed towards competing with [125I]-Sar1Ile8 angiotensin II for binding to the AT1 receptors. 4. Direct comparisons of the pIC50 values of individual compounds for rat AT1A, AT1B and human AT1 receptors revealed only minor differences. 5. It is concluded that compounds based structurally on losartan are unlikely to distinguish between these receptors.

Angiotensin I↗
PubMed1993

Phenoxybenzamine mediated inhibition of the vascular dopamine D1 receptor.

Cultures of rat mesenteric artery vascular smooth muscle cells express both vascular dopamine D1 receptors and beta 2-adrenoceptors but not alpha 1- or alpha 2-adrenoceptors, permitting direct investigation of the dopamine D1 receptor antagonist activity of phenoxybenzamine. After incubating cells with phenoxybenzamine (10(-5) M) for 20 min, an 80% inhibition of dopamine-induced (10(-4) M) cAMP formation was observed. Isoprenaline-induced (10(-5) M) cAMP formation remained unaffected by phenoxybenzamine. Inhibition of the dopamine response following 20 min incubation with phenoxybenzamine, was concentration-related and could not be reversed by repeated washing. Mean IC50 (95% confidence limits) = 4.68 x 10(-6) M (3.86-5.01). Exposure of cells to the selective dopamine D1 receptor partial agonist (+)-SKF 38393 (10(-6) M) prior to phenoxybenzamine incubation, resulted in protection of dopamine-induced cAMP formation. Exposure of cells to the stereo-enantiomer (-)-SKF 38393 (10(-6) M) did not produce any protective effect. The concentration-effect curve for (+)-SKF 38393 mediated protection had a mean EC50 value of 0.11 x 10(-6) M (0.10-0.11), which is comparable with the Ka apparent value (0.06 x 10(-6) M) for this compound when acting as an agonist to induce cAMP formation via the vascular dopamine D1 receptor. Previous studies of the vascular dopamine D1 receptor are likely to have been influenced by the frequent use of phenoxybenzamine, which we have shown to act as a potent antagonist at this site.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Alpha 2-adrenergic inhibition of Cl- transport by opercular epithelium is mediated by intracellular Ca2+.

We isolated the opercular epithelium of sea-water killifish (Fundulus heteroclitus) to study the mediation of catecholamine inhibition of Cl- secretion. The receptors are alpha 2-adrenergic, as they have a high affinity for the alpha 2-adrenergic agonist clonidine over phenylephrine and clonidine action is blocked by yohimbine. Pertussis toxin and indomethacin did not block the clonidine effect; hence inhibitory guanine nucleotide-binding proteins (Gi proteins) and prostaglandins (respectively) are not involved. Intracellular pH (pHi) of single chloride cells was measured microspectrofluorometrically and resting pHi was 7.22 +/- 0.03. However, pHi was unaffected by clonidine; hence pHi and Na+/H+ exchange are not involved. The lipoxygenase inhibitors nordihydroguaiaretic acid and baicalein and the lipoxygenase products (12S)- and (12R)-12-hydroxyeicosatetraenoic acid stimulated Cl- secretion. Protein kinase C is an unlikely site of action because the diacylglycerol kinase inhibitor R59022 had no effect alone and did not block the clonidine effect. Ionomycin (1 microM) in normal but not low-Ca2+ solutions mimicked the action of clonidine and both inhibitions were reversible by isoproterenol. Thapsigargin, a releaser of intracellular Ca2+, inhibited Cl- secretion and this effect was reduced in low-Ca2+ solutions. Low-Ca2+ solutions also blunted but did not block entirely the clonidine response, indicating that the primary Ca2+ release was from intracellular stores. Whereas alpha 1-adrenergic receptors commonly act via the Ca2+/inositol trisphosphate pathway, to our knowledge this is the first report of a Ca(2+)-mediated alpha 2-adrenergic response in a nonmammalian vertebrate.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1993

Gonadotropin action on brook trout sperm duct epithelium: ion transport stimulation mediated by cAMP and Ca2+.

The isolated sperm duct epithelium from the brook trout Salvelinus fontinalis serves as a model for gonadotropin (GtH) action and is the only example of direct GtH stimulation of epithelial ion transport. In response to purified salmonid carbohydrate-rich GtH added to either the luminal or blood side of the epithelium, the duct actively secretes K+ (measured as 86Rb+ fluxes) and actively reabsorbs Na+ (measured by 22Na+ fluxes or as short circuit current, Isc). As a consequence of the ion transport, the seminal plasma has low Na+ concentration and high K+ content that in turn keeps developing sperm quiescent prior to spawning. All of the increase in Na+ transport in response to GtH addition can also be evoked by 1.0 mM db-cAMP + 0.1 mM 3-isobutyl-1-methylxanthine (IBMX), indicating that GtH action on Na+ transport is mediated by cAMP. In contrast, 86Rb+ efflux is only partially stimulated by db-cAMP + IBMX. K+ secretion can be stimulated fully by GtH or with the addition of the Ca2+ ionophore ionomycin (1 microM) in combination with db-cAMP + IBMX. Further, the cAMP-stimulated portion of K+ secretion is resistant to the K+ channel blocker Ba2+ (2.0 mM, added to the luminal side) while the ionomycin-stimulated K+ secretion is Ba(2+)- and quinidine (0.1 mM, luminal side)-sensitive. We conclude that GtH acts by two intracellular messengers in this system. The stimulation of Na+ active reabsorption and a Cl(-)-dependent K+ secretion are both mediated by cAMP. A second, Ba(2+)-sensitive K+ secretion is evoked by intracellular Ca2+ and likely represents a group of Ca(2+)-activated K+ channels on the apical membrane of the epithelium.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Visual orienting deficits in high-functioning people with autism.

There has been renewed interest in the idea that attentional dysfunction may underlie autistic symptomatology (e.g., Bryson, Wainwright-Sharp, & Smith, 1990; Dawson & Lewy, 1989a, 1989b). Existing research indicates problems with overfocused attention (Lovaas et al., 1971; Rincover & Ducharme, 1987), and with shifting attention between sensory modalities (Courchesne et al., 1990). These phenomena were examined further by using Posner's (1978) visual orienting task with a group of high-functioning autistic adolescents and adults, and matched normal controls. Our results indicate that autistic people have difficulty processing briefly presented cue information. Evidence of problems disengaging and shifting attention within the visual modality was also provided. The findings can be seen as consistent with previous behavioral, autonomic, and electrophysiological research which has revealed impairments in the registration, processing, and response to external stimuli.

Adolescent↗
PubMed1993

Pharmacological characterization of the dopamine receptor coupled to cyclic AMP formation expressed by rat mesenteric artery vascular smooth muscle cells in culture.

1. Mesenteric artery vascular smooth muscle cells derived from male Wistar rats and grown in culture were prelabelled with [3H]-adenine and exposed to a range of dopamine receptor agonists and antagonists. Resultant [3H]-cyclic AMP formation was determined and concentration-effect curves constructed, in the presence of propranolol (10-6) M) and the phosphodiesterase inhibitor IBMX (5 x 10(-4) M). 2. Ka apparent values for D1/DA1 dopamine receptor agonists SKF 38393, fenoldopam, 6,7-ADTN, and dopamine were 0.06, 0.59, 4.06 and 5.77 x 10(-6) M respectively. Although fenoldopam and SKF 38393 were more potent than dopamine, they were partial agonists with efficacies, relative to dopamine of approximately 48% and 24% respectively. 6,7-ADTN, in contrast, behaved as a full agonist. 3. Dopamine-stimulated cyclic AMP formation was inhibited in a concentration-dependent manner by the D1/DA1 dopamine receptor selective antagonists, SCH 23390 and cis-flupenthixol (Ki values 0.53 and 36.1 x 10(-1) M respectively). In contrast, the D2/DA2 dopamine receptor selective antagonists, domperidone and (-)-sulpiride, were less potent (Ki values 2.06 and 5.82 x 10(-6) M respectively). Furthermore, the stereoisomers of SCH 23390 and cis-flupenthixol, SCH 23388 and trans-flupenthixol, were at least two orders of magnitude less potent (Ki values 0.14 and 13.2 x 10(-6) M respectively) indicating the stereoselective nature of this receptor. 4. Our results indicate that rat mesenteric artery vascular smooth muscle cells in culture express a dopamine receptor coupled to cyclic AMP formation, which has the pharmacological profile, characteristic of the D1 dopamine receptor subfamily.

Animals↗
PubMed1992

Characterization of the angiotensin II receptor expressed by the human hepatoma cell line, PLC-PRF-5.

Radioligand binding studies were undertaken to establish the expression of angiotensin II (AII) receptors on the human hepatoma cell line, PLC-PRF-5. Cell membranes were shown to express a large number of AII receptors with high and low affinity binding sites having Bmax values of 1269 +/- 365 and 4190 +/- 1055 fmol/mg protein and affinities (Kd) of 2.0 +/- 0.3 nM and 8.7 +/- 0.4 nM, respectively. In intact cells a single class of AII binding site was seen with an affinity (Kd) of 6.7 +/- 1 nM and a Bmax value of 315 +/- 32 fmol/mg. In both membranes and intact cells AII, AIII and the selective angiotensin AT1 receptor antagonist, DuP 753, all had a high affinity for the receptor (Ki values in the nanomolar range), but the selective angiotensin AT2 ligands, PD 123177 and p-aminophenylalanine6 AII, had low affinity (Ki values in the micromolar range). These results indicate that the PLC-PRF-5 cells express the angiotensin AT1 receptor subtype. This was further supported by the demonstration of the sensitivity of the receptor to dithiothreitol (DTT). Pretreatment of membranes with DTT reduced [3H]AII binding in a concentration-dependent manner with an IC50 of 4.2 +/- 0.9 mM. The coupling of the AT1 receptor to signal transduction pathways was investigated. In intact cells AII (100 nM) evoked an increase in intracellular calcium ([Ca2+]i). This increase in [Ca2+]i was unaffected by PD 123177 (100 microM) but was abolished by DuP 753 (100 microM). Furthermore, AII (100 nM) did not inhibit forskolin (0.1-10 microM) stimulated cyclic AMP formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Thiol group identification at or near the agonist binding site of the vascular dopamine receptor.

Cultured mesenteric artery vascular smooth muscle cells derived from male Wistar rats, expressing both beta 2-adrenoceptors and dopamine DA1 receptors, were prelabelled for 2 h with [3H]adenine. [3H]cAMP formation stimulated by the addition of dopamine (plus propranolol 10 microM), isoprenaline or forskolin, in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) (0.5 mM) was then determined. Exposure of cells to the thiol-oxidizing agent DTNB (5,5'-dithiobis-2-nitrobenzoic acid) following prelabelling, and prior to cAMP assay, resulted in a time-dependent inhibition of dopamine (0.1 mM)-induced cAMP formation, which obeyed the rules of first-order kinetics, being complete by 60 min. This inhibitory effect was observed to be dose related with 50% inhibition achieved at a concentration of 0.5 mM. Exposure to DTNB (5 mM) for 45 min abolished the cAMP response to dopamine (0.1 mM) with little effect on the response to forskolin (10 microM) or isoprenaline (10 microM). Prior addition of the dopamine DA1/D1 receptor selective partial agonist (+)-SKF 38393 (1 microM) preserved the dopamine induced cAMP formation despite DTNB exposure, while its stereo-enantiomer (-)-SKF 38393 (1 microM) protected only 25% of the response. Sequential exposure of cells to DTNB (5 mM) and then either vehicle or DTT (DL-dithiothreitol; 1 mM), each for 20 min periods, resulted in a 70% inhibition of dopamine induced cAMP formation which was almost completely reversed by the disulphide bridge cleaving compound DTT.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1992

Induction of the angiotensin AT2 receptor subtype expression by differentiation of the neuroblastoma x glioma hybrid, NG-108-15.

In vitro differentiation of the mouse neuroblastoma-rat glioma hybrid cell line, NG-108-15, with dimethyl sulphoxide (1.5%) and low serum (0.5%), produced a marked increase in the number of angiotensin II receptors, from a level at the limit of sensitivity using labelled angiotensin II with a high specific activity ([125I]angiotensin II), in undifferentiated cells, to a Bmax of 1077 (1070-1268) fmol/mg in 5-day-differentiated cells. The affinity (Kd) of radiolabelled angiotensin II for the receptors in differentiated cells was 8.1 (7.5-10) nM. The recently available selective non-peptide antagonists, DuP 753 and PD 123177 and the peptide analogues of angiotensin II, CGP 42112A and p-aminophenylalanine6 angiotensin II, were used to characterize the angiotensin II receptors by competing for 125I-[Sar1-Ile8]angiotensin II binding to membranes prepared from undifferentiated and differentiated cells. The predominant angiotensin II receptor subtype expressed by undifferentiated cells was AT1 and after differentiation AT2. This change in receptor expression was evident 2 days after initiation of differentiation, was maximal at 4-5 days and was stable for at least 8 days. Administration of angiotensin II induced intracellular Ca2+ mobilization in both undifferentiated and differentiated cells. This was antagonised by the selective AT1 antagonist, DuP 753, indicating an action at the AT1 receptor subtype in both undifferentiated and differentiated cells. The selective AT2 antagonist, PD 123177 was without effect on the angiotensin II induced increase in intracellular Ca2+. This effect of DuP 753 on Ca2+ was specific for angiotensin II since the drug had no effect on bradykinin induced increases in intracellular Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Characterization of the dopamine receptor expressed by rat glomerular mesangial cells in culture.

Incubation of cultured rat glomerular mesangial cells with dopamine caused an increase in cyclic AMP formation in a concentration-dependent manner (Ka apparent 2.2 microM). The selective dopamine D1 receptor agonists, fenoldopam, SKF 38393 and (+/-)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN) also produced concentration-dependent increases in cyclic AMP with mean Ka apparent values of 0.04 microM, 0.02 microM and 1.02 microM, respectively. Although fenoldopam and SKF 38393 were more potent than dopamine, they were partial agonists with efficacies, relative to dopamine, of approximately 60 and 35%, respectively. The dopamine analogue, 6,7-ADTN, in contrast, behaved as a full agonist. Dopamine-stimulated cAMP formation was inhibited in a concentration-dependent manner by the D1-selective antagonist, SCH 23390, with a Ki of 0.06 nM. In contrast, the D2-selective antagonist, domperidone, was four orders of magnitude less potent than SCH 23390, having a Ki of 2072 nM. In addition, SCH 23388, the stereoisomer of SCH 23390, was observed to be two orders of magnitude less potent than SCH 23390, indicating the stereoselective nature of the receptor. The potency series for the selective agonists and antagonists is the same as that described, using identical experimental conditions, for the D1 receptor expressed by a cell line of central origin confirming that the peripheral DA1 and the central D1 dopamine receptor are pharmacologically similar.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Calcium transport by isolated skin of rainbow trout.

The skin overlying the cleithrum bone of freshwater-acclimated rainbow trout contains numerous mitochondria-rich (MR) cells, as detected by DASPEI fluorescence. This tissue was mounted in vitro in an Ussing-style chamber with fresh water on the mucosal surface and saline supplemented with bovine serum albumin on the serosal surface. The preparation developed a high transepithelial resistance and a small transepithelial potential (Vt), positive on the serosal side. Radioisotopic flux measurements indicated that the preparation actively transported Ca2+ from the mucosal to the serosal surface, as assessed by the Ussing flux ratio criterion. Ca2+ transport was positively correlated with MR cell density. Cortisol pretreatment in vivo reduced MR cell density and increased Vt but did not significantly alter Ca2+ fluxes. Ca2+ transport was unaffected by adrenergic agonists (10(-5) mol l-1 adrenaline, clonidine, isoprenaline) or cyclic AMP stimulants (10(-3) mol l-1 dibutyryl cyclic adenosine monophosphate, db-cAMP, plus 10(-4) mol l-1 isobutylmethylxanthine, IBMX) applied to the serosal surface. The Ca2+ ionophore ionomycin (1 x 10(-6)-3.2 x 10(-6) mol l-1 on the mucosal surface) increased both unidirectional Ca2+ fluxes and caused Ca2+ to accumulate within the epithelium. Lanthanum (10(-4) mol l-1) did not inhibit unidirectional Ca2+ fluxes, but apparently displaced Ca2+ from binding sites on the mucosal surface. Unlike Ca2+, movements of Na+ and Cl- across the epithelium were passive, as assessed by the flux ratio criterion, and neither adrenaline nor db-cAMP plus IBMX had any effect on Na+ or Cl- fluxes or electrical properties. These results indicate that ion transport across the skin mediated by MR cells ('chloride cells') contributes to Ca2+ but not to NaCl balance in freshwater trout.

Acclimatization↗
PubMed1991

A closer look at the Autism Behavior Checklist: discriminant validity and factor structure.

The psychometric properties of the Autism Behavior Checklist (ABC; Krug, Arick, & Almond, 1980a, 1980b), a 57-item screening checklist for autism was investigated. Professional Informants completed the ABC on 67 autistic and 56 mentally retarded and learning-disabled children. The autistic children were the total population of autistic children aged 6-15 in two circumscribed suburban and rural regions. Using the total score, the ABC accurately discriminated 91% of the children, with 87% of the autistic and 96% of the nonautistic group correctly classified. Moreover, the accuracy of classification was virtually identical when only the more heavily weighted checklist items were used. A 3-factor model accounted for 32% of the total variance in the checklist. Seventeen items loaded .4 or more on Factor 1, 12 items loaded on Factor 2, and 10 items loaded on Factor 3. The present results fail to provide empirical support for a single unidimensional scale for autism. Also, there is little support for subdividing the checklist into five subscales based on symptom areas.

Adolescent↗
PubMed1991

Differential asymmetries for positive and negative emotion: hemisphere or stimulus effects?

Two experiments were carried out to determine whether expressive asymmetries in facial stimuli might underlie evidence of differential hemispheric responses to positive and negative emotion. Experiment 1 systematically varied stimulus orientation; Experiment 2 included both normally oriented and reversed (mirror-image) faces. We replicated previous reports of a left field advantage for happy faces and a right field superiority for sad faces only when normally oriented faces were used. Mirror-image stimuli tended to produce the opposite pattern of results, and a combination of the two (Exp. 2) eliminated the visual field differences for each emotion. The findings underscore the importance of controlling for stimulus asymmetries in visual laterality studies, and are discussed in terms of current notions about the lateralization of both the perception and expression of emotion.

Adult↗
PubMed1991

Intracellular pH regulation in trout urinary bladder epithelium: Na(+)-H+(NH4+) exchange.

We measured intracellular pH (pHi) of single epithelial cells in situ in the urinary bladder epithelium using microspectrofluorometry and the cytoplasmically trapped pH-sensitive fluorophore, 2',7'-bis(2-carboxyethyl)-5(6)- carboxyfluorescein (BCECF). The resting pHi was 7.21 +/- 0.03 (n = 40 bladders, 489 cells) in pH 7.8 bathing solutions, indicating that H+ is not passively distributed across the plasma membrane and is extruded against its electrochemical gradient. Whereas exposure to hypercapnia (5% CO2 saturation) reversibly decreased pHi, mucosally added 20 mM NH4+ reversibly increased pHi. Recovery from the NH4+ effect was slow and lacked an acid-load pHi undershoot; this is interpreted as suggesting significant NH4+ permeability. Recovery from hypercapnic acidosis was blocked by mucosally added amiloride, indicating that apical Na(+)-H+ exchange is involved in pHi regulation. Addition of 0.5 mM NH4+ to the basolateral side when the mucosal side was bathed in mock urine (2 mM NaCl) significantly increased undirectional mucosal-to-serosal Na+ flux, and the increase was blocked by mucosally added amiloride. We conclude that an apically located Na(+)-H+ exchange is important in pHi regulation and may also accept NH4+ as the counterion for Na+.

Amiloride↗
PubMed1990

Comprehension of concrete and abstract words in autistic children.

This study employed the Stroop paradigm to examine comprehension of single words in autistic children. The words of interest varied along a concrete-abstract dimension. In the Stroop paradigm, subjects are asked to name the color of ink in which color words are printed. Comprehension is indexed by the degree to which the automatic processing of words interferes with the color-naming task. For both concrete and abstract words, autistic children showed the same degree of interference as reading-matched controls. The findings corroborate and extend previous work suggesting that autistic children understand, and by implication, can mentally represent, at least some word meanings.

Adolescent↗
PubMed1989

Gonadotropin stimulation of K+ secretion and Na+ absorption by brook trout (Salvelinus fontinalis) sperm duct epithelium.

The sperm duct epithelium from mature spermiating brook trout (Salvelinus fontinalis) was mounted in vitro to examine control of Na+ absorptive and K+ secretory transport. Na+ absorption (measured as the short-circuit current) and K+ secretion (measured using 86Rb+ as tracer) were stimulated by 3-isobutyl-1-methylxanthine and cyclic AMP while unstimulated tissues had no net ion transport. Purified chum salmon (Oncorhynchus nerka) Con AII carbohydrate-rich gonadotropin produced a rapid, sustained rise in Rb+ secretion and Na+ uptake in a log linear dose-dependent manner. Addition of gonadotropin to either apical (mucosal) or basolateral (serosal) sides evoked the response, but addition to the apical side produced the more rapid effect, indicating that receptors for the hormone are present on both sides of the transporting cells and suggesting that subepithelial tissue may slow the response to serosally added hormone. This is the first indication that gonadotropin may directly regulate ion transport functions of the blood-testis barrier of vertebrates and in this way regulate seminal plasma ionic composition.

Absorption↗