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Biomedical subjects

J Hughes

Publications and source records attributed to J Hughes.

At least 235 records · Page 13Linked to original sources

Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain.

Gabapentin and S-(+)-3-isobutylgaba are anticonvulsant agents that selectively interact with the alpha2delta subunit of voltage-dependent calcium channels. This report describes the activities of these two compounds in a rat model of postoperative pain. An incision of the plantaris muscle of a hind paw induced thermal hyperalgesia and tactile allodynia lasting at least 3 days. Postoperative testing was carried out using the plantar test for thermal hyperalgesia and von Frey hairs for tactile allodynia. A single s.c. dose of gabapentin, 1 h before surgery, dose-dependently (3-30 mg/kg) blocked the development of allodynia and hyperalgesia with a minimum effective dose (MED) of 10 and 30 mg/kg, respectively. The highest dose of gabapentin prevented development of hyperalgesia and allodynia for 24 and 49 h, respectively. Similar administration of S-(+)-3-isobutylgaba also dose-dependently (3-30 mg/kg, s.c.) prevented development of hyperalgesia and allodynia with MED of 3 and 10 mg/kg, respectively. The highest dose of S-(+)-3-isobutylgaba completely blocked development of both nociceptive responses for 3 days. The administration of S-(+)-3-isobutylgaba (30 mg/kg s.c.) 1 h after surgery also completely blocked the maintenance of hyperalgesia and allodynia, but its duration of action was much shorter (3 h). The administration of morphine (1-6 mg/kg s.c.) 0.5 h before surgery prevented the development of thermal hyperalgesia with a MED of 1 mg/kg. However, unlike gabapentin and S-(+)-3-isobutylgaba, it had little effect on the development of tactile allodynia. It is suggested that gabapentin and S-(+)-3-isobutylgaba may be effective in the treatment of postoperative pain.

Acetates↗

Primary immunodeficiency diseases at Red Cross War Memorial Children's Hospital.

OBJECTIVE: To describe the spectrum of primary immunodeficiency diseases (PIDs) diagnosed at Red Cross War Memorial Children's Hospital. DESIGN: Retrospective, descriptive study. SETTING: Tertiary, referral hospital. PATIENTS: All patients investigated by the immunology service because of suspected PIDs, between January 1983 and December 1996. METHODS: Review of immunology service database and hospital case records. RESULTS: During the 14-year review period, 515 patients were investigated, a mean of 36.8 new patients per annum. Ninety-three patients with PIDs were diagnosed, a mean of 6.6 new patients per annum. The spectrum of PIDs was similar to that reported in developed countries. As in other series, antibody deficiencies predominated, accounting for 56% (52/93) of diagnoses. The male/female ratio was 1.5:1; 73% (62/85) came from the Western Cape, the remaining 27% (23/85) resided in five other provinces. Eighty per cent (70/87) presented with recurrent or atypical infection, with or without failure to thrive. Sinopulmonary infections (80%), diarrhoeal disease (19%) and candidiasis (18%) were the most common preceding infections. By the age of 5 years, only 60% had been diagnosed, compared with about 80% in developed countries. During the study period, 20% (19/93) were known to have died. CONCLUSIONS: The results show a pattern of PIDs incidence similar to that in developed countries. Diagnosis was delayed in many patients, which probably contributed to morbidity. To facilitate earlier diagnosis and to improve outcome, children should be considered for an immunological assessment if they exhibit increased susceptibility to infection.

Adolescent↗

Demographic study of port wine stain patients attending a laser clinic: family history, prevalence of naevus anaemicus and results of prior treatment.

All patients with port wine stains (PWS) attending a tunable dye laser clinic were examined by one author (SWL), forming a large group which has allowed study of the demographic data of such patients. Two hundred and eighty-three patients, 217 females (median age 24 years, range 0.5-73) and 66 males (median age 20 years, range 0.75-72), were examined. The PWS were on the face in 226, neck in 69, trunk in 36, upper limb in 35 and lower limb in 29. The commonest lesional colour was purple (63 patients), while 39 naevi were pink/red, 35 pink/ purple and 35 pink. The naevus was flat in 255 patients, cobblestoned in 28, associated with hypertrophy in 31 and with scarring in 22. Seventy-two patients (25.4%) had a positive family history of birthmarks, 20 strawberry haemangiomas and 22 PWS, the family history of PWS being higher than expected for the prevalence of this naevus in the population. One hundred and forty-six patients were also examined for naevus anaemicus which was noted in 12 (8.2%), confirming an association between these two naevi. Ninety-four patients had received previous treatment, most commonly with the argon laser (56 patients), of whom only five reported a good result, and 17 of 22 patients with treatment-related scarring had been treated with this laser. Cosmetic camouflage was used in 109 (38.5%) of patients, who usually had PWS on the face (94%), of whom only 46 (16%) had received advice of its use.

Adolescent↗

Interaction of cells with UHMWPE impregnated with the bioactive peptides RGD, RGE or Poly-L-lysine.

Several reports have suggested that encapsulation of orthopaedic and dental implants with fibrous tissue can lead to implant failure. The binding of cells to the surface of the implants is specific to amino-acid sequences, typically RGD. The specific objective of this study was to investigate the interaction of cultured human peripheral macrophages with specific amino-acid sequences to determine if adherence is due to the specificity of such sequence. Macrophages were seeded at a density of 1 x 10(5) cells on ultra high molecular weight polyethylene (UHMWPE) coated with either amino-acid heteropolymers of RGE, RGD, or amino-acid homopolymer Poly-L-Lysine. Cells were observed daily and morphology was recorded. The results showed that cells growing in the presence of RGD had significantly (p < 0.05) higher numbers of cells adhering and remaining viable, in comparison to cells growing on Poly-L-lysine or RGE. Cells growing on UHMWPE coated with RGE appeared irregularly (elongated and spindle) shaped and unevenly spaced. The cells growing in the presence of Poly-L-Lysine showed cellular disruption and lysis, whereas cells growing on the RGD appeared intact, regularly spaced and began fusing into giant cells. Lactate dehydrogenase activity was used as a measure of membrane integrity, and cells grown on UHMWPE coated with Poly-L-lysine showed a two-fold increase in activity over control and peptide treated groups. Immunochemical analysis for cytokine (IL-1) release as a measure of cellular reactivity revealed an increase level in the experimental groups after 24 hours and remained measurable over the duration of the experiment. Cells incubated on uncoated polyethylene showed no evidence of increased cytokine response. Overall, the results show macrophages can interact with specific coating on the material surface, and these surfaces can affect the adhesion process adherence. Use of RGE, which inhibits binding of the cells, may be a factor that can be used to coat implants to increase their longevity.

Amino Acid Sequence↗

Synovial tissues collected from rheumatoid patients undergoing total joint arthroplasty express markers for acute inflammation.

Rheumatoid arthritis is an autoimmune disease that causes inflammation mainly in synovial tissues. RA manifests as a chronic polyarthritis with intermittent acute inflammatory episodes. The inflammatory sites are characterized by infiltration of activated lymphocytes and macrophages into the synovial membrane, and the proliferation of synovial cells. The local production of a number of cytokines by proliferative synovial cells as well as by infiltrating cells appears to account for many of the pathological and clinical manifestations in rheumatoid arthritis. Tissues were collected from twelve RA patients undergoing joint replacement surgery. The synovium was collected and the cell types were identified, and markers for chronic and acute inflammatory mediators were measured. The cells types found in the synovium are capable of secreting cytokines which are capable of both acute inflammation (IL-1, IL-6, IL-8, MCP-1 and TNF), as well as chronic inflammation (IL-2, IL-10, and IL-4). The results obtained showed that the macrophages-derived acute inflammatory cytokines (IL-1, IL-6 and IL-8) were easily detected at levels of 22.6 +/- 12 pg/mg protein; 48.5 +/- 42 pg/mg protein, and 76 +/- 31 pg/mg protein; respectively. T-cell derived chronic inflammation cytokines (IL-2, IL-4 and IL-10) were rarely detected. Retrieved tissues that immunostained positive for IL-6, IL-1 and IL-8 also is suggestive of an acute inflammatory response. The results clearly demonstrate that the acute response may be responsible for the subsequent need for joint arthroplasties.

Acute Disease↗

The anxiolytics CI-988 and chlordiazepoxide fail to reduce immediate early gene mRNA stimulation following exposure to the rat elevated X-maze.

This study uses immediate early transcription factor gene expression to map neuronal activation after a single exposure to the elevated X-maze. Exposure to this novel environment leads to widespread upregulation in the gene expression of c-fos, NGFI-A and NGFI-B (the nerve growth factor induced genes), but not c-jun nor jun B as shown by in situ hybridization and northern blot analysis. Changes in c-fos were evident after just 5 min exposure to the maze. The cholecystokininB receptor antagonist, CI-988, given intraperitoneally at 1 mg/kg 40 min prior to exposure to the X-maze demonstrated an anxiolytic profile without affecting overall movement around the maze, however it did not reduce the increased levels of gene expression with the methodology used. Likewise the anxiolytic benzodiazepine, chlordiazepoxide at 3 mg/kg did not reduce gene expression. It is concluded that a reduction in an index of behavioural stress/anxiety produced by anxiolytic agents is not concomitantly followed by a detectable reduction in immediate early gene induction.

Animals↗

Characterization of novel peptoid agonists for the CCK-A receptor.

The successful design of peptoid CCK-B receptor antagonists using rational approaches suggested that it might be feasible to develop similar non-peptide small molecule agonists with potential therapeutic applications. We now report the characterization of such a compound with full agonist activity at CCK-A receptors on rat exocrine pancreatic acinar cells. The compound, PD149164, stimulated a similar maximal response to CCK8 from the exocrine pancreas in anaesthetized rats in vivo, and from isolated pancreatic acini in vitro it also generated intracellular Ca2+ oscillations similar to those evoked by CCK8. These effects were inhibited by the CCK-A antagonist L-364,718. Interestingly, the enantiomer of PD149164, PD151932, was a CCK-A antagonist and blocked PD149164 stimulated effects on the exocrine pancreas. The data indicate that it is possible to develop both agonist and antagonist activities in enantiomers of small non-peptide molecules.

Adamantane↗

Clinical and epidemiologic features of primary HIV infection.

BACKGROUND: The acute clinical events surrounding the acquisition of human immunodeficiency virus (HIV) have not been well characterized. OBJECTIVE: To further define the clinical and epidemiologic presentation of primary HIV infection. DESIGN: Descriptive cohort study. SETTING: University research clinic. PATIENTS: 46 adults (43 men and 3 women) with primary HIV infection who enrolled in the study a median of 51 days after HIV seroconversion. MEASUREMENTS: Documentation of recent HIV seroconversion. Standardized collection of demographic characteristics and sexual contact history, results of tests for HIV RNA, HIV culture, and T-cell subsets. RESULTS: 41 of 46 patients (89%) developed an acute retroviral syndrome. Primary HIV infection was infrequently diagnosed at the initial medical encounter, even in persons enrolled in routine HIV screening programs. Median numbers of sexual partners 6 months and 1 month before acquisition of HIV were three and one, respectively; 21 patients (46%) reported having had only one partner in the month before seroconversion. Of the 12 patients who could identify the precise date of and activity leading to seroconversion, 4 reported having only oral-genital contact. CONCLUSIONS: Primary HIV infection causes a recognizable clinical syndrome that is often underdiagnosed, even in persons enrolled in a program of routine surveillance for HIV infection. Frequency of sexual contact and overall numbers of sexual partners in this group of homosexual men who acquired HIV were markedly lower than those seen a decade ago. Acquisition of HIV does occur, even in persons with relatively few sexual partners. Increased attention to oral-genital contact as a means of acquiring HIV appears to be warranted.

Adult↗

Use of a dipeptide chemical library in the development of non-peptide tachykinin NK3 receptor selective antagonists.

The use of a dipeptide library as the source of a micromolar chemical lead compound for the human tachykinin NK3 receptor is described. The screening of a dipeptide library through a cloned human NK3 receptor binding assay resulted in the identification of Boc(S)Phe(S)PheNH2 (1), which has subsequently been developed, following a 'peptoid' design strategy, into a series of high-affinity NK3 receptor selective antagonists. The structure-activity relationship of the C-terminal portion of this dipeptide lead was first explored and led to the identification of the urea derivative Boc(S)Phe(R)alphaMePheNH(CH2)7NHCONH2 (41, PD157672). This modified dipeptide has a Ke of 7 nM in blocking senktide-induced increases in intracellular calcium levels in human NK3 receptors stably expressed in CHO cells. Subsequent optimization of the N-terminal BocPhe group and the alphaMePhe residue side chain of 41 led to the identification of [S-(R*,S*)]-[2-(2,3-difluorophenyl)-1-methyl-1-[(7-ureidoheptyl)ca r bamoyl]ethyl]carbamic acid 2-methyl-1-phenylpropyl ester (60, PD161182), a non-peptide NK3 receptor selective antagonist. Compound 60 blocks the senktide-evoked increases in intracellular calcium levels in cloned human NK3 receptors stably expressed in CHO cells with Ke of 0.9 nM.

Amino Acid Sequence↗

Co-purification from Escherichia coli of a plant beta-glucosidase-glutathione S-transferase fusion protein and the bacterial chaperonin GroEL.

The coding sequence of the mature cyanogenic beta-D-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) (linamarase) of Manihot esculenta Crantz (cassava) was cloned into the vector pGEX-2T and expressed in Escherichia coli. The bacterial chaperonin GroEL [Braig, Otwinowski, Hedge, Boisvert, Joachimiak, Horwich and Sigler (1994) Nature (London) 371, 578-586] was found to be tightly associated with the fusion protein and co-purified with it. In the presence of excess MgATP, release and folding of the fusion beta-glucosidase were demonstrated by a fast increase in both linamarase and p-nitrophenyl-beta-D-glucopyranosidase activity at a low protein concentration. A slow endogenous folding process was also detected by activity measurements. Michaelis constants (Km) and the ratio between the maximal velocities and efficiency constants (Vmax., Vmax./Km) for the hydrolysis of the natural substrate, linamarin, and p-nitrophenyl beta-D-glucopyranoside (PNP-Glc) by the recombinant protein were found to be almost identical with those of the native glycosylated plant enzyme [Keresztessy, Kiss and Hughes (1994) Arch. Biochem. Biophys. 314, 142-152]. Molecular dissociation constants for the free enzyme (pK(E)1, pK(E)2) obtained with linamarin and PNP-Glc, and the enzyme substrate complexes (pK(ES)1, pK(ES)2) were also in accordance with that of the original protein. The reactive substrate analogue N-bromoacetyl beta-D-glucosylamine inactivated the fusion enzyme according to pseudo-first-order kinetics with first-order rate constant (k1=0.007 min-1) and apparent inhibition constants (k1=20 mM) comparable with those of the plant protein [Keresztessy, Kiss and Hughes (1994) Arch. Biochem. Biophys. 315, 323-330]. In comparison with the native glycosylated plant protein, the recombinant protein was, however, found to be extremely sensitive to proteolysis and misfolding.

Acetylglucosamine↗

Hybrid hepatitis B virus core antigen as a vaccine carrier moiety: I. presentation of foreign epitopes.

Hepatitis B virus (HBV) core antigen (HBcAg) is a highly immunogenic subviral particle. Here, we review recent progress in the use of HBcAg as a carrier moiety for heterologous epitopes. To define surface exposed and immunogenic insertion sites for foreign epitopes in HBcAg, peptidic epitopes representing binding sites for virus neutralizing antibodies on the HBV surface antigens were inserted at different positions within HBcAg using genetic engineering in an Escherichia coli expression system (Schödel et al. (1992) J. Virol. 66, 106-114). While fusion to the N-terminus required a linker to become surface accessible, both fusion to the N-terminus and to the C-terminus was compatible with particle assembly and preserved the native antigenicity and immunogenicity of HBcAg. Fusion to an immunodominant internal site of HBcAg reduced the HBcAg immunogenicity and antigenicity and most drastically enhanced the immunogenicity of the inserted foreign epitope. This internal site of HBcAg was used to express circumsporozoite antigen (CS) repeat epitopes of two rodent malaria parasites and of Plasmodium falciparum (Schödel et al. (1994b) J. Exp. Med. 180, 1037-1046 and Schödel et al. (1995a) 95th ASM General Meeting, Washington DC, Abstr. E61). When purified from recombinant Salmonella typhimurium, the hybrid HBcAg-CS proteins were particulate and displayed CS antigenicity as well as reduced HBc antigenicity, as compared to native HBcAg. Immunization of several mouse strains with HBcAg-CS hybrid particles resulted in high titered serum anti-CS antibodies representing all murine IgG isotypes. Immunization of mice with HBcAg or HBcAg-CS particles formulated on alum, complete Freunds or incomplete Freunds adjuvant resulted in equivalent anti-CS and anti-HBc serum antibody titres. The possible influence of carrier-specific immunosuppression was examined and pre-existing immunity to HBcAg did not significantly alter the immunogenicity of hybrid HBcAg particles suggesting that they would be useful carrier moieties for repeated immunizations against multiple haptens or in immune subjects after HBV infection. Examination of T cell recognition of HBcAg-CS particles revealed that HBcAg-specific T cells were universally primed and CS-specific T cells were primed if the insert contained a CS-specific T cell recognition site. This indicates that the internal amino acid position in HBcAg is permissive for the inclusion of heterologous functional T helper as well as B cell epitopes. BALB/c mice immunized with HBcAg-CS1 were protected against P. berghei challenge to 90% and 100%, respectively, in two independent experiments.

Animals↗

Microbial translocation in neonates and infants receiving long-term parenteral nutrition.

OBJECTIVE: To explore whether episodes of endogenous septicemias due to microbial translocation are clinically relevant in neonates and infants who are receiving long-term parenteral nutrition (PN). DESIGN: Prospective observational cohort study of 2 years. SETTING: Neonates and infants who underwent surgical procedures and required PN because of gastrointestinal abnormalities. MEASUREMENTS: Surveillance cultures of the oropharynx and gut were obtained at the first of PN and thereafter twice each week. These cultures were processed for all microorganisms, except for coagulase-negative staphylococci, in a semiquantitative manner to detect overgrowth. A blood sample was taken for culture from both the central venous line and peripheral vein on clinical indication only. Microbial translocation was diagnosed when the microorganisms that were isolated from the blood sample were also carried in the throat and/or rectum within the 2 weeks preceding the episode of septicemia. MAIN RESULTS: Of 94 infants, 10 (11%) experienced 24 episodes of septicemia (ie, 7.3 septicemic episodes per 1000 days of PN). Six infants experienced 15 episodes of microbial translocation due to enteric microorganisms, including Escherichia coli, Klebsiella, Candida species, and enterococci. Microbial translocation occurred after a median of 58 days of PN (range, 32 to 286 days). The enteric organisms that caused septicemia were always present in the throat and/or rectum and in high concentrations ( > 10(5) colony-forming units per gram [ie, overgrowth]) in 60% of the translocation episodes. All but one episode occurred in infants with an abnormal serum bilirubin level ( > 17 mumol/L [0.99 mg/dl]). CONCLUSIONS: In neonates and infants who are receiving PN, septicemia may be a gut-related phenomenon.

Abdominal Muscles↗

Expression of the multifunctional extracellular matrix protein thrombospondin in crescentic glomerulonephritis.

Thrombospondin is a multifunctional 450 kD glycoprotein which may be secreted into the extracellular matrix by a wide variety of cells. Occasional foci of immunoreactive thrombospondin have previously been demonstrated within normal human glomeruli. A specific polyclonal antibody directed against thrombospondin 1 was used to examine the distribution of this regulatory glycoprotein in renal biopsies from patients with a variety of renal diseases, including rapidly progressive glomerulonephritis associated with circulating antibodies to neutrophils, active or quiescent systemic lupus erythematosus, and membranous nephropathy, together with normal renal tissue. The results demonstrated the marked up-regulation of thrombospondin expression in acutely inflamed renal tissue with strongly positive, predominantly extracellular staining of glomerular crescents, although cytoplasmic staining of epithelial cells was also seen, indicating that these cells may contribute to thrombospondin accumulation at these sites. Occasional segmental mesangial staining was seen in cases of active lupus and rapidly progressive glomerulonephritis, while some focal interstitial staining around peritubular capillaries was seen in all renal tissue examined. These results suggest that thrombospondin may play an important role in the regulation of cellular recruitment, proliferation, and function in crescentic glomerulonephritis.

Antibodies, Antineutrophil Cytoplasmic↗

Changes within T cell receptor V beta subsets in infants following measles vaccination.

Measles produces immune suppression which contributes to an increased susceptibility to other infections. Recently, high titered measles vaccines have been linked to increased long-term mortality among some female recipients. Because the mechanisms by which wild-type or attenuated live-vaccine strains of measles virus alter subsequent immune responses are not fully understood, this prompted an examination of the changes within the peripheral blood T cell receptor V beta repertoire following measles immunization. Twenty-four 6- and 9-month-old infants were studied at 2 weeks and 3 months following immunization by semiquantitative reverse transcription-polymerase chain reaction. There was a significant increase in V beta 2 expression (P less than 0.05), and a decrease in the V beta 4 subset (P less than 0.03) 2 weeks following vaccination with subsequent return to baselines at 3 months in vaccine recipients who seroconverted. These data suggest that measles virus may affect immune responses in part by altering the T cell receptor repertoire.

Base Sequence↗

Tetracycline-regulated reporter gene expression in the moss Physcomitrella patens.

As ancestors of higher plants, mosses offer advantages as simple model organisms in studying complex processes such as development and signal transduction. Overexpression of transgenes after genetic transformation is a powerful technique in such studies. To establish a controllable expression system for this experimental approach we expressed a chimeric protein consisting of the Tn1O-encoded Tet repressor and the activation domain of Herpes simplex virion protein 16 in the moss Physcomitrella patens. We showed that this protein activates transcription from a suitable target promoter (Top 1O) containing seven operators upstream of a TATA box. In media containing very low levels of tetracycline (1 mg/l), expression levels of a beta-glucuronidase (GUS) reporter gene dropped to <1% of that in the absence of tetracycline. This regulation is due to interference of tetracycline with the DNA binding activity of the Tet repressor portion of the chimeric transcriptional activator. Stable transformants grown for three weeks on tetracycline-containing media showed negligible GUS activity, whereas GUS was expressed strongly within 24 h of transfer to tetracycline-free media. Potent and stringently regulated expression of other, physiologically active genes is thus readily available in the moss system using the convenient ToplO expression system.

Anti-Bacterial Agents↗

Evidence for aspartate-immunoreactive neurons in the neostriatum of the rat: modulation by the mesencephalic dopamine pathway via D1-subtype of receptor.

Aspartate-like immunoreactivity was visualized in the neostriatum of rats using indirect immunofluorescence techniques and antibodies raised against aspartate conjugated to keyhole limpet hemocyanine. In normal rats only a few aspartate-positive cell bodies with limited processes were observed. A moderate increase was seen after treatment with (+)methamphetamine and haloperidol. A dramatic increase in the number and fluorescence intensity was observed in the unilaterally 6-hydroxy-dopamine lesioned rats after multiple injections of the D1-dopamine receptor agonist SKF 38393. In these rats strongly fluorescent processes as well as extensive terminal varicose fibre networks were observed. This increase could partly be blocked by the D1-dopamine receptor antagonist SCH 23390. Using a modified technique the aspartate-positive cell bodies and processes were observed even when the antiserum was diluted 1:80,000. Positive cell bodies and fibres were also seen on the ipsilateral side outside the neostriatum, for example in the islet of Calleja and in the piriform cortex. The aspartate-positive cells were negative for dopamine- and cyclic AMP-regulated phosphoprotein-32, a marker for neurons bearing dopamine D1-receptor subtype. A proportion of the aspartate-positive neurons (20%) contained neuropeptide tyrosine-like immunoreactivity. On adjacent sections there was a marked up-regulation of preprodynorphin-like immunoreactivity. The up-regulation of dynorphin and aspartate was only observed when there was an almost complete denervation of the neostriatum as visualized with antiserum to tyrosine hydroxylase, a marker for dopamine fibres. The present results raise the possibility that aspartate may act as a neurotransmitter released from interneurons in the neostriatum.

Animals↗

Role of coarse and fine spatial information in face and object processing.

In 4 experiments the role of coarse (low-pass filtered) and fine (high-pass filtered) spatial information in guiding visual processing was studied in a same-different task. The second of a pair of sequential patterns was either a normal image or the first 100 ms was restricted either coarse or fine information before a normal image was shown for the rest of the presentation. This 100-ms cue could be from the immediately succeeding image (relevant) or from other images in the set (irrelevant). Analysis of response times and errors showed relevant coarse- and fine-scale cues were usually equally effective, but any differences favored fine-scale versions. Irrelevant fine-scale cuing was significantly more disruptive than coarse-scale cuing. No evidence of preferential cuing by coarse-scale information occurred in any experiment.

Adult↗