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J A Frost

Publications and source records attributed to J A Frost.

At least 37 records · Page 2Linked to original sources
PubMed2000

Human temporal lobe activation by speech and nonspeech sounds.

Functional organization of the lateral temporal cortex in humans is not well understood. We recorded blood oxygenation signals from the temporal lobes of normal volunteers using functional magnetic resonance imaging during stimulation with unstructured noise, frequency-modulated (FM) tones, reversed speech, pseudowords and words. For all conditions, subjects performed a material-nonspecific detection response when a train of stimuli began or ceased. Dorsal areas surrounding Heschl's gyrus bilaterally, particularly the planum temporale and dorsolateral superior temporal gyrus, were more strongly activated by FM tones than by noise, suggesting a role in processing simple temporally encoded auditory information. Distinct from these dorsolateral areas, regions centered in the superior temporal sulcus bilaterally were more activated by speech stimuli than by FM tones. Identical results were obtained in this region using words, pseudowords and reversed speech, suggesting that the speech-tones activation difference is due to acoustic rather than linguistic factors. In contrast, previous comparisons between word and nonword speech sounds showed left-lateralized activation differences in more ventral temporal and temporoparietal regions that are likely involved in processing lexical-semantic or syntactic information associated with words. The results indicate functional subdivision of the human lateral temporal cortex and provide a preliminary framework for understanding the cortical processing of speech sounds.

Acoustic Stimulation↗
PubMed2000

p21-activated kinase 1 plays a critical role in cellular activation by Nef.

The activation of Nef-associated kinase (NAK) by Nef from human and simian immunodeficiency viruses is critical for efficient viral replication and pathogenesis. This induction occurs via the guanine nucleotide exchange factor Vav and the small GTPases Rac1 and Cdc42. In this study, we identified NAK as p21-activated kinase 1 (PAK1). PAK1 bound to Nef in vitro and in vivo. Moreover, the induction of cytoskeletal rearrangements such as the formation of trichopodia, the activation of Jun N-terminal kinase, and the increase of viral production were blocked by an inhibitory peptide that targets the kinase activity of PAK1 (PAK1 83-149). These results identify NAK as PAK1 and emphasize the central role its kinase activity plays in cytoskeletal rearrangements and cellular signaling by Nef.

Animals↗
PubMed2000

Campylobacter contamination of raw meat and poultry at retail sale: identification of multiple types and comparison with isolates from human infection.

Campylobacter species are the major cause of acute bacterial enteritis reported in the United Kingdom, nonetheless many aspects of campylobacteriosis epidemiology remain poorly understood. The aim of this study was to determine the prevalence of Campylobacter jejuni and Campylobacter coli in fresh bovine, ovine, and porcine liver and chicken portions from retail outlets and compare strain subtype distributions with those associated with cases of human campylobacteriosis occurring within the same period and study area. Meat samples were examined by both enrichment culture and direct plating, and Campylobacter isolates were subjected to the same test procedures (identification, serotyping, phagetyping, resistotyping) applied to the clinical strains. Campylobacter species were isolated from 73.2% of 489 samples examined. Chicken exhibited the highest contamination rate (83.3%), followed by lamb (72.9%), pig (71.7%), and ox (54.2%) liver. C. jejuni predominated in chicken (77.3%), lamb (75.0%), and ox (49.0%) liver, and C. coli predominated in pigs' liver (42.4%). Campylobacter fetus was identified in 12.5% of ox liver samples and also in pig and lamb. Of the human isolates, 89.3% were C. jejuni and 10.7% C. coli. The greatest variation in C. jeuni subtypes was observed among the chicken isolates (57 sero/phage-types), followed by human (48 types) and lamb (30 types). A significant proportion of the chicken and lamb isolates shared identical subtypes with the human strains, indicative of their role as potential sources of infection. Almost 30% of samples yielded multiple strains of Campylobacter, a finding that reinforces the epidemiological importance of selecting and testing more than one presumptive isolate per sample.

Animals↗
PubMed2000

Spread of resistance from food animals to man--the UK experience.

Since 1990 there have been dramatic increase in the occurrence multiply drug-resistant strains of zoonotic pathogens causing infections in humans in many developed countries. Of particular note has been the epidemic spread of MR strains of S. typhimurium DT 104, which now appear to have an almost world-wide distribution. Within DT104 the increasing spectrum of resistance is of considerable concern, with strains with decreased susceptibility to ciprofloxacin increasing in incidence in the United Kingdom and also causing serious disease in humans in other countries. For campylobacters the incidence of ciprofloxacin-resistant organisms is also increasing, with reports of such isolates from numerous countries throughout the world. For VTEC O157, although resistance is increasing, multiple resistance and resistance to ciprofloxacin remains rare. Drug resistance in food-borne pathogens is an unfortunate but almost inevitable consequence of the use of antimicrobials in food animals. Although for some pathogens--e.g., Campylobacter spp., the use of antimicrobials in human medicine is also an important factor (Smith el al 1999), it is the use of antimicrobials in food animals which has been a major factor in the development of decreased susceptibility to antibiotics such as ciprofloxacin in zoonotically-transmitted salmonellas. Such use is quite legitimate. However it is regrettable that recommendations such as propounded in 1992 in the UK by the Expert Group on Animal Feedingstuffs--the Lamming Committee, that any new antibiotics with cross resistance to those used in human medicine should not be used for prophylaxis in animal husbandry, were not accepted (Anonymous, 1992). Although the clock cannot be turned back, to combat the development of resistance to such important drugs as the fluoroquinolones it is hoped that a Code of Practice for their use in food animals will soon be internationally implemented.

Animal Husbandry↗
PubMed2000

Family clusters of campylobacter infection.

Possible family clusters of campylobacter infection among isolates referred to a single, large public health laboratory were reviewed to determine the proportion of clusters associated with more than one strain of campylobacter. A total of 23 clusters, each made up of members of a single household infected within two months of each other, were identified between September 1996 and January 1999. These accounted for about 5% of all campylobacter infections confirmed during the study period. Thirteen of these families were infected with single strains of C. jejuni and one with C. coli. In ten families specimens were taken over intervals ranging from six to 56 days. In eight clusters more than one strain of C. jejuni was identified and in one family two patients were infected with C. jejuni and one with C. lari. These findings are consistent with the observation that potential sources of campylobacter infection may be contaminated with more than one strain.

Age Distribution↗
PubMed1999

Reciprocal signaling between heterotrimeric G proteins and the p21-stimulated protein kinase.

p21-activated protein kinase (PAK)-1 phosphorylated Galpha(z), a member of the Galpha(i) family that is found in the brain, platelets, and adrenal medulla. Phosphorylation approached 1 mol of phosphate/mol of Galpha(z) in vitro. In transfected cells, Galpha(z) was phosphorylated both by wild-type PAK1 when stimulated by the GTP-binding protein Rac1 and by constitutively active PAK1 mutants. In vitro, phosphorylation occurred only at Ser(16), one of two Ser residues that are the major substrate sites for protein kinase C (PKC). PAK1 did not phosphorylate other Galpha subunits (i1, i2, i3, o, s, or q). PAK1-phosphorylated Galpha(z) was resistant both to RGSZ1, a G(z)-selective GTPase-activating protein (GAP), and to RGS4, a relatively nonselective GAP for the G(i) and G(q) families of G proteins. Phosphorylation of Ser(27) by PKC did not alter sensitivity to either GAP. The previously described inhibition of G(z) GAPs by PKC is therefore mediated by phosphorylation of Ser(16). Phosphorylation of either Ser(16) by PAK1 or Ser(27) by PKC decreased the affinity of Galpha(z) for Gbetagamma; phosphorylation of both residues by PKC caused no further effect. PAK1 thus regulates Galpha(z) function by attenuating the inhibitory effects of both GAPs and Gbetagamma. In this context, the kinase activity of PAK1 toward several protein substrates was directly inhibited by Gbetagamma, suggesting that PAK1 acts as a Gbetagamma-regulated effector protein. This inhibition of mammalian PAK1 by Gbetagamma contrasts with the stimulation of the PAK homolog Ste20p in Saccharomyces cerevisiae by the Gbetagamma homolog Ste4p/Ste18p.

Heterotrimeric GTP-Binding Proteins↗
PubMed1999

Phage typing of Campylobacter jejuni and Campylobacter coli and its use as an adjunct to serotyping.

Campylobacter is the most commonly reported cause of gastro-intestinal infection in England and Wales, with over 50,000 reported cases in 1997. The majority of human campylobacter isolates in England and Wales are C. jejuni (c. 90%) with most of the remainder being C. coli. We describe the use of phage typing as an extension to serotyping for more detailed characterization within these two species. The scheme was piloted during a study of 2407 C. jejuni and 182 C. coli strains isolated in Wales between April 1996 and March 1997. Fifty-seven C. jejuni phage types were identified, with the ten most prevalent phage types accounting for 60% of isolates tested; 16% of isolates were untypable. The most common phage type was PT 1 which represented c. 20% of isolates. A further 7% of isolates reacted with the phages but did not conform to a designated type (RDNC). Only 12 phage types were identified among C. coli, with the two most common types, PT 2 and PT 7 accounting for 75.2% of isolates. When used in conjunction with serotyping, the ability of phage typing to identify between 6 and 29 subtypes within each of the predominant HS types has enabled a further level of discrimination to be achieved that enhances the epidemiological typing of C. jejuni and C. coli.

Bacteriophage Typing↗
PubMed1999

Language dominance in neurologically normal and epilepsy subjects: a functional MRI study.

Language dominance and factors that influence language lateralization were investigated in right-handed, neurologically normal subjects (n = 100) and right-handed epilepsy patients (n = 50) using functional MRI. Increases in blood oxygenation-dependent signal during a semantic language activation task relative to a non-linguistic, auditory discrimination task provided an index of language system lateralization. As expected, the majority of both groups showed left hemisphere dominance, although a continuum of activation asymmetry was evident, with nearly all subjects showing some degree of right hemisphere activation. Using a categorical dominance classification, 94% of the normal subjects were considered left hemisphere dominant and 6% had bilateral, roughly symmetric language representation. None of the normal subjects had rightward dominance. There was greater variability of language dominance in the epilepsy group, with 78% showing left hemisphere dominance, 16% showing a symmetric pattern and 6% showing right hemisphere dominance. Atypical language dominance in the epilepsy group was associated with an earlier age of brain injury and with weaker right hand dominance. Language lateralization in the normal group was weakly related to age, but was not significantly related to sex, education, task performance or familial left-handedness.

Acoustic Stimulation↗
PubMed1999

Language processing is strongly left lateralized in both sexes. Evidence from functional MRI.

Functional MRI (fMRI) was used to examine gender effects on brain activation during a language comprehension task. A large number of subjects (50 women and 50 men) was studied to maximize the statistical power to detect subtle differences between the sexes. To estimate the specificity of findings related to sex differences, parallel analyses were performed on two groups of randomly assigned subjects. Men and women showed very similar, strongly left lateralized activation patterns. Voxel-wise tests for group differences in overall activation patterns demonstrated no significant differences between women and men. In further analyses, group differences were examined by region of interest and by hemisphere. No differences were found between the sexes in lateralization of activity in any region of interest or in intrahemispheric cortical activation patterns. These data argue against substantive differences between men and women in the large-scale neural organization of language processes.

Acoustic Stimulation↗
PubMed1999

Drug resistance in Campylobacter jejuni, C coli, and C lari isolated from humans in north west England and Wales, 1997.

AIMS: To test the sensitivity of strains of Campylobacter species isolated from humans in England and Wales against a range of antimicrobial agents for the purpose of monitoring therapeutic efficacy and as an epidemiological marker. METHODS: An agar dilution breakpoint technique was used to screen isolates against ampicillin, chloramphenicol, gentamicin, kanamycin, neomycin, tetracycline, nalidixic acid, ciprofloxacin, and erythromycin. Minimal inhibitory concentrations (MIC) were also determined for a sample of quinolone resistant strains. RESULTS: Approximately 50% of strains tested were resistant to at least one drug. Strains which were resistant to four or more of the drugs tested were classified as multiresistant; this occurred in 11.3% of C jejuni, 19.9% of C coli, and 63.6% of C lari. Resistance to erythromycin occurred in 1.0% of C jejuni and 12.8% of C coli. Resistance to quinolones occurred in 12% of strains, with a ciprofloxacin MIC of > 8 mg/l and a nalidixic acid MIC of > 256 mg/l; a further 4% of strains had intermediate resistance with a ciprofloxacin MIC of between 0.5 and 2 mg/l (fully sensitive strains, 0.25 mg/l or less) and a nalidixic acid MIC of between 32 and 64 mg/l (fully sensitive strains, 8 mg/l or less). CONCLUSIONS: Resistance to quinolones in campylobacters from human infection may relate to clinical overuse or use of fluoroquinolones in animal husbandry. Both veterinary and clinical use should be reconsidered and fluoroquinolone drugs used only as a treatment for serious infections requiring hospital admission. Erythromycin resistance is still rare in C jejuni but much more common in C coli.

Aminoglycosides↗
PubMed1999

Conceptual processing during the conscious resting state. A functional MRI study.

Localized, task-induced decreases in cerebral blood flow are a frequent finding in functional brain imaging research but remain poorly understood. One account of these phenomena postulates processes ongoing during conscious, resting states that are interrupted or inhibited by task performance. Psychological evidence suggests that conscious humans are engaged almost continuously in adaptive processes involving semantic knowledge retrieval, representation in awareness, and directed manipulation of represented knowledge for organization, problem-solving, and planning. If interruption of such 'conceptual' processes accounts for task-induced deactivation, tasks that also engage these conceptual processes should not cause deactivation. Furthermore, comparisons between conceptual and nonconceptual tasks should show activation during conceptual tasks of the same brain areas that are 'deactivated' relative to rest. To test this model, functional magnetic resonance imaging data were acquired during a resting state, a perceptual task, and a semantic retrieval task. A network of left-hemisphere polymodal cortical regions showed higher signal values during the resting state than during the perceptual task but equal values during the resting and semantic conditions. This result is consistent with the proposal that perceptual tasks interrupt processes ongoing during rest that involve many of the same brain areas engaged during semantic retrieval. As further evidence for this model, the same network of brain areas was activated in two direct comparisons between semantic and perceptual processing tasks. This same 'conceptual processing' network was also identified in several previous studies that contrasted semantic and perceptual tasks or resting and active states. The model proposed here offers a unified account of these findings and may help to explain several unanticipated results from prior studies of semantic processing.

Adolescent↗
PubMed1998

Differential effects of PAK1-activating mutations reveal activity-dependent and -independent effects on cytoskeletal regulation.

PAKs are serine/threonine protein kinases that are activated by binding to Rac or Cdc42hs. Different forms of activated PAK1 have been reported to either promote membrane ruffling and focal adhesion assembly or cause focal adhesion disassembly and stress fiber dissolution. To understand the basis for these distinct morphological effects, we have examined the mechanism of mutational activation of PAK1, and characterized the effects of different active PAK1 proteins on cytoskeletal structure in vivo. We find that PAK1 contains an autoinhibitory domain that overlaps with its small G protein binding domain and that two separate activating mutations within this regulatory region each decrease autoinhibitory activity. Because only one of these mutations affects Cdc42hs binding activity, this indicates that activation of PAK1 by these mutations results from interference with the function of the autoinhibitory domain and not with small G protein binding activity. When we examined the morphological effects of these different forms of PAK1 in vivo, we found that PAK1 kinase activity was associated with disassembly of focal adhesions and actin stress fibers and that this may require interaction with potential SH3 domain-containing proteins. Lamellipodia formation and membrane ruffling caused by active PAK1 expression, however, was independent of PAK1 catalytic activity and likely requires interaction among multiple proteins binding to the PAK1 regulatory domain.

Cell Adhesion↗
PubMed1998

The MEK1 proline-rich insert is required for efficient activation of the mitogen-activated protein kinases ERK1 and ERK2 in mammalian cells.

MEK1 and MEK2 contain a proline-rich insert not present in any other known MEK (MAP (mitogen-activated protein)/ERK (extracellular signal-regulated kinase) kinase) family members. We examined the effect of removing the MEK1 polyproline insert on MEK activity, its binding to Raf, and its ability to activate ERKs in cells. Deletion of the insert had no effect on either the activity of MEK1 or on its ability to bind to Raf-1. Both wild type and constitutively active MEK1 coimmunoprecipitated with Raf-1 whether or not the insert was present. Deletion of the insert did not reduce activation of MEK1 by EGF or activated Raf in cells. The proline-rich insert enhanced the ability of an otherwise equally active MEK1 protein to regulate endogenous ERKs in mammalian cells. Overexpression of either constitutively active MEK1 lacking the insert or ERK2 compensates for the weaker in vivo activity of the MEK1 deletion mutant. Expression of the insert in cells reduced activation of ERKs by EGF. We conclude that the proline-rich insert is not the site of the MEK-Raf interaction and that the polyproline insert is required for its efficient activation of downstream ERKs in cells.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Is speech arrest during wada testing a valid method for determining hemispheric representation of language?

BACKGROUND AND OBJECTIVE: The intracarotid amobarbital procedure, or Wada test, is the method of choice to determine hemispheric representation of language, and is routinely used in the presurgical evaluation for intractable epilepsy. Some investigators perform comprehensive language assessments, but others base language lateralization solely on speech arrest. This study sought to determine whether speech arrest alone during Wada testing provides valid data regarding language lateralization. METHODS: The subjects (previously reported) were 21 patients evaluated for intractable epilepsy, who underwent language lateralization by Wada testing and functional MRI (FMRI). For each patient, language representation was determined by calculating: (1) a Wada laterality index based exclusively on speech arrest; (2) a Wada laterality index based on comprehensive language assessment; and (3) an FMRI laterality quotient. Correlation coefficients and categorical classifications were analyzed. RESULTS: There was no significant correlation between the Wada laterality quotient derived from duration of speech arrest and either the comprehensive Wada language laterality score (r =.35, p =.12) or FMRI language laterality score (r =.32, p =.16). Categorical classification as left, right or bilateral language also showed marked discordance between speech arrest and the other two methods. CONCLUSION: Duration of speech arrest during Wada testing is not a valid measure of language dominance.

Amobarbital↗
PubMed1998

A campylobacter outbreak associated with stir-fried food.

An outbreak of gastrointestinal illness affecting 12 of 29 customers of a 'Hawaiian' theme restaurant specializing in stir-fried food occurred in Cardiff, Wales in February 1997. Campylobacter jejuni serotype HS50 phage type 49 (PT49) was isolated from 5 cases. A total of 47 isolates of C. jejuni HS50 PT49 were identified from Wales during 1997, of which 11 were isolated in late February or early March and from the Cardiff area. In the outbreak, illness was associated with eating stir-fried chicken pieces (relative risk 4.81, 95% confidence interval (CI) 0.76-30.44, P=0.03) and a dose-response relationship between risk of illness and amount of chicken consumed was observed (chi2-test for linear trend 3.96, P=0.047). Undercooking of chicken was probably due to a combination of inadequate cooking time and use of large chicken pieces. This is the first time that stir-fried food has been associated with a campylobacter outbreak. The incident also illustrates the value of routine campylobacter subtyping in supporting outbreak investigation.

Campylobacter Infections↗
PubMed1998

Serotyping scheme for Campylobacter jejuni and Campylobacter coli based on direct agglutination of heat-stable antigens.

Campylobacter is now the most frequently reported cause of gastrointestinal disease in England and Wales, yet few isolates are characterized beyond the genus level. The majority of isolates are Campylobacter jejuni (90%), with most of the remainder being Campylobacter coli. We describe an adaptation of the Penner serotyping scheme in which passive hemagglutination has been replaced by detection of heat-stable antigens by direct bacterial agglutination; absorbed antisera are used where appropriate. This scheme has been used to type 2,407 C. jejuni samples and 182 C. coli samples isolated in Wales between April 1996 and March 1997. Forty-seven C. jejuni serotypes were identified, with the 10 most prevalent serotypes accounting for 53% of the isolates tested; 19% of the isolates were untypeable. Only fifteen C. coli serotypes were identified, with three serotypes accounting for 69% of the isolates. This scheme provides a baseline for epidemiological studies of C. jejuni and C. coli.

Agglutination Tests↗
PubMed1998

Side of seizure focus predicts left medial temporal lobe activation during verbal encoding.

OBJECTIVE: Functional MRI (FMRI) was used to investigate the effect of medial temporal lobe (MTL) pathology on activation of language encoding areas in patients with temporal lobe epilepsy (TLE). METHODS: Whole-brain FMRI was obtained. Twenty-eight patients with either left TLE (LTLE) or right TLE (RTLE) performed a semantic decision task alternating with an auditory perceptual task. RESULTS: Activation of language areas in the frontal and parietal lobes was similar in both groups, with no group differences in the total number of active voxels. However, the RTLE group showed much stronger activation of the left MTL, including the hippocampus, parahippocampal gyrus, and collateral sulcus, than did the LTLE group. CONCLUSIONS: Activation of the left MTL during semantic encoding discriminates patients with RTLE and LTLE. This FMRI technique may potentially be of use in determining memory lateralization and for predicting the side of seizure focus in TLE.

Adult↗