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C Miles

Publications and source records attributed to C Miles.

At least 37 records · Page 2Linked to original sources
PubMed1996

Characterization of the first definitive hematopoietic stem cells in the AGM and liver of the mouse embryo.

At day 10 in mouse gestation, the intraembryonic aorta-gonads-mesonephros (AGM) region generates the first definitive hematopoietic stem cells (HSCs) of the adult blood system. By 11 days postcoitum, the liver contains such HSCs. While HSCs of the adult bone marrow and late-stage fetal liver have been extensively characterized for cell surface markers, there has been no phenotypic description of the first HSCs during embryo development. We report here the temporal cell surface phenotype of HSCs from the AGM region and early fetal liver and show that all HSCs reside in the c-kit+ population. c-kit+ HSCs from AGM and liver are mainly CD34+ and in the AGM are in both Mac-1+ and Mac-1 fractions. These results demonstrate that during mouse ontogeny the first definitive HSCs are similar in cell surface phenotype to the HSCs of adult bone marrow but that spatial localization and developmental time are critical factors in the phenotypic assessment of this functional cell population.

Animals↗
PubMed1996

Tactile short-term memory revisited.

In each of three experiments subjects were required to point to the location of a discrete tactile stimulus applied to the underside of the forearm after delays of 10, 15, 20, & 30 seconds. Experiment 1 showed that recall accuracy was impaired independently by both concurrent articulatory suppression and increased delay between stimulation and recall. Experiment 2 compared two types of articulatory suppression task (repeating "the" continuously and counting backwards in threes) and showed that both exert the same effect on recall accuracy. Experiment 3 showed that, in comparison to a quiet condition, recall accuracy was impaired equally by: concurrent articulatory suppression; additional tactile interference; and both applied in combination. It is argued that articulatory suppression and tactile interference operate on separate mechanisms to impair recall accuracy for a tactile stimulus. In particular, tactile interference reduces the discriminability of the target tactile location, whereas articulatory suppression results in a depletion of central processing resources concerned with memorisation of the original location of the tactile stimulus. Such memorisation is not necessarily underpinned by an articulatory code.

Adult↗
PubMed1996

Role of the beta 3-adrenergic receptor locus in obesity and noninsulin-dependent diabetes among members of Caucasian families with a diabetic sibling pair.

Obesity and insulin resistance are important risk factors for the development of noninsulin-dependent diabetes (NIDDM) and are prevalent among predisposed first degree relatives of diabetic individuals. Recent molecular screening and analysis of a common missense mutation of the beta 3-adrenergic receptor gene suggested this locus as a strong candidate for increased obesity, earlier age of diabetes onset, and insulin resistance. To test the hypothesis that the beta 3-adrenergic receptor locus affects diabetes susceptibility, obesity as measured by body mass index, and components of the insulin resistance syndrome, we examined the role of this region in families ascertained for two or more NIDDM siblings. Linkage analysis was conducted using both parametric and nonparametric analyses, including multipoint sibling pair analysis. We found no evidence for linkage to NIDDM as a dichotomous trait and no evidence for linkage to body mass index, waist/hip ratio, insulin levels, or glucose levels as quantitative traits or to reported age of onset among NIDDM individuals. The Trp64 Arg missense mutation was present in 11% of the population. The mutation was not associated with NIDDM, and Arg64 carriers did not have earlier NIDDM onset, higher body mass index, or higher waist/hip ratio than Trp64 homozygotes. Among relatives, Arg64 carriers had significantly lower fasting glucose levels and lower waist/hip ratios than Trp64 homozygotes, but no characteristics of the insulin resistance syndrome. We conclude that the beta 3-adrenergic receptor locus does not play an important role in NIDDM susceptibility or in the insulin resistance syndrome among members of families with a strong predisposition to NIDDM.

Adult↗
PubMed1995

Post-categorical processing and attenuation of the auditory suffix: evidence from both immediate and delayed suffixes.

Recall of the final item in a spoken list is impaired by the presentation of a spoken to-be-ignored item following the list. The nature of the processes responsible for the stimulus suffix effect (as well as its magnitude) can be varied by manipulating the intrinsic characteristics of the relationship between the final list (target) item and suffix. A series of experiments show that systematic manipulation of both typicality of same-category membership of target-item and suffix (Experiment 1), and degree of synonymity between target-item and suffix (Experiment 2) result in differential attenuation in the magnitude of the suffix effect. The effect of the synonymity manipulation persists for up to twenty seconds after the presentation of the target-item (Experiment 3). That post-categorical processing of the suffix occurs provides direct support for semantic coding in short-term memory and contradicts models arguing that short-term memory is organised according to the principle of physical similarity (e.g., LeCompte and Watkins, 1993).

Adult↗
PubMed1995

X-ray evidence that in contracting live frog muscles there exist two distinct populations of myosin heads.

Using synchrotron radiation and whole muscles, 2 ms time-resolved x-ray diffraction patterns were recorded at 8 degrees C. The results show that in both isotonic and isometric contractions, as well as in length changes imposed at maximum tension [Po], the meridional third myosin layer line consists of two distinct reflections with different intensities and spacings that measure approximately 14,623 and 14,412 nm at Po. Although the intensity behavior of the two reflections is strikingly different during quick releases, it is very similar during stretches. Study of the time courses indicates that myosin heads diffracting at Po with the approximately 14.623 nm periodicity are actively involved in tension production. Those diffracting at Po with the periodicity of approximately 14.412 nm appear not be associated with tension production during isometric contraction and releases, but the results suggest that they are recruited during stretches and here contribute to tension production. Our most important conclusion is that under all conditions of contraction we have investigated there exist two populations of myosin heads, each with a well defined axial disposition and configuration.

Animals↗
PubMed1994

Structural requirements for peptides that stimulate a subset of gamma delta T cells.

Hybridomas representing the V gamma 1-positive subset of murine gamma delta T cells secrete lymphokines in response to synthetic peptides representing a short segment of the mycobacterial 60-kDa heat shock protein (HSP-60). Here we show the TCR dependency of this response by transfection of productively rearranged TCR genes derived from an HSP-60 reactive gamma delta T cell hybridoma. We also have defined structural requirements for the stimulatory peptide. The smallest HSP-60 peptide capable of stimulating these hybridomas is seven amino acids long, representing positions 181-187, and having the sequence FGLQLEL. Amino acid-substituted derivatives of this peptide, and another containing the same core, p180-190, revealed amino acids essential for stimulatory activity. Phenylalanine in position 181 and leucine in position 183 seem to be required for stimulation of all HSP-60 reactive cells, whereas others are only required by some. Clonal differences in the responses to these peptides provide indirect evidence for cognate TCR-peptide interactions. The smallest stimulatory peptide, p181-187, represents an area not well conserved among HSP-60 molecules of other species, and stimulates a mycobacteria-specific response unlike the earlier observed cross-reactive responses of the same hybridomas with longer HSP-60 peptides derived from mycobacteria and other species (our manuscript in preparation). We propose that the TCR-dependent multiclonal gamma delta T cell response to HSP-60 peptides and derivatives, which in some ways resembles superantigen responses and in other ways resembles responses to conventional Ag, may be a separate, third type of Ag response by T cells.

Amino Acid Sequence↗
PubMed1994

Fenfluramine-induced modification of palatability: analysis by the taste reactivity test.

The ability of various doses (0, 1.25, 2.5, and 5.0 mg/kg) of fenfluramine to modify the palatability of sucrose and quinine solutions was assessed by means of the taste reactivity test. Although fenfluramine did not modify the positive hedonic ingestive reactions elicited by sucrose solution, it consistently enhanced the negatively hedonic aversive reactions elicited by unpalatable 0.05% quinine solution and moderately palatable 2% sucrose solution. The results suggest that fenfluramine enhances the aversive properties of tastants without suppressing the positive hedonic properties of tastants. The results support a two-dimensional model of palatability.

Animals↗
PubMed1994

Structure of the carboxy-terminal LIM domain from the cysteine rich protein CRP.

The three dimensional solution structure of the carboxy terminal LIM domain of the avian Cysteine Rich Protein (CRP) has been determined by nuclear magnetic resonance spectroscopy. The domain contains two zinc atoms bound independently in CCHC (C = Cys, H = His) and CCCC modules. Both modules contain two orthogonally-arranged antiparallel beta-sheets, and the CCCC module contains an alpha-helix at its C terminus. The modules pack due to hydrophobic interactions forming a novel global fold. The structure of the C-terminal CCCC module is essentially identical to that observed for the DNA-interactive CCCC modules of the GATA-1 and steroid hormone receptor DNA binding domains, raising the possibility that the LIM motif may have a DNA binding function.

Amino Acid Sequence↗
PubMed1993

Market values.

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Hospitals, Public↗
PubMed1993

An injury prevention program in an urban African-American community.

OBJECTIVES: Injury is a major US public health problem, particularly in urban minority communities. This paper evaluates the impact of the Safe Block Project, a comprehensive injury prevention trial, on home hazards and injury prevention knowledge in a poor urban African-American community. METHODS: Nine census tracts in the community were allocated to either the intervention area or the control area. The intervention, carried out by trained community outreach workers, consisted of (1) home modification for simple prevention measures, (2) home inspection accompanied by information about home hazards, and (3) education about selected injury prevention practices. Approximately 12 months after the intervention, random samples of control and intervention homes were assessed for home hazards and injury prevention knowledge. RESULTS: A significantly larger proportion of intervention homes than control homes had functioning smoke detectors, syrup of ipecac, safely stored medications, and reduced electrical and tripping hazards. No consistent differences were observed between control and intervention homes on home hazards requiring major effort to correct. CONCLUSIONS: There was a distinct difference between control and intervention homes with respect to safety knowledge and home hazards requiring minimal to moderate effort to correct. The Safe Block Project could serve as a model for future urban injury prevention efforts.

Accidents, Home↗
PubMed1993

Marketing: its place in organisational structure.

As a result of the reforms, provider units have to compete for contracts from HAs and GPFHs; the function of marketing has an outside focus in understanding, communicating with and providing for customers, and the internal role of ensuring services meet customers' needs. Humphrey Bourne and Christine Miles examine the marketing role in the NHS.

Hospitals, Public↗
PubMed1992

Privileged access by irrelevant speech to short-term memory: the role of changing state.

Memory for visually presented items is impaired by speech that is played as an irrelevant background. The paper presents the view that changing state of the auditory material is an important prerequisite for this disruption. Four experiments studied the effects of sounds varying in complexity in an attempt to establish which features of changing state in the auditory signal lead to diminished recall. Simple unvarying or repetitive speech sounds were not sufficient to induce the irrelevant speech effect (Experiment 1): in addition, simple analogues of speech, possessing regular or irregular envelopes and using a range of carriers, failed to imitate the action of speech (Experiment 2). Variability of between-utterance phonology in the irrelevant stream (Experiment 3) emerged as a crucial factor. Moreover, predictability of the syllable sequence did not reduce the degree of disruption (Experiment 4) suggesting that supra-syllabic characteristics of the speech are of little importance. The results broadly support the idea that disruption of short-term memory only occurs when the speech stream changes in state. It is argued that disruption occurs in memory when cues to serial order based on phonological representations of heard material interfere with the phonological codes of visual origin. It is suggested that cues to changing state of the speech input contaminate those associated with items of visual origin, which are already in a phonological store.

Adolescent↗
PubMed1990

Inhibition of experimental autoimmune encephalomyelitis induction in SJL/J mice by using a peptide with high affinity for IAs molecules.

Blocking of the Ag presenting function of MHC by peptides capable of high affinity binding to this molecule has been proposed as a potential immunotherapeutic intervention in MHC-associated diseases. Recent studies have used this strategy to prevent the induction of experimental allergic encephalomyelitis (EAE) in mice. However, because of the close structural relationship between the inhibitor and encephalitogenic peptides, the results of these previous studies have been difficult to interpret with regard to whether MHC blockade was the mechanism by which the inhibitory peptides functioned. In our study, we have determined the capacity of unrelated peptides capable of binding with high affinity to IAs in inhibiting the induction of EAE in SJL/J mice after immunization with the autoantigenic peptide PLP 139-151. Prevention of the disease was accomplished by two methods: 1) when inhibitor was administered together with the encephalitogenic peptide at the time of immunization, as in previous studies, and 2) when inhibitor was administered at a separate site from the autoantigen 1 day before the immunization with that Ag. Inhibition was due to binding of the inhibitor to IAs, as evidenced by the fact that a control peptide incapable of binding to this MHC had no effect on the course of the disease. The finding that inhibitor could also be efficacious when administered at a separate site has implications for potential use of such a strategy to reverse ongoing autoimmune diseases. The inhibitor had to be present during the time of Ag stimulation, and had no long term inhibitory effects, in that a secondary immune response to the encephalitogenic peptide was not inhibited in animals given the inhibitory peptide before the induction of a primary response. This is compatible with the conclusion that MHC blockade was, in fact, the mechanism of the inhibition, rather than as a result of any long term suppressive effects on immunoreactive T cells. Finally, not only did administration of the inhibitory peptide lead to a prevention of the induction of EAE, but it could also be shown to decrease the T cell proliferative response in vitro to the autoantigen.

Amino Acid Sequence↗
PubMed1990

A novel approach to the generation of high affinity class II-binding peptides.

We have found that if core regions crucial for class II binding are incorporated in multiple copies in the same peptide molecule ("reiterative motifs"), marked enhancement of the binding capacity occurs. Isotype specificity (IAd vs IEd binding capacities) is retained in all three antigenic determinants so far analyzed (lambda rep 12-26, OVA 323-339, and hen egg lysozyme 105-120). The mechanism involved in such an effect is not clear, but experiments involving introduction of a peptide spacer between two repeated core regions do not support the notion that the effect is mediated by cross-linking of more than one MHC molecule, favoring the possibility that conformational effects or distinct subsites of interaction on the MHC molecule may be involved. Based on reiterative structures, a peptide molecule composed of only two different amino acids (Ala and His) has been produced that still retains a very high binding affinity. An 125I-radiolabeled form of this peptide has been used to demonstrate that the high binding detected is mediated by the same binding site involved in the interaction of IAd and OVA 323-339. Inhibition of Ag presentation studies further supports the immunologic relevance of the phenomena observed. Finally, we observed naturally occurring clustered binding sites in proximity of immunodominant protein regions, raising the possibility that the phenomenon might have a physiologic counterpart.

Amino Acid Sequence↗
PubMed1990

Characterization of the specificity of peptide binding to four DR haplotypes.

This study describes the establishment of a peptide-binding assay for purified, detergent-solubilized DR molecules. For each of the DR specificities and peptides studied, a unique pattern of interaction was observed. Excellent correlation was detected between the DR1-, 2-, 5-, and 52a-binding capacities and the known DR restrictions of a panel of synthetic peptides. This supports the immunologic relevance of the binding assay, and emphasizes the importance of determinant selection in defining the immune response of individuals. We have also examined the capacity of a panel of DR-restricted peptides to compete with one another for binding to DR1. The results obtained are compatible with a single peptide-binding site on DR molecules. The peptide-binding capacity of the four different DR types (DR1, DR2, DR5, and DR52a) has been further examined by testing a collection of 133 different peptides. This collection is unbiased with respect to previously known DR binding and restrictions, and includes peptides of eukaryotic, bacterial, and viral origins. It was found that: 1) approximately 15 to 35% of the peptides tested bound any given DR type; 2) DR-binding capacities appeared to correlate with each other, suggesting that different alleles of the DR isotype may recognize related structures on an Ag molecule; and 3) despite the statistical correlation between binding capacity of different DR types, approximately 50% of the peptides that were positive binders still were specific in that they could bind only one of the four DR molecules tested. Degenerate binding (i.e., binding to most or all the DR molecules tested) was detected in only a minority of the cases analyzed (approximately 25%).

Amino Acid Sequence↗
PubMed1990

The use of peptide analogs with improved stability and MHC binding capacity to inhibit antigen presentation in vitro and in vivo.

The identification of a core region for OVA 323-339, which is critical in determining binding to IAd, has enabled us to generate a series of analog peptides in which this core region was extended at both the N and C termini with different amino acid residues. When assessed for binding capacity, several peptides were shown to have increased affinity for IAd compared with the parent sequence, and in addition, some peptides had acquired binding specificities for class II MHC haplotypes not present for OVA 323-339. These peptides were next examined for their ability to inhibit T cell responses in vitro and in vivo. The correlation between binding and the ability to inhibit T cell activation in vitro was good. However, when assessed in vivo, it was clear that high Ia binding was not sufficient in itself to define the inhibitory capacity of a given peptide. That this discrepancy was due to differences in degradation of the core-extended peptides was suggested by 1) results from an inhibition of Ag presentation assay, in which the pulse period with Ag and inhibitor was extended to 20 h; and 2) direct analysis of peptide stability by using reverse phase HPLC. Finally, by protecting the peptide from degradation with N- and C-terminal substitutions of D-amino acids, the inhibitory capacity of an unstable core-extended peptide in vitro could be greatly enhanced. These data indicate that the core extension approach may be one method by which antagonists for MHC class II molecules may be generated.

Animals↗