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Biomedical subjects

C Hughes

Publications and source records attributed to C Hughes.

At least 109 records · Page 6Linked to original sources
PubMed1999

Towards a cognitive phenotype for autism: increased prevalence of executive dysfunction and superior spatial span amongst siblings of children with autism.

Two studies were conducted to examine executive function skills in siblings of children with autism. In Study 1, four computerised tasks (three executive tasks: the ID/ED set-shifting task; a spatial working memory task; and the Tower of London planning task; and a control spatial span task) from the CANTAB battery were used to compare 31 siblings of children with autism with 32 siblings of children with developmental delay and 32 children from unaffected families. In Study 2, the two sibling groups were compared on two manually administered executive tasks (verbal fluency and list recall). As a group, autism siblings showed superior spatial and verbal span, but a greater than expected number performed poorly on the set-shifting, planning, and verbal fluency tasks. There were no group differences in working memory performance. The implications of these findings for the broader phenotype of autism is discussed.

Adolescent↗
PubMed1999

Uniqueness of physical therapy tasks and its relationship to complexity and delegation: a survey of Pennsylvania physical therapists.

Physical therapists' (PTs') perceptions of 26 physical therapy tasks regarding complexity, uniqueness to PTs, and delegation were studied. A questionnaire describing 26 PT tasks was sent to 200 PTs in Pennsylvania identified as working in acute care, rehabilitation, or private practice. The response rate was 45.5%. Eleven of the 26 tasks identified as most unique to PTs were also identified as highly complex. None of these 11 tasks was delegated frequently to a nurse or a PT aide, and only two were delegated to an occupational therapist. All 11 unique tasks were delegated to the physical therapist assistant (PTA), with some level of supervision provided by the majority of respondents. Results indicated there are activities within patient care that are perceived by PTs to be unique to their profession. Also, the role of the PTA may be expanding, warranting further research in this area.

Adult↗
PubMed1998

Substrate-induced assembly of a contiguous channel for protein export from E.coli: reversible bridging of an inner-membrane translocase to an outer membrane exit pore.

The toxin HlyA is exported from Escherichia coli, without a periplasmic intermediate, by a type I system comprising an energized inner-membrane (IM) translocase of two proteins, HlyD and the traffic ATPase HlyB, and the outer-membrane (OM) porin-like TolC. These and the toxin substrate were expressed separately to reconstitute export and, via affinity tags on the IM proteins, cross-linked in vivo complexes were isolated before and after substrate engagement. HlyD and HlyB assembled a stable IM complex in the absence of TolC and substrate. Both engaged HlyA, inducing the IM complex to contact TolC, concomitant with conformational change in all three exporter components. The IM-OM bridge was formed primarily by HlyD, which assembled to stable IM trimers, corresponding to the OM trimers of TolC. The bridge was transient, components reverting to IM and OM states after translocation. Mutant HlyB that bound, but did not hydrolyse ATP, supported IM complex assembly, substrate recruitment and bridging, but HlyA stalled in the channel. A similar picture was evident when the HlyD C-terminus was masked. Export thus occurs via a contiguous channel which is formed, without traffic ATPase ATP hydrolysis, by substrate-induced, reversible bridging of the IM translocase to the OM export pore.

Adenosine Triphosphatases↗
PubMed1998

A gene, yaeQ, that suppresses reduced operon expression caused by mutations in the transcription elongation gene rfaH in Escherichia coli and Salmonella typhimurium.

RfaH is a specialised transcription elongation protein. We isolated from a Salmonella typhimurium rfaH suppressor strain a gene that complements in trans the attenuated transcription of the hlyCABD hemolysin operon caused by an rfaH mutation. The gene is homologous to the uncharacterised Escherichia coli gene yaeQ. YaeQ did not increase hlyCABD-encoded hemolysin activity in the RfaH+ wild type, nor did it increase the level of RfaH protein. YaeQ also complements a rfaH::Tn5 null mutation, indicating that it compensates for loss of RfaH function without interaction between the two proteins.

Bacterial Proteins↗
PubMed1998

Understanding mind and emotion: longitudinal associations with mental-state talk between young friends.

Developmental changes in children's understanding of mind and emotion and their mental-state talk in conversations with friends were examined in a longitudinal study of 50 children (M age at each time point = 3 years 11 months, 4 years 6 months, 5 years 0 months). Significant and related improvements over time were found for both theory-of-mind task performance and affective perspective taking. Associated with these cognitive developments were quantitative and qualitative changes in children's references to mental states in their conversations with friends. Individual differences in theory of mind, emotion understanding, and mental-state talk were strikingly stable over the 13-month period. Although there were no gender differences in children's task performances, girls showed more frequent and more developed mental-state talk than boys.

Child, Preschool↗
PubMed1998

Finding your marbles: does preschoolers' strategic behavior predict later understanding of mind?

The aim of this longitudinal study was to assess (a) stability of individual differences in preschoolers' executive function performance, (b) the external validity of 4 new simple executive function tasks, and (c) whether individual differences in early executive function performance could be used to predict later differences in theory of mind, or vice versa. Fifty children involved in an earlier study of relations between preschoolers' theory of mind, verbal ability, and executive function (C. Hughes, 1998) were followed up and tested 1 year later, using 1st- and 2nd-order false-belief tasks, a set of 4 simple executive function tasks, and a well-established executive test of planning: the Tower of London (T. Shallice, 1982). The results of the study support recent proposals (C. Hughes, 1996; J. Russell, 1996) that young children's understanding of mind is grounded in their growing competence in strategic planning and mental flexibility.

Age Factors↗
PubMed1998

The effects of jet nebulisation on cationic liposome-mediated gene transfer in vitro.

Nebulisation is currently the most acceptable and practical delivery system for repeated applications of gene therapy to the lower airways of cystic fibrosis (CF) patients. We have assessed whether this route of administration offers other benefits with regard to respiratory gene transfer. A standard jet nebuliser (Acorn System 22, Medicaid) was used to transfer the reporter gene beta-galactosidase complexed with the cationic liposome DC-Chol/DOPE to three epithelial cell lines in vitro, two non-CF and one CF, using a novel collection system. In all three cell lines, nebulisation resulted in significantly (P < 0.05) improved transfection efficiency compared with instillation. At a constant DNA: liposome ratio of 1:5 (wt:wt), transfection efficiency was inversely related to increasing concentrations of DNA-liposomes before nebulisation. This effect was not related to the amount of DNA delivered and measurements of both zeta potential and mean aerodynamic particle size before and after nebulisation did not show concentration-related differences. The increased transfection efficiency did not relate either to the physical consequences of the nebulisation processes nor the effects of nebulisation on the complexes before instillation. Significantly increased transfection efficiency was seen following nebulisation with 95% O2/5% CO2 in comparison with 21% O2/78% N2 (air); this did not relate to changes in either the pH or temperature of the solution bathing the cells. The data confirm that nebulisation is appropriate for gene delivery to the lower airways in clinical practice and points to factors that may optimise gene transfer efficiency.

Animals↗
PubMed1998

Effects of four years' treatment with biosynthetic human growth hormone (GH) on glucose homeostasis, insulin secretion and lipid metabolism in GH-deficient adults.

OBJECTIVE: To study the effects of long-term growth hormone (GH) treatment on lipid metabolism and carbohydrate tolerance in GH-deficient adults. DESIGN: Open trial of GH treatment for 4 years. GH dose was (median, range) 0.025 (0.010-0.050) IU/kg daily. PATIENTS: Thirteen GH-deficient hypopituitary adults (seven men, six women), aged (median, range) 47 (24-65) years were followed for 4 years. MEASUREMENTS: Fasting lipids, lipoproteins, apolipoproteins, glucose and insulin concentrations were measured at yearly intervals during GH therapy. A 75-g oral glucose tolerance test (OGTT) was also performed yearly, during which circulating glucose and insulin were measured at 30-minute intervals for 3 h. RESULTS: Fasting total and low density lipoprotein (LDL) cholesterol concentrations decreased on GH therapy, but no change was observed in fasting triglyceride or high density lipoprotein (HDL) concentrations. Compared to pretreatment values, total and LDL cholesterol levels were significantly lower at 1 year (mean +/- SEM) (6.39 +/- 0.46 vs. 5.71 +/- 0.38 mmol/l, P < 0.05; 4.46 +/- 0.36 vs. 3.24 +/- 0.20 mmol/l, P < 0.01, respectively) and the reductions were maintained for the 4 years. Apolipoproteins A-1 and B did not differ significantly from the pretreatment levels. Fasting plasma glucose increased significantly at the first year (4.9 +/- 0.1 vs. 5.3 +/- 0.1 mmol/l, P < 0.05) but it returned to the pretreatment value in the following years. Fasting plasma insulin increased significantly at 1 year (4.3 (1.0-13.6) vs. 11.9 (1.2-26.9) mU/l, P < 0.05) and showed a progressive downward trend but remained significantly raised throughout the subsequent years. The 3-h area under the glucose curve (AUC) during the OGTT tended to be increased at the first year (P = 0.07) and it returned to the pretreatment level in the following years. The AUC of plasma insulin was significantly raised at 1 year (P = 0.024) and it returned to the pretreatment level in the following years. CONCLUSIONS: Four years of GH therapy in GH-deficient adults resulted in a sustained improvement in total and LDL cholesterol concentrations. Mild fasting hyperinsulinaemia persisted, although an initial deterioration in glucose tolerance, associated with post-glucose hyperinsulinaemia, was not sustained.

Adult↗
PubMed1998

Novel genes that upregulate the Proteus mirabilis flhDC master operon controlling flagellar biogenesis and swarming.

By screening for restoration of multicellular migration in a non-swarming but motile Proteus mirabilis mutant lacking the FIgN facilitator of flagella assembly, we identified four distinct genes that, in trans and multicopy, increased flagella production and cell length. Each of the genes upregulated expression of the flhDC master operon that controls flagellar biogenesis, cell division and swarming, not only in the mutant but also in the wild type. The genes were named umoA, umoB, umoC and umoD. Disruption of each of the wild-type chromosomal umo genes caused corresponding reductions in swarming and cell elongation, which correlated with decreased expression of the flhDC operon. The umoA, umoB, umoC and umoD genes are not closely linked, and only umoB is part of an operon. The sequences of the calculated gene products, UmoA (20.6 kDa), UmoB (78.0 kDa), UmoC (15.2 kDa) and UmoD (19.2 kDa), contain putative N-terminal secretion signals and predict a location in the cell membranes or periplasm. UmoB and UmoD have sequence similarity to the Escherichia coli uncharacterized open reading frames YrfF and YcfJ respectively; UmoA and UmoC have no known homologues. The umoB and umoC gene transcripts were present at very low levels, but umoA and umoD expression was similar to that of flhDC and increased in parallel with flhDC expression during differentiation into elongated hyperflagellated swarm cells. Like flhDC, umoA and umoD expression was subject to negative feedback in aflagellar assembly mutant lacking the FlhA inner membrane component of the export machinery. Assays of umo gene expression and cross-complementation indicated that the umo genes do not act in sequence within a pathway to upregulate flhDC, but revealed that umoA and umoD are reciprocally upregulated by FlhDC. Our findings strengthen the picture of the flhDC master operon as a major assimilatory checkpoint in Proteus mirabilis and other Gram-negative bacteria and expand the view of a complex regulatory network coupled to flagellar biogenesis.

Bacterial Proteins↗
PubMed1998

Microsatellite sequences are under-represented in two mite genomes.

Microsatellites are known to be a common feature of eukaryote genomes. Here we investigate the presence of microsatellite sequences in the genome of two mite species, Tetranychus urticae and Amblyseius fallacis, based on screening of both mite genomic libraries and Southern blots of these mites that we compare to two vertebrates. No signal with GT15 or a faint smear with CT10 were obtained in Southern analysis for the two mites, whereas both probes strongly bound with vertebrate DNA. Genomic libraries constructed in plasmid and lambda vectors were probed and only two CT microsatellites were isolated for T. urticae. Among eight trinucleotides probes tested, the strongest hybridization signal was detected for T. urticae with CAT and TGA probes. These two classes of repeats were also the most represented in genomic library screenings. However, only sequences with short numbers of units could be detected (<CAT4 or TGA9). Congruency of Southern analysis and screening of partial genomic libraries indicates an under-representation of microsatellite sequences in the two mite genomes. The potential of the scarce repetitive DNA isolated from mites to serve as population genetics markers is discussed on the basis of preliminary assessment of their polymorphism.

Animals↗
PubMed1998

Value of magnetic resonance imaging with an endovaginal receiver coil in the pre-operative assessment of Stage I and IIa cervical neoplasia.

OBJECTIVE: To assess the value of high resolution endovaginal magnetic resonance images (MRI) of the uterine cervix in planning management of early cervical cancer. DESIGN: Prospective cross-sectional study. SETTING: Specialist gynaecological oncology unit of a postgraduate teaching hospital. PARTICIPANTS: Thirty nine women aged 25-76 years old (mean 42.5 years) with invasive carcinoma Stage I or IIa of the cervix. METHODS: A ring coil was positioned endovaginally around the cervix. Imaging was performed on a 1.0 T HPQ Vista or 0.5 T Asset (Picker, Highland Heights, Ohio, USA) using T1 weighted and T2 weighted sequences in transverse and sagittal planes with thin slices (2.5 mm) and small fields of view (12 cm). Tumour volumes were measured and any extension into adjacent organs and parametrium was noted. The patients were followed up after treatment and the outcome related to the MRI findings. RESULTS: There was one false positive and one false negative result among five Stage Ia patients being assessed for residual disease after cone biopsy or LLETZ. The MRI assessment of the size and distribution of the tumour was confirmed histologically in all 31 patients with Stage Ib or IIa disease who were treated surgically. One of these patients in whom no endocervical tumour was visible on MRI underwent radical trachelectomy. Three patients had radiotherapy as primary treatment. Patients with Stage Ib or IIa disease who had tumour volumes > 10 cm3 with early parametrial extension on MRI had a substantially worse prognosis at 24 months (disease-free survival 58.3% vs 95.5%, P = 0.003). CONCLUSION: High resolution MRI with an endovaginal coil allows precise measurement of tumour volume and identifies patients with small volume disease who might be considered for more conservative therapy. This technique also reveals early parametrial invasion that cannot be identified reliably by any other method. Early parametrial invasion in women with large tumours appears to have a very much worse prognosis.

Adult↗
PubMed1998

Hepatitis C--role of perinatal transmission.

To evaluate the role of perinatal transmission in the spread of hepatitis C virus (HCV), we screened a cohort of pregnant intravenous drug using (IVDU) women for HCV antibody detection; where seropositive HCV RNA detection by polymerase chain reaction (PCR) was found we followed the infants longitudinally for HCV antibody and HCV RNA. Serum prevalence for HCV for this population was 80% with HCV RNA detected in 50%. Recruitment and follow-up over a 3-year period of a cohort of 83 seropositive women, their 91 newborns and 16 siblings of newborns, showed that there had been a 3% perinatal transmission rate with 1 sibling also infected. These positive cases were defined as transient in 1 case (HCV RNA positive by PCR at 1 month, but seronegative and HCV RNA negative at 10 months of age), 2 unevaluable (HCV RNA positive at 2 months of age, but patients lost to follow-up), and 1 chronic infection in a child at 34 months (positive HCV RNA and seropositive 34-month sibling). Maternal HCV RNA levels for those with infected infants was a mean 40-fold greater than those whose babies were uninfected, although this did not reach statistical significance. Of the remaining infants, the majority (93%) had lost passively acquired maternal antibodies by 9 months of age and all by 12 months. Of 18 women who were HCV seropositive and breast feeding (66% of whom were HCV RNA positive in their sera), none had detectable HCV RNA in breast milk. Hence we conclude that transmission of HCV from mother to infant appears to be of low frequency and positivity appears to correlate with maternal circulating viral load.

Adult↗
PubMed1998

Acylation of Escherichia coli hemolysin: a unique protein lipidation mechanism underlying toxin function.

The pore-forming hemolysin (HlyA) of Escherichia coli represents a unique class of bacterial toxins that require a posttranslational modification for activity. The inactive protoxin pro-HlyA is activated intracellularly by amide linkage of fatty acids to two internal lysine residues 126 amino acids apart, directed by the cosynthesized HlyC protein with acyl carrier protein as the fatty acid donor. This action distinguishes HlyC from all bacterial acyltransferases such as the lipid A, lux-specific, and nodulation acyltransferases, and from eukaryotic transferases such as N-myristoyl transferases, prenyltransferases, and thioester palmitoyltransferases. Most lipids directly attached to proteins may be classed as N-terminal amide-linked and internal ester-linked acyl groups and C-terminal ether-linked isoprenoid groups. The acylation of HlyA and related toxins does not equate to these but does appear related to a small number of eukaryotic proteins that include inflammatory cytokines and mitogenic and cholinergic receptors. While the location and structure of lipid moieties on proteins vary, there are common effects on membrane affinity and/or protein-protein interactions. Despite being acylated at two residues, HlyA does not possess a "double-anchor" motif and does not have an electrostatic switch, although its dependence on calcium binding for activity suggests that the calcium-myristoyl switch may have relevance. The acyl chains on HlyA may provide anchorage points onto the surface of the host cell lipid bilayer. These could then enhance protein-protein interactions either between HlyA and components of a host signal transduction pathway to influence cytokine production or between HlyA monomers to bring about oligomerization during pore formation.

Acyl Carrier Protein↗
PubMed1998

Platelets, aspirin, and cardiovascular disease.

Aspirin was first synthesised 100 years ago and its preparation and marketing is generally reckoned to have been the foundation of the pharmaceutical industry. For most of the time since then it has been used for the relief of pain and fever. The modern phase of aspirin use commenced with the reporting in 1974 of a randomised controlled trial in the secondary prevention of death by low-dose aspirin given to patients who had suffered a myocardial infarct. Reports of other trials followed and an overview of the first six trials was presented to the inaugural meeting of the Society for Clinical Trials in Philadelphia in 1980. There have been two further major overviews and the most recent, based on 145 trials, established that low-dose aspirin reduces vascular events by around one third. It has been estimated that, used appropriately, aspirin could prevent 100,000 premature deaths each year worldwide, at a cost of about 250 Pounds ($400) per life saved, and about 80 Pounds ($130) per cardiovascular event prevented. The evidence indicates that it is seriously underused at present. The aspirin story continues and trials are in progress to test other possible uses of aspirin, in vascular dementia, colorectal cancer, and cataract.

Aspirin↗
PubMed1998

What you don't know can hurt you: adverse psychologic effects in members of BRCA1-linked and BRCA2-linked families who decline genetic testing.

PURPOSE: To identify members of hereditary breast and ovarian cancer families who are at risk for adverse psychologic effects of genetic testing. PATIENTS AND METHODS: A prospective cohort study with baseline (preeducation) assessments of predictor variables (ie, sociodemographic factors, cancer history, and cancer-related stress symptoms) was performed. The primary outcome variable (presence of depressive symptoms) was assessed at baseline and at 1- and 6-month follow-up evaluations. Participants were 327 adult male and female members of BRCA1- and BRCA2-linked hereditary breast and ovarian cancer families, who were identified as carriers, noncarriers, or decliners of genetic testing. RESULTS: The presence of cancer-related stress symptoms at baseline was strongly predictive of the onset of depressive symptoms in family members who were invited but declined testing. Among persons who reported high baseline levels of stress, depression rates in decliners increased from 26% at baseline to 47% at 1-month follow-up; depression rates in noncarriers decreased and in carriers showed no change (odds ratio [OR] for decliners v noncarriers=8.0; 95% confidence interval [CI], 1.9 to 33.5; P=.0004). These significant differences in depression rates were still evident at the 6-month follow-up evaluation (P=.04). CONCLUSION: In BRCA1/2-linked families, persons with high levels of cancer-related stress who decline genetic testing may be at risk for depression. These family members may benefit from education and counseling, even if they ultimately elect not to be tested, and should be monitored for potential adverse effects.

Adolescent↗
PubMed1998

Academic medical libraries' policies and procedures for notifying library users of retracted scientific publications.

Academic medical libraries have a responsibility to inform library users regarding retracted publications. Many have created policies and procedures that identify flawed journal articles. A questionnaire was sent to the 129 academic medical libraries in the United States and Canada to find out how many had policies and procedures for identifying retracted publications. Of the returned questionnaires, 59% had no policy and no practice for calling the attention of the library user to retracted publications. Forty-one percent of the libraries called attention to retractions with or without a formal policy for doing so. Several responding libraries included their policy statement with the survey. The increasing number of academic medical libraries that realize the importance of having policies and practices in place highlights the necessity for this procedure.

Academic Medical Centers↗