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Biomedical subjects

R Harris

Publications and source records attributed to R Harris.

At least 19 recordsLinked to original sources
PubMed2006

Load-induced focal adhesion mechanotransduction is altered with aging in the Fischer 344/NNiaHSd x Brown Norway/BiNia rat aorta.

The focal adhesion kinase (FAK) pathway has emerged as a critical component for mediating numerous cellular responses including control of cell growth, differentiation, and adaptation. Here we compared the expression, basal activation, and the ability of increased intraluminal pressure to activate FAK and focal adhesion-associated proteins in the aorta of adult (6 months old) and very aged (36 months old) Fischer 344/NNiaHSd x Brown Norway/BiNia (F344/NXBN) rats. Immunoblot analysis showed increases in the aortic content of FAK (15%), FAK related non-kinase (p41-FRNK) (28%), Src (92%), RhoA (41%), and paxillin (23%) in the very aged aortae. Increased age significantly changed the basal phosphorylation status of FAK and paxillin. Application of aortic intraluminal pressure (200 mm Hg) amplified the phosphorylation of FAK (Tyr 925), Src (Tyr 416), and paxillin (Tyr 188) in adult animals while aortic loading in the very aged animals failed to induce FAK (Tyr 925) phosphorylation. Aging did not alter the load-induced regulation of RhoA; however, FRNK (p41) translocation between cytosolic and membrane compartments was increased. These results confirm previous observations that FAK and focal adhesion-associated proteins are mechanically regulated and expand these studies to suggest that FAK mechanotransduction is altered with aging.

Aging↗
PubMed2006

Abscisic acid stimulates the expression of two isoforms of plasma membrane Ca2+-ATPase in Arabidopsis thaliana seedlings.

AT-ACA8 and AT-ACA9 are two plasma membrane (PM) Ca (2+)-ATPases of ARABIDOPSIS THALIANA. In this article the expression of AT-ACA8, AT-ACA9, and of AT-ACA10, a third isoform of Ca (2+)-ATPase closely related to PM Ca (2+)-ATPases, was analysed and the effect of the hormone abscisic acid (ABA) on the expression level of PM Ca (2+)-ATPase specific transcripts was investigated. In adult plants of A. THALIANA, AT-ACA8 and AT-ACA10 are expressed in all organs considered whereas AT-ACA9 is expressed only in flowers. All isoforms of PM Ca (2+)-ATPases can be detected in young seedlings but the amount of AT-ACA9 mRNA is much lower than those of AT-ACA8 and AT-ACA10. ABA markedly and rapidly stimulates the expression of both AT-ACA8 and AT-ACA9 genes in young seedlings but not that of AT-ACA10. ABA also increases the level of AT-ACA8 protein at the PM, suggesting a role for PM Ca (2+)-ATPases in ABA signalling.

Abscisic Acid↗
PubMed2006

The impact of age on bispectral index values and EEG bispectrum during anaesthesia with desflurane and halothane in children.

BACKGROUND: The relationship between end-tidal sevoflurane concentration, bispectral index (BIS) and the EEG bispectrum in children appears to be age dependent. The aim of this study was to quantify the BIS values at 1 MAC (minimum alveolar concentration) for desflurane and halothane, and explore the relationship with age for these anaesthetic agents in children. METHODS: ECG, EEG and BIS were recorded continuously in 90 children aged 6-170 months requiring anaesthesia for elective surgery. Fifty children were anaesthetized with desflurane, and 40 children with halothane. Recordings were performed through to a steady state of 2 MAC, and thereafter at 1 and 0.5 MAC, respectively. The bispectrum of the EEG was estimated using MATLAB(c) software. A multiple correspondence analysis (MCA) was used. RESULTS: At a steady state of 1 MAC, BIS values were significantly higher with halothane 62 (43-80) than desflurane 34 (18-64). BIS values were significantly correlated with age in both groups: DES (r(2)=0.57; P<0.01) and HALO (r(2)=0.48; P<0.01). Changes in position in the structured model of the MCA (dependent on the pattern of the EEG bispectrum) were different for the two volatile anaesthetic agents. CONCLUSIONS: In children, BIS values are linked to age irrespective of the volatile anaesthetic agent used. The difference in BIS values for different agents at the same MAC can be explained by the specific effect on the EEG bispectrum induced by each anaesthetic agent, bringing into question the ability of the EEG bispectrum to accurately determine the depth of anaesthesia.

Adolescent↗
PubMed2006

CRACK/project prevention: providing a social service or promoting social control?

This paper tests the arguments put forth by Morgan (2004) and several others that the CRACK/Project Prevention programme, which offers substance-abusing women a monetary incentive to choose long-term or permanent birth control, is racist and unethical. Findings from a sample of 521 participants in the programme show that the majority of women chose a birth control method that was not permanent, and race did not play a statistically significant role in explaining the birth control choices among the women. Rather, the participant's age and the number of pregnancies she had experienced were more influential. The findings suggest that the prior criticisms of the programme for targeting minority and inherently vulnerable, addicted women for sterilisation are unsupported. Women in this study appeared to follow the larger trends among women of all races and socioeconomic backgrounds in choosing permanent birth control: they were older and had more children.

Adolescent↗
PubMed2006

Postmodern biology: (adult) (stem) cells are plastic, stochastic, complex, and uncertain.

This chapter will discuss recent findings regarding cell plasticity and stem cell behavior, focusing on ways in which experimental design, observer interference, and inherent stochasticity and complexity are serving to create a new, postmodern biology. The chapter will summarize: (a) the four recognized pathways whereby cell plasticity occurs physiologically; (b) recent findings regarding unexpected epigenetic reversibility of gene restrictions that provide the mechanistic core of plasticity; (c) current evidence for the stochastic nature of gene expression and, therefore, of cell fate decisions. It will be noted that stochastic, however, does not imply completely random; rather, constrained randomness, intermediate between rigid determinism and complete disorder is what is usually seen experimentally. Possible sources of such constrained disorder, from a biomolecular point of view, will be discussed. The chapter will conclude with discussions of how these findings contribute to a Complexity Theory formulation of the body as self-organizing emergence of interacting biomolecules and the implications of such concepts for design and interpretation of experimental results (i.e., a cellular version of Heisenbergian uncertainty).

Adult↗
PubMed2005

Immune response genes in the post-Q-fever fatigue syndrome, Q fever endocarditis and uncomplicated acute primary Q fever.

BACKGROUND: The influence of immune response gene variations on the development of chronic complications of Q fever is presently unclear. AIM: To compare the frequencies of allelic polymorphisms in immune response genes in different Q fever patient groups. DESIGN: Genetic association study. METHODS: We measured the frequencies of immune response gene variants in: (i) an expanded group of 31 post-Q-fever fatigue patients (QFS); (ii) 22 Q fever endocarditis patients (QFE); and (iii) 22 patients who made an uncomplicated recovery from their initial attack of primary acute Q fever, comparing them with various standard control panels from the general population. RESULTS: There were significant differences between the three Q fever groups. QFS patients differed from both QFE and uncomplicated patients and controls in the frequency of carriage of HLA-DRB1*11 and of the 2/2 genotype of the interferon-gamma intron1 microsatellite. Carriage of the HLA DRB1*11 allele was associated with reduced interferon-gamma and IL-2 responses from PBMC stimulated with ligand in short-term culture. QFE showed differences in the IL-10 promoter microsatellites R and G and had higher frequencies of the TNF-alpha receptor II 196R polymorphism. Q fever patients who had made an uncomplicated recovery differed from those with QFS or QFE, but were not significantly different in allelic frequencies to the control panels. DISCUSSION: These immunogenetic differences support the concept of different immune states in chronic Q fever, determined by genetic variations in host immune responses, rather than by solely properties of Coxiella burnetii.

Coxiella burnetii↗
PubMed2005

Effects of aging on pressure-induced MAPK activation in the rat aorta.

With increasing age, the cardiovascular system experiences substantial alterations in cellular morphology and function. Whilst the factors regulating these changes are unknown, the mitogen-activated protein kinase (MAPK) pathways have emerged as critical components for mediating numerous cellular responses including control of cell growth, differentiation and adaptation. Here we compare the expression, basal activation and the ability of increased pressure to activate the MAPK pathways in adult (6-month-old), aged (30-month-old) and very aged (36-month-old) Fischer 344xBrown Norway F1 hybrid rats. Histochemical analysis demonstrated an age-related increase in tunica media thickness of approximately 11 and 21% in aortae from aged and very aged animals, respectively. Western blot analysis of the MAPK family extracellular signal-regulated kinase (ERK 1/2), p38, and c-Jun NH2 -terminal kinase (JNK) MAPKs showed differential expression and activation among these proteins with age. Expression of ERK 1/2, p38, and JNK were unchanged, slightly increased (10+/-17.5%) or significantly increased (72.3+/-27%), respectively, in very aged aortae. In contrast, basal activation levels of these proteins were reduced (-26.2+/-7.4%), markedly increased (97.0+/-16.8%), and slightly increased (14.4+/-4.5%), respectively, in very aged compared with 6-month rat aortae. An acute increase of aortic intraluminal pressure (200 mmHg) indicated that ERK 1/2 regulation differed from p38 or JNK. Pressure loading-induced phosphorylation of ERK1/2 was unchanged or increased with aging while p38 and JNK phosphorylation was attenuated (P<0.01). These observations confirm previous conclusions that MAPK proteins are regulated mechanically and expand these studies to suggest that MAPK expression and the control of activation are changed with aging.

Aging↗
PubMed2005

Impact of age on both BIS values and EEG bispectrum during anaesthesia with sevoflurane in children.

BACKGROUND: The aim of this study was to evaluate the potential relationship between age, BIS (Aspect), and the EEG bispectrum during anaesthesia with sevoflurane. METHODS: BIS and raw EEG were recorded at a steady state of 1 MAC in 100 children, and during a decrease from 2 to 0.5 MAC in a sub-group of 29 children. The bispectrum of the EEG was estimated using MATLAB software. For analysis, the bispectrum was divided into 36 frequencies of coupling (P(i))--the MatBis. A multiple correspondence analysis (MCA) was used to establish an underlying structure of the pattern of each individual's MatBis at 1 MAC. Clustering of children into homogeneous groups was conducted by a hierarchical ascending classification (HAC). The level of statistical significance was set at 0.05. RESULTS: At 1 MAC, the BIS values for all children ranged from 20 to 74 (median 40). Projection of both age and BIS value recorded at 1 MAC onto the structured model of the MCA showed them to be distributed along the same axis, demonstrating that the different values of BIS obtained in younger or older children are mainly dependent on their MatBis. At 1 MAC, six homogeneous groups of children were obtained through the HAC. Groups 5 (30 months; range 23-49) and 6 (18 months; range 6-180) were the younger children and Group 1 (97 months; range 46-162) the older. Groups 5 and 6 had the highest median values of BIS (54; range 50-59) (55; range 26-74) and Group 1 the lowest values (29; range 22-37). CONCLUSION: The EEG bispectrum, as well as the BIS appeared to be strongly related to the age of children at 1 MAC sevoflurane.

Adolescent↗
PubMed2004

The role of dental therapists working in four personal dental service pilots: type of patients seen, work undertaken and cost-effectiveness within the context of the dental practice.

OBJECTIVES: To describe the type of patients seen and work undertaken by dental therapists employed in four personal dental service practices and to report on their cost-effectiveness within the context of the dental practice. METHOD: All members of the dental team used a standard day sheet to record all patient contacts and procedures undertaken in that session. Dental therapists recorded data for 30 consecutive sessions and dentists recorded information for 20 sessions. Items were recorded in sufficient detail to allow later matching with the GDS statement of remuneration and a calculation of the average gross fees and patient charges per session. RESULTS: The role of the dental therapist varied between the practices studied. In two practices the therapist saw a high proportion of child patients, and in one of these this was combined with providing care for a high number of adult patients who were exempt from patient charges. In the two practices where the dental team did not include a dental hygienist, the dental therapist had a relatively high workload providing dental hygiene care for adult patients. It appears that the gross fees and patient charges generated by the dental therapist in all four PDS practices fail to cover the cost of the salary of the dental therapist, dental nurse and associated overheads borne by the practice.

Adult↗
PubMed2004

The passage of trimethylamine across rat and human skin.

Trimethylamine is a volatile low molecular weight tertiary aliphatic amine that has known toxicity and the potential for human exposure from industrial and environmental sources is considerable. It is generally believed that absorption across the skin is an unimportant route of entry but there is little, if any, supporting evidence for this assumption. Passage across rat and human skin has been investigated employing excised skin circles in an in vitro diffusion cell apparatus. Trimethylamine was found to penetrate readily when applied to the epidermal surface of skin at three different dose levels (0.1, 1.0 and 10 mg per skin membrane 0.32 cm2). The apparent dermal flux was calculated as 3.40 +/- 1.60, 58.3 +/- 30.6 and 265.0 +/- 155.0 microg/cm2/h for rat and 0.98 +/- 0.75, 9.21 +/- 3.06 and 92.7 +/- 31.9 microg/cm2/h for human at the three dose levels, respectively. Both rat and human skin was able to act as a reservoir, with the trimethylamine not remaining in the stratum corneum but passing through. When presented to the underneath of rat and human skin circles, both [U-14C]-trimethylamine and [U-14C]-trimethylamine N-oxide were able to pass from the dermis to the epidermis. Small but detectable amounts of trimethylamine were oxidised to its N-oxide during passage through the skin.

Animals↗
PubMed2003

Access to NHS dentistry in South Cheshire: a follow up of people using telephone helplines to obtain NHS dental care.

OBJECTIVE: To follow up calls made to NHS Direct and South Cheshire Dental Helpline concerning getting access to an NHS dentist in South Cheshire. DESIGN: Contact details of callers who had consented to a follow up call were passed by helpline staff to a researcher at regular intervals. In a structured interview, callers were asked why they had telephoned the helpline and whether they had subsequently obtained NHS dental care. Follow up calls continued until a total of 200 replies had been gathered, either by telephone or post (for those where telephone contact could not be made). Follow up calls were made between September 2001 and March 2002. RESULTS: During the study period only three callers from South Cheshire contacted NHS Direct with a dental access query and consented to a follow up call, compared with 219 callers to South Cheshire Dental Helpline. Only 10% were not contacted either by telephone or post. A comparison with figures for calls made to South Cheshire Dental Helpline between April 2000 and March 2001 suggests that during the study period a year later the access problem has improved. However, there were still a few areas in South Cheshire where significant numbers of dental access queries were being received. Twenty five per cent of unregistered and 22% of registered callers still felt that they had problems getting access to NHS dental care after using information from the helplines. CONCLUSION: A small but significant number of people in South Cheshire have problems accessing NHS dental care.

Adolescent↗
PubMed2003

Observation of weak-limit quasiparticle scattering via broadband microwave spectroscopy of a d-wave superconductor.

There has long been a discrepancy between microwave conductivity measurements in high temperature superconductors and the conductivity spectrum expected in the simplest models for impurity scattering in a d-wave superconductor. Here we present a new type of broadband measurement of microwave surface resistance that finally shows some of the spectral features expected for a d(x2-y2) pairing state. Cusp-shaped conductivity spectra, consistent with weak impurity scattering of nodal quasiparticles, were obtained in the 0.6-21 GHz frequency range in highly ordered crystals of YBa2Cu3O6.50 and YBa2Cu3O6.99.

Journal Article↗
PubMed2003

Solution NMR studies of antiamoebin, a membrane channel-forming polypeptide.

Antiamoebin I is a membrane-active peptaibol produced by fungi of the species Emericellopsis which is capable of forming ion channels in membranes. Previous structure determinations by x-ray crystallography have shown the molecule is mostly helical, with a deep bend in the center of the polypeptide, and that the backbone structure is independent of the solvent used for crystallization. In this study, the solution structure of antiamoebin was determined by NMR spectroscopy in methanol, a solvent from which one of the crystal structures was determined. The ensemble of structures produced exhibit a right-handed helical C terminus and a left-handed helical conformation toward the N-terminus, in contrast to the completely right-handed helices found in the crystal structures. The NMR results also suggest that a "hinge" region exists, which gives flexibility to the polypeptide in the central region, and which could have functional implications for the membrane insertion process. A model for the membrane insertion and assembly process is proposed based on the antiamoebin solution and crystal structures, and is contrasted with the assembly and insertion mechanism proposed for other ion channel-forming polypeptides.

Anti-Bacterial Agents↗
PubMed2003

Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases.

This study identifies multiple copies of the AML1 gene on a duplicated chromosome 21, dup(21), as a recurrent abnormality in acute lymphoblastic leukemia (ALL). Clusters of AML1 signals were visible at interphase by fluorescence in situ hybridization (FISH). In metaphase, they appeared tandemly duplicated on marker chromosomes of five distinct morphological types: large or small acrocentrics, metacentrics, submetacentrics or rings. The markers comprised only chromosome 21 material. Karyotypes were near-diploid and, besides dup(21), no other established chromosomal changes were observed. A total of 20 patients, 1.5 and <0.5% among consecutive series of childhood and adult ALL respectively, showed this phenomenon. Their median age was 9 years, white cell counts were low and all had a pre-B/common immunophenotype. Although this series is not the first report of this abnormality, it is the largest, permitting a detailed description of the variety of morphological forms that duplicated chromosome 21 can assume.

Adolescent↗
PubMed2002

Major ear surgery in a paediatric day care unit.

Abstract Traditionally major ear surgery in children has been regarded as an in-patient procedure. Evidence from the USA for adults, however, concludes that it is both safe and effective to perform many major ear procedures as day cases. We have been carrying out major ear operations on children as day cases routinely for six years in a dedicated children's day unit and examined our data to find out whether it was both safe and feasible to perform major ear surgery in children on a day-case basis. As our main outcome measure we used the rate of unplanned admissions. We found that the unplanned admission rate for surgery, excluding mastoid surgery, was 6.7 per cent and that procedures such as myringoplasty, ossiculoplasty, bilateral pinnaplasty, meatoplasty and tympanotomy with excision of cholesteatoma, were eminently suitable for day surgery.

Adolescent↗
PubMed2002

Paediatric day-stay myringoplasty: a review of 74 consecutive cases.

Day-case surgery is particularly attractive for children, allowing post-operative recovery in the safe environment of the family home. Myringoplasty using the traditional method of underlay temporalis fasia is usually performed as an in-patient. From 1995 to 2000, 74 myringoplasties were performed in a dedicated paediatric day surgery unit at the Mayday University Hospital. We have retrospectively reviewed the outcome results of these procedures and reported them here. Only three patients required admission overnight (four per cent) and six grafts failed (8.5 per cent) complying with accepted standards. This series suggests that day-case surgery is a safe and desirable practice for children undergoing myringoplasty. However, there should be the facility for admission if required.

Adolescent↗