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Biomedical subjects

P Gardiner

Publications and source records attributed to P Gardiner.

At least 19 recordsLinked to original sources
PubMed2006

Effects of exercise training on alpha-motoneurons.

Evidence is presented that one locus of adaptation in the "neural adaptations to training" is at the level of the alpha-motoneurons. With increased voluntary activity, these neurons show evidence of dendrite restructuring, increased protein synthesis, increased axon transport of proteins, enhanced neuromuscular transmission dynamics, and changes in electrophysiological properties. The latter include hyperpolarization of the resting membrane potential and voltage threshold, increased rate of action potential development, and increased amplitude of the afterhyperpolarization following the action potential. Many of these changes demonstrate intensity-related adaptations and are in the opposite direction under conditions in which chronic activity is reduced. A five-compartment model of rat motoneurons that innervate fast and slow muscle fibers (termed "fast" and "slow" motoneurons in this paper), including 10 active ion conductances, was used to attempt to reproduce exercise training-induced adaptations in electrophysiological properties. The results suggest that adaptations in alpha-motoneurons with exercise training may involve alterations in ion conductances, which may, in turn, include changes in the gene expression of the ion channel subunits, which underlie these conductances. Interestingly, the acute neuromodulatory effects of monoamines on motoneuron properties, which would be a factor during acute exercise as these monoaminergic systems are activated, appear to be in the opposite direction to changes measured in endurance-trained motoneurons that are at rest. It may be that regular increases in motoneuronal excitability during exercise via these monoaminergic systems in fact render the motoneurons less excitable when at rest. More research is required to establish the relationships between exercise training, resting and exercise motoneuron excitability, ion channel modulation, and the effects of neuromodulators.

Adaptation, Physiological↗
PubMed2006

A qualitative study to develop a tool to examine patients' perceptions of NHS orthodontic treatment.

OBJECTIVE: To identify issues of importance to adolescent patients surrounding the delivery of orthodontic treatment under the National Health Service (NHS), which can form the basis of a tool to examine patients' perceptions of NHS orthodontic treatment. DESIGN: Study using qualitative research methods. SETTING: Patients were recruited from the orthodontic departments at Derriford Hospital and Bristol Dental Hospital, and from Specialist Orthodontic Practices in Plymouth and Solihull. SUBJECTS: A rolling sample of patients from a list of orthodontic patients under treatment at each site was selected. Twenty-six patients took part in five focus group meetings. Three patients took part in semi-structured telephone interviews. METHODS: Participants were invited to participate in either a focus group meeting or a telephone interview. The transcripts of these meetings were analysed by two researchers working independently. Issues of importance to patients regarding the delivery of orthodontic treatment under the NHS were identified. RESULTS: The issues identified included being treated with respect by the clinician and being included in discussions about treatment. Participants tended to rely on their peers for advice about what to expect from treatment. The patients also discussed the benefits to them of undergoing orthodontic treatment. These included an improved appearance and increased self-confidence. CONCLUSION: This qualitative research has identified issues that are important to adolescent orthodontic patients. These issues will be used to form the basis of a patient-centred measure for auditing patients' perceptions of orthodontic treatment under the NHS.

Adolescent↗
PubMed2005

Novel isosorbide-based substrates for human butyrylcholinesterase.

Butyrylcholinesterase [EC 3.1.1.8] present widely in mammalian tissue does not have a precisely defined biological function or known endogenous substrate. However, it plays an important role in the detoxification of certain xenobiotics and is an established vector for the systemic liberation of other drugs from their prodrugs. While investigating a series of isosorbide-based prodrugs, we discovered that BuChE catalyses the hydrolysis of esters of the simple sugar isosorbide with unusually rapidity and in some cases with remarkable regioselectivity. In this study, a series of isosorbide esters were synthesised and their rates of hydrolysis measured by HPLC following incubation in diluted plasma solution. In general, little hydrolysis of the 5-ester group could be observed but the 2-ester group was usually hydrolysed very rapidly and the hydrolysis rate exhibited an unusual dependence on the identity of the 5-group. The results indicate that while the 5-ester group is not itself hydrolysed it is important for productive binding in isosorbide diesters.

Butyrylcholinesterase↗
PubMed2005

Paying research participants: a study of current practices in Australia.

OBJECTIVE: To examine current research payment practices and to inform development of clearer guidelines for researchers and ethics committees. DESIGN: Exploratory email based questionnaire study of current research participant reimbursement practices. A diverse sample of organisations and individuals were targeted. SETTING: Australia. PARTICIPANTS: Contacts in 84 key research organisations and select electronic listservers across Australia. A total of 100 completed questionnaires were received with representations from a variety of research areas (for example, market, alcohol and drug, medical, pharmaceutical and social research). MAIN MEASUREMENTS: Open-ended and fixed alternative questions about type of research agency; type of research; type of population under study; whether payment is standard; amounts and mechanisms of payment; factors taken into account when deciding on payment practices; and whether payment policies exist. RESULTS: Reimbursement practice is highly variable. Where it occurs (most commonly for drug dependent rather than health professional or general population samples) it is largely monetary and is for time and out-of-pocket expenses. Ethics committees were reported to be often involved in decision making around reimbursement. CONCLUSIONS: Research subject payment practices vary in Australia. Researchers who do provide payments to research participants generally do so without written policy and procedures. Ethics committees have an important role in developing guidelines in this area. Specific guidelines are needed considering existing local policies and procedures; payment models and their application in diverse settings; case study examples of types and levels of reimbursement; applied definitions of incentive and inducement; and the rationale for diverse payment practices in different settings.

Australia↗
PubMed2003

A virtue ethics approach to moral dilemmas in medicine.

Most moral dilemmas in medicine are analysed using the four principles with some consideration of consequentialism but these frameworks have limitations. It is not always clear how to judge which consequences are best. When principles conflict it is not always easy to decide which should dominate. They also do not take account of the importance of the emotional element of human experience. Virtue ethics is a framework that focuses on the character of the moral agent rather than the rightness of an action. In considering the relationships, emotional sensitivities, and motivations that are unique to human society it provides a fuller ethical analysis and encourages more flexible and creative solutions than principlism or consequentialism alone. Two different moral dilemmas are analysed using virtue ethics in order to illustrate how it can enhance our approach to ethics in medicine.

Adult↗
PubMed2001

Community-based cancer screening for underserved women: design and baseline findings from the Breast and Cervical Cancer Intervention Study.

BACKGROUND: Underutilization of breast and cervical cancer screening has been observed in many ethnic groups and underserved populations. Effective community-based interventions are needed to eliminate disparities in screening rates and thus to improve prospects for survival. METHODS: The Breast and Cervical Cancer Intervention Study was a controlled trial of three interventions in the San Francisco Bay Area from 1993 to 1996: (1) community-based lay health worker outreach; (2) clinic-based provider training and reminder system; and (3) patient navigator for follow-up of abnormal screening results. Study design and a description of the interventions are reported along with baseline results of a household survey conducted in four languages among 1599 women, aged 40-75. RESULTS: Seventy-six percent of women ages 40 and over had had at least one mammogram, and most had had a clinical breast examination (88%) and Pap smear (89%). Rates were significantly lower for non-English-speaking Latinas and Chinese women (56 and 32%, respectively, for mammography), and maintenance screening (three mammograms in the past 5 years) varied from 7% (non-English-speaking Chinese) to 53% (Blacks). Pap smear screening in the past 3 years was low among non-English-speaking Latinas (72%) and markedly lower among non-English-speaking Chinese women (24%). The strongest predictors of screening behavior were having private health insurance and frequent use of medical services. Having a regular clinic and speaking English were also important. Race/ethnicity, education, household income, and employment status were, overall, not significant predictors of screening behavior. CONCLUSIONS: These baseline results support the importance of cancer screening interventions targeted to persons of foreign origin, particularly those less acculturated.

Adult↗
PubMed2000

Comparative expression and purification of human glutamic acid decarboxylase from Saccharomyces cerevisiae and Pichia pastoris.

The yeast cell factory is a potentially useful source of proteins in general. They include glutamic acid decarboxylase (GAD), which is one of the major autoantigens for Type 1 diabetes. We have created a hybrid form of GAD consisting of amino acids 1-101 of the human GAD67 protein fused to amino acids 96-585 of the human GAD65 protein, and have modified this to include a C-terminal hexa-Histidine (H6) tag sequence. This hybrid GAD67/65-H6 was expressed in two yeast hosts: constitutively under the control of the plasmid phosphoglycerate kinase promoter (PGK1) in Saccharomyces cerevisiae, and inducibly under the control of the chromosomal alcohol oxidase promoter (AOX1) in Pichia pastoris. Enzymatically active hybrid GAD was prepared from yeast lysates by purification either on an affinity column based on the GAD-1 monoclonal antibody, or by metal-affinity chromatography. The purified GAD67/65-H6 was radiolabelled with iodine-125 and tested with Type 1 diabetes sera in a radioimmunoprecipitation assay, and results were compared with those using untagged GAD67/65 and those using porcine brain GAD. The results of enzymatic and immunological assays show hybrid GAD67/65 is isolated at high specific activity and moderate yield, and the addition of the H6 tag sequences or the choice of yeast strain did not appreciably affect enzyme activity, percentage recovery of GAD, protein purification, or the utility in diagnosis of diabetes in terms of specificity and sensitivity to the various sera.

Journal Article↗
PubMed2000

Recent review of complementary and alternative medicine used by adolescents.

In the past decade the use of complementary and alternative medicine (CAM) has dramatically increased in adult, adolescent, and pediatric populations in the United States, Canada, and Western Europe. There are multiple reasons for this, including the search for natural therapies, curative and ameliorative therapies for chronic illnesses that are unresponsive to conventional therapy, attraction to therapists or alternative modalities suggested by friends, and the autonomy of obtaining unregulated products and services. This review will address recent studies concerning adolescent use of specific CAM therapies for asthma, urinary tract infections, headaches, dietary supplements in athletes, and mental health conditions. Health care providers need to be aware of the CAM therapies their patients are using, the potential side effects, and the possibilities for including effective complementary therapies into the conventional care they provide.

Adolescent↗
PubMed2000

The effect of endurance training on phosphoinositide metabolism of extensor digitorum longus in rat.

We tested the hypothesis that endurance training results in changes in inositol triphosphate (InsP3) production from membrane phosphoinositides in trained muscles during contractile activity, which might have implications for fatigue involving calcium-release mechanisms. The extensor digitorum longus (EDL) muscles of endurance-trained rats were measured for membrane phosphoinositides, fatigability, and the production of inositol phosphates resulting from a 10-s tetanic contraction in vitro. In the latter, training resulted in a 22% increase in the production of inositol phosphates, in spite of lower phosphoinositides per muscle. In a separate group of animals, pretreatment of EDL in vitro for 15 min with 20 mM lithium resulted in a gradual decrease in tetanic forces at 100 Hz and increased fatigability. These results show for the first time that this metabolic system adapts to increased use and may contribute to the associated increased fatigue resistance, through its modulation of calcium release by sarcoplasmic reticulum.

Analysis of Variance↗
PubMed1999

Increased activity in the form of endurance training increases calcitonin gene-related peptide content in lumbar motoneuron cell bodies and in sciatic nerve in the rat.

The relative content of calcitonin gene-related peptide in lumbar motoneuron cell bodies (semiquantitative immunohistochemistry) and sciatic nerve was examined in rats who had previously undergone a 16-week period of endurance training on a motor-driven treadmill. Soleus motoneurons were identified in the spinal cord by their fluorescence following injection of FluoroGold into the muscle one week before killing. In sedentary rats, calcitonin gene-related peptide was detectable in 76-90% of motoneurons, with no difference in the proportions of negative cells, or in the mean staining intensity of positive cells, between soleus and neighbouring (presumptive fast hindlimb muscle) unlabelled moto-neurons. In endurance-trained rats, the estimated content of calcitonin gene-related peptide was significantly increased (90%) in cell bodies of soleus and neighbouring motoneurons, with no training-induced alterations in the proportions of calcitonin gene-related peptide-positive cells in either sample. The content of the neuropeptide was also significantly higher (37%) in sciatic nerve of endurance-trained rats. Relative accumulation of calcitonin gene-related peptide proximal to a sciatic nerve ligature applied 4 h before, however, was unchanged. The increases in calcitonin gene-related peptide in motoneuron cell bodies and sciatic nerve axons following endurance training may indicate an up-regulation of the synthesis, transport and terminal release of this neuropeptide, which could play a significant role in other morphological and functional adaptations which are known to occur at the neuromuscular junction following this chronic change in activity level.

Animals↗
PubMed1996

Which is the active moiety of sulfasalazine in ankylosing spondylitis? A randomized, controlled study.

OBJECTIVE: To compare the efficacy of sulfasalazine (SSZ) with its two moieties, 5-aminosalicylic acid (ASA) and sulfapyridine (SP), in patients with active ankylosing spondylitis (AS). METHODS: A 26-week randomized, observer-blinded, 2-center, controlled study of treatment with either SSZ, ASA, or SP was conducted in 90 patients with active AS. Patients were evaluated at baseline and at monthly intervals, using several clinical and laboratory measures of disease activity. A global assessment of treatment efficacy was made by both patients and observers at the end of the study period. RESULTS: There were no significant changes in any of the parameters of disease activity in the ASA treatment group. Levels of serum IgG, IgA, and IgM fell significantly during treatment with SP, but none of the other changes reached statistical significance. Plasma viscosity and IgG and IgA levels fell significantly during treatment with SSZ, as did nocturnal spinal pain and overall spinal pain. Patients and observers reported a favorable outcome after treatment with SSZ or SP significantly more often than with ASA treatment. CONCLUSION: SP appears to be the active moiety in AS, although there was a trend suggesting a better outcome in the SSZ group compared with the SP group, perhaps suggesting the importance of a common sulfonamide structure for efficacy.

Adolescent↗
PubMed1996

Evidence for central nervous system glial cell plasticity in phenylketonuria.

Phenylketonuria (PKU) is caused by mutation(s) in the phenylalanine hydroxylase (PAH) gene which lead to deficient PAH activity and an accumulation of phenylalanine in the blood. The primary pathologic finding is hypomyelination and gliosis of central nervous system white matter. Similar white matter pathology is observed in the Pahenu2 mouse, a genetic model for PKU. We studied this mouse to examine the basis for these neuropathologic changes in PKU and to determine if hypomyelination and gliosis occur independently or are interrelated. Although white matter tracts within PKU brains are hypomyelinated, immunostaining and Western blot analyses revealed that these tracts contain abundant amounts of myelin markers, i.e. myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'phosphohydrolase, and myelin/oligodendrocyte-specific protein (MOSP). However, Western blot analyses also showed that MBP isoform expression was aberrant. Investigation of individual cells was performed by extraction of tissue sections with Triton X-100. Most of the MOSP was extracted, with the remaining MOSP clearly visible in dual labeled cells, i.e. MOSP was colocalized along glial fibrillary acidic protein (GFAP) filaments. Cells expressing both MBP and GFAP were also identified in optic tract. Double labeling with a riboprobe for MBP and antibodies specific for GFAP revealed that the majority of GFAP-positive cells expressed MBP mRNA. Our in vitro studies examined the response of cultured wild type oligodendrocytes to elevated phenylalanine for 4 weeks (wk). Under these conditions, about 50 these conditions, about 50% of the oligodendrocytes expressed GFAP filaments and failed to elaborate membrane sheets. Proliferation of astrocytes appears not to be the source of gliosis, since the nuclei of GFAP-positive cells in the PKU brains did not immunostain for proliferating cell nuclear antigen. Dual-labeled cells were detected in normal mouse brain sections; however, PKU mouse white matter tracts were found to contain about twice the number of dual-labeled cells compared to normal tissue. Taken together, these data suggest that both myelinating and nonmyelinating oligodendrocytes are present in the normal adult brain, and that in response to a toxic factor such as elevated phenylalanine, myelinating oligodendrocytes adopt a nonmyelinating phenotype that expresses GFAP. Since myelinating Schwann cells and GFAP-positive nonmyelinating Schwann cells are normally present in adult peripheral nerve, and the myelinating Schwann cells react to pathologic situations by switching to GFAP-positive nonmyelinating cells, it may be that oligodendrocytes and Schwann cells are more similar than previously thought.

Adult↗
PubMed1996

Is increased voluntary motor activity beneficial or detrimental during the period of motor nerve regeneration/reinnervation?

A model of partial denervation of the rat lateral gastrocnemius was used to investigate the effects of daily activity (treadmill plus voluntary wheel exercise) on the regeneration/reinnervation of motoneurons recovering from nerve crush. It appears that increased activity has no effect on axon regeneration rate, but may be detrimental to the reinnervation process.

Animals↗
PubMed1995

Development of a cleavage-site-specific monoclonal antibody for detecting metalloproteinase-derived aggrecan fragments: detection of fragments in human synovial fluids.

We have developed a monoclonal antibody AF-28 that specifically recognizes a neo-epitope on polypeptides with N-terminal FFGVG ... sequences. This sequence is found at the N-terminus of aggrecan fragments that have been digested with matrix metalloproteinases (MMPs). By immunoblotting, monoclonal antibody AF-28 specifically detected G2 fragments derived from an aggrecan G1-G2 substrate digested with stromelysin, collagenase, gelatinase and matrilysin, but failed to detect G2 fragments obtained from elastase, trypsin or cathepsin B digests. Undigested G1-G2 was not detected. In addition, AF-28 antibody detected fragments derived from whole aggrecan and this detection did not require prior treatment with chondroitinase or keratanase. Competition experiments confirmed that peptides containing internal ... FFGVG ... sequences were not detected by the antibody, while native MMP-digested aggrecan fragments and a synthetic 32-mer peptide with FFGVG ... N-termini were equally competitive on a molar basis. An FFGVG 5-mer, and an FGVGGEEDI9-mer which lacked the N-terminal phenylalanine residue, were 50 times and 230 times respectively less competitive than the FFGVG ... 32-mer. Two fragments from the interglobular domain, F342-F373 and F342-D441, that are predicted products of G1-G2 digestion by neutrophil collagenase but have not previously been detected, could be detected with AF-28. The epitope recognized by AF-28 was also detected in human synovial fluids by Western blot analysis. A broad band of 100-200 kDa was detected in some patients and a dominant band of 40-60 kDa was found in two patients. The size of this small fragment corresponds with that seen for the porcine F342-E373 product and may represent the natural physiological product of aggrecan cleaved in vivo at both the MMP site (... DIPEN341 decreases F342FGVG ...) and the aggrecanase site (... ITEGE373 decreases A374RGSVI ...).

Aggrecans↗
PubMed1995

Antagonism of leukotriene responses in human airways by BAY x7195.

Contractions induced by leukotriene and anti-IgE (sheep antiserum to human IgE) were antagonized by pretreatment of human airways with the cysteinyl leukotriene receptor antagonist BAY x7195 ((4S)-[4-carboxyphenylthio]-7-[4-(4-phenoxybutoxy)-phenyl]-h ept-5-(z)- enoic acid). However, this receptor antagonist did not inhibit either leukotriene D4- or leukotriene C4-induced contractions in human pulmonary veins. The pA2 value for BAY x7195 in human airways against leukotriene D4 was 7.83 +/- 0.16 with a slope of 1.07 +/- 0.15 (means +/- S.E.M; n = 11). The IC50 value for BAY x7195 in human airways contracted with anti-IgE was 0.31 +/- 0.08 microM (n = 11). These results were comparable to those obtained with ICI 204,219 (4-(5-cyclopentyl-oxycarbonylamino-1-methylindol-3-ylmeth yl)-3-methoxy-N-otolyl - sulfonylbenzamide). These data demonstrate that BAY x7195 is a potent selective leukotriene receptor antagonist which may block allergic reactions in the lung.

Antibodies, Anti-Idiotypic↗