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Biomedical subjects

M Bond

Publications and source records attributed to M Bond.

At least 55 records · Page 3Linked to original sources

A-kinase anchoring protein 100 (AKAP100) is localized in multiple subcellular compartments in the adult rat heart.

Stimulation of beta-adrenergic receptors activates type I and II cyclic AMP-dependent protein kinase A, resulting in phosphorylation of various proteins in the heart. It has been proposed that PKA II compartmentalization by A-kinase-anchoring proteins (AKAPs) regulates cyclic AMP-dependent signaling in the cell. We investigated the expression and localization of AKAP100 in adult hearts. By immunoblotting, we identified AKAP100 in adult rat and human hearts, and showed that type I and II regulatory (RI and II) subunits of PKA are present in the rat heart. By immunofluorescence and confocal microscopy of rat cardiac myocytes and cryostat sections of rat left ventricle papillary muscles, we localized AKAP100 to the nucleus, sarcolemma, intercalated disc, and at the level of the Z-line. After double immunostaining of transverse cross-sections of the papillary muscles with AKAP100 plus alpha-actinin-specific antibodies or AKAP100 plus ryanodine receptor-specific antibodies, confocal images showed AKAP100 localization at the region of the transverse tubule/junctional sarcoplasmic reticulum. RI is distributed differently from RII in the myocytes. RII, but not RI, was colocalized with AKAP100 in the rat heart. Our studies suggest that AKAP100 tethers PKA II to multiple subcellular compartments for phosphorylation of different pools of substrate proteins in the heart.

A Kinase Anchor Proteins↗

Object permanence in orangutans (Pongo pygmaeus) and squirrel monkeys (Saimiri sciureus).

The authors tested orangutans (Pongo pygmaeus) and squirrel monkeys (Saimiri sciureus) on object permanence tasks. In Experiment 1, orangutans solved all visible displacements and most invisible displacements except those involving movements into 2 boxes successively. In Experiment 2, performance of orangutans on double invisible displacements and control displacements (assessing simple strategies) was compared. Orangutans did not use the simple strategy of selecting the box visited last by the experimenter. Instead, poorer performance on double invisible displacements may have been related to increased memory requirements. In Experiment 3, squirrel monkeys were tested using the procedure of Experiment 1. Squirrel monkeys solved visible but did not comprehend invisible displacements. Results suggest that orangutans but not squirrel monkeys possess Stage 6 object permanence capabilities.

Animals↗

Retrospective study of radiotherapy for lung cancer in patients aged 75 years and over.

BACKGROUND: Radiotherapy is widely used in the management of lung cancer but there are few data on its use in elderly patients. METHODS: Retrospective review of case notes of all patients aged 75 years and over referred to a regional centre for radiotherapy with a diagnosis of lung cancer over 1 year. RESULTS: Of 149 patients referred, full information was available on 144 (97%); age range 75-93 years (mean 79). Main referral sources were chest physicians [68 (44%)], general physicians [40 (28%)] and geriatricians [20 (14%)]; all patients were accepted for radiotherapy. One hundred and thirty-four (93%) had palliative treatment with most [129 (90%)] receiving 1-5 fractions over 1 week and 117 (81%) having treatment as an outpatient. Palliation appeared good for haemoptysis but less effective for the more common symptoms of dyspnoea and cough. Side effects were reported by 25 patients (18%) and were usually mild. CONCLUSION: Radiotherapy for lung cancer in this selected group of elderly patients is well tolerated with responses similar to those in younger patients.

Age Factors↗

Troponin I phosphorylation and myofilament calcium sensitivity during decompensated cardiac hypertrophy.

We have measured myocyte cell shortening, troponin-I (Tn-I) phosphorylation, Ca2+ dependence of actomyosin adenosinetriphosphatase (ATPase) activity, adenosine 3',5'-cyclic monophosphate (cAMP) levels, and myofibrillar isoform expression in the spontaneously hypertensive rat (SHR) during decompensated cardiac hypertrophy (76 wk old) and in age-matched Wistar-Kyoto rat (WKY) controls. The decreased inotropic response to beta-adrenergic stimulation previously observed in myocytes from 26-wk-old SHR was further reduced at 76 wk of age. In response to beta-adrenergic stimulation, Tn-I phosphorylation was greater in the 76-wk-old SHR than in the WKY, although cAMP-dependent protein kinase A (PKA)-dependent Tn-I phosphorylation in the SHR did not increase with progression from compensated (26 wk) to decompensated (76 wk) hypertrophy. We also observed a dissociation between the increased PKA-dependent Tn-I phosphorylation and decreased cAMP levels in the 76-wk-old SHR versus WKY during beta-adrenergic stimulation. Baseline Tn-I phosphorylation was significantly reduced in 76-wk-old SHR versus WKY and was associated with decreased basal cAMP levels and increased Ca2+ sensitivity of actomyosin ATPase activity. The change in myofilament Ca2+ sensitivity during beta-adrenergic stimulation in the 76-wk-old SHR (0.65 pCa units) was over twofold greater than in the 76-wk-old WKY (0.30 pCa units). We also determined whether embryonic troponin T isoforms were reexpressed in decompensated hypertrophy and observed significant reexpression of the embryonic cardiac troponin T isoforms in the 76-wk-old SHR. The significant decrease in Ca2+ sensitivity with beta-adrenergic stimulation in 76-wk-old SHR may contribute to the severely impaired inotropic response during decompensated hypertrophy in the SHR.

Actin Cytoskeleton↗

Biochemical characterization of recombinant factor IX.

Mature human factor IX is a 55,000-d glycoprotein with a modular domain structure and numerous posttranslational modifications. A recombinant form of human factor IX (rFIX) has been produced from a Chinese hamster ovary cell line that was engineered for high-level protein processing and expression. To ensure that the recombinant molecule contains the requisite structural and functional features of the plasma-derived form, rFIX was subjected to detailed biochemical and biophysical characterization. The laboratory studies showed that the posttranslational modifications and primary, secondary, and tertiary structures of rFIX were similar to those of plasma-derived factor IX (pdFIX). In addition, rFIX displayed a high degree of purity and a product release specification for specific activity that is > or = 200 IU/mg.

Amino Acid Sequence↗

Differential effects of interventions on the therapeutic alliance with patients with personality disorders.

The goal of this study was to examine the relationship between clearly defined therapist interventions and the therapeutic alliance with personality-disordered patients. Transcripts of one psychotherapy session for each of 5 subjects taking part in a long-term psychotherapy research project were rated for therapist interventions and therapeutic alliance to determine if specific interventions were followed by enhanced or diminished therapeutic work. Transference interpretations were followed by a deterioration in the therapeutic alliance when the alliance was weak, but by enhanced work when the alliance was solid. In patients with both strong and weak alliances, defense interpretations and supportive interventions enhanced therapeutic work without increasing defensiveness. Supportive interventions seemed to prepare the way for exploration and to repair ruptured alliances.

Adult↗

Progression of left ventricular hypertrophy does not change the sarcoplasmic reticulum calcium store in the spontaneously hypertensive rat heart.

The spontaneously hypertensive rat (SHR) is characterized by elevated blood pressure and the development of left ventricular hypertrophy. During compensatory hypertrophy in the SHR, (26 weeks) when baseline contractile function is normal or increased, the inotropic response to beta-adrenergic stimulation is impaired. We recently showed by electron probe microanalysis (EPMA) that the amount of Ca2+ stored in the sarcoplasmic reticulum (SR) following sympathetic stimulation is not decreased in the 26-week-old SHR heart. However, with disease progression, cardiac function declines further in the SHR and the response to beta-adrenergic stimulation is more impaired. To determine whether a decreased availability of SR Ca2+ is responsible for the severely depressed inotropic response in the older SHR, we used EPMA to measure directly the amount of Ca2+ stored in the SR following activation of the beta-adrenergic pathway in papillary muscles from 76-week-old SHR and Wistar-Kyoto (WKY) controls. In order to determine if there are other alterations in ion homeostasis, we also compared elemental content of A-band and mitochondria. Papillary muscles from 76-week-old SHR and WKY were stimulated by 10 microM isoproterenol and then rapidly frozen during relaxation. The elemental content of the junctional SR. A-band and mitochondria was measured by EPMA. We observed no significant difference in SR Ca2+ content between SHR and WKY. There was also no strain-dependent difference in mitochondrial or A-band Ca2+. Overall, these results indicate that the impaired response to beta-adrenergic stimulation in the SHR at 76 weeks is not due to altered availability of SR Ca2+.

Adrenergic beta-Agonists↗

Evaluation of specialists' outreach clinics in general practice in England: process and acceptability to patients, specialists, and general practitioners.

OBJECTIVES: The wider study aimed to evaluate specialists' outreach clinics in relation to their costs, processes, and effectiveness, including patients' and professionals' attitudes. The data on processes and attitudes are presented here. DESIGN: Self administered questionnaires were drawn up for patients, their general practitioners (GPs) and specialists, and managers in the practice. Information was sought from hospital trusts. The study formed a pilot phase prior to a wider evaluation. SETTING: Nine outreach clinics in general practices in England, each with a hospital outpatient department as a control clinic were studied. SUBJECTS: The specialties included were ear, nose, and throat surgery; rheumatology; and gynaecology. The subjects were the patients who attended either the outreach clinics or hospital outpatients clinics during the study period, the outreach patients' GPs, the outreach patients' and outpatients' specialists, the managers in the practices, and the NHS trusts which employed the specialists. MAIN OUTCOME MEASURES: Process items included waiting lists, waiting times in clinics, number of follow up visits, investigations and procedures performed, treatment, health status, patients' and specialists' travelling times, and patients' and doctors' attitudes to, and satisfaction with, the clinic. RESULTS: There was no difference in the health status of patients in relation to the clinic site (ie, outreach and hospital outpatients' clinics) at baseline, and all but one of the specialists said there were no differences in casemix between their outreach and outpatients' clinics. Patients preferred, and were more satisfied with, care in specialists' outreach clinics in general practice, in comparison with outpatients' clinics. The outreach clinics were rated as more convenient than outpatients' clinics in relation to journey times; those outreach patients in work lost less time away from work than outpatients' clinic patients due to the clinic attendance. Length of time on the waiting list was significantly reduced for gynaecology patients; waiting times in clinics were lower for outreach patients than outpatients across all specialties. In addition, outreach patients were more likely to be first rather than follow up attenders; rheumatology outreach patients were more likely than hospital outpatients to receive therapy. GPs' referrals to hospital outpatients' clinics were greatly reduced by the availability of outreach clinics. Both specialists and GPs saw the main advantages of outreach clinics in relation to the greater convenience and better access to care for patients. Few of the specialists and GPs in the outreach practices held formal training and education sessions in the outreach clinic, although over half of the GPs felt that their skills/expertise had broadened as a result of the outreach clinic. CONCLUSIONS: The processes of care (waiting times, patient satisfaction, convenience to patients, follow up attendances) were better in outreach than in outpatients' clinics. However, waiting lists were only significantly reduced for gynaecology patients, despite both GPs and consultants reporting reduced waiting lists for patients as one of the main advantages of outreach. Whether these improvements merit the increased cost to the specialists (in terms of their increased travelling times and time spent away from their hospital base) and whether the development of what is, in effect, two standards of care between practices with and without outreach can be stemmed and the standard of care raised in all practices (eg, by sharing outreach clinics between GPs in an area) remain the subject of debate. As the data were based on the pilot study, the results should be viewed with some caution, although statistical power was adequate for comparisons of sites if not specialties.

Attitude of Health Personnel↗

Mitochondrial calcium content in isolated perfused heart: effects of inotropic stimulation.

We tested the hypothesis that in the intact heart, mitochondrial metabolism is activated by mitochondrial Ca2+ uptake during increased work. We measured left ventricular pressure (LVP), pyruvate dehydrogenase (PDH) activity, and mitochondrial and A band elemental content by electron probe microanalysis (EPMA) in Langendorff-perfused hamster hearts under control conditions, after isoproterenol (10(-6) M) stimulation, and after increasing perfusion pressure from 60 to 100 mmHg. Hearts were rapidly frozen, then EPMA was performed on cryosections cut from the surface of the frozen hearts; PDH activity was measured from the same area. Isoproterenol and elevated perfusion pressure increased LVP by 185 +/- 21 and 58 +/- 14%, respectively, versus controls. PDH activity increased from 10.4 +/- 1.5 (mean +/- SE) nmol.min-1. mg protein-1 (controls) to 21.6 +/- 3.5 (isoproterenol) and 18.5 +/- 3.2 nmol.min-1.mg protein-1 (increased perfusion pressure). There was no significant change in mitochondrial Ca1 in response to isoproterenol [1.2 +/- 0.1 (mean +/- SE) mmol/kg dry wt] or increased perfusion pressure (1.1 +/- 0.1) versus controls (1.0 +/- 0.1). These results suggest that, in the intact heart, mechanisms other than mitochondrial Ca2+ uptake may contribute to PDH activation and increased cardiac work.

Animals↗

Troponin I phosphorylation in spontaneously hypertensive rat heart: effect of beta-adrenergic stimulation.

We compared baseline and protein kinase A (PKA)-dependent troponin I (TnI) phosphorylation in 32Pi-labeled left ventricular myocytes from hearts of 26-wk spontaneously hypertensive rats (SHR) and Wistar-Kyoto controls (WKY). TnI phosphorylation was normalized to myosin light chain 2 phosphorylation, which was invariant. There was no difference in baseline TnI phosphorylation in SHR and WKY, but stimulation with isoproterenol, norepinephrine plus prazosin, forskolin, chloroadenosine 3',5'-cyclic monophosphate, or 3-isobutyl-1-methylxanthine caused a greater increase in TnI phosphorylation in the SHR than in the WKY. This was observed both in the presence and absence of the phosphatase inhibitor calyculin A; thus the differences in TnI phosphorylation between SHR and WKY are not due to decreased phosphatase activity in the SHR. After stimulation of the beta-adrenergic pathway, phospholamban phosphorylation was not different in SHR and WKY, indicating that the observed differences may be specific for PKA phosphorylation of TnI. The increased PKA-dependent TnI phosphorylation in the SHR resulted in decreased Ca2+ sensitivity of actomyosin adenosinetriphosphatase activity as compared with the WKY. We conclude that increased PKA-dependent TnI phosphorylation in the SHR may contribute to the impaired response to sympathetic stimulation.

1-Methyl-3-isobutylxanthine↗

Will enrolled nurses feature in the English National Board's equal opportunities policy research?

The English National Board for Nursing, Midwifery and Health Visiting is planning to evaluate the implementation of its equal opportunities policy with reference to the recruitment into nurse education and training of people from ethnic minority groups. This paper argues the case for including in this initiative a close examination of the processes of conversion from enrolled to registered nurse status and of the experiences of those nurses seeking promotion through this route. Past recruitment of many black and ethnic minority people into this level of nursing and their continuing service there makes this a potentially fruitful area of enquiry.

Career Mobility↗

Defense styles, hostility, and psychological risk factors in male patients with personality disorders.

The purpose of this study was to compare ratings of defense styles and hostility in male patients with personality disorders, to determine whether either of these is related to a borderline diagnosis, or to specific psychological risk factors. Subjects with personality disorders were divided into borderline personality disorder (BPD) (N = 61) and non-BPD (N = 60) groups were given both the Defense Style Questionnaire (DSQ) and the Buss-Durkee Guilt-Hostility Inventory (BDHI). Risk factors were measured by a developmental interview and the the Parental Bonding Index. The BPD group reported more maladaptive and image distorting defenses on the DSQ, as well as higher ratings on the BDHI. Ratings on both dependent measures were strongly related to diagnosis, and more weakly to measures of psychological risk factors. Thus, in men with personality disorders, immature defense styles and high levels of hostility are strongly associated with a borderline diagnosis.

Adolescent↗

Making sense of action research through the use of a typology.

Commenting on earlier work in the Journal of Advanced Nursing on action research, this paper takes up the theme of definition and approach and presents an original action research typology. Three key criteria of action research--'reeducation', 'problem focus', and 'improvement and involvement'--are related to four broad types of action research: 'experimental', 'organizational', 'professionalizing' and 'empowering'. The typology is of general relevance not only to action researchers but to any project concerned to resolve problems and bring about improvements in practice, including evaluation research. Following discussion of the typology, it is used to analyse three different action research projects, including one conducted by the authors in collaboration with a project team. It is shown that each of these projects, which are all concerned in some way to improve standards of nursing care in hospitals, contains elements of different types which may at times be in conflict. The ability to recognize this and to be explicit about the different types may assist action researchers in selecting an appropriate approach and in anticipating problems which may arise during the course of a project's life.

Health Services Research↗

Activation of purinergic receptors triggers oscillatory contractions in adult rat ventricular myocytes.

Extracellular ATP is an important neurotransmitter that modulates cardiac function by activation of purinergic receptors. In this study, the effect of P2 purinergic receptor activation on contractions and on [Ca2+]i was investigated in adult rat ventricular myocytes. Fura 2 was used to measure [Ca2+]i, and video edge detection was used to measure contraction. Superfusion of 2-methylthio-adenosine-5'-triphosphate (2-M-S-ATP) over quiescent myocytes induced oscillations in contraction and in [Ca2+]i. The frequency of the oscillatory contractions increased with increasing concentrations of 2-M-S-ATP, but the amplitude of contractions varied from cell to cell and was independent of the concentration of 2-M-S-ATP. During electrical stimulation, activation of purinergic receptors in myocytes potentiated the amplitude of contraction and induced arrhythmias. In populations of quiescent myocytes, the plateau phase of the [Ca2+]i signal evoked by 2-M-S-ATP could be shown to represent summed oscillations in [Ca2+]i in individual cells. Pretreatment of quiescent myocytes with thapsigargin or caffeine reduced or abolished the oscillations in contractions and in [Ca2+]i triggered by 2-M-S-ATP, indicating a dependence of the oscillations on uptake and release of Ca2+ by the sarcoplasmic reticulum. These data demonstrate the novel phenomenon that activation of purinergic receptors in quiescent myocytes stimulates oscillations in [Ca2+]i and contraction. In electrically stimulated myocytes, activation of purinergic receptors triggers oscillatory contractions and potentiates the amplitude of electrically triggered contractions.

Adenosine Triphosphate↗

Decreased inotropic response to beta-adrenergic stimulation and normal sarcoplasmic reticulum calcium stores in the spontaneously hypertensive rat heart.

Cardiac hypertrophy in the spontaneously hypertensive rat has been shown to be accompanied by a diminished inotropic response to beta-adrenergic stimulation. This diminished response has been attributed to abnormalities in various components of the beta-adrenergic signaling system. There is also evidence that regulation of intracellular Ca2+ cycling may be altered in the hypertrophied heart of the spontaneously hypertensive rat. We proposed that the diminished response to beta-adrenergic stimulation may reflect abnormalities in Ca2+ cycling, specifically alterations in the ability of the sarcoplasmic reticulum to effectively release and resequester Ca2+. We have used the unique combination of functional measurements on isolated, isometrically contracting papillary muscles from hearts of 26-week-old spontaneously hypertensive rats and their Wistar-Kyoto controls, together with electron probe microanalysis measurements of sarcoplasmic reticulum Ca2+ content in the same muscles after rapid freezing, to determine the availability of Ca2+ for activation of contraction, following beta-adrenergic stimulation. We observed a significant decrease in the inotropic response to beta-adrenergic stimulation in papillary muscles from the spontaneously hypertensive rats, as compared with Wistar-Kyoto controls, however in these same muscles, frozen during relaxation, there was no evidence of an accompanying decrease in the size of the sarcoplasmic reticulum Ca2+ store. In an additional group of muscles which were frozen during contraction, the amount of Ca2+ remaining in the sarcoplasmic reticulum after stimulated release was also not different in the two strains. These results indicate that the decreased inotropic response to beta-adrenergic stimulation in hypertrophied hearts of the spontaneously hypertensive rat is unlikely to be due to decreased availability of Ca2+ for activation of contraction. Additionally, to determine whether there is intracellular Ca2+ overload in the cardiac muscle cells of hearts of spontaneously hypertensive rats, we measured the amount of Ca2+ in mitochondrial and at the level of the myofilaments by electron probe microanalysis. These results indicate that intracellular Ca2+ overload does not accompany cardiac hypertrophy in the spontaneously hypertensive rat. This study therefore shows no correlation between altered intracellular Ca2+ cycling and the decreased inotropic response to isoproterenol in the spontaneously hypertensive rat at 26 weeks of age.

Actin Cytoskeleton↗

Satisfying solutions? A review of some unresolved issues in the measurement of patient satisfaction.

The measurement of patient satisfaction has been encouraged by a growing consumer orientation in health care, especially since it yields information about consumers' views in a form which can be used for comparison and monitoring. However, drawing on literature from a variety of sources, this paper suggests that there remain several unresolved issues relating to the measurement of satisfaction, and some serious questions about the validity of the concept. It is argued that current approaches to measuring satisfaction may not be grounded in the values and experiences of patients; therefore satisfaction surveys could be denying patients the opportunity to have their opinions included in the planning and evaluation of health care services.

Consumer Advocacy↗

Exploring patient satisfaction with out-patient services.

Despite the widespread use of satisfaction surveys to obtain patients' views about health services, the validity and relevance of self-completion questionnaire surveys has been questioned. This paper reports on an exploratory, qualitative investigation into patients' perspectives on satisfaction and dissatisfaction with out-patient care. Eighty-one new referrals to two out-patient clinics were interviewed before and after their first consultation. Of this initial sample, 23 were interviewed again at their follow-up appointment and a further 10 were interviewed in depth at a location of their choice. The features of the service that drew appreciative comments when they were thought to be present, and criticism when they were felt to be lacking, were: humanity, efficiency, informativeness and continuity of communication. Examples of these features are discussed using patients' own words to illustrate their perspectives. The study demonstrates that unstructured approaches to service evaluation can be employed to develop services which are genuinely listening to their users' views.

Ambulatory Care↗