Setting standards in sports medicine education.
Explore the source record for details and available documents.
Education, Medical↗
Biomedical subjects
M Fraser
Publications and source records attributed to M Fraser.
Multiple centrosomal microtubule organising centres and increased microtubule stability are early features of VP-16-induced apoptosis in CCRF-CEM cells.
Microtubular reorganisation contributing to apoptotic morphology occurs in normal and neoplastic cells undergoing apoptosis induced by cytotoxic drugs [1-3]. The aim of this study was to correlate the changes in the microtubules (MTs) with behavior of the centrosome in apoptotic cells, and to see whether post-translational changes in tubulin occurred with the emergence of apoptotic MT bands. Apoptosis was induced in the human T-cell leukaemia line (CCRF-CEM) by treatment with 17 microM etoposide over a 4 h period. The time course of changes was assessed using flow cytometry (FCM) and immunocytochemistry in cells labelled for a centrosomal antigen (CSP-alpha) or alpha-tubulins. One hour following treatment we observed multiple centrosomal microtubule organising centres (MTOCs) associated with the nucleus and the transient appearance of a subset of stable MTs detected with an antibody specific for acetylated alpha-tubulin, as the bands of MTs which lobulate the nucleus are formed. The altered properties of the MTs thus reflect changes in function as apoptosis progresses.
Antigens↗
How do we increase awareness of osteoporosis?
In the UK and throughout Europe 10 years ago, osteoporosis was not a word that existed in the vocabulary of the general public. The majority of doctors had dismissed osteoporosis as a normal process of ageing, affecting only the very elderly and about which nothing could be done. Why should it matter that awareness of osteoporosis was so low among the general public and the medical professions? For the newly launched National Osteoporosis Society in the UK, several questions needed to be answered: if osteoporosis was not an inevitable part of growing old, was it really a disease and how could action be implemented to treat it and prevent it? If fracture numbers and their costs were so much higher than had been thought, who should be informed of this? And if there were ways of treating and preventing osteoporosis, who should be made more aware, what should they be told, and how could such awareness-raising be done and paid for? Before real action could be undertaken, a considerable awareness programme would be needed to radically-alter traditional beliefs about bone health.
Clinical Competence↗
Developmental regulation of preproenkephalin (PENK) gene expression in the adrenal gland of the ovine fetus and newborn lamb: effects of hypoxemia and exogenous cortisol infusion.
Development of the fetal adrenal gland is crucial not only for maturation of several fetal organ systems and the initiation of parturition, but also for the development of the fetal response to stress. The enkephalin-related peptides are present in the chromaffin cells of the fetal adrenal medulla and are secreted in response to stress and with sympathetic stimulation. However, changes in expression of preproenkephalin (PENK) with gestation and in response to stress have not been studied in detail. Therefore we examined the developmental pattern of PENK gene expression in the adrenal gland of fetal and newborn lambs, and of adult sheep. We also determined whether levels of PENK mRNA in the fetal adrenal gland changed in response to exogenous glucocorticoids in late gestation, or in response to hypoxemia. Adrenal glands were removed from fetal sheep, lambs and adult sheep at different stages of development for measurement of PENK mRNA. Cortisol was infused (5 micrograms/min) for 12, 24 or 96 h beginning on day 124-129 of gestation. Moderate hypoxemia was induced for 48 h beginning on day 126-130, or at day 134-136 of gestation, by lowering the maternal fractional inspired oxygen. At the end of the treatment periods, the ewes and fetuses were euthanized. Adrenal PENK mRNA were measured by Northern blot analysis. PENK mRNA levels in fetal adrenals were significantly higher (P < 0.05) on days 140-141 of gestation than earlier in pregnancy, and then decreased significantly with the onset of parturition (days 142-146). After cortisol infusion to the fetus for 96 h there was a significant reduction in adrenal PENK mRNA levels. Hypoxemia resulted in a significant increase in PENK mRNA levels in fetuses at day 126-130 of gestation, but not at the later time in pregnancy when endogenous plasma cortisol concentrations were higher. We conclude that there is a decrease in levels of PENK mRNA in the fetal adrenal gland before parturition at the time of the endogenous prepartum rise in plasma cortisol. Hypoxemia led to an elevation of PENK mRNA levels in fetuses at less than 130 days, but after that time, when the basal and stimulated cortisol responses had risen, there was no significant effect of hypoxemia on PENK mRNA. Cortisol infusion to the fetus at this stage of pregnancy resulted in a decrease in adrenal PENK mRNA levels. We suggest that cortisol may play an important role in the regulation of fetal adrenal PENK mRNA levels and enkephalin synthesis by the adrenal gland of the fetal sheep.
Adrenal Glands↗
Exploring the everyday world of the patient in isolation.
PURPOSE/OBJECTIVES: To explore the phenomenon of isolation from the perspective of patients cared for in reverse isolation for bone marrow transplant (BMT). DESIGN: Interpretive, phenomenologic. SETTING: Hematology and bone marrow transplant unit of a large teaching hospital in Brisbane, Australia. SAMPLE: Seven patients undergoing BMT. METHODS: Phenomenologic interviews and thematic analysis of transcribed data. MAIN RESEARCH VARIABLE: Patient's day-to-day experiences of reverse isolation. FINDINGS: Although appreciative of the physical care and attention given to them, participants did not convey a sense that healthcare professionals understood the experience of the BMT recipient's isolation or illness from their perspective. Major themes elicited from analysis of the transcripts included (a) striving to take charge, which refers to participants' attempts to maintain control in a seemingly out-of-control situation. (b) intellectualizing the need for isolation, and (c) being in touch: contact with family and staff. CONCLUSIONS: Elements of caring for the patient appeared to dominate the comments associated with staff contact. Other forms of care (e.g., caring about) emphasize the importance of nurses understanding and connecting with peoples' meanings and experiences of their illness and treatment. IMPLICATIONS FOR NURSING PRACTICE: Although all participants were aware that they could ask for information about their diagnosis and treatment at any time, most had not been offered the opportunity to describe their feelings or experiences before. Unless nurses take more initiative to gain insight and a greater appreciation of the patient's understanding of his or her situation, they will continue to focus on unidimensional aspects of care and neglect the multidimensional or holistic nature of nursing care.
Adaptation, Psychological↗
Delayed reactivation of hepatitis B infection after cladribine.
Explore the source record for details and available documents.
Aged↗
Locations and molecular forms of gastrin-releasing peptide-like immunoreactive entities in ovine pregnancy.
Large quantities of gastrin-releasing peptide-like immunoreactivity (GRP-LI) are present in ovine pregnancy fluids (allantoic fluid > fetal plasma > esophageal fluid = amniotic fluid = urine > maternal plasma) and in term endometrium (60 +/- 29 pmol.g-1) and myometrium (4.5 +/- 1.2 pmol.g-1). The larger molecular size [greater than GRP (1-27)] of this GRP-LI entity is not due to a GRP binding protein nor to a C-terminal extension of GRP. In contrast, ovine fetal colon extracts appear to contain the usual GRP (1-27) and GRP (18-27) forms. Hence, the uterus, not the fetus, is the probable source of this novel GRP-like peptide. It apparently acts as a hormone in ovine pregnancy and may play an important role in fetal-placental development.
Amino Acid Sequence↗
Perceived usefulness of the Director of Public Health Annual Report: a consumer survey.
The Annual Report of the Director of Public Health for Forth Valley was evaluated in terms of its usefulness as perceived by recipients. Six months after publication, more than half had retained their copy and a similar proportion had made use of it or anticipated using it in the coming year. Its main use was as a reference. The Report had least impact upon Consultants and General Practitioners.
Attitude of Health Personnel↗
Age-adjusted recurrence risks for relatives of patients with multiple sclerosis.
Familial aggregation is a cardinal epidemiological feature of multiple sclerosis, but few investigators have systematically examined recurrence risks for relatives of affected individuals in the United Kingdom. As part of a cross-sectional study of multiple sclerosis in Cambridgeshire, pedigree details were taken on 674 probands. Sex-specific, crude and age-adjusted recurrence risks were assessed amongst relatives of probands, applying a statistical model based on the observed age at onset of affected individuals and providing risks for clinical counselling. Details on year of birth, present age or age at death, and disease status were available on 11 391 relatives of successive probands. Nineteen percent of patients reported an additionally affected relative; 128 non-proband affected relatives were identified and the highest risk was observed for sisters. There was a systematic reduction in relative risk with genetic distance from the proband and no preferential recurrence for maternal or paternal relatives.
Adult↗
Pattern of 11 beta-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid expression in the ovine uterus during the estrous cycle and pregnancy.
The present study was designed to examine the pattern and cellular localization of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) gene expression in the ovine uterus during pregnancy and at 3 mo postpartum. High levels of 11 beta-HSD1 mRNA were detected in the endometrium from Days 60 to 143 (term = 145 days), and the levels did not change significantly during that time. The level of 11 beta-HSD1 mRNA in the endometrium was always much higher than that in the myometrium, in which the mRNA was not readily detectable throughout pregnancy; at 3 mo postpartum, 11 beta-HSD1 mRNA became undetectable in both endometrium and myometrium. Within the endometrium, intense immunoreactive 11 beta-HSD1 was localized exclusively to the luminal epithelium, and the intensity of 11 beta-HSD1 immunostaining closely followed the level of 11 beta-HSD1 mRNA. To determine whether the level of endometrial 11 beta-HSD1 mRNA was related to the status of ovarian function, tissues from non-pregnant animals at different stages of their reproductive cycle were also examined. It was found that 11 beta-HSD1 mRNA was undetectable in the endometrium of cycling animals up to Day 9 of the estrous cycle but was detectable thereafter. Taken together, these results demonstrate that within the ovine uterus the endometrium is always the dominant site of 11 beta-HSD1 gene expression in relation to the myometrium. Furthermore, the expression of 11 beta-HSD1 mRNA in the endometrium is closely related to the status of the reproductive cycle. The mRNA for 11 beta-HSD1 is highly expressed only during pregnancy and in non-pregnant animals during the late luteal phase. Since circulating levels of progesterone are elevated during both of these periods, the present findings suggest a progesterone effect on uterine 11 beta-HSD1 gene expression.
11-beta-Hydroxysteroid Dehydrogenases↗
Characterization and subcellular localization of human Pmel 17/silver, a 110-kDa (pre)melanosomal membrane protein associated with 5,6,-dihydroxyindole-2-carboxylic acid (DHICA) converting activity.
Pmel 17 is preferentially expressed in pigment cells in a manner suggestive of involvement in melanin biosynthesis. The gene is identical to the silver (si) pigmentation locus in mice. We now produced a recombinant glutathione-S-transferase-human Pmel 17 infusion protein and raised polyclonal antibodies against it to confirm the ultrastructural location and presumed site of action predicted by the deduced primary structure of Pmel 17/silver, and to authenticate the specificity of the DHICA converting function as inherent to the silver-locus protein. Full-length Pmel 17 cDNA also produced in insect cells in a baculovirus expression vector to ensure that activity did not originate from a co-precipitated protein. Natural hPmel 17 from human melanoma cells has an approximate molecular size of 100 kDa. By immunoperoxidase electron microscopic cytochemistry, the antigen was localized to the limiting membranes of premelanosomes and presumed premelanogenic cytosolic vesicles and, to a minor extent, in the premelanosomal matrix. In an in vitro assay, both the natural and the recombinant Pmel 17 accelerated the conversion of DHICA to melanin. This activity was inhibited by the anti-Pmel 17 polyclonal antibodies, indicating that the acceleration of DHICA conversion by natural protein is genuine and cannot be due to contaminating complexed proteins. We suggest that in situ Pmel 17/silver is a component of a postulated premelanosomal/melanosomal complex of membrane-bound melanogenic oxidoreductive enzymes and cofactors, in analogy to the electron transfer chain in mitochondria.
Animals↗
Multiple sclerosis in south Cambridgeshire: incidence and prevalence based on a district register.
STUDY OBJECTIVE: To establish an updated prevalence and incidence figure for multiple sclerosis on 1 July 1993, to determine the fate of the 374 patients prevalent in 1990, and to establish the origin of incident patients. DESIGN: Case ascertainment was from several sources including departmental records, local branches of the Multiple Sclerosis Society, general practitioners, nursing homes, and residential facilities for the disabled. Data collection was by personal interview using a standardised questionnaire and by retrospective analysis of departmental case notes. A prospective incidence register of newly diagnosed patents was maintained from 1990. SETTING: The Cambridge Health District of East Anglia covering 340,910 hectares in area and a population of 290,700. PATIENTS: Altogether 441 patients prevalent on 1 July 1993 were identified, of whom 328 were contacted so that clinical data could be collected. Seventy patients (16%) either declined to take part or access was denied by their general practitioner; 8 (2%) had died; and 35 (8%) were too ill or failed to respond to several requests for contact. MAIN RESULTS: A comprehensive re-evaluation of the south Cambridgeshire multiple sclerosis register revealed a prevalence of 441/290,700 population (152/10(5)) for all disease classifications on 1 July 1993. This represented an increase of 18% from 1990 and was a result of 138 additions and 71 deletions from the original list of 374 patients. The sex ratio of prevalent patients was 2.6 F:M, the mean age at disease onset was 31.7 years, and the mean age was 49 years. Mortality for 1990-93 was 3.3/10(5)/year and prospective maintenance of an incidence register recorded 96 new diagnoses for all classifications of multiple sclerosis over the five year period 1990-94 (6.6/10(5)/year). CONCLUSIONS: The increase in prevalence mainly resulted from improved case ascertainment identifying a further 58 patients who had been prevalent in 1990. Comparisons with other serial studies within the United Kingdom show similarities in proportional increase with successive studies indicating that serial survey may in part account for the observed latitudinal gradient within the United Kingdom. However, the observed prevalence (152/10(5)) in this second survey still falls short of the figure estimated from incidence and mortality data (186/10(5)).
Adolescent↗
Regional blood flow and the endocrine response to sustained hypoxemia in the preterm ovine fetus.
To determine the circulatory response of the preterm fetus to a sustained hypoxic insult, regional blood flow was measured (microsphere technique) in 12 unanesthetized fetal sheep (0.75 gestation) during a normoxic control period, after 1 h and 8 h of sustained hypoxemia, and after a 1-h recovery period. Associated endocrine changes which might relate to organ-specific changes in blood flow were also assessed. Myocardial and cerebral blood flow were increased by 240 and 90%, respectively, such that oxygen delivery to the heart was well maintained throughout the study, whereas that to the brain was significantly decreased by 8 h of hypoxic study. Regional blood flows for all structures within the brain showed similar percent increases, except that for the pituitary gland, where the increase was much smaller, and that for the choroid plexus, where blood flow actually fell. Whereas blood flow to upper body muscle showed no significant change throughout the study, that to the thyroid was increased by 70% by 1 h of hypoxic study but fell thereafter. Adrenal cortical blood flow relative to that of the medulla was increased 3-fold by 8 h of hypoxic study, indicating a differential effect of sustained hypoxia on these vascular beds. Although pituitary and thyroid blood flows showed no relationship to respective trophic and/or secretory hormones measured, values for adrenal cortical flow relative to medullary flow were well correlated with plasma concentrations of ACTH. It is concluded that the "centralization" of blood flow to vital organs in response to a sustained hypoxic insult is qualitatively similar for both the preterm and near term ovine fetus and that hypoxic regulatory mechanisms may be better protective of the heart. Additionally, a role for the functional activation of the adrenal gland in its blood flow response to sustained hypoxemia is suggested.
Acidosis↗
Clinical concordance in sibling pairs with multiple sclerosis.
As part of a linkage study, we obtained clinical, demographic, and genetic information on 210 families with siblings concordant for multiple sclerosis (MS). Twenty-eight pairs were excluded and information was incomplete in a further 16 pairs; intrafamilial comparisons of the clinical course are reported on the remaining 166 families (155 pairs and 11 trios) in whom complete data sets were available. The demographic characteristics were comparable to those of recently performed prevalence studies in the United Kingdom, supporting the application of results in these families for genetic linkage studies in MS. We observed no significant correlation for age at onset after correction for selection bias but found a minor correlation for year at onset, which we speculate is due to earlier recognition of symptoms in second affected siblings. There was no pair-wise concordance for presenting symptoms or disability at time of assessment. However, there was a strong correlation for disease course and to a lesser degree for gender. In addition, the familial recurrence rate was 33%, almost twice that previously recorded in a local prevalence study. These results suggest that the etiology of MS involves random exposure to an, as yet unidentified, environmental trigger and the clinical features of familial disease are modified by inherited factors. That the risk of developing MS is not spread uniformly among families has important implications for the counseling of individuals with familial disease.
Female↗
Dopaminergic regulation of pituitary function in the late-gestation fetal sheep.
Development of the fetal ovine pituitary is essential for normal maturation and initiation of the parturition process, as well as for orchestrating endocrine responses to stress in utero. Increases in the biosynthesis of ACTH and prolactin (PRL) occur in the late-gestation fetal sheep pituitary. In the anterior lobe (AL) of the pituitary, pro-opiomelanocortin (POMC) biosynthesis and processing are primarily regulated by corticotrophin-releasing hormone and vasopressin. However, POMC in the intermediate lobe (IL) and PRL in the AL are known to be primarily regulated by dopamine, via the D2 receptor, in adult sheep. Because of the importance of ACTH and PRL during gestation we have investigated a potential role of dopamine in the control of both IL melanotrophs and AL lactotrophs and corticotrophs, in late gestation. Catheters were implanted into a maternal femoral artery and vein, fetal carotid artery and jugular vein as well as into the amniotic cavity. At day 130 of gestation, fetuses were infused intravenously with either the specific D2 receptor agonist bromocriptine (n = 5) or vehicle (n = 5), for 5 days. Blood samples were taken throughout the experiment and pituitaries were removed at the end of the treatment period. Bromocriptine caused a significant decrease (> 50%) in POMC mRNA levels in the IL. In contrast, bromocriptine had no significant effect on POMC mRNA levels or distribution in the AL. Fetal arterial ACTH and cortisol concentrations were unaffected by the bromocriptine infusion, compared with vehicle-infused controls. There was a dramatic decrease (> 80%) in plasma PRL concentrations, compared with the control fetuses. However, PRL mRNA levels in the AL were not significantly affected by bromocriptine. In conclusion, we have found that bromocriptine inhibits aspects of both melanotroph and lactotroph function in late-gestation fetal sheep. The data indicate that the fetal pituitary possesses functional D2 receptors in late gestation.
Adrenocorticotropic Hormone↗
Characterization of the signal transduction pathway mediating gamma ray-induced inhibition of DNA synthesis in human cells: indirect evidence for involvement of calmodulin but not protein kinase C nor p53.
Cultured cells from patients inheriting the rare cancer-prone and radiotherapy-sensitive disorder ataxia-telangiectasia (A-T) exhibit anomalies in cell cycle control and protein kinase C (PKC)-mediated upregulation of p53 protein following exposure to ionizing radiation. It remains unclear, however, as to whether this irregularity in a p53-dependent signal transduction pathway controlling the G1/S checkpoint is causally linked to the most consistent molecular hallmark of A-T-namely, marked attenuation in the inhibition of replicative DNA synthesis at early times (< or = 2 h) after irradiation [radioresistant DNA synthesis (RDS)]. We report here that treatment of normal human fibroblast strains with inhibitors of calmodulin (CaM) (i.e. W7 and W13) and CaM-dependent protein kinases II and IV (i.e. KN62) prior to radiation exposure elicits an 'A-T-like' RDS phenotype, whereas treatment with PKC inhibitors (e.g. staurosporine) does not produce this response. Moreover, at 1 h post-gamma irradiation A-T fibroblasts undergo normal induction of p53 protein while exhibiting the RDS trait. At later times (e.g. 4 h) following irradiation, however, these A-T cells contain abnormally low levels of p53 protein, as do their lymphoblastoid cell line counterparts during the entire post-gamma ray incubation period. On the other hand, human cells which either lack the p53 gene completely (i.e. HL60 leukemia cells) or harbor a germline mutation in the gene (i.e. Li-Fraumeni syndrome cells) shut down their DNA replication machinery normally upon sustaining radiation damage. We thus conclude that the transitory delay in DNA synthesis routinely experienced by human cells in the face of radiation injury is mediated through a CaM-dependent regulatory cascade which involves neither PKC nor p53 protein. Accordingly, A-T cells appear to be malfunctional in at least two distinct radiation-responsive signalling pathways, one regulating the G1/S checkpoint and governed by p53 and PKC and another controlling passage through S phase and requiring CaM.
Ataxia Telangiectasia↗
Mitochondrial ATP synthase alpha-subunit gene amplified in a retinoblastoma cell line maps to chromosome 18.
The human retinoblastoma cell line Y79 has multiple copies of the MYCN gene and the DEAD box gene DDXI. Both genes have been mapped to chromosome band 2p24. A third gene, encoding the alpha-subunit of mitochondrial ATP synthase (ATPSA), is also amplified in Y79. Here we report that there are at least four human mitochondrial ATPSA-related genes located on four different chromosomes. The ATPSA gene that is amplified in Y79 originates from chromosome 18. In Y79, the amplified copies of both the ATPSA and the MYCN genes are located on a homogeneously staining region (HSR) at chromosome band Ip34.
Animals↗
Gonadotrophin surge-attenuating factor bioactivity is present in follicular fluid from naturally cycling women.
Rat pituitary monolayer bioassays were used to compare gonadotrophin surge-attenuating factor (GnSAF) bioactivity in follicular fluid from 12 follicles in 10 spontaneously cycling women with that in pooled follicular fluid from women undergoing ovulation induction. Expressed as ED50S (microliter follicular fluid/well producing 50% of maximal effect), GnSAF bioactivity was detectable in all spontaneous follicular fluid samples (1.4-33.3 microliters/well) and in follicular fluid from women undergoing ovulation induction (6.8 microliters/well). This GnSAF bioactivity was unaffected by pre-incubation with an inhibin antibody. When the data were grouped according to whether the recovered oocytes fertilized in vitro or not, the fertilized group contained significantly greater GnSAF bioactivity than the unfertilized group (5.3 +/- 1.1 and 14.1 +/- 2.6 microliters/well respectively, P < 0.05). While both inhibin bioactivity (9.7 +/- 1.4 and 28.9 +/- 12.1 microliters/well) and immunoreactivity (36.8 +/- 2.2 and 21.0 +/- 3.0 and ng/ml) were also greater (P < 0.01) in the fertilized compared with the unfertilized groups respectively, there were no other significant differences between the two groups. We conclude that GnSAF is found in follicular fluid from spontaneously cycling women, supporting in-vivo evidence for the involvement of GnSAF in feedback control of the ovary-pituitary axis.
Adult↗