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Biomedical subjects

E Morrison

Publications and source records attributed to E Morrison.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effect of social deprivation on disease severity and outcome in patients with rheumatoid arthritis.

OBJECTIVE: Social deprivation is now recognised to have an important impact on morbidity and mortality. This study sought to ascertain the effect of deprivation, if any, on disease severity, functional disability, and outcome in rheumatoid patients in Glasgow. METHODS: 814 patients with rheumatoid arthritis (RA) were assessed for clinical, functional, and laboratory indices of disease activity. Deprivation categories for individual patients were determined using the Carstairs index. Five year follow up is available for 440 patients. RESULTS: The study population of RA patients live largely in the most deprived areas. Patients from deprived areas have significantly poorer function at outset and at five years as defined by the Health Assessment Questionnaire (HAQ) score. This is not attributable to differences in disease duration in patients from the most deprived regions or compliance with treatment. Furthermore, these patients do not achieve over five years the initial functional level of those living in the most advantaged localities. CONCLUSION: RA patients from deprived areas have poorer function, which is associated with greater need--medical, social, and paramedical. Strategies and resources for healthcare need to be adjusted according to this variation.

Adult↗
PubMed1997

Post-translational processing of proopiomelanocortin in the pituitary and in the brain.

Proopiomelanocortin (POMC) is a neuropeptide precursor molecule which is translocated to the secretory pathway within neuroendocrine cells. It is cleaved by the action of endopeptidases to yield mature peptides like adrenocorticotrophic hormone (ACTH), beta-lipotrophin (beta-LPH), beta-endorphin. In this review we present evidence on the cleavage specificities and structure of endoproteases which cleave neuropeptide precursors at pairs of basic amino acids and on the identity and mode of action of exopeptidases. This information is derived from cloning of their corresponding cDNAs and subsequent expression within neuroendocrine cells; and also from biochemical studies. We discuss the intracellular targeting and sorting mechanisms of POMC within neuroendocrine cells. We also examine the tissue-specific post-translational processing of POMC within the anterior and intermediate lobes of the pituitary gland and within the central nervous system.

Animals↗
PubMed1997

Assessment of guided tissue regeneration procedures in intrabony defects with bioabsorbable and non-resorbable barriers.

THE PURPOSE OF THIS STUDY was to assess periodontal regenerative techniques in intrabony defects utilizing a bioabsorbable, polylactic acid (PLA) barrier or the non-resorbable, expanded polytetrafluoroethylene (ePTFE) barrier. Thirty patients (26 to 64 years old) each with one radiographically evident intrabony periodontal lesion of probing depth > or = 6 mm participated in a 12-month controlled clinical trial. The subjects were randomly divided into two independent groups. The test group (n = 16) received a PLA barrier. The control group (n = 14) received an ePTFE barrier. Plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and bone fill were recorded by a single calibrated examiner not involved with the surgical treatment prior to surgery, and at 6, 9, and 12 months postsurgery. The treatment results were statistically analyzed utilizing two sets of data. The "averaged-site" data set consisted of values computed from the averaging of measurements from all sites encompassing the defect. The second data set was comprised of only the deepest measurement of the defect. Statistical tests used to analyze these data sets included the t-test and paired t-test for parametric data and the Wilcoxon rank sum test and the Wilcoxon signed rank test for non-parametric data. Analyses with both the averaged-site data and deepest-site data resulted in significant improvements in PD reductions, CAL, and bone fill, after 12 months of healing with both the PLA and ePTFE barrier devices. Comparisons of healing response between treatments found no significant differences when the averaged-site data were analyzed. When only the deepest site of the defect was considered, the control group resulted in significantly more attachment gain (ePTFE, 3.36 mm; PLA, 1.75 mm; P < 0.02) and shallower probing depths (ePTFE, 3.29 mm; PLA, 4.69 mm; P < 0.01) than the test group. In intrabony defects, the use of PLA or ePTFE barriers in GTR procedures yielded comparable clinical results; however, in this study, data analysis using the deepest site of the defect found, after 12 months of healing, significantly more attachment gain and shallower probing depths with ePTFE.

Adult↗
PubMed1997

The insulin gene region and susceptibility to insulin-dependent diabetes mellitus in four races; new insights from Afro-Caribbean race-specific haplotypes.

The IDDM2 component of the genetic susceptibility to insulin-dependent diabetes mellitus (IDDM) has been mapped to chromosome 11p15.5. The exact identity of IDDM2 remains uncertain. It has been suggested that IDDM2 maps within the 5' VNTR (variable number tandem repeat) polymorphism upstream of the insulin gene (INS). This has not been confirmed and a contribution from other INS gene region polymorphisms cannot be excluded. We present INS region genotype data from four racial groups: the Japanese, Hong Kong Chinese, North Indian Asians and Afro-Caribbeans (two groups; one born and resident in the UK, one in Jamaica). These races have not been previously studied with the range of INS region polymorphisms included here. No INS polymorphism was associated with IDDM across all races. These data from this study thus do not identify any INS polymorphism as IDDM2. The Afro-Caribbean race showed a very different distribution of INS genotypes from the other races and novel race-specific INS haplotypes were identified. Analysis of these excluded a contribution to susceptibility to IDDM from the- 23HphI INS polymorphism. An Afro-Caribbean INS haplotype which differed only at the VNTR from the very protective INS haplotype (VPH) identified in white Caucasians was detected. Population analysis of this haplotype will allow direct assessment of the role of the VNTR in susceptibility to IDDM. In conclusion, the diverse Afro-Caribbean TH/INS/IGF2 haplotypes identified in this study will be valuable in mapping IDDM2 more precisely.

Diabetes Mellitus, Type 1↗
PubMed1996

Corticotrophin-releasing hormone receptor type 1: generation and characterization of polyclonal antipeptide antibodies and their localization in pituitary cells and cortical neurones in vitro.

Corticotrophin-releasing hormone (CRH) is a 41 amino acid neuropeptide which plays a major role in regulating the endocrine response to stress. CRH acts by first binding to specific receptors on the plasma membrane of target cells. A CRH receptor from a human corticotroph adenoma and rat brain has recently been cloned (CRH-R1). In this paper, we have chosen three different peptide sequences within the CRH-R1 molecule which bear no similarity to other members of this receptor subfamily (or indeed any known protein) and which are likely to be exposed on the surface of the native protein, for antibody production. Some of these fragments produced antipeptide antibodies of good titre which cross-reacted with the CRH-R1 receptor expressed in transiently transfected COS-7 cells and in tissue extracts from rat cerebellum, cortex, pituitary gland and human myometrium, both in Western blots and in liquid-phase radioimmunoassay. We used immunofluorescence techniques to localize the CRH receptor in transiently transfected COS-7 cells, primary cultures of rat anterior pituitary (AP) cells, the corticotroph-tumour cells AtT20 D16-16 and cortical neurons in primary culture. Our results indicate IR-CRH-R1 receptors have a punctate distribution on the plasma membrane of AP cells and AtT20 D16-16 cells. Whilst in AP cells their appearance is a fine punctate pattern, in AtT20 cells, they appear as large patches which could account for receptor clusters. Within primary cortical neurons, their distribution does not appear to be polarized. Our results suggest that distribution of CRH-R1 receptors within the different cell-types investigated depends not only on the amino acid sequence but also on cellular factors.

Animals↗
PubMed1996

Research and continuous improvement: the merging of two entities?

Hospital administrators are under pressure to provide a quality product at reasonable prices. As a result, all aspects of hospital structure and culture are under review, which places continuous improvement (CI) programs addressing quality and satisfaction in a more prominent role. Although the theory, data collection methods, and analysis techniques of continuous improvement have grown considerably since the days of quality assurance, clinical problems in healthcare organizations are also increasingly complex and difficult to solve. From this perspective, research has a great deal to offer our current continuous improvement efforts. This paper proposes that CI and research are similar problem-solving approaches, based on philosophies that provide direction for theorizing, collecting and analyzing data, and identifying solutions. A clinical problem elaborates on the similarities of each approach. Finally, common misconceptions are discussed.

Health Services Research↗
PubMed1995

Effects of the situational context and interactional process on the quality of family caregiving.

A staged theoretical model designed to explain the quality of elder caring by family members was tested. The model posits how the situational context, interactional process, and caregiving burden perceived by the caregiver affect the quality of elder caring. The purpose was to determine the amount of variance explained by the interactional process beyond that explained by the situational context and caregiving burden. Data were collected from 209 elder-caregiver dyads using interviews, observations, and caregiver self-reports. The strongest predictors of caregiving burden were the caregiver's stressful negative life events (situational context) and discrepancy between past and present image of elder (interactional process). The strongest predictors of quality of elder caring were the caregiver's perception of subjective burden and a monitoring role definition on the part of the caregiver (interactional process).

Activities of Daily Living↗
PubMed1995

Co-localisation of autoimmune antibodies specific for double stranded DNA with procorticotrophin-releasing hormone within the nucleus of stably transfected CHO-K1 cells.

Human autoantibodies and corticotrophin-releasing hormone (CRH)-specific antibodies have been used in a double-labelling immunofluorescence technique to demonstrate that immunoreactive CRH structures are co-localised with immunostaining produced by double stranded DNA-specific human autoantibodies within the nucleus of cultured ovarian cells of Chinese hamsters (CHO-K1). This co-localisation was confirmed using confocal microscopy. A metabolic labelling technique was used to investigate the role of the cytoskeleton in mediating nuclear translocation of proCRH within stably transfected CHO-K1 cells and showed that microtubule and actin disrupting agents had no effect upon the nuclear translocation of proCRH. These results, therefore, suggest that nuclear translocation of proCRH is not affected by drugs which disrupt the cytoskeleton and, consequently, modify the diameter of the nuclear pores.

Actins↗
PubMed1995

Synaptogenesis and distribution of presynaptic axonal varicosities in low density primary cultures of neocortex: an immunocytochemical study utilizing synaptic vesicle-specific antibodies, and an electrophysiological examination utilizing whole cell recording.

Low-density primary cultures of neocortical neurons were utilized to examine: (i) early interactions of growing neurites with morphological characteristics of axons with other neuronal elements, and (ii) the distribution of presynaptic axonal varicosities closely apposed to MAP-2 immunoreactive, putatively postsynaptic, dendrites. At the light microscopical level axonal varicosities, presumably presynaptic terminals, were identified using immunocytochemistry incorporating antibodies specific for the synaptic vesicle antigens synaptophysin and synapsin. The presence of synaptophysin- and synapsin-immunoreactive swellings along axonal processes was first detected at 5 days post-plating and was also apparent in axons growing in isolation. At 5-7 days in vitro, immunolabelled axonal varicosities in close apposition to putative postsynaptic dendrites (MAP-2 immunoreactive) dendrites were detected. Electrophysiologically active synaptic contacts can also readily be detected at this stage. After 3 weeks in vitro presynaptic contacts do appear to be distributed heterogeneously along postsynaptic dendrites of many neurons in culture. As the culture matures a higher number of presynaptic profiles can be seen along dendrites, with a centrifugal distribution, e.g. a higher density of presynaptic axonal terminals in close apposition to more distal regions of larger dendrites, putatively considered to be apical dendrites of pyramidal-like neurons. In our cultures, the overall increase in the density and the pattern of distribution of presynaptic axon terminals immunoreactive for synaptic vesicle antigens closely apposed to putative post-synaptic structures mimics the general postnatal increase of synaptic density in the neocortex in vivo. Thus, low density primary cultures of neocortical neurons offer a valuable system to explore and manipulate (i) the molecular and cellular basis of neocortical synaptogenesis, and (ii) the pharmacology of neocortical synaptic transmission.

Animals↗
PubMed1995

Mitogenic effects and nuclear localisation of procorticotrophin-releasing hormone expressed within stably transfected fibroblast cells (CHO-K1).

To investigate the intracellular localisation and biological activity of procorticotrophin-releasing hormone (proCRH), we have established stably transfected CHO-K1 cells expressing the rat pre-proCRH cDNA. Using immunoblot analysis of cell lysates of transfected CHO-K1 cells, we detected a major CRH immunoreactive band with an apparent molecular weight of approximately 19 kDa. This 19 kDa band could account for full length proCRH molecule which has not undergone post-translational modifications. Metabolic labelling followed by immunoprecipitation, SDS-PAGE and autoradiography indicated that no endoproteolytic processing of proCRH takes place within the transfected CHO-K1 cells. Immunofluorescence staining localises the CRH precursor to both the cytoplasm and to the nucleus in transfected CHO-K1 cells. This result was confirmed using subcellular fractionation techniques on radiolabelled CHO-K1 cells expressing immunoreactive CRH. A major CRH-immunoreactive band of 19 kDa was detected both in the microsomal and secreted fractions, indicating the presence of proCRH within the secretory pathway of these cells. This was also evident in the nuclear fraction, therefore confirming the nuclear localisation of proCRH. Analysis of DNA concentration, cell number and DNA synthesis showed that stably transfected CHO-K1 cells expressing proCRH have a higher proliferation and DNA synthesis rate than wildtype CHO-K1 cells or CHO-K1 cells transfected with pEE14 alone. Our results therefore suggest a mitogenic role for the intact proCRH molecule within CHO-K1 cells. Furthermore, treatment of mouse corticotrophic tumour cells (AtT20/D16-16) with conditioned medium from transfected CHO-K1 cells expressing proCRH, stimulated both DNA synthesis and cell proliferation above basal levels. Our results constitute the first reported direct evidence of a mitogenic role for proCRH acting on a corticotrophic cell population.

Animals↗
PubMed1995

Viral infections: arthritis in the human immunodeficiency virus (HIV) infected patient.

Reactive arthritis is common in HIV-positive patients and may be mistaken for septic arthritis. We feel that the association is probably, in part, due to the increased incidence of diarrhoeal diseases in HIV-infected patients rather than a specific effect of HIV on the synovium. Disabling, chronic, sero-negative polyarthritis is common in the later stages of HIV infection and further palliative therapeutic strategies are urgently needed.

Adult↗
PubMed1995

Expression of biologically active procorticotrophin-releasing hormone (proCRH) in stably transfected CHO-K1 cells: characterization of nuclear proCRH.

Corticotrophin-releasing hormone (CRH) is a 41 amino acid neuropeptide which is cleaved at a pair of dibasic amino acids from a larger precursor molecule (pre-proCRH) by the action of endopeptidases. In cells possessing a regulated secretory pathway, sorting of proneuropeptides and prohormones occurs within the trans-Golgi network, where they are finally packaged into secretory vesicles to be released in response to an external stimulus. Such cells also possess a constitutive secretory pathway, and neuropeptides are also translocated into this subcellular compartment. We have recently established stably transfected CHO-K1 cells expressing the rat pre-proCRH cDNA, and shown that proCRH was localized within the secretory pathway and the nucleus of transfected cells. Both the cytoplasmic and nuclear species of IR-CRH displayed an apparent molecular weight approximately 19 kDa, consistent with the size of the uncleaved CRH precursor molecule. In this paper, we further characterized the bitopological, i.e. nuclear and cytoplasmic localization of proCRH within transfected CHO-K1 cells. Immunoreactive nuclear CRH was not extractable using detergents (Triton X-100 and CHAPS), 10 mM salt washes or RNase digestion but could be abolished by digestion with DNase I. These results therefore suggest that nuclear proCRH is in close association with DNA/chromatin. Treatment of transfected cells with inhibitors of protein and RNA synthesis for up to 24 h had no effect upon immunoreactive nuclear CRH, indicating that it is very stable with a long half life. Brefeldin A treatment had no effect upon the nuclear translocation of newly synthesized proCRH, suggesting that late stages of the secretory pathway (i.e. post rough endoplasmic reticulum compartments) of the transfected cells do not play a role in proCRH nuclear transport. We also demonstrate that proCRH synthesized within stably transfected CHO-K1 cells is capable of stimulating ACTH release from primary cultures of anterior pituitary cells, therefore showing for the first time that the intact precursor is also biologically active and could act as an ACTH secretagogue in-vivo.

Adrenocorticotropic Hormone↗
PubMed1995

Assessing the preferences of patients with psoriasis. A quantitative, utility approach.

BACKGROUND AND DESIGN: Patient preferences for health outcomes can be explicitly assessed and expressed in quantitative terms known as utilities. Three standard methods for utility assessment have been used to quantify patient preferences, but these methods have not previously been applied to skin disease. Eighty-seven patients with psoriasis from a tertiary medical center were interviewed, using an interactive, computer-based utility assessment questionnaire, U-Titer. Utilities for three categories of psoriasis severity and potential adverse outcomes of methotrexate therapy were assessed by the vertical rating scale, time trade-off, and standard gamble. RESULTS: Patients assigned a broad range of utilities for each of the health states. Utilities obtained by the vertical rating scale did not correlate well with utilities obtained by standard gamble or time trade-off methods. However, utilities assessed by standard gamble and time trade-off were not significantly different. Patient characteristics such as age, gender, and education were not correlated with utility and did not explain the variation. Indicators of the patients' disease severity were not predictive of utilities for the assessed health states. The relatively high utility for liver biopsy suggests that there is less patient aversion to the procedure than suspected. CONCLUSIONS: Utilities, or quantitative measures of patient preferences for health states, are measurable and vary widely for mild, moderate, and severe psoriasis and possible adverse outcomes of methotrexate treatment. The process of elucidating individual patient utilities for various health outcomes can be used to incorporate patient preferences into the process of clinical decision making. Guidelines that are based solely on severity of symptoms, without input from patients on how they value such symptoms, must be questioned.

Adult↗