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Biomedical subjects

S Ellis

Publications and source records attributed to S Ellis.

At least 73 records · Page 4Linked to original sources

Alterations of benzodiazepine receptors in type II alcoholic subjects measured with SPECT and [123I]iomazenil.

OBJECTIVE: Alterations in cortical benzodiazepine receptor density have been described in postmortem and in vivo studies of alcoholic subjects. The authors attempted to replicate these findings using single photon emission computed tomography and the benzodiazepine receptor radiotracer [123I]iomazenil. METHOD: They measured the distribution volume of benzodiazepine receptors in 11 recently detoxified patients with type II alcoholism and 11 healthy comparison subjects. The tracer was given as a bolus followed by a continuous infusion to achieve sustained binding equilibrium at the benzodiazepine receptors. Data were analyzed by using a region of interest method (regions of interest were identified on coregistered magnetic resonance imaging scans) and by a pixel-by-pixel method (distribution volume maps were analyzed with statistical parametric mapping for between-group differences). RESULTS: The region of interest analysis revealed that alcoholic patients had significantly lower benzodiazepine distribution volume than comparison subjects in the frontal, anterior cingulate, and cerebellar cortices. Statistical parametric mapping revealed two large excursions in which the distribution volume in alcoholic patients was significantly lower than in comparison subjects: the anterior cingulate, extending into the right middle frontal gyrus, and the left occipital cortex. CONCLUSIONS: Benzodiazepine receptor distribution volume is significantly lower in several cortical regions and the cerebellum in alcoholic subjects than in healthy comparison subjects. These results are consistent with previous reports and might indicate either a toxic effect of alcoholism on benzodiazepine receptors or a vulnerability factor for developing alcoholism.

Adult↗

Aftereffects and sense of presence in virtual environments: formulation of a research and development agenda.

This report represents a committee summary of the current state of knowledge regarding aftereffects and sense of presence in virtual environments (VEs). The work presented in this article, and the proposed research agenda, are the result of a special session that was set up in the framework of the Seventh International Conference on Human Computer Interaction. Recommendations were made by the committee regarding research needs in aftereffects and sense of presence, and, where possible, priorities were suggested. The research needs were structured in terms of the short, medium, and long term and, if followed, should lead toward the effective use of VE technology. The 2 most critical research issues identified were (a) standardization and use of measurement approaches for aftereffects and (b) identification and prioritization of sensorimotor discordances that drive aftereffects. Identification of aftereffects countermeasures (i.e., techniques to assist users in readily transitioning between the real and virtual worlds), reduction of system response latencies, and improvements in tracking technology were also thought to be of critical importance.

Adaptation, Physiological↗

Fluorescence properties of autofluorescent granules generated by cultured human RPE cells.

PURPOSE: To compare the fluorescence properties of autofluorescent granules generated by retinal pigment epithelial (RPE) cells in vitro with those of the lipofuscin of RPE in vivo. METHODS: Cultured human RPE cells were maintained in basal medium for as long as 1 year, fed rod outer segments (ROS) daily for as long as 56 days, fed ROS in the presence and absence of leupeptin, or fed liposomes consisting of the major phospholipids in ROS. At different time points, cells were examined for overall fluorescence, and their fluorescence spectra were determined. In addition, chloroform-methanol extracts were examined by thin-layer chromatography and compared with those generated from RPE lipofuscin. RESULTS: Autofluorescent granules accumulated in cultured RPE cells, regardless of the presence of an exogenous substrate or the nature of the substrate. The rate of accumulation of autofluorescent granules was greatest in cells fed ROS. The autofluorescent material generated in cultured RPE cells had some spectral similarities with RPE lipofuscin but differed in solubility and chromatographic mobility of their constituent fluorophores. CONCLUSIONS. The autofluorescent granules generated by cultured RPE, even with different specific substrates, differ from lipofuscin granules in vivo, suggesting that additional properties of RPE cells or of the materials they phagocytose are required to produce autofluorescent materials with the characteristics of lipofuscin.

Aged↗

Involvement of calcium in retinal pigment epithelial cell proliferation and pigmentation.

PURPOSE: The aim of this study is to explore the role of intracellular calcium in the mechanism of co-regulation of retinal pigment epithelial cells (RPE) by vitreous fluid and platelet mitogens, in order to evaluate the use of calcium modulating drugs in preventing RPE cell proliferation and contraction of fibrocellular membranes. METHODS: Monolayers of human RPE cells were loaded with Fura-2-AM and examined in a fluorimeter for changes in intracellular free calcium in response to platelet mitogens (PDGFAB or TGFbeta1) and vitreous fluid (containing vitreous substrate proteins), both alone or in combination. The effect of the calcium antagonists TMB8 and verapamil and the calmodulin antagonists J8 and tamoxifen were then examined on RPE cell proliferation and pigmentation, both in the presence and absence of vitreous substrate and platelet mitogens. RESULTS: We report that co-exposure of RPE cells to platelet mitogens and vitreous fluid produces an increase in intracellular free calcium of greater duration than that with either PDG-FAB, TGFbeta1 or vitreous fluid alone. Calcium and calmodulin antagonists significantly reduce RPE cell proliferation in both the presence and absence of vitreous substrate and platelet mitogens. Calcium antagonists also stimulate the accumulation of autofluorescent granules within RPE cells. CONCLUSIONS: Calcium signalling plays a role in the co-regulation of RPE cells by vitreous substrate and platelet mitogens. Drugs that lower intracellular calcium or inhibit calmodulin may offer an additional approach to preventing the hyperproliferation of RPE cells in PVR.

Adult↗

Assessing health-related quality of life in HIV disease: key measurement issues.

The reliable and valid assessment of health-related quality of life (HRQoL) in human immunodeficiency virus (HIV) clinical research presents both familiar and unique challenges. Consistent with HRQoL research in general, measures of HRQoL in HIV disease must meet a set of standard psychometric properties, produce interpretable results, and be responsive to relatively small treatment effects. Furthermore, as clinical research for a range of diseases and conditions becomes increasingly global, HRQoL investigators are confronted with the formidable task of developing measures that are applicable across a range of cultures and languages within and across national boundaries. In this paper, we present a model of HRQoL to be applied across disease and conditions, with a discussion of the key measurement issues. We then briefly consider the natural history and treatment aspects of HIV that are relevant to HRQoL research. In the final sections of the paper, we describe the elements needed in an 'ideal' HRQoL/HIV instrument and propose a method for evaluating the degree to which current HRQoL measures address the challenges posed by HIV clinical research.

Culture↗

Localization of lesion in denial of hemiplegia after acute stroke.

BACKGROUND AND PURPOSE: Previous studies of lesion localization in dental of hemiplegia have often been confounded by factors such as the cerebral etiology, which aspects of the disorder are denied, and whether delusions are present. Our investigation focuses on denial of hemiplegia, without concomitant delusions, after cerebrovascular accident (CVA). METHODS: The CT scans of 30 patients with denial of hemiplegia after acute stroke were compared with those from 10 CVA patients with hemiplegia and visuospatial neglect but no denial. Lesion sites were detailed using the templates of Damasio and Damasio and, for the deep structures, those of Talairach and Tournoux. RESULTS: Analysis of the CT scans demonstrated that 26 of 30 denial patients had unilateral right-sided lesions and that this group showed a significantly higher incidence of lesions in deep white matter and the basal ganglia. CONCLUSIONS: The results are discussed in relation to recent ideas regarding the role of the basal ganglia and subcortical circuits in movement and executive function.

Aged↗

The SHR as a small animal model for radiocontrast renal failure. Relation of nephrotoxicity to animal's age, gender, strain, and dose of radiocontrast.

The male spontaneously hypertensive rat (SHR), as it ages, suffers many of the renal and cardiovascular complications that are recognized in humans as risk factors for radiocontrast (RC) agent induced renal failure (RF). Knowledge of this led us to test this strain of rats as a small animal model for RC-induced renal failure (RC-RF). Functional studies demonstrated a significant fall in GFR in the recovery period after RC administration. In addition, histopathologic evaluation of the kidneys was done in this study. Our results are based on assigning separate scale values to the histopathological evaluation of the (a) glomeruli, (b) tubules, (c) interstitium, and (d) arteries and arterioles of the kidneys. Saline (S) was administered to one group and the RC agent Hypaque-76 (diatrizoate meglumine sodium) to paired groups of 5-, 8-, 10-, 12-, and 14-month-old male SHR. The results indicated that younger animals (5 and 8 months old) were resistant to the nephrotoxic effects of the RC, but developed susceptibility at 10 months of age, when spontaneous renal pathology became manifest. Both spontaneous renal pathology and RC-induced renal damage (RC-RD) increased as the animals aged. In addition, when the administered dose of RC was repeated after a short interval of only 6 h, the degree of RC-RD increased greatly. In parallel control studies of the influence of gender and strain on the response to RC in 12-month-old rats, neither hypertensive female SHR nor male normotensive Wistar-Kyoto (WKY) rats demonstrated significant spontaneous renal pathology or the marked susceptibility to RC nephrotoxicity shown by their male SHR counterparts. This small animal model for RC-RD, the mature male SHR, has the distinct advantage that risk factors for RC-RD, similar to those characterized in humans for RC-RF, develop spontaneously without requiring any special treatment or surgical intervention.

Age Factors↗

Response to intravenous midazolam sedation in general dental practice.

The object of this study was to grade the response of patients undergoing a variety of dental procedures with the aid of intravenous midazolam sedation in general dental practice and to explore any relationships between the patients preoperative anxiety assessment and the clinician's assessment of co-operation whilst under sedation. One hundred consecutive patients aged between 18 and 58 years (mean 32 years; sd 10 years) and in ASA Class I or II were prospectively studied. Results showed that despite attempts to grade patient's behaviour it was not possible to reliably predict patient's responses under intravenous sedation. In addition to these findings, the great individual variation in sensitivity to midazolam was confirmed.

Adolescent↗

Extracellular truncations of h beta c, the common signaling subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5, lead to ligand-independent activation.

The hypothesis that extracellular truncation of the common receptor subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor, and IL-5 (h beta c) can lead to ligand-independent activation was tested by infecting factor-dependent hematopoietic cell lines with retroviruses encoding truncated forms of h beta c. A truncation, resembling that in v-Mpl, and retaining 45 h beta c-derived extracellular residues, led to constitutive activation in the murine myeloid cell line, FDC-P1. However, infection of cells with retrovirus encoding a more severely truncated receptor, retaining only 7 h beta c-derived extracellular residues, did not confer factor independence on these cells. These experiments show that truncation activates the receptor and define a 37-amino acid segment of h beta c (H395-A431) which contains two motifs conserved throughout the cytokine receptor superfamily (consensus Y/H XX R/Q VR and WSXWS), as essential for factor-independent signaling. The mechanism of activation was also investigated in less severe truncations. A receptor that retains the entire membrane-proximal domain (domain 4) also conferred factor independent growth on FDC-P1 cells; however, a retrovirus encoding a truncated form of h beta c having two intact membrane proximal domains did not have this ability, suggesting that domain 3 may have an inhibitory role in h beta c. The ability of these receptors to confer factor independence was cell specific as demonstrated by their inability to confer factor-independent growth when introduced into the murine IL-3-dependent pro-B cell line BaF-B03. These results are consistent with a model in which activation requires unmasking of an interactive receptor surface in domain 4 and association with a myeloid-specific receptor or accessory component. We suggest that in the absence of ligand intramolecular interactions prevent inappropriate signaling.

Animals↗

Restriction endonuclease analysis of group B streptococcal isolates from two distinct geographical regions.

This study examined isolates of group B streptococci (GBS) by latex seroagglutination and restriction endonuclease analysis (REA). REA analysis was performed with high- and low-frequency cutting enzymes, and fragments were resolved by linear and pulsed-field gel electrophoresis (PFGE), respectively. GBS isolates were derived from a regional acute-care hospital and a tertiary referral obstetric hospital. The most common serotype isolated at the general hospital was serotype V (42%). A high incidence of this serotype V was associated with wound infections, but there was no predominant REA profile. Serotype III was the most common from the obstetric hospital (41%). The majority of these isolates were associated with neonatal GBS infection and there was a predominant restriction pattern. Analysis of restriction patterns of GBS isolated from individual mother/ baby pairs revealed common patterns. These data extend the evidence for vertical transmission of GBS and clones of serotype III GBS with increased pathogenic potential.

DNA Restriction Enzymes↗

Solution properties and computational analysis of an oligodeoxynucleotide containing N-(deoxyguanosin-8-yl)-1-aminopyrene.

An oligodeoxyribonucleotide 5'-d(CTCATGAPATTCC), in which G(AP) denotes N-(guanin-8-yl)-1-aminopyrene, the C8-guanine adduct of reductively activated 1-nitropyrene, was synthesized and characterized by polyacrylamide gel electrophoresis, absorption and fluorescence spectroscopy, circular dichroism, and thermal melting studies. Polyacrylamide gel electrophoresis showed slower mobility of the adducted oligonucleotide in single-stranded form compared to its unmodified counterpart, as expected. In duplex form, however (with a deoxycytidine opposite the adduct), the adducted 11mer migrated faster than the parent duplex. Absorption and fluorescence studies indicated significant interaction of the aminopyrene residue with the DNA bases in the modified 11mer. The spectroscopic data also suggested the presence of one or more conformers in which the aminopyrene residue is quasi-intercalative, as well as one(s) in which the aminopyrene is externally bound. Thermodynamic parameters for the helix-to-coil transitions for the 11mer duplex were determined. The difference in free energy (delta delta G degree) between the unmodified and modified sequences was relatively small (approximately 1.2 kcal/mol). Circular dichroism spectra indicated the presence of essentially B-form DNA. The energy minimizations suggested that the most stable conformers shared a common feature: displacement of the modified guanine from the double helix. In the global minimum, the aminopyrene residue was inserted in the helix in the site of displaced guanine. In other low energy structures, the aminopyrene was also displaced towards the minor groove (in addition to guanine), or partly inserted and partly in the groove. More conventional structures were also encountered, with anti-guanine within the helix and aminopyrene in the major groove, or syn-guanine within the helix, and aminopyrene in the minor groove. Such structures were 12-20 kcal/mol less stable than the global minimum, however. The C8-guanine adduct of aminopyrene thus appears to perturb the B-DNA structure to a greater extent than do the adducts of less bulky amines such as aminofluorene and 4-aminobiphenyl.

Base Sequence↗

From relief to development: the long-term effects of 'temporary' accommodation on refugees and displaced persons in the Republic of Croatia.

The increasing scale of international intervention in conflict is generating new pressures on the humanitarian community. Increased expenditure on emergency relief, static levels of overseas development aid and subsequent lack of funds for development are dictating that agencies design relief projects that positively effect developmental reconstruction. This paper examines the provision of shelter for refugees and displaced persons in the Republic of Croatia and identifies ways in which it has encouraged and discouraged sustainable reconstruction. It argues that to promote lasting reconstruction, programmes must focus on saving livelihoods as well as lives, thus minimising the long-term psychological and physical impacts of aid on refugees, displaced persons and host communities.

Adaptation, Psychological↗

Researching under fire: issues for consideration when collecting data and information in war circumstances, with specific reference to relief and reconstruction projects.

The post-Cold War era has witnessed an increased number of conflicts and higher levels of international intervention by the humanitarian community and the military. Those who undertake to research the actions of relief and development agencies acting in these wars must act within new parameters that require a flexible, innovative and reflective approach. Not much is known about data collection in war. The most relevant publications come from the field of development studies. This paper is a beginning in a much-needed discourse on researching under fire; it is offered not as a definitive work, but as a starting-point for discussion.

Bias↗

In-flight and postflight changes in skeletal muscles of SLS-1 and SLS-2 spaceflown rats.

Spacelab Life Sciences-1 and -2 provided skeletal muscles from rats dissected in flight for the first time and 2 h to 14 days postflight. The muscles permitted the distinguishing of primary adaptations to microgravity from secondary reloading-induced alterations. In microgravity, rats adopted bipedal forelimb locomotion with the hindlimbs relegated to grasping activities. On landing day, body posture was abnormally low and walking was stilted at a rate one-third of normal. The adductor longus (AL) and soleus muscles exhibited decreased myofiber areas that did not recover 14 days postflight. Doubling of the nonmyofiber area indicated interstitial edema in AL muscles 2.3 h postflight. Solei did not manifest edema postflight, and neither muscle showed edema in flight. Sarcomere eccentric contraction-like lesions were detected in 2.6% of AL myofibers 4.5 h postflight; lesions were absent earlier postflight and in flight. At 9 days postflight, these lesions were repaired but regenerating AL myofibers were present, which suggests that myofiber necrosis occurred 1-2 days postflight. These studies demonstrate that muscle atrophy occurs in microgravity, whereas interstitial edema and sarcomere lesions are postflight phenomena.

Adaptation, Physiological↗

Denial of hemiplegia: an investigation into the theories of causation.

A comprehensive study of denial of hemiplegia, with tests chosen to cover the varied proposed hypotheses, was undertaken. Twenty patients with denial of hemiplegia following acute CVA were studied. Their results were compared with those from two patient 'control' groups. A neurological examination and neuropsychological assessment were carried out in all patients and CT brain scan performed in 21 CVA cases. The findings are discussed in relation to previously proposed theories of causation concerning denial of hemiplegia which include personality factors, cognitive ability and the presence/absence of neurological deficits. CT scan analyses showed that patients with denial of hemiplegia have significantly more white matter involvement, particularly the corona radiata, than those with neglect and there was also a trend that patients with denial are more likely to have lesions in the caudate.

Acute Disease↗