Biomedical subjects
R J Simpson
Publications and source records attributed to R J Simpson.
Intravenous amiodarone during prolonged resuscitation from cardiac arrest.
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Cloning and characterization of a cDNA for a new mouse T cell growth factor (P40).
Recently, we described a murine helper T cell-derived molecule with T cell growth factor activity that is functionally and structurally distinct from IL-2, IL-4, and other known growth factors. This molecule, designated P40, was identified as a glycoprotein capable of supporting antigen-independent growth of certain helper T cell clones. Here, we report the cloning and expression of a cDNA for this new growth factor. The predicted mature protein is a cationic cysteine-rich polypeptide of 14 kD without significant homology to previously sequenced proteins.
Effect of orally-administered epidermal growth factor on intestinal iron absorption and mucosal permeability.
A progressive increase in intestinal 59Fe3+ absorption was observed on oral feeding of mice with physiological doses of EGF/UGO. Maximal changes were apparent after 3d and appeared to be dose-dependent. In addition to a small increase in intestinal cell proliferation, as reflected by increased ornithine decarboxylase activity, EGF/UGO-feeding increased mucosal permeability (evaluated with [51Cr]-EDTA): the latter could account for the increase in iron absorption. Sialoadenectomy, to remove the major source of endogenous EGF/UGO, had no appreciable effect on the intestinal absorption of iron.
Brush border membrane non-esterified fatty acids. Physiological levels and significance for mucosal iron uptake in mouse proximal intestine.
Brush border membrane vesicles prepared using divalent cation precipitation methods can contain unphysiological levels of non-esterified fatty acids. Fatty acid production from endogenous lipid during brush border membrane vesicle preparation is effectively prevented by the lipase inhibitor diethyl 4-nitrophenylphosphate plus cooling. Vesicles prepared using this procedure have variable levels of non-esterified fatty acids (range 22-193 nmol mg-1 protein). Changes in non-esterified fatty acid levels in brush border membrane vesicles parallel Fe uptake by vesicles from Fe/ascorbate solutions. Brush border membrane vesicle fatty acids appear to be derived from the diet but hypoxic mice are able to maintain high brush border membrane non-esterified fatty acid levels despite reduced dietary intake. Non-esterified fatty acids in brush border membrane may thus provide a physiological mechanism of mucosal Fe uptake.
Mechanisms of intestinal brush border iron transport.
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Micropreparative procedures for high sensitivity sequencing of peptides and proteins.
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Micropreparative high-performance liquid chromatography of proteins and peptides.
The use of short microbore reversed phase and ion-exchange HPLC columns in the preparation of low level (submicrogram) quantities of proteins and peptides is discussed. The sequential use of columns of differing selectivity to purify complex mixtures is described. An example is given of the use of microbore columns to purify a murine myeloid leukemia inhibitory factor prior to sequence analysis.
Coronary thrombolysis in rural hospitals.
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Identification, isolation, and N-terminal sequencing of style glycoproteins associated with self-incompatibility in Nicotiana alata.
S-Gene-associated glycoproteins (S-glycoproteins) from styles of Nicotiana alata, identified by non-equilibrium two-dimensional electrophoresis, were purified by cation exchange fast protein liquid chromatography with yields of 0.5 to 8 micrograms of protein per style, depending on the S-genotype of the plant. The method relies on the highly basic nature of the S-glycoproteins. The elution profiles of the different S-glycoproteins from the fast protein liquid chromatography column were characteristic of each S-glycoprotein, and could be used to establish the S-genotype of plants in outbreeding populations. In all cases, the S-genotype predicted from the style protein profile corresponded to that predicted from DNA gel blot analysis using S-allele-specific DNA probes and to that established by conventional breeding tests. Amino-terminal sequences of five purified S-glycoproteins showed a high degree of homology with the previously published sequences of N. alata and Lycopersicon esculentum S-glycoproteins.
Effect of exchange transfusion of reticulocytes on in vitro and in vivo intestinal iron (Fe3+) absorption in mice.
The effect of acute changes in erythron demands and in plasma-iron turnover (PIT) on the in vitro and in vivo absorption of 59Fe3+ was studied in the mouse. Hypoxic exposure for 20 h (a time at which intestinal iron absorption is markedly stimulated) induced reticulocytosis with a marked elevation in PIT. More prolonged exposure (3 d) further enhanced the plasma-iron clearance, even though the absorption of 59Fe was not further increased. Recipient mice, exchange transfused with whole blood from phenylhydrazine-treated animals, had a marked reticulocytosis and elevated PIT. However, in vivo studies exhibited only a small enhancement in intestinal 59Fe absorption. In vitro studies, in contrast, showed no changes in the kinetic parameters for duodenal Fe3+ uptake in similarly-transfused mice. Blood cells, rather than plasma, were responsible for the enhanced in vivo absorption in the transfused animals. These data indicate that acute changes in body iron demands and in PIT have only a small effect on iron absorption via a process independent of the adaptive increase in carrier-mediated uptake following chronic (3 d) hypoxia. This regulatory process, however, is inadequate to explain the adaptive changes seen during acute (20 h) hypoxic exposure.
Parathyroid adenoma and nonmedullary thyroid carcinoma association.
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Bradycardia-dependent bundle branch block during Mobitz I second degree heart block.
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Nonemergent cardiac catheterization and risk-stratified revascularization following thrombolytic therapy for acute myocardial infarction. A critical analysis of therapy in the community setting. University of North Carolina Cardiology Consortium.
We evaluated a strategy for administering thrombolytic therapy without emergent cardiac catheterization to patients with acute myocardial infarction in community hospitals. Fifty-nine patients were treated with intravenous streptokinase and heparin, and referred for elective catheterization. Angioplasty or bypass surgery was performed only in patients judged to be at risk for reinfarction. One or more predetermined criteria for infarct segment viability were present in 47 (80%) of 59 patients. Angina recurred in 24 patients and enzyme-positive reinfarction in 9 patients, but only 2 patients developed new Q waves or a creatine kinase rise to over twice the normal value. Of 18 patients judged to be at low risk for reinfarction, only 1 required urgent angioplasty or bypass surgery. Fourteen-day mortality was 7% and infarct vessel patency was 94%. These data indicate that physicians in small community hospitals with a close relationship to a referral center and with a carefully designed protocol can administer thrombolytic therapy safely and effectively. By subsequent stratification of patients according to the risk of recurrent infarction, 22% of patients eligible for revascularization were spared urgent angioplasty or bypass surgery.
Mouse IL-6. A hybridoma growth factor with multiple effects on normal B and T cells.
The effects of IL-6 on plasmacytomas and on normal B and T cells were examined. Evidence was presented to indicate that, in the mouse, IL-6 not only supports the growth of plasmacytomas in vitro, but also that it significantly enhances tumor progression in vivo. Analysis of the response of normal mouse B cells to IL-6 revealed the existence of a unique synergy between IL-6 and IL-1. The results obtained with T cells also highlighted the remarkable effects of the IL-1-IL-6 combination. In several experimental systems, including the generation of allogeneic cytolytic T cell responses, it appeared that accessory cells could be completely replaced by IL-1 and IL-6, whereas either cytokine used by itself was completely inactive. Analysis of the mode of action of IL-6 in T cell activation demonstrated the existence of two distinct mechanisms: induction of IL-2 biosynthesis and enhancement of T cell responsiveness to IL-2 and IL-4. Finally, it was reported that IL-6 is essential only during the early phases of T cell activation, thus indicating as far as T cells are concerned that IL-6 must be considered as a competence factor.
A survey of the work of medical advisers appointed to panels under the adoption; boarding out and fostering regulations (Scotland 1984 and 1985).
Following the implementation of new Adoption Regulations (Scotland) 1984 and Boarding Out and Fostering (Scotland) 1985, a preliminary survey of Scottish Medical Advisers was carried out in December 1987 to examine current background and practice in this area of work. A very high response rate was achieved and the findings and some implications are considered. The growth, actual and expected in this area of health board/social work collaboration, has cost implications for management.
Structural studies on the allergen Der p1 from the house dust mite Dermatophagoides pteronyssinus: similarity with cysteine proteinases.
A major allergen (Der p1) has been purified to homogeneity from faecal particles from the house dust mite Dermatophagoides pteronyssinus. Reversed-phase microbore HPLC was employed to fractionate and purify a number of tryptic peptides generated from approximately 20 nmol of purified Der p1. N-Terminal amino acid sequence analyses were performed on the intact polypeptide and six tryptic peptides yielding 89 unique assignments; this corresponds to 40% of the molecule. These data are compared with the cDNA-deduced amino acid sequence of the Der p1 allergen. There is extensive similarity between the N-terminal amino acid sequence of Der p1 and the cysteine proteases actinidin and papain. A low Mr protein (approximately 17,000) was resolved from S-carboxymethyl Der p1 by gel-permeation chromatography. Edman degradation of the first 24 residues of this material revealed no similarity with Der p1. It is not clear whether this component is a low Mr disulfide-linked chain derived from Der p1 or represents an unidentified mite component.