Tender topics for the NHS.
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Ancillary Services, Hospital↗
Biomedical subjects
R Milne
Publications and source records attributed to R Milne.
A vector that expresses secreted proteins on the cell surface.
A new vector, CDM8PI, has been constructed. It was derived from the plasmid expression vector CDM8, which has been used in the epitope-loss mutant isolation technique to map the epitopes on cell-surface proteins. The new vector allows the production of fusion proteins between normally secreted proteins and the membrane anchor moiety from a cell-surface protein, LFA-3, thereby expressing the fusion proteins on the cell surface. The vector extends the application of the epitope-loss mutant isolation technique to secreted proteins. The vector also allows the easy recovery of mutated proteins in unfused forms after the immunoselection and characterization.
Amino Acid Sequence↗
The elasticity and vertical distribution of stress within stems of Picea sitchensis.
Eight 22-year-old Picea sitchensis (Bong.) Carr. trees growing in a Scottish forest were bent using a winch and cable. The shapes of the bent stems were modeled using the structural theory of a cantilever beam, with non-uniform stem taper and large deflections taken into account. The Young's modulus of elasticity for the stems was estimated to be 2.0-6.4 GPa, which is lower than that reported for sawn green timber of this species, but similar to that for intact green stem sections. The longitudinal distribution of stress along the stems had a maximum at a height that was dependent on taper. Maximum stress occurred higher up in the more tapered stems.
Journal Article↗
Rat monoclonal antibodies to human apolipoprotein B: advantages and applications.
Eight monoclonal antibodies (Mabs) to human serum low density lipoprotein (LDL) were derived from the fusion of spleen cells, from LOU rats immunized with human LDL, and the rat myeloma line IR983F. These Mabs were characterized in terms of isotype, specificity, and affinity. Competitive experiments indicated that the epitopes that were recognized could be grouped into three patterns depending on their apparent affinity for apoB-containing lipoprotein particles such as LDL, very low density lipoproteins (VLDL), or intermediate density lipoproteins (IDL). Six epitopes have been mapped in relation to elements of the sequence of apolipoprotein B-100 (apoB-100) and some have been assigned to the middle part of the median thrombolytic fragment T3, a region not yet well targeted by mouse Mabs. The presence of lipids for the expression of the epitopes was studied and confirmed a lipid dependence for epitopes that are close to the T2/T3 cleavage site. The capacity of binding to the LDL receptor was also tested; among the Mabs we described, one inhibited the uptake and degradation of LDL to HeLa cells receptor. Finally, some antibodies were able to precipitate LDL in gel.
Animals↗
Diet and diabetes revisited.
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Diabetes Mellitus, Type 2↗
Fighting HIV and AIDS--East Berkshire's early experience.
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Acquired Immunodeficiency Syndrome↗
A murine monoclonal antibody against rat atrial natriuretic factor (ANF) which cross-reacts with mouse ANF.
A monoclonal antibody (MAb), 2H2, against rat synthetic atrial natriuretic factor (ANF) (Arg101-Tyr126) recognizes native ANF related peptides. The lack of reactivity of 2H2 with amino-terminal truncated ANF peptides implicates the two amino terminal arginine residues of ANF in the 2H2 epitope. Similarly, poor immunoreactivity of human ANF indicates the participation of isoleucine 110. Arginines 101 and 102 and isoleucine 110 may thus participate in a conformational epitope recognized by 2H2 or alternatively, substitution for, or elimination of these residues may alter the conformation of the 2H2 epitope. The MAb shows little cross-reactivity with extracts of rabbit atria but recognizes ANF related peptides in mouse and hamster atrial extracts. 2H2 also identifies immunoreactive ANF in histological sections of rat, mouse and hamster atria.
Animals↗
Intestinal apoB synthesis, lipids, and lipoproteins in chylomicron retention disease.
Chylomicron retention disease is characterized by fat malabsorption, hypocholesterolemia, normal fasting triglycerides, and marked intestinal steatosis despite the presence of both plasma and intestinal apoprotein B. The defect remains unknown but presumably involves the synthesis or secretion of chylomicrons. The present investigation examines this hypothesis by studying the biosynthesis of chylomicrons in cultured jejunal explants and by defining the quantitative and qualitative abnormalities of plasma lipids and of circulating lipoproteins. Following 2-3 years of a low fat diet supplemented with medium chain triglycerides, six patients with chylomicron retention disease had significantly higher triglyceride (TG) levels coupled with a decrease in both free (FC) and esterified cholesterol (EC) as well as in essential fatty acids and phospholipids (PL) when compared to healthy controls. The low total plasma cholesterol was largely accounted for by low levels of both low density (LDL) and high density lipoprotein (HDL) cholesterol. VLDL and LDL were characterized by a diminished percentage of CE with an increase of TG while HDL contained relatively more FC as well as PL and less CE. The diameter of VLDL was larger whereas those of LDL and HDL were smaller than in normal controls. Jejunal explants, when incubated with [14C]palmitate, were capable of normal biosynthesis of TG, diglycerides, PL, and CE. These lipids, however, except for PL, were retained in the tissue and could not be secreted into the culture medium. Incubation of intestinal biopsies with [3H]leucine and [14C]mannose resulted in normal protein synthesis and reduced glycosylation. The presence of intestinal apoB-48 was confirmed by immunoblot using 2D8 antibodies. These data suggest that the intestinal defect in this disease results from a disorder of the final assembly of chylomicrons or in the mechanism of their exocytosis.
Apolipoproteins B↗
A follow up study of 200 men after vasectomy.
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Adult↗
Distribution of apolipoprotein E phenotypes in Friedreich's ataxia.
Allelic polymorphism at the apolipoprotein E (apo E) gene locus (alleles epsilon 2, epsilon 3, and epsilon 4) is responsible for the existence of 6 discrete electrophoretic phenotypes of plasma apo E. Since the presence of the epsilon 2 allele in the genotype tends to be associated with higher triglyceride levels, a study was undertaken to determine if a higher frequency of this allele could account for the presence of higher plasma triglycerides in subsets of patients with Friedreich's Ataxia. The frequency of the apo E phenotypes was determined in 37 subjects with Friedreich's Ataxia and compared with that of 102 normolipidemic and 102 hyperlipidemic individuals. There was no increased prevalence of the E3/2 phenotype and the epsilon 2 allele in the Friedreich's sample as is found in a hyperlipidemic sample. Furthermore, the epsilon 2 subset did not have significantly higher plasma triglycerides than the non-epsilon 2 subset and the hypothesis was rejected. On the other hand, there was a trend for a decreased frequency of the E4/3 phenotype in the Friedreich's sample relative to the hyperlipidemic group but the difference did not reach statistical significance. The apo E phenotype distribution was also measured in a smaller sample of Charlevoix-Saguenay disease; this led to the discovery of two siblings with the relatively rare E2/2 phenotype and unexpectedly low levels of plasma lipid and lipoprotein concentrations. Plasma apolipoprotein E concentrations in both diseases were within the normal range except for subjects bearing the E2/2 phenotype.
Adolescent↗
Methylphenidate in children with hyperactivity: review and cost-utility analysis.
OBJECTIVE: To evaluate the effectiveness and cost effectiveness of methylphenidate in the treatment of children with hyperkinetic disorder as defined using ICD-10 criteria. DESIGN: Comprehensive literature review and cost utility analysis comparing methylphenidate treatment with placebo. Costs and effects were estimated from a NHS perspective according to the methodology developed by the previous South and West Development and Evaluation Committee. The number of Quality Adjusted Life Years (QALYs) gained was estimated by using the Index of Health Related Quality of Life to model treatment effects. RESULTS: Evidence from good and medium quality randomized controlled trials shows benefits of methylphenidate over weeks and months respectively. Evidence beyond 6 months is poorer and it is uncertain whether effects of methylphenidate persist into adolescence and adulthood. Methylphenidate is of reasonable cost-effectiveness when considering short- and medium- term benefits with an estimated cost per QALY of 7 pounds 400 to 9 pounds 200 at 1997 prices. CONCLUSIONS: Short-term treatment of hyperkinetic children with methylphenidate is effective and cost effective.
Attention Deficit Disorder with Hyperactivity↗
Computer virus infection.
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Computer Security↗
A two-site immunoradiometric assay of proatrial natriuretic factor. Application to tissue extracts.
A "two-site" immunoradiometric assay (IRMA) was developed to specifically measure ANF (1-126), the precursor of ANF. This assay is based on the simultaneous use of antibodies against two different antigenic determinants: murine monoclonal antibody (2H2), which recognizes positions 101 through 103 of ANF, is linked to Immunobeads and employed to extract any ANF C-terminal; a second antibody, which is directed against positions 11 through 37, is radioiodinated and allows binding to any C-terminal-2H2-Immunobead material which bears the N-terminal antigenic site. A curvilinear relationship was obtained between radioactivity and the amount of proANF (1.5 to 400 fmol) added. Optimisation of IRMA was determined by the amount of 2H2-Immunobeads and labeled antibody used, incubation time as well as possible interference by both ANF (99-126) and ANF (1-98). Tissue extracts were used to validate the assay. proANF was detected in decreasing amounts in heart atria, heart ventricles, lungs, kidneys and adrenal glands. Its presence was further confirmed by reverse-phase HPLC followed by radioimmunoassay. IRMA is a simple and rapid method for the direct measurement of proANF in tissue extracts and chromatographic fractions. The presence of proANF in tissues strongly suggests local synthesis.
Adrenal Glands↗
Drinking goal selection in behavioral self-management treatment of chronic alcoholics.
The relationship between individuals' choice of abstinence or moderate drinking during outpatient behavioral management treatment and outcome over 12 months' posttreatment was examined. At the initial assessment, 46% of 106 chronic alcoholic subjects chose abstinence, 44% chose moderate drinking, and 9% were unsure. Over the course of treatment, subjects were more likely to move from moderation to abstinence goals, and after the first 4 weeks of treatment, two-thirds chose abstinence. These subjects were older, had more severe alcohol problems (i.e., higher MAST scores), and were more likely to maintain their weekly alcohol consumption goals during the 16-week treatment period. Moreover, these subjects reported less alcohol use in the 12 month follow-up period, and a greater proportion were judged as having successful outcomes. The implications of these findings are discussed.
Adult↗
Complete protein sequence and identification of structural domains of human apolipoprotein B.
Epidemiological, pathological and genetic studies show a strong positive correlation between elevated plasma concentrations of low-density lipoprotein (LDL) cholesterol and the risk of premature coronary heart disease. Apolipoprotein (apo) B-100 is the sole protein component of LDL and is the ligand responsible for the receptor-mediated uptake and clearance of LDL from the circulation. Apo B-100 is made by the liver and is essential for the assembly of triglyceride-rich very low-density lipoproteins (VLDL) in the cisternae of the endoplasmic reticulum and for their secretion into the plasma. VLDL transports triglyceride to peripheral muscle and adipose tissue, where the triglyceride is hydrolysed by lipoprotein lipase. The resultant particle, relatively enriched in cholesteryl ester, constitutes LDL. LDL delivers cholesterol to peripheral tissues where it is used for membrane and steroid hormone biosynthesis and to the liver, the only organ which can catabolize and excrete cholesterol. Plasma LDL levels are therefore determined by the balance between their rate of production from VLDL and clearance by the hepatic LDL (apo B/E) receptor pathway. Here we report the complete 4,563-amino-acid sequence of apo B-100 precursor (relative molecular mass (Mr) 514,000 (514K] determined from complementary DNA clones. Numerous lipid-binding structures are distributed throughout the extraordinary length of apo B-100 and must underlie its special functions as a nucleus for lipoprotein assembly and maintenance of plasma lipoprotein integrity. A domain enriched in basic amino-acid residues has been identified as important for the cellular uptake of cholesterol by the LDL receptor pathway.
Amino Acid Sequence↗
Piloting short workshops on the critical appraisal of reviews.
This paper describes a pilot programme of short workshops on the critical appraisal of review articles. The twelve workshops, which ran in various parts of the United Kingdom during 1992 and 1993, lasted either one or two half-days, and consisted of a mixture of large-group sessions and critical appraisal in small groups of a systematic review. The 274 participants came from varied backgrounds, though chiefly in public health and purchasing. The workshops were well received and were oversubscribed. Participants reported that they found them useful and that they raised their awareness of the place of evidence about effectiveness in decision-making. The challenge now is to evaluate the impact of such workshops more rigorously.
Health Personnel↗