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Biomedical subjects

D M Taylor

Publications and source records attributed to D M Taylor.

At least 37 records · Page 2Linked to original sources

Rendering practices and inactivation of transmissible spongiform encephalopathy agents.

The authors describe the historic form of rendering and provide details on present-day practice. Possible future directions for the rendering industry are considered. The role of rendered meat-and-bone meal (MBM) as a dietary supplement in propagating the United Kingdom (UK) epidemic of bovine spongiform encephalopathy (BSE) is discussed, together with the role of MBM in spreading BSE outside the UK. Evidence that customarily used rendering processes did not substantially inactivate the agents of BSE or scrapie is presented. In addition, the influence that the abandonment of solvent extraction (as an adjunct to rendering) in the UK might have had on BSE infectivity levels in MBM is discussed. The BSE-related safety of tallow and by-products of tallow are considered. Data that associate the BSE agent with a new variant form of Creutzfeldt-Jakob disease in humans, predominantly but not exclusively, in the UK, are also discussed.

Animal Feed↗

Studies on the removal of a bovine spongiform encephalopathy-derived agent by processes used in the manufacture of human immunoglobulin.

BACKGROUND AND OBJECTIVES: There is still uncertainty over how the agent of variant Creutzfeld-Jakob disease (vCJD) would partition during the manufacture of plasma derivatives. In this study, a BSE-derived agent was used as a vCJD model to determine the extent to which infectivity could be removed by selected steps used in the manufacture of intravenous immunoglobulin (IVIG). MATERIALS AND METHODS: Murine-passaged BSE (strain 301V), in the form of a microsomal fraction prepared from infected brain, was used to "spike" the starting material in three experiments. The partitioning of BSE infectivity was measured over Fraction I+III precipitation, borosilicate microfibre depth filtration and Seitz depth filtration, with these steps being examined individually and in series. RESULTS: Most 301V infectivity partitioned into Fraction I+III (log reduction 2.1). Infectivity remaining in Supernatant I+III was reduced by AP20 glass-fibre depth filtration (log reduction 0.6) and subsequently removed to below the limit of detection by Seitz KS80 depth filtration, giving an overall log reduction of > or = 2.9 for the three steps in series. By contrast, glass-fibre depth filtration gave a log reduction of 2.4 when challenged directly with "spiked" feedstock. Seitz KS80 depth filtration gave a log reduction of > or = 3.1 when challenged directly with 'spiked' feedstock and also removed residual infectivity to below the limit of detection when applied as the final step in series. CONCLUSIONS: Results using a BSE-derived agent suggest that vCJD infectivity should be substantially removed from immunoglobulin G (IgG) solutions by Fraction I+III precipitation and Seitz KS80 depth filtration. The three different process steps examined acted in a complementary manner to one another when operated in series. However, the data demonstrated that it would be inappropriate to add together the reduction factors that had been derived for each step in isolation.

Animals↗

Current perspectives on bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease.

Bovine spongiform encephalopathy (BSE) clearly originated in the UK, where there have now been more than 180 000 cases. However, through the exportation of cattle and cattle-feed additives from the UK, BSE also became established to a lesser extent in other European countries. There is current concern that BSE might have been distributed more widely as a result of the exportation of cattle or BSE-infected feed or foodstuff not only from the UK but also from other European countries that later became affected. It is now recognized that the transmissible agent that causes BSE also causes a new variant form of Creutzfeldt-Jakob disease (vCJD) in humans, and the evidence for this is presented. This probably resulted from dietary exposure to the bovine agent, and the potential role of mechanically recovered meat is discussed. There is a brief discussion on the controversial issue of the nature of the causal agents of diseases like BSE and vCJD. Whether or not sheep or goats could have become infected with BSE, and whether they represent a human health hazard, is also debated. Finally, the question of the control of BSE, and consequently vCJD, is discussed with regard to the rigorous application of the relevant regulations.

Animals↗

Gastric acidity protects mice against prion infection?

BACKGROUND: The transmissible degenerative encephalopathies (TDEs) constitute a distinct group of diseases (scrapie in sheep, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease (CJD) in humans). The causal agents are not fully characterized, but are known to be resistant to most inactivation procedures. Ruminants appear to be particularly susceptible to TDEs. The concentrations of hydrochloric acid in their digestive tracts are significantly lower than in monogastric species. METHODS: The aim of the study was to examine the role of gastric acidity in the protection of mice against infection after intragastric administration of different doses of a scrapie agent. Gastric acidity levels in mice were reduced by adding ranitidine to the drinking water and the animals were observed for neurological symptoms and at sacrifice examined microscopically for spongiform lesions in the brain. RESULTS: The lower doses of infectious material induced disease significantly more often in mice given ranitidine compared with the controls. CONCLUSION: These data indicate that the normal levels of gastric acidity in mice protect them to some extent from infection with low doses of scrapie agent. This finding is potentially relevant to the pathogenesis of the variant form of CJD, which appears to be associated with the consumption of BSE-infected food products.

Achlorhydria↗

Orientation of amide-nitrogen-15 chemical shift tensors in peptides: a quantum chemical study.

Knowledge of the orientation of the nitrogen-15 chemical shift anisotropy (CSA) tensor is critical for a variety of experiments that provide information on protein structure and dynamics in the solid and solution states. Unfortunately, the methods available for determining the orientation of the CSA tensor experimentally have inherent limitations. Rotation studies of a single crystal provide complete information but are tedious and limited in applicability. Solid-state NMR studies on powder samples can be applied to a greater range of samples but suffer from ambiguities in the results obtained. Density functional gauge-including-atomic-orbitals (GIAO) calculations of the orientations of (15)N CSA tensors in peptides are presented here as an independent source of confirmation for these studies. A comparison of the calculated (15)N CSA orientations with the available experimental values from single-crystal and powder studies shows excellent agreement after a partial, constrained optimization of some of the crystal structures used in the calculation. The results from this study suggest that the orientation as well as the magnitudes of (15)N CSA tensors may vary from molecule to molecule. The calculated alpha(N) angle varies from 0 degrees to 24 degrees with the majority in the 10 degrees to 20 degrees range and the beta(N) angle varies from 17 degrees to 24 degrees in good agreement with most of the solid-state NMR experimental results. Hydrogen bonding is shown to have negligible effect on the orientation of (15)N CSA tensor in accordance with recent theoretical predictions. Furthermore, it is demonstrated that the orientation of the (15)N CSA can be calculated accurately with much smaller basis sets than is needed to calculate the chemical shift, suggesting that the routine application of ab initio calculations to the determination of (15)N CSA tensor orientations in large biomolecules might be possible.

Amides↗

Extraction algorithms for cortical control of arm prosthetics.

Now that recordings of multiple, individual action potentials are being made with chronic electrodes, it seems that previous work showing simple encoding of movement parameters in these spike trains can be used as a real-time control signal for prosthetic arms. Efficient extraction algorithms can compensate for the limited ensemble sample acquired with this emerging technology.

Action Potentials↗

Analysis of the study design and manuscript deficiencies in research articles submitted to Emergency Medicine.

OBJECTIVE: To describe and analyse the study design and manuscript deficiencies in original research articles submitted to Emergency Medicine. METHODS: This was a retrospective, analytical study. Articles were enrolled if the reports of the Section Editor and two reviewers were available. Data were extracted from these reports only. Outcome measures were the mean number and nature of the deficiencies and the mean reviewers' assessment score. RESULTS: Fifty-seven articles were evaluated (28 accepted for publication, 19 rejected, 10 pending revision). The mean (+/- SD) number of deficiencies was 18.1 +/- 6.9, 16.4 +/- 6.5 and 18.4 +/- 6.7 for all articles, articles accepted for publication and articles rejected, respectively (P = 0.31 between accepted and rejected articles). The mean assessment scores (0-10) were 5.5 +/- 1.5, 5.9 +/- 1.5 and 4.7 +/- 1.4 for all articles, articles accepted for publication and articles rejected, respectively. Accepted articles had a significantly higher assessment score than rejected articles (P = 0.006). For each group, there was a negative correlation between the number of deficiencies and the mean assessment score (P > 0.05). Significantly more rejected articles ' em leader did not further our knowledge' (P = 0.0014) and ' em leader did not describe background information adequately' (P = 0.049). Many rejected articles had ' em leader findings that were not clinically or socially significant' (P = 0.07). Common deficiencies among all articles included ambiguity of the methods (77%) and results (68%), conclusions not warranted by the data (72%), poor referencing (56%), inadequate study design description (51%), unclear tables (49%), an overly long discussion (49%), limitations of the study not described (51%), inadequate definition of terms (49%) and subject selection bias (40%). CONCLUSIONS: Researchers should undertake studies that are likely to further our knowledge and be clinically or socially significant. Deficiencies in manuscript preparation are more frequent than mistakes in study design and execution. Specific training or assistance in manuscript preparation is indicated.

Australia↗

Quantitative measurement of transcript levels throughout human preimplantation development: analysis of hypoxanthine phosphoribosyl transferase.

We have developed a competitive reverse transcription-polymerase chain reaction (RT-PCR) sensitive enough to detect and quantify as little as 2-fold differences in gene expression in individual oocytes and embryos throughout human preimplantation development. This RT-PCR assay can be tailored for the examination of any specific gene and so will give a unique insight into human preimplantation development. This technique was used to quantify the level of hypoxanthine phosphoribosyl transferase (HPRT) expression during preimplantation development and to correlate this with embryo sex. The amount of HPRT transcripts present in the unfertilized oocyte was equivalent to 7.7 fg of competitor cDNA. At the 4-cell stage there is a significant drop (P: = 0.0006) to approximately 1.2 fg. There was no detectable difference in the HPRT levels between female and male embryos following 2 days of in-vitro culture. In contrast HPRT gene expression was higher in day 3 female embryos than in males. This is the first study to quantify gene transcripts throughout each stage of human preimplantation development and it indicates that the accumulated HPRT transcripts present in the unfertilized human oocyte undergo extensive destruction following fertilization. This work also suggests that X-inactivation occurs beyond the 8-cell stage of human preimplantation development.

Base Sequence↗

Reliability of the ICRP's dose coefficients for members of the public, II. Uncertainties in the absorption of ingested radionuclides and the effect on dose estimates. International Comission on Radiological Protection.

Data on the gastrointestinal absorption of 12 elements have been reviewed. In each case, absorption is expressed as the fraction of the ingested element absorbed to blood, referred to as the f1 value, applying to intakes of unspecified chemical form by average population groups. The level of confidence in individual absorption values has been estimated in terms of lower and upper bounds, A and B, such that there is judged to be roughly a 90% probability that the true central value is no less than A and no greater than B. Ranges are proposed for intakes by adults, 10-year-old children and 3-month-old infants. Uncertainty in f1 values (B/A) ranged from 10% to factors of 100-400. The lowest uncertainties were for the well absorbed elements, H, I and Cs, for which there are good data, and the greatest uncertainties were for less well absorbed elements for which few data are available, particularly Zr and Sb. Ranges were generally wider for children and infants than for adults because of the need to allow for the likelihood of increased absorption with only limited data in support of the proposed values. The largest ranges were for 3-month-old infants, reflective lack of knowledge on the time-course and magnitude of possible increased absorption in the first few months of life. For each age group, ICRP values of absorption tend towards the upper bound of the ranges, indicating a degree of conservatism in th calculation of ingestion dose coefficients. Examination of the effect of the proposed confidence intervals for f1 values on uncertainties in dose coefficients for ingested radionuclides showed that there was no direct relationship. For some radionuclides, uncertainties in effective dose were small despite large uncertainties in f1 values while for others the uncertainties in effective doses approached the corresponding values for uncertainty in f1 values. These differences reflect the relative contributions to effective dose from cumulative activity in the contents of the alimentary tract, which in many cases is insensitive to uncertainties in f1, and cumulative activity of the absorbed radionuclide in systemic tissues, which is proportional to f1. In general, uncertainties in effective close for children and infants exceeded those in adults as a result of greater uncertainties in f1 values for the younger age groups. However, this effect was reduced in some cases by shorter retention times of absorbed nuclides in body tissues and organs.

Adult↗

Using wound fluid analyses to identify trace element requirements for efficient healing.

A series of wound fluid and blood plasma samples from 20 patients with breast cancer were analysed by Potentiometric Stripping Analysis and computer-aided chemical speciation to quantify the concentrations of the trace elements of copper and zinc in the samples and to investigate the individual species of copper and zinc present. Comparisons were made between total concentrations of copper and zinc in wound fluid, pre-operative blood plasma levels and reference values. A wound fluid model constructed using JESS identified the main copper and zinc species present. It was also used to investigate the effects of a change in pH and changes in the total concentrations of certain components on their predominance. The clinical significance of the research is discussed, together with suggestions for a continuation in the research.

Breast Neoplasms↗

Royal Society of Chemistry--sixth international symposium on applied bioinorganic chemistry.

This was the sixth in a series of symposia that began in Beijing, China in 1986. Approximately 100 chemists, environmental and biomedical scientists from 25 countries attended the meeting and presented some 80 papers on topics ranging from cancer chemotherapy to the production of paper. About half the papers presented could be broadly described as having medical implications, and of these, approximately half related directly to the use of platinum and the potential uses of other metals, such as palladium and the lanthanides, as anticancer agents. Many of these papers provided valuable insights into mechanisms of action and offered pointers for future research, but only rarely did they point to potential new drugs that might find early exploitation in clinical medicine. Two of the more exciting clinical developments were the introduction of the insulin-mimetic bis(maltolato)oxovanadium(IV) (KP-102; Kinetek Pharmaceuticals Inc/University of British Columbia) into clinical trials in the UK for the treatment of Type II diabetes, and the increasing importance of the orally active agent 3-hydroxy-pyridin-4-one-deferiprone (Apotex Inc/Cipla Ltd), in the treatment of iron overload in thalassemia.

Journal Article↗

Developments in the theoretical modelling and experimental measurement of the surface potential of condensed monolayers.

In recent years considerable progress has been made in developing a theory for the surface potential of monolayers both at the air-water interface and deposited onto solid supports. This period has also seen the advent of scanning probe technology which has enabled surface potential to be measured to a hitherto undreamed of spatial resolution. This paper traces the key stages in these developments and explores the challenges that remain. Initially, the various models proposed for relating molecular and bond dipole moments to the surface potential are evaluated and the reliability of the moments obtained by applying the models to experimental results investigated. The limitations of the traditional Kelvin probe method of measuring surface potential are then highlighted and how these are overcome in the new generation of scanning force microscopes. Finally, it is suggested that such instruments could readily form the basis of a 'READ' head for a molecular memory based on a self-assembled, macromolecular lattice.

Journal Article↗

Analysis and chemical speciation of copper and zinc in wound fluid.

A novel method for the analysis of trace element chemical speciation at parts per billion (ppb) levels in wound fluid samples both contributes to the fundamental inorganic biochemistry of the healing process and permits improved treatments. Potentiometric Stripping Analysis in combination with acid digestion has been used to quantify the total copper and zinc levels in a series of 0.5 ml samples of fluid obtained from surgical wounds. Further, the degree of blood contamination has been investigated using visible spectroscopy. The prevailing chemical speciation (chemical forms) of these total concentrations of copper and zinc amongst low molecular mass ligands in wound fluid has been investigated by computer modelling using JESS, the Joint Expert Speciation System. The model, involving 38 components, generates in the region of 3500 individual low molecular mass complexes including copper, zinc, iron, calcium and manganese species, and predicts that the majority of low molecular mass (lmm) copper complexes are electrically net-neutral, whilst those of zinc are predominantly charged. Further studies indicate that supplementing the concentrations of histidine and tryptophan may increase the net-neutral zinc fraction, the optimum effect being achieved at pH=7.4. This may be important in transporting zinc into healing cells.

Body Fluids↗

Closely similar values obtained when the ME7 strain of scrapie agent was titrated in parallel by two individuals in separate laboratories using two sublines of C57BL mice.

A single C57BL mouse-brain infected with the ME7 strain of mouse-passaged scrapie agent was used to carry out four parallel infectivity titrations in mice. These were carried out by two individuals in two laboratories using two sublines of C57BL mice. The titre values obtained by the four assays were very similar, and showed no significant differences between the two different operatives, the two different laboratories or the two different sublines of C57BL mice. The data confirm the validity of comparing these types of transmission data generated in different laboratories when a common methodology is used.

Animals↗

Generic models for radionuclide dosimetry: 11C-, 18F- or 75Se-labelled amino acids.

A generic biokinetic model was developed for use in the assessment of the internal dose received by human subjects injected with amino acids labelled with 11C (T1/2 = 0.34 h, beta+, gamma), 18F(T1/2 = 1.83 h, beta+, gamma) or 75Se (T1/2 = 119.8 d, beta-, gamma). This generic model was used in conjunction with the MIRDOSE 3 computer programme to calculate radiation doses to adults; these radiation doses were compared with those calculated using compound-specific models for two [11C]-, and eight [18F]-labelled amino acids and [75Se]selenomethionine. In general, the effective doses, as well as the organ and tissue doses, calculated using the generic model agreed within a factor of 2 or less, with those calculated using compound-specific models; the generic model tended to over-, rather than underestimate the organ and tissue doses. It was concluded that for 11C- and 18F-labelled amino acids and for 75Se-labelled amino acids or their analogues, the single generic biokinetic model could be applied for general radiation protection purposes.

Adult↗