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Biomedical subjects

J D Bell

Publications and source records attributed to J D Bell.

At least 127 records · Page 7Linked to original sources
PubMed1991

In vivo detection of metabolic changes in a mouse model of scrapie using nuclear magnetic resonance spectroscopy.

In vivo proton nuclear magnetic resonance (NMR) spectroscopy studies of scrapie in a mouse model have shown the appearance of an abnormal peak in the brain early in the incubation period. This abnormal peak was detected weeks before the detection of a protease-resistant form of a membrane protein and vacuolar histopathology in vitro, and several months before clinical signs, and the signal increased in intensity as the disease progressed. In the chronic stage of the disease, a reduction in N-acetyl aspartate levels was observed using in vivo and in vitro proton NMR spectroscopy.

Animals↗
PubMed1990

31P magnetic resonance spectroscopy of the human paediatric liver.

Localized 31P NMR spectroscopy was used to study the developing human liver in three neonates and one infant, all with neonatal intracranial problems, but normal liver function. A prominent resonance was present in the phosphomonoester (PME) region of the spectrum of the neonates; the PME/ATP ratio was 1.0 +/- 0.4 (repetition time 1 s), compared to the mean adult liver value of 0.2 +/- 0.1. The saturation factor of PME in the neonates was large, indicating that the increase in PME/ATP reflected an increase in relative PME concentration. The chemical shift of the PME peak in the neonatal liver (6.8 +/- 0.1) was similar to that found in neonatal brain, suggesting that phosphorylethanolamine may be a major constituent. The phosphodiester (PDE)/ATP ratio in these patients (0.4 +/- 0.1) was decreased compared with the mean adult value (1.3 +/- 0.2), and the saturation factor of PDE was small. The results from the infant were different from both the neonates and adults; PME/ATP was decreased compared to the neonates, but increased compared to adults. The saturation factor of PDE was increased compared to neonates. The biochemical implications of the observed changes in PME and PDE in paediatric liver are discussed in relation to membrane turnover.

Brain Diseases↗
PubMed1990

Veterinarians, advertising and competition--three years on.

The views of veterinarians towards the changes that are occurring in professional practice with respect to competition and advertising are examined and compared with the views expressed in a similar study carried out 3 years previously. Data was derived from self completion questionnaires containing 40 Likert scales which were mailed to 300 members of the profession, first in 1985 and then in 1988. The moves made by the New Zealand Veterinary Association since 1985 in relaxing the rules on promotion appear to have largely alleviated any frustrations that were building up amongst the membership at that time. However, the study suggests that the profession will still find the boundaries of acceptable behaviour being tested by entrepreneurial practitioners.

Journal Article↗
PubMed1990

Endovascular treatment of intracranial aneurysms with a new silicone microballoon device: technical considerations and indications for therapy.

Treatment of complex intracranial aneurysms by means of interventional neurovascular techniques is now being performed with a newly developed silicone detachable-microballoon device. The balloon is composed of unique silicone elastomers that are extremely soft and malleable. It therefore conforms to the blood vessel lumen or aneurysm wall and reduces the risk of rupture. It is affixed onto a 2.0-F catheter and can be either directed by flow or guided with the catheter. For aneurysms with a well-defined neck, the balloon is placed directly into the aneurysm, inflated with 2-hydroxyethyl methacrylate for permanent solidification, and detached. The aneurysm is thus excluded from the circulation, and the parent vessel is preserved. For aneurysms without a well-defined neck, test occlusion can be performed, followed by permanent balloon occlusion of the parent vessel. This balloon technique has been successfully used to treat aneurysms in both the anterior and posterior circulations, where standard neurosurgical techniques have failed, and in surgically inaccessible anatomic locations.

Adolescent↗
PubMed1990

Non-steady state kinetic analysis of the regulation of adenylate cyclase by GTP-binding proteins.

The time course of cAMP production by S49 cell membranes in the presence of forskolin and a nonhydrolyzable GTP analog can yield information about the regulation of adenylate cyclase by both the inhibitory and stimulatory GTP-binding proteins (Gi and Gs). The time courses are complex and interpretation in terms of the activities of G1 and Gs requires a quantitative hypothesis. We present a general quantitative hypothesis that defines adenylate cyclase as existing in a distribution of two states, active and inactive. Gi and Gs, in their active states, alter the equilibrium of this distribution. Two distinct models are derived based on this hypothesis to accommodate two different proposed mechanisms for the action of Gi to inhibit adenylate cyclase: 1) a direct interaction between Gi and the catalytic subunit of adenylate cyclase and 2) a direct interaction between Gi and Gs. Perturbations of the regulation of adenylate cyclase by pertussis toxin and phorbol ester are simulated and interpreted using the models. The effect of pertussis toxin is quantitatively reconciled by decreases in the guanine nucleotide-independent adenylate cyclase activity and in the apparent rate of activation of Gi from 2.0/min to 0.01/min. The effect of phorbol ester is best accommodated by the model as a change in the distribution of active and inactive adenylate cyclase from 36% initially active to 47% active after phorbol ester treatment, without postulating any effect of phorbol ester on Gi or Gs. Both of these interpretations are independent of the model used. The effect of forskolin is also examined within the context of the two models. The results of this examination suggest an experimental approach for testing the models. These examples illustrate the usefulness of quantitative analysis of time course data using a model for the regulation of adenylate cyclase. We propose that, with this combined experimental and theoretical approach, one can address the relevance of hypotheses generated from experimental studies with isolated components to the molecular mechanisms of adenylate cyclase regulation in cellular membranes.

Adenylate Cyclase Toxin↗
PubMed1990

Attitudes of dental practitioners towards advertising and competition.

This paper examines the attitudes of dental practitioners towards competition and advertising and the changes that have occurred there between 1985 and 1988. It provides an insight into the views of members of the profession as they dealt with the issue of commercialisation. The study came at a time when proposed legislative changes would profoundly impact upon the profession's stance on business ethics and upon the business practice of its members. The data were derived from a self-completion questionnaire, 1,500 of which were evenly distributed among the members of five professions, doctors, dentists, lawyers, accountants, and veterinarians. The main findings were that the dental profession had moved along the collegiality-competition continuum only slightly, preferring to shun the use of overtly competitive behaviour while seeking to improve the efficiency of practice management.

Advertising↗
PubMed1989

The temporal sequence of events in the activation of phospholipase A2 by lipid vesicles. Studies with the monomeric enzyme from Agkistrodon piscivorus piscivorus.

The substrate dependence of the time courses of hydrolysis of both small and large unilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC) by Agkistrodon piscivorus piscivorus monomeric phospholipase A2 is consistent with an activation process involving enzyme aggregation on the vesicle surface. The time course of hydrolysis of large unilamellar vesicles is particularly complex; a slow initial rate of hydrolysis is followed by an extremely abrupt increase in enzyme activity. The length of this slow phase is a minimum at the phase transition temperature of the vesicles. The intrinsic fluorescence intensity of the phospholipase A2 also abruptly increases (50-60%) after a latency period revealing a strong temporal correlation between enzyme activity and the increase in fluorescence intensity. The length of the latency period before the sudden increase in fluorescence intensity is directly proportional to substrate concentration at DPPC concentrations above 20-100 microM. At lower concentrations, the length of the latency period is inversely proportional to the DPPC concentration. Such biphasic substrate dependence is predicted by a previously proposed enzyme activation model involving dimerization on the surface vesicle. Simultaneous monitoring of the protein fluorescence and hydrolysis demonstrates that the magnitude of the fluorescence change and the rate of hydrolysis are in exact temporal correlation. Furthermore, simultaneous monitoring of the fluorescence of the protein and that of a lipid probe, trimethylammonium diphenylhexatriene, indicates a change in lipid vesicle structure prior to, or coincident with, the abrupt change in protein activation. These results are consistent with the hypothesis that the monomeric phospholipase A2 from A. piscivorus piscivorus initially possesses a low level of intrinsic activity toward large unilamellar DPPC vesicles and that the enzyme slowly becomes further activated on the vesicle surface via dimerization. Eventually, the vesicles undergo an abrupt transition in internal structure leading to sudden rapid activation of the enzyme.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1989

Non-transferrin-bound iron in plasma or serum from patients with idiopathic hemochromatosis. Characterization by high performance liquid chromatography and nuclear magnetic resonance spectroscopy.

The nature of non-transferrin-bound iron in the plasma or serum of iron-overloaded hemochromatosis patients was studied by high performance liquid chromatography (HPLC) and high resolution nuclear magnetic resonance (NMR). 500-MHz proton Hahn spin-echo NMR spectra of plasma or serum, combined with the use of the iron chelator desferrioxamine, suggests complexation of iron ions with citrate and a possible involvement of acetate. Addition of FeCl3 to hemochromatosis samples broadened the NMR signals from citrate. HPLC analysis rigorously confirmed the presence of an iron-citrate complex in ultrafiltrates of plasma or serum studies with added FeCl3 or desferrioxamine supported this conclusion. It is proposed that non-transferrin-bound iron in the plasma of iron-overloaded patients exists largely as complexes with citrate and possibly also as ternary iron-citrate-acetate complexes. The presence of such complexes would account for the ability of non-transferrin-bound iron to be measurable by the bleomycin assay and for its rapid clearance from the circulation by the liver.

Acetates↗
PubMed1989

Thermodynamic and kinetic studies of the interaction of vesicular dipalmitoylphosphatidylcholine with Agkistrodon piscivorus piscivorus phospholipase A2.

The tryptophan fluorescence emission intensity at 340 nm of monomeric phospholipase A2 from Agkistrodon piscivorus piscivorus increased about 70% upon addition of dipalmitoylphosphatidylcholine small unilamellar vesicles (DPPC SUV) at 25 degrees C. The emission spectrum was also blue-shifted 6-8 nm, suggesting that the environment of 1 or more tryptophan residues had become less polar. This effect of SUV on the phospholipase A2 fluorescence was independent of Ca2+ at 25 degrees C, and the apparent association constant for the interaction was approximately 1.7 x 10(4) M-1. The apparent Km for hydrolysis of DPPC SUV was equal to the inverse of the estimated association constant. In the absence of Ca2+, the change in fluorescence intensity decreased with increasing temperature. Thermodynamic analysis of this reversible, temperature-dependent fluorescence change indicated that the A. p. piscivorus monomer phospholipase A2 interacts only with SUV in the true gel phase existing below the pretransition of gel to "ripple" phase lipid in the absence of Ca2+. In contrast, the fluorescence intensity change upon addition of SUV in the presence of Ca2+ was independent of temperature over the range of 25-48 degrees C. Under these conditions, hydrolysis of the lipid occurred concomitantly with the change in fluorescence which could not be reversed by the addition of EDTA. With a nonhydrolyzable analog of DPPC, however, the fluorescence changes upon mixing of SUV, Ca2+, and phospholipase A2 were reversible and temperature-dependent. Thus, the apparent irreversibility of the change in fluorescence observed with Ca2+ and DPPC SUV was correlated with hydrolysis of the vesicles. These results indicate that the magnitude of the initial interaction of enzyme with substrate is reversible, is Ca2+-independent, depends upon the lipid state, and is quantitatively correlated to the maximum rate of hydrolysis.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1989

Maternal and cord blood plasma. Comparative analyses by 1H NMR spectroscopy.

Normal and 'Hahn' spin-echo 500 MHz 1H NMR spectra of 21 pairs of plasma from mother and cord taken at the time of delivery are reported. The concentrations of 'NMR-visible' lactate, alanine, and valine in the cord plasma significantly exceed those in the maternal plasma. In both maternal and cord plasma, measured lactate levels appear to increase with the length of the second stage of labour. Ethanol was unexpectedly detected in five samples of cord plasma. Lipoprotein--CH3 and--(CH2)n--resonances are more intense in the spectra of maternal plasma compared to cord plasma, and are unusual in composition. The intensities of N-acetyl signals from 'acute-phase' plasma glycoproteins are greater in spin-echo spectra of maternal plasma compared to those of cord plasma (mean ratio 2.1 (SD 0.8]. These results suggest that high resolution NMR spectroscopy may provide a useful new insight into the comparative biochemistry of maternal and cord plasma.

Acute-Phase Proteins↗
PubMed1989

1H NMR study of cerebral development in the rat.

1H NMR spectroscopy of brain extracts was used to investigate the metabolic changes that take place during development of the neonatal rat brain. Data were obtained over the range 1-21 days. The concentration of N-acetylaspartate rose by a factor of 9 during this period, the most rapid rise occurring after day 9. The total creatine concentration rose from days 1-21, with a large increase between days 1 and 5. Taurine concentration rose until day 5, then fell from days 5-21. The concentration of choline-containing compounds fell during the 21 day period. The results are discussed in relation to brain development and conventional biochemical data. A major conclusion in relation to spectroscopy of children is that interpretation of changes seen in disease will require adequate data from age-matched controls.

Animals↗
PubMed1989

NMR studies of body fluids.

High resolution, high frequency, in vitro, proton NMR spectra of various body fluids, including urine, sweat, aqueous humour, amniotic fluid, seminal plasma, cerebrospinal fluid, synovial fluid and blood plasma are described and discussed. Applications include the detection of metabolic disorders, investigations of the biochemical basis of drug and xenobiotic metabolism, organ damage, and diagnoses for sick babies. The determination of metabolite concentrations is straightforward for fluids with a low protein content such as urine. In fluids with a high protein content such as blood plasma, it is possible to detect not only small molecules but also mobile regions of macromolecules, and to demonstrate the interaction of anions such as lactate with proteins. It seems likely that these methods will soon become established in modern pathology laboratories.

Body Fluids↗
PubMed1988

NMR-invisible lactate in blood plasma.

Resonances for lactate are broadened in 500 MHz 1H NMR spectra of human blood plasma and only about one-third is visible in Hahn spin-echo spectra. Similar effects are observed for some other carboxylate anions. Lactate added to the high-Mr fraction of plasma can give rise to peaks which are too broad to observe in either single-pulse or spin-echo spectra. Addition of agents such as NH4Cl of SDS dramatically increases the intensities of lactate peaks. Some glycoproteins appear to broaden lactate resonances.

Ammonium Chloride↗
PubMed1988

Metabolic profiling of body fluids by proton NMR: self-poisoning episodes with paracetamol (acetaminophen).

1H NMR spectra of urine and plasma from subjects who had taken paracetamol (acetaminophen) at a therapeutic dose or in self-poisoning episodes (both fatal and nonfatal) are compared. They provide convenient metabolic profiles. For overdose cases, intense resonances corresponding to high levels of both drug and endogenous metabolites are observed. The ratios of glucuronide to sulfate conjugates are unusually high in urine from overdose cases. Elevated levels of the cysteinyl and N-acetyl cysteinyl conjugates reflect increased glutathione conjugation in the liver. The observed excretion of high levels of amino acids by overdose subjects is suggestive of drug-induced hepatic damage. No resonances for drug metabolites are detected in plasma samples. However, characteristic and abnormally intense resonances for the amino acids Phe, Tyr, His, Gln, Pro, Ala, Val, Lys, Met, Ser, and Thr are indicative of severe liver failure and disruption of normal deamination and transamination processes.

Acetaminophen↗
PubMed1988

Factors affecting 1H NMR spectra of blood plasma: cancer, diet and freezing.

Single pulse and Hahn spin-echo 400 and 500 MHz 1H NMR spectra from normal subjects and cancer patients are reported. No significant difference was found between the average -CH3 and -(CH2)n- lipoprotein linewidths of the two groups in contrast to a previous report. Such measurements are shown to be complicated by freezing and thawing of samples which broadens lipoprotein resonances, and by eating which sharpens them. Deconvolution of the composite lipoprotein signals enables these effects to be interpreted. Other notable features of plasma spectra are discussed including resonances for 'acute-phase' glycoproteins, ketone bodies and other small molecules.

Acute-Phase Proteins↗