Biomedical subjects

R Bradley

Publications and source records attributed to R Bradley.

At least 19 recordsLinked to original sources

PubMed1997

BSE: a decade on--Part 2.

Predicted numbers vary widely but the most authoritative estimate is that about 6950 cases of BSE will occur in cattle in the UK during 1997-2001 if new infections via feed have ceased as expected and if 10% maternal transmission occurs in the last half-year of the maternal incubation period. This assumes no culling or premature slaughter. Agreed cull strategies would reduce these numbers considerably and accelerate the observed rate of decline of the disease, but there is no scientific necessity for any cull. Bovine products that were banned as specified bovine offals in 1989/90 and as specified bovine materials by successive legislation are now excluded from the food and feed chains. As this second of the two-part article on BSE shows, there has been slippage in some of our control measures, but public and animal health are adequately protected if the legislation that has been evolved is enforced along present lines. Meanwhile, for human beings, bovine milk is safe to drink and beef is safe to eat.

Animal Feed↗

PubMed1997

BSE: a decade on--Part I.

Bovine spongiform encephalopathy (BSE), popularly known as "mad cow disease", was discovered in 1986 and has accounted for the deaths of over 165,000 cattle in the UK (by the end of January, 1997) with about 34,000 (mainly dairy) herds involved. The syndrome in the cow includes changes in posture and temperament, apprehension, and loss of coordination. There are many parallels with scraple in sheep, with similar neuropathological changes in the hindbrain that give it a spongiform appearance under the microscope. The facts have been broadly reviewed in The Lancet in 1990 and 1993, and in much more detail elsewhere. In a two-part article, the first of which appears here, we now summarise recent developments.

Animal Feed↗

PubMed1997

Neuropathology of scrapie: a study of the distribution patterns of brain lesions in 222 cases of natural scrapie in sheep, 1982-1991.

Detailed neuropathological findings in 222 cases of naturally occurring scrapie from Great Britain are described. The material consisted of formalin-fixed brain from eight breeds of sheep submitted between 1982 and 1991. Paraffin-embedded histological sections were made from several specified brain areas, including the medulla oblongata, cerebellum, pons, mesencephalon, diencephalon, septal area, basal ganglia and frontal cortex. Sections were examined by conventional and polarised light microscopy and the type and distribution of the lesions were recorded. Histologically, the lesions included vacuolation of neuronal perikarya and grey matter neuropil, neuronal degeneration (especially "dark' neurons) and loss, a reactive glial (predominantly astrocytic) response and amyloidosis. Vacuolar lesions were present in the cerebral cortex of 37 per cent of cases, centred around the superior frontal gyrus. Vacuolar lesions were detected in the neocortex for as long as sections have been taken from the superior frontal gyrus and are thus probably not a new feature of the disease. The distribution of vacuolation in the grey matter neuropil could be classified into seven patterns. Data from individual breeds of sheep showed that in some breeds there were significant differences in the age at which animals with different patterns of vacuolation died from scrapie.

Age Factors↗

PubMed1996

Dopamine DRD2/Cys311 is not associated with chronic schizophrenia.

A mutation in the DRD2 receptor gene has been reported in association with schizophrenia in Japanese and Caucasian populations. The variation, Ser to Cys at codon 311, occurs in the third intracellular loop of the receptor and is therefore putatively functional. We report the results of screening US Caucasian schizophrenic and nonschizophrenic populations. We detected the occurrence of the DRD2 Cys311 variant in both schizophrenics and controls. Our data demonstrates no significant difference between the frequency of Cys311 in Caucasian schizophrenic and non-schizophrenic populations, indicating no association with schizophrenia.

Asian People↗

PubMed1996

Cocaine and butyrylcholinesterase (BChE): determination of enzymatic parameters.

In humans, the plasma enzyme, butyrylcholinesterase (E.C. 3.1.1.8), metabolizes cocaine to the water-soluble, pharmacologically inactive compounds, ecgonine methylester and benzoic acid. Homogeneous enzyme was purified from human plasma and used to determine the enzyme kinetic parameters of Km and Vmax with cocaine as the substrate. The KM (11.9 microM) indicates that cocaine is tightly bound to the four active sites of the native tetramer. The Vmax (1.17 microM/min) is 50-fold greater than cocaine catalytic antibodies. Administration of purified human butyrylcholinesterase to a cocaine-intoxicated patient would be expected to shift the metabolism to the inactive metabolites and reduce the toxicity.

Benzoates↗

PubMed1996

Cadherin function is required for axon outgrowth in retinal ganglion cells in vivo.

The cell-cell adhesion molecule N-cadherin strongly promotes neurite outgrowth in cultured retinal neurons. To test whether cadherins regulate process outgrowth in retinal neurons in vivo, we have blocked cadherin function in single cells by expression of a dominant negative N-cadherin mutant. We report that when cadherin function is inhibited, axon and dendrite outgrowth are severely impaired, particularly in retinal ganglion cells. Laminar migration and cell type specification, by contrast, appear unaffected. Further, expression of the catenin-binding domain of N-cadherin, which blocks cadherin-mediated adhesion in early embryos, does not affect axon outgrowth, suggesting that outgrowth and adhesion are mediated by distinct regions of the cytoplasmic domain. These findings indicate that cadherins play an essential role in the initiation and extension of axons from retinal ganglion cells in vivo.

Animals↗

PubMed1995

A stable interaction between separated pyrimidine.purine tracts in circular DNA.

Pyrimidine.purine tracts are widespread in eukaryotic genomes and have the potential to form a number of unusual structures including triplexes. Two such tracts, which could form triplexes with each other but not with themselves, were cloned into a plasmid at separate sites. Upon lowering the pH, linear, open circular and relaxed plasmid molecules formed a number of novel structures that were observed on agarose gels and directly by electron microscopy. In open circles a stable join was formed between the two Pyr.Pur tracts giving rise to molecules resembling dumbells, trefoils and tetrafoils, which collectively are termed T-loops. The structure was stable at pH 8 and contains a single-stranded region that was sensitive to P1 nuclease. Thus, there is no apparent topological impediment to the formation of triplex-mediated loops in circular molecules. These structures may be important for gene regulation and chromosome condensation.

Base Sequence↗

PubMed1995

Health status of preterm low-birth-weight infants. Comparison of maternal reports.

BACKGROUND: Developers of measures of child health status have documented acceptable reliability and some validity, but less attention has been paid to the concurrent and predictive validity of these measures. METHODS: We examined the concurrent and predictive validity of the RAND General Health Rating Index, the Stein-Jessop Functional Status II-R, and the mother's global assessment of her child's health on a 5-point scale, in a sample of preterm low-birth-weight children (n = 608) who were followed up as controls in the Infant Health and Development Program. We compared maternal-reported measures assessed at 24 months with other measures of growth, morbidity, functioning, and health care utilization assessed concurrently and at 36 months in bivariate and multivariate analyses. RESULTS: After controlling for other factors, the RAND General Health Rating Index and the Stein-Jessop Functional Status II-R were unrelated to the growth, utilization, or functioning measures. The RAND General Health Rating Index was significantly, but weakly, related to future morbidity. The mother's global perception of health was significantly related to outpatient utilization and behavior problems. CONCLUSIONS: Clinicians may find that maternal assessment of overall child health is a sensitive but nonspecific indicator of the mother's concern. For researchers, none of these measures seems likely to serve as a proxy for health care utilization or morbidity in studies of other phenomena, or as an indicator of detailed health outcomes.

Adult↗

PubMed1994

Digital rectal examination, serum prostate specific antigen, and prostatic ultrasound: how effective is this diagnostic triad?

Ninety-nine of 105 consecutive men who underwent transrectal prostatic ultrasound (TRUS) at Highland Park Hospital had the results correlated with digital rectal examination (DRE), serum prostate specific antigen (PSA), and biopsy results. Ninety-six cases had evaluable ultrasound studies. Thirty-two of the 99 who underwent biopsy had primary carcinoma of the prostate. Prostate volume, predicted PSA, a ratio of observed/predicted PSA, and Gleason score were examined. There was no correlation between age and prostate volume, volume and the presence of carcinoma, or PSA and Gleason score. Thirty-one point six percent of the abnormal DREs, 36.6% of the abnormal TRUSs, and 40.6% of the elevated PSAs occurred in men with prostatic carcinoma (PCa). If PSA was normal (less than or equal to 4.0 ng/ml) and either DRE or TRUS was abnormal, then the risk of carcinoma was 2.9%. If PSA was elevated, regardless of the other two tests, the risk of finding PCa was at least 38%. If all three tests were abnormal, the risk of carcinoma was 38% in our series and 68% in a meta-analysis. Many men with PSA values between 4 and 10 ng/ml have benign biopsies. However, close future follow-up with consideration of repeat biopsy should be strongly considered.

Aged↗

PubMed1994

Production of PEG-modified bovine hemoglobin: economics and feasibility.

Bovine hemoglobin has many advantages as a blood substitute: a) it's ready availability; b) it's low cost; c) it's oxygen carrying capacity; and d) the ease with which it can be modified with polyethylene glycol (PEG) to improve its pharmacokinetic profile. This study investigates the potential of PEG-modified bovine hemoglobin as a cost-effective blood substitute.

Animals↗

PubMed1994

Effect of phospholipase C and apolipophorin III on the structure and stability of lipophorin subspecies.

Four distinct subspecies of the insect hemolymph lipoprotein, lipophorin, that range in diacylglycerol (DAG) content from approximately 100 to 1000 molecules per particle, were treated with phospholipase C. Lipid analysis demonstrated that both phosphatidylcholine and phosphatidylethanolamine were hydrolyzed to DAG. Phospholipase C was used to remove 74-82% of the phospholipid of different lipophorins and these were analyzed for aggregation. Low density lipophorin (LDLp), the largest subspecies, with a diameter of approximately 23 nm, developed turbidity (monitored by sample absorbance at 340 nm) suggesting the formation of lipoprotein aggregates. High density lipophorin-adult (HDLp-A) and high density lipophorin-wanderer 1 (HDLp-W1) also displayed an increase in A340 when incubated with phospholipase C, although the maximal increase observed was considerably less than that for LDLp on a per particle basis. Phospholipase C caused only a minimal increase in A340 in a fourth subspecies, high density lipophorin-wanderer 2 (HDLp-W2), which contains an even lower amount of DAG. Electron microscopy was used to evaluate changes in particle morphology as a result of phospholipid depletion. HDLp-W2 and HDLp-W1 showed signs of progressive aggregation and particle fusion. A similar aggregation/fusion was seen in the case of high density lipophorin adult (HDLp-A) while LDLp samples contained multiple aggregation/fusion foci and resultant very large particles. In the presence of exogenous apolipophorin III (apoLp-III), phospholipase C-induced lipophorin aggregation/fusion was prevented. Electron microscopy of LDLp and HDLp-A samples revealed that apoLp-III-stabilized, phospholipase C-treated particles had a morphology similar to that of control particles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Responses of children to booster immunization with their primary conjugate Haemophilus influenzae type B vaccine or with polyribosylribitol phosphate conjugated with diphtheria toxoid.

Children primed with one of four conjugate Haemophilus influenzae type b vaccines received booster immunization with their primary vaccine or with polyribosylribitol phosphate conjugated with diphtheria toxoid. The latter vaccine produced postbooster antibody levels that equaled or exceeded those produced by boosting with the original vaccine, and thus may be used as a booster irrespective of the original vaccine.

Antibodies↗

PubMed1993

Immunologic and molecular biologic studies of prion proteins in bovine spongiform encephalopathy.

Bovine spongiform encephalopathy (BSE) is a transmissible neurodegenerative disease. Six brain regions from 11 cattle were examined for the presence of the abnormal isoform of the prion protein (PrPBSE). The highest concentrations of PrPBSE were found in the brain stem, where the greatest degree of spongiform change was observed. Molecular cloning of the bovine PrP gene showed that it encodes a protein of 256 or 264 amino acids with five or six Gly:Pro-rich octarepeats, respectively, in contrast to all other mammalian PrP genes, which encode only five octarepeats. The bovine PrP gene is single copy, and the entire open-reading frame lies within a single exon. Since the transmission of prions across species seems to be restricted by differences in PrP sequence, the high degree of homology between sheep and bovine PrP (98%) correlates with the proposed cause of BSE.

Amino Acid Sequence↗

PubMed1993

Epidemiology and control of bovine spongiform encephalopathy (BSE).

BSE is a new disease of cattle. The first clinical case occurred in April 1985 but the existence of a new disease was first confirmed microscopically in November 1986. Epidemiological studies show that cattle suddenly became effectively exposed to a scrapie-like agent in ruminant-derived feed in the form of meat and bone meal in 1981/2. Most cases have occurred in Holstein Friesian dairy cattle and have been exposed as calves. There is no evidence that cattle to cattle transmission sufficient to maintain the epidemic occurs. The principle animal health control measures are bans on the feeding of ruminant derived protein to ruminant animals and on the use of specified bovine offals (SBO) for feeding to any species of animal or birds. Human health is protected by compulsory slaughter and destruction of suspect animals, and a ban on the use of their milk, and by prohibiting the use of SBO in food. The SBO are those tissues which, in clinically healthy cattle incubating BSE, might conceivably harbour infectivity. The effectiveness of the bans is supported by recent evidence of a decline in the cattle epidemic. There is no evidence that BSE is a zoonosis.

Animals↗

PubMed1993

Pyridostigmine toxicity. Electrophysiological study.

A 54-year-old neurotic patient developed pyridostigmine-induced proximal weakness with daily 3600 mg of pyridostigmine. Detailed analysis of the RNS test showed three different types of responses which were reproduced in the in vitro nerve-muscle preparation, confirming that three different responses represent the different degree of pyridostigmine toxicity. One of responses was a pattern, thought to be typical of anticholinesterase toxicity: repetitive discharge and the maximal decrement in the second response followed by an increment (dip phenomenon). With reduction of pyridostigmine, clinical and electrophysiological improvement followed.

Action Potentials↗

PubMed1993

The research programme on transmissible spongiform encephalopathies in Britain with special reference to bovine spongiform encephalopathy.

Research into bovine spongiform encephalopathy (BSE) commenced immediately following its discovery in November 1986. Formal epidemiological studies commenced in June 1987 and were part of a large research programme set up mainly at the Central Veterinary Laboratory Weybridge and the Institute for Animal Health, AFRC/MRC Neuropathogenesis Unit in Edinburgh. This programme also covered the clinicopathology of BSE, transmission studies and molecular chemistry. Research results have shown that BSE is a member of the group of diseases known as the sub-acute spongiform encephalopathies caused by unconventional transmissible agents and which includes scrapie of sheep, from which BSE was probably derived, and Creutzfeldt Jakob disease (CJD) of man. The agent causing BSE closely resembles strains of the scrapie agent but is not identical. Spongiform encephalopathy has developed in sheep, goats, pigs, cattle, marmosets and mice but not hamsters following experimental inoculation of brain material from confirmed clinical cases of BSE. BSE agent has been detected by mouse bio-assay in brain from cows from several sources confirmed to have BSE. Infectivity has not been detected in spleen, buffy coat, semen, muscles, placenta and bone marrow (all following parenteral inoculation) nor in milk/mammary gland, spleen, placenta and a variety of lymph nodes following substantial oral exposure. This latter route successfully transmitted disease to mice with brain/cerebrospinal fluid. The introduction of modified rendering systems, which did not employ hydrocarbon solvent extraction, were probably responsible for an increase in exposure of cattle from 1981-1988 sufficient to cause the disease. Experiments are in progress to investigate the effectiveness of different rendering systems used in the European Community and of chemical and physical de-activating procedures for destroying BSE and scrapie infectivity. A clear genetic influence on disease susceptibility has been suggested but is not yet proven. The Agricultural and Food Research Council have set up a large Biology of Spongiform Encephalopathies Research Programme to address some of the more fundamental unknowns of this group of diseases but it is too early to report results. As with scrapie, no epidemiological relationship has been demonstrated between BSE and the human diseases through the monitoring programme that has been established by the Department of Health to detect such an occurrence. BSE research results so far show that controls to protect animal and human health and based initially on scrapie research findings, are sound.(ABSTRACT TRUNCATED AT 400 WORDS)

Academies and Institutes↗

PubMed1992

Recommendations of the International Roundtable Workshop on Bovine Spongiform Encephalopathy.

Recommendations of the working party were summarized as follows: Determine the status in all countries of their national cattle herds with respect to BSE. Attempt to develop a test to recognize BSE-infected animals before they become clinically ill. Establish procedures to prevent spread of BSE agent into the cattle populations, especially by eliminating feeds containing rendered ruminant proteins. Review the rendering processes, identify the sources and destinations of rendered products, and suggest appropriate changes if needed. Especially needed are standardized rendering procedures in regard to use of organic solvents, temperature, and duration of heat treatment. Review import and export regulations to reduce the risk of spreading BSE and to maximize opportunities for safe trading in cattle and cattle products. The scrapie-free certification program of the USDA was supported, and similar programs might be considered by other countries. If BSE/scrapie is diagnosed in a given country, determine baseline incidence of CJD in those countries and consider contributing to an international registry. The WHO should address the problems of BSE, formulate policy, participate in and coordinate research, and provide training opportunities for veterinary and human health care workers from eastern European countries and developing nations. Government and private agencies should consider increasing support for research on transmissibility and pathogenesis of CJD, BSE, CWD, scrapie, and transmissible mink encephalopathy. Prepare and publish a critical neuropathologic review of all spongiform encephalopathies, naturally and experimentally transmitted, defining the characteristics of each disease in the various species known to be susceptible. Consider producing guidelines for the biological and pharmaceutical industries with regard to sourcing, collecting, and processing bovine and ovine materials.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Comparative trial in infants of four conjugate Haemophilus influenzae type b vaccines.

We performed a double-blind, randomized trial to compare the immunogenicity and reactogenicity of four conjugate Haemophilus influenzae type b vaccines given to infants 2, 4, and 6 months of age. Adverse reactions attributable to the vaccines were few and minor. The rates of systemic reactions did not differ among the various vaccines and were similar to those seen among children receiving conventional diphtheria-tetanus-pertussis vaccine. However, the four conjugate H. influenzae type b vaccines differed markedly in ability to stimulate antibody production. Mean antibody levels after three injections of polyribosylribitol phosphate conjugated with mutant diphtheria protein (PRP-CRM) or polyribosylribitol phosphate conjugated with tetanus toxoid (PRP-T) were 3.08 micrograms/ml and 3.64 micrograms/ml, respectively, significantly higher than those after the use of polyribosylribitol phosphate conjugated with outer-membrane protein of Neisseria meningitidis (PRP-OMP) (1.14 micrograms/ml) or polyribosylribitol phosphate conjugated with diphtheria toxoid (PRP-D) (0.28 microgram/ml). Only PRP-OMP produced a clinically pertinent elevation in antibody level after two injections (0.84 microgram/ml); the third injection of PRP-OMP produced a modest but statistically significant further elevation in mean antibody level (1.14 micrograms/ml). Only 29% of infants receiving PRP-D had antibody levels of 1 micrograms/ml, compared with 55%, 75%, and 83% of those receiving PRP-OMP, PRP-CRM, and PRP-T, respectively. We conclude that all four vaccines are safe and that all but PRP-D appear appropriate for use in a primary immunization series during infancy. The unique serologic response to PRP-OMP offers both advantages and disadvantages in comparison with PRP-CRM and PRP-T.

Antibody Formation↗