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Biomedical subjects

M Murray

Publications and source records attributed to M Murray.

At least 109 records · Page 6Linked to original sources
PubMed1998

Studies on host resistance to tick infestations among trypanotolerant Bos indicus cattle breeds in east Africa.

Recent epidemiological studies carried out in East Africa have indicated that some Bos indicus cattle breeds such as the Orma Boran and Maasai Zebu have a degree of trypanotolerance worth exploitation by their introduction into trypanosomosis endemic areas where other cattle breeds cannot survive. However, in most areas of East Africa, trypanosomosis, ticks, and tick-borne diseases occur together. It is therefore important to obtain information on the susceptibility of these breeds to tick infestation and tick-borne diseases. This study was therefore designed to determine the susceptibility of these cattle breeds to tick infestations. They were compared with the Galana Boran (trypanosusceptible) and the Friesian (susceptible to tick infestations, tick-borne diseases, and trypanosomosis). The four breeds of cattle were exposed to natural tick challenge for a period of seven months and whole body weekly tick counts were done on each animal. Significant differences to tick infestations among the four breeds were observed. For both Rhipicephalus appendiculatus and Boophilus decoloratus, susceptibility to infestation increased in the order, Maasai Zebu, Orma Boran, Galana Boran and Friesian. The results generated by this pilot study so far suggest that variation in susceptibility to tick infestations exists among the four breeds. The Orma Boran and Maasai Zebu showed greater resistance to tick-infestations than the Galana Boran and Friesian. This suggests that utilization of these trypanotolerant cattle breeds could be feasible even in the face of tick challenge and should therefore be considered when planning integrated trypanosomosis and tick control strategies.

Africa, Eastern↗
PubMed1998

Comparative induction of CYP3A and CYP2B in rat liver by 3-benzoylpyridine and metyrapone.

3-Benzoylpyridine (3BP) is a major metabolite of HGG-12, and oxime that has been synthesized as a potential antidote to the toxic effects of soman and other anticholinesterases. Structural similarities exist between 3BP, the cytochrome P450 (CYP)-inducer metyrapone (MET) and other 3-substituted pyridines that interact with CYPs. The present study evaluated the regulatory effects of 3BP on CYP expression in rat liver. Both 3BP and MET (100 mg/kg) increased total hepatic microsomal holo-CYP content significantly 24 h after administration to male rats. Pronounced increases in activities mediated by CYP2B (androstenedione 16 beta-hydroxylation and 7-pentylresorufin O-depentylation) were produced by 3BP and MET, which correlated with respective 9- and 14-fold increases in CYP2B immunoreactive protein. In addition, both agents slightly increased rates of microsomal CYP3A-dependent steroid 6 beta-hydroxylation, troleandomycin metabolite complex formation and total CYP3A immunoreactive protein. Induction of the dexamethasone-inducible CYP3A23 mRNA to 4.5- and 2.5-fold of control was detected in liver of MET- and 3BP-induced rats; CYP3A2 mRNA levels were unchanged. Analogous in vitro studies revealed that MET was a preferential inhibitor of CYP3A-mediated steroid 6 beta-hydroxylation activity, but 3BP was inactive against constitutive steroid hydroxylase CYPs. These findings indicate that the structurally related 3BP and MET elicit similar induction effects on CYPs 2B and 3A23 in rat liver after in vivo administration, but differential inhibitory effects of the chemicals on CYP activity in vitro. Recent reports have implicated a microsomal binding site in the induction of CYP3A1/3A23 in rat liver. In light of the present findings, substituted pyridines like 3BP may be useful tools in structure-activity studies to evaluate the physicochemical requirements for binding to this protein.

Androstenedione↗
PubMed1998

Intraspinal grafting of fibroblasts genetically modified by recombinant adenoviruses.

Intracerebral or intraspinal grafting of genetically modified primary fibroblasts has been shown to enhance functional recovery in several models of CNS disease, including spinal cord injury. Most of these studies utilized retrovirus vectors. In this report, we describe in vitro conditions for genetically modifying primary fibroblasts with recombinant adenovirus vectors carrying the lacZ or green fluorescent protein (GFP) genes. As intraspinal allografts in animals immunosuppressed by cyclosporin A, the genetically modified cells survived and expressed the transgenes for at least 2 months. We conclude that recombinant adenovirus vectors are efficient and convenient tools for ex vivo gene therapy in the CNS.

Adenoviridae↗
PubMed1998

Application of probability techniques to the objective interpretation of veterinary clinical biochemistry data.

Methods for the interpretation of veterinary clinical biochemistry have not developed as rapidly as biochemical technology. However, the results of clinical biochemistry tests are only of value when they are interpreted appropriately. A retrospective study was undertaken to investigate the equine biochemistry data which had been stored in a veterinary hospital database. By applying percentile analysis and Bayesian probability methods to the clinical biochemistry and corresponding diagnosis data, a novel method for the interpretation of clinical biochemistry data has been developed. The method allows clinicians to determine whether a biochemistry value is abnormal, its degree of abnormality, and the most likely associated diagnoses. The method could be used to investigate a practice-based population and may have significant implications for the interpretation of clinical biochemistry data in veterinary medicine in the future.

Animals↗
PubMed1998

Identification of a novel transcriptional silencer in the protein-coding region of the human CYP2C9 gene.

A novel regulatory element (27 bp) which confers transcriptional repression was identified within the protein-coding region immediately after the translation start codon in the human cytochrome P450 (CYP) 2C9 gene. Deletion of this element increased transcriptional activity in HepG2 cells by transient transfection assay. Nuclear protein extracts from HepG2 cells and human liver were found in electrophoretic mobility shift assays to bind specifically to the 27 bp element. A putative binding protein was partially purified by DNA-affinity chromatography and was determined by Southwestern blotting to have a molecular weight of approx. 100 kDa. Studies with mutated competitor oligonucleotides established that binding of the nuclear protein to the 27 bp cis-element was dependent upon two 6 bp direct repeats (5'-CTTGTG-3') that were separated by three bases. It is possible that this novel cis-acting element may be involved in the negative regulation of CYP2C9.

Aryl Hydrocarbon Hydroxylases↗
PubMed1998

Formation of a dihydropyridine derivative as a potential cross-link derived from malondialdehyde in physiological systems.

Malondialdehyde is a major oxidation product of lipids which is capable of cross-linking the collagen of the cardiovascular system. Identification of cross-links usually involves degradative procedures. In this paper, we use a novel, direct, approach using nuclear magnetic resonance to identify early and labile products. Initial model studies show that malondialdehyde reacts with lysine to form a dihydropyridine derivative rather than the unstable imidopropene Schiff base previously reported. The aldehydes on the pyridine ring could react further to cross-link collagen and stiffen the aorta, thereby promoting further glycation, a process that would be accelerated in diabetes.

Cross-Linking Reagents↗
PubMed1998

Critical interval for rescue of axotomized neurons by transplants.

To determine whether embryonic spinal cord transplants retained the ability to prevent retrograde death of Clarke's nucleus (CN) neurons if supplied after a delay, we hemisected adult rats at the T8 spinal cord segment and placed transplants of fetal tissue into the hemisection cavity immediately or up to 14 days later. Transplants provided in the first 7 days after injury prevented virtually all of the 30% loss of CN neurons at L1 ipsilateral to hemisection that occurs without a transplant. Transplants supplied at 14 days post-hemisection were ineffective. Because prevention of retrograde neuron death is one mechanism by which transplants may contribute to locomotor recovery after spinal cord injury, this window of effectiveness should be considered in the design of clinical trials.

Animals↗
PubMed1998

Neurotrophin-3 prevents death of axotomized Clarke's nucleus neurons in adult rat.

In the present investigation, we studied whether neurotrophin-3 (NT-3) contributes to the rescue of axotomized Clarke's nucleus (CN) neurons in adult rats. A significant (24%) loss of CN neurons occurred at L-1 ipsilateral to T-8 hemisection by 14 days, which reached 31% at 2 months and then stabilized. Axotomized CN neurons had also atrophied by 14 days, but mean cell size did not decrease further. Animals that received gelfoam soaked in nerve growth factor, brain derived neurotrophic factor, or ciliary neurotrophic factor at the lesion site also showed a 30% neuron loss at 2 months, and a 40% reduction in average cell area. Rats receiving NT-3 showed a 15% neuron loss, which was not improved by additional neurotrophins in combination with NT-3. None of the treatments prevented neuron atrophy. Bioassay of the gelfoam showed that NT-3 bioactivity remained at 5 days after surgery but not at 14 days. Additional rats with hemisections that received NT-3 continuously via mini-pump for 2 months showed a 15% neuron loss, the same as with NT-3 given via gelfoam. These results indicate that even limited exposure of axotomized CN neurons to NT-3 produces permanent rescue of 50% of the neurons. The virtually complete rescue that we had previously observed with transplants of fetal central nervous system (CNS) tissues may, therefore, be due at least in part to NT-3, but the exogenous administration of a single neurotrophic factor or a combination of neurotrophic factors is less effective than transplants in producing long-term survival of axotomized CNS neurons.

Animals↗
PubMed1998

Induction of presynaptic reexpression of an adhesion protein in lamina II after dorsal root deafferentation in adult rat spinal cord.

Limbic system-associated membrane protein (LAMP), a 64-kDa membrane protein, is an axon guidance adhesion molecule expressed by neurons in limbic system-related areas of the CNS. During development, LAMP is expressed on growing axons, growth cones, and their target neurons, but in adults it is restricted to membranes of somata and dendrites. In the adult spinal cord, LAMP immunoreactivity is found only on neurons of lamina II, lamina X, and the intermediolateral cell column and its ultrastructural localization is entirely postsynaptic. We studied changes in the expression of LAMP in lamina II of adult rat spinal cord after L1-S2 dorsal rhizotomy, a procedure that partially deafferents lamina II neurons and induces axonal sprouting by spared systems in lamina II. At the light microscopic level, LAMP immunoreactivity in lamina II was decreased in density at 3, 10, and 60 days postoperatively. This decrease in immunoreactivity suggests that LAMP expression by lamina II neurons may normally be regulated by specific afferent activity. Ultrastructurally, in control lamina II and after deafferentation in both control and deafferented lamina II at 3 and 60 days postoperatively, LAMP expression was restricted to postsynaptic membranes. Ten days after deafferentation, however, when axons are actively sprouting, LAMP was expressed on both axonal and postsynaptic membranes. The reexpression of LAMP on axonal profiles after deafferentation may identify axons that undergo sprouting in response to deafferentation.

Afferent Pathways↗
PubMed1998

NK1, NMDA, 5HT1a, and 5HT2 receptor binding sites in the rat lumbar spinal cord: modulation following sciatic nerve crush.

Quantitative receptor binding autoradiography was used to study the NK1, NMDA, 5HT1a, and 5HT2 receptor binding densities in the adult rat lumbar spinal cord from 3 days to 20 weeks following a unilateral crush lesion of the sciatic nerve. NK1 binding density increased unilaterally in the superficial dorsal horn on the side of the sciatic crush to reach levels 60% above controls by 4 weeks following the lesion and returned to control values by 12 weeks. NMDA binding density increased bilaterally and equally in both the dorsal and ventral horns to reach 300% of control values at 2 weeks following the crush and returned to near control values by 20 weeks following the lesion. Serotonergic receptor binding did not change. The changes in NK1 receptor binding density on postsynaptic dorsal horn cells are consistent with a response to the decrease and recovery in the synthesis and transport of tachykinins by the dorsal root ganglion cells following peripheral nerve injury. the bilateral changes in NMDA receptor binding are more likely mediated by polysynaptic pathways in the spinal cord that respond to the changes in metabolic events of the dorsal root ganglion cells evoked by axotomy and regeneration.

Animals↗
PubMed1998

Long-chain alkenes of the haptophytes Isochrysis galbana and Emiliania huxleyi.

The major alkenes of the haptophytes Isochrysis galbana (strain CCAP 927/14) and Emiliania huxleyi (strains CCAP 920/2 and VAN 556) have been identified by nuclear magnetic resonance spectroscopy and by mass spectrometric analysis of their dimethyl disulfide adducts. The dominant alkene in I. galbana is (22Z)-1 ,22-hentriacontadiene, with 1,24-hentriacontadiene and 1,24-tritriacontadiene present in much lower abundance; (22Z)-1,22-hentriacontadiene also occurs in E. huxleyi (strain CCAP 920/2), together with (2Z,22Z)-2,22-hentriacontadliene (the major hydrocarbon) and (3Z,22Z)-3,22-hentriacontadiene. Minor abundances of 2,24-hentriacontadiene and 2,24-tritriacontadiene are also present in this strain. In contrast, the dominant alkene in E. huxleyi (strain VAN 556) is (15 E,22E)-1,16,23-heptatriacontatriene with the related alkatriene 1,15,22-octatriacontatriene also present and (22Z)-1,22-hentriacontadiene occurring as a minor component. From structural relationships (15E,22E)-1,15,22-heptatriacontatriene is proposed to derive from the same biosynthetic pathway as that of the characteristic C37 alkenones which occur in both E. huxleyi and I. galbana. The C31 and C33 dienes likely derive from chain extension and decarboxylation of (Z)-9-octadecenoic acid or (Z)-7-hexadecenoic acid, using a pathway analogous to that elucidated previously in the chlorophyte Botryococcus braunii. Therefore, long-chain dienes and trienes, which can co-occur in haptophytes, may have distinct biosynthetic pathways.

Alkenes↗
PubMed1998

Health-related quality of life assessment in euthymic and depressed patients with bipolar disorder. Psychometric performance of four self-report measures.

The purpose of this study was to evaluate the psychometric properties of selected health-related quality of life (HRQL) self-report measures in 62 euthymic and depressed patients diagnosed with bipolar disorder. Patients completed the Quality of Life in Depression Scale (QLDS), Mental Health Index-17 (MHI-17), Cognitive Function Scale, and Medical Outcomes Study Short Form-36 (SF-36) at baseline and 8 weeks following treatment. Hamilton and Young Rating Scales were used to assess clinical status and validate the HRQL measures. The MHI-17, Cognitive Function Scale, QLDS, and SF-36 social function, vitality, role limitations-emotional, and mental health scales have good reliability and validity, and are responsive to changes in clinical status in patients with bipolar disorder. Although the small sample size limits generalizablity, euthymic and depressed outpatients with bipolar disorder appear to contribute reliable self reports on selected aspects of their quality of life.

Adult↗
PubMed1998

Objective interpretation of bovine clinical biochemistry data: application of Bayes law to a database model.

With the advent of animal-side biochemistry analysers in veterinary practice, the requirement for ready access to reliable means for interpretation of the results is of increasing importance. At the University of Glasgow Veterinary School (GUVS), a large computerised hospital database containing extensive clinical, laboratory, and pathological information has been maintained. A retrospective study was undertaken to investigate plasma biochemistry results and corresponding post mortem diagnosis data from 754 unwell cattle which had presented to GUVS over the study period. Initial analysis of the clinical biochemistry data from this unwell population revealed that the parameters did not follow a normal distribution. This finding suggested that the accepted reference range method for the interpretation of clinical biochemistry data may provide limited information about the unwell animal. By applying a combination of percentile analysis and conditional probability techniques to the hospital data, the development of a means of clinical biochemistry interpretation was developed whereby a clinician could determine whether a value was abnormal, the degree of abnormality, and the most likely associated diseases. For example, a urea value of 30 mmol/l lay within the top 5% of results, and one of the most common diseases associated with this urea value was pyelonephritis. Furthermore, a Bayesian approach allowed the quantification of the relationship between any plasma biochemistry value and disease through the generation of a ratio termed the 'biochemical factor'. Using the same example, given a urea value of 30 mmol/l, pyelonephritis was eight times more likely than before any biochemistry information was known. The results from the study were used to form the basis of a software system which may ultimately be used by the clinical to aid in the recognition, treatment and prevention of disease in the veterinary domain.

Animals↗
PubMed1998

Susceptibility to trypanosomosis of three Bos indicus cattle breeds in areas of differing tsetse fly challenge.

Studies to assess the differences in susceptibility to trypanosomosis among Bos indicus cattle breeds (Maasai Zebu, Orma Boran and Galana Boran) were conducted under conditions of varying tsetse fly challenge at the Nguruman escarpment in south-western Kenya, for a period of 1 year. It was found that under tsetse challenge quantified as high, Maasai Zebu and Orma Boran were less susceptible than Galana Boran to trypanosome infections, as judged by the significantly lower incidence of infection, development of less severe anaemia, fewer requirements for trypanocidal drug treatments, higher growth rates and fewer mortalities. In the area where tsetse challenge was considered low as a result of a tsetse fly control operation using odour-baited traps, only the Maasai Zebu and Orma Boran were compared. No significant differences in the incidence of infection, degree of anaemia or growth rates were observed between the two breeds, but all were significantly different from their counterparts in the high tsetse challenge area. These results suggest that there is variation in resistance to trypanosomosis among Bos indicus cattle breeds that could be exploited as part of the integrated trypanosomosis control programmes in East Africa.

Anemia↗