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Biomedical subjects

M Murray

Publications and source records attributed to M Murray.

At least 55 records · Page 3Linked to original sources
PubMed2001

Transplantation and gene therapy: combined approaches for repair of spinal cord injury.

Motor and sensory functions are lost after spinal cord injury because neurons die or atrophy and axons fail to regenerate. Until fairly recently, it was believed that damaged neurons could not be replaced and injured axons could not regenerate, and, therefore, functions dependent on injured neurons could not be recovered. We now know that damaged neurons can be rescued by providing therapeutic factors or replaced by grafting. In addition, the adult CNS contains a population of precursor cells with a potential to generate new neural cells, whose numbers and composition can be modified by extrinsic factors. The pioneering studies of Aguayo demonstrated that CNS axons could regenerate in the right environment. Subsequent studies have revealed the identity of some of the inhibitory molecules in myelin and scar tissue, and we now have a better understanding of how the CNS environment can be modified to become more permissive to regeneration. Axons that regenerate must find an appropriate target, but it may not be essential to reestablish the precise topography for some functions to be restored. There are now new and promising strategies for delivery of therapeutic genes to protect neurons and to stimulate regeneration. The ability to engineer cells by gene therapy combines the therapeutic values of cell transplantation and gene delivery. These remarkable developments from many disciplines have generated a new level of optimism in the search for a cure for CNS injury and in particular spinal cord injury. In this review, the authors summarize recent progress in these strategies and some of the challenges that remain in elucidating the most efficacious protocols for rescuing injured neurons, encouraging regeneration of their axons, and promoting recovery of function.

Adult↗
PubMed2001

Transplantation of genetically modified fibroblasts expressing BDNF in adult rats with a subtotal hemisection improves specific motor and sensory functions.

OBJECTIVE: We have previously reported that grafting fibroblasts genetically modified to express brain-derived neurotrophic factor (BDNF) into a subtotal cervical hemisection site that destroys the entire lateral funiculus will promote regeneration of rubrospinal axons and growth of other axons, prevent atrophy and death of axotomized red nucleus neurons, and improve forelimb use during spontaneous vertical exploration. We have now extended these studies by using additional sensorimotor tests to examine recovery. METHODS: The range of tests used included those in which the intervention did not improve recovery, those in which the intervention was associated with recovery, and those that showed little deficit. The selected tasks tested both sensory and motor functions and both forelimb and forelimb function. We used the open-field locomotor rating scale (BBB), locomotion on a narrow beam, forelimb use during swimming, horizontal rope walking, and a somatosensory asymmetry (patch-removal) test. After testing during an 8-week recovery period, a second lesion was made just rostral to the initial lesion/transplant site to test the role of the transplant in recovery. The rats were then retested for a further 5 weeks after the repeated lesion. RESULTS: The horizontal rope, swim, and patch-removal tests were reliably sensitive to the subtotal hemisection injury. Fb/BDNF-transplanted animals recovered motor functions on the horizontal rope-crossing test, and this recovery was abolished by a second lesion just rostral to the first lesion/transplant. In the patch-removal test, the latency to contact the affected limb was shorter in Fb/BDNF-treated rats than in the control group, and this effect was completely abolished by a second lesion. CONCLUSIONS: The rope-crossing and patch-removal tests are particularly useful tasks for assessing the beneficial effects of BDNF-expressing grafts in this injury model.

Animals↗
PubMed2001

Achievements of the Grand River Conservation Authority, Ontario, Canada.

Winning the 2000 International River prize resulted from a significant investment by the community of Ontario over a long period of time in the Grand River Conservation Authority, GRCA. Innovative partnerships with the business community, government, universities, First Nations tribes, environment groups and the general community have been the hallmark of a broad-based river management program that has returned the Grand River to a healthy environment and usable resource. Recognising this, the Grand River received special recognition from the Canadian Heritage Rivers Board--as a designated Heritage River. Not content with the achievements of the past, the GRCA has turned its attention to the future needs of this river system and to increasing the depth and breadth of community partnerships.

Awards and Prizes↗
PubMed2000

The influence of relative resistance and urea-supplementation on deliberate infection with Teladorsagia circumcincta during winter.

The consequences for lambs of infection over the winter with Teladorsagia circumcincta were quantified by deliberate, trickle infection of selected animals at 7 months of age. Infected and control uninfected animals were each allocated into four groups, relatively resistant animals on a normal diet, relatively resistant animals on an isocaloric diet supplemented with urea, and relatively susceptible animals on the same two diets. Resistance and susceptibility was assessed by faecal egg counts following natural infection during the summer preceding the deliberate infection. During the deliberate infection egg counts remained low and most parasites recovered at necropsy were inhibited larvae. Nonetheless, infection reduced weight gain, decreased albumin and fructosamine concentrations and provoked a noticeable pepsinogen and eosinophil response. As most larvae were inhibited these responses may have been largely a consequence of immuno-inflammatory responses in the host rather than the direct action of parasites themselves. Relatively resistant animals on the supplemented diet allowed fewer larvae to establish and had higher fructosamine concentrations, higher albumin concentrations and decreased pepsinogen responses. Therefore, a combination of relatively resistant sheep and nutritional supplementation appears most efficient at controlling infection.

3-Hydroxybutyric Acid↗
PubMed2000

Entropy-driven hydrogen bonding: stereodynamics of a protonated, N,N-chiral "proton sponge".

The C2-symmetric ("[DL]") and achiral ("[meso]") diastereoisomers of the hydrogen iodide salt of 1,8-bis-(N-benzyl-N-methylamino)naphthalene ([2H]-[I] ) interconvert in solution. Direct interconversion of the diastereoisomers of [2H]+ must involve hydrogen bond fission (to give "[nonHB-2H+]") and rotation-inversion of the non-protonated nitrogen centre. The global activation parameters (deltaH++ and deltaS++) for diastereoisomer interconversion in [D7]DMF have been determined from rate data obtained by temperature-drop and magnetisation-transfer 13C NMR spectroscopy over a temperature range of 170 degrees C. The process is found to have a high entropy of activation in both directions (deltaS++=163(+/-4) and 169(+/-4) JK(-1)mol(-1)) and this is suggested to arise through hydrogen bonding of the ammonium centre in [nonHB-2H+] with the solvent ([D7]DMF). Comparison of the enthalpy of activation (deltaH++) with that earlier found for diastereoisomer interconversion of the free-base form 2 suggests that the intramolecular hydrogen bond in [2H]+ is roughly equal in enthalpic strength (deltaH) with that made with the solvent ([D7]DMF) in the non-hydrogen-bonded intermediate [nonHB-2H+]. As such, the hydrogen bonding in [2H]+ may be considered as predominantly an entropically driven process, without any unusual enthalpic strength.

Journal Article↗
PubMed2000

Diastereoisomeric cationic pi-allylpalladium-(P,C)-MAP and MOP complexes and their relationship to streochemical memory effects in allylic alkylation.

The axially chiral ligands 2-(diphenylphosphanyl)-2'-methoxy-1,1'-binaphthalene (MOP; 6) and 2'-dimethylamino-2-(diphenylphosphanyl)-1,1'-binaphthalene (MAP; 7) coordinate to a cationic allylpalladium fragment in an unusual bidentate (P,C)-mode through the triarylphosphane and ipso-carbon atom (C1'). The readily prepared MAP and MOP complexes [Pd[(P,C)-(L)](n3-allyl)][OTf] (9 (L = 7) and 10 (L = 6)) have been characterised in solution (NMR), in which two diastereoisomeric rotamers are observed. The stereochemical identity of the rotamers is established by one- and two-dimensional NMR spectroscopy experiments. In both the solid state and in solution, the allyl unit is shown to coordinate in a slightly distorted n3-mode that results in a more alkene-like character at the allyl terminus trans to phosphane ligand. The opposite allyl terminus, which is trans to the ipsocarbon atom (C1'), is more strongly bound and the dominant allyl stereodynamic process involves C-C bond rotation in an n'-allyl intermediate bound through this carbon. Palladium complexes of MAP and MOP are very efficient catalysts for allylic alkylation of racemic cyclopentenyl pivalate with [NaCH(CO2Me)2] in THF. Isotopic desymmetrisation revealed that the reaction occurs with powerful stereochemical memory effects and consequently with low global ee values. The memory effect is suggested to arise through selective generation of diastereoisomeric [Pd[(P,C)-L](n3-cyclopentenyl)]+ ions (L = MAP or MOP) and subsequent capture by nucleophile before ion-pair collapse or equilibration occurs.

Journal Article↗
PubMed2000

Scottish consortium for development and education in dental primary care.

A national consortium for dental primary care in Scotland has been formed as a result of integrated planning by groups involved in managing and delivering postgraduate dental education in Scotland. In 1998 a partnership was formed with representatives from the Scottish Council for Postgraduate Medical and Dental Education (SCPMDE) and the three Scottish dental institutions at Dundee, Edinburgh and Glasgow Universities. The principal aim of the Consortium is to promote evidence-based dental care through postgraduate education and research. The activities of the Consortium will provide a broadly based adjunct to current postgraduate provision with partner institutions contributing in different ways. Since its inception the Consortium has focused on two main areas: 'Higher Training' for Primary Care. Scottish Dental Practice Based Research Network.

Dental Research↗
PubMed2000

NIPP1-mediated interaction of protein phosphatase-1 with CDC5L, a regulator of pre-mRNA splicing and mitotic entry.

NIPP1 is a regulatory subunit of a species of protein phosphatase-1 (PP1) that co-localizes with splicing factors in nuclear speckles. We report that the N-terminal third of NIPP1 largely consists of a Forkhead-associated (FHA) protein interaction domain, a known phosphopeptide interaction module. A yeast two-hybrid screening revealed an interaction between this domain and a human homolog (CDC5L) of the fission yeast protein cdc5, which is required for G(2)/M progression and pre-mRNA splicing. CDC5L and NIPP1 co-localized in nuclear speckles in COS-1 cells. Furthermore, an interaction between CDC5L, NIPP1, and PP1 in rat liver nuclear extracts could be demonstrated by co-immunoprecipitation and/or co-purification experiments. The binding of the FHA domain of NIPP1 to CDC5L was dependent on the phosphorylation of CDC5L, e.g. by cyclin E-Cdk2. When expressed in COS-1 or HeLa cells, the FHA domain of NIPP1 did not affect the number of cells in the G(2)/M transition. However, the FHA domain blocked beta-globin pre-mRNA splicing in nuclear extracts. A mutation in the FHA domain that abolished its interaction with CDC5L also canceled its anti-splicing effects. We suggest that NIPP1 either targets CDC5L or an associated protein for dephosphorylation by PP1 or serves as an anchor for both PP1 and CDC5L.

Amino Acid Sequence↗
PubMed2000

Patient care: access.

Explore the source record for details and available documents.

Health Services Accessibility↗
PubMed2000

Immunogenetic influences on tick resistance in African cattle with particular reference to trypanotolerant N'Dama (Bos taurus) and trypanosusceptible Gobra zebu (Bos indicus) cattle.

In sub-Saharan Africa, tick infestation and tick-borne infections together with tsetse-transmitted trypanosomosis arguably constitute the main parasitological disease complex constraining livestock production. Resistance to tick attack and tick-borne micro-organisms (TBMs) varies among different breeds of cattle. The magnitude of losses due to these parasites is related to an extent to the degree of breed resistance. Generally, zebu (Bos indicus) cattle possess a higher resistance to ticks and TBMs than European (Bos taurus) cattle. The host's immune system would appear to be the single most important factor that regulates this resistance. This paper reports on the main effector immune mechanisms governing resistance against ticks and TBMs. The cellular immune response appears more effective and stable than humoral immunity in modulating resistance to ticks and TBMs. Similarities between the immune mechanisms employed by trypanotolerant N'Dama (B. taurus) cattle, when infected with trypanosomes, and those elicited by tick bites and TBMs seem to exist, particularly at the skin level in the early phases of parasitic invasion. Moreover, there is evidence that in the N'Dama breed, resistance against ticks per se also has a genetic basis. Therefore, the N'Dama appears to be a unique breed in that it exhibits resistance to several parasitic diseases and/or infections, including helminths, when compared to other cattle breeds in West Africa. It is concluded that the multi-parasite resistant traits of the N'Dama breed should be exploited in those areas where trypanosomosis, ticks and tick-borne diseases constrain animal production. This should be of benefit for low-input farming systems where the use of chemicals for prophylaxis and therapy is limited by their relatively high cost. Additionally, the potential contribution of multiple disease resistant N'Dama cattle should be considered in crossbreeding programmes with exotic dairy breeds for increasing milk production in West Africa.

Africa South of the Sahara↗
PubMed2000

Measles outbreak in a northern Pakistani village: epidemiology and vaccine effectiveness.

In the spring of 1990, local community health workers reported a measles outbreak in several partially vaccinated villages in the Punial Valley in northern Pakistan. The authors conducted an investigation in one of these villages to assess vaccine coverage and vaccine efficacy and to describe the patterns of measles outbreaks that prevailed in this community. The results of a survey of the entire village revealed two major gaps in vaccine coverage: the small minority Sunni community and children over 3 years of age. Vaccine efficacy was estimated to range from 73 to 90% but was markedly reduced in children who were vaccinated under 12 months of age. The occurrence of an outbreak in a community in which a relatively new vaccination program is primarily directed at younger children has been predicted by theoretical models of measles dynamics and is consistent with the experience of other vaccination programs in the developing world. These observations suggest that, in some areas of the developing world, the age groups targeted to receive measles vaccinations may need to be broadened to ensure adequate coverage to prevent recurrent outbreaks.

Adolescent↗
PubMed2000

Enhancement of (45)Ca(2+) influx and voltage-dependent Ca(2+) channel activity by beta-amyloid-(1-40) in rat cortical synaptosomes and cultured cortical neurons. Modulation by the proinflammatory cytokine interleukin-1beta.

Beta-amyloid protein is thought to underlie the neurodegeneration associated with Alzheimer's disease by inducing Ca(2+)-dependent apoptosis. Elevated neuronal expression of the proinflammatory cytokine interleukin-1beta is an additional feature of neurodegeneration, and in this study we demonstrate that interleukin-1beta modulates the effects of beta-amyloid on Ca(2+) homeostasis in the rat cortex. beta-Amyloid-(1-40) (1 microM) caused a significant increase in (45)Ca(2+) influx into rat cortical synaptosomes via activation of L- and N-type voltage-dependent Ca(2+) channels and also increased the amplitude of N- and P-type Ca(2+) channel currents recorded from cultured cortical neurons. In contrast, interleukin-1beta (5 ng/ml) reduced the (45)Ca(2+) influx into cortical synaptosomes and inhibited Ca(2+) channel activity in cultured cortical neurons. Furthermore, the stimulatory effects of beta-amyloid protein on Ca(2+) influx were blocked following exposure to interleukin-1beta, suggesting that interleukin-1beta may govern neuronal responses to beta-amyloid by regulating Ca(2+) homeostasis.

Amyloid beta-Peptides↗
PubMed2000

The reliability and validity of two health status measures for evaluating outcomes of home care nursing.

The reliability, validity, and sensitivity of the Medical Outcome Study Short Form (SF-36) and the Quality of Life Profile: Senior Version (QOLPSV) for measuring outcomes of home care nursing were evaluated. Data were collected from 50 clients receiving home care nursing services. Twenty-two registered nurses and six registered practical nurses collected client and nursing data on each home visit. Client baseline and outcome measures were collected by two independent evaluators at admission and discharge from the home care service. Internal consistency reliability ranged from.76 to.94 for the eight subscales of the SF-36. Internal consistency reliability ranged from.47 to.82 for the nine subscales of the QOLPSV. The subscales of both instruments had minimal problems with missing responses. The SF-36 was found to be more sensitive than the QOLPSV to change over time. In addition, the subscales of the SF-36 were found to be more sensitive than the subscales of the QOLPSV to several of the nursing variables, such as intensity of the client's nursing condition and skill mix.

Community Health Nursing↗
PubMed2000

Trace element homeostasis during continuous sedation with propofol containing EDTA versus other sedatives in critically ill patients.

OBJECTIVE: To evaluate changes in serum and urinary zinc, cobalt, copper, iron, and calcium concentrations in critically ill patients receiving propofol containing disodium edetate (disodium ethylenediaminetetraacetic acid [EDTA]) versus sedative agents without EDTA. DESIGN: This was a randomised, open-label, parallel-group study with randomisation stratified by baseline Acute Physiology and Chronic Health Evaluation (APACHE II) scores. SETTING: Intensive care units (ICU) in 23 medical centres. PATIENTS: Medical, surgical, or trauma ICU patients 17 years of age or older who required mechanical ventilator support and sedation. INTERVENTIONS: A total of 106 patients received propofol containing 0.005 % EDTA (propofol EDTA), and 104 received other sedative agents without EDTA (non-EDTA). Only the first 108 patients were assessed for urinary trace metal excretion. Twenty-four-hour urine samples were collected on days 2, 3, and 7 and every 7 days thereafter for determination of zinc, cobalt, copper, iron, and calcium excretion; EDTA levels; urine osmolality; albumin levels; and glucose levels. The first 143 patients were assessed for serum concentration of zinc, cobalt, copper, iron, and calcium; creatinine; blood urea nitrogen; and albumin at baseline and once during each 24-hour urine collection. MEASUREMENTS AND RESULTS: For the assessment of trace metals, patients receiving propofol EDTA demonstrated increased mean urinary excretion of zinc, copper, and iron compared with the normal range. All patients receiving sedatives demonstrated increased urinary excretion of zinc and copper above normal reference values. Compared with the non-EDTA sedative group, the propofol EDTA group demonstrated increased urinary excretion of zinc and iron. Mean serum concentrations of zinc and total calcium were decreased in both patient groups. Serum zinc concentrations increased from baseline to day 3 in the non-EDTA sedative group but not in the propofol EDTA group. Renal function, measured by blood urea nitrogen, serum creatinine, and creatinine clearance, did not deteriorate during ICU sedation with either regimen. CONCLUSION: This study showed that critical illness is associated with increased urinary losses of zinc, copper, and iron. Propofol EDTA-treated patients had greater urinary losses of zinc and iron and lower serum zinc concentrations compared with the non-EDTA sedative group. No adverse events indicative of trace metal deficiency were observed in either group. The clinical significance of trace metal losses during critical illness is unclear and requires further study.

APACHE↗
PubMed2000

Testosterone dehydrogenase activity in koala liver: characterisation of cofactor and steroid substrate differences.

We have studied the hepatic microsomal 17beta-hydroxysteroid dehydrogenase (17beta-HSD) capacity of koala (Phascolarctos cinereus) and tammar wallaby (Macropus eugenii). A detailed comparison of the activity in hepatic fractions from koala and rat was made. Hepatic microsomal NADP-supported 17beta-HSD activity was significantly higher in koala (11.64+/-3.35 nmoles/mg protein/min), (mean+/-S.D.) than in tammar wallaby liver (1.52+/-0.79 nmoles/mg protein/min). However, when NAD was utilised as cofactor the activity was similar in both marsupial species (2.83+/-2.03 nmoles/mg protein/min, koala; 0.70+/-0.71 nmoles/mg protein/min, tammar wallaby). Data for rat indicated a cofactor preference for NAD rather than NADP (17.94+/-6.40 nmoles/mg protein/min, NAD; 2.18+/-1.04 nmoles/mg protein/min, NADP). Michaelis-Menten parameters for the kinetics of 17beta-HSD testosterone oxidation by NADP and NAD were determined in the koala. The Km for testosterone was of the order of 10.0-24.0 microM (n = 6) irrespective of the cofactor used, whilst the Km for NADP was 0.28-0.43 microM (n = 2) and for NAD was 13.9-18.5 microM (n = 2). 17beta-estradiol was found to be an inhibitor of both NAD- and NADP- supported 17beta-HSD activity. These findings indicate that NADP-mediated, but not NAD-mediated testosterone dehydrogenation is a major pathway of steroid biotransformation in koala liver; the reaction is less extensive in fractions from wallaby, human and rat. Such species-related differences in cofactor preference may contribute along with species differences in gene expression to observed rates of 17beta-HSD activity in mammals.

17-Hydroxysteroid Dehydrogenases↗
PubMed2000

Arachidonic acid-mediated cooxidation of all-trans-retinoic acid in microsomal fractions from human liver.

The quantitative importance of prostaglandin H synthase (PGHS)-mediated cooxidation of all-trans-retinoic acid (ATRA) was evaluated in human liver microsomes (n=17) in relation to CYP-dependent ATRA 4-hydroxylation. Observed rates of ATRA cooxidation (4.6 - 20 pmol mg protein(-1) min(-1)) and 4-hydroxylation (8.7 - 45 pmol mg protein(-1) min(-1)) were quantitatively similar and exhibited similar individual variation (4 and 5 fold, respectively). From kinetic studies cooxidation was an efficient process in human hepatic microsomes (V(max) K(m)(-1)=0.25) compared with NADPH- and NADH-mediated 4-hydroxylation by CYP (V(max) K(m)(-1)=0.14 and 0.02, respectively). The capacity of lipid hydroperoxide metabolites of arachidonic acid to mediate ATRA oxidation was established directly, but downstream products (D, E, F and I-series prostaglandins) were inactive. cDNA-expressed CYPs supported ATRA oxidation by lipid hydroperoxides. Whereas CYPs 2C8, 2C9 and 3A4, but not CYPs 1A2 or 2E1, were effective catalysts of the NADPH-mediated reaction, cooxidation supported by 15(S)-hydroperoxyeicosatetraenoic acid was mediated by all five CYPs. The cooxidation reaction in human hepatic microsomes was inhibited by the CYP inhibitor miconazole. These findings indicate that ATRA oxidation is quantitatively significant in human liver. Lipid hydroperoxides generated by intracellular enzymes such as prostaglandin synthase and lipoxygenases are sources of activated oxygen for CYP-mediated deactivation of ATRA to polar products.

Arachidonic Acid↗