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Biomedical subjects

M Murray

Publications and source records attributed to M Murray.

At least 19 recordsLinked to original sources
PubMed1995

Distribution of Big tau in the central nervous system of the adult and developing rat.

The diversity of neuronal morphology and function is correlated with specific expression of various microtubule associated proteins (MAPs). One of the major neuronal MAPs, tau, has multiple isoforms formed as a result of alternative splicing and phosphorylation that are differentially expressed during development. Big tau is a high molecular weight isoform that contains an additional large exon (4a) and is expressed primarily by neurons in the peripheral nervous system (PNS). We cloned the complete 4a exon in an expression vector, isolated the recombinant protein and produced antibodies specific to Big tau that were used to localize Big tau in the developing spinal cord and in the adult central nervous system (CNS). In developing spinal cord, Big tau is first expressed in the central projections of the dorsal root ganglia neurons and in motor neurons at embryonic day 18 and postnatal day 2, respectively. In the adult rat CNS, almost all neurons that extend processes into the PNS express Big tau, including all cranial nerve motor nuclei and central processes of most sensory ganglia; of these ganglia, only the bipolar neurons of the olfactory, vestibular and spiral ganglia did not express Big tau. Retinal ganglion cells are the only CNS neurons, whose processes remain entirely within the CNS, that express high levels of Big tau. The limited and specific distribution of Big tau is consistent with a role in stabilizing microtubules in axons that are subjected to great shear forces.

Animals↗
PubMed1995

Regenerative axonal sprouting in the cat trochlear nerve.

Following peripheral trochlear nerve axotomy in the cat, the normal number of myelinated axons is restored despite significant motor neuron death, suggesting regulation of the number of myelinated axons in the regenerated nerve. In this study we used light and electron microscopy to examine the production and maintenance of axonal sprouts at different locations in the nerve and at different postoperative intervals. Despite proliferative sprouting and an overproduction of nonmyelinated axons in the regenerating trochlear nerve, the number of myelinated axons was strictly regulated. Only approximately 1,000 regenerated axons were eventually remyelinated, but many nonmyelinated axons were still present 6-8 months postaxotomy. Regenerated axons were remyelinated in a proximal-to-distal direction between 3 and 4 weeks postaxotomy. We also examined the maturation of regenerated myelinated axons by measuring axon diameter and myelin index (an expression of myelin thickness). Mean myelinated axon diameter remained significantly below normal in long-term regenerated nerves. Mean myelin index was not different from normal at 4 weeks postaxotomy but was significantly decreased at long postoperative intervals, reflecting a slightly thicker myelin sheath relative to the axon diameter. This relative increase in mean myelin thickness could serve to restore normal conduction velocity despite the decrease in mean axon diameter. We suggest that the regulation of the number of myelinated axons at the normal number despite cell death and the increase in mean myelin thickness may both be compensatory mechanisms that function to restore preoperative conditions and maximize functional recovery.

Animals↗
PubMed1995

Macrophages, microglia, and astrocytes are rapidly activated after crush injury of the goldfish optic nerve: a light and electron microscopic analysis.

Several matrix and adhesion molecules in fish optic nerve, which are constitutively expressed, are increased during axonal regeneration and are primarily associated with nonneuronal cells (W.P. Battisti, Y. Shinar, M. Schwartz, P. Levitt, and M. Murray [1992] J. Neurocytol. 21:557-573). The current study examines the reactions of specific cell types to optic nerve crush and axonal regeneration. The goldfish optic nerve contains macroglia and microglia as well as a population of monocyte-derived cells (granular macrophages) unique to goldfish. Two cell types were OX-42 positive (granular macrophages and microglia), indicating monocyte lineage, each with a distinct morphology and distribution within the nerve. Within hours of the optic nerve crush, the number of OX-42-labeled cell profiles increased near the crush site, remained elevated during the time axons were elongating, and then declined. Microglia, but not granular macrophages, were phagocytically active. Astrocytes are readily identified in the normal optic nerve, but they exhibited marked morphologic changes within hours of injury, which is consistent with the contribution these cells make to the altered environment. Oligodendroglia could not be reliably identified in regenerating optic nerves until myelin was formed. A comparison of the distribution of OX-42-labeled cells with that of transforming growth factor beta-1 (TGF-beta 1) and tenascin suggests that these molecules are expressed by granular macrophages. Tenascin staining may be additionally associated with astrocytes and/or microglia. The rapid response of these nonneuronal cells to injury, their rapid phagocytic activity, and the secretion of growth-promoting factors by these cells likely contributes to the environment that supports robust regeneration by optic axons in the goldfish.

Animals↗
PubMed1995

Pre-translational regulation of cytochrome P450 genes is responsible for disease-specific changes of individual P450 enzymes among patients with cirrhosis.

We have recently reported that disease-specific differential alterations in the hepatic expression of xenobiotic-metabolizing cytochrome P450 (CYP P450) enzymes occur in patients with advanced liver disease. In order to determine whether the observed changes in CYP proteins are modulated at pre- or post-translational levels, we have now examined the hepatic levels of mRNA for CYPs 1A2, 2C9, 2E1 and 3A4 by solution hybridization in the same livers of 20 controls (surgical waste from histologically normal livers), 32 cases of hepatocellular and 18 of cholestatic severe chronic liver disease. CYP1A2 mRNA and CYP1A immunoreactive protein were both reduced in livers with hepatocellular and cholestatic types of cirrhosis. In contrast, CYP3A4 mRNA and protein were reduced only in livers from patients with hepatocellular diseases. For 1A2 and 3A4 there were significant correlations between mRNA species and the respective protein contents (rS1A2 = 0.74, rS3A4 = 0.64, P < 0.0001). CYP2C9 mRNA was reduced in patients with both cholestatic and hepatocellular types of liver disease, but 2C protein was reduced only in patients with cholestatic dysfunction. The correlation between CYP2C9 mRNA and protein, was also significant (rs = 0.36, P < 0.005) but mRNA levels accounted for only 13% of the variability in protein rankings. This is probably a consequence of other CYP2C proteins apart from 2C9 being detected by the anti-2C antibody. CYP2E1 mRNA and protein were reduced in patients with cholestatic liver disease, but in hepatocellular disease the expression of only CYP2E1 mRNA was decreased. CYP2E1 mRNA was significantly correlated with CYP2E1 protein but accounted for only 18% of the variability in protein rankings (rs = 0.43, P < 0.0005). Taken collectively these data indicate that the disease-specific alterations of xenobiotic-metabolizing CYP enzymes among patients with cirrhosis is due, at least in part, to pre-translational mechanisms. The lack of a strong correlation between CYP2E1 mRNA and protein suggests that this gene, like its rat orthologue, may be subject to pre-translational as well as translational and/or post-translational regulation.

Cytochrome P-450 Enzyme System↗
PubMed1995

Cranial meninges of goldfish: age-related changes in morphology of meningeal cells and accumulation of surfactant-like multilamellar bodies.

In the optic tectum of goldfish, the outer, middle and inner layers of the endomeninx were evident in animals ranging in age from 1 month to several years. The outer layer in young animals consisted of closely overlapping cells with intertwined processes, whereas in the older animals it contained large extracellular spaces. The intermediate layer cells were always arranged in a single continuous layer, but in young animals they overlapped extensively with one another toward their edges whereas in the oldest animals they became extremely flat and non-overlapping. The inner layer included an outer tier of cells with their bases adhering to the intermediate layer, and an inner tier of cells detached from both the intermediate layer and the basal lamina overlying the brain parenchyma. Inner layer cells contained many large vacuoles that were in continuity with the extracellular space. With age, the extracellular space and the vacuolar system expanded, and the inner layer evolved into a meshwork of attenuated cytoplasmic processes embedded in the granular extracellular matrix. Another age-related feature was the accumulation adjacent to the basal lamina of uniform disc-shaped membranous structures, resembling multilamellar bodies of lung surfactant. These "disc bodies" were apparently generated by the coalescence of vesicles formed at the surface of the inner layer cells, possibly as a by-product of protein secretion by these cells.

Aging↗
PubMed1995

Plasticity of complex terminals in lamina II in partially deafferented spinal cord: the cat spared root preparation.

Projections to the dorsal horn change in adult mammals in response to complete or partial deafferentation. The number of synaptic terminals remains constant after complete lumbosacral deafferentation, indicating replacement of lost dorsal root terminals by newly formed terminals from spared intrinsic systems. The density of a spared central projection of a dorsal root is increased in dorsal horn after partial deafferentation, consistent with sprouting by the axons in the spared root. In this study, we have used electron microscopy to study morphological changes in a specific class of terminals in the dorsal horn induced by partial deafferentation. Complex terminals (CTs) in the dorsal horn originate exclusively from dorsal roots and are readily distinguished morphologically. The CTs and the postsynaptic densities (PSDs) associated with CTs were measured in lamina II at L5 and L6 in cats subjected to unilateral spared root (L6) dorsal rhizotomies and compared to CTs in the control side. Acutely following partial deafferentation, the number of CT profiles decreased. At more chronic survivals, the number of CT profiles were restored to normal levels, and both the number and the length of PSDs were increased. The changes in CTs and PSDs suggest sprouting and synaptogenesis by the spared dorsal root fibers that produce changes in the postsynaptic neuron. Spared root deafferentation thus elicits compensatory changes in presynaptic terminals of the spared root and also in their postsynaptic target neurons.

Animals↗
PubMed1995

Pretranslational down-regulation of cytochromes P450 2C11 and 3A2 in male rat liver by tumor necrosis factor alpha.

BACKGROUND & AIMS: The cytokine tumor necrosis factor alpha (TNF-alpha) is a primary inflammatory mediator after liver injury. Several cytokines impair the regulation of cytochrome P450 (CYP) genes in liver, but the specificity of these effects remains unclear. This study investigated the effects of recombinant murine TNF-alpha on the expression of specific constitutive CYPs in male rat liver. METHODS: Microsomal steroid hydroxylation was used to indicate the activities of specific CYPs after TNF-alpha treatment and immunoblotting to correlate CYP activities with protein contents. CYP messenger RNA levels were measured by solution hybridization. RESULTS: Testosterone 2 alpha/16 alpha- and 6 beta-hydroxylations, mediated respectively by CYPs 2C11 and 3A2, were decreased after TNF-alpha treatment, whereas 7 alpha-hydroxylation (CYP 2A1) was unchanged. Similarly, progesterone 2 alpha/16 alpha- (CYP 2C11) and 6 beta-hydroxylations (CYP 3A2), but not 21-hydroxylation (CYP 2C6), were decreased after TNF-alpha treatment. 2C11 and 3A2 apoproteins and messenger RNAs, but not 2A1 apoprotein, were decreased after TNF-alpha treatment; changes in messenger RNAs were evident 4 hours after treatment. CONCLUSIONS: TNF-alpha down-regulates CYPs 2C11 and 3A2 in male rat liver at a pretranslational level, whereas two other constitutive CYPs, 2A1 and 2C6, seem refractory to TNF-alpha. Thus, impaired CYP regulation by TNF-alpha resembles the combined effects of autologous interferons (on 3A2) and interleukins (on 2C11).

Analysis of Variance↗
PubMed1995

The repeatability of faecal egg counts, peripheral eosinophil counts, and plasma pepsinogen concentrations during deliberate infections with Ostertagia circumcincta.

Faecal egg counts, peripheral blood eosinophil counts and plasma pepsinogen concentrations were monitored during 2 successive, deliberate infections in 24 Scottish Blackface sheep. For all 3 techniques, the repeatability of replicate counts or of measurements made at short intervals were high which suggests that all 3 assays were reliable. Within an infection the repeatability of different samples from the same animal decreased as the interval between samples increased. The repeatability between infections was only moderate for faecal egg counts but high for peripheral eosinophil counts and plasma pepsinogen concentrations. Of the 3 variables, faecal egg count was the most strongly associated with the worm burden. Together, the three variables accounted for, in a statistical sense, one half of the variation in worm burden. The three variables, if measured concurrently, should provide a more effective identification of resistant and susceptible lambs.

Animals↗
PubMed1995

Influence of supplementation with dietary soyabean meal on resistance to haemonchosis in Hampshire down lambs.

The influence of dietary protein supplementation on resistance to haemonchosis was examined in Hampshire down lambs fed either a basal diet or a diet supplemented with soyabean. At seven months of age the lambs were challenged with an initial loading dose of Haemonchus contortus, followed by a trickle infection three times a week. Blood and faecal samples were collected three times a week and bodyweights were recorded weekly. After 10 weeks the lambs were slaughtered and their worm burdens and carcase composition determined. Although their mean worm burdens were similar, the lambs given the basal diet had higher faecal egg counts, lower packed red cell volumes and lower concentrations of total plasma protein and plasma albumin than the lambs given the supplemented diet. The dietary supplementation also improved the carcase composition of the lambs.

Animal Feed↗
PubMed1995

Different patterns of faecal egg output following infection of Scottish blackface lambs with Ostertagia circumcincta.

Faecal nematode egg counts were monitored in 184 Scottish Blackface lambs during natural exposure to a mixed, predominantly Ostertagia circumcincta infection and 12 lambs were selected which showed consistently zero (low count group; nine lambs) or consistently positive faecal egg counts (high count group; three lambs). These lambs were then treated with anthelmintic and challenged with 50,000 infective larvae of O. circumcincta and monitored thrice-weekly for 38 weeks; they were then re-challenged with another 50,000 infective larvae of O. circumcincta and monitored for a further 8 weeks. All sheep gave positive egg counts following deliberate infection. However, there was considerable variation among sheep in the size and timing of the peak in egg production. In particular, the pattern of mean values for faecal egg counts was different in the two groups. Egg counts were lower in the later periods of the extended infection in both groups of sheep. During the first half of the extended infection, egg counts were lower in sheep from the low count group, but during the second half of the infection the pattern was reversed and egg counts were lower in sheep from the high count group. There was a weak positive correlation between egg counts following anthelmintic treatment and 28 days exposure to natural infection and egg counts 28 days after a deliberate infection. Egg counts in the later stages of the deliberate infection were strongly but negatively correlated with egg counts following natural infection. The results of these studies show that differences in egg count following natural infection can be reproduced in experimental infections and that there is substantial variation in the pattern of egg production over time in different sheep. They also suggest that naturally resistant lambs are better able to delay worm development than naturally susceptible lambs.

Abomasum↗
PubMed1995

Local and plasma antibody responses to the parasitic larval stages of the abomasal nematode Ostertagia circumcincta.

Ovine isotype-specific antibody responses to the parasitic larval stages of the abomasal nematode Ostertagia circumcincta were measured in a simple, indirect enzyme-linked immunosorbent assay. Analysis of variance of replicate tests showed that the assay was very reliable. There was substantial variation among individual sheep in their IgA and IgG1 responses even though the sheep had been matched for breed, age and sex, were born on the same farm, were reared identically and had the same history of exposure and challenge with O. circumcincta. The local IgA responses to a somatic extract of fourth-stage larvae were very similar to responses to excretory-secretory products of fourth-stage larvae. The responses to third stage larvae were correlated with the responses to fourth stage larvae. There was a negative correlation between parasite-specific plasma IgG1 and parasite-specific plasma IgA responses. There was only a moderate association between IgA responses in the mucus and the plasma. Therefore, antibody responses measured in plasma cannot be easily extrapolated to antibody responses in the abomasal mucus.

Abomasum↗
PubMed1995

The expression and distribution of tau proteins and messenger RNA in rat dorsal root ganglion neurons during development and regeneration.

Microtubule-associated proteins contribute to the balance between stability and plasticity of the neuronal cytoskeleton by modulating assembly and disassembly of microtubules. The tau microtubule-associated proteins exist in several isoforms which are developmentally regulated and differentially distributed. Our objective was to characterize the distribution of tau isoforms in developing and mature dorsal root ganglia neurons and during axonal regeneration following sciatic nerve axotomy. Immunocytochemical analysis was carried out using antibodies that recognize all tau isoforms and a novel antibody that specifically recognizes the high molecular weight isoform. The expression of tau is highly regulated during development. At E14, all dorsal root ganglion neurons express only the low molecular weight tau isoforms. These isoforms are still present in all dorsal root ganglion neurons in neonates, whereas high molecular weight tau isoforms are expressed in a subset of dorsal root ganglion neurons. The switch from low to exclusively high molecular weight tau expression begins at E18 and is completed during the first postnatal week. In the adult, high molecular weight tau is restricted to small- and medium-sized dorsal root ganglion neurons; its distribution largely coincides with the population of substance P and calcitonin gene related peptide peptidergic neurons. This differential distribution was observed in the cell body, dorsal roots and sciatic nerve axons. In contrast to the protein, however, the distribution of high molecular weight tau messenger RNA is not restricted; all dorsal root ganglion neurons express similar tau messenger RNA levels. The discrepancy between the distribution of protein and messenger RNA suggests control at the post-transcriptional or translational levels. Sciatic nerve axotomy which is followed by axonal regeneration did not alter the differential distribution of high molecular weight tau immunostaining. We conclude that the distribution and expression of tau isoforms during axonal regeneration in adult does not recapitulate the developmental pattern.

Aging↗
PubMed1995

The role of a nurse practitioner in a chronic dialysis unit.

Nurse practitioners play a major role in promoting and maintaining the health care of many individuals. Nurse practitioners who work in a chronic dialysis unit can use their education and experience to function as case managers to provide quality and comprehensive care to these clients.

Academic Medical Centers↗
PubMed1995

The distribution of faecal nematode egg counts in Scottish Blackface lambs following natural, predominantly Ostertagia circumcincta infection.

Faecal samples were taken in 2 consecutive years from Scottish Blackface lambs on a commercial farm in central Scotland to examine variation among lambs in the number of nematode eggs in their faeces. Samples were taken at intervals of 4 weeks from 1 to 5 months of age. Lambs were treated with a broad-spectrum anthelmintic at each sample date. Ewes and lambs were naturally infected by grazing pasture contaminated with mixed, predominantly Ostertagia circumcincta, nematode species. The ewes were removed from the lambs when the lambs were three months old. Only 3 of the 6 sets of samples taken prior to removal of the ewes fitted a negative binomial distribution but all sets of samples taken after this did so. The mean and the variance differed with the month and year of sampling. The amount of variation among lambs increased as the lambs grew from 3 to 5 months of age, possibly because of heterogeneity in the rate of development of protective responses. Counts taken in August and September, when the lambs were 4 and 5 months of age, were positively correlated with each other. In contrast, counts taken at 1 or 2 months of age were negatively correlated with counts taken when the lambs were 3-5 months old. Sex, date of birth, sire and dam were all associated with variation in faecal egg counts but the size and significance of their influence was dependent upon the date when faecal samples were taken. Four factors: sire, dam, sex and year accounted for over two-thirds of the variation among older lambs in faecal egg counts.

Animal Husbandry↗
PubMed1995

A controlled seroprevalence survey of primate handlers for evidence of asymptomatic herpes B virus infection.

Herpes B virus (BV) is a common cause of recurring mucocutaneous infections in monkeys of the genus Macaca. Like its human counterpart, herpes simplex virus (HSV), BV establishes lifelong latency and can be reactivated from infected monkeys symptomatically or asymptomatically. Incidental infection of humans handling BV-shedding monkeys can result in fatal meningoencephalitis. To determine whether humans exposed to infected monkeys can acquire asymptomatic BV infections, 480 subjects were evaluated in a controlled seroprevalence study. Sera from 321 primate handlers, including many with repeated injuries inflicted by Macaca monkeys, and 159 people never exposed to monkeys were tested in blinded fashion by both competition ELISA and Western blot to determine the prevalence of BV and HSV seropositivity. Although 293 persons proved positive for HSV antibodies, no primate handlers or control subjects showed BV-specific antibody responses. There is no serologic evidence that BV causes asymptomatic infections in humans.

Adult↗
PubMed1995

German risk structure compensation: enhancing equity and effectiveness.

Prior to the 1992 German Health Care Structure Reform Law, Germany experienced inequitable and inefficient competition among its health insurers, known as "sickness funds." That situation was due to limitations on individuals' choice of insurer and the resulting risk segmentation. In 1994, the country implemented risk structure compensation to increase equity among sickness funds and enhance efficiency. This article describes the German risk structure compensation mechanism and its effects, and points out implications for the U.S. insurance market.

Adult↗
PubMed1995

Downregulation of male-specific cytochrome P450s 2C11 and 3A2 in bile duct-ligated male rats: importance to reduced hepatic content of cytochrome P450 in cholestasis.

The effects of bile duct ligation (BDL) on the activity and content of individual hepatic mixed-function oxidases (MFOs) was examined. Five days after BDL, hepatic microsomal total cytochrome P450 (CYP) content and NADPH-cytochrome P450-reductase (P450-reductase) activity were reduced to 56% and 57% of control, respectively. MFO activities attributable to the sexually undifferentiated CYPs 1A, 2A1, 2C6, and 2E1 were decreased to 32% to 52% of control, but the activities of two male sex-specific CYPs, 2C11 and 3A2, were reduced to a significantly greater extent (P < .05). The microsomal contents of CYP proteins 2C6 and 2E1 were decreased after BDL to 61% and 63% of control, whereas 2C11 and 3A2 proteins were 21% and 45% of control. Corresponding reductions of the messenger RNA (mRNA) species for CYP 2C11 (9% of control) and 3A2 (37%) were detected, whereas there was no reduction of 2C6 mRNA. These findings are consistent with downregulation of the CYP 2C11 and 3A2 genes. Nuclear run-on studies performed 3 days after BDL showed that there was a generalized impairment of gene transcription after BDL, but a disproportionate reduction in transcription of CYPs 2C11 and 3A2. A possible explanation for downregulation of CYP 2C11 and 3A2 was provided by the observation that serum estradiol concentrations were threefold greater in BDL male rats, while serum testosterone was reduced; estradiol is known to downregulate CYPs 2C11 and 3A2. It is concluded that male sex-specific CYP enzymes are decreased to a greater extent than other microsomal proteins in BDL male rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗