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Biomedical subjects

M Murray

Publications and source records attributed to M Murray.

At least 307 records · Page 17Linked to original sources
PubMed1991

The Endstage Renal Disease Severity Index (ESRD-SI).

Measures of disease severity are required as experimental, control and outcome variables in studies of the psychosocial aspects of physical illness. The Endstage Renal Disease Severity Index (ESRD-SI) was developed for these purposes during a prospective study of patient adjustment to dialysis and endstage renal disease (ESRD). It was found to have adequate inter-rater reliability, test-retest reliability, and construct and predictive validity in two subsamples (total N = 233) of dialysis patients. The ESRD-SI is suitable as a sensitive indicator of disease severity in these patients.

Adaptation, Psychological↗
PubMed1991

Susceptibility of N'Dama and Boran cattle to tsetse-transmitted primary and rechallenge infections with a homologous serodeme of Trypanosoma congolense.

Eight trypanotolerant N'Dama cattle controlled an infection of Trypanosoma congolense ILNat 3.1 transmitted by Glossina morsitans centralis, more efficiently than a group of similarly infected trypanosusceptible Boran cattle. All eight N'Damas maintained their PCV above 15% throughout the primary infection whereas the PCV of six of the eight Borans dropped below 15%; these latter animals were treated with diminazene aceturate to prevent possible death. Lymphocyte, neutrophil and platelet counts also decreased in the Boran during the primary infection. In contrast, a lymphocytosis was observed in the N'Dama; and although the neutrophil and platelet counts decreased, the drop was less severe than in the Boran. Two years after the primary infection and immediately prior to a homologous rechallenge infection, all eight N'Damas had neutralizing anti-metacyclic trypanosome variant-specific antibodies present in their sera compared to five of the eight Borans. Following the homologous rechallenge infection the eight N'Damas became parasitaemic but there were no alterations in their erythrocyte or leukocyte counts. The Borans became highly parasitaemic and developed severe, chronic anaemia and leukopaenia. Thus, the trypanotolerant N'Damas controlled a primary infection of T. congolense more efficiently than trypanosusceptible Boran cattle and eliminated a homologous rechallenge infection without the pathology associated with the disease.

Animals↗
PubMed1991

Susceptibility of N'Dama and Boran cattle to sequential challenges with tsetse-transmitted clones of Trypanosoma congolense.

The susceptibility of N'Dama cattle (Bos taurus) to four consecutive infections with different tsetse-transmitted clones of Trypanosoma congolense was compared with that of Borans (Bos indicus). All animals were aged 13 months at the start of the study and had been born and raised free from trypanosomiasis under the same management and nutritional conditions, thereby limiting environmental factors that could have influenced susceptibility. While cattle of both breeds were equally susceptible to the establishment of trypanosome infections, the N'Damas exhibited superior resistance. Despite infection with virulent parasites, the N'Damas gained weight at the same rate as uninfected control animals, they did not develop anaemia to the extent that trypanocidal drug treatment was required, and all made a spontaneous recovery to normal haematological values within two to four months. In contrast, all the Borans needed treatment during the course of the four infections because of severe anaemia and showed markedly reduced liveweight gains. These clinical differences in the N'Damas were associated with two repeatable characteristics, namely, the ability to control parasitaemia and to 'resist' anaemia, processes that did not appear to be linked. Also in contrast to the Borans, the N'Damas were able to mount accelerated haemopoietic responses, resulting in the reduced severity of anaemia following a primary infection. These findings pose the question as to whether the ability to control parasitaemia and to 'resist' anaemia could be used as criteria for identifying resistant or trypanotolerant cattle.

Anemia↗
PubMed1991

Immunopathology of experimental African sleeping sickness: detection of cytokine mRNA in the brains of Trypanosoma brucei brucei-infected mice.

The immunopathology of Trypanosoma brucei brucei in the central nervous system was studied by using an experimental model of chronic meningoencephalitis in outbred CD-1 mice. Mice infected with T. b. brucei were treated with a subcurative dose of the trypanocidal compound diaminazine aceturate. These mice relapsed and were again drug treated. The brains were examined histologically and by immunocytochemistry to identify activated astrocytes. The polymerase chain reaction was used to detect cytokine RNA transcripts. The infected and treated animals developed severe chronic meningoencephalitis characterized by large numbers of inflammatory cells and widespread astrocyte proliferation. In uninfected controls, only interleukin 1 and beta-actin RNA transcripts were detected while transcripts for beta-actin, tumor necrosis factor alpha, macrophage inflammatory protein 1 and interleukins 1 and 4 were demonstrated in the brains of infected animals. Gamma interferon and interleukin 6 were also detected in a few of the infected animals, but interleukin 2 was not found in any of these animals.

Animals↗
PubMed1991

Persistent polyclonal B lymphocytosis with Epstein-Barr virus antibodies and subsequent malignant pulmonary blastoma.

Persistent polyclonal B lymphocytosis (PPBL), a rare benign lymphoproliferative disorder, occurred in a 25 year old woman. The lymphocytes showed the phenotype cIgM+, FMC7+, CD19+, CD20+, which was similar to that seen in Waldenstrom's macroglobinaemia, but the proliferation was repeatedly shown to be polyclonal both immunologically and by immunoglobulin gene rearrangement studies. Eleven years after presentation the patient developed a malignant pulmonary blastoma, a rare pulmonary tumour of combined epithelial and mesenchymal origin. The failure to develop a lymphoid malignancy over 11 years together with immunological and genetic evidence of polyclonality confirms that PPBL is a benign lymphoproliferative disorder. The subsequent occurrence of a nonhaemopoietic malignancy suggests that benign lymphoid proliferations, like their malignant counterparts, may predispose to the development of neoplasia. A role for Epstein-Barr virus in the pathogenesis of one or both of these rare conditions is suggested by the finding of raised Epstein-Barr viral capsid antigen titres.

Adult↗
PubMed1991

Antimicrobial testing using oxygen consumption as the indicator of susceptibility.

In the presence of inhibitory concentrations of antibiotics, a decrease in oxygen consumption precedes and predicts changes in growth rates, bacterial stasis, or death of bacteria. The susceptibility of bacteria to various antibiotics was determined by growing the microorganisms in liquid media in the presence of varying concentrations of antibiotics. The oxygen consumption was then measured with an electrode at a specified time at each concentration of the antibiotic plus a positive and negative control. The decrease in oxygen consumption by the bacteria inhibited by the antibiotic precedes changes in numbers of bacteria and is predictive of the outcome of the standard minimum inhibitory concentration. This method determines antibiotic susceptibilities in approximately 3 hours and the minimum inhibitory concentration obtained corresponds with literature values and current minimum inhibitory concentration techniques.

Anti-Bacterial Agents↗
PubMed1990

Plasticity of dorsal root and descending serotoninergic projections after partial deafferentation of the adult rat spinal cord.

Plasticity of dorsal root (DR) and descending serotoninergic (5-HT) projections following dorsal rhizotomy from L2 to S1 sparing L5 was studied by means of an intra-animal comparison in the adult rat spinal cord. Projections of the chronically and acutely spared root were compared by cholera-toxin conjugated horseradish peroxidase (CT-HRP) injected into the sciatic nerves as the transganglionic tracer. Projections in unoperated controls, operated controls (acute bilateral spared root), and in experimental animals (chronic spared root on one side and acute spared root on the other) were mapped and the density was measured with an image analysis system. Labeled DRG cells and motor neurons were counted to determine if there were differences in the delivery of the label between the two sides. Measurements of the area of the dorsal horn and, separately, of the superficial laminae were made to control for shrinkage. DR projections were symmetrical in operated and unoperated controls, but a significant increase in DR projection density was found from L6 to L3 in the dorsal horn and Clarke's nucleus at L1 on the chronic spared root side in animals in which an equal number of DRG cells was labeled on the two sides. Density of 5-HT immunoreactivity was symmetrical in controls. Ipsilateral to chronic spared root rhizotomy, the area fraction occupied by 5-HT projections increased in Clarke's nucleus and in the superficial dorsal horn of all partially deafferented segments except L5, the spared root segment. Partial deafferentation of the adult rat lumbosacral spinal cord may therefore elicit sprouting from the spared dorsal root and, outside of the dorsal root projection zone, sprouting from the spared descending 5-HT system. Plasticity of dorsal root projections and of 5-HT projections occur in different regions; in regions of the increased spared root projection, no increase in seen in 5-HT projections, suggesting that sprouting in the adult rat spinal cord is regulated, perhaps by competitive or hierarchical mechanisms.

Animals↗
PubMed1990

17 Beta-hydroxysteroid oxidoreductase activity: age-dependent profile in rat liver and kinetic properties of the hepatic microsomal enzyme in relation to cytochrome P450-dependent steroid hydroxylation.

The functional relationship between the microsomal cytochrome P450 and 17 beta-hydroxysteroid oxidoreductase (HSOR) enzymes involved in steroid metabolism was investigated in rat liver. In male and female rat hepatic microsomes the NADPH-dependent conversion of androstenedione (AD) to testosterone (T) was approx. 4-fold greater at 6 weeks of age than in 1 week old animals. In hepatic microsomes from 15 week old rats the activity of the HSOR pathway was greater in males than in females (1.51 compared to 0.80 nmol T formed/min/mg protein). However, oestradiol administration to intact adult male rats did not decrease HSOR activity. Thus, androgen is not essential for maintenance of HSOR enzymes. Instead, it is likely that irreversible androgen imprinting of the HSOR enzyme occurs during the prepubertal period. The in vitro characteristics of HSOR activity were also assessed. The Km for NADH-dependent reduction of AD to T was 9.2 microM and the Vmax was 3.0 nmol/min/mg protein but the NAD-mediated formation of AD from T did not follow Michaelis-Menton kinetics. pH markedly influenced HSOR-mediated AD/T interconversion with 17-ketosteroid reduction facilitated at low pH, and 17 beta-hydroxysteroid dehydrogenation about 2-fold more efficient at pH 8.0 than at pH 5.5. Product steroid activation of HSOR activity was noted. 17 beta-Hydroxysteroids, including T and oestradiol, activated the rate of conversion of AD to T and 17-ketosteroids such as oestrone and AD activated the NAD-dependent dehydrogenation of T. Activation was not observed at low steroid substrate concentrations so that it was not possible to analyse this phenomenon by a conventional kinetic approach.

17-Hydroxysteroid Dehydrogenases↗
PubMed1990

Growth of injured rabbit optic axons within their degenerating optic nerve.

Spontaneous growth of axons after injury is extremely limited in the mammalian central nervous system (CNS). It is now clear, however, that injured CNS axons can be induced to elongate when provided with a suitable environment. Thus injured CNS axons can elongate, but they do not do so unless their environment is altered. We now show apparent regenerative growth of injured optic axons. This growth is achieved in the adult rabbit optic nerve by the use of a combined treatment consisting of: (1) supplying soluble substances originating from growing axons to be injured rabbit optic nerves (Schwartz et al., Science, 228:600-603, 1985), and (2) application of low energy He-Ne laser irradiation, which appears to delay degenerative changes in the injured axons (Schwartz et al., Lasers Surg. Med., 7:51-55, 1985; Assia et al., Brain Res., 476:205-212, 1988). Two to 8 weeks after this treatment, unmyelinated and thinly myelinated axons are found at the lesion site and distal to it. Morphological and immunocytochemical evidence indicate that these thinly myelinated and unmyelinated axons are growing in close association with glial cells. Only these axons are identified as being growing axons. These newly growing axons transverse the site of injury and extend into the distal stump of the nerve, which contains degenerating axons. Axons of this type could be detected distal to the lesion only in nerves subjected to the combined treatment. No unmyelinated or thinly myelinated axons in association with glial cells were seen at 6 or 8 weeks postoperatively in nerves that were not treated, or in nerves in which the two stumps were completely disconnected. Two millimeters distal to the site of injury, the growing axons are confined to a compartment comprising 5%-30% of the cross section of the nerve. A temporal analysis indicates that axons have grown as far as 6 mm distal to the site of injury, by 8 weeks postoperatively. Anterograde labeling with horseradish peroxidase, injected intraocularly, indicates that some of these newly growing axons arise from retinal ganglion cells.

Animals↗
PubMed1990

Evidence for complexation of P-450 IIC6 by an orphenadrine metabolite.

Removal of the orphenadrine metabolite from its complex with rat liver P-450 IIB1 is associated with a discrepancy in the reactivation of IIB1 activity. Two possible explanations are that either (1) NADPH-P-450-reductase is inaccessible to the restored IIB1, or (2) complexation of other P-450s may occur. Exogenous P-450 reductase increased all pathways of steroid hydroxylation (1.9 to 3.6-fold) but did not enhance reactivation of IIB1-dependent steroid 16 beta-hydroxylation. Instead, P-450 IIC6-dependent progesterone 21-hydroxylase activity was increased after dissociation to 122% of control. IIC6 activity was also inhibited in vitro in microsomes from phenobarbital-induced rats (ki = 151 microM). Thus, orphenadrine appears to complex P-450 IIC6 as well as IIB1 in rat liver.

Androstenedione↗
PubMed1990

Parasite kinetics and cellular responses in goats infected and superinfected with Trypanosoma congolense transmitted by Glossina morsitans centralis.

Trypanosoma congolense infected tsetse were fed on the flanks of goats at sites drained by the prefemoral lymph node. The efferent lymphatic of this lymph node was surgically cannulated and the lymph was collected daily and examined for appearance of parasites, lymph flow and cells. Trypanosomes were detected in the lymph 4 days after infection, which was 2 days prior to the appearance of the local skin reaction or the presence of parasites in the blood. Once the animal became parasitaemic, trypanosomes were found to recirculate in the lymphatic system, appearing in the lymph of the contralateral lymph node 11 days after infection. In goats infected with T. congolense and superinfected 12 or 13 days later with a different tsetse-transmitted T. congolense serodeme, parasites belonging to the second serodeme were apparently delayed in their development in the skin and appeared up to 7 days later in the efferent lymph when compared to control animals. This delay in development might have implications for field situations where superinfections frequently occur; it might result in limiting the number of serodemes of T. congolense an animal can be infected with at any one time.

Animals↗
PubMed1990

Modification of astrocytes in the spinal cord following dorsal root or peripheral nerve lesions.

Glial fibrillary acidic protein (GFAP) immunocytochemistry was used to monitor the response of astrocytes in the rat spinal cord to either dorsal root or sciatic nerve lesions. Image analysis methods were used to provide a quantitative correlate of the reactive gliosis. Multiple dorsal root section elicited a rapid increase in GFAP immunoreactivity of astrocytes unilaterally within the spinal cord along the pathway of the degenerating dorsal root axons in the dorsal and ventral horns and this gliosis persisted in the dorsal horn beyond the time at which active phagocytosis of degenerative debris occurred. Labeling of proliferating cells using [3H]thymidine revealed that none of the dividing cells contained detectable GFAP, suggesting that the increased GFAP labeling represents primarily a hypertrophy rather than a proliferation of astrocytes. Comparison of animals that had been deafferented in the early neonatal period with those deafferented as adults indicated that the GFAP immunoreactive response persisted following neonatal lesions but that it was markedly less intense than after adult lesions. Sciatic nerve section in adults does not result in extensive frank degeneration but it does evoke a rapid and marked increase in staining of astrocytes both in the dorsal horn and in the ventral horn. Transganglionic changes in GFAP staining in the dorsal horn occur by 3 days post-operatively, which is much earlier than the time of dorsal root ganglion neuron death caused by the sciatic nerve lesion. These experiments indicate that astrocytes can respond to signals from a variety of changes in neurons, including not only Wallerian degeneration, but also retrograde and transganglionic changes.

Animals↗
PubMed1990

Stage-specific cuticular proteins of Ostertagia circumcincta and Ostertagia ostertagi.

In this study we have shown that NHS-biotin and I125-streptavidin can detect cuticular polypeptides of Ostertagia spp. The labelled polypeptide profile of intact nematodes is simple compared to the profile obtained by labelling homogenates. None of the major internal polypeptides are labelled and the subset of proteins labelled in intact nematodes appears to be mainly surface associated. The results presented here demonstrate that NHS-biotin may be used as a reagent for the analysis of surface polypeptides. The surface polypeptide profiles of the five major developmental stages (L1, L2, L3, L4 and adult) of Ostertagia circumcincta show a series of stage-specific molecules with no polypeptides common to all stages, indicating that the cuticle is a dynamic structure which changes throughout the life cycle. Similarily comparison of Ostertagia ostertagi L3 and L4 stage surface profiles showed that each stage is clearly distinct; comparison of these stages between the two species shows an overall similarity.

Animals↗