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Biomedical subjects

M Murray

Publications and source records attributed to M Murray.

At least 451 records · Page 25Linked to original sources

Recovery of substance P but not somatostatin in the cat spinal cord after unilateral lumbosacral dorsal rhizotomy: a quantitative study.

The dorsal horn of the cat spinal cord contains substance P and somatostatin within nerve endings which arise from cells located in dorsal root ganglia and from cells within the neuraxis. Previous studies from this laboratory have demonstrated that dorsal rhizotomy depletes both peptides from the dorsal horn. However, the changes in the two peptides differ. Substance P is at first severely depleted by dorsal rhizotomy and then recovers in part, whereas somatostatin is diminished less but does not recover. In the present experiments the validity of these conclusions which were based on anatomical observations has been evaluated quantitatively with the use of radioimmunoassay. After a 74% reduction at 10-14 days postoperative, substance P immunoreactivity in the deafferented dorsal horn shows a small, statistically significant recovery by 30 days to 60% of normal values. In contrast, somatostatin is reduced by 46% at 10-14 days but does not return significantly. As previously suggested by immunocytochemistry, dorsal rhizotomy produces no significant decline of either peptide in the ventral horn. The differing response of the two peptides is consistent with the hypothesis that intrinsic spinal substance P-containing neurons increase their projections (or their production of substance P) in the deafferented dorsal horn, but that somatostatin-containing neurons do not. Because synaptic number returns to normal in at least the deafferented lamina II of the cat yet substance P recovers only partially, it is likely that axons which contain transmitters other than substance P or somatostatin also increase the numbers of their terminals in response to dorsal rhizotomy.

Animals↗

Experimental studies on the interaction between infections of Ostertagia leptospicularis and other bovine Ostertagia species.

Experimental infections of calves were carried out with either isolates of predominantly Ostertagia ostertagi, pure O. leptospicularis or a mixed isolate of equal numbers of both these species. The total worms established on day 21 for the mixed species from a total inoculum of 100 000 infective larvae, was 1.2 times greater than from 100 000 larvae of the O. ostertagi isolate and 3.3 times that of the pure O. leptospicularis isolate. The increased establishment in the mixed inoculum referred to both O. ostertagi and O. leptospicularis (days 17 and 21). These differences were both highly significant (P less than 0.01). The severity of the pathological changes was also greater in the mixed infections. It is suggested that these findings must be taken into account when control measures involving alternate grazing of sheep and cattle are being employed.

Abomasum↗

Viability of retinal ganglion cells after optic nerve crush in adult rats.

The response of retinal ganglion cells to optic nerve crush was examined in the hooded rat. Intracranial nerve crush produces a transient shrinkage of the retinal ganglion cells during the first several weeks postoperatively but partial recovery of cell size then appears to occur. This transient response is considered to be a direct response to axotomy. Retrograde transport of horseradish peroxidase (HRP) is clearly demonstrated at 2 weeks postoperatively. Transport of newly synthesized protein progressively decreases over the first 2 postoperative months. The ganglion cell therefore retains viability for at least the first few weeks after axotomy. Loss of 60% of the neurons in the ganglion cell layer occurs between 3 and 7 months postoperatively. This late occurring retrograde response is considered to result at least in part from loss of sustaining trophic influences rather than as a direct result of the lesion.

Animals↗

Interactions of nitrogen heterocycles with cytochrome P-450 and monooxygenase activity.

Three groups of isomeric nitrogen heterocycles, phenylpyridines, phenylimidazoles and pyridylimidazoles were studied in relation to the effect of steric factors on type II binding to cytochrome P-450 and inhibition of aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH) activity in hepatic microsomes from phenobarbital(PB)- and beta-naphthoflavone(beta NF)-induced rats. Type II binding affinity was lower (higher Ks) in compounds with substituents on the carbon adjacent to the nitrogen undergoing ligand interaction than in those where steric hindrance near the nitrogen was minimal. Binding affinities of the compounds as measured by their Ks values, were quite similar in both PB- and beta NF-induced microsomes. In PB-induced microsomes, type II binding affinity was generally reflected by the ability of the compounds to inhibit AHH activity. In contrast, most of the compounds evaluated were inactive as AHH inhibitors in beta NF-induced microsomes.

Animals↗

Abnormality of insulin binding and receptor phosphorylation in an insulin-resistant melanoma cell line.

The insulin receptor possesses an insulin-stimulated tyrosine-kinase activity; however, the significance of receptor phosphorylation in terms of the binding and signaling function of the receptor is unclear. To help clarify this problem, we have studied insulin binding and receptor phosphorylation in a Cloudman S91 melanoma cell line and two of its variants: the wild type (1A) in which insulin inhibits cell growth, an insulin-resistant variant (111) in which insulin neither stimulates or inhibits growth, and a variant (46) in which insulin stimulates cell growth. 125I-insulin binding to intact cells was similar for the wild-type 1A and insulin-stimulated variant 46. The insulin-resistant variant 111, in contrast, showed approximately 30% decrease in insulin binding. This was due to a decrease of receptor affinity with no major difference in receptor number. When the melanoma cells were solubilized in 1% Triton X-100 and the insulin receptor was partially purified by chromatography on wheat germ agglutinin-agarose, a similar pattern of binding was observed. Phosphorylation was studied by incubation of the partially purified receptor with insulin and [gamma-32P]ATP, and the receptor was identified by immunoprecipitation and NaDodSO4 PAGE. Insulin stimulated phosphorylation of the 95,000-mol-wt beta-subunit of the receptor in all three cells types with similar kinetics. The amount of 32P incorporated into the beta-subunit in the insulin-resistant cell line 111 was approximately 50% of that observed with the two other cell lines. This difference was reflected throughout the entire dose-response curve (10(-9) M to 10(-6) M). Qualitatively similar results were obtained when phosphorylation was studied in the intact cell. Peptide mapping of the beta-subunit using tryptic digestion and reverse-phase high-performance liquid chromatography column separation indicated three sites of phosphorylation in receptor from the wild type and variant 46, but only two major sites of phosphorylation of variant 111. These data suggest that the insulin-resistant variant melanoma 111 possesses a specific defect in the insulin receptor which alters both its binding and autophosphorylation properties, and also suggests a possible role of receptor phosphorylation in both the binding and the signaling function of the insulin receptor.

Binding, Competitive↗

Genetic resistance to African Trypanosomiasis.

Genetic resistance to African trypanosomiasis occurs in certain breeds of livestock, many species of wildlife, some strains of mice, and possibly humans. The term trypanotolerance is used to describe this trait, which in domestic livestock is best exhibited by the indigenous West African taurine breeds of cattle, N'Dama and West African Shorthorn, that have been in Africa for 5,000 to 7,000 years. Confirmation not only that these breeds are genetically resistant to trypanosomiasis but also that they are at least as productive as other indigenous breeds is currently leading to their increased use in livestock-development projects in tsetse-infested areas. Trypanotolerance appears to be related to the control of parasitemia, a capacity associated with an event that regulates parasite growth and determines how rapidly the immune response is triggered. Identification of the factors that regulate this event and definition of their genetic basis may have important implications for the development of novel strategies for control of African trypanosomiasis.

Anemia↗

Changes in levels of actin and tubulin mRNAs upon the lectin activation of lymphocytes.

The expression of beta-actin, gamma-actin, alpha-tubulin, and beta-tubulin mRNA during the lectin activation of human peripheral blood lymphocytes was examined with specific cDNA clones. The resting lymphocyte has a low level of both alpha- and beta-tubulin mRNAs, and these increase 10-fold after 72 h of lectin stimulation in which maximum cell transformation is achieved. Although there is a slight increase in tubulin mRNA during the first 6 h, most of the increase occurs between 6 and 24 h as the cells start to increase their RNA content and progress from G0 into G1. Both beta- and gamma-actin mRNAs are more abundant than the tubulin mRNAs in resting cells, with beta-actin mRNA being the major species. Upon activation, beta-actin mRNA increases threefold, whereas gamma-actin mRNA increases almost sixfold. Both beta- and gamma-actin mRNA are elevated 2.5-fold as early as 6 h, the gamma-actin mRNA level then increasing more than beta-actin between 6 and 24 h, resulting in the reduced beta-actin/gamma-actin mRNA ratio. The lectin-stimulated lymphocyte has a similar beta-actin/gamma-actin mRNA ratio as that of the human leukemic T-lymphoblast cell line CCRF-CEM. These increases are over and above the general increase in polyadenylated RNA content upon lectin activation. On returning to a noncycling state, the levels of these cytoskeletal mRNAs decrease. There were two beta-tubulin mRNAs present in lymphocyte cytoplasm, one of 1.8 kilobases and one of 2.8 kilobases in length. The nongrowing lymphocytes had relatively lower levels of the larger sized mRNA. Upon stimulation, the relative level of the larger mRNA was increased, and at 72 h the cells had approximately equal levels of both mRNAs as did the leukemic lymphoblasts.

Actins↗

School characteristics and adolescent smoking. Results from the MRC/Derbyshire Smoking Study 1974-8 and from a follow up in 1981.

In the MRC/Derbyshire Smoking Study a cohort of about 6000 adolescents was surveyed annually from 1974 when they entered secondary school aged 11-12 years until 1978 when they reached 15-16 years. In 1981 after the adolescents had left school they were again surveyed by post. Each year from 1974 to 1978 and again in 1981 they answered a questionnaire on their smoking behaviour and other issues. Information on the schools attended by these adolescents was obtained from their teachers and headteachers. This paper examines the relation between the school environment and the adolescents' smoking behaviour both before and after leaving school. The prevalence of smoking was higher among those boys who attended schools that were single sex, non-denominational, or had a parent-teacher association, no health education, no female teachers, or whose headteacher smoked cigarettes. Among girls the prevalence of smoking was higher if they attended a school that had optional school uniform and no health or antismoking education. The importance of these findings for the development of effective preventive measures is discussed.

Adolescent↗

Long term effect of a school based antismoking programme.

In the winters of 1977-8 and 1978-9 about 400 children in seven junior schools in northern England were taught the "My Body" health education programme. In the springs of 1980 and of 1982 these children, and an age matched control group, answered a questionnaire about their smoking behaviour, knowledge, and attitudes. Comparison of the two groups suggested that the programme had had a positive effect on the boys but a negligible, or even negative, effect on the girls. Various suggestions as to the reasons for this differential impact are discussed.

Adolescent↗

Effects of dihydrosafrole on cytochromes P-450 and drug oxidation in hepatic microsomes from control and induced rats.

Changes in cytochromes P-450, aminopyrine N-demethylase (APDM), aromatic hydrocarbon (benzo[a]pyrene) hydroxylase (AHH), and type III spectral complex formation were measured in hepatic microsomes of control, phenobarbital (PB)-, and beta-naphthoflavone (beta NF)-induced rats after a single dose of dihydrosafrole (4-n-propyl-1,2-methylenedioxybenzene, DHS). Time profiles of changes in these microsomal parameters were complex and showed that APDM activities and cytochrome P-450 levels decreased immediately after treatment and were associated with concurrent increases in the intensity of the type III methylenedioxyphenyl (MDP) metabolite/cytochrome P-450 spectral complex. In noninduced rats, both APDM activity and cytochrome P-450 levels returned to control levels between 12 and 24 hr after treatment with DHS and subsequently increased above control levels. In PB- and beta NF-induced animals, the inhibitory phases were more prolonged and activity never returned to levels higher than the corresponding controls. AHH activity was increased substantially (two- to three-fold) in all cases after DHS administration. Although displacement of the MDP metabolite/cytochrome P-450 complex with 2-methylbenzimidazole generally led to a marked restoration of cytochrome P-450 levels and partially reversed the inhibition of APDM, it had little or no effect on AHH activities.

Aminopyrine N-Demethylase↗