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Biomedical subjects

M Murray

Publications and source records attributed to M Murray.

At least 469 records · Page 26Linked to original sources
PubMed1983

Interactions between insulin and the cyclic AMP system of Cloudman S91 mouse melanoma cells.

Insulin inhibits the proliferation of wild-type Cloudman S91 mouse melanoma cells. The effects, which are mediated through specific, high-affinity receptors for insulin, appear to involve interactions with the cAMP system. Our evidence is as follows: 1) Cloudman cells have a cAMP requirement for proliferation and pigmentation. Exposure of cells to insulin results in a lowering of intracellular cAMP levels and inhibition of both cell division and pigment formation. 2) The effects of insulin are reversed by agents which raise cAMP levels, or by the cAMP analogue dibutyryl cAMP. 3) A mutant cell line with a temperature-dependent requirement for cAMP is most sensitive to the growth inhibitory effects of insulin when its requirements for cAMP are maximal. 4) Mutants selected only for alterations in their response to insulin frequently have concomitant alterations in their cAMP systems. 5) The melanotropin-responsive adenylate cyclase system is stimulated following prolonged exposure of cells in culture to insulin. Although we do not know the mechanism(s) for the interactions between the insulin and the cAMP system, our initial findings suggest that protein phosphorylation/dephosphorylation reactions are involved.

Adenylyl Cyclases↗
PubMed1983

The binding to oxidised cytochromes P-450 and inhibition of mixed-function oxidases by aryl-substituted benzimidazoles and related compounds.

A series of benzimidazole derivatives containing additional fused and non-fused aromatic groupings were effective inhibitors of aryl hydrocarbon hydroxylase (PB/AHH) and aminopyrine N-demethylase (ADPM) activities in hepatic microsomes from phenobarbitone(PB)-induced rats. Two structurally similar nitrogen heterocycles, 6-ethoxy-2-methylbenzoxazole and 6-methoxy-2-methylbenzothiazole, were moderately potent inhibitors of PB/AHH and APDM. Only phenanthro(9,10-d)imidazole (I50 = 2.2 X 10(-5) M) and 2-(2'-chlorophenoxy)methylbenzimidazole (I50 = 5.2 X 10(-5) M) were potent inhibitors of AHH activity in hepatic microsomes from 3-methylcholanthrene (3-MC)-induced rats. Five of the compounds were evaluated for the ability to bind to oxidised cytochromes P-450 in microsomal suspensions from induced rats. All compounds except phenanthro(9,10-d)imidazole elicited a type II spectral change with oxidised cytochrome P-450 in PB-induced microsomes, whereas only two compounds produced the type II change in 3-MC-induced microsomes. Two other compounds produced the type I spectral change in 3-MC-induced microsomal suspensions, and phenanthro-(9,10-d)imidazole elicited a reverse type I spectral change in both types of induced microsomes. These results indicate that the precise structure of the benzimidazole derivative can determine the binding type that is observed in oxidised microsomes. It is possible, therefore, that more than a single mode of inhibition of monooxygenase activity is occurring and that inhibition, as well as binding type, is dependent on structure.

Aminopyrine N-Demethylase↗
PubMed1983

New regulatory factors for melanogenesis: developmental changes in neonatal mice of various genotypes.

The biosynthesis of melanin occurs through sequential steps known as the Mason-Raper pathway. The initial steps are the conversion of tyrosine to dihydroxyphenylalanine (dopa) and of dopa to dopaquinone by the enzyme tyrosinase (EC 1.10.3.1). Until recently it was assumed that once these first two conversions were completed, the subsequent reactions occurred spontaneously. However, studies with mouse melanoma cells in culture revealed that subsequent steps in the pathway are also regulated. In this report, we demonstrate that these steps are also regulated in skins of fetal and newborn mice. The specific activities of the regulatory factors change during the first week after birth and differ in mice of different genotypes. The findings provide new insights into genetic and developmental regulation of the pigmentary system in mammals.

Albinism↗
PubMed1983

Trypanosoma congolense: susceptibility of cattle to cyclical challenge.

Cattle primed by cyclical infection with Glossina morsitans morsitans infected with cloned derivatives of Trypanosoma congolense and treated with the trypanocidal drug Berenil after 3 or 4 weeks were immune to cyclical challenge with homologous clones 3 to 5 weeks later. In these animals, localized skin reactions (chancres) and parasitemia did not develop. The same results were obtained in cattle given a homologous superinfection without prior treatment. On the other hand, cattle subjected to a cyclical challenge with heterologous clones were completely susceptible as demonstrated by the development of chancres. Immunity to homologous challenge was achieved irrespective of the bloodstream variable antigenic types used to infect the tsetse. It was concluded that for a given serodeme the variable antigen composition of the metacyclic population which develops in the tsetse is constant and characteristic. Immunity to cyclical challenge was also obtained with uncloned stocks, providing the same stock was used for challenge. On the other hand, cattle immune to homologous cyclical challenge with cloned material were not always immune to cyclical challenge with parent stock, indicating that certain stocks consist of more than one serodeme. On the basis of these findings, it may be possible to use the chancre as a marker for serodeme analysis.

Animals↗
PubMed1983

The development of smoking during adolescence--the MRC/Derbyshire Smoking Study.

Each year from 1974, when they entered secondary school, to 1978, when they reached school-leaving age, a cohort of over 6000 schoolchildren from Derbyshire, England, answered a questionnaire about their own and their family's smoking practices and their social activities. Their replies revealed a steady increase in the prevalence of smoking during adolescence. Those children who in 1974 smoked, had friends of the opposite sex, were highly involved in social activities, experienced peer pressure to smoke and rejected the health hazards of smoking were more likely to be regular smokers in 1978 than were other children. Similarly, those children who, when aged 11-12 years, had parents or siblings who smoked, had friends of the opposite sex, and were highly involved in social activities increased their smoking rapidly in subsequent years. Sex and social class differences in the strength of these associations suggest that an understanding of the development of smoking during adolescence requires knowledge of the particular character of the social relationships among different subgroups of that age-group and the various meanings of smoking to them.

Adolescent↗
PubMed1983

Role conflict and intention to leave nursing.

To test the hypothesis that one of the reasons why nurses leave their job is that they find it difficult to meet the public expectations 246 student and qualified nurses answered a questionnaire to assess this form of role conflict. It emerged that role conflict was highest among second and third year students and that particular aspects of it were strongly related to an expressed intention to leave nursing. The implications of these findings are discussed.

Conflict, Psychological↗
PubMed1983

The task of nursing and risk of smoking.

A survey of hospital nurses was conducted to determine whether certain aspects of nurses' working and living conditions could explain their smoking practices. Nurses (246) of all grades answered a questionnaire about their smoking practices, job characteristics, job satisfaction, life satisfaction and anxieties. The prevalence of regular smoking was low among first and second year student nurses but reached 22% among final year students and 27% among staff nurses. Those nurses who reported stress at work, high and low overall job satisfaction, low lifestyle satisfaction and high anxiety about patients were more likely to smoke. The importance of these factors was especially marked among final year students. It seems that the changes in the life and work routine of nurses during their final year of training appear to increase their risk of regular smoking.

Anxiety↗
PubMed1983

Regulation of the growth and differentiation of Trypanosoma (Trypanozoon) brucei brucei in resistant (C57Bl/6) and susceptible (C3H/He) mice.

While Trypanosoma brucei brucei GUTat 3 were equally infective for C3H/He and for C57Bl/6 mice at doses ranging from 5 to 5 x 10(3) organisms and had similar prepatent periods in both strains of mice, infected C57Bl/6 mice displayed lower parasitaemia, shorter times to parasite wave remission and survived for a longer time than infected C3H/He mice. Parasite growth and differentiation rates and host immune responses were similar for the first 5 days in both strains of mice after infection with 10(3) T.b.brucei GUTat 3 but, thereafter, parasite differentiation proceeded more rapidly and specific antibodies reached higher titres in C57Bl/6 than in C3H/He mice. In contrast, parasite growth and differentiation rates were similar in irradiated mice of both strains. Furthermore, following inoculation of intact mice with irradiated T.b.brucei GUTat 3, C3H/He mice actually mounted higher titred antibody responses than C57Bl/6 mice showing that they were not intrinsically defective in their capacity to respond to GUTat 3 antigens. Parasite differentiation occurred at the same rate in irradiated (650r) C57Bl/6 mice and in irradiated C57Bl/6 mice reconstituted with syngeneic spleen cells although T.b.brucei GUTat 3 specific antibody was detected in the latter mice prior to peak parasitaemia. Furthermore, it was shown directly in C57Bl/6 mice that there was no selective destruction of slender form T.b.brucei GUTat 3 parasites during the phase of accumulation of stumpy form parasites. These studies indicate that the more rapid differentiation of T.b.brucei GUTat 3 parasites in infected C57Bl/6 mice as compared to infected C3H/He mice was unlikely to be directly related to the more efficient antibody response in the infected C57Bl/6 mice. The observations suggest that there might be an association between host mechanisms which regulate differentiation of T.b.brucei parasites and those which regulate antibody responses.

Animals↗
PubMed1983

Trimethoprim and rifampin in combination for chemoprophylaxis of household contacts of patients with invasive infections due to Haemophilus influenzae type b.

We compared the effectiveness of rifampin-trimethoprim in fixed combination (3.75:1) to rifampin alone in the eradication of Haemophilus influenzae type b carriage among contacts of patients with invasive infection caused by this organism. The study population was composed of 127 index patients and 620 contacts. Twenty-six percent of contacts were colonized. Rifampin-trimethoprim eradicated carriage in 77.6% of contacts (71.1% in contacts less than 5 years, 84.2% in contacts greater than or equal to 5 years) whereas rifampin eradicated carriage in 69.9% of contacts (56.4% in contacts less than 5 years, 81.8% in contacts greater than or equal to 5 years). A single isolate resistant to rifampin and rifampin-trimethoprim was encountered. The eradication rate achieved with this regimen of rifampin-trimethoprim was too low to recommend its routine use. However, a higher dose or longer course might merit clinical trial.

Carrier State↗
PubMed1983

The interaction of arylalkybenzimidazoles and related compounds with microsomal oxidation.

A series of 2-arylalkyl- and 2-(4'-alkyl)phenoxymethylbenzimidazoles was synthesized and evaluated as inhibitors of mixed-function oxidase activity in phenobarbitone- and beta-naphthoflavone-induced rat liver microsomes. Higher homologues of the 2-arylalkyl series were more potent inhibitors than lower homologues against all mono-oxygenase activities except aniline p-hydroxylation. Smaller 2-substituents were associated with relatively low-affinity reverse type I spectral binding behaviour, whereas larger substituents were associated with type I binding of high affinity.

Aminopyrine N-Demethylase↗
PubMed1983

Structure-activity relationships in the interactions of alkoxymethylenedioxybenzene derivatives with rat hepatic microsomal mixed-function oxidases in vivo.

Following in vivo administration to rats of equimolar amounts of a series of 4-n-alkoxymethylenedioxybenzene (AMDB) derivatives, hepatic microsomal aryl hydrocarbon hydroxylase (AHH) activities, total cytochrome P-450 levels, and AMDB metabolite-cytochrome P-450 spectral complex (455 nm) formation were well correlated in parabolic relationships with pi, the hydrophobic constant of the n-alkoxy substituent. Each of these parameters increased progressively over control values with increasing carbon chain length of the alkoxy substituent, passed through an optimal value in compounds containing five or six carbon atoms, and subsequently decreased with the higher homologues. AHH activity was highly correlated in linear relationships with total (complexed plus uncomplexed) cytochrome P-450 content and intensity of the 455-nm spectral complex. Aminopyrine N-demethylase activities in microsomes from AMDB-treated rats were not well correlated with cytochrome P-450 levels or spectral complex formation. AMDB metabolite-ferricytochrome P-450 complexes varied considerably in their relative ease of displacement following treatment with 2-n-heptylbenzimidazole, those derived from the n-butoxy to n-hexoxy derivatives being particularly stable toward the displacer. The results are discussed in relation to the possible mechanisms involved in the interactions of methylenedioxyphenyl compounds with cytochrome P-450 and drug oxidation.

Animals↗