Search PubMed⌕ Search

Biomedical subjects

G Murphy

Publications and source records attributed to G Murphy.

At least 433 records · Page 24Linked to original sources

Relationship between x-ray exposure and malignant transformation in C3H 10T1/2 cells.

The appearance of transformed foci after x-irradiation of the C3H 10T1/2 line of murine cells requires extensive proliferation followed by prolonged incubation under conditions of confluence. When the progeny of irradiated cells are resuspended and plated to determine the number of potential transformed foci, the absolute yield is constant over a wide range of dilutions and is similar to that observed in cultures that have not been resuspended. In addition, for cells exposed to a given x-ray dose, the number of transformed foci per dish is independent of the number of irradiated cells. These observations suggest that few, if any, of the transformed clones occur as a direct consequence of the x-ray exposure and challenge the hypothesis that transformed foci are the clonal products of occasional cells that have experienced an x-ray-induced mutational change. Rather, it appears that at least two steps are involved. We suggest that exposure to x-rays result in a change, for example, the induction or expression of some cell function, in many or all of the cells and that this change is transmitted to the progeny of the surviving cells; a consequence of this change is an enhanced probability of the occurrence of a second step, transformation, when these cells are maintained under conditions of confluence.

Animals↗

Effect of time and duration of exposure to 12-O-tetradecanoylphorbol-13-acetate on x-ray transformation of C3H 10T 1/2 cells.

We have confirmed our previous observations that the tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) enhances transformation induced by low doses of X-rays. We report here that TPA exerts its effect primarily on actively proliferating cells and has little promoting effect once the cells have reached confluency. However, previously irradiated cells seeded at low density, allowed to reach confluency and then reseeded at low density maintain the capacity to respond to TPA treatment during this second round of proliferation. These results indicate that: (a) as in vivo, TPA is effective even when treatment begins a long time after exposure to the initiating agent; (b) the enhancement of expression of X-ray transformation by TPA is not due to a simple stimulation of cell proliferation; (c) TPA enhancement does not result primarily from the conversion of premutational lesions in DNA to mutations; and (d) the promotional effects of TPA are probably not related to an effect on a DNA repair process.

Animals↗

Comparison of behavioral effects of systemic L-DOPA and intracranial dopamine in mesolimbic forebrain of nonhuman primates.

The systemic administration of L-DOPA and carbidopa to six rhesus and four squirrel monkeys produced an initial period of depressed activity followed by increased locomotion, hypervigilance, involuntary oral-facial movements and a gnawing syndrome. The squirrel monkey exhibited a depressed phase, locomotor stimulation, searching behavior, stereotypic grooming and gnawing syndrome. Most of these activities were prevented by pretreatment with 0.1 mg/kg haloperidol. Bilateral injection of 100 microgram dopamine into the mesolimbic forebrain of four squirrel monkeys also produced an initial depression followed by hyperactivity similar to that produced by L-DOPA, but without gnawing. A stereotyped submissive or juvenile posturing occurred in three animals. These DA-induced activities were blocked by 0.1 mg/kg haloperidol. Similar injection of 100 microgram L-norepinephrine produced a profound depression followed by moderate activity coupled with loss of extensor muscle strength in the legs. Bilateral injection of 300 microgram dopamine into the nucleus accumbens of a rhesus monkey produced stereotypic pacing. These data confirm in primates the importance of dopaminergic mechanisms of the mesolimbic forebrain in locomotor activity and behavior.

Animals↗

Proteinase inhibitors of bovine nasal cartilage.

Extracts from bovine nasal cartilage with 1 M-guanidinium chloride were fractionated by ultrafiltration. Gel chromatography of the low-molecular-weight material resolved three distinct fractions with inhibitory activity against (a) collagenases (22000 mol.wt.), (b) thiol proteinases cathepsin B and papain (13000 mol.wt.), and (c) trypsin and other serine proteinases (7000 mol.wt.).

Animals↗

Airborne spread of measles in a suburban elementary school.

A measles epidemic in a modern suburban elementary school in upstate New York in spring, 1974, is analyzed in terms of a model which provides a basis for apportioning the chance of infection from classmates sharing the same home room, from airborne organisms recirculated by the ventilating system, and from exposure in school buses. The epidemic was notable because of its explosive nature and its occurrence in a school where 97% of the children had been vaccinated. Many had been vaccinated at less than one year of age. The index case was a girl in second grade who produced 28 secondary cases in 14 different classrooms. Organisms recirculated by the ventilating system were strongly implicated. After two subsequent generations, 60 children had been infected, and the epidemic subsided. From estimates of major physical and biologic factors, it was possible to calculate that the index case produced approximately 93 units of airborne infection (quanta) per minute. The epidemic pattern suggested that the secondaries were less infectious by an order of magnitude. The exceptional infectiousness of the index case, inadequate immunization of many of the children, and the high percentage of air recirculated throughout the school, are believed to account for the extent and sharpness of the outbreak.

Air↗

Effect of ioglycamide (Biligram) on bile flow and biliary lipid secretion in man.

Twenty-one anicteric patients with a t-tube in situ were studied between the ninth and 11th postoperative days. Eleven patients were given an intravenous infusion of the biliary contrast agent ioglycamide (Biligram), while the other 10 acted as controls. Bile flow was recorded and the biliary concentrations of ioglycamide, bile salt, phospholipid, and cholesterol estimated in the two groups. The biliary excretion of ioglycamide was associated with a significant choleresis which was probably due to the obligatory coupling of the osmotically active contrast agent molecules with water. Biliary ioglycamide excretion did not significantly alter bile salt secretion rates. In contrast, the biliary secretion of both phospholipid and cholesterol was significantly lowered (P less than 0.001). Unlike chenodeoxycholic acid, ioglycamide significantly reduced bile acid independent cholesterol secretion (P less than 0.01), although secretion rate in terms of mumol of bile acid was essentially unchanged.

Bile↗

A new factor that may control collagen resorption.

Specific collagenases responsible for the initial enzymic step leading to degradation of the collagen fibrils of connective tissues have been found in both latent and active forms. The most important factor controlling the local activity of collagenase extracellularly may be an inhibitor that is synthesised by connective tissues, and it is proposed that latent enzymes are all enzyme-inhibitor complexes.

Animals↗

The detection and characterisation of collagenase inhibitors from rabbit tissues in culture.

As tissue cultures, rabbit bone, skin and non-gravid uterus synthesise inhibitors of collagenase (EC 3.4.24.3). An assay for the inhibitors is described and their action on collagenase from different tissue sources demonstrated. Evidence for the involvement of the tissue inhibitors of collagenase in the latency of the enzyme in culture media is presented. Latent collagenase was activated by treatment with 4-aminophenylmercuric acetate, and then reacted with the inhibitors to form inactive complexes with properties similar to the naturally occurring latent enzyme forms. The associated changes in molecular weight are detailed, and discussed in relation to the observations of other workers concerning the extracellular control of collagenase activity.

Animals↗

Evidence that latent collagenases are enzyme-inhibitor complexes.

Specific collagenase from the culture media of various rabbit tissues and cells exists in active and latent forms. Latent collagenase is most effectively activated with 4-aminophenylmercuric acetate, a thiol-blocking reagent, strongly suggesting that latent forms are enzyme-inhibitor complexes. A collagenase inhibitor from bone cultures, which may be closely related to the inhibitor of such latent enzyme complexes, was partially characterized.

Animals↗

Collagenase is a component of the specific granules of human neutrophil leucocytes.

Azurophil and specific granules were isolated from human polymorphonuclear neutrophil leucocytes. Collagenase was almost exclusively a component of the specific granules. This finding is in contrast with the distribution of other proteolytic enzymes, which are localized in the azurophil (or lysosomal) granules.

Electrophoresis, Polyacrylamide Gel↗

Chemotherapy of advanced carcinoma of the prostate with 5-fluorouracil, cyclophosphamide and adriamycin.

There were 33 patients with clinically relapsing advanced prostatic carcinoma (stages C and D) treated by 2 different combinations of chemotherapy. The 13 patients in group 1 received 5-fluorouracil and cyclophosphamide and 20 patients in group 2 received adriamycin and cyclophosphamide. The over-all response was 69.3 per cent in group 1 and 65 per cent in group 2. Our preliminary results should encourage further evaluation of these drug combinations by other investigators under carefully controlled conditions.

Adenocarcinoma↗

A comparison of the survival of H-Y incompatible ear, tail, and body skin grafts.

In the H-Y incompatible C57BL/6 male to female system, both tail and ear skin grafts were found to persist longer than body (thorax) skin grafts of the same size and shape. Ear skin grafts of long standing did not affect the survival of subsequent body skin grafts but, in one case, a long-term tail skin graft prolonged the survival of a subsequent body skin gratf, both transplants persisting throughout the life of the host. Whereas ear skin grafts from which cartilage was removed were invariably rejected, several ear skin grafts with cartilage intact survived permanently.

Animals↗

Patulin biosynthesis: the metabolism of m-hydroxybenzyl alcohol and m-hydroxybenzaldehyde by particulate preparations from Penicillium patulum.

The ring hydroxylation of m-hydroxybenzyl alcohol to gentisyl alcohol by a particulate preparation from Penicillium patulum has been characterised. The activity was shown to be closely associated with, but not necessarily identical to, m-cresol 2-hydroxylase activity of the 105 000 X g microsomal fraction. As with both the m-cresol hydroxylases of this system, m-hydroxybenzyl alcohol hydroxylase required oxygen and NADPH for activity. A Km value for m-hydroxybenzyl alcohol of 15 muM was measured. Inhibition of the hydroxylase activity and its reversal by light, as well as the action of cytochrome c, KCN and other effectors suggested a mixed-function oxidase reaction of the cytochrome P-450, NADPH-cytochrome reductase type. m-Hydroxybenzaldehyde was not ring hydroxylated by any preparation from P. patulum. Apart from the previously described conversion to m-hydroxybenzyl alcohol by a predominantly soluble dehydrogenase, m-hydroxybenzaldehyde was metabolized to m-hydroxybenzoic acid by a particulate fraction. This activity required NADPH. It was concluded that the main biosynthetic pathway to patulin must be through m-hydroxybenzyl alcohol, gentisyl alcohol and gentisaldehyde.

Benzaldehydes↗