Showing papers by "University of Melbourne published in 1972"

Atropine resistant excitation of the urinary bladder: The possibility of transmission via nerves releasing a purine nucleotide

Abstract: 1. The possibility that a purine nucleotide is involved in excitatory transmission to the urinary bladder has been tested. All the purine compounds tested which contained a pyrophosphate bond produced contraction, adenosine triphosphate (ATP) being the most potent. Adenosine and adenosine monophosphate caused relaxation. 2. The response to ATP closely mimicked the nerve-mediated contraction, both being characterized by a rapid contraction which was not maintained. A lack of sensitivity to ATP was noted in some preparations of the rat urinary bladder. 3. Both nerve-mediated contractions and contractions caused by ATP were blocked by quinidine, while the response to acetylcholine persisted. 4. Nerve-mediated responses were depressed during tachyphylaxis produced by high concentrations of ATP. Tachyphylaxis did not occur when low concentrations were used. Possible explanations for these results are discussed. 5. The results are consistent with the hypothesis that non-cholinergic excitatory nerves to the guinea-pig bladder release a purine nucleotide, but do not provide critical evidence for it.

Prostaglandin F2α identified as a Luteolytic Hormone in Sheep

Abstract: Prostaglandin F2α is released from the uterus of the sheep in a cyclic fashion, acts primarily in a local manner on the ovary via a counter-current mechanism and is responsible for the periodic regression of the corpus luteum in this species.

Cigarette smoking and plasma levels of nicotine.

Abstract: THE changes in blood levels and tissue distribution of nicotine and its metabolites have been studied in experimental animals after administration of tobacco smoke or smoking doses of nicotine1–3, but there is no comparable information for man. Such data are important in ascribing a role to nicotine in smoking. Recently, methods have been described for measurement of nicotine levels in human venous blood4,5, but they are complicated and have not been used to follow changes in blood levels of nicotine in any detail. We have improved our method1 by using the newly developed alkali flame ionization detector6 (AFID) with the gas-liquid chromatograph (GLC) so that it is sensitive to 1 ng/ml. of nicotine in a 2.5 ml. sample and have used it for assay of plasma nicotine.

Analysis of changes in the renin-angiotensin system during pregnancy.

Abstract: 1. Determinations of plasma renin activity (PRA), plasma renin concentration (PRC) and renin substrate (RS) were made on single plasma samples from thirty-four women at various stages of pregnancy. Comparisons were made with non-pregnant control subjects. 2. All three variables were elevated above controls throughout pregnancy, but whereas the mean value of PRA was equally high between the first and the second halves of pregnancy, PRC was higher in the first and RS higher in the second half of pregnancy. 3. Kinetic studies indicated that, in spite of high concentrations of RS in late pregnancy, the renin-renin substrate reaction remains substrate dependent when proceeding at physiological pH values. 4. No differences in enzyme-substrate affinity were detected between the plasmas of pregnant and non-pregnant women. 5. In each of three deliveries RS was lower in the foetus than in the mother but PRA and PRC did not display consistent gradients. 6. PRC in uterine venous blood was slightly lower ( P = 0·05) than in peripheral blood during caesarian section at term. 7. On deriving PRC from PRA by using the Michaelis-Menten equation, a physiologically inactive component in maternal PRC became apparent. It is suggested that this component is activated by the acid treatment used in the direct PRC methodology. Its concentration is highest in early pregnancy and circumstantial evidence suggests that it originates from foetal chorion.

A comparison of the excitatory and inhibitory effects of non‐adrenergic, non‐cholinergic nerve stimulation and exogenously applied ATP on a variety of smooth muscle preparations from different vertebrate species

Abstract: 1. The responses to non-adrenergic, non-cholinergic nerve stimulation have been compared with those to exogenously applied ATP on seventeen different tissues from a number of vertebrate classes.2. Stimulation of all the mammalian gut preparations studied (with the exception of the guinea-pig ileum) after blockade of the effects of adrenergic and cholinergic nerve stimulation by guanethidine (3.5 muM) and hyoscine (1.3 muM) caused inhibition; exogenously applied ATP mimicked this inhibitory response.3. Stimulation of the guinea-pig ileum in the presence of hyoscine and guanethidine, usually caused a diphasic response, relaxation followed by contraction; exogenously applied ATP mimicked this response, in contrast to acetylcholine and noradrenaline which caused excitation and relaxation respectively.4. Stimulation of preparations of lower vertebrate gut and guinea-pig bladder in the presence of hyoscine and guanethidine caused contraction; exogenously applied ATP mimicked this contractile response.5. In each preparation the time course of the response to ATP was similar or identical to the response to non-adrenergic, non-cholinergic nerve stimulation.6. The results are consistent with the hypothesis that a purine nucleotide may be the transmitter substance released from non-adrenergic, non-cholinergic nerves supplying smooth muscle preparations from a number of vertebrate classes.

Sympathetic ganglia in culture. I. Neurons.

Abstract: The accessory cells of rat, guinea-pig and chick sympathetic ganglia have been studied in tissue culture with phase-contrast microscopy, time-lapse cinematography and fluorescence histochemistry. Small intensely fluorescent (SIF) cells have been described for the first time in culture. Satellite cells, which are closely associated with nerve cell bodies, and interstitial cells, which are dispersed throughout the ganglion, appeared to be identical cell types; they do not correspond to oligodendrocytes of the central nervous system as has been suggested previously. However, a small number of cells closely resembling central oligodendrocytes were present. Astrocyte-like cells have also been seen occasionally, although their identity is not clear. Several other cell types were present and have been identified as Schwann cells, sheath cells, fibroblasts, perineural epithelium, macrophages and endothelial cells.

Plasma Deoxycorticosterone Levels in Man with Simultaneous Measurement of Aldosterone, Corticosterone, Cortisol and 11-Deoxycortisol

Abstract: A double isotope derivative dilution procedure has been developed to measure deoxycorticosterone (DOC) in human peripheral plasma. The method involves the addition of [14C]-DOC as internal recovery indicator and [3H]-acetic anhydride for derivative formation. The method shows adequate specificity, precision and accuracy. Simultaneously, aldosterone, corticosterone, cortisol and 11-deoxycortisol have been measured with DOC. Normal plasma DOC levels were found to be 6.3 ± 1.0 ng/100 ml (mean ± se, n = 17). The corresponding levels of aldosterone, corticosterone, cortisol and 11-deoxy cortisol were 6.5 ± 1.0 ng/100 ml, 0.42 ± 0.09 μg/100 ml, 13.9 ± 1.4 μg/100 ml and 0.060 ± 0.013 μg/100 ml respectively. ACTH administered to 6 subjects produced a mean increase in plasma DOC from 4.7 to 32.4 ng/100 ml. Angiotensin II infused at subpressor doses for 2 hr into 8 subjects did not increase mean plasma DOC. Similarly, dietary sodium restriction for 5 days or postural change did not increase plasma DOC. These result...

Monoamine mediation of the morphine-induced activation of mice.

Abstract: Summary 1 . The dose-response relationship for hyperactivity in grouped mice following the injection of morphine sulphate has been established. 2 . The activation response can be modified by drugs which affect either catecholamines or indoleamines. 3 . The monoamine precursors l-DOPA and 5-hydroxytryptophan potentiate the response. 4 . The monoamine synthesis inhibitors α-methyl-p-tyrosine and p-chlorophenylalanine reduce the response. 5 . Inhibition of monoamine oxidase activity by pargyline caused a great increase in the response. The simultaneous administration of reserpine resulted in a further potentiation. 6 . Reserpine blocked the response whenever it was given alone, either before, with or after the injection of morphine. 7 . Blockade of α-adrenoceptors with phentolamine or phenoxybenzamine reduced the response. 8 . Blockade of tryptaminergic receptors with methysergide or cinanserin also antagonized the response. 9 . The major tranquillizers haloperidol and chlorpromazine reduced the response. Haloperidol was especially effective in this regard. 10 . The tricyclic antidepressant drug imipramine potentiated the response. 11 . The morphine antagonist nalorphine completely prevented the response. 12 . The anticholinergic agent atropine and the antihistaminic drug mepyramine did not affect the response. 13 . We conclude that dopamine, noradrenaline and 5-hydroxytryptamine are all involved in the normal activation response of grouped mice to morphine, with dopaminergic mechanisms being of primary importance.

The Growth of Bone Marrow Cells in Liquid Culture

Abstract: Summary. Liquid suspension cultures of mouse bone marrow cells at high and low density were prepared in supplemented Eagle's medium containing 10% of a partially purified extract of mouse embryos and pregnant mouse uterus (PMU). In the low cell density cultures the number of cells decreased for 2 days; by 4 days the agar colony-forming cells (agar CFC) had risen ten-fold and the spleen colony-forming units (spleen CFU) had fallen to one tenth; between 4 and 8 days the total cell count showed a four-fold increase and the final cell number exceeded the number of the original culture. The cells produced were mainly macrophages. If PMU was not included in the culture the agar CFC disappeared after 4 days and there was no cell multiplication. In the high cell density cultures a similar pattern was observed; in the presence of PMU the agar CFC showed an increase in number, the spleen CFU decreased and an increase in cell number occurred between 4 and 8 days. However, the cells produced were predominantly granulocytes. In the absence of PMU from this cell culture, agar CFC were maintained for 6 days and the cell population remained predominantly granulocytic. These methods of growing cell enable cell recovery from the cultures to be made at any stage and provide an opportunity to study the kinetics and functional capacity of the cells produced.

The Hamilton Rating Scale for depression: a factor analysis.

Abstract: A factor analysis was carried out of ratings on the Hamilton Scale on a group of 134 male and 213 female depressed patients The original data covered a wide range of severity of illness and the distribution of severity scores was not biased from normal Hamilton's general factor was confirmed but his bipolarity between agitated and retarded depression did not emerge Sex differences in factor patterns were found and a preliminary experiment showed that factor scores could isolate anxiety features and personality factors

Ketogenesis from butyrate and acetate by the caecum and the colon of rabbits.

Abstract: 1. When studied in vitro, tissue from the caecum and the proximal colon of rabbits converted butyrate into ketone bodies. The conversion was similar to that observed with liver slices. The ketogenic activity was associated with the mucosa rather than the muscle of the gut wall and, in the colon, diminished as the distance from the caecal-colonic junction increased. 2. Tissue from the wall of the ileum, caecum, proximal colon and distal colon was also shown to metabolize [1-(14)C]butyrate to carbon dioxide. 3. Enzyme assays showed that in both liver tissue and caecal mucosa the activity of hydroxymethylglutaryl-CoA synthase was more than ten times that of acetoacetyl-CoA deacylase. Labelling experiments in vitro gave confirmation of the hydroxymethylglutaryl-CoA pathway. 4. The significance of the conversion of butyrate into ketone bodies is discussed.

Dislocation group dynamics III. similarity solutions of the continuum approximation

Abstract: The continuum approximation replaces a group of discrete dislocations by a continuous dislocation density. It is shown that this formalism possesses similarity solutions of the equations of motion with an arbitrary power law stress-velocity relationship in parallel with the similarity motions of the discrete group. The time scale is identical in the two cases. As with the static continuum approximation, the dynamic approximation leads to a much larger range of explicit solutions than is available for the discrete group.