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Showing papers by "University of Melbourne published in 1988"


Journal ArticleDOI
15 Jul 1988-Gene
TL;DR: Plasmid expression vectors have been constructed that direct the synthesis of foreign polypeptides in Escherichia coli as fusions with the C terminus of Sj26, a 26-kDa glutathione S-transferase (GST; EC 2.5.1.18) encoded by the parasitic helminth Schistosoma japonicum.

6,003 citations


Journal ArticleDOI
TL;DR: Decisions concerning the choice of scoring interval, experimental design, and statistical analysis for VAS have in some instances been based on convention, assumption and convenience, highlighting the need for more comprehensive assessment of individual scales if this versatile and sensitive measurement technique is to be used to full advantage.
Abstract: Visual Analogue Scales (VAS) provide a simple technique for measuring subjective experience. They have been established as valid and reliable in a range of clinical and research applications, although there is also evidence of increased error and decreased sensitivity when used with some subject groups. Decisions concerned with the choice of scoring interval, experimental design, and statistical analysis for VAS have in some instances been based on convention, assumption and convenience, highlighting the need for more comprehensive assessment of individual scales if this versatile and sensitive measurement technique is to be used to full advantage.

1,792 citations


Journal ArticleDOI
TL;DR: In this paper, a Pascal computer program, thermocalc, is described for various thermodynamic calculations using the thermodynamic dataset presented in earlier papers in this series (Holland & Powell, 1985; Powell & Holland, 1985).
Abstract: This paper provides methods and a description of a Pascal computer program, thermocalc, for various thermodynamic calculations using the thermodynamic dataset presented in earlier papers in this series (Holland & Powell, 1985; Powell & Holland, 1985). The dataset involves uncertainties on the thermodynamic parameters and therefore allows uncertainties to be calculated on results, for example in geothermometry and geobarometry. Recommendations are made for the uncertainties on activities to be used in calculations on rocks, particular emphasis being placed on preventing underestimates of these uncertainties at small mole fractions. Apposite examples of phase diagram and rock calculations are presented with ouput from thermocalc, demonstrating the utility of the program. Of the rock calculations, the most valuable are considered to be those involving simultaneous combination ‘least squares’of calculated conditions for a set of reactions applicable to a rock. This set of reactions involves the independent reactions which can be written between the end-members in the minerals in a rock and in the thermodynamic dataset. In contrast to an approach based on specific geothermometers and geobarometers, this approach maximizes the benefit of having an internally consistent thermodynamic dataset. thermocalc is available in IBM PC and Mac versions, from Roger Powell for A$25 or Tim Holland for £10 per version.

1,431 citations


Journal ArticleDOI
TL;DR: The authors examined the background and development of motivational hypotheses in social identity theory, revealing two general motives for intergroup discrimination: a desire for cognitive coherence, or good structure; and a need for positive self-esteem.
Abstract: The background and development of motivational hypotheses in social identity theory are examined, revealing two general motives for intergroup discrimination: a desire for cognitive coherence, or good structure; and a need for positive self-esteem. The latter (self-esteem hypothesis: SEH) has received most attention. Both the theoretical and empirical bases of the SEH are largely rooted in research using the minimal group paradigm. However, it remains unclear whether self-esteem is to be considered primarily as a cause or an effect of discrimination. When real social groups are considered the SEH appears to provide only a partial explanation, and a variety of more or less powerful alternative social motives may underlie discriminatory behaviour. We explore some social-structural, individual and interpersonal limits to the SEH, and we call for an awareness of these motives and a re-examination of the good-structure thesis. The SEH, as it stands, provides only a partial contribution to our understanding of the relationship between social identity and discriminatory intergroup behaviour.

1,067 citations


Journal ArticleDOI
TL;DR: Results indicate that osteoblastic cells are required for the differentiation of osteoclast progenitors in splenic tissues into multinucleated osteoclasts.
Abstract: We developed a co-culture system with mouse spleen cells and osteoblastic cells to examine the role of osteoblasts in osteoclast formation. When mouse spleen cells and osteoblastic cells isolated from fetal mouse calvariae were co-cultured in the presence of 10 nM 1 alpha, 25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], numerous tartrate-resistant acid phosphate (TRACP)-positive mononuclear and multinucleated cells were formed within 8 days. Neither the same co-cultures without the vitamin nor separate cultures of either spleen cells or osteoblastic cells with the vitamin produced TRACP-positive cells. Salmon calcitonin (CT) markedly increased cAMP production in the co-cultures treated with 1 alpha,25(OH)2D3. Autoradiographic studies clearly demonstrated that [125I]-CT specifically bound to the TRACP-positive cells formed in the co-cultures with the vitamin. When spleen cells and osteoblastic cells were co-cultured on dentine slices in the presence of 1 alpha,25(OH)2D3, numerous resorption lacunae were formed on the slices. Neither co-cultures of alveolar macrophages and osteoblastic cells nor those of spleen cells and mouse skin-derived fibroblasts induced TRACP-positive cells even in the presence of 1 alpha,25(OH)2D3. When spleen cells and osteoblastic cells were cultured separately from each other by a membrane filter (0.45 micron), no TRACP-positive cells were formed. These results indicate that osteoblastic cells are required for the differentiation of osteoclast progenitors in splenic tissues into multinucleated osteoclasts.

926 citations


Book
01 Feb 1988

516 citations


Journal ArticleDOI
TL;DR: In this paper, a continuum theory for dilute suspensions of large-aspect-ratio particles is applied to the flow of fiber suspensions through contractions, which incorporates the statistical orientation distribution function into the stress equation.
Abstract: A continuum theory for dilute suspensions of large-aspect-ratio particles is applied to the flow of fiber suspensions through contractions. The theory, which incorporates the statistical orientation distribution function into the stress equation, predicts that the flow of dilute suspensions will differ qualitatively from the flow of the suspending fluid. The theory is in excellent agreement with experiments on the flow of suspensions of chopped-glass fibers through axisymmetric contractions, where substantial enlargement of the recirculating corner vortex is observed at volume fractions of 0.1% and less.

335 citations


Journal ArticleDOI
TL;DR: In this paper, an 18-parameter family of integrable reversible mappings of the plane is presented, which are shown to occur in soliton theory and in statistical mechanics.

311 citations


01 Jun 1988

298 citations


Journal ArticleDOI
TL;DR: Parathyroid hormone (PTH)-like bioactivity, assayed as adenylate cyclase response in UMR 106-01 osteogenic sarcoma cells, was present in extracts of sheep fetal and maternal parathyroid glands and placenta and may contribute to the relative hypercalcaemia of the fetal lamb.
Abstract: Parathyroid hormone (PTH)-like bioactivity, assayed as adenylate cyclase response in UMR 106-01 osteogenic sarcoma cells, was present in extracts of sheep fetal and maternal parathyroid glands and placenta. Preincubation of extracts with PTH(1-34) antiserum inhibited approximately 40% of the bioactivity in fetal parathyroid extracts, 50% in maternal parathyroid extracts, but only 10% of the bioactivity in the placental extract. Partial purification of placental extracts by chromatography yielded fractions containing PTH-like bioactivity which were similar in behaviour to that of PTH-related protein (PTHrP) from a human lung cancer cell line (BEN). An antiserum against synthetic PTHrP(1-16) partially inhibited the bioactivity of the placental extract and synthetic PTHrP(1-34), but had no effect on the bioactivity of bovine PTH(1-34) or bovine PTH(1-84). The placental PTH-like bioactivity was higher in mid- than in late gestation. Fetal parathyroid glands contained the highest PTH-like bioactivity. Thyroparathyroidectomy of one fetal twin lamb in each of 16 ewes between 110 and 125 days of gestation resulted in decreases of the plasma calcium concentration and reversal of the placental calcium gradient that existed between the ewe and the intact fetus. Perfusion of the placenta of each twin in anaesthetized ewes was carried out sequentially with autologous fetal blood in the absence of the exsanguinated fetus. The plasma calcium concentration in the blood perfusing the placenta of each twin increased, but reached a plateau at a lower concentration in the perfusing blood of thyroparathyroidectomized fetuses than in that of the intact fetuses. Addition of extracts of fetal parathyroid glands or of partially purified PTHrP resulted in further increases in plasma calcium in the autologous blood perfusing the placentae of thyroparathyroidectomized fetuses, but addition of bovine PTH(1-84) or rat PTH(1-34) had no effect. The presence of this PTH-like protein in the fetal parathyroid gland and placenta may contribute to the relative hypercalcaemia of the fetal lamb. This protein, which is similar to PTHrP associated with humoral hypercalcaemia of malignancy, stimulates the placental calcium pump responsible for maintaining a relative fetal hypercalcaemia during gestation.

276 citations


Journal Article
TL;DR: A deeper knowledge of the factors that control smooth muscle phenotype is essential to an understanding of the mechanisms underlying the pathogenesis of atherosclerosis.
Abstract: In 1968, Professor Robert Wissler published a landmark review on the role of smooth muscle cells in atherogenesis. He suggested that in future studies more attention should be given to the cytologic and metabolic characteristics of these multifunctional mesenchymal cells. This article summarizes some of our studies inspired by these words and indicates a few of the many questions that still need to be addressed. We have shown that smooth muscle cells of different phenotypes from that expressed in normal arterial media exist in regions of diffuse intimal thickenings adjacent to atheroma and also in vessels following injury. Cells of equivalent phenotype can exist in cell culture, and we have shown that they have all the characteristics of smooth muscle in atherogenesis, ie, they proliferate in response to mitogens, readily synthesize increased amounts of extracellular matrix, and accumulate large amounts of lipid. In contrast, smooth muscle cells of the phenotype that normally exists in the unaffected artery do not express these characteristics and their major function is maintenance of vessel tone. Thus a deeper knowledge of the factors that control smooth muscle phenotype is essential to an understanding of the mechanisms underlying the pathogenesis of atherosclerosis.

Journal ArticleDOI
10 Mar 1988-Nature
TL;DR: Transgenic mice bearing a mutant α1(I) collagen gene into which specific glycine substitutions have been engineered show a dominant lethal phenotype characteristic of the human disease, and demonstrate that as little as 10% mutant gene expression can disrupt normal collagen function.
Abstract: Substitutions of single glycine residues of alpha 1(I) collagen have previously been associated with the inherited disease osteogenesis imperfecta type II. Transgenic mice bearing a mutant alpha 1(I) collagen gene into which specific glycine substitutions have been engineered show a dominant lethal phenotype characteristic of the human disease, and demonstrate that as little as 10% mutant gene expression can disrupt normal collagen function.

Journal ArticleDOI
TL;DR: The increase in serum CSFs occurred before the peak in bone marrow granulocyte-macrophage progenitors and before the reduction in bacterial numbers which follows the onset of specific cell-mediated immunity.
Abstract: After infection of mice with Listeria monocytogenes, elevated levels of colony-stimulating factors (CSFs) in the serum were quantitated by six different assays: ability to stimulate colony formation, the proliferation of 2 suspension of bone marrow cells (both measuring total colony-stimulating activity), a radioimmunoassay for macrophage-CSF (CSF-1), the WEHI-3B differentiation assay for granulocyte-CSF, and proliferation of 32D-c1-3 and FDC-P1 cell lines (specific for multi-CSF and either multi- or granulocyte-macrophage-CSFs, respectively). The great bulk of serum colony-stimulating activity represented macrophage- and granulocyte-CSFs, with small but measurable amounts of granulocyte-macrophage-CSF. The degree of elevation of serum CSF depended on the infecting dose used and the numbers of bacteria growing in the spleens and livers of the two mouse strains compared, i.e., L. monocytogenes-resistant C57BL/10 and susceptible BALB/cJ. The increase in serum CSFs occurred before the peak in bone marrow granulocyte-macrophage progenitors and before the reduction in bacterial numbers which follows the onset of specific cell-mediated immunity.

Journal ArticleDOI
TL;DR: The relationship between reduced track density, ϱ/ϱ 0, and reduced mean confined track length, L/L 0, during annealing has been studied for both spontaneous and induced tracks in four apatite samples with different chemical composition, compositional range, and origin this paper.

Journal ArticleDOI
TL;DR: The ballistic movement is defined as a rapid voluntary movement which is motor programmed and in which visual feedback for path correction is not possible and is determined by the combined factors of Fitts' Index of Difficulty and movement amplitude.
Abstract: The ballistic movement is defined as a rapid voluntary movement which is motor programmed and in which visual feedback for path correction is not possible. A discrete ballistic movement is of short movement duration (less than about 200 msec) with a triphasic pattern in the electromyograph (EMG) for muscle activity and has an acceleration pattern which approximates a sinusoidal waveform. When the Index of Difficulty for such a movement is less than 3·0, the movement time is found to be related to the square root of the movement amplitude. The occurrence of ballistic movement is determined by the combined factors of Fitts' Index of Difficulty and movement amplitude.

Journal ArticleDOI
TL;DR: It is proposed that the active shedding of surface antIGens may serve as an important source of parasite antigens available to the immune system in a form in which they can be taken up and processed by antigen-presenting dendritic cells, macrophages and certain B cells for presentation to T helper cells.
Abstract: Parasitic helminths excrete or secrete (ES) a variety of molecules into their mammalian hosts. The effects of these ES products on the host's immune responses are reviewed. Investigations into the source of antigenic or immunoregulatory ES products have identified the cuticular and tegumental surfaces of some nematodes and trematodes respectively as being important sources of ES products; other ES molecules are released through specialized excretory or secretory organs. It is proposed that the active shedding of surface antigens may serve as an important source of parasite antigens available to the immune system in a form in which they can be taken up and processed by antigen-presenting dendritic cells, macrophages and certain B cells for presentation to T helper cells. The ES products of nematodes, trematodes and cestodes contribute to immune evasion strategies of the parasites through mechanisms including shedding of surface-bound ligands and cells, alteration of lymphocyte, macrophage and granulocyte functions and modulation of complement and other host inflammatory responses. Immunopathology may be induced by ES products as in the development of granulomas around entrapped schistosome eggs. In some host-parasite systems ES antigens may induce host-protective immune responses and this source of protective antigens has been utilized in the successful vaccination against helminth infections, particularly against infection with trichurid nematodes and the metacestode stage of cestode parasites. The use of ES antigens in immunodiagnosis of helminth infection is also briefly discussed.

Book ChapterDOI
01 Jan 1988
TL;DR: In this article, it was shown that nearby diffeomorphisms must also have transversal homoclinic points and hence also infinitely many periodic points, and that the property of having infinitely many points cannot, in general, be perturbed away.
Abstract: Smale [12,13] studied diffeomorphisms with transversal homoclinic points and showed that the dynamics are chaotic in the neighbourhood of the orbit of such a point, in the sense that there is a compact invariant set on which the action of some iterate of the diffeomorphism is topologically conjugate to the action of the Bernoulli shift. One immediate consequence of this is Birkhoff’s result that the diffeomorphism has infinitely many periodic points. It also turns out that nearby diffeomorphisms must also have transversal homoclinic points and hence also infinitely many periodic points. Thus the property of having infinitely many periodic points cannot, in general, be perturbed away.

Journal ArticleDOI
TL;DR: An electroporation procedure for the plasmid-mediated genetic transformation of intact cells of StrePTococcus cremoris and Streptococcus lactis was performed and yielded transformant colonies in 14 to 24 h.
Abstract: An electroporation procedure for the plasmid-mediated genetic transformation of intact cells of Streptococcus cremoris and Streptococcus lactis was performed. Ten different strains were transformed. The method was simple and rapid and yielded transformant colonies in 14 to 24 h. The method was optimized for S. lactis LM0230, and transformation frequencies of between 1 × 104 and 5 × 105 transformants per μg of purified plasmid (pMU1328) were achieved routinely. The optimized procedure involved lysozyme treatment of cells. Transformation of LM0230 occurred at comparable frequencies with pLS1 (4.4 kilobase pair [kbp]), pMU1328 (7.4 kbp), and pAMβ1 (26.5 kbp). Plasmid DNA isolated from transformants had not undergone detectable deletions or rearrangements. Transformation was possible with plasmid DNA which was religated after restriction endonuclease digestion. Phage DNA-dependent transfection of S. lactis LM0230 and S. lactis C6 was also achieved. Images

Journal ArticleDOI
01 Sep 1988-Genetics
TL;DR: Changes in fluctuating asymmetry reflect changes in fitness, as in the case of the fitness modifier, its effect to be dominant and data consistent with the fitness/asymmetry modifier being the same gene (gene complex).
Abstract: Genetic evidence suggests that the evolution of resistance to the insecticide diazinon in Lucilia cuprina initially produced an increase in asymmetry. At that time resistant flies were presumed to be at a selective disadvantage in the absence of diazinon. Subsequent evolution in natural populations selected modifiers to ameliorate these effects. The fitness and fluctuating asymmetry levels of resistant flies are currently similar to those of susceptibles. Previous genetic analyses have shown the fitness modifier to co-segregate with the region of chromosome III marked by the white eyes, w, locus, unlinked to the diazinon resistance locus, Rop-1, on chromosome IV. This study maps the asymmetry modifier to the same region, shows, as in the case of the fitness modifier, its effect to be dominant and presents data consistent with the fitness/asymmetry modifier being the same gene (gene complex). These results suggest changes in fluctuating asymmetry reflect changes in fitness.

Journal ArticleDOI
TL;DR: In this article, a data set of stream flows with a global coverage is used to produce a classification of seasonal flow regimes based on a cluster analysis of the monthly mean flows expressed as percentages of the mean annual flow.

Journal ArticleDOI
TL;DR: The results are discussed in relation to autoregulatory changes which occur following changes in the K+ concentration of cerebrospinal fluid.
Abstract: 1. The resting membrane potentials of proximal and distal segments of the arterioles which arise from the rat middle cerebral artery were determined. Proximal segments had stable membrane potentials with a mean value of -69 mV. The membrane potentials of distal segments were less negative and often unstable. 2. When the extracellular concentration of potassium ions [( K+]o) was increased proximal segments of arteriole were depolarized whereas distal ones were hyperpolarized. When [K+]o was decreased both proximal and distal segments were depolarized, the changes being more marked in proximal arterioles. 3. The membranes of proximal segments of arteriole displayed inward rectification at potentials near rest; inward rectification in distal segments of arteriole, when detected, was less pronounced. 4. The activation curve for inward rectification in proximal segments of arteriole was changed by changing the extracellular concentration of K+. A reduction in [K+]o caused the activation curve to move to such negative potentials that the inward rectifier no longer contributed to the resting conductance. 5. Increasing [K+]o changed the activation curve for inward rectification in distal segments of arteriole so that more K+ current flowed at potentials near resting. At the same time the membrane potential hyperpolarized. 6. The results are discussed in relation to autoregulatory changes which occur following changes in the K+ concentration of cerebrospinal fluid.

Patent
20 Jun 1988
TL;DR: In this paper, a drug infusion pump has a drive system including a drive motor (49), a worm gear (53) on the output shaft of said motor, a worm wheel (55) meshing with said worm gear and a clutch means (62) associated with said output gear (60) for disengaging drive to a drive head (61) engaged by a drive belt (83) which is permanently connected to a syringe actuator (7) to cause controlled infusion of the contents of the syringe under the control of a central control system.
Abstract: A drug infusion pump having a drive system including a drive motor (49), a worm gear (53) on the output shaft of said motor, a worm wheel (55) meshing with said worm gear (53) and constructed to drive an output reduction gear (60) and clutch means (62) associated with said output gear (60) for disengaging drive to a drive head (61) engaged by a drive belt (83) which is permanently connected to a syringe actuator (7) to cause controlled infusion of the contents of a syringe under the control of a central control system including a microprocessor (20) and programmable memory means (21 and 23) which determine the manner in which the infusion is performed. A syringe clamping arm (5) is associated with a potentiometer (24) which provides to the controller diameter information regarding the syringe. The programmable memory means (23) includes data relating to one or more standard syringe sizes to enable automatic operation on insertion of a standard syringe. In the event that a non-standard syringe is to be used, the infusion pump may be simply programmed to allow such non-standard syringes to be used.

Journal ArticleDOI
TL;DR: Marked differences in the percentage of certain lymphocytes subsets were apparent within the compartments examined, suggesting that lymphocyte subsets leave the blood with differing efficiencies.
Abstract: The surface phenotypes (CD1, CD4, CD5, CD8, SBU-T19, MHC class I, MHC class II, and sIg) of cells in blood, lymph nodes, and lymph were determined to examine simultaneously the distribution of lymphocyte subsets circulating in blood, afferent lymph, and efferent lymph of a peripheral lymph node. Marked differences in the percentage of certain lymphocyte subsets were apparent within the compartments examined, suggesting that lymphocyte subsets leave the blood with differing efficiencies. Lymphocyte subsets also appeared to be extracted from the blood at different rates by lymph node as opposed to subcutaneous vascular endothelium. Endothelial cells in different vascular beds may express different numbers of molecules complementary to a set of migration-related cell surface molecules specific for each lymphocyte subset. Accordingly, the vascular endothelium would be the key factor in regulating nonrandom cell migration.

Journal ArticleDOI
TL;DR: In this article, a regional fission-track dating study in northern Victoria Land (NVL) provides information on the amount, timing and variable rates of uplift of the Transantarctic Mountains (TAM) at their northernmost extent.
Abstract: A regional fission-track dating study in northern Victoria Land (NVL) provides information on the amount, timing and variable rates of uplift of the Transantarctic Mountains (TAM) at their northernmost extent. Apatite ages increase systematically with elevation and together with confined track length distributions, define a two-stage uplift history, although a variety of thermal histories, resolvable by use of confined track length distributions, exist for different parts of NVL. A pronounced “break in slope” in the apatite age-elevation profile for results from most of NVL occurs at ∼ 50 Ma, approximating the start of uplift of the mountains. This marks the base of an uplifted apatite annealing zone. Prior to uplift, samples above this break lay within the apatite annealing zone whereas those samples below it had an apatite fission-track age of zero. For most of NVL, ∼ 5 km of uplift have been calculated. In the southeastern coastal region, however, uplift of the order of 10 km has been estimated, exposing apatite ages of only 25–35 Ma. Sphene and zircon ages from this area also appear reduced relative to the regional pattern, suggesting that the partial annealing zones for these minerals have been revealed. Confined track length distributions from the lower part of the apatite age profile indicate an initially rapid period of uplift (∼ 200–400 m Ma−1) from ∼ 50 Ma. In the Lichen Hills-Outback Nunataks area, in the west of NVL, apatites have not been completely overprinted by the Jurassic thermal event associated with emplacement of the Ferrar Dolerite, and uplift here is of the order of only 4 km. Block faulting associated with uplift of the TAM is considered to be the same event as Rennick Faulting leading to the formation of the Rennick Graben.

Journal ArticleDOI
TL;DR: It is concluded that the amounts and Mr values of hyaluronan released from the tissues into peripheral lymph can be significantly underestimated by analysis of efferent lymph, i.e. lymph that has passed through lymph nodes.
Abstract: Afferent lymph vessels entering popliteal lymph nodes of sheep were infused with [3H]acetyl-labelled hyaluronan of high Mr (4.3 x 10(6)-5.5 x 10(6)) and low Mr (1.5 x 10(5)). Analysis of efferent lymph and of residues in the nodes showed that hyaluronan presented by this route is taken up and degraded by lymphatic tissue. Labelled residues isolated in node extracts by gel chromatography and h.p.l.c. included N-acetylglucosamine, acetate, water and a fraction provisionally identified as N-acetylglucosamine 6-phosphate. Between 48 and 75% of the infused material was unrecovered, and had been presumably eliminated through the bloodstream as diffusible residues. Rates of degradation reached as high as 43 micrograms/h in a node of 2 g wt. infused with 56 micrograms/h. Some HA passed into efferent lymph and some was detected in the nodes, but fractions of Mr greater than 1 x 10(6) were not found in either. It is concluded that the amounts and Mr values of hyaluronan released from the tissues into peripheral lymph can be significantly underestimated by analysis of efferent lymph, i.e. lymph that has passed through lymph nodes. A substantial role in the normal metabolic turnover of at least one major constituent of intercellular matrix and connective tissue may now be added to the established functions of the lymphatic system.

Journal ArticleDOI
TL;DR: In this paper, it was shown that constant-temperature annealing can be adapted to temperatures which vary with time using the "principle of equivalent time" which assumes that at any moment, a track which has been annealed to a certain degree r (= l/l0) behaves during further annaling in a manner which is independent of the conditions which caused the prior anneal, but which depends only on the degree of anneeling that has occurred, and the prevailing conditions of temperature and time.
Abstract: Despite considerable attention to isothermal behaviour in the literature, no satisfactory description of the variable temperature annealing behaviour of fission tracks in apatite has been given to date. Here, we show that our recently published constant-temperature annealing description can be adapted to temperatures which vary with time using the “principle of equivalent time”. This assumes that at any moment, a track which has been annealed to a certain degree r (= l/l0) behaves during further annealing in a manner which is independent of the conditions which caused the prior annealing, but which depends only on the degree of annealing that has occurred, and the prevailing conditions of temperature and time. Comparison of predictions of mean track length based on this assumption with observed values in a large number of laboratory variable-temperature annealing experiments shows good agreement, suggesting that the assumption is valid. Detailed inspection of the behaviour of tracks during heating and cooling shows that annealing is much more rapid at higher temperatures, and that temperature is the dominant factor in fission-track annealing in apatite. Extension of this treatment to geological situations is not straightforward and is left to a future paper.

Journal ArticleDOI
TL;DR: Several new regions of vasopressin receptor binding have been identified, possibly due to the advantages of a radioiodinated ligand with high receptor affinity without binding to neurophysins, confirming and extending previous findings of V1 receptors in the rat brain.

Journal ArticleDOI
19 Aug 1988-Science
TL;DR: Results provide direct support for the concept that the pseudosubstrate structure binds the active site and that the role of calmodulin is to modulate this interaction.
Abstract: The myosin light chain kinase requires calmodulin for activation Tryptic cleavage of the enzyme generates an inactive 64-kilodalton (kD) fragment that can be further cleaved to form a constitutively active, calmodulin-independent, 61-kD fragment Microsequencing and amino acid analysis of purified peptides after proteolysis of the 61- and 64-kD fragments were used to determine the amino-terminal and carboxyl-terminal sequences of the 64-kD fragment Cleavage within the calmodulin-binding region at Arg505 generates the catalytically inactive 64-kD fragment, which is incapable of binding calmodulin Further digestion removes a carboxyl-terminal fragment, including the pseudosubstrate sequence Ser484-Lys-Asp-Arg-Met-Lys-Lys-Tyr-Met- Ala-Arg-Arg-Lys-Trp-Gln-Lys-Thr-Gly-His-Ala-Val-Arg505 and results in a calmodulin-independent 61-kD fragment Both the 61- and 64-kD fragments have the same primary amino-terminal sequences These results provide direct support for the concept that the pseudosubstrate structure binds the active site and that the role of calmodulin is to modulate this interaction Pseudosubstrates may be utilized in analogous ways by other allosterically regulated enzymes

Journal ArticleDOI
TL;DR: Reperfusion with hypoxic buffer after 60 min ischaemia did not alter Ca2+ gain, but readmission of oxygen after a period of hypoxic post-ischaemic reperfusion triggered a further gain in Ca2+.

Journal ArticleDOI
TL;DR: Three patients are presented in whom life-threatening cardiac arrhythmias dominated the clinical presentation, and a proposed management scheme is detailed, including intravenously-administered propranolol as the preferred first-line antiarrhythmic agent.
Abstract: The purpose of this review is to highlight the toxicity of chloral hydrate and to review the management of overdoses with chloral hydrate. Three patients are presented in whom life-threatening cardiac arrhythmias dominated the clinical presentation. These arrhythmias were resistant to standard antiarrhythmic therapy. Also, we have reviewed selected features in eight patients who took overdoses of chloral hydrate who were admitted to an intensive care unit between 1981 and 1988. The pharmacology and toxicology of chloral hydrate are discussed with particular reference to the cardiac arrhythmias that are seen with overdosage. A proposed management scheme is detailed, including intravenously-administered propranolol as the preferred first-line antiarrhythmic agent. A case may be made for the discontinuation of the usage of chloral hydrate. (Med JAust 1988; 149: 686-688) C hlo ra l hydrate was synthesized in 1832, and was introduced as an hypnotic agent by Liebreich in 1869.' Liebreich reported acute and chronic poisoning and, in 1890, Borntrager penned an article that detailed the first 44 chloral hydraterelated deaths.' In 1910, Erben labelled chloral hydrate the most dangerous of the hypnotic drugs at a time when heroin and opium were in common use. 1 Chloral hydrate still is used extensively as an hypnotic agent in our community and a mistakenly-held belief exists that it is a safe drug. The incidence of overdose with chloral hydrate is unknown. However, in a survey of consecutive overdoses, Ray et al. showed that chloral hydrate was involved in approximately 1010 of cases that were admitted to a metropolitan teaching-hospital accident and emergency centre, and that most overdoses involved multiple drugs.' In a five-year review of poisonings in Brisbane, White showed that 62010 of fatalities were a result of therapeutic agents. Notable among these were: chloral hydrate, 10010; narcotic drugs, 14010; barbiturate agents, 13010; and tricyclic drugs, II 010. 3 Ethanol and barbiturates are the most common drugs to be coadministered in overdose; both are capable of potentiating the actions of chloral hydrate. This series and review was prompted by a continued lack of awareness in the medical community of the toxicity of chloral hydrate, and of the appropriate management of an overdose with