Provision of 4-1BB ligand enhances effector and memory CTL responses generated by immunization with dendritic cells expressing a human tumor-associated antigen

Up-regulation of receptor-ligand pairs during interaction of an MHC-presented epitope on dendritic cells (DCs) with cognate TCR may amplify, sustain, and drive diversity in the ensuing T cell immune response. Members of the TNF ligand superfamily and the TNFR superfamily contribute to this costimulatory molecule signaling. In this study, we used replication deficient adenoviruses to introduce a model tumor-associated Ag (the E7 oncoprotein of human papillomavirus 16) and the T cell costimulatory molecule 4-IBBL into murine DCs, and monitored the ability of these recombinant DO to elicit E7-directed T cell responses following immunization. Splenocytes from mice immunized with DCs expressing E7 alone elicited E7-directed effector and memory CTL responses. Coexpression of 4-1BBL in these E7-expressing DO increased effector and memory CTL responses when they were used for immunization. 4-1BBL expression up-regulated CD80 and CD86 second signaling molecules in DO. We also report an additive effect of 4-IBBL and receptor activator of NF-kappaB/receptor activator of NF-kappaB ligand coexpression in E7-transduced DC inummogens on E7-directed effector and memory CTL responses and on MHC class II and CD80/86 expression in DCs. Additionally, expression of 4-1BBL in E7-transduced DCs reduced nonspecific T cell activation characteristic of adenovirus vector-associated immunization. The results have generic implications for improved or tumor Ag-expressing DC vaccines by incorporation of exogenous 4-1BBL. There are also specific implications for an improved DC-based vaccine for human papillomavirus 16-associated cervical carcinoma.

Ventilatory responses of healthy subjects to intravenous combinations of morphine and oxycodone under imposed hypercapnic and hypoxaemic conditions

Aims Previous isobolographic analysis revealed that coadministration of morphine and oxycodone produces synergistic antinociception in laboratory rodents. As both opioids can produce ventilatory depression, this study was designed to determine whether their ventilatory effects were synergistic when coadministered to healthy human subjects. Methods A placebo-controlled, randomized, crossover study was performed in 12 male volunteers. Ventilatory responses to hypoxaemia and hypercapnia were determined from 1-h intravenous infusions of saline ('placebo'), 15 mg morphine sulphate (M), 15 mg oxycodone hydrochloride (O), and their combination in the dose ratios of 1 : 2, 1 : 1, 2 : 1. Drug and metabolite concentrations in serial peripheral venous blood samples were measured by high-performance liquid chromatography-MS/MS. Results 'Placebo' treatment was without significant ventilatory effects. There were no systematic differences between active drug treatments on either the slopes or intercepts of the hypoxaemic and hypercapnia ventilation responses. During drug treatment, the mean minute ventilation at PETCO2 = 55 mmHg (V-E55) decreased to 74% of the subjects' before treatment values (95% confidence interval 62, 87), 68% (57, 80), 69% (59, 79), 68% (63, 73), and 61% (52, 69) for M15, M10/O5, M7.5/O7.5, M5/O10 and O15, respectively. Recovery was more prolonged with increasing oxycodone doses, corresponding to its greater potency and lower clearance compared with morphine. Conclusions Although adverse ventilatory effects of these drugs were found as expected, no unexpected or disproportionate effects of any of the morphine and oxycodone treatments were found that might impede their use in combination for pain management.

Comparison between Eysenck's and Gray's models of personality in the prediction of motivational work criteria

Impulsivity based on Gray's [Gray, J. A. (1982) The neuropsychology of anxiety: an enquiry into the function of the septo-hippocampal system. New York: Oxford University Press: (1991). The neurophysiology of temperament. In J. Strelau & A. Angleitner. Explorations in temperament: international perspectives on theory and measurement. London. Plenum Press]. physiological model of personality was hypothesised to be more predictive of goal oriented criteria within the workplace than scales derived From Eysenck's [Eysenck. H.J. (1967). The biological basis of personality. Springfield, IL: Charles C. Thompson.] physiological model of personality. Results confirmed the hypothesis and also showed that Gray's scale of Impulsivity was generally a better predictor than attributional style and interest in money. Results were interpreted as providing support for Gray's Behavioural Activation System which moderates response to reward. (C) 2001 Elsevier Science Ltd. All rights reserved.

Use of a thermodilution catheter to measure core body temperature, central venous pressure and cardiac output during anaesthesia and surgery in the dog

The use of thermodilution and other methods of monitoring in dogs during surgery and critical care was evaluated. Six Greyhounds were anaesthetised and then instrumented by placing a thermodilution catheter into the pulmonary artery via the jugular vein. A catheter in the dorsal pedal artery also permitted direct measurement of arterial pressures. Core body temperature (degreesC) and central venous pressure (mmHg) were measured, while cardiac output (mL/min/kg) and mean arterial pressure (mmHg) were calculated. A mid-line surgical incision was performed and the physiological parameters were monitored for a total of two hours. All physiological parameters generally declined, although significant increases (P<0.05) were noted for cardiac output following surgical incision. Central venous pressure was maintained at approximately 0mmHg by controlling an infusion of sterile saline. Core body temperature decreased from 37.1+/-0.6degreesC (once instrumented) to 36.6+/-0.60degreesC (at the end of the study), despite warming using heating pads. Physiological parameters indicative of patient viability will generally decline during surgery without intervention. This study describes an approach that can be undertaken in veterinary hospitals to accurately monitor vital signs in surgical and critical care patients.

Adaptive responses of wild mungbean (Vigna radiata ssp sublobata) to photo-thermal environment. I. Phenology

The phenology of 11 diverse accessions of wild mungbean was observed under natural and artificial photoperiod - temperature conditions, in order to examine whether genotypic differences might be attributed to adaptive responses to photo-thermal conditions. There was large variation in phenological response among accessions and across environments, much of which was due to differences in the duration of the pre-flowering phase. Accessions that flowered earlier tended to flower for longer, apart from 2 earlier flowering, inland Australian lines that were also earlier maturing. The patterns of response in time from sowing to flowering over environment were consistent with quantitative short-day photoperiodic adaptation, a conclusion supported by the effects of artificial day-length extension and by 'goodness of fit' of the observed responses to standard models relating rate of development to photoperiod and temperature. The fitted models indicated that rate of development towards flowering was hastened by warmer temperatures, and delayed by longer day lengths, with differential sensitivity between accessions to both factors. The models also suggested that photoperiod was more important for accessions collected closer to the equator, which were generally later flowering as a consequence. Conversely, temperature was relatively more important in lines from higher latitudes. Modelling also suggested that the period from first flowering to maturity was sensitive to photoperiod and temperature. Again, longer days appeared to prolong growth and delay maturity. However, cooler temperatures accelerated rather than slowed maturity, by suppressing further vegetative growth. The variation observed indicated that there is considerable scope for using the wild population to broaden the adaptation of cultivated mungbean. In particular, the unusual response of a late-flowering, photoperiod-insensitive accession warrants further study to establish whether the wild population contains a unique 'long juvenile' trait analogous to that being used for improving phenological adaptation in soybean.

Male-by-female interactions influence fertilization success and mediate the benefits of polyandry in the sea urchin Heliocidaris erythrogramma

Numerous studies have reported that females benefit from mating with multiple males (polyandry) by minimizing the probability of fertilization by genetically incompatible sperm. Few, however, have directly attributed variation in female reproductive success to the fertilizing capacity of sperm. In this study we report on two experiments that investigated the benefits of polyandry and the interacting effects of males and females at fertilization in the free-spawning Australian sea urchin Heliocidaris erythrogramma. In the first experiment we used a paired (split clutch) experimental design and compared fertilization rates within female egg clutches under polyandry (eggs exposed to the sperm from two males simultaneously) and monandry (eggs from the same female exposed to sperm from each of the same two males separately). Our analysis revealed a significant fertilization benefit of polyandry and strong interacting effects of males and females at fertilization. Further analysis of these data strongly suggested that the higher rates of fertilization in the polyandry treatment were due to an overrepresentation of fertilizations due to the most compatible male. To further explore the interacting effects of males and females at fertilization we performed a second factorial experiment in which four mates were crossed with two females (in all eight combinations). In addition to confirming that fertilization success is influenced by male X female interactions, this latter experiment revealed that both sexes contributed significant variance to the observed patterns of fertilization. Taken together, these findings highlight the importance of male X female interactions at fertilization and suggest that polyandry will enable females to reduce the cost of fertilization by incompatible gametes.

Use of an Arrhenius model to predict rheological behaviour in some Australian honeys

Rheological properties of nine unprocessed unifloral Australian honeys (bloodwood, blue top iron bark, gum top, heath, narrow leafed iron bark, stringy bark, tea tree yapunyah and yellow box) were analysed over a range of temperatures (1-40 degreesC) The temperature effect on the viscosity follow ed an Arrhenius-type relationship and ail honey varieties exhibited Newtonian behaviour. if the Arrhenius equation constants (mu (0) and E-a) for a particular honey are known, the Arrhenius model can be used to calculate the viscosity of these honeys at specific temperatures, negating the need for tedious viscosity determination. (C) 2000 Academic Press.