24 resultados para Donor Lymphocyte Infusions

em Deakin Research Online - Australia


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In the matter of Re Patrick, Guest J of the Family Court of Australia held that a sperm donor, known to the lesbian mother of the child, had a right under Australian law to regular contact with the child to the extent that this was in the child's best interests. However, his Honour also held that due to the way in which particular provisions of the Family Law Act 1975 (Cth) are drafted, a sperm donor cannot be regarded as the "parent" of the child, and accordingly called for legislative reform to recognise the rights of known sperm donors wanting involvement with the child. In this article, the authors will first explore the facts and decision in Re Patrick, and then outline a proposal to amend the Family Law Act 1975 so that sperm donors can apply for an order to be a 'parent' under the Act.

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This paper examines the potential for using service blueprinting to assist non-profit organizations in better managing donor exchanges. In many cases organizations are unclear of donors' expectations in relation to the overall giving experience. Failure to deliver on expectations could potentially result in donor 'dissatisfaction', which in turn may result in reductions of future donations to these organizations. This article begins with a review of blueprinting and the benefits of using such as tool as to assist in understanding the donation exchange. Zeithaml and Bitner's (2000) steps in building a blueprint are explained in the context of non-profit-donor exchanges. An example of a hypothetical blueprint provided to highlight the complexity and divergence encountered in such exchanges and used to identify potential problems associated with the various aspects of the donation experience. Finally, implications for managing giving and suggestions for future research are offered.

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A class of new conjugated copolymers containing a donor (thiophene)−acceptor (2-pyran-4-ylidene-malononitrile) was synthesized via Stille coupling polymerization. The resulting copolymers were characterized by 1H NMR, elemental analysis, GPC, TGA, and DSC. UV−vis spectra indicated that the increase in the content of the thiophene units increased the interaction between the polymer main chains to cause a red-shift in the optical absorbance. Cyclic voltammetry was used to estimate the energy levels of the lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO) and the band gap (Eg) of the copolymers. The basic electronic structures of the copolymers were also studied by DFT calculations with the GGA/B3LYP function. Both the experimental and the calculated results indicated an increase in the HOMO energy level with increasing the content of thiophene units, whereas the corresponding change in the LUMO energy level was much smaller. Polymer photovoltaic cells of a bulk heterojunction were fabricated with the structure of ITO/PEDOT/PSS (30 nm)/copolymer−PCBM blend (70 nm)/Ca (8 nm)/Al (140 nm). It was found that the open-circuit voltage (Voc) increased (up to 0.93 V) with a decrease in the content of thiophene units. Although the observed power convention efficiency is still relatively low (up to 0.9%), the corresponding low fill factor (0.29) indicates considerable room for further improvement in the device performance. These results provided a novel concept for developing high Voc photovoltaic cells based on donor-π-acceptor conjugated copolymers by adjusting the donor/acceptor ratio.

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Hev b 6.01 is a major allergen of natural rubber latex with sensitization of 70–86% of latex glove-allergic subjects. Recently, we mapped the immunodominant T cell sites of Hev b 6.01 to the highly IgE-reactive hevein (Hev b 6.02) domain. Hev b 6.01 contains 14 cysteine residues with multiple disulphide bridges stabilizing tertiary conformation. With the goal of a standardized specific immunotherapy we developed hypoallergenic Hev b 6.01 mutants by site-directed mutagenesis of selected cysteine residues (3, 12, 17, and 41) within the Hev b 6.02 domain. Peptides corresponding to the Hev b 6.02 domain of two of the mutants were also synthesized. These mutants and peptide variants showed markedly decreased or ablated latex-allergic patient serum IgE binding by immunoblotting and ELISA. Basophil activation testing confirmed markedly decreased activation with successive cysteine substitutions of the mutants and complete abrogation with the Hev b 6.02 (Cys 3, 12, 17, 41 Ala) peptide. Retention of T cell reactivity is crucial for effective specific immunotherapy and all mutants and peptide variants maintained their latex-specific T cell reactivity. The ablated allergenicity but retained T cell reactivity of the Hev b 6.02 (Cys 3, 12, 17, 41 Ala) peptide suggests this peptide is a suitable candidate for inclusion in a latex immunotherapy preparation.

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Nitric oxide (NO) has been implicated as an important signaling molecule in the insulin-independent, contraction-mediated glucose uptake pathway and may represent a novel strategy for blood glucose control in patients with type 2 diabetes (T2DM). The current study sought to determine whether the NO donor, sodium nitroprusside (SNP) increases glucose uptake in primary human skeletal muscle cells (HSkMC) derived from both healthy individuals and patients with T2DM. Vastus lateralis muscle cell cultures were derived from seven males with T2DM (aged 54 ± 2 years, BMI 31.7 ± 1.2 kg/m2, fasting plasma glucose 9.52 ± 0.80 mmol/L) and eight healthy individuals (aged 46 ± 2 years, BMI 27.1 ± 1.5 kg/m2, fasting plasma glucose 4.69 ± 0.12 mmol/L). Cultures were treated with both therapeutic (0.2 and 2 μM) and supratherapeutic (3, 10 and 30 mM) concentrations of SNP. An additional NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) was also examined at a concentration of 50 μM. Glucose uptake was significantly increased following both 30 and 60 min incubations with the supratherapeutic SNP treatments (P = 0.03) but not the therapeutic SNP doses (P = 0.60) or SNAP (P = 0.54). There was no difference in the response between the healthy and T2DM cell lines with any treatment or dose. The current study demonstrates that glucose uptake is elevated by supratherapeutic, but not therapeutic doses of SNP in human primary skeletal muscle cells derived from both healthy volunteers and patients with T2D. These data confirm that nitric oxide donors have potential therapeutic utility to increase glucose uptake in humans, but that SNP only achieves this in supratherapeutic doses. Further study to delineate mechanisms and the therapeutic window is warranted.

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In 1991, the World Health Assembly approved a set of Guiding Principles which emphasize voluntary donation, non-commercialization and a preference for cadavers over living donors” (World Health Organization). The objective of this paper is to identify the factors that affect the ratio of cadaveric transplants to all transplants. This paper first provides informational background on problems surrounding kidney transplants and then uses a theoretical framework which employs standard economic assumptions but incorporates a setup where the persons needing kidneys can obtain it from their compatible relatives or purchase it from individuals who are willing to sell one of their kidneys. The methods of economic theoretical analyses are used where following definitions and assumptions some conclusions are drawn. This paper finds that factors such as inequality, rule of law and religion have significant effect on the ratio of cadaveric transplants to all transplants. The paper concludes that improvement in equality and in rule of law will increase the use of cadaveric kidney transplants. In addition, fighting religious beliefs against cadaveric kidney transplants too will lead to a higher ratio of cadaveric transplants to all transplants.

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Extracellular adenosine 5′-triphosphate (ATP) is an agonist for the P2Z receptor of human leukaemic lymphocytes and opens a Ca 2+-selective ion channel, which also conducts Ba2+, Sr2+ and the small fluorescent dye, ethidium+. A wide range of receptor agonists, many of which raise cytosolic [Ca2+] activate phospholipase D (PLD). In the present study, it was shown that both ATP and 3′-O-(4-benzoylbenzoyl)-ATP (BzATP) stimulated PLD activity in a concentration-dependent manner, and the inhibitory effects of suramin, oxidised ATP, extracellular Na+ and Mg2+ suggested that the effect of these agonists is mediated by P2Z receptors. The role of divalent cations in ATP-stimulated PLD activity was investigated. Several agonists (eg ATP, thapsigargin, ionomycin) stimulated a rise in cytosolic [Ca2+] in human lymphocytes, but only ATP and ionomycin stimulated PLD activity. When Ca2+ influx was prevented by EGTA, the majority of ATP-stimulated and all of ionomycin-stimulated PLD activity was inhibited. Preloading cells with the Ca2+ chelator, BAPTA, reduced cytosolic [Ca2+] and, paradoxically, ATP-stimulated PLD activity was potentiated. ATP-stimulated PLD activity was supported by both Ba2+ and Sr2+ when they were substituted for extracellular Ca2+. Furthermore, both ATP-stimulated PLD activity and ATP-stimulated 133Ba2+ influx showed a linear dependence on extracellular [Ba2+]. Thus it was concluded that ATP stimulated PLD activity in direct proportion to the influx of divalent cations through the P2Z ion channel and this PLD activity was insensitive to changes in bulk cytosolic [Ca2+]. The calmodulin (Ca2+/CaM) inhibitor, trifluoperazine (TFP) inhibited ionomycin- and ATP-stimulated PLD activity and ATP-stimulated apoptosis, but had no effect on PLD activity already activated by ATP. However, TFP inhibited ATP-stimulated Ca2+, Ba2+ and ethidium+ fluxes, at concentrations below those which inhibit Ca2+/CaM, suggesting that TFP inhibits the P2Z receptor. Similarly, the isoquinolinesulphonamide, KN-62, a selective inhibitor of Ca2+/CaM-dependent protein kinase II (CaMKII), also prevented ATP-stimulated apoptosis, but had no effect on pre-activated PLD. In addition, KN-62, and an analogue, KN-04, which has no effect on CaMKII, potently inhibited ATP-stimulated Ba2+ influx (IC50 12.7 ± 1.5 and 17.3 ± 2.7 nM, respectively), ATP-stimulated ethidium+ uptake (IC50 13.1 ± 2.6 and 37.2 ± 8.9 nM, respectively), ATP-stimulated phospholipase D activity (50% inhibition 5.9 ± 1.2 and 9.7 ± 2.8 nM, respectively) and ATP-induced shedding of the surface adhesion molecule, L-selectin (IC50 31.5 ± 4.5 and 78.7 ± 10.8 nM, respectively). They did not inhibit phorbol ester- or ionomycin-stimulated PLD activity or phorbol ester-induced L-selectin shedding. Neither KN-62 nor KN-04 (both 500 nM) have any effect on UTP-stimulated Ca2+ transients in fura-2-loaded human neutrophils, a response which is mediated by the P2Y2 receptor, neither did they inhibit ATP-stimulated contractile responses mediated by the P2X1 receptor of guinea pig urinary bladder. Thus, KN-62 and KN-04 are almost equipotent as P2Z inhibitors with IC50s in the nanomolar, indicating that their actions cannot be due to CaMKII inhibition, but rather that they are potent and direct inhibitors of the P2Z receptor. Extracellular ATP-induced shedding of L-selectin from lymphocytes into the medium is a Ca2+-independent response. L-selectin is either cleaved by a metalloproteinase or a PLD with specificity for glycosylphosphatidylinositol (GPI). The novel hydroxamic acid-based zinc chelator, Ro-31-9790 blocks ATP-induced L-selectin shedding, but was without effect on ATP-induced Ba2+ influx or ATP-stimulated PLD activity. Furthermore, another zinc chelator, 1,10-phenanthroline, an inhibitor of a GPI-PLD, potentiated rather than inhibited ATP-stimulated PLD activity, suggesting that ATP-induced L-selectin shedding and ATP-stimulated PLD activity are independent of each other. Although extracellular ATP is the natural ligand for the lymphocyte P2Z receptor, it is less potent than BzATP in stimulating Ba2+ influx. Concentration-response curves for BzATP- and ATP-stimulated ethidium+ influx gave EC50s 15.4 ± 1.4 µM and 85.6 ± 8.8 µM, respectively. The maximal response to ATP was only 69.8 ± 1.9% of that for BzATP. Hill coefficients were 3.17 ± 0.24 and 2.09 ± 0.45 for BzATP and ATP respectively, suggesting greater positive cooperativity for BzATP than for ATP in opening the P2Z-operated ion channel. A rank order of agonist potency of BzATP > ATP = 2MeSATP > ATPγS was observed for agonist-stimulated ethidium+ influx, while maximal influxes followed a rank order of BzATP > ATP > 2MeSATP > ATPγS. When ATP (300 -1000 µM) was added simultaneously with 30 µM BzATP (EC90), it reduced both ethidium+ and Ba2+ fluxes by 30 - 40% relative to values observed with BzATP alone. KN-62, previously shown to be a specific inhibitor of the lymphocyte P2Z receptor, was a less potent antagonist of BzATP-induced fluxes than ATP, when maximal concentrations of both agonists (50 and 500 µM respectively) were used. However, when BzATP (18 µM) was used at a concentration equiactive with a maximally effective ATP concentration, KN-62 showed the same inhibitory potency for both agonists. The ecto-ATPase antagonist, ARL-67156, inhibited both ATP- and BzATP-stimulated Ba2+ influx, suggesting that the lower efficacy of ATP compared with BzATP was not due to preferential hydrolysis of ATP. Thus, the natural ligand, ATP, is a partial agonist for the P2Z receptor while BzATP is a full agonist. Moreover the competitive studies show that only a single class of P2-receptor (P2Z class) is expressed on human leukaemic lymphocytes. Both ATP- and BzATP-stimulated PLD activity were significantly inhibited (P < 0.05) when cells were suspended in iso-osmotic choline Cl medium. Choline+ was found to be a permeant for the P2Z ion channel, since ATP induced a large uptake of [14C]choline+ (60 to 150 µmol/ml intracellular water) during a 5 min incubation, which remained in the cells for several hours, and ATP was used to load cells with these levels of choline+. Intracellular choline+ inhibited ATP-, BzATP-, PMA- and ionomycin-stimulated PLD activity. Brief exposure of lymphocytes to ATP increased the subsequent basal rate of ethidium+ uptake, and this was prevented by intracellular choline+. It is proposed that P2Z-mediated Ca2+ influx in lymphocytes activates PLD leading to significantly changes of the phospholipid composition of the plasma membrane, which subsequently produces a permeability lesion, which in turn contributes to cell death.

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The study, carried out within an infertility support group, concern disclosure of donor conception and its possible effects upon our constructions of conception, kinship and identity. It also examines perceptions of rights, information and its access or denial, knowledge/power, secrecy and the medicalization of reproduction.

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This paper reports an empirical study of the factors affecting burden sharing among OECD's 22 DAC members in 'bankrolling' the multilateral aid agencies. Annual data over 1970–2000, pooled across the donor countries, form the basis for the empirical estimation of each donor's share in the ODA aid receipts for each multilateral agency. Our findings suggest the existence of reverse exploitation, i.e., the financial burden of the agencies is disproportionally carried by the smaller donors. The study also finds that factors such as inherent donor generosity, donor concern for domestic egalitarianism, and the extent to which donors are pro-poor in their bilateral aid policies have an impact on their readiness to support multilateral agencies financially. Size of the donor government and its budgetary balance positively influence burden sharing of contributions to other multilateral agencies. But neither the phase of economic cycle nor the rate of economic growth affects the burden-sharing responsibility of donors. It was also observed that contributions by EU members to the EC do not appear to crowd-out their contributions to other multilateral aid agencies and that right-wing donor governments are generally more parsimonious with regard to financial assistance to multilateral aid agencies. The preferred alternative, particularly among EU member countries, appears to be the EC.

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1. The renal haemodynamic and glomerular filtration rate (G.F.R.) responses to intravenous and intrarenal infusions of noradrenaline were studied in conscious dogs, either with or without prior blockade of angiotensin II formation with teprotide.

2. Infusion noradrenaline by either route resulted in dose-related rises in plasma renin activity.

3. Pretreatment with teprotide reduced the rise in mean arterial pressure and abolished the rise in G.F.R. seen during intravenous infusions of noradrenaline (0.1, 0.2 and 0.4 microgram/kg . min). Noradrenaline also reduced filtration fraction more after teprotide pretreatment.

4. Renal blood flow rose and renal vascular resistance fell in response to I.V. noradrenaline infusions. This renal vasodilatation was unaffected by pretreatment of the dogs with teprotide, indomethacin or DL-propranolol. However after pentolinium pretreatment, I.V. noradrenaline infusion caused a dose-related renal vasoconstriction.

5. Infusion of noradrenaline into the renal artery (0.02, 0.05 and 0.1 microgram/kg . min) resulted in rises in mean arterial pressure and G.F.R. which were abolished by teprotide pretreatment. Filtration fraction rose when noradrenaline was administered alone but fell when it was infused after teprotide treatment.

6. Thus angiotensin II formed as the result of increased renin release acted to maintain G.F.R. and filtration fraction during noradrenaline infusion. In addition, I.V. noradrenaline infusions in conscious dogs caused reflex vasodilatation of the renal vasculature.

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In the February 2011 report on its inquiry into the past and present practices of donor conception in Australia, the Australian Senate Legal and Constitutional Affairs References Committee called for the introduction of legislation to regulate donor conception in all jurisdictions that do not have it in place "as a matter of priority". It further called for the establishment, "as a matter of priority", of a national register of donors to enable donor-conceived individuals to access identifying information about their donor. The Senate Committee left open the question as to whether the legislation and central register should have retrospective effect. This article focuses upon that question. It shows that arguments concerning the privacy, confidentiality and anonymity of some donors who may wish to remain anonymous are outweighed by the manifest injustice faced by donor-conceived individuals who are denied access to such information, as well as their families and donors who wish to exchange this information.