Interleukin 2 in the treatment of acute leukemia

Recent immunohistochemical analysis of cell cycle-related proteins such as p27, a cell cycle inhibitory protein, and Ki-67, a proliferation marker, indicated their possible values in predicting the biologic behavior of various human neoplasms. In this study, we performed an immunohistochemical analysis of p27 and Ki-67 in 42 adrenocortical neoplasms (12 adrenocortical carcinomas, 24 adrenocortical adenomas) and 6 normal adrenal glands to evaluate their possible values in diagnosing adrenocortical malignancy and in predicting the biologic behavior of carcinomas. We detected Ki-67 and p27 immunoreactivity in the nuclei of all of our cases, and we observed a significant negative correlation (r = -0.572, P < .001) between the p27 and Ki-67 labeling indexes (LIs). The LIs of p27 and Ki-67 were 61.7+/-2.6 and 0.28+/-0.08 in the normal adrenal cortex and 59.4+/-6.5 and 0.33+/-0.11 in the adenomas, respectively, with no significant differences between the LIs of the adenomas and normal adrenals. The LIs of p27 and Ki-67 in the carcinomas were 48.9+/-7.5 and 630+/-6.21, respectively. The LI of p27 in the carcinomas was significantly lower than that in the adenomas. The LI of Ki-67 in the carcinomas was significantly higher than that in the adenomas (P < .01). Among carcinoma cases, the Ki-67 LI in living cases tended to be lower than that in deceased cases, and the p27 LI in living cases tended to be higher than that in deceased cases, but these differences did not reach statistical significance. These results indicated that decreased p27 protein expression might cause increased cell proliferation in adrenocortical carcinoma cells in combination with other positive and/or negative regulators of the cell cycle. These results also suggested that immunohistochemical analysis of p27 and Ki-67 might be useful in distinguishing between adrenocortical adenoma and carcinoma     

Lipochitin Oligosaccharides Immobilized through Oximes in Glycan Microarrays Bind LysM Proteins

Glycan microarrays have emerged as novel tools to study carbohydrate–protein interactions. Here we describe the preparation of a covalent microarray with lipochitin oligosaccharides and its use in studying proteins containing LysM domains. The glycan microarray was assembled from glycoconjugates that were synthesized by using recently developed bifunctional chemoselective aminooxy reagents without the need for transient carbohydrate protecting groups. We describe for the first time the preparation of a covalent microarray with lipochitin oligosaccharides and its use for studying proteins containing LysM domains. Lipochitin oligosaccharides (also referred to as Nod factors) were isolated from bacterial strains or chemoenzymatically synthesized. The glycan microarray also included peptidoglycan‐related compounds, as well as chitin oligosaccharides of different lengths. In total, 30 ligands were treated with the aminooxy linker molecule. The identity of the glycoconjugates was verified by mass spectrometry, and they were then immobilized on the array. The presence of the glycoconjugates on the array surface was confirmed by use of lectins and human sera (IgG binding). The functionality of our array was tested with a bacterial LysM domain‐containing protein, autolysin p60, which is known to act on the bacterial cell wall peptidoglycan. P60 showed specific binding to Nod factors and to chitin oligosaccharides. Increasing affinity was observed with increasing chitin oligomer length.     

Automated separation for heterogeneous immunoassays

Beside general requirements for modern automated systems, immunoassay automation involves specific requirements as a separation step for heterogeneous immunoassays. Systems are designed according to the solid phase selected: dedicated or open robots for coated tubes and wells, systems nearly similar to chemistry analysers in the case of magnetic particles, and a completely original design for those using porous and film materials.     

Cytokines and malignant hemopathies: leukemias and bone marrow graft

Cytokines are now part of the modern armentarium utilized against malignant blood diseases. The essentially lymphocytic haematopoietic growth factors (G-CSF, GM-CSF, IL-3) reduce the infectious morbidity associated with the deep and prolonged neuropoenia induced by the myelo-ablative conditioning for autologous or allogeneic bone marrow transplantations, and widening their indications is tempting. The reluctance expressed about their use in chemotherapy of acute myeloid leukaemia is abating now that controlled studies have shown that they preserve the complete response rate and shorten the duration of leucopoenia. Moreover, they modify the leukaemia biological response, which makes it possible to increase the cytotoxicity of certain drugs and constitutes a new approach to drug-resistant leukaemias. Immuno-modulating cytokines (interferon alpha, interferon gamma, interleukin-2) act through mechanisms that are still ill-defined: antitumoral activity, modification of biological responses, immunoactivation. Nevertheless, interferon alpha has revolutionized the treatment of hairy cell leukaemia and myeloid leukaemia, with a 70% remission rate. The scarcity of complete responses (10% of hairy cell leukaemias) or cytogenetic responses (20% of chronic myeloid leukaemias) justifies a combined treatment (chemotherapy+immunotherapy?) to improve these patients' cure rate. The anti-leukaemic activity of interleukin-2, observed in patients with refractory relapses, produces 33% of responses, including 10% of complete responses, and it is tempting to test the impact of this immunotherapy on the control of residual leukaemia as adjuvant of complete remission using randomized trials.     

Human cortical responses evoked by dichotically presented tones of different frequencies

In vivo brain microdialysis was used to investigate the influence of lobeline on dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) overflow in the core of the nucleus accumbens of freely-moving rats pretreated with nicotine (0.4 mg x kg(-1), s.c., once per day for 5 days). Locomotion was also recorded. Lobeline, at doses of 0.7, 4.0 and 10.0 mg x kg(-1), i.p., failed to elicit any significant changes in extracellular dopamine or dihydroxyphenylacetic acid levels during the 60 min following its administration and did not stimulate locomotor. The dopamine responses to nicotine (0.4 mg x kg(-1), s.c.), were abolished (P<0.01) if the nicotine challenge was administered 10 min but not 60 min, after lobeline doses of 4.0 and 10.0 mg kg(-1), i.p., but were unaffected following lobeline at the lowest dose tested (0.7 mg x kg(-1), i.p.) at either time. The increase in locomotor activity was significantly attenuated (P<0.01), to a similar extent, when the nicotine was injected 10 min, but not 60 min, after all three doses of lobeline (0.7, 4.0 and 10.0 mg kg(-1), i.p.) when compared with the saline-treated rats. The results suggest that lobeline is a short-acting antagonist of the nicotinic AChRs which mediate the effects of nicotine on mesolimbic dopamine activity and locomotor stimulation.     

Plasmon enhanced solar-to-fuel energy conversion

Future generations of photoelectrodes for solar fuel generation must employ inexpensive, earth-abundant absorber materials in order to provide a large-scale source of clean energy. These materials tend to have poor electrical transport properties and exhibit carrier diffusion lengths which are significantly shorter than the absorption depth of light. As a result, many photoexcited carriers are generated too far from a reactive surface and recombine instead of participating in solar-to-fuel conversion. We demonstrate that plasmonic resonances in metallic nanostructures and multilayer interference effects can be engineered to strongly concentrate sunlight close to the electrode/liquid interface, precisely where the relevant reactions take place. On comparison of spectral features in the enhanced photocurrent spectra to full-field electromagnetic simulations, the contribution of surface plasmon excitations is verified. These results open the door to the optimization of a wide variety of photochemical processes by leveraging the rapid advances in the field of plasmonics.     

Similitude between the NGD function and filter gain behaviours

This paper deals with the similitude between the behaviours of linear filter gain and negative group delay (NGD) function. The transposition method of low‐pass/high‐pass, low‐pass/band‐pass and low‐pass/band‐stop NGD circuits is established. To the best of the author knowledge, it acts as the first paper devoted on the NGD function generalized theory. The introduced transform relationships simplify the synthesis of any NGD circuits from simple elementary low‐pass NGD topologies. Families of innovative NGD topologies are identified. To verify the relevance of the concept proposed, frequency‐ and time‐domain analysis results from realistic proofs of concept demonstrating the feasibility of developed NGD transforms were performed. Thanks to the NGD phenomenon, the possibility of the ultra‐wideband pulse signals propagating in time‐advance is verified. Finally, potential applications of NGD circuits are discussed. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis of n-way active topology for wide-band RF/microwave applications

A simple circuit consisting of a linear differential amplifier IC chip and a few components is described which would provide the over-voltage and current protection for regulated power supplies. The circuit is also capable of providing under-voltage indication and both the over- and under-voltages can be preset by simple potentiometric adjustment.     

Evaluation of the acute, chronic and teratogenic effects of a mixture of eleven pharmaceuticals on the cnidarian, Hydra attenuata

Pharmaceuticals have recently emerged as novel pollutants of potential concern in the aquatic environment where they are commonly introduced as complex mixtures via municipal effluent. In the present experiment, the freshwater cnidarian Hydra attenuata was exposed to a mixture of 11 pharmaceuticals (ibuprofen, naproxen, gemfibrozil, bezafibrate, carbamazepine, sulfapyridine, oxytetracycline, novobiocin, trimethoprim, sulfamethoxazole and caffeine) up to 10 000 times (×) the concentration found in municipal effluent. Hydra regeneration and teratogenicity was measured, having an IC₅₀ of 781× and was found to be non teratogenic with an A/D value of ∼ 1. Toxicity was investigated using both lethal (based on morphology) and sub-lethal (based on morphology, feeding behaviour, hydranth number and attachment) endpoints. The pharmaceutical mixture incurred a significant decrease in morphology at 0.1, 10 and 100× but a significant increase at 1000×. All parameters were significantly reduced at 10 000×. An EC₅₀ of 425× and 65× based on morphology and feeding respectively and a toxicity threshold (TT) of 3.2× were calculated. When compared to the toxicity of each pharmaceutical exposed individually as previously reported [Quinn B, Gagné F, Blaise C. An investigation into the acute and chronic toxicity of eleven pharmaceuticals found in wastewater effluent on the cnidarian, H. attenuata. Sci Total Environ 2008a; 389: 306-314], the compounds in the mixture were present at concentrations 2 to 3 orders of magnitude lower for the equivalent toxicity (EC₅₀ and TT). These results indicate that pharmaceuticals act additively in a mixture, having sub-lethal effects at environmentally relevant (µg/L-ng/L) concentrations and that their combined concentrations could potentially prove significantly ecotoxic to Hydra and possibly to other aquatic taxa.