Non-amphetaminic mechanism of stimulant locomotor effect of modafinil in mice

Previously established dose-response curves indicated that modafinil 20-40 mg/kg i.p. elicited in mice an obvious stimulation of locomotor activity roughly similar to that induced by (+)amphetamine 2-4 mg/kg. The effects of various agents modifying dopamine transmission were compared on the locomotor response to both drugs. The preferential D2 dopamine receptor antagonist haloperidol 37.5-150 micrograms/kg i.p. suppressed the stimulant effect of (+)amphetamine in a dose dependent manner, but not that of modafinil. The D1 dopamine receptor antagonist SCH 23390 (7.5-30 micrograms/kg s.c.) reversed the (+)amphetamine but not the modafinil induced hyperactivity. The tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (200 mg/kg) suppressed the hyperactivity induced by 4 mg/kg dexamphetamine but not that induced by 20 mg/kg modafinil. Associating L-DOPA 150 mg/kg and benserazide 37.5 mg/kg with (+)amphetamine 2 mg/kg resulted in stereotyped climbing behavior, that was not observed with modafinil 10-80 mg/kg. The profound akinesia induced by reserpine (4 mg/kg s.c.; 5 h before testing) was reversed by (+)amphetamine 2 mg/kg but not by modafinil 40 mg/kg. Finally, on synaptosomes prepared from mouse striata preloaded with [3H]dopamine, modafinil 10(-5) M did not increase the spontaneous [3H]dopamine release whereas (+)amphetamine, at the same concentration, doubled it. From all these differences between the two drugs, it is concluded that the mechanism underlying the modafinil induced stimulant locomotor effect differs completely from that of (+)amphetamine.     

Significance of Z-value statistics of Smith-Waterman scores for protein alignments

The Z-value is an attempt to estimate the statistical significance of a Smith-Waterman dynamic alignment score (SW-score) through the use of a Monte-Carlo process. It partly reduces the bias induced by the composition and length of the sequences. This paper is not a theoretical study on the distribution of SW-scores and Z-values. Rather, it presents a statistical analysis of Z-values on large datasets of protein sequences, leading to a law of probability that the experimental Z-values follow. First, we determine the relationships between the computed Z-value, an estimation of its variance and the number of randomizations in the Monte-Carlo process. Then, we illustrate that Z-values are less correlated to sequence lengths than SW-scores. Then we show that pairwise alignments, performed on 'quasi-real' sequences (i.e., randomly shuffled sequences of the same length and amino acid composition as the real ones) lead to Z-value distributions that statistically fit the extreme value distribution, more precisely the Gumbel distribution (global EVD, Extreme Value Distribution). However, for real protein sequences, we observe an over-representation of high Z-values. We determine first a cutoff value which separates these overestimated Z-values from those which follow the global EVD. We then show that the interesting part of the tail of distribution of Z-values can be approximated by another EVD (i.e., an EVD which differs from the global EVD) or by a Pareto law. This has been confirmed for all proteins analysed so far, whether extracted from individual genomes, or from the ensemble of five complete microbial genomes comprising altogether 16956 protein sequences.     

Defensins purified from human granulocytes bind C1q and activate the classical complement pathway like the transmembrane glycoprotein gp41 of HIV-1

BACKGROUND: We previously reported the isolation of aptamer irreversible inhibitors of human neutrophil elastase. We now report on the application of aptamer technology to the field of diagnostic imaging. RESULTS: The enzyme elastase has been reported to bind to the surface of activated neutrophils. Using a fluorescent flow cytometry assay, we showed that an aptamer inhibitor of elastase also binds preferentially to activated neutrophils. We then tested the ability of the aptamer to image inflammation in vivo in a rat reverse passive Arthus reaction model. The aptamer achieved a peak target-to-background (T/B) ratio of 4.3 +/- 0.6 in 2 hours. IgG, which is used clinically to image inflammation, took a longer time to achieve a lower T/B: 3.1 +/- 0.1 at 3 hours. The difference in T/B values is due to the faster clearance of the aptamer signal from the blood pool. CONCLUSIONS: It is feasible to apply aptamer ligands for use in diagnostic imaging, where they may offer significant advantages over monoclonal antibodies and other reagents.     

Assessment of myometrial invasion in endometrial cancer by transvaginal ultrasonography

Transvaginal ultrasound was used in 52 women to characterise endometrial cancer with respect to myometrial invasion according to International Federation of Gynaecologist and Obstetricians (FIGO) recommendations for surgical staging of endometrial cancer. Endometrial cancer was diagnosed on the basis of dilatation and curettage and the degree of invasion was evaluated preoperatively by transvaginal ultrasound. The ultrasound data were compared to macroscopic finding of the uterine specimen and to histopathology. Evaluation with transvaginal sonography was accurate in 46 of 52 cases (accuracy 88%, sensitivity 86%, specificity 90%, positive predictive value 92%, negative predictive value 83%). Cervical tumor extension was correctly diagnosed in seven of ten women in which it was present. Transvaginal ultrasound seems to be a reliable method for assessing tumor invasion. This non-invasive method could be included as an important tool in te establishment of individualised treatment program in case of women with endometrial cancer.     

The Austrian PCRV project with a hot liner — A status report

The analysis of the problem PCRV safety leads to a new vessel concept in which the pressure transmitting insulation with its cooling system is outside the hot linear. A control and adjustment system for vessel wall temperature ensures that, under all working conditions, the liner suffers only elastic compression. Outside the thermal insulation (special concrete) a cold steel barrier is placed, which can be constructed as a second liner, so that leaks are limited and can be detected and evacuated. After preliminary development work in the field of high temperature insulating concrete, prestressed concrete technology and instrumentation at elevated temperature, a large experimental ring has been constructed and tested extensively. As part of an experimental high temperature gas loop a large scale model vessel is being built at the Research Center, Seibersdorf, Austria. Construction is nearly complete and a pressure test is scheduled for early 1975. It will be followed by tests under working conditions of PWRs and later of HTGRs. The reference design of such a PCRV with a hot liner for a 1500 MW(e) pressurized water reactor will be finished at the same time as the model vessel.     

Producing a composite material based on zircon concentrate and nanocrystalline zirconium dioxide

The effects have been examined of adding nanocrystalline zirconium dioxide powder stabilized by yttrium oxide on the production and properties of a composite material based on zircon. It is found that the zirconium dioxide particles at the boundaries of the zircon grains slow the consolidation of the zircon matrix in sintering and zircon grain growth.     

Two-Stage Production of Multilayer Composites Containing a Heat-Resistant Superalloy and an Oxide Ceramic

Russian Engineering Research - The influence of the parameters of spark plasma sintering on the structural evolution within composites consisting of a superalloy, binder, and a zirconium-oxide...     

Hepatosplenic gamma/delta T-cell lymphoma: a report of two cases in immunocompromised patients, associated with isochromosome 7q

Two cases of peripheral T-cell lymphoma, characterized by hepatosplenic presentation and gamma/delta T-cell receptor phenotype on malignant cells, are reported. Little is known about the chromosomal changes in these peculiar lymphomas. We report the cytogenetic analysis of these two patients. Isochromosome 7q and trisomy 8 were observed. These abnormalities were reported previously in five cases of gamma/delta T-cell lymphoma. These two patients had lymphomatous infiltration of the spleen, liver, bone marrow, and (in one case) lymph nodes. These abnormalities occurred in immunocompromised patients (i.e., immunosuppressive therapy for kidney transplantation and chemotherapy for Hodgkin's disease), without Epstein-Barr virus infection stigmata in tumor cells.