Activation of expression of p15, p73 and E-cadherin in leukemic cells by different concentrations of 5-aza-2'-deoxycytidine (Decitabine).

Background: Inactivation of genes that suppress neoplasia by aberrant DNA methylation is a key event that occurs during the development of leukemia. The inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5AZA), which can re-activate these genes, is under clinical investigation for therapy of leukemia. The objective of this study was to determine the concentrations of 5AZA that will re-activate target silent genes in human leukemic cell lines.

A fission yeast strain expressing human CDC25A phosphatase: a tool for selectivity studies of pharmacological inhibitors of CDC25.

Fission yeast is a simple eukaryotic model organism in which many aspects of cell cycle control can be explored. We examined by homologous recombination whether the human CDC25A phosphatase could substitute for the function of the fission yeast Cdc25. We first show: (a).

Regulation of glycolysis in Kluyveromyces lactis: role of KlGCR1 and KlGCR2 in glucose uptake and catabolism.

In Kluyveromyces lactis, the casein kinase I (Rag8p) regulates the transcription of glycolytic genes and the expression of the low-affinity glucose transporter gene RAG1. This control involves the transcription factor Sck1p, a homologue of Sgc1p of Saccharomyces cerevisiae. SGC1 is known to interact genetically with ScGCR1 and ScGCR2, which code for regulators of glycolytic gene expression.

In vitro infection of human primary adipose cells with HIV-1: a reassessment.

We reassessed the infection ability of human primary preadipocytes. The use of X4, R5 or VSV-G-pseudotyped viral particles indicated that viral entry is the limiting step. However, transfection with HIV-1 receptors restored efficient infection.

Reduction of ischemic brain damage by nitrous oxide and xenon.

Neuronal death after ischemia-induced brain damage depends largely upon the activation of the N-methyl-D-aspartate (NMDA) excitatory glutamate receptor that is a target for many putative neuroprotective agents. Whereas the NMDA receptors mediate ischemic brain damage, blocking them is deleterious in humans. Here, the authors investigated whether nitrous oxide or xenon, which are gaseous anesthetics with a remarkably safe clinical profile that have been recently demonstrated as effective inhibitors of the NMDA receptor, may reduce the following: (1) ischemia-induced brain damage in vivo, when given after occlusion of the middle cerebral artery (MCAO), a condition needed to make these potentially neuroprotective agents therapeutically valuable; or (2) NMDA-induced Ca2+ influx in cortical cell cultures, a major critical event involved in excitotoxic neuronal death.

Isolation of a glycoprotein E-deleted bovine herpesvirus type 1 strain in the field.

During a field trial to evaluate the efficacy of repeated vaccinations with bovine herpesvirus type 1 (BHV-1) marker vaccines, a glycoprotein E (gE)-negative BHV-1 strain was isolated from the nasal secretions of two cows, eight months after vaccination with a gE-negative live-attenuated vaccine, initially given intranasally, then intramuscularly. The strain isolated was characterised using immunofluorescence, restriction analysis and PCR. All the techniques used identified the isolated virus as a gE-negative BHV-1 phenotypically and genotypically identical to the Za strain used as a control.

Social recognition task in the rat.

Among the numerous tasks designed for assessing distinct memory processes, the social recognition task in the rat offers the opportunity to evaluate a form of short-term working memory in the domain of social cognition, and its modification by pharmacological agents or physiopathological states, such as aging. Social cognition in humans is obviously of great importance and its deficits, e.g.

Verdazyl radicals as oligopyridine mimics: structures and magnetic properties of M(II) complexes of 1,5-dimethyl-3-(2,2'-bipyridin-6-yl)-6-oxoverdazyl (M = Mn, Ni, Cu, Zn).

The verdazyl radical 1,5-dimethyl-3-(2,2'-bipyridin-6-yl)-6-oxoverdazyl (3) was prepared, and its homoleptic metal complexes M(3)(2)(2+).2X(-) (5, M = Mn(II); 6, M = Ni(II); 7, M = Cu(II); 8, M = Zn(II); X = ClO(4), PF(6)) were characterized by single-crystal X-ray diffraction and variable-temperature magnetic susceptibility measurements. Relevant crystallographic parameters are as follows: 5, monoclinic space group Pna2(1), a = 18.

Distribution of STI-571 to the brain is limited by P-glycoprotein-mediated efflux.

The adequate distribution of STI-571 (Gleevec) to the central nervous system (CNS) is critical for its effective use in CNS tumors. P-glycoprotein-mediated efflux in the blood-brain barrier may play a role in the CNS delivery of this drug. Whether STI-571 is a substrate of P-glycoprotein was determined by examining the directional flux of [(14)C]STI-571 in parental and MDR1-transfected Madin-Darby canine kidney (MDCK) II epithelial cell monolayers.

A new material for selective removal of nitrogen compounds from gasoils towards more efficient HDS processes.

A selective removal of nitrogen compounds from gasoils is proposed, using a recyclable sorbent capable of forming charge-transfer complexes; the selective elimination of nitrogen compounds strongly improves the hydrodesulfurization (HDS) of denitrogenated feed.

Effects of cannabinoid receptor ligands on psychosis-relevant behavior models in the rat.

Rationale: Marijuana is known to have psychotropic effects in humans. In this study, we used rat models of sensorimotor gating, hyperactivity and stereotypy to explore whether CB(1) receptor stimulation or blockade induces behavioral changes consistent with psychotomimetic or antipsychotic agents, respectively.

Objectives: We determined whether (a) the cannabinoid agonist CP 55940 decreased pre-pulse inhibition (PPI) as might be expected from a psychotomimetic agent, and (b) the selective CB(1) receptor antagonist, SR 141716A, had any effect on PPI on its own or following disruptions by psychotomimetic agents.

The Ccr4-not complex and yTAF1 (yTaf(II)130p/yTaf(II)145p) show physical and functional interactions.

The Saccharomyces cerevisiae Ccr4-Not complex is a global regulator of transcription that is thought to regulate TATA binding protein (TBP) function at certain promoters specifically. In this paper, we show interactions between the essential domain of Not1p, which interacts with Not4p and Not5p, and the N-terminal domain of yTAF1. We isolated a temperature-sensitive nonsense allele of TAF1, taf1-4, which is synthetically lethal at the permissive temperature when combined with not4 and not5 mutants and which produces high levels of a C-terminally truncated yTAF1 derivative.

The cuff leak test to predict failure of tracheal extubation for laryngeal edema.

Objective: Laryngeal edema secondary to endotracheal intubation may require early re-intubation. Prior to extubation the absence of leak around an endotracheal tube may predict laryngeal edema after extubation. We evaluated the usefulness of a quantitative assessment of such a leak to identify the patients who will require early re-intubation for laryngeal edema.

Synthesis and coordination chemistry of a water-soluble verdazyl radical. structures and magnetic properties of M(H2O)2(vdCO2)(2).2H2O (M = Co, Ni; vdCO2 = 1,5-dimethyl-6-oxo-verdazyl-3-carboxylate).

The synthesis of a verdazyl radical with a carboxylate substituent renders the radical highly soluble in water, thereby permitting the aqueous synthesis of Ni(II) and Co(II) verdazyl complexes which have been structurally and magnetically characterized.

New perspectives in CNS safety pharmacology.

International requirements for central nervous system (CNS) safety pharmacology are reviewed. Procedures for initial CNS safety screening (core battery studies) can be conducted from the beginning of the drug discovery process, but at latest before first studies in man. They should include assessment of general behaviour, locomotor activity and motor coordination, but can also include studies of pain sensitivity, convulsive threshold and interaction with hypnotics.

Polymer-supported catalysts: enantioselective hydrogenation and hydrogen transfer reduction.

Different types of heterogenized catalysts were involved in asymmetric reactions. Hydrogen transfer reduction was performed with amino alcohols derived from poly((S)-(GMA-co-EGDMA or DVB)) and hydrogenation with BINAP grafted onto PEG or copolymerized with isocyanates as ligands. Attempts of catalysts recycling are reported.

Regulation of glycolysis by casein kinase I (Rag8p) in Kluyveromyces lactis involves a DNA-binding protein, Sck1p, a homologue of Sgc1p of Saccharomyces cerevisiae.

The casein kinase I (Rag8p) of Kluyveromyces lactis has previously been shown to regulate the transcription of the low-affinity glucose transporter gene RAG1. To study this regulation, we have isolated multicopy suppressors of the rag8 mutation. One of them, SCK1 (suppressor of casein kinase), was characterised.

Data from amplified fragment length polymorphism (AFLP) markers show indication of size homoplasy and of a relationship between degree of homoplasy and fragment size.

We investigate the distribution of sizes of fragments obtained from the amplified fragment length polymorphism (AFLP) marker technique. We find that empirical distributions obtained in two plant species, Phaseolus lunatus and Lolium perenne, are consistent with the expected distributions obtained from analytical theory and from numerical simulations. Our results indicate that the size distribution is strongly asymmetrical, with a much higher proportion of small than large fragments, that it is not influenced by the number of selective nucleotides nor by genome size but that it may vary with genome-wide GC-content, with a higher proportion of small fragments in cases of lower GC-content when considering the standard AFLP protocol with the enzyme MseI.

Selective cytotoxic lesions of the retrohippocampal region produce a mild deficit in social recognition memory.

Although a number of studies have implicated the hippocampal formation in social recognition memory in the rat, a recent study in this laboratory has demonstrated that selective cytotoxic lesions, confined to the hippocampus proper (encompassing the four CA subfields and the dentate gyrus), are without effect on this behaviour. This finding suggests that the hippocampus proper does not subserve social recognition memory in the rat, but does not preclude the possibility that other areas of the hippocampal formation, such as the entorhinal cortex or subiculum, could support this form of learning. The present study addressed this issue by examining the effects of selective cytotoxic retrohippocampal (RHR) lesions (including both the entorhinal cortex and subiculum) on social recognition memory in the rat.

Induction of protective immunity to bovine herpesvirus type 1 in cattle by intranasal administration of replication-defective human adenovirus type 5 expressing glycoprotein gC or gD.

Replication-defective human adenoviruses type 5 (HAd5) expressing the bovine herpesvirus type 1 (BHV-1) glycoprotein gC or gD under the control of the human cytomegalovirus immediate-early promoter/enhancer (AdCMVgC or AdCMVgD) or the 5' regulatory region of the human desmin gene (AdDESMgC or AdDESMgD) were generated. A preliminary experiment performed on rabbits showed that the intranasal administration of AdCMV elicited higher levels of BHV-1 neutralizing antibodies than the intramuscular administration of AdDESM. The obtained results allowed to select the replication-defective AdCMVgC and AdCMVgD for further assessment of their potential as a recombinant vaccine in cattle.

Mesangial IgG glomerulonephritis: a distinct type of primary glomerulonephritis.

Fourteen cases of mesangial IgG glomerulonephritis characterized by exclusive or predominant mesangial IgG deposits are reported. The median age at onset was 19 yr (range, 13 to 47 yr). No patient exhibited evidence of systemic lupus erythematous or other systemic diseases.

Brain pharmacokinetics of a nonpeptidic corticotropin-releasing factor receptor antagonist.

Corticotropin-releasing factor (CRF) is known to play an important role in the body response to stress. Butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-ethylamine (CP-154,526) is a CRF(1) antagonist showing anxiolytic activities in rats in behavioral models, suggesting that CP-154,526 crosses the blood-brain barrier. However, there is no direct evidence for this.