Complexes of 1-thia-4,7,10-triazacyclododecane ([12]aneN(3)S) - Synthesis, structure and stability constants

The 12-membered macrocyclic ligand 1-thia-4,7, 10-triazacyclododecane ([12]aneN(3)S) has been synthesised, although upon crystallization from acetonitrile a product in which carbon dioxide had added to one secondary amine in the macrocyclic ring (H[12]aneN(3)SCO(2). H2O) was isolated and subsequently characterised by X-ray crystallography. The protonation constants for [12]aneN(3)S and stability constants with Zn(II), Pb(II), Cd(II) and Cu(II) have been determined either potentiometrically or spectrophotometrically in aqueous solution, and compared with those measured or reported for the ligands 1-oxa-4,7,10-triazacyclododecane ([12]aneN(3)O) and 1,4,7,10-tetraazacyclododecane ([12]aneN(4)). The magnitudes of the stability constants are consistent with trends observed previously for macrocyclic ligands as secondary amine donors are replaced with oxygen and thioether donors although the stability constant for the [Hg([12]aneN(4))](2+) complex has been estimated from an NMR experiment to be at least three orders of magnitude larger than reported previously. Zinc(II), mercury(II), lead(II), copper(II) and nickel(II) complexes of [12]aneN(3)S have been isolated and characterised by X-ray crystallography. In the case of copper(II), two complexes [Cu([12]aneN(3)S)(H2O)](ClO4)(2) and [Cu-2([12]aneN(3)S)(2)(OH)(2)](ClO4)(2) were isolated, depending on the conditions employed. Molecular mechanics calculations have been employed to investigate the relative metal ion size preferences of the [3333], asym-[2424] and sym-[2424] conformation isomers. The calculations predict that the asym-[2424] conformer is most stable for M-N bond lengths in the range 2.00-2.25 Angstrom whilst for the larger metal ions the [3333] conformer is dominant. The disorder seen in the structure of the [Zn([12]aneN(3)S)(NO3)](+) complex is also explained by the calculations. (C) 1999 Elsevier Science Ltd. All rights reserved.

Differentiated dendritic cells expressing nuclear RelB are predominantly located in rheumatoid synovial tissue perivascular mononuclear cell aggregates

Objective. Differentiated dendritic cells (DC) and other antigen-presenting cells are characterized by the nuclear location of RelB, a member of the nuclear factor kappa B/Rel family. To characterize and enumerate differentiated DC in rheumatoid arthritis (RA) peripheral blood (PB), synovial fluid (SF), and synovial tissue (ST), the expression and location of RelB were examined. Methods. RelB protein expression and cellular location were determined in RA PB, SF, and ST by flow cytometry and immunohistochemical analysis of purified cells or formalin-fixed tissue. DNA-binding activity of RelB was determined by electrophoretic: mobility shift-Western immunoblotting assays. Results. Circulating RA PBDC resembled normal immature PBDC in that they did not express intracellular RelB protein. In RA ST serial sections, cells containing nuclear RelB (nRelB) were enriched in perivascular regions. A mean +/- SD of 84 +/- 10% of these cells were DC. The remaining nRelB+,HLA-DR+ cells comprised B cells and macrophages. Only 3% of sorted SFDC contained nRelB, However, RelB present in the nucleus of these SFDC was capable of binding DNA, and therefore capable of transcriptional activity. Conclusion. Circulating DC precursors differentiate and express RelB after entry into rheumatoid ST. Differentiated DC can thus be identified by immunohistochemistry in formalin-fixed ST. Signals for DC maturation may differ between RA ST and SF, resulting in nuclear location of RelB predominantly in ST. This is likely to have functional consequences for the DC in these sites.

Expression of RANTES and CCR1 in oral lichen planus and association with mast cell migration

Background: T lymphocytes and mast cells infiltrate the lamina propria in oral lichen planus (OLP). Chemokines and their receptors are involved in T cell and mast cell migration and accumulation during the inflammatory process. Methods: In the present study, we investigated the role of RANTES and its receptors in OLP using immunohistochemistry, RT-PCR and an in vitro chemotaxis assay. Results: RANTES and CCR1 were expressed on T cells and mast cells in OLP, while OLP lesional T cell supernatants stimulated CCR1 mRNA expression in a human leukemia mast cell line (HMC-1). TNF-alpha stimulated CCR1, CCR4 and CCR5 mRNA expression in the same cell line. OLP lesional T cell supernatants stimulated HMC-1 migration, which was partly inhibited by anti-RANTES antibody. Conclusions: The present study shows, for the first time, the distribution of RANTES and CCR1 in OLR It is hypothesized that RANTES and CCR1 may play important roles in mast cell trafficking and related events in OLP.

Acute high-intensity interval training improves T-vent and peak power output in highly trained males.

This study examined the effects of four high-intensity interval-training (HIT) sessions performed over 2 weeks on peak volume of oxygen uptake (VO2peak), the first and second ventilatory thresholds (UT VT2) and peak power output (PPO) in highly trained cyclists. Fourteen highly trained male cyclists (VO2peak = 67.5 +/- 3.7 ml . kg(-1) . min(-1)) performed a ramped cycle test to determine VO2peak VT1 VT2, and PPO. Subjects were divided equally into a HIT group and a control group. The HIT group performed four HIT sessions (20 x 60 s at PPO, 120 s recovery); the V-02peak test was repeated <I wk after the HIT program. Control subjects maintained their regular training program and were reassessed under the same timeline. There was no change in V0(2peak) for either group; however, the HIT group showed a significantly greater increase in VT1, (+22% vs. -3%), VT2 (+15% vs. -1%), and PPO (+4.3 vs. -.4%) compared to controls (all P <.05). This study has demonstrated that HIT can improve VT1, VT2,, and PPO, following only four HIT sessions in already highly trained cyclists.

Attenuation of perceptual asymmetries in patients with early-onset schizophrenia: Evidence in favour of reduced hemispheric differentiation in schizophrenia?

Lateral biases in visual perception have been demonstrated in normal individuals and in patients with unilateral brain lesions. It has been suggested that the absence of structural and functional asymmetries in schizophrenia could be due to a failure in lateralisation that may be most pronounced in those patients whose illness onset is at an early age. Here we examined lateral biases in patients with schizophrenia of an early onset (N = 21) and a late onset.(N = 19), and their respective age-matched control groups, using the greyscales task, a sensitive measure of asymmetries in visual processing. The stimuli consisted of two rectangles, one above the other, shaded in opposite directions and matched overall for darkness. Participants judged which of the two rectangles looked darker overall. Previous studies using this task in healthy participants have reported a reliable bias, such that the rectangle with the darker end on the left is selected preferentially. Whereas the late-onset patients in this study exhibited a perceptual bias of similar direction and magnitude to that of controls, this was not the case for the early-onset patients, who exhibited significantly less bias than their control group. The reduced perceptual bias seen in the early-onset group, but not the late-onset group, suggests an attenuation of right hemisphere mechanisms dedicated to processing vistiospatial information. The attenuated perceptual asymmetry in the early-onset group only may be consistent with the view that (i) an earlier illness onset reflects a greater loss of hemispheric differentiation and (ii) reduced functional asymmetries in the early-onset group are a manifestation of a failure to allocate functions to one or the other hemisphere.

A comparison of the performance and biological efficiency of new knapsack sprayers and a controlled droplet application (CDA) sprayer for the control of the diamondback moth, Plutella xylostella L. (Lepidoptera : Plutellidae)

Field trials and laboratory bioassays were undertaken to compare the performance and efficacy (mortality of diamondback moth larvae) of insecticides applied to cabbages with three high volume hydraulic knapsack sprayers (NS-16, PB-20 and Selecta 12V) and a controlled droplet application (CDA) sprayer. In field experiments, the high volume knapsack sprayers (application rate 500-600 L ha(-1)) provided better spray coverage on the upper and lower surfaces of inner leaves, the upper surfaces of middle and outer leaves, and greater biological efficacy than the CDA sprayer (application rate 20similar to40 L ha(-1)). The PB-20 provided better spray coverage on the upper surface of middle leaves and both surfaces of outer leaves when compared with the Selecta 12V. However, its biological efficacy in the field was not significantly different from that of the other high volume sprayers. Increasing the application rate from 20 to 40 L ha(-1) for the CDA sprayer significantly increased droplet density but had no impact on test insect mortality. Laboratory evaluations of biological efficacy yielded higher estimates than field evaluations and there was no significant difference between the performance of the PB-20 and the CDA sprayer. Significant positive relationships were detected between insect mortality and droplet density deposited for both the PB-20 and the CDA sprayers.

Functional CD40-ligand is expressed by T cells in rheumatoid arthritis

CD40-1igand (CD40-L), a member of the tumour necrosis family of transmembrane glycoproteins, is rapidly and transiently expressed on the surface of recently activated CD4+ T cells. CD40 is expressed by B cells, monocytes and dendritic cells. Interactions between CD40-L and CD40 induce B cell proliferation, differentiation, immunoglobulin production and isotype switching as well as monocyte activation and dendritic cell differentiation. Since the rheumatoid synovium is characterized by T cell activation, B cell immunoglobulin production, monocyte cytokine production and dendritic cell differentiation, the expression and function of CD40-L in RA was examined. RA synovial fluid (SF) T ceils expressed CD40-L mRNA, as well as low level cell surface CD40-L. A subset of CD4+ RA synovial fluid T cells could express cell surface CD40-L within 15 rain of in vitro activation even in the presence of cycloheximide. CD40-L expressed by RA SF T cells was functional, since RA SF T cells, but not normal PB T cells, stimulated CD40-L dependent B cell immunoglobulin production in the absence of in vitro T cell activation. These data indicate that SF T cells express functionally significant levels of surface CD40-L, and have the potential for rapid upregulation of surface expression from preformed CD40-L stores. Thus, CD40-L is likely to play a central role in the perpetuation of RA by induction of Ig synthesis, cytokine production and dendritic cell differentiation. Moreover, the data provide important evidence of recent activation of RA synovial T cells. Of importance, blockade of CD40-L may prove highly effective as a disease modifying therapy for RA.