Linearly stratified salt solutions of different Prandtl number were subjected to turbulent stirring by a horizontally oscillating vertical grid in a closed laboratory system. The experimental set-up allowed the independent direct measurement of a root mean square turbulent lengthscale Lt, turbulent diffusivity for mass Kρ, rate of dissipation of turbulent kinetic energy ε, buoyancy frequency N and viscosity v, as time and volume averaged quantities. The behaviour of both Lt and Kρ was characterized over a wide range of the turbulence intensity measure, ε/vN2, and two regimes were identified.In the more energetic of these regimes (Regime E, where 300 < ε/vN2 < 105), Lt was found to be a function of v, κ and N, whilst Kρ was a function of v, κ and (ε/vN2)1/3. From these expressions for Lt and Kρ, a scaling relation for the root mean square turbulent velocity scale Ut was derived, and this relationship showed good agreement with direct measurements from other data sets.In the weaker turbulence regime (Regime W, where 10 < ε/vN2 < 300) Kρ was a function of v, κ and ε/vN2.For 10 < ε/vN2 < 1000, our directly measured diffusivities, Kρ, are approximately a factor of 2 different to the diffusivity predicted by the model of Osborn (1980). For ε/vN2 > 1000, our measured diffusivities diverge from the model prediction. For example, at ε/vN2 ≈ 104 there is at least an order of magnitude difference between the measured and predicted diffusivities.

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Mycobacterium leprae induces T cell reactivity and protective immunity in the majority of exposed individuals, but the minority that develop leprosy exhibit various types of immunopathology. Thus, the definition of epitopes on M. leprae antigens that are recognized by T cells from different individuals might result in the development of an effective vaccine against leprosy. A sequence from the 65-kD protein of this organism was recognized by two HLA-DR2-restricted, M. leprae-specific helper T cell clones that were derived from a tuberculoid leprosy patient. Synthetic peptides were used to define this epitope as Leu-Gln-Ala-Ala-Pro-Ala-Leu-Asp-Lys-Leu. A similar peptide that was derived from the third hypervariable region of the HLA-DR2 chain, Glu-Gln-Ala-Arg-Ala-Ala-Val-Asp-Thr-Tyr, also activated the same clones. The unexpected cross-reactivity of this M. leprae-specific DR2-restricted T cell epitope with a DR2 peptide may have to be considered in the design of subunit vaccines against leprosy.

The highly regulated enzyme HMG-CoA reductase generates mevalonate, the precursor of a complex series of isoprenoids that posttranslationally modify (isoprenylate) certain proteins (e.g., the low-molecular-weight GTP-binding proteins) or that are incorporated into cholesterol and other end products. We recently reported that isoprenoids are required for NADPH oxidase activity in granulocytes via LMW GTP-binding protein isoprenylation. In this study, we evaluated the effects of isoprenoid depletion on the expression of proinflammatory genes in human monocytic THP-1 cells. We selected conditions under which pretreatment for 24 h with isoprenoid synthesis inhibitors (HMG-CoA reductase inhibitor lovastatin or compactin at 10 microM) did not compromise cell viability but markedly suppressed H2O2 generation. Under these conditions interleukin-8 (IL-8) production was attenuated (by 50-90%) in response to lipopolysaccharide, granulocyte-macrophage colony-stimulating factor, and phorbol myristate acetate. Coincubation of reductase inhibitor-treated cells with mevalonate prevented the attenuation of IL-8 production by reductase inhibitors. The effects of isoprenoid depletion on cytokine production were selective: IL-1 beta generation was not inhibited but the production of IL-6 and IL-8 was concomitantly suppressed. IL-8 induction was suppressed at least in part through attenuation of the increase in mRNA in stimulated cells. We conclude that isoprenoid generation through the mevalonate pathway is a requirement for IL-8 induction by activated monocytic cells in vitro. Isoprenylation inhibitors have the potential to alter monocyte proinflammatory function.