The measurement of regional rates of cerebral protein synthesis in vivo

Special issue dedicated to Dr. Louis Sokoloff.     

Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

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Treatment of Early Breast Cancer: A Report after Ten Years of a Clinical Trial

A controlled clinical trial has been carried out to compare radical mastectomy with wide excision (extended tylectomy) in the treatment of early breast cancer. Only patients aged 50 and over were included and 370 entered the trial during a period of 10 years. Postoperative radiotherapy was given in each case. In patients with clinically involved axillary nodes there was a significantly higher incidence of local and distant recurrence in those having a wide excision, and the survival of these patients was significantly less than those who had a radical mastectomy. In patients with clinically uninvolved nodes, although there was a significantly higher incidence of local recurrence in those having a wide excision, there was no increased incidence of distant recurrence and the survival rate was similar to those having a radical mastectomy.     

Transferrin receptor cycling by human lymphoid cells: lack of effect from inhibition of microtubule assembly

Flow cytometry was used to follow the uptake and release of fluorescein-conjugated ferro-transferrin by CCRF-CEM human T - leukaemia cells on an individual cell basis. Pretreatment with the stathmokinetic agent vincristine for 5 hr had no effects on the cycling of transferrin, although microscopic examination of the cells showed a substantial proportion to be arrested in metaphase with cytoplasmic dispersal of tubulin, indicating inhibition of microtubule assembly. Tubulin is therefore unlikely to play a major role in the transferrin cycle of exponentially-growing cells, despite earlier reports that the cytoskeleton is involved in receptor clustering and down regulation.     

Inflammation-associated S100 proteins: new mechanisms that regulate function

This review focuses on new aspects of extracellular roles of the calgranulins. S100A8, S100A9 and S100A12 are constitutively expressed in neutrophils and induced in several cell types. The S100A8 and S100A9 genes are regulated by pro- and anti-inflammatory mediators and their functions may depend on cell type, mediators within a particular inflammatory milieu, receptors involved in their recognition and their post-translational modification. The S100A8 gene induction in macrophages is dependent on IL-10 and potentiated by immunosuppressive agents. S100A8 and S100A9 are oxidized by peroxide, hypochlorite and nitric oxide (NO). HOCl generates intra-chain sulfinamide bonds; stronger oxidation promotes cross-linked forms that are seen in human atheroma. S100A8 is >200-fold more sensitive to oxidative cross-linking than low-density lipoprotein and may reduce oxidative damage. S100A8 and S100A9 can be S-nitrosylated. S100A8–SNO suppresses mast cell activation and inflammation in the microcirculation and may act as an NO transporter to regulate vessel tone in inflammatory lesions. S100A12 activates mast cells and is a monocyte and mast cell chemoattractant; a G-protein-coupled mechanism may be involved. Structure–function studies are discussed in relation to conservation and divergence of functions in S100A8. S100A12 induces cytokines in mast cells, but not monocytes/macrophages. It forms complexes with Zn²⁺ and, by chelating Zn²⁺, S100A12 significantly inhibits MMPs. Zn²⁺ in S100A12 complexes co-localize with MMP-9 in foam cells in atheroma. In summary, S100A12 has pro-inflammatory properties that are likely to be stable in an oxidative environment, because it lacks Cys and Met residues. Conversely, S100A8 and S100A9 oxidation and S-nitrosylation may have important protective mechanisms in inflammation.