In the presence of an excess of pyridine ligand L, osmium tetroxide oxidizes tertiary silanes (Et(3)SiH, (i)Pr(3)SiH, Ph(3)SiH, or PhMe(2)SiH) to the corresponding silanols. With L = 4-tert-butylpyridine ((t)Bupy), OsO(4)((t)Bupy) oxidizes Et(3)SiH and PhMe(2)SiH to yield 100 +/- 2% of silanol and the structurally characterized osmium(VI) mu-oxo dimer [OsO(2)((t)Bupy)(2)](2)(mu-O)(2) (1a). With L = pyridine (py), only 40-60% yields of R(3)SiOH are obtained, apparently because of coprecipitation of osmium(VIII) with [Os(O)(2)py(2)](2)(mu-O)(2) (1b). Excess silane in these reactions causes further reduction of the OsVI products, and similar osmium "over-reduction" is observed with PhSiH(3), Bu(3)SnH, and boranes. The pathway for OsO(4)(L) + R(3)SiH involves an intermediate, which forms rapidly at 200 K and decays more slowly to products. NMR and IR spectra indicate that the intermediate is a monomeric Os(VI)-hydroxo-siloxo complex, trans-cis-cis-Os(O)(2)L(2)(OH)(OSiR(3)). Mechanistic studies and density functional theory calculations indicate that the intermediate is formed by the [3 + 2] addition of an Si-H bond across an O=Os=O fragment. This is the first direct observation of a [3 + 2] intermediate in a sigma-bond oxidation, though such species have previously been implicated in reactions of H-H and C-H bonds with OsO(4)(L) and RuO(4).

Background FOXP3+ regulatory T cells (Tregs) are critical for controlling inflammation in the gastrointestinal (GI) tract. There is a paradoxical increase of mucosal FOXP3+ T cells in patients with inflammatory bowel disease (IBD). These FOXP3+ cells were recently shown to include IL-17A-producing cells in Crohn’s disease, resembling Th17 cells implicated in autoimmune diseases. FOXP3 inhibits IL-17A production, but a naturally-occurring splice variant of FOXP3 lacking exon 2 (Δexon2) cannot. Aims We hypothesized that IBD patients preferentially express the Δexon2 variant of FOXP3 so the paradoxically increased mucosal Tregs in IBD could represent cells expressing only Δexon2. Methods We used antibodies and primers that can distinguish between the full-length and Δexon2 splice variant of FOXP3 to evaluate expression of these isoforms in human intestinal tissue by immunohistochemistry (IHC) and quantitative PCR, respectively. Results No difference in the expression pattern of Δexon2 relative to full length FOXP3 was seen in ulcerative colitis (UC) or Crohn’s disease versus non-IBD controls. By immunofluorescence microscopy and flow cytometry, we also did not find individual cells which expressed FOXP3 protein exclusively in the Δexon2 isoform in either IBD or control tissue. FOXP3+ mucosal CD4+ T cells from both IBD and control specimens were able to make IL-17A in vitro after PMA and ionomycin stimulation, but these cells did not preferentially express Δexon2. Conclusions Our data do not support the hypothesis that selective expression of FOXP3 in the Δexon2 isoform accounts for the inability of copious FOXP3+ T cells to inhibit inflammation or IL-17 expression in IBD.

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Despite the prevalence of anemia in cancer, recombinant erythropoietin (Epo) has declined in use because of recent Phase III trials showing more rapid cancer progression and reduced survival in subjects randomized to Epo. Since Epo receptor (EpoR), Jak2, and Hsp70 are well-characterized mediators of Epo signaling in erythroid cells, we hypothesized that Epo might be especially harmful in patients whose tumors express high levels of these effectors. Because of the insensitivity of immunohistochemistry for detecting low level EpoR protein, we developed assays to measure levels of EpoR, Jak2 and Hsp70 mRNA in formalin-fixed paraffin-embedded (FFPE) tumors. We tested 23 archival breast tumors as well as 136 archival head and neck cancers from ENHANCE, a Phase III trial of 351 patients randomized to Epo versus placebo concomitant with radiotherapy following complete resection, partial resection, or no resection of tumor. EpoR, Jak2, and Hsp70 mRNA levels varied >30-fold, >12-fold, and >13-fold across the breast cancers, and >30-fold, >40-fold, and >30-fold across the head and neck cancers, respectively. Locoregional progression-free survival (LPFS) did not differ among patients whose head and neck cancers expressed above-versus below-median levels of EpoR, Jak2 or Hsp70, except in the subgroup of patients with unresected tumors (n 5 28), where above-median EpoR, above-median Jak2, and belowmedian Hsp70 mRNA levels were all associated with significantly poorer LPFS. Our results provide a framework for exploring the relationship between Epo, cancer progression, and survival using archival tumors from other Phase III clinical trials.

Organic chemistry Z 0200 Stoichiometric Oxidations of σ-Bonds: Radical and Possible Non-Radical Pathways -[79 refs.]. -(MAYER, J. M.; MADER, E. A.; ROTH, J. P.; BRYANT, J. R.; MATSUO, T.; DEHESTANI, A.; BALES, B. C.; WATSON, E. J.; OSAKO, T.; VALLIANT-SAUNDERS, K.; et al.; J. Mol. Catal. A: Chem. 251 (2006) 1-2, 24-33; Dep. Chem., Univ. Wash., Seattle, WA 98195, USA; Eng.) -Lindner 03-228