Significant salivary changes in relation to oral mucositis following autologous hematopoietic stem cell transplantation.

The aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1×/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3×/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (≥2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p < 0.001 95% CI [1.14, 3.29]). Twelve months post-ASCT, salivary protein levels were similar to baseline except for log total IgA, which was higher (UWS: p < 0.001 95% CI [0.49, 1.29], SWS: p < 0.001 95% CI [0.72, 1.45]). No differences between uOM and non-uOM groups were observed. Changes in salivary proteins indicated an inflammatory reaction in salivary glands coinciding with mucosal and systemic reactions in response to high-dose melphalan.

Sequential 1H and 15N nuclear magnetic resonance assignments and secondary structure of the lipoyl domain of the 2-oxoglutarate dehydrogenase complex from Azotobacter vinelandii. Evidence for high structural similarity with the lipoyl domain of the pyruvate dehydrogenase complex.

A 79-amino-acid polypeptide, corresponding to the lipoyl domain of the succinyltransferase component of the 2-oxoglutarate dehydrogenase multienzyme complex from Azotobacter vinelandii, has been sub-cloned and produced in Escherichia coli. Complete sequential 1H and 15N resonance assignments for the lipoyl domain have been obtained by using homo- and hetero-nuclear NMR spectroscopy. Two antiparallel beta-sheets of four strands each were identified from characteristic NOE connectivities and 3JHN alpha values. The lipoyl-lysine residue is found in a type-I turn connecting two beta-strands. The secondary structure of the lipoyl domain very much resembles the secondary solution structure of the N-terminal lipoyl domain of the A. vinelandii pyruvate dehydrogenase complex, despite the sequence identity of 25%. A detailed comparison of the NMR-derived parameters of both lipoyl domains, i.e. chemical shifts, NH-exchange rates, NOEs, and 3JHN alpha values suggests a high structural similarity in solution between the two lipoyl domains. Preliminary tertiary-structure calculations confirm that these lipoyl domains have very similar overall folds. The observed specificity of the 2-oxo acid dehydrogenase components of both complexes for these lipoyl domains is discussed in this respect.