Preparation of a multiple antigen glycopeptide (MAG) carrying the Tn antigen. A possible approach to a synthetic carbohydrate vaccine

The glycosidic tumor-associated Tn antigen was conjugated to a lysine backbone containing a helper T-cell epitope in order to activate immune responses specific for some types of carcinomas. As opposed to traditional protein conjugates, this multiple antigen glycopeptide (MAG) offers the advantages of the lack of immunogenicity of the polylysine core and of accurate chemical definition. The MAG construction was assembled by conventional solid-phase peptide synthesis. The analysis of its antigenicity demonstrated that the Tn antigen on the MAG is recognized by Tn-specific monoclonal antibodies. © Munksgaard 1997.     

Sequence and solution conformation of the 20-residue peptaibols,saturnisporins SA II and SA IV

Saturnisporins SA II and SA 1V are the major components of the 20-residue peptaibol mixture isolated from a culture of the fungus Trichoderma saturnisporum. These peptides exhibit antibiotic activity against Staphylococcus aureus. Their sequences were derived from unequivocal methodology implying the combined use of positive ion FAB mass spectrometry and NMR: the majority of the sequences result from mass spectrometry fragmentations and the location of isomeric residues arises either from analysis of ROESY cross-peaks between contiguous amide protons or from heteronuclear ²J or ³J ¹H-¹³C couplings detected in long-range ¹H-¹³C COSY experiments. The sequence specific ¹H and ¹³C NMR assignments are described. Saturnisporins SA II and SA IV exhibit similar secondary structures, as deduced from their ROESY patterns and ³J_NHCαH coupling constant values, together with amide hydrogen-deuterium exchange rates and temperature coefficients of amide and carbonyl groups. An overall α-helical structure is proposed, maintaining two regions of distortion to this regular structure; i)the N-terminal part, which contains 3₁₀ and mixed α-3₁₀ turns, and ii) the Aib10-Val15 region, including a Pro residue which accommodates a bend stabilized by two 3₁₀ H-bonds.     

False Aneurysm of the Aortic Root and Right Ventricular Outflow Obstruction

Aortic root abscess often complicates the course of aortic valve endocarditis. In severe cases, left ventricular-aortic discontinuity may occur, providing challenging technical problems for the surgeon. Moreover, surgical intervention sometimes takes place in a semi-emergency context, and the patches and prosthesis are sutured into friable tissues and subjected to high systemic pressures. Subsequently, paravalvular leaks and prosthesis dehiscence are not uncommon; postoperative false aneurysm of the aortic root is a much more unusual complication. We report one case of right ventricular outflow obstruction that occurred after surgical treatment of an aortic root abscess. Echocardiographic data were useful, but magnetic resonance imaging provided valuable information about the anatomic extent of the cavity.     

Isolation and sequence determination of trichorzianines A antifungal peptides from Trichoderma harzianum

Trichorzianines A, membrane active peptides of the peptaibol class, were isolated from cultures of the mould Trichoderma harzianum. Trichorzianines A were separated into pure components by HPLC on octadecyl bonded and SiO₂ phases successively. Nine trichorzianines A (IIa, IIIa, IIIb, IIIc, IVb, Vb, VIa, VIb and VII) were isolated from the complex microheterogeneous mixture. Their N-terminal amino acid is acetylated, the C-terminal amino alcohol is either tryptophanol or phenylalaninol, 7 to 8 of the 19 residues are α-aminoisobutyric acid. Gas chromatography on a chiral phase showed isovaline to have the d -configuration and all the other optically active amino acids and amino alcohols to have the l -configuration. The amino acid sequences were determined from their positive ion FAB mass spectra which exhibited the preferential cleavage of the Aib 12-Pro 13 amide bond as a main fragmentation. The resulting fragments subsequently underwent amide bond ruptures that generated two series of abundant acylium ions which enabled direct determination of the 1–19 sequence. The relative position of the isomeric amino acids in the sequence of trichorzianine AVII was assigned from analysis of the N- and C-terminal oligopeptides yielded by its selective acidic hydrolysis. The microheterogeneity of trichorzianines A results mainly from single or multiple substitution of amino acids at the specific positions 5, 14, 16 and 19.     

Prognostic factors in elderly acute lymphoblastic leukaemia

A retrospective study was performed on 46 unselected acute lymphoblastic leukaemia (ALL) elderly patients aged 60 years or more. Only 50% of these patients were included in the EORTC cooperative clinical trials, thus confirming the important selection bias in most of the published series on elderly ALL patients. 43% of the elderly patients achieved a complete remission (CR). The median survival was 10 months and the 5-year overall survival was only 7.6±4%. In multivariate analysis, W.H.O. performance status and peripheral blast counts at day 7 were found to significantly influence achievement of CR and survival. In patients with W.H.O. performance status 2, 35% died during induction treatment versus 4% in patients with W.H.O. performance status <2. Patients >70 years old showed a marked drop of the CR rate (27%) compared to those aged 60–69 (67%), and a very high death rate during the induction period (38% versus 4%). This suggests that ALL protocol treatments should be proposed until 70 years in patients with good-performance status, whereas less intensive treatment should be offered to elderly patients with performance status 2 and/or age 70. Peripheral blast counts at day 7 may help to adjust the treatment during induction phase.     

Differential effects of recombinant human interleukin-13 on the in vitro growth of human haemopoietic progenitor cells

Summary. Effects of recombinant human interleukin (IL)-13 on in vitro haemopoiesis from non-adherent mononuclear cells (NAMC) or highly enriched CD34⁺ cells of human cord blood (CB) were studied. IL-13 significantly increased megakaryocyte (MK) colony formation from either NAMC or CD34⁺ cells cultured in a plasma clot system supplemented with aplastic anaemia serum (AAS) and phytohaemag-glutinin-stimulated human peripheral blood leucocyte-conditioned medium (PHA-LCM) in a dose-dependent manner. Experiments using a modified plasma clot culture, in which normal AB serum and various cytokines were added to replace AAS and PHA-LCM, demonstrated an increased MK colony number in the presence of IL-13, especially in combination with IL-3. However, IL-13 had no stimulatory effect, but rather a slight inhibitory effect in some cases on granulocyte-macrophage (GM) colony formation in both plasma clot cultures. Furthermore, the growth of GM progenitor cells in a methylcellulose culture system in the presence of IL-3, GM-CSF, Epo, G-CSF or in combination was significantly inhibited by the addition of IL-13. On the other hand, high concentrations (lOOng/ml) of IL-13 were needed to cause a slight inhibition on the growth of BFU-E-derived colonies under the same methylcellulose culture. These results indicate that IL-13, alone and synergistically with the effect of IL-3, promotes MK colony formation, but it inhibits the growth of GM and erythroid progenitor cells in vitro.     

The gp 130 family cytokines IL-6, LIF and OSM but not IL-11 can reverse the anti-proliferative effect of dexamethasone on human myeloma cells

Summary. In order to understand the mechanisms supporting steroid escape in patients with multiple myeloma (MM), three IL-6 autocrine human myeloma cell lines, LP1, OPM2 and L363, have been treated with dexamethasone in the presence or absence of cytokines belonging to the gp 130 family: IL-6, LIF, OSM and IL-11. With pharmacological doses of dexamethasone, a dramatic growth arrest was observed in all the cell lines. IL-6 completely reversed this inhibition. Of note, this IL-6 induced reversion was still seen with very low amounts of IL-6 (12 pg/ml). Finally, whereas LIF and OSM had clear growth-promoting effects on OPM2 only, both cytokines (but not IL-11) reversed the dexa-methasone-induced growth arrest in all the cell lines. Therefore the high levels of IL-6 (ng/ml) observed in the MM intermediate milieu and the putative presence of LIF and OSM can easily counteract the effects of dexamethasone in vivo.