Extracellular superoxide dismutase is a major determinant of nitric oxide bioavailability: in vivo and ex vivo evidence from ecSOD-deficient mice.

The bioavailability of nitric oxide (NO) within the vascular wall is limited by superoxide anions (O2.-). The relevance of extracellular superoxide dismutase (ecSOD) for the detoxification of vascular O2.- is unknown. We determined the involvement of ecSOD in the control of blood pressure and endothelium-dependent responses in angiotensin II-induced hypertension and renovascular hypertension induced by the two-kidney, one-clip model in wild-type mice and mice lacking the ecSOD gene. Blood pressure was identical in sham-operated ecSOD+/+ and ecSOD-/- mice. After 6 days of angiotensin II-treatment and 2 and 4 weeks after renal artery clipping, blood pressure was significantly higher in ecSOD-/- than ecSOD+/+ mice. Recombinant ecSOD selectively decreased blood pressure in hypertensive ecSOD-/- mice, whereas ecSOD had no effect in normotensive and hypertensive ecSOD+/+ mice. Compared with sham-operated ecSOD+/+ mice, sham-operated ecSOD-/- mice exhibited attenuated acetylcholine-induced relaxations. These responses were further depressed in vessels from clipped animals. Vascular O2.-, as measured by lucigenin chemiluminescence, was higher in ecSOD-/- compared with ecSOD+/+ mice and was increased by clipping. The antioxidant tiron normalized relaxations in vessels from sham-operated and clipped ecSOD-/-, as well as from clipped ecSOD+/+ mice. In contrast, in vivo application of ecSOD selectively enhanced endothelium-dependent relaxation in vessels from ecSOD-/- mice. These data reveal that endogenous ecSOD is a major antagonistic principle to vascular O2.-, controlling blood pressure and vascular function in angiotensin II-dependent models of hypertension. ecSOD is expressed in such an abundance that even in situations of high oxidative stress no relative lack of enzyme activity occurs.

Influence of substrates and in vitro preconditioning treatments on ex vitro acclimatization of Arachis retusa

The objective of this work was to evaluate the influence of substrate and preconditioning treatments on the acclimatization of in vitro plants of Arachis retusa. Plants were transferred to Plantmax or sand, and fertilized with Hoagland's nutrient solution. Plants maintained in sand, with or without fertilizer, showed the highest survival rates. In order to evaluate the influence of in vitro preconditioning treatments, stem segments were cultured on MS medium supplemented with different sucrose concentrations. The highest survival and developmental rates were observed in plants from two accessions cultured on MS supplemented with 1.5% and 3% sucrose. Flowering and fruit production were observed after five months.

Ex vivo detectable human CD8 T-cell responses to cancer-testis antigens.

Clinical trials have shown that strong tumor antigen-specific CD8 T-cell responses are difficult to induce but can be achieved for T-cells specific for melanoma differentiation antigens, upon repetitive vaccination with stable emulsions prepared with synthetic peptides and incomplete Freund's adjuvant. Here, we show in four melanoma patients that ex vivo detectable T-cells and thus strong T-cell responses can also be induced against the more universal cancer-testis antigens NY-ESO-1 and Mage-A10. Interestingly, all patients had ex vivo detectable T-cell responses against multiple antigens after serial vaccinations with three peptides emulsified in incomplete Freund's adjuvant. Antigen-specific T-cells displayed an activated phenotype and secreted IFNgamma. The robust immune responses provide a solid basis for further development of human T-cell vaccination.

1.° Hilperici tractatus de arte calculatoria : praemittitur calendarium ad usum Cisterciensium. — 2.° Ratio Gaii Caesaris de ordine anni per duodecim menses. — 3.° Bedae opusculum de loquela digitorum. — 4.° Expositio tabulae de luna quotidiè per rationem epactarum invenienda. — 5.° Excerptum ex etymologiis Isidori, de coelo ejusque luminaribus. — 6.° Carmen de temporibus anni. — 7.° Ratio epactarum. — 8.° Anonymi expositio super tabulam Dionysii Exigui, Abbatis. — 9.° Fragmentum Macrobii de mensura terrae. — 10.° Anonymi figurata expositio duodecim signorum zodiaci. — 11.° Scholium de temporibus et aetatibus mundi. — 12.° Alcuini opusculum de vita Antichristi. — 13.° Hieronymus de quindecim signis praecedentibus diem judicii. — 14.° Beda de die judicii. — 15.° Anonymi chronicon in epitomen contractum, et à mundi creatione ad Leonis III. imperium productum. — 16.° Provincialis Romanae Ecclesiae fragmentum.

Colbertinus

1.° Tractatus de proportionibus in genere. — 2.° Tractatus de proportionibus motuum. — 3.° Fragmentum elementorum geometriae. — 4.° Tractatus de minutiis, sive de fractionibus. — 5.° Ludus rethimachiae, sive potiùs, arithmomachiae, id est, de numerorum pugna : ad calcem subjecti versiculi de eodem ludo, excerpti ex carmine de vetula, quod Ovidio tribuitur. — 6.° Anonymi tractatus de perspectiva, sive potiùs, tractatus de optica, dioptrica et catoptrica.

Mentellianus

1.° Anonymi canones in Alphonsi Regis tabulas. — 2.° Tractatus de duodecim domibus coeli, ex diversis authoribus concinnatus. — 3.° Sigilla Magistri Arnaldi de Villanova. — 4.° Compilatio Leopoldi, Ducis Austriae filii, de astrorum scientia. — 5.° Anonymus de judiciis astrorum ad medicinam pertinentibus. — 6.° Speculum Alberti Magni de nominibus librorum astronomiae.

Philiberti de la Mare

1.° Francisci Maurolyci demonstrationes in duodecimum librum Euclidis elementorum. — 2.° Ejusdem modus fabricandi astrolabium, cum demonstrationibus geometricis. — 3.° Ejusdem opusculum de fabrica et usu quadrati horarii, ad omnem horisontem accommodati. — 4.° Collectanea ex fabula et historia antiqua.

Colbertinus

1.° Theonis, ex traditione Pappi, datorum libri duo : interprete Francisco Maurolyco ; cum ejusdem Maurolyci additionibus. — 2.° Euclidis phaenomena, cum expositione Maurolyci.

Colbertinus

1.° Opus cujus is est titulus : tractatus instrumenti astronomici Magistri Leonis Judaei de Balneolis, ad summum Pontificem Clementem VI. ex hebraïca lingua in latinam anno Incarnationis 1342. conversus. — 2.° Anonymi tractatus de Deo ab aeterno, sive pars operis theologici majoris. — 3.° Anonymi postillae in epistolam ad Romanos ; et considerationes super passione Domini et Scriptura sacra.

Colbertinus

Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers.

Over the past decade, many efforts have been made to identify MHC class II-restricted epitopes from different tumor-associated Ags. Melan-A/MART-1(26-35) parental or Melan-A/MART-1(26-35(A27L)) analog epitopes have been widely used in melanoma immunotherapy to induce and boost CTL responses, but only one Th epitope is currently known (Melan-A51-73, DRB1*0401 restricted). In this study, we describe two novel Melan-A/MART-1-derived sequences recognized by CD4 T cells from melanoma patients. These epitopes can be mimicked by peptides Melan-A27-40 presented by HLA-DRB1*0101 and HLA-DRB1*0102 and Melan-A25-36 presented by HLA-DQB1*0602 and HLA-DRB1*0301. CD4 T cell clones specific for these epitopes recognize Melan-A/MART-1+ tumor cells and Melan-A/MART-1-transduced EBV-B cells and recognition is reduced by inhibitors of the MHC class II presentation pathway. This suggests that the epitopes are naturally processed and presented by EBV-B cells and melanoma cells. Moreover, Melan-A-specific Abs could be detected in the serum of patients with measurable CD4 T cell responses specific for Melan-A/MART-1. Interestingly, even the short Melan-A/MART-1(26-35(A27L)) peptide was recognized by CD4 T cells from HLA-DQ6+ and HLA-DR3+ melanoma patients. Using Melan-A/MART-1(25-36)/DQ6 tetramers, we could detect Ag-specific CD4 T cells directly ex vivo in circulating lymphocytes of a melanoma patient. Together, these results provide the basis for monitoring of naturally occurring and vaccine-induced Melan-A/MART-1-specific CD4 T cell responses, allowing precise and ex vivo characterization of responding T cells.