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51.
Giuseppe Fossati Andrea Balsari Donatella Taramelli Maria Luisa Sensi Giuseppe Pellegris Maurizio Nava Giorgio Parmiani 《Cancer immunology, immunotherapy : CII》1982,14(2):99-104
Summary Peripheral blood lymphocytes (PBL) of melanoma patients were sensitized in vitro with lymphocytes of a single donor or with a pool of lymphocytes of 5–20 different donors. After 6–7 days, the cytotoxic activity of the sensitized PBL was tested against cultured autologous tumor cells and lymphocytes in a 51Cr-release assay. Tumor lysis was observed in 13 of 16 cases in which patients' PBL (Pt-PBL) were stimulated by a pool of allogeneic lymphocytes and in five out of seven cases when single sensitization was performed. In no case was lysis of autologous normal lymphocytes or blasts seen. Cultivation of Pt-PBL with irradiated autologous tumor cells never led to the induction of lymphocytes cytotoxic to melanoma cells. Lysability by pool-activated autologous Pt-PBL of fresh cryopreserved tumor cells was compared to that of short-term cultured tumor cells, and no significant differences were observed. Cold-target inhibition experiments indicated that the cytotoxicity of Pt-PBL was tumor-restricted since only autologous melanoma cells but not lymphocytes were able to inhibit the reaction. These results indicate that activation of Pt-PBL is necessary in order to elicit or amplify their antitumor activity. 相似文献
52.
George W. Arana Ross J. Baldessarini Michael Herschel Maurizio Fava 《Life sciences》1981,29(2):121-133
The binding of low concentrations of [3H](?)apomorphine to preparations of calf and rat forebrain tissue was evaluated. Fractionation of crude homogenates to prepare a membrane fraction (P4) of striatal or caudate homogenates increased the proportion of saturable to total binding from 33% to over 80%, and increased the apparent density of binding sites from 94 to 681 fmol/mg protein. Binding in calf caudate P4 tissue was protein-dependent and optimal at pH = 7.0 to 7.5, and T = 20 to 25°C; at higher temperatures tissue binding sites appeared to degrade. The half-time of association and dissociation at 22°C were, respectively, 14.0 and 18.5 min; equilibration was complete in 60 min. Kinetic characteristics of high-affinity binding obtained from association and dissociation constants and from saturation isotherms were similar (Kd = 2.1 to 3.4 nM). The pharmacology of competition for 3H-APO suggests selectivity for dopamine-agonist interactions. These results indicate that the P4 membrane preparation may be useful for the evaluation of dopamine-agonist binding sites or “receptors.” 相似文献
53.
Andreas Gescher Maurizio DIncalci Roberto Fanelli Pierluigi Farina 《Life sciences》1980,26(2):147-154
N-Hydroxymethylpentamethylmelamine (HMPMM) was identified by HPLC and by GLC-MS after derivatization, as a metabolite of the anticancer drug hexamethylmelamine (HMM) in incubation mixtures with fortified mouse liver 9000 × g and microsomal preparations. HMPMM formation was dependent on the presence of NADPH and oxygen. N-demethylated metabolites were also found. HMPMM displays appreciable chemical stability and 29% was recovered after 60 min incubation in buffer. HMPMM constituted more than 50% of total HMM metabolites in 30 min incubations. The known chemical reactivity of carbinolamines means that HMPMM could be involved in the pharmacological or toxic effects of HMM. 相似文献
54.
The carrier-mediated transport of GABA in rat brain synaptosomes was strongly and permanently inhibited byl-2,4-diaminobutyric acid (DAB). In order to discriminate between carrier-mediated and non-carrier-mediated release of [3H]GABA, synaptosomes prelabeled with 0.5 M [3H]GABA in the presence of 100 M DAB, or with 0.2 M [3H]GABA without DAB, were superfused in conditions stimulating the release of [3H]GABA. Only the release elicited by unlabeled GABA or DAB (by homo- and heteroexchange, respectively) was strongly inhibited in DAB-pretreated synaptosomes. The spontaneous release and the release induced by 56 mM KCl in the presence of CaCl2, by the ionophore A23187, by ouabain, by lack of K+, or by purified black widow spider toxin were unaffected or only barely decreased in DAB-treated synaptosomes, and therefore do not seem to be mediated by the DAB-blocked GABA carrier. 相似文献
55.
The effects of the ionophore A23187 and of ouabain on the release of [3H]GABA and [3H]norepinephrine were studied in superfused rat brain synaptosomes. Each of the two drugs moderately stimulated the spontaneous release of [3H]GABA, but greatly potentiated the release of [3H]GABA induced by unlabeled GABA. In contrast, the ionophore and norepinephrine showed an additive, but not a supraadditive, releasing effect on synaptosomal [3H]norepinephrine. Ouabain modestly and transiently potentiated the norepinephrine-induced [3H]norepinephrine release, which, however, was inhibited by the drug after a few minutes. It is suggested that in the new intrasynaptosomal ionic conditions determined by the two drugs, the stoichiometry of the basal homoexchange of GABA is changed in a direction favoring net outward transport. 相似文献
56.
Gonzalo Almanza Alex E. Clark Valentina Kouznetsova Eduardo Olmedillas Andrea Castro Igor F. Tsigelny Yan Wu George F. Gao Sandra L. Leibel William Bray Erica Ollmann Saphire Aaron F. Carlin Maurizio Zanetti 《PLoS pathogens》2022,18(7)
Successful control of the COVID-19 pandemic depends on vaccines that prevent transmission. The full-length Spike protein is highly immunogenic but the majority of antibodies do not target the virus: ACE2 interface. In an effort to affect the quality of the antibody response focusing it to the receptor-binding motif (RBM) we generated a series of conformationally-constrained immunogens by inserting solvent-exposed RBM amino acid residues into hypervariable loops of an immunoglobulin molecule. Priming C57BL/6 mice with plasmid (p)DNA encoding these constructs yielded a rapid memory response to booster immunization with recombinant Spike protein. Immune sera antibodies bound strongly to the purified receptor-binding domain (RBD) and Spike proteins. pDNA primed for a consistent response with antibodies efficient at neutralizing authentic WA1 virus and three variants of concern (VOC), B.1.351, B.1.617.2, and BA.1. We demonstrate that immunogens built on structure selection can be used to influence the quality of the antibody response by focusing it to a conserved site of vulnerability shared between wildtype virus and VOCs, resulting in neutralizing antibodies across variants. 相似文献
57.
Cutolo M Capellino S Montagna P Ghiorzo P Sulli A Villaggio B 《Arthritis research & therapy》2005,7(5):R1124-R1132
Sex hormones seem to modulate the immune/inflammatory responses by different mechanisms in female and male rheumatoid arthritis
patients. The effects of 17β-oestradiol and of testosterone were tested on the cultured human monocytic/macrophage cell line
(THP-1) activated with IFN-γ in order to investigate their role in cell proliferation and apoptosis. Activated human THP-1
cells were cultured in the presence of 17β-oestradiol and testosterone (final concentration, 10 nM). The evaluation of markers
of cell proliferation included the NF-κB DNA-binding assay, the NF-κB inhibition complex, the proliferating cell nuclear antigen
expression and the methyl-tetrazolium salt test. Apoptosis was detected by the annexin V-propidium assay and by the cleaved
poly-ADP ribose polymerase expression. Specific methods included flow analysis cytometry scatter analysis, immunocytochemistry
and western blot analysis. Cell growth inhibition and increased apoptosis were observed in testosterone-treated THP-1 cells.
Increased poly-ADP ribose polymerase-cleaved expression and decreased proliferating cell nuclear antigen expression, as well
as an increase of IκB-α and a decrease of the IκB-α phosphorylated form (ser 32), were found in testosterone-treated THP-1
cells. However, the NF-κB DNA binding was found increased in 17β-oestradiol-treated THP-1 cells. The treatment with staurosporine
(enhancer of apoptosis) induced decreased NF-κB DNA binding in all conditions, but particularly in testosterone-treated THP-1
cells. Treatment of THP-1 by sex hormones was found to influence cell proliferation and apoptosis. Androgens were found to
increase the apoptosis, and oestrogens showed a protective trend on cell death – both acting as modulators of the NF-κB complex. 相似文献
58.
Maurizio Lambardi Kiran K. Sharma Trevor A. Thorpe 《In vitro cellular & developmental biology. Plant》1993,29(4):189-199
Summary Studies were undertaken to optimize tissue culture conditions for micropropagation of Aleppo pine (Pinus halepensis Mill.) from mature embryos and various explants of the embryo. Over 90% of the embryo explants gave rise to adventitious
buds within 4 wk. Intact embryos were the most suitable explants for shoot bud induction. Both isolated cotyledons and hypocotyls
produced adventitious buds, but these developed slowly and failed to elongate. N6-Benzyladenine (BA) alone at 5.0μM was the most effective cytokinin when added to gelled to gelled von Arnold and Eriksson’s (AE) medium containing 3% sucrose.
Adventitious bud development was achieved on hormone-free AE medium, and shoot elongation was optimum on three quarter-strength
Bornman’s MCM medium, with 0.1% conifer-derived activated charcoal. Shoots were multiplied on three-quarter strength MCM medium,
containing 5μM BA. To induce adventitious roots on the elongated shoots, pulse treatment with 1 mM IBA for 6 h, followed by the transfer of the shoots to sterile peat:vermiculite (1:1) mixture, was beneficial. After acclimatization
for 3 to 4 wk under mist, almost all the rooted shoots could be transplanted successfully to the greenhouse, where the plants
exhibited normal growth habit. Histologic studies on the ontogeny of adventitious shoot formation from mature embryo explants
revealed temporal structural changes in different parts of the explant. Induction of mitotic divisions on the shoot-forming
medium resulted in the formation of meristemoids in the epidermal and subepidermal layers of the explant, located initially
at both the tips of the cotyledons and the axils of adjacent cotyledons. Shoot buds arising in the axils of adjacent cotyledons
were due to new cell division and not to any preexisting meristem. 相似文献
59.
60.
Corrochano S Renna M Tomas-Zapico C Brown SD Lucas JJ Rubinsztein DC Acevedo-Arozena A 《Autophagy》2012,8(3):431-432
Huntington and Parkinson diseases (HD and PD) are two major neurodegenerative disorders pathologically characterized by the accumulation of the aggregate-prone proteins mutant huntingtin (in HD) and α-synuclein (in PD). Mutant huntingtin is an autophagy substrate and autophagy modulators affect HD pathology both in vitro and in vivo. In vitro, α-synuclein levels are able to modulate autophagy: α-synuclein overexpression inhibits autophagy, whereas downregulation promotes autophagy. Here, we review our recent studies showing that α-synuclein levels modulate mutant huntingtin toxicity in mouse models. This phenotypic modification is accompanied by the in vivo modulation of autophagosome numbers in mouse brains from both control and HD mice expressing different levels of α-synuclein. 相似文献