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Biomedical subjects

F Sinigaglia

Publications and source records attributed to F Sinigaglia.

159 records · Page 9Linked to original sources

Identification of a sialoglycopeptide released by self-digestion from human erythrocyte membranes.

Membranes from human O Rhesus-positive erythrocyte 'ghosts' were tested in vitro for their ability to digest their own glycoproteins. 'Ghost' membranes incubated in Tris/HCl buffer, pH 7.4, release a sialoglycopeptide, which contains glucosamine, galactosamine, galactose and mainly polar amino acids. Chemical composition, molecular size and aggregation properties suggest that this glycopeptide may be a fragment of glycophorin.

Chromatography, Gel↗

Proliferative responses to selected peptides of IA-2 in identical twins discordant for Type 1 diabetes.

BACKGROUND: The aim of the study was to define T lymphocyte reactivity to selected peptides of an islet antigen IA-2, associated with Type 1 diabetes. METHODS: We used 10 peptides selected from the IA-2 molecule due to their predicted ability to bind to HLA-DRB1*0401, a Type 1 diabetes-associated allele. We tested 21 identical twin pairs discordant for the disease and 15 control subjects and then followed them prospectively; seven non-diabetic twins developed diabetes. RESULTS: Twins of identical pairs tended to respond to different peptides suggesting that the T cell response is, to a degree, shaped by non-genetically determined factors (p<0. 0001). However, there was no difference in the T cell responses between diabetic twins and either their non-diabetic identical twins or control subjects and the response was heterogenous. T cell responses did not differ in those seven non-diabetic twins who developed diabetes from those twins who did not. T cell responses to peptide 11 (amino acids 502-514) was immunodominant in diabetic twins as well as their non-diabetic twins and controls; responses were not correlated with HLA, IA-2 antibodies, age or duration of disease. CONCLUSION: We conclude that T cell responses to selected IA-2 peptides are not genetically determined, heterogeneous, not strictly HLA controlled and did not distinguish diabetic or prediabetic twins from non-diabetic twins or controls. The identification of an immunodominant T cell response to IA-2 peptide 502-514 raises the possibility that this, or similar, epitopes may be of therapeutic value in disease prevention.

Adolescent↗

Type I interferons and the Th1/Th2 paradigm.

During the past year significant advances have been made in our understanding of the factors contributing to the differentiation of CD4+ T helper cell subsets. These have been driven, in part, by the realization that cytokines from the innate immune response, such as interleukin-12 (IL-12) and interferons (IFNs), play a critical role in T cell subset differentiation. This review covers some of the most recent data concerning the divergent role that IFNs have in the differentiation of human versus mouse T helper cell subsets. In this review we discuss the molecular basis for the specie-specific effect of type I IFN on the selective induction of Th1 type immune responses. Furthermore, since IFN-beta is used in the treatment of multiple sclerosis (MS) we discuss the potential effects of such treatment and the value of the Th1/Th2 paradigm in MS.

Animals↗

A malaria T-cell epitope recognized in association with most mouse and human MHC class II molecules.

An ideal vaccine should elicit a long lasting immune response against the natural parasite, both at the T- and B-cell level. The immune response should occur in all individuals and be directed against determinants that do not vary in the natural parasite population. A major problem in designing synthetic peptide vaccines is that T cells generally recognize peptide antigens only in association with one or a few of the many variants of major histocompatibility complex (MHC) antigens. During the characterization of epitopes of the malaria parasite Plasmodium falciparum that are recognized by human T cells, we analysed a sequence of the circumsporozoite protein, and found that synthetic peptides corresponding to this sequence are recognized by T cells in association with many different MHC class II molecules, both in mouse and in man. This region of the circumsporozoite protein is invariant in different parasite isolates. Peptides derived from this region should be capable of inducing T-cell responses in individuals of most HLA-DR types, and may represent good candidates for inclusion in an effective anti-malaria peptide vaccine.

Amino Acid Sequence↗

Changes in composition of platelet membranes after "in vitro" incubation.

Platelet membranes were isolated by the glycerol lysis technique and incubated in Krebs-Ringer phosphate buffer, to determine their chemical modifications occurring during "in vitro" incubation. The main changes observed at the end of the incubation consist in a significant loss of protein components and in the nearly equimolar decrease of sialic acid and galactosamine. Aminoacid analysis indicate that mainly polar aminoacids are lost. SDS-polyacrylamide gel electrophoresis indicates that high molecular weight proteins disappear after incubation, while no relevant differences in the relative ratios between PAS-stained bands were evident. The reported modifications are quite similar to those described in the membranes of in vivo and in vitro aged red cells.

Amino Acids↗

Cryopreservation of human platelets using dimethyl sulfoxide and glycerol-glucose: effects on "in vitro" platelet function.

BACKGROUND: The technique of freezing blood platelets could be very useful in the transfusion support of thrombocytopenic patients. The best method of platelet cryopreservation still remains an object of debate, though it has been suggested that dimethyl sulfoxide (DMSO) is more effective than glycerol-glucose as a cryopreservative. However, few studies have directly compared platelets cryopreserved with different methods. METHODS: We compared "in vitro" function of platelets cryopreserved with 5% dimethyl sulfoxide (DMSO) or 3% glycerol-glucose at -140 degrees C. Platelet aggregation and release reaction were studied with a Lumi aggregometer, thromboxane B2 (TxB2) production by radioimmunoassay, and Ca++ movement by the Fura 2 method. RESULTS: Cryopreservation with both of the methods dramatically reduced the ability of platelets to release ATP and to aggregate in response to single agonists. In contrast, cryopreserved platelets maintained their ability to aggregate after stimulation with paired agonists and to produce TxB2. Cytoplasmic Ca++ increase induced by thrombin was observed in the glycerol-preserved platelets, while it was nearly absent in the DMSO-preserved ones. CONCLUSIONS: We suggest that cryopreservation with glycerol-glucose or DMSO induces similar defects of platelet function. The damage is severe, but platelets are still able to respond to strong stimulation.

Blood Platelets↗