Biomedical subjects

E Simone

Publications and source records attributed to E Simone.

7 recordsLinked to original sources

PubMed2000

Dual overlapping peptides recognized by insulin peptide B:9-23 T cell receptor AV13S3 T cell clones of the NOD mouse.

T cells isolated from islets of non-obese diabetic (NOD) mice are enriched for insulin-reactive cells. The great majority of these T cells recognize insulin B chain peptide (B:9-23). B:9-23 reactive T cell clones are diabetogenic and show a dramatic TCR alpha -chain restriction (predominant AV13S3). We have studied the reactivity of five different B:9-23 reactive T cell clones to truncated peptides and alanine substituted analogues of B:9-23. Amongst these AV13S3 T cell clones, one reacted with peptide B:9-16 and four with B:13-23. The two peptides have in common only four amino acids (B:13-16; EALY). Having defined minimal peptide epitopes, we evaluated a mutant insulin sequence (B:13 glutamine) which retains metabolic activity. As predicted, this single amino acid change abrogated T cell reactivity. In addition, we have created a modified I-A(g7)gene with the B:9-23 peptide covalently linked to I-A(g7). Antigen presenting cells transfected with this construct were excellent presenting cells for all clones studied. The definition of dual peptide motifs and creation of bioactive covalent I-A(g7)-B:9-23 should facilitate studies of the pathogenic significance and antigen recognition by B:9-23 reactive diabetogenic T cells.

Alanine↗

PubMed1998

Chloride-sulphate exchange chemically measured in human erythrocyte ghosts.

The purpose of this paper is to provide a clear description of a new chemical method to measure and analyze the net anion exchange (Cl-/SO4--) in resealed human erythrocyte ghosts. With this technique, we measured the influx of an inorganic divalent anion (SO4--) against a monovalent anion (Cl-) as a function of temperature. We found an apparent activation enthalpy Ea of 21-24 Kcal/mol. Besides the Cl-/SO4-- influx pH - dependence, measured under condition of electric anion equilibrium, shows a bell shape with a maximum around pH 6.3. In addition we accounted for the extracellular pH changes during the exchange of chloride for sulphate across the erythrocyte ghosts when bicarbonate is present in the medium. The pH drops sharply, then increases for the remaining experimental time course.

Antiporters↗

PubMed1997

T cell receptor restriction of diabetogenic autoimmune NOD T cells.

Restricted use of T cell receptor (TCR) gene segments is characteristic of several induced autoimmune disease models. TCR sequences have previously been unavailable for pathogenic T cells which react with a defined autoantigen in a spontaneous autoimmune disease. The majority of T cell clones, derived from islets of NOD mice which spontaneously develop type I diabetes, react with insulin peptide B-(9-23). We have sequenced the alpha and beta chains of TCRs from these B-(9-23)-reactive T cell clones. No TCR beta chain restriction was found. In contrast, the clones (10 of 13) used V alpha13 coupled with one of two homologous J alpha segments (J alpha45 or J alpha34 in 8 of 13 clones). Furthermore, 9 of 10 of the V alpha13 segments are a novel NOD sequence that we have tentatively termed V alpha13.3. This dramatic alpha chain restriction, similar to the beta chain restriction of other autoimmune models, provides a target for diagnostics and immunomodulatory therapy.

Amino Acid Sequence↗

PubMed1996

Chronic autoimmunity of type I diabetes.

A considerable body of data supports the hypothesis that type I diabetes is a chronic progressive autoimmune disorder. Individuals with very high probability of progressing to diabetes can now be readily identified. Assays for autoantibodies reacting with insulin (IAA), glutamic acid decarboxylase (GAD65AA), and the neuroendocrine tyrosine phosphatase ICA512/IA-2 (ICA512AA) allow for the identification of more than 95% of individuals developing type I diabetes. The expression of a single autoantibody does not indicate high risk for diabetes and in general, prediabetic individuals express a series of biochemically defined autoantibodies. Levels of such autoantibodies are usually stable over years of follow-up. Unusual variants of autoantibody expression (e.g. GAD-ICA with high titers of GAD65 autoantibodies as the sole autoantibody) have low prognostic significance. Given the presence of multiple autoantibodies, low first phase insulin secretion (following intravenous glucose) is the best predictor of time to diabetes onset. Measurement of autoantibodies can now be automated and applied to large populations such that screening and prediction in the general population is now feasible. We favor the hypothesis that insulin may be the primary autoantigen for type I diabetes, and therapies which after the immune response to insulin may lead to safe and effective preventive modalities.

Autoantibodies↗

PubMed1988

Reference frame effects on shape perception in two versus three dimensions.

Three experiments are reported in which it is tested whether the Gestalt effect of configural orientation on shape perception operates on two-dimensional (2-D) or three-dimensional (3-D) representations of space. It is known that gravitationally defined squares and diamonds take longer to discriminate in diagonal arrays than in horizontal or vertical arrays. In the first experiment it is shown that this interference effect decreases dramatically in magnitude when pictorial depth information is added so that subjects perceive the target shapes in different depth planes. In the second experiment this difference is shown not to be due to relative size of the target shapes or to occlusion of a background plane. It is also shown, in the final experiment, that this difference is not due to linear perspective information or merely to perception of the target figures in a 3-D scene. The overall pattern of results supports the position that this configural reference frame effect arises primarily when the elements of the configuration are coplanar, and that the principal organization underlying it is the structure of the perceived 3-D environment rather than that of the 2-D image. In all three experiments, however, there is also a small interference effect in the noncoplanar 3-D conditions. This might be due either to some aspect of reference frame selection operating on the 2-D image representation or to the failure of subjects to see depth in the 3-D stimuli on some proportion of the trials.

Attention↗

PubMed1987

Adult height in thalassaemia major without hormonal treatment.

Height and sitting height were measured in all the 28 patients (19 females and 9 males) of our Thalassaemic Centre who exhibited evidence of cessation of growth. Their average final stature, which had been spontaneously achieved at an age ranging from 15.0-21.5 years (mean 17.9), was slightly lower with respect to the mean standards for women (159.1 +/- 8.4 vs 160.0 +/- 6.0 cm) and men (167.8 +/- 6.4 vs 172.5 +/- 6.0 cm). Height deficiency exceeded 2 SD scores in only 3/28 patients. If compared to the familial target height, patients' stature fell within the familial range in 19/24 cases and in only one case was it below the lower limit. In the whole sample the patients' height was positively related to their familial target height (r = 0.72, P less than 0.0002) and also to mid-parental stature (r = 0.45, P less than 0.05). Heights of both females and males were superimposable on those of their own mothers and fathers respectively. Average values of either SH (76.4 +/- 3.8 vs 79.9 +/- 3.4 cm, 2 P less than 0.02) or SH/H ratio (48.9 +/- 2.5 vs 51.5 +/- 1.0, 2 P less than 0.005) were significantly lower in the female thalassaemics than in the sex-matched controls. Three females and one male showed subnormal values of both SH and SH/H ratio. Two out of these patients with eunochoid body proportions and another one with a decreased SH/H ratio have hypogonadotropic hypogonadism and are undergoing a chronic substitutive treatment with sexual hormones, which was instituted after the achievement of final stature.

Adolescent↗

PubMed1975

The coordination of mental health services at the neighborhood level.

The neighborhood health center is becoming a major locus of mental health care delivery. Because of their strategic position at the neighborhood level, mental health care systems in the comprehensive health center locus have been able to develop linkages with both general health and community mental health systems to provide a broad continuum of coordinated health and mental health care. Four models identified in a survey of 19 neighborhood mental health programs are described. The authors suggest that persistent problems in coordination of care between neighborhood mental health and other caregiving systems would be considerably alleviated by a fiscal reimbursement scheme that rewarded integration rather than fragmentation of care.

Community Health Centers↗