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B Gran

Publications and source records attributed to B Gran.

32 records · Page 2Linked to original sources

Predictable TCR antigen recognition based on peptide scans leads to the identification of agonist ligands with no sequence homology.

The potential of CD4+ T cells for cross-recognition of self and foreign Ags has important implications for the understanding of thymic selection, lymphocyte survival, and the occurrence of autoimmune diseases. Here, we define the extensive flexibility of Ag recognition for three human CD4+ autoreactive T cell clones (TCC) by using ligands with single and multiple amino acid (aa) substitutions. Our results demonstrate that the spectrum of tolerated ligands and the resulting stimulatory potency of peptides for a TCC can be predicted by the relative influence of each aa. Using this approach, we have identified stimulatory ligands not sharing a single aa in corresponding positions with the Ag used to establish the TCC. These results argue for an independent contribution of each aa in the peptide sequence to the affinity of the MHC/peptide complex to the TCR.

Amino Acid Sequence↗

Immunosuppressive activity of 13-cis-retinoic acid in rats: aspects of pharmacokinetics and pharmacodynamics.

Pharmacokinetics and pharmacodynamics of 13-cis-retinoic acid (13-cRA) administered at doses that suppress experimental autoimmune encephalomyelitis (EAE) have been investigated in rats. Serum concentration of the drug measured following oral administration of 37 mg/kg/12 h reached a peak of 1.8 x 10(-5) M in 2 h and linearly declined to 7.8 x 10(-7) M at hour 12. When spleen cells (SC) collected from 13-cRA-administered animals were cultured in vitro, their proliferative response to the T-cell mitogen concanavalin A (ConA) was suppressed and this effect was dependent on in vivo serum concentrations of the drug. In addition, in vitro exposure of antigen-specific T-cell lines to 13-cRA concentrations equivalent to those observed in vivo caused a dose-dependent suppression of the proliferation induced by the antigen as well as by T-cell mitogens. On a molar basis, 13-cRA showed a stronger in vitro immunosuppressive activity than two immunosuppressive agents used in human therapy, cyclosporin A and 6-mercaptopurin.

Animals↗

Transforming growth factor-beta 1 inhibits the proliferation of rat astrocytes induced by serum and growth factors.

A number of cytokines and growth factors may affect astrocyte proliferation and functions. Transforming growth factor-beta 1 (TGF-beta 1) is a pleiotropic cytokine which exerts multiple effects on growth and differentiation of different cell types. TGF-beta 1 is present in low amounts in the normal brain. TGF-beta 1 gene expression, however, is increased in the central nervous system (CNS) in several pathological conditions. In this study we examined the in vitro effects of TGF-beta 1 on the proliferative response of rat astrocytes to serum and growth factors. Astrocyte cultures were established from the cerebellum and cortex of newborn Lewis rats. The proliferative response of these cultures to serum and growth factors [platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-1), IGF-2, interleukin 1 (IL-1)] was studied by [3H]-thymidine incorporation test in the presence or absence of TGF-beta 1. TGF-beta 1 significantly inhibited the proliferative response of astrocyte cultures to both autologous and heterologous serum. In addition, a strong inhibition of bFGF-, EGF-, and PDGF-induced proliferation was observed. The effect of TGF-beta 1 on the proliferative response to IL-1 was less evident but still significant. No effect was observed when TGF-beta 1 was added to IGF-1 and IGF-2 stimulated cultures. These data confirm previous reports showing a down-regulating activity of TGF-beta on astrocyte proliferation and suggest that this cytokine may play physiological and pharmacological roles in the regulation of reactive astrocytosis in the CNS.

Animals↗

Major differences in cardiovascular risk indicators by educational status. Results from a population based screening program.

All people aged 30-59 years living in one primary health care center's catchment area were invited to participate in a population based screening program. A total of 2642 people (68%) participated. An overall risk index for having a heart attack within 5 years (Ps) was calculated based on diastolic BP, smoking status, total cholesterol, and age. Other risk indicators registered were Body Mass Index, and physical activity. A highly significant association between education level and age-adjusted overall risk index for both men (p = 0.001) and women (p < 0.001) was found. Also Body Mass Index, total cholesterol, smoking status, and, for women, diastolic blood pressure showed similar significant variation with education level with higher education associated to lower risk. These findings imply the possibility of a great variation in the "risk" of receiving pharmacological treatment for one's CVD risk factors.

Adult↗

Population based CVD health risk appraisal. A method to create a "critical mass" of health-conscious people.

This study used a population based screening procedure as a means for a combined strategy for targeting individuals at high risk of cardiovascular disease while aiming for a low-risk population. During a five month period 68% of the total target population (2642 out of 3880) men and women attended the screening. We found, 1) that a broad population based health risk appraisal activity, supported by a personal computer as an educational tool and as a means to speed up the handling of each test, was feasible, 2) that it was easy to identify high risk individuals, to be able to offer them further follow-up, and 3) that there is evidence supporting the view that reaching a large proportion of the population in a limited time period, a "critical mass", will contribute to a growing health awareness not only among participants but also among the general population in the actual area.

Adult↗

Hemispheric asymmetry for the auditory recognition of true and false statements.

A group of right-handed adult subjects (24 males and 24 females) were asked to judge phrases as to their truthfulness of falsehood, by listening to them via earphones either with the right or with the left ear. These phrases, which had been previously recorded by two non-actors (1 male and 1 female) and two actors (1 male and 1 female), were either true or false. The number of correct judgements made by the subjects was significantly higher than the number of wrong judgements. The subjects correctly recognised significantly more true phrases than false ones. Moreover, they better recognised true phrases pronounced by the actors and false phrases pronounced by the non-actors. True phrases pronounced by male speakers and false phrases pronounced by female speakers were better recognised. A left-ear advantage was found in the recognition of true statements.

Adult↗

Hemispheric specialization for semantic and syntactic components of language in simultaneous interpreters.

Hemispheric specializations for semantic and syntactic components in Italian (L1) and English (L2) were studied with a dichotic listening test, simulating simultaneous interpretation tasks in 24 right-handed female interpretation students at the Scuola Superiore di Lingue Moderne per Interpreti e Traduttori (SSLM) of the University of Trieste and in 12 right-handed female professional interpreters at the European Communities (EEC). The test involved the recognition of correct translations, translations with semantic errors, and translations with syntactic errors from L1 to L2 and vice versa. As an overall result, both students and interpreters gave significantly more correct answers when sentences in L2 as the target language were sent to the left ear. Students recognized significantly more sentences containing syntactic errors than did professional interpreters, while professional interpreters recognized significantly more sentences with semantic errors than did interpreting students. In regard to hemispheric specialization in interpreting students, no significant asymmetries were revealed in the recognition of semantic and syntactic errors. Professional interpreters showed a significant right-ear superiority in recognizing semantic errors in L1 and a significant left-ear superiority in recognizing semantic errors in L2. In the recognition of syntactic errors, professional interpreters showed significant left-ear superiority for L1 and significant right-ear superiority for L2. The prolonged practice in simultaneous interpreting strategies in EEC professional interpreters may account for some of their peculiar hemispheric specializations for languages revealed by this study.

Adult↗

Non-pharmacological methods reduce drug use in the treatment of hypertension. A two-year trial in general practice.

In a primary-care based study, 122 patients who were taking antihypertensive drugs took part in a two-year trial that aimed at establishing the feasibility of non-pharmacological methods in the treatment of hypertension in general practice. The patients could choose from among 14 non-pharmacological methods of blood pressure reduction. Increased physical exercise; weight reduction, low-sodium and low-fat diet, relaxation training, and home-monitoring of blood pressure were the most popular methods. The use of anti-hypertensive drugs was reduced by 55% in the participants, with the defined daily dose (DDD) being lowered from 1.18 to 0.55 (P less than 0.001). At the end of the study, 46% of the participants were free from anti-hypertensive drugs. Significant reductions occurred in body mass index (27.1 to 26.4 kg/m2, P = 0.001) and serum cholesterol (6.89 to 6.48 mmol/l, P less than 0.001). According to some measures used, the study group's experience of "quality of life" was not reduced.

Adult↗