Showing papers by "University of Perugia published in 1989"

Stochastic resonance in bistable systems.

Abstract: The relaxation properties of a stochastic bistable system perturbed by a periodic low-frequency forcing term is investigated by means of analog simulation. The so-called stochastic resonance phenomenon is revealed under diverse experimental conditions. Its dependence on the parameters of both the periodic perturbation and the forced system is explained theoretically.

Frontal lobe dysfunction in Parkinson's disease: prognostic value for dementia?

Abstract: The purpose of this longitudinal study was to investigate if the presence of frontal motor deficits in parkinsonians without signs of global intellectual impairment may have a predictive value for the development of a progressive dementing process during the course of the illness. An examination of the higher level of motor organization, using skills thought to depend upon the integrity of the frontal regions, was performed by 30 parkinsonian patients who did not present any signs of general intellectual impairment. According to their performance, as compared with controls, they were divided into two subgroups: those with and those without frontal dysfunctions. After a mean period of 4 years, a second neuropsychological examination was carried out to assess any eventual change of mental status. The results suggest that frontal dysfunctions may be observed several years before the appearance of generalized intellectual impairment and may be considered one of the predictive factors for development of dementia in Parkinson’s disease. Careful consideration of these defects during examination of motor abilities may be of value in the clinical management of parkinsonian patients.

Distribution of T cells bearing different forms of the T cell receptor gamma/delta in normal and pathological human tissues.

Abstract: Frozen sections from normal and pathologic human tissues were immunostained by the APAAP technique with three mAb directed against different epitopes of the TCR gamma delta; TCR delta 1 which binds to all cells bearing the TCR gamma delta; BB3 and delta TCS1 which, by immunoprecipitation studies, appear to react respectively with the disulfide-linked and nondisulfide-linked form of the TCR gamma delta. In normal thymus, TCR delta 1+ cells accounted for approximately 2% of the CD3+ thymocytes and were about three times more numerous in the medulla than in the cortex. TCR delta 1+ cells were mostly constituted by the delta TCS1 reactive subset (average ratio delta TCS1/BB3: 3.7). In the tonsil, the TCR delta 1+ cells (about 3% of CD3+ elements) were mainly located in the interfollicular area, where they frequently tended to arrange around high endothelium venules. In most samples, TCR delta 1+ cells were distributed beneath to the tonsil epithelium. Unlike thymus, the majority of TCR delta 1+ cells were usually constituted by the BB3-reactive subset (average BB3/delta TCS1 ratio: 2.0). A similar predominance of BB3+ over delta TCS1+ cells was also observed in normal peripheral blood. The spleen was the organ with the highest concentration of TCR delta 1+ cells that, like in the thymus, were mostly represented by delta TCS1+ elements. Noteworthy, the TCR delta 1+ cells were preferentially located in the splenic sinusoids while TCR alpha beta-bearing lymphocytes mostly occupied the periarteriolar sheaths of penicilliary arteries. The majority of neoplastic T cell proliferations studied lacked to express the TCR gamma delta. Two cases of beta F1-(TCR alpha beta-) T lymphoblastic lymphoma, however, were TCR gamma delta+ (delta TCS1+/BB3-). Both of them showed a stage II cortical phenotype, e.g., CD1+/CD3+/CD4+/CD8+/TCR delta 1+. Among inflammatory conditions, an increase of BB3+ cells was observed in close association with necrotic areas in cases of Kikuchi's and tuberculous lymphadenitis. The significance of this finding is under study.

Heterogeneity of Hematopoietic Cells Immortalized by v-myc/v-raf Recombinant Retrovirus Infection of Bone Marrow or Fetal Liver

Abstract: The J2 recombinant retrovirus expressing v-myc/v-raf (also known as MYC/RAF1) immortalized macrophages from the bone marrow of lipopolysaccharide-responsive mouse strains, producing the ANA-1 cell line from C57BL/6 mice and the INF-3A cell line from C3H/HeN mice. In contrast, J2 recombinant retrovirus infection of the fetal liver from C57BL/6-Ly-5a mice immortalized a cell line (GGD) that did not exhibit the characteristics of mature macrophages. The GGD cell line was classified as leukocytic on the basis of its expression of the Ly-6B.2, Fc gamma R, and Ly-5.2 antigens. Our results indicate that the J2 recombinant retrovirus selectively immortalizes macrophages from the bone marrow of C57BL/6 and C3H/HeN mice but immortalizes cells without definitive macrophage characteristics from murine fetal liver under the same culture conditions.

Contribution of cortisol to glucose counterregulation in humans

Abstract: To test the hypothesis that cortisol secretion plays a counterregulatory role in hypoglycemia in humans, four studies were performed in eight normal subjects. In all studies, insulin (15 mU.m-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 1 microU/ml). In study 1, plasma glucose concentration and glucose fluxes [( 3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored, and plasma glucose decreased from 89 +/- 2 to 52 +/- 2 mg/dl for 12 h. In study 2, (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretion (except for catecholamines) was prevented by somatostatin (0.5 mg/h, iv) and metyrapone (0.5 g/4 h, per os), and glucagon, cortisol, and growth hormone were infused to reproduce the concentrations of study 1. In study 3 (lack of cortisol increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma cortisol at basal levels, and glucose was infused, whenever needed, to reproduce plasma glucose concentration of study 2. Study 4 was identical to study 3, but exogenous glucose was not infused. Isolated lack of cortisol increase caused a approximately 22% decrease in hepatic glucose production (P less than 0.01) and a approximately 15% increase in peripheral glucose utilization (P less than 0.01), which resulted in greater hypoglycemia (37 +/- 2 vs. 52 +/- 2 mg/dl, P less than 0.01) despite compensatory increases in plasma epinephrine. Lack of cortisol response also reduced plasma free fatty acid, beta-hydroxybutyrate, and glycerol concentrations approximately 50%. We conclude that cortisol normally plays an important counterregulatory role during hypoglycemia by augmenting glucose production, decreasing glucose utilization, and accelerating lipolysis.

Periodically time-modulated bistable systems: Stochastic resonance

Abstract: We characterize the notion of stochastic resonance for a wide class of bistable systems driven by a periodic modulation. On developing an adiabatic picture of the underlying relaxation mechanism, we show that the intensity of the effect under study is proportional to the escape rate in the absence of perturbation. The adiabatic model of stochastic resonance accounts for the role of finite damping and finite noise correlation time as well. Our predictions compare well with the results of analogue simulation.

Principal Properties for Aromatic Substituents. A Multivariate Approach for Design in QSAR

Abstract: A set of a hundred aromatic substituents were multivariately characterized by nine descriptor variables taken from the literature. From the 9*100 data set were calculated four principal properties for the aromatic substituents as the four first dimensions in a principal components analysis, PCA. The first three principal properties were used to develop a strategy for selecting substituents from eight subgroups according to a factorial design.

Demonstration of a role for growth hormone in glucose counterregulation

Abstract: To test the hypothesis that growth hormone secretion plays a counterregulatory role in prolonged hypoglycemia in humans, four studies were performed in nine normal subjects. Insulin (15 mU.M-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 2 microU/ml), and plasma glucose decreased from 88 +/- 2 to 53 +/- 1 mg/dl for 12 h. In study 1, plasma glucose, glucose fluxes (D-[3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored. In study 2 (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretions (except for catecholamines) were prevented by somatostatin (0.5 mg/h iv) and metyrapone (0.5 g/4 h po), and glucagon, cortisol, and growth hormone were reinfused to reproduce the concentrations of study 1. In study 3 (lack of growth hormone increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma growth hormone at basal levels, and glucose was infused whenever needed to reproduce plasma glucose concentration of study 2. Study 4 was identical to study 3, but exogenous glucose was not infused. Isolated lack of a growth hormone response caused a decrease in hepatic glucose production and an increase in glucose utilization that resulted in an approximately 25% greater hypoglycemia despite compensatory increases in plasma catecholamines. Plasma free fatty acid, 3-beta-hydroxybutyrate, and glycerol concentrations were reduced approximately 50%. It is concluded that growth hormone normally plays an important counterregulatory role during hypoglycemia by augmenting glucose production, decreasing glucose utilization, and accelerating lipolysis.

Role of L3T4+ lymphocytes in protective immunity to systemic Candida albicans infection in mice.

Abstract: Protective immunity to lethal Candida albicans challenge in vivo and activation of splenic macrophages with highly candidacidal activity in vitro were detected in mice infected with low-virulence agerminative yeast cells of the variant strain PCA-2, at a time when a strong delayed-type hypersensitivity (DTH) reaction to C. albicans occurred in the footpads of PCA-2-treated mice. The DTH reaction was transferable with spleen cell populations from these animals, and enrichment of splenic lymphocytes in L3T4+ cells significantly increased the footpad swelling. The reactivity transferred by L3T4+ cells was a radiosensitive (2,500 rads in vitro) phenomenon that required collaboration with radioresistant, silica-sensitive syngeneic cells in the host and was inhibited by treatment of recipient mice with antibodies to the L3T4 antigen or murine gamma interferon. In vitro, the PCA-2-immune L3T4+ cells produced various lymphokine activities upon incubation with C. albicans, including gamma interferon and granulocyte-macrophage colony-stimulating factor. Anti-L3T4 monoclonal antibody treatment of PCA-2-infected mice significantly impaired their footpad reaction and resistance to C. albicans, as shown by increased recovery of yeast cells from the kidneys of anti-L3T4-treated mice. These results suggested that the mechanisms of anti-Candida resistance induced by PCA-2 may involve specific induction of a DTH response mediated by inflammatory L3T4+ T cells and lymphokine-activated phagocytic effectors. However, the survival rate of the PCA-2-immune mice challenged with C. albicans was not significantly modified by administration of the anti-L3T4 antibody, thus allowing for the conclusion that compensatory mechanisms lead to considerable anti-Candida resistance when the activity of L3T4+ cells is deficient.

Effects of physical training on peripheral vascular disease: a controlled study.

Abstract: The effects of physical exercise on 8 stage II peripheral vascular disease (PVD) patients were observed after a six-month training program. Doppler velocimetry (including the treadmill test), strain gauge plethysmography, and transcutaneous oxygen pressure were used to quantify the results, which were compared with those obtained in a control group of another 8 stage II PVD patients, under placebo therapy for six months. The results show physical exercise increased the walking capacity, both the pain-free walking time and the maximum walking time. No significant difference was observed in the other parameters studied, in either the exercise patients or the control group.

A predictive study on the beginning of the pollen season for Gramineae and olea europaea L.

Abstract: On the basis of the results of seven years (1982–1988) of pollen and meteorological monitoring in the atmosphere of Perugia and Ascoli Piceno (central Italy) beginning of pollen season forecasts for Gramineae and Olea europaea L. are reported. The beginning of the pollen season for grass varied between May 2 nd and May 27th while for Olea it varied between May 26 th and June 23rd. By a statistical analysis of these data several significant correlations were found between the onset of the principal period of pollination and the air temperature in the preceding months and the number of «heat units» required to flower. Utilizing multiple regressions a predictive method of the beginning of pollen season for both the taxa is reported.

Characterization of N,N'-bis(3-picolyl)-4-methoxy-isophtalamide (picotamide) as a dual thromboxane synthase inhibitor/thromboxane A2 receptor antagonist in human platelets.

Abstract: Picotamide (G137 or N,N'-bis[3-picolyl]-4-methoxy-isophtalamide), a drug which has shown platelet inhibitory effects in vitro and ex vivo, was investigated for its mechanism of action on human platelets in vitro. This compound suppresses the aggregation of human platelets induced by arachidonic acid (IC50: 1.8 x 10(-5) M), low-dose collagen (IC50: 3.5 x 10(-4) M), U46619 (IC50: 1 1.4 x 10(-4) M) and by authentic TxA2 (IC50: 1 x 10(-4) M), without affecting the aggregation induced by A23187 or primary aggregation by ADP. Picotamide inhibits dose-dependently TxA2 synthesis by platelets (IC50: 1.5 x 10(-4) M) and enhances the formation of PGE2. Picotamide-treated platelets also favour the formation of PGI2 by aspirinated endothelial cells; in addition, the drug appears to exert a direct stimulatory effect on PGI2-synthesis, at least at high concentrations. Finally, in platelet-rich plasma stimulated with arachidonic acid, picotamide increases intraplatelet cAMP while no effects on cAMP are detected in unstimulated platelets. In conclusion, picotamide is a dual thromboxane-synthase inhibitor/thromboxane-receptor antagonist in human platelets and introduces a new class of agents potentially useful in antithrombotic therapy.

Periodically time-modulated bistable systems - nonstationary statistical properties

Abstract: The relaxation properties of a one-dimensional overdamped system modulated by an external periodic force are studied analytically by means of a perturbation approach. The validity of the approximations introduced is discussed in detail. The nonstationary nature of the process is illustrated by evaluating explicitly the autocorrelation function for the relaxation in a bistable potential. The predictions thus obtained are shown to compare favorably with the results of analogue simulation for the case of a quartic double-well potential. The stochastic resonance mechanism is proven to set in only when the periodic perturbation breaks the symmetry of the bistable potential.

Comparative study of airborne pollen concentrations in central Italy and the Netherlands (1982–1985)

Abstract: Airborne pollen concentrations, measured continuously with a volumetric method at two places in central Italy and in The Netherlands, are compared with respect to both their quantitative and seasonal aspects. Special attention was given to three taxa which occur in the two geographically distinct regions and are known to cause allergic sensitization: Alnus (alder), Poaceae (wild grasses), and Artemisia (mugwort). Averagely, total pollen concentrations are slightly higher in central Italy. The start and the main period in early spring of the season of Alnus pollen, which is more common in The Netherlands, is rather variable from year to year, in both regions correlated with the air temperature in the preceding months. Poaceae pollen, making up to 10 to 20% of the total annual pollen concentrations in both regions, has its start and main season in late spring about one month earlier in central Italy than in The Netherlands, strongly correlated with air temperatures in April and May. The main period...

Activation of cord T lymphocytes. I. Evidence for a defective T cell mitogenesis induced through the CD2 molecule.

Abstract: A study was carried out on cord blood T cell activation via the CD2-mediated pathway. Despite similar percentages of circulating CD3+ and CD2+ cells in adult and cord blood, the proliferation of cord PBMC to the anti-CD3 mAb and cord T cells to anti-CD2 mAb were defective. The T cell CD3-surface structure was normally able to control CD2-mediated activation, as its modulation by a non-mitogenic anti-CD3 mAb blocked cord PBMC proliferation induced by anti-CD2 mAb. CD2-stimulated cord T cells did not proliferate and did not produce a significant amount of IL-2 in culture, although they expressed the IL-2R. This observation was confirmed by the optimal proliferation of CD2-induced cord T cells when rIL-2 was added. Despite the alternative T cell activation pathway is monocyte-independent in adults, the defective cord T cell activation via the CD2 molecule could also be bypassed by the addition of PMA, small amounts of either autologous or allogeneic adult and cord AC or simply rIL-1 alone. Our findings provide evidence for an intrinsic functional defect in cord CD2-mediated T cell activation, which is linked to an impaired increase of free cytoplasmic calcium, as confirmed by the effectiveness of calcium ionophore A23187 in restoring a good CD2-induced cord T cell proliferation and by measurement of cellular calcium uptake after activation via the CD2 molecule. The characteristics of cord T cells revealed by this study recall the thymocyte functional pattern and may represent functional expression of the previously described phenotypic immaturity of cord T cells.

Immunocytochemical localization of S-100b protein in degenerating and regenerating rat sciatic nerves

Abstract: We studied the cellular and subcellular distribution of S-100b protein in normal, crushed, and transected rat sciatic nerves by an immunocytochemical procedure. In uninjured nerves, S-100b protein was restricted to the cytoplasm and membranes of Schwann cells, with no reaction product present in the nucleus or in axons. Similar images were seen from the first to the thirtieth day after the crush in activated Schwann cells during the degeneration period, i.e., up to the seventh post-lesion day, and in normal Schwann cells reappearing during the regeneration period, i.e., after the seventh post-lesion day, in the zone of the crush and proximal and distal to it. By the technique employed, there seemed to be no differences in the intensity of the immune reaction product in normal and activated Schwann cells. Also, similar images were seen in the proximal stump of transected nerves. Only a slight S-100b protein immune reaction product could be observed in the rare activated Schwann cells present in the distal stump around the seventh post-lesion day, the majority of cell types being represented by fibroblasts and elongated cells at this stage and thereafter. By immunochemical assays, similar results as those presented here have been reported and interpreted as indicative of the presence of S-100 protein in axons or, alternatively, of axonal control over expression of S-100 protein in Schwann cells. Our immunocytochemical data clearly show that the strong reduction in the S-100 protein content of the distal stump of transected nerves is owing to the paucity of Schwann cells and to the decrease in the S-100 protein content of these cells, rather than to degeneration of axons.

Evolutionary conservation in various mammalian species of the human proliferation-associated epitope recognized by the Ki-67 monoclonal antibody

Abstract: The human proliferation-associated epitope recognized by the Ki-67 monoclonal antibody (MAb) was detected in proliferating normal and neoplastic cells of many mammalian species (lamb, calf, dog, rabbit, rat) besides human. In contrast, Ki-67 stained proliferating cells from other species weakly (mouse) or not at all (swine, cat, chicken, pigeon). The immunostaining pattern of Ki-67 in animal tissues was identical to that previously described in human: Ki-67 reacted only with cells known to proliferate (e.g., germinal center cells, cortical thymocytes) but not with resting cells (e.g., hepatocytes, brain cells, renal cells); this MAb produced a characteristic nuclear staining pattern (e.g., stronger labeling of nucleoli than of the rest of the nuclei and staining of chromosomes in mitotic figures); and Ki-67 crossreacted with the squamous epithelium in both animal and human tissues. In vitro studies showed that when quiescent (Ki-67-negative) NIH 3T3 fibroblasts or bovine peripheral blood lymphocytes were ...