פרסומים

BACKGROUND: Eotaxin/CCL11 plays an important role in asthma. It acts through the chemokine receptor CCR3 expressed on hematopoietic and nonhematopoietic cells in the lung. OBJECTIVE: To determine whether eotaxin/CCL11 modulates lung and bronchial fibroblast properties and thereby might contribute to airway remodeling. METHODS: CCR3 expression was characterized on a lung fibroblast line (MRC-5; flow cytometry, fluorescent microscopy, RT-PCR, and Northern blotting), on primary bronchial fibroblasts (flow cytometry), and on fibroblasts in human lung tissue (confocal laser microscopy). The effects of eotaxin/CCL11 on lung fibroblast migration (Boyden chamber), proliferation (tritiated thymidine incorporation), alpha-smooth muscle actin expression (ELISA), 3-dimensional collagen gel contraction (floating gel), pro-alpha1(I) collagen mRNA (Northern blotting), total collagen synthesis (tritiated proline incorporation), matrix metalloproteinase activity (gelatin zymography), and TGF-beta(1) release (ELISA) were evaluated. The contribution of eotaxin/CCL11/CCR3 binding on lung fibroblasts was also investigated by neutralizing experiments. RESULTS: CCR3 is constitutively expressed in cultured lung and primary bronchial fibroblasts and colocalizes with specific surface markers for human fibroblasts in lung tissue. Eotaxin/CCL11 selectively modulates fibroblast activities by increasing their proliferation, matrix metalloproteinase 2 activity, and collagen synthesis but not their differentiation into myofibroblasts, contractility in collagen gel, or TGF-beta(1) release. Eotaxin/CCL11 enhances migration of lung fibroblasts in response to nonspecific chemoattractants, and this effect is completely inhibited by anti-CCR3-neutralizing antibodies. CONCLUSION: These data demonstrate that eotaxin/CCL11 has a direct and selective profibrogenic effect on lung and bronchial fibroblasts, providing a novel mechanism whereby eotaxin/CCL11 can participate in airway remodeling in asthma.

Eosinophils are involved in a variety of allergic, parasitic, malignant, and idiopathic disorders by releasing a variety of factors including specific granule proteins, lipid mediators, and proinflammatory and immunoregulatory cytokines and chemokines. In addition, they interact with various cell types in the inflamed tissue. Yet, the mechanism of eosinophil activation is still poorly understood. Recently, we described the expression and function of the CD2-subfamily of receptors and especially 2B4 on human eosinophils. In this study we focus on CD48, the high-affinity ligand of 2B4. CD48 is a GPI-anchored protein involved in cellular activation, costimulation, and adhesion, but has not been studied on eosinophils. We demonstrate that human eosinophils from atopic asthmatics display enhanced levels of CD48 expression and that IL-3 up-regulates CD48 expression. Furthermore, cross-linking CD48 on human eosinophils triggers release of eosinophil granule proteins. Assessment of CD48 expression in a murine model of experimental asthma revealed that CD48 is induced by allergen challenge and partially regulated by IL-3. Additionally, anti-IL-3 reduces CD48 expression and the degree of airway inflammation. Thus, CD48 is an IL-3-induced activating receptor on eosinophils, likely involved in promoting allergic inflammation.

Fifteen years ago the gene responsible for cystic fibrosis (CF), the most common severe autosomal recessive disorder among Caucasians, was identified. In this chapter we describe the cloning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the spectrum of the CFTR mutations and classification of the mutations by their mechanisms of CFTR dysfunction. Last but not least, we summarize the contribution of all these data to the development of mutation-specific therapy.

In the present report the changes in mussels Mytilus galloprovincialis protein profile, as a reaction of water pollution, is presented. The antioxidant capacity was determined by the efficacy to scavenge the derived radical in mussel samples using the Trolox Equivalent Antioxidant Capacity (TEAC) assay. The highest percentage of inhibition was estimated in protein mussels from the dirty area (DM) in comparison with the clean samples (CM). The amounts of both zinc and copper determined by atomic spectroscopy were significantly higher in the protein mussels from the dirty than from the clean areas (P<0.05). Fourier Transform Infrared (FT-IR) spectroscopy and fluorescence revealed specific qualitative changes in secondary and tertiary structures of mussel proteins from the dirty area by the shift in the amides I and II positions and fluorescence intensity. Estimated temperature and enthalpy of denaturation in the protein mussels well correlated with fluorescence and spectroscopic measurements and showed the changes influenced by water pollution.

Long chain n-alkanethiol self-assembled monolayers (SAMs) on a hanging Hg drop electrode were studied in detail for the 1st time by impedance spectroscopy (IS) and potentiometry. IS reveals the detailed behavior of the monolayers in the absence and presence of 2 1-electron redox couple: hexaammineruthenium(III) (Ru(NH3)63+) and tris(2,2’-bipyridine)cobalt(III) (Co(bpy)33+). The pinholes-free layers behave as almost ideal capacitors and are permeable to some extent to redox species, depending on their hydrophobicity. Co(bpy)33+ that exhibits sluggish kinetics on a bare Hg electrode reveals a more facile kinetics than Ru(NH3)63+ on an n-octadecanethiol/Hg interface. Potentiometric measurements recorded upon immersing the bare and SAM modified Hg electrode into a soln. contg. a mixt. of the oxidized and reduced forms of the redox couples provide invaluable information on the charge transfer across the monolayer and its ohmic resistance. While Ru(NH3)63+ cannot freely penetrate into the monolayer and therefore establishes a p.d. across the monolayer; penetration of Co(bpy)32+ into the film causes the Fermi level of the Hg surface to attain the Nernst potential of the soln. Finally, increasing the length of the alkane chain of the thiols increases linearly the ohmic resistance of the layer. [on SciFinder(R)]

Organoleptically acceptable chewing gums (composed of a gum base, at least one edible acid, and optionally other ingredients) are characterized by high adherence to plaque bacteria. Thus, a ratio between gum base and malic acid of 60:1.8 may be used. A method for prepg. the chewing gum includes triturating a coloring agent (e.g., carmoisine). A method for com. producing and marketing the chewing gums includes testing the chewing gums for adhesion to bacteria, such as plaque bacteria. [on SciFinder(R)]

Even with ample time and data at their disposal, people often make do with small samples, which increases their risk of making the wrong decision. A theoretical analysis indicates, however, that when the decision involves selecting among competing, adaptive agents who are eager to be selected, an error-prone evaluation may be beneficial to the decision maker. In this case, the chance of an error can motivate competitors to exert greater effort, improving their level of performance which is the prime concern of the decision maker. This theoretical argument was tested empirically by comparing the effects of two levels of scrutiny of performance. Results show that minimal scrutiny can indeed lead to better performance than full scrutiny, and that the effect is conditional on a bridgeable difference between the competitors. We conclude by pointing out that error-prone decisions based on small samples may also maintain competition and diversity in the environment.

A vast corpus of Sanskrit poetry (kāvya) was produced over the last thousand years; most of these works reveal a vital and organic relation to the crystallising regional traditions of the subcontinent and to emerging vernacular literatures. Thus we have, for example, the Sanskrit literatures of Kerala, of Bengal-Orissa, of Andhra, and so on. These works, often addressed primarily to local audiences, have remained largely unknown and mostly undervalued, despite their intrinsic merits and enormous importance for the cultural history of India. We explore the particular forms of complex expressivity, including rich temporal and spatial modalities, apparent in such poems, focusing in particular on Vedânta Deśika's Hamsasandeśa, a fourteenth-century messenger-poem modelled after Kālidāsa's Meghasandeśa. We hypothesise a principle: as localisation increases, what is lost in geographical range is made up for by increasing depth. Sanskrit poetry thus comes to play a critical, highly original role in the elaboration of regional cultural identities and the articulation of innovative cultural thematics; a re-conceptualised ecology of Sanskrit genres, including entirely new forms keyed to local experience, eventually appears in each of the regions. In short, rumours of the death of Sanskrit after 1000 A.D. are greatly exaggerated.

Mast cell development, function, and survival are likely to be regulated by a complex interplay of cellular signaling. Usually, these signals derive from the cellular milieu associated with the specific mast cell environment in health or disease conditions. A major methodological issue in studying in vitro mast cells, as well as any other tissue dwelling cell, is the essential lack of all the tissue-derived signals. Because some of the signals can be unknown, the in vivo system they form is virtually impossible to mimic completely in vitro. The mast cell-fibroblast co-culture system partially overcomes this problem and is the main topic of this chapter. The experimental importance of mast cell-fibroblast co-culture for the mast cells derives mainly from two reasons: first, fibroblasts constitute a major cellular scaffold of the tissues where mast cells dwell in the body, and as such are one of the fundamental cells participating in mast cell regulation in vivo and, second, there is an analogy with the traditional model of allergic inflammation, where the late, chronic phase is characterized by mast cell-structural cell crosstalk and eventual fibrotic outcome. Therefore, the co-culture system can be viewed as a suitable tool to investigate mast cell-fibroblast crosstalk.