Phenotype of T cell clones obtained from bronchial biopsies and peripheral blood from three asthmatics.

Establishment of T cell clones derived from bronchial biopsies and peripheral blood from allergic asthmatics has shown that they secret a different IL-4 and IFN-γ pattern of cytokines, suggesting that the micro-environment of the bronchi may influence the phenotype of the T cells.     

Modelling the growth of a methanotrophic biofilm: Estimation of parameters and variability

This article discusses the growth of methanotrophic biofilms. Several independent biofilm growths scenarios involving different inocula were examined. Biofilm growth, substrate removal and product formation were monitored throughout the experiments. Based on the oxygen consumption it was concluded that heterotrophs and nitrifiers co-existed with methanotrophs in the biofilm. Heterotrophic biomass grew on soluble polymers formed by the hydrolysis of dead biomass entrapped in the biofilm. Nitrifier populations developed because of the presence of ammonia in the mineral medium. Based on these experimental results, the computer program AQUASIM was used to develop a biological model involving methanotrophs, heterotrophs and nitrifiers. The modelling of six independent growth experiments showed that stoichiometric and kinetic parameters were within the same order of magnitude. Parameter estimation yielded an average maximum growth rate for methanotrophs, μ_m, of 1.5 ± 0.5 d⁻¹, at 20 °C, a decay rate, b_m, of 0.24 ± 0.1 d⁻¹, a half saturation constant, , of 0.06 ± 0.05 mg CH₄/L, and a yield coefficient, , of 0.57 ±: 0.04 g X/g CH₄. In addition, a sensitivity analysis was performed on this model. It indicated that the most influential parameters were those related to the biofilm (i.e. density; solid-volume fraction; thickness). This suggests that in order to improve the model, further research regarding the biofilm structure and composition is needed.     

Synthesis and biological evaluation of conformationally restricted derivatives of tryptophan as NK1/NK2 ligands

Chemical modifications on the NK₁ competitive antagonist L-732,138, with a view to creating a dual NK₁/NK₂ ligand, led to the tryptophan derivative 1 possessing the protected Gly-Leu sequence of the C-terminus of substance P and neurokinin A. Modifications in the nature of the carbamate function increased the selectivity for the NK₁ receptor, whereas the inclusion of the indole moiety in -carboline or carbazole rings decreased the affinity for both receptors. Free indolylmethyl and Cbz carbamate groups were shown to be essential for NK₂ affinity.     

Immunohistochemical properties of nerve fibres supplying accessory male genital glands in the pig. A colocalisation study

 Immunohistochemical studies have been performed to investigate the occurrence and coexistence of two catecholamine-synthesising enzymes, tyrosine hydroxylase and dopamine-β-hydroxylase, and several neuropeptides, including neuropeptide Y, vasoactive intestinal polypeptide, Leu⁵-enkephalin, somatostatin, calcitonin gene-related peptide and substance P, in nerve fibres supplying porcine accessory genital glands, the seminal vesicles, prostate (body and the disseminated part) and bulbourethral glands. Three major populations of nerve fibres supplying non-vascular elements of the glands have been distinguished (from the largest to the smallest one): (1) noradrenergic fibres, the majority of which contain Leu⁵-enkephalin, neuropeptide Y or, to a lesser extent, somatostatin, (2) non-noradrenergic, putative cholinergic fibres containing vasoactive intestinal polypeptide, neuropeptide Y and/or somatostatin and, (3) non-noradrenergic, presumably sensory fibres, containing calcitonin gene-related peptide and substance P. Whilst the coexistence patterns within nerves supplying particular glands are similar, the density of innervation varies between the organs. The innervation of the seminal vesicles and prostatic body is more developed than that of the disseminated part of the prostate and bulbourethral glands. The majority of noradrenergic fibres related to blood vessels contain neuropeptide Y only, while the non-noradrenergic nerves contain mainly vasoactive intestinal polypeptide. The possible function and origin of particular nerve fibre populations are discussed. Accepted: 16 November 1998     

N-(4-hydroxyphenyl) retinamide inhibits cystogenesis by polycystic epithelial cell lines in vitro.

Primary tubular epithelial cells develop spherical monolayered cysts when cultured in collagenI matrix, a model that has been used to study the mechanism of cystogenesis. In an attempt to block cystogenesis, we have evaluated the effect of N-(4-hydroxyphenyl) retinamide (HPR), a synthetic derivative of retinoic acid, on both formation and growth of cysts in a human model of polycystic kidney cells. Number, dimension and submicroscopical characteristics of cysts were evaluated after 2 and 4 weeks from treatment with HPR. A marked inhibitory effect of HPR on cystogenesis was found at concentration of 1 microM, while a complete block was observed at concentration between 5 and 10 microM. Furthermore, treatment with HPR of already formed cysts resulted in their disruption. HPR at 10 microM also induced apoptosis of several tubular epithelial cell models suggesting a correlation between the two phenomena. Taken together these observations demonstrate that HPR blocks cystogenesis by polycystic kidney cells "in vitro" and that it also reverts the fate of already formed cysts. Apoptosis may be the mechanism which mediates the inhibitory effect on cystogenesis in this model.     

Tetraspanins connect several types of Ig proteins: IgM is a novel component of the tetraspanin web on B-lymphoid cells

The tetraspanins form a family of about 30 molecules mainly expressed on the cell surface. They have been reported to be involved in many physiological or pathological processes, such as fertilization, immune response, development of the nervous system, and metastasis, as well as in infectious diseases (HCV, malaria, etc.). The tetraspanins may play a role as organizers of multimolecular complexes on the cell surface associating numerous proteins, the tetraspanin web. To better define the composition of the tetraspanin web, its characterization has been recently performed using mass spectrometry and proteomics. We report the proteomic analysis of tetraspanin complexes on B-lymphoid cells. Immunoprecipitation experiments were performed using mAbs directed against the tetraspanin CD9, and associated molecules were identified by MALDI-TOF (matrix assisted laser desorption ionization time of flight) mass spectrometry. This led to the identification of IgM as a novel component of the complexes. Thus, tetraspanins may connect several types of proteins with Ig domains, including HLA-DR, EWI-2, and IgM, that may play a role in immune responses.This work was presented at the first Cancer Immunology and Immunotherapy Summer School, 8–13 September 2003, Ionian Village, Bartholomeio, Peloponnese, Greece.     

Hereditary deafness: molecular genetics

This article outlines recent advances in explaining hereditary deafness in molecular terms, focusing on isolated (i.e. nonsyndromic) hearing loss. The number of genes identified (36 to date) is growing rapidly. However, difficulties inherent in genetic linkage analysis, coupled with the possible involvement of environmental causes, have so far prevented the characterization of the main genes causative or predisposing to the late-onset forms of deafness.