Non-allergic non-infectious perennial rhinitis. Pathogenesis and treatment

Rhinitis is a very common disorder. Most people suffer from an infectious rhinitis at least once a year. The symptoms usually disappear within a week. The patients with chronic rhinitis pose a much greater problem. At least 10 % of the general population are affected by a chronic allergic or non-allergic non-infectious rhiilltis (l). The impact of the nasal complaints such as in rhinitis is often underestimated. Bousquet and Juniper demonstrated that the impact of the disease on the quality of life is greater in rhinitis than in asthma patients (2-4). There is no generally accepted system for the definition, classification and terminology of rhinitis (5). A distinction can be made between rhinitis of known and unknown etiology. Known causes for rhinitis can be subdivided in mechanical Jactors (e.g. septal deviation, foreign body,), injections (viral, bacterial, fungal), miscellaneous causes (e.g. rhinitis medicarnentosa, pregnancy, cystic fibrosis) and allergy. Syndromes of unknown etiology include non-allergic non-infectious perennial rhinitis (NANIPER), nasal polyposis and nonallergic rhinitis with eosinophilia (NARES). The subject of this thesis is the pathogenesis and treatment of NANIPER. As this teml suggests the disorder is diagnosed through the exclusion of the known causes for rhinitis. Available studies are often difficult to compare. Different authors use different methods to exclude "the known causes". The patients are sometimes presented in a study as NANIPER patients without further specification. The way in which an allergic pathogenesis is excluded varies from skin prick tests, senllu testing for specific IgE, total IgE, nasal provocation tests or a combination of these methods. To exclude infection some authors rely on the history (chronicity of the illness, lack of purulent secretions and or the classic symptoms of acute rhinosinusitis), some rely on laboratory parameters (sedimentation rate, white blood cell count, nasal smears), others use negative radiological findings (noffilal sinus X-ray or CATscan), all with or without the use of a nasal symptom score

Comparative genomic analysis of the biotechnological potential of the novel species Pseudomonas wadenswilerensis CCOS 864T and Pseudomonas reidholzensis CCOS 865T

In recent years, the use of whole-cell biocatalysts and biocatalytic enzymes in biotechnological applications originating from the genus Pseudomonas has greatly increased. In 2014, two new species within the Pseudomonas putida group were isolated from Swiss forest soil. In this study, the high quality draft genome sequences of Pseudomonas wadenswilerensis CCOS 864T and Pseudomonas reidholzensis CCOS 865T were used in a comparative genomics approach to identify genomic features that either di ered between these two new species or to selected members of the P. putida group. The genomes of P. wadenswilerensis CCOS 864T and P. reidholzensis CCOS 865T were found to share genomic features for the degradation of aromatic compounds or the synthesis of secondary metabolites. In particular, genes encoding for biocatalytic relevant enzymes belonging to the class of oxidoreductases, proteases and isomerases were found, that could yield potential applications in biotechnology. Ecologically relevant features revealed that both species are probably playing an important role in the degradation of soil organic material, the accumulation of phosphate and biocontrol against plant pathogens

Draft genome sequence of the commercial biocontrol strain Pantoea agglomerans P10c

We report here the draft genome sequence of the biocontrol strain Pantoea agglomerans P10c, composed of a draft chromosome and two plasmids: the 559-kb large Pantoea plasmid 1 (pPag3) and a 182-kb plasmid (pPag1). A genomic island containing pantocin A biosynthesis genes was identified

The effect of nasal steroid aqueous spray on nasal complaint scores and cellular infiltrates in the nasal mucosa of patients with nonallergic, noninfectious perennial rhinitis

Topical corticosteroids are the therapy of choice for nonallergic, noninfectious perennial rhinitis (NANIPER). However, the efficacy of steroid therapy in NANIPER is controversial, as is its mode of action. To our surprise, of 300 patients initially diagnosed as having NANIPER, only 65 reached threshold nasal symptom scores. Patients were randomized into four different treatment regimens: placebo administered twice daily (BD) for 8 weeks, fluticasone propionate aqueous nasal spray (FPANS) (200 microg) once daily (OD) and placebo OD for 8 weeks, FPANS (200 microg) OD and placebo OD for 4 weeks followed by FPANS (200 microg) BD for 4 weeks, and FPANS (200 microg) BD for 8 weeks. A small decrease in nasal symptoms was found, which only reached significance for sneezing in the FPANS 200 microg BD group. A significant dose-dependent decrease in immunocompetent cells was found in nasal biopsy specimens obtained before, after 4 weeks, and after 8 weeks of treatment. We conclude that FPANS did not significantly reduce nasal symptoms in this group of selected NANIPER patients, even though a significant effect on cells in the nasal mucosa was see

Inhibition of T Cell and Promotion of Natural Killer Cell Development by the Dominant Negative Helix Loop Helix Factor Id3

Bipotential T/natural killer (NK) progenitor cells are present in the human thymus. Despite their bipotential capacity, these progenitors develop predominantly to T cells in the thymus. The mechanisms controlling this developmental choice are unknown. Here we present evidence that a member(s) of the family of basic helix loop helix (bHLH) transcription factors determines lineage specification of NK/T cell progenitors. The natural dominant negative HLH factor Id3, which blocks transcriptional activity of a number of known bHLH factors, was expressed in CD34+ progenitor cells by retrovirus-mediated gene transfer. Constitutive expression of Id3 completely blocks development of CD34+ cells into T cells in a fetal thymic organ culture (FTOC). In contrast, development into NK cells in an FTOC is enhanced. Thus, the activity of a bHLH transcription factor is necessary for T lineage differentiation of bipotential precursors, in the absence of which a default pathway leading to NK cell development is chosen. Our results identify a molecular switch for lineage specification in early lymphoid precursors of humans

Phylogenomic, pan-genomic, pathogenomic and evolutionary genomic insights into the agronomically relevant enterobacteria Pantoea ananatis and Pantoea stewartii

Pantoea ananatis is ubiquitously found in the environment and causes disease on a wide range of plant hosts. By contrast, its sister species, Pantoea stewartii subsp. stewartii is the host-specific causative agent of the devastating maize disease Stewart's wilt. This pathogen has a restricted lifecycle, overwintering in an insect vector before being introduced into susceptible maize cultivars, causing disease and returning to overwinter in its vector. The other subspecies of P. stewartii subsp. indologenes, has been isolated from different plant hosts and is predicted to proliferate in different environmental niches. Here we have, by the use of comparative genomics and a comprehensive suite of bioinformatic tools, analyzed the genomes of ten P. stewartii and nineteen P. ananatis strains. Our phylogenomic analyses have revealed that there are two distinct clades within P. ananatis while far less phylogenetic diversity was observed among the P. stewartii subspecies. Pan-genome analyses revealed a large core genome comprising of 3,571 protein coding sequences is shared among the twenty-nine compared strains. Furthermore, we showed that an extensive accessory genome made up largely by a mobilome of plasmids, integrated prophages, integrative and conjugative elements and insertion elements has resulted in extensive diversification of P. stewartii and P. ananatis. While these organisms share many pathogenicity determinants, our comparative genomic analyses show that they differ in terms of the secretion systems they encode. The genomic differences identified in this study have allowed us to postulate on the divergent evolutionary histories of the analyzed P. ananatis and P. stewartii strains and on the molecular basis underlying their ecological success and host range