Innovative in vitro method to study ventilator induced lung injury.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMechanical ventilation (MV) is a life-saving therapy for critically ill patients, alleviating the work of breathing and supporting adequate gas exchange. However, MV can cause ventilator induced lung injury (VILI) by baro/volu- and atelectrauma, even lead to acute respiratory distress syndrome (ARDS), and substantially augment mortality. There is a need for specific biomarkers and novel research platforms for VILI/ARDS research to study these detrimental disorders and seek ways to avoid or prevent them. Previous in vitro studies on bronchial epithelium, cultured in air-liquid interface (ALI) conditions, have generally utilized static or constant pressure. We have developed a Cyclical Pressure ALI Device (CPAD) that enables cyclical stress on ALI cultured human bronchial cells, with the aim of mimicking the effects of MV. Using CPAD we were able to analyze differentially expressed VILI/ARDS and innate immunity associated genes along with increased expression of associated proteins. CPAD provides an easy and accessible way to analyze functional and phenotypic changes that occur during VILI and may provide a platform for future drug testing.Technology development fund - Icelandic research council University of Iceland Land-spitali, University Hospital, Science fun

Psoriasis: a complex clinical and genetic disorder

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPsoriasis is associated with arthritis in approximately 10% of patients. The skin disease and arthritis have a strong but complex genetic component. Several susceptibility loci have been reported including one major locus that maps very close to the human leukocyte antigen-C gene on chromosome 6p. No causative gene has so far been conclusively identified. A recent genetic analysis that only included patients with psoriatic arthritis revealed a highly significant susceptibility locus on chromosome 16q approximately 20 cM from the NOD2 gene that has been associated with Crohn's disease. This locus was barely detectable when the entire cohort of psoriasis patients was analyzed as a homogeneous entity. A further clinical stratification of psoriasis patients has revealed novel strongly suggestive loci and also increased the logarithm of the odds scores of some previously reported loci. It is concluded that a careful documentation of clinical features and phenotypic stratification may help to analyze complex genetic disorders

HLA-Cw6-positive and HLA-Cw6-negative patients with Psoriasis vulgaris have distinct clinical features.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPsoriasis is associated with HLA-Cw6, and Caucasians who carry this allele have about a 10-fold increased risk of developing psoriasis. We have HLA-C typed 369 patients with familial psoriasis and compared the clinical features of the patients carrying HLA-Cw6 against those carrying other HLA-C types. Some striking clinical differences were observed between the two groups. Patients who are Cw6 positive had a lower age at onset (p=3x10(-7)). Cw6-positive women had an earlier disease onset than Cw6-positive men (p =0.02), but such a difference was not observed for the Cw6-negative patients. The guttate-type onset of psoriasis was mostly confined to this group (p=2x10(-4)) and persistent disseminated guttate-like papules were also predominantly observed in the Cw6-positive patients (p <10(-)4). The Cw6-positive patients also had more extensive plaques on their arms, legs, and trunk (p =0.001), more severe disease (p =0.003), higher incidence of the Koebner's phenomenon (p =0.005), reported more often that their psoriasis got worse during or after throat infections (p =0.02), and more often a favorable response to sunlight (p =0.008) In contrast, dystrophic nail changes were more common in the Cw6-negative patients (p =0.002) and also psoriatic arthritis, although this was not significant (p =0.135). It is concluded that patients with psoriasis have different clinical features depending on whether they are HLA-Cw6 positive or negative

Genetics of psoriasis in Iceland: evidence for linkage of subphenotypes to distinct Loci

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPsoriasis is a chronic inflammatory skin disease with overlapping subphenotypes. It has a strong complex genetic component, but has been problematic to identifying significant loci. We evaluated 1000 patients with chronic plaque psoriasis and documented several subphenotypes. Here we report results of genome-wide linkage scans for psoriasis genes in 238 Icelandic families with 874 patients. MHC linkage was confirmed with LOD score of 10.9. When the entire cohort was analyzed, two other loci with LOD scores of 2.5 and 1.5 were observed on 16q and 4q, respectively. Stratification into subphenotypes revealed additional loci with LOD scores exceeding or approaching significance. A LOD score of 5.7 appeared on 16q in PsA patients with analysis conditioned on parental inheritance. A LOD score of 3.6 on 4q was detected when disease occurred at or older than 17 y, our median cohort age. This locus was defined by a marker near one reportedly displaying significant linkage in a Chinese psoriasis population and near suggestive linkage in a Caucasian population. A LOD of 3.0 was observed on 10q when disease onset occurred in the scalp. Furthermore, clinical stratification either revealed or increased LOD scores when compared to unstratified analysis and some coincided with previous reports

Distinct clinical differences between HLA-Cw*0602 positive and negative psoriasis patients--an analysis of 1019 HLA-C- and HLA-B-typed patients

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldA major susceptibility gene for psoriasis is located in the major histocompatibility complex class I region on chromosome 6 very close to the HLA-Cw6 gene. We collected a cohort of 1,019 patients with chronic plaque psoriasis. The patients were typed for HLA-C and HLA-B. A total of 654 (64.2%) were HLA-Cw*0602 positive but 365 (35.8%) carried other HLA-C alleles. We confirmed that HLA-Cw*0602 positive patients have younger age of onset (17.5 vs 24.3 years, P<10(-10)), higher incidence of guttate and the eruptive type of psoriasis (P<0.0001), more frequent exacerbations with throat infections (P=0.01), higher incidence of the Koebner's phenomenon (P=0.01), and more extensive disease (P=0.03). A striking new finding was a diverging pattern of disease severity in HLA-Cw*0602 positive and negative patients depending on the age of onset of the disease (P=0.0006). HLA-Cw*0602 positive women also had more frequent remissions during pregnancy (P<0.0001). All types of nail changes were, however, more common in the Cw*0602 negative patients (P=0.003) and they more often had multiple types of nail lesions (P<0.0001). The three ancestral haplotypes of Cw*0602 all conferred an increase in odds ratio but showed no difference in any of the clinical features studied. Our findings indicate that the genetic factor on chromosome 6 has a strong influence on the phenotype of the disease, and underline that differences in clinical features of psoriasis may be to a large extent genetically determined

A Susceptibility Gene for Psoriatic Arthritis Maps to Chromosome 16q: Evidence for Imprinting

Several genetic loci have been reported for psoriasis, but none has been specifically linked to psoriatic arthritis (PsA), a condition that affects >10% of patients with psoriasis. A genetic component for PsA is suggested by segregation within families and high concordance among identical twins. We performed a linkage scan to map genes contributing to PsA. We identified 178 patients with PsA out of 906 patients who were included in our genetic study of psoriasis. Using a comprehensive genealogy database, we were able to connect 100 of these into 39 families. We genotyped the patients using a framework marker set of 1,000 microsatellite markers, with an average density of 3 cM, and performed multipoint, affected-only, allele-sharing linkage analysis using the Allegro program. On the basis of the initial results, we genotyped more markers for the most prominent loci. A linkage with a LOD score of 2.17 was observed on chromosome 16q. The linkage analysis, conditioned on paternal transmission to affected individuals, gave a LOD score of 4.19, whereas a LOD score of only 1.03 was observed when conditioned for maternal transmission. A suggestive locus on chromosome 16q has previously been implicated in psoriasis. Our data indicate that a gene at this locus may be involved in paternal transmission of PsA

David Lichine as The Prodigal Son, in Le fils prodigue, Covent Garden Russian Ballet, Australian tour, His Majesty's Theatre, Melbourne, March 1939 (6) [picture] /

Also performed 11-12 April 1939.; From: Le fils prodigue (The prodigal son) : scene in three tableaux / music by Sergey Prokofiev.; Inscription: "2F/37".; Part of the collection: Hugh P. Hall collection of photographs, 1938-1940.; Choreography by David Lichine ; scenery and costumes by Georges Roualt ; scenery executed by Prince A. Schervachidze ; costumes executed by V. Soudeikine.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn4175232. One of a collection of photographs taken by Hugh P. Hall of 28 ballet productions performed by the Covent Garden Russian Ballet (toured Australia 1938-1939) and the Original Ballet Russe (toured Australia 1939-1940). These are the second and third of the three Ballets Russes companies which toured Australasia between 1936 and 1940. The photographs were taken from the auditorium during a live performance in His Majesty's Theatre, Melbourne and mounted on cardboard for display purposes. For conservation and storage, the photographs have been demounted. The original arrangement of the photographs has been recorded, and details are available from the Pictures Branch of the National Library