Per Kania - Academia.edu (original) (raw)

Papers by Per Kania

Leukemia, Apr 28, 2000

In the present study, we analysed 34 de novo diffuse large B cell lymphoma (DLCL) from a populati... more In the present study, we analysed 34 de novo diffuse large B cell lymphoma (DLCL) from a population-based lymphoma registry for alterations of the RB1 pathway at the genetic (RB1 and CDK4) and protein (pRb, cyclin D1, cyclin D3, CDK4, and E2F-1) level. The results were correlated with the data from our previous studies of CDKN2A deletion and hypermethylation, other p53 pathway components, p27 Kip1 expression, and proliferation, as well as with clinical outcome, including prognosis. We found aberrant pRb expression in four (12%) of 34 DLCLs. One of these had a point mutation in intron 3 10 bp downstream of exon 3 generating a novel splice signal. Seven tumours (21%) showed cyclin D3 overexpression, including all three thyroid lymphomas (P 5 0.006). Cyclin D3 overexpression and p16 INK4A /pRb aberrations were mutually exclusive, supporting an oncogenic role for cyclin D3 in DLCL. p16 INK4A inactivation, cyclin D3 overexpression, or aberrant pRb expression was identified in 18 of 34 DLCLs (53%). Combining these results with our previous p53 pathway studies showed that 82% of the de novo DLCLs had alterations of these pathways, and that both pathways were altered in 13 cases (38%). Low E2F-1 expression was associated with treatment failure (P 5 0.020), and multivariate analysis of overall survival identified both low E2F-1 expression (relative risk 5 6.9; P 5 0.0037) and p16 INK4A inactivation (relative risk 5 3.3; P 5 0.0247) as independent prognostic markers. These data support a role of E2F-1 as tumour suppressor gene in lymphoma and strongly suggest that the RB1 and p53 pathways are important in the development of de novo DLCL. Furthermore, low E2F-1 expression and p16 INK4A inactivation may serve as prognostic markers for patients with this type of lymphoma. Leukemia (2000) 14,

Aquaculture Reports, Nov 1, 2015

Expression of stress-related genes was investigated in the marine copepod Acartia tonsa in relati... more Expression of stress-related genes was investigated in the marine copepod Acartia tonsa in relation to heat shock at two different salinities (10 and 32‰), and it was furthermore investigated whether experimentally induced epibiont infestation led to elevated expression of stress-related genes. Expression of the genes ferritin, Hsp90 and Hsp70 were analyzed in adult copepods by conducting reverse transcriptionquantitative real time PCR (RT-qPCR). The expression of Hsp70 and Hsp90 was significantly up-regulated after heat shock and the expression levels were higher in copepods cultivated at 10‰ salinity seawater than in copepods cultivated at 32‰. Significant up-regulation of ferritin (3.3 fold increase) was observed as a response to infestation with the epibiotic euglenid Colacium vesiculosum. Results suggest that (i) A. tonsa responds more pronounced to thermal shock when cultivated in low salinity seawater (10‰) as compared to optimal salinity seawater (32‰) and (ii) epibiont infestation does cause a measureable physiological response in the host.

Vaccines, Feb 25, 2020

Protection facilitated by the widespread use of mineral oil adjuvanted injection vaccines in salm... more Protection facilitated by the widespread use of mineral oil adjuvanted injection vaccines in salmonid fish comes with adverse effects of varying severity. In this study, we characterized the immunological profiles of two alternative vaccine formulations, both with proven efficacy and an improved safety profile in rainbow trout. Experimental injection vaccines were prepared on an identical whole-cell Aeromonas salmonicida bacterin platform and were formulated with CpG oligodeoxynucleotides, a liposomal (CAF01) or a benchmark mineral oil adjuvant, respectively. A naïve group, as well as bacterin and saline-injected groups were also included. Following administration, antigen-specific serum antibody titers, the tissue distribution of immune cell markers, and the expression of immune-relevant genes following the in vitro antigenic restimulation of anterior kidney leukocytes was investigated. Immunohistochemical staining suggested prolonged antigen presentation for the particulate formulations and increased mucosal presence of antigen-presenting cells in all immunized fish. Unlike the other immunized groups, the CAF01 group only displayed a transient elevation in specific antibody titers and immunohistochemical observations, and the transcription data suggest an increased role of cell-mediated immunity for this group. Finally, the transcription profile of the CpG formulation approached that of a T H1 profile. When compared to the benchmark formulation, CAF01 and CpG adjuvants induce slight, but distinct differences in the resulting protective immune responses. This is important, as it allows a broader immunological approach for the future development of safer vaccines.

Fish & Shellfish Immunology, Aug 1, 2019

Fish & Shellfish Immunology, Jun 1, 2016

Immersion-vaccines (bacterins) are routinely used for aquacultured rainbow trout to protect again... more Immersion-vaccines (bacterins) are routinely used for aquacultured rainbow trout to protect against Yersinia ruckeri (Yr). They consist of formalin killed bacteria and during immersion, lasting at least 30 seconds, rainbow trout take up and process the antigens, which induce protection. However, uptake mechanisms and processing are still insufficiently elucidated. We have used zebrafish as a model organism to study uptake mechanisms and subsequent antigen transport in fish. A genetically modified Yr was developed to constitutively express GFP (green fluorescent protein) and subsequently used for bacterin production. Larval, juvenile and adult transparent zebrafish (tra:nac mutant) were immersed in the bacterin for up to 30 minutes. Samples were taken after 1 min, 15 min, 30 min, 2 h, 12 h and 24 h. At each sampling point two fish were used for live imaging using a fluorescence stereomicroscope and three fish were also sampled for immunohistochemistry (IHC). Bacteria could be traced in scale pockets, skin, esophagus, intestine and fins of adult fish. However, within two hours post-immersion Yr-antigens were visible in the spleen and within 24 h in liver and kidney. Bacteria were associated with the gills but uptake at this location was limited. Antigens were not seen in the nares and rarely in the blood. In juvenile fish the nares and intestine were major uptake sites, whereas scale pockets did not stain positive. Antigens were detectable in the spleen 12 h post immersion. Zebrafish larvae exhibited Yr uptake in mid-intestine enterocytes 24 h following immersion. The different zebra fish life stages varied with regard to uptake locations, but the gut was consistently a major uptake site in all stages. Zebrafish and rainbow trout tend to have similar uptake mechanisms following immersion vaccination, which may suggest zebrafish as a suitable model organism for this aquacultured species.

International Journal for Parasitology: Parasites and Wildlife

Marine Ecology Progress Series, 2018

Journal of Fish Diseases, 2016

Diseases of Aquatic Organisms, 2019

Aquaculture Reports, Apr 1, 2022

Aquaculture, Sep 1, 2020

Abstract Infection of rainbow trout with the parasitic ciliate Ichthyophthirius multifiliis induc... more Abstract Infection of rainbow trout with the parasitic ciliate Ichthyophthirius multifiliis induces a stress response which can be monitored by serum cortisol measurements reflecting involvement of the pituitary-interrenal cell axis in parasite infected fish. Molecular mechanisms associated with the stress response have been less well elucidated - especially with regard to stress effects on metabolism and growth in infected gills – which is the focus of the present study. A controlled experimental infection was performed followed by serum and gill sampling at day 8 post-infection. The stress reactions in the fish were elucidated by measurements of serum cortisol and lysozyme activity, and expression in gills of genes associated with stress, metabolism, and growth. Infection induced a marked elevation of serum cortisol and lysozyme levels, and major changes of metabolic processes in gills. A number of key genes involved in stress (hsps, foxo, saa) and energy metabolism (cyps, pfkfb3, rrm2, mthfd1l) were activated in response to infection whereas several central genes related to growth factors (wnt7a, igfbp7, insr, fgf7, tgfb3, tgfbr1, tgfbr3) were suppressed. A number of potential transcription factors including myc, e2f1, stat1, jun, e2f2, e2f3, and gli2 were found associated with regulation of genes in gills during infection. Mechanisms linking infection of mucosal surfaces and systemic responses are discussed.

Parasite Immunology, Sep 5, 2017

Inflammatory bowel disease (IBD) in developed countries is linked with elevated hygienic standard... more Inflammatory bowel disease (IBD) in developed countries is linked with elevated hygienic standards. One of several factors involved in this question may be reduced exposure to the immunomodulatory effects of parasitic helminths. Several investigations on treatment of mice and humans with helminth-derived substances have supported this notion, but underlying mechanisms remain unclear. The present study therefore dissects to what extent a series of immune-related genes are modulated in zebrafish with experimentally induced colitis following exposure to excretory-secretory (ES) products isolated from larval Anisakis, a widely distributed fish nematode. Adult zebrafish intrarectally exposed to the colitisinducing agent TNBS developed severe colitis leading to 80% severe morbidity but if coinjected (i.p.) with Anisakis ES-products the morbidity rate was 50% at the end of the experiment (48 hours post exposure). Gene expression studies of TNBS treated zebrafish showed clear upregulation of a range of genes encoding inflammatory cytokines and effector molecules and some induction of genes related to the adaptive response. A distinct innatedriven immune response was seen in both TNBS and TNBS+ES group, but expression values were significantly depressed for several important pro-inflammatory genes in the TNBS+ES group, indicating protective mechanisms of Anisakis ES compounds on intestinal immunopathology in zebrafish.