| 1. |
- Berglöf, Anna
(författare)
-
Models for infections in immunodeficiency
- 2002
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Increased susceptibility to infections in immunodeficient patients is a well-known phenomenon. The spectrum of infections reflects the underlying defect. Experimental infections in mouse strains with different types of defined immunodeficiencies allow studying the course of infectious diseases in immunocompromised hosts. In such models it is possible to investigate the relationship between immunity and infection and the role of the immune system both in the protection against microorganisms and in the pathogenesis. However, analogous mutations in man and mice do not always result in similar phenotype. Another obstacle is that there is strong host specificity for some microorganisms, and establishment of relevant mouse models for human infections can be a problem. Within this project we have been working with three pathogens: human pathogen Campylobacter jejuni and mouse pathogens polyomavirus and Mycoplasma pulmonis. Several rodent models have been developed in order to mimic human campylobacteriosis but none of them has gained acceptance as universal model of the infection, since it was impossible to produce illness similar to that seen in humans. The aim of our study (paper I) was to examine the possibility of developing a relevant animal model of campylobacteriosis by infecting scid mice, lacking both B and T cells, with enterotoxin producing C. jejuni strain. In addition, the mice underwent antibiotic treatment prior to infection in order to disrupt the intestinal flora, and enhance gut colonisation. Both immunocompetent controls and scid mice became colonised by C. jejuni for 7 weeks. Any clinical and histological signs of the disease were, however, not observed. This suggests that other factors than normal intestinal flora and acquired immunity must be involved in the resistance of mice to this bacterium. Mycoplasma infections were performed with M. pulmonis which is a causative agent of murine respiratory disease (papers III, IV, V). M. pulmonis infection in mice resembles in many aspects human disease caused by M. pneumoniae, thus providing a relevant model of the infection. Several mouse strains with severe combined immunodeficiencies (scid/beige, scid), B cell deficiencies (xid, Btk-/-, muMT, lambda5-/-) and immunocompetent control strains of respective backgrounds were infected. Bacteriological, histological and immunological analyses were performed. The results can be summarised to: 1) the course of mycoplasmal disease is highly dependent on the immune status of the host 2) antibodies have a protective role regarding systemic disease, 3) humoral immunity is involved in the pathogenesis of pulmonary lesions, 4) proinflammatory cytokines, locally produced in the chondrocytes, may contribute to the aetiology of Mycoplasma-associated arthritis, 5) different genetic backgrounds of mouse strains influence the severity of the mycoplasmosis. The importance of antibodies for elimination of polyomavirus infection was also studied (paper II). B cell deficient xid and muMT (referred in the paper as IgM-/-) mice, CD8-/-/muMT double k.o. mice, and normal control mice were infected with polyomavirus as adults. The mice were tested for presence of polyoma DNA with a polyoma specific polymerase chain reaction during 6 weeks post infection. A protective role of antibodies with regard to prevention against persistent polyomavirus infection was shown.
|
|
| 2. |
|
|
| 3. |
- Lane, Anna-Lena, et al.
(författare)
-
System Efficiency Index, SEI A key performance indicator for field measurements of refrigeration, air conditioning and heat pump systems
- 2014
-
Ingår i: 3rd IIR International Conference on Sustainability and the Cold Chain. - 9782362150036 ; , s. 695-702
-
Konferensbidrag (refereegranskat)abstract
- At present there is a lack of a concept which can be used to evaluate and compare efficiency for installed refrigeration systems using short term measurements. Traditionally COP (Coefficient of Performance) has been used but it has a weakness as a comparator as it is strongly dependent on operating conditions. System Efficiency Index (SEI) is the ratio between the measured COP and the COP for an ideal process, known as the Carnot efficiency operating between the same temperature levels. In collaboration between SP Technical Research Institute of Sweden, IOR and VDMA the method has been further developed. This paper will focus on the method and results from the implementation of SEI from field measurements for, in the first step, condensing units and chillers. The principle is the same for all kind of refrigeration systems. In the next step more measurements for refrigeration systems will be evaluated.
|
|
| 4. |
- Nevalainen, Nina, et al.
(författare)
-
Glial cell line-derived neurotrophic factor is crucial for long-term maintenance of the nigrostriatal system
- 2010
-
Ingår i: Neuroscience. - : Elsevier. - 0306-4522 .- 1873-7544. ; 171:4, s. 1357-1366
-
Tidskriftsartikel (refereegranskat)abstract
- Glial cell line-derived neurotrophic factor (GDNF) is a potent factor for the ventral mesencephalic dopamine neurons. However, studies on the Gdnf gene deleted (Gdnf(-/-)) mouse have been limited to fetal tissue since these mice die prematurely. To evaluate long-term effects of Gdnf gene deletion, this study involves co-grafts of ventral mesencephalon (VM) and lateral ganglionic eminence (LGE) derived from different Gdnf genotypes. The VM/LGE co-grafts were evaluated at 3, 6, and 12 months for tyrosine hydroxylase (TH) -positive cell survival and nerve fiber formation in the LGE co-transplant, visualized by dopamine- and cyclic AMP-regulated phosphoprotein relative molecular mass 32,000 (DARPP-32) -immunoreactivity. Cell counts revealed no difference in TH-positive neurons between Gdnf genotypes at 3 months postgrafting. At 6 months, a significant reduction in cell number was observed in the Gdnf(-/-) grafts. In fact, in the majority of the Gdnf(-/-) VM/LGE transplant had degenerated. At 12 months, a reduction in cell number was seen in both Gdnf(-/-) and Gdnf(+/-) compared to wild type transplants. In the Gdnf(-/-) grafts, TH-negative inclusion-like structures were present in the cytoplasm of the TH-positive neurons at 3 months. These structures were also found in the Gdnf(+/-) transplants at 12 months, but not in Gdnf(+/+) controls at any time point. In Gdnf(+/+) grafts, TH-positive nerve fiber innervation of the striatal co-grafts was dense and patchy and overlapped with clusters of DARPP-32-positive neurons. This overlap did mismatch in the Gdnf(+/-) grafts, while the TH-positive innervation was sparse in the Gdnf(-/-) transplants and the DARPP-32-positive neurons were widespread distributed. In conclusion, GDNF is essential for long-term maintenance of both the VM TH-positive neurons and for the striatal tissue, and appears crucial for generation of a proper organization of the striatum.
|
|
| 5. |
- Schaafsma, Gerard C.P., et al.
(författare)
-
BTKbase, Bruton Tyrosine Kinase Variant Database in X-Linked Agammaglobulinemia : Looking Back and Ahead
- 2023
-
Ingår i: Human Mutation. - 1059-7794. ; 2023
-
Tidskriftsartikel (refereegranskat)abstract
- BTKbase is an international database for disease-causing variants in Bruton tyrosine kinase (BTK) leading to X-linked agammaglobulinemia (XLA), a rare primary immunodeficiency of antibody production. BTKbase was established in 1994 as one of the first publicly available variation databases. The number of cases has more than doubled since the last update; it now contains information for 2310 DNA variants in 2291 individuals. 1025 of the DNA variants are unique. The human genome contains more than 500 protein kinases, among which BTK has the largest number of unique disease-causing variants. The current version of BTKbase has numerous novel features: the database has been reformatted, it has moved to LOVD database management system, it has been internally harmonized, etc. Systematics and standardization have been increased, including Variation Ontology annotations for variation types. There are some regions with lower than expected variation frequency and some hotspots for variations. BTKbase contains, in addition to variant descriptions at DNA, RNA and protein levels, also laboratory parameters and clinical features for many patients. BTKbase has served clinical and research communities in the diagnosis of XLA cases and provides general insight into effects of variations, especially in signalling pathways. Amino acid substitutions and their effects were investigated, predicted, and visualized at 3D level in the protein domains. BTKbase is freely available.
|
|
