| 1. |
- Lindström, Lisa, et al.
(författare)
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Bronchopneumonia in Swedish lambs: a study of pathological changes and bacteriological agents
- 2018
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Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 60
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the most common post-mortem inspection finding of sheep and lambs in Sweden, following routine slaughter is pneumonia and its prevalence is increasing. To our knowledge, the aetiology of pneumonia in lambs is not well-known for Swedish conditions. Chronic bronchopneumonia, also known as "atypical" or chronic non-progressive pneumonia, is a common disease worldwide, affecting lambs up to 12 months old. It is therefore of interest to elucidate if this disease complex is also a common cause of pneumonia among Swedish lambs. Chronic bronchopneumonia has a characteristic macroscopic and histopathologic appearance, and Mycoplasma ovipneumoniae is the microbial agent most frequently found. Although this bacterium is important for the pathogenesis, multiple agents are presumed to be involved. The aim of this study was to describe the macroscopic and histopathologic lung lesions in routinely slaughtered lambs with pneumonia, and to determine the bacterial agents involved.Results: A total of 41 lungs with gross lesions consistent with pneumonia were examined. Of these, 35 lungs displayed the typical gross appearance of chronic bronchopneumonia, with several or all of the characteristic histological features. M. ovipneumoniae was detected in 83% of the 35 lungs and Mannheimia haemolytica was isolated in 71%. Pneumonia associated with M. ovipneumoniae could be correlated to specific gross lesions consistent with the gross description of chronic bronchopneumonia in lambs.Conclusion: In this study, chronic bronchopneumonia was the most common lung disease in routinely slaughtered Swedish lambs. This diagnosis was based on the characteristic macroscopic and histopathologic pulmonary findings and the frequent presence of the bacterium M. ovipneumoniae. The macroscopic appearance of chronic bronchopneumonia could therefore be used during routine investigation of the lamb carcasses at slaughter, to determine the most likely cause of pneumonia.
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| 2. |
- Lindström, Lisa, et al.
(författare)
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Characterization of gamma-tubulin filaments in mammalian cells
- 2018
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Ingår i: Biochimica et Biophysica Acta - Molecular Cell Research. - : Elsevier BV. - 0167-4889. ; 1865:1, s. 158-171
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Tidskriftsartikel (refereegranskat)abstract
- Overexpression of γ-tubulin leads to the formation of filaments, but nothing is known about such filaments with regard to possible presence in cells, structure and probable dynamics. Here, we used mammalian cell lines to investigate the ability of γ-tubulin to form filaments. We found that γ-tubulin produces fibers called γ-tubules in a GTP-dependent manner and that γ-tubules are made up of pericentrin and the γ-tubulin complex proteins 2, 3, 5 and 6. Furthermore, we noted that the number of cells with cytosolic γ-tubules is increased in non-dividing cells. Our experiments showed that γ-tubules are polar structures that have a low regrowth rate compared to microtubules. Also, we observed that γ-tubules were disassembled by treatment with cold, colcemid, citral dimethyl acetal, dimethyl fumarate or mutation of γ-tubulin GTPase domain, but were increased in number by treatment with taxol or by stable expression of the γ-tubulin1–333 GTPase domain. Our results demonstrate that γ-tubulin forms filaments, and such assembly is facilitated by the GTPase domain of γ-tubulin.
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| 3. |
- Lindström, Lisa
(författare)
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The gamma-tubulin meshwork as a therapeutic target
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer is a heterogeneous disease and treatment regime is dependent on type and location of the tumor. Several of the commonly used chemotherapeutics target the functions of the microtubules. One of the major problems with these drugs is the adverse effects associated with their use. Another problem many of the chemotherapeutics today face is resistance. Therefore there is a constant need for development of new drugs in the fight against cancer. Many tumors achieve independent growth by carrying mutations in the retinoblastoma (pRB) signaling pathway. It has been shown that reduced protein levels of nuclear gamma-tubulin in tumor cells lacking pRB expression induce cell death. Consequently inhibiton of gamma-tubulin might be used as a new strategy for therapy of pRB-negative tumors with fewer side-effects.The aim of this thesis was to evaluate gamma-tubulins’ potential as a novel therapeutic target in the treatment of tumors with a deregulated pRB and to characterize the gamma-tubulin meshwork. We searched for compounds that specifically interfere with the nuclear activity of gamma-tubulin and the effect of the substances were studied in silico, in vitro and in vivo. Among the tested substances we found one, citral dimethyl acetal (CDA), that was specific for gamma-tubulin. CDA caused cell death in cell lines with non-functional pRB and reduced tumor growth in a mice xenograft model. We also showed that CDA interact with gamma-tubulin at the amino acid cysteine 13 at the GTPase domain of gamma-tubulin. Our results demonstrate that it is possible to develop new chemotherapeutics that target the nuclear activity of gamma-tubulin and give rise to fewer side-effects.We also observed that gamma-tubulin form a meshwork in cells that connects the nuclear and cytoplasmic compartments. The network is important in mitosis during formation of the nuclear envelope (NE) where it is responsible for recruitment of the lamina to the chromatin. We also observed that gamma-tubulin form cytosolic tubules together with several other proteins, including GCP2, GCP3, GCP6 and pericentrin. The gamma-tubulin meshwork also interacts with the mitochondria. In addition, we provide evidence for that the gamma-tubulin GTPase domain is involved in regulation of mitochondria organization and homeostasis.
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| 4. |
- Lindström, Lisa, et al.
(författare)
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The GTPase domain of gamma-tubulin is required for normal mitochondrial function and spatial organization
- 2018
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1:https://doi.org/10.1038/s42003-018-0037-3
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Tidskriftsartikel (refereegranskat)abstract
- In the cell, γ-tubulin establishes a cellular network of threads named the γ-string meshwork. However, the functions of this meshwork remain to be determined. We investigated the traits of the meshwork and show that γ-strings have the ability to connect the cytoplasm and the mitochondrial DNA together. We also show that γ-tubulin has a role in the maintenance of the mitochondrial network and functions as reduced levels of γ-tubulin or impairment of its GTPase domain disrupts the mitochondrial network and alters both their respiratory capacity and the expression of mitochondrial-related genes. By contrast, reduced mitochondrial number or increased protein levels of γ-tubulin DNA-binding domain enhanced the association of γ-tubulin with mitochondria. Our results demonstrate that γ-tubulin is an important mitochondrial structural component that maintains the mitochondrial network, providing mitochondria with a cellular infrastructure. We propose that γ-tubulin provides a cytoskeletal element that gives form to the mitochondrial network.
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| 5. |
- Lindström, Lisa, et al.
(författare)
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Therapeutic Targeting of Nuclear Gamma-Tubulin in RB1-negative Tumors.
- 2015
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Ingår i: Molecular Cancer Research. - 1557-3125. ; 13:7, s. 1073-1082
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Tidskriftsartikel (refereegranskat)abstract
- In addition to its cytosolic function, gamma-tubulin is a chromatin-associated protein. Reduced levels of nuclear gamma-tubulin increase the activity of E2 promoter-binding factors (E2F) and raise the levels of retinoblastoma (RB1) tumor suppressor protein. In tumor cells lacking RB1 expression, decreased gamma-tubulin levels induce cell death. Consequently, impairment of the nuclear activity of gamma-tubulin has been suggested as a strategy for targeted chemotherapy of RB1-deficient tumors; thus, tubulin inhibitors were tested to identify compounds that interfere with gamma-tubulin. Interestingly, citral increased E2F activity but impaired microtubule dynamics while citral analogs, like citral dimethyl acetal (CDA), increased E2F activity without affecting microtubules. The cytotoxic effect of CDA on tumor cells was attenuated by increased expression of either RB1 or gamma-tubulin, and increased by reduced levels of either RB1 or gamma-tubulin. Mechanistic study, in silico and in vitro, demonstrated that CDA prevents GTP binding to gamma-tubulin and suggested that the FDA approved drug dimethyl fumarate is also a gamma-tubulin inhibitor. Finally, in vivo growth of xenograft tumors carrying defects in the RB1 signaling pathway were inhibited by CDA treatment. These results demonstrate that inhibition of gamma-tubulin has the potential to specifically target tumor cells and may aid in the design of safer and more efficient chemotherapeutic regimes.
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| 6. |
- Lindström, V., et al.
(författare)
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Prehospital care in Sweden : From a transport organization to advanced healthcare
- 2015
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Ingår i: Notfall & Rettungsmedizin. - : Springer. - 1434-6222 .- 1436-0578. ; 18:2, s. 107-109
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prehospital care, starting from the patient’s first contact with the emergency medical call centre and including medical care provided in the ambulance, is part of the continuum of care defined as emergency medicine (EM). Sweden has a network of emergency medical call centres that are all reached by one telephone number and staffed by nurses, among other personnel.Objective: This review presents a summary of the prehospital care systems currently in place in Sweden, the role of the physician and the future challenges in this evolving and important field.Results and conclusions: Since 2005, the presence of registered nurses in ambulance teams has become a requirement. This proved to be a turning point in the development of advanced care in the prehospital setting in Sweden. Due to overcrowding in emergency departments, the ambulance services work to steer patients from the ambulance directly to definitive care. Although there are limited numbers of physicians in the prehospital setting today, this should change as the specialty of EM grows stronger.
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| 7. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 8. |
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| 9. |
- Nielsen, Tove, et al.
(författare)
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High-frequency ultrasound of Peyer's patches in the small intestine of young cats
- 2016
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Ingår i: Journal of Feline Medicine and Surgery. - 1098-612X .- 1532-2750. ; 18, s. 303-309
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Tidskriftsartikel (refereegranskat)abstract
- Objectives A previously unreported, asymmetrically positioned hypoechoic extra layer (APHEL) in the submucosa of the feline distal jejunum and ileum has been recognised using high-frequency ultrasound. The objectives of this study were to characterise the APHEL histologically, and to describe the prevalence and ultrasonographic features of the APHEL in a population of clinically healthy young cats.Methods In an anatomical study, two cats were autopsied and histopathology of the small intestine was performed. An APHEL was detected with ultrasound in the distal jejunum and ileum ante-mortem in the first cat and post mortem in the second cat. Samples for histopathology were obtained from these areas. In the second, prospective part of the study, to document the presence or absence of an APHEL, high-frequency (18 MHz) ultrasound was performed of the intestinal tract in 20 other cats. These cats were client-owned cats aged 6-18 months presented for neutering. The cats were included in the study based on a normal clinical examination, lack of previous or concurrent signs of disease, and having no abnormalities detected at abdominal ultrasound.Results Histopathology from the distal jejunum and ileum in the two cats in the anatomical part of the study showed that the APHEL represented asymmetrically positioned normal lymphatic tissue (Peyer's patches) in the lamina propria and submucosa. In the second part of the study, an APHEL was identified in the submucosa of the distal part of the jejunum and ileum in all 20 cats. Additionally, a similar layer could also be seen further proximally in the jejunum in 10 (50%) of the cats. The thickness of the APHEL was 1.0 mm in both jejunum and ileum.Conclusions and relevance Presumed normal lymphatic tissue in the small intestinal submucosa can be seen with high-frequency ultrasound and is a common finding in young cats.
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| 10. |
- Ostrowska, Justyna, et al.
(författare)
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Computed tomography characteristics of equine paranasal sinus cysts—a case series
- 2016
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Ingår i: Veterinary Radiology and Ultrasound. - 1058-8183 .- 1740-8261. ; 57, s. 654-654
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- COMPUTEDTOMOGRAPHYCHARACTERISTICSOFEQUINEPARANASALSINUSCYSTS-ACASESERIESJ.Ostrowska,T.T´oth,L.Lindstr¨om,K.Hansson,M.Uhlhorn,C.J.Ley.FromtheUniversityAnimalHospital(Ostrowska,T´oth,Uhlhorn),DepartmentofClinicalSciences(Hansson,Ley),andDepartmentofBiomedicalSciencesandVeterinaryPublicHealth,SwedishUni-versityofAgriculturalSciences,UppsalaSE-75007,Sweden(Lindstr¨om).Introduction/Purpose:Differentiatingparanasalsinuscysts(PSC)fromotherparanasalsinusdiseasesinhorsesbasedondiagnosticimagingischallenging.TheaimofthisstudywastoidentifythepatternofCTfeatures,typicalforPSC,byretrospectivecomparisontootherdiseasesoftheequineparanasalsinuses. Methods:NineCTscansofeighthorses(diseasereoccurredafter1yearinonehorse)withtypicalsurgicalappearanceofPSC(sevenconfimedwithhistopathology)wereretrospectivelyre-viewed(group-1).Imagingfndingswerecomparedtoagroupof11horseswithparanasalsinusdiseaseofotherorigin(twoneoplasia,sevenchronicsinusits/granuloma,twopro-gressiveethmoidhematoma),withallhorsesinthisgrouphavingsurgery/necropsyandculture/histopathologyconfimationofthediagnosis(group-2).Thirteenofthehorsesre-ceivedcontrast;IVIohexol300mgI/ml,20ml/s,400ml/horse,scannedapproximately2and7minpostcontrast.MeanHounsfielUnits(HU)valuesofthesofttissue/fluidensitylesionswereobtainedforthreeregionsofinterestinthreedifferentslices.Studentt-testforindependentsamples,P<0.05consideredsignificantwasusedtocomparemeandensityofthecysticcontentwithfreesinusfluiingroup-1andsofttissue/fluidensitylesionsingroup-2.Results:Insixhorsesthepresumedwallofthecystwasatleastpartiallymineralized.Subtlepost-contrastenhancementofthecysticwallwasseenintwohorsesinwhichthemineralizedwallwasabsent.Presenceoffocalorspicule-like,peripheralmineralizationswereseenintwogroup-1horsesandinonegroup-2horsewithaparanasalsinusgranuloma.Allcystswerefillewithsofttissue/fluidensity(mean±SD,25±11HU),exceptonethatcontainedonlyair.Nosignificandifferencewasfoundbetweenthemeandensityofthecysticcontentandthesofttissue/fluidensitylesionsingroup-2(mean±SD,25±11vs.42±23HU,P=0.06),orbetweenthefreesinusfluisurroundingthecysts(mean±SD,25±11HUvs.34±17HU,P=0.2).Corticaldestructionwasdetectedinfourgroup-1andtwogroup-2horses.Sevenhorsesineachgrouphadcancellousbonethinning/destruction,whichalwaysinvolvedatleasttheinfraorbitalcanal.Bonedistortionwasmostfrequent/severeingroup-1horsesandboneproductionwasmostcommoningroup-2horseswithsinusitis.Discussion/Conclusions:ParanasalsinuscystsoftenhavemineralizationinthecystwallandthisfeaturemaybeusefultodifferentiatePSCfromotherparanasalsinusesdiseasesinCTimages.DespitethebenigncharacterofPSCcorticaldestructioniscommoninhorseswithPSC.ThereisconsiderableoverlapbetweenHUvaluesofthecontentsofPSCandthefluid/tissupresentinotherparanasalsinusdiseases.
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| 11. |
- Rosselló, Catalina Ana, et al.
(författare)
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γ-Tubulin⁻γ-Tubulin Interactions as the Basis for the Formation of a Meshwork
- 2018
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 19:10
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Forskningsöversikt (refereegranskat)abstract
- In cytoplasm, protein γ-tubulin joins with various γ-tubulin complex proteins (GCPs) to form a heterotetramer γ-tubulin small complex (γ-TuSC) that can grow into a ring-shaped structure called the γ-tubulin ring complex (γ-TuRC). Both γ-TuSC and γ-TuRC are required for microtubule nucleation. Recent knowledge on γ-tubulin with regard to its cellular functions beyond participation in its creation of microtubules suggests that this protein forms a cellular meshwork. The present review summarizes the recognized functions of γ-tubulin and aims to unite the current views on this protein.
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| 12. |
- Rossello Castillo, Catalina Ana, et al.
(författare)
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Gamma-tubulin coordinates nuclear envelope assembly around chromatin
- 2016
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 2:9
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Tidskriftsartikel (refereegranskat)abstract
- The cytosolic role of γ-tubulin as a microtubule organizer has been studied thoroughly, but its nuclear function is poorly understood. Here, we show that γ-tubulin is located throughout the chromatin of demembranated Xenopus laevis sperm and, as the nucleus is formed, γ-tubulin recruits lamin B3 and nuclear membranes. Immunodepletion of γ-tubulin impairs X. laevis assembly of both the lamina and the nuclear membrane. During nuclear formation in mammalian cell lines, γ-tubulin establishes a cellular protein boundary around chromatin that coordinates nuclear assembly of the daughter nuclei. Furthermore, expression of a γ-tubulin mutant that lacks the DNA-binding domain forms chromatin-empty nuclear like structures and demonstrate that a constant interplay between the chromatin-associated and the cytosolic pools of γ-tubulin is required and, when the balance between pools is impaired, aberrant nuclei are formed. We therefore propose that the nuclear protein meshwork formed by γ-tubulin around chromatin coordinates nuclear formation in eukaryotic cells.
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| 13. |
- Sjölin, Helena, et al.
(författare)
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Common core content in education for nurses in ambulance care in Sweden, Finland and Belgium
- 2019
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Ingår i: Nurse Education in Practice. - : Churchill Livingstone. - 1471-5953 .- 1873-5223. ; 38, s. 34-39
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Tidskriftsartikel (refereegranskat)abstract
- There is no consensus regarding the required education content and competence needed for professionals working in the emergency medical services and only a few countries in Europe staff ambulances with registered nurses. This study aimed to identify common core content in Swedish, Finnish and Belgian university curricula in the education on advanced level for registered nurses in ambulance care and to describe the teachers' perception of the necessary content for the profession as a registered nurse in ambulance care.A deductive research design was used. Three Universities, one from each country; Sweden, Finland and Belgium, participated. Data was generated from curricula and interviews with teachers and analyzed with different approaches of qualitative content analysis.The results showed commonness with respect to core content; the emphasis was mainly on medical knowledge but the content concerning contextual subjects differed between the three universities.The teachers, however, aimed for the students' to acquire a broad competence in clinical reasoning by implementing theory into practice, as well as developing the students' personal aptitude and instilling a scientific awareness. The results suggest that it is possible to create a common curriculum for training of RNs for working in ambulance care.
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| 14. |
- Sjölin, Helena, et al.
(författare)
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What an ambulance nurse needs to know : a content analysis of curricula in the specialist nursing programme in prehospital emergency care
- 2015
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Ingår i: International Emergency Nursing. - : Elsevier. - 1755-599X .- 1878-013X. ; 23:2, s. 127-132
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Tidskriftsartikel (refereegranskat)abstract
- In Sweden, ambulances must be staffed by at least one registered nurse. Twelve universities offer education in ambulance nursing. There is no national curriculum for detailed course content and there is a lack of knowledge about the educational content that deals with the ambulance nurse practical professional work. The aim of this study was to describe the content in course curricula for ambulance nurses. A descriptive qualitative research design with summative content analysis was used. Data were generated from 49 courses in nursing and medical science. The result shows that the course content can be described as medical, nursing and contextual knowledge with a certain imbalance with largest focus on medical knowledge. There is least focus on nursing, the registered nurses' main profession. This study clarifies how the content in the education for ambulance nurses in Sweden looks today but there are reasons to discuss the content distribution.
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| 15. |
- van Leeuwen, F., et al.
(författare)
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Gaia Data Release 1 : Open cluster astrometry: Performance, limitations, and future prospects
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 601
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Tidskriftsartikel (refereegranskat)abstract
- Context. The first Gaia Data Release contains the Tycho-Gaia Astrometric Solution (TGAS). This is a subset of about 2 million stars for which, besides the position and photometry, the proper motion and parallax are calculated using Hipparcos and Tycho-2 positions in 1991.25 as prior information. Aims. We investigate the scientific potential and limitations of the TGAS component by means of the astrometric data for open clusters. Methods. Mean cluster parallax and proper motion values are derived taking into account the error correlations within the astrometric solutions for individual stars, an estimate of the internal velocity dispersion in the cluster, and, where relevant, the effects of the depth of the cluster along the line of sight. Internal consistency of the TGAS data is assessed. Results. Values given for standard uncertainties are still inaccurate and may lead to unrealistic unit-weight standard deviations of least squares solutions for cluster parameters. Reconstructed mean cluster parallax and proper motion values are generally in very good agreement with earlier Hipparcos-based determination, although the Gaia mean parallax for the Pleiades is a significant exception. We have no current explanation for that discrepancy. Most clusters are observed to extend to nearly 15 pc from the cluster centre, and it will be up to future Gaia releases to establish whether those potential cluster-member stars are still dynamically bound to the clusters. Conclusions. The Gaia DR1 provides the means to examine open clusters far beyond their more easily visible cores, and can provide membership assessments based on proper motions and parallaxes. A combined HR diagram shows the same features as observed before using the Hipparcos data, with clearly increased luminosities for older A and F dwarfs.
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