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  • 101. Ehlén, Åsa
    et al.
    Nodin, Björn
    Rexhepaj, Elton
    Brändstedt, Jenny
    Uhlén, Mathias
    Alvarado-Kristensson, Maria
    Pontén, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Brennan, Donal J
    Jirström, Karin
    RBM3-regulated genes promote DNA integrity and affect clinical outcome in epithelial ovarian cancer2011Inngår i: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 4, nr 4, s. 212-221Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The RNA-binding motif protein 3 (RBM3) was initially discovered as a putative cancer biomarker based on its differential expression in various cancer forms in the Human Protein Atlas (HPA). We previously reported an association between high expression of RBM3 and prolonged survival in breast and epithelial ovarian cancer (EOC). Because the function of RBM3 has not been fully elucidated, the aim of this study was to use gene set enrichment analysis to identify the underlying biologic processes associated with RBM3 expression in a previously analyzed EOC cohort (cohort 1, n = 267). This revealed an association between RBM3 expression and several cellular processes involved in the maintenance of DNA integrity. RBM3-regulated genes were subsequently screened in the HPA to select for putative prognostic markers, and candidate proteins were analyzed in the ovarian cancer cell line A2780, whereby an up-regulation of Chk1, Chk2, and MCM3 was demonstrated in siRBM3-treated cells compared to controls. The prognostic value of these markers was assessed at the messenger RNA level in cohort 1 and the protein level in an independent EOC cohort (cohort 2, n = 154). High expression levels of Chk1, Chk2, and MCM3 were associated with a significantly shorter survival in both cohorts, and phosphorylated Chk2 was an adverse prognostic marker in cohort 2. These results uncover a putative role for RBM3 in DNA damage response, which might, in part, explain its cisplatin-sensitizing properties and good prognostic value in EOC. Furthermore, it is demonstrated that Chk1, Chk2, and MCM3 are poor prognostic markers in EOC.

  • 102.
    Ehrstedt, Christoffer
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Kristiansen, Ingela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Ahlsten, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Casar Borota, Olivera
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Dahl, Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Libard, Sylwia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Strömberg, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Clinical characteristics and late effects in CNS tumours of childhood: Do not forget long term follow-up of the low grade tumours2016Inngår i: European journal of paediatric neurology, ISSN 1090-3798, E-ISSN 1532-2130, Vol. 20, nr 4, s. 580-587Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To investigate clinical characteristics and late effects of CNS tumours in childhood with a special focus on low-grade tumours, especially low-grade astrocytoma and glib neuronal tumours. Methods: A retrospective population based study was performed at Uppsala University Children's Hospital, a tertiary referral centre for children with CNS tumours. Patients were identified from the National Brain Tumour Registry and the National Epilepsy Surgery Registry. Hospital medical records were analysed for patients with a follow up of >= 5 years after diagnosis. A re-evaluation of the neuro-pathological diagnosis was performed. Results: A total of 193 patients (age 0-17.99 years) during a twelve-year period (1995-2006) were included; 149 survived >= 5 years. Three larger subgroups could be identified: astrocytic, embryonal and glioneuronal tumours. A supratentorial location was found in 52%. Medical late effects were mainly neurological and endocrinological, affecting 81% and 26% of surviving patients. Cognitive late effects were a frequent finding in the whole group but also in low-grade astrocytoma and glioneuronal tumours (53% and 67%). Thirty per cent had some kind of pedagogic support in school. Conclusion: Late effects are common in long-term survivors of CNS tumours in childhood. Low-grade astrocytoma and glioneuronal tumours are no exception, and the findings support the need for long-term follow up.

  • 103.
    Elfving, Hedvig
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Mattsson, Johanna Sofia Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Lindskog, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Backman, Max
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Menzel, Uwe
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Programmed Cell Death Ligand 1 Immunohistochemistry: A Concordance Study Between Surgical Specimen, Biopsy, and Tissue Microarray2019Inngår i: Clinical Lung Cancer, ISSN 1525-7304, E-ISSN 1938-0690, Vol. 20, nr 4, s. 258-262.e1Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Programmed cell death ligand 1 (PD-L1) expression within the same lung cancer tissue is variable. In this study we evaluated if the PD-L1 expression on small biopsy specimens represent the PD-L1 status of the corresponding resection specimen. Our results indicate a relative good agreement between biopsy and surgical specimens, with a discordance in approximately 10% of the cases. Background: The immunohistochemical analysis of programmed cell death ligand 1 (PD-L1) expression in tumor tissue of non-small-cell lung cancer patients has now been integrated in the diagnostic workup. Analysis is commonly done on small tissue biopsy samples representing a minimal fraction of the whole tumor. The aim of the study was to evaluate the correlation of PD-L1 expression on biopsy specimens with corresponding resection specimens. Materials and Methods: In total, 58 consecutive cases with preoperative biopsy and resected tumor specimens were selected. From each resection specimen 2 tumor cores were compiled into a tissue microarray (TMA). Immunohistochemical staining with the antibody SP263 was performed on biopsy specimens, resection specimens (whole sections), as well as on the TMA. Results: The proportion of PD-L1-positive stainings were comparable between the resection specimens (48% and 19%), the biopsies (43% and 17%), and the TMAs (47% and 14%), using cutoffs of 1% and 50%, respectively (P > .39 all comparisons). When the resection specimens were considered as reference, PD-L1 status differed in 16%/5% for biopsies and in 9%/9% for TMAs (1%/50% cutoff). The sensitivity of the biopsy analysis was 79%/82% and the specificity was 90%/98% at the 1%/50% cutoff. The Cohens kappa value for the agreement between biopsy and tumor. was 0.70 at the 1% cutoff and 0.83 at the 50% cutoff. Conclusion: The results indicate a moderate concordance between the analysis of biopsy and whole tumor tissue, resulting in misclassification of samples in particular when the lower 1% cutoff was used. Clinicians should be aware of this uncertainty when interpreting PD-L1 reports for treatment decisions.

  • 104.
    Elfving, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin.
    Epidemiological and Bacteriological Aspects of Spotted Fever Rickettsioses in Humans, Vectors and Mammals in Sweden2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Rickettsiae are obligate intracellular gram-negative bacteria transmitted by arthropod vectors. Rickettsiae sometimes cause disease in humans, typically with high fever, headache and occasionally an eschar.

    In Sweden, Rickettsia helvetica, belonging to the spotted fever group, is the only tick-transmitted rickettsia found free in nature. The pathogenic roll of R. helvetica has not been fully investigated, but it has been implicated in aneruptive fever and cardiac disease.

    This thesis describes parts of the transmission pathways of rickettsiae in Sweden. Rickettsia infection rates in ticks collected from birds were analysed, and the birds’ role as disseminators and reservoirs was studied. We found that more than one in ten ticks was infected with rickettsia bacteria, predominantly R. helvetica, and that migrating birds contribute not only to long-distance dispersion of bacteria, but also to an inflow of novel and potentially pathogenic rickettsia species, in this case R. monacensis and R. sp. strain Davousti-like species, into Sweden.

    Further, wild and domestic animals were found to have seroreactivity against R. helvetica, which shows that they are exposed and susceptible to rickettsia. Their role as reservoirs has not been determined, yet they may indirectly be involved in transmission of rickettsia to humans by infected ticks feeding on them.

    The seroreactivity in humans was also studied. Patients investigated for suspected Borrelioses and blood donors had detectable antibodies against Rickettsia spp., with the highest prevalence detected in the suspected Borreliosis group. This shows that humans in Sweden are exposed to and develop an immune response against rickettsia. The suspicion that R. helvetica may cause severe symptoms was verified by a patient with subacute meningitis where the bacterium was shown for the first time to cause an invasive infection with CNS involvement and where the bacterium was isolated from the patient’s cerebrospinal fluid.

    Growth characteristics and morphology of R. helvetica were studied to better understand invasiveness and virulence. The findings indicate that the invasiveness is comparable with other rickettsia, though R. helvetica seems to have a stable but slightly slower growth. 

    Rickettsia helvetica is endemic in Sweden and therefore needs to be considered when investigating disease after a tick bite.

    Delarbeid
    1. Seroprevalence of Rickettsia spp. infection among tick-bitten patients and blood donors in Sweden
    Åpne denne publikasjonen i ny fane eller vindu >>Seroprevalence of Rickettsia spp. infection among tick-bitten patients and blood donors in Sweden
    2008 (engelsk)Inngår i: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 40, nr 1, s. 74-77Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Serum samples from 236 Swedish patients with symptoms of infectious disease appearing after a tick bite were analysed for the presence of antibodies to Rickettsia helvetica, the only rickettsial species so far isolated from ticks in Sweden. Of these subjects, 137 had tested seropositive for Borrelia burgdorferi. For control purposes, sera from 161 healthy blood donors were examined. A total of 10/397 samples (2.6%) showed IgG-antibodies to R. helvetica at or above a titre of 1/80 as cut-off. 6/137 (4.4%) belonged to the Borrelia positive group, 3/99 (3.0%) to the tick-bitten but Borrelia negative group and 1/161 (0.6%) to the control group. The difference between the tick-exposed groups and the control group was significant in Pearson's 2-sided chi(2) test. In 1 serum sample the presence of antibodies to R. helvetica was further confirmed by Western immunoblot. The study shows that infection with Rickettsia spp. as well as coinfection with Lyme borreliosis needs to be considered in the diagnosis of tick-transmitted infections in Sweden. Owing to a known occurrence of immunological cross-reactivites, however, the results must be cautiously interpreted with regard to species of Rickettsia involved.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-103987 (URN)10.1080/00365540701509907 (DOI)000252311200014 ()17852905 (PubMedID)
    Tilgjengelig fra: 2009-05-26 Laget: 2009-05-26 Sist oppdatert: 2018-02-25bibliografisk kontrollert
    2. Dissemination of Spotted Fever Rickettsia Agents in Europe by Migrating Birds
    Åpne denne publikasjonen i ny fane eller vindu >>Dissemination of Spotted Fever Rickettsia Agents in Europe by Migrating Birds
    Vise andre…
    2010 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, nr 1, s. e8572-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Migratory birds are known to play a role as long-distance vectors for many microorganisms. To investigate whether this is true of rickettsial agents as well, we characterized tick infestation and gathered ticks from 13,260 migratory passerine birds in Sweden. A total of 1127 Ixodes spp. ticks were removed from these birds and the extracted DNA from 957 of them was available for analyses. The DNA was assayed for detection of Rickettsia spp. using real-time PCR, followed by DNA sequencing for species identification. Rickettsia spp. organisms were detected in 108 (11.3%) of the ticks. Rickettsia helvetica, a spotted fever rickettsia associated with human infections, was predominant among the PCR-positive samples. In 9 (0.8%) of the ticks, the partial sequences of 17kDa and ompB genes showed the greatest similarity to Rickettsia monacensis, an etiologic agent of Mediterranean spotted fever-like illness, previously described in southern Europe as well as to the Rickettsia sp.IrITA3 strain. For 15 (1.4%) of the ticks, the 17kDa, ompB, gltA and ompA genes showed the greatest similarity to Rickettsia sp. strain Davousti, Rickettsia japonica and Rickettsia heilongjiangensis, all closely phylogenetically related, the former previously found in Amblyomma tholloni ticks in Africa and previously not detected in Ixodes spp. ticks. The infestation prevalence of ticks infected with rickettsial organisms was four times higher among ground foraging birds than among other bird species, but the two groups were equally competent in transmitting Rickettsia species. The birds did not seem to serve as reservoir hosts for Rickettsia spp., but in one case it seems likely that the bird was rickettsiemic and that the ticks had acquired the bacteria from the blood of the bird. In conclusion, migratory passerine birds host epidemiologically important vector ticks and Rickettsia species and contribute to the geographic distribution of spotted fever rickettsial agents and their diseases.

    Emneord
    Ixodes, ticks, birds, infestation, rickettsia, spotted fever
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-113683 (URN)10.1371/journal.pone.0008572 (DOI)000273338500015 ()20052286 (PubMedID)
    Tilgjengelig fra: 2010-02-02 Laget: 2010-02-02 Sist oppdatert: 2018-01-12bibliografisk kontrollert
    3. Rickettsia helvetica in patient with meningitis, Sweden, 2006
    Åpne denne publikasjonen i ny fane eller vindu >>Rickettsia helvetica in patient with meningitis, Sweden, 2006
    2010 (engelsk)Inngår i: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 16, nr 3, s. 490-492Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Pathogenicity of Rickettsia helvetica is relatively unknown. We isolated a spotted fever group rickettsial organism from a patient with subacute meningitis. Nucleotide sequences of the 16S rRNA, ompB, and 17kDa genes identified the isolate as R. helvetica. This organism may be associated with serious infections such as central nervous system disorders.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-125294 (URN)10.3201/eid1603.090184 (DOI)000275404700018 ()20202426 (PubMedID)
    Tilgjengelig fra: 2010-05-14 Laget: 2010-05-14 Sist oppdatert: 2018-03-02bibliografisk kontrollert
    4. Life cycle, growth characteristics and host cell response of Rickettsia helvetica in a Vero cell line
    Åpne denne publikasjonen i ny fane eller vindu >>Life cycle, growth characteristics and host cell response of Rickettsia helvetica in a Vero cell line
    2012 (engelsk)Inngår i: Experimental & applied acarology, ISSN 0168-8162, E-ISSN 1572-9702, Vol. 56, nr 2, s. 179-187Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Rickettsia helvetica, a spotted fever rickettsia and emerging pathogen with Ixodes ricinus ticks as the main vector, is an agent of human disease and may cause febrile illness as well as meningitis. In three parallel series the isolated standard type of R. helvetica, obtained from a PCR-positive I. ricinus tick, was high-passaged and propagated in a Vero cell line. By using quantitative real-time PCR, the generation time from inoculation to stationary phase of growth was calculated to 20-22 h. In the static cultivation system the stationary phase was observed from the seventh day after inoculation, and there was no observed degradation of R. helvetica DNA during the 14 days studied. Microscopy showed that the organisms invaded the host cells rapidly and were primarily found free in the cytoplasm and only occasionally located in the nucleus. Four days after inoculation some of the host cells were broken and many indifferent stages of cytoplasmic organic decomposition were seen. However the R. helvetica organism did not show any morphologic alterations and the number of organisms was stable after the replication peak which may indicate that R. helvetica is adapted to growth in a Vero cell line and/or that the phase of degradation occurs later than the 14 days studied. The findings differ from what has been reported for other rickettsiae of the spotted fever group and may be of importance for invasiveness and virulence of R. helvetica.

    Emneord
    rickettsia, qPCR, vero cells, life cycle, ultrastructure
    HSV kategori
    Forskningsprogram
    Infektionssjukdomar
    Identifikatorer
    urn:nbn:se:uu:diva-166778 (URN)10.1007/s10493-011-9508-7 (DOI)000299078900010 ()
    Merknad

    Correction in: Experimental and Applied Acarology, Vol 56, Issue 2, pp 189-190

    DOI: 10.1007/s10493-011-9509-6

    Tilgjengelig fra: 2012-01-13 Laget: 2012-01-13 Sist oppdatert: 2017-12-08bibliografisk kontrollert
    5. Seroreactivity to Rickettsia spp. in Wild and Domestic Mammals in Sweden
    Åpne denne publikasjonen i ny fane eller vindu >>Seroreactivity to Rickettsia spp. in Wild and Domestic Mammals in Sweden
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Sera were collected from wild and domestic mammals in Sweden and tested using indirect immunofluorescence assay to detect antibodies against Rickettsia spp. Considering sera with a titre > 1:64 as positive, 23.1% (104/450) of the animals scored positive. The percentages of seropositivity were: 21.5% (23/107) in deer, 23.3% (21/90) in moose, 36.5% (23/61) in horses, 22.2% (20/90) in cats and 17.0% (17/100) in dogs. In deer, 85% (91/107) also tested positive for Anaplasma phagocytophilum with a titre cut-off of 1:80. The findings indicate that these animal species may act as reservoir hosts of Rickettsia spp. and that deer may act as hosts for both tested organisms.

    Emneord
    Rickettsia, Anaplasma, Serology, Host, Moose, Deer
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-197803 (URN)
    Tilgjengelig fra: 2013-04-04 Laget: 2013-04-04 Sist oppdatert: 2013-08-30
    Fulltekst (pdf)
    fulltext
  • 105.
    Elobeid, Adila
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Libard, Sylwia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Leino, Marina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Popova, Svetlana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Altered proteins in the aging brain2016Inngår i: Journal of Neuropathology and Experimental Neurology, ISSN 0022-3069, E-ISSN 1554-6578, Vol. 75, nr 4, s. 316-325Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We assessed the prevalence of common altered brain proteins in 296 cognitively unimpaired subjects ranging from age 50 to 102 years. The incidence and the stage of hyperphosphorylated-tau (HP tau), beta-amyloid, alpha-synuclein (alpha S), and transactive response DNA (TDP) binding protein 43 (TDP43)-immunoreactivity (-IR) increased with age. HP tau-IR was observed in 98% of the subjects; the locus coeruleus was solely affected in 46%, and 79% of the subjects were in Braak stages a to II. beta-Amyloid was seen in 47% of subjects and the Thal phase correlated with the HP tau Braak stage and age. Intermediate Alzheimer disease-related pathology (ADRP) was seen in 12%; 52% of the subjects with HP tau-IR fulfilled criteria for definite primary age-related tauopathy (PART). The incidence of concomitant pathology (alpha S, TDP43) did not differ between those with PART and those with ADRP but the former were younger. TDP43-IR was observed in 36%; the most frequently affected region was the medulla; alpha S-IR was observed in 19% of subjects. In 41% of the subjects from 80 to 89 years at death, 3 altered proteins were seen in the brain. Thus, altered proteins are common in the brains of cognitively unimpaired aged subjects; this should be considered while developing diagnostic biomarkers, particularly for identifying subjects at early stages of neurodegenerative diseases.

    Fulltekst (pdf)
    fulltext
  • 106.
    Emami Khoonsari, Payam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Musunri, Sravani
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Herman, Stephanie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Svensson, Camilla I
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden..
    Tanum, Lars
    Department of R&D in Mental Health, Akershus University Hospital, Lørenskog, Norway..
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Systematic Analysis of the Cerebrospinal Fluid Proteome of Fibromyalgia patients2019Inngår i: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, s. 35-43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fibromyalgia (FM) is a syndrome characterized by widespread muscular pain, fatigue and functional symptoms, which is known to be difficult to diagnose as the various symptoms overlap with many other conditions. Currently, there are no biomarkers for FM, and the diagnosis is made subjectively by the clinicians. We have performed shotgun proteomics on cerebrospinal fluid (CSF) from FM patients and non-pain controls to find potential biomarker candidates for this syndrome. Based on our multivariate and univariate analyses, we found that the relative differences in the CSF proteome between FM patients and controls were moderate. Four proteins, important to discriminate FM patients from non-pain controls, were found: Apolipoprotein C-III, Galectin-3-binding protein, Malate dehydrogenase cytoplasmic and the neuropeptide precursor protein ProSAAS. These proteins are involved in lipoprotein lipase (LPL) activity, inflammatory signaling, energy metabolism and neuropeptide signaling.

  • 107. Emblem, Kyrre E
    et al.
    Nedregaard, Baard
    Nome, Terje
    Due-Tonnessen, Paulina
    Hald, John K
    Scheie, David
    Casar-Borota, Olivera
    Olivera Casar-Borotas publikationer.
    Cvancarova, Milada
    Bjornerud, Atle
    Glioma grading by using histogram analysis of blood volume heterogeneity from MR-derived cerebral blood volume maps.2008Inngår i: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 247, nr 3, s. 808-17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: To retrospectively compare the diagnostic accuracy of an alternative method used to grade gliomas that is based on histogram analysis of normalized cerebral blood volume (CBV) values from the entire tumor volume (obtained with the histogram method) with that of the hot-spot method, with histologic analysis as the reference standard.

    MATERIALS AND METHODS: The medical ethics committee approved this study, and all patients provided informed consent. Fifty-three patients (24 female, 29 male; mean age, 48 years; age range, 14-76 years) with histologically confirmed gliomas were examined with dynamic contrast material-enhanced 1.5-T magnetic resonance (MR) imaging. CBV maps were created and normalized to unaffected white matter (normalized CBV maps). Four neuroradiologists independently measured the distribution of whole-tumor normalized CBVs and analyzed this distribution by classifying the values into area-normalized bins. Glioma grading was performed by assessing the normalized peak height of the histogram distributions. Logistic regression analysis and interobserver agreement were used to compare the proposed method with a hot-spot method in which only the maximum normalized CBV was used.

    RESULTS: For the histogram method, diagnostic accuracy was independent of the observer. Interobserver agreement was almost perfect for the histogram method (kappa = 0.923) and moderate for the hot-spot method (kappa = 0.559). For all observers, sensitivity was higher with the histogram method (90%) than with the hot-spot method (55%-76%).

    CONCLUSION: Glioma grading based on histogram analysis of normalized CBV heterogeneity is an alternative to the established hot-spot method, as it offers increased diagnostic accuracy and interobserver agreement.

  • 108.
    Enblad, Gunilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Karlsson, Hannah
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Gammelgård, Gustav
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Wenthe, Jessica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Lövgren, Tanja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Wikstrom, Kristina I.
    Karolinska Univ Hosp Huddinge, VECURA, Stockholm, Sweden.
    Essand, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Savoldo, Barbara
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
    Hallböök, Helene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Dotti, Gianpietro
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
    Brenner, Malcolm K.
    Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Loskog, Angelica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia2018Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 24, nr 24, s. 6185-6194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: The chimeric antigen receptor (CAR) T-cell therapy has been effective for patients with CD19(+) B-cell malignancies. Most studies have investigated the second-generation CARs with either CD28 or 4-1BB costimulatory domains in the CAR receptor. Here, we describe the first clinical phase I/IIa trial using third-generation CAR T cells targeting CD19 to evaluate safety and efficacy.

    Patients and Methods: Fifteen patients with B-cell lymphoma or leukemia were treated with CAR T cells. The patients with lymphoma received chemotherapy during CAR manufacture and 11 of 15 were given low-dose cyclophosphamide and fludarabine conditioning prior to CAR infusion. Peripheral blood was sampled before and at multiple time points after CAR infusion to evaluate the persistence of CAR T cells and for immune profiling, using quantitative PCR, flow cytometry, and a proteomic array.

    Results: Treatment with third-generation CAR T cells was generally safe with 4 patients requiring hospitalization due to adverse reactions. Six of the 15 patients had initial complete responses [4/11 lymphoma and 2/4 acute lymphoblastic leukemia (ALL)], and 3 of the patients with lymphoma were in remission at 3 months. Two patients are still alive. Best predictor of response was a good immune status prior to CAR infusion with high IL12, DC-Lamp, Fas ligand, and TRAIL. Responding patients had low monocytic myeloid-derived suppressor cells (MDSCs; CD14(+)CD33(+)HLA(-)DR(-)) and low levels of IL6, IL8, NAP3, sPDL1, and sPDL2.

    Conclusions: Third-generation CARs may be efficient in patients with advanced B-cell lymphoproliferative malignancy with only modest toxicity. Immune profiling pre- and posttreatment can be used to find response biomarkers.

  • 109.
    Enblad, Gunilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Martinsson, Gustaf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Hesselager, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Population-based experience on primary central nervous system lymphoma 2000-2012: the incidence is increasing2017Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, nr 4, s. 599-607Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Primary central nervous system lymphomas (PCNSL) are rare lymphomas with a poor prognosis. Recently, an increased incidence has been reported. The present study is a population-based study of all patients with PCNSL in the Uppsala/Örebro region of middle Sweden.

    PATIENTS AND METHODS: All patients diagnosed with a PCNSL at Uppsala University Hospital 2000-2012 were identified. Altogether, 96 patients (50 women and 46 men) were included. The median age at diagnosis was 66 years (17-95).

    RESULTS: There was a statistically significant increase in age-standardized incidence during the study period, 30 patients were diagnosed in the first half and 66 in the second half of the period. No patient had an HIV-infection. Two patients had undergone kidney transplantation and were treated with immunosuppressive drugs. A high proportion of the patients, 29%, had a history of an autoimmune or inflammatory disease. The prognosis was poor with a median survival of only four months. In the 70 (73%) patients treated with curative intention the median survival was 12 months. Patients treated with high-dose methotrexate, radiotherapy and/or temozolomide appeared to have a better survival. There was no improvement in survival during the study period or after the introduction of rituximab. There also was no difference in any of the analyzed variables that could explain the increased incidence.

    CONCLUSION: In this population-based study we could confirm the previously described increased incidence of PCNSL. The prognosis remains poor despite the inclusion of treatment with rituximab during the study period. A high proportion of the patients had a history of an autoimmune or inflammatory disease not previously described but there was no increase during the study period.

  • 110.
    Englund, Annika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Molin, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Karlén, Jonas
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Glimelius, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Ljungman, Gustaf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    The role of tumour-infiltrating eosinophils, mast cells and macrophages in Classical and Nodular Lymphocyte Predominant Hodgkin Lymphoma in children2016Inngår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 97, nr 5, s. 430-438Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To study Hodgkin lymphoma (HL) microenvironment in a Swedish paediatric population and its relation to clinical parameters.

    METHODS: Tumour tissue from classical HL (cHL) (n=87) and nodular lymphocyte predominant HL (NLPHL) (n=11) was investigated for Epstein-Barr Virus (EBV) and analysed for eosinophils, mast cells and macrophages.

    RESULTS: In cHL, EBV positivity was more common in low age (p<0.001) and in mixed cellularity (MC) (p<0.001). Higher mast cell infiltration was seen in stage III-IV (p<0.001), and with presence of B-symptoms (p=0.01). Cases with high mast cell counts displayed higher erythrocyte sedimentation rate (ESR), lower haemoglobin and albumin levels. Higher macrophage infiltration was seen in stage III-IV (p=0.02) and there was elevated ESR and neutrophil count. All NLPHL cases were EBV negative, had lower rates of inflammatory cells and lower degree of inflammatory reaction in laboratory parameters. There was no difference in survival estimates with regard to infiltration of inflammatory cells.

    CONCLUSIONS: Higher levels of mast cells and macrophages in cHL tumours reflected the clinical presentation in laboratory parameters, B-symptoms and more advanced stages. NLPHL differs from cHL in numbers of inflammatory cells in the tumour, and in laboratory parameters. This article is protected by copyright. All rights reserved.

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  • 111.
    Englund, Sofia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Verification of a method for sexual hormone-binding globulin analysis and estimation of free testosterone2012Independent thesis Advanced level (professional degree), 10 poäng / 15 hpOppgave
    Abstract [en]

    Introduction: Sexual hormone-binding globulin (SHBG) is a protein that binds to androgens and oestrogens, especially testosterone. The fraction of testosterone that is not bound to SHBG is the biologically active fraction which makes its determination more relevant than determining the total amount of circulating testosterone. It is difficult to measure the plasma concentration of free testosterone; therefore calculations using the concentrations of testosterone and SHBG are used to estimate the amount of free testosterone. A few calculations include the concentration of albumin because testosterone also binds to albumin. The main aims of this study were to verify a method for the determination of SHBG and to calculate a reference interval for free androgen index (FAI, testosterone/SHBG) in women. Other calculations for determination of the free testosterone fraction were compared.

    Methods: Testosterone, SHBG and albumin were measured in serum from 20 men and 100 women. Testosterone and SHBG was measured using immunoassays on a Roche Modular E instrument (ECLIA). Albumin was measured with a c8000 Architect instrument. Four calculations, two with only testosterone and SHBG and two with testosterone, SHBG and albumin were compared.  Results/Conclusion: The verification of the SHBG method was successful which means that the method can be taken into routine use. A reference interval for FAI was constructed. It was difficult to show if other estimation of free testosterone would work better than FAI in clinical practice. This is discussed.

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  • 112. Enlund, Fredrik
    et al.
    Helenius, Gisela
    Palmqvist, Richard
    Edsjö, Anders
    Sundström, Magnus
    Avdelningen för molekylärpatologi, sektionen för klinisk patologi och cytologi, Akademiska sjukhuset, Uppsala, Sweden.
    Mutationsanalys av KRAS inför riktad terapi vid kolorektalcancer: Kvalitetskontroll av molekylärpatologiska metoder i Sverige2010Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, nr 5, s. 255-259Artikkel i tidsskrift (Fagfellevurdert)
  • 113.
    Eriksson, Oskar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Studies on Tissue Factor with Focus on Cell Signaling and Cancer2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis have explored the functions of the protein Tissue Factor (TF), which together with its ligand coagulation factor VII/VIIa (FVII/FVIIa) forms a proteolytic complex that functions in initiation of blood coagulation and activation of cell signaling.

    In paper I, the mechanisms behind the observation that TF/FVIIa signaling protects cells from apoptosis were further investigated. Using cell culture models, we found that antiapoptotic signaling by TF/FVIIa requires signaling by the Insulin-like growth factor I receptor (IGF-1R), as synthetic IGF-1R inhibitors and IGF1-R siRNA knock-down abolished the antiapoptotic effect of FVIIa. Furthermore, the IGF-1R translocated to the cell nucleus after FVIIa stimulation, implying a role in regulation of gene expression.

    Papers II and III describe the discovery that the Eph tyrosine kinase receptors EphB2 and EphA2 are proteolytically cleaved directly by TF/FVIIa. By using mass spectrometry and N-terminal Edman sequencing, the exact cleavage site was identified after a conserved arginine residue in the EphA2/EphB2 ligand binding domains, in agreement with the cleavage preferences of FVIIa. TF and EphA2/EphB2 co-localized in cancer cell lines and FVIIa potentiated ligand-dependent Eph signaling by increasing cytoskeletal remodeling and cell repulsion, demonstrating a novel proteolytical event that modulates Eph receptor signaling.

    In paper IV, expression of TF was investigated in colorectal cancer in both the stromal and tumor cell compartments by immunohistochemistry using an anti-TF-antibody developed and validated by the Human Protein Atlas project. In normal large intestine, TF was strongly expressed in the innermost pericryptal sheath cell layer lining the epithelium, in a cell population distinct from intestinal pericryptal myofibroblasts. We evaluated TF expression in two colorectal cancer materials, and found that TF was variably present in both the stromal and tumor cell compartments. TF expressed by pericryptal sheath cells was progressively lost after the adenoma-to-carcinoma transition and was a strong predictor of survival in rectal but not colon cancer patients independently of disease stage, histological tumor grade and age.

    In summary, this thesis demonstrates novel signaling mechanisms for the TF/FVIIa complex, and provides evidence of a hitherto unknown role of TF expressed by a specific population of stromal cells in colorectal cancer.

    Delarbeid
    1. Tissue factor/factor VIIa induces cell survival and gene transcription by transactivation of the insulin-like growth factor 1 receptor
    Åpne denne publikasjonen i ny fane eller vindu >>Tissue factor/factor VIIa induces cell survival and gene transcription by transactivation of the insulin-like growth factor 1 receptor
    2014 (engelsk)Inngår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 111, nr 4, s. 748-760Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The insulin-like growth factor 1 receptor (IGF-1R) is known to promote survival and has also been implicated in the pathogenesis of several disease states, including cardiovascular disorders and cancer. Recently, we showed that binding of coagulation factor VIIa (FVIIa) to its receptor tissue factor (TF) protects cancer cells from TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis. Here we present evidence that this biological function of TF/FVIIa is dependent on the IGF-1R. IGF-1R inhibitors AG1024 and PPP as well as siRNA-mediated downregulation of IGF-1R, abolished the TF/FVIIa-mediated protection against TRAIL-induced apoptosis. Moreover, FVIIa rapidly induced a time- and concentration-dependent tyrosine phosphorylation of the IGF-1R in MDA-MB-231 breast cancer cells and in primary human monocytes, an event that was accompanied by IGF-1R chromatin binding and gene transcription. We hereby present novel evidence of a cross-talk between the coagulation and IGF-1R signalling systems, and propose that the IGF-1R is a key player in mediating TF/FVIIa-induced cell survival.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-223990 (URN)10.1160/TH13-07-0593 (DOI)000334152900024 ()24336871 (PubMedID)
    Tilgjengelig fra: 2014-04-29 Laget: 2014-04-29 Sist oppdatert: 2018-01-11bibliografisk kontrollert
    2. The Eph Tyrosine Kinase Receptors EphB2 and EphA2 Are Novel Proteolytic Substrates of Tissue Factor/Coagulation Factor VIIa
    Åpne denne publikasjonen i ny fane eller vindu >>The Eph Tyrosine Kinase Receptors EphB2 and EphA2 Are Novel Proteolytic Substrates of Tissue Factor/Coagulation Factor VIIa
    Vise andre…
    2014 (engelsk)Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 289, nr 47Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Tissue factor (TF) binds the serine protease factor VIIa (FVIIa) to form a proteolytically active complex that can trigger coagulation or activate cell signaling. Here we addressed the involvement of tyrosine kinase receptors (RTKs) in TF/FVIIa signaling by antibody array analysis and subsequently found that EphB2 and EphA2 of the Eph RTK family were cleaved in their ectodomains by TF/FVIIa. We used N-terminal Edman sequencing and LC-MS/MS analysis to characterize the cleaved Eph isoforms and identified a key arginine residue at the cleavage site, in agreement with the tryptic serine protease activity of FVIIa. Protease-activated receptor 2 (PAR2) signaling and downstream coagulation activity was non-essential in this context, in further support of a direct cleavage by TF/FVIIa. EphB2 was cleaved by FVIIa concentrations in the subnanomolar range in a number of TF expressing cell types, indicating that the active cellular pool of TF was involved. FVIIa caused potentiation of cell repulsion by the EphB2 ligand ephrin-B1, demonstrating a novel proteolytical event to control Eph-mediated cell segregation. These results define Eph RTKs as novel proteolytical targets of TF/FVIIa and provide new insights into how TF/FVIIa regulates cellular functions independently of PAR2.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-240089 (URN)10.1074/jbc.M114.599332 (DOI)000345335000001 ()25281742 (PubMedID)
    Tilgjengelig fra: 2015-01-05 Laget: 2015-01-05 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    3. Tissue Factor/coagulation factor VIIa potentiates ligand-dependent EphA2 signaling in cancer cells
    Åpne denne publikasjonen i ny fane eller vindu >>Tissue Factor/coagulation factor VIIa potentiates ligand-dependent EphA2 signaling in cancer cells
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-245804 (URN)
    Tilgjengelig fra: 2015-03-01 Laget: 2015-03-01 Sist oppdatert: 2015-04-17
    4. Tissue Factor in pericryptal sheath cells identifies a specific intestinal cell population and constitutes a candidate prognostic biomarker for rectal cancer
    Åpne denne publikasjonen i ny fane eller vindu >>Tissue Factor in pericryptal sheath cells identifies a specific intestinal cell population and constitutes a candidate prognostic biomarker for rectal cancer
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-245803 (URN)
    Tilgjengelig fra: 2015-03-01 Laget: 2015-03-01 Sist oppdatert: 2015-04-17
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    presentationsbild
  • 114.
    Eskelund, Christian W.
    et al.
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Kolstad, Arne
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway..
    Jerkeman, Mats
    Univ Lund Hosp, Dept Oncol, Lund, Sweden..
    Raty, Riikka
    Univ Helsinki, Dept Haematol, Cent Hosp, Helsinki, Finland..
    Laurell, Anna
    Univ Uppsala Hosp, Dept Oncol, Uppsala, Sweden..
    Eloranta, Sandra
    Karolinska Inst, Clin Epidemiol Unit, Dept Med Solna, Stockholm, Sweden..
    Smedby, Karin E.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med Solna, Stockholm, Sweden..
    Husby, Simon
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Pedersen, Lone B.
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Andersen, Niels S.
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Eriksson, Mikael
    Univ Lund Hosp, Dept Oncol, Lund, Sweden..
    Kimby, Eva
    Karolinska Inst, Dept Haematol, Stockholm, Sweden..
    Bentzen, Hans
    Aarhus Univ Hosp, Dept Haematol, Aarhus, Denmark..
    Kuittinen, Outi
    Oulu Univ Hosp, Dept Radiotherapy & Oncol, Oulu, Finland..
    Lauritzsen, Grete F.
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway..
    Nilsson-Ehle, Herman
    Sahlgrens Univ Hosp, Sect Haematol & Coagulat Med, Gothenburg, Sweden..
    Ralfkiaer, Elisabeth
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Ehinger, Mats
    Univ Lund Hosp, Dept Pathol, Lund, Sweden..
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi. Univ Uppsala Hosp, Dept Genet & Pathol, Uppsala, Sweden..
    Delabie, Jan
    Oslo Univ Hosp, Dept Pathol, Oslo, Norway..
    Karjalainen-Lindsberg, Marja-Liisa
    Univ Helsinki, Dept Pathol, Cent Hosp, Helsinki, Finland..
    Workman, Christopher T.
    Tech Univ Denmark, Dept Syst Biol, Lyngby, Denmark.;Univ Copenhagen, Dept Hlth Sci, Copenhagen, Denmark..
    Garde, Christian
    Tech Univ Denmark, Dept Syst Biol, Lyngby, Denmark.;Univ Copenhagen, Dept Hlth Sci, Copenhagen, Denmark..
    Elonen, Erkki
    Univ Helsinki, Dept Haematol, Cent Hosp, Helsinki, Finland..
    Brown, Peter
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Gronbaek, Kirsten
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Geisler, Christian H.
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau2016Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 175, nr 3, s. 410-418Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 114years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 127 and 85years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.

  • 115. Evang, J Arild
    et al.
    Casar Borota, Olivera
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi. Dept. of laboratory medicine/pathology Umeå university hospital.
    Melum, Espen
    Holm, Ruth
    Ramm-Pettersen, Jon
    Bollerslev, Jens
    Berg, Jens P
    HDAC2 expression and variable number of repeats in exon 1 of the HDAC2 gene in corticotroph adenomas2010Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 73, nr 2, s. 229-235Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Alterations in protein expression of histone deacetylase 2 (HDAC2) have been demonstrated in various neoplasms, and lack of nuclear expression of HDAC2 has previously been shown in some human and canine corticotroph adenomas. This study aimed to examine HDAC2 expression in a Norwegian cohort of corticotroph adenomas, screen for exonic HDAC2 gene variants in the adenomas and correlate the results with clinical data.

    PATIENTS AND DESIGN: Forty-four patients with verified Cushing's disease or Nelson's syndrome, positive ACTH staining and tissue available for immunohistochemistry and/or DNA sequencing were included. Ninety-four controls were chosen from the Norwegian Bone Marrow Registry.

    RESULTS: Histone deacetylase 2 expression examined by immunohistochemistry was strongly reduced in 3/30 adenomas. There were no association between HDAC2 expression and clinical variables. A previously unidentified insertion of three bases in a region coding for a polyserine cluster in exon 1 of the HDAC2 gene was identified in 6/32 adenomas. No other mutations in HDAC2 exons were found. Examination of DNA extracted from peripheral blood confirmed germ-line origin of the exon 1 insertion. The same insertion was also found in 28/94 of the controls (i.e., not significantly different from the patients).

    CONCLUSIONS: Strongly reduced HDAC2 protein expression was confirmed in a small portion of corticotroph tumours. Mutations in HDAC2 exons are unlikely to play an important role in the development of corticotroph adenomas.

  • 116. Evang, Johan Arild
    et al.
    Berg, Jens Petter
    Casar-Borota, Olivera
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Lekva, Tove
    Kringen, Marianne Kristiansen
    Ramm-Pettersen, Jon
    Bollerslev, Jens
    Reduced levels of E-cadherin correlate with progression of corticotroph pituitary tumours2011Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 75, nr 6, s. 811-818Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES:

    Loss of E-cadherin is an important marker of epithelial tumour progression. The aims of this study were to explore whether E-cadherin expression and localization correlate to corticotroph tumour progression, relate the expression of the E-cadherin gene (CDH1) to immunohistochemical E-cadherin staining pattern, and study whether the E-cadherin levels were correlated to methylation status of the CDH1 promoter region.

    DESIGN:

    Immunohistochemical analyses of E-cadherin protein were performed, as was RT-qPCR of the CDH1 and the POMC genes. Methylation pattern of the promoter region of CDH1 was measured using pyrosequencing of bisulfite-treated DNA.

    PATIENTS:

    Forty-five patients operated at a tertiary referral centre in Oslo, Norway. Adenoma tissue sections and RNA samples from patients with verified Cushing's disease or Nelson's syndrome were collected.

    MEASUREMENTS:

    Expression of E-cadherin mRNA and protein in pituitary corticotroph adenomas and average percentage of methylated cytosines in a cytosine-phosphate-guanosine island of the CDH1 promoter.

    RESULTS:

    Correlations were observed between tumour progression and both nuclear expression of E-cadherin and reduced CDH1 mRNA. The E-cadherin expression was not determined by the methylation pattern of the CDH1 promoter.

    CONCLUSIONS:

    Corticotroph tumour progression was associated with reduced expression of the epithelial marker E-cadherin.

  • 117.
    Falk Delgado, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Fahlström, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Nilsson, Markus
    Lund Univ, Bioimaging Ctr, Lund, Sweden..
    Berntsson, Shala G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Zetterling, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Libard, Sylwia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    van Westen, Danielle
    Lund Univ, Clin Sci Lund, Diagnost Radiol, Lund, Sweden..
    Lätt, Jimmy
    Skane Univ Healthcare, Dept Imaging & Funct, Lund, Sweden..
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Diffusion kurtosis imaging of gliomas grades II and III: a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation2017Inngår i: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 51, nr 2, s. 121-129Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Diffusion kurtosis imaging (DKI) allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM) differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas).

    Patients and methods. Forty-eight patients with suspected low-grade glioma were prospectively recruited to this institutional review board-approved study and investigated with preoperative DKI at 3T after written informed consent. Patients with histologically proven glioma grades II or III were further analyzed (n=35). Regions of interest (ROIs) were delineated on T2FLAIR images and co-registered to diffusion MRI parameter maps. Mean DKI data were compared between perilesional and contralesional NAWM (student's t-test for dependent samples, Wilcoxon matched pairs test). Histogram DKI data were compared between glioma types and glioma grades (multiple comparisons of mean ranks for all groups). The discriminating potential for DKI in assessing glioma type and grade was assessed with receiver operating characteristics (ROC) curves.

    Results. There were significant differences in all mean DKI variables between perilesional and contralesional NAWM (p=< 0.000), except for axial kurtosis (p=0.099). Forty-four histogram variables differed significantly between glioma grades II (n=23) and III (n=12) (p=0.003-0.048) and 10 variables differed significantly between ACs (n=18) and ODs (n=17) (p=0.011-0.050). ROC curves of the best discriminating variables had an area under the curve (AUC) of 0.657-0.815.

    Conclusions. Mean DKI variables in perilesional NAWM differ significantly from contralesional NAWM, suggesting altered microstructure by tumor infiltration not depicted on morphological MRI. Histogram analysis of DKI data identifies differences between glioma grades and subtypes.

    Fulltekst (pdf)
    fulltext
  • 118.
    Fall, Tove
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hedman, Anna
    Karolinska Institutet.
    Pershagen, Göran
    Karolinska Institutet.
    Andolf, Ellika
    Karolinska Institutet.
    Almqvist, Catarina
    Karolinska Institutet.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Reference Intervals for Fecal Calprotectin in Pregnant Women Using a Particle Enhanced Turbidimetric Assay2019Inngår i: Clinical Laboratory, ISSN 1433-6510, Vol. 65, nr 7, s. 1293-1297Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Fecal calprotectin is widely used as a marker for inflammatory bowel diseases (IBD). IBD often affects women during their reproductive years, but there are no established reference intervals during pregnancy. The aim of the present study was to define reference values during pregnancy and in the postpartum period to allow comparisons between patient results and reference values.

    METHODS: Fecal samples were collected from 84 healthy females during pregnancy week 26 to 28 and a second sample was collected six months after delivery. The samples were weighed, extracted, and centrifugated to remove debris. The extracted samples were then analyzed on a chemistry analyzer using a particle enhanced turbidimetric immunoassay reagent.

    RESULTS: The calculated reference interval during pregnancy was < 127 μg/g (90% confidence interval, 90 - 164 μg/g) and the corresponding reference interval during the postpartum period was < 143 μg/g (60 - 226 μg/g). There were no significant statistical differences between F-calprotectin values analyzed at the two sampling times.

    CONCLUSIONS: The reference values are slightly higher than the cutoff values of 50 - 100 μg/g often used as General cutoff for fecal calprotectin.

  • 119.
    Fellström, Bengt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Soveri, Inga
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Wu, Ping-Hsun
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Thulin, Måns
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
    Ärnlöv, Johan
    Dalarna Univ, Dept Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females2020Inngår i: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 40, nr 2, s. 71-74Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There exists a close relationship between cardiovascular diseases and chronic kidney disease. Apolipoprotein A1 and high-density lipoprotein (HDL) cholesterol are widely used as cardiovascular risk markers but they also have anti-inflammatory properties. The aim of this study was to investigate any associations between HDL levels and cytokine levels in urine. We randomly selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The samples were analyzed with 2 multiplex assays, Multiplex Inflammation I and Cardiovascular II kits (Olink Bioscience, Uppsala, Sweden). We analyzed the correlations between 158 cytokines in urine with apolipoprotein A1, HDL cholesterol, apolipoprotein B, and low-density lipoprotein cholesterol. There were strong correlations for apolipoprotein A1 and HDL cholesterol with individual cytokines. After adjustment for multiplicity testing, there were 33 significant correlations between apolipoprotein A1 and cytokine levels and 14 of these were also significantly correlated with HDL cholesterol. The strongest associations were observed for IL-1 alpha, SPON2, RAGE, PAR-1, TRAIL-R2, IL-4RA, TNFRSF11A, and SCF. A total of 28 out of 33 correlations were negative, indicating a negative relationship between apolipoprotein A1 and urinary cytokines. The study shows a negative correlation between apolipoprotein A1 and HDL cholesterol and urinary cytokine levels. The finding is in agreement with the anti-inflammatory properties of HDL.

  • 120. Fend, Falko
    et al.
    Cabecadas, José
    Gaulard, Philippe
    Jaffe, Elaine S
    Kluin, Philip
    Kuzu, Isinsu
    Peterson, Loann
    Wotherspoon, Andrew
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Early lesions in lymphoid neoplasia: Conclusions based on the Workshop of the XV. Meeting of the European Association of Hematopathology and the Society of Hematopathology, in Uppsala, Sweden2012Inngår i: Journal of hematopathology, ISSN 1865-5785, Vol. 5, nr 3, s. 169-199Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The increasing use of immunophenotypic and molecular techniques on lymphoid tissue samples without obvious involvement by malignant lymphoma has resulted in the increased detection of "early" lymphoid proliferations, which show some, but not all the criteria necessary for a diagnosis of malignant lymphoma. In most instances, these are incidental findings in asymptomatic individuals, and their biological behaviour is uncertain. In order to better characterize these premalignant conditions and to establish diagnostic criteria, a joint workshop of the European Association for Haematopathology and the Society of Hematopathology was held in Uppsala, Sweden, in September 2010. The panel reviewed and discussed more than 130 submitted cases and reached consensus diagnoses. Cases representing the nodal equivalent of monoclonal B-cell lymphocytosis (MBL) were discussed, as well as the "in situ" counterparts of follicular lymphoma (FL) and mantle cell lymphoma (MCL), topics that also stimulated discussions concerning the best terminology for these lesions. The workshop also addressed the borderland between reactive hyperplasia, and clonal proliferations such as pediatric marginal zone lymphoma and pediatric FL, which may have very limited capacity for progression. Virus-driven lymphoproliferations in the grey zone between reactive lesions and manifest malignant lymphoma were covered. Finally, early manifestations of T-cell lymphoma, both nodal and extranodal, and their mimics were addressed. This workshop report summarizes the most important conclusions concerning diagnostic features, as well as proposals for terminology and classification of early lymphoproliferations and tries to give some practical guidelines for diagnosis and reporting.

  • 121. Feodoroff, Benjamin
    et al.
    Lauhio, Anneli
    Ellström, Patrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk bakteriologi.
    Rautelin, Hilpi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk bakteriologi.
    A Nationwide Study of Campylobacter jejuni and Campylobacter coli Bacteremia in Finland over a 10-Year Period, 1998-2007, with Special Reference to Clinical Characteristics and Antimicrobial Susceptibility2011Inngår i: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 53, nr 8, s. e99-e106Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Campylobacter bacteremia is an uncommon condition, usually diagnosed in elderly and immunocompromised patients.

    Methods: Blood culture isolates and clinical information were collected for patients with diagnoses of Campylobacter jejuni or Campylobacter coli bacteremia in Finland from 1998 through 2007. Bacterial species were identified by means of polymerase chain reaction analysis, and minimal inhibitory concentrations for ciprofloxacin, clindamycin, doxycycline, erythromycin, gentamicin, meropenem, and metronidazole were determined with an agar dilution method. Medical records and mortality data within 1 year after the bacteremic episode were reviewed.

    Results: The study included 76 patients (median age, 46 years), for whom bacterial isolates (C. jejuni in 73, C. coli in 3) and clinical information were available. Most patients (70%) had no significant underlying diseases. The majority (82%) of the isolates were susceptible for all antimicrobial agents tested. However, antimicrobial therapy seemed to have only a limited effect, because no differences could be detected between patients with appropriate empirical antimicrobial treatment and those with delayed appropriate, inappropriate, or no antimicrobial therapy, either in the duration of hospitalization (median, 4 days for both groups) or in attributable mortality. The outcome of the infection was severe in 4 patients infected with C. jejuni; 2 died within 30 days, spondylodiscitis developed in 1, and Guillain-Barré syndrome developed in 1.

    Conclusions: C. jejuni and C. coli bacteremia occurred mainly in moderately young individuals without severe underlying diseases. The bacterial isolates were predominantly susceptible to antimicrobial agents, and the outcome of the disease was typically good, regardless of appropriate or inappropriate antimicrobial treatment given in the hospital.

  • 122.
    Feresiadou, Amalia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Casar Borota, Olivera
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Dragomir, Anca
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Oldfors, Carola Hedberg
    Univ Gothenburg, Inst Biomed, Dept Pathol & Genet, Gothenburg, Sweden..
    Stålberg, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Oldfors, Anders
    Univ Gothenburg, Inst Biomed, Dept Pathol & Genet, Gothenburg, Sweden..
    Tubular aggregates in congenital myasthenic syndrome2018Inngår i: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 28, nr 2, s. 174-175Artikkel i tidsskrift (Annet vitenskapelig)
  • 123.
    Ferrandis, Maria-José
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Rydén, Ingvar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lindahl, Tomas L
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Ruling out cardiac failure: Cost-benefit analysis of a sequential testing strategy with NT-proBNP before echocardiography2013Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, nr 2, s. 75-79Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives

    To estimate the possible economic benefit of a sequential testing strategy with NT-proBNP to reduce the number of echocardiographies.

    Methods

    Retrospective study in a third-party payer perspective. The costs were calculated from three Swedish counties: Blekinge, Östergötland, and Uppland. Two cut-off levels of NT-proBNP were used: 400 and 300 pg/mL. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for echocardiographies.

    Results

    The estimated costs for NT-proBNP tests and echocardiographies per county were reduced by 33%-36% with the 400 pg/mL cut-off and by 28%-29% with the 300 pg/mL cut-off. This corresponded to a yearly cost reduction of approximately €2-5 million per million inhabitants in these counties.

    Conclusion

    The use of NT-proBNP as a screening test could substantially reduce the number of echocardiographies in the diagnostic work-up of patients with suspected cardiac failure, as well as the associated costs.

  • 124. Fougner, Stine L
    et al.
    Casar Borota, Olivera
    Oslo University.
    Berg, Jens Petter
    Hald, John K
    Ramm-Pettersen, Jon
    Bollerslev, Jens
    The clinical response to somatostatin analogues in acromegaly correlates to the somatostatin receptor subtype 2a protein expression of the adenoma.2008Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 68, nr 3, s. 458-65Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Reduced expression of the somatostatin receptor subtype 2 (SSTR2) has been suggested as an explanation for the poor response to octreotide in acromegaly, but studies correlating levels of SSTR2 mRNA to octreotide efficacy have been contradictory. Some studies have found better responses to somatostatin analogues in G-protein alpha subunit (Gsalpha) mutation (gsp oncogene)-positive adenomas. The aim of this study was to determine adenoma SSTR2a protein expression and gsp status in a large group of patients with acromegaly, and relate this to the clinical effect of octreotide.

    PATIENTS: Seventy-one patients were included. All underwent transsphenoidal surgery, 23 patients after preoperative octreotide treatment.

    MEASUREMENTS: The adenoma SSTR2a expression was examined by immunohistochemistry and Western blot analysis, and gsp status determined. An acute octreotide test was performed, and the change in IGF-1 level after 6 months preoperative octreotide treatment was recorded.

    RESULTS: The acute octreotide response in non-pretreated patients and the preoperative long-term octreotide response were significantly better in patients with adenomas containing a large proportion of cells that stained positively for SSTR2a by immunohistochemistry. However, the SSTR2a protein level assessed by Western blot did not correlate with the octreotide response. The preoperatively treated group had lower SSTR2a protein levels and fewer adenomas with a large percentage of positively stained cells. The gsp oncogene was detected in 43% of the adenomas but did not correlate to the octreotide response.

    CONCLUSION: The clinical effect of octreotide correlates with the proportion of cells positive for SSTR2a in immunohistochemical staining, rather than the adenoma SSTR2a protein level. There may be a down-regulation of SSTR2a during octreotide treatment.

  • 125. Fougner, Stine Lyngvi
    et al.
    Casar-Borota, Olivera
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Heck, Ansgar
    Berg, Jens Petter
    Bollerslev, Jens
    Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly2012Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 76, nr 1, s. 96-102Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONTEXT:

    Somatotroph adenomas have been classified into densely granulated (DG) and sparsely granulated (SG) tumours with a transitional, intermediate group. Gsp oncogenes are activating mutations in the Gsα subunit gene, found in approximately 40% of somatotroph adenomas.

    OBJECTIVES:

    To explore granulation pattern and presence of gsp oncogene in acromegaly with correlations to clinical and biochemical variables and to the effect of treatment with somatostatin analogues (SA), as well as to describe granulation pattern in adenomas with and without SA pretreatment.

    DESIGN/SETTINGS/PATIENTS:

    Seventy-eight patients with active acromegaly were included. Long-term SA efficacy was evaluated in 29 patients treated preoperatively and in ten treated postoperatively. Granulation pattern was examined, as were immunohistochemical analyses for E-cadherin and SSTR2a. Protein levels of E-cadherin and SSTR2a were measured (Western blot). Gsp mutation analysis was available for 74 adenomas.

    RESULTS:

    DG adenomas and the transitional group had higher serum levels of IGF-1 per tumour volume than SG (P = 0·009; P = 0·005). Acute and long-term SA responses were lower in SG (P = 0·001; P = 0·043). No correlation between gsp mutation and granulation was found, and no difference in granulation pattern according to preoperative SA treatment was demonstrated. A significant correlation between granulation and E-cadherin was found, where SG had lowest immunohistochemical expression, substantiated by protein levels, and a highly significant gradient was observed from DG, through the transitional group, to SG.

    CONCLUSIONS:

    Densely granulated adenomas were highly responsive to somatostatin analogues in contrast to SG adenomas. The transitional group behaved clinically more like DG adenomas. However, based on E-cadherin, a marker of dedifferentiation, the transitional group seemed to be a true intermediate.

  • 126. Fougner, Stine Lyngvi
    et al.
    Lekva, Tove
    Casar Borota, Olivera
    Olivera Casar-Borotas publikationer.
    Hald, John K
    Bollerslev, Jens
    Berg, Jens Petter
    The expression of E-cadherin in somatotroph pituitary adenomas is related to tumor size, invasiveness, and somatostatin analog response2010Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, nr 5, s. 2334-2342Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONTEXT: Appropriate cell-to-cell adhesion is fundamental for the epithelial phenotype of pituitary cells. Loss of the adhesion protein E-cadherin has been associated with invasiveness, metastasis, and poor prognosis in cancers of epithelial origin. In somatotroph adenomas, a variable and reduced expression of E-cadherin has been demonstrated. In addition, nuclear translocation of E-cadherin was found to correlate with pituitary tumor invasion.

    OBJECTIVE: The objective was to examine the protein expression of E-cadherin in somatotroph pituitary adenomas in relation to adenoma size, invasiveness, and somatostatin analog (SMS) efficacy.

    PATIENTS AND METHODS: Eighty-three patients were included, and 29 were treated preoperatively with SMS. Adenoma E-cadherin protein expression was analyzed by Western blot (61 patients) and immunohistochemistry (IHC) (80 patients) with antibodies directed against both extracellular and intracellular domains (IHC). The acute (direct surgery group) and long-term (preoperatively treated group) SMS responses were evaluated. Baseline tumor volume and invasiveness were measured on magnetic resonance imaging scans.

    RESULTS: Membranous E-cadherin was lost in several adenomas. Nine of these were nuclear E-cadherin positive. The E-cadherin protein expression correlated negatively to tumor size and positively to acute SMS response. Low E-cadherin levels (preoperatively treated group only) and loss of membranous E-cadherin correlated to tumor invasiveness. The E-cadherin level correlated positively to tumor reduction after SMS treatment, and adenomas with nuclear E-cadherin staining had lower IGF-I reduction and tumor shrinkage. Preoperatively treated adenomas had reduced E-cadherin protein levels, but the IHC expression was unaltered.

    CONCLUSION: Reduced E-cadherin expression may correlate to a dedifferentiated phenotype in the somatotroph pituitary adenomas.

  • 127. Fraenkel, Carl-Johan
    et al.
    Melhus, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin, Klinisk bakteriologi.
    Enterococcus faecium coisolated with Lactobacillus species can mimic vancomycin-resistant enterococci2011Inngår i: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 1, s. 7335-Artikkel i tidsskrift (Fagfellevurdert)
  • 128.
    Frisk, Sofia
    et al.
    Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Univ Lab, Dept Clin Genet, Stockholm, Sweden.
    Taylan, Fulya
    Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden.
    Blaszczyk, Izabela
    Umea Univ Hosp, Dept Surg & Perioperat Sci, Hand & Plast Surg, Umea, Sweden.
    Nennesmo, Inger
    Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden.
    Annerén, Göran
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Herm, Bettina
    Ostersunds Hosp, Child & Adolescent Habilitat Ctr, Ostersund, Sweden.
    Stattin, Evalena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Zachariadis, Vasilios
    Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden.
    Lindstrand, Anna
    Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Univ Lab, Dept Clin Genet, Stockholm, Sweden.
    Tesi, Bianca
    Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Univ Lab, Dept Clin Genet, Stockholm, Sweden.
    Laurell, Tobias
    Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden.
    Nordgren, Ann
    Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Karolinska Univ Lab, Dept Clin Genet, Stockholm, Sweden.
    Early activating somatic PIK3CA mutations promote ectopic muscle development and upper limb overgrowth2019Inngår i: Clinical Genetics, ISSN 0009-9163, E-ISSN 1399-0004, Vol. 96, nr 2, s. 118-125Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PIK3CA-related overgrowth spectrum is a group of rare genetic disorders with asymmetric overgrowth caused by somatic mosaic PIK3CA mutations. Here, we report clinical data and molecular findings from two patients with congenital muscular upper limb overgrowth and aberrant anatomy. During debulking surgery, numerous ectopic muscles were found in the upper limbs of the patients. DNA sequencing, followed by digital polymerase chain reaction, was performed on DNA extracted from biopsies from hypertrophic ectopic muscles and identified the somatic mosaic PIK3CA hotspot mutations c.3140A > G, p.(His1047Arg) and c.1624G > A, p.(Glu542Lys) in a male (patient 1) and a female (patient 2) patient, respectively. Patient 1 had four ectopic muscles and unilateral isolated muscular overgrowth while patient 2 had 13 ectopic muscles and bilateral isolated muscular overgrowth of both upper limbs, indicating that her mutation occurred at early pre-somitic mesoderm state. The finding of PIK3CA mutations in ectopic muscles highlights the importance of PIK3CA in cell fate in early human embryonic development. Moreover, our findings provide evidence that the disease phenotype depends on the timing of PIK3CA mutagenesis during embryogenesis and confirm the diagnostic entity PIK3CA-related muscular overgrowth with ectopic accessory muscles.

    Fulltekst (pdf)
    FULLTEXT01
  • 129.
    Galant, Natalie J.
    et al.
    Univ Toronto, Dept Med Biophys, Univ Hlth Network, Princess Margaret Canc Ctr, TMDT 4-305,101 Coll St, Toronto, ON M5G 1L7, Canada.;Univ Toronto, Dept Biochem, Univ Hlth Network, Princess Margaret Canc Ctr, TMDT 4-305,101 Coll St, Toronto, ON M5G 1L7, Canada..
    Bugyei-Twum, Antoinette
    Univ Toronto, Dept Med Biophys, Univ Hlth Network, Princess Margaret Canc Ctr, TMDT 4-305,101 Coll St, Toronto, ON M5G 1L7, Canada.;Univ Toronto, Dept Biochem, Univ Hlth Network, Princess Margaret Canc Ctr, TMDT 4-305,101 Coll St, Toronto, ON M5G 1L7, Canada..
    Rakhit, Rishi
    Stanford Univ, Dept Chem & Syst Biol, Stanford, CA 94305 USA..
    Walsh, Patrick
    Univ Toronto, Dept Biochem, Hosp Sick Children, Mol Struct & Funct Program, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada..
    Sharpe, Simon
    Univ Toronto, Dept Biochem, Hosp Sick Children, Mol Struct & Funct Program, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada..
    Arslan, Pharhad Eli
    Univ Toronto, Dept Med Biophys, Univ Hlth Network, Princess Margaret Canc Ctr, TMDT 4-305,101 Coll St, Toronto, ON M5G 1L7, Canada.;Univ Toronto, Dept Biochem, Univ Hlth Network, Princess Margaret Canc Ctr, TMDT 4-305,101 Coll St, Toronto, ON M5G 1L7, Canada..
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Higaki, Jeffrey N.
    Prothena Biosci Inc, Dept Biochem, San Francisco, CA 94080 USA.;Prothena Biosci Inc, Dept Histopathol, San Francisco, CA 94080 USA..
    Torres, Ronald
    Prothena Biosci Inc, Dept Biochem, San Francisco, CA 94080 USA.;Prothena Biosci Inc, Dept Histopathol, San Francisco, CA 94080 USA..
    Tapia, Jose
    Prothena Biosci Inc, Dept Biochem, San Francisco, CA 94080 USA.;Prothena Biosci Inc, Dept Histopathol, San Francisco, CA 94080 USA..
    Chakrabartty, Avijit
    Univ Toronto, Dept Med Biophys, Univ Hlth Network, Princess Margaret Canc Ctr, TMDT 4-305,101 Coll St, Toronto, ON M5G 1L7, Canada.;Univ Toronto, Dept Biochem, Univ Hlth Network, Princess Margaret Canc Ctr, TMDT 4-305,101 Coll St, Toronto, ON M5G 1L7, Canada..
    Substoichiometric inhibition of transthyretin misfolding by immune-targeting sparsely populated misfolding intermediates: a potential diagnostic and therapeutic for TTR amyloidoses2016Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikkel-id 25080Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Wild-type and mutant transthyretin (TTR) can misfold and deposit in the heart, peripheral nerves, and other sites causing amyloid disease. Pharmacological chaperones, Tafamidis (R) and diflunisal, inhibit TTR misfolding by stabilizing native tetrameric TTR; however, their minimal effective concentration is in the micromolar range. By immune-targeting sparsely populated TTR misfolding intermediates (i.e. monomers), we achieved fibril inhibition at substoichiometric concentrations. We developed an antibody (misTTR) that targets TTR residues 89-97, an epitope buried in the tetramer but exposed in the monomer. Nanomolar misTTR inhibits fibrillogenesis of misfolded TTR under micromolar concentrations. Pan-specific TTR antibodies do not possess such fibril inhibiting properties. We show that selective targeting of misfolding intermediates is an alternative to native state stabilization and requires substoichiometric concentrations. MisTTR or its derivative may have both diagnostic and therapeutic potential.

    Fulltekst (pdf)
    fulltext
  • 130.
    Galant, Natalie J.
    et al.
    Univ Toronto, Univ Hlth Network, Princess Margaret Canc Ctr, Dept Med Biophys, TMDT 4-305,101 Coll St, Toronto, ON M5G 1L7, Canada..
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Higaki, Jeffrey N.
    Prothena Biosci Inc, San Francisco, CA 94080 USA..
    Chakrabartty, Avijit
    Univ Toronto, Univ Hlth Network, Princess Margaret Canc Ctr, Dept Med Biophys, TMDT 4-305,101 Coll St, Toronto, ON M5G 1L7, Canada..
    Transthyretin amyloidosis: an under-recognized neuropathy and cardiomyopathy2017Inngår i: Clinical Science, ISSN 0143-5221, E-ISSN 1470-8736, Vol. 131, nr 5, s. 395-409Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Transthyretin (TTR) amyloidosis (ATTR amyloidosis) is an underdiagnosed and important type of cardiomyopathy and/or polyneuropathy that requires increased awareness within the medical community. Raising awareness among clinicians about this type of neuropathy and lethal form of heart disease is critical for improving earlier diagnosis and the identification of patients for treatment. The following review summarizes current criteria used to diagnose both hereditary and wild-type ATTR (ATTRwt) amyloidosis, tools available to clinicians to improve diagnostic accuracy, available and newly developing therapeutics, as well as a brief biochemical and biophysical background of TTR amyloidogenesis.

  • 131. Gantelius, Stefan
    et al.
    Hedström, Yvette
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Pontén, Eva
    Higher Expression of Myosin Heavy Chain IIx in Wrist Flexors in Cerebral Palsy2012Inngår i: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 470, nr 5, s. 1272-1277Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Children with cerebral palsy (CP) use their paretic arm less than normal but have a relative overactivity of wrist flexors, causing an impairing flexed position of the wrist. Voluntary use of a muscle downregulates myosin heavy chain (MyHC) IIx, but it is unclear whether the relative overactivity of wrist flexors and extensors in children with CP affects MyHC expression compared to normal subjects.

    QUESTIONS/PURPOSES:

    We therefore asked whether MyHC expression composition differs in wrist flexors compared to extensors in children with CP and in controls and whether it is related to clinical findings.

    METHODS:

    We took muscle biopsies from wrist flexors and extensors during hand surgery in children with CP (n = 9) and during open reduction of forearm fractures in control children (n = 5). The expression of the MyHC I, IIa, and IIx isoforms were determined on silver-stained 6% SDS-PAGE.

    RESULTS:

    CP flexors showed a higher proportion of MyHC IIx (40%) than control flexors (16%) and CP extensors (20%). MyHC IIa isoform proportion was lower in CP flexors (27%) than in control flexors (46%) and in CP extensors (45%). MyHC I expression was lower in CP (36%) than in controls (46%) for wrist extensors only.

    CONCLUSIONS:

    Both the brain injury in CP and the different demands on flexors and extensors affect the expression of MyHCs. The higher amount of MyHC IIx in CP could be caused by a decreased voluntary use of the hemiplegic arm.

    CLINICAL RELEVANCE:

    More information on the structural difference between flexors and extensors in normal and spastic muscle could improve the understanding of strain of wrist extensors and possibly the development of flexion contractures in CP.

  • 132.
    Garwicz, Daniel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wadelius, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Farmakogenetisk analys kan avslöja risk för statinbiverkningar: [Pharmacogenetic analysis can predict adverse effects of statins]2013Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, nr 19-20, s. 951-952Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    Mer än var tionde vuxen i Sverige behandlas med statiner. 

    Muskelsvaghet, -trötthet och -värk är kända biverkningar. I sällsynta fall ses rabdomyolys, som kan leda till akut njursvikt och någon gång dödsfall. 

    Statiners kemiska egenskaper och serumkoncentration påverkar risken för allvarliga biverkningar. Serumkoncentrationen beror på dos och på patientens förmåga att omsätta läkemedlet.

    Akademiska sjukhuset har som första svenska sjukhus infört analys av en genetisk variant (SLCO1B1*5) som kan förutsäga ökad risk för sällsynta, allvarliga muskelbiverkningar vid statinbehandling.

  • 133. Geisler, Christian H.
    et al.
    Kolstad, Arne
    Laurell, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Räty, Riikka
    Jerkeman, Mats
    Eriksson, Mikael
    Nordström, Marie
    Kimby, Eva
    Boesen, Anne Marie
    Nilsson-Ehle, Herman
    Kuittinen, Outi
    Lauritzsen, Grete F.
    Ralfkiaer, Elisabeth
    Ehinger, Mats
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Delabie, Jan
    Karjalainen-Lindsberg, Marja-Liisa
    Brown, Peter
    Elonen, Erkki
    The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the International Prognostic Index (IPI) in predicting survival following intensive first-line immunochemotherapy and autologous stem cell transplantation (ASCT)2010Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 115, nr 8, s. 1530-1533Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mantle cell lymphoma (MCL) has a heterogeneous clinical course. The recently proposed Mantle Cell Lymphoma International Prognostic Index (MIPI) predicted the survival of MCL better than the International Prognostic Index in MCL patients treated with conventional chemotherapy, but its validity in MCL treated with more intensive immunochemotherapy has been questioned. Applied here to 158 patients of the Nordic MCL2 trial of first-line intensive immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation, the MIPI and the simplified MIPI (s-MIPI) predicted survival significantly better (P < .001) than the International Prognostic Index (P > .004). Both the MIPI and the s-MIPI mainly identified 2 risk groups, low and intermediate versus high risk, with the more easily applied s-MIPI being just as powerful as the MIPI. The MIPI(B) (biological), incorporating Ki-67 expression, identified almost half of the patients as high risk. We suggest that also a simplified MIPI(B) is feasible.

  • 134.
    Georgiou, Konstantinos
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Immunol, Huddinge, Sweden..
    Chen, Longyun
    Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Immunol, Huddinge, Sweden.;BGI Shenzhen, Shenzhen, Peoples R China..
    Berglund, Mattias
    Karolinska Inst, Dept Biosci & Nutr, Solna, Sweden..
    Ren, Weicheng
    Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Immunol, Huddinge, Sweden..
    de Miranda, Noel F. C. C.
    Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands..
    Lisboa, Susana
    Univ Porto, Portuguese Oncol Inst, Dept Genet, Rua Campo Alegre 823, P-4100 Oporto, Portugal.;Univ Porto, Abel Salazar Biomed Sci Inst, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Fangazio, Marco
    Columbia Univ, Inst Canc Genet, New York, NY USA..
    Zhu, Shida
    BGI Shenzhen, Shenzhen, Peoples R China..
    Hou, Yong
    BGI Shenzhen, Shenzhen, Peoples R China..
    Wu, Kui
    BGI Shenzhen, Shenzhen, Peoples R China..
    Fang, Wenfeng
    Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China.;Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, Guangzhou 510275, Guangdong, Peoples R China..
    Wang, Xianhuo
    Tianjin Med Univ Canc Inst & Hosp, Dept Lymphoma, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjin, Peoples R China..
    Meng, Bin
    Tianjin Med Univ Canc Inst & Hosp, Dept Lymphoma, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjin, Peoples R China..
    Zhang, Li
    Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China.;Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, Guangzhou 510275, Guangdong, Peoples R China..
    Zeng, Yixin
    Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China.;Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, Guangzhou 510275, Guangdong, Peoples R China..
    Bhagat, Govind
    Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA..
    Nordenskjold, Magnus
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden.;Karolinska Univ Hosp, Solna, Sweden..
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Dalla-Favera, Riccardo
    Columbia Univ, Inst Canc Genet, New York, NY USA..
    Zhang, Huilai
    Tianjin Med Univ Canc Inst & Hosp, Dept Lymphoma, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjin, Peoples R China..
    Teixeira, Manuel R.
    Univ Porto, Portuguese Oncol Inst, Dept Genet, Rua Campo Alegre 823, P-4100 Oporto, Portugal.;Univ Porto, Abel Salazar Biomed Sci Inst, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Pasqualucci, Laura
    Columbia Univ, Inst Canc Genet, New York, NY USA..
    Peng, Roujun
    Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China.;Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, Guangzhou 510275, Guangdong, Peoples R China..
    Pan-Hammarstrom, Qiang
    Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Immunol, Huddinge, Sweden..
    Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas2016Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 127, nr 24, s. 3026-3034Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Diffuse large B-cell lymphoma (DLBCL) is one of the most common and aggressive types of B-cell lymphoma. Deregulation of proto-oncogene expression after a translocation, most notably to the immunoglobulin heavy-chain locus (IGH), is one of the hallmarks of DLBCL. Using whole-genome sequencing analysis, we have identified the PD-L1/PD-L2 locus as a recurrent translocation partner for IGH in DLBCL. PIM1 and TP63 were also identified as novel translocation partners for PD-L1/PD-L2. Fluorescence in situ hybridization was furthermore used to rapidly screen an expanded DLBCL cohort. Collectively, a subset of samples was found to be affected by gains (12%), amplifications (3%), and translocations (4%) of the PD-L1/PD-L2 locus. RNA sequencing data coupled with immunohistochemistry revealed that these cytogenetic alterations correlated with increased expression of PD-L1 but not of PD-L2. Moreover, cytogenetic alterations affecting the PD-L1/PD-L2 locus were more frequently observed in the non-germinal center B cell-like (non-GCB) subtype of DLBCL. These findings demonstrate the genetic basis of PD-L1 overexpression in DLBCL and suggest that treatments targeting the PD-1-PD-L1/PD-L2 axis might benefit DLBCL patients, especially those belonging to the more aggressive non-GCB subtype.

  • 135.
    Gholiha, Alex R.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Hollander, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Hedström, Gustaf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Molin, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Smedby, Karin E
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Hjalgrim, Henrik
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Glimelius, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    High tumour plasma cell infiltration reflects an important microenvironmental component in classic Hodgkin lymphoma linked to presence of B-symptoms2019Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 184, nr 2, s. 192-201Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Plasma cells are important prognostic actors in different malignancies. The tumour microenvironmental composition in classic Hodgkin lymphoma (cHL) is a major prognostic key element; however, clinicopathological studies regarding plasma cells in cHL are lacking. The aim of this study was to investigate CD138+ (also termed SDC1+) plasma cell and IgG4 producing (IgG4+) plasma cells infiltration in the microenvironment of cHL. Immunohistochemistry with anti-CD138 and IgG4 antibodies was performed on diagnostic tumour biopsies from 124 patients with cHL, on tissue micro array (TMA). In 120 cases, CD138+ plasma cell-infiltration was associated with the presence of B-symptoms (P = 0·028) and advanced stage, IIB-IVB (P = 0·009). In multivariate analysis, CD138+ plasma cells correlated with eosinophil infiltration (P = 0·013). The subgroup of IgG4+ plasma cells was analysed in 122 cases and only correlated to CD138+ plasma cells (P = 0·004). Patients with high proportion of tumour infiltrating CD138+ plasma cells (defined as ≥10%), had a more inferior event-free survival (P = 0·007) and overall survival (P = 0·004) than patients with a low proportion of infiltrating CD138+ plasma cells (<10%), although significance was not maintained in multivariate analysis. In summary, a high proportion of tumour-associated plasma cells in cHL reflect an important component in the microenvironment of cHL.

  • 136.
    Glimelius, Bengt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Melin, Beatrice
    Umeå Univ, Dept Radiat Sci, Umeå.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Beskow, Anna H.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Birgisson, Helgi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Björ, Ove
    Umeå Univ, Dept Radiat Sci, Umeå.
    Edqvist, Per-Henrik D
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Hansson, Tony
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Helleday, Thomas
    Karolinska Inst, Div Translat Med & Chem Biol, Dept Med Biochem & Biophys, Sci Life Lab, Stockholm.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Henriksson, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Hesselager, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hultdin, Magnus
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Höglund, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Jonsson, Håkan
    Umeå Univ, Dept Radiat Sci, Umeå.
    Larsson, Chatarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Lindman, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Ljuslinder, Ingrid
    Umeå Univ, Dept Radiat Sci, Umeå.
    Mindus, Stephanie
    Akad Sjukhuset, Lung & Allergy Clin, Uppsala.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Ponten, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Riklund, Katrine
    Umeå Univ, Dept Radiat Sci, Umeå.
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Sandin, Fredrik
    Uppsala Univ Hosp, RCC Uppsala Örebro, Uppsala.
    Schwenk, Jochen M.
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, Solna.
    Stenling, Roger
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Stålberg, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Stålberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Thellenberg Karlsson, Camilla
    Umeå Univ, Dept Radiat Sci, Umeå.
    Westermark, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Bergh, Anders
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Claesson-Welsh, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi.
    Palmqvist, Richard
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Sjöblom, Tobias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.2018Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 2, s. 187-194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

    Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

    Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

    Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

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  • 137. Greiser, Anne
    et al.
    Winter, Theresa
    Mahfoud, Hala
    Kallner, Anders
    Ittermann, Till
    Masuch, Annette
    Lubenow, Norbert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Kohlmann, Thomas
    Greinacher, Andreas
    Nauck, Matthias
    Petersmann, Astrid
    The 99th percentile and imprecision of point-of-care cardiac troponin I in comparison to central laboratory tests in a large reference population2017Inngår i: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 50, nr 18, s. 1198-1202Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Determination of cardiac troponin (cTn) is central in the emergency department (ED) for the diagnosis of myocardial infarction. In view of adverse effects of long waiting time on patient outcome, implementation of point-of-care-testing (POCT) is suggested if the turn-around-time is longer than 60min. The present study aimed to determine the 99th percentile and imprecision of two POCT in a healthy population measuring cTnI and cTnT and compare these analytical characteristics against three central laboratory test (CLT) for cTnI.

    DESIGN & METHODS: CTnI and cTnT were determined in parallel by means of the AQT90 FLEX analyzer in about 2250 plasma samples from individuals with known health status. Results were compared to previously determined performance data of three CLT.

    RESULTS: The 99th percentile of cTnI in the POCT was determined at 19ng/L, the lowest concentration with an imprecision of 10% was reached at 22ng/L while an imprecision of 20% was reached at 13ng/L. Age, sex, or physical activity did not affect the 99th percentile of cTnI. Compared to CLT the AQT90 cTnI POCT the analytical performance was equivalent. The cTnT POCT could not be assessed due a considerable number of high values and an inadequate imprecision profile.

    CONCLUSION: While the cTnI POCT showed analytical performance comparable to CLT, the results of the cTnT assay on the same device did not suffice to determine a reliable 99th percentile. The present evaluation supports the usage of the cTnI POCT, but application of the cTnT POCT needs further evaluation.

  • 138.
    Gremel, Gabriela
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Djureinovic, Dijana
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Niinivirta, Marjut
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Laird, Alexander
    Univ Edinburgh, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Edinburgh Urol Canc Grp, Edinburgh, Midlothian, Scotland..
    Ljungqvist, Oscar
    Atlas Antibodies AB, Stockholm, Sweden..
    Johannesson, Henrik
    Atlas Antibodies AB, Stockholm, Sweden..
    Bergman, Julia
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Edqvist, Per-Henrik D
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Navani, Sanjay
    Lab Surgpath, Bombay, Maharashtra, India..
    Khan, Naila
    Lab Surgpath, Bombay, Maharashtra, India..
    Patil, Tushar
    Lab Surgpath, Bombay, Maharashtra, India..
    Sivertsson, Asa
    Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Uhlen, Mathias
    Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Harrison, David J.
    Univ St Andrews, Sch Med, St Andrews, Fife, Scotland..
    Ullenhag, Gustav
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Stewart, Grant D.
    Univ Edinburgh, Inst Genet & Mol Med, Edinburgh Urol Canc Grp, Edinburgh, Midlothian, Scotland.;Univ Cambridge, Addenbrookes Hosp, Acad Urol Grp, Box 43,Cambridge Biomed Campus,Hills Rd, Cambridge CB2 0QQ, England..
    Pontén, Fredrik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma2017Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 17, artikkel-id 9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: There is an unmet clinical need for better prognostic and diagnostic tools for renal cell carcinoma (RCC). Methods: Human Protein Atlas data resources, including the transcriptomes and proteomes of normal and malignant human tissues, were searched for RCC-specific proteins and cubilin (CUBN) identified as a candidate. Patient tissue representing various cancer types was constructed into a tissue microarray (n = 940) and immunohistochemistry used to investigate the specificity of CUBN expression in RCC as compared to other cancers. Two independent RCC cohorts (n = 181; n = 114) were analyzed to further establish the sensitivity of CUBN as RCC-specific marker and to explore if the fraction of RCCs lacking CUBN expression could predict differences in patient survival. Results: CUBN was identified as highly RCC-specific protein with 58% of all primary RCCs staining positive for CUBN using immunohistochemistry. In venous tumor thrombi and metastatic lesions, the frequency of CUBN expression was increasingly lost. Clear cell RCC (ccRCC) patients with CUBN positive tumors had a significantly better prognosis compared to patients with CUBN negative tumors, independent of T-stage, Fuhrman grade and nodal status (HR 0.382, CI 0.203-0.719, P = 0.003). Conclusions: CUBN expression is highly specific to RCC and loss of the protein is significantly and independently associated with poor prognosis. CUBN expression in ccRCC provides a promising positive prognostic indicator for patients with ccRCC. The high specificity of CUBN expression in RCC also suggests a role as a new diagnostic marker in clinical cancer differential diagnostics to confirm or rule out RCC.

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  • 139. Grinberg, Marianna
    et al.
    Djureinovic, Dijana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Brunnström, Hans R R
    Mattsson, Johanna Sofia Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Edlund, Karolina
    Hengstler, Jan G
    La Fleur, Linnea
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ekman, Simon
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Koyi, Hirsh
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Branden, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Ståhle, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Jirström, Karin
    Tracy, Derek K
    Ponten, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Botling, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Rahnenführer, Jörg
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Reaching the limits of prognostication in non-small cell lung cancer: an optimized biomarker panel fails to outperform clinical parameters.2017Inngår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 30, nr 7, s. 964-977Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Numerous protein biomarkers have been analyzed to improve prognostication in non-small cell lung cancer, but have not yet demonstrated sufficient value to be introduced into clinical practice. Here, we aimed to develop and validate a prognostic model for surgically resected non-small cell lung cancer. A biomarker panel was selected based on (1) prognostic association in published literature, (2) prognostic association in gene expression data sets, (3) availability of reliable antibodies, and (4) representation of diverse biological processes. The five selected proteins (MKI67, EZH2, SLC2A1, CADM1, and NKX2-1 alias TTF1) were analyzed by immunohistochemistry on tissue microarrays including tissue from 326 non-small cell lung cancer patients. One score was obtained for each tumor and each protein. The scores were combined, with or without the inclusion of clinical parameters, and the best prognostic model was defined according to the corresponding concordance index (C-index). The best-performing model was subsequently validated in an independent cohort consisting of tissue from 345 non-small cell lung cancer patients. The model based only on protein expression did not perform better compared to clinicopathological parameters, whereas combining protein expression with clinicopathological data resulted in a slightly better prognostic performance (C-index: all non-small cell lung cancer 0.63 vs 0.64; adenocarcinoma: 0.66 vs 0.70, squamous cell carcinoma: 0.57 vs 0.56). However, this modest effect did not translate into a significantly improved accuracy of survival prediction. The combination of a prognostic biomarker panel with clinicopathological parameters did not improve survival prediction in non-small cell lung cancer, questioning the potential of immunohistochemistry-based assessment of protein biomarkers for prognostication in clinical practice.Modern Pathology advance online publication, 10 March 2017; doi:10.1038/modpathol.2017.14.

  • 140.
    Grootens, Jennine
    et al.
    Karolinska Inst, Dept Med Solna, S-17164 Stockholm, Sweden;Karolinska Univ Hosp, S-17164 Stockholm, Sweden.
    Ungerstedt, Johanna S.
    Karolinska Inst, Dept Med Huddinge, S-14186 Stockholm, Sweden;Karolinska Univ Hosp, Hematol Ctr, S-17176 Stockholm, Sweden.
    Ekoff, Maria
    Karolinska Inst, Dept Med Solna, S-17164 Stockholm, Sweden;Karolinska Univ Hosp, S-17164 Stockholm, Sweden.
    Rönnberg, Elin
    Karolinska Inst, Dept Med Solna, S-17164 Stockholm, Sweden;Karolinska Univ Hosp, S-17164 Stockholm, Sweden.
    Klimkowska, Monika
    Karolinska Univ Hosp Huddinge, Dept Clin Pathol & Cytol, S-14186 Stockholm, Sweden.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Arock, Michel
    Ecole Normale Super, Mol & Cellular Oncol, F-94235 Cachan, France;Hop La Pitie Salpetriere, Clin Hematol Lab, F-75013 Paris, France.
    Söderlund, Stina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Mattsson, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Nilsson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi. Karolinska Inst, Dept Med Solna, S-17164 Stockholm, Sweden;Karolinska Univ Hosp, S-17164 Stockholm, Sweden.
    Dahlin, Joakim S.
    Karolinska Inst, Dept Med Solna, S-17164 Stockholm, Sweden;Karolinska Univ Hosp, S-17164 Stockholm, Sweden.
    Single-cell analysis reveals the KIT D816V mutation in haematopoietic stem and progenitor cells in systemic mastocytosis2019Inngår i: EBioMedicine, E-ISSN 2352-3964, Vol. 43, s. 150-158Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Systemic mastocytosis (SM) is a haematological disease characterised by organ infiltration by neoplastic mast cells. Almost all SM patients have a mutation in the gene encoding the tyrosine kinase receptor KIT causing a D816V substitution and autoactivation of the receptor. Mast cells and CD34(+) haematopoietic progenitors can carry the mutation: however, in which progenitor cell subset the mutation arises is unknown. We aimed to investigate the distribution of the D816V mutation in single mast cells and single haematopoietic stem and progenitor cells.

    Methods: Fluorescence-activated single-cell index sorting and KIT D816V mutation assessment were applied to analyse mast cells and >10,000 CD34(+) bone marrow progenitors across 10 haematopoietic progenitor subsets. In vitro assays verified cell-forming potential.

    Findings: We found that in SM 60-99% of the mast cells harboured the KIT D816V mutation. Despite increased frequencies of mast cells in SM patients compared with control subjects, the haematopoietic progenitor subset frequencies were comparable. Nevertheless, the mutation could be detected throughout the haematopoietic landscape of SM patients, from haematopoietic stem cells to more lineage-primed progenitors. In addition, we demonstrate that Fc epsilon RI+ bone marrow progenitors exhibit mast cell-forming potential, and we describe aberrant CD45RA expression on SM mast cells for the first time.

    Interpretation: The KIT D816V mutation arises in early haematopoietic stem and progenitor cells and the mutation frequency is approaching 100% in mature mast cells, which express the aberrant marker CD45RA.

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  • 141. Guaraldi, Federica
    et al.
    Casar Borota, Olivera
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Jaffrain-Rea, Marie-Lise
    Hypophysitis2018Inngår i: Encyclopedia of Endocrine Diseases: Volume 2 / [ed] Ilpo Huhtaniemi & Luciano Martini, Academic Press, 2018, 2, s. 325-338Kapittel i bok, del av antologi (Fagfellevurdert)
  • 142. Gullsby, Karolina
    et al.
    Hallander, Hans O
    Bondeson, Kåre
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin.
    Performance of Bordetella pertussis IS481 real-time PCR in a vaccine trial setting2007Inngår i: Apmis, Vol. 115, nr 12, s. 1370-1375Artikkel i tidsskrift (Fagfellevurdert)
  • 143. Gullsby, Karolina
    et al.
    Storm, Martin
    Bondeson, Kåre
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin.
    Simultaneous detection of Chlamydophila pneumoniae and Mycoplasma pneumoniae by use of molecular beacons in a duplex real-time PCR2008Inngår i: Journal of clinical microbiology, Vol. 46, nr 2, s. 727-731Artikkel i tidsskrift (Fagfellevurdert)
  • 144.
    Gulyas, Miklos
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Fillinger, Janos
    Koranyi Natl Inst Pulmonol, Dept Pathol & Cytol, Budapest, Hungary.
    Kaposi, Andras D.
    Semmelweis Univ, Dept Biophys & Radiat Biol, Budapest, Hungary.
    Molnar, Miklos
    Semmelweis Univ, Inst Pathophysiol, Budapest, Hungary.
    Use of cholesterol and soluble tumour markers CEA and syndecan-2 in pleural effusions in cases of inconclusive cytology2019Inngår i: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 72, nr 8, s. 529-535Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims In order to improve diagnostics in pleural effusions, additional value of effusion cholesterol, carcinoembryonic antigen (CEA) and syndecan-2 assays to cytology was studied. Methods Biomarkers were measured in effusion supernatants from 247 patients, of whom 126 had malignant pleural involvement, and their additional diagnostic efficacy to cytology was assessed. Results Syndecan-2 measurement, although gave detectable concentrations in all effusions with highest median value in mesotheliomas, was non-discriminative between different pathological conditions. CEA concentrations exceeding 5 ng/mL cut-off point indicated carcinomas, regardless of pleural involvement, which gave a sensitivity of 62% and specificity of 100% for carcinoma. Cholesterol concentration over 1.21 mmol/L cut-off value indicated neoplastic pleural involvement with 99% sensitivity and 'merely' 69% specificity, the latter mainly due to raised levels being associated also with benign inflammatory effusions. Combined CEA and cholesterol determinations increased the sensitivity for diagnosing carcinomatosis from 70% with cytology alone to 84% and established the correct diagnosis in 16 of 31 carcinomatosis cases with inconclusive cytology. Cholesterol measurement alone, with elevated level, in combination with absence of substantial number of inflammatory cells in effusion sediment proved to be a magnificent marker for neoplastic pleural involvement with 99% efficacy, and recognised all 36 such cases with inconclusive cytology. Conclusions Simultaneous measurement of CEA and cholesterol concentrations in effusion, or at least cholesterol alone, in combination with non-inflammatory fluid cytology, provides additional specific information about neoplastic pleural involvement, and can therefore be used as an adjunct to cytology, above all, in inconclusive cases.

    Fulltekst (pdf)
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  • 145.
    Gulyas, Miklos
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Mattsson, Johanna Sofia Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Lindgren, Andrea
    Ek, Lars
    Lamberg, Kristina
    Behndig, Annelie
    Holmberg, Erik
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Bergman, Bengt
    COX-2 expression and effects of celecoxib in addition to standard chemotherapy in advanced non-small cell lung cancer.Inngår i: Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Inhibition of cyclooxygenase-2 (COX-2) is proposed as a treatment option in several cancer types. However, in non-small cell lung cancer (NSCLC), phase III trials have failed to demonstrate a benefit of adding COX-2 inhibitors to standard chemotherapy. The aim of this study was to analyse COX-2 expression in tumor and stromal cells as predictive biomarker for COX-2 inhibition.

    Methods: In the multicenter phase III trial, 316 patients with advanced NSCLC were randomized to receive celecoxib (400 mg b.i.d.) or placebo up to one year in addition to a two-drug platinum-based chemotherapy combination. In a subset of 122 patients, archived tumor tissue was available for immunohistochemical analysis of COX-2 expression in tumor and stromal cells.

    Results: An updated analysis of all 316 patients included in the original trial, and of the 122 patients with available tumor tissue, showed no survival differences between the celecoxib and placebo arms (HR 1.01; 95%CI 0.81-1.27 and HR 1.12; 95%CI 0.78-1.61, respectively). Similarly, in patients with high COX-2 expression in tumor cells (n=71) or stromal cells (n=55), survival did not differ significantly between patients who received celecoxib or placebo (HR 1.07; 95%CI 0.74-1.54 and HR 0.80; 95%CI 0.56-1.15). No significant interaction effect between COX-2 score in tumor or stromal cells and celecoxib effect on survival was detected (p=0.48 and 0.25, respectively).

    Conclusion: In this subgroup analysis of patients with advanced NSCLC, we could not detect any significant interaction between COX-2 expression in tumor or stromal cells and outcome of celecoxib treatment in addition to standard chemotherapy.

  • 146.
    Gulyas, Miklos
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Mattsson, Johanna Sofia Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Lindgren, Andrea
    Linköping Univ, Dept Clin & Expt Med, Allergy Ctr, Fac Hlth Sci.
    Ek, Lars
    Skåne Univ Hosp, Pulm Med, Lund.
    Lamberg Lundström, Kristina
    Akad Hosp, Pulm Med, Uppsala.
    Behndig, Annelie
    Norrland Univ Hosp, Pulm Med, Umeå.
    Holmberg, Erik
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Oncol, Gothenburg.
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Bergman, Bengt
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Resp Med.
    COX-2 expression and effects of celecoxib in addition to standard chemotherapy in advanced non-small cell lung cancer.2018Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 2, s. 244-250Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: Inhibition of cyclooxygenase-2 (COX-2) is proposed as a treatment option in several cancer types. However, in non-small cell lung cancer (NSCLC), phase III trials have failed to demonstrate a benefit of adding COX-2 inhibitors to standard chemotherapy. The aim of this study was to analyze COX-2 expression in tumor and stromal cells as predictive biomarker for COX-2 inhibition.

    Methods: In a multicenter phase III trial, 316 patients with advanced NSCLC were randomized to receive celecoxib (400 mg b.i.d.) or placebo up to one year in addition to a two-drug platinum-based chemotherapy combination. In a subset of 122 patients, archived tumor tissue was available for immunohistochemical analysis of COX-2 expression in tumor and stromal cells. For each compartment, COX-2 expression was graded as high or low, based on a product score of extension and intensity of positively stained cells.

    Results: An updated analysis of all 316 patients included in the original trial, and of the 122 patients with available tumor tissue, showed no survival differences between the celecoxib and placebo arms (HR 1.01; 95% CI 0.81–1.27 and HR 1.12; 95% CI 0.78–1.61, respectively). High COX-2 scores in tumor (n = 71) or stromal cells (n = 55) was not associated with a superior survival outcome with celecoxib vs. placebo (HR =0.96, 95% CI 0.60–1.54; and HR =1.51; 95% CI 0.86–2.66), and no significant interaction effect between COX-2 score in tumor or stromal cells and celecoxib effect on survival was detected (p = .48 and .25, respectively).

    Conclusions: In this subgroup analysis of patients with advanced NSCLC treated within the context of a randomized trial, we could not detect any interaction effect of COX-2 expression in tumor or stromal cells and the outcome of celecoxib treatment in addition to standard chemotherapy.

  • 147. Gupta, Anindya
    et al.
    Suveer, Amit
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Lindblad, Joakim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Dragomir, Anca
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Sintorn, Ida-Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Sladoje, Natasa
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    False positive reduction of cilia detected in low resolution TEM images using a convolutional neural network2017Inngår i: Swedish Symposium on Image Analysis, Swedish Society for Automated Image Analysis , 2017Konferansepaper (Annet vitenskapelig)
    Fulltekst (pdf)
    fulltext
  • 148.
    Gupta, Anindya
    et al.
    Tallinn Univ Technol, TJ Seebeck Dept Elect, Tallinn, Estonia.
    Suveer, Amit
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Lindblad, Joakim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion. Serbian Acad Arts & Sci, Math Inst, Belgrade, Serbia.
    Dragomir, Anca
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Sintorn, Ida-Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion. Vironova AB, Stockholm, Sweden.
    Sladoje, Nataša
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion. Serbian Acad Arts & Sci, Math Inst, Belgrade, Serbia.
    Convolutional neural networks for false positive reduction of automatically detected cilia in low magnification TEM images2017Inngår i: Image Analysis: Part I, Springer, 2017, s. 407-418Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Automated detection of cilia in low magnification transmission electron microscopy images is a central task in the quest to relieve the pathologists in the manual, time consuming and subjective diagnostic procedure. However, automation of the process, specifically in low magnification, is challenging due to the similar characteristics of non-cilia candidates. In this paper, a convolutional neural network classifier is proposed to further reduce the false positives detected by a previously presented template matching method. Adding the proposed convolutional neural network increases the area under Precision-Recall curve from 0.42 to 0.71, and significantly reduces the number of false positive objects.

  • 149. Haji Younes, Amil
    et al.
    Melas, Nikolaos
    Kilincalp, Serta
    Egerszegi, Péter
    Gavle sjukhus - Klinisk patologi och cytologi Gavle, Sweden Gavle sjukhus - Gastroenterologmottagning Gavle, Sweden..
    [Argon plasma coagulation effective treatment of solitary rectal ulcer syndrome].2019Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116, artikkel-id FR4TArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    Solitary rectal ulcer syndrome (SRUS) is a rare disorder likely to be caused by a traumatic and ischemic mucosal injury related to latent or overt rectal prolapse. Mucosal damage can vary between erythema and up to intractable ulceration. The typical symptoms of SRUS may resemble those of inflammatory bowel disease (IBD)-related proctitis or rectal malignancy with mucus- and blood-mixed defecation with urgency and sometimes transient incontinence. The purpose of this paper is to raise awareness of this rare, quality-of-life impacting and difficult-to-treat disease and the not so well-known argon plasma coagulation (APC) treatment that can provide very good and long lasting symptom relief.

  • 150.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Collin, Sofie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Wadelius, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Preventivt arbete kan minska läkemedelsbiverkningar2017Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, artikkel-id ERYWArtikkel i tidsskrift (Annet vitenskapelig)
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