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  • 1. Aalto, J
    et al.
    Pelkonen, S
    Kalimo, H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Finne, J
    Mutant bacteriophage with non-catalytic endosialidase binds to bothbacterial and eukaryotic polysialic acid and can be used as probe for itsdetection.2001In: Glycoconj J, Vol. 18, p. 751-Article in journal (Refereed)
  • 2. Aaltonen, Kirsimari
    et al.
    Ahlin, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Salonen, Laura
    Fjällskog, Marie Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Heikkilä, Pävi
    Nevanlinna, Heli
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Reliability of cyclin A assessment on tissue microarrays in breast cancer compared to conventional histological slides2006In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 94, no 11, p. 1697-1702Article in journal (Refereed)
    Abstract [en]

    Cyclin A has in some studies been associated with poor breast cancer survival, although all studies have not confirmed this. Its prognostic significance in breast cancer needs evaluation in larger studies. Tissue microarray (TMA) technique allows a simultaneous analysis of large amount of tumours on a single microscopic slide. This makes a rapid screening of molecular markers in large amount of tumours possible. Because only a small tissue sample of each tumour is punched on an array, the question has arisen about the representativeness of TMA when studying markers that are expressed in only a small proportion of cells. For this reason, we wanted to compare cyclin A expression on TMA and on traditional large sections. Two breast cancer TMAs were constructed of 200 breast tumours diagnosed between 1997-1998. TMA slides and traditional large section slides of these 200 tumours were stained with cyclin A antibody and analysed by two independent readers. The reproducibility of the two readers' results was good or even very good, with kappa values 0.71-0.87. The agreement of TMA and large section results was good with kappa value 0.62-0.75. Cyclin A overexpression was significantly (P<0.001) associated with oestrogen receptor and progesterone receptor negativity and high grade both on TMA and large sections. Cyclin A overexpression was significantly associated with poor metastasis-free survival both on TMA and large sections. The relative risks for metastasis were similar on TMA and large sections. This study suggests that TMA technique could be useful to study histological correlations and prognostic significance of cyclin A on breast cancer on a large scale.

  • 3. Aaltonen, Minna
    et al.
    Soukka, Hanna
    Halkola, Lauri
    Jalonen, Jarmo
    Kalimo, Hannu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Holopainen, Irma E
    Kääpä, Pekka O
    Inhaled nitric oxide treatment inhibits neuronal injury after meconium aspiration in piglets2007In: Early Human Development, ISSN 0378-3782, E-ISSN 1872-6232, Vol. 83, no 2, p. 77-85Article in journal (Refereed)
    Abstract [en]

    Background: Meconium aspiration-induced hypertensive lung injury is frequently associated with neuronal damage. Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension, but its effects on the brain are poorly known. Aims: The aim of this study was to determine the effects of iNO treatment on the neuronal tissue after meconium aspiration. Study design: 71 anesthetized, catheterized and ventilated newborn piglets were studied for 6 h. Thirty-five piglets were instilled with a bolus of human meconium intratracheally and 36 piglets with saline instillation served as controls. Nineteen meconium piglets and 17 control piglets were continuously treated with 20 ppm of iNO, started at 30 min after the insult. The extent of neuronal injury was analysed histologically, and the levels of brain tissue lipid peroxidation products, reduced glutathione (GSH), myeloperoxidase activity and oxidized DNA were analysed as indicators of oxidative stress. Results: iNO treatment diminished the pulmonary hypertensive response caused by meconium aspiration, but did not change systemic or carotid hemodynamics. NO administration was associated with reduced neuronal injury and diminished amount of oxidized DNA in the hippocampus of the meconium piglets. Further, iNO treatment was associated with decreased level of GSH in the cortex, but no change in lipid peroxidation production or myeloperoxidase activity was detected in any of the studied brain areas. Conclusions: Our results suggest that iNO treatment may inhibit DNA oxidation and neuronal injury in the hippocampus, associated with newborn meconium aspiration.

  • 4. Aaltonen, Minna
    et al.
    Soukka, Hanna
    Halkola, Lauri
    Kalimo, Hannu
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology. Pathology.
    Holopainen, Irma E
    Kääpä, Pekka O
    Meconium aspiration induces neuronal injury in piglets.2005In: Acta Paediatr, ISSN 0803-5253, Vol. 94, no 10, p. 1468-75Article in journal (Refereed)
  • 5.
    Aase, Karin
    et al.
    Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, SE-17176 Stockholm, Sweden.
    Ernkvist, Mira
    Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, SE-17176 Stockholm, Sweden.
    Ebarasi, Lwaki
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
    Jakobsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Majumdar, Arindam
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
    Yi, Chunling
    Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
    Birot, Olivier
    Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, SE-17176 Stockholm, Sweden.
    Ming, Yue
    Department of Clinical Neuroscience, Section of Ophthalmology and Vision, Karolinska Institutet, St Erik’s Hospital, SE-11284 Stockholm, Sweden.
    Kvanta, Anders
    Department of Clinical Neuroscience, Section of Ophthalmology and Vision, Karolinska Institutet, St Erik’s Hospital, SE-11284 Stockholm, Sweden.
    Edholm, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Aspenström, Pontus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Kissil, Joseph
    Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
    Claesson-Welsh, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Shimono, Akihiko
    Vertebrate Body Plan, Center for Developmental Biology, RIKEN Kobe, Chuou-ku, Kobe 650-0047, Japan.
    Holmgren, Lars
    Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, SE-17176 Stockholm, Sweden.
    Angiomotin regulates endothelial cell migration during embryonic angiogenesis2007In: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 21, no 16, p. 2055-2068Article in journal (Refereed)
    Abstract [en]

    The development of the embryonic vascular system into a highly ordered network requires precise control over the migration and branching of endothelial cells (ECs). We have previously identified angiomotin (Amot) as a receptor for the angiogenesis inhibitor angiostatin. Furthermore, DNA vaccination targeting Amot inhibits angiogenesis and tumor growth. However, little is known regarding the role of Amot in physiological angiogenesis. We therefore investigated the role of Amot in embryonic neovascularization during zebrafish and mouse embryogenesis. Here we report that knockdown of Amot in zebrafish reduced the number of filopodia of endothelial tip cells and severely impaired the migration of intersegmental vessels. We further show that 75% of Amot knockout mice die between embryonic day 11 (E11) and E11.5 and exhibit severe vascular insufficiency in the intersomitic region as well as dilated vessels in the brain. Furthermore, using ECs differentiated from embryonic stem (ES) cells, we demonstrate that Amot-deficient cells have intact response to vascular endothelial growth factor (VEGF) in regard to differentiation and proliferation. However, the chemotactic response to VEGF was abolished in Amot-deficient cells. We provide evidence that Amot is important for endothelial polarization during migration and that Amot controls Rac1 activity in endothelial and epithelial cells. Our data demonstrate a critical role for Amot during vascular patterning and endothelial polarization.

  • 6.
    Abdsaleh, Shahin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Azavedo, E
    Lindgren, P G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Comparison of core needle biopsy and surgical specimens in malignant breast lesions regarding histological features and hormone receptor expression2008In: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 52, no 6, p. 773-775Article in journal (Refereed)
  • 7. Abdul-Majid, KB
    et al.
    Stefferl, A
    Bourquin, C
    Lassmann, H
    Linington, C
    Olsson, T
    Kleinau, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Harris, RA
    Fc receptors are critical for autoimmune inflammatory damage to the central nervous system in experimental autoimmune encephalomyelitis.2002In: Scand J Immunol, Vol. 55, p. 70-Article in journal (Refereed)
  • 8.
    Abelson, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Genetic Risk Factors for Systemic Lupus Erythematosus: From Candidate Genes to Functional Variants2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis has been to identify genetic variants that increase the susceptibility for Systemic Lupus Erythematosus (SLE), an autoimmune disease caused by a complex interplay between various genetic and environmental factors.

    Five different candidate genes were selected through different strategies, and were analysed for association with SLE in an attempt to distinguish some of the underlying mechanisms of this disease. Two of these genes, PD-L1 and PD-L2, appeared not to contain any major risk factors for SLE in the analysed European and Latin American populations. In two other genes, CD24 and STAT4, there appeared to be population-specific effects. The A57V amino acid substitution in the CD24 gene, previously implicated with multiple sclerosis, was associated in a Spanish cohort, with a weak trend in German samples, and no association in Swedish. The previously reported and highly convincing association of the STAT4 transcription factor gene was confirmed in all our cohorts. Interestingly, the results indicate the presence of at least two independent risk variants: the first, represented by a previously reported SNP, was the strongest in individuals of Northern European ancestry, and the second was more pronounced in individuals from Southern Europe and Latin America. We also report the identification of a novel susceptibility gene. The BANK1 gene, encoding a scaffold protein involved in B-cell activation, contains functional variants affecting important domains, which are associated in all investigated cohorts from Europe and Latin America.

    These results confirm the existence of replicable associations between genetic variants and SLE, which are common and present in many populations. The results also illustrate a certain degree of heterogeneity, where some risk factors could have variable effect in different populations.

    List of papers
    1. No evidence of association between genetic variants of the PDCD1 ligands and SLE
    Open this publication in new window or tab >>No evidence of association between genetic variants of the PDCD1 ligands and SLE
    Show others...
    2007 (English)In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 8, no 1, p. 69-74Article in journal (Refereed) Published
    Abstract [en]

    PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.

    Keyword
    systemic lupus erythematosus, genetic association, linkage disequilibrium, autoimmunity, PD-L1, PD-L2
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-97760 (URN)10.1038/sj.gene.6364360 (DOI)000243783500009 ()17136123 (PubMedID)
    Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2017-12-14Bibliographically approved
    2. Association of a CD24 Gene Polymorphism with Susceptibility to Systemic Lupus Erythematosus
    Open this publication in new window or tab >>Association of a CD24 Gene Polymorphism with Susceptibility to Systemic Lupus Erythematosus
    Show others...
    2007 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 56, no 9, p. 3080-3086Article in journal (Refereed) Published
    Abstract [en]

    Objective. To determine the potential role of the CD24 A57V gene polymorphism in systemic lupus erythematosus (SLE).

    Methods. We studied 3 cohorts of Caucasian patients and controls. The Spanish cohort included 696 SLE patients and 539 controls, the German cohort included 257 SLE patients and 317 controls, and the Swedish cohort included 310 SLE patients and 247 controls. The CD24 A57V polymorphism was genotyped by polymerase chain reaction, using a predeveloped TaqMan allele discrimination assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

    Results. In the Spanish cohort there was a statistically significant difference in the distribution of the CD24 V allele between SLE patients and controls (OR 3.6 [95% CI 2.13-6.16], P < 0.0001). In addition, frequency of the CD24 V/V genotype was increased in SLE patients compared with controls (OR 3.7 [95% CI 2.16-6.34], P < 0.00001). We sought to replicate this association with SLE in a German population and a Swedish population. A similar trend was found in the German group. The CD24 V/V genotype and the CD24 V allele were more frequent in SLE patients than in controls, although this difference was not statistically significant. No differences were observed in the Swedish group. A meta-analysis of the Spanish and German cohorts demonstrated that the CD24 V allele has a risk effect in SLE patients (pooled OR 1.25 [95% Cl 1.08-1.46], P = 0.003). In addition, homozygosity for the CD24 V risk allele significantly increased the effect (pooled OR 2.1,9 [95% Cl 1.50-3.22], P = 0.00007).

    Conclusion. These findings suggest that the CD24 A57V polymorphism plays a role in susceptibility to SLE in a Spanish population.

    Keyword
    Antigens; CD24/*genetics, Cohort Studies, Female, Genetic Predisposition to Disease, Humans, Lupus Erythematosus; Systemic/*genetics, Male, Polymorphism; Genetic
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-97761 (URN)10.1002/art.22871 (DOI)000249832600030 ()17763438 (PubMedID)
    Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2017-12-14Bibliographically approved
    3. Functional Variants in the B-Cell Gene BANK1 are Associated with Systemic Lupus Erythematosus
    Open this publication in new window or tab >>Functional Variants in the B-Cell Gene BANK1 are Associated with Systemic Lupus Erythematosus
    Show others...
    2008 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 40, no 2, p. 211-216Article in journal (Refereed) Published
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies and complex genetic inheritance(1-3). In a genome-wide scan using 85,042 SNPs, we identified an association between SLE and a nonsynonymous substitution (rs10516487, R61H) in the B-cell scaffold protein with ankyrin repeats gene, BANK1. We replicated the association in four independent case-control sets (combined P = 3.7 x 10(-10); OR = 1.38). We analyzed BANK1 cDNA and found two isoforms, one full-length and the other alternatively spliced and lacking exon 2 (Delta 2), encoding a protein without a putative IP3R-binding domain. The transcripts were differentially expressed depending on a branch point-site SNP, rs17266594, in strong linkage disequilibrium (LD) with rs10516487. A third associated variant was found in the ankyrin domain (rs3733197, A383T). Our findings implicate BANK1 as a susceptibility gene for SLE, with variants affecting regulatory sites and key functional domains. The disease-associated variants could contribute to sustained B cell-receptor signaling and B-cell hyperactivity characteristic of this disease.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-97762 (URN)10.1038/ng.79 (DOI)000252732900020 ()
    Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2017-12-14Bibliographically approved
    4. STAT4 Associates with SLE through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk
    Open this publication in new window or tab >>STAT4 Associates with SLE through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk
    Show others...
    2009 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 68, no 11, p. 1746-1753Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: To confirm and define the genetic association of STAT4 and systemic lupus erythematosus, investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5. METHODS: 30 tag SNPs were genotyped in an independent set of Spanish cases and controls. SNPs surviving correction for multiple tests were genotyped in 5 new sets of cases and controls for replication. STAT4 cDNA was analyzed by 5'-RACE PCR and sequencing. Expression levels were measured by quantitative PCR. RESULTS: In the fine-mapping, four SNPs were significant after correction for multiple testing, with rs3821236 and rs3024866 as the strongest signals, followed by the previously associated rs7574865, and by rs1467199. Association was replicated in all cohorts. After conditional regression analyses, two major independent signals represented by SNPs rs3821236 and rs7574865, remained significant across the sets. These SNPs belong to separate haplotype blocks. High levels of STAT4 expression correlated with SNPs rs3821236, rs3024866 (both in the same haplotype block) and rs7574865 but not with other SNPs. We also detected transcription of alternative tissue-specific exons 1, indicating presence of tissue-specific promoters of potential importance in the expression of STAT4. No interaction with associated SNPs of IRF5 was observed using regression analysis. CONCLUSIONS: These data confirm STAT4 as a susceptibility gene for SLE and suggest the presence of at least two functional variants affecting levels of STAT4. Our results also indicate that both genes STAT4 and IRF5 act additively to increase risk for SLE.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-102290 (URN)10.1136/ard.2008.097642 (DOI)000270700900016 ()19019891 (PubMedID)
    Available from: 2009-05-06 Created: 2009-05-06 Last updated: 2017-12-13Bibliographically approved
  • 9.
    Abelson, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Delgado-Vega, Angélica Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Kozyrev, Sergey V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sánchez, Elena
    Velázquez-Cruz, Rafael
    Eriksson, Niclas
    Wojcik, Jerome
    Linga Reddy, Prasad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Lima, Guadalupe
    D'Alfonso, Sandra
    Migliaresi, Sergio
    Baca, Vicente
    Orozco, Lorena
    Witte, Torsten
    Ortego-Centeno, Norberto
    Abderrahim, Hadi
    Pons-Estel, Bernardo A.
    Gutiérrez, Carmen
    Suárez, Ana
    González-Escribano, Maria Francisca
    Martin, Javier
    Alarcón-Riquelme, Marta E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    STAT4 Associates with SLE through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk2009In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 68, no 11, p. 1746-1753Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To confirm and define the genetic association of STAT4 and systemic lupus erythematosus, investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5. METHODS: 30 tag SNPs were genotyped in an independent set of Spanish cases and controls. SNPs surviving correction for multiple tests were genotyped in 5 new sets of cases and controls for replication. STAT4 cDNA was analyzed by 5'-RACE PCR and sequencing. Expression levels were measured by quantitative PCR. RESULTS: In the fine-mapping, four SNPs were significant after correction for multiple testing, with rs3821236 and rs3024866 as the strongest signals, followed by the previously associated rs7574865, and by rs1467199. Association was replicated in all cohorts. After conditional regression analyses, two major independent signals represented by SNPs rs3821236 and rs7574865, remained significant across the sets. These SNPs belong to separate haplotype blocks. High levels of STAT4 expression correlated with SNPs rs3821236, rs3024866 (both in the same haplotype block) and rs7574865 but not with other SNPs. We also detected transcription of alternative tissue-specific exons 1, indicating presence of tissue-specific promoters of potential importance in the expression of STAT4. No interaction with associated SNPs of IRF5 was observed using regression analysis. CONCLUSIONS: These data confirm STAT4 as a susceptibility gene for SLE and suggest the presence of at least two functional variants affecting levels of STAT4. Our results also indicate that both genes STAT4 and IRF5 act additively to increase risk for SLE.

  • 10. Abelson, Anna-Karin
    et al.
    Johansson, Cecilia
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Kozyrev, Sergey
    Alarcón-Riquelme, Marta
    The PD-1 Pathway in Systemic Lupus Erythematosus: The Ligands of PD-1, PD-L1 and PD-L2, are also Susceptibility FactorsManuscript (Other academic)
  • 11.
    Abelson, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Johansson, Cecilia M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Kozyrev, Sergey V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Kristjansdottir, Helga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gunnarsson, Iva
    Svenungsson, Elisabet
    Jönsen, Andreas
    Lima, Guadalupe
    Scherbarth, Hugo R
    Gamron, Susana
    Allievi, Alejandro
    Palatnik, Sergio A
    Alvarellos, Antonio
    Paira, Sergio
    Graf, Cesar
    Guillerón, Carlos
    Catoggio, Luis J
    Prigione, Carlos
    Battagliotti, Cesar G
    Berbotto, Guillermo A
    García, Mercedes A
    Perandones, Carlos E
    Truedsson, Lennart
    Steinsson, Kristjan
    Sturfelt, Gunnar
    Pons-Estel, Bernardo
    Alarcón-Riquelme, Marta E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    No evidence of association between genetic variants of the PDCD1 ligands and SLE2007In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 8, no 1, p. 69-74Article in journal (Refereed)
    Abstract [en]

    PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.

  • 12. Abramsson, Alexandra
    et al.
    Kurup, Sindhulakshmi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Yamada, Shuhei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lindblom, Per
    Schallmeiner, Edith
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Ledin, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ringvall, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Kjellén, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bondjers, Göran
    Li, Jin-Ping
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lindahl, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Spillmann, Dorothe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Gerhardt, Holger
    Defective N-sulfation of heparan sulfate proteoglycans limits PDGF-BB binding and pericyte recruitment in vascular development2007In: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 21, no 3, p. 316-331Article in journal (Refereed)
    Abstract [en]

    During vascular development, endothelial platelet-derived growth factor B (PDGF-B) is critical for pericyte recruitment. Deletion of the conserved C-terminal heparin-binding motif impairs PDGF-BB retention and pericyte recruitment in vivo, suggesting a potential role for heparan sulfate (HS) in PDGF-BB function during vascular development. We studied the participation of HS chains in pericyte recruitment using two mouse models with altered HS biosynthesis. Reduction of N-sulfation due to deficiency in N-deacetylase/N-sulfotransferase-1 attenuated PDGF-BB binding in vitro, and led to pericyte detachment and delayed pericyte migration in vivo. Reduced N-sulfation also impaired PDGF-BB signaling and directed cell migration, but not proliferation. In contrast, HS from glucuronyl C5-epimerase mutants, which is extensively N- and 6-O-sulfated, but lacks 2-O-sulfated L-iduronic acid residues, retained PDGF-BB in vitro, and pericyte recruitment in vivo was only transiently delayed. These observations were supported by in vitro characterization of the structural features in HS important for PDGF-BB binding. We conclude that pericyte recruitment requires HS with sufficiently extended and appropriately spaced N-sulfated domains to retain PDGF-BB and activate PDGF receptor β (PDGFRβ) signaling, whereas the detailed sequence of monosaccharide and sulfate residues does not appear to be important for this interaction.

  • 13. Abrink, M
    et al.
    Larsson, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Hellman, L
    Demethylation of ERV3, an endogenous retrovirus regulating the Kruppel related Zinc finger gene H-plk, in several human cell lines arrested during early monocytic development.1998In: DNA and Cell Biology, Vol. 17, p. 17-Article in journal (Refereed)
  • 14.
    Abrink, Magnus
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Larsson, Erik
    Department of Genetics and Pathology.
    Gobl, Anders
    Department of Medical Sciences.
    Hellman, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Expression of lactoferrin in the kidney:implications for innate immunity and iron metabolism2000In: Kidney Int, Vol. 57, p. 2004-Article in journal (Refereed)
  • 15. Adami, Hans-Olov
    et al.
    Persson, I.
    Ekbom, A.
    Wolk, Alicja
    Pontén, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Trichopoulos, D.
    The aetiology and pathogenesis of human breast cancer1995In: Mutation research, ISSN 0027-5107, E-ISSN 1873-135X, Vol. 333, no 1-2, p. 29-35Article in journal (Refereed)
    Abstract [en]

    Whilst investigators have clearly shown that non-hereditary factors dominate the aetiology of human breast cancer, they have failed to identify quantitatively important causes, and prospects for prevention remain indeed limited. However, progress in epidemiological and basic research has taken place during the last few years. Current evidence suggests that breast cancer may be affected by the intra-uterine environment, that exposures during adolescence are particularly important, and that pregnancy has a dual effect on breast cancer risk: an early increase followed by long-term protection. Great variation exists in the structural development of the breast ductal system already in the newborn--and by inference in utero--and a pregnancy induces permanent structural changes in the mammary gland. We suggest that these observations fit into an aetiological model with the following key components: (1) breast cancer risk depends on the number of cells at risk, the susceptibility of individual cells to malignant transformation, and on the degree of cellular proliferation, notably cells which can act as founders of breast cancer; (2) the number of target cells is determined by the hormonal environment mainly early in life, perhaps already in utero; (3) in adult life, hormones which are non-genotoxic, increase breast cancer risk by increasing selective cell proliferation and thus number of target cells and the risk of retention of spontaneous somatic mutations; (4) while a pregnancy stimulates the growth of already malignant cells or cells close to malignant transformation (and thereby entails a short-term risk increase) the dominating long-term protection occurs due to permanent structural changes, terminal differentiation and perhaps decreased cell proliferation and carcinogen-binding in combination.

  • 16.
    Adde, Magdalena
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Enblad, Gunilla
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hagberg, Hans
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sundström, Christer
    Department of Genetics and Pathology.
    Laurell, Anna
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Outcome for young high-risk aggressive B-cell lymphoma patients treated with CHOEP-14 and rituximab (R-CHOEP-14).2006In: Med Oncol, ISSN 1357-0560, Vol. 23, no 2, p. 283-93Article in journal (Refereed)
  • 17.
    Afink, Gijs
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Nister, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Stassen, B H G J
    Joosten, P H L J
    Rademakers, P J H
    Bongcam-Rudloff, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    van Zoelen, E J J
    Moselman, S
    Molecular cloning and functional characterization of the human platelet-derived growth factor a receptor gene promoter.1995In: Oncogene, Vol. 10, p. 1667-Article in journal (Refereed)
  • 18.
    Afrakhte, M
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Heldin, NE
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Westermark, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Inhibition of G1 cyclin-dependent kinase activity in cell density- dependent growth arrest in human fibroblasts.1998In: Cell Growth Differ, Vol. 9, p. 983-Article in journal (Refereed)
  • 19.
    Afrakhte, M
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Nistér, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Östman, A
    Westermark, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Paulsson, Y
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Production of cell-associated PDGF-AA by a human sarcoma cell line: Evidence for a latent autocrine effect1996In: Int J Cancer, Vol. 68, p. 802-809Article in journal (Refereed)
  • 20.
    Afrakhte, Mozhgan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Growth control mechanisms in normal and neoplastic mammalian cells1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The main theme of the studies presented in this thesis is, the growth control mechanisms whose loss in normal cells predispose to or cause cancer. The balance between growth inhibitory and stimulatory mechanisms is crucial for the development and maintenance of a normal animal.

    PDGF, a growth factor for cells of mesenchymal origin, is implicated in normal developmental processes as well as neoplasia. The alternative splicing of exon 6 in PDGF-A gene transcripts gives rise to two different proteins with different compartmentalization properties. The PDGF-A chain homodimers, PDGF-AAL, encoded PDGF A-splice variant remain associated with the cell membrane. Studies of a human fibrosarcoma cell line, U-2197, revealed a high expression level of the cell associated PDGF-AAL which upon release increased autophosphorylation of the endogenous PDGF receptors, suggesting an autocrine loop. PDGF-A gene and PDGFR-α gene found to be co-amplified in the U-2197, indicating an optimised system for growth in these cells, i.e. amplified growth factor receptor as well as a local autocrine supply of the mitogen.

    Members of TGFβ superfamily are potent regulators of the growth and differentiation of a wide range of cell types. Intracellular mediators of TGF-β signalling, SMADs, transduce signals from serine/threonine kinase receptors to the nucleus where they affect transcription of target genes. A new class of SMAD proteins has been identified whose members, the inhibitory SMADS, antagonise TGF-β signals by interfering with agonistic SMADs activity. Smad6 and Smad7 are two closely related TGF-β antagonists identified in mammalian cells. Overexpression of Smad7 inhibited the cellular response to TGF-β whereas expression of an anti-sense Smad7 construct showed an enhancing effect on this response. The inhibitory SMADs may act in a negative feedback loop, as their expression is induced by the same ligands whose action they antagonise.

    Density dependent growth inhibition is a growth control mechanism often lost in transformed and malignant cells. Cells in dense culture are refractory to the mitogen stimulation although, the mitogenic signals were shown to be processed to some extent. The expression of immediate-early genes in dense culture stimulated with mitogen was induced. The activity of cyclin dependent kinases (CDKs), the pivotal kinases in G1/S transition, showed to be density dependent and decreased by increasing cell density. pRb, a tumour suppressor and growth regulatory protein, remained unphosphorylated in mitogen treated dense culture. The cessation of CDKs kinase activity in dense cultures was shown to be accompanied with increasing expression of inhibitory proteins of these kinases, CKIs. The impaired expression of a positive regulator of CDKs, Cdc25A phosphatase, was another feature of dense cultures.

  • 21.
    Afrakhte, Mozhgan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Morén, Anita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Jossan, Surinder
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Itoh, Susumu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Sampath, Kuber
    Westermark, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Heldin, Carl-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Heldin, Nils-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    ten Dijke, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Induction of inhibitory Smad6 and Smad7 mRNA by TGF-beta family members1998In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 249, no 2, p. 505-11Article in journal (Refereed)
    Abstract [en]

    Smad6 and Smad7 function as intracellular antagonists in transforming growth factor-beta (TGF-beta) signaling. Here we report the isolation of human Smad6, which is closely related to Smad7. Smad6 and Smad7 mRNAs were differentially expressed in lung cancer cell lines and were rapidly and directly induced by TGF-beta1, activin and bone morphogenetic protein-7. Cross-talk between TGF-beta and other signaling pathways was demonstrated by the finding that epidermal growth factor (EGF) induced the expression of inhibitory SMAD mRNA. Moreover, whereas the phorbol ester PMA alone had no effect, it potentiated the TGF-beta1-induced expression of Smad7 mRNA. Ectopic expression of anti-sense Smad7 RNA was found to increase the effect of TGF-beta1, supporting its role as a negative regulator in TGF-beta signaling. Thus, expression of inhibitory Smads is induced by multiple stimuli, including the various TGF-beta family members, whose action they antagonize.

  • 22. Agardh, D
    et al.
    Dahlbom, I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Daniels, T
    Lörinc, E
    Ivarsson, SÅ
    Lernmark, Å
    Hansson, Tony
    Department of Rheumatology, Karolinska Institute.
    Autoantibodies Against Soluble and Immobilized Human Recombinant Tissue Transglutaminase in Children with Celiac Disease.2005In: J Pediatr Gastroenterol Nutr., Vol. 41, no 3, p. 322-327Article in journal (Refereed)
  • 23. Agardi, D
    et al.
    Pigg, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Sjoholm, AG
    Truedsson, PJ
    Spath, PJ
    Kuijper, EJ
    Tijssen, CC
    Tranebjerg, L
    Gustavson, K-H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Ulfendahl, P-J
    Wadelius, C
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Fluorescent detection of microsatellite polymorphisms: properdin deficiency linked to PFC microsatellite.1995In: Experimental and Clinical Immunogenetics, Vol. 12, p. 111-Article in journal (Refereed)
  • 24. Agaton, C
    et al.
    Galli, J
    Hoiden Guthenberg, I
    Janzon, L
    Hansson, M
    Asplund, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Brundell, E
    Lindberg, S
    Ruthberg, I
    Wester, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Wurtz, D
    Hoog, C
    Lundeberg, J
    Stahl, S
    Ponten, F
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Uhlen, M
    Affinity proteomics for systematic protein profiling of chromosome 21 geneproducts in human tissues.2003In: Mol Cell Proteomics, Vol. 2, p. 405-Article in journal (Refereed)
  • 25.
    Agnarsdóttir, Margrét
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Carlén, Birgitta
    Willén, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Malacoplakia and spermatic granuloma complicating vasectomy2006In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 111, no 2, p. 227-230Article in journal (Refereed)
    Abstract [en]

    Malacoplakia is a granulomatous disease with a histiocytic infiltrate containing calcified structures called Michaelis-Gutmann bodies. These structures are considered to represent an abnormal response to infection involving defective lysosomes and abnormal microbubular assembly. The disease most frequently involves urinary and genital tracts, but has also been described from most other organs. Here we present the first case of malacoplakia only involving the vas deferens.

  • 26.
    Agnarsdóttir, Margrét
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wagenius, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Mucci, Lorelei
    Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA, Department of Epidemiology, Harvard School of Public Health, Boston, USA .
    Magnusson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eaker-Fält, Sonja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    MITF as a Prognostic Marker in Cutaneous Malignant MelanomaManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Microphthalmia associated transcription factor (MITF) protein has a central role in the differentiation and survival of melanocytes. The aim of the study was to investigate whether MITF can be employed as a prognostic marker in patients operated on for cutaneous malignant melanoma.

    Methods: A cohort study design based on information collected from population-based registers. For included patients tissue microarrays and immunohistochemistry were employed to study the protein expression of MITF in the primary malignant melanoma tumors by estimating the fraction of positive tumor cells and the staining intensity.

    Results: The vast majority of tumors expressed MITF in >25% of the tumor cells with a strong staining intensity and looking at these factors individually these patients had a better prognosis. When cell fraction and intensity were combined a high-risk group dying of malignant melanoma was identified as those with 25% -75% of tumor cells staining with weak intensity and those with <25% of tumor cells staining with strong intensity. However, the majority of the deaths occurred in the lower risk groups.

    Conclusions: Although a high-risk group for death in malignant melanoma was identified we conclude that MITF is not useful as a prognostic marker because of the distribution of that particular expression in the population.

    Impact: Our results indicate a bi-phasic pattern of MITF expression and although not useful as a prognostic marker these results are in line with other experimental studies and are relevant to explore further.

     

  • 27.
    Agnarsdóttir, Margrét
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Rexhepaj, Elton
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Ireland.
    Magnusson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Patil, Tushar
    Lab Surgpath, Mumbai, India.
    Johansson, Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Jirström, Karin
    Center for Molecular Pathology, Department of Laboratory Medicine, Skåne University Hospital, Lund University, Malmö, Sweden .
    Uhlen, Mathias
    Department of Proteomics, School of Biotechnology, AlbaNova University Center, KTH-Royal Institute of Technology, SE-10691 Stockholm, Sweden .
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Gallagher, William
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Ireland. .
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Protein Biomarkers in Malignant Melanoma: An Image Analysis-Based Study on Melanoma Markers of Potential Clinical RelevanceManuscript (preprint) (Other academic)
    Abstract [en]

    The thickness of a primary malignant melanoma tumor is the most important prognostic indicator for a patient with primary cutaneous malignant melanoma. To optimize the management and treatment of melanoma patients there is an unmet need to identify characteristics that can further stratify melanoma patients into high or low risk for progressive disease. Despite numerous studies no single marker has yet been shown to add significant prognostic information. An algorithmic approach, combining data from several markers provides an attractive model to identify patients of increased risk of dying from malignant melanoma. The primary aim of the present study was to analyze the correlation between clinical outcome and protein expression patterns of multiple proteins in malignant melanoma tumors using immunohistochemistry and tissue microarrays. Candidate proteins were identified based on a selective and differential expression pattern in melanoma tumors and tested in a cohort of 143 melanoma patients. Protein expression was analyzed using both manual scoring and automated image analysis-based algorithms. We found no single marker of prognosis that was independent of tumor thickness. When combining potential prognostic markers we could define a prognostic index, based on RBM3, MITF, SOX10 and Ki-67, that was independent of tumor thickness in multivariate analysis. Our findings suggest that a good prognosis signature can be identified in melanoma patients with tumors showing a low fraction of Ki-67 positive tumor cells and a high fraction of RBM3 positive tumor cells combined with low intensity levels of SOX10 and MITF.

     

  • 28.
    Agnarsdóttir, Margrét
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sooman, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Bolander, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Strömberg, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Rexhepaj, Elton
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Ireland.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gallagher, William
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Ireland.
    Lennartsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Uhlen, Mathias
    Department of Proteomics, School of Biotechnology, AlbaNova University Center, KTH-Royal Institute of Technology, Stockholm, Sweden.
    Hedstrand, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    SOX10 expression in superficial spreading and nodular malignant melanomas2010In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 20, no 6, p. 468-478Article in journal (Refereed)
    Abstract [en]

    SOX10 is a transcription factor expressed in nerve cells and melanocytes. The aim of this study was to investigate the protein expression pattern of SOX10 in malignant melanoma tumors and to analyze whether the results correlated with clinical parameters and the proliferation marker Ki-67. Furthermore, proliferation and migration were analyzed in three different cell lines employing SOX10 small interfering RNA-mediated silencing. Expression patterns were determined in 106 primary tumors and 39 metastases in addition to 16 normal skin samples and six benign nevi employing immunohistochemistry and tissue microarrays. The immunohistochemical staining was evaluated manually and with an automated algorithm. SOX10 was strongly expressed in the benign tissues, but for the malignant tumors superficial spreading melanomas stained stronger than nodular malignant melanomas (P=0.008). The staining intensity was also inversely correlated with T-stage (Spearman's ρ=-0.261, P=0.008). Overall survival and time to recurrence were significantly correlated with SOX10 intensity, but not in multivariate analysis including T-stage. With the automated algorithm there was an inverse correlation between the SOX10 staining intensity and the proliferation marker, Ki-67 (ρ=-0.173, P=0.02) and a significant difference in the intensity signal between the benign tissues, the primary tumors and the metastases where the metastases stained the weakest (P≤0.001). SOX10 downregulation resulted in variable effects on proliferation and migration rates in the melanoma cell lines. In conclusion, the SOX10 intensity level differed depending on the tissue studied and SOX10 might have a role in survival. No conclusion regarding the role of SOX10 for in-vitro proliferation and migration could be drawn.

  • 29.
    Ahlbom, BE
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Yaqoob, M
    Anneren, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Larsson, A
    Ilicki, A
    Wadelius, C
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Linkage analysis excludes familial congenital hypothyroidism from chromosome 21.1999In: Genet Couns, Vol. 9, p. 265-Article in journal (Refereed)
  • 30.
    Ahlbom, BE
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Yaqoob, M
    Anneren, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Larsson, A
    Ilicki, A
    Wadelius, C
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Linkage analysis excludes familial congenital hypothyroidism fromchromosome 21.1998In: Genet Couns, Vol. 9, p. 265-Article in journal (Refereed)
  • 31.
    Ahlbom, BE
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Yaqoob, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Gustavsson, P
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Abbas, HG
    Anneren, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Larsson, A
    Wadelius, C
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Linkage analysis identifies the thyroglobulin gene region as a major locusfor familial congenital hypothyroidism.2002In: Hum Genet, Vol. 110, p. 145-Article in journal (Refereed)
  • 32.
    Ahlbom, Bidil Edman
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Wahlström , Jan
    Saalman, R
    Wadelius, Claes
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Annerén , Göran
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Severe psychomotor retardation in a boy with a supernumerary derivative chromosome resulting in partial trisomy 21 and partial trisomy 7p.2003In: Ann Genet, Vol. 46, p. 29-Article in journal (Refereed)
  • 33.
    Ahlgren, S
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Li, L G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Olsson, Y
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Accumulation of beta-amyloid precursor protein and ubiquitin in axons after spinal cord trauma in humans:immunohistochemical observations on autopsy material.1996In: Acta Neuropathol, Vol. 92, p. 49-Article in journal (Refereed)
  • 34.
    Ahlin, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Aaltonen, Kirsimari
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Nevanlinna, Heli
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ki67 and cyclin A as prognostic factors in early breast cancer: What are the optimal cut-off values?2007In: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 51, no 4, p. 491-498Article in journal (Refereed)
    Abstract [en]

    AIMS: To find the optimal cut-off values for cyclin A and Ki67 in early breast cancer tumours and to evaluate their prognostic values. METHODS AND RESULTS: Tissue microarray (TMA) slides were constructed from 570 T1-4 N0-1 M0 breast cancer tumours. The TMA slides were stained for cyclin A and Ki67 using immunohistochemistry with commercial antibodies. To investigate the optimal cut-off values for cyclin A, Ki67 average and maximum values the material was split into two parts at cut-offs defined by dividing it into deciles. For each cut-off value the relative risk (RR) for metastasis-free survival (MFS) and overall survival (OS) was calculated comparing patients with high versus low cyclin A or Ki67 expression. When using a cut-off value around the seventh decile, cyclin A and Ki67 score correlated with the highest RR ratio for MFS in the chemotherapy-naïve subgroup. Among patients having received adjuvant chemotherapy, no statistically significant differences in MFS or OS were found. CONCLUSIONS: The optimal cut-off value for cyclin A average is 8% and for cyclin A maximum value 11%; for Ki67 the corresponding values are 15% and 22%. Additional studies are needed to verify these results.

  • 35.
    Ahlin, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Zhou, Wenjing
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Holmqvist, Marit
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Nilsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Jirström, Karin
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Cyclin A is a proliferative marker with good prognostic value in node-negative breast cancer2009In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 18, no 9, p. 2501-2506Article in journal (Refereed)
    Abstract [en]

    Background: Proliferative markers are not recommended as prognostic   factors for clinical use in breast cancer due to lack of   standardization in methodology. However, proliferation is driving   several gene expression signatures emphasizing the need for a reliable   proliferative marker IF or clinical use. Studies suggest that cyclin A   is a prognostic marker with satisfying reproducibility. We investigated   cyclin A as a prognostic marker in node-negative breast cancer using   previously defined cutoff values.   Patients and Methods: In a case-control study, we defined 190 women who   died from breast cancer as cases and 190 women alive at the time for   the corresponding case's death as controls. Inclusion criteria were   tumor size <= 50 mm, no lymph node metastases and no adjuvant   chemotherapy. Tumor tissues were immunostained for cyclin A using   commercially available antibodies.   Results: We found a statistically significant association between   expression of cyclin A and breast cancer death in a univariate model:   odds ratio for cyclin A(ave) 2.7 [95% confidence interval (CI),   1.7-4.3] and cyclin A(max) 3.4 (CI, 2.1-5.5). Corresponding odds ratio   for Ki67 were Ki67(ave) 1.9 (CI, 1.2-3.1) and Ki67(max) 1.7 (CI,   1.1-2.7) and for grade 3.1 (CI, 1.8-5.1). Cyclin A was strongly   correlated to Ki67 and grade why a model including all was not   appropriate.   Conclusions: Cyclin A is a prognostic factor for breast cancer death in   node-negative patients using standardized methodology regarding scoring   and cutoff values. Adding cyclin A as a proliferative marker to established clinicopathologic factors will improve the separation of  low and high risk breast cancer.

  • 36. Ahmadian, A
    et al.
    Ren, ZP
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Williams, C
    Ponten, F
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Odeberg, J
    Ponten, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Uhlen, M
    Lundeberg, J
    Genetic instability in the 9q22.3 region is a late event in thedevelopment of squamous cell carcinoma.1998In: Oncogene, Vol. 17, p. 1837-Article in journal (Refereed)
  • 37. Aho, Leena
    et al.
    Pikkarainen, Maria
    Hiltunen, Mikko
    Leinonen, Ville
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Immunohistochemical Visualization of Amyloid-β Protein Precursor and Amyloid-β in Extra- and Intracellular Compartments in the Human Brain2010In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 20, no 4, p. 1015-1028Article in journal (Refereed)
    Abstract [en]

    Amyloid-beta (Abeta) peptide, a cleavage product of the amyloid-beta protein precursor (AbetaPP), has been reported to be detected in the intracellular compartment. Most studies reporting the presence of intracellular Abeta are based on the use of immunohistochemistry. In this study, the presence of AbetaPP and Abeta was assessed by applying immunohistochemistry in postmortem human brain tissue samples obtained from 10 neurologically intact subjects, the youngest being 2 years of age, one aged with mild cognitive impairment, 14 neurologically diseased, and in one brain biopsy sample obtained from a subject with normal pressure hydrocephalus. Intracellular immunoreactivity was detected in all ages independent of the disease state or existence of extracellular Abeta aggregates with all antibodies directed to AbetaPP, with three Abeta antibodies (4G8, 6E10, and 82E1), clones that are unable to distinguish Abeta from AbetaPP. These results suggest that it is AbetaPP rather than Abeta that is detected intracellularly when using the antibodies listed above. Furthermore, the staining results varied when different pretreatment strategies were applied. Interestingly intracellular Abeta was detected with antibodies directed to the C-terminus of Abeta (neoepitope) in subjects with Alzheimer's disease. The lack of intracellular immunoreactivity in unimpaired subjects, when using antibodies against neoepitopes, may be due to a lack or a low level of the protein that is thus undetectable at light microscopic level by immunohistochemistry method. The staining results and conclusions depended strongly on the chosen antibody and the pretreatment strategy and thus multiple antibodies must be used when assessing the intracellular accumulation of Abeta.

  • 38. Akhoondi, Shahab
    et al.
    Sun, Dahui
    von der Lehr, Natalie
    Apostolidou, Sophia
    Klotz, Kathleen
    Maljukova, Alena
    Cepeda, Diana
    Fiegl, Heidi
    Dofou, Dimitra
    Marth, Christian
    Mueller-Holzner, Elisabeth
    Corcoran, Martin
    Dagnell, Markus
    Nejad, Sepideh Zabihi
    Nayer, Babak Noori
    Zali, Mohammad Reza
    Hansson, Johan
    Egyhazi, Susanne
    Petersson, Fredrik
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nordgren, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Grander, Dan
    Reed, Steven I
    Widschwendter, Martin
    Sangfelt, Olle
    Spruck, Charles
    FBXW7/hCDC4 is a general tumor suppressor in human cancer2007In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 67, no 19, p. 9006-9012Article in journal (Refereed)
    Abstract [en]

    The ubiquitin-proteasome system is a major regulatory pathway of protein degradation and plays an important role in cellular division. Fbxw7 (or hCdc4), a member of the F-box family of proteins, which are substrate recognition components of the multisubunit ubiquitin ligase SCF (Skpl-Cdc53/ Cullin-F-box-protein), has been shown to mediate the ubiquitin-dependent proteolysis of several oncoproteins including cyclin El, c-Myc, c-Jun, and Notch. The oncogenic potential of Fbxw7 substrates, frequent allelic loss in human cancers, and demonstration that mutation of FBXW7 cooperates with p53 in mouse tumorigenesis have suggested that Fbxw7 could function as a tumor suppressor in human cancer. Here, we carry out an extensive genetic screen of primary tumors to evaluate the role of FBXW7 as a tumor suppressor in human tumorigenesis. Our results indicate that FBXW7 is inactivated by mutation in diverse human cancer types with an overall mutation frequency of ∼ 6%. The highest mutation frequencies were found in tumors of the bile duct (cholangio-carcinomas, 35%), blood (T-cell acute lymphocytic leukemia, 31%), endometrium (9%), colon (9%), and stomach (6%). Approximately 43% of all mutations occur at two mutational "hotspots," which alter Arg residues (Arg465 and Arg479) that are critical for substrate recognition. Furthermore, we show that Fbxw7Arg465 hotspot mutant can abrogate wild-type Fbxw7 function through a dominant negative mechanism. Our study is the first comprehensive screen of FBXW7 mutations in various human malignancies and shows that FBXW7 is a general tumor suppressor in human cancer.

  • 39.
    Akhtar, Sultan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Experimental Physics.
    Strömberg, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Zardán Gómez de la Torre, Teresa
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Russell, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gunnarsson, Klas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Nilsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Svedlindh, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Leifer, Klaus
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Experimental Physics.
    Real-Space Transmission Electron Microscopy Investigations of Attachment of Functionalized Magnetic Nanoparticles to DNA-Coils Acting as a Biosensor2010In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 114, no 41, p. 13255-13262Article in journal (Refereed)
    Abstract [en]

    The present work provides the first real-space analysis of nanobead-DNA coil interactions. Immobilization of oligonucleotide-functionalized magnetic nanobeads in rolling circle amplified DNA-coils was studied by complex magnetization measurements and transmission electron microscopy (TEM), and a statistical analysis of the number of beads hybridized to the DNA-coils was performed. The average number of beads per DNAcoil using the results from both methods was found to be around 6 and slightly above 2 for samples with 40 and 130 nm beads, respectively. The TEM analysis supported an earlier hypothesis that 40 nm beads are preferably immobilized in the interior of DNA-coils whereas 130 nm beads, to a larger extent, are immobilized closer to the exterior of the coils. The methodology demonstrated in the present work should open up new possibilities for characterization of interactions of a large variety of functionalized nanoparticles with macromolecules, useful for gaining more fundamental understanding of such interactions as well as for optimizing a number of biosensor applications.

  • 40.
    Akyurek, Levent M
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Paul, Leendert C
    Funa, Keiko
    Larsson, Erik
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Fellstrom, Bengt C
    Department of Medical Sciences.
    Smooth muscle cell migration into intima and adventitia during development of transplant vasculopathy.1996In: Transplantation, Vol. 62, p. 1526-Article in journal (Refereed)
  • 41.
    Akyurek, LM
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Fellstrom, B
    Department of Medical Sciences.
    Yang, Z-Q
    Funa, K
    Hansson, G K
    Larsson, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Inducible and endothelial nitric oxide synthase expression during development of transplant arteriosclerosis in rat aortic grafts.1996In: Am J Pathol, Vol. 149, p. 1981-Article in journal (Refereed)
  • 42.
    Akyurek, LM
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Funa, K
    Wanders, A
    Department of Medical Sciences.
    Larsson, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Fellstrom, BC
    Department of Medical Sciences.
    Inhibition of transplant arteriosclerosis in rat aortic grafts by lowmolecular weight heparin derivatives.1995In: Transplantation, Vol. 59, p. 1517-Article in journal (Refereed)
  • 43.
    Akyurek, LM
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Johnsson, C
    Department of Surgical Sciences.
    Lange, D
    Georgii-Hemming, P
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Larsson, Erik
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Fellstrom, Bengt
    Department of Medical Sciences.
    Funa, Keiko
    Tufveson, Gunnar
    Department of Surgical Sciences.
    Tolerance induction ameliorates allograft vasculopathy in rat aortic transplants. Influence of Fas-mediated apoptosis.1998In: J Clin Invest, Vol. 101, p. 2889-Article in journal (Refereed)
  • 44.
    Akyurek, LM
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Larsson, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Funa, K
    Wanders, A
    Department of Medical Sciences.
    Kaijser, M
    Department of Medical Sciences.
    Fellstrom, B
    Department of Medical Sciences.
    Inhibition by Angiopeptin and low molecular weight heparin derivatives.1995In: Transpl Proc, Vol. 27, p. 3555Other (Other scientific)
  • 45.
    Akyurek, LM
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Larsson, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Zhong-qun, Yan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Hansson, GK
    Funa, K
    Fellstrom, B
    Department of Medical Sciences.
    Nitric oxide synthase isoforms in transplant vessels.1997In: Transpl Proc, Vol. 29, p. 2571Other (Other scientific)
  • 46.
    Akyurek, M L
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Wanders, A
    Department of Medical Sciences.
    Aurivillius, M
    Funa, K
    Larsson, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Fellstrom, B
    Department of Medical Sciences.
    Effects of angiopeptin on transplant arteriosclerosis in the rat.1995In: Transpl Int, Vol. 2, p. 103-Article in journal (Refereed)
  • 47.
    Akyurek, ML
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Funa, K
    Wanders, A
    Larsson, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Fellstrom, BC
    Department of Medical Sciences.
    Expression of CD11b and ICAM-1 in an in vivo model of transplantarteriosclerosis.1995In: Transpl Immunol, Vol. 3, p. 107-Article in journal (Refereed)
  • 48.
    Akyurek, ML
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Larsson, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Funa, K
    Wanders, A
    Kaijser, M
    Fellstrom, BC
    Experimental transplant arteriosclerosis: inhibition by angiopeptin andlow molecular weight heparin derivatives.1995In: Transplant Proc, Vol. 27, p. 3555-Article in journal (Refereed)
  • 49.
    Alarcon-Riquelme, Marta E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology. Medicinsk Genetik.
    The genetics of systemic lupus erythematosus.2005In: J Autoimmun, ISSN 0896-8411, Vol. 25 Suppl, p. 46-8Article, review/survey (Other (popular scientific, debate etc.))
  • 50.
    Alarcon-Riquelme, Marta E.
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Fernández, C
    CDR3 regions in the preimmune Vh B cell repertoire of lpr mice1995In: Clin Exp Immunol, Vol. 101, p. 73-Article in journal (Refereed)
1234567 1 - 50 of 3128
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