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  • 1.
    Aasebö, Kristine Ö.
    et al.
    Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Mezheyeuski, Artur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Edqvist, Per-Henrik D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Eide, Geir Egil
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Lifestyle Epidemiol Grp, Bergen, Norway;Haukeland Hosp, Ctr Clin Res, Bergen, Norway.
    Pontén, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Pfeiffer, Per
    Odense Univ Hosp, Dept Oncol, Odense, Denmark.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sorbye, Halfdan
    Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Oncol, Bergen, Norway.
    Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors: A population-based cohort of metastatic colorectal cancer patients2019In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 8, no 7, p. 3623-3635Article in journal (Refereed)
    Abstract [en]

    Background: Immunotherapy for patients with microsatellite-instable (MSI-H) tumors or BRAF-inhibitors combination treatment for BRAF-mutated (mutBRAF) tumors in metastatic colorectal cancer (mCRC) is promising, but the frequency of these molecular changes in trial patients are low. Unselected population-based studies of these molecular changes are warranted.

    Methods: A population-based cohort of 798 mCRC patients in Scandinavia was studied. Patient and molecular tumor characteristics, overall survival (OS) and progression-free survival (PFS) were estimated.

    Results: Here, 40/583 (7%) tumor samples were MSI-H and 120/591 (20%) were mutBRAF; 87% of MSI-H tumors were mutBRAF (non-Lynch). Elderly (>75 years) had more often MSI-H (10% vs 6%) and MSI-H/mutBRAF (9% vs 4%) tumors. Response rate (5% vs 44%), PFS (4 vs 8 months), and OS (9 vs 18 months) after first-line chemotherapy was all significantly lower in patients with MSI-H compared to patients with microsatellite stable tumors. MSI-H and mutBRAF were both independent poor prognostic predictors for OS (P = 0.049, P < 0.001) and PFS (P = 0.045, P = 0.005) after first-line chemotherapy. Patients with MSI-H tumors received less second-line chemotherapy (15% vs 37%, P = 0.005).

    Conclusions: In unselected mCRC patients, MSI-H and mutBRAF cases were more common than previously reported. Patients with MSI-H tumors had worse survival, less benefit from chemotherapy, and they differed considerably from recent third-line immunotherapy trial patients as they were older and most had mutBRAF tumor (non-Lynch).

  • 2.
    Avenel, Christophe
    et al.
    CADESS Med AB, Uppsala, Sweden.
    Tolf, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Carlbom, Ingrid
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. CADESS Med AB, Uppsala, Sweden.
    Glandular Segmentation of Prostate Cancer: An Illustration of How the Choice of Histopathological Stain Is One Key to Success for Computational Pathology2019In: Frontiers in Bioengineering and Biotechnology, E-ISSN 2296-4185, Vol. 7, article id 125Article in journal (Refereed)
    Abstract [en]

    Digital pathology offers the potential for computer-aided diagnosis, significantly reducing the pathologists' workload and paving the way for accurate prognostication with reduced inter-and intra-observer variations. But successful computer-based analysis requires careful tissue preparation and image acquisition to keep color and intensity variations to a minimum. While the human eye may recognize prostate glands with significant color and intensity variations, a computer algorithm may fail under such conditions. Since malignancy grading of prostate tissue according to Gleason or to the International Society of Urological Pathology (ISUP) grading system is based on architectural growth patterns of prostatic carcinoma, automatic methods must rely on accurate identification of the prostate glands. But due to poor color differentiation between stroma and epithelium from the common stain hematoxylin-eosin, no method is yet able to segment all types of glands, making automatic prognostication hard to attain. We address the effect of tissue preparation on glandular segmentation with an alternative stain, Picrosirius red-hematoxylin, which clearly delineates the stromal boundaries, and couple this stain with a color decomposition that removes intensity variation. In this paper we propose a segmentation algorithm that uses image analysis techniques based on mathematical morphology and that can successfully determine the glandular boundaries. Accurate determination of the stromal and glandular morphology enables the identification of the architectural pattern that determine the malignancy grade and classify each gland into its appropriate Gleason grade or ISUP Grade Group. Segmentation of prostate tissue with the new stain and decomposition method has been successfully tested on more than 11000 objects including well-formed glands (Gleason grade 3), cribriform and fine caliber glands (grade 4), and single cells (grade 5) glands.

  • 3.
    Cedervall, Jessica
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Saupe, Falk
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Zhang, Yanyu
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ärnlöv, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Divis Family Med, Huddinge, Sweden.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Dimberg, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Olsson, Anna-Karin
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice.2017In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 6, no 8, article id e1320009Article in journal (Refereed)
    Abstract [en]

    Renal insufficiency is a frequent cancer-associated problem affecting more than half of all cancer patients at the time of diagnosis. To minimize nephrotoxic effects the dosage of anticancer drugs are reduced in these patients, leading to sub-optimal treatment efficacy. Despite the severity of this cancer-associated pathology, the molecular mechanisms, as well as therapeutic options, are still largely lacking. We here show that formation of intravascular tumor-induced neutrophil extracellular traps (NETs) is a cause of kidney injury in tumor-bearing mice. Analysis of clinical biomarkers for kidney function revealed impaired creatinine clearance and elevated total protein levels in urine from tumor-bearing mice. Electron microscopy analysis of the kidneys from mice with cancer showed reversible pathological signs such as mesangial hypercellularity, while permanent damage such as fibrosis or necrosis was not observed. Removal of NETs by treatment with DNase I, or pharmacological inhibition of the enzyme peptidylarginine deiminase 4 (PAD4), was sufficient to restore renal function in mice with cancer. Tumor-induced systemic inflammation and impaired perfusion of peripheral vessels could be reverted by the PAD4 inhibitor. In conclusion, the current study identifies NETosis as a previously unknown cause of cancer-associated renal dysfunction and describes a novel promising approach to prevent renal failure in individuals with cancer.

  • 4.
    Dragomir, Anca
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Assessment of chloride transport in epithelial cells with reference to cystic fibrosis2001Licentiate thesis, monograph (Other scientific)
  • 5.
    Dragomir, Anca
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Andersson, Charlotte
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Roomans, Godfried M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Measurement of chloride transport in nasal epithelial cells by X-ray microanalysis.2004In: J of Cystic Fibrosis, no 3, p. 177-179Article in journal (Refereed)
  • 6.
    Dragomir, Anca
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Björstad, Johan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Hjelte, Lena
    Roomans, Godfried
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Curcumin does not stimulate cAMP-mediated chloride transport in cystic fibrosis airway epithelial cells.2004In: Biophys Biochem Res Commun, no 322, p. 447-451Article in journal (Refereed)
  • 7.
    Dragomir, Anca
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    de Wit, Meike
    Johansson, Christine
    Uhlen, Mathias
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    The role of SATB2 as a diagnostic marker for tumors of colorectal origin: Results of a pathology-based clinical prospective study2014In: American Journal of Clinical Pathology, ISSN 0002-9173, E-ISSN 1943-7722, Vol. 141, no 5, p. 630-638Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Immunohistochemistry is an important extension to clinical information and morphology, and prevails as an invaluable tool for establishing a correct cancer diagnosis in clinical diagnostic pathology. The applicability of immunohistochemistry is limited by the availability of validated cell- and cancer-type specific antibodies, rendering an unmet need to discover, test, and validate novel markers. The SATB2 protein is selectively expressed in glandular cells from the lower gastrointestinal tract and expression is retained in a large majority of primary and metastatic colorectal cancers.

    METHODS: We analyzed the expression of SATB2 in all clinical cases (n = 840), in which immunohistochemistry for detection of CK20 was deemed necessary for a final diagnosis.

    RESULTS: SATB2 showed a high sensitivity (93%) and specificity (77%) to determine a cancer of colorectal origin and in combination with CK7 and CK20, the specificity increased to 100%.

    CONCLUSIONS: We conclude that SATB2 provides a new and advantageous supplement for clinical differential diagnostics.

  • 8.
    Dragomir, Anca
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Hjelte, Lena
    Lagerfeld, L
    Roomans, Godfried
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Heparin improves the viability of transfected cyctic fibrosis cell lines.2004In: Lice Sci, no 75, p. 2203-2216Article in journal (Refereed)
  • 9.
    Dragomir, Anca
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Roomans, Godfried
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Increased chloride efflux in colchicine-resistant airway epithelial cell lines.2004In: Biochem Pharmacol, no 68, p. 253-261Article in journal (Refereed)
  • 10.
    Feresiadou, Amalia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Casar Borota, Olivera
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Oldfors, Carola Hedberg
    Univ Gothenburg, Inst Biomed, Dept Pathol & Genet, Gothenburg, Sweden..
    Stålberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Oldfors, Anders
    Univ Gothenburg, Inst Biomed, Dept Pathol & Genet, Gothenburg, Sweden..
    Tubular aggregates in congenital myasthenic syndrome2018In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 28, no 2, p. 174-175Article in journal (Other academic)
  • 11. Gupta, Anindya
    et al.
    Suveer, Amit
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Lindblad, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Sintorn, Ida-Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Sladoje, Natasa
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    False positive reduction of cilia detected in low resolution TEM images using a convolutional neural network2017In: Swedish Symposium on Image Analysis, Swedish Society for Automated Image Analysis , 2017Conference paper (Other academic)
  • 12.
    Gupta, Anindya
    et al.
    Tallinn Univ Technol, TJ Seebeck Dept Elect, Tallinn, Estonia.
    Suveer, Amit
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Lindblad, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Serbian Acad Arts & Sci, Math Inst, Belgrade, Serbia.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Sintorn, Ida-Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Vironova AB, Stockholm, Sweden.
    Sladoje, Nataša
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Serbian Acad Arts & Sci, Math Inst, Belgrade, Serbia.
    Convolutional neural networks for false positive reduction of automatically detected cilia in low magnification TEM images2017In: Image Analysis: Part I, Springer, 2017, p. 407-418Conference paper (Refereed)
    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.

  • 13. Harris, Ceinwen M
    et al.
    Mendes, Filipa
    Dragomir, Anca
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Doull, Iolo J M
    Carvalho-Oliviera, I
    Bebok, Szuszanna
    Clancy, John P
    Eubanks, Valerie
    Sorscher, Eric J
    Roomans, Godfried M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Amaral, Margarida D
    McPherson, Margaret A
    Penque, Deborah
    Dormer, Robert L
    Assessment of CFTR locatisation in native airway epithelial cells obtained by nasal brushing.2004In: J Cystic Fibrosis, no 3, p. 43-48Article in journal (Refereed)
  • 14.
    Hotz, A.
    et al.
    Univ Freiburg, Inst Human Genet, Fac Med, Med Ctr, Freiburg, Germany..
    Fagerberg, C.
    Odense Univ Hosp, Dept Clin Genet, Odense, Denmark..
    Vahlquist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Bygum, A.
    Odense Univ Hosp, Dept Dermatol, Odense, Denmark.;Odense Univ Hosp, Allergy Ctr, Odense, Denmark..
    Törmä, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Rauschendorf, M-A
    Univ Freiburg, Inst Human Genet, Fac Med, Med Ctr, Freiburg, Germany..
    Zhang, Hanqian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Heinz, L.
    Univ Freiburg, Inst Human Genet, Fac Med, Med Ctr, Freiburg, Germany.;Univ Freiburg, Fac Biol, Freiburg, Germany..
    Bourrat, E.
    Hop St Louis, Ctr Reference Genodermatoses, Paris, France..
    Hausser, I.
    Univ Hosp Heidelberg, Inst Pathol, Heidelberg, Germany..
    Vestergaard, V.
    Odense Univ Hosp, Dept Clin Pathol, Odense, Denmark..
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Zimmer, A. D.
    Univ Freiburg, Inst Human Genet, Fac Med, Med Ctr, Freiburg, Germany..
    Fischer, J.
    Univ Freiburg, Inst Human Genet, Fac Med, Med Ctr, Freiburg, Germany..
    Identification of mutations in SDR9C7 in six families with autosomal recessive congenital ichthyosis2018In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 178, no 3, p. E207-E209Article in journal (Other academic)
  • 15. Larsson, Anna
    et al.
    Karnevi, Emelie
    Nodin, Bjorn
    Sorbye, Halfdan
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Pfeiffer, Per
    Qvortrup, Camilla
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Expression of podocalyxin-like protein and epidermal growth factor receptor in metastatic colorectal cancer: Prognostic impact and relationship with response to cetuximab.2018Conference paper (Refereed)
  • 16.
    Lindahl, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Astrom, Eva
    Karolinska Univ Hosp, Pediat Neurol, Astrid Lindgren Childrens Hosp, Stockholm, Sweden;Karolinska Inst, Dept Woman & Child Hlth, Stockholm, Sweden.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Symoens, Sofie
    Univ Hosp Ghent, Dept Med Genet, Ghent, Belgium.
    Coucke, Paul
    Univ Hosp Ghent, Dept Med Genet, Ghent, Belgium.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Paschalis, Eleftherios
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Roschger, Paul
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Gamsjaeger, Sonja
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Klaushofer, Klaus
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Fratzl-Zelman, Nadja
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy2018In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 114, p. 268-277Article in journal (Refereed)
    Abstract [en]

    Background: Mutations of the endoplasmic reticulum (ER) stress transducer OASIS (encoded by CREB3L1), cause severe recessive osteogenesis imperfecta (OI) not compatible with surviving the neonatal period, as has been shown in two unrelated families through a whole gene deletion vs. a qualitative alteration of OASIS Heterozygous carriers in the described families have exhibited a mild phenotype. OASIS is a transcription factor highly expressed in osteoblasts, and OASIS(-/-) mice exhibit severe osteopenia and spontaneous fractures. Here, we expand the clinical spectrum by a detailed phenotypic characterization of the first case of OASIS-associated OI surviving the neonatal period, with heterozygous family members being unaffected.

    Methods: All OI-associated genes were sequenced. Primary human osteoblast-like cell (hOB) and fibroblast (FB) cultures were obtained for qPCR, and steady-state collagen biochemistry. FB, hOB and skin biopsies were ultrastructurally analyzed. Bone was analyzed by |mu CT, histomorphometry, quantitative backscattered electron imaging (qBEI), and Raman microspectroscopy.

    Results: The proband, a boy with severe OI, had blue sclera and tooth agenesis A homozygous CREB3L1 stop codon mutation was detected by sequencing, while several family members were heterozygotes Markedly low levels of CREB3L1 mRNA were confirmed by qPCR in hOBs (16%) and FB (21%), however, collagen I levels were only reduced in hOBs (5-10%) Electron microscopy of hOBs showed pronounced alterations, with numerous myelin figures and diminished RER vs. normal ultrastructure of FB. Bone histomorphometry and qBEI were similar to collagen I OI, with low trabecular thickness and mineral apposition rate, and increased bone matrix mineralization. Raman microspectroscopy revealed low level of glycosaminoglycans. Clinical response to lifelong bisphosphonate treatment was as expected in severe OI with steadily increasing bone mineral density, but despite this the boy suffered repeated childhood fractures.

    Conclusions: Deficiency of OASIS can cause severe OI compatible with surviving the neonatal period A marked decrease of collagen type I transcription was noted in bone tissue, but not in skin, and ultrastructure of hOBs was pathological. Results also suggested OASIS involvement in glycosaminoglycan secretion in bone.

  • 17.
    Mezheyeuski, Artur
    et al.
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Belarusian State Med Univ, Dept Pathol, Minsk, Byelarus..
    Lindh, Maja Bradic
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Guren, Tormod Kyrre
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway.;Oslo Univ Hosp, KG Jebsen Colorectal Canc Res Ctr, Oslo, Norway..
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Pfeiffer, Per
    Univ Southern Denmark, Dept Oncol, Odense, Denmark..
    Kure, Elin H.
    Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway..
    Ikdahl, Tone
    Akershus Univ Hosp, Lorenskog, Norway..
    Skovlund, Eva
    Univ Oslo, Sch Pharm, Oslo, Norway.;Norwegian Inst Publ Hlth, Oslo, Norway..
    Corvigno, Sara
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Strell, Carina
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Pietras, Kristian
    Lund Univ, Div Translat Canc Res, Lund, Sweden..
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Mulder, Jan
    Karolinska Inst, Sci Life Lab, Dept Neurosci, Stockholm, Sweden..
    Qvortrup, Camilla
    Univ Southern Denmark, Dept Oncol, Odense, Denmark..
    Portyanko, Anna
    Belarusian State Med Univ, Dept Pathol, Minsk, Byelarus..
    Tveit, Kjell Magne
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway..
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sorbye, Halfdan
    Haukeland Hosp, Dept Oncol, Bergen, Norway..
    Östman, Arne
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 27, p. 41948-41958Article in journal (Refereed)
    Abstract [en]

    Perivascular cells (PC) were recently implied as regulators of metastasis and immune cell activity. Perivascular heterogeneity in clinical samples, and associations with other tumor features and outcome, remain largely unknown. Here we report a novel method for digital quantitative analyses of vessel characteristics and PC, which was applied to two collections of human metastatic colorectal cancer (mCRC). Initial analyses identified marker-defined subsets of PC, including cells expressing PDGFR-beta or alpha-SMA or both markers. PC subsets were largely independently expressed in a manner unrelated to vessel density and size. Association studies implied specific oncogenic mutations in malignant cells as determinants of PC status. Semi-quantitative and digital-image-analyses-based scoring of the NORDIC-VII cohort identified significant associations between low expression of perivascular PDGFR-alpha and -beta and shorter overall survival. Analyses of the SPCRC cohort confirmed these findings. Perivascular PDGFR-alpha and -beta remained independent factors for survival in multivariate analyses. Overall, our study identified host vasculature and oncogenic status as determinants of tumor perivascular features. Perivascular PDGFR-alpha and -beta were identified as novel independent markers predicting survival in mCRC. The novel methodology should be suitable for similar analyses in other tumor collections.

  • 18.
    Mezheyeuski, Artur
    et al.
    Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, R8 03, Stockholm, Sweden;Belarusian State Med Univ, Dept Pathol, Minsk, Byelarus.
    Strell, Carina
    Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, R8 03, Stockholm, Sweden.
    Hrynchyk, Ina
    City Clin Pathologoanat Bur, Minsk, Byelarus.
    Guren, Tormod Kyrre
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway;Oslo Univ Hosp, KG Jebsen Colorectal Canc Res Ctr, Oslo, Norway.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Doroshenko, Tatyana
    Republ Res & Prod Ctr Transfusiol & Med Biotechno, Lab Antibodies & Cytokines Biotechnol, Minsk, Byelarus.
    Pashkova, Oksana
    Republ Res & Prod Ctr Transfusiol & Med Biotechno, Lab Antibodies & Cytokines Biotechnol, Minsk, Byelarus.
    Gorgun, Julia
    Belarusian Med Acad Postgrad Educ, Dept Gastroenterol & Nutr, Minsk, Byelarus.
    Ruksha, Kseniya
    NN Alexandrov Natl Canc Ctr Belarus, Minsk, Byelarus.
    Pfeiffer, Per
    Univ Southern Denmark, Dept Oncol, Odense, Denmark.
    Kure, Elin H.
    Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway.
    Sorbye, Halfdan
    Haukeland Hosp, Dept Oncol, Bergen, Norway.
    Edler, David
    Karolinska Univ Hosp Solna, Dept Mol Med & Surg, S-17176 Stockholm, Sweden.
    Martling, Anna
    Karolinska Univ Hosp Solna, Dept Mol Med & Surg, S-17176 Stockholm, Sweden.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ostman, Arne
    Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, R8 03, Stockholm, Sweden.
    Portyanko, Anna
    Belarusian State Med Univ, Dept Pathol, Minsk, Byelarus.
    Treatment-related survival associations of claudin-2 expression in fibroblasts of colorectal cancer2018In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 472, no 3, p. 395-405Article in journal (Refereed)
    Abstract [en]

    Claudin-2 is a trans-membrane protein-component of tight junctions in epithelial cells. Elevated claudin-2 expression has been reported in colorectal cancer (CRC). The aim of this study was to investigate the expression patterns of claudin-2 in human CRC samples and analyze its association with clinical characteristics and treatment outcome. TMAs of primary tumors from two cohorts of metastatic CRC (mCRC) were used. Claudin-2 IHC staining was evaluated in a semi-quantitative manner in different regions and cell types. Claudin-2 expression was also analyzed by immunofluorescence in primary cultures of human CRC cancer-associated fibroblasts (CAFs). Initial analyses identified previously unrecognized expression patterns of claudin-2 in CAFs of human CRC. Claudin-2 expression in CAFs of the invasive margin was associated with shorter progression-free survival. Subgroup analyses demonstrated that the survival associations occurred among cases that received 5-FU+oxaliplatin combination treatment, but not in patients receiving 5-FU +/- irinotecan. The finding was validated by analyses of the independent cohort. In summary, previously unreported stromal expression of claudin-2 in CAFs of human CRC was detected together with significant association between high claudin-2 expression in CAFs and shorter survival in 5-FU+oxaliplatin-treated mCRC patients.

  • 19. Munkonge, Felix
    et al.
    Alton, Eric WFW
    Andersson, Charlotte
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Davidson, Heather
    Dragomir, Anca
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Edelman, Aleksander
    Farley, Ray
    Hjelte, Lena
    McLachlan, Gerry
    Stern, Myra
    Roomans, Godfried
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Measurement of halide efflux from cultured and primary airway epithelial cells using fluorescence indicators.2004In: J Cystic Fibrosis, no 3, p. 171-176Article in journal (Refereed)
  • 20.
    Niinivirta, Marjut
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University Hospital, Department of Oncology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University Hospital, Department of Oncology.
    Edqvist, Per-Henrik D
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University Hospital, Department of Oncology.
    Tumoral ANXA1 Is a Predictive Marker for Sunitinib Treatment of Renal Cancer Patients2017In: Journal of Cancer, ISSN 1837-9664, E-ISSN 1837-9664, Vol. 8, no 19, p. 3975-3983Article in journal (Refereed)
    Abstract [en]

    Background and aims: There is no established predictive marker for the treatment of renal cancer. Metastatic renal cell carcinoma (mRCC) patients are often treated with sunitinib, a tyrosine kinase inhibitor. Sunitinibs anti-cancer effect is at least partly mediated through interfering with angiogenesis. Our aim with the current study was to assess annexin A1 (ANXA1), which stimulates angiogenesis, as a predictive marker for sunitinib therapy in mRCC patients. Since previous studies have indicated a predictive potential for cubilin, we also investigated the predictivity of ANXA1 combined with cubilin.

    Methods: ANXA1 expression was analysed in tumor tissue from a cohort of patients with advanced RCC (n= 139) using immunohistochemistry. Ninety-nine of the patients were treated with sunitinib in the first or second-line setting. Twenty-two of these were censored because of toxicity leading to the termination of treatment and the remaining (n= 77) were selected for the present study.

    Results: Twenty-five (32%) out of seventy-seven of the tumors lacked ANXA1 in the cytoplasm. On statistical analyses using Kaplan-Meier method, aNXA1 negative tumors were significantly associated with a longer treatment benefit in terms of progression free survival (PFS). Overall survival was also significantly better for patients with ANXA1 negative tumors. The combined ANXA1 positive and cubilin negative expression could more accurately than ANXA1 alone define the group not benefitting from treatment.

    Conclusions: Our results indicate that cytoplasmic expression of ANXA1 is a negative predictive marker for sunitinib therapy in mRCC patients. A possible explanation for this finding is that sunitinibs anti-angiogenic effect cannot overcome the pro-angiogenic drive from many ANXA1 proteins.

  • 21.
    Niinivirta, Marjut
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ullenhag, Gustav J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Tumoral cubilin is a predictive marker for treatment of renal cancer patients with sunitinib and sorafenib2017In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 143, no 6, p. 961-970Article in journal (Refereed)
    Abstract [en]

    Purpose Tyrosine kinase inhibitors like sunitinib and sorafenib are commonly used to treat metastatic renal cell cancer patients. Cubilin is a membrane protein expressed in the proximal renal tubule. Cubilin and megalin function together as endocytic receptors mediating uptake of many proteins. There is no established predictive marker for metastatic renal cell cancer patients and the purpose of the present study was to assess if cubilin can predict response to treatment with tyrosine kinase inhibitors.

    Methods Cubilin protein expression was analyzsed in tumor tissue from a cohort of patients with metastatic renal cell cancer (n = 139) using immunohistochemistry. One hundred and thirty six of the patients were treated with sunitinib or sorafenib in the first- or second-line setting. Thirty of these were censored because of toxicity leading to the termination of treatment and the remaining (n = 106) were selected for the current study.

    Results Fifty-three (50%) of the tumors expressed cubilin in the membrane. The median progression-free survival was 8 months in patients with cubilin expressing tumors and 4 months in the cubilin negative group. In addition, the overall survival was better for patients with cubilin positive tumors. We also found that the fraction of cubilin negative patients was significantly higher in the non-responding group (PFS ≤3 months) compared to responding patients (PFS >3 months).

    Conclusions We show for the first time that tumoral expression of cubilin is a positive predictive marker for treatment of metastatic renal cell cancer patients with sunitinib and sorafenib.

  • 22.
    Niinivirta, Marjut
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Department of Oncology, Uppsala University Hospital, Entrance 78, 751 85 Uppsala, Sweden.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Department of Oncology, Uppsala University Hospital, Entrance 78, 751 85 Uppsala, Sweden.
    Lindskog, Cecilia
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Pontén, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Surgical Pathology, Uppsala University Hospital, 75185 Uppsala, Sweden.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Department of Oncology, Uppsala University Hospital, Entrance 78, 751 85 Uppsala, Sweden.
    Tumoral pyruvate kinase L/R as a predictive marker for the treatment of renal cancer patients with sunitinib and sorafenib2019In: Journal of Cancer, ISSN 1837-9664, Vol. 10, no 14, p. 3224-3231Article in journal (Other academic)
    Abstract [en]

    Background and aims: Treatment with tyrosine kinase inhibitors (TKI) like sunitinib and sorafenib has improved the prognosis of patients with metastatic renal cell cancer (mRCC). No predictive marker is available to select patients who will gain from these treatments. Tumoral pyruvate kinase L/R (PKLR) is a membrane protein with highly specific expression in the renal tubule. We have previously shown that the tumoral expression of cubilin (CUBN) is associated with progression free survival (PFS) in mRCC patients treated with sunitinib and sorafenib. The aim of the present study was to investigate if PKLR can predict response in these patients, alone and/or in combination with CUBN.

    Methods: A tissue microarray (TMA) was constructed of tumor samples from 139 mRCC patients. One hundred and thirty-six of these patients had been treated with sunitinib or sorafenib in the first or second-line setting. Thirty patients suffered from early severe toxicity leading to the termination of treatment. The remaining patients (n=106) were selected for the current study.

    Results: Fifty-five (52%) of the tumors expressed membranous PKLR. Patients with PKLR tumor expression experienced a significantly longer PFS compared to patients with no expression (eight versus five months, p = 0.019). Overall survival (OS) was also significantly better for patients with PKLR expression. In addition, the combined expression of PKLR and CUBN resulted in a higher predictive value than either marker alone.

    Conclusions: In this real world study we show that tumoral PKLR membrane expression is a positive predictive biomarker for sunitinib and sorafenib treatment in patients suffering from mRCC. Our results also indicate that the combined expression with cubilin more accurately than PKLR alone can select patients with no benefit from treatment.

  • 23.
    Nilsson, Harriet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ahlander, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Johannesson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Roomans, Godfried M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Effects of hyperosmotic stress on cultured airway epithelial cells2007In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 330, no 2, p. 257-269Article in journal (Refereed)
    Abstract [en]

    Inhalation of hyperosmotic solutions (salt, mannitol) has been used in the treatment of patients with cystic fibrosis or asthma, but the mechanism behind the effect of hyperosmotic solutions is unclear. The relation between osmolarity and permeability changes was examined in an airway cell line by the addition of NaCl, NaBr, LiCl, mannitol, or xylitol (295–700 mOsm). Transepithelial resistance was measured as an indicator of the tightness of the cultures. Cell-cell contacts and morphology were investigated by immunofluorescence and by transmission electron microscopy, with lanthanum nitrate added to the luminal side of the epithelium to investigate tight junction permeability. The electrolyte solutions caused a significant decrease in transepithelial resistance from 450 mOsm upwards, when the hyperosmolar exposure was gradually increased from 295 to 700 mOsm; whereas the nonelectrolyte solutions caused a decrease in transepithelial resistance from 700 mOsm upwards. Old cultures reacted in a more rigid way compared to young cultures. Immuno-fluorescence pictures showed weaker staining for the proteins ZO-1, claudin-4, and plakoglobin in treated samples compared to the control. The ultrastructure revealed an increased number of open tight junctions as well as a disturbed morphology with increasing osmolarity, and electrolyte solutions opened a larger proportion of tight junctions than nonelectrolyte solutions. This study shows that hyperosmotic solutions cause the opening of tight junctions, which may increase the permeability of the paracellular pathway and result in increased transepithelial water transport.

  • 24.
    Nilsson, Harriet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ahlander, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ljungkvist, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Roomans, Godfried M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    A modified technique for the impregnation of lanthanum tracer to study the integrity of tight junctions on cells grown on a permeable substrate2006In: Microscopy research and technique (Print), ISSN 1059-910X, E-ISSN 1097-0029, Vol. 69, no 10, p. 776-783Article in journal (Refereed)
    Abstract [en]

    Ionic lanthanum is commonly used to trace permeability pathways across epithelia and endothelia in biological electron microscopy. A method for obtaining a uniformly dense precipitate of lanthanum is described. The method, which is a modification of the technique described by Shaklai and Tavassoli (1977) was suitable for fixation of cell cultures grown on permeable filter inserts and was successfully applied to study opening of tight junctions by hypertonic solutions in the airway epithelial cell line 16HBE14o(-). The preparation method formed the basis for a semi-quantitative morphological determination in which the tight junctions were subdivided as "intact," "weakened," and "open." By using this modified technique, it could be demonstrated that opening of tight junctions in airway epithelial cells increased, with increasing osmolarity with electrolytes having a stronger effect than nonelectrolytes. A significant linear relationship was found between the osmolarity of the medium and the open state of the tight junctions (as determined by the semi-quantitative morphological technique) or the transepithelial electrical resistance.

  • 25.
    Roomans, Godfried M.
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Dragomir, Anca
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    X-ray microanalysis in the scanning electron microscope2007In: Electron Microscopy: Methods & Protocols: 2’nd Edition, Humana Press Inc. , 2007Chapter in book (Refereed)
  • 26. Schlipf, N A
    et al.
    Vahlquist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Teigen, N
    Virtanen, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Fismen, S
    Barenboim, M
    Manke, T
    Rösler, B
    Zimmer, A
    Fischer, J
    Whole-exome sequencing identifies novel autosomal recessive DSG1 mutations associated with mild SAM syndrome2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 174, no 2, p. 444-448Article in journal (Refereed)
  • 27.
    Servetnyk, Zhanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Krjukova, Jelena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Gaston, Benjamin
    Zaman, Khalequz
    Hjelte, Lena
    Roomans, Godfried M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Activation of chloride transport in CF airway epithelial cell lines and primary CF nasal epithelial cells by S-nitrosoglutathione2006In: Respiratory research (Online), ISSN 1465-9921, E-ISSN 1465-993X, Vol. 7, p. 124-Article in journal (Refereed)
    Abstract [en]

    Background: It has been suggested that low mu M concentrations of S-nitrosoglutathione (GSNO), an endogenous bronchodilator, may promote maturation of the defective cystic fibrosis (CF) transmembrane conductance regulator ( CFTR). Because nitric oxide ( NO) and GSNO levels appear to be low in the CF airway, there is an interest in the possibility that GSNO replacement could be of therapeutic benefit in CF.

    Methods: The effect of GSNO on chloride (Cl-) transport was investigated in primary nasal epithelial cells obtained from CF patients homozygous for the delF508 mutation, as well as in two CF cell lines (CFBE and CFSME), using both a fluorescent Cl- indicator and X-ray microanalysis. Maturation of delF508 CFTR was determined by immunoblotting.

    Results: Treatment with 60 mu M GSNO for 4 hours increased cAMP-induced chloride efflux in nasal epithelial cells from 18 out of 21 CF patients, but did not significantly affect Cl- efflux in cells from healthy controls. This Cl- efflux was confirmed by measurements with a fluorescent Cl- indicator in the CFBE and CFSME cell lines. The effect of GSNO on Cl- efflux in CFBE cells could be inhibited both by a specific thiazolidinone CFTR inhibitor (CFTRinh-172) and by 4,4'-diisothiocyanatodihydrostilbene- 2,2'-disulfonic acid (H2DIDS). X-ray microanalysis showed that, following 4 hours incubation with 60 mu M GSNO, cAMP agonists caused a decrease in the cellular Cl- concentration in CFBE cells, corresponding to Cl- efflux. GSNO exposure resulted in an increase in the protein expression and maturation, as shown by immunoblot analysis. GSNO did not increase the cytosolic Ca2+ concentration in cultured airway epithelial cells.

    Conclusion: Previous studies have suggested that treatment with GSNO promotes maturation of delF508-CFTR, consistent with our results in this study. Here we show that GSNO increases chloride efflux, both in the two CF cell lines and in primary nasal epithelial cells from delF508-CF patients. This effect is at least in part mediated by CFTR. GSNO may be a candidate for pharmacological treatment of the defective chloride transport in CF epithelial cells.

  • 28.
    Siesing, Christina
    et al.
    Lund Univ, Skane Univ Hosp, Div Oncol & Pathol, Dept Clin Sci, Lund, Sweden..
    Sorbye, Halfdan
    Univ Bergen, Haukeland Univ Hosp, Dept Oncol, Bergen, Norway.;Univ Bergen, Dept Clin Sci, Bergen, Norway..
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala Univ, Uppsala Univ Hosp, Sect Pathol, Uppsala, Sweden.
    Pfeiffer, Per
    Odense Univ Hosp, Dept Oncol, Odense, Denmark..
    Qvortrup, Camilla
    Odense Univ Hosp, Dept Oncol, Odense, Denmark..
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala Univ, Uppsala Univ Hosp, Sect Pathol, Uppsala, Sweden.
    Jirström, Karin
    Lund Univ, Skane Univ Hosp, Div Oncol & Pathol, Dept Clin Sci, Lund, Sweden..
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Eberhard, Jakob
    Lund Univ, Skane Univ Hosp, Div Oncol & Pathol, Dept Clin Sci, Lund, Sweden..
    High RBM3 expression is associated with an improved survival and oxaliplatin response in patients with metastatic colorectal cancer2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 8, article id e0182512Article in journal (Refereed)
    Abstract [en]

    Background: High expression of the RNA-binding motif protein 3 (RBM3) has been shown to correlate, with prolonged survival in several malignant diseases and with the benefit of platinumbased chemotherapy in ovarian cancer. The aim of this study was to evaluate RBM3 in metastatic colorectal cancer (mCRC) as a prognostic factor for overall survival and in relation to benefit of first-line chemotherapy.

    Methods: Immunohistochemical staining was conducted and evaluated in tumours from 455 mCRC patients. Kaplan- Meier analysis and Cox regression proportional hazards models were used to access the impact of RBM3 expression on overall survival (OS) and progressionfree survival (PFS).

    Results: High RBM3 expression, both nuclear and cytoplasmic, was an independent prognostic factor for prolonged OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.50-0.90 and HR 0.66, 95% CI 0.48-0.91, respectively). PFS was significantly longer in patients with high RBM3 expression who had received first-line oxaliplatin based treatment, compared to those who had received irinotecan based treatment, both regarding nuclear and cytoplasmic expression (p-value 0.020 and 0.022 respectively).

    Conclusion: High RBM3 expression is an independent predictor of prolonged survival in mCRC patients, in particular in patients treated with first-line oxaliplatin based chemotherapy.

  • 29. Sorbye, Halfdan
    et al.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Pfeiffer, Per
    Thunberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Bergfors, Monica
    Department of Pathology, Uppsala University Hospital, Uppsala, Sweden.
    Aasebo, Kristine
    Eide, Geir Egil
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Qvortrup, Camilla
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    High BRAF Mutation Frequency and Marked Survival Differences in Subgroups According to KRAS/BRAF Mutation Status and Tumor Tissue Availability in a Prospective Population-Based Metastatic Colorectal Cancer Cohort2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, article id e0131046Article in journal (Refereed)
    Abstract [en]

    RAS and BRAF mutations impact treatment and prognosis of metastatic colorectal cancer patients (mCRC), but the knowledge is based on trial patients usually not representative for the general cancer population. Patient characteristics, treatment and efficacy according to KRAS, BRAF and MSI status were analyzed in a prospectively collected unselected population-based cohort of 798 non-resectable mCRC patients. The cohort contained many patients with poor performance status (39% PS 2-4) and elderly (37% age>75), groups usually not included in clinical trials. Patients without available tissue micro array (TMA) (42%) had worse prognostic factors and inferior survival (all patients; 7m vs 11m, chemotherapy-treated; 12m vs 17m). The 92 patients (21%) with BRAF mutation had a poor prognosis regardless of microsatellite instability, but receipt of 1-2nd chemotherapy was similar to wildtype BRAF patients. Median survival in this cohort varied from 1 month in BRAF mutated patients not given chemotherapy to 26 months in wildtype KRAS/BRAF patients <75 years in good PS. TMA availability, BRAF mutation and KRAS mutation were all independent prognostic factors for survival. The observed 21% BRAF mutation incidence is higher than the previously and repeatedly reported incidence of 5-12% in mCRC. Screening for BRAF mutations before selection of treatment is relevant for many patients, especially outside clinical trials. A BRAF mutation only partly explained the very poor prognosis of many mCRC patients. Survival in unselected metastatic colorectal cancer patients is extremely variable and subgroups have an extremely short survival compared to trial patients. Patients without available TMA had worse prognostic factors and shorter survival, which questions the total generalizability of present TMA studies and implies that we lack information on the biologically worst mCRC cases. Lack of available tissue is an important underexposed issue which introduces sample bias, and this should be recognized more clearly when conclusions are made from translational mCRC studies.

  • 30.
    Suveer, Amit
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Sladoje, Natasa
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Lindblad, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Sintorn, Ida-Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Cilia ultrastructural visibility enhancement by multiple instance registration and super-resolution reconstruction2017In: Swedish Symposium on Image Analysis, Swedish Society for Automated Image Analysis , 2017Conference paper (Other academic)
  • 31.
    Suveer, Amit
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Sladoje, Nataša
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Serbian Acad Arts & Sci, Math Inst, Belgrade, Serbia.
    Lindblad, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Serbian Acad Arts & Sci, Math Inst, Belgrade, Serbia.
    Dragomir, Anca
    Uppsala University Hospital.
    Sintorn, Ida-Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Automated detection of cilia in low magnification transmission electron microscopy images using template matching2016In: Biomedical Imaging (ISBI), 2016 IEEE 13th International Symposium on, IEEE, 2016, p. 386-390Conference paper (Other academic)
    Abstract [en]

    Ultrastructural analysis using Transmission Electron Microscopy (TEM) is a common approach for diagnosing primary ciliary dyskinesia. The manually performed diagnostic procedure is time consuming and subjective, and automation of the process is highly desirable. We aim at automating the search for plausible cilia instances in images at low magnification, followed by acquisition of high magnification images of regions with detected cilia for further analysis. This paper presents a template matching based method for automated detection of cilia objects in low magnification TEM images, where object radii do not exceed 10 pixels. We evaluate the performance of a series of synthetic templates generated for this purpose by comparing automated detection with results manually created by an expert pathologist. The best template achieves a detection at equal error rate of 47% which suffices to identify densely populated cilia regions suitable for high magnification imaging.

  • 32.
    Suveer, Amit
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Sladoje, Nataša
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Lindblad, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Sintorn, Ida-Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Enhancement of cilia sub-structures by multiple instance registration and super-resolution reconstruction2017In: Image Analysis: Part II, Springer, 2017, p. 362-374Conference paper (Refereed)
    Abstract [en]

    Ultrastructural analysis of cilia cross-sectional images using transmission electron microscopy (TEM) assists the pathologists to diagnose Primary Ciliary Dyskinesia, a genetic disease. The current diagnostic procedure is manual and difficult because of poor signal-to-noise ratio in TEM images. In this paper, we propose an automated multi-step registration approach to register many cilia cross-sectional instances. The novelty of the work is in the utilization of customized weight masks at each registration step to achieve good alignment of the specific cilium regions. Registration is followed by super-resolution reconstruction to enhance the substructural information. Landmarks matching based evaluation of registration results in pixel alignment error of 2.35&#x00B1;1.82" role="presentation">2.35±1.82 pixels, and the subjective analysis of super-resolution reconstructed cilium shows a clear improvement in the visibility of the substructures such as dynein arms, radial spokes, and central pair.

  • 33.
    Vahlquist, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Virtanen, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Hellström-Pigg, M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Ryberg, K.
    Wilson, N. J.
    Ostman-Smith, I.
    Lu, L.
    McGrath, J. A.
    Smith, F. J. D.
    A Scandinavian case of skin fragility, alopecia and cardiomyopathy caused by DSP mutations2014In: Clincal and Experimental Dermatology, ISSN 0307-6938, E-ISSN 1365-2230, Vol. 39, no 1, p. 30-34Article in journal (Refereed)
    Abstract [en]

    Congenital skin fragility is a heterogeneous disorder with epidermolysis bullosa and various skin infections as the leading causes. However, even rare diseases must be considered in the differential diagnosis of neonatal skin blistering, including some genetic syndromes with extracutaneous involvement. One such syndrome is ectodermal dysplasia due to deficiency of desmoplakin, a desmosomal protein essential for cellular cohesion in both epithelia and cardiac tissues. Desmoplakin is encoded by the DSP gene, which is localized on chromosome 6p24. Both dominant and recessive mutations in this gene have been reported to cause skin fragility and keratinization defects. We report a child born with a fragile epidermis, alopecia, thick nails, and focal hyperkeratoses on the digits and knees. She was found to have a deficiency of desmoplakin caused by compound heterozygous DSP mutations. She has gradually developed signs of a left ventricular cardiomyopathy.

  • 34.
    Vahlquist, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Virtanen, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Hellström-Pigg, Maritta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Ryberg, K.
    Wilson, N. J.
    Lu, L.
    McGrath, J. A.
    Smith, F. J. D.
    Ultrastructure of desmosomes as a diagnostic clue in a case of congenital skin fragility syndrome2014In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 134, no 4, p. 1172-1172Article in journal (Other academic)
  • 35.
    Vahlquist, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Virtanen, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Hellström-Pigg, Maritta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Ryberg, K.
    Wilson, N. J.
    Lu, L.
    McGrath, J. A.
    Smith, F. J. D.
    Ultrastructure of desmosomes as a diagnostic clue in a case of congenital skin fragility syndrome2014In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 134, no 4, p. 1176-1176Article in journal (Other academic)
  • 36.
    Vanthanouvong, V
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Kozlova, I
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Johannesson, M
    Department of Women's and Children's Health.
    Nääs, E
    Nordvall, L
    Department of Women's and Children's Health.
    Dragomir, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Roomans, G M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Composition of nasal airway surface liquid in cystic fibrosis and other airway diseases determined by X-ray microanalysis.2006In: Microsc Res Tech, ISSN 1059-910X, Vol. 69, no 4, p. 271-6Article in journal (Refereed)
1 - 36 of 36
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