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  • Dictor, Michael, et al. (författare)
  • Abnormal cell cycle regulation in malignancy
  • 1999
  • Ingår i: American Journal of Clinical Pathology. - 0002-9173. ; 112:1 Suppl 1, s. 40-52
  • Forskningsöversikt (refereegranskat)abstract
    • The cell cycle consists of an initial growth phase (G1), DNA replication (S), a gap phase (G2), and mitosis (M), after which the cell may differentiate or enter the resting state (G0). The cycle is driven by a number of positive and negative regulatory phosphorylation and dephosphorylation events, involving protein kinases, protein phosphatases, cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors, that ultimately impinge on the activity of transcription factors. Unreplicated or damaged DNA blocks the progression of the cell cycle at checkpoints, including a late G1 checkpoint regulated by the dephosphorylated retinoblastoma protein and a late G2 checkpoint regulated by the phosphorylation of cyclin-dependent kinase 1 complexed with cyclin B. Many cell cycle regulator genes may be considered proto-oncogenes or tumor suppressor genes, and point mutations, amplifications, deletions, or rearrangements involving their loci, particularly those in the "RB pathway," are associated with various tumors. A number of molecular techniques may be used to detect genomic alterations or posttranscriptional modifications, but immunohistochemistry remains the most common method to determine expression levels of a regulatory protein. Multivariate analysis of the usefulness in prognosis has been applied most often for the general proliferation antigen Ki-67.
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  • Dragomir, Anca, et al. (författare)
  • The Role of SATB2 as a Diagnostic Marker for Tumors of Colorectal Origin
  • 2014
  • Ingår i: American Journal of Clinical Pathology. - 0002-9173 .- 1943-7722. ; 141:5, s. 630-638
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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  • Dragomir, Anca, et al. (författare)
  • The role of SATB2 as a diagnostic marker for tumors of colorectal origin : Results of a pathology-based clinical prospective study
  • 2014
  • Ingår i: American Journal of Clinical Pathology. - 0002-9173 .- 1943-7722. ; 141:5, s. 630-638
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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  • Ehinger, Mats, et al. (författare)
  • A Subset of CD5- Diffuse Large B-Cell Lymphomas Expresses Nuclear Cyclin D1 With Aberrations at the CCND1 Locus.
  • 2008
  • Ingår i: American Journal of Clinical Pathology. - 1943-7722 .- 0002-9173. ; 129:4, s. 630-638
  • Tidskriftsartikel (refereegranskat)abstract
    • In 231 diffuse large B-cell lymphomas, the expression of cyclin D1 and CD5 was evaluated. All cases were CD5-. Ten (4.3%) were positive for cyclin D1 and were subjected to fluorescence in situ hybridization at the CCND1 locus. One case showed the t(11;14). In another case, the telomeric probe signal for cyclin D1 was lost in most tumor cells, and in a small proportion of the cells, there were fluorescence signals indicative of the t(11;14). Two other cases displayed additional cyclin D1 signals in the absence of the t(11;14). All cases but 1 were positive for bcl-6 or MUM1, disfavoring the possibility of misdiagnosed blastoid variants of CD5- mantle cell lymphomas. Thus, contrary to the current view, there seems to exist a certain number of cyclin D1+ and CD5- diffuse large B-cell lymphomas, some of which have structural aberrations at the CCND1 locus, including the t(11;14).
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  • Gerdin, E, et al. (författare)
  • Immunohistochemical identification of receptors for epidermal growth factor in tumor endothelium may be affected by cross-reactivity to blood group A antigen.
  • 1993
  • Ingår i: American Journal of Clinical Pathology. - 0002-9173 .- 1943-7722. ; 99:1, s. 28-31
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been reported that endothelium in malignant glioma stains with a commercial antibody raised against the receptor for epidermal growth factor (EGFr) on A431 cells (clone 29.1). In this report, this antibody was used to study the immunohistochemical expression of EGFr in benign and malignant ovarian, mid-gut carcinoid, and thyroid neoplasms using the avidin-biotin-peroxidase complex technique. Eighteen of the 37 ovarian neoplasms, 4 of the 10 thyroid neoplasms, and 14 of 28 mid-gut carcinoid tumors expressed strong and distinct endothelial staining, whereas staining results of the remaining tumors were negative. The endothelial nature of the staining was verified by staining serial sections with Ulex europaeus agglutinin-I. The staining was independent of that obtained with an antibody raised against a synthetic peptide consisting of residues 985 to 996 from the cytoplasmic domain of EGFr (clone F4). All positive staining occurred in patients determined to be of blood groups A or AB, whereas samples from patients with blood groups B or O were negative. Immunoabsorption of the antibody with centrifuged erythrocytes from a blood group A donor, but not from a blood group B donor, abolished the positive staining. The data indicate that positive staining of tumor endothelium with this antibody is due to cross-reactivity with blood group A antigen. The results obtained challenge the validity of previously performed immunohistochemical studies in which monoclonal antibodies raised against the EGFr of A431 cells have been used, and in which the epitope for the monoclonal antibody has not been determined.
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  • Jacobsson, Stefan, 1951, et al. (författare)
  • Low megakaryocyte ploidy in Ph-positive chronic myelogenous leukemia measured by flow cytometry.
  • 1999
  • Ingår i: American journal of clinical pathology. - 0002-9173. ; 111:2, s. 185-90
  • Tidskriftsartikel (refereegranskat)abstract
    • In chronic myeloproliferative disorders, the megakaryocytes differ in size and maturation compared with those of healthy individuals. In the present study, by using a 2-color flow cytometry technique, we determined the frequency of bone marrow megakaryocytes in different ploidy classes in 13 newly diagnosed and untreated patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) and in 12 healthy volunteers. The results showed a significant difference in megakaryocyte ploidy distributions between these 2 study groups. On the average, patients with CML had 59% of their megakaryocytes in ploidy classes 2N to 8N; in contrast, the healthy volunteers had only 22% of their megakaryocytes in classes 2N to 8N. Two patients with complex Ph translocation and 2 patients with a small clone with a chromosome abnormality in addition to Ph had the same ploidy distribution as those with only Ph translocation. The platelet count did not correlate with the megakaryocyte mean ploidy.
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  • Jonsson, BH, et al. (författare)
  • What is hidden in tattoos?
  • 2015
  • Ingår i: American journal of clinical pathology. - : Oxford University Press (OUP). - 1943-7722 .- 0002-9173. ; 143:6, s. 908-909
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Karah, Nabil, et al. (författare)
  • Teleclinical Microbiology : An Innovative Approach to Providing Web-Enabled Diagnostic Laboratory Services in Syria
  • 2022
  • Ingår i: American Journal of Clinical Pathology. - : Oxford University Press. - 0002-9173 .- 1943-7722. ; 157:4, s. 554-560
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Telemedicine can compensate for the lack of health care specialists in response to protracted humanitarian crises. We sought to assess the usability of a teleclinical microbiology (TCM) program to provide diagnostic services in a hard-to-reach region of Syria.Methods: A semimobile station was equipped with conventional micrograph and macrograph digital imaging systems. An electronic platform (Telemicrobiology in Humanitarian Crises, TmHC) was created to facilitate sharing, interpreting, and storing the results. A pilot study was conducted to identify the bacterial species and antimicrobial susceptibility pattern of 74 urinary clinical isolates. An experience survey was conducted to capture the feedback of 8 participants in the program.Results: The TmHC platform (https://sdh.ngo/tmhc/) enabled systematic transmission of the laboratory records and co-interpretation of the results. The isolates were identified as Escherichia coli (n = 61), Klebsiella pneumoniae (n = 12), and Proteus mirabilis(n = 1). All the isolates were multidrug resistant. The performance of our TCM module was rated 4 (satisfying) and 5 (very satisfying) by 6 and 2 users, respectively. Data security of and cost-effectiveness were the main perceived concerns.Conclusions: Although we encountered several context-related obstacles, our TCM program managed to reach a highly vulnerable population of 4 million people confined in the northwest region of Syria.
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  • Kushnir, Mark M., et al. (författare)
  • High-Sensitivity Tandem Mass Spectrometry Assay for Serum Estrone and Estradiol
  • 2008
  • Ingår i: American Journal of Clinical Pathology. - 0002-9173 .- 1943-7722. ; 129:4, s. 530-539
  • Tidskriftsartikel (refereegranskat)abstract
    • High-sensitivity measurement of serum estrogens is important in adult and pediatric endocrinology and oncology. We developed a high-sensitivity liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous measurement of estrone (E-1) and estradiol (E-2). Aliquots of 200 mu L of serum were spiked with internal standard, extracted, derivatized with dansyl chloride, and analyzed by LC-MS/MS using 2-dimensional chromatographic separation. Total imprecision for the method was less than 11%; the limit of quantitation was 1 pg/mL. Reference intervals were established with samples from more than 900 healthy postmenopausal women, men, girls, and boys. Concentrations of estrogens in children reached adult levels by Tanner stage 3. In men and postmenopausal women, the median concentrations of total estrogens (E-1 + E-2) were 39 and 22 pg/mL, and the median E-2/E-1 ratios were 0.98 and 0.55, respectively. The method requires a small sample volume and has adequate sensitivity and specificity for analyzing estrogens in samples from postmenopausal women, men, and children.
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  • Mucchiano, Gerd I., et al. (författare)
  • Apolipoprotein A-I–Derived Amyloid in Atherosclerosis : Its Association With Plasma Levels of Apolipoprotein A-I and Cholesterol
  • 2001
  • Ingår i: American Journal of Clinical Pathology. - 0002-9173 .- 1943-7722. ; 115, s. 298-303
  • Tidskriftsartikel (refereegranskat)abstract
    • Wild-type apolipoprotein A-I (apo A-I)–derived amyloid commonly occurs in atherosclerotic plaques. To clarify apo A-I amyloid formation, plasma levels of apo A-I and cholesterol were related to the presence of amyloid in atherosclerotic plaques in 15 patients with peripheral atherosclerosis, subjected to arterial reconstruction. Plasma levels of apo A-I and high-density lipoprotein (HDL) cholesterol were slightly higher in patients with apo A-I–derived amyloid than in those without, but the difference was not significant. Levels of low-density lipoprotein cholesterol and total cholesterol were significantly higher in the group with amyloid. High concentrations of apo A-I in the arterial intima are probably of greater importance to amyloid formation than high plasma levels of the protein. During atherosclerosis, the acute phase reactant serum amyloid A may displace apo A-I from HDL, leading to increased concentration of lipid-free apo A-I in the intima and conformational changes of apo A-I, which make it more fibrillogenic. Some forms of amyloid fibrils have been shown to be cytotoxic. Apo AI–derived amyloid is possibly a pathogenically important factor in atherosclerosis.
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  • Ridell, Börje, et al. (författare)
  • Dysplastic megakaryopoiesis with thrombocytopenia and chromosomal aberration.
  • 1992
  • Ingår i: American journal of clinical pathology. - 0002-9173. ; 98:2, s. 227-30
  • Tidskriftsartikel (refereegranskat)abstract
    • A case of isolated thrombocytopenia with decreased platelet production and abnormal megakaryopoiesis is described. In the bone marrow, a chromosomally aberrant clone, 45,XX,-11,-18,+der (11;18)(11q13;18p11), was found. These findings indicate a myelodysplastic nature of the abnormal thrombocytopoiesis. The described case demonstrates the value of a bone marrow examination including histopathology with immunologic techniques to evaluate the megakaryopoiesis in thrombocytopenia and the interest of cytogenetic studies not only in instances with overt hematologic malignancies or complete myelodysplastic syndromes, but also when morphologic abnormalities occur in a single cell line.
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  • Rubio, Carlos A., et al. (författare)
  • Quantitative assessment of the subepithelial collagen band does not increase the accuracy of diagnosis of collagenous colitis
  • 2008
  • Ingår i: American Journal of Clinical Pathology. - 0002-9173 .- 1943-7722. ; 130:3, s. 375-381
  • Tidskriftsartikel (refereegranskat)abstract
    • The thickness of eosinophilic band in collagenous colitis (CC) was assessed by 3 methods: histologic estimates (22 observers), conventional measurements using a calibrated micrometric scale (1 observer), and semiautomatic micrometric measurements (1 observer). By the histologic estimate technique, 7.4% of the results failed to diagnose CC; by calibrated micrometry, the failure was 6% and by semiautomatic micrometry, 6%. The main difficulty in measuring the thickness of the CC band is that the deeper border of the band appears fuzzy and hairy-irregular. CC should be defined not exclusively on the basis of the thickness of the collagen table, but as a microscopic constellation characterized by a distorted superficial cell arrangement, with areas of epithelial denudation and inflammatory cells in the superficial epithelium and the lamina propria. In agreement with Lazenby's statement: "Focusing solely on the collagen band can result in both over- and underdiagnosis"
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  • Rusanganwa, Vincent, 1966-, et al. (författare)
  • Clinical Referral Laboratories in Rwanda : The Status of Quality Improvement After 7 Years of the SLMTA Program
  • 2018
  • Ingår i: American Journal of Clinical Pathology. - : Oxford University Press. - 0002-9173 .- 1943-7722. ; 150:3, s. 240-245
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: We investigated the quality system performance in Rwandan referral laboratories to determine their progress toward accreditation.Methods: We conducted audits across five laboratories in 2017, using the Stepwise Laboratory Quality Improvement Process Towards Accreditation checklist. Laboratories were scored based on the World Health Organization grading scale (0-5 stars scale) and compared with earlier audits.Results: Between 2012 and 2017, only one laboratory progressed (from four to five stars). Four of the five laboratories decreased to one (three laboratories) and zero (one laboratory) stars from four and three stars. Management reviews, evaluation, audits, documents, records, and identification of nonconformities showed a low performance.Conclusions: Four of five laboratories are not moving toward accreditation. However, this target is still achievable by energizing responsibilities of stakeholders and monitoring and evaluation. This would be possible because of the ability that laboratories showed in earlier audits, coupled with existing health policy that enables sustainable quality health care in Rwanda.
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  • Rusanganwa, Vincent, et al. (författare)
  • Clinical Referral Laboratory Personnel’s Perception of Challenges and Strategies for Sustaining the Laboratory Quality Management System : A Qualitative Study in Rwanda
  • 2019
  • Ingår i: American Journal of Clinical Pathology. - : Oxford University Press (OUP). - 0002-9173 .- 1943-7722. ; 152:6, s. 725-734
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To explore challenges explaining the decrease in quality performance and suggest strategies to improve and sustain laboratory quality services.Methods: Twenty key informants’ interviews from laboratory personnel were conducted in five laboratories. Four had previously shown a decrease in quality performance. Interviews were transcribed verbatim and analyzed using inductive thematic analysis.Results: Two themes emerged: (1) insufficient coordination and follow-up system towards accreditation, where lack of coordination, follow-up, and audits explained the decrease in performance; (2) inadequate resource optimization, where insufficient knowledge in Laboratory Quality Management System (LQMS), ownership by laboratory workforce, and insufficient stakeholders’ communication contributed to low-quality performance.Conclusions: The coordination, follow-up, and assessments of LQMS, in conjunction with training of laboratory workforce, would establish an institutional culture of continuous quality improvement (CQI) towards accreditation and sustainment of quality health care. To achieve CQI culture, routine gap checking and planning for improvement using a system approach is required.
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  • Strosberg, C., et al. (författare)
  • Update on Neuroendocrine Carcinomas of the Larynx
  • 2019
  • Ingår i: American Journal of Clinical Pathology. - : Oxford University Press (OUP). - 0002-9173 .- 1943-7722. ; 152:6, s. 686-700
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Laryngeal neuroendocrine carcinomas are heterogeneous neoplasms characterized by neuroendocrine differentiation. Their prognoses are dependent on tumor type, therefore different classifications have been developed. Moreover, other tumors have overlapping pathologic features posing a range of diagnostic possibilities. Methods: A review of the literature was performed to comprehensively understand the classification and diagnosis of these tumors. Results: We review the past and present classification systems, with emphasis to the latest 2017 World Health Organization Classification of Head and Neck Tumors. We highlight salient clinicopathologic features and discuss the presumptive etiologic role of human papilloma virus. We share a practical algorithmic approach to the diagnosis of suspected neuroendocrine neoplasms of the larynx including a novel marker for neuroendocrine differentiation, insulinoma-associated protein 1. Conclusions: Accurate diagnosis and grading of laryngeal neuroendocrine carcinomas is critical for prognostication and therapeutic decision making. The use of an algorithm is instrumental in assuring the exclusion of mimickers.
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  • Vidarsdottir, Halla, et al. (författare)
  • Comparison of Three Different TTF-1 Clones in Resected Primary Lung Cancer and Epithelial Pulmonary Metastase
  • 2018
  • Ingår i: American Journal of Clinical Pathology. - : Oxford University Press (OUP). - 0002-9173 .- 1943-7722. ; 150:6, s. 533-544
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Immunohistochemical staining against thyroid transcription factor 1 (TTF-1) is often used to distinguish lung adenocarcinoma from squamous cell carcinoma and pulmonary metastasis.Methods: TTF-1 expression was examined using the antibody clones 8G7G3/1, SPT24, and SP141 on tissue microarrays from 665 cases of resected lung cancers and 428 pulmonary metastases.Results: Most lung adenocarcinomas, 89%, 93%, and 93%, were positive with TTF-1 clones 8G7G3/1, SPT24, and SP141, respectively. The corresponding figures for lung squamous cell carcinomas were 0%, 6%, and 8%. In total, five (2%), 19 (7%), and 21 (8%) of the pulmonary metastases from colorectal adenocarcinomas were positive with clones 8G7G3/1, SPT24, and SP141, respectively. Other TTF-1-positive pulmonary metastases (n = 8) were thyroid, urothelial, pancreatic, small bowel, and cervix carcinomas.Conclusions: TTF-1 expression in lung cancer and pulmonary metastases differs between clones, with 8G7G3/1 being more specific but less sensitive compared with SPT24 and SP141.
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  • Xu, HT, et al. (författare)
  • Abnormal beta-catenin and reduced axin expression are associated with poor differentiation and progression in non-small cell lung cancer
  • 2006
  • Ingår i: American Journal of Clinical Pathology. - 0002-9173 .- 1943-7722. ; 125:4, s. 534-541
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the expression of axin and beta-catenin and their relation to clinicopathologic factors in 100 non-small cell lung cancers (NSCLCs) by immunohistochemical analysis. The mutation in exon 3 of the beta-catenin gene was examined by polymerase chain reaction and direct sequencing. Preserved axin expression was significantly higher in well- and moderately differentiated NSCLC samples than in poorly differentiated ones. Reduced membranous expression of beta-catenin was shown in 80 cases, whereas 26 cases had aberrant nuclear expression. Poor differentiation and lymph node metastasis were associated significantly with reduced beta-catenin expression. Lower axin expression was related significantly to higher nuclear beta-catenin expression. However, this study failed to detect any exon 3 mutation in the beta-catenin gene in the 100 NSCLC samples. We conclude that reduced beta-catenin and axin expression might predict poor differentiation in NSCLC. Reduced axin expression, but not mutation in exon 3, might be an important explanation for the abnormal beta-catenin expression in NSCLC.
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