| 1. |
- Aaltonen, Kirsimari, et al.
(författare)
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Cyclin D1 expression is associated with poor prognostic features in estrogen receptor positive breast cancer
- 2009
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 113:1, s. 75-82
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Tidskriftsartikel (refereegranskat)abstract
- Cyclins D1 and E play an important role in breast carcinogenesis. High cyclin E expression is common in hormone receptor negative and high grade aggressive breast cancer, whereas cyclin D1 in hormone receptor positive and low grade breast cancer. Experimental data has suggested that cyclin D1 and E mediate cell proliferation by different mechanisms in estrogen receptor (ER) positive and negative breast cancer. To test this hypotheses in large breast cancer material and to clarify the histopathological correlations of cyclin E and D1, especially the association with proliferation, we analyzed cyclin E and D1 immunohistochemical expression on breast tumour microarrays consisting of 1348 invasive breast cancers. High cyclin D1 expression was associated with high grade (P < 0.0005), high cyclin A (P < 0.0005) and Ki67 (P < 0.0005) expression among ER positive but with low grade (P = 0.05) and low Ki67 (P = 0.01) expression among ER negative breast cancers. Cyclin E and D1 expression correlated positively in ER positive (P < 0.0005) but had a negative correlation in ER negative tumours (P = 0.004). Cyclin E associated with high grade among all tumours (P < 0.0005). In conclusion, the findings of this study show that cyclin D1 has separate roles, and proliferation is driven by different mechanisms in ER positive and negative breast cancers.
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| 2. |
- Abd, Hadi, et al.
(författare)
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Ante mortem diagnosis of amoebic encephalitis in a haematopoietic stem cell transplanted patient
- 2009
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 41:8, s. 619-622
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Acanthamoeba species are widely distributed free-living amoebae showing an increased role as human pathogens causing encephalitis, keratitis, pneumonitis and dermatitis. A haematopoietic stem cell transplanted (HSCT) patient developed purulent meningitis while awaiting regrafting. The meningitis was thought to be an endogenous infection arising from the mucous membranes primarily involving the cervicofacial regions, probably due to haematogenous spread facilitated by surgery. We diagnosed a fatal case of granulomatous amoebic encephalitis caused by Acanthamoeba castellanii by direct microscopy of a cerebrospinal fluid sample (CSF), Acanthamoeba cultivation, Giemsa staining, polymerase chain reaction and sequencing.
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| 3. |
- Abdel-Hamid, Mohamed, et al.
(författare)
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Genetic diversity in hepatitis C virus in Egypt and possible association with hepatocellular carcinoma
- 2007
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 88:5, s. 1526-1531
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Tidskriftsartikel (refereegranskat)abstract
- Egypt has one of the world's highest prevalences of hepatitis C virus (HCV) infection, with a majority of genotype 4 infections. To explore the genetic diversity of HCV in Egypt, sera from 131 Egyptians [56 from community studies, 37 chronic hepatitis patients, 28 hepatocellular carcinoma (HCC) patients and 10 patients with non-Hodgkin's lymphoma] were genotyped by restriction fragment-length polymorphism and phylogenetic analyses of sequences from the mid-core and non-structural 5B regions. The different genotyping methods showed good agreement. The majority of the viruses (83 of 131; 63 %) were of subtype 4a, but five other subtypes within genotype 4 were also observed, as well as three genotype 1b, five genotype 1g and one genotype 3a samples. Interestingly, subtype 4o, which was easily identifiable in all three genomic regions, 3 showed an association with HCC (P=0.017), which merits further investigation.
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| 4. |
- Abdurahman, Samir, 1965-, et al.
(författare)
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Isolation and characterization of a small antiretroviral molecule affecting HIV-1 capsid morphology
- 2009
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Ingår i: Retrovirology. - : Springer Science and Business Media LLC. - 1742-4690. ; 6, s. 34-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Formation of an HIV-1 particle with a conical core structure is a prerequisite for the subsequent infectivity of the virus particle. We have previously described that glycineamide (G-NH2) when added to the culture medium of infected cells induces non-infectious HIV-1 particles with aberrant core structures. Results: Here we demonstrate that it is not G-NH2 itself but a metabolite thereof that displays antiviral activity. We show that conversion of G-NH2 to its antiviral metabolite is catalyzed by an enzyme present in bovine and porcine but surprisingly not in human serum. Structure determination by NMR suggested that the active G-NH2 metabolite was alpha-hydroxy-glycineamide (alpha-HGA). Chemically synthesized alpha-HGA inhibited HIV-1 replication to the same degree as G-NH2, unlike a number of other synthesized analogues of G-NH2 which had no effect on HIV-1 replication. Comparisons by capillary electrophoresis and HPLC of the metabolite with the chemically synthesized alpha-HGA further confirmed that the antiviral G-NH2-metabolite indeed was alpha-HGA. Conclusion: alpha-HGA has an unusually simple structure and a novel mechanism of antiviral action. Thus, alpha-HGA could be a lead for new antiviral substances belonging to a new class of anti-HIV drugs, i.e. capsid assembly inhibitors.
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| 5. |
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| 6. |
- Abelson, Anna-Karin, et al.
(författare)
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No evidence of association between genetic variants of the PDCD1 ligands and SLE
- 2007
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:1, s. 69-74
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Tidskriftsartikel (refereegranskat)abstract
- PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.
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| 7. |
- Abraham-Nordling, Mirna, et al.
(författare)
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Incidence of hyperthyroidism in Stockholm, Sweden, 2003-2005
- 2008
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 158:6, s. 823-827
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the incidence of hyperthyroidism in Stockholm County in those patients who were diagnosed with hyperthyroidism for the First time during the years 2003-2005. Design: All new cases of hyperthyroidism >= 18 years of age were prospectively registered to calculate the total incidence of hyperthyroidism, as well as the incidence of the subgroups: Graves' disease (GD), toxic multinodular goitre and solitary toxic adenoma (STA). Eight specialized units/hospitals in Stockholm County participated in the registration. The participating physicians were all specialists in medical endocrinology. oncology, nuclear medicine or surgery. Results: Duringa 3-year period, 1431 new patients of hyperthyroidism were diagnosed in a well-defined adult population (>18 years of age) of in average 1 457 036 inhabitants. This corresponds to a mean annual incidence of hyperthyroidism of 32.7/100 000. The incidence of GD was 24.5/100 000 per year. toxic nodular goitre was 3.3/100 000 per year and STA was 4.9/100 000 per year. Conclusions: The total incidence of hyperthyroidism in Stockholm County was found to be 32.7/100 000 per year. of which 75% had GD. There were a higher percentage of smokers among the patients with hyperthyroidism compared with the overall population in Stockholm, but no difference in the frequency of smoking between patients with GD and toxic nodular goitre.
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| 8. |
- Abrahamsson, Jonas, 1954, et al.
(författare)
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Improved outcome after relapse in children with acute myeloid leukaemia.
- 2007
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Ingår i: British journal of haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 136:2, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- In the Nordic Society for Paediatric Haematology and Oncology paediatric study acute myeloid leukaemia (AML) 93, event-free survival was 50% and overall survival was 66%, indicating that many patients were cured following relapse. Factors influencing outcome in children with relapsed AML were investigated. The study included all 146 children in the Nordic countries diagnosed with AML between 1988 and 2003, who relapsed. Data on disease characteristics and relapse treatment were related to outcome. Sixty-six percentage achieved remission with survival after relapse (5 years) 34 +/- 4%. Of 122 patients who received re-induction therapy, 77% entered remission with 40 +/- 5% survival. Remission rates were similar for different re-induction regimens but fludarabine, cytarabine, granulocyte colony-stimulating factor-based therapy had low treatment-related mortality. Prognostic factors for survival were duration of first complete remission (CR1) and stem cell transplantation (SCT) in CR1. In early relapse (<1 year in CR1), survival was 21 +/- 5% compared with 48 +/- 6% in late relapse. For children receiving re-induction therapy, survival in early relapse was 29 +/- 6% and 51 +/- 6% in late. Patients treated in CR1 with SCT, autologous SCT or chemotherapy had a survival of 18 +/- 9, 5 +/- 5 and 41 +/- 5%, respectively. Survival was 62 +/- 6% in 64 children given SCT as part of their relapse therapy. A significant proportion of children with relapsed AML can be cured, even those with early relapse. Children who receive re-induction therapy, enter remission and proceed to SCT can achieve a cure rate of 60%.
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| 9. |
- Adewumi, Oluseun, et al.
(författare)
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Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
- 2007
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816
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Tidskriftsartikel (refereegranskat)abstract
- The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
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| 10. |
- Agardh, Carl-David, et al.
(författare)
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Clinical evidence for the safety of GAD65 immunomodulation in adult-onset autoimmune diabetes.
- 2005
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Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 19:4, s. 238-246
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this Phase II study was to evaluate if alum-formulated human recombinant GAD65 is safe and does not compromise beta cell function. The study was conducted as a randomized, double blind, placebo-controlled, dose-escalation clinical trial in a total of 47 Latent Autoimmune Diabetes in Adults (LADA) patients who received either placebo or 4, 20, 100, or 500 μg Diamyd subcutaneously at Weeks 1 and 4. Safety evaluations, including neurology, beta cell function tests, diabetes status assessment, hematology, biochemistry, and cellular and humoral immunological markers, were repeatedly assessed over 24 weeks. None of the patients had significant study-related adverse events (AE). Fasting c-peptide levels at 24 weeks were increased compared with placebo (P=.0015) in the 20 μg but not in the other dose groups. In addition, both fasting (P=.0081) and stimulated (P=.0236) c-peptide levels increased from baseline to 24 weeks in the 20 μg dose group. GADA log levels clearly increased (P=.0002) in response to 500 μg Diamyd. The CD4+CD25+/CD4+CD25− cell ratio increased (P=.0128) at 24 weeks in the 20 μg group. No sudden increase in HbA1c or plasma glucose or decrease in beta cell function was observed in any of the dose groups. These positive findings for clinical safety further support the clinical development of Diamyd as a therapeutic to prevent autoimmune diabetes.
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