| 1. |
- Bergman, Anna Carin, et al.
(författare)
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dUTPase from the Retrovirus Equine Infectious Anemia Virus: High-Level Expression in Escherichia coli and Purification
- 1995
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Ingår i: Protein Expression and Purification. - : Elsevier BV. - 1046-5928. ; 6:3, s. 379-387
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Tidskriftsartikel (refereegranskat)abstract
- Deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase, EC 3.6.1.23) catalyzes the hydrolysis of dUTP to dUMP and pyrophosphate, and plays important roles in nucleotide metabolism and DNA replication. The dUTPase gene of the retrovirus equine infectious anemia virus (EIAV) was cloned and overexpressed in Escherichia coli using the T7 RNA polymerase expression system. The recombinant vector (pET-3a/EDU), constructed by mutagenic PCR, was transformed into E. coli BL21(DE3) pLysS cells, resulting in expression of EIAV dUTPase at about 40% of the extracted protein, This level of overproduction is very high compared to previous reports on heterologous expression of dUTPases in E. coli. A one-step purification procedure using phosphocellulose chromatography results in a homogeneous preparation of the enzyme in a yield of 45 mg liter−1 of bacterial culture. The purified EIAV dUTPase, run on a sodium dodecyl sulfate-polyacrylamide gel electrophoresis, shows an apparent molecular mass of 15.1 kDa in accordance with the gene structure. The isoelectric point (pI) was determined to 5.6. Gel filtration under nondenaturating conditions gives a retention volume corresponding to a molecular mass of 40.8 kDa, suggesting a trimeric organization of the enzyme. The amino acid composition and amino-terminal sequence of the recombinant dUTPase are in agreement with predictions from the DNA sequence.
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| 2. |
- Bergman, Peter, et al.
(författare)
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Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial
- 2021
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 74
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.
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| 3. |
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| 4. |
- Bergman, Stefan, 1959-, et al.
(författare)
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Chronic Widespread Pain in Adolescents Is Highly Associated to Stress and Anxiety
- 2015
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Ingår i: Arthritis & Rheumatology. - Hoboken, NJ : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 67:Suppl. S10
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Tidskriftsartikel (refereegranskat)abstract
- Background/Purpose: Chronic widespread pain (CWP), one of the hallmarks of fibromyalgia, is not uncommon in adolescents and it has previously been shown that adolescents with pain often become young adults with pain. CWP often co-varies with anxiety, depression, and stress symptoms in adults, but the knowledge regarding this is small in youth and young adults.The aim was to study the associations between CWP, anxiety, depression and stress in adolescents attending first year of high school.Methods: A computerized questionnaire to 296 adolescents attending Swedish high school, with validated questions regarding presence and distribution of pain (Epipain mannequin), stress symptoms (ELO question), anxiety and depression (Hospital Anxiety and Depression Scale – HADS), and health related quality of life (HRQL as measured by EQ5D). Pain was considered chronic when persistent for more than three months, and the subgroup CWP was defined according to the 1990 ACR criteria for fibromyalgia. Statistical analyses in SPSS v21 with comparison of means by Student’s t-test and proportions by chi2-test or Fischer’s exact test.Results: 257 (87%) out of 296 eligible students, mean (SD) age 16.1 (0.7) and 65.8% girls, responded to the questionnaire. Prevalence of chronic pain was 20.8% and that of the subgroup CWP was 4.7%, without any gender differences (boys 18.2% vs girls 22.2%; p=0.224, and 3.4% vs 5.4%; p=0.692). High level (4 or 5 on a 5 point scale) of stress symptoms were less common in boys (16.0% vs 28.2%; p=0.015), as was possible or probable anxiety (17.1% vs 44.4%; p<0.001), but not depression (10.3% vs 12.5%; p=0.764). Students with high level of stress reported CWP five times more often than those with less stress (30.4% vs 5.8%; p=0.001). Students with probable anxiety reported CWP ten times more often than students with no anxiety (17.6% vs 1.8%; p=0.001), and CWP was also more common, but not statistically significant, in students with probable depression (20.0% vs 3.1%; p=0.163). Those reporting CWP had significantly lower HRQL (0.58 vs 0.87; p=0.038) than students with no chronic pain.Conclusion: The high prevalence of chronic pain and the strong associations between CWP and reports of stress and anxiety in adolescents highlights that a multifactorial background to chronic pain must be considered early in life. An apparent lower score in EQ5D also indicates that the presence of CWP has an marked impact on HRQL also in adolescents.
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| 5. |
- Bergman, Anna-Carin, et al.
(författare)
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Kinetic properties and stereospecificity of the monomeric dUTPase from herpes simplex virus type 1
- 1998
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Ingår i: FEBS Letters. - 1873-3468. ; 441:2, s. 327-330
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Tidskriftsartikel (refereegranskat)abstract
- Kinetic properties of the monomeric enzyme dUTPase from herpes simplex virus type 1 (HSV) were investigated and compared to those previously determined for homotrimeric dUTPases of bacterial and retroviral origins. The HSV and Escherichia coli dUTPases are equally potent as catalysts towards the native substrate dUTP with a kcat/KM of about 107 M-1 s-1 and a KM of 0.3 μM. However, the viral enzymes are less specific than the bacterial enzyme. The HSV and E. coli dUTPases show the same stereospecificity towards the racemic substrate analogue dUTPαS (2'-deoxyuridine 5'-(α-thio)triphosphate), suggesting that they have identical reaction mechanisms.
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| 6. |
- Bergman, Anna-Carin
(författare)
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Viral dUTPases, Recombinant Expression, Purification and Characterization
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The enzyme deoxyuridine 5’-triphosphate nucleotidohydrolase (dUTPase, EC 3.6.1.23) catalyzes the hydrolysis of dUTP to dUMP and pyrophosphate. The reaction suppresses misincorporation of uracil into DNA and provides dUMP for the de novo synthesis of dTTP. dUTPase is a widespread enzyme and the fact that many viruses encode a dUTPase of their own suggests the enzyme to be important for the viral life cycle and thereby a potential target for development of new antiviral drugs. Most of the known dUTPases are homotrimers with the active sites located at the subunit interfaces. The amino acid residues, which form the active site, are conserved and clustered into five regions (motifs) of the polypeptide chain. dUTPases from the herpes virus family have 2-3 times longer polypeptide chains and display a rearranged order of the conserved motifs compared to the trimeric enzymes. dUTPase encoded by herpes simplex virus type 1 (HSV-1) has been found to be monomeric. dUTPase from the retrovirus mouse mammary tumor virus (MMTV) shows another special feature by being amino-terminally fused to the retroviral nucleocapsid protein. In this thesis, the dUTPases from HSV-1 and from the retroviruses MMTV and equine infectious anemia virus (EIAV) as well as the nucleocapsid protein from MMTV were overexpressed in E. coli by using the T7 RNA polymerase expression system. The recombinant proteins and HSV-1 dUTPase from infected Vero (green monkey kidney) cells were purified by phosphocellulose chromatography. The final yields of purified recombinant enzyme differ, from about 45 mg per liter of bacterial culture for the EIAV dUTPase to 10 mg in the case of HSV-1 dUTPase. Gel-filtration experiments suggest the two retroviral enzymes to be trimers. The specific enzyme activities range from 8 micromol/min mg for the MMTV dUTPase to 120 micromol/min mg for the EIAV enzyme. The kinetic properties of HSV-1 dUTPase were determined and compared to those of dUTPase from the bacterium Escherichia coli. The HSV-1 dUTPase shows a specificity constant (kcat/KM) of the same order of magnitude (10exp7) as the highly specific bacterial enzyme. KM for dUTP was found to be 0.3 microM and the inhibitor 2’-deoxyuridine 5’-(alpha,beta-imido)triphosphate has an inhibition constant of 0.9 microM. Experiments with racemic 2’-deoxyuridine 5’-(alpha-thio)triphosphate led to the conclusion that the catalytic mechanism involves interaction of a divalent metal ion with the alpha-phosphate of the substrate.
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| 7. |
- Bergman-Jungeström, Malin, 1967-, et al.
(författare)
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Association between CYP17 gene polymorphism and risk of breast cancer in young women
- 1999
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Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 84, s. 350-353
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Tidskriftsartikel (refereegranskat)abstract
- Long-term exposure to oestrogens is a well-recognised risk factor for breast cancer, whereas little is known about the influence of polymorphisms of genes involved in oestrogen biosynthesis and metabolism. A candidate, containing a single bp polymorphism, T→C, (designated, A2 allele), might be the CYP17 gene, which codes for an enzyme involved in oestrogen synthesis. This polymorphism creates an additional Sp1-type promoter site (CCACC box), which has been shown to be associated with increased serum oestrogen levels. We performed a case-control study, to evaluate association of the CYP17 gene polymorphism with risk of breast cancer in young women (younger than 37 years). We found a statistically significant increased risk in carriers of at least 1 A2 allele [odds ratio (OR), 2.0; 95% confidence interval (CI), 1.1–3.5, p = 0.027], and a trend toward a gene-dose effect illustrated by a slightly higher risk for A2-homozygous subjects (OR, 2.8) than for heterozygous women (OR, 1.9). Furthermore, when we investigated the CYP17 genotype in relation to tumour characteristics, breast cancer patients with 1 or 2 A2 alleles tended to have lower oestrogen receptor levels (risk ratio, 0.70; CI, 0.41–1.2, p = 0.44). Our findings suggest that CYP17 gene polymorphism influences breast carcinogenesis in young women.
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| 8. |
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Codex and Code : Aestethcis, Language and Politics in an Age of Digital Media, NORLIT 2009, Stockholm, August 6-9, 2009
- 2010
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- The conference Codex and Code: Aesthetics, Language and Politics in an Age of Digital Media (NorLit 2009)was held at the Royal Institute of Technology (KTH) in Stockholm, August 6–9, 2009. The conference was organized by the Nordic Association for Comparative Literature (NorLit); the Department of Culture and Communication, Linköping University; the School of Computer Science and Communication, Royal Institute of Technology (KTH); the Department of Comparative Literature, Stockholm University; the Department of Culture and Communication, Södertörn University College; and the Department of Comparative Literature, Uppsala University. The aim of the conference was to develop the study of Comparative Literature through Nordic collaboration both in its own discipline and in Modern Language and Cultural studies. As the title for the conference suggests, the principal question for the conference was the challenge that the study of literature encounters in an age of digitalization and globalization. It was our aim to encourage discussion of how literary studies respond to the ongoing changes in media and technology, politics and economy. Many have argued that the Humanities currently are in a state of crisis. We believe that the discipline seldom has found itself in such an interesting and fruitful historical moment. Several of these questions have surfaced during earlier media system changes, in particular during Romanticism and Modernism, which provided the conference with an historical frame. The conference Codex and Code also addressed questions of authenticity and originality, identity and gender, literary genres and reading practices, media and materiality, culture and popular culture, language and history, world literature, work aesthetics, translations, and canon formation. The conference Codex and Code wanted to stimulate interdisciplinary scholarly research of the literary in a broad sense. The conference was open to scholars in Comparative Literature and in Classical and Modern Languages, Aesthetics, Media and Communication studies, Film and Theatre studies, Philosophy and adjacent disciplines. The conference was organized around a number of thematic sessions in which researchers and scholars presented and discussed papers. The conference has received generous financial support from the Bank of Sweden Tercentenary Foundation, Magnus Bergwall foundation, Granholms foundation, Linköping University, School of Computer Science and Communication, Royal Institute of Technology, Svenska litteratursällskapet; the Swedish Academy, Swedish Science Council, and Vitterhetsakademien.
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| 9. |
- Lundin, Anna-Carin, et al.
(författare)
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Association of breast cancer progression with a vitamin D receptor gene polymorphism
- 1999
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 59:10, s. 2332-2334
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Tidskriftsartikel (refereegranskat)abstract
- The vitamin D3 receptor gene (VDR) contains a TaqI RFLP that is associated with increased VDR mRNA stability, increased serum levels of 1α,25-dihydroxyvitamin D3 (1,25-D3), and decreased risk for prostate cancer. Determination of the TaqI genotype, in a group of young women with breast cancer (n = 111; age, <37 years) and a control population (n = 130), revealed no overall association to risk for breast cancer. However, patients without TaqI site (TT genotype) showed a significantly increased risk for lymph node metastasis (relative risk, 1.8, 95% confidence interval, 1.3- 2.6). Furthermore, a tendency toward an increased survival was found among estrogen receptor-positive, tamoxifen-treated patients who were homozygous for the TaqI site (P = 0.075). We conclude that polymorphism in the VDR gene may influence tumor progression and tamoxifen treatment response in early- onset breast carcinomas.
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| 10. |
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NORLIT 2009, Codex and Code: Aestethcis, Language and Politics in an Age of Digital Media : Stockholm, August 6-9, 2009
- 2010
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Proceedings (redaktörskap) (refereegranskat)abstract
- The aim of the conference was to develop the study of Comparative Literature through Nordic collaboration both in its own discipline and in Modern Language and Cultural studies. As the title for the conference suggests, the principal question for the conference was the challenge that the study of literature encounters in an age of digitalization and globalization. It was our aim to encourage discussion of how literary studies respond to the ongoing changes in media and technology, politics and economy. Many have argued that the Humanities currently are in a state of crisis. We believe that the discipline seldom has found itself in such an interesting and fruitful historical moment. Several of these questions have surfaced duringearlier media system changes, in particular during Romanticism and Modernism, which provided the conference with an historical frame. The conference Codex and Code also addressed questions of authenticity and originality, identity and gender, literary genres and reading practices, media and materiality, culture and popular culture, language and history, world literature, work aesthetics, translations, and canon formation.
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