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| 4. |
- Cepeda, D., et al.
(author)
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CDK-mediated activation of the SCFFBXO28 ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer
- 2013
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In: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 5:7, s. 999-1018
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Journal article (peer-reviewed)abstract
- SCF (Skp1/Cul1/F-box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F-box protein, FBXO28 that controls MYC-dependent transcription by non-proteolytic ubiquitylation. SCFFBXO28 activity and stability are regulated during the cell cycle by CDK1/2-mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway. Depletion of FBXO28 or overexpression of an F-box mutant unable to support MYC ubiquitylation results in an impairment of MYC-driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCFFBXO28 plays an important role in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK-FBXO28-MYC axis as a potential molecular drug target in MYC-driven cancers, including breast cancer. FBXO28 is identified as part of a SCF complex acting as a regulator of tumor cell proliferation and an important modifier of MYC function. FBXO28 may be a new prognostic factor in breast cancer and a new potential drug target in MYC- driven tumors.
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| 5. |
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| 6. |
- Hogberg, L, et al.
(author)
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The impact of active intervention on the spread of penicillin-resistant streptococcus pneumoniae in Swedish day-care centres
- 2004
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 36:9, s. 629-635
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Journal article (peer-reviewed)abstract
- Policies for handling cases of penicillin-non-susceptible Streptococcus pneumoniae (PNSP) in day-care groups vary between different counties in Sweden. The aim of this study was to evaluate the epidemiological effect of excluding PNSP-carriers from children's day-care centres (DCC). We followed the incidence in 14 DCC groups with ongoing PNSP-spread, by repeated group screens until no further cases could be identified. All identified carriers were excluded from DCC attendance in study area A (Skane region) while they remained in the group in study area B (Goteborg and Orebro), according to local policies. The intervention effect was evaluated by comparing the number of additional cases after the baseline screen (start of the intervention period) between the 2 study areas. All PNSP-isolates were characterized by resistance pattern, serotype and pulse-field gel electrophoresis. The relative risk for children in DCCs without active intervention was 6.4 (95% CI: 2.0-20.7). Each prevented case in area A can be estimated to have demanded the exclusion of 2 other children from day care for approximately 4 weeks each. The total cost-benefit outcome of this action has to be seen in the light of the local situation with regard to the population prevalence and the distribution of other risk factors.
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| 7. |
- Johansson, Henrik J., et al.
(author)
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Breast cancer quantitative proteome and proteogenomic landscape
- 2019
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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Journal article (peer-reviewed)abstract
- In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.
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| 8. |
- Lagerström, Folke, 1955-, et al.
(author)
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Microbiological etiology in clinically diagnosed community-acquired pneumonia in primary care in ╓rebro Sweden
- 2003
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In: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 9:7, s. 645-652
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Journal article (peer-reviewed)abstract
- Objective. To study the etiology of clinically diagnosed community-acquired pneumonia (CAP) in antibiotically naive patients attending a primary care center and treated at their homes. Methods. A three-year prospective study was carried out, and 177 patients presenting with clinical signs of CAP were included. All patients had chest X-rays after inclusion, and 82 (46%) showed infiltrates. Nasopharyngeal swab culture was performed on all patients, and 51% produced a representative sputum sample. Paired sera were obtained from 176 patients. Results. Among the 82 patients with radiographically proven CAP, Streptococcus pneumoniae was detected in 26 patients (32%), Haemophilus influenzae in 23 (28%), Mycoplasma pneumoniae in 15 (18%), and Chlamydia pneumoniae in four (5%). Serologic evidence of a viral infection was found in 13 patients (16%). Among the 95 patients without infiltrates, S. pneumoniae was found in 21 (22%), H. influenzae in 14 (15%), M. pneumoniae in two (2%), and C. pneumoniae in five (5%). Viral infection was detected in 19 (20%) of these 95 patients. Conclusion. In primary care in Sweden, the initial antibiotic treatment in any patient with pneumonia should be effective against S. pneumonia and H. influenzae. In addition, M. pneumoniae should be targeted during recurrent epidemics. C. pneumoniae, and especially Legionella, seem to be uncommon in primary care.
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| 9. |
- Lagerström, Folke, et al.
(author)
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Sputum specimens can be obtained from patients with community-acquired pneumonia in primary care
- 2004
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In: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 22:2, s. 83-86
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Journal article (peer-reviewed)abstract
- Objective - To improve the aetiological diagnosis in community-acquired pneumonia (CAP) increased efforts were made to obtain expectorated sputum specimens from patients with CAP. Design - A prospective, clinical study. Patients were encouraged to cough spontaneously and to expectorate a sputum specimen. If unsuccessful, they were asked to inhale nebulized hypertonic saline to induce secretion and cough. Setting - One primary health care centre in Örebro, Sweden. Subjects - Patients attending the Health Centre with acute symptoms of CAP. Main outcome measures - Availability and quality of sputum specimen from patients with CAP in primary care. Results - 177 patients were included, 63% were women and the mean age was 51years. 28% were smokers and 46% showed infiltrates on chest X-ray. Sputum specimens were obtained from 125 patients. Fifty-nine were expectorated spontaneously and 66 were induced. Ninety-one of the specimens were found to be acceptable, whereas 34 were discarded. Potential pathogens were found in 57% of the 91 specimens. Conclusion - Acceptable sputum specimens can be obtained with some effort from approximately half of the patients in primary care. Sputum culture might improve the knowledge of the bacterial aetiology of CAP in selected patients and in epidemiological studies.
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| 11. |
- Bauer, H G, et al.
(author)
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Effect of two kinds of pectin and guar gum on 1,2-dimethylhydrazine initiation of colon tumors and on fecal beta-glucuronidase activity in the rat
- 1981
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In: Cancer Research. - 0008-5472. ; 41:6, s. 23-2518
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Journal article (peer-reviewed)abstract
- The effect of 5% low-methoxylated pectin, high-methoxylated pectin, and guar gum on 1,2-dimethylhydrazine initiation of colon cancer was investigated using groups of 30 rats. The growth of the rats in the different groups was very similar to that of control group fed a fiber-free diet. Both kinds of pectin increased the multiplicity of color tumors, whereas guar gum did not significantly influence carcinogenesis. Bacterial beta-glucuronidase activity in feces and colonic content was the same in pectin-fed rats and controls but significantly lower in the guar gum group. Thus, it was not related to the number of tumors in each group.
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| 12. |
- Berglund, T, et al.
(author)
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Reemergence of gonorrhea in Sweden
- 1999
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In: Sexually transmitted diseases. - : Ovid Technologies (Wolters Kluwer Health). - 0148-5717. ; 26:7, s. 390-391
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Journal article (other academic/artistic)
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| 13. |
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| 15. |
- Fjeldsoe-Nielsen, H, et al.
(author)
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Phenotypic and genotypic characterization of prolyliminopeptidase-negative Neisseria gonorrhoeae isolates in Denmark.
- 2005
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In: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 24:4, s. 280-283
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Journal article (peer-reviewed)abstract
- In the study presented here 26 recent Danish clinical isolates of prolyliminopeptidase (PIP)-negative Neisseria gonorrhoeae were phenotypically and genotypically characterized to investigate whether one or more PIP-negative strains are circulating in the Danish community. The profiles of these isolates were compared with those of three isolates from a recent outbreak of PIP-negative N. gonorrhoeae infection in the UK. Twenty-five of the Danish isolates and all three UK isolates had similar antibiograms and were designated serovar IB-4. Genotypic characterization by pulsed-field gel electrophoresis, porB1b gene sequencing, and opa-typing revealed that these isolates were indistinguishable or closely related. The results indicate that at least one PIP-negative N. gonorrhoeae strain is currently circulating in the Danish community, and this strain is indistinguishable from the one that caused an outbreak in the UK.
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| 16. |
- Fredlund, H, et al.
(author)
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A case of diphtheria in Sweden, October 2011
- 2011
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In: Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. - 1560-7917. ; 16:50, s. 10-11
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Journal article (peer-reviewed)
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| 17. |
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| 18. |
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| 19. |
- Golparian, Daniel, 1984-, et al.
(author)
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Four treatment failures of pharyngeal gonorrhoea with ceftriaxone (500 mg) or cefotaxime (500 mg), Sweden, 2013 and 2014
- 2014
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In: Eurosurveillance. - : European Centre for Disease Prevention and Control (ECDC). - 1025-496X .- 1560-7917. ; 19:30, s. 2-5
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Journal article (peer-reviewed)abstract
- We describe four cases in Sweden of verified treatment failures of pharyngeal gonorrhoea with ceftriaxone (500 mg; n=3) or cefotaxime (500 mg; n=1) monotherapy. All the ceftriaxone treatment failures were caused by the internationally spreading multidrug-resistant gonococcal NG-MAST genogroup 1407 clone. Increased awareness of treatment failures is crucial particularly when antimicrobial monotherapy is used. Frequent test of cure and appropriate verification/falsification of suspected treatment failures, as well as implementation of recommended dual antimicrobial therapy are imperative.
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| 20. |
- Hadad, Ronza, 1984-, et al.
(author)
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GENOMIC EPIDEMIOLOGY OF NEISSERIA GONORRHOEAE ISOLATES IN SWEDEN-2016 NATIONAL STUDY
- 2021
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In: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 97:Suppl. 1, s. A135-A135
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Journal article (other academic/artistic)abstract
- Background: The number of reported cases of gonorrhoea in Sweden continuously increased from an incidence of 7.8 per 100 000 inhabitants in 2009 to 31.4 in 2019. The largest increase in incidence was observed during 2016–2017. No national molecular epidemiological study investigating the population of N. gonorrhoeae circulating in Sweden has been performed in the last two decades. Our aim was to examine the antimicrobial resistance (AMR) and genome-based epidemiology, in conjunction to patient epidemiological data, of all gonococcal isolates (n=1279; one isolate per case) from gonorrhoea cases in Sweden during 2016.Methods: AMR testing was performed using Etest, and MICs were interpreted using current clinical resistance breakpoints from EUCAST. All isolates were whole genome sequenced using Illumina HiSeq X platform. Patient epidemiological data was obtained from the Public Health Agency of Sweden.Results: The gonorrhoea patients consisted of 252 (19.7%) women and 1027 men (80.3%). The medium age of the women was 27.4 years and of the men 32.1 years. Regarding sexual orientation, 619 (48.4%) reported homosexual, 605 (47.3%) heterosexual, 31 (2.4%) bisexual, and 24 (1.9%) did not report. Most prevalent countries of infection were Sweden (n=875, 68.4%), followed by Thailand (n=70, 5.5%) and Germany (n=32, 2.5%).Overall, the phenotypic AMR was as follows: ceftriaxone and spectinomycin (0%), cefixime (1.7%), azithromycin (1.3%) and ciprofloxacin (51.1%). A high concordance between phenotypic AMR and molecular AMR determinants was found. Results from the genome-based epidemiology are currently in final analysis.Conclusions: AMR in N. gonorrhoeae in Sweden remains low, in particular to ceftriaxone and azithromycin that is recommended internationally for dual therapy. The incidence increases in Sweden appear to be driven by increased spread among men-who-have-sex-with-men but also younger heterosexuals of both genders. This is the first national genome-based epidemiological study for N. gonorrhoeae in Sweden and final genomic results are pending.
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| 21. |
- Hugosson, S, et al.
(author)
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Glycosphingolipid binding specificities of Neisseria meningitidis and Haemophilus influenzae: detection, isolation, and characterization of a binding-active glycosphingolipid from human oropharyngeal epithelium.
- 1998
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In: Journal of biochemistry. - 0021-924X. ; 124:6, s. 1138-52
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Journal article (peer-reviewed)abstract
- The glycosphingolipid binding specificities of Haemophilus influenzae and Neisseria meningitidis were investigated as to the binding of radiolabeled bacteria to glycosphingolipids on thin-layer chromatograms. Thereby, similar binding profiles, for the binding of the two bacteria to lactosylceramide, isoglobotriaosylceramide, gangliotriaosylceramide, gangliotetraosylceramide, lactotetraosylceramide, neolactotetraosylceramide, and sialylneolactohexaosylceramide, were obtained. On a closer view the binding preferences of the bacteria could be differentiated into three groups. The first specificity is recognition of lactosylceramide. The second specificity is binding to gangliotriaosylceramide and gangliotetraosylceramide, since conversion of the acetamido group of the N-acetylgalactosamine of gangliotriaosylceramide and gangliotetraosylceramide to an amine prevented the binding of the bacteria, and thus the binding to these two glycosphingolipids represents a separate specificity from lactosylceramide recognition. Preincubation of H. influenzae with neolactotetraose inhibited the binding to neolactotetraosylceramide, while the binding to lactosylceramide, gangliotetraosylceramide, or lactotetraosylceramide was unaffected. Thus, the third binding specificity is represented by neolactotetraosylceramide, and involves recognition of other neolacto series glycosphingolipids with linear N-acetyllactosamine chains, such as sialyl-neolactohexaosylceramide. The relevance of the detected binding specificities for adhesion to target cells was addressed as to the binding of the bacteria to glycosphingolipids from human granulocytes, epithelial cells of human nasopharyngeal tonsils and human plexus choroideus. Binding-active neolactotetraosylceramide was thereby detected in human granulocytes and the oropharyngeal epithelium.
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| 22. |
- Jansson, Jan-Håkan, et al.
(author)
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Snus (Swedish smokeless tobacco) use and risk of stroke: pooled analyses of incidence and survival
- 2014
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In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 276:1, s. 87-95
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Journal article (peer-reviewed)abstract
- Background. Snus is a moist smokeless tobacco product with high nicotine content. Its use has a short-term effect on the cardiovascular system, but the relationship between snus use and stroke is unclear. Objective. The aim of this study was to assess the associations between use of snus and incidence of and survival after stroke, both overall and according to subtypes. Methods. Pooled analyses of eight Swedish prospective cohort studies were conducted, including 130 485 men who never smoked. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of incidence and death after diagnosis using Cox proportional hazard regression models and case fatality and survival using logistic regression and Kaplan-Meier methods, respectively. Results. No associations were observed between the use of snus and the risk of overall stroke (HR 1.04, 95% CI 0.92-1.17) or of any of the stroke subtypes. The odds ratio (OR) of 28-day case fatality was 1.42 (95% CI 0.99-2.04) amongst users of snus who had experienced a stroke, and the HR of death during the follow-up period was 1.32 (95% CI 1.08-1.61). Conclusion. Use of snus was not associated with the risk of stroke. Hence, nicotine is unlikely to contribute importantly to the pathophysiology of stroke. However, case fatality was increased in snus users, compared with nonusers, but further studies are needed to determine any possible causal mechanisms.
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| 23. |
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| 24. |
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| 25. |
- Lucidarme, J., et al.
(author)
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An international invasive meningococcal disease outbreak due to a novel and rapidly expanding serogroup W strain, Scotland and Sweden, July to August 2015
- 2016
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In: Eurosurveillance. - Stockholm, Sweden : European Centre for Disease Prevention and Control (ECDC). - 1025-496X .- 1560-7917. ; 21:45, s. 15-23
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Journal article (peer-reviewed)abstract
- The 23rd World Scout Jamboree in 2015 took place in Japan and included over 33,000 scouts from 162 countries. Within nine days of the meeting ending, six cases of laboratory-confirmed invasive serogroup W meningococcal disease occurred among scouts and their close contacts in Scotland and Sweden. The isolates responsible were identical to one-another by routine typing and, where known (4 isolates), belonged to the ST-11 clonal complex (cc11) which is associated with large outbreaks and high case fatality rates. Recent studies have demonstrated the need for high-resolution genomic typing schemes to assign serogroup W cc11 isolates to several distinct strains circulating globally over the past two decades. Here we used such schemes to confirm that the Jamboree-associated cases constituted a genuine outbreak and that this was due to a novel and rapidly expanding strain descended from the strain that has recently expanded in South America and the United Kingdom. We also identify the genetic differences that define the novel strain including four point mutations and three putative recombination events involving the horizontal exchange of 17, six and two genes, respectively. Noteworthy outcomes of these changes were antigenic shifts and the disruption of a transcriptional regulator.
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| 26. |
- Mestdagh, Pieter, et al.
(author)
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The miR-17-92 MicroRNA Cluster Regulates Multiple Components of the TGF-beta Pathway in Neuroblastoma
- 2010
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In: Molecular Cell. - : Elsevier BV. - 1097-4164 .- 1097-2765. ; 40:5, s. 762-773
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Journal article (peer-reviewed)abstract
- The miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains elusive. Using SILAC and quantitative mass spectrometry, we examined the effects of activation of the miR-17-92 cluster on global protein expression in neuroblastoma (NB) cells. Our results reveal cooperation between individual miR-17-92 miRNAs and implicate miR-17-92 in multiple hallmarks of cancer, including proliferation and cell adhesion. Most importantly, we show that miR-17-92 is a potent inhibitor of TGF-beta signaling. By functioning both upstream and downstream of pSMAD2, miR-17-92 activation triggers downregulation of multiple key effectors along the TGF-beta signaling cascade as well as direct inhibition of TGF-beta-responsive genes.
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| 32. |
- Unemo, M, et al.
(author)
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Experiences with the new genetic variant of Chlamydia trachomatis in Orebro county, Sweden - proportion, characteristics and effective diagnostic solution in an emergent situation
- 2007
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In: Eurosurveillance. - 1560-7917 .- 1025-496X. ; 12:4
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Journal article (peer-reviewed)abstract
- A Chlamydia trachomatis variant that contains a 377 bp deletion in the cryptic plasmid was recently reported in Sweden. This deletion includes the targets for Cobas Amplicor, Cobas TaqMan48, and Abbott m2000. We examined the proportion and characteristics of this variant in Örebro county, Sweden and developed an effective diagnostic solution. In total, 2,401 consecutive C. trachomatis culture samples and 536 PCR samples from symptomatic and asymptomatic patients and screened females were included. Culture, Cobas Amplicor, and LightMix 480HT were used for diagnosis. A mutant-specific PCR, plasmid sequencing, omp1 sequencing and multilocus sequence typing (MLST) were used to identify and characterise mutants. In total, 162 (6.7%) of the cultured samples were positive for C. trachomatis. However, 61 (38%) of those were negative when using Cobas Amplicor, and 60 of these were subsequently confirmed as the new variant. 13 of these mutant isolates were further characterised genetically, and all were of identical genotype E and the unique MLST sequence type: 21, 19, 1, 2, 1. Of all culture-positive samples, 161 of 162 were positive in the LightMix 480HT assay. The single negative sample was only weakly positive in culture, and negative in all PCRs. Of the 536 PCR samples, 37 were positive in both Cobas Amplicor and LightMix 480HT, 13 were only positive in LightMix 480HT (mutants), and two were only positive in Cobas Amplicor. Mutated C. trachomatis were prevalent in Örebro county in the period from October 2006 to February 2007, and it appeared to be a single clone. LightMix 480HT seemed sensitive, specific, and enabled high throughput diagnostics. However, rare low positive samples may be false-negative. Frequent surveillance and evaluations of diagnostic methods worldwide are crucial.
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| 33. |
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