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1.
  • Andersson, Kristin, et al. (författare)
  • Prospective study of genital human papillomaviruses and nonmelanoma skin cancer.
  • 2013
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 133:8, s. 1840-1845
  • Tidskriftsartikel (refereegranskat)abstract
    • Genital high-risk human papillomaviruses (HPVs) cause cervical cancer and are also found in a small proportion of nonmelanoma skin cancers (NMSCs). We used cancer registry linkages to follow the 856,000 serum donors included in the Southern Sweden Microbiology Biobank or the Janus Biobank in Norway, for incident skin cancers occurring up to 30 years after serum donation. Serum samples taken before diagnosis of squamous cell carcinoma (SCC) (N = 633), basal cell carcinoma (BCC) (N = 1990) or other NMSC (N = 153) and matched samples from control donors were tested for antibodies to the genital HPV types 16 and 18. Both HPV 16 and 18 were associated with increased risk for SCC [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.6 and OR 1.7, 95% CI 1.1-2.5, respectively] and other NMSC (OR 2.3, 95% CI 1.0-5.2 and OR 3.5, 95% CI 1.4-8.7, respectively), but not for BCC. Tumor blocks from HPV16 or 18 seropositive cases were tested with real-time polymerase chain reaction for presence of HPV16 or 18 DNA. No HPV18 DNA was found and only four of 79 SCC cases (two of which were from the perineum/perianal area), one of 221 BCC cases and zero of five cases with other NMSC contained HPV16 DNA. In conclusion, we found prospective evidence that HPV16 and 18 antibodies associate with SCC and other NMSC risk, but not with BCC risk. As only a small proportion of seropositive subjects had evidence of the corresponding HPV DNA in the tumor, most of this excess risk is likely to be due to confounders associated with genital HPV infection.
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2.
  • Andersson, Kristin, et al. (författare)
  • Prospective Study of Human Papillomavirus Seropositivity and Risk of Nonmelanoma Skin Cancer
  • 2012
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 175:7, s. 685-695
  • Tidskriftsartikel (refereegranskat)abstract
    • Cutaneous human papillomaviruses (HPVs) have been associated with squamous cell carcinoma (SCC) in case-control studies, but there are limited data from prospective studies assessing whether virus exposure predicts risk of future cancer development. Two major biobanks, the Southern Sweden Microbiology Biobank (1971-2003) and the Janus Biobank (1973-2003) in Norway, containing samples from 850,000 donors, were searched for incident skin cancer for up to 30 years using registry linkages. Altogether, 2,623 donors with samples taken before diagnosis of SCC or basal cell carcinoma (BCC) of the skin were identified. Prediagnostic samples and samples from 2,623 matched controls were tested for antibodies against 33 types of HPV. Baseline seropositivity to HPV types in genus beta species 2 was associated with SCC risk (odds ratio = 1.3, 95% confidence interval: 1.1, 1.7); this was also the case for samples taken more than 18 years before diagnosis (odds ratio = 1.8, 95% confidence interval: 1.1, 2.8). Type-specific persistent seropositivity entailed elevated point estimates for SCC risk for 29 HPV types and decreased point estimates for only 3 types. After multiple hypothesis adjustment, HPV 76 was significantly associated with SCC risk and HPV 9 with BCC risk. In summary, seropositivity for certain HPV types was associated with an increased risk for future development of SCC and BCC.
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3.
  • Byg, Luise M., et al. (författare)
  • NF-kappa B signalling is attenuated by the E7 protein from cutaneous human papillomaviruses
  • 2012
  • Ingår i: Virus Research. - : Elsevier BV. - 1872-7492 .- 0168-1702. ; 169:1, s. 48-53
  • Tidskriftsartikel (refereegranskat)abstract
    • The high-risk Alpha-types of human papillomavirus (HPV) are the causative agent of cervical cancer, which is the second major cause of death among women worldwide. Recent investigations have shown that E7 from the Alpha-papillomavirus HPV-16 interacts with IKK alpha and IKK beta of the IKK complex in the NF-kappa B pathway leading to an attenuation of the activity. There is a possible link between development of non-melanoma skin cancer and cutaneous Beta-papillomavirus but if these HPV types attenuate the NF-kappa B pathway is unclear. Seven different E7 proteins, representing four out of the five different species of the Beta genus (HPV-20, -37, -38, -92, -93 and -96) and one from the Gamma genus (HPV-4) were investigated for potential modulation of the NF-kappa B pathway in U2OS cells. Our results demonstrate that E7 from all the cutaneous HPV types were capable of inhibiting the NF-kappa B activity as well as E7 from HPV-16. In addition, E7 proteins from the cutaneous HPV types demonstrated interaction with IKK alpha but not with IKK beta. The deregulation of the NF-kappa B pathway by cutaneous HPVs might contribute to the pathogenesis of non-melanoma skin cancers and its precursors. (C) 2012 Elsevier B.V. All rights reserved.
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4.
  • Bzhalava, Davit, et al. (författare)
  • Deep sequencing extends the diversity of human papillomaviruses in human skin.
  • 2014
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4:Jul 24
  • Tidskriftsartikel (refereegranskat)abstract
    • Most viruses in human skin are known to be human papillomaviruses (HPVs). Previous sequencing of skin samples has identified 273 different cutaneous HPV types, including 47 previously unknown types. In the present study, we wished to extend prior studies using deeper sequencing. This deeper sequencing without prior PCR of a pool of 142 whole genome amplified skin lesions identified 23 known HPV types, 3 novel putative HPV types and 4 non-HPV viruses. The complete sequence was obtained for one of the known putative types and almost the complete sequence was obtained for one of the novel putative types. In addition, sequencing of amplimers from HPV consensus PCR of 326 skin lesions detected 385 different HPV types, including 226 previously unknown putative types. In conclusion, metagenomic deep sequencing of human skin samples identified no less than 396 different HPV types in human skin, out of which 229 putative HPV types were previously unknown.
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5.
  • Bzhalava, Davit, et al. (författare)
  • Unbiased Approach for Virus Detection in Skin Lesions
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:6
  • Tidskriftsartikel (refereegranskat)abstract
    • To assess presence of virus DNA in skin lesions, swab samples from 82 squamous cell carcinomas of the skin (SCCs), 60 actinic keratoses (AKs), paraffin-embedded biopsies from 28 SCCs and 72 kerathoacanthomas (KAs) and fresh-frozen biopsies from 92 KAs, 85 SCCs and 92 AKs were analyzed by high throughput sequencing (HTS) using 454 or Ion Torrent technology. We found total of 4,284 viral reads, out of which 4,168 were Human Papillomavirus (HPV)-related, belonging to 15 known (HPV8, HPV12, HPV20, HPV36, HPV38, HPV45, HPV57, HPV59, HPV104, HPV105, HPV107, HPV109, HPV124, HPV138, HPV147), four previously described putative (HPV 915 F 06 007 FD1, FA73, FA101, SE42) and two putatively new HPV types (SE46, SE47). SE42 was cloned, sequenced, designated as HPV155 and found to have 76% similarity to the most closely related known HPV type. In conclusion, an unbiased approach for viral DNA detection in skin tumors has found that, although some new putative HPVs were found, known HPV types constituted most of the viral DNA.
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7.
  • Darlin, Lotten, et al. (författare)
  • Vaginal self-sampling without preservative for human papillomavirus testing shows good sensitivity.
  • 2013
  • Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 56:1, s. 52-56
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Several strategies have been used to reach non-attending women in organized cervical-cancer-screening programs, with varying success. Self-sampling (SS) for HPV is effective for increasing coverage in screening programs, but requires expensive commercial sampling kits. OBJECTIVE: We aimed to evaluate if vaginal SS, without commercial preservatives was adequate for HPV testing. STUDY DESIGN: Women with abnormal cervical smears as determined from the organized screening program were invited to a colposcopy clinic. The 121 women were asked to insert a cotton swab into the vagina and rotate it, put the cotton swab into a sterile cryotube, break the upper part of the stick and put the cap on. Thereafter, the gynaecologist collected a liquid based cytology (LBC) sample. The presence of HPV-types in SS and LBC samples was analysed with PCR and luminex-based typing. RESULTS: High-risk-HPV (hr-HPV) DNA was found in 65 of the tested 108 SS (60%; 95% CI 0.50-0.69), whereas LBC found hr-HPV in 64/108 samples (59%; 95% CI 0.49-0.69). The agreement between sampling with SS and LBC was good, kappa value 0.67 (95% CI; 0.53-0.81). The sensitivity for SS with hr-HPV to find HSIL was 81% (95% CI; 67-95%), specificity 49% (95% CI; 37-60%) and the sensitivity for LBC with hr-HPV to find HSIL was 90% (95% CI 80-100%), specificity53% (95% CI; 42-65%). CONCLUSIONS: This new vaginal self-sampling method detects hr-HPV-infections with similar sensitivity as a cervical smear taken by a gynaecologist. This self-sampling method is cost-effective and well tolerated, and the kit is suitable for regular mail transport.
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8.
  • Eklund, Carina, et al. (författare)
  • Global Improvement in Genotyping of Human Papillomavirus DNA: the 2011 HPV LabNet International Proficiency Study.
  • 2014
  • Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 52:2, s. 449-459
  • Tidskriftsartikel (refereegranskat)abstract
    • Accurate and internationally comparable human papillomavirus (HPV) DNA genotyping is essential for HPV vaccine research and for HPV surveillance. The HPV Laboratory Network (LabNet) has designed international proficiency studies that can be issued regularly and in a reproducible manner. The 2011 HPV genotyping proficiency panel contained 43 coded samples composed of purified plasmids of 16 HPV types (HPV6, -11, -16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -68a, and -68b) and 3 extraction controls. Tests that detected 50 IU of HPV16 and HPV18 and 500 genome equivalents for the other 14 HPV types in both single and multiple infections were considered proficient. Ninety-six laboratories worldwide submitted 134 data sets. Twenty-five different HPV genotyping assay methods were used, including the Linear Array, line blot/INNO-LiPA, PapilloCheck, and PCR Luminex assays. The major oncogenic HPV types, HPV16 and HPV18, were proficiently detected in 97.0% (113/116) and 87.0% (103/118) of the data sets, respectively. In 2011, 51 data sets (39%) were 100% proficient for the detection of at least one HPV type, and 37 data sets (28%) were proficient for all 16 HPV types; this was an improvement over the panel results from the 2008 and 2010 studies, when <25 data sets (23% and 19% for 2008 and 2010, respectively) were fully proficient. The improvement was also evident for the 54 laboratories that had also participated in the previous proficiency studies. In conclusion, a continuing global proficiency program has documented worldwide improvement in the comparability and reliability of HPV genotyping assay performances.
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9.
  • Eklund, Carina, et al. (författare)
  • The 2010 global proficiency study of Human Papillomavirus genotyping in vaccinology.
  • 2012
  • Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 50:7, s. 2289-2298
  • Tidskriftsartikel (refereegranskat)abstract
    • Accurate and internationally comparable Human Papillomavirus (HPV) DNA genotyping is essential both for evaluation of HPV vaccines and for effective monitoring and implementation of vaccination programs. World Health Organisation (WHO) HPV Laboratory Network (LabNet) regularly issues international proficiency studies. The 2010 HPV genotyping proficiency panel for HPV vaccinology contained 43 coded samples composed of purified plasmids of sixteen HPV types (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68a and 68b) and 3 coded extraction controls. Proficient typing was defined as detection in both single and multiple infections of 50 International Units (IU) of HPV 16 and HPV 18 DNA and 500 genome equivalents (GE) for the other 14 HPV types. Ninety-eight laboratories worldwide submitted a total of 132 datasets. Twenty-four different HPV genotyping assay methods were used, with Linear Array being most commonly used. Other major assays used were Lineblot/Inno-LiPa, CLART, type-specific real-time PCR, PCR-Luminex and different microarray assays. Altogether 72 data sets were proficient for detection of more than one type, only 26 data sets proficiently detected all sixteen HPV types. The major oncogenic HPV types, 16 and 18, were proficiently detected in 95.0% (114/120) and 87.0% (94/108) of datasets, respectively. Forty-six datasets reported multiple false positive results and were considered non-proficient. A trend towards increased sensitivity of assays was seen for the 41 laboratories that participated in both 2008 and 2010. In conclusion, continued global proficiency studies will be required for establishing comparable and reliable HPV genotyping services for vaccinology worldwide.
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10.
  • Ekström, Johanna, et al. (författare)
  • Diversity of human papillomaviruses in skin lesions
  • 2013
  • Ingår i: Virology. - : Elsevier BV. - 0042-6822 .- 1096-0341. ; 447:1-2, s. 300-311
  • Tidskriftsartikel (refereegranskat)abstract
    • Pools of frozen biopsies from patients with squamous cell carcinoma (SCC) (n=29) actinic keratosis (AK) (n=31), keratoacanthoma (n=91) and swab samples from 84 SCCs and 91 AKs were analysed with an extended HPV general primer PCR and high-throughput sequencing of amplimers. We found 273 different HPV isolates (87 known HPV types, 139 previously known HPV sequences (putative types) and 47 sequences from novel putative HPV types). Among the new sequences, five clustered in genus Betapapillomavirus and 42 in genus Gammapapillomavirus. Resequencing of the three pools between 21 to 70 times resulted in the detection of 283 different known or putative HPV types, with 156 different sequences found in only one of the pools. Type-specific PCRs for 37 putative types from an additional 296 patients found only two of these putative types. In conclusion, skin lesions contain a large diversity of HPV types, but most appeared to be rare infections. (C) 2013 Elsevier Inc. All rights reserved.
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11.
  • Ekström, Johanna, et al. (författare)
  • High throughput sequencing reveals diversity of human papillomaviruses in cutaneous lesions.
  • 2011
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 129, s. 2643-2650
  • Tidskriftsartikel (refereegranskat)abstract
    • There are at least 120 completely characterized human papillomavirus (HPV) types and putative new types are continuously found. Both squamous cell carcinoma of the skin (SCC) and other skin lesions commonly contain multiple cutaneous HPV types. The objective of this study was to achieve an improved resolution of the diversity of HPV types in lesions such as SCCs, actinic keratoses (AKs) and keratoacanthomas (KAs). Fresh frozen biopsies from 37 SCC lesions, 36 AK lesions and 92 KA lesions and swab samples from the top of the lesion from 86 SCCs and 92 AKs were amplified using the general HPV primers FAP and mixed to three pools followed by high throughput sequencing. We obtained 2196 reads with homology to HPV. In the pool of SCC/AK biopsies 48 different HPV types were found. Eighty-three types were found in the pool of SCC/AK swab samples and 64 types in the KA biopsies, respectively. For 9 novel putative HPV types most of the amplimer sequence was obtained, whereas for an additional 35 novel putative HPV types only partial amplimer sequences were obtained. Most of the novel putative types belonged to the genus Gamma. In conclusion, high throughput sequencing was an effective means to identify both known and previously unknown HPV types in putatively HPV-associated lesions and has revealed an extended diversity of HPV types.
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12.
  • Ekström, Johanna, et al. (författare)
  • Three novel papillomaviruses (HPV109, HPV112 and HPV114) and their presence in cutaneous and mucosal samples.
  • 2010
  • Ingår i: Virology. - : Elsevier BV. - 1096-0341 .- 0042-6822. ; 397, s. 331-336
  • Tidskriftsartikel (refereegranskat)abstract
    • To expand our knowledge of the genomic diversity of human papillomaviruses (HPVs), we searched for new HPVs in squamous cell carcinomas of the skin (SCC) and seemingly HPV-negative, otherwise typically HPV-associated lesions. We describe the characterization of three novel HPV types. HPV109 was isolated from an SCC, HPV112 from a condyloma and HPV114 from a low-grade cervical lesion. Pairwise alignment of the L1 sequences classified HPV114 to genus alpha species 3, whereas HPV112 defined a new species in the genus gamma. HPV109 had uncertain classification because of a low and about equal similarity in the L1 gene (between 60% and 65%) to different genera. Type-specific real-time PCRs of cervical samples, a majority from women with low grade atypical cytology, (n=2856) and various cutaneous samples (n=538), found HPV114 in 1.7% (48/2856) of the genital samples, whereas both HPV109 and 112 were rare viruses found at high viral loads only in their index samples.
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13.
  • Faust, Helena, et al. (författare)
  • Pseudovirion-binding and neutralizing antibodies to cutaneous Human Papillomaviruses correlated to presence of HPV DNA in skin.
  • 2013
  • Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 94, s. 1096-1103
  • Tidskriftsartikel (refereegranskat)abstract
    • We compared seroreactivity to Human papillomavirus (HPV) antigens measured with two different high-throughput assays. One method used GST-L1 fusion proteins and the other heparin-bound HPV pseudovirions as antigens and both methods used multiplexed fluorescent beads for detection. For six HPV types (5, 6, 15, 16, 32 and 38), seroreactivity could be measured in parallel for 434 serum samples from non-immunosuppressed patients with skin lesions (squamous cell carcinoma of the skin, basal cell carcinoma of the skin, actinic keratosis and benign skin lesions). Biopsies from the skin lesions were tested for presence of HPV DNA using three different PCR methods, with typing by sequencing. Among the types included in the serological tests, HPV DNA of types HPV5, 15, 38 and 76 were most frequently detected in the tumours. Serum samples from subjects with HPV DNA positive biopsies and randomly selected serum samples from subjects with HPV DNA negative biopsies were also tested with neutralization assays with HPV5, 38 and 76 pseudovirions. Agreement of the three serological methods varied from poor to moderate and showed limited consistency. Type-specific seroprevalences among patients positive for the same type of HPV DNA (sensitivity of serology) was improved with the pseudovirion-based method (average of 40%, maximum 63%) compared to the GST-L1 method (average of 20%, maximum of 25%). Neutralization was the most sensitive assay for HPV38 (50%). In summary, the pseudovirion-based methods appeared to have an improved sensitivity.
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14.
  • Faust, Helena, et al. (författare)
  • Validation of multiplexed human papillomavirus serology using pseudovirions bound to heparin coated beads.
  • 2010
  • Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 91, s. 1840-1848
  • Tidskriftsartikel (refereegranskat)abstract
    • We developed and validated a high-throughput human papillomavirus (HPV) serology method based on Luminex technology, using pseudovirions (PsVs) of eight mucosal HPV types (HPV 6, 11, 16, 18, 31, 45, 52 and 58) and two cutaneous HPV types (HPV 5 and 38) bound to heparin coated beads. Analysis with neutralising type-specific monoclonal antibodies against included HPV types indicated type-specificity of the assay. Analysis of negative control serum samples from 63 children and 71 middle-aged women with up to one lifetime sexual partner indicated high specificity. Positive control serum samples from subjects with known HPV DNA status or clinical diagnosis found expected sensitivities for most of the HPV types in 219 European serum samples, but less than expected in 124 samples from Africa. HPV 45 and 52 did not react as expected with the human serum samples. The Pseudovirion-Luminex method was used to determine the HPV-seropositivity-associated relative risk for future cervical cancer using 208 serum samples from a prospective study of 18814 women followed for 23 years, previously analysed with standard HPV 16 ELISA. The Pseudovirion-Luminex method gave similar results as ELISA (Kappa= 0.77). As expected, HPV seropositivities assayed using the Pseudovirion-Luminex method found increased risk for cervical cancer for HPV 16 (OR=7.7, CI 95%=2.6-23) and HPV 31(OR=4.1, CI 95%=1.6-10.8), non-significant tendencies for increased risk for other mucosal HPV types and no risk for the cutaneous HPV types. In summary, multiplexed HPV serology using mammalian-derived pseudovirions selected for native conformation by binding to heparin-coated beads is validated as a high-throughput HPV serological method, for most of the analysed HPV types.
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15.
  • Forslund, Anders, 1982, et al. (författare)
  • MULTIDISCIPLINARY ROBUSTNESS EVALUATIONS OF AERO ENGINE STRUCTURES
  • 2011
  • Ingår i: XX International Symposium on Air Breathing Engines 2011 (ISABE 2011), Proceedings of a meeting held 12-16 September 2011, Gothenburg, Sweden.
  • Konferensbidrag (refereegranskat)abstract
    • This paper presents a case study made to investigate the functional robustness of a jet engine turbine frame. Using virtual tools, a multidisciplinary analysis involving eight disciplines is performed on 50 non-nominal geometries. These geometries are obtained by varying the positions of the locators in the locating schemes on some parts of the assembly. Results show that geometrical variation can significantly affect the structural stresses on the product, and should thus be investigated further.
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16.
  • Forslund, Ola, et al. (författare)
  • Regarding human cytomegalovirus in neuroblastoma.
  • 2014
  • Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 3:4, s. 1038-1040
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Wolmer-Solberg et al., reported that six human neuroblastoma cell lines and the vast majority of clinical neuroblastoma samples contained HCMV DNA and expressed HCMV proteins. We could not replicate the data and therefore remain skeptical towards the prevalence of HCMV DNA in neuroblastomas.
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17.
  • Forslund, Ola, et al. (författare)
  • The nasal mucosa contains a large diversity of human papillomavirus from the Beta- and Gammapapillomavirus genera.
  • 2013
  • Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 208:8, s. 1335-1341
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Human papillomavirus (HPV) types from the Beta- and Gammapapillomavirus genera are common at cutaneous sites. The aim of this study was to analyze the prevalence of these HPV types in oral and nasal samples.Methods. Nasal and oral samples were taken from 312 volunteers of Danish health-care staff (240 women and 72 males, with mean age of 42 years). Of these 311 oral and 304 nasal samples were eligible for HPV DNA analysis.HPV types were detected by the use of PCR with MGP- and FAP-primers and identified by Luminex (MGP), and direct sequencing or cloning prior to sequencing (FAP).Results. HPV DNA was detected in 6% of the oral samples and 50% of the nasal samples. A large diversity of 75 HPV types/putative HPV types was identified. HPV types within genus Alpha-, Beta- and Gammapapillomaviruses were detected in 3%, 31%, and 23% of the nasal samples, respectively. A putative subtype of HPV76, originally isolated from a feline oral SCC, was detected in seven nasal samples.Conclusion. A large spectrum of HPV types from Beta- and Gammapapillomavirus have tropism for the nasal mucosa. The implication of the relatively high prevalence of these viruses in the nasal mucosa is unknown.
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18.
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19.
  • Johansson, Hanna K, et al. (författare)
  • Characterization of human papillomavirus subtype 72b.
  • 2014
  • Ingår i: Genome Announcements. - 2169-8287. ; 2:6
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the characterization of human papillomavirus (HPV) subtype 72b of the genus Alphapapillomavirus isolated from an oral rinse sample of a healthy woman. The HPV72b L1 open reading frame (ORF) was 90.2% identical to that of HPV72, indicating a subtype close to the border of a novel HPV type.
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22.
  • Kofoed, Kristian, et al. (författare)
  • Prevalence of Human Papillomavirus in Anal and Oral Sites Among Patients with Genital Warts
  • 2014
  • Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 94:2, s. 207-211
  • Tidskriftsartikel (refereegranskat)abstract
    • Genital warts are caused by human papillomavirus (HPV). HPV is a leading cause of anogenital malignancies and a role of HPV in the aetiology of oro-pharyngeal cancers has been demonstrated. The frequency of oral HPV infection in patients with genital warts and the association between concomitant genital, anal and oral infection is unclear. A total of 201 men and women with genital wart-like lesions were recruited. Swab samples were obtained from the genital warts and the anal canal and an oral rinse was collected. Anal HPV was found in 46.2% and oral HPV in 10.4% of the participants. Concordance between anal and genital wart HPV types was 78.1%, while concordance between oral and genital wart types was 60.9%. A lower concordance of 21.7% was observed between anal and oral HPV types. Significantly more women than men had multiple HPV types and anal HPV. In conclusion, extra genital HPV is common in patients with genital warts. A gender inequality seems to exist.
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23.
  • Leinonen, M. K., et al. (författare)
  • Type- and age-specific distribution of human papillomavirus in women attending cervical cancer screening in Finland
  • 2013
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 109:11, s. 2941-2950
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Large-scale data on type-specific HPV prevalences and disease burden are needed to monitor the impact of HPV vaccination and to plan for HPV-based cervical screening. Methods: 33 043 women (aged 25-65) were screened for HPV by a Hybrid Capture 2 (HC2) in a population-based programme. HPV-positive women (n = 2574) were triaged by cytology and HPV genotyped using PCR-Luminex. Type-specific prevalence of HPV infection and its correlation to findings in cytology triage and histology as well as Population Attributable Fractions for a referral to colposcopy and findings in histology were calculated. Results: Among HC2-positive women, 61.5% had normal, 23.1% had ASC-US and 15.5% had LSIL or more severe (LSIL+) results in cytology. Out of HC2-positive samples, 57% contained the 13 Group 1/2A HPV types, which were targeted by the HC2, 15% contained Group 2B types, 8.5% Group 3 types and 30% were found to be negative in HPV genotyping. The proportion of samples positive for HPV by the HC2, but negative in HPV genotyping increased with age and decreased with increasing cytological abnormality. The most frequent types were HPV 16 (0.9% of screened women and 12.1% of the HC2-positive women), HPV 31 (0.7% and 8.9%, respectively) and HPV 52 (0.5% and 6.3%, respectively). The prevalence of Group 1/2A HPV types increased with increasing CIN grade and attributed 78.3% (95% CI 53.4-89.9) of the CIN 3+ lesions, while HPV 16 attributed 55.8% (40.0-67.5) of them. Conclusion: The type-specific prevalence of HPV were slightly lower than the average in international meta-analyses. Genotyping for HPV 16 better identified women with CIN 3+ than cytology triage at the threshold of LSIL+. The high proportion of women that were HC2-positive but HPV-negative in genotyping suggests that HPV genotyping may be useful also for validation of results in HPV screening. The large-scale HPV genotyping data were found to be directly useful for planning further preventive efforts for cervical cancer.
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24.
  • Li, Jian, et al. (författare)
  • Array Comparative Genomic Hybridization of Keratoacanthomas and Squamous Cell Carcinomas: Different Patterns of Genetic Aberrations Suggest Two Distinct Entities
  • 2012
  • Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 132:8, s. 2060-2066
  • Tidskriftsartikel (refereegranskat)abstract
    • Keratoacanthoma (KA) is a benign keratinocytic neoplasm that spontaneously regresses after 3-6 months and shares features with squamous cell carcinomas (SCCs). Furthermore, there are reports of KAs that have metastasized, invoking the question of whether KA is a variant of SCC (Hodak et al., 1993). To date, no reported criteria are sensitive enough to discriminate reliably between KA and SCC, and consequently there is a clinical need for discriminating markers. Our previous study analyzed 132 KAs and 29 SCCs and revealed significantly different regions of genomic aberrations using chromosomal comparative genomic hybridization (CGH). In the present study, we applied array CGH to investigate 98 KAs and 22 SCCs from the above samples. The result shows that all KAs and SCCs have some degree of genetic aberrations. The distribution of numbers of aberrant clones per sample differed significantly between KAs and SCCs (P<0.02), which also demonstrated recurrent aberrations that differed significantly (P<0.001), as illustrated by unsupervised cluster analysis. Classifiers for clinicopathological parameters of KAs were established based on t-test statistics and permutation tests. Tumor size, fibrosis, and inflammation, which are related to the developmental stages of KAs, showed significant (t-test, permutation test) associations with aberrations of selected genomic regions. This suggests chromosomal instability during the whole life cycle of KAs.
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25.
  • Michael, K. M., et al. (författare)
  • Bead-Based Multiplex Genotyping of 58 Cutaneous Human Papillomavirus Types
  • 2011
  • Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 49:10, s. 3560-3567
  • Tidskriftsartikel (refereegranskat)abstract
    • Cutaneous human papillomaviruses (HPVs) are a heterogeneous, nonmonophyletic assembly, comprising about 50 characterized types and at least 133 isolates putatively representing new types. Their natural history of infection and potential association with nonmelanoma skin cancer are not well understood. Several PCR systems have been developed that amplify a broad spectrum of cutaneous HPVs. However, amplicon genotyping by sequencing or reverse line blot assays are complex and not well suited for high-throughput analyses. We developed a novel multiplex cutaneous papillomavirus genotyping (McPG) assay for 38 defined and 20 putative cutaneous HPVs of the beta, gamma, mu, and nu genera. Viral DNA was amplified by the use of a modified single-tube nested "hanging-droplet" FAP PCR. The amplifiable papillomavirus (PV) spectrum was enlarged by the use of 9 outer and 13 inner primers. Biotinylated PCR products were hybridized to type-specific oligonucleotide probes coupled to fluorescence-labeled polystyrene beads and analyzed using Luminex technology. Analytical sensitivity was analyzed for 38 defined HPVs and was <= 100 genome copies for all types. Integrated beta-globin primers allow for simultaneous DNA quality control. McPG is characterized by high reproducibility (kappa = 0.84, 95% confidence interval = 0.79 to 0.88), good concordance with the original nested FAP PCR, followed by sequencing (70.2% complete or partial agreement) when 322 skin biopsy DNA samples were analyzed, and improved ability to detect multiple infections (on average 2.5 HPV types per HPV-positive sample compared to 1.7 HPV types with nested FAP-PCR). In conclusion, McPG is a powerful tool for genotyping multiple cutaneous HPVs in a high-throughput format and is thus suitable for large-scale epidemiological studies.
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26.
  • Nordén, Johanna, et al. (författare)
  • Nutrition impact symptoms and body composition in patients with COPD
  • 2014
  • Konferensbidrag (refereegranskat)abstract
    • RATIONALE: Anorexia or lack of appetite is common in chronic obstructive pulmonary disease (COPD) and may be caused or augmented by several symptoms affecting appetite and eating. We aimed to investigate and quantify the extent of nutrition impact symptoms (NIS) in patients with COPD and to explore relationships between NIS and fat free mass depletion.METHODS: The results in this cross-sectional study are based on 169 COPD patients (62 % females). Body composition was assessed using bioelectrical impedance spectroscopy and the patients reported NIS by two newly developed questionnaires; Eating Symptoms Questionnaire (ESQ) and Disease Related Appetite Questionnaire (DRAQ).RESULTS: Symptoms with the highest prevalence were dry mouth (71%), stomach ache (39%), pain or aches affecting appetite (36%) and constipation (35%). Problems with diarrhoea and feeling affected by smells were more severe among women compared to men (p<0.05). Thirty-six percent of the patients were depleted (FFMI < 15 kg/m² for women and FFMI < 16 kg/m² for men). Depleted patients had more NIS (p<0.05), and also rated appetite and taste of food as worse compared to non-depleted (p < 0.05).CONCLUSION: Nutrition impact symptoms are common in patients with COPD and depleted patients have more severe symptoms. To investigate how these symptoms are best prevented and/or managed and if NIS prevention/treatment can affect development of malnutrition in patients with COPD is a challenge for the future.
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27.
  • Sehic, Daniel, et al. (författare)
  • Absence of Epstein-Barr and Cytomegalovirus Infection in Neuroblastoma Cells by Standard Detection Methodologies.
  • 2013
  • Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 60:9, s. 91-93
  • Tidskriftsartikel (refereegranskat)abstract
    • Indications exist in the scientific literature that infection with human herpes family viruses may contribute to the pathogenesis of neuroblastoma (NB). However, systematic investigations regarding viral presence in NB cells have been scarcely reported. Here, the presence of DNA from Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) was assessed by PCR in 12 NBs, supplemented with RNA in situ hybridization, immunohistochemical detection, and high-throughput DNA sequencing. These standard methods did not detect infection by EBV or HCMV in NB cells in any tumor, while occasional immune cells were positive for EBV RNA or HCMV protein in four cases. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
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28.
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29.
  • Ure, Agustin, et al. (författare)
  • Characterization of the complete genomes of Camelus dromedarius papillomavirus types 1 and 2
  • 2011
  • Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 92:8, s. 1769-1777
  • Tidskriftsartikel (refereegranskat)abstract
    • Camel papillomatosis has been described previously, but the genome of the suspected papillomavirus (PV) has not been identified. An outbreak of papillomatosis occurred in a dromedary farm of 55 animals in Sudan during August 2009. The disease was only present in young animals aged about 3-7 months, of which 44% (11/25) were affected with lesions, mainly on the lips and lower jaw. This study reports for the first time the complete genomes of Camelus dromedarius papillomavirus types 1 (CdPV1) and 2 (CdPV2), isolated from a cauliflower-like nodule and a round oval raised nodule, respectively. Pairwise comparisons of their L1 nucleotide sequences revealed 69.2% identity, and phylogenetic analyses suggested that these two PV types are grouped within the genus Deltapapillomavirus. Both viruses were isolated from fibropapillomas, although no putative E5 proteins homologous to that of bovine papillomavirus type 1 were identified. The genetic information will be useful for evolutionary studies of the family Papillomaviridae, as well as for the development of diagnostic methods for surveillance of the disease in dromedaries.
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30.
  • Ure, Agustín Enrique, et al. (författare)
  • Characterization of human papillomavirus type 154 and tissue tropism of gammapapillomaviruses.
  • 2014
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The novel human papillomavirus type 154 (HPV154) was characterized from a wart on the crena ani of a three-year-old boy. It was previously designated as the putative HPV type FADI3 by sequencing of a subgenomic FAP amplicon. We obtained the complete genome by combined methods including rolling circle amplification (RCA), genome walking through an adapted method for detection of integrated papillomavirus sequences by ligation-mediated PCR (DIPS-PCR), long-range PCR, and finally by cloning of four overlapping amplicons. Phylogenetically, the HPV154 genome clustered together with members of the proposed species Gammapapillomavirus 11, and demonstrated the highest identity in L1 to HPV136 (68.6%). The HPV154 was detected in 3% (2/62) of forehead skin swabs from healthy children. In addition, the different detection sites of 62 gammapapillomaviruses were summarized in order to analyze their tissue tropism. Several of these HPV types have been detected from multiple sources such as skin, oral, nasal, and genital sites, suggesting that the gammapapillomaviruses are generalists with a broader tissue tropism than previously appreciated. The study expands current knowledge concerning genetic diversity and tropism among HPV types in the rapidly growing gammapapillomavirus genus.
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31.
  • Ure, Agustin, et al. (författare)
  • Lack of Methylation in the Upstream Region of Human Papillomavirus Type 6 from Aerodigestive Tract Papillomas
  • 2012
  • Ingår i: Journal of Virology. - 1098-5514. ; 86:24, s. 13790-13794
  • Tidskriftsartikel (refereegranskat)abstract
    • Methylation of the high-risk human papillomavirus type 16 (HPV16) upstream regulatory region (URR) has been described, but whether methylation is present among low-risk HPVs is unknown. The methylation status of the HPV6 URR was analyzed in papillomas from the upper aerodigestive tract of six adult patients. All CpGs in the URR were unmethylated, from both basal/intermediate and superficial cells, suggesting that methylation is not involved in the regulation of transcription from the HPV6 URR, regardless of epithelial differentiation.
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32.
  • Wagersten, Ola S, 1976, et al. (författare)
  • Robust Design and Quality Assurance
  • 2011
  • Ingår i: Entering the Tiger's Cave - Perspectives on Japanese and Swedisch Product Development. Dag Bergsjö (Ed.). ; , s. 37-44
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Robust design aims at reducing the effects of variation on a design, without eliminating the variation itself. It is a method of improving product quality with little or no additional manufacturing costs.Robust design methodology was pioneered by Japanese statistician Genichi Taguchi in the 1960s. His work is believed to have had a large influence on Japanese engineering tradition, and he is credited with playing a part in the Japanese industrial boom of the 1970s and 1980s. Today, robust design methodology is employed in companies all over the world, and extensive research has been conducted on the subject.
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