Institutt for medisinsk biologi

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Institutt for medisinsk biologi

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• Artikler, rapporter og annet (medisinsk biologi) [230]
• Mastergradsoppgaver i biologi (Helsefak) [22]
• Mastergradsoppgaver i medisinske laboratoriefag [0]
• Mastergradsoppgaver i molekylær bioteknologi [6]

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• Partial characterization of predicted ABCC5 inhibitors by the aid of human erythrocyte inside-out vesicles

  Ørvoll, Elin (Master thesis; Mastergradsoppgave, 24-Jun-2011)

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  Abstract:

  ABCC5 is a member of the superfamily of ABC-transporters, and it has been identified as an efflux transporter of cGMP. This transporter is also involved in export of antibiotic and cytostatic drugs from target cells, and as such represents a challenge in treatment of cancer and infectious diseases. In order to find inhibitors to ABCC5 mediated drug efflux, compounds predicted as potent inhibitors by virtual ligand screening (VLS) were chosen for in-vitro studies by the use of human erythrocyte inside-out vesicles (IOV). The procedure for IOV preparation was improved, and transport assays were performed where the inhibiting effects of the various compounds on transport of cGMP into inside-out vesicles were measured. Several of these compounds showed a potent inhibiting effect on cGMP transport, and the few that were chosen for further characterization showed more potent inhibition of ABCC5 than the known ABCC5 and PDE5 inhibitor sildenafil.

  URI:

  http://hdl.handle.net/10037/5137

  File(s) in this item: 1

  thesis.pdf   (2.443Mb)
• HPV mRNA testing in triage of women with ASC-US cytology may reduce the time for CIN2+ diagnosis compared with repeat cytology.

  Sørbye, Sveinung Wergeland; Fismen, Silje; Gutteberg, Tore Jarl; Mortensen, Elin Synnøve; Skjeldestad, Finn Egil (Journal article; Tidsskriftartikkel; Peer reviewed, 2013)

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  Abstract:

  Background: In delayed HPV triage women with atypical squamous cells of uncertain significance (ASC-US) cytology are retested after 6-12 months in order to decide whether they should be referred for colposcopy, further follow-up cytology or routine screening in three years. Triage using a specific HPV E6/E7 mRNA test may reduce referrals for colposcopy of women with ASC-US cytology compared to HPV DNA testing. We explored whether HPV mRNA triaging could reduce the time from ASC-US index cytology to biopsy compared with repeat cytology, and whether the positive predictive value (PPV) of the HPV mRNA test for high grade cervical intraepithelial neoplasia (CIN2+) was comparable with the PPV of repeat cytology. Material and methods: We used repeat cytology and the HPV mRNA test PreTect HPV-Proofer, which detects E6/E7 mRNA from HPV subtypes 16, 18, 31, 33 and 45, in the triage of women with ASC-US. We included all women from the two northernmost counties of Norway with a first ASC-US cytology during the period 2004-2008. Two triage methods were evaluated 1) only repeat cytology (n=964) and 2) both HPV mRNA testing and cytology (n=542). Histologically confirmed CIN2+ was the study endpoint. Results: Among 1506 women with an ASC-US index cytology, 59 women (3.9%) had biopsy taken, of whom 49 women had CIN2+ (PPV 83.1%). The mean time from index ASC-US cytology until the case was resolved (biopsy or return to screening) was 10.6 months in the repeat cytology group and 7.3 months in the HPV group (P<0.001). Of the 964 women in the group with repeat cytology only, 35 women (3.6%) had biopsy and 30 had CIN2+ (PPV 85.7%). Of the 542 women in the group with both HPV test and cytology, 24 women (4.4%) had biopsy and 19 had CIN2+ (PPV 79.2%). Conclusion: In triage of women with ASC-US, the HPV mRNA test significantly reduced the time from the first abnormal cytology until biopsy and had predictive values comparable with those of repeat cytology.

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  http://hdl.handle.net/10037/5132

  File(s) in this item: 1

  article.pdf   (140.8Kb)
• Symptoms of respiratory tract infection and associated care-seeking in subjects with and without obstructive lung disease; The Tromso Study: Tromso 6.

  Melbye, Hasse; Joensen, Lisa; Risør, Mette Bech; Halvorsen, Peder Andreas (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)

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  Abstract:

  Respiratory tract infections (RTIs) may be more severe in those with asthma or COPD and these patients are more frequently in need of health care. The aim of the study was to describe the frequency of RTI symptoms in a general adult population and how care-seeking is associated with the presence of obstructive lung disease. Cross-sectional data including spirometry and self-reported chronic diseases were collected among middle-aged and elderly subjects in the Tromso population survey (Tromso 6). Self- reported RTI symptoms, consultations and antibiotic use were the main outcome variables. Possible predictors of RTI symptoms were evaluated by multivariable logistic regression. Of the 6414 subjects included, 798 (12.4 %) reported RTI symptoms in the previous week. RTI symptoms were reported less frequently by subjects aged 75 years or above, than by those younger than 55 years (OR 0.5). Winter season (OR 1.28), current smoking (OR 1.60), low self-rated health (OR 1.26) and moderate to severe bronchial obstruction (OR 1.51), were also statistically significant independent predictors of RTI symptoms, but these variables did not predict RTI symptoms that had started within the previous seven days. Among subjects with RTI symptoms, 5.1 % also reported a consultation with a doctor. In those with bronchial obstruction by spirometry, who did not report asthma or COPD, this frequency was 2.4 %. Antibiotic treatment was reported by 7.4 % of the participants, among whom one third had consulted a doctor. Antibiotics were taken more frequently when asthma or COPD was reported (13.7 %), but not in subjects with bronchial obstruction who did not report these diseases (7.2 %). RTI symptoms seldom led to consultation with a doctor and not even in subjects with obstructive lung disease. This was in particular the case in subject who did not know about their obstructive lung disease. Strategies for early diagnosis of COPD and providing health care to subjects with such disease cannot rely on their doctor visits due to respiratory symptoms.

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  http://hdl.handle.net/10037/5122

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  article.pdf   (178.0Kb)
• Prognostic impact of Skp2, ER and PGR in male and female patients with soft tissue sarcomas

  Sørbye, Sveinung Wergeland; Kilvær, Thomas Karsten; Valkov, Andrey Yurjevich; Dønnem, Tom; Smeland, Eivind; Al-Shabli, Khalid; Bremnes, Roy M.; Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2013)

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  Abstract:

  BACKGROUND: S-phase kinase-associated protein 2 (Skp2) is a member of mammalian F-box proteins. The purpose of this study is to clarify the prognostic significance of expression of Skp2 related to gender, estrogen receptor (ER) and progesterone receptor (PGR) in soft tissue sarcomas (STS). Optimized treatment of STS requires better identification of high-risk patients who will benefit from adjuvant therapy. Skp2 has been demonstrated to display an oncogenic function since its overexpression has been observed in many human cancers. The prognostic significance of Skp2 related to ER and PGR in STS has not been sufficiently investigated. METHODS: Tissue microarrays from 193 STS patients were constructed from duplicate cores of viable and representative neoplastic tumor areas. Immunohistochemistry was used to evaluate the expression of Skp2, ER and PGR. RESULTS: In univariate analyses, high tumor expression of Skp2 correlated (p = 0.050) with reduced disease-specific survival (DSS). In subgroup analyses expression of PGR in males (p = 0.010) and in patients older than 60 years (p = 0.043) were negative prognostic factors for DSS. Expression of ER in females was a positive prognostic factor for DSS (p = 0.041). In co-expression analyses in the whole cohort, low expression of Skp2 in combination with low expression of ER was positive for DSS (p = 0.049). In females high expression of Skp2 in combination with low expression of ER was a negative prognosticator (p = 0.021). In the multivariate analyses, age (p = 0.012), malignancy grade (p < 0.001), wide resection margins (P = 0.010), ER negative / PGR positive co-expression profile (p = 0.002) and ER positive / PGR negative co-expression profile (p = 0.015) were independent negative prognostic factors for DSS. In females expression of Skp2 (p = 0.006) was associated with shorter DSS. CONCLUSIONS: We found diverse prognostic impacts of expression of Skp2, ER, PGR and DSS in male and female patients with STS. In men, but not women, ER positive / PGR negative co-expression profile was an independent negative prognostic factor for DSS. In women, but not men, high expression of Skp2 was associated with reduced DSS.

  URI:

  http://hdl.handle.net/10037/5049

  File(s) in this item: 1

  article.pdf   (1.325Mb)
• Cohort profile: The Tromsø Study

  Jacobsen, Bjarne K.; Eggen, Anne Elise; Mathiesen, Ellisiv B.; Wilsgaard, Tom; Njølstad, Inger (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)

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  Abstract:

  The Tromsø Study was initiated in 1974 in an attempt to help combat the high mortality of cardiovascular diseases in Norway, that was particularly pronounced among middle-aged men. In the mid-1970s, Norwegian men had a 20% risk of dying of myocardial infarction (MI) before the age of 75 years. The situation in Northern Norway was even worse.1 The primary aim of the Tromsø Study was to determine causes of the high cardiovascular mortality, and also to develop ways of preventing heart attacks and strokes. This was reflected through the first name of the study: The Tromsø Heart Study. However, during the 37 years since the first examination of the Tromsø Study took place, increasing emphasis has been put on other chronic diseases and conditions, in particular atrial fibrillation, venous thromboembolism, diabetes mellitus, osteoporosis and fractures. It has been a deliberate policy to invite a wide range of faculty research groups to join in with subprojects in the surveys, and there are currently some 100 different ongoing research projects based on the data from the consecutive six surveys. The study was initially funded by the University of Tromsø, and has been so for the entire period since 1974, but there have also been substantial contributions, directly and indirectly from, for example, the National Screening Services, the Research Council of Norway, Northern Norway Regional Health Authority, Norwegian Council on Cardiovascular Diseases and Norwegian Foundation for Health and Rehabilitation. Teams of investigators approach public research programmes for funding of the different examinations conducted. Tromsø is the largest city in Northern Norway. It is situated ∼400 km north of the Arctic Circle, and has approximately 67 000 inhabitants. The physical living conditions are dominated by dramatic changes in the light with 2 months of midnight sun and 2 months of the polar night. However, due to the Gulf Stream, the climate is relatively mild, the latitude (69°N) taken into account.

  URI:

  http://hdl.handle.net/10037/5048

  File(s) in this item: 1

  article.pdf   (137.1Kb)

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