Showing papers by "University of Bergen published in 2001"

Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications

Abstract: The purpose of this study was to classify breast carcinomas based on variations in gene expression patterns derived from cDNA microarrays and to correlate tumor characteristics to clinical outcome. A total of 85 cDNA microarray experiments representing 78 cancers, three fibroadenomas, and four normal breast tissues were analyzed by hierarchical clustering. As reported previously, the cancers could be classified into a basal epithelial-like group, an ERBB2-overexpressing group and a normal breast-like group based on variations in gene expression. A novel finding was that the previously characterized luminal epithelial/estrogen receptor-positive group could be divided into at least two subgroups, each with a distinctive expression profile. These subtypes proved to be reasonably robust by clustering using two different gene sets: first, a set of 456 cDNA clones previously selected to reflect intrinsic properties of the tumors and, second, a gene set that highly correlated with patient outcome. Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospective study showed significantly different outcomes for the patients belonging to the various groups, including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups.

Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study.

Abstract: Objective: To assess whether mothers and fathers have a higher long term risk of death, particularly from cardiovascular disease and cancer, after the mother has had pre-eclampsia. Design: Population based cohort study of registry data. Subjects: Mothers and fathers of all 626 272 births that were the mothers9 first deliveries, recorded in the Norwegian medical birth registry from 1967 to 1992. Parents were divided into two cohorts based on whether the mother had pre-eclampsia during the pregnancy. Subjects were also stratified by whether the birth was term or preterm, given that pre-eclampsia might be more severe in preterm pregnancies. Main outcome measures: Total mortality and mortality from cardiovascular causes, cancer, and stroke from 1967 to 1992, from data from the Norwegian registry of causes of death. Results: Women who had pre-eclampsia had a 1.2-fold higher long term risk of death (95% confidence interval 1.02 to 1.37) than women who did not have pre-eclampsia. The risk in women with pre-eclampsia and a preterm delivery was 2.71-fold higher (1.99 to 3.68) than in women who did not have pre-eclampsia and whose pregnancies went to term. In particular, the risk of death from cardiovascular causes among women with pre-eclampsia and a preterm delivery was 8.12-fold higher (4.31 to 15.33). However, these women had a 0.36-fold (not significant) decreased risk of cancer. The long term risk of death was no higher among the fathers of the pre-eclamptic pregnancies than the fathers of pregnancies in which pre-eclampsia did not occur. Conclusions: Genetic factors that increase the risk of cardiovascular disease may also be linked to pre-eclampsia. A possible genetic contribution from fathers to the risk of pre-eclampsia was not reflected in increased risks of death from cardiovascular causes or cancer among fathers. What is already known on this topic Maternal and fetal genes (including those inherited from the father) may contribute to pre-eclampsia, which occurs in 3-5% of pregnancies One set of candidate genes for pre-eclampsia is the maternal genes for thrombophilia, which may increase the mother9s risk of death from cardiovascular disease What this study adds Women who have pre-eclampsia during a pregnancy that ends in a preterm delivery have an eightfold higher risk of death from cardiovascular disease compared with women who do not have pre-eclampsia and whose pregnancy goes to term Fathers of pregnancies in which pre-eclampsia occurred have no increased risk of death from cardiovascular disease These results are compatible with maternal genes for thrombophilia having an effect on the risk of pre-eclampsia and of death from cardiovascular disease

Hospital Anxiety and Depression (HAD) scale: factor structure, item analyses and internal consistency in a large population.

Abstract: Background The Hospital Anxiety and Depression (HAD) rating scale is a commonly used questionnaire. Former studies have given inconsistent results as to the psychometric properties of the HAD scale. Aims To examine the psychometric properties of the HAD scale in a large population. Method All inhabitants aged 20-89 years ( n =92 100) were invited to take part in The Nord-Trondelag Health Study, Norway. A total of 65 648 subjects participated, and only completed HAD scale forms ( n =51 930) formed the basis for the psychometric examinations. Results Principal component analysis extracted two factors in the HAD scale that accounted for 57% of the variance. The anxiety and depression sub-scales shared 30% of the variance. Both subscales were found to be internally consistent, with values of Cronbach's coefficient (α) being 0.80 and 0.76, respectively. Conclusions Based on data from a large population, the basic psychometric properties of the HAD scale as a self-rating instrument should be considered as quite good in terms of factor structure, intercorrelation, homogeneity and internal consistency.

Scientific literacy for citizenship: Tools for dealing with the science dimension of controversial socioscientific issues

Abstract: This article offers a general framework for examining the science dimension of controversial socioscientific issues. Eight specific content-transcending topics to be emphasized in science education are proposed. The topics are grouped under the headings science as a social process, limitations of science, values in science, and critical attitude. Each topic is explored, and it is argued that knowledge of the topics can serve as tools for students' examination of science-related claims in controversial socioscientific issues. The underlying perspective here is empowerment and the needs of students as lay people. The need of society as a whole for decisions to be made on a broad and firm basis is nevertheless also included. The main reason for suggesting the eight content-transcending topics is to provide focal points for the future development of teaching models aimed at science education for citizenship. © 2001 John Wiley & Sons, Inc. Sci Ed85:291–310, 2001.

The Saccharomyces cerevisiae Set1 complex includes an Ash2 homologue and methylates histone 3 lysine 4

Abstract: The SET domain proteins, SUV39 and G9a have recently been shown to be histone methyltransferases specific for lysines 9 and 27 (G9a only) of histone 3 (H3). The SET domains of the Saccharomyces cerevisiae Set1 and Drosophila trithorax proteins are closely related to each other but distinct from SUV39 and G9a. We characterized the complex associated with Set1 and Set1C and found that it is comprised of eight members, one of which, Bre2, is homologous to the trithorax-group (trxG) protein, Ash2. Set1C requires Set1 for complex integrity and mutation of Set1 and Set1C components shortens telomeres. One Set1C member, Swd2/Cpf10 is also present in cleavage polyadenylation factor (CPF). Set1C methylates lysine 4 of H3, thus adding a new specificity and a new subclass of SET domain proteins known to methyltransferases. Since methylation of H3 lysine 4 is widespread in eukaryotes, we screened the databases and found other Set1 homologues. We propose that eukaryotic Set1Cs are H3 lysine 4 methyltransferases and are related to trxG action through association with Ash2 homologues.

Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease.

Abstract: We describe here a previously unknown, dominantly inherited, late-onset basal ganglia disease, variably presenting with extrapyramidal features similar to those of Huntington's disease (HD) or parkinsonism. We mapped the disorder, by linkage analysis, to 19q13.3, which contains the gene for ferritin light polypeptide (FTL). We found an adenine insertion at position 460–461 that is predicted to alter carboxy-terminal residues of the gene product. Brain histochemistry disclosed abnormal aggregates of ferritin and iron. Low serum ferritin levels also characterized patients. Ferritin, the main iron storage protein, is composed of 24 subunits of two types (heavy, H and light, L) which form a soluble, hollow sphere1. Brain iron deposition increases normally with age, especially in the basal ganglia, and is a suspected causative factor in several neurodegenerative diseases2 in which it correlates with visible pathology3, possibly by its involvement in toxic free-radical reactions4. We found the same mutation in five apparently unrelated subjects with similar extrapyramidal symptoms. An abnormality in ferritin strongly indicates a primary function for iron in the pathogenesis of this new disease, for which we propose the name 'neuroferritinopathy'.

Correlates of Environmental Behaviors: Bringing Back Social Context

Abstract: Surveys are an efficient and convenient means of collecting data on individuals’ environmental concerns and environmental behaviors, two domains between which a tenuous relationship is often observ...

Neonatal diabetes mellitus due to complete glucokinase deficiency.

Abstract: Diabetes mellitus is a heterogeneous disorder that can occur at any age.1 Neonatal diabetes mellitus, defined as insulin-requiring hyperglycemia within the first month of life, is a rare disorder that is usually associated with intrauterine growth retardation.2 Like diabetes in general, neonatal diabetes is heterogeneous and can be either transient or permanent. Transient neonatal diabetes is associated with abnormalities of chromosome 6,2,3 whereas mutations in insulin promoter factor 1 result in pancreatic agenesis and permanent neonatal diabetes.4 We describe two patients in whom complete deficiency of the glycolytic enzyme glucokinase, a key regulator of glucose metabolism in pancreatic beta . . .

Pesticide effects on bacterial diversity in agricultural soils – a review

Abstract: According to guidelines for the approval of pesticides, side-effects on soil microorganisms should be determined by studying functional parameters such as carbon or nitrogen mineralisation. However, the microbial diversity may have been markedly changed following pesticide use despite unaltered metabolism, and such changes may affect soil fertility. This review evaluates new methods for measuring pesticide effects on bacterial diversity, and discusses how sampling should take temporal and spatial heterogeneity into account. Future research on pesticide approval protocols should establish the relationships between mineralisation assays and new and rapid bacterial diversity profiling methods, and should include the possible ecological implications of altered bacterial diversity for soil fertility.

The evolution of agriculture in beetles (curculionidae: scolytinae and platypodinae)

Abstract: Beetles in the weevil subfamilies Scolytinae and Platypodinae are unusual in that they burrow as adults inside trees for feeding and oviposition. Some of these beetles are known as ambrosia beetles for their obligate mutualisms with asexual fungi—known as ambrosia fungi—that are derived from plant pathogens in the ascomycete group known as the ophiostomatoid fungi. Other beetles in these subfamilies are known as bark beetles and are associated with free-living, pathogenic ophiostomatoid fungi that facilitate beetle attack of phloem of trees with resin defenses. Using DNA sequences from six genes, including both copies of the nuclear gene encoding enolase, we performed a molecular phylogenetic study of bark and ambrosia beetles across these two subfamilies to establish the rate and direction of changes in life histories and their consequences for diversification. The ambrosia beetle habits have evolved repeatedly and are unreversed. The subfamily Platypodinae is derived from within the Scolytinae, near the tribe Scolytini. Comparison of the molecular branch lengths of ambrosia beetles and ambrosia fungi reveals a strong correlation, which a fungal molecular clock suggests spans 60 to 21 million years. Bark beetles have shifted from ancestral association with conifers to angiosperms and back again several times. Each shift to angiosperms is associated with elevated diversity, whereas the reverse shifts to conifers are associated with lowered diversity. The unusual habit of adult burrowing likely facilitated the diversification of these beetle-fungus associations, enabling them to use the biomass-rich resource that trees represent and set the stage for at least one origin of eusociality.

The Hordaland Homocysteine Studies

Abstract: The Hordaland Homocysteine Study is a population-based screening of total plasma homocysteine (tHcy) in ∼18,000 men and women aged 40–67 yr that took place in 1992–1993 in the county of Hordaland in Western Norway. In this cohort, tHcy was associated with several physiologic and life-style factors, including age and gender, blood pressure, serum cholesterol, smoking, alcohol and coffe consumption, physical activity, diet, and vitamin status. All associations with established cardiovascular risk factors were in the direction expected to confer increased risk. In a subset of 5,883 women aged 40–42 yr, tHcy was associated with previous pregnancy outcomes, including preeclampsia, placental abruption, and neural tube defects. This article reviews the published results from the Hordaland Homocysteine Study in the light of relevant literature. The Hordaland Homocysteine cohort will be used for future investigations of the stability of tHcy and vitamin status over time, and to investigate associations with mortality and morbidity including cancer incidence.

Validation of an in vitro Biofilm Model of Supragingival Plaque

Abstract: The study of biofilm structure and function mandates the use of model systems for which a host of environmental variables can be rigorously controlled. We describe a model of supragingival plaque containing Actinomyces naeslundii, Veillonella dispar, Fusobacterium nucleatum, Streptococcus sobrinus, and Streptococcus oralis wherein cells are cultivated anaerobically in a saliva-based medium on hydroxyapatite discs coated with a salivary pellicle, with material and pieces of apparatus common to all microbiology laboratories. After 0.5 hr, 16.5 hrs, 40.5 hrs, and 64.5 hrs, the composition of adherent biofilms was analyzed by culture techniques, live/dead fluorescence staining, and confocal laser scanning microscopy. Repeated independent trials demonstrated the repeatability of biofilm formation after 40.5 hrs and 64.5 hrs. Brief exposures of biofilms to chlorhexidine or Triclosan produced losses in viability similar to those observed in vivo. This biofilm model should prove very useful for pre-clinical testing of prospective anti-plaque agents at clinically relevant concentrations.

Subjective health complaints in adolescence. A cross-national comparison of prevalence and dimensionality

Abstract: Background: The purpose of this work was to study the prevalence and dimensionality of subjective health complaints in a cross-national population of adolescents. Methods: The analyses were based on data from a WHO cross-national survey, Health Behaviour in School-aged Children (HBSC). The study included a representative sample of 11, 13 and 15-year-old adolescents from Finland, Norway, Poland and Scotland. Data were collected in 1993–1994 and the total sample included 20, 324 adolescents. Subjective health complaints were measured by the HBSC Symptom Checklist (HBSC-SCL), including headaches, abdominal pain, backache, feeling low, irritability, nevousness, sleeping difficulties and dizziness. Descriptive analyses, MANOVA and structural equation modelling (EQS) were conducted. Results: Patterns of reporting were consistent for all four countries. A large number of students reported a high level of symptoms. The reporting of most symptoms increased with age. Girls reported significantly more symptoms than boys and the gender differences also increased with age. Structural equation modelling suggests a model of two correlated factors, which can be labelled psychological and somatic. Conclusion: The findings of this study indicate that students report a high level of subjective health complaints already at the age of 11 years. The reporting of most symptoms increases with age and more so for girls than for boys. The finding of two dimensions that differ qualitatively, suggests that these dimensions may have different etiologies.

J-Express: exploring gene expression data using Java.

Abstract: J-Express is a Java application that allows the user to analyze gene expression (microarray) data in a flexible way giving access to multidimensional scaling, clustering, and visualization methods in an integrated manner. Specifically, J-Express includes implementations of hierarchical clustering, k-means, principal component analysis, and self-organizing maps. At present, it does not include methods for comparing two or more experiments for differentially expressed genes. The application is completely portable and requires only that a Java runtime environment 1.2 is installed on the system. Its efficiency allows interactive clustering of thousands of expression profiles on standard personal computers.

Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer.

Abstract: TP53 status [mutations, immunostaining, and loss of heterozygosity (LOH)], expression of c-erbB-2, bcl-2, and histological grading were correlated to the response to doxorubicin monotherapy (14 mg/m 2 ) administered weekly to 90 patients with locally advanced breast cancer. Mutations in the TP53 gene, in particular those affecting or disrupting the loop domains L2 or L3 of the p53 protein, were associated with lack of response to chemotherapy ( P = 0.063 for all mutations and P = 0.008 for mutations affecting L2/L3, respectively). Similarly, expression of c-erbB-2 ( P = 0.041), a high histological grade ( P = 0.023), and lack of expression of bcl-2 ( P = 0.018) all predicted chemoresistance. No statistically significant association between either p53 immunostaining or TP53 LOH and response to therapy was recorded, despite the finding that both were associated with TP53 mutation status (p53 immunostaining, P P = 0.021). Lack of immunostaining for p53 despite mutation of the TP53 gene was particularly seen in tumors harboring nonsense mutations or deletions/splices (7 of 10 negative for staining compared with 4 of 16 with missense mutations). TP53 mutations (total/affecting L2/L3 domains) were associated with expression of c-erbB-2 ( P P = 0.001 and P = 0.025), and bcl-2 negativity ( P = 0.003 and P = 0.002). TP53 mutations, histological grade, and expression of bcl-2 (but not LOH or c-erbB-2 expression) all predicted for relapse-free as well as breast cancer-specific survival in univariate analysis ( P s between P = 0.01 and P = 0.0007, respectively). Our data are consistent with the hypothesis that certain TP53 mutations predict for resistance to doxorubicin in breast cancer patients. However, the observation that the majority of patients with TP53 mutations affecting or disrupting the L2/L3 domains with LOH in addition ( n = 12) obtained a partial response ( n = 4) or stabilization of disease ( n = 5) during chemotherapy suggests redundant mechanisms to compensate for loss of p53 function. Our findings are consistent with the hypothesis that other defects may act in concert with loss of p53 function, causing resistance to doxorubicin in breast cancers.

Hip disease and the prognosis of total hip replacements. A review of 53,698 primary total hip replacements reported to the Norwegian Arthroplasty Register 1987-99.

Abstract: We studied the rates of revision for 53,698 primary total hip replacements (THRs) in nine different groups of disease. Factors which have previously been shown to be associated with increased risk of revision, such as male gender, young age, or certain types of uncemented prosthesis, showed important differences between the diagnostic groups. Without adjustment for these factors we observed an increased risk of revision in patients with paediatric hip diseases and in a small heterogeneous 'other' group, compared with patients with primary osteoarthritis. Most differences were reduced or disappeared when an adjustment for the prognostic factors was made. After adjustment, an increased relative risk (RR) of revision compared with primary osteoarthritis was seen in hips with complications after fracture of the femoral neck (RR = 1.3, p = 0.0005), in hips with congenital dislocation (RR = 1.3, p = 0.03), and in the heterogenous 'other' group. The analyses were also undertaken in a more homogenous subgroup of 16,217 patients which had a Charnley prosthesis implanted with high-viscosity cement. The only difference in this group was an increased risk for revision in patients who had undergone THR for complications after fracture of the femoral neck (RR = 1.5, p = 0.0005). THR for diagnoses seen mainly among young patients had a good prognosis, but they had more often received inferior uncemented implants. If a cemented Charnley prosthesis is used, the type of disease leading to THR seems in most cases to have only a minor influence on the survival of the prosthesis.

Holocene glacier fluctuations of Flatebreen and winter-precipitation changes in the Jostedalsbreen region, western Norvay, based on glaciolacustrine sediment records:

Abstract: The history of Holocene glacier variations of Flatebreen, an independent glacier close to the SW part of the Jostedalsbreen ice cap, has been reconstructed from lacustrine sediments in the proglacial lake Jarbuvatnet. The sedimentary succession shows evidence of three maini episodes of Holocene glacier expansion. The first is recorded in the basal part of the core up to 370 cm. According to the age/depth relationship in the sediment core (based on 12 AMS radiocarbon dates), this glacier expansion episode terminated about 10200 cal. yr BP. The second major glacier phase lasted from 8400 to 8100 cal. yr BP, while the third was initiated around 4000 cal. yr BP and has continued up to the present. At 43 cm in the core, the medium silt content increases significantly, accompanied by a minor increase in the sand content. This textural change is interpreted as the first time that the tenninus of Flatebreen extended inlto an] upstream lake at 1083 m a.s.l. The age model suggests that this event took place around ...

Satisfaction with life among international students: An exploratory study

Abstract: The study examines self-reported satisfaction with life and thefactors predicting it among 304 international students (159 malesand 145 females) at the University of Bergen, Norway Thestudents had on the average lived 234 years (SD = 231) inNorway The students reported on the whole good satisfactionwith life However, students from Europe and North America wereon the whole more satisfied than their peers from Africa andAsia It was also found that factors such as the number offriends, satisfaction with finances, perceived discrimination andinformation received prior to the foreign sojourn significantlyaffected the student's life satisfaction The importance ofthese factors differed for students from developing and developedcountries where some paradoxical findings came out Theseparadoxical findings may be the result of the Norwegian contextof the study Language proficiency (with respect to host andEnglish languages), and having a host national friend did notshow significant effect on life satisfaction

Local endostatin treatment of gliomas administered by microencapsulated producer cells

Abstract: We describe a technique for the treatment of malignant brain tumors based on local delivery of the anti-angiogenic protein endostatin from genetically engineered cells encapsulated in ultrapure sodium alginate. Alginate consists of L-guluronic and D-mannuronic acid, which in the presence of divalent cations forms an extended gel network, in which cells reside and remain immunoisolated, when implanted into the rat brain. Here, we show that endostatin-transfected cells encapsulated in alginate maintain endostatin secretion for at least four months after intracerebral implantation in rats. During the implantation period 70% of the encapsulated cells remained viable, as opposed to 85% in in vitro-cultured capsules. Rats that received transplants of BT4C glioma cells, together with endostatin-producing capsules (0.2 μg/ml per capsule), survived 84% longer than the controls. The endostatin released from the capsules led to an induction of apoptosis, hypoxia, and large necrotic avascular areas within 77% of the treated tumors, whereas all the controls were negative. The encapsulation technique may be used for many different cell lines engineered to potentially interfere with the complex microenvironment in which tumor and normal cells reside. The present work may thus provide the basis for new therapeutic approaches toward brain tumors.

Bacterial colonization associated with fixed orthodontic appliances. A scanning electron microscopy study

Abstract: This investigation was undertaken to assess bacterial plaque accumulation adjacent to orthodontic brackets. Experiments were carried out on 11 subjects who were scheduled for orthodontic treatment including extraction of two or four premolars. Metal brackets were bonded to the premolars to be extracted using macro-filled bonding composite. A conventional elastomeric ring was placed around one bracket and a steel ligature wire around the bracket on the contralateral tooth. The subjects were told to continue their normal oral hygiene regimen. Teeth were extracted at 1, 2, or 3 weeks after bracket bonding. Scanning electron microscopic (SEM) examination of brackets, excess composite, and buccal enamel revealed that mature plaque was present on excess composite at 2 and 3 weeks after bonding, whereas plaque on the gingival enamel surface was still at an early stage of development. The results demonstrate that excess composite around the bracket base is the critical site for plaque accumulation due to its rough surface and the presence of a distinct gap at the composite-enamel interface. The method of ligation does not appear to influence the bacterial morphotypes on both composite and enamel surfaces.