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P Møller

Publications and source records attributed to P Møller.

At least 19 recordsLinked to original sources
PubMed2006

An optical supernova associated with the X-ray flash XRF 060218.

Long-duration gamma-ray bursts (GRBs) are associated with type Ic supernovae that are more luminous than average and that eject material at very high velocities. Less-luminous supernovae were not hitherto known to be associated with GRBs, and therefore GRB-supernovae were thought to be rare events. Whether X-ray flashes--analogues of GRBs, but with lower luminosities and fewer gamma-rays--can also be associated with supernovae, and whether they are intrinsically 'weak' events or typical GRBs viewed off the axis of the burst, is unclear. Here we report the optical discovery and follow-up observations of the type Ic supernova SN 2006aj associated with X-ray flash XRF 060218. Supernova 2006aj is intrinsically less luminous than the GRB-supernovae, but more luminous than many supernovae not accompanied by a GRB. The ejecta velocities derived from our spectra are intermediate between these two groups, which is consistent with the weakness of both the GRB output and the supernova radio flux. Our data, combined with radio and X-ray observations, suggest that XRF 060218 is an intrinsically weak and soft event, rather than a classical GRB observed off-axis. This extends the GRB-supernova connection to X-ray flashes and fainter supernovae, implying a common origin. Events such as XRF 060218 are probably more numerous than GRB-supernovae.

Journal Article↗
PubMed2006

Nordic collaborative study of the BARD1 Cys557Ser allele in 3956 patients with cancer: enrichment in familial BRCA1/BRCA2 mutation-negative breast cancer but not in other malignancies.

BACKGROUND: BARD1 was originally identified as a BRCA1-interacting protein but has also been described in tumour-suppressive functions independent of BRCA1. Several studies have indicated that the BARD1 gene is a potential target for germline changes predisposing to breast and ovarian cancer. The C-terminal Cys557Ser change has previously been uncovered to associate with an increased risk of breast cancer and was recently shown to result in defective apoptotic activities. AIM AND METHODS: Conformation-sensitive gel electrophoresis, minisequencing, TaqMan assays, denaturing high-performance liquid chromatography analysis and DNA sequencing were used to investigate the prevalence of the Cys557Ser allele in a large Nordic case-control study cohort consisting of 2906 patients with breast or ovarian cancer, 734 with prostate cancer, 188 with colorectal cancer, 128 men with breast cancer, and 3591 controls from Finland, Iceland, Denmark, Sweden and Norway. RESULTS: The frequency of the BARD1 Cys557Ser variant seemed to increase among patients from families with breast or ovarian cancer lacking BRCA1 or BRCA2 mutations: a significant difference was obtained compared with controls (6.8% v 2.7%; p<0.001; odds ratio (OR) 2.6; 95% confidence interval (CI) 1.7 to 4.0) and with patients from BRCA1/BRCA2 mutation-positive families (6.8% v 2.2%; p = 0.01; OR 3.2; 95% CI 1.2 to 8.3). In contrast, no major association with male breast, ovarian, colorectal or prostate cancer was observed. Additionally, a novel BARD1 allele resulting in Ser558Pro was identified in familial breast cancer cases. CONCLUSION: These results provide further evidence that BARD1 Cys557Ser confers a slightly increased risk of breast cancer in women.

Adolescent↗
PubMed2004

Regional and inter annual patterns of heavy metals, organochlorines and stable isotopes in narwhals (Monodon monoceros) from West Greenland.

Samples of 150 narwhals obtained in different years from two West Greenland areas, Avanersuaq and Uummannaq, were compared for concentrations of and regional differences in heavy metals and organochlorines and stable-carbon and nitrogen isotopes. Cadmium, Hg, and Se concentrations increased in the first 3-4 years of the animal's life, after which no dependence on age was observed. Females had significantly higher concentrations of Cd in all tissues and of Hg and Se in liver than males. No consistent difference in metal levels between narwhals from Avanersuaq and Uummannaq was found. Year-to-year variation in metal levels at one location was larger than the geographical variation. Metal levels were within the range of previous published results for narwhals from Arctic Canada. Organochlorine (OC) concentrations in blubber of narwhals were dependent on age and sex. Females showed decreasing OC concentration in the first 8-10 years, while for males increases were detected in the first few years of life, after which the concentrations became stable. Few statistical differences in mean OC concentrations among individuals were observed. However, narwhals from Avanersuaq in 1993 had the lowest levels, indicating a temporal decrease of SigmaPCBs. SigmaPCBs, DDTs, HCHs and toxaphenes seem to be at similar levels in West Greenland and Arctic Canada, which can be explained by the close winter distributions of populations as well as large ranges in concentrations, time span, number of analyses and the size/age composition of the data. PCB and DDT concentrations in West Greenland narwhals were half those found in East Greenland and Svalbard. Stable-carbon isotope ratios in muscle of 150 narwhals showed a decreasing trend in the first year when they gradually reduced their dependency on mother's milk, after which they became relatively stable. delta15 N values were significantly higher in samples from Uummannaq in 1993 compared to samples from Avanersuaq in 1984 and 1985 indicating that the diet of the narwhals in Uummannaq was at a higher trophic level. However, only a few significant correlations were found between stable isotope ratios and metal and OC concentrations.

Age Factors↗
PubMed2004

Commonly consumed and naturally occurring dietary substances affect biomarkers of oxidative stress and DNA damage in healthy rats.

The influence of black currant juice, Bowman-Birk protease inhibitor (BBI), kolaviron (a biflavonoid fraction of Garcinia kola seed), sugars, vitamin C and tert-butyl hydroperoxide on a wide range of biomarkers for oxidative stress, DNA damage and sugar or lipid metabolism has been investigated in male F 344 rats. The selected pro-oxidant control, tert-butyl hydroperoxide, significantly increased plasma and liver 2-amino-adipic semialdehyde (AAS), a marker of protein oxidation (p <0.05) whereas lipid oxidation assessed as malon dialdehyde (MDA) and DNA oxidation were not significantly increased. Feeding BBI also increased the level of oxidized protein in plasma and liver at the higher dose level (0.5%). No effect was observed at the lower dose level (0.25%), which even decreased lipid oxidation in plasma. BBI did not affect background levels of DNA strand breaks or oxidation (comets). In rats exposed to black currant juice, a statistically significant decrease in liver AAS and MDA was observed. This effect could not be explained by its content of sugars or of the known redox active constituent, vitamin C. The lowering effect of black currant juice on protein and lipid oxidation was similar in magnitude to that of the known liver protectant, kolaviron. In rats treated with kolaviron (200 mg/kg body weight), background AAS levels were significantly reduced in both plasma and liver whereas the effect on MDA only reached statistical significance in plasma. Kolaviron was the only extract tested which decreased oxidative damage to DNA in the liver. The erythrocyte antioxidant enzyme activities, catalase and glutathione peroxidase were decreased in rats treated with tert-butyl hydroperoxide (p <0.05) but were not affected by the other treatments. Black currant juice and sugars increased plasma triglyceride levels and black currant juice increased plasma cholesterol but neither of them nor any other treatment affected blood glucose, erythrocyte HbA1c or fructosamine. We conclude that markers of oxidative stress may be modified by several mechanisms after feeding rats with complex dietary factors and that both pro- and antioxidant effects may consequently be observed simultaneously after short-term feeding of antioxidant-rich foods, herb medicines, or known pro- and antioxidants.

Animals↗
PubMed2004

Ex-vivo and in vitro protective effects of kolaviron against oxygen-derived radical-induced DNA damage and oxidative stress in human lymphocytes and rat liver cells.

The present study reports the protective effects of kolaviron, a Garcinia biflavonoid from the seeds of Garcinia kola widely consumed in some West African countries against oxidative damage to molecular targets ex-vivo and in vitro. Treatment with hydrogen peroxide (H2O2) at a concentration of 100 micromol/L increased the levels of DNA strand breaks and oxidized purine (formamidopyrimidine glycosylase (FPG) and pyrimidine (endonuclease III (ENDO III) sites) bases in both human lymphocytes and rat liver cells using alkaline single cell gel electrophoresis (the comet assay). Kolaviron was protective at concentrations between 30-90 micromol/L and decreased H2O2-induced DNA strand breaks and oxidized bases. Neither alpha-tocopherol nor curcumin decreased H2O2-induced DNA damage in this assay. In lymphocytes incubated with Fe3+/GSH, Fe3+ was reduced to Fe2+ by GSH initiating a free radical generating reaction which induced 11.7, 6.3, and 4.9 fold increase respectively in strand breaks, ENDO III and FPG sensitive sites compared with control levels. Deferoxamine (2 mmol/L), an established iron chelator significantly inhibited GSH/Fe3+-induced strand breaks and oxidized base damage. Similarly, kolaviron at 30 and 90 micromol/L significantly attenuated GSH/Fe3+-induced strand breaks as well as base oxidation. Kolaviron (100 mg/kg bw) administered to rats for one week protected rat liver cells against H2O2-induced formation of strand breaks, ENDO III, and FPG sensitive sites, Fe3+/EDTA/ascorbate-induced malondialdehyde formation and protein oxidation using gamma-glutamyl semialdehyde (GGS) and 2-amino-adipic semialdehyde (AAS) as biomarkers of oxidative damage to proteins. We suggest that kolaviron exhibits protective effects against oxidative damage to molecular targets via scavenging of free radicals and iron binding. Kolaviron may therefore be relevant in the chemoprevention of oxidant-induced genotoxicity and possibly human carcinogenesis.

Animals↗
PubMed2004

Costs and benefits of diagnosing familial breast cancer.

Costs and benefits are ill-defined terms; this review discusses some interpretations and some ways of assessing costs and benefits. Cost-benefit calculation is a misconception in health care, in that costs should be considered together with what the patients gain in terms of prolonged life and life quality. In the emerging commercialization of Western health care, however, money benefit is to be calculated in order to ask for funding. As professionals we are dealing with inherited breast cancer. We come to know the families and the individual women within these families. We care, we cure, we prevent and we are gaining knowledge. We are doing good, not harm. We are profoundly involved, and we are so deeply and personally involved that we may not even try to be objective in a debate on choosing between our patients and patients cared for by others. As we present our arguments, society has to decide. There is no argument to provide service for other inherited disorders based on ethical standards alone, and to deprive women at risk for breast cancer the life-saving health service they need because of money costs. The money needed is based on a number of rapidly fluctuating factors: the most stable costs are genetic counseling and physical examinations to demonstrate disease, while laboratory costs are rapidly decreasing. The overall conclusion is that economical cost-benefit analysis as an argument for our activity is outside our professional ethics, and should never become a reason for our continued endeavors.

Breast Neoplasms↗
PubMed2003

The Norwegian founder mutations in BRCA1: high penetrance confirmed in an incident cancer series and differences observed in the risk of ovarian cancer.

We aimed to describe the penetrances of the four Norwegian founder mutations in BRCA1 (816delGT, 1135insA, 1675delA and 3347delAG) with regard to breast and ovarian cancers in families ascertained through cancer family clinics or a consecutive series of women with breast or ovarian cancer. We have extended the families as far as possible and tested all family members that asked for genetic testing. Penetrance is based upon counting the mutation carriers. The series contains sufficient numbers of mutation carriers to minimise variation in the estimates due to a limited sample set. The penetrances for all four mutations were high, both with respect to breast and ovarian cancers. This is in accordance with other reports from cancer family clinics, but contrasts with reports from population-based series of mutation carriers. Risks of first cancer (breast or ovarian), breast cancer, and ovarian cancer at age 50 years were 43, 30 and 17%, respectively. Corresponding risks at age 70 years were 84, 58 and 58%. Risks for breast cancer before age 30 years and for ovarian cancer before 35 years were low. Penetrances with regard to ovarian cancer were different for the four mutations. The risk of ovarian cancer was doubled in carriers of the 1675delA mutation when compared with the 816delGT mutation (24 versus 12% at age 50 years, P=0.004). The mutations analysed are high penetrance alleles. No differences in penetrance between the series ascertained through the cancer family clinic or the series of consecutive cancer patients was observed. There are discrepancies between our findings and the low penetrances reported for other mutations in other populations. This may be due to methodological differences, but may reflect differences between mutations and/or modifying factors in different populations.

Adult↗
PubMed2003

Effect of sensory perception of foods on appetite and food intake: a review of studies on humans.

OBJECTIVE: How much do the sensory properties of food influence the way people select their food and how much they eat? The objective of this paper is to review results from studies investigating the link between the sensory perception of food and human appetite regulation. CONTENT OF THE REVIEW: The influence of palatability on appetite and food intake in humans has been investigated in several studies. All reviewed studies have shown increased intake as palatability increased, whereas assessments of the effect of palatability using measures of subjective appetite sensations have shown diverging results, for example, subjects either feel more hungry and less full after a palatable meal compared to a less palatable meal, or they feel the opposite, or there is no difference. Whether palatability has an effect on appetite in the period following consumption of a test meal is unclear. Several studies have investigated which sensory properties of food are involved in sensory-specific satiety. Taste, smell, texture and appearance-specific satieties have been identified, whereas studies on the role of macronutrients and the energy content of the food in sensory-specific satiety have given equivocal results. Different studies have shown that macronutrients and energy content play a role in sensory-specific satiety or that macronutrients and energy content are not a factor in sensory-specific satiety. Sensory-specific satiety may have an important influence on the amount of food eaten. Studies have shown that increasing the food variety can increase food and energy intake and in the short to medium term alter energy balance. Further knowledge about the importance of flavour in appetite regulation is needed, for example, which flavour combinations improve satiety most, the possible connection between flavour intensity and satiety, the effect of persistence of chemesthetic sensation on palatability and satiety, and to what extent genetic variation in taste sensitivity and perception influences dietary habits and weight control.

Appetite↗
PubMed2002

Comparison of adhesion of the food spoilage bacterium Shewanella putrefaciens to stainless steel and silver surfaces.

AIMS: To compare the number of attached Shewanella putrefaciens on stainless steel with different silver surfaces, thus evaluating whether silver surfaces could contribute to a higher hygienic status in the food industry. METHODS AND RESULTS: Bacterial adhesion to three types of silver surface (new silver, tarnished silver and sulphide-treated silver) was compared with adhesion to stainless steel (AISI 316) using the Malthus indirect conductance method to estimate the number of cfu cm(-2). The number of attached bacteria on new silver surfaces was lower than on steel for samples taken after 24 h. However, this was not statistically significant (P > 0.05). The numbers of attached bacteria were consistently lower when tarnished silver surfaces were compared with stainless steel and some, but not all, experiments showed statistical significance (P < 0.05). Treating new silver with sulphide to reproduce a tarnished silver surface did not result in a similar lowering of adhering cells when compared with steel (P > 0.05). CONCLUSIONS: New or tarnished silver surfaces caused a slight reduction in numbers of attached bacteria; however, the difference was only sometimes statistically significant. SIGNIFICANCE AND IMPACT OF THE STUDY: The lack of reproducibility in differences in numbers adhering to the different surfaces and lack of statistical significance between numbers of adhered viable bacteria do not indicate that the tested silver surfaces can be used to improve hygienic characteristics of surfaces in the food industry.

Bacterial Adhesion↗
PubMed2001

[Information to families with hereditary breast and ovarian cancer].

BACKGROUND: Under Norwegian legislation, persons at risk should make the initial contact with the proper health personnel, and not vice versa. It may be argued that the physician should be allowed to make contact with persons at risk of preventable or curable disorders. MATERIAL AND METHODS: We identified all first-degree relatives of all 75 BRCA1 mutation carriers diagnosed within a given period of time and asked them whether or not they had been informed by their relatives. RESULTS: After two years, 60/63 (95%) adult sisters and daughters had made contact with us; the remaining three (5%) had been informed. In comparison, 18/45 (40%) adult brothers and sons had contacted us. INTERPRETATION: The legislation constituted no barrier to offering health services to the target group. Information on our services had reached all close relatives who could benefit from them. This may be representative for curable inherited disorders. We examined inherited cancer limited to females; similar studies on inherited cancers in males and on other curable inherited disorders should be performed. Outside the framework of the present study, we are aware of rare examples of distant cousins who have not been properly informed through their families. One legally acceptable way of identifying mutation carrier families is to test all patients with breast or ovarian cancer for causative mutations. Health services should be monitored to make future decisions based on empirical evidence.

Adult↗
PubMed2001

Functional analysis of BRCA1 C-terminal missense mutations identified in breast and ovarian cancer families.

Germline mutations in the breast and ovarian cancer susceptibility gene BRCA1 are responsible for the majority of cases involving hereditary breast and ovarian cancer. Whereas all truncating mutations are considered as functionally deleterious, most of the missense variants identified to date cannot be readily distinguished as either disease-associated mutations or benign polymorphisms. The C-terminal domain of BRCA1 displays an intrinsic transactivation activity, and mutations linked to disease predisposition have been shown to confer loss of such activity in yeast and mammalian cells. In an attempt to clarify the functional importance of the BRCA1 C-terminus as a transcription activator in cancer predisposition, we have characterized the effect of C-terminal germline variants identified in Scandinavian breast and ovarian cancer families. Missense variants A1669S, C1697R, R1699W, R1699Q, A1708E, S1715R and G1738E and a truncating mutation, W1837X, were characterized using yeast- and mammalian-based transcription assays. In addition, four additional missense variants (V1665M, D1692N, S1715N and D1733G) and one in-frame deletion (V1688del) were included in the study. Our findings demonstrate that transactivation activity may reflect a tumor-suppressing function of BRCA1 and further support the role of BRCA1 missense mutations in disease predisposition. We also report a discrepancy between results from yeast- and mammalian-based assays, indicating that it may not be possible to unambiguously characterize variants with the yeast assay alone. We show that transcription-based assays can aid in the characterization of deleterious mutations in the C-terminal part of BRCA1 and may form the basis of a functional assay.

Adult↗
PubMed2001

[Perilymphatic fistula].

BACKGROUND: Perilymphatic fistula is leakage of perilymph from the inner ear to the middle ear. The perilymph surrounds the endolymphatic system in the inner ear (cochlea and the vestibular apparatus) and is most likely a cerebrospinal fluid filtrate. Leakage can occur through the fenestra vestibuli (the oval window), the fenestra cochleae (the round window), or pathological openings in the otic capsule. The cause of perilymphatic fistula can be trauma (barotrauma, head trauma, whiplash injury, iatrogenic trauma during ear surgery or ear syringing), chronic otitis media with cholesteatoma, congenital malformations or idiopathic. MATERIAL AND METHODS: We present 15 patients operated at Haukeland University Hospital from 1980 to 1997. RESULTS: Symptoms and signs are not very consistent, but dizziness and hearing loss are usual. The fistula test has low sensitivity and specificity, and otomicroscopy is not diagnostic. Imaging techniques with CT and MRI are seldom helpful unless in cases of inner ear abnormalities. Surgical exploration of the middle ear can be diagnostic, but even then it may in some cases be difficult to determine if a perilymphatic fistula is present. INTERPRETATION: The treatment of suspected perilymphatic fistula is primarily bed rest with elevated head, and avoidance of straining to facilitate spontaneous closure of a possible fistula. If the symptoms continue, or get worse, surgical exploration is indicated. The results are good regarding dizziness, but more uncertain as far as hearing improvement is concerned. Hearing improvement seems to be negatively correlated with the length of the delay before the fistula is closed.

Adult↗
PubMed2001

The BRCA1 syndrome and other inherited breast or breast-ovarian cancers in a Norwegian prospective series.

Inherited breast cancer is a heterogenous group of diseases. We examined this heterogeneity in a prospective series of inherited breast and ovarian cancers, previously demonstrated to include 84% of inherited cancers. Ninety-two tumours (65 breast and 27 ovarian) in 82 patients from 70 kindreds were prospectively diagnosed. Fifteen of the breast cancers were in situ, 50 were infiltrating. 40 (49%) of the 82 women carried a BRCA1 mutation, whereas no mutation in BRCA2 was found. Approximately, two-thirds of the BRCA1 mutation carriers had one of the four most frequent Norwegian founder mutations. Ninety-five per cent of the epithelial ovarian cancers occurred in BRCA1 mutation carrying women versus 38% of infiltrating breast cancers and 7% of carcinoma in situ of the breast. The BRCA1 syndrome was phenotypically distinct with invasive, high grade, oestrogen receptor-negative breast cancers and epithelial ovarian cancers. Non-BRCA1/2 inherited breast cancers included carcinoma in situ and lobular carcinoma and were frequently bilateral. Non-BRCA1/2 inherited breast cancer is not associated with epithelial ovarian cancer and in breast cancers has distinct biological characteristics, indicating that the different subgroups of inherited breast cancer may need different healthcare services.

Adult↗
PubMed2001

Genetic epidemiology of BRCA1 mutations in Norway.

Familial breast-ovarian cancer has been demonstrated to be frequent but unevenly distributed in Norway. This was assumed to be caused by the reduced population size created by the medieval Bubonic plagues 25 generations ago, and by the following rapid expansion. We have previously reported that four mutations account for 68% of the BRCA1 mutation carriers. Subsequent analysis has resulted in a total of 100 separate families carrying one of these founder mutations. The four mutations occurred on one specific BRCA1 haplotype each. The 1675delA, 816delGT and 3347delAG families originated from the South-West coast of Norway with a few families in the north, while the traceable ancestors of the 1135insA families clustered along the historical inland road from the South-East to mid-Norway. The carriers of each of the four mutations today are descendants of one or a few individuals surviving the plagues. We may identify the majority of BRCA1 mutation carriers in Norway by screening for local founder mutations.

Breast Neoplasms↗
PubMed2001

Prediction of the outcome of genetic testing in HNPCC kindreds using the revised Amsterdam criteria and immunohistochemistry.

BACKGROUND AND AIMS: Hereditary non-polyposis colorectal cancer (HNPCC) may be caused by mutations in the mismatch repair (MMR) genes MLH1, MSH2 or MSH6. Family history (Amsterdam criteria) has traditionally been used to select patients for mutation testing. It has been demonstrated that germline mutations in the MMR genes are associated with lack of the corresponding gene product as assessed with immunohistochemistry (IHC) in tumour specimens. The aim of the study was to assess the value of the Amsterdam criteria II and IHC in predicting germline mutations. METHODS: Fifty-six families that were previously tested for MLH1, MSH2 and MSH6 mutations were selected for this study. All pedigrees were extended and verified and the families were scored according to the original (I) and the revised Amsterdam criteria (II). The probabilities for MLH1 and MSH2 mutations were calculated by logistic regression. In addition, all available tumour material from indexed family members was examined by IHC for the presence of the three gene products. RESULTS: Three out of seven (39%) families where the mutation could be identified complied with the Amsterdam criteria I, while all seven (100%) met the Amsterdam criteria II. All families carrying a MLH1 or MSH2 mutation had > 15% calculated probability of finding a mutation. Tumours from all seven mutation carriers lacked the immunohistochemical expression of the corresponding MMR gene. CONCLUSION: The results indicate that the Amsterdam criteria II in combination with immunohistochemistry of the mismatch repair proteins in tumours may be a cost-effective approach to select families for mutation analysis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Pharmacological coal tar induces G:C to T:A transversion mutations in the skin of muta mouse.

Coal tar is a by-product of the distillation of coal. It consists of a complex chemical mixture of aromatic and aliphatic hydrocabons, with high concentrations of polycyclic aromatic hydrocarbons such as benzo[a]pyrene. We have previously shown that single painting on skin of mice increases the mutation frequency 16 times in murine epidermis cells (Thein et al. 2000). Here, we have determined the mutations by DNA sequencing. Coal tar was found to primarily induce G:C to T:A transversions and one-base pair deletions of G:C base pairs. More than half of the mutations were at CpG sites. The mutational spectrum is in agreement with that of benzo[a]pyrene and other polycyclic aromatic hydrocarbon mixtures.

Animals↗