| 1. |
- Antoniou, A, et al.
(författare)
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Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: A combined analysis of 22 studies
- 2003
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 72:5, s. 1117-1130
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Tidskriftsartikel (refereegranskat)abstract
- Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context. Estimates based on multiple-case families may be enriched for mutations of higher risk and/or other familial risk factors, whereas risk estimates from studies based on cases unselected for family history have been imprecise. We pooled pedigree data from 22 studies involving 8,139 index case patients unselected for family history with female (86%) or male (2%) breast cancer or epithelial ovarian cancer (12%), 500 of whom had been found to carry a germline mutation in BRCA1 or BRCA2. Breast and ovarian cancer incidence rates for mutation carriers were estimated using a modified segregation analysis, based on the occurrence of these cancers in the relatives of mutation-carrying index case patients. The average cumulative risks in BRCA1-mutation carriers by age 70 years were 65% (95% confidence interval 44%-78%) for breast cancer and 39% (18%-54%) for ovarian cancer. The corresponding estimates for BRCA2 were 45% (31%-56%) and 11% (2.4%-19%). Relative risks of breast cancer declined significantly with age for BRCA1-mutation carriers ( P trend .0012) but not for BRCA2-mutation carriers. Risks in carriers were higher when based on index breast cancer cases diagnosed at <35 years of age. We found some evidence for a reduction in risk in women from earlier birth cohorts and for variation in risk by mutation position for both genes. The pattern of cancer risks was similar to those found in multiple-case families, but their absolute magnitudes were lower, particularly for BRCA2. The variation in risk by age at diagnosis of index case is consistent with the effects of other genes modifying cancer risk in carriers.
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| 2. |
- Bergthorsson, J.T., et al.
(författare)
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BRCA1 and BRCA2 mutation status and cancer family history of Danish women affected with multifocal or bilateral breast cancer at a young age
- 2001
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 38:6, s. 361-368
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Tidskriftsartikel (refereegranskat)abstract
- Introduction - A small fraction of breast cancer is the result of germline mutations in the BRCA1 and BRCA2 cancer susceptibility genes. Mutation carriers frequently have a positive family history of breast and ovarian cancer, are often diagnosed at a young age, and may have a higher incidence of double or multiple primary breast tumours than breast cancer patients in general. Objectives - To estimate the prevalence and spectrum of BRCA1 and BRCA2 mutations in young Danish patients affected with bilateral or multifocal breast cancer and to determine the relationship of mutation status to family history of cancer. Subjects - From the files of the Danish Breast Cancer Cooperative Group (DBCG), we selected 119 breast cancer patients diagnosed before the age of 46 years with either bilateral (n=59) or multifocal (n=61) disease. Methods - DNA from the subjects was screened for BRCA1 and BRCA2 mutations using single strand conformation analysis (SSCA) and the protein truncation test (PTT). Observed and expected cancer incidence in first degree relatives of the patients was estimated using data from the Danish Cancer Registry. Results - Twenty four mutation carriers were identified (20%), of whom 13 had a BRCA1 mutation and 11 carried a BRCA2 mutation. Two mutations in BRCA1 were found repeatedly in the material and accounted for seven of the 24 (29%) mutation carriers. The mutation frequency was about equal in patients with bilateral (22%) and multifocal breast cancer (18%). The incidence of breast and ovarian cancer was greatly increased in first degree relatives of BRCA1 and BRCA2 mutation carriers, but to a much lesser degree in relatives of non-carriers. An increased risk of cancer was also noted in brothers of non-carriers. Conclusions - A relatively broad spectrum of germline mutations was observed in BRCA1 and BRCA2 and most of the mutations are present in other populations. Our results indicate that a diagnosis of bilateral and multifocal breast cancer is predictive of BRCA1 and BRCA2 mutation status, particularly when combined with information on the patients' age at diagnosis and family history of breast/ovarian cancer.
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| 3. |
- Bichao, H., et al.
(författare)
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Identification of plant odours activating receptor neurones in the weevil Pissodes notatus F. (Coleoptera, Curculionidae)
- 2003
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Ingår i: Journal of Comparative Physiology A. Sensory, neural, and behavioral physiology. - : Springer Science and Business Media LLC. - 0340-7594 .- 1432-1351. ; 189:3, s. 203-212
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Tidskriftsartikel (refereegranskat)abstract
- Plants release complex mixtures of volatiles important in the interaction with insects and other organisms. In the search for compounds that contribute to the perception of odour quality in the weevil Pissodes notatus, single olfactory receptor neurones on the antennae were screened for sensitivity to naturally produced plant volatiles by the use of gas chromatography linked to single cell recordings. We here present 60 olfactory neurones responding to 25 of the numerous compounds released by host and non-host plants. All the neurones show high selectivity and are classified into 12 distinct types. The two most abundant types respond to alpha-pinene, beta-pinene, and 3-carene (n = 17), and to isopinocamphone and pinocamphone (n = 17), respectively. Other neurone types respond to limonene (n = 9), beta-phellandrene (n = 3), and fenchone (n = 4). Responses to beta-caryophyllene (n = 1) and to ethanol (n = 4) are also shown. Except for two pairs, the neurone types do not show overlap of the molecular receptive range. The active compounds are present in the host, Pinus pinaster, as well as in non-hosts, supporting the idea that plant odour quality is mediated by the ratio of the compounds rather than specific odorants.
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| 4. |
- Johannsdottir, HK, et al.
(författare)
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Deletions on chromosome 4 in sporadic and BRCA mutated tumors and association with pathological variables
- 2004
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Ingår i: Anticancer research. - 1791-7530. ; 24:5A, s. 2681-2687
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chromosomal aberrations in breast tumors from BRCA1 and BRCA2 germ-line mutation carriers are considerably more frequent than what is seen in sporadic breast tumors. According to Comparative Genomic Hybridisation analysis (CGH), deletions on chromosome 4 are one of the most frequent events in BRCA1-associated tumors, suggesting inactivation of specific tumor suppressor genes. Materials and Methods: In the present study, 16 microsatellite markers covering chromosome 4 were used to map loss of heterozygosity (LOH) in tumors from BRCA1 (n =41) as well as in tumors from BRCA2 (n = 66) mutation carriers and in tumors from unselected cases of breast cancer (n = 68). Results: The frequency of LOH in these groups ranged from 16-73% in BRCA1-associated tumors, 13-42% in BRCA2-associated tumors and 8-33% in unselected tumors. LOH was significantly more frequent in BRCA1-associated tumors as compared to BRCA2-associated tumors and unselected tumors, and particularly high (over 70%) at 4q35.2. Pathological variables that were found significantly associated (pless than or equal to0.05) with LOH at specific markers were: high percentage of cells in S-phase, negative estrogen receptor status, young age at diagnosis and large tumors. Deletion mapping indicates the existence of seven non-overlapping regions at chromosome 4, which were identified in all three groups of tumors. Three of these seven regions, 4p16.3-p16.1, 4q27-q32.1 and 4q35.1-4qter, have not been reported in breast cancer previously. Conclusion: The results manifest the frequent alterations of chromosome 4 in BRCA1-associated breast tumors and indicate the location of several genes of potential importance in breast cancer development.
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| 5. |
- Moller, P, et al.
(författare)
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Survival in prospectively ascertained familial breast cancer: Analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy
- 2002
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 101:6, s. 555-559
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Tidskriftsartikel (refereegranskat)abstract
- Dedicated clinics have been established for the early diagnosis and treatment of women at risk for inherited breast cancer, but the effects of such interventions are currently unproven. This second report on prospectively diagnosed inherited breast cancer from the European collaborating centres supports the previous conclusions and adds information on genetic heterogeneity and the effect of oophorectomy. Of 249 patients, 20% had carcinoma in situ (CIS), 54% had infiltrating cancer without spread (CaNO) and 26% had cancer with spread (CaN+). Five-year survival was 100% for CIS, 94% for CaNO and 72% for CaN+ (p = 0.007). Thirty-six patients had BRCA1 mutations, and 8 had BRCA2 mutations. Presence of BRCA1 mutation was associated with infiltrating cancer, high grade and lack of oestrogen receptor (p < 0.05 for all 3 characteristics). For BRCA1 mutation carriers, 5-year survival was 63% vs. 91% for noncarriers (p = 0.04). For CaNO patients, mutation carriers had 75% S-year disease-free survival vs. 96% for noncarriers (p = 0.01). Twenty-one of the mutation carriers had undergone prophylactic oophorectomy, prior to or within 6 months of diagnosis in 13 cases. All but I relapse occurred in the I S who had kept their ovaries, (p < 0.01); no relapse occurred in those who had removed the ovaries within 6 months (p = 0.04) Contralateral cancer was more frequently observed in mutation noncarriers, but this finding did not reach statistical significance. Our findings support the concept that BRCA1 cancer is biologically different from other inherited breast cancers. While current screening protocols appear satisfactory for the majority of women at risk of familial breast cancer, this may not be the case for BRCA1 mutation carriers. The observed effect of oophorectomy was striking.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Balldin, J, et al.
(författare)
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A 6-month controlled naltrexone study: Combined effect with cognitive behavioral therapy in outpatient treatment of alcohol dependence
- 2003
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Ingår i: Alcoholism: Clinical and Experimental Research. - 0145-6008 .- 1530-0277. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: In several studies, patients with alcohol dependence treated with the opioid antagonist naltrexone have shown fewer relapses to heavy drinking than those receiving placebo. An interaction between the naltrexone effect and the type of psychological therapy has been observed. Methods: A 6-month, double-blind, placebo-controlled, parallel-group study was performed at 10 different investigation sites. After a placebo run-in period of 1 week, 118 patients were randomized into 4 treatment groups—50 mg of naltrexone daily or placebo in combination with either cognitive behavioral therapy (CBT) or supportive therapy. The CBT was performed over nine sessions according to the manual of Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity). The supportive therapy was defined as "the treatment as usual." Alcohol consumption, craving, carbohydrate-deficient transferrin, medication compliance by tablet count, and adverse clinical events were assessed at all visits. Other liver enzymes and psychiatric symptoms were also determined. Results: Ninety-one (77%) patients completed the study, and 92 (78%) were 80% compliant with the medication regimen. A lower percentage of heavy-drinking days was shown in the naltrexone group (p = 0.045) compared with the placebo group, as was a lower craving score (p = 0.029). These results are supported by the lower levels of liver enzyme activities (p < 0.010 for aspartate aminotransferase, alanine aminotransferase, and γ-glutamyltransferase), but not by the carbohydrate-deficient transferrin levels, in the naltrexone group. The mean time period before the first day of heavy drinking was longer for the group treated with CBT (p = 0.010), especially in combination with naltrexone (p = 0.007). Naltrexone was well tolerated, and no patients discontinued the study due to side effects. Conclusions: This study supports the effect of naltrexone in outpatient treatment of alcohol dependence and suggests that a beneficial interaction effect with CBT can be expected.
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| 10. |
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| 11. |
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| 12. |
- Borg, H., et al.
(författare)
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High levels of antigen-specific islet antibodies predict future β-cell failure in patients with onset of diabetes in adult age
- 2001
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X. ; 86:7, s. 3032-3038
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Tidskriftsartikel (refereegranskat)abstract
- It is unclear whether high levels of antigen-specific islet antibodies [GADA (glutamic acid decarboxylase 65 antibodies) and IA2-ab (protein tyrosine phosphatase-like protein antibodies)] predict β-cell failure in patients with onset of diabetes in adult age. Therefore, GADA and IA2-ab levels at the diagnosis of diabetes were related to fasting plasma C-peptide levels 5 yr later in 148 patients with diabetes onset in adult age (age at onset, 20-77 yr; median, 57 yr). Classical islet cell antibodies (ICA) were also determined. Complete β-cell failure (undetectable fasting plasma C-peptide) was only present in 4 patients at diagnosis of diabetes, but in 21 patients 5 yr thereafter. At diagnosis, ICA were detected in 20 of 21 (95%) patients with β-cell failure after 5 yr and in only 7 of 127 (5%) without, whereas GADA and/or IA2-ab (>97.5 percentile of healthy controls) were detected in all 21 (100%) with but also in 23 of 127 (18%) patients without β-cell failure after 5 yr. Thus, ICA had a higher positive predictive value (74%) than GADA and/or IA2-ab (47%; P < 0.05). With high cutoff values for GADA and IA2-ab, however, GADA and/or IA2-ab were detected in 19 of 21 (90%) patients with β-cell failure vs. only in 5 of 127 (4%) without, giving a positive predictive value of 79%. Slightly elevated GADA levels in IA2-ab-negative patients were associated with progressive but not complete β-cell failure within the study period. Hence, high GADA and/or IA2-ab levels predict a future complete β-cell failure, whereas low GADA levels predict slowly progressive β-cell insufficiency.
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| 13. |
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| 14. |
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| 15. |
- Borg, Jacqueline, et al.
(författare)
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The serotonin system and spiritual experiences
- 2003
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 160:11, s. 1965-1969
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The serotonin system has long been of interest in biological models of human personality. The purpose of this positron emission tomography (PET) study was to search for relationships between serotonin 5-HT(1A) receptor density and personality traits. METHOD: Fifteen normal male subjects, ages 20-45 years, were examined with PET and the radioligand [(11)C]WAY100635. Personality traits were assessed with the Swedish version of the Temperament and Character Inventory self-report questionnaire. Binding potential, an index for the density of available 5-HT(1A) receptors, was calculated for the dorsal raphe nuclei, the hippocampal formation, and the neocortex. For each region, correlation coefficients between 5-HT(1A) receptor binding potential and Temperament and Character Inventory personality dimensions were calculated and analyzed in two-tailed tests for significance. RESULTS: The authors found that the binding potential correlated inversely with scores for self-transcendence, a personality trait covering religious behavior and attitudes. No correlations were found for any of the other six Temperament and Character Inventory dimensions. The self-transcendence dimension consists of three distinct subscales, and further analysis showed that the subscale for spiritual acceptance correlated significantly with binding potential but not with the other two subscales. CONCLUSIONS: This finding in normal male subjects indicated that the serotonin system may serve as a biological basis for spiritual experiences. The authors speculated that the several-fold variability in 5-HT(1A) receptor density may explain why people vary greatly in spiritual zeal.
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| 16. |
- Borg, K. I., et al.
(författare)
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Force on a spinning sphere moving in a rarefied gas
- 2003
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Ingår i: Physics of fluids. - : AIP Publishing. - 1070-6631 .- 1089-7666. ; 15:3, s. 736-741
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Tidskriftsartikel (refereegranskat)abstract
- The force acting on a spinning sphere moving in a rarefied gas is calculated. It is found to have three contributions with different directions. The transversal contribution is of opposite direction compared to the so-called Magnus force normally exerted on a sphere by a dense gas. It is given by F=-alpha(tau)xi2/3piR(3)mnomegaxv, where alpha(tau) is the accommodation coefficient of tangential momentum, R is the radius of the sphere, m is the mass of a gas molecule, n is the number density of the surrounding gas, omega is the angular velocity, and v is the velocity of the center of the sphere relative to the gas. The dimensionless factor xi is close to unity, but depends on omega and kappa, the heat conductivity of the body.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Kainu, T, et al.
(författare)
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Somatic deletions in hereditary breast cancers implicate 13q21 as a putative novel breast cancer susceptibility locus
- 2000
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Ingår i: Proceedings of the National Academy of Sciences. - 1091-6490. ; 97:17, s. 9603-9608
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Tidskriftsartikel (refereegranskat)abstract
- A significant proportion of familial breast cancers cannot be explained by mutations in the BRCA1 or BRCA2 genes. We applied a strategy to identify predisposition loci for breast cancer by using mathematical models to identify early somatic genetic deletions in tumor tissues followed by targeted linkage analysis. Comparative genomic hybridization was used to study 61 breast tumors from 37 breast cancer families with no identified BRCA1 or BRCA2 mutations. Branching and phylogenetic tree models predicted that loss of 13q was one of the earliest genetic events in hereditary cancers. In a Swedish family with five breast cancer cases, all analyzed tumors showed distinct 13q deletions, with the minimal region of loss at 13q21-q22. Genotyping revealed segregation of a shared 13q21 germ-line haplotype in the family. Targeted linkage analysis was carried out in a set of 77 Finnish, Icelandic, and Swedish breast cancer families with no detected BRCA1 and BRCA2 mutations. A maximum parametric two-point logarithm of odds score of 2.76 was obtained for a marker at 13q21 (D13S1308, theta = 0.10). The multipoint logarithm of odds score under heterogeneity was 3.46. The results were further evaluated by simulation to assess the probability of obtaining significant evidence in favor of linkage by chance as well as to take into account the possible influence of the BRCA2 locus, located at a recombination fraction of 0.25 from the new locus. The simulation substantiated the evidence of linkage at D13S1308 (P < 0.0017). The results warrant studies of this putative breast cancer predisposition locus in other populations.
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| 25. |
- Koul, A., et al.
(författare)
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BRCA1 and BRCA2 mutations in ovarian cancer : Covariation with specific cytogenetic features
- 2000
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Ingår i: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 10:4, s. 289-295
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by screening the entire coding regions of both genes. Seven predicted truncating mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2 were found to be of germline origin. All eight BRCA-positive tumors were serous or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were poorly differentiated. The correlation between tumor karyotype and BRCA status showed that clonal chromosomal aberrations were present in all BRCA-positive tumors (8/8) compared with 20 of 29 BRCA-negative ones. The most consistently affected region in BRCA-positive tumors was the long arm of chromosome 6; alterations within this arm with a breakpoint in band 6q21 were seen in four of five BRCA1-positive and in two of three BRCA2-positive tumors, but only in four of 20 karyotypically abnormal tumors without BRCA mutations, suggesting that the genetic pathways of tumor progression differ in the two groups. The high frequency of germline BRCA mutations detected in this pilot study (16% of 37 invasive carcinomas) points to the need for more extended analyses of population-based series of patients to determine the true contribution of these predisposing genes to the overall incidence of ovarian cancer in this population.
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| 26. |
- Krop, I, et al.
(författare)
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Lack of HIN-1 methylation in BRCAl-linked and "BRCA1-like" breast tumors
- 2003
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Ingår i: Cancer Research. - 1538-7445 .- 0008-5472. ; 63:9, s. 2024-2027
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Tidskriftsartikel (refereegranskat)abstract
- We recently identified a candidate tumor suppressor gene, HIN-1, that is silenced due to methylation in the majority of sporadic breast carcinomas and is localized to 5q33-qter, an area frequently lost in BRCA1 tumors and thought to harbor a BRCA1 modifier gene. To establish whether germ-line mutations in HIN-1 may influence breast cancer risk, we sequenced the HIN-1 coding region in 10 familial breast cancer patients with positive logarithm of the odds scores of at least one of the markers flanking HIN-1. We also sequenced the HIN-1 coding region in 15 BRCA1 and 35 sporadic breast tumors to determine whether HIN-1 is the target of the frequent 5q loss in BRCA1 tumors. No sequence alterations were found in any of the cases analyzed. However, analysis of HIN-1 promoter methylation status revealed that in striking contrast to sporadic cases, there is a nearly complete lack of HIN-1 methylation in BRCA1 tumors (P < 0.0001). Sporadic breast tumors with a "BRCA1-like" histopathological phenotype also demonstrated significantly lower frequency of HIN-1 promoter methylation (P = 0.01) compared with other cancer types, and there was also a difference among tumors based on their estrogen receptor and HER2 status (P = 0.006), suggesting that HIN-1 methylation patterns are associated with specific breast cancer subtypes.
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| 27. |
- Legrand, S., et al.
(författare)
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Hydroxy-methoxybenzoic methyl esters : Synthesis and antifeedant activity on the pine weevil, Hylobius abietis
- 2004
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Ingår i: Zeitschrift für Naturforschung. B, A journal of chemical sciences. - : Walter de Gruyter GmbH. - 0932-0776 .- 1865-7117. ; 59:7, s. 829-835
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Tidskriftsartikel (refereegranskat)abstract
- The pine weevil Hylobius abietis (L.) (Coleoptera: Curculionidae) feeds on the bark of coniferous seedlings and is the economically most important forestry restocking pest in large parts of Europe. Substances with an antifeedant effect may offer an environmentally friendly alternative to insecticides for the protection of planted seedlings. Bioassays were performed on commercial and synthetic methyl hydroxy-methoxybenzoates in order to determine their possible antifeedant activity. Two methyl hydroxy-methoxybenzoates were synthesized by esterification and mono-O-methylation of two dihydroxybenzoic acids. A regioselective protection-deprotection strategy was used in the synthetic pathway of the other non-commercial esters, esterification and selective pivaloylation of the less-hindered hydroxyl group of other commercial dihydroxybenzoic acids gave diester intermediates, which then were O-methylated before methanolysis of the pivaloyl group which yielded the desired non-commercial methyl hydroxy-methoxybenzoates. The five synthesized methyl hydroxy-methoxybenzoic esters were complemented with commercial samples of the five other isomers of methyl hydroxy-methoxybenzoate and spectrometric data were collected for the complete set of isomers. All ten isomers were tested for their antifeedant effect on the pine weevil. The effect varied considerably among the hydroxy-methoxybenzoic esters. Methyl 2-hydroxy-3-methoxybenzoate showed the highest effect and may thus be a candidate for practical use in pine weevil pest management.
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| 28. |
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| 29. |
- Loman, N, et al.
(författare)
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Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a population-based series of early-onset breast cancer
- 2001
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 93:16, s. 23-1215
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: BRCA1 and BRCA2 are the two major susceptibility genes involved in hereditary breast cancer. This study was undertaken to provide reliable population-based estimates of genetic influence and to characterize the nature and prevalence of BRCA1 and BRCA2 germline mutations in early-onset breast cancer.METHODS: In a series comprising all women diagnosed with breast cancer under the age of 41 years in southern Sweden during 1990 through 1995 (n = 262), family history of cancer was evaluated in 95% (n = 250) of the case subjects and germline mutations in BRCA1 and BRCA2 were analyzed in 89% (n = 234). All statistical tests were two-sided.RESULTS: A total of 97 case subjects had at least one first- or second-degree relative with breast or ovarian cancer; 34 (14%; 95% confidence interval [CI] = 9.6% to 18%) cases had at least two first- or second-degree relatives, 22 (8.8%; 95%CI = 5.3% to 12%) had one first-degree relative, and 41 (16%; 95% CI = 12% to 21%) had one second-degree relative with either cancer. If two females affected with breast or ovarian cancer who were related through an unaffected male were also defined as first-degree relatives, then a higher number of case subjects, 120 (48%; 95% CI = 42% to 54%), had at least one first-degree or second-degree relative with breast or ovarian cancer. Sixteen (6.8%; 95% CI = 4.0% to 11%) BRCA1 mutation carriers and five (2.1%; 95% CI = 0.70% to 4.9%) BRCA2 mutation carriers were identified. Among case subjects with one first- or more than one first- or second-degree relative with breast or ovarian cancer, BRCA mutations were more frequent (P<.001) than among the case subjects without this degree of family history. BRCA mutations were also statistically significantly more common among women with bilateral breast cancer than among women with unilateral breast cancer (P =.002). BRCA mutations were more common among younger case subjects than among older ones (P =.0027).CONCLUSIONS: Almost half (48%) of women in southern Sweden with early-onset breast cancer have some family history of breast or ovarian cancer, and 9.0% of early-onset breast cancer cases are associated with a germline mutation in BRCA1 or BRCA2. Mutation carriers were more prevalent among young women, women with at least one first- or second-degree relative with breast or ovarian cancer, and women with bilateral breast cancer.
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| 30. |
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| 31. |
- Mozuraitis, R., et al.
(författare)
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(-)-germacrene D increases attraction and oviposition by the tobacco budworm moth Heliothis virescens
- 2002
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Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 27:6, s. 505-509
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Tidskriftsartikel (refereegranskat)abstract
- The sesquiterpene germacrene D (GD) activates a major type of olfactory receptor neuron on the antennae of the heliothine moths. In Heliothis virescens females, 80% of the recordings have shown activity of one neuron type responding with high sensitivity and selectivity to GD. With the aim of determining the behavioural significance of this sesquiterpene, we have used a two-choice wind-tunnel to study the preference of mated H. virescens females for host plants with and without (-)-GD added. Tobacco plants containing dispensers with low release rate of (-)-GD had a greater attractiveness than tobacco plants without this substance. In addition, a significant increase of oviposition was found on the plants with (-)-GD.
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| 32. |
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| 33. |
- Ohlsson, Bodil, et al.
(författare)
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Continuous infusion of cholecystokinin leads to down-regulation of the cholecystokinin-A receptor in the rat pancreas
- 2000
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 35:6, s. 612-618
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Infusion of sulphated cholecystokinin-8 (CCK-8S) in rats transiently increased the proliferation of pancreatic acinar cells, whereas the CCK-A receptor antagonist devazepide decreased such proliferation. This effect ceased after 3 days. CCK-8S or devazepide injected twice daily induced a persistent effect on the cell proliferation involving the major cells of the exocrine pancreas. The aim of this study was to examine the effect of continuous infusion of CCK-8S and devazepide on CCK-A receptor gene expression. METHODS: Male Sprague-Dawley rats received subcutaneous continuous infusion of 5 microg/kg/h CCK-8S, 200 microg/kg/h devazepide, or 1% bovine serum albumin (BSA) by means of osmotic minipumps. The rats were killed after 4 days; I h before being killed they received 5-bromo-2-deoxyuridine (BrdU) intraperitoneally. Plasma was collected for analysis of CCK. The pancreas was dissected, and indirect immunofluorescence for BrdU and CCK-A receptor was performed. In situ hybridization to CCK-A receptor mRNA was performed for examination and semiquantification of receptor gene expression. RESULTS: Continuous infusion of CCK-8S led to a sixfold increase in plasma CCK and a 40% increase in pancreatic weight. Devazepide did not affect the CCK level but decreased the pancreatic weight by 24% compared with BSA-infused rats. The BrdU labeling indicated that CCK-8S had no effect on cell proliferation. Immunofluorescence for the CCK-A receptor showed a decreased labeling intensity after CCK-8S infusion. The mean optical density of in situ hybridization labeling of the sections from CCK-8S-treated rats was decreased to 37% +/- 3% of that in controls. Devazepide did not affect the CCK-A receptor gene expression. CONCLUSIONS: Continuous stimulation of the CCK-A receptor led to a downregulation of the receptor gene expression in pancreatic acinar cells and decreased labeling of the receptor at immunohistochemistry. The results suggest that down-regulation of the receptor is a protective mechanism against overstimulation.
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| 34. |
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| 35. |
- Rostelien, T., et al.
(författare)
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Selective receptor neurone responses to E-beta-ocimene, beta-myrcene, E,E-alpha-farnesene and homo-farnesene in the moth Heliothis virescens, identified by gas chromatography linked to electrophysiology
- 2000
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Ingår i: Journal of Comparative Physiology A. Sensory, neural, and behavioral physiology. - : Springer Science and Business Media LLC. - 0340-7594 .- 1432-1351. ; 186:9, s. 833-847
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Tidskriftsartikel (refereegranskat)abstract
- An important question in olfaction is for which odorants receptor neurones have evolved. In the present study, olfactory receptor neurones on the antennae of the tobacco budworm moth Heliothis virescens were screened for sensitivity to naturally occurring plant-produced volatiles by the use of gas chromatography linked to electrophysiology. Volatiles of host as well as non-host: plants collected by headspace techniques were used for stimulating the neurones, sequentially via two columns, one polar and one nonpolar installed in parallel in the gas chromatograph. Three types of neurones presented in this paper responded to one, two or three compounds for which the retention times were determined ill both column types. The chemical structures of the active components were determined on the basis of mass spectrometry linked to gas chromatography, indicating E-beta -ocimene and beta -myrcene as stimulants for neurone type 1, E,E,alpha -farnesene for neurone type 2 and homo-farnesene for neurone type 3. Re-testing authentic materials verified the identifications for the type I neurones. The results demonstrate a high specificity for the three types of neurones by strong responses to one or two structurally similar compounds out of hundreds present in a large variety of plants. The study exemplifies plant odour detection by narrowly tuned receptor neurones in a polyphagous moth species.
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| 36. |
- Rostelien, T., et al.
(författare)
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The plant sesquiterpene germacrene D specifically activates a major type of antennal receptor neuron of the tobacco budworm moth Heliothis virescens
- 2000
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Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 25:2, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Plants release hundreds of volatiles that are important in interactions with insects or other organisms. However, knowledge is scarce as to which of the compounds are detected by the organism's olfactory receptor neurons. In the present study, single receptor neurons on the antennae of the tobacco budworm moth, Heliothis virescens, were screened far their sensitivities to naturally produced plant volatiles by the use of gas chromatography linked to electrophysiological recordings from single cells (GC-SCR). Plant volatiles, collected by aeration of host and non-host plants, were tested on each receptor neuron via parallel GC-columns. Thus, simultaneous recordings of the gas chromatogram and the neuron responses to each component were obtained. One type of receptor neuron, appearing in 80% of all experiments, responded with high sensitivity and selectivity to one particular component, present in host as well as non-host mixtures. The component, identified as a sesquiterpene hydrocarbon by linked gas chromatography-mass spectrometry, was isolated from a sesquiterpene fraction of cubebe oil and identified by NMR as germacrene D. The purified compound was then re-tested via gas chromatography on the same receptor neuron type, verifying the identification. A weaker response to another sesquiterpene hydrocarbon was also recorded.
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| 37. |
- Rozenblum, E, et al.
(författare)
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A genomic map of a 6-Mb region at 13q21-q22 implicated in cancer development: identification and characterization of candidate genes
- 2002
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 1432-1203 .- 0340-6717. ; 110:2, s. 111-121
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomal region 13q21-q22 harbors a putative breast cancer susceptibility gene and has been implicated as a common site for somatic deletions in a variety of malignant tumors. We have built a complete physical clone contig for a region between D13S1308 and AFM220YE9 based on 18 yeast artificial chromosome and 81 bacterial artificial chromosome (BAC) clones linked together by 22 genetic markers and 61 other sequence tagged sites. Combining data from 47 sequenced BACs (as of June 2001), we have assembled in silico an integrated 5.7-Mb genomic map with 90% sequence coverage. This area contains eight known genes, two hypothetical proteins, 24 additional Unigene clusters, and approximately 100 predicted genes and exons. We have determined the cDNA and genomic sequence, and tissue expression profiles for the KIAA1008 protein (homologous to the yeast mitotic control protein dis3+), KLF12 (AP-2 repressor), progesterone induced blocking factor 1, zinc finger transcription factor KLF5, and LIM domain only-7, and for the hypothetical proteins FLJ22624 and FLJ21869. Mutation screening of the five known genes in 19 breast cancer families has revealed numerous polymorphisms, but no deleterious mutations. These data provide a basis and resources for further analyses of this chromosomal region in the development of cancer.
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| 38. |
- Schölin, Anna, et al.
(författare)
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Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults : a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden
- 2004
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 255:3, s. 384-391
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- ObjectivesTo establish the prevalence of remaining β-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later.DesignPopulation-based cohort study.SettingNationwide from all Departments of Medicine and Endocrinology in Sweden.SubjectsA total of 312 young (15–34 years old) adults diagnosed with diabetes during 1987–88.Main outcome measurePlasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved β-cell function was defined as measurable C-peptide levels. Three islet antibodies – cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies – were measured.ResultsAmongst 269 islet antibody positives (ab+) at diagnosis, preserved β-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m−2, respectively; P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively; P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively; P = 0.007) at diagnosis compared with ab+ without remaining β-cell function. Amongst the 241 patients without detectable β-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up.ConclusionsSixteen per cent of patients with autoimmune type 1 diabetes had remaining β-cell function 8 years after diagnosis whereas 5.8% with β-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up.
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| 39. |
- Stranden, M., et al.
(författare)
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(-)-germacrene D receptor neurones in three species of heliothine moths : structure-activity relationships
- 2003
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Ingår i: Journal of Comparative Physiology A. Sensory, neural, and behavioral physiology. - : Springer Science and Business Media LLC. - 0340-7594 .- 1432-1351. ; 189:7, s. 563-577
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Tidskriftsartikel (refereegranskat)abstract
- Specificity of olfactory receptor neurones plays an important role in food and host preferences of a species, and may have become conserved or changed in the evolution of polyphagy and oligophagy. We have identified a major type of plant odour receptor neurones responding to the sesquiterpene germacrene D in three species of heliothine moths, the polyphagous Heliothis virescens and Helicoverpa armigera and the oligophagous Helicoverpa assulta. The neurones respond with high sensitivity and selectivity to (-)-germacrene D, as demonstrated by screening via gas chromatography with numerous mixtures of plant volatiles. Germacrene D was present in both host and non-host plants, but only in half of the tested species. The specificity of the neurones was similar in the three species, as shown by the 'secondary' responses to a few other sesquiterpenes. The effect of (-)-germacrene D was about ten times stronger than that of the (+)-enantiomer, which again was about ten times stronger than that of (-)-alpha-ylangene. Weaker effects were obtained for (+)-beta-ylangene, (+)-alpha-copaene, beta-copaene and two unidentified sesquiterpenes. The structure-activity relationship shows that the important properties of (-)-germacrene D in activating the neurones are the ten-membered ring system and the three double bonds acting as electron-rich centres, in addition to the direction of the isopropyl-group responsible for the different effects of the germacrene D enantiomers.
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| 40. |
- Stranden, M., et al.
(författare)
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Receptor neuron discrimination of the germacrene D enantiomers in the moth Helicoverpa armigera
- 2002
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Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 27:2, s. 143-152
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Tidskriftsartikel (refereegranskat)abstract
- Plants release complex mixtures of volatiles, including chiral constituents. In the search for the biologically relevant plant odorants, gas chromatography linked to electrophysiological recordings from single receptor neurons has been employed. In heliothine moths, including the females of the Eurasian cotton bollworm moth Helicoverpa armigera, a major type of receptor neurons is identified, showing high sensitivity and selectivity for the sesquiterpene germacrene D. In the present study, gas chromatography with a chiral column linked to single cell recordings were performed. It was found that all germacrene D neurons belonged to one type; all responded to both enantiomers, but (-)-germacrene D had similar to 10 times stronger effect than (+)-germacrene D. Parallel dose-response curves for the two enantiomers were obtained by direct stimulations. The enantiomeric composition of germacrene D, which differed in six plant species and in different individuals of one species, was determined on the basis of the neuron responses. The results, showing the presence of one neuron type for receiving the information about germacrene D in the various plants, suggests that the two enantiomers mediate the same kind of information to the moth, but with different intensity.
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| 41. |
- Stranden, M., et al.
(författare)
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Receptor neurones in three heliothine moths responding to floral and inducible plant volatiles
- 2003
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Ingår i: Chemoecology. - : Springer Science and Business Media LLC. - 0937-7409 .- 1423-0445. ; 13:3, s. 143-154
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Tidskriftsartikel (refereegranskat)abstract
- Some plant volatiles are produced in response to herbivory of several insect species, including heliothine larvae. In the present study of female heliothine moths, four co-located receptor neurone types were identified, of which three types responded strongest to the inducible compounds E-beta-ocimene, E,E-alpha-farnesene and E,E-TMTT, respectively. The fourth type responded strongest to geraniol, which is a common floral volatile. The narrow tuning of each receptor neurone type was demonstrated by responses to a few structurally-related monoterpenes, sesquiterpenes, homo-terpenes and monoterpene alcohols, respectively, out of hundreds of plant constituents tested. The four neurone types showed the same relation of spike amplitudes and ranking of effective compounds in the three heliothine species; the polyphagous Heliothis virescens and Helicoverpa armigera and the oligophagous Helicoverpa assulta. The results indicate the presence of functionally similar types of plant odour-receptor neurones in the three related species, and suggest conservation or reappearance of functionally similar olfactory receptors in related species, independent of the evolution of polyphagy and oligophagy.
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| 42. |
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| 43. |
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