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Biomedical subjects

E Lund

Publications and source records attributed to E Lund.

At least 109 records · Page 6Linked to original sources
PubMed1997

Selection and nuclear immobilization of exportable RNAs.

The intracellular distribution of RNAs depends on interactions of cis-acting nuclear export elements or nuclear retention elements with trans-acting nuclear transport or retention factors. To learn about the relationship between export and retention, we isolated RNAs that are exported from nuclei of Xenopus laevis oocytes even when most RNA export is blocked by an inhibitor of Ran-dependent nucleocytoplasmic transport, the Matrix protein of vesicular stomatitis virus. Export of the selected RNAs is saturable and specific. When present in chimeric RNAs, the selected sequences acted like nuclear export elements in promoting efficient export of RNAs that otherwise are not exported; the pathway used for export of these chimeric RNAs is that used for the selected RNAs alone. However, these chimeric RNAs, unlike the selected RNAs, were not exported in the presence of Matrix protein; thus, the nonselected sequences can cause retention of the selected RNA sequences under conditions of impaired nucleocytoplasmic transport. We propose that most RNAs are transiently immobilized in the nucleus and that release of these RNAs is an essential and early step in export. Release correlates with functional Ran-dependent transport, and the lack of export of chimeric RNAs may result from interference with the Ran system.

Animals↗
PubMed1997

Inhibition of Ran guanosine triphosphatase-dependent nuclear transport by the matrix protein of vesicular stomatitis virus.

Transport of macromolecules into and out of nuclei, essential steps in gene expression, are potential points of control. The matrix protein (M protein) of vesicular stomatitis virus (VSV) was shown to block transport of RNAs and proteins between the nucleus and cytoplasm of Xenopus laevis oocytes. The pattern of inhibition indicated that M protein interfered with transport that is dependent on the ras-like nuclear guanosine triphosphatase (GTPase) Ran-TC4 and its associated factors. This inhibition of nuclear transport by M protein explains several observations about the effects of VSV infection on host cell gene expression and suggests that RNA export is closely coupled to protein import.

Animals↗
PubMed1997

Control of mouse U1 snRNA gene expression during in vitro differentiation of mouse embryonic stem cells.

Early in mouse development, two classes of U1 RNAs, mU1a and mU1b, are synthesized, but as development proceeds, transcription of the embryo-specific mU1b genes is selectively down-regulated to a barely detectable level. We show here that during in vitro differentiation of mouse embryonic stem (ES) cells, both exogenously introduced and endogenous U1b genes are subject to normal developmental regulation. Thus, ES cells represent a convenient isogenic system for studying the control of expression of developmentally regulated snRNA genes. Using this system, we have identified a region in the proximal 5'flanking region, located outside the PSE element, that is responsible for differential transcription of the mU1a and mU1b genes in both developing cells and transiently transfected NIH 3T3 cells.

3T3 Cells↗
PubMed1997

Physical activity and the risk of breast cancer.

BACKGROUND: Because physical activity may affect hormonal concentrations and energy balance, we decided to investigate whether everyday exercise is related to the risk of breast cancer. METHODS: During 1974 to 1978 and 1977 to 1983, a total of 25,624 women, 20 to 54 years of age at entry, enrolled in health surveys and answered questionnaires about leisure-time and work activity. RESULTS: During a median follow-up of 13.7 years, we identified 351 cases of invasive breast cancer among the 25,624 women in the cohort. Greater leisure-time activity was associated with a reduced risk of breast cancer, after adjustments for age, body-mass index (the weight in kilograms divided by the square of the height in meters), height, parity, and county of residence (relative risk, 0.63; 95 percent confidence interval, 0.42 to 0.95), among women who exercised regularly, as compared with sedentary women (P for trend=0.04). In regularly exercising women, the reduction in risk was greater in premenopausal women than in postmenopausal women, and greater in younger women (<45 years at study entry) than in older women (> or =45 years) (relative risk, 0.38; 95 percent confidence interval, 0.19 to 0.79). In stratified analyses the risk of breast cancer was lowest in lean women (body-mass index, <22.8) who exercised at least four hours per week (relative risk, 0.28; 95 percent confidence interval, 0.11 to 0.70). The risk was also reduced with higher levels of activity at work, and again there was a more pronounced effect among premenopausal than postmenopausal women. CONCLUSIONS: Physical activity during leisure time and at work is associated with a reduced risk of breast cancer.

Adult↗
PubMed1997

In vivo selection of RNAs that localize in the nucleus.

Nuclear localization of an RNA is affected by cis-acting elements (NLEs) that lead to nuclear import or retention or to blockage of export from the nucleus. To identify such elements, we selected and analyzed transcripts that localized in the nuclei of Xenopus laevis oocytes. The RNAs were isolated from a collection of m7G-capped RNAs in which a combinatorial library (n = 20) of sequences had been inserted. One class of selected RNAs (Sm+) had a consensus Sm binding site (AAUUUUUGG) and bound Sm proteins in the cytoplasm; these RNAs resembled small nuclear RNAs like U1 and U5 RNAs in their bi-directional nucleocytoplasmic transport and their 5'-cap hypermethylation. Another class, Sm- RNAs, contained sequences that masked the m7G-caps of the RNAs and promoted interaction with La protein. These RNAs were retained within nuclei after nuclear injection and were imported when injected into the cytoplasm. Their nuclear import and retention were independent of a 5'-cap, required an imperfect double-stranded stem near the 5' end, and depended on interaction with La protein. Import of the Sm- RNAs, while using the import pathway of proteins, was distinct from that of U6 RNA.

Animals↗
PubMed1997

The vertebrate GLFG nucleoporin, Nup98, is an essential component of multiple RNA export pathways.

The 97-kD O-linked glycoprotein, Nup98, is a component of the Xenopus laevis nuclear pore complex and the only vertebrate GLFG nucleoporin identified (Powers, M.A., C. Macauley, F. Masiarz, and D.J. Forbes. 1995. J. Cell Biol. 128:721-736). We have investigated possible roles of xNup98 in the nucleocytoplasmic transport of proteins and RNAs by analyzing the consequences of injecting monospecific polyclonal antibodies to xNup98 into X. laevis oocytes. We show here that nuclear injection of anti-xNup98 inhibited the export of multiple classes of RNAs, including snRNAs, 5S RNA, large ribosomal RNAs, and mRNA. In contrast, the export of tRNA was unaffected. Injection of anti-xNup98 into the oocyte cytoplasm had no effect on export of any of the RNAs. Significantly, nuclear injection of anti-xNup98 antibodies did not inhibit import of either karyophilic proteins or snRNPs. This latter result is in agreement with our previous finding that Nup98 is not an essential element of the protein import pathway. Thus, Nup98 plays a role specifically in RNA export from the nucleus, and it appears to be an essential component of multiple RNA export pathways.

Animals↗
PubMed1997

The influence of physical activity on lung-cancer risk: A prospective study of 81,516 men and women.

Physical activity is inversely related to mortality from respiratory diseases including lung cancer. Physical activity improves pulmonary function but its impact on lung-cancer risk has not been studied much. During 1972-1978, 53,242 men and 28,274 women, aged 20 to 49 years, participated in a population-based health survey and were followed until 31 December 1991. We observed a total of 413 men and 51 women with lung cancer. Leisure activity and work activity were assessed using a questionnaire in 4 categories. In a sub-cohort, physical activity was assessed twice at an interval of 3 to 5 years. Leisure but not work activity was inversely related to lung-cancer risk in men after adjustment for age, smoking habits, body-mass index and geographical residence (p for trend = 0.01). Men who exercised at least 4 hours a week had a lower risk than men who did not exercise [relative risk (RR) = 0.71; 95% confidence interval (CI) = 0.52-0.97]. Reduced risk of lung cancer was particularly marked for small-cell carcinoma (RR = 0.59; 95% CI = 0.38-0.94) and for adenocarcinoma (RR = 0.65; 95% CI = 0.41-1.05), with no association seen for squamous-cell carcinoma. In the sub-cohort in which physical activity was assessed twice, the risk of lung cancer was particularly reduced among men who were most active at both assessments (RR = 0.39; 95% CI = 0.18-0.85). No consistent association between physical activity and lung-cancer risk was observed among women. Our results suggest that leisure physical activity has a protective effect on lung-cancer risk in men. The small number of incident cases, combined with the narrow range of physical activity reported, may have limited our ability to detect an association between physical activity and lung cancer in women.

Adenocarcinoma↗
PubMed1997

Coupling of nuclear RNA export and protein import in vertebrate cells.

Nuclear RNA export is a highly dynamic process in which factors that carry the RNAs out of the nucleus must be re-imported. These RNA export factors are bifunctional molecules that recognize specific RNA sequences or structures and interact with shared nuclear proteins, including components of the nuclear pore complex. Inhibition of protein import by inactivation of the GTPase Ran, or its associated activating and recycling factors, blocks RNA export. However a few classes of RNAs escape this inhibition, perhaps because they do not use shuttling export factors or their factors have been stockpiled in the nucleus. Because of its critical role in gene expression, RNA export is a target for control by both cells and viruses.

Journal Article↗
PubMed1997

Diet and the risk of papillary and follicular thyroid carcinoma: a population-based case-control study in Sweden and Norway.

A population-based case-control study was conducted in two regions of Sweden and Norway to investigate the association between dietary habits and the risk of thyroid cancer. The consumption of selected foods was reported in a self-completed food-frequency questionnaire by 246 cases with histologically confirmed papillary (n = 209) and follicular (n = 37) thyroid carcinoma, and 440 age- and gender-matched controls. Odds ratios (OR) and their 95 percent confidence interval (CI) were calculated as estimates of the relative risk using conditional logistic regression. High consumption of butter (OR = 1.6, CI = 1.1-2.5) and cheese (OR = 1.5, CI = 1.0-2.4) was associated with increased risks. Residence in areas of endemic goiter in Sweden was associated with an elevated risk, especially among women (OR = 2.5, CI = 1.3-4.9). High consumption of cruciferous vegetables was associated with increased risk only in persons who ever lived in such areas. A decreased risk was associated with consumption of iodized salt in northern Norway, and with use of iodized salt during adolescence among women (OR = 0.6, CI = 0.6-1.0). The results of this study suggest a role of diet and environment in the risk of thyroid cancer.

Adolescent↗
PubMed1997

Serum phospholipid fatty acid composition and habitual intake of marine foods registered by a semi-quantitative food frequency questionnaire.

OBJECTIVE: To examine the relation between consumption of fish and fish products registered by a comprehensive food frequency questionnaire and the composition of fatty acids in serum phospholipids. DESIGN: Cross-section study. SETTING: Cardiovascular screening centre in Trondheim, Mid-Norway. SUBJECTS: Of 256 eligible women 242 agreed to participate in the present study. Altogether 234 middle-aged women (91.4%) completed the questionnaire and gave a valid blood sample. RESULTS: Total frequency consumption of fish for dinner showed only weak association with serum phospholipid fatty acid composition. In separate analyses of lean and fatty fish, consumption of fatty fish was negatively associated with n-6 and positively associated with n-3 fatty acids in serum phospholipids, while no significant associations were found for lean fish consumption. Cod liver oil consumption was strongly related to the phospholipid fatty acid composition. The associations improved moderately when adding portion size information. Spearman's correlation coefficient between dietary intake of eicosapentaenoic acid (EPA) and serum phospholipid EPA was 0.58, and Spearman's correlation coefficient between intake of docosahexaenoic acid (DHA) and serum phospholipid DHA was 0.53. CONCLUSIONS: This study suggests that in populations with a high consumption of fish and cod liver oil, habitual intake can be reflected in serum phospholipids. However, as the fat content of fish is highly variable, separate registration of lean and fatty fish consumption is needed.

Adult↗
PubMed1997

Childbearing and mortality from cancer of the corpus uteri.

BACKGROUND: To investigate the mortality from cancer of the corpus uteri in relation to parity and age at first and last birth. METHODS: A cohort of 431,604 married women aged 45-74 years at the Norwegian Census in 1970 was followed over 15 years. A total of 752 deaths from cancer of the corpus uteri were diagnosed during follow-up. RESULTS: All age groups showed significant trends of decreasing mortality rates with increasing number of children. The age-adjusted reduction in mortality was 9.2% (95% CI 5.2-13.0) for each child. Women with 8-11 children had a relative risk of 0.35 (95% CI 0.14-0.85) compared to nulliparous women. For first birth at age > = 35 years versus < = 19 years, the relative risk was 0.53 (95% CI 0.34-0.83). No significant effect of age at last birth was found. CONCLUSIONS: This study supports the notion that high parity and postponing the first delivery may reduce the risk of uterine cancer death.

Age Factors↗
PubMed1997

K-ras mutations and prognosis in large-bowel carcinomas.

BACKGROUND: Colorectal carcinogenesis is regarded as a multistep process involving several genetic alterations, with mutation in the K-ras gene in about half of the tumours. We aimed at clarifying the role of this genetic alteration related to survival and clinicopathologic variables. METHODS: One hundred large-bowel carcinomas operated on between 1978 and 1982 were studied for the presence of point mutations in codons 12 and 13 of the K-ras gene, using enriched polymerase chain reaction amplification, restriction fragment length polymorphism analysis, and direct sequencing. RESULTS: Forty mutations were found (40%): 31 in codon 12 and 9 in codon 13, 7 different types. There was no relationship between tumours with and without K-ras mutations with regard to Dukes' stages, age or sex of the patient, tumour localization, histologic grade, DNA ploidy pattern, HLA-DR staining pattern, or survival. Samples from 5 different localizations in 7 carcinomas showed identical K-ras mutation pattern, as did 19 recurrences/ metastases originating from 11 carcinomas. CONCLUSIONS: When present, the primary tumour shows homogeneous distribution of K-ras mutation, and the mutation follows the carcinoma in the secondary deposit, regardless of lymphogenous or hematogenous spread. The presence of K-ras mutation does not seem to have prognostic significance for the patient, and the precise nucleotide change is furthermore not predictive of tumour behaviour.

Adult↗
PubMed1996

[Health effects of plutonium pollution--assessment after the Thule disaster in 1968].

On 21 January 1968 a B-52 airplane with four nuclear weapons crashed on the ice close to the Thule air base in northern Greenland. Approximately six kilograms of plutonium was dispersed in the surroundings. Since 1968, the possible health impacts among the Danish civilian workers who assisted at the clean-up have been discussed regularly. A Nordic expert group was appointed by the Danish government to examine the evidence. The group concluded in May 1995 that no conclusive evidence of damage to the health of the worker as a result of plutonium pollution had been reported. However, they recommended continued follow-up of record linkage studies on cancer and a closer investigation of the rare skin disease parapsoriasis en plaque.

Accidents, Aviation↗
PubMed1996

The oxysterols cholest-5-ene-3 beta,4 alpha-diol, cholest-5-ene-3 beta,4 beta-diol and cholestane-3 beta,5 alpha,6 alpha-triol are formed during in vitro oxidation of low density lipoprotein, and are present in human atherosclerotic plaques.

Isolated human low density lipoprotein (LDL) was oxidized with either cupric ions or soybean lipoxygenase and linoleic acid. Cholesterol oxidation products (oxysterols) were determined by isotope dilution gas chromatography-mass spectrometry. A new cholestane-3,5,6-triol isomer, cholestane-3 beta,5 alpha,6 alpha-triol, which has not previously been recognized as a cholesterol autoxidation product, was found at similar concentrations as the well-known cytotoxic cholestane-3 beta,5 alpha,6 beta-triol during both copper- and lipoxygenase-mediated LDL oxidation. Furthermore, two epimeric cholest-5-ene-3 beta,4-diols were identified in the oxidized LDL at similar concentrations. These two isomers were also identified in human atherosclerotic tissue in a ratio of 1:1 at a concentration more than 10-times higher than in non-atherosclerotic vessels. In vitro oxidation of LDL under an 18O2 atmosphere revealed that molecular oxygen was the only source of the oxygen functions at C-4 in the cholest-5-ene-3 beta,4-diols. Taken together, these findings suggest that the cholest-5-ene-3 beta,4-diols in atherosclerotic plaques are formed by autoxidation.

Arteriosclerosis↗
PubMed1996

Detection of defective 3 beta-hydroxysterol delta 7-reductase activity in cultured human fibroblasts: a method for the diagnosis of Smith-Lemli-Opitz syndrome.

Patients with the autosomal recessive disorder Smith-Lemli-Optiz syndrome (SLO) have recently been shown to have markedly increased tissue levels of certain cholesterol biosynthesis intermediates, most notably 7-dehydrocholesterol. The findings strongly suggest a block in the step that catalyses reduction of 7-dehydrocholesterol to cholesterol. The accumulation of 7-dehydrocholesterol can generally easily be detected in serum by gas chromatography-mass spectrometry. However, it could not be totally ruled out that SLO patients with less severe enzyme defects could escape detection by this method. A more direct way of diagnosing a defect in 7-dehydrocholesterol reduction would be to assay the conversion of 7-dehydrocholesterol to cholesterol in cultured fibroblasts from patients with suspected SLO. In the present work, an assay for the conversion of [3H]lathosterol to [3H]cholesterol in cultured human fibroblasts is described. Lathosterol is the immediate precursor of 7-dehydrocholesterol in the cholesterol biosynthetic pathway and was chosen for the assay instead of 7-dehydrocholesterol owing to the difficulty in preparation and handling of the latter compound. Fibroblasts from control subjects converted [3H]lathosterol to [3H]cholesterol efficiently, whereas in fibroblasts from SLO patients the conversion did not go beyond 7-dehydrocholesterol. It is concluded that the present method is useful for the diagnosis of SLO.

Cells, Cultured↗
PubMed1996

Spiritual healing among Norwegian hospitalised cancer patients and patients' religious needs and preferences of pastoral services.

In a national questionnaire-based multicentre study, the use of 'alternative medicine', here called non-proven therapy (NPT), was examined. Five questions about the patients' religious beliefs and their preferences concerning pastoral services in the hospitals were included. Among the 911 invited patients, 642 (70.5%) were included in the analysis. Spiritual healing, defined as faith healing and healing by hand, was the most frequently used NPT among Norwegian cancer patients. Almost 50% of cancer patients using spiritual healing had used NPTs, mainly spiritual healing, prior to the diagnosis of cancer. Women, elderly people and patients using faith healing described themselves more often as religious. 139 (23%) of the responding patients reported a strengthening of their religious belief after the diagnosis of cancer. Patients less than 45 years of age and better educated patients expressed more frequently that all patients should be offered pastoral services during the hospital stay. Older patients, in spite of being more religious, expressed that the patients themselves had to request such services.

Adolescent↗
PubMed1996

Physical activity and risk of colorectal cancer in men and women.

We examined the association between self-reported occupational and recreational physical activity and the subsequent risk of colorectal cancer in a population-based cohort in Norway. During a mean follow-up time of 16.3 years for males and 15.5 years for females, 236 and 99 colon cancers and 170 and 58 rectal cancers were observed in males and females, respectively, among 53,242 males and 28,274 females who attended the screening between 1972 and 1978. Physical activity at a level equivalent to walking or bicycling for at least four hours a week during leisure-time was associated with decreased risk of colon cancer among females when compared with the sedentary group (RR = 0.62, 95% CI 0.40-0.97). Reduced risk of colon cancer was particularly marked in the proximal colon (RR = 0.51, 95% CI 0.28-0.93). This effect was not observed for occupational physical activity alone, probably due to a narrow range of self-reported physical activity at work among females. However, by combining occupational and recreational physical activity we observed an inverse dose-response effect as increasing total activity significantly reduced colon cancer risk (P for trend = 0.04). Among males 45 years or older at entry to the study, an inverse dose-response effect was observed between total physical activity and colon cancer risk (P for trend = 0.04). We also found in males a stronger preventive effect for physical activity in the proximal as compared to distal colon. In addition, we found a borderline significant decrease in colon cancer risk for occupational physical activity in males 45 years or older when compared to the sedentary group (RR = 0.74, 95% CI 0.53-1.04). All results were adjusted for age, body mass index, serum cholesterol and geographic region. No association between physical activity and rectal cancer was observed in males or females. The protective effect of physical activity on colon cancer risk is discussed in regard to energy balance, dietary factors, age, social class, body mass index and gastrointestinal transit time.

Adult↗