PubMed Health⌕ Search

Biomedical subjects

E Lund

Publications and source records attributed to E Lund.

At least 19 recordsLinked to original sources
PubMed1995

A common maturation pathway for small nucleolar RNAs.

We have shown that precursors of U3, U8 and U14 small nucleolar RNAs (snoRNAs) are not exported to the cytoplasm after injection into Xenopus oocyte nuclei but are selectively retained and matured in the nucleus, where they function in pre-rRNA processing. Our results demonstrate that Box D, a conserved sequence element found in these and most other snoRNAs, plays a key role in their nuclear retention, 5' cap hypermethylation and stability. Retention of U3 and U8 RNAs in the nucleus is saturable and relies on one or more common factors. Hypermethylation of the 5' caps of U3 RNA occurs efficiently in oocyte nuclear extracts lacking nucleoli, suggesting that precursor snoRNAs are matured in the nucleoplasm before they are localized to the nucleolus. Surprisingly, m7G-capped precursors of spliceosomal small nuclear RNAs (snRNAs) such as pre-U1 and U2, can be hypermethylated in nuclei if the RNAs are complexed with Sm proteins. This raises the possibility that a single nuclear hypermethylase activity may act on both nucleolar and spliceosomal snRNPs.

Animals↗
PubMed1995

Predicting acute maxillary sinusitis in a general practice population.

OBJECTIVE: To evaluate the diagnostic value of symptoms, signs, erythrocyte sedimentation rate, and C reactive protein for acute maxillary sinusitis. DESIGN: Prospective cohort study. SETTING: Danish general practice in cooperation with the otorhinolaryngology and neuroradiology department at Aalborg County Hospital. SUBJECTS: 174 patients aged 18-65 years who were suspected by the general practitioner of having acute maxillary sinusitis. MAIN OUTCOME MEASURE: The independent association of symptoms, signs, erythrocyte sedimentation rate, and concentration of C reactive protein in patients with acute maxillary sinusitis defined as purulent or mucopurulent antral aspirate. RESULTS: Only raised erythrocyte sedimentation rate (P = 0.01) and raised C reactive protein (P = 0.007) were found to be independently associated with a diagnosis of acute maxillary sinusitis. The combination of the two variables had a sensitivity of 0.82 and a specificity of 0.57. CONCLUSION: Erythrocyte sedimentation rate and C reactive protein are useful diagnostic criteria for acute maxillary sinusitis.

Acute Disease↗
PubMed1995

Diverse effects of the guanine nucleotide exchange factor RCC1 on RNA transport.

Transport of RNAs within nuclei and through nuclear pore complexes (NPCs) are essential, but poorly understood, steps in gene expression. In experiments with mammalian cells, RCC1, the abundant nuclear guanine nucleotide exchange factor for the guanosine triphosphatase Ran/TC4, was shown to be required for nucleocytoplasmic transport of precursors of spliceosomal small nuclear RNAs (snRNAs), intranuclear transport of U3 snRNA, and processing of ribosomal RNAs, but not for export of transfer RNAs. It is proposed that guanosine triphosphate (GTP)-bound Ran/TC4 associates with ribonucleoprotein particles (RNPs) during intranuclear movement, and that GTP hydrolysis promotes deposition of RNPs at targeted sites such as NPCs or nucleoli.

Biological Transport↗
PubMed1995

Comparison of additive and multiplicative models for reproductive risk factors and post-menopausal breast cancer.

The mathematical multistage model of carcinogenesis proposed by Breslow and Day indicates that if hormonal risk factors for breast cancer are late-stage carcinogens then the use of an additive model (excess absolute risk) should be preferrable to the present standard use of the multiplicative model (excess relative risk). To test different models, information from a large prospective study of 431,604 women aged 45-74 years in 1970 with follow-up to 1985 on reproductive factors and post-menopausal breast cancer mortality was used to compute goodness-of-fit statistics. The relative risk function, ranging from multiplicative to additive, was explored by changing the exponent in a power transformation. The analysis found evidence of better fit by the additive compared with the multiplicative models, consistent with the proposed mathematical model.

Aged↗
PubMed1995

Determination of cholesterol oxidation products in human plasma by isotope dilution-mass spectrometry.

A method based on isotope dilution-mass spectrometry was developed for the determination of nine cholesterol oxidation products in human plasma. The cholesterol oxidation products determined were cholest-5-ene-3 beta,7 alpha-diol, cholest-5-ene-3 beta,7 beta-diol (7 alpha- and 7 beta-hydroxycholesterol, respectively), 3 beta-hydroxycholest-5-en-7-one(7-oxocholesterol),5,6 alpha-epoxy-5 alpha- cholestan-3 beta-ol (cholesterol-5 alpha,6 alpha-epoxide),5,6 beta-epoxy-5 beta-cholestan-3 beta-ol (cholesterol-5 beta,6 beta-epoxide), (cholesterol-5 beta,6 beta-epoxide), cholestane-3 beta,5 alpha,6 beta-triol, cholest-5-ene-3 beta,24-diol (24-hydroxycholesterol), cholest-5-ene-3 beta,25-diol (25-hydroxycholesterol), and cholest-5-ene-3 beta,27-diol (27-hydroxycholesterol). A corresponding deuterium-labeled internal standard, containing 3 to 6 deuterium atoms, was synthesized for each cholesterol oxidation product except 5 beta,6 beta-epoxycholesterol which was determined using the internal standard for 5 alpha,6 alpha-epoxycholesterol. Plasma from 31 healthy volunteers was analyzed by the new method and 27-, 24-, and 7 alpha-hydroxycholesterol were the most abundant cholesterol oxidation products (mean values 154, 64, and 43 ng/ml, respectively). The other oxysterols determined were present in concentrations lower than 30 ng/ml. Males had higher 27-hydroxycholesterol concentrations in plasma than females. The 5,6-oxygenated products were present mainly unesterified while the other oxidation products were mostly in esterified form.

Cholesterol↗
PubMed1995

Prevalence and some clinical aspects of atopic dermatitis in the community of Sør-Varanger.

A study of the prevalence of atopic dermatitis among 7-12-year-old children was carried out in a rural community in Northern Norway close to the Russian border. Of the 424 children investigated, 37% had a past and/or present history of atopic dermatitis (cumulative incidence), whereas 23% were classified as having atopic dermatitis by clinical examination (point prevalence). A history of atopic dermatitis during the past year was reported by 26% of the children. Flexural lichenified dermatitis was present in 88%, and 12% of the children had facial and extensor involvement with or without hand dermatitis. Two thirds of the children showed mild and one third moderate symptoms; only 3 children had severe symptoms confirmed by clinical examination. The ratio of girls with atopic dermatitis to boys with atopic dermatitis was about 1.3:1. Onset of atopic dermatitis within the first 2 years of life occurred in 64% of cases, with no sex differences. Remission of atopic dermatitis occurred in 1 of 8 before the age of 5, with earlier cessation in boys. Mucous membrane atopy alone was reported by 13% of them and in combination with atopic dermatitis also in 13%. Parental history of atopic diseases was reported by 37% of all children, more frequently in mothers than in fathers. In families with no parental history of atopic diseases, 41% of the children appeared to develop some kind of atopic disease; this increased to 63% with a single and to 75% with a double parental history.(ABSTRACT TRUNCATED AT 250 WORDS)

Age of Onset↗
PubMed1995

Use of non-proven therapies. Differences in attitudes between Norwegian patients with non-malignant disease and patients suffering from cancer.

A comparative study was conducted between a group of patients with non-malignant diseases in general practice and a group of cancer patients seen in the Department of Oncology at the University Hospital of Tromsø. The aim of the study was to investigate the prevalent use of 'alternative medicine', here called non-proven therapies (NPTs), among cancer patients and general practice patients, and to investigate whether there are any differences in opinion between the two groups regarding the beneficial effects of NPTs as treatment modalities for cancer. A total of 305 general practice patients and 252 cancer patients were included in the final analysis. In both groups close on 20% had been or were present users of NPTs. Among cancer patients the most preferred NPTs methods were healing by laying on of hands and faith healing. The patients with non-malignant disease expressed a more positive view on the possible benefits of NPTs in the fight against cancer than that expressed by the cancer patients. A total of 63.4% of patients from general practice stated that NPTs ought to be an option for cancer patients within Norwegian hospitals.

Adolescent↗
PubMed1994

Physical activity and the risk of prostate and testicular cancer: a cohort study of 53,000 Norwegian men.

The associations between recreational and occupational physical activity and the subsequent risk of prostate and testicular cancer were examined in a population-based cohort study of 53,242 men in Norway. Age at study entry was 19 to 50 years. Information on physical activity was based on questionnaire responses and a brief clinical examination. A total of 220 prostate and 47 testicular cancer cases were recorded in the Cancer Registry of Norway during a mean follow-up time of 16.3 years. We found a nonsignificant, reduced, adjusted relative risk (RR) of prostate cancer with increased level of physical activity at work and among those men with the greatest recreational physical activity. When occupational and recreational physical activity were combined, a reduced adjusted risk of prostate cancer was observed among men who walked during occupational hours and performed either moderate recreational activity (RR = 0.61, 95 percent confidence interval [CI] = 0.36 to 1.01) or regular recreational training (RR = 0.45, CI = 0.20 to 1.01) relative to sedentary men (test for trend, P = 0.03). Physically active men who were older than 60 years of age at diagnosis showed a reduced adjusted RR of borderline significance, while no association was observed for younger men. No evidence was found for any association between physical activity and testicular cancer regardless of physical activity at work and recreation.

Adolescent↗
PubMed1992

Evidence that 24- and 27-hydroxylation are not involved in the cholesterol-induced down-regulation of hydroxymethylglutaryl-CoA reductase in mouse liver.

Several authors have suggested that 27-hydroxycholesterol may be an important physiological regulator of cholesterol homeostasis. In the present study we investigated the possibility that 24- or 27-hydroxylation of cholesterol is of importance for the down-regulation of hydroxymethylglutaryl (HMG)-CoA reductase in mouse liver induced by dietary cholesterol. Using an accurate method based on isotope dilution-mass spectrometry with deuterated internal standards, we were able to detect significant levels of both 24- and 27-hydroxycholesterol in liver homogenates from normal mice. Feeding cholesterol, 2% for 4 days, increased the levels by 80 and 30%, respectively. No significant hepatic levels of 25-hydroxycholesterol could be demonstrated in untreated mice, and the level of this steroid in cholesterol-treated mice was just above the detection limit. Mouse liver mitochondria were able to catalyze 24- as well as 27-hydroxylation, but not 25-hydroxylation of cholesterol. There was no such conversion in liver microsomes. When using 24-2H2- or 23,23,24,24,25-2H5-labeled cholesterol as substrate a kinetic isotope effect of about 4.5 was observed for the mitochondrial 24-hydroxylation. When using 26,26,26,27,27,27-2H6-labeled cholesterol as substrate a kinetic isotope effect of about 2.5 was observed for the 27-hydroxylation. Use of those deuterium-labeled cholesterol species thus allowed a specific suppression of the rate of 24- and 27-hydroxylation. Feeding mice with 0.05% unlabeled pure cholesterol in the diet for 24 h inhibited the hepatic HMG-CoA reductase activity by about 50%. The same degree of suppression was obtained after feeding with 23,23,24,24,25-2H5- and 26,26,26,27,27,27-2H6-labeled cholesterol. Were mitochondrial 24- and 27-hydroxylation of importance, one would expect reduced suppression of HMG-CoA reductase when feeding deuterated cholesterol, due to the isotope effects. As this was not the case, it is concluded that neither 24-hydroxylation nor 27-hydroxylation are critical for the cholesterol-induced down-regulation of HMG-CoA reductase in mouse liver.

Animals↗
PubMed1992

[Centralization of obstetric care and perinatal mortality in Norwegian counties 1986-90. Analysis based on public statistics from the medical birth registry].

The relationship between centralization of obstetric care and perinatal mortality was studied in 19 Norwegian counties for the period 1986-90. No significant trend was found. However, during the period 1988-1990 prenatal mortality was significantly higher, with a relative risk of 1.21 (95% confidence interval 1.00-1.45), in the three counties with only one obstetric department than it was in all other counties. The analysis did not support the notion that greater centralization of obstetric care would decrease perinatal mortality.

Centralized Hospital Services↗
PubMed1992

Control of mouse U1a and U1b snRNA gene expression by differential transcription.

The expression of mouse embryonic U1 snRNA (mU1b) genes is subject to stage- and tissue-specific control, being restricted to early embryos and adult tissues that contain a high proportion of stem cells capable of further differentiation. To determine the mechanism of this control we have sought to distinguish between differential RNA stability and regulation of U1 gene promoter activity in several cell types. We demonstrate here that mU1b RNA can accumulate to high levels in permanently transfected mouse 3T3 and C127 fibroblast cells which normally do not express the endogenous U1b genes, and apparently can do so without significantly interfering with cell growth. Expression of transfected chimeric U1 genes in such cells is much more efficient when their promoters are derived from a constitutively expressed mU1a gene rather than from an mU1b gene. In transgenic mice, introduced U1 transgenes with an mU1b 5' flanking region are subject to normal tissue-specific control, indicating that U1b promoter activity is restricted to tissues that normally express U1b genes. Inactivation of the embryonic genes during normal differentiation is not associated with methylation of upstream CpG-rich sequences; however, in NIH 3T3 fibroblasts, the 5' flanking regions of endogenous mU1b genes are completely methylated, indicating that DNA methylation serves to imprint the inactive state of the mU1b genes in cultured cells. Based on these results, we propose that the developmental control of U1b gene expression is due to differential activity of mU1a and mU1b promoters rather than to differential stability of U1a and U1b RNAs.

3T3 Cells↗
PubMed1992

On the mechanism of oxidation of cholesterol at C-7 in a lipoxygenase system.

Incubation of [7-2H2]cholesterol with soybean lipoxygenase and linoleic acid in the presence of oxygen gave a mixture of 5-cholestene-3 beta,7 alpha-diol, 5-cholestene-3 beta,7 beta-diol, 3 beta-hydroxy-5-cholesten-7-one,5 alpha,6 alpha-epoxycholestan-3 beta-ol, and 5 beta,6 beta-epoxycholestan-3 beta-ol. The conversion into the 7-oxygenated products was associated with a very high intermolecular isotope effect (KH/KD = 15-17), suggesting that the rate-limiting step in the overall conversion is likely to be the abstraction of hydrogen at C-7 in a radical reaction. Evidence that linoleic acid is to some extent directly involved was obtained with the use of [7-3H]cholesterol. Incubation of [7-3H]cholesterol resulted in a significant incorporation of 3H in the reisolated linoleic acid fraction. The isotope effect associated with conversion of [7 alpha-2H]cholesterol into 7-oxygenated products in the lipoxygenase system was 2-3, indicating that the extraction of hydrogen is nonstereospecific. Incubation of [7-2H2]cholesterol with 13-hydroperoxy-9,11-octadecadienoic acid gave the above 7-oxygenated products with relatively small isotope effects (KH/KD = 3-4). It is concluded that the most important mechanism for oxidation of cholesterol at C-7 in the lipoxygenase system involves participation of radicals and that a carbon-centered linoleic acid radical can extract hydrogen directly from cholesterol. Fatty acid hydroperoxides and their secondary products seem to be less important as initiators in connection with oxidation of cholesterol.

Cholesterol↗