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Biomedical subjects

E Lund

Publications and source records attributed to E Lund.

At least 127 records · Page 7Linked to original sources
PubMed1996

K-ras mutations and HLA-DR expression in large bowel adenomas.

A total of 72 sporadic colorectal adenomas in 56 patients were studied for the presence of point mutations in codons 12 and 13 of the K-ras gene and for HLA-DR antigen expression related to clinicopathological variables. Forty K-ras mutations in 39 adenomas were found (54%): 31 (77%) in codon 12 and nine (23%) in codon 13. There was a strong relationship between the incidence of K-ras mutations and adenoma type, degree of dysplasia and sex. The highest frequency of K-ras mutations was seen in large adenomas of the villous type with high-grade dysplasia. Fourteen out of 15 adenomas obtained from 14 women above 65 years of age carried mutations. HLA-DR positivity was found in 38% of the adenomas, large tumours and those with high-grade dysplasia having the strongest staining. Coexpression of K-ras mutations and HLA-DR was found significantly more frequently in large and highly dysplastic adenomas, although two-way analysis of variance showing size and grade of dysplasia to be the most important variable. None of the adenomas with low-grade dysplasia showed both K-ras mutation and HLA-DR positivity (P = 0.004). K-ras mutation is recognised as an early event in colorectal carcinogenesis. The mutation might give rise to peptides that may be presented on the tumour cell surface by class II molecules, and thereby induce immune responses against neoplastic cells.

Adenoma↗
PubMed1996

Importance of a novel oxidative mechanism for elimination of intracellular cholesterol in humans.

We have recently demonstrated that cultured human alveolar macrophages efficiently convert cholesterol into excretable 27-oxygenated products. We show here that increasing the intracellular concentration of cholesterol by a factor of 10 leads to about a twofold increase in the excretion of 27-oxygenated products from cultured macrophages. Inhibition of the sterol 27-hydroxylase caused a significant intracellular accumulation of cholesterol. A direct comparison was made between flux of cholesterol and 27-oxygenated products from macrophages preloaded with [4-14C]cholesterol. Under the specific conditions employed with fetal calf serum in the culture medium, the flux of 27-oxygenated products was about 10% of that of cholesterol. Since the sterol 27-hydroxylase, which converts cholesterol to 27-oxygenated products, is present in many cell types, we suggest that 27-oxygenation is a general mechanism for removal of intracellular cholesterol. To evaluate this hypothesis, we measured the net uptake by the human liver of circulating 27-oxygenated products, which was found to be about 20 mg/24 h. This uptake corresponds to approximately 4% of the bile acid production, assuming quantitative conversion into bile acids. It is concluded that the 27-hydroxylase pathway is of significance for elimination of extrahepatic cholesterol.

Cells, Cultured↗
PubMed1996

Reproductive history and cigarette smoking as risk factors for thyroid cancer in women: a population-based case-control study.

A population-based case-control study was conducted in Northern Norway and Central Sweden to investigate hormonal and reproductive factors and cigarette smoking as determinants of papillary and follicular thyroid carcinoma in women. Information on 191 histologically confirmed cases and 341 age-matched controls was included. No clear association was found with regard to the number of live births, number of pregnancies, a history of incomplete pregnancies, or the use of oral contraceptives or hormonal replacement therapy. However, an early first childbirth (before 20 years of age, or less than 5 years after menarche) was associated with an increased risk of thyroid cancer. There was an increased risk of thyroid cancer among women with a history of artificial menopause compared to those with a spontaneous menopause [odds ratio (OR), 2.52; 95% confidence interval (CI), 0.96-6.62], which was more pronounced for the papillary carcinoma and after adjustment for age at menopause and use of replacement therapy. Cigarette smokers had a decreased risk of borderline statistical significance compared to nonsmokers (OR, 0.69; 95% CI, 0.47-1.01), particularly among premenopausal women (OR, 0.60; 95% CI, 0.38-0.96). This negative association persisted after adjustment for parity, hormonal treatments, and education. Women who started smoking before the age of 15 experienced a marked reduction in risk (OR, 0.38%; 95% CI, 0.18-0.80¿). Moreover, there was a suggestion of a dose-response effect with the amount of cigarettes smoked daily and with duration of the habit. Both the increased risk of artificial menopause and the negative association with smoking are compatible with a relation between levels of estrogens and thyroid cancer among women.

Adenocarcinoma, Follicular↗
PubMed1996

Preliminary report of trace elements in mothers and newborns living in the Kola Peninsula and Arkhangelsk region of Russia compared to Norwegian populations.

Recently, considerable attention has been allotted to the possible health effects of the industrial pollution in the regions adjoining the Norwegian-Russian border. As a measure of general health, the status of trace elements and some clinical-chemical parameters in serum and blood that reflect general health was assessed for 50 consecutive obstetric patients presenting at delivery departments of local hospitals in the Kola Peninsula, Arkhangelsk and selected centres in Norway. A written questionnaire and consent form were completed by each participant. Specimens of maternal and cord blood were collected. Corresponding samples were analyzed for copper, zinc, selenium, iron and ferritin. We found a lower birth weight in the Russian centres. The measurement of trace elements showed a higher iron status for the Russian females and relatively low serum zinc levels were observed in both the Russian and the Norwegian communities. It may be concluded that with the exception of zinc, the mineral status in the Norwegian and Russian arctic centres considered appears to be satisfactory.

Arctic Regions↗
PubMed1996

Novel pathways for elimination of cholesterol by extrahepatic formation of side-chain oxidized oxysterols.

Recently, we described a new pathway whereby peripheral cells can eliminate intracellular cholesterol by conversion into the more polar oxysterols 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid. The latter steroids are easily excreted from the cells and transported to the liver for conversion into bile acids. Our attempts to evaluate the importance of this new mechanism are reviewed here and also our investigations on the possible presence of additional similar pathways for removal of extrahepatic cholesterol. Human alveolar macrophages in culture were shown to have a high capacity to convert cholesterol into 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid and to excrete these steroids into the culture medium. Treatment of the macrophages with cyclosporin A, an inhibitor of sterol 27-hydroxylase, reduced the excretion of the 27-hydroxylated products by more than 90%, with a concomitant accumulation of intracellular cholesterol. The quantitative importance of the mechanism in relation to reverse cholesterol transport was investigated in 14C-cholesterol labelled macrophages exposed to HDL. At very low concentrations of HDL, possibly similar to those present in tissues, the two pathways were about equally effective. At optimal concentrations of HDL, however, reverse cholesterol transport was about 10-fold more effective than the sterol 27-hydroxylase pathway. The net uptake of 27-oxygenated steroids by the liver was measured in volunteers by comparison of the levels in the hepatic vein with those in a peripheral artery. Approximately 20 mg of 27-oxygenated oxysterols was taken up by the liver during 24 hours. Quantitative conversion of these oxysterols into bile acids would correspond to 4% of the total bile acid formation. It is evident that this new pathway contributes significantly to cholesterol elimination. The possibility that the sterol 27-hydroxylase pathway is of importance for cholesterol homeostasis in the brain was investigated by measuring oxysterols in the internal jugular vein and in an artery of healthy volunteers. There was no net flux of 27-hydroxycholesterol from the brain into the circulation. There was, however, a significant flux of 24-hydroxycholesterol, corresponding to elimination of about 4 mg cholesterol/24 hours. This flux is higher than the estimated rate of synthesis of cholesterol in the human brain. To summarize, we have demonstrated two mechanisms for cholesterol elimination from extrahepatic cells by specific oxygenases capable of oxidizing the steroid side-chain. The efficiency of these mechanisms is based on the fact that side-chain hydroxylated cholesterol species are both translocated through lipophilic membranes and converted into bile acids at a much faster rate than cholesterol itself. The importance of the sterol 27-hydroxylase-mediated mechanism is illustrated by the fact that patients who lack this enzyme develop xanthomas and premature atherosclerosis in spite of normal levels of circulating cholesterol.

Cholesterol↗
PubMed1995

Time course of oxysterol formation during in vitro oxidation of low density lipoprotein.

Cholesterol oxidation products (oxysterols) have been implicated in several aspects of atherogenesis; they affect key enzymes in cholesterol homeostasis, induce calcification in vascular cells and possess cytotoxic properties. Oxysterols are formed during oxidative modification of low density lipoprotein (LDL). Using a recently developed method based on isotope dilution-mass spectrometry, the kinetics of formation of oxysterols during oxidation of LDL by cupric ions or soybean lipoxygenase was studied. The same products, mainly 7- and 5-oxygenated cholesterol, were formed by the two oxidation methods. Virtually no side-chain oxidized oxysterols were formed. During the oxidations, preferentially esterified cholesterol was consumed and consumption of polyunsaturated fatty acids and formation of conjugated dienes preceded the appearance of oxysterols. Cholesterol 7-hydroperoxides potential cytotoxins, were present in LDL oxidized by copper or lipoxygenase.

Cholesterol↗
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

The use of non-proven therapy among patients treated in Norwegian oncological departments. A cross-sectional national multicentre study.

A national multicentre study was performed to investigate the prevalent use of "alternative medicine", here called "non-proven therapies (NPT)", applied among Norwegian cancer patients. Of 911 patients invited to take part in the study, 642 were included in the analysis. Demographic characteristics were collected for all patients. The participating physicians gave information about the patients' clinical characteristics. Among 630 evaluable patients, 20% had been or were present users of NPTs for their oncological disease. The preferred methods were healing by hand and faith healing. Herbs, vitamins, diets and Iscador were other popular methods. As many as 40% of the users of NPTs had used NPTs earlier for non-malignant diseases. Elderly patients were less likely to use NPTs. Use was high in the northern part of Norway.

Adolescent↗