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Biomedical subjects

E Lund

Publications and source records attributed to E Lund.

At least 145 records · Page 8Linked to original sources

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↗

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↗

Reverse 5' caps in RNAs made in vitro by phage RNA polymerases.

We show that about one-third of the RNAs produced in vitro by viral RNA polymerases in the presence of m7GpppG dinucleotides have unusual 5' caps. In these RNAs, the initiating dinucleotide is incorporated in an orientation opposite to that expected so that the 7-methyl guanine (m7G) nucleotide is adjacent to the body of the RNA, making a "reverse" cap. The doubly methylated dinucleotide, m7GpppGm, containing a 2' O-methylated guanine (Gm) is incorporated only in the reverse orientation. Precursors of U1 snRNAs containing reverse caps are recognized by antibodies specific for the m7G cap structure. When injected into Xenopus laevis oocyte nuclei, reverse-capped pre-U1 RNAs are exported considerably more slowly than normal. Furthermore, U1 RNAs with reverse caps exhibit a striking defect in nuclear import that can be attributed to the failure of reverse caps to be hypermethylated to m2,2,7G caps. Thus, the presence of reverse-capped RNAs in RNA preparations may affect conclusions about the efficiency and extent of certain m7G cap-dependent processes.

Animals↗

In vivo selection of RNA sequences involved in nucleocytoplasmic RNA trafficking.

We used Xenopus oocytes and microinjection techniques to select for RNAs containing nuclear localization signals. A 20 nucleotide long randomized sequence was inserted into a U1-like carrier RNA giving a pool of over 10(12) possible RNA sequences. RNAs that were found in the nucleus 20 hours after nuclear or cytoplasmic injection were amplified and used for the next round of selection and amplification. After 12 rounds, the pools were highly enriched for RNAs that remained in, or were transported into, the nucleus. When individual RNAs of these pools were cloned and sequenced two different types of nuclear localization signals were identified. Some RNAs contain a binding site (whose consensus is AAUUUUUGG) for the Sm proteins common to spliceosomal snRNPs; the 5' caps of these RNAs are hypermethylated during nuclear localization and the RNAs follow the transport pathway of snRNAs. Other molecules could be folded to make long duplexes at their 5' ends; nuclear localization of these RNAs is independent of the 5' caps, and transport from the cytoplasm resembles the pathway for protein import.

Animals↗

Atherosclerosis and sterol 27-hydroxylase: evidence for a role of this enzyme in elimination of cholesterol from human macrophages.

27-Hydroxycholesterol was found in surprisingly high amounts in atherosclerotic human femoral arteries. When human macrophages were cultured in a medium containing serum, there was a significant transfer of 27-hydroxy-cholesterol and 3 beta-hydroxy-5-cholestenoic acid from the cells into the medium. Sterol 27-hydroxylase (EC 1.14.13.15) is likely to be responsible for formation of the two products as shown by use of immunoblotting, a specific inhibitor, and the 18O-labeling technique. Sterol 27-hydroxylase has the unusual ability to hydroxylate the same methyl group three times to give a carboxylic acid; thus, 3 beta-hydroxy-5-cholestenoic acid is likely to be a direct product of the enzyme. The production of these steroids increased after addition of cholesterol to the culture medium. By using deuterium-labeled cholesterol, it was ascertained that most of the oxidized products were formed from exogenous cholesterol taken up by the cells. 27-Hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid are present in the circulation and are efficiently converted into bile acids in human liver. It is suggested that conversion of cholesterol into 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid represents a general defence mechanism for macrophages and possibly also other peripheral cells exposed to cholesterol. Absence of this defence mechanism may contribute to the premature atherosclerosis known to occur in patients with sterol 27-hydroxylase deficiency (cerebrotendinous xanthomatosis).

Aged↗

Studies on rat liver phosphatidate phosphohydrolase and plasma lipids: effect of HMG-CoA reductase inhibitors.

Normolipidemic rats were treated with HMG-CoA reductase inhibitors (lovastatin or pravastatin) for periods of 1-3 days. Administration of these drugs reduced plasma triacylglycerol levels. Lovastatin-treated rats displayed a 30% lower hepatic triacylglycerol secretion rate compared to controls as estimated using Triton WR-1339. Lovastatin in a dose of 0.1% in the diet for 3 days increased hepatic phosphatidate phosphohydrolase (PAP) activity 2- to 3-fold, both in the cytosolic and microsomal fractions. Similar effects were seen in the presence of 0.2% pravastatin. PAP in both fractions was stimulated to a lesser extent by treatment with 0.1% pravastatin. These differences in PAP activity obtained by different treatment regimens were preserved during purification of cytosolic PAP on hydroxylapatite. The increase in PAP activity upon treatment with lovastatin or pravastatin was gradual and occurred simultaneously with the apparent increase in HMG-CoA reductase activity. In rats treated with the reductase inhibitors, the activity of microsomal and cytosolic PAP was inversely correlated to plasma triacylglycerol levels. The results indicate that hepatic triacylglycerol and cholesterol synthesis might be co-ordinately regulated, and also suggest that the activity of PAP is rapidly modulated in concert with changes in plasma triacylglycerol levels.

Animals↗

Down-regulation of hepatic HMG-CoA reductase in mice by dietary cholesterol: importance of the delta 5 double bond and evidence that oxidation at C-3, C-5, C-6, or C-7 is not involved.

It has been suggested that the down-regulation of hepatic HMG-CoA reductase by dietary cholesterol requires modification of the cholesterol molecule before it can exert its suppressive action. In a recent study [Lund, E., Breuer, O., & Björkhem, I. (1992) J. Biol. Chem. 267, 25092-25097], we showed that side-chain hydroxylation is not likely to be of importance for this down-regulation in male C57BL/6J mice. In this study, we studied the possibility that modification of cholesterol in the region around the delta 5 double bond is required for the suppression. It was shown that cholestanol, which does not have a delta 5 double bond but is otherwise identical to cholesterol, is a poor suppressor of HMG-CoA reductase activity. Groups of mice were fed with diets containing cholestanol, epicholesterol, 6-methylcholesterol, 6-fluorocholesterol, [3 alpha-2H]cholesterol, and [7,7-2H2]cholesterol with control groups fed cholesterol or a cholesterol-free diet. These cholesterol analogues were selected to interfere with potential in vivo modifications and to clarify structural requirements for the down-regulation. After sacrifice, the hepatic HMG-CoA reductase activity was assayed. Cholesterol, 6-methylcholesterol, and 6-fluorocholesterol were efficient suppressors whereas cholestanol and epicholesterol only had a low suppressive capacity. Differences in the degree of absorption from the intestine or degree of esterification were too small to explain the differences in HMG-CoA reductase suppressing capacity. The two deuterated cholesterol species had a suppressive capacity similar to that of unsubstituted cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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↗

Oral contraceptives and prognosis in breast cancer: effects of duration, latency, recency, age at first use and relation to parity and body mass index in young women with breast cancer.

The aim of this study was to examine associations between oral contraceptive (OC) use, body mass index (BMI = weight/height2) and prognosis in invasive breast cancer diagnosed before the age of 45. Survival analyses of a consecutive sample of breast cancer patients were undertaken. The cases were initially registered in a nationwide case-control study of OC use and risk of premenopausal breast cancer in Sweden and Norway. All 422 cases were under 45 years of age at diagnosis, and recruited from the reports to cancer registries (Sweden) or from surgical departments (Norway) during May 1984 through May 1985. Detailed information about OC exposure was obtained in the initial face-to-face interview. With Cox's proportional hazards analyses, a significantly lower hazard rate [relative hazard (RH) = 0.54; 0.31-0.94] was seen in short-term users (< 4 years)--but not in long-term (> or = 4 years) users--than in never-users of OC. Non-significant estimates for RHs lower than 1.0, i.e. better prognosis, with long recency (> 5 years) and latency (> or = 10 years) of OC use were noted. Prognosis was not influenced by age at first OC use or of its timing in relation to the first pregnancy. A higher BMI was associated with a poorer prognosis, RH 5.9 (2.0-17.8) for BMI > or = 29 versus BMI < 19, but BMI was not a confounder or an effect modifier of the association between OC use and prognosis. This study does not indicate that OC use prior to the diagnosis of breast cancer has any adverse effect on the prognosis, at least not in women under 45 years of age at diagnosis.

Adult↗

A pre-export U1 snRNP in Xenopus laevis oocyte nuclei.

We demonstrate that precursors of U1 snRNA are associated with nuclear proteins prior to export to the cytoplasm. The approximately 15S complexes containing pre-U1 RNA, which we call pre-export U1 snRNPs, were identified in extracts of Xenopus laevis oocyte nuclei that were synthesizing U1 RNAs from injected U1 genes. The U1 snRNP-specific A protein was associated with nuclear pre-U1 RNA since both this protein and the RNA were co-precipitated by antibodies directed against either the m7G-cap of the precursor RNA or the U1-A protein. The interaction of the U1-A protein with pre-U1 RNA required sequences in the loop II region although this region of U1 RNA was not necessary for the association of U1 A protein with mature U1 snRNPs. The U1 A protein helps protect pre-U1 RNA against degradation in the nucleus.

Animals↗

[Long-term treatment with octreotide of patients with acromegaly].

We bring our experiences with and results of octreotide treatment for 0.5 to seven years in 26 highly selected acromegalic patients, i.e. they had almost all been operated upon before or were for other reasons not first-choice neurosurgical candidates. Sixteen patients responded immediately to octreotide and achieved good control of symptoms and average serum growth hormone levels below 5 micrograms/l. Five additional patients responded adequately to octreotide after a renewed neurosurgical attempt, and two other patients achieved satisfactory control after successful neurosurgery. Thus we had to resort to radiation therapy in three out of these 26 patients. We should like to emphasize the fact that acromegalic patients, who initially do not respond adequately to octreotide therapy, may often do so after a renewed partial adenomectomy. Octreotide therapy has in our hands been practically without side effects, apart from gastrointestinal symptoms during the initial days of treatment. All 26 patients had an ultrasound-scan of the gallbladder and biliary tracts before and during long-term octreotide administration, and with the exception of one patient with gallbladder sediment, in whom no pretreatment scanning had been performed, we had no development of biliary tract abnormalities in these up to 65 year old patients. This may be due to composition and timing of meal intake in relation to that of octreotide. Fecal fat excretion, D-vitamin metabolites in serum and prothrombin time were similar in octreotide-treated and untreated acromegalic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

Sterol 27-hydroxylase in bile acid biosynthesis. Mechanism of oxidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,27-tetrol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid.

The sequence of reactions catalyzed by sterol 27-hydroxylase (CYP27) in the oxidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,27-tetrol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid was studied with apparently homogeneous preparations of the cytochrome P-450 from rabbit liver mitochondria. Conditions are described for the formation and characterization of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestane-27-al as an enzymatically generated intermediate in the oxidation process. Incubation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol or 5 beta-cholestane-3 alpha,7 alpha,12 alpha,27-tetrol with sterol 27-hydroxylase in 18O2 atmosphere resulted in the incorporation of one or two 18O atoms in the carboxyl group of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid. Similar incubations with 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestane-27-al resulted in the incorporation of one 18O atom in the 27-carboxyl group. The results strongly indicate that the sterol 27-hydroxylase performs multiple monooxygenations in the conversion of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid. The following reaction sequence (Reaction 1) at carbon 27 is proposed. [formula: see text] Reaction 1.

Animals↗

Analysis of ginsenosides by chromatography and mass spectrometry: release of 20 S-protopanaxadiol and 20 S-protopanaxatriol for quantitation.

To facilitate studies on the possible presence of ginseng products in serum, tissues, and excretions, a procedure to optimize the analysis of the ginseng specific products, i.e., ginsenosides, had to be worked out. With the present method the two sapogenins, 20S-protopanaxadiol and 20S-protopanaxatriol, can be produced from ginsenosides Rb1, Rc, Rd, Re, and Rg1 in 80% yield by using an improved alkaline cleavage procedure. In contrast to previously described acid hydrolysis procedures for ginsenosides, our alkaline conditions caused no epimerization, no hydroxylation, and no cyclization of the side chain. Furthermore, no unchanged ginsenosides were recovered. The products of alkaline and acidic cleavage were separated, identified, and characterized by GC, GC-MS, and HPLC. In contrast to alkaline cleavage, treatment with acid afforded a number of side products. The C-20S-epimers of the ginseng sapogenins could be distinguished from C-20R epimers by difference in mass spectra and retention time after trimethylsilylation.

Chromatography, Gas↗