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E Lund

Publications and source records attributed to E Lund.

At least 163 records · Page 9Linked to original sources
PubMed1993

24-, 25- and 27-hydroxylation of cholesterol by a purified preparation of 27-hydroxylase from pig liver.

Pig liver mitochondria were found to catalyze 27-, 25- and 24-hydroxylation of cholesterol at relative rates of about 1:0.2:0.04. An apparently homogeneous preparation of pig liver mitochondrial cytochrome P-450-27 was found to catalyze the same three hydroxylations at about the same relative rates when reconstituted with adrenodoxin and adrenodoxin reductase. The 24-hydroxycholesterol formed was shown to consist of one of the two possible stereoisomers. When using specifically deuterium-labeled substrates a significant isotope effect was observed in the case of 24-hydroxylation (KH/KD > 10), but not 25-hydroxylation (KH/KD = 1.1), or 27-hydroxylation (KH/KD = 1.1). The difference between the 24-hydroxylation and the other two hydroxylations may be due to different interactions between cholesterol and the same enzyme, with a resulting difference with respect to the rate-limiting step in the reaction. The physiological significance of the mitochondrial 24-hydroxylation is discussed.

Animals↗
PubMed1993

Suicide among women related to number of children in marriage.

The hypothesis of a negative association between rates of suicide and number of children in marriage was investigated in a prospective study of 989,949 women followed up for 15 years (1970 through 1985) with 1190 deaths from suicide. Women who had never married exhibited higher relative risks for suicide than married parous and married nonparous women for all age groups younger than 65 years at the start of follow-up. Among the married, the parous women had lower relative risks than nonparous women for all ages. For both premenopausal and postmenopausal women, a strong linear decrease in relative risk for suicide with increasing number of children in marriage was found. The effect of number of children was independent of social class measured as years of completed schooling. The findings provide the first empirical support for theories of parenthood and suicide advanced by Durkheim almost 100 years ago.

Adult↗
PubMed1993

Reduced breast cancer mortality among fishermen's wives in Norway.

International comparisons show that populations having a high consumption of fish experience low incidence of breast cancer. We compared death rates from breast cancer among socioeconomic groups in a prospective study of 533,276 Norwegian women aged 35-54 years who were followed from 1970 through 1985. Compared with the reference group (wives of unskilled workers) the fishermen's wives had a decreased risk of breast cancer with a relative risk (RR) of 0.67 (95% confidence interval [CI] = 0.47-0.94) adjusted for age and the number of children. Among fishermen's wives who were parous, adjustment for age at first birth gave an RR of 0.62 (CI = 0.43-0.91). This study supports the hypothesis that certain aspects of diet, i.e., fish consumption, may be associated with lower breast-cancer mortality.

Adult↗
PubMed1993

Infection studies with canine distemper virus in harbour seals.

Infection studies in harbour seal (Phoca vitulina) were conducted with the Snyder-Hill strain of canine distemper virus (CDV) that is virulent for dog and mink. The inoculated seals showed clinical symptoms which were to some degree similar to those observed in CDV infections of sensitive species of carnivores. Viral replication in lymphoid cells was followed by an extended period of immunosuppression. The results did not provide conclusive evidence for viral replication in surface epithelia of seals, and accordingly no spread of the infection to contact seals and mink was demonstrated. The pathogenicity of the infection did not increase upon a second viral passage in seal. The serological data showed that CDV-infected seals mounted an early virus specific antibody response. Overall, the results indicated that the harbour seal was not especially sensitive to CDV infection. The differences in the in vivo biological properties of CDV and PDV add to the distinction between these viruses at the genomic and antigenic levels.

Animals↗
PubMed1993

Strong HLA-DR expression in large bowel carcinomas is associated with good prognosis.

One hundred large bowel carcinomas operated on between 1978 and 1982 were studied immunohistochemically with regard to expression of HLA-DR antigens. Three sections from each tumour were investigated by a semiquantitative scoring system, and a mean score for each patient established. Based on this scoring system, the tumours were divided into three groups: 0; 0.1-1.0; and > 1.0. All patients were followed until death (n = 68) or until June 1, 1992, and all cancer-specific deaths (n = 56) have been recorded. Analysis of survival in the whole patient group showed significant difference between the three levels of tumour HLA-DR expression (P = 0.006); patients who had tumours with strong HLA-DR expression showing the best survival. In a stratified analysis after Dukes' stages there was still a significant difference (P > 0.001) between the three levels of HLA-DR staining intensity. After a multiple regression analysis (Cox) with correction for different variables, the HLA-DR expression maintained its significance as a risk factor. To our knowledge this is the first time a relationship between intensity of tumour DR expression and survival has been shown in large bowel carcinoma.

Adult↗
PubMed1993

Multiple cis-acting signals for export of pre-U1 snRNA from the nucleus.

We have identified cis-acting sequences that promote nuclear export of pre-U1 RNA injected into Xenopus oocyte nuclei. At least three elements, the 5' m7G cap, the 3'-terminal stem-loop structure, and sequences in the 5'-terminal 124 nucleotides, contribute to efficient export of this RNA. Both the 5' and 3' export signals can function separately and do so independently of the cap structure. Experiments using hybrid RNAs indicate that the 5' and 3' export sequences of U1 RNA are sufficient to direct export of the heterologous, otherwise nonexportable, U6 RNA. The absence of comparable export signals in U6 RNA appears to be responsible for its retention in the nucleus. Stability of the pre-snRNAs in the nucleus depends on the presence of both a 5' cap structure and a 3' base-paired stem. The 5' m7G cap is neither sufficient nor necessary for nuclear export. The m7G cap by itself did not promote export of U6 RNA or nonspecific small RNAs. Moreover, substitution of this cap with either an AppG cap or gamma-mppG cap did not eliminate export of either full-length or a "minimal" U1 RNA (lacking most of the internal U1 RNA sequences), but it reduced the rate of export by about two to threefold. However, in the absence of the 3' stem-loop, substitution of the m7G cap led to a greater decrease in export rate, underscoring the cooperative action of the three different export elements of pre-U1 RNA. The m7G cap analog, m7GpppG, selectively destabilized pre-U1 RNA within the nucleus. Thus, nuclear components that recognize the 5' m7G cap may be important for both the stability and the export of pre-U1 RNA.

Animals↗
PubMed1993

Prognostic factors in patients with nasopharyngeal carcinoma.

From 1971 to 1985 a total of 122 patients with non-distant metastatic nasopharyngeal carcinoma were treated at the Norwegian Radium Hospital with radiation doses that increased from 50 Gy (at 2 Gy/fractions) to 70 Gy (at 2 Gy/fractions) during the treatment period. Possible relationship between the increase in dose and survival time was investigated. The median cancer-specific survival time was 50 months, and the median crude survival time 38 months. No correlation was found between radiation dose and survival time. In a multivariate analysis histology was found to be the most important prognostic factor for survival with a relative risk of death from cancer of 3.4 and 3.2 for non-keratinizing carcinoma and squamous cell carcinoma respectively compared with undifferentiated carcinoma. When assessed in terms of N category the relative death risk for N2/N3 was 2.1 compared to N0/N1.

Adolescent↗
PubMed1993

Peroxisomal chain-shortening of thromboxane B2: evidence for impaired degradation of thromboxane B2 in Zellweger syndrome.

We have shown that rat liver peroxisomes can chain-shorten prostaglandins to dinor- and tetranor-metabolites. In a recent in vivo study we could demonstrate that peroxisomes are of major importance for chain-shortening of prostaglandin F2 alpha in humans (1991, Diczfalusy et al. J. Clin. Invest. 88:978-984). This was shown by identifying the major urinary metabolites of radiolabeled prostaglandin F2 alpha given intravenously to a patient lacking functional peroxisomes (Zellweger syndrome). In the present investigation we have studied the peroxisomal chain-shortening of thromboxane B2, a compound structurally related to prostaglandins. Isolated rat liver peroxisomes oxidized thromboxane B2 to a chain-shortened metabolite in an NAD(+)-dependent reaction. The metabolite was identified as 9,11,15-trihydroxy-2,3,4,5-tetranor-thromb-13-enoic acid (tetranor-thromboxane B1). The urinary excretion of the major beta-oxidized metabolites of thromboxane B2 and prostacyclin was determined in three Zellweger patients and six age-matched controls. The controls excreted on an average 1.7 and 1.1 ng/mg creatinine of 2,3-dinorthromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha, respectively. In none of the three Zellweger patients could these dinor-metabolites be detected, i.e., the urinary excretion was less than 0.2 ng/mg creatinine. This shows that peroxisomes play an important role in the degradation of the carboxyl side chain of thromboxane B2 in vivo.

Animals↗
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↗
PubMed1992

Cyclic 2',3'-phosphates and nontemplated nucleotides at the 3' end of spliceosomal U6 small nuclear RNA's.

Spliceosomal U6 small nuclear RNA (U6 RNA) in species as diverse as man, frog, fruitfly, and soybean have at their 3' ends a cyclic 2',3'-phosphate (greater than p) apparently derived from uridylic acid residues that were added post-transcriptionally. The 3' ends of U6 RNA's from various sources may be processed in different ways, or to different extents, depending on the organism or stage of development. The presence of a greater than p terminus on U6 RNA may influence the activity of U6 RNA either directly during splicing or indirectly by ensuring that the RNA has a defined length or proper conformation (or both).

Animals↗
PubMed1992

[SAMDATA--hospital statistics without quality assurance].

The author discusses problems related to systematic bias in the hospital information used for official statistics, SAMDATA. The lack of systematic evaluation of information on hospital diagnosis is a serious disadvantage when using the information to compare hospital diagnosis in different counties and over time. Another problem is lack of adequate standardization of the data by age and sex.

Data Interpretation, Statistical↗
PubMed1992

Long-term efficacy and tolerability of octreotide treatment in acromegaly.

Twenty-five acromegalic patients were studied during 6 years of treatment with octreotide, with a particular focus on the following parameters: (1) Administration schedule: in 10 patients, continuous subcutaneous (SC) octreotide infusion was compared with injections of octreotide at three dose levels (100, 250, and 1,500 micrograms/24 h) and was found to induce a greater and less-fluctuating 24-hour growth hormone (GH) suppression. (2) Carbohydrate tolerance: average 24-hour blood glucose levels were unaffected by octreotide, regardless of administration schedule. Oral carbohydrate tolerance and intravenous (IV) glucose tolerance were unaffected by continuous octreotide infusion. However, octreotide injection given shortly before the tests reduced carbohydrate tolerance. (3) Thyroid function: octreotide and somatostatin acutely reduce the response of thyroid-stimulating hormone (TSH) to thyrotropin-releasing hormone (TRH). After a few days of treatment, it was demonstrated that octreotide slightly inhibits iodothyronine deiodination and induces a transient reduction in serum triiodothyronine (T3), rapidly compensated for by a persistent slight elevation of serum TSH. (4) Fat absorption was estimated as 24-hour fecal fat content and found to be in the same high-normal range before and after octreotide treatment. Vitamin K and D absorption were unaffected by octreotide. The incidence of gallstone formation was not greater than in the general Danish population, possibly due to the schedule used for octreotide injections. (5) Foot volume was regularly estimated and found to decrease with time, on average by 12% during the first 18 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1992

Chemotherapy with or without high-dose medroxyprogesterone acetate in oestrogen-receptor-negative advanced breast cancer. Norwegian Breast Cancer Group.

In a randomised study 142 patients with advanced oestrogen-receptor-negative breast cancer in the tumour tissue received chemotherapy alone or chemotherapy combined with high doses (1000 mg daily) of oral medroxyprogesterone acetate (HD-MPA). Of the 126 fully evaluable for response, the response rates were 46% for chemotherapy alone and 73% for chemotherapy with HD-MPA (P = 0.005). There was no significant difference with regard to duration of response. Of the 138 patients evaluable for survival and toxicity, survival was shorter in the combined treatment group; median survival of 9 versus 13 months (P less than 0.05). Considerable toxicity was seen from HD-MPA, especially weight gain and fluid retention. The present study provides evidence that in concordance with preclinical studies an interaction between chemotherapy and HD-MPA may exist in breast cancer normally resistant to hormone therapy. The side-effects from MPA were substantial, however, and the survival data are of great concern.

Antineoplastic Agents↗
PubMed1992

Mortality from ovarian cancer among women with many children.

The exposure range for number of children as a risk factor for ovarian cancer has been severely restricted in most studies. This study is the first to describe the effect of many children, i.e. six or more, on the risk for death from ovarian cancer. The association between number of children in the current marriage given at the Norwegian Census in 1970 and mortality from ovarian cancer was investigated in a prospective study of 800,814 women followed over 15 years. Among postmenopausal women a strong negative trend between number of children and mortality from ovarian cancer was found; women with 8-11 children had a relative risk (RR) of 0.30 (95% confidence interval (CI): 0.17-0.54). For postmenopausal women the rate differences according to parity were constant across age strata indicating an additive model. No significant effect was found for age at first birth or social class. The study indicates that low parity could be the major risk factor for death from postmenopausal ovarian cancer.

Adult↗