Biomedical subjects
B Andersen
Publications and source records attributed to B Andersen.
Consistent production of phenolic compounds by Penicillium brevicompactum for chemotaxonomic characterization.
A consistently produced group of fungal secondary metabolites from Penicillium brevicompactum has been purified and identified as the Raistrick phenols. These compounds are shown to exist separately as an equilibrium mixture in aqueous solutions. The Raistrick phenols have all been included in the metabolite profile of P. brevicompactum. By means of thin layer chromatography-scanning and high performance liquid chromatography-UV diode array detection, the chromatographic and spectroscopic data can be used in the chemotaxonomic characterization of the fungus.
Pancreatic secretion of zinc and copper in normal subjects and in patients with chronic pancreatitis.
Pancreatic secretion of zinc and copper in duodenal juice were measured in 7 healthy persons and in 9 patients with chronic pancreatitis. Stimulation with cholecystokinin and secretin increased secretion of zinc in healthy persons but not in patients. Copper secretion was not influenced. In patients with chronic pancreatitis, the correlations between zinc secretion, and amylase and trypsin secretion were significant while in healthy subjects they were not. Possibly pancreatic zinc secretion in the duodenal juice might be used as a measure of exogenic pancreatic function, and determination of zinc in duodenal juice may replace enzyme determinations in the diagnosis of chronic pancreatitis.
Estradiol inhibits transcription of the human glycoprotein hormone alpha-subunit gene despite the absence of a high affinity binding site for estrogen receptor.
Chronic administration of estradiol inhibits transcription of the gene encoding the alpha-subunit of pituitary glycoprotein hormones. Here, we show, using transfection analyses and a filter binding assay, that 1500 basepairs of proximal 5' flanking sequence of the human alpha-subunit gene lack a functional estrogen response element when transfected into heterologous cell lines, and fail to bind estrogen receptor purified from calf uterus. Yet, this same region of the alpha-subunit gene confers estradiol responsiveness (transcriptional suppression) to the bacterial chloramphenicol acetyltransferase gene in transgenic mice. A smaller promoter fragment of the bovine alpha-subunit gene also confers responsiveness to estradiol in transgenic mice, suggesting that the same element may mediate the steroid responsiveness of both promoters. Furthermore, regulation by estradiol of the chimeric human or bovine alpha-chloramphenicol acetyltransferase genes is pituitary specific, underscoring the physiological significance of these studies. Based on these results, we conclude that estradiol regulates expression of the alpha-subunit gene in vivo through a mechanism that does not involve high affinity binding of estrogen receptor to the alpha-subunit gene. Whether this mechanism is manifest at the level of the pituitary or hypothalamus remains to be determined.
The effect of the benzodiazepine antagonist flumazenil on the sequels of diazepam given before upper gastrointestinal endoscopy. A double-blind randomized trial.
The prolonged sedation of benzodiazepines may be inconvenient for the patient. Reversal of sedation, therefore, would be desirable. Accordingly, we assessed the efficacy of the benzodiazepine antagonist flumazenil in a placebo-controlled randomized trial including 40 adults undergoing upper gastrointestinal endoscopy under diazepam (Diazemuls) sedation. We found no significant differences between groups with regard to either performance (two tests) or duration (within 240 min) of sedation. There were no noticeable side effects.
Surgical treatment of morbid obesity. A survey of overall outcome 1968-1989.
This survey evaluates benefits and costs from a policy of employing surgical treatment in selected cases of morbid obesity. Between 1968 and 1978, we used end-to-side jejunoileal bypass. Despite many satisfied patients, complications were frequent and severe. For the next decade, we employed various types of gastric surgery. We eventually assessed a gastric balloon, but without success. Median duration of follow-up was 132 months in 145 patients with jejunoileostomy, 103 months in seven gastric bypass patients, and 36 months in 108 gastroplasty patients. Three patients were lost to follow-up. There have been four deaths after intestinal shunt and one after gastroplasty. The median re-admission rate was 1.6 per patient, while the median number of re-operations was 2.0 after intestinal shunt and 0.8 after gastric interventions. The median weight loss in our 260 patients was 32.1% of the preoperative weight. Outcome was good in 38.8%, acceptable in 40.4% and poor in 11.5% while there were 9.2% failures. Truly satisfactory outcomes, however, were rare, owing possibly to a negative relationship between weight loss and complications. Only 8.8% have obtained a stable normal weight without any side-effects.
A cis-acting element located between the cAMP response elements and CCAAT box augments cell-specific expression of the glycoprotein hormone alpha subunit gene.
Several cis-acting elements interact through their cognate trans-acting factors to confer placenta-specific expression to the alpha subunit gene of glycoprotein hormones. These elements include two tandemly arranged cAMP response elements (CREs, located between base pairs (bp) -146 and -111 relative to the transcription start site), an upstream regulatory element (URE, located between -180 and -150), and a CCAAT box (located between bp -100 and -80). Here, we identify a new regulatory region, junctional regulatory element (JRE), with critical nucleotides located between the CREs and CCAAT box (bp -120 to -100). Although the binding site of the JRE abuts the 3' CRE, methylation interference assays indicate that no overlap occurs between the contact points of the proteins that bind to the JRE and CRE. This new regulatory element is highly conserved across species and contains a palindromic binding site for a 50-kDa nuclear factor(s) which is distinct from the factors that bind the URE, CRE, and CCAAT box of the alpha subunit gene. Finally, gene transfer studies suggest that, although JRE binding activity is found in several cell types, this element acts relatively cell-specifically. We conclude that this element and its cognate trans-acting factor act in conjunction with the complexes formed over the URE, CREs, and CCAAT box to enhance the placenta-specific activity of the alpha subunit promoter.
The human alpha subunit glycoprotein hormone gene utilizes a unique CCAAT binding factor.
Placenta-specific expression of the gene encoding the alpha subunit of glycoprotein hormones involves the interaction of at least two different cis-acting elements: the upstream regulatory element (URE), which binds a placenta-specific trans-acting factor; and two tandem cAMP-response elements (CREs), which bind a ubiquitous protein (CRE-binding protein). To identify additional elements required for promoter activity, we used block replacement mutagenesis to produce a series of 10-base pair transversion mutations throughout the proximal promoter-regulatory region of the human alpha subunit gene. Transient expression of these constructs in choriocarcinoma cells enabled the identification of several closely spaced transcriptional control elements in addition to the previously identified URE and CREs. Gel mobility shift assays, methylation interference analyses, and UV cross-linking permitted identification of a factor that binds specifically to a canonical CCAAT box contained within the proximal promoter-regulatory of the human alpha subunit gene. This factor, which we refer to as alpha subunit CCAAT-binding factor (alpha CBF), is found in a variety of cell types and appears to be distinct from the previously characterized CCAAT-binding factors CTF/NF1, C/EBP, CP1, and NF-Y. We suggest that interaction of alpha CBF with factors binding to the URE and CREs may be required for maximal activity of the alpha subunit promoter in placental cells.
Colostomy irrigation: a clinical and scintigraphic comparison between three different irrigation volumes.
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Bromazepam in generalized anxiety. Randomized, multi-practice comparisons with both chlorprothixene and placebo.
Bromazepam was compared with placebo and with chlorprothixene in a randomized, double-blind group-comparative multicenter trial in general practice. Two hundred and forty-five patients with generalized anxiety disorder (DSM-III 1980) were treated for 2 weeks with two daily doses of bromazepam, 3 mg or chlorprothixene, 15 mg or placebo. Median reductions in Hamilton Anxiety rating were 12 (bromazepam), 10.3 (chlorprothixene) and 7.3 (placebo). The study revealed significant superiority of bromazepam over placebo (median differences 3.3, 95% confidence limits: 0.3 and 6.1) but not over chlorprothixene (median difference 1.4, 95% confidence limits -0.8 and +3.5). Significantly higher rates of tiredness, sedation and hypersomnia were found on bromazepam and chlorprothixene compared to placebo. Tolerance was rated as "at least good" in 85.6% on bromazepam, in 86% on chlorprothixene and in 87.8% on placebo. Neither previous psychopharmacological treatment nor presence of psychosocial stress were of perceptible influence. Bromazepam and chlorprothixene are both superior to placebo in generalized anxiety states treated in general practice, but spontaneous improvements/placebo effects are substantial.
Effects of beta-carotene repletion on beta-carotene absorption, lipid peroxidation, and neutrophil superoxide formation in young men.
The chemopreventive effects of beta-carotene are usually attributed to its antioxidant properties. To determine the effects of beta-carotene supplementation on different parameters of oxidative metabolism, 15 normal young male subjects (18-30 yrs) were placed on a carotenoid-free liquid diet for two weeks prior to entry into the study. Blood was then measured for five carotenoids, retinol, retinyl palmitate, retinol-binding protein, alpha-tocopherol, vitamin C, zinc, lipid peroxides, and neutrophil superoxide production. Absorption tests were performed with 15 mg of beta-carotene to determine absorption curves for each subject. Subjects were then divided into two groups and given either 15 (n = 7) or 120 (n = 8) mg of beta-carotene daily for four weeks along with the same carotenoid-free liquid diet. The absorption test and the blood measurements were repeated. After repletion with beta-carotene, serum lipid peroxide levels decreased in both groups (p less than 0.05), but no other changes were noted in either the neutrophil superoxide production or in the levels of any of the vitamins measured. In contrast to vitamin E, the superoxide scavenging ability of beta-carotene apparently does not contribute to its effects in lowering serum lipid peroxide levels.
Randomized double-blind comparison of tolfenamic acid and paracetamol in migraine.
In a double-blind cross-over study we compared tolfenamic acid with paracetamol in out-patients with common migraine (migraine without aura). Each patient was treated during (at least) 4 attacks with one of the following alternatives: tolfenamic acid 200 mg, tolfenamic acid 400 mg, paracetamol 500 mg or paracetamol 1000 mg in a randomized sequence. The same sequence of treatments was applied to (preferably) 4 more attacks. Dosage was repeated after 2 h if the attack had not abated. Escape medication was allowed after 4 h if the treatment was inefficient. A total of 83 patients were admitted to the study, but 3 dropped out, while 10 completed less than 4 attacks. Seventy completed 4 attacks, and 58 completed all 8. The total number of attacks treated was 545. We found a significant superiority of tolfenamic acid over paracetamol with regard to effect on pain after 2 h (p less than 0.01), patients' global evaluation (p less than 0.001), and use of escape medication (p less than 0.02). The trend was the same for duration of attacks, confinement to bed during attack and nausea, but the results were not statistically significant. There was no significant difference between the smaller and the larger dose of either drug nor between the need for escape medication, although the trend favoured tolfenamic acid. Side effects were few. Tolfenamic acid is evidently valuable in treatment of migraine.
Ethanol in pancreatic juice after oral and intravenous administration.
Six patients with a drain in the main pancreatic duct were studied. Ethanol was given orally with individually adjusted doses aiming at a blood value of 0.8/1000 (17.6 mmol/l). Concentrations of ethanol in venous blood and pancreatic juice were recorded for three hours. Similar studies were made when ethanol was administered as an intravenous priming dose followed by a maintenance infusion. After orally administered ethanol, pancreatic juice values were higher than those in blood for a short period of time. The relations between median concentrations and time were incongruous curves consistent with a significant treatment by time interaction. Intravenous administration resulted in a similar pattern, but the interaction was not statistically significant. These findings indicate that the human pancreas may secrete ethanol.
Amplification of the transcriptional signal mediated by the tandem cAMP response elements of the glycoprotein hormone alpha-subunit gene occurs through several distinct mechanisms.
cAMP stimulates transcription of the human glycoprotein hormone alpha-subunit gene in choriocarcinoma cells. Combined treatment with phorbol esters potentiates this effect. Tandem cAMP response elements (CREs) in the proximal 5'-flanking sequence mediate the effect of cAMP. In this report, we show that the CREs can also mediate the synergistic effect of phorbol esters. In addition to serving as an inducible cis-acting element, the two CREs act synergistically to increase basal transcription. We now provide direct evidence via equilibrium binding studies that tandem CREs bind their trans-acting factors cooperatively. However, the level of cooperativity is insufficient to explain the high degree of transcriptional synergism, suggesting that another element in the alpha-subunit promoter may be required for complete synergism. In support of this hypothesis, we show that synergism is drastically reduced when the CREs are removed from the context of their native promoter and linked to a heterologous promoter. Thus, amplification of the transcriptional signal mediated by the tandem CREs occurs through at least three distinct mechanisms. First, at the level of signal transduction by convergence of the A- and C-kinase pathways; second, through homotropic interactions of trans-acting factors binding to tandem CREs; and finally through heterotropic interaction of the two CREs with another, as yet, undefined cis-acting element(s) in the human alpha-subunit promoter.
Salicylazosulfapyridine (Salazopyrin) effect on endotoxin-induced production of interleukin-1-like factor from human monocytes in vitro.
Monocytes (M phi) were simultaneously preincubated with salicylazosulfapyridine (Salazopyrin) (SAZ), 0.78-12.5 mM, and lipopolysaccharide from E. coli, 1 X 10(-9) g/ml. Presence of SAZ resulted in a dose-dependent decrease in the co-stimulatory activity in M phi culture supernatants, corresponding to a 50% reduction by SAZ, 2.0 mM. Co-stimulatory activity was estimated by the mitogen-induced thymocyte proliferation assay (THY assay). The results indicate an inhibitory effect of SAZ in vitro on the production of IL-1 and other possible co-stimulatory factors. This inhibitory effect was not due to decreased M phi viability, production of suppressive substances, or to drug interference with the THY assay. Equimolar preincubations with sulfapyridine, 5-aminosalicylic acid and N-acety-1-5-aminosalicylic acid were without effect on the production of co-stimulatory factors.
[Anticoagulants in treating patients with atrial fibrillation].
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Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study.
From November, 1985, to June, 1988, 1007 outpatients with chronic non-rheumatic atrial fibrillation (AF) entered a randomised trial; 335 received anticoagulation with warfarin openly, and in a double-blind study 336 received aspirin 75 mg once daily and 336 placebo. Each patient was followed up for 2 years or until termination of the trial. The primary endpoint was a thromboembolic complication (stroke, transient cerebral ischaemic attack, or embolic complications to the viscera and extremities). The secondary endpoint was death. The incidence of thromboembolic complications and vascular mortality were significantly lower in the warfarin group than in the aspirin and placebo groups, which did not differ significantly. 5 patients on warfarin had thromboembolic complications compared with 20 patients on aspirin and 21 on placebo. 21 patients on warfarin were withdrawn because of non-fatal bleeding complications compared with 2 on aspirin and none on placebo. Thus, anticoagulation therapy with warfarin can be recommended to prevent thromboembolic complications in patients with chronic non-rheumatic AF.
[Scientific articles in Ugeskrift for Laeger during a 25-year period. Types of articles and experimental design].
The purpose of this study was to examine possible trends in the research designs used in Ugeskrift for Laeger during 25 years. The scientific articles in 12 issues of the journal selected at random from each of the years 1959, 1964, 1969, 1974, 1979, and 1984 were reviewed. From each article, the following information was obtained: type of article (original paper, case report, or review), origin of the paper and number of authors. For the original papers, it was noted whether it was a longitudinal or a cross-sectional study, and whether it was a cohort or a trohoc study. Furthermore the number of subjects and the use of control group, randomization and blinding were registered. The number of articles and the number of authors per article increased during the period. Contrary to similar studies of some widely circulated English-language journals, we could not demonstrate any increase of the frequency of studies with weak research design. On the other hand, no striking improvement was observed either. Most studies had no control group and randomization and blinding were used in less than 10% of the original papers. The present study does not permit an evaluation of whether the research designs used i Ugeskrift for Laeger are satisfactory.