Search PubMed⌕ Search

Biomedical subjects

S Hansen

Publications and source records attributed to S Hansen.

At least 145 records · Page 8Linked to original sources
PubMed1996

Oxidative stress is involved in the UV activation of p53.

In many vertebrate cells exposure to ultraviolet light lead to a dramatic increase in the cellular levels of the tumour suppressor protein p53, followed by a biological response of either growth arrest or programmed cell death. Ultraviolet light can be absorbed directly by cellular macromolecules, leading to photochemical modification of DNA and proteins. Additionally, it also causes free radical formation, resulting in oxidative stress. Whereas ultraviolet light and ionizing radiation both induce DNA lesions which trigger an activation of the p53 pathway, the magnitude of the p53 response elicited by ionizing radiation is comparatively low. Following irradiation with ultraviolet light two populations of p53-reactive cells are induced: a population accumulating high levels of p53 protein and a population with comparatively low levels of p53, similar in magnitude to the p53 response following ionizing radiation. Pretreatment of cells with N-acetylcysteine, an agent known to counteract oxidative stress, attenuates the cellular p53 response to ultraviolet light by reducing the number of cells with high p53 levels but does not affect the response to ionizing radiation. We demonstrate that N-acetylcysteine pretreatment does not prevent the inflicted DNA damage and therefore conclude that oxidative stress is a causative agent in the ultraviolet light activation of the p53 pathway.

3T3 Cells↗
PubMed1995

Evidence for sodium dodecyl sulfate/protein complexes adopting a necklace structure.

Structural analysis by cryo-electron microscopy and small-angle X-ray scattering of ten sodium dodecyl sulfate/protein complexes in 25 mM Tris/HCl, 0.192 M glycine, pH 8.3, showed necklace-like structures of spherical micelles dispersed along the unfolded peptide chain. The micelles of most SDS/protein complexes had a constant diameter (approximately 6.2 nm), slightly larger than pure SDS micelles (approximately 5.7 nm), all micelles possessing a degree of surface roughness. The micelle-associated polypeptide is mostly situated at the interface of the sulfate head groups and hydrocarbon core, intruding into the core rather than outward from the surface. Proteins with a molecular mass less than about 20 kDa formed complexes with a single SDS micelle. Multi-micellar SDS/protein complexes had centre-to-centre intermicellar distances in the range 7.0-12.0 nm. Our findings on the constancy of micellar size, number of micelles/complex, and the relationship between the degree of occupancy of micelles and a polypeptide's molecular mass, have enabled us to speculate on the correlation between the electrophoretic mobility of a polypeptide in SDS/PAGE and its molecular mass. The anomalous electrophoretic behaviour observed for the sodium dodecyl sulfate/histone H5 complex is accounted for by the large micelle of its complex.

Freezing↗
PubMed1995

Consequence of long-term exposure to corticosterone or dexamethasone on ethanol consumption in the adrenalectomized rat, and the effect of type I and type II corticosteroid receptor antagonists.

The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a baseline period (1 week), following adrenalectomy (1 week) and for 3 weeks following SC implantation of hormone pellets containing corticosterone (CORT) or dexamethasone (DEX). Ethanol consumption dropped during the first week of adrenalectomy (ADX) but increased again in the absence of hormone replacement to reach preoperative levels during the ensuing weeks. The CORT treatment, which produced plasma hormone levels similar to the 24-h mean concentration of adrenally intact rats, not only reversed the effect of ADX on alcohol consumption but also enhanced it to levels above those observed in intact rats. Water intake was not affected by the CORT treatment. DEX implants stimulated water intake, but did not enhance the drinking of ethanol. SC injections of RU 28318 (type I corticosterone receptor antagonist; 10 mg/kg) or mifepristone (RU 38486; type II receptor antagonist; 25 mg/kg) at the beginning and halfway through three daily, 6-h tests failed to affect ethanol drinking in adrenally intact rats or in ADX rats bearing CORT implants. Similarly, there was no effect of giving the two antagonists in combination. These results suggest that exogenous CORT can induce excessive alcohol intake in genetically unselected rats and that this facilitatory effect may be mediated by non-genomic cellular mechanisms.

Adrenalectomy↗
PubMed1995

Significance of adrenal corticosteroid secretion for the food restriction-induced enhancement of alcohol drinking in the rat.

Male Wistar rats with continuous access to 6% ethanol solution and water in their home cages were subjected to food restriction (FR). Reduction of body weight to 80% of normal was associated with a significant increase in ethanol drinking. It is known that the stress of FR gives rise to increased corticosterone secretion, and in line with these findings it was found that the weight of the thymus (whose size is inversely related to corticosterone levels) was reduced to 55% of normal in the present FR rats. Two subsequent experiments indicated that this adrenal activation contributed to the FR-induced enhancement of alcohol drinking. Firstly, adrenalectomized rats showed no evidence of enhanced alcohol drinking during food restriction, suggesting that adrenal corticosterone hypersecretion contributes to the enhanced ethanol consumption during FR. Secondly, treatment of FR rats with the enzyme inhibitor cyanoketone, which blocks stress-induced but not basal corticosterone secretion, at least partly prevented the FR-induced increase in ethanol drinking. These results add further evidence that sustained exposure to corticosterone facilitates ethanol consumption in the rat.

Adrenal Cortex Hormones↗
PubMed1995

Neural regeneration and neuronal migration following injury. I. The endocrine hypothalamus and neurohypophyseal system.

Central to this investigation are several basic hypotheses that are designed to test the role of nitric oxide (NO) in the complex process of central regeneration and plasticity in a well established model system of the mammalian brain. We have employed histochemical techniques at the light and ultrastructural level coupled with correlative scanning electron microscopy, immunoelectron microscopy, and in situ hybridization in order to determine the functional significance of the increased expression of nitric oxide synthase (NOS) in neurons of the supraoptic (SON) and paraventricular (PVN) nuclei which accompanies regeneration of their axotomized neurites following hypophysectomy. The aim of this investigation was to determine the potential role and temporal up-regulation of NOS in this basic regenerative process and to establish the ultrastructural and neuroanatomical correlates during critical periods of regeneration and regrowth of SON and PVN axons following hypophysectomy in the endocrine hypothalamus of the rat. Our data support the hypothesis that NO may serve as a second messenger molecule that may act in some fashion to govern not only the process of central regeneration and regrowth of magnocellular (SON/PVN) axons into the median eminence, neural stem, and neural lobe (the neurohypophyseal system) but may also influence the regeneration of neurites into new neuroanatomical domains such as the adjacent lumen of the third cerebral ventricle. We have demonstrated a distinct temporal relationship between injury (axotomy) of SON/PVN axons and the establishment of new neurovascular zones following hypophysectomy with the up-regulation of NOS. This up-regulation appears to correlate well with successful regeneration in the mammalian neurohypophyseal system. We have also successfully inhibited axonal regeneration with the use of nitroarginine, a competitive antagonist of NO. NOS up-regulation attendant to regeneration of SON and PVN axons may have inestimable clinical implications, particularly with respect to closed head injury and cerebral contusion that involves the mechanical shearing of the infundibular stalk. In addition, this investigation has reaffirmed that large numbers of bona fide neurons migrate and emerge upon the floor of the adjacent third cerebral ventricle shortly following hypophysectomy (within 2 weeks). The origin and mechanisms of neuronal migration and plasticity following hypophysectomy are the subject of interpretation and discussion in this investigation.

Amino Acid Oxidoreductases↗
PubMed1995

Incidence of myelodysplastic syndromes in a Swedish population.

The myelodysplastic syndromes (MDS) have attracted great interest during the last decade. Unfortunately there is not much material published concerning the incidence of these conditions. We present epidemiologic data on MDS based on case registration of patients in a well-defined population and as a comparison similar data on acute myeloid leukaemia (AML). Between the years 1978-1992 we registered 120 cases of MDS and 146 cases of AML. The median age for all the MDS cases was 74.1 years for men and 78.2 years for women. Among haematologists there is a suspicion that the incidence of MDS is rising. Our study does not support this opinion. We have divided the study period into 5-year periods and the crude incidence has been 3.2, 4.1 and 3.5/100,000/year for each period. In the age group over 70 years MDS was more frequent than AML and in the last 5-year period the incidence was 15.0/100,000/year for MDS compared to 10.2/100,000/year for AML. In conclusion MDS is quite common among elderly people and there is no evidence for a rising incidence during the last 15 years.

Acute Disease↗
PubMed1995

Cutaneous complications in heart transplant recipients in Norway 1983-1993.

All Norweigian heart transplant recipients with more than one year's survival (n = 140) were investigated for dermatological disorders. Observation time after transplantation was 1-10 years (mean 5.0 years). Patients alive at the end of 1993 (n = 122) were examined clinically, and medical records for all patients were reviewed. The histopathological diagnoses of excised skin specimens were reevaluated. Malignant skin tumours (i.e. basal cell carcinoma, squamous cell carcinoma and malignant melanoma) and/or premalignant skin tumours (i.e. morbus Bowen (carcinoma in situ), solar keratosis and keratoacanthoma) were found in 34 patients (24.3%), of which 18 patients (12.9%) had malignant skin tumours. Seventeen lesions diagnosed as keratoacanthoma and two lesions diagnosed as morbus Bowen had primarily been diagnosed as squamous cell carcinoma. Five patients (3.6%) had multiple keratoacanthomas. Other frequent dermatological diagnoses included hypertrichosis (86.9%), steroid-induced skin features (59.8%), common warts (42.6%) and seborrheic skin disorders (20.5%). This study demonstrates the importance of dermatological surveillance in the follow-up of heart transplant recipients.

Adolescent↗
PubMed1995

Screening for oligoalbuminuria by means of Micral-Test II. A new immunological test strip.

A new dip-and-read test strip for systematic detection of oligoalbuminuria was assessed. The test is based on a competition for gold-labelled anti-albumin antibodies between specimen albumin and albumin molecules immobilised in the test strip. The final detection area is coloured by excess free antibodies. The colour reaction is compared to a colour scale reflecting 0, 20, 50 and 100 mg/l albumin. Method comparison with an immuno-turbidimetric quantitative technique was performed on 747 unselected specimens. The correlation coefficient was 0.938, the Spearman rank coefficient 0.863. In spite of considerable overlap of the results attributed to the 4 colour blocks, the test was found to be perfectly useful as a 2-class-test, as there were practically no false negative tests and as all the specimens yielding reactions stronger than the 20 mg/l colour block were found to contain 20 mg/l albumin or more by the reference method. The colour block 20 mg/l represents the inevitable grey zone, results in this range being found to be normal and increased above this pathological cut-off by the reference method. Follow-up by quantitative albumin dosage in timed morning urine for all specimens found positive by the dipstick confirms the existence of oligoalbuminuria, eliminating the cases of orthostatic albuminuria, of oligoalbuminuria simulated by low diuresis and the false positives due to oversensitivity of the test strip. The test strip is easy to handle. The reaction time is short and the colour reaction is stable and easy to read. Systematic use of this test in routine urine chemistry is suggested.

Albuminuria↗
PubMed1994

Helicobacter pylori infection and gastric lymphoma.

BACKGROUND: Helicobacter pylori infection is a risk factor for gastric adenocarcinoma. We examined whether this infection is also a risk factor for primary gastric non-Hodgkin's lymphoma. METHODS: This nested case-control study involved two large cohorts (230,593 participants). Serum had been collected from cohort members and stored, and all subjects were followed for cancer. Thirty-three patients with gastric non-Hodgkin's lymphoma were identified, and each was matched to four controls according to cohort, age, sex, and date of serum collection. For comparison, 31 patients with nongastric non-Hodgkin's lymphoma from one of the cohorts were evaluated, each of whom had been previously matched to 2 controls. Pathological reports and specimens were reviewed to confirm the histologic type of the tumor. Serum samples from all subjects were tested for H. pylori IgG by an enzyme-linked immunosorbent assay. RESULTS: Thirty-three cases of gastric non-Hodgkin's lymphoma occurred a median of 14 years after serum collection. Patients with gastric lymphoma were significantly more likely than matched controls to have evidence of previous H. pylori infection (matched odds ratio, 6.3; 95 percent confidence interval, 2.0 to 19.9). The results were similar in both cohorts. Among the 31 patients with nongastric lymphoma, a median of six years had elapsed between serum collection and the development of disease. No association was found between nongastric non-Hodgkin's lymphoma and previous H. pylori infection (matched odds ratio, 1.2; 95 percent confidence interval, 0.5 to 3.0). CONCLUSIONS: Non-Hodgkin's lymphoma affecting the stomach, but not other sites, is associated with previous H. pylori infection. A causative role for the organism is plausible, but remains unproved.

Aged↗
PubMed1994

Early amniocentesis--a cytogenetic evaluation of over 1500 cases.

We report our cytogenetic experience of 1554 early amniocenteses between weeks 11 and 14 of gestation, of which 44 per cent were performed prior to week 14. The mean culture time was 14.5 days. Karyotyping was successful in 99.7 per cent of cases. In 9.9 per cent of cases, there was pseudomosaicism with a high rate of loss of an X-chromosome and structural aberration of chromosome 1, which may be due to the Chang medium. The mosaic rate was 0.5 per cent. The overall aberration rate was 2.8 per cent. Our data confirm the reliability of early amniocentesis, which is a serious alternative to standard amniocentesis and chorionic villus sampling (CVS).

Adult↗
PubMed1994

The aggregation behavior of zinc-free insulin studied by small-angle neutron scattering.

The aggregation behavior of zinc-free insulin has been studied by small-angle neutron scattering as a function of pH and ionic strength of the solution. The pair distance distribution functions for the 12 samples have been obtained by indirect Fourier transformation. The results show that the diameter of the aggregates is 40 A at pH 11 and 10 mM NaCl, independent of the protein concentration. The largest diameter of about 120 A is found for pH 8, 100 mM NaCl, and a protein concentration of 10 mg/ml. Estimates of the pair distance distribution functions, free of inter-particle correlation effects, were obtained by an indirect Fourier transformation, omitting the data at small scattering vectors, which are influenced by these effects. By this procedure the weight-averaged molecular mass and the average radius of gyration were determined. These parameters vary from 1.3 times the monomer mass and 14 A, to 6.8 times the monomer mass and 31 A, respectively. The mass distribution between the oligomers was determined by a model based on the crystal structure of zinc-free insulin. The results from this model and the Fourier transformations have been compared to an equilibrium model recently introduced by Kadima et al. (1993). The neutron scattering results agree well with the predictions of this model except that broader mass distributions are suggested by neutron scattering.

Crystallization↗
PubMed1994

Maternal behavior of female rats with 6-OHDA lesions in the ventral striatum: characterization of the pup retrieval deficit.

The present experiments characterized the impairment in pup retrieval previously observed in maternal rats following dopamine-depleting 6-hydroxydopamine (6-OHDA) infusions in the ventral striatum. Video recordings of 30-min pup retrieval tests revealed that 6-OHDA mothers spent most of the time feeding (Experiment 1). Denying the mothers the opportunity to eat during testing failed to reestablish pup retrieval. Similarly unsuccessful was an attempt to evoke food-motivated pup retrieving in 6-OHDA mothers by coating the stimulus pups' skin with a 4% sucrose solution (Experiment 2). However, restoration of pup retrieval was observed in 6-OHDA mothers that had been separated from their pups for 3-6 h (Experiments 3 and 4). Stimulation of ultrasonic callings by clonidine treatment of the stimulus pups, or leaving pups in the nest during testing, were not significantly effective (Experiment 3). These data suggest that separation-induced increases in maternal motivation can override the inhibitory effect of ventral striatal dopamine depletion on pup retrieval.

Animals↗
PubMed1994

Effects of ventral striatal 6-OHDA lesions or amphetamine sensitization on ethanol consumption in the rat.

Female rats with continuous access to water and 6% ethanol were given bilateral ventral striatal 6-OHDA infusions, which induced pronounced striatal depletions of dopamine. The postoperative ethanol consumption of these rats was not significantly affected in comparison to vehicle-infused controls. In a second experiment, female rats received escalating doses of d-amphetamine over a 5-week period (from 1 to 9 mg/kg/injection). Control females were given saline injections. Following a 3-month drug-free interval, the females were given access to ethanol, the concentration of which was gradually increased from 2% to 12% with weekly intervals. Amphetamine-sensitized rats consumed significantly more alcohol than the saline-treated controls. Taken together, these results suggest that striatal dopaminergic mechanisms, while not necessary for basal ethanol drinking, can facilitate alcohol drinking.

Alcohol Drinking↗
PubMed1994

Metyrapone-induced suppression of corticosterone synthesis reduces ethanol consumption in high-preferring rats.

The fluid intake of male Wistar rats with simultaneous access to water and 6% ethanol was determined between 0900 and 1500 h. In high-preferring males (normally covering > 60% of their daily fluid consumption in the form of ethanol), two injections with the corticosterone synthesis inhibitor metyrapone (50 mg/kg) at 0900 h and 1200 h for 4 consecutive days significantly reduced ethanol preference such that they preferred water over alcohol. Treatment with corticosterone (0.6 mg/kg) 2 h before each metyrapone injection partially cancelled this effect of the synthesis inhibitor. By contrast, there was no significant effect of metyrapone treatment on the drinking of ethanol in low-preferring rats (normally covering < 30% of their daily fluid consumption in the form of ethanol). These results suggest that the adrenal secretion of corticosterone directly or indirectly modulates the intake of alcohol in high-preferring rats.

Alcohol Drinking↗
PubMed1994

A proposal for the catalytic mechanism in phospholipase C based on interaction energy and distance geometry calculations.

The non-specific phospholipase C from Bacillus cereus preferentially hydrolyses phosphatidylcholine but is also active against phosphatidylserine, phosphatidylethanolamine and at a much lower level, sphingomyelin. A minimal substrate model containing all required structural and configurational elements of a high affinity substrate was docked into the active site. The enzyme-substrate attachment points were from molecular interaction energy calculations using the program GRID and from a previous phosphate inhibitor complex structure. Available conformational space for the substrate was sampled by distance geometry calculations using the program DGEOM. This investigation clearly identifies the attacking nucleophile, a catalytically favourable orientation of the phosphate group in its tetra-, as well as its penta-, coordinated state and a crucial stabilizing environment for the alkoxide intermediate. Based on this information a complete catalytic cycle is proposed.

Bacillus cereus↗
PubMed1994

Precision and accuracy of a noninvasive inert gas washin method for determination of cardiac output in men.

Stout et al. (J. Appl. Physiol. 38:913-918, 1975) suggested an open-circuit multibreath (MB) inert gas method for determining pulmonary capillary blood flow (Qc) in anesthetized dogs receiving artificial ventilation. In the present work we investigated the accuracy and reproducibility of the MB method in nine healthy human subjects at spontaneous ventilation, and we compared the MB method with the inert gas rebreathing (RB) method. Qc was calculated at rest and during exercise at 50 or 100 W, and experimental errors were evaluated in computer simulations of a two-alveoli lung model. The calculated mean Qc values of the MB method were 5.56 +/- 1.23 (SD), 10.02 +/- 0.78, and 13.2 +/- 0.84 l/min, and the mean difference (MB Qc - RB Qc) was not significantly different (P > 0.05). The variation in Qc of the MB method was found to be significantly larger than that in Qc of the RB method (P < 0.01). Random measurement errors and uneven distribution of ventilation contributed to the experimental errors. We conclude that the MB method is inferior to the RB method but that the MB method may be useful under exercise conditions.

Adult↗