Biomedical subjects

O Andersen

Publications and source records attributed to O Andersen.

At least 109 records · Page 6Linked to original sources

PubMed1994

Evaluation of mercury in hair, blood and muscle as biomarkers for methylmercury exposure in male and female mice.

Recently established reference intervals demonstrate that blood mercury is significantly higher in women than in men. Mercury in blood and hair are both used as biomarkers for human methylmercury exposure and employed in risk assessment without considering possible sex-related differences in toxicokinetics of methylmercury. In an experimental study using male and female mice of three different strains, the validity of mercury in hair, blood and muscle as indicators of methylmercury exposure was evaluated. Significant sex-related differences in the toxicokinetics of methylmercury were observed in the mice and it is concluded that hair and blood levels of mercury are of questionable relevance as indicators of both body burden and target organ concentrations of mercury. However, blood concentrations might be used as an indicator of brain deposition and the correlation improves after corrections due to sex-related differences in toxicokinetics.

Adipose Tissue↗

PubMed1994

Effect of tetraethylthiuramdisulphide and diethyl-dithiocarbamate on nickel toxicokinetics in mice.

A new experimental pharmacokinetic model using the gamma-emitting isotope 57Ni for studying nickel toxicokinetics was employed in a recent investigation (Nielsen et al. 1993) in order to quantitatively study, for the first time, the effect of tetraethylthiuram disulphide (disulfiram, Antabuse, TTD) and sodium diethyldithiocarbamate (DDC) on whole-body retention and organ distribution of nickel in mice. TTD or its decomposition product DDC given orally by stomach tube shortly after oral administration of a low dose of nickel chloride labelled with 57Ni resulted in an approximately ten times higher whole-body retention of nickel compared to the retention in a control group exposed to nickel only. These chelators increased the whole-body retention of nickel also when given by intraperitoneal injection shortly after oral or intraperitoneal administration of nickel. Oral administration of a single dose of TTD or DDC rapidly after an oral dose of nickel chloride also resulted in extensive changes in the organ distribution of nickel, thus the nickel content in the brain was at least 700 times higher than in a control group given the same dose of nickel only. If DDC was given intraperitoneally after nickel given orally, the relative organ distribution of nickel to most organs was the same as if the chelator was given orally, though the contents of the liver and lungs were lower. That TTD and DDC resulted in a transport of nickel to the brain, is underlined by the fact that after 20 hr, approximately 15% and after 45-50 hr, 30% of the total body burden of Ni was found in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1994

Calcium-enhanced aggregation of serum amyloid P component and its inhibition by the ligands heparin and heparan sulphate. An electron microscopic and immunoelectrophoretic study.

Serum amyloid P component (SAP) is a pentraxin found in the circulation and in all forms of amyloid deposits. Its physiological and pathophysiological functions are largely unknown. Electron microscopy showed purified human SAP to consist of double pentameric discs compatible with the results of size chromatography. The formation of double pentamers did not require calcium ions. The outer diameter of the discs arranged face-to-face was 11.6 nm and the inner diameter 3.2 nm. The thickness of single and double pentamers was 4.1 and 8.7 nm, respectively. Quadruple pentamers were occasionally seen. The self-aggregation of human SAP molecules was investigated in the presence and absence of calcium ions at different concentrations. In calcium-free solutions few and mostly small SAP aggregates were seen. After addition of calcium at increasing concentration the aggregates grew in size and crystalline-like structures were formed already at 2 mM calcium. At 25 mM calcium, large aggregates with a crystalline array occasionally exhibiting cylinders predominated. Binding of the ligands heparin and heparan sulphate to SAP completely abolished the calcium-enhanced aggregation, but the distribution of the SAP molecules was affected, resulting in strands or groups of adjacent molecules. The electrophoretic mobility of SAP was moreover significantly altered after its calcium-dependent reaction with these ligands. We conclude that purified SAP has a tendency to double pentamer formation and self-aggregation also in the absence of calcium ions. However, aggregation is greatly enhanced even at low concentrations (2 mM) of calcium. SAP's tendency to self-aggregation is abolished after its binding to heparin or heparin sulphate. Furthermore, our TEM studies indicate that purified human SAP freed of its natural ligands has the double pentameric form, whereas the electrophoretic investigations suggest that SAP's interaction with low-molecular-weight natural ligands in serum prevents homodimerization and self-aggregation.

Blotting, Western↗

PubMed1994

Experimental localization of intestinal uptake sites for metals (Cd, Hg, Zn, Se) in vivo in mice.

The intestinal uptake process consists of two separable steps: transport over the luminal membrane into epithelial cytoplasm and transport over the basolateral membrane into serosal fluid. A compound's residence time in mucosal epithelial cytoplasm depends on rates of the two transport processes and, if the rate of the second step is low, on the rate of mucosal sloughing. Using gamma-emitting metal isotopes, in vivo labeling profiles of the intestinal tract were obtained from mice eating their normal diet. The results pertain to processes in the functioning, undisturbed intestinal tract. Single-dose chase experiments indicated that intestinal uptake processes were in fact studied. The labeling profiles varied considerably for different metals. Thus, Cd++ was absorbed mainly in duodenum and early jejunum, while Zn++ was taken up in jejunum and ileum. The uptake profile of Hg++ indicated most rapid uptake in proximal jejunum. Selenomethionine labeled the entire intestinal tract, most rapidly the duodenum, the following intestinal segments were labeled with falling rate. This experimental method is rapid and simple. Further studies aim at developing a quantitative model suited for studying interactions between essential and toxic metals at the level of intestinal metabolism.

Animals↗

PubMed1994

Dose and time relations in Hg(++)-induced tubular necrosis and regeneration.

Mercuric chloride is a well-known human and animal nephrotoxicant. Previous studies have demonstrated an inverse relationship between dose size and relative whole-body retention of mercury after oral administration of mercuric chloride to mice. The present study indicates that this inverse relationship is caused by a dose-related induction of kidney damage leading to increasing leakage of mercury through the kidneys. Histopathologic investigation revealed extensive necrosis of the proximal tubules in kidneys from mice exposed to 100 mumole HgCl2/kg or higher doses. Moreover, maximum renal damage occurred between days 2 and 3 after administration. The renal damage was followed by regeneration, which was observed between days 3 and 7 at increasing dose levels up to 100 mumole HgCl2/kg. The amount of glutathione and the glutathione peroxidase activity in kidney decreased with increasing doses of mercuric chloride. The reduced glutathione peroxidase activity was due to a reduction in selenium-dependent glutathione peroxidase activity. The level of lipid peroxidation was not changed by increasing doses of mercuric chloride, and hence was not a primary toxic mechanism in acute nephrotoxicity induced by mercuric chloride.

Animals↗

PubMed1994

Effects of simultaneous low-level dietary supplementation with inorganic and organic selenium on whole-body, blood, and organ levels of toxic metals in mice.

Classical experiments have demonstrated that Se compounds protect against the toxicity of several toxic metals in acute experiments with simultaneous parenteral administration of high doses of Se and the toxic metal. Blood and organ levels of the toxic metals were increased, conceivably due to formation of inert Se complexes. Less is known about effects of long-term Se status on the toxicokinetics of toxic metals. Possible Se interactions in toxic metal biokinetics should therefore be studied at Se levels ranging from those just sufficient to avoid Se deficiency and up to those believed to be optimum in relation to antioxidative and other beneficial effects of Se. The toxic-metal exposure levels investigated should be similar to those occurring in human populations that are not occupationally exposed. To study interactions between Se and toxic metals at ultralow exposure levels, mice were fed semisynthetic diets containing different levels of Se. The mice were given ultralow doses of metal salts either as a single oral dose by stomach tube or as prolonged exposure in the drinking water. Diets with high or normal Se levels slightly, but nonsignificantly increased the whole-body retention (WBR) of Hg++ and CH3Hg+ compared to a diet low in Se. The dietary Se level was, however, without effect on the WBR of Cd2+ and Ag2+ in single-dose experiments. During prolonged exposure, the diets fortified with Se increased the WBR of Ag2+, had no effect on WBR of Hg2+, and reduced the WBR of CH3Hg+ and Cd2+. During prolonged exposure, the diets fortified with Se reduced blood Hg++ while organ levels were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Incidence of juvenile thyrotoxicosis in Denmark, 1982-1988. A nationwide study.

The objective of this study was to ascertain the annual incidence density of thyrotoxicosis in children under the age of 15 years in Denmark in 1982-1988. The design was based on computerized hospital registration of patient admittances in all departments of paediatrics and internal medicine of Denmark (Faroe Islands and Greenland excluded). Fifty-six children (48 girls and 8 boys) had a confirmed diagnosis of thyrotoxicosis, giving a national incidence density of 0.79/100,000 person-years. In children aged 0-4 years the incidence was very low (0.1/100,000), with no sex difference. In boys aged 5-9 years a similar low incidence was found, while in boys aged 10-14 years the incidence increased to 0.48/100,000. In girls aged 5-9 years the incidence increased to 0.96/100,000, reaching a maximum of 3.01 in the 10-14-year-old girls. In children of > 4 years of age a female preponderance of 6.7:1 was significant. It is concluded that thyrotoxicosis is a rare disorder in Danish children under the age of 15 years, and the incidence increases with age. Female preponderance is significant from early childhood.

Adolescent↗

PubMed1994

Spinal arteriovenous malformations. Health-related quality of life after embolization.

The overall function, pain and mood disturbances of 19 patients with spinal arteriovenous malformations (AVM), treated by embolization between 1983 and 1988, were studied. The after-care had taken place in different hospitals and clinics. The patients demonstrated markedly poorer physical function (Sickness Impact Profile) and poorer psychological well-being (Mood Adjective Check List) than control population samples and a comparison group of traumatic incomplete paraplegics. The degree of decrease of mood levels implied possible depressive disorder (Hospital Anxiety and Depression scale) in 16% of the patients and differed from that of the paraplegic comparison group. Furthermore, the AVM patients reported more disturbance of their family and social life than the paraplegics and they were more seldom gainfully employed. Patients recorded a wide range of pain scores, significantly worse than the paraplegics, and their pain was closely linked to overall quality of life (QL) perception. The QL scores were consistently related to all measures of functional and emotional status, but no connection with neurological lesion levels or medical complications was found. Specialised programmes after embolization, such as those offered in spinal injury units, would appear appropriate for AVM patients to improve their physical functioning and to provide a more rewarding social life.

Activities of Daily Living↗

PubMed1994

Hormone conference at Sahlgren's University Hospital: polycythemia and inappropriately high serum erythropoietin concentration in a 62-year-old man.

A 62-year-old man with a history of coronary insufficiency complained at his scheduled visit to the outpatient clinic of symptoms suggestive of gastritis. His blood hemoglobin concentration, however, was markedly increased. Results of a hematological work-up suggested an erythropoietin-producing tumor. Signs of increased intracranial pressure then led to the finding of a cerebellar tumor, which could explain his vertigo and abdominal symptoms. This cystic capillary hemangioblastoma probably was responsible for the erythropoietin production and also seemed to produce basic fibroblast growth factor. The clinical evaluation of polycythemia as well as erythropoietin biochemistry and clinical application are reviewed.

Capillaries↗

PubMed1993

Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis.

Familial amyloid polyneuropathy (FAP) is a fatal autosomal dominant disorder. Progressive peripheral and autonomic neuropathy are associated with neural and visceral deposition of amyloid, derived most commonly from the Met-30 variant of the plasma protein transthyretin. We have reported previously that orthotopic liver transplantation causes prompt replacement of variant transthyretin by the donor wild-type in the plasma. We now report clinical outcome 1-2 years after transplantation. Three of the first four patients have improved general wellbeing, walking ability, and bowel function, and one of them has regained normal bladder and bowel function. There has been little objective improvement in peripheral neuropathy. The fourth patient, who had the most severe neurological deficits and a complicated postoperative course, has not improved but there has been no further deterioration in contrast to the inexorable progression before transplantation. Quantitative scintigraphy with radiolabelled serum amyloid P component showed visceral amyloid deposits in all three patients studied; in two who were followed serially the deposits regressed after transplantation in association with the clinical improvement. Another FAP patient who was also monitored prospectively for 2 years but who did not undergo transplantation, showed, as expected, progression of neuropathy and increased visceral amyloid deposition. Liver transplantation does therefore have important benefits in FAP during the first 2 years after surgery. Neurological decline is halted and amyloid deposits can be mobilised. The best timing and long-term results of the procedure must now be established.

Adult↗

PubMed1993

Adhesion molecule expression on cerebrospinal fluid T lymphocytes: evidence for common recruitment mechanisms in multiple sclerosis, aseptic meningitis, and normal controls.

The expression of T-cell surface antigens was investigated in the cerebrospinal fluid (CSF) and peripheral blood of 11 patients with multiple sclerosis, 6 patients with aseptic meningitis, and 16 healthy subjects. A panel of monoclonal antibodies to adhesion and activation proteins was used in combination with an anti-CD3 antibody in dual-color flow cytometry. The problem of low cell numbers in the CSF from normal individuals was overcome by use of a modified staining procedure in microtiter plates, enabling analysis of as few as 5,000 cells. The majority of T cells in the CSF of the three patient groups exhibited the phenotype of memory cells (CD45RO+). CSF T cells also expressed significantly higher levels of several adhesion and activation molecules, including very late activation (VLA) antigens 3 through 6, lymphocyte function-associated (LFA) antigen 1, LFA-3, CD2, CD26, and CD44. Comparison between the different categories revealed that peripheral blood T cells from patients with multiple sclerosis expressed significantly lower amounts of the VLA integrins 4 and 5 as well as their common beta subunit CD29, compared with normal control subjects. No differences between patients with multiple sclerosis and control subjects could, however, be seen regarding the distribution of memory/naive cells or CD4+/CD8+ cells in peripheral blood. Our data support a hypothesis that memory T cells with a high expression of several adhesion molecules are selectively recruited to the central nervous system compartment, under both pathological and normal conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Prophylactic cranial irradiation increases the risk of testicular damage in adult males surviving ALL in childhood.

By combining three series of Scandinavian patients, we were able to compare the late testicular sequelae in 41 adult males whose therapy had included chemotherapy alone or chemotherapy with cranial irradiation without other radiotherapy for ALL in childhood. In multivariate analysis, cranial irradiation was associated with a decrease of 5.7 (95% confidence limits 1.5-9.9) cm (P = 0.010) in height, and a decrease of 4.8 (0.3-9.2) ml (P = 0.036) in testicle size. Cyclophosphamide was associated with increases of 8.2 (-0.5-16.9) (P = 0.065) and 3.9 (0.3-7.4) U/L (P = 0.036) in serum FSH and LH concentrations, respectively. Of the 12 patients who had received both cranial irradiation and cyclophosphamide therapy, 4 (33%) had delayed pubertal development as compared with 1 (3.5%) of the other 29 patients (P = 0.008). Patients 12-16 years of age at diagnosis had larger testicles (P = 0.051) and higher testosterone concentrations (P = 0.026) than others. Neither sexual activity nor semen findings correlated with the preceding treatment. Our data indicate that prophylactic cranial irradiation may be associated with impaired growth and pubertal development in boys with ALL.

Adolescent↗

PubMed1993

Toxicokinetics of nickel in mice studied with the gamma-emitting isotope 57Ni.

The gamma-emitting isotope 57Ni was generated in a cyclotron to allow whole-body counting of laboratory animals dosed with nickel. 57NiCl2 was administered either orally by gastric intubation or by intraperitoneal injection to groups of mice in doses equivalent to the average human daily dietary nickel intake per mass unit. When given orally, the whole-body retention (WBR) was 0.02-0.36% of the administered dose at 45-75 hr. When given intraperitoneally, the WBR was 1-6% at 20-50 hr. After adjustment for the rapid excretion of systemic nickel, the intestinal absorption could be estimated to be 1.7-10%. The relative WBR did not vary with the magnitude of the dose within 0.05-5 mumol Ni/kg given orally or 0.005-0.5 mumol/kg given intraperitoneally. At 8 hr, the tissue concentration was highest in the kidneys, followed by the carcass, lungs, testicles, liver, and the spleen. After 20 hr, the highest concentrations were still found in the kidneys followed by the lungs, the liver, and the carcass. At 20 hr after oral administration, 50-70% of 57Ni retained in the body was within the carcass. The second highest nickel content was found in the kidneys, followed by the liver and lungs. Whereas nickel in the kidneys was rapidly excreted, the elimination from the lungs and liver was relatively slow, thereby, after 40 hr, resulting in a higher nickel content in the liver than that in the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1993

A nationwide population-based study of the familial aggregation of type 1 (insulin-dependent) diabetes mellitus in Denmark. Danish Study Group of Diabetes in Childhood.

The objective of the present study was to assess the prevalence of familial aggregation of Type 1 (insulin-dependent) diabetes mellitus among Danish families with a diabetic child aged 20 years or less and to compare epidemiological data for familial and sporadic cases. We attempted to identify all patients with Type 1 diabetes aged 0-19 years in Denmark treated at paediatric departments or at departments of internal medicine. This comprises more than 98% of all patients with Type 1 diabetes in this age group. Patients were identified through the local diabetic out-patient registry and asked to complete a questionnaire regarding data on diabetes onset and family history. Of 1574 probands 1419 agreed to participate (90.2%). Additional cases of Type 1 diabetes were found in 171 families (12.8%). Of these 115 were parent-offspring affected families, and in 56 families at least two siblings had Type 1 diabetes and healthy parents. Significant correlation in age at onset of Type 1 diabetes in concordant siblings was observed (r = 0.5, p = 0.0004). Significantly more probands had an affected father with Type 1 diabetes than a mother affected (p < 0.0001). Heterogeneity in epidemiological characteristics was observed between familial and sporadic cases, i.e. familial index cases were younger at onset of the disease, their parents were younger at birth of the index case, and there was no difference in gender of familial cases in contrast to sporadic cases where significantly more males were found. Over a 4-year period (1986-1989) an increasing trend in incidence was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Peripheral neuropathy associated with monoclonal IgM antibody to glycolipids with a terminal glucuronyl-3-sulfate epitope.

Twenty-nine patients with paraproteinaemia, 12 with neuropathy and 17 without a previous record of neurological symptoms were clinically characterized. All 12 neuropathy patients had a moderate to severe sensorimotor demyelinating neuropathy. The patients were examined with regard to serum antibodies to gangliosides, including GM1, GD1a, GD1b, GT1b, and LM1, and other acidic glycolipids, including LK1 and sulphatide, of human brain and peripheral nerve. Sera from 80 blood donors, 40 men and 40 women 20-60 years of age, were used as normal controls. The sera were analysed with an ELISA performed on thin-layer chromatography plates. At a dilution of 1/400 none of the control sera gave a detectable reaction and a titre of > or = 1:400 was considered as a positive test. In 11 of the 12 neuropathy patients the paraproteinaemia was of IgM type and 10 of them had a positive antibody titre against LK1 and Hex-LK1, acidic glycolipids with a terminal glucuronyl-3-sulphate group. The antibody titre against LK1 in 1 patient was 1:400 and varied between 1:5,000 and 1:3,200,000 in the other 9. One of the patients also had a positive titre, 1:64,000, to sulphatide. None of the sera from the 17 paraproteinaemia patients without a previous record of neurological symptoms contained antibodies to LK1 or to any glycolipid antigen examined, except for sulphatide. A positive titre (> or = 1:400) of antibodies to sulphatide was found in sera from 4 of these patients, the titres being < or = 3,200.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study.

A neurological surveillance was combined with prospective recording of upper respiratory and gastrointestinal infections and serological diagnosis of five common viral infections in 60 benign multiple sclerosis patients, with a mean follow-up of 31 months. During 4-week at risk (AR) periods encompassing common infections, a significant excess of MS relapses was found in the AR period, with a relative risk of 1.3. A seasonal variation of the MS relapse rate was found with a minimum in summer. There was a significant correlation between the number of AR relapses and the number of common infections per month explaining the periannual distribution of relapses. The non-AR relapses showed no seasonal variation. There was a significant correlation between adenovirus CF titre rises associated with upper respiratory infections and the occurrence of a major MS relapse in the AR period (n = 7), while influenza infections were not followed by a major MS relapse (n = 6). Linear homologies have been demonstrated between adenovirus and basic myelin protein. The epidemiological approach is essential to our understanding of systemic antigens triggering multiple sclerosis activity.

Adult↗

PubMed1993

Susceptibility to demyelinating polyneuropathy in plasma cell dyscrasia may be influenced by amino acid position 9 of the HLA-DR beta chain.

Fifty-five patients with plasma cell dyscrasias were investigated by genomic typing for HLA-DR and -DQ genes by restriction fragment length polymorphism, neurophysiology and for presence of anti-myelin-associated glycoprotein (MAG) antibodies. In 26 patients, a polyneuropathy (PN) of demyelinating type was established. Among these individuals, an association was found with the presence of a tryptophan amino acid residue at position 9 of the DR beta chain (P < 0.01). This position is part of the first hypervariable region of the DR beta chain, and may be of importance in determining preferential peptide-binding capacity of the HLA-DR molecule. The presence of anti-MAG antibodies in 15 out of 17 patients with an IgM M-component and demyelinating PN (14 of these 15 individuals carrying a tryptophan at position 9) supports the pathogenic role of an autoimmune response against MAG. The finding of an HLA class II association may indicate a pathogenic role of T cell immunity in this condition.

Adult↗

PubMed1993

Estrogen receptor binds to the salmon GnRH gene in a region with long palindromic sequences.

Footprinting and gel shift assays demonstrated that the human estrogen receptor (hER) specifically binds to two estrogen response element (ERE)-like motifs in the gonadotropin releasing hormone (GnRH) gene promoter region of Atlantic salmon (Salmo salar). The two ER binding sites are situated approximately 1.5 kb upstream of the transcriptional start site of the GnRH gene and are localized 49 bp from each other. Each ERE-like motif is composed of two palindromic ERE half-sites interspaced by 8 and 9 nucleotides, respectively. The salmon GnRH gene promoter region contains an almost perfect 426-bp-long palindromic sequence that might form a cruciform structure.

Animals↗