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Biomedical subjects

O Andersen

Publications and source records attributed to O Andersen.

At least 19 recordsLinked to original sources
PubMed2000

Multiple variants of the peroxisome proliferator-activated receptor (PPAR) gamma are expressed in the liver of atlantic salmon (Salmo salar).

A full-length cDNA encoding the peroxisome proliferator-activated receptor (PPAR) has for the first time been characterized from a fish species. The Atlantic salmon PPARgamma cDNA of 2528 nucleotides (nt) was amplified from liver mRNA by reverse transcription (RT)-polymerase chain reaction (PCR). The deduced protein of 544 amino acids (aa) shares approximately 47% overall sequence identity with mammalian PPARgamma. The N-terminal A/B region contains a repeated decapeptide motif and shows a low homology with other PPARs. In contrast, the central DNA-binding domain (DBD) and the C-terminal ligand-binding domain (LBD) show a high sequence identity to mammalian and Xenopus PPARgamma. The salmon PPARgamma LBD contains nine additional residues in a flexible loop that might affect ligand binding. Northern blot analysis of salmon liver RNA revealed a prominent transcript of about 1.7 kilo bases (kb), in addition to several mRNA species of about 2.4-2.6kb, which is consistent with the presence of multiple putative polyadenylation sites in the 3' untranslated region (UTR) of the 2528nt long PPARgamma cDNA. Two additional PPARgamma cDNAs of 1719 and 2357nt were then isolated. The 2357nt long transcript encodes full-length PPARgamma and seems to be ubiquitously expressed in salmon, whereas the liver-specific transcript of 1719nt encodes a truncated variant of PPARgamma. The truncated form lacks 39 C-terminal residues including the conserved activation function-2 (AF-2) motif, known to be associated with crucial cofactors. Three-dimensional modelling studies indicated that the C-terminal truncation would result in important alterations of the ligand-binding pocket. The presence of a truncated form with drastic changes in both ligand- and cofactor-binding sites is likely to modulate PPARgamma activity in salmon liver.

Amino Acid Sequence↗
PubMed2000

[Fatal outcome of Strongyloides stercoralis infection in a patient with no previously known immunosuppression].

A case of fatal infection with Strongyloides stercoralis in a previously healthy young African with no known immunosuppression is reported. The patient suffered severe gastrointestinal bleeding and despite intensive treatment died of multiorgan failure. Postmortem, signs of ulcerating T-cell lymphoma were found in a jejunal specimen, and the patient was found to be infected with HTLV-1. Gastrointestinal bleeding in relation to infection with Strongyloides stercoralis is discussed as well as possible relations between the severity of infection, lymphoma and HTLV-1.

Adult↗
PubMed2000

Effects of cadmium exposure on volume regulation in the lugworm, Arenicola marina.

Effects of hypo-osmotic stress and Cd (cadmium) exposure, applied singly or in combination, on volume regulation were investigated in Arenicola marina, the common European lugworm. In short-term experiments, the combined exposure to Cd and hypo-osmotic stress mainly affected the worm's capacity for regulating the coelomic fluid volume without significantly affecting the regulation of intracellular fluid volume. Exposure to Cd increased the worm's sensitivity to hypo-osmotic stress noted as increased mortality compared to the mortality in groups exposed only to Cd or hypo-osmotic stress. In long-term Cd exposure experiments, the capacity for coelomic fluid volume regulation was affected even at constant external osmolarity and the tissue water concentration decreased slightly. The results could not be explained by changes in Apparent Water Permeability (AWP) as Cd did not significantly affect this. The glycogen content of the chloragogenous tissue did, however, increase during long-term Cd exposure suggesting a metabolic effect. The results demonstrate that two stressors, each without serious effects when applied alone, may have fatal effects when applied in combination. The kind of osmotic stress applied in these experiments is common in many biotopes inhabited by the lugworm. The severe effects of the combination with Cd exposure indicate that classical ecotoxicology testing could conceivably underestimate the toxicity of chemical compounds due to not considering combined effects of natural and anthropogenic stressors.

Journal Article↗
PubMed2000

Incidence of CSF abnormalities in siblings of multiple sclerosis patients and unrelated controls.

We found that 19% (9/47) of healthy siblings of patients with clinically definite multiple sclerosis had an intrathecal immunological reaction with two or more 2 CSF-enriched oligoclonal bands (OCBs), in contrast to (4%) (2/50) unrelated healthy controls. Furthermore, in this group of nine healthy sibs the measles CSF IgG antibody titers were higher than that of the other sibs and that of controls. There were also differences in the serum titers for measles IgG antibody, which were higher in the group of all healthy sibs than in healthy volunteers, and (as with CSF titers) higher in the subgroup of healthy sibs with two or more 2 CSF-enriched OCBs than the other sibs. Thus a significant proportion of healthy siblings to MS patients have a partially hyperimmune condition similar to that occurring in MS, which in 19% manifested itself as an OCB reaction, in 9% as increased CSF measles IgG antibody titers, and in 21% as increased serum measles IgG antibody titers, these phenomena tending to occur in the same individuals. This condition is characterized by CSF-enriched OCBs with undefined specificity, although some increased antiviral reactivity is found both in the serum and CSF. While it needs further characterization, a genetic trait interacting with common infections is suggested. The recurrence risk of this condition is approximately five times higher than the 3-4% recurrence risk for manifest MS reported for sibs.

Adolescent↗
PubMed2000

Antiemetic efficacy of combination therapy with granisetron plus prednisolone plus the dopamine D2 antagonist metopimazine during multiple cycles of moderately emetogenic chemotherapy in patients refractory to previous antiemetic therapy.

Effective antiemetic treatment of patients who have previously experienced chemotherapy-induced nausea and vomiting is difficult. The aim of this study was to evaluate the antiemetic efficacy of a single intravenous dose of granisetron plus a 3-day oral treatment with prednisolone 25 mg once a day plus metopimazine 30 mg four times a day in patients refractory to previous antiemetic treatment with granisetron or with prednisolone plus metopimazine. The study population was made up of 25 consecutive women with stage I or II breast cancer, who were treated with multiple cycles of adjuvant cyclophosphamide, fluorouracil plus methotrexate or cyclophosphamide, epirubicin plus fluorouracil given i.v. every 3 weeks. Patients received the three-drug combination of antiemetics during a total of 113 cycles of chemotherapy. No emetic episodes were reported in 88.9% cycles on day 1, in 94.7% cycles on days 2 through 5 and in 85.8% cycles on days 1 through 5 after chemotherapy. No nausea was reported in 43.4% cycles on day 1, in 49.6% cycles on days 2 through 5 and in 34.5% cycles on days 1 through 5. Nineteen patients (76.0%) completed the scheduled nine cycles of chemotherapy, 1 being withdrawn because of > or =5 emetic episodes and 5, because they were not satisfied with the antiemetic treatment. The treatment was well tolerated. In conclusion, granisetron plus prednisolone plus metopimazine is a highly effective antiemetic treatment in patients receiving moderately emetogenic chemotherapy refractory to antiemetic therapy with granisetron or prednisolone plus metopimazine.

Adult↗
PubMed2000

Salmon antithrombin has only three carbohydrate side chains, and shows functional similarities to human beta-antithrombin.

Antithrombin, a major coagulation inhibitor in mammals, has for the first time been cDNA cloned from a fish species. The predicted mature liver antithrombin of Atlantic salmon (Salmo salar) consists of 430 amino acids and shows about 67% sequence identity to mammalian and chicken antithrombins. Due to a single nucleotide replacement, Asn135 of the antithrombin in higher vertebrates is substituted by Asp in the salmon homolog. Hence, in contrast to the vertebrate antithrombins known so far, salmon antithrombin lacks the potential glycosylation site located close to the heparin binding site. The existence of only three N-linked side chains is evidenced by the sequential removal of three carbohydrate chains from salmon antithrombin during timed-digestion with N-glycosidase F. The high heparin binding affinity of the salmon inhibitor, Kd of 2.2 and 48 nM at I = 0.15 and 0.3, respectively, is very similar to that of the minor human isoform beta-antithrombin, which is not glycosylated at Asn135. Furthermore, the invariant third-position Ser137 at this glycosylation site of mammalian and chicken antithrombins is substituted by Thr in the salmon, a replacement that has been shown to induce full glycosylation in human antithrombin. Thus a rapidly reacting pool of antithrombin may have evolved in two different ways: absence of a glycosylation site in lower vertebrates vs. incomplete glycosylation of a part of the circulating antithrombin in higher vertebrates. Salmon antithrombin appears to have three complex oligosaccharide side chains containing sialic acid terminally linked alpha(2-3) to galactose, while trace amounts of Galbeta(1-4)GlcNAc suggest microheterogeneity due to partial loss of sialic acid.

Amino Acid Sequence↗
PubMed2000

Myelitis.

Acute transverse myelitis (ATM) with moderate symptomatology and smaller multiple magnetic resonance imaging lesions is often caused by multiple sclerosis. Severe ATM with extensive magnetic resonance imaging lesions with or without associated meningitis often has a viral cause, particularly in the younger age groups, whereas vascular disorders may prevail among older patients. Previously, one had to rely on indirect evidence such as viral serology or viral identification in throat washings to confirm a diagnosis of myelitis. Thus, mycoplasma myelitis may occur coincident with a mycoplasma pneumonia. Viral myelitis is now often diagnosed by specific polymerase chain reaction of the cerebrospinal fluid, for echovirus, Coxsackie virus, mumps virus, herpes simplex virus or varicella-zoster virus, but an autoimmune component may still be important. An anterior horn syndrome may be produced by the tick-borne encephalomyelitis virus. Severe ATM may also be a postinfectious or postvaccinal disorder [i.e. a partial acute disseminated encephalomyelitis (ADEM)]. Neuromyelitis optica, a combination of severe myelitis and optic neuritis, is often a manifestation of ADEM or systemic lupus erythematosus. Many of these disorders are potentially treatable with specific antiviral agents or immunosuppression. 'Idiopathic' ATM is probably a consequence of inadequate examination and follow up. The differential diagnoses-viral myelitis, multiple sclerosis, ADEM, neuromyelitis optica, spinal arteriovenous malformation and arteritis-should be considered and are usually identified by a rapid diagnostic work-up, leaving few ATM cases undiagnosed.

Acute Disease↗
PubMed2000

A quality network model for the daily care of multiple sclerosis.

The urgent need to optimise treatment strategies for patients with Multiple Sclerosis (MS) was recognised by the participants at the 1998 European Charcot Foundation (ECF) symposium in Nice. The 'Nice Declaration' led to the formation of a Task Force Essentials Group charged with developing measures of the quality of MS care in Europe. Algorithms for nine critical domains (disability, spasticity, ataxia, pain, cognition, mood, fatigue, bladder function and sexual activity) and 'educated guesses' have been developed to measure interventions and outcomes which reflect the quality of clinical decision-making processes. A generic model called a 'quality network', consisting of a group of clinics connected to a central server, has been successfully applied to the care of diabetes across Europe. This model will now be developed and applied to MS management, to provide clinicians with longitudinal epidemiological data and, to evolve treatment algorithms and further quality measures. The ECF will next validate the system in a 1-year pilot study using a net of 10 clinics. Finally, an extended European network working in a learning environment will continuously assess, update and improve the quality of care of MS patients. Multiple Sclerosis (2000) 6 231 - 236

Algorithms↗
PubMed2000

N-methoxyindole-3-carbinol is a more efficient inducer of cytochrome P-450 1A1 in cultured cells than indol-3-carbinol.

The well-documented reduction of cancer risk by high dietary cruciferous vegetable intake may in part be caused by modulation of cytochrome P-450 (CYP) expression and activity by indoles. The purpose of the present experiments was to study the mechanism of CYP 1A1 induction by N-methoxyindole-3-carbinol (NI3C) in cultured cells and to compare the CYP-inducing potential of NI3C and indole-3-carbinol (I3C) administered to rats. NI3C induced 7-ethoxyresorufin-O-deethylase (EROD) activity in Hepa-1c1c7 cells in a concentration-dependent manner with 10-fold higher efficiency than I3C. Inasmuch as NI3C induced binding of the aryl hydrocarbon receptor (AhR) to the dioxin-responsive element and induced expression of endogenous CYP 1A1 mRNA and an AhR-responsive chloramphenicol acetyl transferase construct, we conclude that NI3C can activate the AhR. Besides the induction of CYP 1A1, we observed an inhibition of EROD activity, with a concentration causing 50% inhibition of 6 microM. Oral administration of NI3C at 570 mumol/kg body wt to male Wistar rats increased the hepatic CYP 1A1 and 1A2 protein levels, as well as the EROD and 7-methoxyresorufin O-demethylase activities at 8 and 24 hours after administration, but the responses were less pronounced than after administration of I3C at 570 mumol/kg body wt. Furthermore, NI3C did not induce hepatic 7-pentoxyresorufin O-depentylase activity, as I3C did. Ascorbigen, another indolylic compound formed during degradation of glucobrassicin in the presence of ascorbic acid, was tested in the same animal model, and ascorbigen only weakly induced hepatic CYP 1A1 and 1A2, but not CYP 2B1/2. In conclusion, NI3C is a more efficient inducer of CYP 1A1 in cultured cells than I3C but is less active when administered to rodents.

Animals↗
PubMed2000

Rapid method to characterize mutations in transthyretin in cerebrospinal fluid from familial amyloidotic polyneuropathy patients by use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

BACKGROUND: Familial amyloidotic polyneuropathy (FAP) type I, the most common dominantly inherited form of amyloidosis, is caused by a Val-to-Met point mutation at position 30 (Val(30)-->Met) in the protein transthyretin. Mass spectrometric analysis can identify modification of proteins, such as point mutations, acetylation, phosphorylation, sulfation, oxidation, and glycosylation. METHODS: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) spectra from cerebrospinal fluid (CSF) drawn from a patient with FAP were compared with CSF from controls. We also isolated transthyretin with a Centrisart molecular size cutoff filter and performed high-accuracy peptide mass mapping to localize the site of the amino acid substitution (Val(30)-->Met). RESULTS: Mass spectra of transthyretin were produced directly from human CSF as well as from CSF after a simple prepurification method without immunoprecipitation. On-target tryptic digestion and MALDI-MS verified mass spectrometric peak identification. The point mutation was still detectable in CSF after hepatic transplantation. CONCLUSIONS: It is possible to diagnose FAP by a rapid MALDI-TOF MS analysis using only 100 microL of CSF, with only 250 nL actually consumed on target. The approach may also be useful to monitor production of mutated transthyretin by choroid plexus, especially after liver transplantation.

Adult↗
PubMed1999

Nitric oxide metabolites in CSF of patients with MS are related to clinical disease course.

In this study, we have analyzed the stable metabolites of nitric oxide (NO), nitrite and nitrate, in the CSF of patients with MS, lymphocytic meningitis, and in healthy control subjects. Patients with MS with an active disease course exhibited increased CSF nitrite levels compared with patients with stable MS and healthy control subjects, whereas CSF nitrate levels did not differ between these groups. High CSF levels of both metabolites were seen in patients with meningitis. These data indicate that CSF nitrite levels may reflect clinical disease activity in MS.

Humans↗
PubMed1999

Feasibility of neonatal screening for toxoplasma infection in the absence of prenatal treatment. Danish Congenital Toxoplasmosis Study Group .

BACKGROUND: The best method for prevention and control of congenital toxoplasma infection is uncertain. Prenatal screening is done in Austria and France, but the effect of treatment during pregnancy is not well documented. The aim of our study was to find out the maternofetal transmission rate and outcome in infants born to mothers who were not treated during pregnancy. METHODS: We analysed 89873 eluates from phenylketonuria (PKU) cards from neonates and paired first-trimester serum samples from the mothers for specific IgG antibodies to Toxoplasma gondii. Children born to mothers who seroconverted during pregnancy were followed-up clinically and serologically to 12 months of age. In addition, 21144 PKU cards were analysed for toxoplasma-specific IgM antibodies during the last 12 months of the study. FINDINGS: In 24989 (27.8%) cases both the PKU eluate and the first-trimester samples were IgG positive, which indicates previous maternal infection. 139 of the 64884 seronegative women acquired toxoplasma infection during pregnancy and gave birth to 141 infants (two sets of twins). 27 of these children were diagnosed with congenital toxoplasma infection. The transmission rate was 19.4% (95% CI 13.2-27.0). Clinical signs and symptoms were found in four (15%) of the 27 children. The additional analysis for toxoplasma-specific IgM antibodies from the PKU card identified seven of nine children with congenital toxoplasma infection. The false-positive rate for the IgM test was 0.19 per 1000, and no false-negatives were found. INTERPRETATION: The risks of transmission of infection and of disease in the infant are low in an area with a low risk of toxoplasma infection. A neonatal screening programme based on detection of toxoplasma-specific IgM antibodies alone will identify between 70% and 80% of cases of congenital toxoplasmosis.

Adult↗
PubMed1999

Modulation of drug-metabolising enzyme expression by condensation products of indole-3-ylcarbinol, an inducer in cruciferous vegetables.

Indole-3-ylcarbinol (13C) is formed during processing of cruciferous vegetables and is suggested to be one of the modulators of drug-metabolising enzymes. Indole-3-ylcarbinol is a far less efficient inducer of hepatic enzymes after parenteral than after oral administration, due to formation of active metabolites in the gastrointestinal tract. As indole-3-ylcarbinol is unstable in weakly acidic aqueous solutions, non-active condensation products may be formed from indole-3-ylcarbinol, that cannot be transformed to the active products when reaching the stomach. The purpose of the present study was to test the ability of the condensation products formed at a pH corresponding to that of fresh vegetable juice to modulate the metabolism of xenobiotics. Indole-3-ylcarbinol was incubated in vitro at room temperature in the dark at pH 5.5 and samples taken at various times, for oral administration to rats and for chemical analysis. Indole-3-ylcarbinol was rapidly transformed into various oligomeric products. The 7-ethoxyresorufin O-deethylase activities (marker of cytochrome Cytochrome P450 1A enzymes, CYP1A) in liver, kidney and colon increased with the duration of the in vitro condensation period whereas the formation of 6beta-, 15beta- and and 2alpha-hydroxytestosterone was not affected significantly, indicating no effect on CYP2C11 or CYP3A enzymes. The hepatic metabolism of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). was increased by indole-3-ylcarbinol condensation products and the 4'-OH-PhIP/N-OH-PhIP ratio was decreased due to a significantly increased formation of the proximate genotoxic metabolite. N-OH-PhIP. The activities of DT-diaphorase and glutathione S-transferase were not changed significantly in the rat organs. These experiments clearly indicate that indole-3-ylcarbinol is not the definitive CYP1A inducer and that indole-3-ylcarbinol at near-neutral pH, is transformed to compounds that are inducers by themselves or may be further converted into inducing compounds in the rat stomach. Also, the enzyme inducing potency of indole-3-ylcarbinol containing vegetable juice is apparently enhanced by incubation in vitro before the intake.

Animals↗
PubMed1999

Modulation of cytochrome P-450 and glutathione S-transferase isoform expression in vivo by intact and degraded indolyl glucosinolates.

Various dietary substances modulate the xenobiotic metabolism and may thereby protect against toxicity and carcinogenicity of food toxins. The effects of pure indolyl glucosinolates, which are present in cruciferous vegetables, on induction of specific cytochrome P-450 (CYP) and glutathione S-transferase (GST) isoforms have not been studied previously. In the present study, glucobrassicin (GB) and neoglucobrassicin (NeoGB) were purified from broccoli by use of a single-column method. Furthermore, a mixture containing 48% GB, 36% NeoGB, and 16% 4-methoxyglucobrassicin was obtained. The modulatory effects of the pure GB, NeoGB, and the mixture on activities and levels of hepatic CYP 1A, 2B1/2, and 2E1 and alpha- and mu-GST isoforms were investigated in male Wistar rats. The indolyl mixture was the most powerful and NeoGB the weakest inducer of microsomal hepatic CYP 1A1 protein and 7-ethoxyresorufin O-deethylase activity. Furthermore, intact indolyl glucosinolates were more powerful inducers than the in vitro myrosinase-degraded indolyl glucosinolates. The hepatic 7-methoxyresorufin O-deethylase activities, but not CYP 1A2 protein, were induced by pure GB, whereas the mixture and NeoGB showed only minor effects. Neither CYP 2B1/2 nor 2E1 was induced by the indolyl glucosinolates. None of the hepatic GST subunits analyzed, rGST A1/2, A3, or M3, was induced significantly by the purified indolyl glucosinolates.

Animals↗
PubMed1999

Occupational class and ischemic heart disease mortality in the United States and 11 European countries.

OBJECTIVES: Twelve countries were compared with respect to occupational class differences in ischemic heart disease mortality in order to identify factors that are associated with smaller or larger mortality differences. METHODS: Data on mortality by occupational class among men aged 30 to 64 years were obtained from national longitudinal or cross-sectional studies for the 1980s. A common occupational class scheme was applied to most countries. Potential effects of the main data problems were evaluated quantitatively. RESULTS: A north-south contrast existed within Europe. In England and Wales, Ireland, and Nordic countries, manual classes had higher mortality rates than nonmanual classes. In France, Switzerland, and Mediterranean countries, manual classes had mortality rates as low as, or lower than, those among nonmanual classes. Compared with Northern Europe, mortality differences in the United States were smaller (among men aged 30-44 years) or about as large (among men aged 45-64 years). CONCLUSIONS: The results underline the highly variable nature of socioeconomic inequalities in ischemic heart disease mortality. These inequalities appear to be highly sensitive to social gradients in behavioral risk factors. These risk factor gradients are determined by cultural as well as socioeconomic developments.

Adult↗