[Treatment of enuresis nocturna--for the last time--this time].
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Child↗
Biomedical subjects
O Andersen
Publications and source records attributed to O Andersen.
No evidence for spumavirus or oncovirus infection in relapsing-remitting multiple sclerosis.
Polymerase chain reaction analysis was used to investigate the possible role of human spumaretrovirus and oncoretroviruses (human T-cell lymphotropic virus types I [HTLV-I] and II [HTLV-II]) in multiple sclerosis. Eleven patients with relapsing-remitting multiple sclerosis in exacerbation and 11 normal blood donors were included in the study. Cerebrospinal fluid cells, peripheral blood mononuclear cells, and plasma were cocultured with allogeneic mononuclear cells for 6 weeks. Cultured cells were subjected to polymerase chain reaction analysis with primers selected for the pol and gag (human spumaretrovirus), pol and env (HTLV-I), and pol (HTLV-II) genes. Polymerase chain reaction was negative in all patient and blood donor control samples, whereas positive controls were consistently reactive with high sensitivity. No culture exhibited cytopathic effects and supernatants were negative for reverse transcriptase activity. Thus, our results do not support a role for these retroviruses in the pathogenesis of multiple sclerosis.
Adult↗
Effects of dietary lipids on whole-body retention and organ distribution of organic and inorganic mercury in mice.
The effect has been investigated of dietary lipids on the whole-body retention and organ distribution of organic and inorganic mercury in mice. A single oral dose of methylmercury chloride or mercuric chloride labelled with 203Hg was given to female NMRI mice fed semi-synthetic diets containing varying amounts (5, 10, 20 or 50%) of energy derived from lipid (coconut oil, soya oil, or cod liver oil). The whole-body retention and relative organ distribution of mercury depended on diet composition. Thus, a significant reduction of the whole-body retention of mercury was seen in mice fed a diet containing 50% cod liver oil compared with mice fed a diet containing 50% coconut oil. After oral administration of mercuric chloride the relative deposition of mercury in the kidneys increased while that in the liver decreased with increasing concentrations of soya oil or coconut oil in the diet. The whole-body retention of mercury after treatment with methylmercury chloride was significantly decreased in mice fed cod liver oil compared with mice fed coconut oil; there was no difference between mice fed cod liver oil and those fed soya oil. The relative disposition of mercury was significantly higher in all organs of mice fed a diet containing 20% energy from cod liver oil compared with mice fed a diet containing 20% energy from soya oil. The present study demonstrates that diet composition is of major importance to the toxicokinetics of methylmercury and mercuric mercury.
Administration, Oral↗
The toxicokinetics of mercury in mice offspring after maternal exposure to methylmercury--effect of selenomethionine.
Human evidence indicates fetotoxicity of methylmercury at exposure levels inducing only slight and reversible maternal toxicity, but experimental animal data demonstrate, that fetotoxicity may occur despite absence of noticeable maternal toxicity. However, in contrast to the long-term exposure in humans, the key point in the experimental design of the majority of experimental studies has been administration of few doses of methylmercury late in gestation. The present study in mice therefore used long-term maternal exposure to methylmercury (1 nmol/ml in drinking water) and a cross-fostering design to investigate separately in different offsprings the toxicokinetics of transplacentally absorbed mercury and mercury retained during lactation. Further, the influence of seleno-L-methionine (3 micrograms/ml in drinking water) on the toxicokinetics of methylmercury in these mice was studied. The present study demonstrated, that independent on seleno-L-methionine supplementation, offspring deposited equal amounts of mercury during lactation and during gestation. Moreover, the organ distribution and rate of excretion of mercury in transplacentally exposed mice were considerably different from those in mice exposed postnatally and from adult mice in studies using comparable dosages. Seleno-L-methionine only slightly affected the toxicokinetics of mercury in offspring.
Animals↗
The Atlantic salmon prepro-gonadotropin releasing hormone gene and mRNA.
Screening for the gene encoding salmon gonadotropin releasing hormone (sGnRH) in an Atlantic salmon (Salmo salar) genomic library resulted in isolation of a positive clone designated lambda sGnRH-1. An anchor polymerase chain reaction (PCR) technique was used to amplify GnRH cDNA derived from salmon hypothalamic mRNA. The cDNA sequence was aligned to the 7607 base pair genomic sequence which was shown to encode the entire prepro-GnRH gene. The cDNA proved that the cloned gene is expressed in the hypothalamus of mature salmon. The coding domain of sGnRH differs from the mammalian GnRH by six nucleotide changes which allow the two amino acid differences between the two GnRH variants. Salmon GnRH associated peptide (GAP) differs extensively in sequence and size from the mammalian counterpart. Compared to the GnRH cDNA of a cichlid species the similarity is 69.3% in the protein coding sequence.
Amino Acid Sequence↗
Purification, subunit characterization and ultrastructure of three soluble bovine lectins: conglutinin, mannose-binding protein and the pentraxin serum amyloid P-component.
Conglutinin and mannose-binding protein (MBP) are members of the C-type lectins which are widely present in mammalian plasma. Serum amyloid P-component (SAP) is a member of the pentraxin family with lectin properties. A scheme for the partial purification of all three lectins by carbohydrate affinity chromatography and selective elution was developed. The purification was monitored by SDS-PAGE, Western blotting and electron microscopy. Binding of the lectins to Sephadex-iC3b, their collagenase sensitivity, and the size and antibody reactivity of their subunits was investigated. The demonstration, by SDS-PAGE, of 25-kDa subunits, which were unaffected by collagenase treatment but bound to Sephadex-iC3b and antibodies to human SAP, indicated the existence of bovine SAP. Bovine conglutinin (BK) also showed calcium-dependent binding to Sephadex-iC3b, whereas bovine MBP did not. The binding of BK was inhibitable with GlcNAc. A 3000-fold increase in BK activity (ELISA) was obtained in eluates from Sephadex-iC3b. SDS-PAGE analyses of BK and MBP revealed subunits with an Mr of 43 kDa and 30 kDa, respectively. These subunits were sensitive to collagenase treatment which reduced the Mr to 20 kDa. Electron micrographs revealed a prominent flexible tetramer molecule (diameter 96 nm) in the BK preparations, a predominantly hexameric structure (diameter 30 nm) in the MBP preparations, and single annular pentameric disc-like molecules (diameter 11 nm) in the SAP preparations.
Animals↗
Use of immunoreactive synthetic HTLV-1 peptides in the search for antibody reactivity in multiple sclerosis.
The possible association between multiple sclerosis (MS) and antibodies to human T-cell lymphotropic virus type 1 (HTLV-1) was studied. Five synthetic and highly immunoreactive HTLV-1 peptides, four from the envelope (env) region and one from the core (gag) region, were used in an indirect enzyme-linked immunosorbent assay (ELISA). Presence of HTLV-1-specific antibodies in paired serum and cerebrospinal fluid (CSF) samples from 41 MS patients were investigated. No antibody reactivity was demonstrable in samples from 40 of them, whereas one reacted in one serum sample against the gag-peptide. Serum and CSF specimens from 15 with other neurologic diseases (OND), and negative control specimens, i.e. serum and CSF from 9 non-neurologic controls and CSF from 9 healthy controls, did not demonstrate any reactivity in the peptide-ELISAs. Our results do not support involvement of HTLV-1 infection in the etiology of MS.
Adolescent↗
Remission rate after thymectomy in myasthenia gravis when the bias of immunosuppressive therapy is eliminated.
The clinical course of all 86 myasthenia gravis (MG) patients who were thymectomized at Sahlgrenska Hospital between 1955 and 1980 was evaluated in order to estimate what the rate of complete clinical remission (with or without anticholinesterase medication) would be without immunosuppressive (IS) therapy; 19 of 73 patients without thymoma received IS therapy. A suitable way of dissociating the course after thymectomy from the influence of IS therapy is the Markov method. The calculated probability of remission was 0.18, 0.35, 0.43, 0.53 and 0.56 in the 0-1, 2-3, 4-5, 5-10 and more than 10-year periods after thymectomy. A similar result (53 +/- 7%) was obtained by a life-table method with censoring of IS-treated patients when they received such therapy. Time to remission was significantly shorter for patients with age of MG onset before 35 years. Timing of IS therapy after thymectomy is discussed, considering the post-thymectomy remission rate.
Adult↗
Localization of gastrointestinal deposition of mercuric chloride studied in vivo.
During the last 5 years, the site of gastrointestinal absorption of inorganic mercury has been attempted identified mainly by experiments using perfused intestinal segments in vitro or in situ. The present investigation will discuss the localization of the absorption site for mercuric chloride based on a completely undisturbed in vivo experimental model in mice. As the mice were allowed to eat their normal diet during the experimental period, the present results would independently add to existing knowledge on intestinal absorption sites for inorganic mercury. The mice were given 203Hg labelled mercuric chloride orally, either through stomach tube or in the drinking water, and were killed after various time intervals. Mercury was localized and quantified in various segments of the gastrointestinal tract by gamma-counting. Time course analysis of the segmental deposition of mercury demonstrated that the deposition mainly takes place in the proximal jejunum and suggested that a larger part of the jejunum than previously reported is involved in absorption of mercury. Using this in vivo model, tetraethylthiuram disulfide was demonstrated to increase the intestinal deposition and absorption without changing the site of deposition.
Animals↗
Immunochemical and clinical effects of immunosuppressive treatment in monoclonal IgM neuropathy.
A pathogenic role of the M protein in monoclonal IgM neuropathy has been suggested. This is based among other things on a close relation between immunosuppressive treatment, lowered concentration of M protein, and clinical effect. We studied five patients with monoclonal IgM and antibodies to peripheral nerve myelin. The immunosuppressive treatment was beneficial in three of the patients. In three patients there was a relationship between antibody concentration and clinical effect (in one there was no change in antibody concentrations and correspondingly no change in clinical status, and in two patients clinical improvement corresponded to decreased antibody concentrations). In two patients, however, there was no clear correlation, since one patient improved despite increasing antibody concentrations and one patient did not improve despite a lowered antibody concentration. It is therefore possible that other mechanisms may contribute to the effect of treatment.
Adult↗
Factors affecting the intestinal uptake of cadmium from the diet.
Human data on the effects of diet composition on intestinal cadmium uptake are almost completely lacking but animal experiments indicate that it may profoundly influence the intestinal uptake of ionic cadmium. Thus, rats and mice fed human dietary items absorbed 5-8 times more cadmium than animals fed ordinary rodent pellets. All the data currently available indicates that, both in humans and in experimental animals, the bioavailability of dietary cadmium is not very different from that of ionic cadmium. However, diet composition may markedly affect the uptake of the latter. Accordingly, a valid assessment of the bioavailability of cadmium can be made in experiments where ionic cadmium is administered mixed with the diet. It is important, however, to discriminate between diet composition at the time of administration and dietary status. A better understanding of the factors affecting intestinal cadmium uptake is necessary in assessing the risk associated with dietary cadmium exposure and further studies are therefore urgently needed.
Animals↗
Transplacental passage and fetal deposition of mercury after low-level exposure to methylmercury--effect of seleno-L-methionine.
Previous experimental studies on transplacental passage and possible fetotoxicity of methylmercury have almost exclusively used a single dosage or 2-4 repeated doses of mercury on specific days during gestation and often used at relatively high dose levels. In previous studies, selenium supplementation considerably increased the concentration of mercury in the blood of offspring after maternal exposure of rats to methylmercury, whereas whole-body retention and organ deposition of mercury in mice were unaffected. The present study in mice, which involved exposure for 5 weeks to a low dose of methylmercury in the drinking water (1 nmol/ml) before and during pregnancy, demonstrates that mercury is deposited in offspring both in utero and during lactation, and that transplacentally absorbed mercury is not, or only very slowly, excreted. Seleno-L-methionine increased the deposition of mercury in offspring, but the effect was due to slightly higher deposition in the dams. Selenomethionine significantly reduced the kidney deposition of mercury in offspring, whereas liver deposition of mercury was unaffected. These results indicate that interactions between organo-selenium compounds and methylmercury orally administered at low doses is of less importance than previously believed on the basis of experiments with higher doses of selenite injected or supplemented to the diet.
Adolescent↗
Segregation and manifestations of the mtDNA tRNA(Lys) A-->G(8344) mutation of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome.
We have studied the segregation and manifestations of the tRNA(Lys) A-->G(8344) mutation of mtDNA. Three unrelated patients with myoclonus epilepsy and ragged-red fibers (MERRF) syndrome were investigated, along with 30 of their maternal relatives. Mutated mtDNA was not always found in the offspring of women carrying the tRNA(Lys) mutation. Four women had 10%-33% of mutated mtDNA in lymphocytes, and no mutated mtDNA was found in 7 of their 14 investigated children. The presence of mutated mtDNA was excluded at a level of 3:1,000. Five women had a proportion of 43%-73% mutated mtDNA in lymphocytes, and mutated mtDNA was found in all their 12 investigated children. This suggests that the risk for transmission of mutated mtDNA to the offspring increases if high levels are present in the mother and that, above a threshold level of 35%-40%, it is very likely that transmission will occur to all children. The three patients with MERRF syndrome had, in muscle, both 94%-96% mutated mtDNA and biochemical and histochemical evidence of a respiratory-chain dysfunction. Four relatives had a proportion of 61%-92% mutated mtDNA in muscle, and biochemical measurements showed a normal respiratory-chain function in muscle in all cases. These findings suggest that > 92% of mtDNA with the tRNA(Lys) mutation in muscle is required to cause a respiratory-chain dysfunction that can be detected by biochemical methods. There was a positive correlation between the levels of mtDNA with the tRNA(Lys) mutation in lymphocytes and the levels in muscle, in all nine investigated cases. The levels of mutated mtDNA were higher in muscle than in lymphocytes in all cases. In two of the patients with MERRF syndrome, muscle specimens were obtained at different times. In both cases, biochemical measurements revealed a deteriorating respiratory-chain function, and in one case a progressive increase in the amount of cytochrome c oxidase-deficient muscle fibers was found.
Adult↗
[Treatment of chronic occupational lead poisoning with dimercaptosuccinic acid (DMSA)].
2,3-dimercaptosuccinic acid (DMSA) mobilizes lead from superficial depots. In comparison with other chelating agents, DMSA has a high therapeutic index and has the additional advantage that it can be administered orally. We have used DMSA for treatment of chronic occupational lead poisoning in a 54-year old male with signs of neurotoxic effects. The treatment resulted in a rapid decrease in the blood-lead concentration, followed by a slow increase after the treatment and subsequent stabilization at a blood-lead level lower than prior to treatment. During the first course of treatment, almost 100 mumols lead was excreted in the urine. As a result of successive courses of treatments, the patient's condition was improved. However, during the third course of treatment, he developed a mucocutaneous rash which faded again after withdrawal of DMSA; this reaction was subsequently provoked by sub-therapeutic doses, and continued treatment was therefore cancelled. Only minor, reversible side effects of DMSA have hitherto been reported, and DMSA must therefore be regarded a promising agent for long-term, out-patient chelation treatment of chronic lead poisoning.
Humans↗
[Treatment of enuresis nocturna--once again].
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Child↗
[Mortality among filling station attendants].
At the Danish census on 9 November 1970, 4,055 men and 1,195 women aged 20-64 years indicated an employment that was coded as retail sale of oil and petrol; almost all individuals probably worked as petrol station attendants. Record linkage at Danmarks Statistik showed that 529 men had died during the following 17 years. Respiratory cancer (75 deaths) was the only cause of death that showed a significant excess (standardized mortality ratio, 1.58; 95% confidence interval, 1.25-2.00) when compared to all men gainfully employed at the time of the census. An increased mortality due to the group of cardiovascular disease could not be related to any particular subgroup. The mortality in women did not differ from expected rates. These results are in accordance with data from other countries on occupational groups exposed to high concentrations of exhaust fumes.
Adult↗
Lung cancer in filling station attendants.
At the Danish census on 9 November 1970, 4,055 men and 1,195 women aged 20-64 years indicated an employment that was coded as retail sale of oil and gasoline; almost all individuals probably worked as filling station attendants. Record linkage at Danmarks Statistik showed that 529 of the men had died during the following 17 years. Respiratory cancer (75 deaths) was the only cause of death that showed a significant excess (standardized mortality ration, 1.58; 95% confidence interval, 1.25-2.00) when compared to all men gainfully employed at the time of the census. An increased mortality due to cardiovascular disease could not be related to any particular diagnostic subgroup; the mortality in women did not differ from expected rates. These results are in accordance with data from other countries on occupational groups exposed to high levels of exhaust fumes.
Adult↗
Leber's hereditary optic neuropathy and complex I deficiency in muscle.
We investigated a family with Leber's hereditary optic neuropathy in which affected individuals were homoplasmic for the point mutation of the NADH-dehydrogenase 4 gene of mitochondrial DNA, described by Wallace and colleagues in 1988. The proband had bilateral optic atrophy, tremor, dystonia, and sharply defined lesions in the putamen on magnetic resonance images. Optic atrophy was found in another 3 of 13 investigated relatives on the maternal side. Additional neurological signs were found but only in patients with optic neuropathy. The morphological appearance and the respiratory chain function of muscle tissue were investigated in the proband, his mother, and 3 siblings. Polarographic measurements revealed complex I deficiency in the 5 investigated subjects. Morphological changes of mitochondria were found in 4 of these subjects. There was no decrease in complex I activity measured as NADH ferricyanide reductase or rotenone-sensitive NADH cytochrome c reductase activities. In other cases with complex I deficiency, good agreement between polarographic and spectrophotometric measurements was found. This study showed that there is decreased activity of complex I of the respiratory chain in muscle and that cerebral striatal lesions occur in Leber's hereditary optic neuropathy with the NADH-dehydrogenase 4 gene point mutation.
Adolescent↗