Search PubMed⌕ Search

Biomedical subjects

O Andersen

Publications and source records attributed to O Andersen.

At least 145 records · Page 8Linked to original sources

Organotin compounds induce aneuploidy in human peripheral lymphocytes in vitro.

In vitro exposure of PHA-stimulated human lymphocytes to organotin compounds resulted in statistically significant increases in the frequencies of hyperdiploid cells. When taken together with our previous study demonstrating spindle inhibiting effects of the same organotin compounds by an indirect method (Jensen et al., 1989), the present study strongly indicates that organotin compounds are able to induce aneuploidy, probably by affecting spindle function.

Adult↗

Mercuric chloride-induced kidney damage in mice: time course and effect of dose.

The rate of elimination of mercury after a single oral or intraperitoneal administration of HgCl2 to male or female mice has recently been demonstrated to be inversely related to the dose size (Nielsen and Andersen, 1989, 1990). The present study demonstrates dose-related induction of renal tubular damage, followed by regeneration, after oral administration of HgCl2 to female mice. Dose-related increased fractional urinary mercury excretion (expressed as percent of dose) was also demonstrated. At increasing dose of HgCl2, the renal activity of selenium-dependent glutathione peroxidase decreased, and was only 50% of the activity in untreated controls after administration of 200 mumol HgCl2/kg. At higher doses, the renal concentration of glutathione was significantly reduced as well. The degree of tissue damage was inversely related to the fractional deposition of mercury in the kidneys. This study indicates that the reduction in fractional whole-body retention of mercury with increasing dose size previously demonstrated is due to increased urinary mercury excretion during transient renal damage followed by regeneration, as extensive leakage took place before extensive regeneration was noted.

Administration, Oral↗

Effects of organotin compounds on mitosis, spindle structure, toxicity and in vitro microtubule assembly.

Di- and tri-methyl, -butyl and phenyl tin, all as chlorides were tested for toxicity and spindle disturbances in V79 Chinese hamster cells and for effects on in vitro assembly of bovine brain tubulin. The V79 cells were treated for 30 min and in general, loss of a stainable spindle could be demonstrated at slightly higher concentrations than c-mitosis. Both these effects were observed at low, non-toxic concentrations. The c-mitotic activity of the compounds was found to increase with increasing lipophilicity and it was best described by a regression on both lipophilicity (partition coefficient octanol/water) and loss of spindle stain. All compounds showed a concentration dependent inhibition of microtubule assembly and all but diphenyltin induced disassembly of preassembled microtubules. An effect on the rate of polymerization was suggested for tributyl- and triphenyltin. The results further indicate that the inhibition of microtubule assembly is through direct interaction with tubulin but does not involve the sulfhydryls of the protein. Thus, the organotins seem to act through two different cooperative mechanisms, inhibition of microtubule assembly and interaction with hydrophobic sites. The latter mechanism might involve Cl-/OH- exchange across cellular membranes. Previous studies have demonstrated chromosomal supercontraction and aneuploidy in human lymphocytes exposed to low concentrations of organotin in vitro and it is suggested that exposure to these compounds may increase the risk of aneuploidy in humans.

Animals↗

Gonadotropin releasing hormone (GnRH)--a novel olfactory stimulant in fish.

The aim of this study was to elucidate the putative role of the gonadotropin releasing hormone (GnRH or LHRH) as an olfactory stimulant in fish. We report for the first time extreme sensitivity of the olfactory organ in the rainbow trout (Oncorhynchus mykiss) to GnRH. Recordings of the electroolfactogram (EOG) showed an electrophysiological response to 10(-16) M GnRH four times the amplitude of the response to a fresh water control stimulus. By stimulating the olfactory epithelium with several GnRH analogs and fragments of the decapeptide, the biologically active region of GnRH could be partly elucidated. The response profile of GnRH differed from that of the positive control odorant L-alanine, suggesting that separate receptors or receptor cells are involved. We propose that this potent odorant may act as a reproductive pheromone in fish.

Amino Acid Sequence↗

Conglutinin binds the HIV-1 envelope glycoprotein gp 160 and inhibits its interaction with cell membrane CD4.

The highly glycosylated envelope glycoprotein (gp 160) of human immunodeficiency virus (HIV) interacts with the CD4 molecule present on the membrane of CD4+ cells and is involved in the pathobiology of HIV infection. Lectins bind glycoproteins through non-covalent interactions with specific hexose residues. The mammalian C-type lectin bovine conglutinin was examined for its ability to interact with recombinant gp160 (rgp160) produced in vaccinia virus-infected BHK21 cells. Specific binding of conglutinin to rgp160 was demonstrated by ELISA. The interaction of bovine conglutinin with rgp160 was calcium-dependent, which is characteristic of the binding of a C-type lectin to its ligand, and the binding was inhibited in a dose-dependent manner with N-acetyl-D-glucosamine. Deglycosylation of rgp160 abrogated the conglutinin binding. In addition, conglutinin exerted a dose-dependent inhibition of the binding of rgp160 to the CD4 receptor on CEM 13 cells, as demonstrated by FACS analyses. These results indicate that conglutinin may inhibit the infection with HIV-1 through its interaction with the viral envelope glycoprotein.

Acetylglucosamine↗

Biochemical effect of liver transplantation in two Swedish patients with familial amyloidotic polyneuropathy (FAP-met30).

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disorder characterized by progressive peripheral and autonomic neuropathy, associated with neural and systemic amyloid deposits. The amyloid fibrils contain a variant transthyretin (TTR) molecule (TTR met30), over 90% of which is produced in the liver. After liver transplantation in two patients with severe symptomatic FAP, only normal TTR was detectable in circulation. The two patients are being monitored at regular intervals, and, although in one patient there was no evidence of reduction in the quantity of amyloid present at 6 months, there had been no further progression of the neuropathy.

Adult↗

Methyl mercuric chloride toxicokinetics in mice. I: Effects of strain, sex, route of administration and dose.

The toxicokinetics of methyl mercury is studied most intensively in the rat. However, the toxicokinetics of methyl mercury in man is closer to the toxicokinetics in the mouse. This study describes the effects of dose, route of administration, and strain and sex on the toxicokinetics of methyl mercuric chloride in mice. Half-time values, fractional whole-body retentions and relative organ distributions of mercury were compared after a single oral or intraperitoneal administration of methyl mercuric chloride. The intestinal absorption was almost complete in accordance with earlier published results. The route of methyl mercury administration did not affect the whole-body retention of mercury significantly, but male mice retained lower amounts of mercury than did female mice. The elimination of mercury was demonstrated to follow first order kinetics during the two week study period independently of administration route, strain or sex. An inverse relationship between administered dose and whole-body retention was observed and by indirect evidence demonstrated not to be caused by an effect on the intestinal uptake mechanism. Absorbed and retained mercury at day 14 was primarily deposited in the carcass, but major deposits were also found in liver, kidneys and intestinal tract. Dose and route of administration did not affect the relative organ distribution of mercury significantly. However, the relative kidney deposition in male mice was about twice that in females. A significant difference in whole-body retention of mercury was observed between different strains of inbred mice at day 14 after administration. The relative organ distribution of mercury also varied significantly between different strains of mice.

Administration, Oral↗

Methyl mercuric chloride toxicokinetics in mice. II: Sexual differences in whole-body retention and deposition in blood, hair, skin, muscles and fat.

This article reports the time course for deposition of methyl mercury administered as a single oral dose in whole body, total carcass, liver, kidneys, brain, blood, fat, muscle, bone, skin and hair of male and female Bom:NMRI mice. The whole-body elimination initially approximated first order kinetics with half-times around 7 days and 12 days for males and females respectively, although a decreased elimination rate was observed during the last 10 days. The elimination of mercury from carcass was slower than the elimination from the whole-body, causing an increasing relative carcass deposition with time in both male and female mice and explaining the observed deviation from first order elimination kinetics. Thus, first order kinetics is observed only during 2-3 weeks after dosage. Throughout the experimental period, male mice had significantly lower levels of mercury in both blood, brain and muscles than had female mice, whereas renal deposition of mercury in male mice was significantly higher than in female mice. At day 30 the females had about twice as much mercury in liver, brain and hair (median values) as had male mice. Despite the fact that comparable whole-body retention and carcass deposition were observed in male and female mice, the blood concentrations in male mice was only about half that in female mice. Furthermore, half-times for mercury in blood did not differ much between male and female mice and were close to whole-body half-time in male mice, although the absolute amounts of mercury in both blood and whole-blood at day 20 were significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Epidemiological investigation of the association between infectious mononucleosis and multiple sclerosis.

By matching a cohort of 494 infectious mononucleosis (IM) cases with a multiple sclerosis (MS) register, 3 MS cases were retrieved. The interval between IM and MS was 12 years. This corresponds to a relative risk of 3.7 for MS to occur subsequent to IM (p = 0.05). This relationship between a manifestation of a relatively late Epstein-Barr virus infection and MS may indicate that a microbiologically shielded environment is important in the pathogenesis of MS.

Adolescent↗

Effect of four thiol-containing chelators on disposition of orally administered mercuric chloride.

Acute toxicity and the disposition of inorganic mercury depends on the route of exposure. Most previous studies on effect of chelators on inorganic mercury toxicity and toxicokinetics employed parenteral administration of both metal and chelator. However, the most prominent routes for human inorganic mercury exposure are the oral or pulmonary. BAL was previously considered the drug of choice in human intoxications with most heavy metals. This recommendation has been questioned during recent years due to the advent of the less toxic hydrophilic BAL analogues DMSA and DMPS. The present study, using oral administration of HgCl2 labelled with 203Hg, demonstrates that DMPS is superior to the other chelators in preventing mortality. Moreover, both DMSA and DMPS are superior to BAL and NAPA in alleviating acute toxicity and in preventing the undesirable distribution of orally administered mercury, especially to the brain. Further, oral administration of these chelators were more efficient than parenteral administration in reducing whole-body retention and organ deposition of orally administered mercuric chloride, most likely due to the prevention of intestinal uptake of mercury.

Administration, Oral↗

A comparison of the effects of sodium selenite and seleno-L-methionine on disposition of orally administered mercuric chloride.

Previous studies demonstrated extensive effects of the administration of selenite on the biokinetics of simultaneously injected inorganic mercury. As the results of simultaneous administration might well be of questionable value for the assessment of the interaction between mercury and selenium during the long-term exposures relevant for human beings, the present study was performed. The purpose of the present study was to compare the effects of prolonged oral exposure to sodium selenite and seleno-L-methionine (7.5, 37.5, or 75 mumol/L drinking water) on the biokinetics of a single oral dose of 203Hg-labelled mercuric chloride (5 or 25 mumol/kg b.w.) in mice. Both selenium compounds caused a dose-dependent decrease in the excretion of absorbed mercury, as indicated by a 2-7 fold increase in whole-body retention of mercury. Selenite caused a significantly higher whole-body retention of mercury at day 14 than did seleno-L-methionine. Both selenium compounds affected the relative deposition of mercury in most organs, but the effect depended on the type of selenium compound, on the dose of mercury as well as on the molar ratio between mercury and the selenium compound. The amounts of mercury deposited in the liver, kidneys and spleen increased, whereas the amounts deposited in the uteri and the brain were unaffected by the selenium supplementation. Significant differences in relative organ deposition of mercury between mice given selenite and mice given seleno-L-methionine were observed in the stomach, intestinal tract and the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Conglutinin exhibits a complement-dependent enhancement of the respiratory burst of phagocytes stimulated by E. coli.

Conglutinin is a mammalian C-type lectin which shows anti-bacterial activity when tested in vivo and in vitro. This study concerns the effect of conglutinin on the respiratory burst of murine spleen cells, using a chemiluminescence assay for measurement of generated reactive oxygen metabolites. Conglutinin enhances, in a dose-dependent manner, the respiratory burst of spleen cells stimulated with serum-opsonized Escherichia coli. The enhancement was only demonstrable in the presence of a functional complement system. The conglutinin-mediated enhancement of the respiratory burst was inhibited in the presence of a N-acetyl-D-glucosamine, D-mannose and N-acetyl-D-mannosamine, monosaccharides reported to inhibit conglutinin-binding to zymosan and the complement factor iC3b. On the other hand, N-acetyl-D-galactosamine was non-inhibitory.

Animals↗

The distribution of cadmium within the human prostate.

Five normal prostates from autopsies of humans aged 61-76 yr were divided into 2 x 24 topographically well-defined pairs of slices that were analyzed for cadmium (Cd) and examined histologically. The corresponding kidney cortex concentrations were also determined. The concentrations in ng Cd/g wet wt were in the range of 50-500 in the prostates and 8,000-39,000 in the kidneys with good mutual correlation. Large variations in Cd concentrations within the prostates were found. The concentrations were highest at the base (near the bladder) and lowest at the apex of the gland. Furthermore, large variations within horizontal layers were found, and this variation was not correlated to the histological amount of stroma or glands.

Aged↗

Mechanism of action of oral contraceptives on carbohydrate metabolism at the cellular level.

Although the available scientific data on the undesired metabolic effects of sex steroids have accumulated rapidly, most are of a descriptive nature, and only a few studies elucidate the impact at the cellular level and the possible interrelationship between different metabolic systems. This review summarizes the influence of different contraceptive steroid combinations on glucose metabolism and points to the possible mechanisms behind a disturbance of the euglycemic homeostasis with a concomitant change in lipid metabolism. Today the general concept is that the influence of combined sex steroid products on glucose metabolism is mainly caused by the progestogen components, although artificial estrogens may act synergistically. The diabetogenic effects of the progestogens make it important to consider the development during the last decade of the new more selective progestogens of the gonane type. From recent studies it seems, however, that intake of contraceptive combinations of ethinyl estradiol in combination with these types of gonanes, such as desogestrel and gestodene, may also be accompanied by increased insulin resistance, specifically, a hyperinsulinemic response to a glucose challenge despite unchanged glucose values compared with a baseline test. This is similar to observations made with combinations of ethinyl estradiol and other more traditional types of progestogens of the gonane and estrane type. It is conceivable that the diabetogenic effects of the progestogens are caused by a change in insulin receptor binding or a postreceptor defect in the cellular insulin action. The clinical implications of the diabetogenic effects of the sex steroids are hard to interpret, but more long-term exposure of arterial tissue to elevated concentrations of glucose and insulin results in inhibition of lipolysis and synthesis of cholesterol and triglycerides, which result in the development of lipid-filled lesions--fatty streaks--similar to those of early atherosclerosis.

Blood Glucose↗

Purification and characterization of Atlantic salmon growth hormone and evidence for charge heterogeneity.

Highly purified growth hormone (GH) has been isolated from Atlantic salmon (Salmo salar) pituitaries by extraction with acid acetone, acidic precipitation, and reversed-phase high-performance liquid chromatography (HPLC). The yield was 2.5 mg/g wet tissue. The Atlantic salmon GH (sGH) emerged as a single symmetrical peak after HPLC on a reverse phase C18 column. SDS-gel electrophoresis revealed only one band with an estimated molecular weight of 23,000. Atlantic sGH showed a uniform molecular weight, but two-dimensional (2D) gel electrophoresis of the purified sGH revealed charge heterogeneity with pI's ranging from 6.5 to 8.2. Treatment of the purified sGH with alkaline phosphatase concentrated these different forms into a single more alkaline position (pI 8.2) indicating removal of acidic groups. These results were documented using both silver- and immunostaining of the 2D SDS gels. The purified sGH was phosphorylated in vitro by a calmodulin-dependent protein kinase. Phosphorylation of sGH may be a post-translational modification resulting in several molecular forms with variable acidity. Analysis of the amino acid composition of Atlantic sGH revealed homology with GHs isolated from other teleost species and the amino-terminal sequence showed only three different amino acids within the first 25 residues compared to GH isolated from chum salmon (Oncorhynchus keta) and coho salmon (Oncorhynchus kisutch) pituitaries. Atlantic sGH had a methionine as the amino-terminal residue. Antibodies against chum sGH cross-reacted with Atlantic sGH. Antibodies against either Atlantic or chinook (Oncorhynchus tschawytscha) salmon prolactin or human GH did not cross-react with Atlantic sGH. Atlantic sGH was shown to have a slight growth-promoting activity in the rat tibia assay.

Alkaline Phosphatase↗

Effects of recombinant human growth hormone in juvenile Nile crocodiles (Crocodylus niloticus).

1. Recombinant human growth hormone (hGH) showed somatotropic activity in juvenile Nile crocodiles (Crocodylus niloticus). 2. Body weight of crocodiles receiving 3.25 micrograms hGH/g body weight twice a week was increased by 49% after five weeks of treatment, compared to 31% increase in controls. 3. Total length was increased by 15 and 5%, respectively, in the two groups. 4. Food conversion efficiency increased from 28% in the controls to 36% in the hormone injected animals. 5. Cessation of hormone treatment was followed by reduced appetite and decreasing body growth.

Alligators and Crocodiles↗

Disposition and retention of mercuric chloride in mice after oral and parenteral administration.

The present study compares effects of dose size on whole-body retention and relative organ distribution of 203HgCl2, after oral and intraperitoneal administration to female mice of two strains (inbred CBA/Bom and outbred Bom:NMRI). Using whole-body retention data of oral and intraperitoneal administration, an estimated "true absorption" of a single oral dose of inorganic mercury was calculated to be about 20% at two different dose levels. At the highest oral dose, a delay in fecal elimination of nonabsorbed mercury was observed, indicating a decreased peristaltic rate. The relative hepatic deposition was larger after oral than after intraperitoneal administration, presumably due to a first-pass effect, and a correspondingly lower relative renal deposition was seen. Increasing doses at both exposure routes resulted in increasing relative deposition in liver, stomach, intestines, and spleen but decreasing relative deposition in lungs and kidneys. Bom:NMRI mice deposited a larger fraction of the whole-body burden in the kidneys and a smaller fraction in the livers than did CBA/Bom mice. Comparison to a previous study with male mice (Nielsen and Andersen, 1989) demonstrates that male and female mice deposit similar fractions of their body burden in the liver, while male mice deposit significantly larger amounts of mercury in the kidneys and smaller amounts in the carcass than do female mice. Thus, the toxicokinetics of inorganic mercury in mice depend on dose size, administration route, and sex; the mouse strain is of less importance than the other factors investigated. The absorption of inorganic mercury was estimated to be about 20%, that is, twice as high as earlier estimates.

Absorption↗