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Biomedical subjects

K Bergman

Publications and source records attributed to K Bergman.

At least 19 recordsLinked to original sources

Methylation of rat and mouse DNA by the mushroom poison gyromitrin and its metabolite monomethylhydrazine.

Consumption of false morel (Gyromitra esculenta Fr.) has been associated not only with acute poisoning, but also with a carcinogenic risk. The hydrolysis of acetaldehyde-N-methyl-N-formylhydrazone (gyromitrin, the main toxic component of false morel) results in the formation of the methylating agents N-methyl-N-formylhydrazine (MFH) and N-methylhydrazine (MMH) (by further hydrolysis of MFH). This study reports traces of N-7-methylguanine (N7MeGu) in liver DNA from mice and a rat treated with gyromitrin. After repeated administration of MMH, N7MeGu was identified in rat liver DNA. In mice exposed to MMH according to a dosing scheme identical to that reported to induce tumours in this species, O6-methylguanine was present in liver and kidney DNA. The results indicate that a relatively low carcinogenic risk is associated with false morel consumption. The risk may be greater in individuals with a decreased detoxification rate (acetylation) of MFH, in whom larger amounts of MMH are formed from gyromitrin.

Acetaldehyde

Studies of embryotoxicity and the incidence of external malformations after continuous intravenous infusion of alpha-chaconine in pregnant rats.

Embryotoxicity and effects on the incidence of external malformations of the major potato glycoalkaloid alpha-chaconine (alpha-cha) were studied in rats. Pregnant Sprague-Dawley rats (n = 17) were given a continuous intravenous infusion of alpha-cha via implanted osmotic minipumps (1.7 mg/kg/day), to maintain a stable blood concentration on days 6-13 of gestation. Control animals received physiological saline solution or were left untreated, respectively. Blood serum levels of alpha-cha were monitored at selected time intervals during the treatment using a specific HPLC method. The foetal body weights and the number of resorbed or dead foetuses per litter in the alpha-cha treated group were not significantly different from the control groups. No case of malformation was detected among 143 foetuses inspected in the treated group. The average maternal blood serum concentration of alpha-cha measured during the experiment was 340 ng/ml. This is more than 20 times the average peak serum level previously reported for human volunteers after intake of potatoes with a total glycoalkaloid content at the upper safe limit for acute adverse effects. The results support the view that potato glycoalkaloids, at levels normally found in potatoes, do not present a risk for teratogenicity in humans.

Animals

Functional benefit of an adaptive myoelectric prosthetic hand compared to a conventional myoelectric hand.

Eight patients with a traumatic unilateral upper limb amputation, who used conventional myoelectric prostheses, were also fitted with a commercially available myoelectric prosthetic hand with an adaptive grip, in order to compare the functional benefit of the two types of prostheses. Comparisons were made regarding width of grip, force of grip, scores in a standardised grip function test and prosthesis preference. The conventional prosthesis showed significantly better results regarding these parameters. The adaptive hand does not appear to be fully developed for practical use in prosthetic rehabilitation.

Adaptation, Physiological

Milk transfer of inorganic mercury to suckling rats. Interaction with selenite.

The transport of mercury into rat milk, and uptake in the suckling offspring was studied after peroral administration of inorganic mercury to lactating control rats, and to rats fed selenite in the diet. On day 8, 9, 10, or 11 of lactation, dams were administered a single oral dose of 0.1, 0.4, 0.7, 1.3, or 5.8 mg Hg/kg bw labeled with 203mercuric acetate. There was a linear relationship between mercury concentrations in dam's plasma and milk. The level of mercury in milk was approximately 25% of the level in plasma. After 3 d, milk levels were reduced to half the levels at 24 h. In the suckling offspring, exposed to mercury via milk during 3 d, the mercury level in blood was approximately 1% of the level in maternal blood. Mercury concentration in milk was linearly correlated to the levels in kidney, liver, and brain in the suckling offspring after 3 d exposure to mercury via milk. Selenite treatment of rats, 1.3 micrograms Se/g diet for 5 mo, resulted in increased transport of mercury to milk, probably because of increased plasma levels of mercury. However, selenite treatment of the dams did not cause any increased tissue levels of mercury in the suckling offspring.

Animals

Mutations in the two flagellin genes of Rhizobium meliloti.

The previously cloned DNA fragment which complements the behavioral defects of the che-1 and che-3 mutations of Rhizobium meliloti codes for two nearly identical (93%) flagellin genes. A wild-type copy of one of the two genes (flaA) but not the other (flaB) can complement the mutations. The behavior and flagellar morphology of newly isolated strains carrying insertion and deletion mutations or various combinations of these mutations demonstrated that either gene product alone can form functional flagellar filaments but when both gene products are present they interact in the formation of filaments. Both the nucleic acid sequences of the genes and the deduced amino acid sequences of the proteins from strain Rm1021 showed significant differences from the sequences determined previously for strain RU10406. (E. Pleier and R. Schmitt, J. Bacteriol. 171:1467-1475, 1989). The tandem arrangement of the two genes is stable, although in vitro recombination between them gave rise to a strain with wild-type behavior.

Amino Acid Sequence

Effects of dietary sodium selenite supplementation on salicylate-induced embryo- and fetotoxicity in the rat.

The effects of dietary supplementation with sodium selenite (3.0 or 4.5 ppm Se) for 8 weeks prior to and throughout gestation on sodium salicylate induced embryo- and fetotoxicity (resorptions, fetal deaths, malformations, fetal weight reduction) have been studied in the rat. Salicylate was administered either as daily intragastric bolus doses of 250 mg/kg on gestation days 6-13 (maternal peak and trough salicylate levels of 222-120 micrograms/ml whole-blood) or via constant rate intravenous infusion of 150 mg/kg/day on the same gestation days via implanted osmotic minipumps (stable average maternal blood salicylate level of 120 micrograms/ml = human antirheumatic concentration). Both gavage and infusion of salicylate resulted in an increase of resorptions and fetal deaths as well as a decrease of fetal body weights. Gavage with salicylate also produced about 50% malformed fetuses. Selenite did not protect against the embryotoxic effects of salicylate administered as intragastric bolus doses. However, selenite was found to significantly increase fetal survival rate in the infusion experiment, although it did not counteract the decrease of fetal body weight. In animals fed selenite only, no negative effects on fetal body development were noted. The protective effect of selenite against salicylate induced embryotoxicity is difficult to explain, since very little is known about the mechanisms of salicylate embryotoxicity and the biological effects of selenium. However, an interaction between selenium, via glutathione peroxidase, and salicylate at the level of prostaglandin synthesis could be possible.

Animals

Life events: the reliability of rating changes in routine and environment.

Alterations in routine and environment can affect clinical state in patients suffering from cognitive impairment. A method for rating life events for changes in routine and environment is described and found to be highly reliable even when used by inexperienced raters after brief training.

Activities of Daily Living

Accumulation and turnover of metabolites of toluene and xylene in nasal mucosa and olfactory bulb in the mouse.

Autoradiography of male mice following inhalation of the radioactively labelled solvents, toluene, xylene, and styrene, revealed an accumulation of non-volatile metabolites in the nasal mucosa and olfactory bulb of the brain. Since no accumulation occurred after benzene inhalation, it was assumed that the activity represented aromatic acids, which are known metabolites of these solvents. This was supported by the finding that also radioactive benzoic acid (main metabolite of toluene) and salicylic acid accumulated in the olfactory bulb. High-performance liquid chromatography revealed that after toluene inhalation (for 1 hr), nasal mucosa and olfactory bulb contained mainly benzoic acid, with a strong accumulation in relation to blood plasma, and considerably less of its glycine conjugate, hippuric acid. After xylene inhalation, on the other hand, methyl hippuric acid dominated over the non-conjugated metabolite, toluic acid. The results indicate a specific, possibly axonal flow-mediated transport of aromatic acids from the nasal mucosa to the olfactory lobe of the brain. The toxicological significance of these results remains to be studied.

Animals

PET imaging in obsessive compulsive disorder with and without depression.

Obsessive compulsive disorder (OCD) is a classic psychoneurosis which is frequently complicated by major depression. Recent positron emission tomography neuroimaging studies, when taken in the context of a variety of other data, implicate a brain dysfunction involving the orbital prefrontal cortex and the striatum in the mediation of OCD behaviors and those of the related Gilles de la Tourette's syndrome. The anterolateral prefrontal cortex is implicated in the secondary major depressions often complicating OCD.

Brain

Thoracic vascular injuries: a post mortem study.

We reviewed the coroner's records for all pediatric (less than 16 years of age) trauma fatalities in Ontario (population, 9.5 million) for the period January 1, 1985, through December 31, 1987. Twenty-six (8%) of the 322 cases for which complete autopsy data were available had major thoracic vascular injuries. Twenty-five deaths occurred within 6 hours of injury. The majority of patients had at least one AIS 6 injury. The aorta was the most frequently injured vessel. Major thoracic vascular injuries are more common among children than previous reports suggest, probably because they are rapidly fatal. Many deaths occur in the field, at local hospitals, or in transit before the patient can reach a trauma center. Efforts to reduce the number of total thoracic vascular injuries should focus on primary and secondary prevention.

Adolescent

Physiology of behavioral mutants of Rhizobium meliloti: evidence for a dual chemotaxis pathway.

Wild-type and nonchemotactic mutant strains of Rhizobium meliloti were tested for attraction to localized sites on alfalfa roots and for attraction to numerous small molecules, including sugars, amino acids, and two fractions derived from alfalfa root extracts. Four strains (carrying mutations che-6, che-11, che-12, and che-26) lost all responses and were classified as generally nonchemotactic mutants. One strain (carrying mutation che-7) lost responses to a group of structurally unrelated amino acids but retained all other responses and was classified as a putative sensory transducer mutant. Two strains (carrying mutations che-1 and che-3) lost responses to all the amino acids and sugars tested but retained normal responses to localized sites on roots and to the root fractions. These two mutant strains could not be classified according to the generally accepted model for a sensory pathway, derived from studies of enteric bacteria, and provided evidence for a dual chemotaxis pathway in R. meliloti.

Amino Acids

Collective dose to the Swedish population from intraoral radiography.

In 1984 the Swedish National Institute of Radiation Protection (SSI) undertook an investigation (KAST) of 400 randomly selected dental offices to check the extent to which the new rules and recommendations concerning radiation protection (SSI 1978, 1980) were applied. Data for calculation of the energy imparted per bitewing examination of an adult were available. The information obtained was utilized for estimating the collective dose in Sweden from intraoral radiography. The mean value of the energy imparted from an ordinary bitewing examination was 0.48 mJ. The quotient between the sum of all imparted energy during 1984, 5,519 J, and the number of inhabitants in that year was 0.66 mJ. This corresponds to 1.5 ordinary bitewing examinations per individual in Sweden. The collective effective dose equivalent is 79 manSv after transformation from the total energy imparted. The average energy imparted from the annual natural irradiation in Sweden is 100 mJ, with variations between 35 and 350 mJ, giving totally to the population 830,000 J. The dose contribution from intraoral radiography is thus considered of minor importance when taking into account the variations of the natural irradiation as well as the benefit of the diagnostic gain in dentistry and the enhancement of public dental health.

Adult

Di-(2-ethylhexyl)adipate: absorption, autoradiographic distribution and elimination in mice and rats.

Whole-body autoradiography was used to study the tissue distribution of the plasticizer di-(2-ethylhexyl) adipate (DEHA), labelled in the acid [carbonyl-14C] or alcohol [2-ethylhexyl-1-14C]moiety, after iv or ig administration to male mice and rats and pregnant mice. With both DEHA preparations, during the first 24 hr after administration high levels of radioactivity were observed particularly in the body fat, liver and kidneys (after iv and ig administration) and in the intestinal contents (after ig administration) of both species. After administration of [carbonyl-14C]DEHA, radioactivity was also registered in the adrenal cortex, corpora lutea of the ovary, bone marrow, forestomach mucosa, salivary glands and Harder's gland in both species. [2-ethylhexyl-1-14C]DEHA derived radioactivity was found in the bronchi in male mice. Radioactivity was observed in the foetal liver, intestine and bone marrow during the first 24 hr after iv or ig administration of [carbonyl-14C]DEHA to pregnant mice. There was very little accumulation of [2-ethylhexyl-1-14C]DEHA in the mouse foetus but some was found in the urinary bladder, liver and intestinal contents as well as in the amniotic fluid. In an absorption/elimination study in rats of doses of 25 microCi/kg body weight of [14C]DEHA administered ig, dissolved in corn oil or dimethylsulphoxide, blood levels of radioactivity increased somewhat faster and were two or three times higher when DMSO was the vehicle indicating poor absorption of DEHA from the corn oil solution which more accurately reflects human contact with DEHA. Little radioactivity from [carbonyl-14C]DEHA was recovered in the bile, whereas [2-ethylhexyl-1-14C]DEHA was excreted in the bile in significant amounts particularly when DMSO was the vehicle. There was evidence of enterohepatic circulation of DEHA. Radioactivity was also excreted in the urine. As shown by autoradiograms obtained 4 days after the administration of [14C]DEHA there was no retention of DEHA and/or its metabolites in the tissues of mice.

Adipates

Mapping and cloning of a fla-che region of the Rhizobium meliloti chromosome.

We constructed a genetic map of the fla-che region of the Rhizobium meliloti chromosome using cotransduction with bacteriophage phi M12. Several other chromosomal markers located in the general area are included in the map. We isolated plasmids carrying wild-type DNA inserts that complement the mapped mutations from a genomic library carried in the broad-host-range vector pLAFR1. The complementation data obtained from the clones confirmed the contransduction map and clarified the exact order of several of the behavioral genes. A restriction map of this area was developed by using the cloned DNA. One of the five individual EcoRI fragments subcloned from the original clones complemented two of the behavioral mutations.

Cell Movement

Effects of vitamin A on the metabolism and mutagenicity of 2AAF in vitro and on the covalent binding to rat liver DNA/RNA in vivo.

Vitamin A has been shown to affect the in vitro metabolism of 2AAF. At low concentrations of retinol or retinyl palmitate, a decreased production of ring-hydroxylated as well as deacetylated and N-hydroxylated metabolites was observed, measured by high performance liquid chromatography. The increased mutagenicity of 2AAF observed after addition of vitamin A in the Ames test cannot therefore be explained as a result of stimulated N-hydroxylation. However, the addition of retinol was found to enhance the mutagenicity of the metabolite N-OH-2AAF in the presence of an S-9 fraction of rat liver homogenate. No differences with regard to the covalent binding of 2AAF or its metabolites to rat liver DNA/RNA in vivo could be demonstrated in animals fed diets with normal or high vitamin A content.

2-Acetylaminofluorene

Autoradiographic distribution of 14C-labeled 3H-imidazo[4,5-f]quinoline-2-amines in mice.

The highly mutagenic heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), are formed during heating of protein-rich foods. In order to gain information about the distribution and fate of IQ and MeIQ in vivo, a whole-body autoradiographic study of i.v.-injected 14C-labeled IQ and MeIQ has been performed in male NMRI, pregnant NMRI, and female C3H mice. IQ and MeIQ showed similar distribution patterns. At short survival times, the autoradiograms were characterized by an accumulation of radioactivity in metabolic and excretory organs (liver, kidney, bile, urine, gastric and intestinal contents, salivary glands, nasal mucosa, and Harder's gland), as well as in lymphomyeloid tissues (bone marrow, thymus, spleen and lymph nodes) and in endocrine and reproductive tissues (adrenal medulla, pancreatic islets, thyroid, hypophysis, testis, epididymis, seminal vesicles, ampulla, and prostate). The liver and kidney cortex were identified as sites of retention of nonextractable radioactivity. IQ and MeIQ showed a strong affinity for melanin. IQ and MeIQ passed the placenta, but no radioactivity was retained in fetal tissues. The results pinpoint the liver as a site of IQ- and MeIQ-mediated toxicity. Future studies of IQ and MeIQ may be guided by and clarify the role of other tissue localizations in the toxicity of IQ and MeIQ.

Animals