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Biomedical subjects

P Holmgren

Publications and source records attributed to P Holmgren.

11 recordsLinked to original sources

Uptake and incorporation in pteridines of externally supplied GTP in normal and pigment-deficient eyes of Drosophila melanogaster.

Some aspects of the synthesis of drosopterins in the eyes of Drosophila melanogaster have been studied in flies with different levels of white gene expression. The activity of GTP cyclohydrolase was found to differ between wild-type and yellow-eyed mutants in vivo but not in vitro. To elucidate the uptake of substrate, we measured the removal of labeled GTP from the incubation medium by excised pupal eyes and followed the subsequent fate of this label. It was found that GTP was dephosphorylated to guanosine extracellularly before label was taken up by the eye tissue. The uptake was much lower in yellow and white eyes than in wild-type eyes, and in the latter, a considerable part of the label was present in pteridine compounds. The strain differences in the uptake of label seem to be due to different rates of intracellular utilization of guanine derivatives in pteridine synthesis. We suggest that this is caused by a hampered transport of precursor (possibly GTP) in white and zeste eyes through the membrane of red pigment granules.

Animals

Fatal intoxications in the Nordic countries. A forensic toxicological study with special reference to young drug addicts.

Fatal intoxications in the 15-34 age group in the five Nordic countries during the years 1984 and 1985 (Sweden only in 1984) were investigated. The known drug addicts were studied separately. The highest incidence of intoxications, calculated per 10(5) population, was found in Finland (11.3), followed by Denmark (10.3), Sweden (8.5), Iceland (7.2) and Norway (6.6). The percentage of intoxications caused by drugs was 92 in Denmark, 71 in Norway, 66 in Sweden, 50 in Finland and 17 in Iceland. Ethanol intoxications were seen 5-7 and 2-3 times as frequently in Finland and in Iceland, respectively, than in the other three countries. Carbon monoxide intoxications accounted for two-thirds of all fatal intoxications in Iceland. Drug addicts accounted for 62% of all fatal intoxications in the Danish material. The corresponding figures were 33% in the Norwegian, 16% in the Swedish and 5% in the Finnish material. No deaths in drug addicts were found in Iceland. Most drug addicts in Denmark, Norway and Sweden died of hard drugs and most in Norway and Sweden, from heroin or morphine, whereas in Denmark other strong analgesics, such as methadone, dextropropoxyphene and ketobemidone, accounted for 40% of all hard-drug-related fatal intoxications. To a certain extent the results reflect differences in the legal autopsy routines in the various Nordic countries. However, the ascertainment of drug addicts is assumed to be near-complete in each country.

Adolescent

[Fatal poisoning in Scandinavia--narcotic addicts are a high-risk group].

This study on fatal intoxications in the Nordic countries indicates an over-representation of drug addicts in Denmark, Norway and Sweden. All cases of fatal intoxications in persons 15-34 years of age submitted to medicolegal autopsy and subsequent toxicological examination in the Nordic countries during 1984-1985 included in the study. A comparison between the Nordic countries is possible because the same definition of a drug addict and classification of drugs are used. The numbers of fatal intoxications among drug addicts per 10(5) population were 6.3 in Denmark, 2.1 in Norway, 1.3 in Sweden, 0.6 in Finland and none in Iceland. About 70 per cent of the drug addicts in Norway and Sweden died from heroin/morphine intoxication. In Denmark only 55 per cent of the drug addicts died from heroin/morphine and 36 per cent died from overdoses of the legal drugs methadone, dextropropoxyphene and ketobemidone.

Adolescent

Content of histone H1 and histone phosphorylation in relation to the higher order structures of chromatin in Drosophila.

The amount of histone H1 relative to core histones has been determined in three Drosophila species (D. melanogaster, D. texana and D. virilis) in chromatin from several tissues differing in chromatin structure and genetic activity. Low levels of H1 were found in relatively undifferentiated, early embryos as well as in a line of cultured cells. In late embryos the content of H1 was highest in D. virilis which possesses larger amounts of and a partially more compacted constitutive heterochromatin than the two other species. Polytene chromatin from larval salivary glands showed increased levels of H1 compared with diploid chromatin and the degree of phosphorylation of this histone was relatively low. The degree of phosphorylation of H2A was found to be drastically reduced in polytene as compared with diploid embryonic chromatin, which parallels the extensive underreplication of constitutive heterochromatin. Also, in diploid chromatin a qualitative correlation was observed between the relative amounts of heterochromatin and the levels of H2A phosphorylation. These findings suggest a connection between H2A phosphorylation and heavy compaction of interphase chromatin.

Animals

Drugs in motorists traveling Swedish roads: on-the-road-detection of intoxicated drivers and screening for drugs in these offenders.

This paper deals with the police officer's or police doctor's ability to find drivers under the influence of drugs. We have also studied whether the protocol on the driver's previous histories of drug intake is useful for directing the chemist in his analytical approach to revealing intoxicants in the suspects' body fluids. A comprehensive procedure for screening traffic-hazardous drugs in the urine was found necessary and is described. By using this method, we have studied the incidence of drunken drivers with detectable medicinal or illicit agents. The results demonstrate that 91% of those drivers found by the officer or doctor of the police to be on intoxicants other than ethanol, carried some kind of traffic-hazardous drug in their body fluids, and that the doctor was a better judge than the police in identifying these offenders. By using a series of chemical methods for drug screening, we found that every third driver suspected of drunken driving due to ethanol, but not to other intoxicants, held some kind of a traffic-hazardous drug substance in his urine; benzodiazepines and cannabinoids were the most common findings. The data imply that 34% of these suspects revealed their intakes of traffic-dangerous intoxicants. We conclude that the judgements of both the officer and doctor of the police are needed for an efficacious detection of drivers under the influence of drugs. Moreover, the results infer that the chemist has to screen for intoxicants to reveal these in a suspect driver. We also conclude that drugs, particularly the benzodiazepines or cannabinoids, may be commonly encountered in drunken drivers, suspected of being inebriated by ethanol but no other toxicants.

Alcoholic Intoxication

Lethal intoxications with morphine in Sweden 1966-1974.

Fatal intoxications with morphine derivatives have become increasingly common in Sweden. Toxicologic data and pathologic findings in 34 cases of morphine intoxications from 1966 to 1974 in Sweden are presented. From 1972 on when morphine the black market, lethal intoxications with centrally stimulation amines.

Adolescent

Histone content in relation to amount of heterochromatin and developmental stage in three species of Drosophila.

Relative amounts of various histone fractions in Drosophila chromatin were estimated densitometrically on electrophoretic gel separations. Several consistent and highly significant differences were obtained between larval and adult chromatin. The arginine-rich histones showed the most conspicuous changes: higher amounts of H4 in larvae, higher H3 in adults. The level of modification of these histones was clearly higher in larval than in adult chromatin. The modification of the two slower subfractions of H4 involved, in all probability, phosphorylation as well as acetylation. In all types of Drosophila chromatin studied 50% or more of the H2a molecules were phosphorylated--a remarkably high proportion. The species differences observed in relative amounts of histone were consistent in both stages of development. D. melanogaster differed from D. hydei and D. virilis in all histones except H2b, while the latter two species were generally similar. The interspecific variation in histone pattern was generally not correlated to differences in content of heterochromatin. The level of modification of H2 was, however, presumably an exception, as it was significantly lower for both larvae and adults in D. virilis than in the other two species. These differ from D. virilis in containing appreciably lower proportions of heterochromatic chromosome segments.

Animals

Lethal intoxications with centrally stimulating amines in Sweden 1966-1973.

Fatal intoxications with centrally stimulating amines (CSA) have become increasingly common in Sweden. Toxicological data and pathological findings of 32 cases of amphetamine and phenmetrazine intoxications which occurred from 1966-1973 in Sweden are described. Furthermore, 13 cases where these drugs were not the cause of death, but found in urine and organs, are reported.

Accidents

Fatal seizures associated with trimipramine poisoning.

The present report describes a witnessed, fatal attack of seizures. Very high levels of trimipramine were found in the blood collected at autopsy. The cause of death would most likely have been misinterpreted as a suicidal intoxication if the attack had not been witnessed. Conversely, if toxicologic examination had not been undertaken, the fatality would probably have been registered as epilepsia.

Cause of Death