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Biomedical subjects

B O Bengtsson

Publications and source records attributed to B O Bengtsson.

At least 19 recordsLinked to original sources
PubMed1998

Clomipramine and imipramine suppress clinical signs and T and B cell response to myelin proteins in experimental autoimmune neuritis in Lewis rats.

5-Hydroxytryptamine (5-HT) reuptake inhibitors of the zimeldine-type have induced polyneuropathies similar to Guillain-Barré syndrome (GBS) in patients with endogenous depression. Some monoamine neurotransmitters have been shown to affect immune reactions in vivo and in vitro in a concentration-dependent manner. We therefore studied the effect of the monoamine reuptake inhibitory anti-depressants, clomipramine and imipramine on specific immune response and the clinical course of experimental autoimmune neuritis (EAN), the animal model of GBS in humans. Clomipramine and imipramine both suppressed clinical signs of EAN induced by immunization with bovine peripheral nerve myelin (BPM), when given at a dose of 20 mg/kg/day intraperitoneally, via osmotic pumps. Clomipramine and imipramine reduced the numbers of Th1 cells secreting IFN-gamma in response to the neuritogenic myelin proteins BPM, P0 and P2 among lymph node mononuclear cells (MNC) from rats with EAN. The levels of cells secreting IgG antibodies to BPM, P2 and GM1 in lymph nodes were reduced at the height of EAN in clomipramine and imipramine treated animals. The action of clomipramine and imipramine on induced IFN-gamma and anti-myelin antibodies suggests that the mechanism for the suppressive effect of those substances on EAN symptoms may be due to an action on myelin T and B cell autoreactivity. Considering that the main common pharmacological principle of clomipramine and imipramine is to increase the functional activity of the nor-adrenaline (NA) and serotonin (5-HT) of the monoamines, it seems justified to postulate that the actions of clomipramine and imipramine demonstrated in this study to some extent involve NA and/or 5-HT. The immunomodulatory effects of clomipramine and imipramine call for further research on the potential role of drugs acting on the monoamine system in the treatment of autoimmune diseases, and for further studies of immunological mechanisms in the pathogenesis of depressive disorders.

Adrenergic Uptake Inhibitors↗
PubMed1996

Genetic conflicts.

Self-promoting elements (also called ultraselfish genes, selfish genes, or selfish genetic elements) are vertically transmitted genetic entities that manipulate their "host" so as to promote their own spread, usually at a cost to other genes within the genome. Examples of such elements include meiotic drive genes and cytoplasmic sex ratio distorters. The spread of a self-promoting element creates the context for the spread of a suppressor acting within the same genome. We may thus say that a genetic conflict exists between different components of the same genome. Here we investigate the properties of such conflicts. First we consider the potential diversity of genomic conflicts and show that every genetic system has potential conflicts. This is followed by analysis of the logic of conflicts. Just as Evolutionarily Stable Strategy (ESS) terminology provides a short cut for discussion of much in behavioral ecology, so the language of modifier analysis provides a useful terminology on which to base discussions of conflicts. After defining genetic conflict, we provide a general analysis of the conflicting parties, and note a distinction between competing and conflicting genes. We then provide a taxonomy of possible short- and long-term outcomes of conflicts, noting that potential conflict in an unconstrained system can never be removed, and that the course of evolution owing to conflict is often unpredictable. The latter is most particularly true for strong conflicts in which suppressors may take surprising forms. The possibility of extended conflicts in the form of "arms races" between element and suppressor is illustrated. The peculiar redundancy of these systems is one possible trace of conflict, and others are discussed. That homologous conflicts may find highly different expression is discussed by referring to the mechanistic differences that are thought to underlie the action of the two best-described meiotic drive genes, and by the multiplicity of forms of cytoplasmic sex ratio distorters. The theoretical analysis establishes a logical basis for thinking about conflicts, but fails to establish the importance of conflict in evolution. We illustrate this contentious issue through consideration of some phenomena for whose evolution conflict has been proposed as an important force: the evolution of sex, sex determination, species, recombination, and uniparental inheritance of cytoplasmic genes. In general, it is proposed that conflict may be a central force in the evolution of genetic systems. We conclude that an analysis of conflict and its general importance in evolution is greatly aided by application of the concept of genetic power. We consider the possible components of genetic power and ask whether and how power evolves.

Animals↗
PubMed1996

Genetic variation in the strongly canalized sex pheromone communication system of the European corn borer, Ostrinia nubilalis Hübner (Lepidoptera; Pyralidae).

The major difference in pheromone production between the so-called E and Z strains of the European corn borer Ostrinia nubilalis is controlled by two alleles at a single autosomal locus. E-strain females produce an (E)-11-tetradecenyl acetate pheromone with 1-3% of the Z isomer, whereas Z-strain females produce the opposite blend. In laboratory-reared insects we found that F1 females produced, on average, a 71:29 E/Z ratio, but the distribution was clearly bimodal. The variability in pheromone blend produced by heterozygous females could be explained by the existence of two different alleles in the Z strain which in combination with the E-strain allele for the major production locus cause the production of a component mixture either high or low in the F isomer. In addition, evidence was found for an independently inherited factor, existing in the E strain, with a dominant effect on the amount of E isomer produced by females homozygous for Z-alleles at the major production locus. Thus, the low variability normally found in the pheromone mixture produced by O. nubilalis and other moth females may, by canalization, hide a considerable amount of underlying genetic variation.

Animals↗
PubMed1994

Adverse experiences during treatment with zimeldine on special licence in Sweden.

Adverse experiences during licensed treatment with the antidepressant serotonin (5-HT) reuptake inhibitor zimeldine in Sweden are presented. Data were obtained from a written inquiry of 694 patients and 67 reports to the Medical Products Agency. The spectrum of adverse symptoms was in agreement with those reported in previous studies on zimeldine. The most frequent adverse experiences were headache, nausea, myalgia, signs of liver function disturbance, arthralgia, neurological symptoms, fever and insomnia. No new case of the Guillain-Barré syndrome was found. The estimated frequency of the zimeldine-induced hypersensitivity syndrome (HSS), comprising fever, myalgia and/or arthralgia and signs of liver function disturbance, ranged from 1.4% to 13% in the inquiry and from 0.63% to 3.4% in the report part of the study. Adverse experiences usually had a considerably higher incidence during the first 6 weeks of zimeldine treatment than thereafter. This is in agreement with the clinical experience that most of the adverse reactions occur early during zimeldine treatment. However, a number of adverse experiences did occur with a later onset. This may justify a prolongation of the compulsory 4 weeks' testing of liver function that is required during licensed treatment. There were significantly fewer patients who developed fever among the patients who had experienced previous zimeldine treatment than among those who had not. Otherwise there was no statistically significant difference in frequency of adverse symptoms between these two groups. Consequently zimeldine treatment per se does not seem to predispose to development of an HSS or other types of adverse reactions during subsequent therapy.

Adolescent↗
PubMed1994

Effect of zimeldine and its metabolites on [3H]thymidine incorporation in lymphocyte cultures from psychiatric patients with or without a hypersensitivity reaction during zimeldine therapy.

Lymphocyte transformation test (LTT) was applied to 28 patients who had developed a hypersensitivity syndrome (HSS) during treatment with the antidepressant drug zimeldine. Twenty-seven patients treated with zimeldine without any symptom of an HSS were matched controls. Zimeldine and its metabolites norzimeldine and CPP 200 all induced statistically significant increased [3H]thymidine incorporation in cultured lymphocytes from the HSS patients compared with the controls, norzimeldine being the most potent inducer. The results indicate an immunoreactive process in the development of the HSS induced by zimeldine.

Adult↗
PubMed1994

Ornithine decarboxylase activity and concentrations of polyamines in embryos of diabetic rats.

Previous studies have demonstrated high concentrations of polyamines in neoplastic tissue and embryos and these compounds are therefore believed to play a role in cellular growth and embryonic development. Maternal diabetes causes embryonic dysmorphogenesis and alterations in embryonic polyamine concentrations may contribute to this process. In the present study we have measured the contents of DNA, putrescine, spermidine and spermine in embryos on days 10 and 11 of gestation in normal and diabetic rats. We also estimated the activity of ornithine decarboxylase (ODC) in embryos on days 9-11. We found that maternal diabetes causes delayed growth as reflected by decreased content of DNA on day 11 in the embryos of the diabetic group. Both the polyamine content and ODC activity were altered in the embryos of diabetic rats. Thus, the polyamines were increased on day 10 and decreased on day 11, and the ODC activity was decreased in a down-regulated manner in day-10 embryos of the diabetic rats. These findings suggest that polyamine metabolism is involved in the dysmorphogenesis of diabetic pregnancy.

Animals↗
PubMed1993

Chiasma and recombination data in plants: are they compatible?

It has long been considered that the number of chiasmata formed during meiosis corresponds to the number of crossovers indicated by the genetic map. However, recent investigations in plants show an unexpected discrepancy in the results obtained when calculating the total number of crossover events per meiosis by these two methods. Is this discrepancy due to methodological difficulties? Or is there something fundamentally wrong with our understanding of crossovers and chiasmata?

Crossing Over, Genetic↗
PubMed1993

Measuring genome reorganization from synteny data.

Two measures of the degree of genome reorganization based on synteny data are presented. The first, q, measures how far the original syntenic relationships have decayed during the separation of two taxa. The second measure, Q, is a logarithmic transformation of q, so constructed that Q increases unlimitedly while q deflects when reorganization becomes substantial. Numerical examples are given for the genomic reorganizations that have occurred during the evolution of humans, mice and rats. The degree of genome reorganization between the mouse and the rat is estimated to be about 1/5 of the degree of reorganization between humans and the rodent species.

Animals↗
PubMed1992

Effects of zimeldine and its metabolites, clomipramine, imipramine and maprotiline in experimental allergic neuritis in Lewis rats.

The influence of the selective serotonin (5-HT) reuptake inhibiting antidepressant zimeldine and its metabolite norzimeldine was tested on experimental allergic neuritis (EAN) in Lewis rats, which is an animal model of the Guillain-Barré syndrome (GBS) in man. Zimeldine and norzimeldine both suppressed clinical signs of actively induced EAN when given at a dose of 20 mg/kg/day intraperitoneally via osmotic pumps. The effects of zimeldine, its metabolites norzimeldine and CPP 200 as well as of the antidepressants clomipramine, imipramine and maprotiline on in vitro immune response were tested. Thereby we used an immunospot assay for interferon-gamma (IFN-gamma) produced by lymph node mononuclear cells (MNC), which reflects number of memory T lymphocytes activated by antigen or lectin, in this experiment bovine peripheral nerve myelin (BPM) and phytohemagglutinin (PHA), respectively. In the IFN-gamma secretion assay zimeldine, CPP 200, clomipramine and maprotiline all in a concentration-dependent mode reduced the number of IFN-gamma secreting cells while norzimeldine and imipramine did not affect the IFN-gamma secretion. In assays for proliferation in response to antigen or lectin, the concentration 10(-4) M was judged toxic for all substances tested, and at concentrations below that all but zimeldine showed a dose-dependent slight reduction of MNC proliferation. The action of several drugs on induced T cell secretion of IFN-gamma suggests that the mechanisms for the suppressive effect of zimeldine and norzimeldine on EAN symptoms can be due to an action on myelin T cell autoreactivity. All the monoamine reuptake inhibiting antidepressants tested in this study showed immunomodulatory effects by either a reduction of the number of IFN-gamma-secreting cells or the MNC proliferation. These observations call for further studies of immunological mechanisms in the pathogenesis of mental disorders as well as on the potential role of drugs acting on the monoamine systems in the treatment of recognized autoimmune diseases.

Animals↗
PubMed1992

Deleterious mutations and the origin of the meiotic ploidy cycle.

A population genetical model is investigated in which the organism either alternates between diploid and haploid states or lives entirely in the haploid state. The behavior of the organism is determined by the genotype at a modifier locus. At an independent locus deleterious mutations occur at a low but constant frequency. It is found that the haploid behavior is always an evolutionarily attainable stable trait, while the ploidy-cyclic behavior is an evolutionarily attainable stable trait only when a certain condition holds. This condition depends on the strength of selection, the degree of "sheltering" given by the heterozygote state, and the degree of linkage between the modifier locus and the locus under selection. The last result leads to the speculation that the eukaryotes are derived from an organism which first developed more than one chromosome before it evolved the ploidy cycle.

Genetics, Population↗
PubMed1990

Population structure of the human pseudoautosomal boundary.

The mammalian sex chromosomes are composed of two genetically distinct segments: the pseudoautosomal region, where recombination occurs between the X and Y chromosomes, and the sex chromosome-specific parts. Between these two segments the human sex chromosomes differ by the insertion of an Alu element on the Y chromosome. We have surveyed the sequence variation in the boundary region using the polymerase chain reaction. Fifty seven Y and sixty X chromosomes from ten different human populations were analysed. The X chromosomes were found to be polymorphic at five positions in a 300-base-pair region. By contrast, all Y chromosomes were identical except for one distal polymorphism shared with the X chromosome.

Base Sequence↗
PubMed1990

Cytoplasmic male sterility in beta is associated with structural rearrangements of the mitochondrial DNA and is not due to interspecific organelle transfer.

Chloroplast (ct) and mitochondrial (mt) DNAs from four cytoplasmic male sterile (cms) and 22 normal fertile sugar beet lines and accessions of wild beets from the genus Beta have been compared with restriction analyses and Southern hybridizations. We have used restriction analyses of ctDNA as a phylogenetic marker to confirm the taxonomic relationships between the different cytoplasms. According to the ctDNA data, all four cms cytoplasms belong to the same taxonomic section, Beta. Restriction patterns of ct and mtDNA from fertile accessions produced analogous trees of similarity and showed a close correlation between the organellar DNA diversity and the accepted taxonomic classification of the species studied. However, the mt-DNA restriction profiles of the four cms types differed dramatically from each other and from those of all fertile accessions from the genus. No indication of cytoplasmic introgression was found in any of the four investigated cms types. Southern hybridization to mtDNA revealed variant genomic arrangements in the different fertile and cms cytoplasms, indicating that rearrangement of the mitochondrial genome is a common denominator to the different cms systems in Beta. It may, indeed, be a common property to spontaneously occurring cms in all or most species.

Chloroplasts↗
PubMed1990

Evolution of the segregation ratio: modification of gene conversion and meiotic drive.

We compare the evolutionary pressures that direct the modification of gene conversion and meiotic drive at loci subject to purifying and overdominant viability selection. Gene conversion differs from meiotic drive in that modifers do not affect their own segregation ratios, even when linked to the viability locus. Segregation distortion generates gametic level disequilibria between alleles at the viability locus and modifiers of gene conversion and meiotic drive: enhancers of segregation distortion become positively associated with driven alleles. Suppression of gene conversion evolves if the driven allele is marginally disadvantageous (overdominant viability selection), and higher rates evolve if the driven alleles are relatively advantageous (purifying viability selection). Gametic disequilibria permit enhancers of meiotic drive that are linked to the driven locus to promote their own segregation. We attribute the failure of genetic modifiers of gene conversion and meiotic drive to maximinize mean fitness to the generation of such associations.

Biological Evolution↗
PubMed1990

The effect of biased conversion on the mutation load.

The mutation load is sensitive to changes in the segregation ratio caused, for example, by biased conversion. If the distortion, measured by the force of conversion, is greater than the loss of fitness in the mutation heterozygotes, then the mutation load will be far away from its normal value. Examples are given where a small positive bias together with realistic fitness parameters increase the mutation load by more than two orders of magnitude. In practical terms this implies that great restrictions should be placed on the use of substances and treatments that may induce mutations associated with a positive conversion bias.

Gene Conversion↗