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Biomedical subjects

J Marcusson

Publications and source records attributed to J Marcusson.

At least 55 records · Page 3Linked to original sources
PubMed1988

[3H]imipramine binding of protein nature in human platelets: inhibition by 5-hydroxytryptamine and 5-hydroxytryptamine uptake inhibitors.

The nature of [3H]imipramine binding to human platelets was investigated. Desipramine and 5-hydroxytryptamine (5-HT) displaced the same amount of binding and the binding was sensitive to protease treatment. The nature of pharmacological inhibition of [3H]imipramine binding was investigated in saturation experiments. Increases in KD without changes in Bmax were noted with the addition of 5-HT, desipramine, norzimeldine, or 5-methoxytryptoline. Reductions in Bmax without alterations in KD were obtained when citalopram or clomipramine was added. It is concluded that the [3H]imipramine binding site in human platelets is of protein nature and that this binding site contains the substrate recognition site for 5-HT uptake. In addition, [3H]imipramine and other 5-HT uptake inhibitors have bonds to other parts of the 5-HT uptake carrier or to the surrounding lipid membrane. This additional binding outside the substrate recognition site is not one single site but most likely represents sites that are specific for the chemical structure of each uptake inhibitor, respectively.

Binding Sites↗
PubMed1985

"Specific" binding of [3H]imipramine to protease-sensitive and protease-resistant sites.

A number of 5-hydroxytryptamine (5-HT) uptake inhibitors have been shown to displace the binding of [3H]imipramine to rat cortical membranes in a complex manner with Hill slopes less than unity. Norzimeldine displaced the binding of [3H]imipramine in a biphasic manner with IC50 values for the two components of about 30 nM and 30 microM. This latter site alone was found in tissues that had been treated with a protease. Binding to both of these sites was displaced by 10 microM desipramine. The protease-sensitive [3H]imipramine binding sites were found to be saturable, high-affinity binding sites with a KD of 8 nM. The number of these sites varied between brain regions and was positively correlated with the regional distribution of [14C]5-HT but not [3H]noradrenaline uptake. This was not the case however for the protease-resistant but desipramine-displaceable binding sites. Since most previous [3H]imipramine binding studies have been performed with high concentrations of desipramine (10 microM) to define "specific binding," these data would suggest that either protease-sensitivity or displacability by 1 microM norzimeldine would give more reliable estimates of the specific binding.

Animals↗
PubMed1984

Serotonin concentrations in normal aging human brains: relation to serotonin receptors.

Concentrations of serotonin (5-HT) and its deaminated metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in 7 regions of normal human brains and, in some of the regions, were compared to the number of serotonin receptors (S1 and S2). Neither 5-HT nor 5-HIAA concentrations correlated significantly with increasing age (from 17-100 years) in any of the regions investigated. Positive correlations between 5-HT and 5-HIAA were found in all regions studied, significantly (p less than 0.05) so in 5 of the areas. When comparing 5-HT transmitter and metabolite concentrations to the number of S1 and S2 receptors, no significant correlations were found either within any brain area of between different brain regions. These data confirm that 5-HT transmitter concentrations are not altered by increasing age, support the ideas that S1 and S2 receptors are not presynaptic and also that 5-HT transmitter concentrations and receptor densities are separately controlled.

Adolescent↗
PubMed1984

Effect of age on human brain serotonin (S-1) binding sites.

The effect of age on the binding of [3H]5-hydroxytryptamine [( 3H]5-HT, serotonin) to postmortem human frontal cortex, hippocampus, and putamen from individuals between the ages of 19 and 100 years was studied. One high-affinity binding site was observed in adult brains, with a mean KD of 3.7 nM and 3.2 nM for frontal cortex and hippocampus, respectively, and 9.2 nM for putamen. Decreased binding capacities (Bmax) with age were detected in frontal cortex and hippocampus. In putamen a decrease in affinity was noted. Postmortem storage did not significantly contribute to the age-related changes. No significant sex differences were detected. [3H]5-HT binding was also studied in brains from human neonates. The specific binding was 1.5-3 times lower than in adult frontal cortex and putamen, and Scatchard analysis suggested more than one binding site. In infant hippocampus a single binding site was observed and except for a premature individual, the binding capacity approximated adult values.

Accidents↗
PubMed1983

Serotonin binding in mouse brains. Some methodological aspects.

The binding of (3H)5-hydroxytryptamine ([3H]5-HT, serotonin) to crude homogenates of brains from three different strains of mice has been studied. The strains, C57/BL, DBA and BALB did not show significant differences in the binding characteristics, with Kd values around 6-7 nM and Bmax 270-310 fmoles/mg protein. Various methodological aspects were investigated and found to be important for the binding assay. The presence of ascorbic acid (5.7 mM) thus caused a significant increase in Bmax by 30% without any change in the Kd values. This increase seemed to be due to a decrease in the non-specific binding rather than to an increase in the total binding of serotonin. The presence of a specific MAO-A inhibitor, clorgyline (10 microM), during the assay, resulted in a significant reduction of Bmax by 20% without any change in the affinity for serotonin, when tissue which had been frozen was used. Less than 2% of added serotonin was metabolized during the binding procedure in the absence of clorgyline. Thus, the decrease in binding capacity caused by clorgyline, may be due to a non-competitive blocking effect of the serotonin binding structure. These results indicate that the use of MAO inhibitors in (3H)5-HT binding assays on frozen tissue, rather than being necessary, might negatively affect the result. Neither storage of the brains at -70 degrees nor postmortem storage of the animals for 60 hours at 4 degrees resulted in obvious changes in the (3H)5-HT binding characteristics.

Animals↗
PubMed1982

The binding of [3H]-5-hydroxytryptamine to homogenates of human brain.

The binding of [3H]-5-hydroxytryptamine ([3H]-5-HT) to homogenates of human brain has been studied. The specific binding is saturable, with a Kd (frontal cortex) of 12 /+- 2 nM, and is inhibited by non-radioactive 5-HT (IC50=26 nM) and D-Lysergic acid diethylamide (IC50=20 nM). Specific, but not non-specific binding of [3H]-5-TH was inhibited by incubation of the homogenates at 50 degrees C. The binding of [3H]-5-HT across the human brain was not uniform, the highest binding being found in the substantia nigra and hippocampus, and the lowest in the thalamus and pons. The Kd of the binding sites towards 5-HT did, however, appear to be similar for the different brain regions.

Animals↗
PubMed1982

Age-correlated loss of dopaminergic binding sites in human basal ganglia.

Human caudate nucleus, putamen, substantia nigra, and nucleus accumbens were analyzed for the effects of age on dopaminergic binding sites. Decreases in the number of dopaminergic binding sites were detected with age in caudate nucleus (44 specimens from three sample groups) and substantia nigra (n = 12). In caudate nucleus, the decline in [3H]2-amino-6, 7-dehydroxy-1, 2, 3, 4-tetrahydronaphthalene sites was three times greater than for [3H]spiperone, but age changes were significant in only two of the three sampling groups. No age changes in binding were detected in the putamen (n = 44) or nucleus accumbens. Age, sex, and tissue source all significantly contributed to variance. However, cause of death, time from death to tissue freezing, and length of storage did not influence dopaminergic binding in the caudate nucleus or putamen. Relative to the life-span, the age-correlated decrease in dopaminergic binding sites of human brain approximates that in aging rodent striatum. Comparisons of altered dopaminergic binding with other age-correlated changes suggest that neuronal loss may not be involved in the loss of binding sites before midlife.

Adolescent↗
PubMed1981

Genetic aspects of psoriasis: mode of inheritance and action of PUVA on DNA.

The results of some family and experimental studies related to psoriasis are summarized. Complex segregation analysis of Lomholt's classical family material of psoriasis from the Faroe Islands gave clear evidence of a major locus (additive gene with a frequency of 0.07) plus a strong polygenic component (genetic heritability 0.87). An analysis of another family material showed complete linkage between the major locus for psoriasis and the HLA region. Treatment of cells with 8-methoxypsoralene plus a small dose of UVA induces monoadducts, some of which appear to remain in the DNA for at least 7 days of post-treatment incubation. These monoadducts can be activated to form DNA cross-links by a second, larger UVA dose. 8-Methoxypsoralene plus UVA-induced DNA cross-links can be modified by a repair process which involves the formation of DNA breaks. This process in not observed in XPA cells.

DNA↗
PubMed1980

Titration of human brain monoamine oxidase -A and -B by clorgyline and L-deprenil.

The interaction of clorgyline and L-deprenil with the -A and -B forms of human brain monoamine oxidase (MAO) has been studied. Both compounds inhibit cerebrocortical MAO in a manner consistent with a 'suicide' inactivation of the enzyme. The interaction of clorgyline with the -A form of the enzyme appears to take place almost entirely at specific binding sites, and the conditions required for this inhibitor to 'titrate' the concentrations of MAO-A have been elucidated. L-Deprenil has also been used to titrate the concentration of the -B form of MAO in cerebrocortical homogenates, but there is a considerable degree of non-specific binding of this compound. The two inhibitors have been used to titrate the concentrations of the two enzyme forms in frontal cortex homogenates from different age groups. There was a significantly higher MAO-B activity for the age range 73--95 years than for the age range 2--63 years. No significant differences between the two age groups were found for MAO-A. The activity of MAO-A in the samples correlated very well with the concentration of this enzyme form. Titration of the B-form of the enzyme with L-deprenil indicated an increased enzyme concentration with age, although other factors, such as the non-specific binding of this compound, could contribute to this effect.

Adult↗
PubMed1980

The effect of age on the activity and molecular properties of human brain monoamine oxidase.

The effect of age upon monoamine oxidase -A and -B (MAO-A and -B) in 23 different, regions of human brain was determined. There was a significant positive correlation with age in 19 out of 23 regions for MAO-B, but no positive correlation with age was found for MAO-A. The increased MAO-B activity was found, in 5 out of 5 regions tested, to be due entirely to an increased enzyme concentration, rather than due to an increased molecular turnover number of the enzyme. The responses of the mitochondrial marker enzymes succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) were studied in 5 brain regions, and no consistent change in activity found with age. The lysosomal enzyme acid phosphatase was found to tend towards an increased activity with age. No difference in either the specific activities or molecular characteristics of MAO were found between men and women. Cross-correlation studies of the data, after compensation for the effects of age, indicated that the activities of the two enzyme forms are under some form of organized control across the whole brain. Such a finding is consistent with a genetic regulation of the enzyme forms.

Adult↗
PubMed1979

HLA antigens in a psoriatic family: comparative studies with MLC, HTC, PLT and serological HLA-DR determinations.

HLA genotypes were characterized in a large family of 48 individuals in three generations. In this family, carriers of the proband's disease-predisposing haplotype commonly expressed clinical signs of illness, manifested as psoriasis and/or arthritic lesions. From these data, and from other family studies, presented previously, we have concluded that cutaneous and/or joint lesions may be signs of disease in carriers of the predisposing HLA haplotype. We have investigated HLA-A, B, C and D/DR antigens in the family members. This gave us the opportunity to evaluate the validity of different assays for the determination of HLA-D alleles in a family material where the MLC tests formed the basis for a correct assignment of HLA-D determinants. The HTC method and the PLT assay were both afflicted with specific typing problems, partly due to the existence of cellular cross-reactions between HLA-D determinants, which seemed to be reminiscent of serological DR crossreactions.

Alleles↗
PubMed1978

Psoriasis and arthritic lesions in relation to the inheritance of HLA genotypes: a family study.

This family consists of forty-eight subjects, all of whom have been examined with regard to the presence of psoriasis and nearly all for the presence of arthritic lesions (sacroiliitis and peripheral arthritis). All the members have been tissue-typed not only for HLA-A, B and C locus products but also for D locus products. This has enabled us to study the entire HLA chromosomal region. In the family concerned we have found that those subjects haploidentical with the proband have, to a very large degree, either one or all clinical manifestations, which demonstrates a close genetic relationship between joint (especially sacroiliitis) and cutaneous manifestations. These findings prompt us to repeat our previously made proposal about different phenotypic expressions of the same genotype. In this family study the disease-associated haplotypes did not contain the genes for B13, 17 or 37 antigens which are known to occur frequently in psoriatic patients. However, not all psoriasis patients have these antigens. Despite that, we believe that the gene(s) which increase the likelihood of developing psoriasis are identical in all patients and therefore family studies where the proband does not carry the particular psoriasis associated B-alleles are equally illuminating as to the inheritance pattern of disease.

Adolescent↗
PubMed1976

Psoriasis, sacro-iliitis and peripheral arthritis occurring in patients with the same HLA haplotype. A preliminary family report and a hypothetical explanation of the interaction between MHS products.

The present family investigation has shown that genes within the MHS are mainly responsible for the development of psoriasis or psoriasis-associated arthritic lesions (peripheral arthritis and sacroiliitis). We have hypothetically discussed the possibility that multiple genes, all located within the MHS, act in concert to increase the risk of developing disease to very high levels. This implies that at least two MHS linked genes act in complementary fashion for the development of disease, these genes seem to be able to operate both in the cis and in the trans position. One of these genes would be situated in the chromosomal portion of the MHS which carries the HLA-D locus. Families with a high incidence of disease would show inheritance according to the cis position of genes, when it can be shown that most of the carriers of the specific disease-associated haplotype are affected by disease, whereas in other families, complementarity between two distinct HLA haplotypes with genes acting in the trans position would result in disease.

Adolescent↗