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Biomedical subjects

L Oreland

Publications and source records attributed to L Oreland.

At least 73 records · Page 4Linked to original sources
PubMed1997

Levels of L-methionine S-adenosyltransferase activity in erythrocytes and concentrations of S-adenosylmethionine and S-adenosylhomocysteine in whole blood of patients with Parkinson's disease.

In the present study, levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in whole blood as well as L-methionine S-adenosyltransferase (MAT) activity in erythrocytes were assayed in a series of 20 patients with Parkinson's disease and 12 healthy control subjects. A significant difference was found with regard to SAM levels between patients and controls, with the detected levels being 383.1 +/- 41.5 nM for the parkinsonian patients and 680.6 +/- 30.9 nM for the controls. With regard to SAH, we found no difference between the groups. The catalytic activity of MAT was increased by 30% in patients compared to controls, with the Vmax for methionine being 17.9 +/- 3.7 and 13.9 +/- 2.2 pmol/mg/h, respectively.

Antiparkinson Agents↗
PubMed1997

Different molecular forms of cholecystokinin and CCKB receptor binding in the rat brain after chronic antidepressant treatment.

Cholecystokinin (CCK) is a neuropeptide recently implicated in affective disorders. This study aimed at measuring the levels of different molecular forms of CCK and the binding characteristics of CCKB receptors in the rat brain after three weeks of treatment with four different antidepressants, imipramine, amitriptyline, desipramine, and citalopram (all at the dose of 10 mg/kg once per day i.p.). Chronic treatment with imipramine and desipramine had a significant immobility-reducing effect in the Porsolt's swim test. The effect of amitriptyline, albeit in the same direction, was not significant, and citalopram had no effect in this test. In the elevated plus-maze test of anxiety, all drugs tended to increase the number of open arm entries and the ratio open/total arm entries, but only the effects of imipramine were statistically significant. None of the treatments affected the total levels of CCK or the levels of CCK-8-sulphated, CCK-8-nonsulphated, CCK-5, or CCK-4 in the frontal cortex. There was no effect of the treatments on CCKB receptor binding in the frontal cortex, hippocampus, or striatum. Imipramine and amitriptyline, however, increased the affinity of CCKB receptor binding in the hypothalamus. Thus, no consistent effect of chronic antidepressant treatment on the CCK-ergic neurotransmission in the rats was found.

Animals↗
PubMed1997

Clinical characteristics and biological parameters in temperamental clusters of suicide attempters.

A sample of 215 suicide attempters was categorized in a cluster analysis into four groups according to temperamental trails. Monoamine metabolites in the cerebrospinal fluid were analysed (n = 106). Dexamethasone suppression tests (DST) were performed (n = 154) and the activity of the enzyme monoamine oxidase in platelets (pl-MAO) was assessed (n = 103). Patients belonging to the two clusters with the most deviant temperament profiles (nos 2 and 3) were young and scored high on the Beck Hopelessness Scale and the Suicide Assessment Scale. "Cluster 3" ("neurotic, impulsive, aggressive") patients often had dysthymia and axis II, cluster B diagnoses (e.g. borderline or histrionic personality). "Cluster 2" ("neurotic and introverted") patients often had major depression. The "Cluster 1", with on the whole a normal temperament profile, had significantly higher levels of post-DST cortisol than the other clusters. The "Cluster 4" had a normal temperament profile. Adjustment disorders were most common in "Cluster 1" and "Cluster 4". The monoamine metabolite levels did not differ between the clusters, and the differences in pl-MAO activity disappeared after adjusting for age and gender. The results suggest that temperament profiles in suicide attempters are related to psychiatric diagnoses, suicidality, hopelessness, and post-DST cortisol, but are not predictive of completed suicide.

Adolescent↗
PubMed1997

Staurosporine differentiated human SH-SY5Y neuroblastoma cultures exhibit transient apoptosis and trophic factor independence.

The use of chemically differentiated neuroblastoma cells in the study of neuronal function has become a common alternative to primary neuronal cell cultures in recent years, particularly in the area of cell death. Staurosporine, a nonselective protein kinase inhibitor, has been demonstrated to be a particularly strong inducer of differentiation in the SH-SY5Y human neuroblastoma cell line. However, at present, no data exist on the long-term effects of this compound. We have compared the effects of staurosporine with 12-O-tetradecanoyl phorbol-13 acetate and retinoic acid in terms of long-term cell viability and neuronal function in the SH-SY5Y cell line. In the presence of serum, staurosporine-treated cells underwent apoptosis, which ultimately resulted in total cell loss. In contrast, when cultured in defined serum-free medium, a cessation of apoptosis occurred after approximately 1 week, at which point viability could be maintained in excess of 1 month. The addition of aurintricarboxylic acid, which has been demonstrated to prevent apoptosis in a variety of cell models, completely prevented both apoptosis and differentiation in staurosporine-treated cells both under serum-supplemented and serum-free conditions. Apoptosis was not prevented by the protein synthesis inhibitor, cycloheximide. The removal of staurosporine from the culture medium after 3 weeks had no effect on cellular morphology, function, or proliferation, indicating that the attained neuronal phenotype was terminal. Voltage-gated calcium channel sensitivity, used as a measurement of neuronal function, was highest in staurosporine-treated cells. On the basis that apoptosis and neurotrophin independence are hallmarks of the maturation of dorsal root ganglion neurons, results suggest that staurosporine-differentiated SH-SY5Y cells may bear a similar phenotype to that found in vivo. Furthermore, this model may provide for an excellent means of obtaining a stable and homogenous population of postmitotic monoaminergic neurons for investigating neuronal function and differentiation.

Apoptosis↗
PubMed1997

Methodological aspects for in vitro characterization of receptor binding using 11C-labeled receptor ligands: a detailed study with the benzodiazepine receptor antagonist [11C]Ro 15-1788.

As a complement to in vivo studies with positron emission tomography (PET), it is desirable to perform in vitro characterization of newly developed 11C tracers. In this report we describe the technique for determination of receptor-ligand kinetics utilizing ligands labeled with the short-lived radionuclide 11C. The limitations and advantages are discussed. The benzodiazepine antagonist [11C]Ro 15-1788 was used as a model substance, and the use of storage phosphor plates for quantification of radioactivity was validated. Storage phosphor plates showed an excellent linear range (approximately 10[3]) and acceptable resolution (approximately 0.5 mm). Receptor-ligand kinetics, including depletion, association and dissociation, saturation and displacement were evaluated with good results through the use of short-lived radiotracers and storage phosphor plates.

Animals↗
PubMed1997

Platelet monoamine oxidase activity in relation to alleles of dopamine D4 receptor and tyrosine hydroxylase genes.

Human personality characteristics and vulnerability to psychopathology are to a large extent dependent upon genetic factors which have yet to be fully defined. The allele distribution of the dopamine D4 receptor (D4DR) and thrombocyte monoamine oxidase (trbc MAO) activity have both been associated with personality traits which are supposedly related, namely 'sensation seeking' according to Zuckerman and 'novelty seeking' according to Cloninger, respectively. In this report, the D4DR allele distribution and trbc MAO activity were studied in 31 psychiatric patients and 21 control subjects. Trbc MAO activity is a biochemical marker of personality that has been shown to be under strong genetic influence. However, no association between the D4DR alleles and trbc MAO could be observed in this material. To our knowledge, this is the first report comparing these two markers, and based upon the results obtained, we speculate that they may be connected with different types of overlapping personality characteristics. The allele distribution of the tyrosine hydroxylase (TH) gene was also determined. TH is the rate-limiting enzyme in the biosynthesis of catecholamines, and it is believed to be involved in different kinds of psychopathology. No covariation between TH gene alleles and trbc MAO activity or D4DR alleles was observed in this material.

Alleles↗
PubMed1997

Neuroleptic-induced mitochondrial enzyme alterations in the rat brain.

For years, it has been known that neuroleptics have the capacity to interfere with the mitochondrial respiratory chain in vitro. We report that haloperidol and fluphenazine, classical neuroleptics, cause a generalized reduction in the activity of NADH: ubiquinone oxidoreductase (complex I) in the rat brain in vivo, an effect that was not observed with the atypical neuroleptic, clozapine. MPTP, which bears significant structural similarities with haloperidol, also demonstrated a significant reduction in complex I activity after low-dose, chronic administration. Interestingly, an increase in the activity of cytochrome-c oxidase (complex IV), probably reflecting enhanced functional neuronal activity, was observed in the frontal cortex of all chronically treated animals, an effect that is unlikely to result from compensation for the inhibition of complex I. Results suggest that previous findings, in which a reduction in the activity of cytochrome-c oxidase was observed in postmortem brain samples from schizophrenics, are not dependent on treatment with neuroleptics.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

Human brain contains high levels of heteroplasmy in the noncoding regions of mitochondrial DNA.

We have analyzed the level of intraindividual sequence variability (heteroplasmy) of mtDNA in human brain by denaturing gradient gel electrophoresis and sequencing. Single base substitutions, as well as insertions or deletions of single bases, were numerous in the noncoding control region (D-loop), and 35-45% of the molecules from a single tissue showed sequence differences. By contrast, heteroplasmy in coding regions was not detected. The lower level of heteroplasmy in the coding regions is indicative of selection against deleterious mutations. Similar levels of heteroplasmy were found in two brain regions from the same individual, while no heteroplasmy was detected in blood. Thus, heteroplasmy seems to be more frequent in nonmitotic tissues. We observed a 7.7-fold increase in the frequency of deletions/insertions and a 2.2-fold increase in the overall frequency of heteroplasmic mutations in two individuals aged 96 and 99, relative to an individual aged 28. Our results show that intraindividual sequence variability occurs at a high frequency in the noncoding regions of normal human brain and indicate that small insertions and deletions might accumulate with age at a lower rate than large rearrangements.

Aging↗
PubMed1996

Platelet monoamine oxidase activity in patients with winter seasonal affective disorder.

The aim of the present study was to examine whether high or low levels of platelet monoamine oxidase (MAO) activity were associated with an increased risk of winter seasonal affective disorder (SAD) or of developing characteristic vegetative symptoms during episodes of the disorder. We also investigated the relationship between MAO activity and the Global Seasonality Scale (GSS), a measure of seasonal variation in sleep length, social activity, mood, weight, appetite, and energy level. Patients with SAD (n = 49), patients with subsyndromal SAD (n = 11), and normal volunteers (n = 25) participated in the study. We found significantly higher levels of platelet MAO activity in females but did not observe significant differences across age groups or between groups of patients tested in different seasons or mood states. MAO activity (whether high or low) was not associated with a significant increase in risk of SAD or of developing hypersomnia, hyperphagia, or carbohydrate craving during episodes of winter depression. We found no significant relationship between GSS and MAO activity. Patients who had made suicide attempts during an episode of SAD had significantly lower mean levels of platelet MAO activity than other patients.

Adult↗
PubMed1996

Characterization and partial purification of human monoamine oxidase-B expressed in Escherichia coli.

Monoamine oxidases (MAO-A and MAO-B) are enzymes that play a key role in the degradation of endogenous and dietary monoamines. A full-length cDNA of the B-type of MAO, isolated from a human liver cDNA library, was cloned into a prokaryotic expression vector (pET11c). Escherichia coli which was transfected with the recombinant plasmid expressed an insoluble protein product with the expected molecular weight (65 kDa). However, in the inclusion body fraction, where most of the recombinant protein was present, no MAO activity was observed. In contrast, the membrane fraction of the bacterial lysates expressed catalytic activity as estimated by oxidative deamination of beta-phenylethylamine and tyramine. The active enzyme protein was solubilized with Triton X-100 and partly purified (80-fold) on a DEAE-Sepharose column. This enzyme activity showed properties very similar to those of human brain and platelet MAO-B. Moreover, a single band of the expected molecular size was observed on an immunoblot. The peak fraction from the DEAE-Sepharose separation was further purified on a tyramine-Sepharose column, yielding a highly purified enzyme (190-fold), visible as a band on a sodium dodecyl sulfate-containing polyacrylamide gel.

Blood Platelets↗
PubMed1996

Cholecystokinin peptides and receptors in the rat brain during stress.

Cholecystokinin (CCK) has been implicated in stress and anxiety disorders. We have studied the levels of different molecular forms of CCK and CCK receptor characteristics in rats kept for 1 h in individual cages and exposed to decapitation of conspecifics, and a control group which was decapitated immediately. Total CCK concentration was found to be increased in the hippocampus of stressed animals in the first experiment: this finding was not confirmed in further studies. No effect of stress was found on total CCK levels in the frontal cortex, hypothalamus, striatum, and septum. CCK-8-sulphated, CCK-8-nonsulphated, CCK-5, and CCK-4 were separated by HPLC and measured with two antibodies with different selectivity: no effect of stress was found on the levels of any of these molecular forms of CCK. Injection procedure and diazepam (5 mg/kg) administration had no effect on total CCK levels. Exposition of rats to the decapitation procedure increased [3H]-CCK-8 binding in the frontal and cerebral (whole-frontal) cortex. This effect could not be blocked by diazepam pretreatment. Injection procedure itself increased CCK receptor binding in the cerebral cortex, but the effect of this type of stress was smaller in magnitude. The upregulation of CCK receptors in stressed animals was due to the increased binding of radioligand on CCKB receptor subtype.

Animals↗
PubMed1996

Cholecystokinin peptides and receptor binding in Alzheimer's disease.

Cholecystokinin (CCK) is a peptide that can be found in the cerebral cortex in high concentrations and is involved in learning and memory as well as neurodegenerative processes. Cortical brain samples from 9 patients with Alzheimer's disease and 9 matched control cases were studied with respect to the concentrations of various molecular forms of CCK and the CCK receptor binding characteristics. No differences were found between patients and controls in any of these measures. Significant correlations were found between the concentrations of CCK-8 sulphated and the three nonsulphated CCK peptides measured. In addition, the concentrations of CCK-4 and CCK-5 showed a highly significant and positive correlation.

Age of Onset↗
PubMed1996

Influence of vitamin B12 on brain methionine adenosyltransferase activity in senile dementia of the Alzheimer's type.

The influence of vitamin B12 on the activity of methionine adenosyltransferase (MAT) in postmortem brains of patients with senile dementia of the Alzheimer's type (SDAT) was investigated. In samples of cortex gyrus frontalis from SDAT patients with normal and low levels of serum B12, MAT Vmax was significantly increased by 25% and 19%, respectively. MAT Vmax from a SDAT group chronically treated with B12 was similar to controls. In contrast to cortex gyrus frontalis, no significant alterations were seen in MAT activity in nucleus caudatus. This study provides evidence that SDAT is associated with significant alterations in transmethylation mechanisms in specific regions of the brain. The relationship between blood levels of B12 and the actual status of this vitamin in the brain influencing the rates of synthesis of both methionine and SAM may, however, be far more complex and cannot be directly clarified on the basis of the present human brain results.

Age of Onset↗
PubMed1996

Depression as a spreading neuronal adjustment disorder.

The outlines of a theory of the pathophysiology of depression are presented. The classic monoamine theory of depression as well as its more recent elaborations suggests that a deficit in monoamine neurotransmitters in the synaptic cleft is the primary cause of depression. We suggest that the primary defect emerges in the regulation of firing rates in brainstem monoaminergic neurons, which brings about a decrease in the tonic release of neurotransmitters in their projection areas, an increase in postsynaptic sensitivity and, concomitantly, exaggerated responses to acute increases in presynaptic firing rate and transmitter release. We propose that the initial defect involves, in particular, the noradrenergic innervation from the locus coeruleus, which in turn leads to dysregulation of 5-HT-ergic and dopaminergic neurotransmission.

Brain Stem↗
PubMed1996

Psychopathy, platelet MAO activity and criminality among former juvenile delinquents.

Psychopathy-related personality traits as well as platelet monoamine oxidase (MAO) activity and criminality from the age of 15 years were studied in a group of 68 male former juvenile delinquents and 32 control subjects. The former juvenile delinquents registered for crime as adults were found to have higher Psychopathy Check List (PCL) scores and lower platelet MAO activity than either juvenile delinquents who were not registered criminals from the age of 15 years or non-criminal controls. Although PCL scores and platelet MAC activity were unrelated, a configural frequency analysis showed a significant interaction. Individuals with PCL scores, low platelet MAO activity and persistent criminal behaviour constituted a significant "type'. Among the 27 former juvenile delinquents who developed persistent criminality, 21 subjects (78%) had PCL scores greater than 0 and low platelet MAO activity, while none of these persistent criminals were characterized by a combination of zero PCL score and high platelet MAO activity.

Adolescent↗
PubMed1996

Personality disorders according to DSM-III-R and thrombocyte monoamine oxidase activity in type 1 and type 2 alcoholics.

OBJECTIVE: Several criteria used to distinguish type 2 alcoholics from Type 1 alcoholics, as well as the incidence of lower platelet monoamine oxidase (MAO) activity in the former group, would indicate that personality disorders might be more common in Type 2 alcoholics. The purpose of the present study was to investigate the relation between personality disorders, according to DSM-III-R, platelet MAO activity and Type 1/Type 2 alcoholism. METHOD: The occurrence of personality disorders, according to DSM-III-R, was studied in a series of 34 male inpatients with alcohol dependence, subclassified into Type 1 (n = 18) and Type 2 (n = 16). Platelet MAO activity was studied in the same series of patients. RESULTS: Patients with Type 2 alcoholism had significantly higher frequencies of self-defeating, schizotypal, antisocial and borderline personality disorders than Type 1 alcoholics. Patients with Type 2 alcoholism had significantly lower mean activity of platelet MAO than Type 1 alcoholics. No correlation was found between platelet MAO activity and personality disorders according to DSM-III-R. CONCLUSIONS: Disorders of the antisocial personality and borderline personality types as well as low platelet MAO can all predict the occurrence of Type 2 alcoholism with rather high specificity but with a comparatively low degree of sensitivity.

Adult↗
PubMed1996

[The development of medical pharmacology in Uppsala with an outlook towards Europe].

The history of pharmacology at the University of Uppsala (founded in 1477) until 1925 is briefly outlined. The development of modern experimental pharmacology under the great influence by Buchheim and Schmiedeberg in Dorpat/Tartu and Strassburg during the latter part of the 19th century has been dealt with in greater detail, also from a Nordic and European perspective.

Europe↗