Showing papers by "Karolinska Institutet published in 1987"

Leukotrienes and lipoxins: structures, biosynthesis, and biological effects

Abstract: Arachidonic acid is released from membrane phospholipids upon cell stimulation (for example, by immune complexes and calcium ionophores) and converted to leukotrienes by a 5-lipoxygenase that also has leukotriene A4 synthetase activity. Leukotriene A4, an unstable epoxide, is hydrolyzed to leukotriene B4 or conjugated with glutathione to yield leukotriene C4 and its metabolites, leukotriene D4 and leukotriene E4. The leukotrienes participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. Recent studies also suggest a neuroendocrine role for leukotriene C4 in luteinizing hormone secretion. Lipoxins are formed by the action of 5- and 15-lipoxygenases on arachidonic acid. Lipoxin A causes contraction of guinea pig lung strips and dilation of the microvasculature. Both lipoxin A and B inhibit natural killer cell cytotoxicity. Thus, the multiple interaction of lipoxygenases generates compounds that can regulate specific cellular responses of importance in inflammation and immunity.

Primary sensory neurons of the rat showing calcitonin gene-related peptide immunoreactivity and their relation to substance P-, somatostatin-, galanin-, vasoactive intestinal polypeptide- and cholecystokinin-immunoreactive ganglion cells.

Abstract: By use of the indirect immunofluorescence technique the distribution of calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) has been analyzed in cervical and lumbar dorsal root ganglia of untreated and colchicine-treated rats. In addition, lumbar ganglia were examined 2 weeks after transection of the sciatic nerve. The occurrence of CGRP-positive cells in relation to ganglion cells containing substance P-, somatostatin-, galanin-, cholecystokinin (CCK)-, and vasoactive intestinal polypeptide (VIP)/peptide histidine isoleucin (PHI)-LI has been evaluated on consecutive sections as well as using elution-restaining and double-staining techniques.

Markers for vulnerability to psychopathology: Temperament traits associated with platelet MAO activity

Abstract: The functional linkage between platelet MAO activity and psychopathology was explored by analyzing temperamental correlates in 40 male subjects by means of scales from the Eysenck Personality Questionnaire (EPQ), the Zuckerman Sensation Seeking Inventory, and the Karolinska Scales of Personality (KSP). Linear correlations were found with two sensation seeking scales, replicating earlier findings. However, nonlinear correlations predominated. Subjects with intermediate platelet MAO activity had higher scores in conformity scales and lower scores in anxiety and hostility scales than low and high MAO subgroups. Low MAO subjects showed a pattern of higher scores in KSP Impulsiveness, EPQ Neuroticism, and KSP Somatic Anxiety and Irritability and lower scores in KSP Socialization, in line with personality profiles found in alcoholics, psychopaths, and suicide attempters who also tend to have low platelet MAO activity. High MAO subjects scored lower in sensation seeking and conformity scales and higher in KSP Psychasthenia, Muscular Tension and Suspicion scales, consistent with clinical links between high platelet MAO activity and anxiety and paranoia.

The Approaching Era of the Tumor Suppressor Genes

Abstract: Genes that can inhibit the expression of the tumorigenic phenotype have been detected by the fusion of normal and malignant cells, the phenotypic reversion of in vitro transformants, the induction of terminal differentiation of malignant cell lineages, the loss of "recessive cancer genes," the discovery of regulatory sequences in the immediate vicinity of certain oncogenes, and the inhibition of tumor growth by normal cell products Such tumor suppressor genes will probably turn out to be as, if not more, diversified as the oncogenes Consideration of both kinds of genes may reveal common or interrelated functional properties

Partial least squares analysis with cross‐validation for the two‐class problem: A Monte Carlo study

Abstract: A method for statistical analysis of two independent samples with respect to difference in location is investigated. The method uses the partial least squares projections to latent structures (PLS) with cross-validation. The relation to classical methods is discussed and a Monte Carlo study is performed to describe how the distribution of the test-statistic employed depends on the number of objects, the number of variables, the percentage variance explained by the first PLS-component and the percentage missing values. Polynomial approximations for the dependency of the 50 per cent and the 5 per cent levels of the test-statistic on these factors are given. The polynomial for the 50 per cent level is complicated, involving several first-, second- and third-degree terms, whereas the polynomial for the 5 per cent level is dependent only on the number of objects and the size of the first component. A separate Monte Carlo experiment indicates that a moderate difference in sample size does not affect the distribution of the test-statistic. The multi-sample location problem is also studied and the effect of increasing the number of samples on the test-statistic is shown in simulations.

Effects of anti-estrogens on bone in castrated and intact female rats

Abstract: The effects of the antiestrogens tamoxifen and keoxifene on the bone density of intact and ovariectomized female rats were determined after 4 months of therapy. The antiestrogens did not cause a decrease in bone density in intact animals, although uterine wet weight did decrease. Ovariectomy caused an increase in body weight (25%) and a significant decrease in femur density (P<0.01). Antiestrogens did not further decrease the bone density of ovariectomized rats but rather helped to maintain bone density. Antiestrogens as well as estrogen (oral estradiol benzoate 25µg daily) helped to maintain bone density in the range observed for the intact rats, but inhibited estrogen stimulation of uterine weight. These contrasting pharmacological actions of antiestrogens suggest that patients receiving long-term adjuvant tamoxifen therapy for breast cancer should be evaluated to determine whether tamoxifen can retard the development of osteoporosis.

Peripheral, autonomic regulation of locus coeruleus noradrenergic neurons in brain: putative implications for psychiatry and psychopharmacology.

Abstract: In 1946 von Euler identified the major transmitter of sympathetic nerve fibers, norepinephrine (NE), and about a decade later Vogt (1954) provided the first evidence that NE may also serve as a neurotransmitter in the central nervous system (CNS). Since that time, a literal explosion in CNS neurotransmitter research has taken place involving histological, biochemical, physiological, pharmacological and clinical investigations. Yet, it is only now that we are beginning to understand the biological function of NE in brain, in particular because of recent advances regarding the physiology and regulation of NE neurons in locus coeruleus (LC), a bilateral pontine structure with a uniquely wide-spread terminal network reaching throughout the neuroaxis and in primates accounting for about 70% of all brain NE. Recently, the neurobiology of the LC noradrenergic network was extensively reviewed by Foote et al. (1983), and its implication in vigilance as well as global orientation of behavior towards imperative, environmental sensory stimuli was outlined. Yet, more recent information regarding the peripheral, autonomic regulation of LC neurons in brain provides fundamentally new biological aspects on behavior and mental function which seem to allow a more integrated view of the role of brain NE in the overall function of the individual than previously understood. The purpose of this review is to summarize these findings and, furthermore, to outline some putative implications for psychiatry and neuropsychopharmacology.(ABSTRACT TRUNCATED AT 250 WORDS)

Characteristics of alcohol/polyol dehydrogenases. The zinc-containing long-chain alcohol dehydrogenases.

Abstract: Sixteen characterized alcohol dehydrogenases and one sorbitol dehydrogenase have been aligned. The proteins represent two formally different enzyme activities (EC 1.1.1.1 and EC 1.1.1.14), three different types of molecule (dimeric alcohol dehydrogenase, tetrameric alcohol dehydrogenase, tetrameric sorbitol dehydrogenase), metalloproteins with different zinc contents (1 or 2 atoms per subunit), and polypeptide chains from different kingdoms and orders (mammals, higher plants, fungus, yeasts). Present comparisons utilizing all 17 forms reveal extensive variations in alcohol dehydrogenase, but with evolutionary changes that are of the same order in different branches and at different times. They emphasize the general importance of particular residues, suggesting related overall functional constraints in the molecules. The comparisons also define a few coincidences between intron positions in the genes and gap positions in the gene products. Only 22 residues are strictly conserved; half of these are Gly, and most of the remaining ones are Pro or acidic residues. No basic residue, no straight-chain hydrophobic residues, no aromatic residues, and essentially no branched-chain or polar neutral residues are invariable. Tentative consensus sequences were calculated, defining 13 additional residues likely to be typical of but not invariant among the alcohol dehydrogenases. These show a predominance of Val, charged residues, and Gly. Combined, the comparisons, which are particularly relevant to the data base for protein engineering, illustrate the requirements for functionally important binding interactions, and the extent of space restrictions in proteins with related overall conformations and functions.

Coexistence of peptides with classical neurotransmitters

Abstract: In the present article the fact is emphasized that neuropeptides often are located in the same neurons as classical transmitters such as acetylcholine, 5-hydroxy-tryptamine, catecholamines, γ-aminobutyric acid (GABA) etc. This raises the possibility that neurons produce, store and release more than the one messenger molecule. The exact functional role of such coesisting peptides is often difficult to evaluate, especially in the central nervous system. In the periphery some studies indicate apparently meaningful interactions of different types with the classical transmitter, but other types of actions including trophic effects have been observed. More recently it has been shown that some neurons contain more than one classical transmitter, e.g. 5-HT plus GABA, further underlining the view that transfer of information across synapses may be more compex than perhaps hitherto assumed.

Newly identified 'glutamate interneurons' and their role in locomotion in the lamprey spinal cord

Abstract: A new class of excitatory premotor interneurons that are important in the generation of locomotion in the lamprey has now been described In the isolated spinal cord, these neurons act simultaneously with their postsynaptic motoneurons during fictive swimming They are small and numerous, and they monosynaptically excite both motoneurons and inhibitory premotor interneurons The excitatory postsynaptic potentials are depressed by an antagonist of excitatory amino acids These interneurons receive reticulospinal input from the brain stem and polysynaptic input form skin afferents A model of the network underlying locomotion based on the synaptic interactions of these neurons can now be proposed for the lamprey

Transplantation in Parkinson's disease: two cases of adrenal medullary grafts to the putamen.

Abstract: Autologous adrenal medullary tissue was transplanted unilaterally to the putamen in two patients with severe Parkinson's disease. The first patient exhibited a transient, two-day improvement of motor performance in the limbs contralateral to the implantation site. He also had significantly longer episodes of normal function for about two months. The second patient reported a minor improvement of balance and gait, again lasting for two months. Electrophysiological studies of the motor readiness and auditory evoked potentials were consistent with increased catecholaminergic activity in the basal ganglia after transplantation in both patients. Positron emission tomography showed no postoperative alteration of receptor density in the putamen. No significant adverse effects of the transplantation were observed in the patients' performance on neurological and psychological tests or in their quantitative electroencephalogram and cerebral blood flow recordings. Immediately after the grafting, one patient showed transient signs of sympathetic hyperactivity, probably caused by release of catecholamines from the implanted tissue into the peripheral circulation. We conclude that catecholamine-rich cellular implants in the basal ganglia have transient beneficial effects in patients with severe Parkinson's disease.

PET analysis of human dopamine receptor subtypes using 11C-SCH 23390 and 11C-raclopride.

Abstract: Tracer doses of 11C-SCH 23390 and 11C-raclopride, selective D1-dopamine and D2-dopamine receptor antagonists, respectively, were injected intravenously into three healthy male volunteers and two drug-treated schizophrenic patients. Regional radioactivity in brain and plasma was followed during 1 h by positron emission tomography (PET). After injection of both ligands a high accumulation of radioactivity was observed in the dopamine-rich caudate putamen. Experiments with 11C-SCH 23390, but not 11C-raclopride, showed a conspicuous accumulation of radioactivity also in the neocortex. None of the ligands accumulated in the dopamine-poor cerebellum. Specific binding of 11C-raclopride in the putamen was reduced by more than 80% in schizophrenic patients treated with antipsychotic doses of sulpiride or cis(Z)-flupentixol decanoate. 11C-SCH 23390 binding was slightly reduced in both the cortex and the putamen after treatment with cis(Z)-flupentixol decanoate but not after sulpiride. The results indicate that clinical antipsychotic drug treatment with sulpiride and cis(Z)-flupentixol decanoate causes a substantial blockade of D2-dopamine receptors in the basal ganglia but has only a minor effect on D1-dopamine receptors.

Histopathological criteria for progressive dementia disorders: clinical-pathological correlation and classification by multivariate data analysis.

Abstract: Autopsied brains from 55 patients with dementia between 59-95 years of age (mean age 77.9 +/- 8.1 years) and 19 non-demented individuals between 46-91 years of age (mean age 74.3 +/- 10.5 years) were examined to establish histopathological criteria for normal ageing, primary degenerative [Alzheimer's disease (AD)/senile dementia of Alzheimer type (SDAT)] and vascular (multi-infarct) dementia (MID) disorders. Senile/neuritic plaques, neurofibrillary tangles, microscopic infarcts and perivascular serum protein deposits were quantified in the frontal lobe (Brodmann area 10) and in the hippocampus. The demented patients were classified according to the DSM-III criteria into AD/SDAT and MID. Operationally defined histopathological criteria for dementias, based on the degree/amount of the histopathological changes seen in aged non-demented patients, were postulated. The demented patients were clearly separable into three histopathological types, namely AD/SDAT, MID and AD-MID, the dementia type where both the degenerative and the vascular changes are coexistent in greater extent than are seen in the non-demented individuals. Using general clinical, gross neuroanatomical and histopathological data three separate dementia classes, namely AD/SDAT, MID and AD-MID, were visualized in two-dimensional space by multivariate data analysis. This analysis revealed that the pathology in the AD-MID patients was not merely a linear combination of the pathology in AD/SDAT and MID, indicating that AD-MID might represent a dementia type of its own. The clinical diagnosis for AD/SDAT and MID was certain in only half of the AD/SDAT and one third of the MID cases when evaluated histopathologically and by multivariate data analysis. AD/SDAT, MID and AD-MID were histopathologically diagnosed in 49%, 24% and 27%, respectively, of all the dementia cases studied. Opposite correlation between the number of tangles, plaques and the patient age in non-demented and AD/SDAT cases were observed, indicating that the pathogenesis of tangles and plaques in the two groups of patients might be different and that AD/SDAT might not be a form of an exaggerated ageing process.

Staff observation aggression scale, SOAS: Presentation and evaluation

Abstract: A new psychiatric report and rating scale assessing severity and frequency of aggressive behaviour is presented and evaluated. It is based on the staff's standardized reports of aggressive incidents. By using a special aggression report form, comprehensive and standardized information is obtained, thereby permitting scoring and further analysis of different aspects of aggressive incidents. The reliability of scoring is tested and found to be good as is the scale's capacity to discriminate between different patterns of aggressive behaviour in different groups of patients. As a result of this and because of the simplicity of the scale, it is thought to be a potentially useful tool in scientific research on aggressive behaviour from psychiatric inpatients.

Cigarette smoking and alveolar bone height in subjects with a high standard of oral hygiene

Abstract: Smokers and non-smokers were compared with respect to alveolar bone height. The study covered 235 subjects aged 21-60 years, 72 of whom were smokers. Oral hygiene status and dental care habits were above average and of equal standard in both groups (PlI = 0.9). Alveolar bone height was assessed on radiographs and expressed as % of the root length. Alveolar bone height was significantly reduced in smokers as compared to non-smokers, the mean +/- SEM being 77.9 +/- 1.3% and 82.8 +/- 0.6%, respectively (P less than 0.001). Regression analysis suggested that periodontal breakdown judged from loss of alveolar bone over time was more accelerated in smokers than non-smokers. The lower bone height in smokers remained when age and oral hygiene were allowed for. It is concluded that smoking is a risk factor for periodontal health.

Immune function in unemployed women.

Abstract: Immunologic effects of unemployment were prospectively studied in women over a period of 8 months. Subjects were classified into three groups depending on their employment history, and were studied concomitantly. Group A consisted of unemployed women who were recipients of traditional support from the Swedish welfare state. Group B was composed of unemployed women who were given the opportunity to participate in a psychosocial program, in addition to receiving the traditional unemployment benefits received by group A. Group C, the control, consisted of securely employed women. Phytohemagglutinin (PHA) reactivity of lymphocytes decreased significantly in both groups of unemployed women after 9 months of unemployment. The psychosocial program did not counteract this decrease. Reactivity to purified protein derivative (PPD) of tuberculin also decreased significantly in the unemployed subjects. No changes were observed in the securely employed women. There were no significant differences among the groups in T cell subpopulations, B cells, and serum cortisol. The data suggest that some aspects of the immune system may be altered at a specific time period following the loss of work. Further studies are needed to see if this effect is only temporary or more long lasting.

Adaptations to changing speed in human locomotion: speed of transition between walking and running

Abstract: The transition speed between walking and running was determined in 18 healthy males (23-38 years) of various statures (range of leg length 0.86-1.09 m) during acceleration and deceleration of different magnitudes (0.05-0.11 ms-2) on a motor-driven treadmill. The speed of the treadmill belt and the duration of the stance phases of each foot were recorded. A transition step was identified and the speed of transition was taken as the average speed value of the stance phase of that step. The overall mean value for the transition speed was 1.88 m s-1 (range 1.30-2.55). Deceleration resulted in a somewhat lower speed of transition than acceleration. There was a tendency towards increasing values for transition speed with increasing leg length. This could partly be explained by differences in natural frequency. The reasons for the switch between walking and running at a speed which is not extreme for either mode of progression are unclear. The subjective feeling that a transition will lead to a more comfortable situation might be based on previous experience combined with information from peripheral receptors and activity in central networks controlling locomotion.