Showing papers by "Karolinska Institutet published in 1979"
TL;DR: Fetal rat dopamine-containg neurons were implanted adjacent to the caudate nucleus of adult recipients whose endogenous dopaminergic input had been destroyed to suggest that such implants may be potentially useful in reversing deficits after circumscribed destruction of brain tissue.
Abstract: In order to determine if brain tissue grafts can provide functional input to recipient central nervous system tissue, fetal rat dopamine-containg neurons were implanted adjacent to the caudate nucleus of adult recipients whose endogenous dopaminergic input had been destroyed. The grafts showed good survival and axonal outgrowth. Motor abnormalities, which had been induced by the destruction of the endogenous dopaminergic input to the caudate, were significantly reduced after grafting of the fetal brain tissue. These data suggest that such implants may be potentially useful in reversing deficits after circumscribed destruction of brain tissue.
945 citations
TL;DR: A heptacosapeptide with potent gastrin releasing activity has been isolated from porcine non-antral gastric and intestinal tissue and striking homology in the C-terminal region is seen with bombesin, accounting for the similar bioactivities of the two peptides.
853 citations
TL;DR: A central network of neurones in the spinal cord has been shown to produce a rhythmic motor output similar to locomotion after suppression of all afferent inflow, and it is concluded that there is at least one network for each limb.
Abstract: A central network of neurones in the spinal cord has been shown to produce a rhythmic motor output similar to locomotion after suppression of all afferent inflow. The experiments were performed mainly in acute spinal cats (th. 12), which had received DOPA i.v. and the monoamine oxidase inhibitor Nialamide. In some preparations all dorsal roots supplying the spinal cord were transected, in others phasic afferent activity was suppressed by curarization. The activity was recorded as neurograms from nerve filaments or as electromyograms.
845 citations
TL;DR: High performance liquid chromatography with electrochemical detection has been compared to a radioenzymatic method for the determination of plasma catecholamines and showed an excellent agreement between the methods.
590 citations
TL;DR: Using the retrograde transport of horseradish peroxidase, projections to the ventral tegmental area of Tsai (VTA) and related dopaminergic cell groups are made and regions of the brain labelled by VTA injections are assessed in relation to control injections and the limitations of the HRP technique.
Abstract: Using the retrograde transport of horseradish peroxidase (HRP), a study has been made of projections to the ventral tegmental area of Tsai (VTA) and related dopaminergic cell groups (A 10). In order to minimise the possibility of damage to fibres of passage, a technique was evolved for the microiontophoresis of HRP such that minimal current strengths and durations were applied. In addition to a sham injection, control injections were also made to the medial leminiscus, red nucleus, deep tegmental decussations, mesencephalic reticular formation and brachium conjunctivum. Following HRP injections confined to the areas of the VTA containing the dopamine cell groups, labelled neurons appeared in prefrontal cortex, dorsal bank of rhinal sulcus, nucleus accumbens, bed nucleus of stria terminalis, amygdala, diagonal band of Broca, substantia innominata, magnocellular preoptic area, medial and lateral preoptic areas, anterior, lateral and postero-dorsal hypothalamus, lateral habenular, nucleus parafascicular nucleus of thalamus, superior colliculus, nucleus raphe dorsalis, nucleus raphe magnus and pontis, dorsal and ventral parabrachial nuclei, locus coeruleus and deep cerebellar nuclei. Regions containing catecholamine goups A 1, A 5, A 6, A 7, A 9, A 13 and the serotonin group B 7 corresponded to the topography of labeled cell groups. Injections of HRP to the interfascicular nucleus resulted in labeling predominantly confined to the medial habenular and median raphe nuclei. The results are discussed in relation to the known connections of these regions. Other regions of the brain labelled by VTA injections are assessed in relation to control injections and the limitations of the HRP technique.
A review of the organisation of some of these afferents in relation to the known cortical-subcortical-mesencephalic projection systems, suggests that the VTA is in a position to receive information from a massively convergent system derived ultimately from the entire archi-, paleo-, and neo-cerebral cortices. In addition A 10 dopaminergic neurons are known to project to restricted regions of both pre-frontal and entorhinal cortices, which themselves also receive massively convergent association cortico-cortical connections. It would appear reasonable to propose that these neurons perform a correspondingly important integrative function.
547 citations
TL;DR: Preliminary data indicate that, whereas acetylcholine directly stimulates sweat secretion, VIP may cooperate in the production of sweat by increasing local blood flow and may be responsible for the atropine-resistant vasodilatation in sweat glands and other exocrine glands.
488 citations
TL;DR: It is reported here that a mutant gene in the mouse called beige (bgJ), leads to a complete and selective impairment of naturally occurring killer lymphocytes, whereas all other forms of cell-mediated lysis are apparently normal.
Abstract: GERM LINE mutations affecting defined cell populations are often valuable tools in elucidating the function of these cells in complex biological systems such as tumour rejection. We report here that a mutant gene in the mouse called beige (bgJ), leads to a complete and selective impairment of naturally occurring killer lymphocytes, whereas all other forms of cell-mediated lysis are apparently normal. The defective gene product may lie within the lytic pathway subsequent to tumour cell contact. Because many cell types, including natural killer (NK) cells, T cells and macrophages, may be involved in tumour resistance in vivo1, these mice will provide a critical test of the hypothesis that it is NK cells which provide a first line of defence against neoplasia2. It is likely that this mutant will be invaluable for further investigations in tumour immunology just as the nude mouse has been indispensable in evaluating the role of thethymus in the development of the T-lymphoid system and the role of T cells in the rejection of tumours.
468 citations
TL;DR: Ibotenic acid has the advantage of being less toxic to the animals and of producing more discrete lesions, possibly due to faster metabolism and/or other fundamental biochemical differences, and seems to represent a valuable new tool in the morphological and functional analysis of central neuronal systems.
Abstract: Possible neurotoxic actions of intracerebral injections of ibotenic acid, a conformationally restricted analogue of glutamic acid, have been evaluated in rat brain and compared with those of kainic acid.
448 citations
TL;DR: Some of the increasing evidence that adenosine may be physiological modulator of several biological functions and that theophylline in low doses antagonizes the actions of this purine nucleoside are presented.
415 citations
TL;DR: By this approach RNA molecules up to a size of 37 kb can be eluted undegraded with a recovery of 60–90% and eluted DNA can be correctly cleaved with restriction endonucleases as shown for λDNA using Eco RI.
412 citations
TL;DR: n-Butyrate was found to increase the number of virus producer cells to a dramatic extent in the Epstein-Barr virus-carrying P3HR-1 and B95-8 lines, raising interesting questions on the mechanism of EBV induction, and its possible relationship to the known differentiation inducing ability of n-butyrate.
TL;DR: In short term exercises, such as jumping and sprinting, performance is reduced at low Tm and enhanced at Tm above normal, primarily as a result of a variation in maximal dynamic strength.
Abstract: The influence of muscle temperature (Tm) on maximal muscle strength, power output, jumping, and sprinting performance was evaluated in four male subjects. In one of the subjects the electromyogram (EMG) was recorded from M. vastus lateralis, M. biceps femoris, and M. semitendinosus. Tm ranged from 30.0 degrees C to 39 degrees C. Maximal dynamic strength, power output, jumping, and sprinting performance were positively related to Tm. The changes were in the same order of magnitude for all these parameters (4-6% x degrees C-1) Maximal isometric strength decreased by 2% x degrees C-1 with decreasing Tm. The force-velocity relationship was shifted to the left at subnormal Tm. Thus in short term exercises, such as jumping and sprinting, performance is reduced at low Tm and enhanced at Tm above normal, primarily as a result of a variation in maximal dynamic strength.
TL;DR: The immune system in higher animals has as a major distinguishing feature a high degree of complexity and can be considered to represent the gradual accumulation of preserved experiences during phylogeny where primitive as well as sophisticated reactions occur in parallel during the immune response.
Abstract: The immune system in higher animals has as a major distinguishing feature a high degree of complexity. The diversified machinery in this system can be considered to represent the gradual accumulation of preserved experiences during phylogeny where primitive as well as sophisticated reactions occur in parallel during the immune response. Interactions of complicated nature are known to occur within the system and the actual effector part (s) in causing the actual rejection of, e.g. an invading organism, is frequently difficult to dissect free from other contributing factors. The cellular part of the immune system can be divided in many ways. One approach is to talk about specific cells (most people would then mean lymphocytes of B and T type that effectuate their functions via their own, antigen-specific receptors) in contrast to nonspecific cells (here often granulocytes and monocytes-macrophages are linked together). Specific cells can function via selective production of their unique antigen-
TL;DR: Differences exist between different regions of adipose tissue in their lipolytic responsiveness to noradrenaline, which seems related to the balance between alpha- and beta-adrenergic receptor response.
Abstract: Omental fat cells were 30% smaller than those in subcutaneous regions. In omental fat cells with a mean diameter of 95 mu, the basal cAMP concentration was 50% lower, but the basal rate of glycerol release was three times as rapid as in subcutaneous (epigastric) fat cells of identical size. Added at maximal effective concentration, noradrenaline increased the level of cAMP and the rate of glycerol release more markedly in the omental than in the subcutaneous adipocytes, whereas the response to isopropyl noradrenaline was similar. Before starvation the lipolytic effects of noradrenaline and isopropyl noradrenaline, respectively, were identical in the two regions of subcutaneous adipose tissue investigated (femoral and hypogastric). The findings were well related to the tissue levels of cAMP induced by the two agents. During starvation noradrenaline and isopropyl noradrenaline increased the cAMP level and the rate of lipolysis in fat cells obtained from the hypogastric region, whereas noradrenaline decreased these parameters in femoral adipocytes. Starvation was associated with a more prominent inhibitory effect of phenylephrine on basal and isopropyl-noradrenaline-induced lipolysis in femoral than in hypogastric adipose tissue. In conclusion, differences exist between different regions of adipose tissue in their lipolytic responsiveness to noradrenaline, which seems related to the balance between alpha- and beta-adrenergic receptor response.
TL;DR: In this paper, retrograde tracing with the fluorescent dye "True Blue" is combined with the indirect immunofluorescence technique for visualizing enkephalin-like immunoreactivity.
TL;DR: The substituent of Leukotriene C, a “Slow Reacting Substance” from mouse mast cell tumors, was earlier shown to be a derivative of 5-hydroxy-7,9,11,14-eicosatetraenoic acid with a cysteine containing substitution in thioether linkage at C-6, has been identified as γ-glutamylcysteinylglycine (glutathione).
TL;DR: The results may be explained by the displacement of digoxin from binding sites in tissue by quinidine, causing a rise in the plasma concentration ofdigoxin, and the reduction in renal clearance of dig toxin, which may result also from inhibition of renal secretion ofDigoxin byQuinidine.
Abstract: Several recent reports have shown that plasma concentrations of digoxin increase when quinidine is administered along with digoxin; the present study was designed to explore the pharmacokinetics of this digoxin-quinidine interaction in six subjects. The elimination half-life of digoxin, although variable, did not change appreciably (42 vs. 44 hours) when quinidine was administered. Other pharmacokinetic values were substantially reduced in the presence of quinidine: total body clearance (from 3.08 to 1.96 ml per minute per kilogram), renal clearance (from 1.64 to 1.09 ml per minute per kilogram) and volume of distribution (from 10.87 to 7.35 liters per kilogram). The results may be explained by the displacement of digoxin from binding sites in tissue by quinidine, causing a rise in the plasma concentration of digoxin. The reduction in renal clearance of digoxin may result also from inhibition of renal secretion of digoxin by quinidine.
TL;DR: It is proposed that SRS is formed from a previously described unstable epoxide intermediate in the formation of dihydroxylated arachidonic acid metabolites in leukocytes and introduced for compounds which like SRS are non-cyclized C20 carboxylic acids with one or two oxygen substituents and three conjugated double bonds.
TL;DR: The [3H]-triamcinolone acetonide-labeled glucocorticoid receptor from rat liver cytosol was purified to 85% homogeneity according to sodium dodecyl sulfate gel electrophoresis as discussed by the authors.
TL;DR: It was found that the half-life of ascorbic acid was inversely related to the dosage and that the pool could be increased to about 20 mg/kg bodyweight by increasing the dosage.
TL;DR: Evidence is shown for a further small but cytoarchitecturally distinct dopaminergic group called the interfascicular nucleus that lies anterorly and ventrally in the ventral tegmentum in the midline, dorsal to the rostral portion of the interpeduncular nucleus and interped uncular fossa.
Abstract: The cytoarchitecture of the ventral tegmental area of Tsai (VTA) has been studied in detail in the rat with the acid of both conventional techniques and glyoxylic acid-fluorescence histochemistry. Three main dopamine containing cells groups can be distinguished: nucleus paranigralis, nucleus parabrachialis pigmentosus, nucleus linearis raphe caudalis. Nucleus parabrachialis pigmentosus lies dorsally, and nucleus paranigaralis ventrally in the VTA, while nucleus linearis continues posteriorly and medially from VTA and extends dorsally in the midline up towards the dorsal raphe nucleus. Fluorescent neurons in these three groups correspond to the A10 group. In addition to these previously described findings, the present study shows evidence for further small but cytoarchitecturally distinct dopaminergic group called the interfascicular necleus. This lies anteriorly and ventrally in the ventral tegmentum in the midline, dorsal to the rostral portion of the interpeduncular nucleus and interpeduncular fossa. The significance of these cytoarchitectural findings is discussed in relation to the known connections of the region.
TL;DR: The karyotypes of pristane-induced mouse plasmacytomas support the theory that the nonrandom chromosomal changes in lymphoproliferative malignancies are associated with the type of the target cell, rather than with the etiological agent.
TL;DR: The data indicate that fat is an important stimulus for the release of NTLI from the small intestine and it is suggested that neurotensin, or a metabolite, in blood may be a hormone involved in the postprandial inhibition of gastric motility and gastric acid secretion elicited from theSmall intestine.
Abstract: The effect of ingestion of amino acids (Vamin N), glucose, and fat (Intralipid) on the concentration of neurotensin-like immunoreactivity (NTLI) in plasma was determined in 6 healthy male volunteers. After ingestion of Intralipid (55 ml, 200 mgxml-1) there was a significant increase in the plasma concentration of NTLI. The calculated integrated total NTLI response (6.7 +/- 2.5 nM over 180 min) was statistically significant. Although isocaloric amounts of Vamin and glucose also increased the plasma concentration of NTLI, these increases were not statistically significant. The data indicate that fat is an important stimulus for the release of NTLI from the small intestine. It is suggested that neurotensin, or a metabolite, in blood may be a hormone involved in the postprandial inhibition of gastric motility and gastric acid secretion elicited from the small intestine.
TL;DR: The therapeutic action of antidepressant drugs may in part be due to a reduced functional activity of some central 5-HT systems, and a new indoleamine hypothesis of depression is presented.
Abstract: The effects of antidepressant drugs on central 5-HT receptor activity were studied in rats and mice. Antidepressant drugs were evaluated for their ability to displace3H-5-HT and3H-d-LSD from membrane binding sites in the dorsal neocortex of ratsin vitro and for their ability to block 5-HTP and d-LSD induced behavioral effects in mice. The degree of blockade of head-twitches in mice produced by the antidepressants was highly correlated with their affinity for3H-d-LSD binding sites. A number of antidepressant drugs such as amitriptyline, nortriptyline, mianserine, doxepine, nomifensine and dibenzepine appear to possess marked 5-HT receptor blocking activity at some types of 5-HT receptors in brain. New antidepressant drugs such as zimelidine, which specifically inhibit 5-HT reuptake and do not block 5-HT receptor sites, may after chronic treatment also reduce the functional activity of 5-HT systems by producing adaptive changes in postsynaptic 5-HT mechanisms. Thus, a new indoleamine hypothesis of depression is presented: the therapeutic action of antidepressant drugs may in part be due to a reduced functional activity of some central 5-HT systems.
TL;DR: Evidence has been presented, based on measurement of melatonin by radioimmunoassay in 12 healthy males, that the urinary excretion ofmelatonin follows a circadian pattern in humans during sleep deprivation when the subjects are exposed to light.
TL;DR: A rapid and simple technique using solvent extraction, ion‐pairing extraction, and high pressure liquid chromatography with electrochemical detection has been developed for the determination of 3‐methoxytyramine in striata of rats killed by microwave irradiation.
Abstract: A rapid and simple technique using solvent extraction, ion-pairing extraction, and high pressure liquid chromatography with electrochemical detection has been developed for the determination of 3-methoxytyramine in striata of rats killed by microwave irradiation. The method is specific and reproducible (coefficient of variation among replications, +/- 4%); recovery of authentic 3-methoxytyramine added to the samples is 45-50%. 3-Methoxytyramine levels found with this technique in rat striata were 15 +/- 1.7 ng/g. The method has a sensitivity of about 0.2 pmol per brain sample. Monoamine oxidase inhibition with pargyline increased 3-methoxytyramine levels in rat striata, while catechol-O-methyltransferase inhibition with 3',4'-dihydroxy-2 methylpropiophenone completely depleted 3-methoxytyramine. The effects of nomifensine, quipazine, caroxazone, piribedil, and D-amphetamine were also examined. The 3-methoxytyramine concentrations in the brains of animals killed by decapitation or by microwave irradiation were compared.
01 Jan 1979
TL;DR: Later generations of Chinese Americans show a decline in NPC mortality, but it is not clear whether this is due to their changed environment or to the intermarriage of different Chinese ehtnic subgroups with differing incidences of NPC.
Abstract: Nasopharyngeal carcinoma (NPC) shows great ethnic variations between different human populations (see Muir, 1971, 1972, 1975; Ho, 1972, 1975; Muir and Shanmugaratnam, 1967; Clifford, 1970; Shanmugaratnam, 1971). It has been suggested that both genetic and environmental factors contribute to its etiology. Its frequency is remarkably high in certain areas of southern China, the Kwang-tung Province in particular. First generation immigrants of southern Chinese origin maintain a high frequency of NPC (Barr, 1974; Ho, 1975). In Singapore, different Chinese dialect groups show frequencies that correspond to their points of origin in China (Shanmugaratnam and Muir, 1967). Later generations of Chinese Americans show a decline in NPC mortality, but it is not clear whether this is due to their changed environment or to the intermarriage of different Chinese ehtnic subgroups with differing incidences of NPC.
TL;DR: Functional analysis of B lymphocyte populations in murine systems has been greatly facilitated by the use of polyclonal B cell activators (PBA) to provide a nonspecific stimulus to maturation and immunoglobulin synthesis of large number of clones and by theUse of the plaque assays as a sensitive technique for detection of antibody synthesis at the cellular level.
Abstract: The understanding of the human immune system has been governed by technical developments. The description of electrophoresis and immunoelectrophoresis allowed the monoclonality and class specificity of myeloma proteins to be analyzed, and the recognition of agammaglobulinaemia. The description of myelomas aided development of the clonal selection theory and the variety of agammaglobulinaemias allowed speculation about lymphoid differentiation. In the humoral limb of the immune response the next major development was the discovery of B lymphocyte surface markers (Moller 1961, Coombs et al. 1969, Dickler & Kunkel 1972), which allowed characterization of B lymphocyte populations in ontogeny, immunodeficiency and leukemias (Cooper et al. 1973, Seligmann 1973). Surface markers in resting cells have proved to be poor indicators of B cell function since many agammaglobulinaemias bear a normal complement of resting B cells which are, however, unable to synthesize immunoglobulin. Functional analysis of B lymphocyte populations in murine systems has been greatly facilitated by the use of polyclonal B cell activators (PBA) to provide a nonspecific stimulus to maturation and immunoglobulin synthesis of large number of clones and by the use of the plaque assays as a sensitive technique for detection of antibody synthesis at the cellular level. Pokeweed mitogen (PWM) has been the most studied human B cell mitogen and its use has yielded valuable information in agammaglobulinaemia and in human B lymphocyte ontogeny. Activation has been assessed by morphological blast formation, cytoplasmic immunoglobulin synthesis or released immunoglobulin
TL;DR: Biopsies from bladder tumors of 41 patients were investigated by flow‐cytofluorometric DNA analysis and compared with exfoliated cells, and the degree of proliferation appears to be of major biological significance.
Abstract: Biopsies from bladder tumors of 41 patients were investigated by flow-cytofluorometric DNA analysis and compared with exfoliated cells. The degrees of ploidy and proliferation were determined. Good agreement was found between the degrees of ploidy and proliferation in the biopsies and the exfoliated cell material. Tumors Grade I-II were either euploid or aneuploid. All Grade III tumors were aneuploid. The S-phase fractions were about 6% in the diploid tumors and 17% with large variations in the aneuploid tumors. The histological grading was well correlated to the number of S-phase cells and the occurrence of aneuploidy. When the Grade II tumors were divided into two groups having lesser and more pronounced atypia, the two groups differed significantly with regard to their degrees of proliferation. In addition to aneuploidy as an important criterium for malignancy, the degree of proliferation appears to be of major biological significance.
TL;DR: The presence of cysteine, N -acetylcystine, or methionine in the medium protects hepatocytes from bromobenzene toxicity by providing intracellular Cysteine for GSH biosynthesis and it is suggested that an inhibitory effect on amino acid uptake may contribute to the cytotoxicity of bromOBenzene in hepatocytes.