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Showing papers by "Karolinska Institutet published in 1981"


OtherDOI
TL;DR: The sections in this article are:==================PREGNSSI and EMG information as mentioned in this paper, Biomechanical and Electromyographical Information, Biophysics, Physiology and Physiological Information.
Abstract: The sections in this article are: 1 Biomechanical and Electromyographical Information 1.1 Single Limb During Locomotion 1.2 Interlimb Coordination 1.3 Treadmill Versus Overground Locomotion 1.4 Trunk Movements During Locomotion 1.5 Pathological Gaits 1.6 Summary 2 Neural Generation of “Basic Locomotor Synergy” 2.1 Central Versus Peripheral 2.2 Parts of CNS of Primary Importance for Neural Control of Basic Locomotor Synergy 2.3 Spinal Centers for Locomotion—Behavioral Results 2.4 Reflex Control of Basic Locomotor Synergy 2.5 Activity in Certain Spinal, Cerebellar, and Brain Stem Neurons and in Certain Reflex Pathways During Locomotion 2.6 Cerebellum and Locomotion 2.7 Initiation of Locomotion—Brain Stem Circuitry 2.8 Central Organization of Spinal Pattern Generation 2.9 Possible Rhythm-Generating Mechanisms and Models—Facts and Fiction 2.10 Developmental Aspects 2.11 Summary 3 Adapting Basic Locomotor Synergy to Animal's Needs 3.1 Changing Speed 3.2 Goal-Directed Locomotion—Turning and Walking Along Curvatures 3.3 Modifications of “Locomotor Posture” 3.4 Positioning of Limb in Each Step 3.5 Reflex Adaptation of Step 3.6 Summary 4 Concluding Remarks

1,264 citations


Journal ArticleDOI
TL;DR: The adaptive potential of muscle provedes a logical framework for understanding neural influences on the emergence of fiber types during muscle development and is also relevant to the study of pathological conditions which may involve a sustained departure from normal postural and locomotor patterns of activity.
Abstract: Skeletal muscle undergoes profound changes in morphological, physiological, and biochemical character when subjected to prolonged periods of increased use. Although increased use may be brought about in a variety of ways, the results show consistent features. In particular, endurance exercise and chronic stimulation differ only in degree: the properties which change in response to exercise are also those which change at an early stage of stimulation; the properties which are resistant to change under exercise conditions change only after prolonged stimulation. There is therefore a hierarchy of stability in the properties of skeletal muscle which is revealed in its response to changing functional demands. The adaptive potential of muscle provides a logical framework for understanding neural influences on the emergence of fiber types during muscle development. It is also relevant to the study of pathological conditions which may involve a sustained departure from normal postural and locomotor patterns of activity.

738 citations


Journal ArticleDOI
TL;DR: Evidence was obtained that at least some cell bodies in the medullary raphe nuclei and adjacent areas contained all three compounds, 5-hydroxytryptamine, thyrotropin releasing hormone (TRH) and substance P immunoreactive neurons in normal and colchicine-treated rats.

700 citations


Journal ArticleDOI
Klein G1
26 Nov 1981-Nature
TL;DR: Analysis of chromosome translocations associated with B-cell derived tumours and studies of chromosome-15 trisomy in murine leukaemia support the theory, emerging from recent work on tumour viruses, that cancer can be associated with DNA rearrangements which result in the increased expression of normal cellular genes.
Abstract: Analysis of chromosome translocations associated with B-cell derived tumours and studies of chromosome-15 trisomy in murine leukaemia support the theory, emerging from recent work on tumour viruses, that cancer can be associated with DNA rearrangements which result in the increased expression of normal cellular genes.

610 citations


Journal ArticleDOI
TL;DR: It is concluded that saline and saliva offer good protection against root resorption during the extra-alveolar period.

433 citations


Journal ArticleDOI
01 Sep 1981-Blood
TL;DR: It is suggested that leukotrienes, and to a lesser degree compounds I and II, stimulated migration and adhesion, could be of importance for the emigration of neutrophils from blood vessels to areas of inflammation.

398 citations


Journal ArticleDOI
TL;DR: Biopsies from the soleus muscles of 5 healthy males suffering from pronounced exercise-induced delayed muscle soreness showed that the contractile machinery of overloaded muscle fibres seemed to be partially distorted several days following exercise.
Abstract: Biopsies, taken up to 1 week postexercise, from the soleus muscles of 5 healthy males (20--34 years old) suffering from pronounced exercise-induced delayed muscle soreness were analyzed morphologically. There was no evidence for ischemic tissue injury or mechanical fibre disruption. However, at the subcellular level frequent myofibrillar disturbances, especially with regard to the Z-bands, were noted. Thus, the contractile machinery of overloaded muscle fibres seemed to be partially distorted several days following exercise.

364 citations


Journal ArticleDOI
TL;DR: The structure of a triclinic complex between liver alcohol dehydrogenase, reduced coenzyme NADH, and the inhibitor dimethylsulfoxide has been determined and the structural basis for the suggested mechanism of action based on studies of the apoenzyme structure is confirmed.

352 citations


Journal ArticleDOI
TL;DR: The results support the conclusion that in hepatocytes catalase has a relatively minor role in catabolism of H2O2 at low rates of H 2O2 generation in the endoplasmic reticulum, but that theCatalase function increases as the rate of H1O2 production is enhanced.

331 citations


Journal ArticleDOI
TL;DR: It is postulated that physical removal or extended drying of the periodontal ligament initiates a rapid osteogenesis in the alveolus which establishes an ankylosis which, in most cases, persisted after 8 weeks.
Abstract: The effect of limited drying or removal of the periodontal ligament upon periodontal healing after replantation of incisors was studied in green Vervet monkeys. All teeth were examined histologically either 2-, 4- or 8 weeks after replantation. The drying experiment demonstrated that an area of ankylosis was established after 2 weeks corresponding to the dried portion of the root and was removed by a resorptive process in the majority of cases after 8 weeks. The removal of the periodontal ligament led to development of surface-, inflammatory- and replacement resorption. Furthermore, 1 mm2 and 4 mm2 lesions on the root surface developed transient ankylosis which disappeared after 8 weeks while lesions of 9 mm2 or 16 mm2 in size resulted in an ankylosis which, in most cases, persisted after 8 weeks. Based on these findings, it is postulated that physical removal or extended drying of the periodontal ligament initiates a rapid osteogenesis in the alveolus which establishes an ankylosis. If the damaged area is placed next to a zone on the root surface with a vital periodontal ligament, a later resorptive process is established from this zone, whereby the ankylosis area is gradually resorbed. It is estimated that the extent of this process in this experiment amounted to possibly 1 -- 1.5 mm.

314 citations


Journal ArticleDOI
TL;DR: It is suggested that cells in the dopamine-rich areas of the mesencephalon can be characterized both on the basis of their content of peptide and/or catecholamine and of their responsiveness to cholecystokinin-like peptides.

Journal ArticleDOI
TL;DR: The results demonstrate that the effects of Capsaicin are not confined to substance P immunoreactive primary sensory neurons, and the possibility is discussed that capsaicin effects specifically functioning rather than chemically specific primary sensory cells.
Abstract: After neonatal treatment of rats with capsaicin, the spinal cord, the spinal trigeminal nucleus and spinal and trigeminal ganglia were analysed with immunohistochemistry using antisera to several peptides and 5-hydroxytryptamine. A marked decrease was observed in substance P-, cholecystokinin-, somatostatin- and VIP-like immunoreactivity present in the central branches of primary sensory neurons in the spinal cord and in substance P- and somatostatin-like immunoreactivity in sensory ganglion cells. No definite depleting effect of capsaicin could be established on 5-hydroxytryptamine and peptides, such as enkephalin and neurotensin, present in centrally originating fibres in the dorsal horn of the spinal cord. The results demonstrate that the effects of capsaicin are not confined to substance P immunoreactive primary sensory neurons. The possibility is discussed that capsaicin effects specifically functioning rather than chemically specific primary sensory neurons.

Journal ArticleDOI
TL;DR: Studying of the formation of lignans in man, by means of selective antibiotic administration, confirm that these new compounds are formed by intestinal microflora, and indicate that clostridia may be responsible for the Formation of these highly aromatic compounds.

Journal ArticleDOI
TL;DR: The formation of a novel dihydroxy-acid, 5S,12S-dihydroxy-6-trans,8-cis,lOtrans,l4-c is-eicosatetraenoic acid (SS,12SDHETE), in preparations of human leukocytes is reported and further conversion of this trihydroxy acid to a dicarboxylic acid (20-COOH-LTB4).

Journal ArticleDOI
TL;DR: The quantitative excretion of HBBL and HBBD was found to exhibit a cyclic pattern during the menstrual cycle of humans and monkeys, maximum excretion occurring in the luteal phase and elevated levels were found in urine collected during early pregnancy.

Journal ArticleDOI
TL;DR: Both 5HIAA and HVA were positively and significantly correlated to platelet MAO activity in the healthy subjects, but not in any of the patient groups.
Abstract: Platelet monoamine oxidase (MAO) activity and cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA), and 4-hydroxy-3-methoxyphenylglycol (HMPG) were simultaneously measured in 20 currently depressed patients, 11 recovered depressed patients, 15 nondepressed suicide attempters, and 42 healthy control subjects. Both 5HIAA and HVA were positively and significantly correlated to platelet MAO activity in the healthy subjects, but not in any of the patient groups. Suicide attempters had significantly lower CSF 5HIAA than nonsuicidal patients.

Journal ArticleDOI
03 Dec 1981-Nature
TL;DR: (D-Pro2, D-Trp7,9)-SP antagonized the contractile response to applied SP and to non-cholinergic, non-adrenergic nerve stimulation in the isolated guinea pig taenia coli and rabbit iris sphincter pupillae muscle, suggesting that SP, or a closely related peptide, is indeed a motor excitatory transmitter.
Abstract: Nerve fibres containing substance P (SP) are widely distributed in the body1–3 and seem to innervate autonomic ganglia, blood vessels, epithelial structures and smooth muscle. SP stimulates secretion from exocrine glands, causes vasodilation and contracts non-vascular smooth muscle4. The presence of SP in primary sensory neurones has lent support to the view that it is associated with sensory nerve conduction, conceivably as a transmitter5, and that it is a causative factor in the ‘irritative’ response to antidromic stimulation of sensory nerves6. Gut smooth muscle contracts in response to non-cholinergic, non-adrenergic nervous stimulation7,8, and it has been suggested that SP acts as an excitatory transmitter in intramural neurones in the gut wall2,3,9,10. Recently, a series of synthetic analogues of SP with antagonist activity to SP has been developed11,12. We report here that a new analogue, (D-Pro2, D-Trp7,9)-SP, exercises a specific, possibly competitive antagonism to SP. While being a partial agonist it antagonized the contractile response to applied SP and to non-cholinergic, non-adrenergic nerve stimulation in the isolated guinea pig taenia coli and rabbit iris sphincter pupillae muscle, suggesting that SP, or a closely related peptide, is indeed a motor excitatory transmitter. In contrast, (D-Pro2, D-Trp7,9)-SP did not inhibit the contractile response to non-cholinergic, non-adrenergic nerve stimulation of smooth muscle from the guinea pig urinary bladder.


Journal ArticleDOI
22 Jan 1981-Nature
TL;DR: It is demonstrated here that in vitro CSA has no apparent effect on Epstein-Barr virus (EBV)-induced B-lymphocyte activation, but totally inhibits the T-cell dependent pokeweed mitogen (PWM) B-cell response.
Abstract: Cyclosporin A (CSA) is a fungal metabolite which exerts profound effects on the immune system and has potential as a selective immuno-suppressive agent1. Clinical trials with human renal allograft recipients have confirmed this potential but there have been disturbing reports of lymphoma in a significant number of patients2,3. Despite extensive animal studies, the specificity of this drug for human lymphocyte subpopulations is largely unknown4. We demonstrate here that in vitro CSA has no apparent effect on Epstein-Barr virus (EBV)-induced B-lymphocyte activation, but totally inhibits the T-cell dependent pokeweed mitogen (PWM) B-cell response. In addition, CSA markedly facilitates the outgrowth of B-lymphoblastoid cell lines from both EBV-infected and non-infected lymphocytes of EBV immune donors cultured in vitro. These results indicate that CSA can interfere with the lymphocytes normally responsible for maintaining the life-long carrier state initiated by primary infection with EBV, allowing outgrowth of the persistently infected cells circulating in the peripheral blood.

Journal ArticleDOI
TL;DR: In mice exposed to 74 As-labeled trivalent or pentavalent inorganic arsenic, dimethylarsinic acid was found to be the major urinary metabolite and methylation was, however, much lower in the rats and the possibility that this might be one reason for the extremely high retention of arsenic in the rat is discussed.

Journal ArticleDOI
TL;DR: By the use of intracellular staining with horseradish peroxidase (HRP), the dendric systems of spinal γ‐motoneurons of the adult cat were studied with a light microscope.
Abstract: By use of intracellular staining with horseradish peroxidase (HRP), the dendritic systems of spinal gamma-motoneurons of the adult cat were studied with a light microscope. The dendrites extended in various directions up to 1.5 mm from the cell body. The dendritic branching was sparse and even unbranched dendrites were occasionally seen. The number and combined diameter of the first-order dendrites increased in parallel with the mean cell body diameter. The number of dendritic end branches, the combined dendritic length, the membrane surface area, and the volume of the entire dendrite correlated positively with the diameter of the parent first-order dendrite. In comparison with the alpha -motoneurons (Ulfhake and Kellerth, '81) the gamma -motoneurons had smaller values for mean cell body diameter and mean diameter of the first-order dendrites and they also had a smaller number of first-order dendrites. The dendrites of the gamma-motoneurons were also found to have fewer branching points and larger values for combined dendritic length. The relation between the diameter of the first-order dendrite and the surface area of the entire dendrite was almost identical for the two types of motoneurons.

Book ChapterDOI
TL;DR: The chapter discusses an experimental model in which intracellular organelles are introduced into the lysosomal apparatus of Kupffer cells by means of heterophagy, and the study of the heterophagic model has advantages over induced autophagy because the degradation of each membrane constituent or cell organelle can be separately studied.
Abstract: Publisher Summary This chapter describes the mechanisms of intralysosomal degradation with a special reference to autophagocytosis and heterophagocytosis of cell organelles. Autophagy is the process of sequestration of intracellular components and their subsequent degradation by the lysosomes. The process of degradation is of fundamental importance in cell function because under steady-state conditions subcellular components are broken down and resynthesized many times during the life span of the cells. Autophagy contributes to the turnover of cell constituents during physiological cell conditions. Autophagy is induced by numerous treatments, conditions, or agents that cause cell dysfunction. Biological components from the extracellular space can also enter the lysosomal compartment and become degraded through the process of heterophagy. The chapter discusses an experimental model in which intracellular organelles are introduced into the lysosomal apparatus of Kupffer cells by means of heterophagy. The study of the heterophagic model has advantages over induced autophagy because the degradation of each membrane constituent or cell organelle can be separately studied. The heterophagy model is also useful to evaluate the capacity of lysosomes to degrade various membrane components in vivo .

Journal ArticleDOI
TL;DR: The strong correlation between the total plasma clearance of NT and the metabolic clearance by E‐10‐hydroxylation shows that this metabolic reaction is important in the disposition of the drug.
Abstract: Eight healthy subjects [who were phenotyped with a debrisoquine (D) hydroxylation test] were selected to cover a wide range in the ratio between D and 4-hydroxydebrisoquine (4-OH-D) in the urine. After a single oral dose of nortriptyline (NT) the metabolic clearance by 10-hydroxylation in the E-position, but not in the Z-position, correlated closely to the metabolic ratio D/4-OH-D (rs = -0.88, p less than 0.01). This indicates that common enzymatic mechanisms are involved in the hydroxylation of D and the E- but not the Z-10-hydroxylation of NT. Slow hydroxylators of NT and D excreted less 10-hydroxynortriptyline in urine and had lower plasma clearance of NT than the rapid hydroxylators. The strong correlation (r = 0.96) between the total plasma clearance of NT and the metabolic clearance by E-10-hydroxylation shows that this metabolic reaction is important in the disposition of the drug.

Journal ArticleDOI
TL;DR: There is a notable absence of functional B lymphocytes studies performed on the developing human, particularly outside the immediate neonatal period, and it is only with sequential cell functional studies that the process of B lymphocyte functional maturation can be clarified.
Abstract: Infections remain a leading cause of neonatal death in spite of improvements in public health and medical care including the use of antibiotics. The incidence of life threatening viral and bacterial infections in human newborns is much higher than in adults. Intense studies of the reasons for this have led to various and sometimes conflicting conclusions. Lack of earlier antigenic experience, intrinsic immaturity of lymphocyte functions and active cellular suppressive mechanisms, or a combination of these possibilities, are suggested explanations (Lawton et al. 1972, Stiehm 1975, Xanthou et al. 1976, Hayward & Lawton 1977, Oldstone et al. 1977, Miller 1978). Many conclusions about human B lymphocyte function in the neonate have been derived from the immunochemical analysis of immunoglobulins present in the serum of the neonate and developing infant. Such studies have been fraught with difficulty both because of the presence of passively transferred maternal IgG and its secondary interference with any attempts to induce in vivo antigenic challenge. In viiro specific antigenic responses have, with a few notable exceptions (Hoffman 1980. Saxon & Stevens 1980), proved difficult even in the adult human, probably principally because peripheral blood is the only logistic source of lymphocytes. Such studies become impossible in the neonate where even blood is available only in minimal quantities. There is, therefore, a notable absence of functional B lymphocyte studies performed on the developing human, particularly outside the immediate neonatal period. It is only with sequential cell functional studies that the process of B lymphocyte functional maturation can be clarified.

Journal ArticleDOI
TL;DR: There was a variation in oral bioavailability of 15% to 64% and an interindividual variation in terminal half‐life from 58 to 467 min and these data warrant careful adjustment of the oral dose under close supervision of the patient at the onset of therapy.
Abstract: Oral and intravenous morphine kinetics were studied in seven patients with cancer who needed continuous treatment with morphine because of severe chronic pain. Single oral (20 to 30 mg) and intravenous (4 mg) doses were given on separate days, followed by repetitive blood sampling for morphine analysis by gas chromatography. Volume of distribution ranged from 0.95 to 3.75 l/kg and serum clearance from 5.0 to 16.1 ml/min/kg. Oral morphine in doses that were more than five times the intravenous dose gave concentrations (at 10 and 120 min after dose) between 38 and 112 ng/ml. During the 0.25- to 8-hr period after the oral dose serum concentrations were higher than after the intravenous dose. There was a variation in oral bioavailability of 15% to 64% and an interindividual variation in terminal half-life from 58 to 465 min. These data warrant careful adjustment of the oral dose under close supervision of the patient at the onset of therapy.

Journal ArticleDOI
TL;DR: The role of LTB4, SQ,12(S)-DHETE and their o-oxida- tion products in leukocyte degranulation in vitro is investigated.

Journal ArticleDOI
TL;DR: The present determination confirms that the GIP preparation is heterogeneous, and shows that the major secondary component appears to be identical to the most abundant component except that it lacks the first two residues of the latter.

Journal ArticleDOI
TL;DR: In this paper, the effects of four xanthines (theophylline, 8-phenyltheophyllanine, isobutylmethylxanthine (IBMX), and 7-benzyl-IBMX) were studied in the hippocampal slice in vitro.
Abstract: The effects of four xanthines (theophylline, 8-phenyltheophylline, isobutylmethylxanthine (IBMX), and 7-benzyl-IBMX) were studied in the hippocampal slice in vitro. These agents increased the excitability of this preparation with 8-phenyltheophylline being the most potent, 7-benzyl-IBMX the least potent, and theophylline and IBMX having intermediate potencies. A similar rank order was observed in terms of the potencies of these xanthines in antagonizing a) electrophysiological responses to adenosine, and b) adenosine-stimulated cyclic AMP formation. These results indicate that the excitatory actions of xanthines in the in vitro hippocampus can be most easily explained on the basis of their ability to block adenosine's actions; the CNS excitatory actions of these drugs in vivo may depend upon a similar mechanism of action.

Journal ArticleDOI
TL;DR: The findings underline the existence of a new type of γ-aminobutyrate-containing Golgi type I neuron, controlling activity in the substantia innominata and in the outflow from Calleja's islands of the olfactory tubercle and the view that γ -aminobUTyrate may play a role in synaptic processes in all parts of the brain and the spinal cord.

Journal ArticleDOI
11 Sep 1981-Science
TL;DR: Freshly isolated hepatocytes from phenobarbital-treated rats were incubated in the presence or absence of extracellular calcium with three differently acting liver cell toxins, namely carbon tetrachloride, bromobenzene, and ethylmethanesulfonate and these three compounds were far more toxic to the cells than in its presence.
Abstract: Freshly isolated hepatocytes from phenobarbital-treated rats were incubated in the presence or absence of extracellular calcium with three differently acting liver cell toxins, namely carbon tetrachloride, bromobenzene, and ethylmethanesulfonate. In the absence of extracellular calcium these three compounds were far more toxic to the cells than in its presence. This result is inconsistent with the hypothesis that an influx of extracellular calcium is required as the final step in toxic liver cell injury.