Intraepithelial lymphocytes expressing TCR gamma delta in human gingival tissues.
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Adolescent↗
Biomedical subjects
C Lundqvist
Publications and source records attributed to C Lundqvist.
Intermittent ethanol exposure of adult rats: hippocampal cell loss after one month of treatment.
The effects of intermittent intraperitoneal ethanol exposure (3 g/kg body weight twice daily) on hippocampal cells of adult rats were examined after a 1-month exposure period. Continuous oral exposure to ethanol in the drinking water (20%) over the same time period was used for comparison. Pyramidal cells from the CA3 region and granule cells from the dentate gyrus were also qualitatively assessed using electron microscopy. One month of intermittent, peaking, exposure induced a significant loss of CA2-CA3 pyramidal cells and an increase in the number of lipofuscin granules in the remaining cells. A significant reduction in thickness of the dentate gyrus granule cell layer was also seen in the same animals. No significant reduction in pyramidal cell number or granule cell layer thickness was seen in continuously orally exposed animals in spite of a higher total ethanol intake. These studies thus demonstrate the harmful effect of intermittent high ethanol peaks and repeated withdrawal phases on hippocampal cells of the mammalian brain and emphasize the importance of considering the differential effects of different ethanol exposure patterns when assessing ethanol-induced cellular damage.
Administration, Oral↗
Transarterial embolization of cerebral arteriovenous malformations: improvement of results with experience.
PURPOSE: To present the treatment outcome after embolization of arteriovenous malformations. METHODS: All patients with cerebral arteriovenous malformations treated in 1987 and 1988 (27 patients, group I) and in 1992 and 1993 (35 patients, group II) were compared regarding treatment results and clinical outcome. RESULTS: Complications of the treatment occurred in 52% of group I and 22% of group II patients. Severe complications occurred in 11 % and 0%, respectively. There were no treatment deaths. Thirty percent of the arteriovenous malformations in the first group were totally occluded or made accessible for gamma knife treatment, compared with 69% of the arteriovenous malformations in the second group. The clinical outcome improved from 56% with an excellent or good outcome in group I, to 89% in group II. The follow-up time is much shorter in group II, 1.5 versus 5.5 years in group I. CONCLUSION: A definite improvement in treatment outcome has been achieved. The clinical outcome seems to have improved as well, although the shorter follow-up time makes this conclusion less certain.
Adolescent↗
Phosphatidylethanol formation and degradation in brains of acutely and repeatedly ethanol-treated rats.
The formation of the abnormal phospholipid phosphatidylethanol (PEth) was studied in hippocampus, cerebellum and cerebrum of rat brain after intraperitoneal ethanol administration. Prior to analysis by high performance thin layer chromatography PEth was purified. After one injection, PEth levels reached a maximum after 2 h and remained detectable for 14-24 h in all three regions. Repeated injections led to additional accumulation. Maximum in vivo levels of 30-50 nmol/g wet wt. were reached.
Animals↗
Cytokine profile and ultrastructure of intraepithelial gamma delta T cells in chronically inflamed human gingiva suggest a cytotoxic effector function.
We have shown that gamma delta T cells in human gingiva have an intraepithelial location and, that in the chronic inflammatory disease periodontitis, the expression of CD45RO and CD8 or CD4 is induced on gamma delta T cells. To study the role of gamma delta T cells in local antibacterial responses, we determined the cytokine profiles of isolated human gingival cells. Different T cell subpopulations, isolated by positive selection with mAb-coated magnetic beads and macrophages, as well as epithelial cells, were analyzed for expression of mRNA for 15 cytokines by reverse transcriptase-PCR. The ultrastructure of gingival gamma delta T cells was also studied. The gamma delta T cells expressed mRNA for IFN-gamma, TNF-alpha, TGF-beta 1, and IL-6. Expression of IFN-gamma was a consequence of inflammation. CD4+ gamma delta T cells expressed IFN-gamma only, whereas CD8+ gamma delta T cells expressed all four cytokines. CD8+ cells expressing IFN-gamma, TNF-alpha, and IL-6 in combination suggest a cytotoxic effector function. Gingival gamma delta T cells contained cytoplasmic electron-dense membrane-bound granules and multivesicular bodies that are ultrastructural characteristics of cytotoxic cells. Epithelial cells from inflamed gingiva expressed HLA-DR, CD1a, CD1c, and heat shock protein 60 on the cell surface. They also expressed mRNA for IL-1 beta, IL-6, IL-8, TNF-alpha, and TGF-beta 1. Thus, epithelial cells may function as accessory cells in immune activation and, at the same time, be target cells for CD8+ gamma delta T cells reactive with CD1 Ag or heat shock protein. These results suggest that gamma delta T cells constitute a first line of defense in gingiva, preventing entrance of pathogens by cytotoxicity against infected and stressed epithelial cells, and by control of epithelial cell growth through secretion of regulatory cytokines.
Chronic Disease↗
High expression of V gamma 8 is a shared feature of human gamma delta T cells in the epithelium of the gut and in the inflamed synovial tissue.
We have analyzed the V-gene usage in gamma delta T cells of the human gut and joint by using a new mAb (B18) specific for V gamma 8 of human TCR-gamma delta+ T cells. The B18+ population constituted a minor subset of the gamma delta T cells in peripheral blood (PB) of healthy persons (6 +/- 5%) and only 1 of 35 gamma delta T cell clones analyzed was positive. In contrast, the B18+ subset was a dominant gamma delta T cell population among intraepithelial lymphocytes (IEL) derived from the human intestine (74 +/- 29, p < 0.002), and two of three IEL clones from patients with coeliac disease were B18+. Interestingly, a higher proportion of B18+ gamma delta T cells was found in the synovial fluid of patients with rheumatoid arthritis (RA) (21 +/- 18%, 0.02 < p < 0.05) compared with normal PB. Furthermore, the B18+ subset was more frequent among IL-2-expanded gamma delta T cells (42 +/- 20%) derived from synovial tissue than among IL-2-expanded cells derived from synovial fluid (p < 0.002) and PB from RA patients (p < 0.02) as well as normal PB (p < 0.002). The V-gene usage of 13 gamma delta T cell clones from the synovial fluid of arthritic patients was analyzed. All B18+ clones (n = 7) expressed mRNA for V gamma 8 together with mRNA for V delta 1 (n = 5) or mRNA for V delta 3 (n = 2). None of the B18- clones expressed V gamma 8 (n = 6). We conclude that the gamma delta T cell that expresses V gamma 8, together with mainly V delta 1, is a major gamma delta T cell subset among the IEL of the gut and a highly frequent subset in the synovial tissue of patients with RA. This subset may correspond to the mouse V gamma 7+ IEL, which has a high degree of amino acid sequence homology with the human V gamma 8 protein.
Adult↗
Adaptation of signal transduction in brain.
Cell culture models were used to study the effects of long-term ethanol exposure on neuronal cells. Effects on phospholipase C and phospholipase D mediated signal transduction were investigated by assaying receptor-binding, G protein function, activities of lipases, formation of second messengers and c-fos mRNA. The signal transduction cascades displayed abnormal activities from 2 to 7 days of exposure which differed from the acute effects. Phosphatidylethanol formed by phospholipase D is an abnormal lipid that may harmfully affect nerve cell function.
Acclimatization↗
Long-term effects of intermittent versus continuous ethanol exposure on hippocampal synapses of the rat.
The hippocampus is known to be very sensitive to a large spectrum of different neurotoxins including ethanol. Ethanol administered continuously or intermittently may affect the hippocampus in different ways. Intermittent administration of ethanol has many features in common with the low level electrical stimulation protocols which lead to the functional changes associated with the phenomenon of kindling. In this study, the differential effects of intermittent intraperitoneal ethanol injections (3 g/kg twice daily) and continuously administered ethanol in drinking water (20%) on hippocampal synapses in the rat were studied using ethanolic phosphotungstic acid staining and electron microscopy. After 1 month of intermittent exposure a significant reduction (18%) of synapses was seen in the stratum lucidum of the CA3 region. Continuously treated animals showed no significant change over this time despite a higher total ethanol intake. In the dentate gyrus, a compensatory increase in supragranular synaptic number was seen only in continuously treated animals. These findings demonstrate the sensitivity of synapses of the hippocampus to the presence of ethanol and the larger effects of peaking ethanol concentrations compared to more constant levels. These results emphasize the need to consider the differential effects of various types of ethanol consumption also on the human brain.
Animals↗
Agonist-stimulated and basal phosphatidylethanol formation in neutrophils from alcoholics.
Phospholipase D has been shown to be a key enzyme in the signal transduction systems involved in neutrophil activation. In the presence of ethanol, the enzyme catalyzes a transphosphatidylation reaction through which phosphatidylethanol is formed instead of the normal product phosphatidic acid. The effects of ethanol on the formation of phosphatidylethanol and phosphatidic acid was studied in neutrophils from human alcoholics in vitro. Neutrophils were isolated and cellular lipids were labeled with [3H]oleate, whereafter the cells were preincubated with cytochalasin B. Subsequently, cells were stimulated with the chemotactic peptide formyl-Met-Leu-Phe in the presence of ethanol concentration ranging from 0 to 200 mM. In the presence of ethanol, both neutrophils from alcoholics and controls produced phosphatidylethanol, with a concomitant reduction of the production of phosphatidic acid. The amounts of phosphatidyl-ethanol and phosphatidic acid formed were dependent on the concentration of ethanol. In neutrophils from alcoholics, a higher apparent Km for the phospholipase D-mediated transphosphatidylation reaction was noted (58 mM ethanol compared with 28 mM in controls). The in vivo mass of phosphatidylethanol in recently drinking alcoholics was also analyzed in neutrophils. Measurable phosphatidyl-ethanol levels (average 5.6 pmol/10(8) neutrophils) were found in alcoholics up to 23 hr after the last intake of ethanol. Thus, in addition to the ethanol-induced changes in the normal production of phosphatidic acid, phosphatidylethanol accumulated in vivo in alcoholics may be expected to influence neutrophil function.
Adult↗
Spinal arteriovenous malformations. Health-related quality of life after embolization.
The overall function, pain and mood disturbances of 19 patients with spinal arteriovenous malformations (AVM), treated by embolization between 1983 and 1988, were studied. The after-care had taken place in different hospitals and clinics. The patients demonstrated markedly poorer physical function (Sickness Impact Profile) and poorer psychological well-being (Mood Adjective Check List) than control population samples and a comparison group of traumatic incomplete paraplegics. The degree of decrease of mood levels implied possible depressive disorder (Hospital Anxiety and Depression scale) in 16% of the patients and differed from that of the paraplegic comparison group. Furthermore, the AVM patients reported more disturbance of their family and social life than the paraplegics and they were more seldom gainfully employed. Patients recorded a wide range of pain scores, significantly worse than the paraplegics, and their pain was closely linked to overall quality of life (QL) perception. The QL scores were consistently related to all measures of functional and emotional status, but no connection with neurological lesion levels or medical complications was found. Specialised programmes after embolization, such as those offered in spinal injury units, would appear appropriate for AVM patients to improve their physical functioning and to provide a more rewarding social life.
Activities of Daily Living↗
[Superselective catheterization. Treatment of sinus thrombosis directly in the thrombi].
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Adult↗
Receptor-mediated phospholipase D activity in primary astroglial cultures.
Phospholipase D, an enzyme involved in signal transduction cascades, catalyses the formation of phosphatidic acid and, when ethanol is present, the formation of phosphatidylethanol. In the present study we demonstrate that stimulation of muscarinic acetylcholine receptors as well as P2-purinergic receptors induces activation of phospholipase D in primary cultures of astroglial cells. Both the hydrolysis and the transphosphatidylation reactions were stimulated by receptor agonists. Carbachol and ATP induced a rapid increase in the amount of [3H]phosphatidic acid in astroglial cells prelabelled with [3H]oleic acid. When ethanol (150 mM) was present, phosphatidylethanol was formed. Furthermore, the receptor-mediated increase in the concentration of phosphatidic acid was inhibited by ethanol, indicating that the phosphatidic acid production was indeed mediated by phospholipase D. The formation of phosphatidylethanol was concentration dependent, with a half-maximal effective concentration of 5 x 10(-5) M for carbachol and 10(-5) M for ATP. The carbachol-induced response was almost completely inhibited by atropine, indicating activation of phospholipase D via muscarinic receptors. The purinergic response is most probably mediated via P2-receptors since ADP was almost as efficient as ATP in inducing phosphatidylethanol formation, whereas AMP was significantly less potent. We conclude that astroglial cells in primary culture display muscarinic and purinergic receptors coupled to phospholipase D. The relationship to cell function needs to be further investigated.
Adenosine Triphosphate↗
Phosphatidylethanol affects inositol 1,4,5-trisphosphate levels in NG108-15 neuroblastoma x glioma hybrid cells.
Phosphatidylethanol is formed by phospholipase D in animal cells exposed to ethanol. Previous reports have demonstrated that the degradation of phosphatidylethanol is slow, indicating that this lipid may be present in the cells after ethanol itself has disappeared. Accumulation of an abnormal alcohol metabolite may influence cellular functions. In the present study, cultivation of NG108-15 neuroblastoma x glioma hybrid cells in the presence of ethanol resulted in an accumulation of phosphatidylethanol and a simultaneous increase in basal inositol 1,4,5-trisphosphate levels. The direct effects of phosphatidylethanol on the phosphoinositide signal transduction system were examined through incorporation of exogenous phosphatidylethanol into membranes of ethanol-naive cells. An incorporation amounting to 2.8% of cellular phospholipids was achieved after a 5-h incubation with 30 microM phosphatidylethanol. Phosphatidylethanol was found to cause a time- and dose-dependent increase in the basal levels of inositol 1,4,5-trisphosphate. The effects on inositol 1,4,5-trisphosphate levels of exogenously added phosphatidylethanol and ethanol exposure for 2 days were not additive. No effect on bradykinin-stimulated inositol 1,4,5-trisphosphate production could be detected. However, the increase in basal inositol 1,4,5-trisphosphate levels indicates that phosphatidylethanol affects inositol 1,4,5-trisphosphate turnover and emphasizes the importance of considering phosphatidylethanol as a possible mediator of ethanol-induced effects on cellular processes.
Animals↗
T-cell receptor gamma delta-expressing intraepithelial lymphocytes are present in normal and chronically inflamed human gingiva.
The phenotypic profile of leucocytes in diseased and normal gingival tissue was studied in situ and in isolated gingival mononuclear cell (GMC) preparations. T-cell receptor (TcR)gamma delta + cells showed preferential localization to epithelium, both in normal and inflamed gingiva, and were present in crevicular as well as oral epithelium. In normal gingiva > or = 30% of the isolated leucocytes expressed TcR gamma delta, of which the majority were CD4- CD8-, and expressed CD45RA. The proportion of TcR gamma delta + cells in GMC from periodontitis tissue varied between 2 and 32%. In contrast to normal gingiva the majority of TcR gamma delta + cells in diseased tissue were CD8+ and expressed CD45RO. Thus expression of the CD8 antigen on gingival TcR gamma delta + cells is probably a consequence of immune activation. Numerous Langerhans' cells and keratinocytes expressing the major histocompatibility complex (MHC) class I-like antigen, CD1, were present within normal and inflamed gingival epithelium in close proximity to the TcR gamma delta + cells. Most CD1a+ cells were scattered within oral epithelium. CD1c+ cells were localized close to the basal layer of crevicular epithelium. No CD1b+ cells were found. TcR alpha beta + cells, CD4+ and B cells were restricted to lamina propria of periodontitis lesions. The presence of intraepithelial TcR gamma delta + cells in normal gingiva suggests that they constitute the 'first line of defence' against the potentially harmful microflora in the oral cavity. Induction of CD8 and CD45RO antigens on TcR gamma delta + cells in periodontitis tissue indicate that they play a significant role in the disease. CD1 molecules on Langerhans' cells and keratinocytes may be the restriction elements for the CD8+ TcR gamma delta + cells.
Adolescent↗
Isolation of functionally active intraepithelial lymphocytes and enterocytes from human small and large intestine.
A mild purification method has been developed for the isolation of human intraepithelial lymphocytes (IEL) and enterocytes from the same individual. The isolation procedure includes mechanical disruption of the mucosal layer, treatment with reducing agent and sedimentation followed by Percoll gradient centrifugation. Finally, epithelial cells are removed from the IEL fraction using magnetic beads coated with the anti-epithelial antigen monoclonal antibody (mAb) BerEP4. Leucocytes are removed from the enterocyte fraction using magnetic beads coated with mAbs directed against common leucocyte antigen (CD45). Using this procedure IEL and enterocytes have been isolated from apparently normal jejunal, ileal and colonic tissue specimens. Recoveries of IEL were 7 x 10(5), 4 x 10(5) and 1 x 10(5)/cm2 mucosa from jejunum, ileum and colon respectively. 1-2 x 10(6) enterocytes/cm2 mucosa were recovered from small intestine while the corresponding value for colonic biopsies was approximately 2 x 10(5) enterocytes/cm2. The IEL fraction was pure as judged by the low percentages of B cells, macrophages and BerEP4 positive cells (less than 4%) present in the purified fraction. The enterocyte fraction contained less than 2% CD45+ cells. The two cell fractions were viable and expanded in vitro. Enterocytes expanded spontaneously while IEL required initial stimulation with mitogens. The isolation procedure described here will make it possible to study the function of human IEL, interactions between IEL and enterocytes and the role of both cell types in local immunity.
Adult↗
Spinal cord injuries. Clinical, functional, and emotional status.
Ninety-eight patients with traumatic spinal cord injury, at a median age of 33.5 years (range, 16-72 years), with nonremarkable distributions of neurologic characteristics were investigated at a median of 2.3 years (range, 0.1-23 years) after injury. Functioning, mood disturbances, and overall quality of life were recorded with established self-assessment instruments. Physical dysfunction levels were moderate, being proportionate to neurologic impairment. Psychosocial functions, mood states, and quality-of-life perceptions did not differ from those of a control population sample. Psychosocial function and mood disturbances varied greatly during the first 4 years after injury, but patients' later recordings expressed predominantly a balanced emotional state and a rewarding social life. Progress in this direction consisted of clearly lessened physical dysfunction 1 year after injury and better psychosocial function and well-being after 2 years, whereas patterns of social activities and contacts became gradually less inhibited during a 4-year period after injury. Analysis of complications in patients' histories that affected function and mood showed severe pain to be the only complication that related to lower quality-of-life scores. Urinary incontinence and infection and autonomous dysreflexia related to inhibited self-care performance; spasticity related to impaired ambulation and feeding skills. Gainful employment was the only demographic factor linked to high quality-of-life scores.
Activities of Daily Living↗
Sexual ability, activity, attitudes and satisfaction as part of adjustment in spinal cord-injured subjects.
Changes in different aspects of sexuality were investigated and related to overall quality of life and physical, psychological and social adjustment in 73 SCI subjects, who were sexually active both before and after injury. Items on sexual interest and satisfaction were treated as one composite variable, the SIS scale, measuring sexual adjustment after injury. Despite severe genital dysfunction, more than half of the subjects (57%) rated their sexual relations after injury as satisfying or at least rather satisfying. The majority continued having intercourse, although many of them more seldom than before, and about half experienced orgasm. Sexual adjustment after injury was closely and positively correlated to frequency of intercourse, willingness to experiment with alternative sexual expressions and young age at injury. Physical and social independence and a high mood level were further positive determinants of sexual adaptation after injury, whereas the neurological level and completeness of injury showed no significant correlation with sexuality. It is suggested that sexual information and counselling should be integrated in the total care of the SCI patient to reduce the negative effects on sexuality, caused by the injury.
Adolescent↗
The quality of life of three functional spinal cord injury subgroups in a Swedish community.
Vast community provisions in Sweden are intended to offer spinal cord injury (SCI) subjects equal opportunities and the same living standards as the able-bodied. This study on all 56 subjects representing 3 distinct functional subgroups, out of a consecutive series treated at a Spinal Unit, explored the skills used in a wide range of community living activities and the details of these subjects' quality of life (QL). C6-tetraplegics with complete lesions (n = 15), wheelchair-bound paraplegics (n = 23) and ambulant paraplegics (n = 18) varied in physical independence in proportion to their disabilities but disturbances of mood states and QL perception did not differ between groups or from a control population sample. Eighty per cent of the subjects were engaged in gainful employment or education. Work/education, home management and mobility in the neighbourhood were clearly restricted by more severe disability but social and recreational activities were not. Degree of social activity and ability to drive a car were closely associated with levels of mental well-being and of perceived QL. Access to transport and home-help services, appropriate housing and technical aids included few unmet subjective needs, possibly explaining why these environmental factors did not inhibit the activity levels of the study population. Extensive society support and stimulation can satisfy important needs and expectations of well-functioning SCI subjects.
Activities of Daily Living↗