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Biomedical subjects

B K Pedersen

Publications and source records attributed to B K Pedersen.

At least 163 records · Page 9Linked to original sources
PubMed1995

Defective natural immunity: an early manifestation of human immunodeficiency virus infection.

Cytotoxicity mediated by natural killer (NK) and lymphokine-activated killer (LAK) cells may be of significance in host defense against viral infections. This study included 347 patients infected with human immunodeficiency syndrome virus (HIV) type 1 and 110 controls. The NK cell activity, either unstimulated or stimulated with interferon-alpha (IFN-alpha) or interleukin-2 (IL-2), and the LAK cell activity were suppressed in patients, but the NK/LAK cell activity did not differ between patients with AIDS and patients without AIDS. However, the IFN-alpha-stimulated NK cell activity and LAK cell activity were reduced in patients with symptoms of HIV disease (CDCIV) when compared with asymptomatic patients (CDCII+III). When the data were analyzed by multiple linear regression, the percentage of CD4+ cells had a positive effect on these two parameters in patients without AIDS, whereas the percentage of CD4+ cells had no significant effect on unstimulated and IL-2-stimulated NK cell activity in these patients. In controls and AIDS patients, the percentage of CD4+ cells had no effect on NK/LAK cell activity in multiple linear models. The total number of CD16+ cells was low in patients compared to controls, whereas the percentages of CD16+, CD56+, and CD16+CD56+ were either normal or elevated. Therefore, the decrease in NK cell subpopulations did not contribute to the observed depression in NK/LAK cell activity in vitro. It is concluded that natural immunity is suppressed in HIV-seropositive patients primarily because of a qualitative defect of the NK/LAK cells. This qualitative defect includes a reduced responsiveness to IFN-alpha, which is progressive until the onset of symptoms, and possibly related to the loss of CD4+ cells.

Adult↗
PubMed1995

Effects of isoniazid treatment on human lymphocyte proliferative response, lymphocyte subsets and natural killer cell activity.

The effect of isoniazid on proliferative response, natural killer (NK) cell activity and lymphocyte subset distribution of blood mononuclear cells (BMNC) was investigated. To evaluate the effect of treatment with isoniazid in pharmacologic concentrations, twenty healthy HIV-seronegative volunteers were randomized into two groups: one group received isoniazid tablets plus pyridoxin tablets once a day for 30 days, the other group received pyridoxin only. Blood samples were collected on day 0 and day 30. Inhibition of the PHA-induced proliferative response was demonstrated in lymphocyte cultures from isoniazid-treated volunteers (p < 0.001). However, no effect was seen on the IL-2- or antigen (PPD)-induced proliferative response or the NK cell activity of isolated BMNC. Inhibition of the PHA-induced proliferative response could not be related to changes in the distribution of CD3+, CD4+, CD8+, CD14, or CD19+ lymphocyte subsets. The effects, in vitro, were investigated by addition of isoniazid to cultures of BMNC isolated from either HIV-seroposive or HIV-seronegative donors who did not receive any treatment. We found that isoniazid did not influence the mitogen- or antigen-stimulated proliferative response or the NK cell activity.

Adult↗
PubMed1995

Pentoxifylline therapy in HIV seropositive subjects with elevated TNF.

Tumor necrosis factor-alpha (TNF-alpha) is thought to induce cachexia in subjects infected with human immunodeficiency virus (HIV), and it has been suggested that HIV-seropositive patients would benefit from treatment with pentoxifylline, a known suppressor of TNF-alpha production. The purpose of the present study was to examine how pentoxifylline at a dose of 800 mg thrice daily would influence the cellular immune system in HIV-seropositive persons with elevated TNF-alpha. Six HIV-seropositive subjects with elevated amounts of TNF-alpha in plasma at least at two occasions were included in an open, controlled, randomized, cross-over study consisting of a 6 week treatment period and a 6 week control period. Blood samples were collected before and at the end of each period. Pentoxifylline treatment did not influence the concentration of plasma-TNF-alpha, subpopulations of blood mononuclear cells, the proliferative responses nor the natural killer (NK), and lymphokine activated killer (LAK) cell activities. Furthermore, pentoxifylline treatment did not influence the weight, temperature, well being, or tiredness of the subjects. However, the patients frequently reported gastrointestinal side effects. In vitro, however, pentoxifylline at suprapharmacological concentrations inhibited the blood mononuclear cell (BMNC) proliferative responses, NK, and LAK cell activities.

Adolescent↗
PubMed1995

Restricted pulmonary diffusion capacity after exercise is not an ARDS-like injury.

Pulmonary diffusion capacity (DLCO) is reduced 2 h after various types of exercise, such as rowing, treadmill running, arm cranking and marathon running. The decrease in DLCO may involve alterations in the alveolar-capillary membrane as well as depletion of the central blood volume. We hypothesized that the reduction in DLCO might also be influenced by oxygen free radicals, acute phase proteins and endotoxin, which are also involved in the adult respiratory distress syndrome (ARDS). Ten competitive male oarsmen performed a 6 min 'all-out' ergometer row. Single breath DLCO was determined before and 2 h after rowing and venous blood samples were also obtained during the row. Absolute DLCO decreased by 11% (range 0-20%) 2 h after rowing, whereas the concentration of endotoxin did not change significantly and interleukin (IL)-1-alpha, IL-8 and tumour necrosis factor (TNF)-alpha were below the levels of detection before, during and 2 h after rowing. Oxygen free radicals were evaluated by oxidative modification of amino acids and DNA. Corrected for creatinine in urine voided 3 h post-exercise, the DNA repair product 8-oxo-7,8-dehydro-2-deoxyguanosine (8-oxodG) did not change significantly. The ratio of fluorescence due to dityrosine to that due to tryptophan in plasma proteins increased after exercise. This might reflect an effect of oxygen free radicals, but it might also indicate an altered relative composition of plasma proteins. These results suggest that the reduced pulmonary diffusion capacity following exercise is unrelated to factors typically associated with ARDS.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Natural killer cell response to exercise in humans: effect of hypoxia and epidural anesthesia.

For the response of immunologically competent blood cells to exercise, the importance of afferent nerve impulses was evaluated. On separate days, seven males cycled in a recumbent position approximately 60% of maximal O2 uptake with and without sensory nerve blockade by lumbar epidural anesthesia. Blood samples were collected after 60 min of rest, 20 min of exercise, and 120 min postexercise. Subsequently, on each day, the subjects were exposed to 11.5% O2-88.5% N2 for 10 min. This was followed by 20 min of hypoxic exercise at the same work rate, and a final blood sample was obtained. The concentrations of lymphocytes expressing the cluster designation (CD) cell-surface antigens CD3, CD4, CD8, and CD14 became elevated during exercise, and these responses were enhanced by hypoxia (P < or = 0.01). The most pronounced changes were within the concentrations of CD16+ and CD56+ natural killer cells, which increased twofold during normoxic and fivefold during hypoxic exercise (P < or = 0.01). Sensory nerve blockade decreased the number of CD3+ and CD4+ cells and increased the percentage of CD16+ cells, independent of exercise and hypoxia (P < or = 0.05). Sensory nerve blockade caused minor enhancement in the increase of unstimulated natural killer cell activity during exercise (P = 0.07) and enhanced the interferon-alpha-stimulated activity at normoxia (P < or = 0.05), whereas no effect was detected at hypoxia. The results demonstrate that the responses of immunological competent cells to normoxic and hypoxic exercise are not abolished by blockade of nerve impulses from active muscle.

Adult↗
PubMed1995

Effect of eccentric exercise on natural killer cell activity.

The effect of eccentric one-legged exercise on natural killer (NK) cell activity was studied in eight healthy males. To distinguish between local and systemic effects, blood samples were collected from veins in the exercising leg and resting arm. However, the results did not significantly differ between the leg and arm. To eliminate diurnal variations, the results were compared with a control group that did not exercise but had blood samples collected at the same time points. In the exercising group, plasma creatine kinase increased progressively during and up to 4 days after exercise. The percentage of CD16+ NK cells increased during exercise, which was paralleled by an increase in the NK cell activity per fixed number of blood mononuclear cells. The NK cell activity on a per NK cell basis did not change. The percentage of CD3+, CD4+, CD8+, CD19+, and CD14+ cells did not change significantly during exercise. The present study thus showed that eccentric exercise with a relatively small muscle mass (1 quadriceps femoris muscle) causes systemic effects on NK cells. It is suggested that the increase in plasma epinephrine during eccentric exercise is responsible for the observed increase in the percentage of CD16+ cells.

Adult↗
PubMed1995

Effects of glutamine on the immune system: influence of muscular exercise and HIV infection.

Glutamine increased the proliferative response and the lymphokine-activated killer cell activity of blood mononuclear cells isolated from normal healthy subjects (n = 6) in a dose-dependent manner, with optimum at 0.3-1.0 mM. The relative fraction of CD3+, CD4+, CD8+, CD14+, CD16+, and CD19+ cells was not changed by glutamine at a concentration of 0.6 mM, except in the phytohemagglutinin-stimulated proliferation experiment where the fraction of CD4+, and therefore CD3+ cells, increased. The natural killer cell activity was not influenced by glutamine. Human immunodeficiency virus (HIV)-seropositive subjects (n = 8) who performed concentric bicycle exercise for 1 h at 75% of maximal O2 consumption had an overall lower phytohemagglutinin-stimulated proliferative response, compared with the HIV-seronegative control group (n = 7). The proliferation during exercise was lower in both the HIV-seropositive and the HIV-seronegative group. Addition of glutamine in vitro did not normalize the lower proliferation in the HIV-seropositive group or the attenuated proliferation seen during exercise in both groups.

Adult↗
PubMed1995

How physical exercise influences the establishment of infections.

During exercise, leucocytes are recruited to the blood, and if muscle damage occurs the cytokine level is enhanced. After prolonged, intense exercise the number of lymphocytes in the blood is reduced, and the function of natural killer cells is suppressed; furthermore, secretory immunity is impaired. During this time of immunodepression, often referred to as 'the open window', the host may be more susceptible to micro-organisms bypassing the first line of defence. This is of interest to top athletes who perform frequent severe exercise. Clinical observations regarding an increased risk of infections in top athletes are compatible with this model. However, in those performing regular moderate exercise the immune system will often be temporarily enhanced and this will protect these individuals from infections.

Chronic Disease↗
PubMed1995

Beta-endorphin and the immune system--possible role in autoimmune diseases.

The immune system and the neuroendocrine system are closely interconnected having such means of bidirectional communication and regulation. In this review, a hypothesis is put forward regarding the possible role of beta-endorphins in the pathogenesis of autoimmune diseases: It is suggested that the increased cytokine production in immunoinflammatory disorders induces production of beta-endorphins from the pituitary and the lymphocytes; the enhanced level of beta-endorphin causes inhibition of human T helper cell function, which potentially down-regulate the antibody production. Also the beta-endorphin-induced enhancement of the natural killer cell activity may suppress the B cell function. In addition, beta-endorphin also exerts a direct inhibitory effect on the antibody production. Thus, in autoimmune disorders the enhanced cytokine level may via stimulation of the production of beta-endorphins exert a negative feed back on the antibody production and potentially so on the production of autoantibodies.

Amino Acid Sequence↗
PubMed1994

[Chronic fatigue syndrome--a controlled cross-sectional study].

Twenty-one patients fulfilling the Center for Disease Control criteria for chronic fatigue syndrome (CFS) were examined in a controlled study. Viral antibodies and tests evaluating the immune system were investigated in the patients and in a control group of 21 sex- and age-matched individuals. Production in vitro of the predominantly T-cell-derived cytokines interleukin-2 and interferon-gamma was significantly higher in patients with CFS compared the control group. Furthermore, the serum concentrations of IgA and IgE were significantly lower in patients with CFS; however, the values were within the normal reference range. All other variables were similar in the two groups. This study does not suggest a clearly disordered immune system or a chronic viral infection as a major pathogenetic factor in CFS. Longitudinal studies of immunological and virological parameters in CFS are warranted as are studies on patients that are severely handicapped.

Adolescent↗
PubMed1994

[Significance of fatty acid composition in plasma and in food for cellular immune function in elderly men].

The relation between fatty acid composition in plasma and natural killer (NK) cell activity and the relation between fatty acid composition of diet and NK cell activity was evaluated in healthy elderly men. The correlations between basal NK activity and the fraction of plasma fatty acids consisting of total polyunsaturated fatty acids (PUFA), total n-6 fatty acids and linoleic acid were r = -0.68, p = 0.006, r = 0.62, p = 0.014 and r = 0.52, p = 0.048, respectively. Significant negative correlations were also found between alpha-interferon stimulated NK cell activity and the three groups of fatty acids and between interleukin-2 stimulated NK cell activity and PUFA. Likewise, negative correlations between grammes of PUFA in diet, determined from two four-day registration-periods, and basal NK and alpha-interferon stimulated NK cell activity were found. No significant negative correlation between percentage intake of n-3 fatty acids and NK cell activity was found. It is concluded that the type of dietary fatty acids influence NK cell activity in elderly men. A high intake of n-6 polyunsaturated fatty acids may be detrimental to cellular immune defence mechanisms in the elderly.

Aged↗
PubMed1994

[Cemented hip alloplasty. 11-13-year follow-up study of the Richards' series 2 hip prostheses].

The study comprises a follow-up (11-13 years) of an orthopaedic department's first 131 consecutive cemented total hip arthroplasties (THA). All operations were performed with Richards' Series 2. Posterior approach, plug, lavage, cementation with cement pistol, antibiotics and low-dose heparin. At the time of follow-up 44 patients (38%) were dead (= 49 THA), and 56 patients representing 65 THA (50%) were available for the follow-up, on average 11.95 years (11-13 years) after the operation. The patients hip/hips were examined as regards a) pain b) walking ability and c) hip-mobility (M. d'Aubigné) (HFI). A frontal x-ray of the pelvis and hip/hips was taken. The examining surgeon evaluated the hip/hips based on a clinical examination and the x-ray as 1 = stable, 2 = perhaps loose, 3 = most likely loose and 4 = definitely loose both with regard to the acetabular and femoral component. Pre-operatively 78% of the patients had an ideopathic coxarthrosis. Eight patients had considerable postoperative complications. Ten patients (7.8%) were reoperated during the examination period: two due to loosening of the total prosthesis, one due to loosening of the cup, three due to loosenings of the femoral component, two because of recurring luxations, one late (deep) infection and one fracture of the femur near the prosthesis. Preoperatively the patients' HFI was at 8.6, at follow-up 15.8. The clinical and the radiographic examination showed that 86% of the acetabular cups and 63% of the femoral components were fixed solidly.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Exercise and the immune system: a model of the stress response?

Exercise influences natural immunity, T- and B-cell functions, and cytokine responses, through circulatory (hemodynamic) changes and by endocrine hormones secreted in response to physical stress. The magnitude of the effects on the immune system reflects the intensity, duration and chronicity of the exercise. In this review, Laurie Hoffman-Goetz and Bente Klarlund Pedersen suggest that exercise-immune interactions can be viewed as a subset of stress immunology.

B-Lymphocytes↗
PubMed1994

Evidence that the effect of bicycle exercise on blood mononuclear cell proliferative responses and subsets is mediated by epinephrine.

The present study was designed to test the hypothesis that the exercise-induced changes in blood mononuclear cell (BMNC) subsets, BMNC proliferative responses and lymphokine activated killer (LAK) cell activity are mediated by increased epinephrine concentrations. Healthy male volunteers 1) exercised on a bicycle ergometer (75% of VO2max, 1 h) and 2) on another day were given epinephrine as an intravenous infusion to obtain plasma epinephrine concentrations comparable with those seen during exercise. Blood samples were collected in the basal state, during the last minutes of exercise or epinephrine infusion and 2 h later. During both perturbations the %CD3+ and %CD4+ T cells declined and the %CD16+ NK cells increased. Two h afterwards the CD14+ monocytes increased, while no changes were observed in %CD8+ T cells or %CD20+ B cells. The phytohemagglutinin (PHA) response declined during both epinephrine infusion and exercise experiments. The changes in interleukin-2 (IL-2) effect on proliferation and cytotoxic activity (LAK cell activity) were more pronounced in exercise experiments than during epinephrine. Exercise and epinephrine caused increase in concentrations of lymphocytes and neutrophils, but the changes were more pronounced in exercise experiments. The results indicate that, in response to physical exercise, the rise in plasma epinephrine may contribute to the changes in cellular immunity.

Adult↗
PubMed1994

The immune system during exposure to extreme physiologic conditions.

It is not clear how the immune system is modulated in response to physical stress (e.g. trauma, surgery, burn and sepsis). In order to better understand the stress-induced immune changes, effects of isolated stressors are evaluated. Human experiments include hypoxia, head-up tilt, hyperthermina and exercise, which influence all lymphocyte subtypes and especially so the natural killer (NK) cells. In essence, the immune response is enhanced even by light physical stress, but suppressed after prolonged, intense stress.

Exercise↗
PubMed1994

Effect of diet and plasma fatty acid composition on immune status in elderly men.

The relationship between fatty acids in plasma and basal (B), interleukin-2-(IL-2), and interferon-alpha (IFN-alpha)-stimulated natural killer (NK) cell activity was studied in healthy elderly men aged on average 70.5 y (65-81 y). B-NK correlated significantly with the fraction of plasma fatty acids consisting of total polyunsaturated fatty acids (PUFAs), total n-6 fatty acids, and linoleic acid (r = -0.68, r = -0.62, and r = -0.52, respectively). Significant negative correlations were also found between IFN-alpha stimulated NK cells and the three groups of fatty acids and between IL-2-stimulated NK cells and PUFAs. Likewise, negative correlations between PUFAs in the diet and B-NK, IL-2 and IFN-alpha stimulated NK cell activity were found. The number of NK cells increased significantly but NK cell activity did not change after 5 wk on a diet lower in fat but higher in PUFAs than the subjects' habitual diet. It is concluded that the amount and type of dietary fatty acids influence in vitro measures of immune function in elderly men. From an immunological point of view, a high intake of n-6 PUFAs may be inadvisable.

Aged↗
PubMed1994

Non-major histocompatibility complex-restricted cytotoxic activity of blood mononuclear cells stimulated with secreted mycobacterial proteins and other mycobacterial antigens.

Several observations indicate that non-major histocompatibility complex (MHC)-restricted cytotoxicity, mediated for example by natural killer cells and lymphokine-activated killer cells, may serve as an important antimicrobial defense mechanism. The purpose of the present study was to investigate the influences of different mycobacterial antigens on non-MHC-restricted cytotoxicity and further to investigate the ways by which various lymphocyte subpopulations contribute to the development of this cytotoxicity. Non-MHC-restricted cytotoxicity was induced following stimulation of mononuclear cells with tuberculin purified protein derivative, Mycobacterium bovis bacillus Calmette-Guérin (BCG), short- and long-term culture filtrates of virulent Mycobacterium tuberculosis H37Rv, and 30-31-kDa secreted mycobacterial protein. These antigens also induced proliferation and production of gamma interferon. The CD4+ cells proliferated and expressed interleukin-2 receptors following stimulation with mycobacterial antigens. Depletion studies after antigen stimulation showed that the cytotoxic effector cells were CD16+ CD56+ and CD4-; the CD4+ cells alone did not mediate non-MHC-restricted cytotoxicity. To evaluate the influence of CD4+ cells on the development of non-MHC-restricted cytotoxicity, blood mononuclear cells were depleted of CD4+ cells before antigen stimulation. When mononuclear cells were incubated with purified protein derivative or short-term culture filtrate in the absence of CD4+ cells, cytotoxic activity was reduced. This reduction was abolished by interleukin-2 but not by gamma interferon. We conclude that several mycobacterial antigens are able to induce non-MHC-restricted cytotoxicity. This study indicates that non-MHC-restricted cytotoxicity following stimulation with mycobacterial antigens is induced by cytokines released by antigen-specific activated CD4+ cells.

Antigens, Bacterial↗