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Biomedical subjects

B K Pedersen

Publications and source records attributed to B K Pedersen.

At least 73 records · Page 4Linked to original sources
PubMed2000

Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection.

Human immunodeficiency virus-1 (HIV-1) infection has been shown to result in up-regulation of the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes in vitro and in vivo. The objective of this study was to investigate whether this up-regulation is paralleled by higher serum levels of soluble uPAR (suPAR) in patients with advanced HIV-1 disease and whether the serum level of suPAR is predictive of clinical outcome. Using an enzyme-linked immunosorbent assay, the level of suPAR was measured retrospectively in serum samples from 314 patients with HIV-1 infection. By Kaplan-Meier and Cox regression analyses, the serum suPAR levels were correlated to survival with AIDS-related death as the end point. High levels of serum suPAR (greater than median) were associated with poor overall survival, and Kaplan-Meier analysis on patients stratified by suPAR level demonstrated a continuous increase in mortality rates with higher suPAR levels. After adjustment for accepted prognostic markers-including Centers for Disease Control and Prevention-defined clinical stages, CD4 counts, viral load, beta2-microglobulin, and age-the prognostic strength of suPAR remained highly significant, indicating that the serum suPAR level is a novel, strong, and independent predictor of survival in HIV-1 infection. This report is the first to demonstrate an important association between the plasminogen activator system and disease progression in HIV-1 infection.

Adolescent↗
PubMed2000

TNF-alpha, leptin, and lymphocyte function in human aging.

Aging is associated with increased inflammatory activity and concomitant decreased T cell mediated immune responses. Leptin may provide a link between inflammation and T cell function in aging. The aim of the study was to investigate if plasma levels of tumor necrosis factor (TNF)-alpha were associated with leptin, circulating interleukin-2 receptors (sIL-2R), and phytohaemagglutinin (PHA) induced IL-2 production in whole blood in elderly humans. Circulating levels of TNF-alpha and sIL-2R were higher in elderly humans (N=42) compared to a young control group (N=37) whereas there was no difference with regard to IL-2 production. Furthermore, there were no age-related differences in serum levels of leptin. However, women had higher levels than men. In the elderly people, serum levels of leptin were correlated with TNF-alpha in univariate regression analysis and in a multiple linear regression analysis adjusting for the effect of gender and body mass index. Furthermore, TNF-alpha, but not leptin, was positively correlated to sIL-2R and negatively correlated to IL-2 production. In conclusion, increased plasma levels of TNF-alpha in aging is associated with poor IL-2 production ex vivo and lymphocyte activation in vivo. These associations do not seem to involve leptin.

Adolescent↗
PubMed2000

Muscle contractions induce interleukin-6 mRNA production in rat skeletal muscles.

1. The present study explored the hypothesis that interleukin-6 (IL-6) might be locally produced in response to skeletal muscle contractions and whether the production might reflect the type of muscle contraction performed. Rats were anaesthetized and the calf muscles of one limb were stimulated electrically for concentric or eccentric contractions (4 x 10 contractions with 1 min of rest between the 4 series, 100 Hz). The contralateral muscles served as unstimulated controls. The mRNA levels for IL-6, the glucose transport protein GLUT-4 and beta-actin in the rat muscles (white and red gastrocnemius and soleus) were quantified by quantitative competitive RT-PCR. 2. The IL-6 mRNA level, measured 30 min after the stimulation, increased after both eccentric and concentric contractions and there were no significant differences in IL-6 mRNA levels between the different muscle fibre types. No significant increase in IL-6 mRNA level was seen in the unstimulated contralateral muscle fibres. 3. No increase in GLUT-4 mRNA level was detected, indicating that the increase in IL-6 mRNA level was not due to general changes in transcription. 4. We conclude that IL-6 is locally produced after muscle contraction, with no significant differences between different muscle fibre types. This local production of IL-6 is not due to general changes in transcription, since no changes in the level of GLUT-4 mRNA were found. The fact that increased IL-6 mRNA levels were seen after both concentric and eccentric contractions indicates that the production of IL-6 is not solely due to muscle damage, seen primarily after eccentric exercise.

Actins↗
PubMed2000

[Treatment of respiratory syncytial virus infections in immunocompromised hematological patients].

Respiratory syncytial virus (RSV) accounts for considerable morbidity among infants and elderly, that are otherwise immunocompetent. Immunocompromised haematological patients--in particular bone marrow transplant (BMT) recipients with leukopenia--are at high risk for severe, usually fatal, RSV-pneumonia. No randomized, placebo-controlled studies of aerosolized ribavirin for BMT patients with RSV-pneumonia have been conducted, or can be anticipated. We summarize existing case reports providing circumstantial evidence in favour of an active diagnostic and early therapeutic approach to these patients.

Aerosols↗
PubMed2000

[Human infection immunology. Basic scientific findings and clinical consequences].

During the last years studies on human immune responses to specific micro-organisms have contributed to an increased understanding of the structure and function of the immune system. T lymphocytes with a special antigen receptor (gamma/delta cells) are thus probably important in some infectious diseases such as malaria and tuberculosis. The discovery of T-cell responses to protein-free fractions of mycobacteria and Leishmania parasites has lead to the identification of non-protein T-cell antigens. T-cells that express the CD4 receptor on their surface and are capable of lysing infected target cells have been found in viral infections. It has furthermore been found, that the composition of the signal mediators (cytokines) secreted by activated T-cells can determine the outcome of a number of infections. In the future it may be possible to include enhancement of protective immune reactions in the treatment of infectious diseases to a higher extent than now.

Animals↗
PubMed2000

Prevalence and prognostic significance of infection with TT virus in patients infected with human immunodeficiency virus.

No clear association between human disease and TT virus (TTV) has been documented. A possible pathogenic role of TTV was investigated in patients infected with human immunodeficiency virus (HIV). TTV serum concentrations were estimated in 185 HIV-infected patients by dilution polymerase chain reaction. Of these, 149 (76%) were TTV-positive, compared with 18 (7%) of 252 Danish blood donors (P<. 001). Of the HIV-infected patients who were TTV-positive, 72 (51%) had high TTV viremia (>/=5 times the highest concentration observed among blood donors, i.e., >/=3.5x105 TTV/mL of serum). High TTV viremia was associated with decreased survival (P<.001; relative hazard [RH], 2.0). There was a correlation between lower CD4+ T cell counts and higher TTV titers (P<.01). In a Cox regression model, CD4+ T cell count (P<.001), age (P<.001), HIV viral load (P<.001), beta2 microglobulin (P<.02), and high TTV viremia (P<.01; RH, 1.9) were independent predictors of survival. TTV is suspected to be an opportunistic pathogen with an independent influence on HIV progression.

AIDS-Related Opportunistic Infections↗
PubMed2000

[Non-antibiotic treatment of sepsis].

Treatment of patients with sepsis with monoclonal antibodies against lipopolysaccharide, tumour necrosis factor or treatment with soluble TNF-receptors or interleukin-1 receptor antagonist have not had any effect on mortality. Treatment with intravenous polyclonal nonspecific immunoglobulin has been shown to have beneficial efficacy on mortality. However, the number of patients included in the latter treatment studies are limited, the patients studied are heterogeneous and do not allow to conclude that sepsis patients should be routinely treated with immunoglobulins.

Animals↗
PubMed2000

Changes in plasma concentrations of interleukin-6 and interleukin-1 receptor antagonists in response to adrenaline infusion in humans.

To investigate the possible role of adrenaline in the response of interleukin (IL)-6 and IL-1 receptor antagonists (ra) to extreme physiological conditions such as trauma and exercise, we examined the concentrations in the plasma of these cytokines during an adrenaline infusion. Given the fact that HIV infected patients have elevated levels of IL-6 in plasma, 12 HIV seropositive subjects and 6 HIV seronegative control subjects received a 1-h adrenaline infusion. Baseline concentrations of IL-6 and IL-1ra were higher in the HIV patients compared with the controls (P<0.05 and P<0.01, respectively), being most pronounced in the untreated subgroup of HIV infected patients (n = 6). The plasma concentration of adrenaline had increased 24-fold after 15 min of adrenaline infusion. The plasma concentration of IL-6 had increased by two- to threefold after 45 min of adrenaline infusion (P<0.01) and was still elevated 1 h after the infusion had ended (P<0.001 and P<0.05 in controls and HIV infected patients, respectively). The plasma concentration of IL-1ra had increased two- to threefold 1 h after ceasing the adrenaline infusion (P<0.05 and P<0.01 in controls and HIV infected patients, respectively). The relative increase in the cytokine levels was similar in controls and HIV infected patients. Thus, HIV infection did not influence the effect of adrenaline on IL-6 and IL-1ra. The present study supports the existence of a relationship between the plasma concentration of adrenaline and IL-6. It is possible that an increased adrenaline concentration in plasma induces a continued de novo synthesis of IL-6, thereby increasing plasma IL-6 in a time-dose dependent manner.

Adult↗
PubMed2000

Physical activity and plasma interleukin-6 in humans--effect of intensity of exercise.

The present study included data from three marathon races to investigate the hypothesis that a relationship exists between running intensity and elevated concentrations of interleukin (IL)-6 in plasma. The study included a total of 53 subjects whose mean age was 30.6 [95% confidence interval (CI) 1.4] years, mean body mass 77.7 (95% CI 2.0) kg, mean maximal oxygen uptake (VO2max) 59.3 (95% CI 1.4) ml x min(-1) x kg(-1), and who had participated in the Copenhagen Marathons of 1996, 1997 or 1998, achieving a mean running time of 206 (95% CI 7) min. Running intensity was calculated as running speed divided by VO2 max. The concentration of IL-6 in plasma peaked immediately after the run. There was a negative correlation between peak IL-6 concentration and running time (r = -0.30, P<0.05) and a positive correlation between peak IL-6 concentration and running intensity (r = 0.32, P<0.05). The IL-1 receptor antagonist (IL-1ra) plasma concentration peaked 1.5 h after the run and there was a positive correlation between the peak plasma concentrations of IL-6 and IL-1ra (r = 0.39, P<0.01). Creatine kinase (CK) plasma concentration peaked on the 1st day after the run, but no association was found between peak concentrations of IL-6 and CK. In conclusion, the results confirmed the hypothesized association between plasma IL-6 concentration and running intensity, but did not confirm the previous finding of a connection between IL-6 plasma concentration and muscle damage.

Adult↗
PubMed2000

Training and natural immunity: effects of diets rich in fat or carbohydrate.

The purpose of the study was to investigate whether a carbohydrate-rich versus fat-rich diet influenced the effect of training on the immune system. Ten untrained young men ingested a carbohydrate-rich diet [65 energy percent (E%) carbohydrate] and ten subjects a fat-rich diet (62E% fat) while endurance training was performed 3-4 times a week for 7 weeks. Maximal oxygen uptake increased by 11% in both groups. Blood samples for immune monitoring were collected before and at the end of the study. Blood samples were also collected, in parallel, from 20 age-matched subjects, and data from these subjects were used to eliminate day-to-day variation in the immunological tests. Independently of diet, training increased the percentage of CD3-CD16+ CD56+ natural killer (NK) cells from [mean (SEM)] 14 (1) % to 20 (3) % (P = 0.05), whereas the NK-cell activity, either unstimulated or stimulated with interleukin (IL)-2 or interferon (IFN)-alpha, did not change. Furthermore, training did not influence the percentages of CD3+, CD4+, CD8+, CD19+ or CD14+ cells. However, when the two diet groups were compared, it was found that the NK-cell activity had increased in the group on the carbohydrate-rich diet [from 16 (3)% to 27 (2)%] and decreased in the group on the fat-rich diet [from 26 (2)% to 20 (4)%] in response to training. The effect of training on unstimulated NK-cell activity was significantly different between the groups (P = 0.007). These data indicate that diet manipulation during training may influence natural immunity, and suggest that ingestion of a fat-rich diet during training is detrimental to the immune system compared to the effect of a carbohydrate-rich diet.

Adult↗
PubMed2000

Adrenaline-induced mobilization of T cells in HIV-infected patients.

The present study aimed to investigate lymphocyte mobilization from peripheral cell reservoirs in HIV-infected patients. Nine HIV-infected patients on stable highly active anti-retroviral therapy (HAART), eight treatment-naive HIV-infected patients and eight HIV- controls received a 1-h adrenaline infusion. The adrenaline infusion induced a three-fold increase in the concentration of lymphocytes in all three groups. All HIV-infected patients mobilized significantly higher numbers of CD8+ cells but less CD4+ cells. All subjects mobilized CD45RA+CD62L+ and CD8+CD28+ cells to a lesser extent than CD45RO+CD45RA- and CD8+CD28-cells. Furthermore, high numbers of CD8+CD38+ cells were mobilized only in the HIV-infected patients. It was therefore predominantly T cells with an activated phenotype which were mobilized after adrenaline stimulation. It is concluded that the HIV-associated immune defect induced an impaired ability to mobilize immune-competent cells in response to stress stimuli. Furthermore, the study does not support the idea that CD4+ T cells are trapped in lymph nodes by HIV antigens, because untreated and HAART-treated HIV-infected patients mobilized similar numbers of CD4+ T cells. Finally, no evidence was found for the existence of a HAART-induced non-circulating pool of CD4+ T cells.

ADP-ribosyl Cyclase↗
PubMed2000

Proliferative responses of blood mononuclear cells (BMNC) in a cohort of elderly humans: role of lymphocyte phenotype and cytokine production.

Age-related impaired T cell function is associated with increased mortality risk. The purpose of the present study was therefore to identify factors associated with the age-related decreased phytohaemagglutinin (PHA)-induced proliferative response of lymphocytes in a cohort of 174 81-year-old humans and in 91 young controls. Decreased proliferation was associated with a reduced number of true naive CD4+ cells (CD62L+CD45RO-). Furthermore, a low IL-2-stimulated proliferation was correlated with a decreased PHA response in the elderly cohort, whereas reciprocal interactions of IL-10- and IL-2-producing cells were of importance in both elderly and young subjects. Accordingly, a minimum of true naive CD4+ cells was required for a normal proliferative response to PHA, perhaps by providing sufficient IL-2 which is critical for growth of naive as well as memory cells.

Adult↗
PubMed2000

Ageing, tumour necrosis factor-alpha (TNF-alpha) and atherosclerosis.

Ageing is associated with increased inflammatory activity in the blood. The purpose of this study was to investigate if age-related increased plasma levels of TNF-alpha were associated with atherosclerosis in a cohort of 130 humans aged 81 years. The elderly cohort had increased circulating levels of TNF-alpha, C-reactive protein (CRP), total cholesterol (TC), low-density lipoproteins (LDL) and a low high-density lipoprotein (HDL)/TC ratio compared with a young control group (n = 44). The elderly cohort was divided by tertiles into three subgroups with low, intermediate, and high levels of TNF-alpha, respectively. In the group with high TNF-alpha concentrations a significantly larger proportion had clinical diagnoses of atherosclerosis. Furthermore, weak correlations were found between TNF-alpha on one hand and blood concentrations of triglycerides, leucocytes, CRP and a low HDL/TC ratio on the other which are known as risk factors of atherogenesis and thromboembolic complications. No correlations were found between TNF-alpha, TC, LDL, or the body mass index. In conclusion, the present study shows that in a cohort of 81-year-old humans, high levels of TNF-alpha in the blood were associated with a high prevalence of atherosclerosis.

Adult↗
PubMed2000

Effects of subcutaneous interleukin-2 therapy on phenotype and function of peripheral blood mononuclear cells in human immunodeficiency virus infected patients.

In the context of clinical therapy with recombinant human interleukin-2 (IL-2), we monitored immunological alteration in 10 human immunodeficiency virus type-I (HIV-1)-infected individuals, on stable antiretroviral therapy, who had a CD4+ cell count between 200 and 500 cells/mm3. Subcutaneous IL-2 was prescribed thrice weekly (at a dose of 3 x 10(6) IU) for 24 weeks and the patients were followed-up for 32 weeks. IL-2 treatment induced an increase in the CD4+ percentage (P<0.001) and CD4+ cell count (P<0.009). Furthermore. natural killer (NK) cell activity was increased (P<0.001) at week 8 of treatment, whereas lymphokine-activated killer (LAK) cell activity showed a transient, nonsignificant increase at week 8 and was reduced (P<0.001) at 32 weeks. However, the cytotoxic T-lymphocyte (CTL) activity decreased against HIV antigens, and the proliferative response to Candida, IL-2 and phytohaemagglutinin (PHA) declined during the first 8 weeks (P<0.05) and returned to baseline levels after 32 weeks. The HIV RNA level did not change during IL-2 therapy; however, after 8 weeks of follow-up a significant increase (P<0.001) in viral load was observed. In

Adult↗