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Biomedical subjects

M Jensen

Publications and source records attributed to M Jensen.

At least 55 records · Page 3Linked to original sources

Exercise and the immune system--influence of nutrition and ageing.

In essence, the immune system is enhanced during moderate and severe exercise, and only intense long-duration exercise is followed by impairment of the immune system. The latter includes suppressed concentration of lymphocytes, suppressed natural killer cell activity, lymphocyte proliferation and secretory IgA in saliva. During the time of immune impairment, referred to as "the open window", microbial agents, especially viruses may invade the host and infections may be established. One reason for the "overtraining effect" seen in elite athletes could be that this window of opportunism for pathogens is longer and the degree of immunosuppression more pronounced. Alterations in metabolism and metabolic factors may contribute to exercise-associated changes in immune function. Reductions in plasma-glutamine concentrations, altered plasma-glucose level, free oxygen radicals and prostaglandins (PG) released by the elevated number of neutrophils and monocytes may influence the function of lymphocytes and contribute to the impaired function of the later cells. Thus, nutritional supplementation with glutamine, carbohydrate, anti-oxidants or PG-inhibitors may, in principle, influence exercise-associated immune function. Although several intervention studies have been performed, it is premature to make recommendations regarding nutritional supplementation to avoid post-exercise impairment of the immune system.

Aging↗

Exercise and immune function: effect of ageing and nutrition.

Strenuous exercise is followed by lymphopenia, neutrophilia, impaired natural immunity, decreased lymphocyte proliferative responses to mitogens, a low level of secretory immunoglobulin A in saliva, but high circulating levels of pro- and anti-inflammatory cytokines. These exercise-induced immune changes may provide the physiological basis of altered resistance to infections. The mechanisms underlying exercise-induced immune changes are multifactorial and include neuroendocrinological and metabolic mechanisms. Nutritional supplementation with glutamine abolishes the exercise-induced decline in plasma glutamine, but does not influence post-exercise immune impairment. However, carbohydrate loading diminishes most exercise effects of cytokines, lymphocyte and neutrophils. The diminished neutrophilia and elastase (EC 3.4.21.37) responses to eccentric exercise in elderly subjects were enhanced to levels comparable with those of young subjects by fish oil or vitamin E supplements. However, although vitamin C supplementation may diminish the risk of contracting an infection after strenuous exercise, it is not obvious that this effect is linked to an effect of vitamin C on exercise-induced immune changes. In conclusion, it is premature to make recommendations regarding nutritional supplementation to avoid post-exercise impairment of the immune system.

Aging↗

EEG slowing and cerebrospinal fluid tau levels in patients with cognitive decline.

We explored the relationship between cerebrospinal fluid (CSF) tau levels as indirect markers of tau-related pathology in Alzheimer's disease (AD) and EEG slowing, a typical neurophysiological finding in the disease. A positive correlation between CSF tau levels and ratio of alpha/delta global field power was found in 14 AD patients (r = 0.65, p = 0.01). This relationship was better approximated by polynomial fit of 2nd degree (p = 0.002). A subgroup of AD patients (n = 7) with higher tau levels and shorter duration of illness showed a strong relationship between CSF tau levels and alpha/theta (r = 0.83, p = 0.02), and alpha/delta (r = 0.87, p = 0.01) ratios of the global field power. There were no significant correlations between EEG slowing and CSF tau levels in 12 patients with mild cognitive dysfunction or in 14 healthy control subjects. That a strong inverse linear correlation exists in AD patients with higher levels of tau and shorter duration of illness may imply that with longer illness duration CSF tau levels decrease due to neuronal death.

Aged↗

Calcium absorption from small soft-boned fish.

The prevalence of osteoporosis in developing countries is low compared to most industrialised countries despite an apparent low Ca intake. It is possible, however, that food surveys have overlooked important Ca sources in developing countries. Small fish eaten with the bones can be a rich source of Ca, even though Ca from bone may be considered unavailable for absorption. In the present study, absorption of Ca from indigenous Bengali small fish was compared with the Ca absorption from milk. Ca absorption from single meals was determined in 19 healthy men and women (21-28 y). Each subject received two meal types on two separate occasions. Both meals consisted of white wheat bread, butter and ultra pure water with the main Ca source being either small Bengali fish (397 mg Ca in total) or skimmed milk (377 mg Ca in total). The meals were extrinsically labelled with 47Ca, and whole-body retention was measured on day 8, 12, 15 and 19 after intake of each meal. The labelling procedure was evaluated by an in vitro method. The calculated absorption of Ca as measured with 47Ca whole-body retention was 23.8 +/- 5.6% from the fish meal and 21.8 +/- 6.1% from the milk meal (mean +/- SD), which was not significantly different (p = 0.52). Even after correction for an incomplete isotope exchange, as indicated by the in vitro study, Ca absorption was similar from the two meal types. It was concluded that Ca absorption from small Bengali fish was comparable that from skimmed milk, and that these fish may represent a good source of Ca.

Absorption↗

Fluorodeoxyglucose uptake in dysfunctional myocardium subtended by an occluded coronary artery. Relation to dobutamine contractile reserve and Sestamibi uptake.

BACKGROUND: Myocardial segments with impaired function may have the potential for functional recovery. Augmented exogenous glucose uptake in relation to blood flow estimated by [2-18F]2-fluorodeoxyglucose (FDG) and positron emission tomography (PET) frequently indicates functional reversibility. The spectrum of FDG uptake levels in relation to Sestamibi uptake and dobutamine contraction reserve in areas with impaired function subtended by an occluded coronary artery has never been reported. METHODS AND RESULTS: Seventeen patients with stable angina pectoris and dysfunctional myocardium subtended by an occluded coronary artery were studied with FDG-PET, low-dose dobutamine echocardiography and Sestamibi-Single Photon Emission Computerized Tomography. In a 16 segment model dysfunctional myocardial segments showed a normally distributed FDG uptake ranging from 34% to 150% when normalized to peak segmental Sestamibi uptake. Low FDG uptake was associated with both lack of dobutamine induced contractile reserve and low Sestamibi uptake (in 73% of the segments) whereas high FDG uptake displayed both contractile reserve and Sestamibi uptake (57%). Segments with intermediate FDG uptake had either contractile reserve or a preserved Sestamibi uptake (62%). CONCLUSION: Dysfunctional myocardium subtended by an occluded coronary artery represents a continuum of metabolic states with a high degree of heterogeneity with regard to contractile reserve and Sestamibi uptake.

Adult↗

CD20 is a molecular target for scFvFc:zeta receptor redirected T cells: implications for cellular immunotherapy of CD20+ malignancy.

The CD20 molecule was evaluated as a B-cell lymphoma target epitope for T cells expressing a CD20-specific single-chain FvFc-zeta (scFvFc:zeta) chimeric receptor. A cDNA construct consisting of a murine kappa leader sequence, CD20-specific scFv, human immunoglobulin (Ig) G1 hinge-C(H)2-C(H)3, the human CD4 transmembrane, and the intracellular signaling domain of the human CD3 complex's zeta chain was synthesized by polymerase chain reaction splice-overlap extension. The human CD4+ Jurkat cell line was electroporated with the CD20-specific scFvFc:zeta construct cloned into the mammalian expression vector pcDNAneo. Western blot analysis of transfectant whole cell lysate with an anti-zeta antibody demonstrated the expression of both endogenous zeta and the chimeric receptor protein, with a mobility consistent with the expected molecular weight of 66 kD under reducing conditions; nonreduced lysate revealed a chimeric receptor complex of approximately 132 kD. The scFvFc:zeta receptor was present on the cell surface as detected by flow cytometry of T-cell transfectants stained with an anti-mouse Fab-specific antibody and anti-human Fc gamma-specific monoclonal antibody. Coculture of Jurkat transfectants with CD20+ lymphoma cells resulted in the accumulation of interleukin (IL)-2 in culture supernatants as detected by ELISA. IL-2 production was triggered by the specific interaction between the CD20 molecule and the scFvFc:zeta as IL-2 was not detected in cultures with mock transfected Jurkat cells or CD20- stimulator cells. Furthermore, IL-2 production was inhibited by the addition of a soluble anti-CD20 monoclonal antibody to cocultured Jurkat transfectants and CD20+ stimulator cells. The capacity of CD20 to trigger the lytic machinery of scFvFc:zeta-expressing cytotoxic T lymphocytes (CTLs) was assessed using the murine allo-specific CD8+ CTL clone 2c. CD20-specific redirected cytolytic activity against human lymphoma targets was observed with 2c transfectants in a 4-hour chromium release assay. These results demonstrate that CD20 can serve as a target epitope for scFvFc:zeta receptor-expressing T cells.

Antibodies, Monoclonal↗

Ego Identity Status in cross-cultural context: a comparison of Norwegian and United States university students.

To examine patterns of identity development for late adolescents raised in the Norwegian mixed liberal welfare-state economic system compared with late adolescents raised in the free-market economic system of the United States, ego identity status scores and distributions were examined for 56 (37 women, 19 men). Norwegian and 1498 (814 women, 684 men) United States undergraduate university students using the Extended Objective Measure of Ego Identity Status-2. The United States sample was drawn from four geographic regions and comprised of those who had participated in prior studies performed by Adams. Significant differences were found between the two nations on all identity status subscales in the ideological and interpersonal domains for each sex. The more moderate identity status scale scores evidenced by the Norwegian sample may reflect a cultural trend toward greater moderation in the exploration and commitment process.

Cross-Cultural Comparison↗

Metabolic and hemodynamic evaluation of brain metastases from small cell lung cancer with positron emission tomography.

Brain metastases from small cell lung cancer respond to chemotherapy, but response duration is short and the intracerebral concentration of chemotherapy may be too low because of the characteristics of the blood-brain barrier. Positron emission tomography has been applied in a variety of tumors for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor rCMRglu, rCBF, and rCBV exerted a broad variability, but were higher than the corresponding values in white matter and higher than or similar to those of gray matter. Tumor rCMRglu and rCBF were highly correlated (P < 0.01, r = 0.79). No correlation between survival and metabolic or hemodynamic parameters could be demonstrated. After radiotherapy, mean tumor rCMRglu decreased from 0.40 to 0.31 micromol/g/min (not significant), and rCBF and rCBV remained unchanged. However, cortical rCBF demonstrated a trend of increased values after radiotherapy from 0.37 to 0.49 ml/g/min (P = 0.13). No change in rCMRglu was observed in gray or white matter after radiotherapy. Global CBF seems to be reversibly depressed by the metastases, but local hemodynamic changes in the tumor could not be detected with positron emission tomography in this study. An association between high tumor rCMRglu and rCBF as an indicator of hypoxia was not observed. Other methods for noninvasive in vivo analysis of tumor hemodynamics are needed, especially for discrimination between tumor necrosis and hypoxia.

Adolescent↗

Cerebrospinal fluid apolipoprotein E (apoE) levels in Alzheimer's disease patients are increased at follow up and show a correlation with levels of tau protein.

Apolipoprotein E (apoE) levels were compared in cerebrospinal fluid (CSF) taken on two occasions, with an average 15 months follow up, from groups of patients with Alzheimer's disease (AD: n = 18), mild cognitive impairment (MCI; n = 9) and other dementia disorders (ODD; n = 9). In these groups, CSF apoE levels were between 2-3-fold higher than values for a group of 27 healthy age-matched controls. CSF apoE levels in the AD group were significantly increased at follow up, compared to levels obtained on the first sampling occasion. For the same cases it had been shown previously that CSF tau protein levels were increased at follow up [Blomberg, M., Jensen, M., Basun, H., Lannfelt, L. and Wahlund, L-O., Neurosci. Lett., 214 (1996) 163-166]. The AD, but not MCI, ODD or control groups, also showed statistically significant correlations between CSF apoE and tau protein levels at both the first (r = 0.585, P < 0.01) and follow up (r = 0.695, P > 0.001 ) samplings. It is concluded that CSF measures of both apoE and tau may reflect an intimate relationship between these two proteins in AD and could prove useful in monitoring the progression of this condition.

Adult↗

Isolation of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes that lyse Reed-Sternberg cells: implications for immune-mediated therapy of EBV+ Hodgkin's disease.

A subset of Hodgkin's disease (HD) patients have detectable Epstein-Barr virus (EBV) genomes in the malignant Reed-Sternberg (R-S) cells. R-S cells express only a limited set of latent EBV proteins, but only LMP1 and LMP2 can potentially elicit a CD8+ cytotoxic T-lymphocyte (CTL) response. We have evaluated if either of these proteins could be used as targets for specific adoptive T-cell therapy for EBV-positive (EBV+) HD. The success of this strategy requires that R-S cells are susceptible to lysis by CD8+ CTL, and that CTL specific for LMP1 and LMP2 can be detected and potentially amplified in HD patients. Antigen presentation and CTL sensitivity was evaluated with an in vitro maintained, phenotypically representative R-S cell line, HDLM-2. The R-S cells were able to process and present viral proteins, and to be efficiently lysed by specific CTL in a Class I-restricted manner. Since CTL responses to LMP1 and LMP2 do not represent the dominant responses to EBV, we examined if CTL clones specific for these proteins could be isolated despite the presence of weak or nondetectable responses in polyclonal T-cell lines. LMP-specific clones were generated from individuals either by cloning from the polyclonal EBV-reactive T-cell lines or by direct stimulation of peripheral blood mononuclear cells (PBMC) with cells expressing LMP1 or LMP2 as the only EBV protein. Our ability to isolate CTL specific for LMP proteins from individuals with HD and the sensitivity of R-S cells for CTL-mediated lysis suggest that the pursuit of specific adoptive immunotherapy represents a viable strategy for the subset of HD patients with EBV+ tumors.

Aged↗

Effect of casein phosphopeptides on zinc and calcium absorption from bread meals.

Animal studies suggest that casein phosphopeptides (CPP), formed by proteolytic digestion of casein, have a positive effect on Ca availability. The aim of this study was to investigate the ability of CPP to improve Zn and Ca absorption from phytate-containing bread meals. Secondly, it was tested whether the Ca content of the meal influenced the effect of CPP on Zn absorption from a high-phytate meal. Zn and Ca absorption from single model meals was determined by extrinsic labeling with 65Zn and 47Ca and measurement of whole-body retention. Thirty-one healthy adults (19-30 y) divided into three groups received one of three meal types based on white-wheat rolls with different phytate and Ca content: A: low-phytate/high-Ca (n = 10), B: high-phytate/high-Ca (n = 10) and C: high-phytate/low-Ca (n = 11). Each individual received the same meal type at three different occasions with 0, 250 and 1000 mg CPP added. CPP had no effect on Zn absorption: A: 14.3 +/- 4.4% (mean +/- SD) (0 mg CPP), 16.7 +/- 6.6% (250 mg CPP) and 16.0 +/- 8.8% (1000 mg CPP); B: 7.0 +/- 1.6%, 7.7 +/- 3.0% and 8.0 +/- 2.6%; C: 7.7 +/- 2.5%, 7.0 +/- 2.3% and 6.5 +/- 1.6%, respectively. Addition of 1000 mg CPP reduced fractional Ca absorption from meal A: 33.8 +/- 7.1%, 30.5 +/- 6.3% and 25.9 +/- 8.7% (p < 0.05), whereas CPP had no effect in meal B: 29.3 +/- 8.3%, 27.0 +/- 7.4% and 27.6 +/- 11.0%. However, the absolute quantity of Ca absorbed was unaffected. In conclusion, Zn and Ca absorption from these meals were not significantly influenced by the addition of CPP, Ca addition could not explain the failure of CPP to improve Zn absorption.

Absorption↗

Specific activation of resting T cells against tumour cells by bispecific antibodies and CD28-mediated costimulation is accompanied by Th1 differentiation and recruitment of MHC-independent cytotoxicity.

Specific activation of resting lymphocytes for tumour targeting can be achieved by bispecific monoclonal antibodies (bi-MoAbs) with specificity for tumour antigens and T cell-activating antigens in combination with a costimulatory anti-CD28 antibody. In this study we focus on the immunomodulatory function of an anti-CD3/CA19-9 bi-MoAb in combination with a costimulatory anti-CD28 antibody which may result not only in antigen-specific, T cell-mediated tumour cell lysis but also in recruitment of other cellular effector functions. In combination with costimulatory anti-CD28 antibodies, resting peripheral lymphocytes could be activated specifically to secrete high amounts of Th1 cytokines (IL-2, interferon-gamma (IFN-gamma)) characterizing a cellular immune response. In contrast, no IL-4 and only low amounts of IL-10 could be detected. Furthermore, bi-MoAb-mediated CA19-9-specific activation of T cells was accompanied by recruitment of MHC- and CA19-9-independent cytotoxicity, as was determined by lysis of different CA19-9-cell lines. This MHC-independent cytotxicity was mediated at least in part by activated natural killer (NK) cells, as depletion of CD16+ NK cells resulted in substantial decrease of cytotoxicity against CA19-9- targets. Our results indicate that specific activation of resting T cells with CD3-associated bi-MoAbs in combination with an anti-CD28 antibody leads to a Th1 differentiation pathway and is accompanied by recruitment of MHC-independent lymphokine-activated killer (LAK) cell cytotoxicity which can possibly be directed against a heterogeneous tumour.

Antibodies, Bispecific↗

Specific activation of resting T cells against CA19-9+ tumor cells by an anti-CD3/CA19-9 bispecific antibody in combination with a costimulatory anti-CD28 antibody.

Specific activation of resting lymphocytes for tumor targeting can be achieved by bispecific monoclonal antibodies (bi-mAb) with specificity for tumor antigens and T-cell-activating antigens, respectively, in combination with a costimulatory anti-CD28 antibody. We describe the generation and function of a bi-mAb with specificity for CD3 and for the tumor antigen CA19-9. The bi-mAb OKT3/NSI19-9 was generated by somatic fusion of two hybridoma lines secreting antibodies against CA19-9 and CD3, respectively. A hybrid/hybridoma was established, and its bi-mAb was characterized. In combination with a costimulatory anti-CD28 mAb resting peripheral lymphocytes could be activated specifically with T-cell proliferation and secretion of high amounts of interferon-gamma. On specific T-cell activation, bi-mAb OKT3/NSI19-9 could also redirect the cytotoxic effects of these T cells toward CA19-9+ tumor cells in vitro. Our results indicate that specific activation of resting T cells with bi-mAb OKT3/NSI19-9 in combination with an anti-CD28 mAb can activate resting T cells specifically and leads to antigen-dependent bi-mAb-mediated cytotoxicity against CA19-9+ target cells. This approach may offer new perspectives for the specific immunotherapy of CA19-9+ tumors.

Antibodies, Bispecific↗

Casein phosphopeptides improve zinc and calcium absorption from rice-based but not from whole-grain infant cereal.

BACKGROUND: Casein phosphopeptides (CPP) are phosphorus-rich peptide fragments of casein, assumed to contribute to the high bioavailability of calcium from milk. METHODS: The effect of casein phosphopeptides on calcium and zinc absorption from infant foods was investigated. Twenty-two men and women were given single test meals extrinsically labeled with Ca and Zn. Absorption was calculated from measurements on whole-body retention of the radioisotopes. Each subject was given either rice-based cereal (n = 11) or whole-grain cereal (n = 11) on three occasions together with 250 ml water and added 0, 1, and 2 g CPP in random order. One serving of rice-based cereal contained 481 mg Ca and 1.29 mg Zn; whole-grain cereal contained 541 mg Ca and 1.77 mg Zn. One and 2 g of CPP contributed with additional 69 and 138 mg Ca, respectively. RESULTS: From rice-based cereal, fractional calcium absorption was not affected by CPP addition (mean +/- SD): 16.0 +/- 4.0% (no CPP), 17.6 +/- 4.5% (1 g CPP), and 15.8 +/- 4.3% (2 g CPP), while the total quantity of calcium absorbed was significantly improved: 7 +/- 19 mg, 97 +/- 25 mg, and 98 +/- 26 mg, respectively (p = 0.0004). Fractional zinc absorption as well as total quantity of zinc absorbed were increased with addition of CPP: 19.4 +/- 9.0% (0.25 +/- 0.12 mg), 25.2 +/- 7.5% (0.33 +/- 0.10 mg) and 23.9 +/- 5.4% (0.31 +/- 0.07 mg) at the three CPP levels (p = 0.04). From whole-grain cereal, CPP had no effect on the percentage or actual quantity of calcium absorbed: 17.0 +/- 3.2% (92 +/- 18 mg), 17.2 +/- 4.5% (105 +/- 27 mg), and 15.0 +/- 4.6% (102 +/- 31 mg), respectively. Zinc absorption was also not influenced by CPP: 16.0 +/- 5.1% (0.28 +/- 0.09 mg), 15.3 +/- 3.1% (0.27 +/- 0.06 mg) and 18.1 +/- 4.4% (0.32 +/- 0.08 mg), respectively. CONCLUSIONS: CPP addition improved calcium and zinc absorption from rice-based cereal, while no effect was seen from whole-grain cereal.

Adult↗

Increasing cerebrospinal fluid tau levels in a subgroup of Alzheimer patients with apolipoprotein E allele epsilon 4 during 14 months follow-up.

The concentration of tau protein is elevated in the cerebrospinal fluid (CSF) in Alzheimer's disease (AD), suggesting that CSF tau may be a useful biochemical diagnostic marker for this disorder. We investigated CSF tau concentrations on two occasions in AD (n = 18), mild cognitive impairment (MCI, n = 9) and other dementing disease (OD, n = 9) by ELISA (Innotest hTau Antigen, Innogenetics, Belgium). Tau levels were statistically significant higher in the AD group than in MCI and OD groups on both occasions. Twelve of the AD patients showed increasing values of tau at follow-up and six demonstrated diminished values. All AD patients with increasing tau were carriers of one or two epsilon 4 alleles of the apolipoprotein E (APOE, gene. Of those AD cases with decreasing tau levels only three individuals had the epsilon 4 allele, a difference that was statistically significant (P < 0.05). These findings suggest that there may be apolipoprotein E (apoE) isoform-specific differences of tau regulation in AD.

Adult↗

[Nutritional and fluid supplementation for neonates. Types and use of supplementation in maternity wards].

The objective of the study was to evaluate the practice of giving supplementary feeding to newborns on maternity wards according to type of supplement, use and choice of supplement in different clinical settings, recommended frequency of breast-feeding, recommended types of infant formula and finally the influence of paediatric department and geographic site on the use of different types and use of supplements at the wards. Sixty maternity wards (95%) in Denmark filled in and returned the questionnaire. The maternity wards offered six different kinds of supplements and 36% of the maternity wards offered human milk. The study gave the impression of a large consumption of supplements on the maternity wards. Most of the maternity wards (83%) would recommend hydrolysed infant formula for infants with a family history of allergy, and almost the same number (88%) would recommend traditional infant formula for infants without a family history of allergy. Mothers' request for hydrolysed infant formula for infants without a family history of allergy was refused in 20% of the maternity wards. There were no differences between the recommended frequencies of breast-feeding. Maternity wards in hospitals with paediatric departments would significantly more frequently offer the infants supplements than maternity wards in hospitals without paediatric departments. The same maternity wards would significantly more often use water and human milk and more rarely water with glucose than maternity wards in hospitals without paediatric departments. In the western part of Denmark the maternity wards significantly more often used traditional infant formula and water with glucose than in the eastern part of Denmark. In conclusion, the investigation showed a considerable variation in the different types of supplements used in the maternity wards. The variation was influenced by the presence of a paediatric department in the hospital as well as by the geographic site. To ensure a higher and more uniform quality in this area it would be desirable if The National Board of Health in collaboration with the Allergy committee in the Danish Society of Paediatricians would publish recommendations to all who work professionally with mothers and infants.

Denmark↗