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- Bridel, Claire, et al.
(author)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Research review (peer-reviewed)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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- Båth, Magnus, 1974, et al.
(author)
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A conceptual optimisation strategy for radiography in a digital environment.
- 2005
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In: Radiation protection dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 114:1-3, s. 230-5
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Journal article (peer-reviewed)abstract
- Using a completely digital environment for the entire imaging process leads to new possibilities for optimisation of radiography since many restrictions of screen/film systems, such as the small dynamic range and the lack of possibilities for image processing, do not apply any longer. However, at the same time these new possibilities lead to a more complicated optimisation process, since more freedom is given to alter parameters. This paper focuses on describing an optimisation strategy that concentrates on taking advantage of the conceptual differences between digital systems and screen/film systems. The strategy can be summarised as: (a) always include the anatomical background during the optimisation, (b) perform all comparisons at a constant effective dose and (c) separate the image display stage from the image collection stage. A three-step process is proposed where the optimal setting of the technique parameters is determined at first, followed by an optimisation of the image processing. In the final step the optimal dose level-given the optimal settings of the image collection and image display stages-is determined.
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- Hansson, Jonny, et al.
(author)
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An optimisation strategy in a digital environment applied to neonatal chest imaging.
- 2005
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In: Radiation protection dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 114:1-3, s. 278-85
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Journal article (peer-reviewed)abstract
- The aim of this study was to find the optimum tube voltage for neonatal chest imaging in computed radiography. The study was designed to take full advantage of the benefits of digital imaging, for example, by comparing the tube voltages at constant effective dose. A phantom study using a living rabbit was first conducted. Images were collected at tube voltages ranging from 40 to 90 kV(p). The reproduction of four structures (central vessels, peripheral vessels, carina and thoracic vertebrae) was rated by 10 radiologists. The reproduction of both central and peripheral vessels was relatively independent of tube voltage. The carina was better reproduced at higher tube voltages whereas the opposite was true for the thoracic vertebrae. Based on the higher importance of the reproduction of the carina it was decided that 90 kV(p) was the optimal tube voltage. To validate the result from the phantom study, a follow-up study was conducted in which images of neonates collected at the tube voltage regularly used at Sahlgrenska University Hospital (70 kV(p)) were compared with images collected at the tube voltage proposed by the phantom study. The follow-up study confirmed the results from the phantom study that the reproduction of the carina was better at 90 than at 70 kV(p). In conclusion, for neonatal chest imaging-given the same effective dose-90 kVp gives better reproduction of important structures than the regularly used 70 kV(p).
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- Hansson, Markus, 1974, et al.
(author)
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Histamine protects T cells and natural killer cells against oxidative stress.
- 1999
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In: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. - 1079-9907. ; 19:10, s. 1135-44
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Journal article (peer-reviewed)abstract
- Oxidative stress inflicted by monocytes/macrophages (MO) is recognized as an important immunosuppressive mechanism in human neoplastic disease. We report that two types of lymphocytes of relevance for protection against malignant cells, T cells and natural killer (NK) cells, became anergic to the T cell and NK cell activator interleukin-2 (IL-2) after exposure to MO-derived reactive oxygen metabolites and subsequently acquired features characteristic of apoptosis. The MO-induced anergy and apoptosis in T cells and NK cells were reversed by histamine, an inhibitor of reactive oxygen metabolite synthesis in MO. We propose that strategies to circumvent oxidative inhibition of lymphocytes may be of benefit in immunotherapy of neoplastic disease.
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8. |
- Hansson, Markus, 1974
(author)
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Phagocyte-induced apoptosis in natural killer cells and T cells. Role of reactive oxygen species and regulation by histamine
- 2000
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Doctoral thesis (other academic/artistic)abstract
- Malignant tumors frequently contain an infiltrate of leukocytes, usually cells of the monocyte/macrophage lineage and lymphocytes with anti-tumor activity such as natural killer (NK) cells and T cells. Clinical and experimental data suggest that monocytes/macrophages in tumors inhibit functions of adjacent NK cells/T cells and thereby suppress lymphocyte-dependent anti-tumor immunity. Recently, much attention has been focused on the capacity of monocytes/macrophages to generate reactive oxygen species, which are toxic for many cells ('oxidative stress'), as a mechanism contributing to the state of immunosuppression in malignant tumors.In this thesis, the function and fate of human NK cells and T cells were studied in vitro in a reconstituted environment of oxidative stress inflicted by monocyte-derived reactive oxygen species, aimed at mimicking the microenvironment in malignant tumors. It is reported that monocytes inhibit NK cell functions, including the cytotoxicity against tumor cells and cytokine gene transcription and production, and that monocytes also inhibit the activation of NK cells and T cells induced by interleukin-2 (IL-2). In addition, monocytes induced suicidal cell death (apoptosis) in a significant fraction of NK cells and T cells. The monocyte-induced suppression and apoptosis were triggered by reactive oxygen species and mimicked by other phagocytes such as neutrophilic granulocytes. It is further shown that malignant granulocytes, recovered from patients with chronic myelogenous leukemia (CML), inhibit NK cell cytotoxicity and induce apoptosis in NK cells and in T cells. As was the case for non-malignant granulocytes, the CML cell-induced suppression of NK cells and T cells was mediated by reactive oxygen species. Anti-oxidative agents such as histamine, diphenylene iodonium, and catalase were found to protect NK cells and T cells from phagocyte-induced apoptosis and functional inhibition. The results may shed further light on the mechanisms by which malignant tumors escape anti-tumor immunity. Revealing and understanding these mechanisms and their regulation may form a basis for improved immunotherapy of neoplastic diseases.
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- Hellstrand, Kristoffer, 1956, et al.
(author)
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Alleviating oxidative stress in cancer immunotherapy: a role for histamine?
- 2000
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In: Medical oncology (Northwood, London, England). - 1357-0560. ; 17:4, s. 258-69
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Journal article (peer-reviewed)abstract
- Interleukin-2 is a remarkable activator of lymphocytes with anti-neoplastic properties such as T-cells or natural killer cells, but tumor regression only rarely occurs in interleukin-2-treated cancer patients. In this review, we focus on interactions between monocytes/macrophages and T-cells/natural killer-cells, and in particular the role of such interactions for the outcome of cancer immunotherapy with interleukin-2. We propose that interleukin-2 therapy should be supplemented with compounds that alleviate toxicity inflicted by monocyte/macrophage-derived reactive oxygen metabolites within and around tumors. The hypothesis is founded on data demonstrating that (i) functions of intratumoral lymphocytes in many human malignant tumors are inhibited by reactive oxygen metabolites, generated by neighboring monocytes/macrophages, (ii) interleukin-2 only weakly activates T-cells or natural killer cells in an environment of oxidative stress, and (iii) inhibitors of the formation of reactive oxygen metabolites or scavengers of reactive oxygen metabolites synergize with interleukin-2 to activate these lymphocyte subsets. We also review the preclinical background to the use of histamine dihydrochloride, an inhibitor of reactive oxygen metabolite formation in monocytes/macrophages, as a supplement to cancer immunotherapy with interleukin-2.
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10. |
- Hellstrand, Kristoffer, 1956, et al.
(author)
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Histamine: a novel approach to cancer immunotherapy
- 2000
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In: Cancer investigation. - : Informa UK Limited. - 0735-7907 .- 1532-4192. ; 18:4, s. 347-55
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Journal article (peer-reviewed)abstract
- The functions of intratumoral lymphocytes in many human malignant tumors are inhibited by reactive oxygen species (ROS), generated by adjacent monocytes/macrophages (MO). In vitro data suggest that immunotherapeutic cytokines such as interleukin-2 (IL-2) or interferon-alpha (IFN-alpha) only weakly activate T cells or natural killer (NK) cells in a reconstituted environment of oxidative stress and that inhibitors of the formation of ROS or scavengers of ROS synergize with IL-2 and IFN-alpha to activate T cells and NK cells. In this review, we focus on the immunoenhancing properties of histamine, a biogenic amine. Histamine inhibits ROS formation in MO via H2-receptors; thereby, histamine protects NK cells from MO-mediated inhibition and synergizes with IL-2 and IFN-alpha to induce killing of NK cell-sensitive human tumor cells in vitro. Histamine also optimizes cytokine-induced activation of several subsets of T cells by affording protection against MO-inflicted oxidative inhibition. The putative clinical benefit of histamine as an adjunct to immunotherapy with IL-2 and/or IFN-alpha is currently evaluated in clinical trials in metastatic malignant melanoma and acute myelogenous leukemia.
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