| 61. |
- Olsson, Bob, 1969, et al.
(författare)
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Increased number of B-cells in the red pulp of the spleen in ITP
- 2012
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Ingår i: Annals of Hematology. - : Springer Science and Business Media LLC. - 1432-0584 .- 0939-5555. ; 91:2, s. 271-277
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Tidskriftsartikel (refereegranskat)abstract
- Platelets are targeted by autoantibodies and destroyed in the reticuloendothelial system in the spleen, liver and bone marrow in patients with immune thrombocytopenia (ITP). Other mechanisms such as destruction by cytotoxic T-cells and defective production of platelets in the bone marrow also exist. Splenectomy normalizes the platelet count in 70% of ITP patients, however, precious little is known about the spleen in this disease. Our aim was therefore to investigate the splenic morphology and especially the number and localization of splenic leukocytes in patients with ITP and controls and to evaluate factors predicting outcome of splenectomy. Spleen sections from 29 ITP patients and 11 individuals splenectomized due to trauma were analyzed by immunohistochemistry. All except one of the ITP patients had a normalized platelet count 12months after splenectomy and the platelet count was inversely correlated with age. ITP patients had an increased number of B-cells in the red pulp. The number of white pulp B-cells and number of T-cells in both compartments was unchanged. In conclusion, B-cells are increased in the red pulp of the spleen and together with cytotoxic T-cells, helper T-cells and macrophages line the sinusoids enabling the immunological attack on platelets in ITP.
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| 62. |
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| 63. |
- Olsson, Bob, 1969, et al.
(författare)
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Microglial markers are elevated in the prodromal phase of Alzheimer's disease and vascular dementia.
- 2013
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908 .- 1387-2877. ; 33:1, s. 45-53
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Tidskriftsartikel (refereegranskat)abstract
- Microglia manage immunosurveillance and mediate inflammation, both suggested to be important in Alzheimer's disease (AD). The aim of this study was to investigate if microglial markers could differentiate, firstly between AD and controls, and secondly between stable mild cognitive impairment (MCI) and those progressing to AD and vascular dementia (VaD). Furthermore, we investigated if these markers were sufficiently stable to be used in clinical trials. We quantified YKL-40 and sCD14 in cerebrospinal fluid (CSF) from 96 AD patients, 65 healthy controls, and 170 patients with MCI from baseline and over 5.7 years. For the stability analysis, two CSF samples were collected from 52 AD patients with a six-month interval in between. YKL-40, but not sCD14, was significantly elevated in AD compared with healthy controls (p = 0.003). Furthermore, YKL-40 and sCD14 were increased in MCI patients who converted to VaD (p = 0.029 and p = 0.008), but not to AD according to NINCDS-ADRDA. However, when stratified according to CSF levels of tau and Aβ42, YKL-40 was elevated in those with an AD-indicative profile compared with stable MCI with a normal profile (p = 0.037). In addition, YKL-40 and sCD14 were very stable in AD patients with good correlation between time-points (r = 0.94, p = 3.4 × 10-25; r = 0.77, p = 2.0 × 10-11) and the cortical damage marker T-tau. Thus, microglial markers are stable and may be used as safety markers for monitoring CNS inflammation and microglia activation in clinical trials. Moreover, YKL-40 differentiates between AD and controls and between stable MCI to AD and those that convert to AD and VaD.
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| 64. |
- Olsson, Bob, 1969, et al.
(författare)
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NFL is a marker of treatment response in children with SMA treated with nusinersen
- 2019
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 266:9, s. 2129-2136
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Tidskriftsartikel (refereegranskat)abstract
- Background Recently, the anti-sense oligonucleotide drug nusinersen was approved for spinal muscular atrophy (SMA) and our aim was to find a response marker for this treatment. Methods Twelve children with SMA type 1 and two copies of the SMN2 gene were included in a consecutive single-center study. The children were sampled for CSF at baseline and every time nusinersen was given intrathecally. The neuronal biomarkers NFL and tau and the glial biomarker GFAP were measured. Motor function was assessed using CHOP INTEND. Eleven similarly aged children, who were investigated to rule out neurological or infectious disease, were used as controls. Results Baseline levels of NFL (4598 +/- 981 vs 148 +/- 39, P = 0.001), tau (939 +/- 159 vs 404 +/- 86, P = 0.02), and GFAP (236 +/- 44 vs 108 +/- 26, P = 0.02) were significantly higher in SMA children than controls. Motor function improved by nusinersen treatment in median 13 points corresponding to 5.4 points per month of treatment (P = 0.001). NFL levels typically normalized ( < 380 pg/ml) between the fourth and fifth doses [- 879.5 pg/mL/dose, 95% CI (- 1243.4, - 415.6), P = 0.0001], tau levels decreased [- 112.6 pg/mL/dose, 95% CI (- 206-7, - 18.6), P = 0.01], and minor decreases in GFAP were observed [- 16.9 pg/mL/dose, 95% CI (- 22.8, - 11.2), P = 0.02] by nusinersen treatment. Improvement in motor function correlated with reduced concentrations of NFL (rho = - 0.64, P = 0.03) and tau (rho = - 0.85, P = 0.0008) but not GFAP. Conclusions Nusinersen normalized the axonal damage marker NFL and correlated with motor improvement in children with SMA. NFL may, therefore, be a novel biomarker to monitor treatment response early in the disease course.
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| 65. |
- Olsson, Bob, 1969, et al.
(författare)
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Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA-4 and CX3CR1.
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 112:4, s. 1078-84
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Tidskriftsartikel (refereegranskat)abstract
- In idiopathic thrombocytopenic purpura (ITP), platelets are destroyed in the spleen, liver, and bone marrow (BM) by autoantibodies and cytotoxic T cells. In a DNA microarray screen of peripheral blood T cells, we found that VLA-4, CX3CR1, and CXCR4, involved in T-cell homing, had increased expression in ITP patients compared with controls. However, we only found increased protein expression of VLA-4 on T cells from peripheral blood by flow cytometry. To address a possible recruitment of T cells into the organs involved in platelet destruction, we analyzed T cells in BM. In BM, T-cell surface expression of VLA-4 and CX3CR1 was increased in ITP patients compared with controls. Furthermore, the number of CD3(+) T cells in BM, but not in blood, was increased in ITP patients compared with controls. This finding was confirmed by immunohistochemistry of BM biopsies. The number of regulatory T cells (CD4(+)/CD25(bright)) was decreased in the BM of ITP patients, whereas Fas expression was increased. In conclusion, ITP is associated with accumulation and activation of T cells in the BM. Recruitment of T cells into the target organ (eg, BM) is plausible and may be facilitated through increased VLA-4 and CX3CR1 expression. These molecules might serve as new treatment targets in ITP.
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| 66. |
- Olsson, Bob, 1969, et al.
(författare)
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T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura.
- 2003
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 9:9, s. 1123-4
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Tidskriftsartikel (refereegranskat)abstract
- Chronic idiopathic thrombocytopenic purpura (ITP) is a bleeding disorder that is characterized by increased platelet destruction and is believed to be autoantibody mediated. In this study, CD3+ T cells from ITP patients had increased expression of genes involved in cell-mediated cytotoxicity. In addition, cytotoxic cell-mediated lysis of autologous platelets was shown in active ITP. Our data suggest that T-cell-mediated cytotoxicity is an alternative mechanism for platelet destruction in ITP.
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| 67. |
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| 68. |
- Olsson, Bob, 1969, et al.
(författare)
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The glial marker YKL-40 is decreased in synucleinopathies.
- 2013
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Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 28:14, s. 1882-1885
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Tidskriftsartikel (refereegranskat)abstract
- Microglia are resident immunosurveillant cells in the central nervous system, and astrocytes are important for blood flow, plasticity, and neurotransmitter regulation. The aim of this study was to investigate whether astrocyte and microglial activation, estimated through markers in cerebrospinal fluid and serum, differed between synucleinopathies, tauopathies, and controls.
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| 69. |
- Olsson, Bob, 1969
(författare)
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The role of GH in the regulation of energy homeostasis, lipid metabolism and cardiovascular function in transgenic mice
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was, using two transgenic models, to investigate some metabolic diseases associated with acromegaly e.g. hypertension and alterations in lipid and lipoprotein metabolism. We also studied the positive effect of Growth Hormone (GH), and possible molecular causes, on body composition and energy homeostasis using these GH transgenic models.We have used two different GH transgenic mouse models, one model overexpressing GH generally, controlled by the metallothionine promoter (Mt-bGH), and one model where the GH overexpression is restricted to the CNS, using the glial fibrillary acidic protein promoter (GFAP-bGH).Using telemetric technique, we have found that Mt-bGH transgenic mice have a salt-insensitive hypertension. Furthermore, the Mt-bGH transgenic mice have altered lipoprotein profiles and serum lipids, hyperinsulinemia and hyperglycaemia. Moreover, the hepatic gene expression profiles analysed by micro-array, revealed decreased gene expression of PPARa and SREBP-1 together with decreased expression of genes involved in fatty acid activation, b-oxidation, ketone body formation, lipogenesis, cholesterol metabolism, gluconeogenesis and amino acid catabolism. When analysed by indirect calorimetry, the Mt-bGH transgenic mice also had an increased resting metabolic rate on a normal diet that was enhanced by a Western diet, increased body temperature and increased hepatic gene expression of UCP2. Furthermore, the Mt-bGH transgenic mice had an increased respiratory exchange rate and food intake on both diets but still a lean body composition.The GFAP-bGH mice had an increased food intake resulting in massive obesity along with an increased expression of AGRP and NPY. These mice also had alterations in lipid and lipoprotein metabolism, hyperinsulinemia and pancreatic islet hypertrophy but normal blood glucose levels.GH stimulates food intake by increasing the hypothalamic gene expression of AGRP and NPY. This results in obesity in the GFAP-bGH transgenic mice but the high circulating levels of GH in the Mt-bGH mice, resulting in elevated RMR, body temperature, and T3 levels prevent obesity and result in a lean body composition. We have also found several risk factors for cardiovascular disease in these two GH transgenic models, such as high LDL cholesterol, insulin resistance, hypertension and indications of a decreased reverse cholesterol transport. These models may be useful tools in understanding the underlying mechanisms for cardiovascular disease in patients with acromegaly.
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| 70. |
- Olsson, Bob, 1969, et al.
(författare)
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The use of cerebrospinal fluid biomarkers to measure change in neurodegeneration in Alzheimer's disease clinical trials
- 2017
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Ingår i: Expert Review of Neurotherapeutics. - : Informa UK Limited. - 1473-7175 .- 1744-8360. ; 17:8, s. 767-775
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: All recent phase 3 trials of potentially disease-modifying therapies for Alzheimer's disease (AD) have so far failed. Potential reasons include enrolling subjects whose disease is too advanced or who do not have AD pathology, or simply incorrect drug targets. The goal of disease-modifying AD trials is to halt the progress of neuronal damage and death and this can be assessed in vivo using cerebrospinal fluid (CSF) biomarkers.Areas covered: The authors conducted a literature search of the use of CSF biomarkers in disease-modifying AD clinical trials using PubMed. The authors show that CSF biomarkers have only sparsely been used as outcome measures, and where they have, only in small subsets of patients. No clinical trials have yet showed any substantial effects on CSF biomarkers of neurodegeneration.Expert commentary: In future trials, the authors advocate that CSF biomarkers be used more extensively to optimize the chance of detecting positive drug effects. This includes the identification of potential AD patients - already in the early prodromal stage - for inclusion, for stratification, as readout i.e. proximity markers for changes in axonal/neurodegeneration between treatment and placebo groups - this also enables proof of principle verification in the discovery/dose finding phase, and for monitoring of side effects.
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