| 51. |
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| 52. |
- Heslegrave, Amanda, et al.
(författare)
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Increased cerebrospinal fluid soluble TREM2 concentration in Alzheimer's disease.
- 2016
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Ingår i: Molecular neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The discovery that heterozygous missense mutations in the gene encoding triggering receptor expressed on myeloid cells 2 (TREM2) are risk factors for Alzheimer's disease (AD), with only the apolipoprotein E (APOE) ε4 gene allele conferring a higher risk, has led to increased interest in immune biology in the brain. TREM2 is expressed on microglia, the resident immune cells of the brain and has been linked to phagocytotic clearance of amyloid β (Aβ) plaques. Soluble TREM2 (sTREM2) has previously been measured in cerebrospinal fluid (CSF) by ELISA but in our hands commercial kits have proved unreliable, suggesting that other methods may be required. We developed a mass spectrometry method using selected reaction monitoring for the presence of a TREM2 peptide, which can be used to quantify levels of sTREM2 in CSF.
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| 53. |
- Hesse, Camilla, et al.
(författare)
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The N-terminal domain of α-dystroglycan is released as a 38kDa protein and is increased in cerebrospinal fluid in patients with Lyme neuroborreliosis.
- 2011
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 412:3
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Tidskriftsartikel (refereegranskat)abstract
- α-Dystroglycan is an extracellular adhesion protein that is known to interact with different ligands. The interaction is thought to stabilize the integrity of the plasma membrane. The N-terminal part of α-dystroglycan may be proteolytically processed to generate a small 38kDa protein (α-DG-N). The physiological significance of α-DG-N is unclear but has been suggested to be involved in nerve regeneration and myelination and to function as a potential biomarker for neurodegenerative and neuromuscular diseases. In this report we show that α-DG-N is released into different body fluids, such as lachrimal fluid, cerebrospinal fluid (CSF), urine and plasma. To investigate the significance of α-DG-N in CSF we examined the levels of α-DG-N and known neurodegenerative markers in CSF from patients diagnosed with Lyme neuroborreliosis (LNB) and healthy controls. In untreated acute phase LNB patients, 67% showed a significant increase of CSF α-DG-N compared to healthy controls. After treatment with antibiotics the CSF α-DG-N levels were normalized in the LNB patients.
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| 54. |
- Jakobsson, Gunnar, et al.
(författare)
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Increased Levels of Inflammatory Immune Mediators in Vitreous From Pseudophakic Eyes
- 2015
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 56:5, s. 3407-3414
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To determine if pseudophakic eyes have an increased and sustained level of inflammatory immune mediators in the vitreous compared to phakic eyes. METHODS. Vitreous fluid samples were obtained from 73 patients undergoing elective pars plana vitrectomy (PPV) as a result of a macular hole, epiretinal membrane, vitreous macular traction, or vitreous floaters. Forty eyes were pseudophakic and had previously undergone uncomplicated cataract surgery, ranging from a few months to several years prior to PPV. The vitreous samples were analyzed for 29 different inflammatory immune mediators using multiplex bead immunoassays. RESULTS. A total of 14 cytokines (eotaxin, interferon-c-induced protein-10 [IP-10], monocyte chemotactic protein-1 [MCP-1], macrophage derived chemokine [MDC], macrophage inflammatory protein [MIP]-1 alpha, MIP-1 beta, thymus activation regulated chemokine [TARC], IL-12p40, IL-15, IL-16, IL-7, VEGF, IL-6, and IL-8) were detected in the vitreous of both study groups. Using multiple linear regression analysis, pseudophakiawas significantly correlated with higher levels of vitreous immune mediators compared to phakia. Elevated vitreous levels were estimated to decrease over time for IL-6, IL-8, IL-15, IL-16, and VEGF, though they remained elevated for many months and even years compared to the levels detected in phakic eyes. CONCLUSIONS. This is the first study to demonstrate that cataract surgery and pseudophakia can induce increased vitreous levels of a substantial range of inflammatory immune mediators. The elevated levels seem to be maintained for a long period of time. These increased levels of cytokines may be involved in inflammatory processes leading to several complications to cataract surgery, both early and late.
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| 55. |
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| 56. |
- Jons, Daniel, 1974, et al.
(författare)
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Axonal injury in asymptomatic individuals preceding onset of multiple sclerosis
- 2022
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 9:6, s. 882-887
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Tidskriftsartikel (refereegranskat)abstract
- Axonal loss is the main cause of irreversible disability in multiple sclerosis (MS). Serum neurofilament light (sNfL) is a biomarker of axonal disintegration. In this nested case-control study, blood samples from 519 presymptomatic persons (age range 4-39 years) who later received an MS diagnosis showed higher sNfL concentrations than 519 matched controls (p < 0.0001), noticeable at least 10 years before clinical MS onset. Mean values for pre-MS and control groups were 9.6 pg/mL versus 7.4 pg/mL 0-5 years before onset, and 6.4 pg/mL versus 5.8 pg/mL 5-10 years before onset. These results support that axonal injury occurs early in MS pathogenesis.
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| 57. |
- Jons, Daniel, et al.
(författare)
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Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage
- 2023
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 1468-330X .- 0022-3050.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple sclerosis (MS) and presymptomatic axonal injury appear to develop only after an Epstein-Barr virus (EBV) infection. This association remains to be confirmed across a broad preclinical time range, for lytic and latent EBV seroreactivity, and for potential cross-reacting antigens. Methods: We performed a case-control study with 669 individual serum samples obtained before clinical MS onset, identified through cross-linkage with the Swedish MS register. We assayed antibodies against EBV nuclear antigen 1 (EBNA1), viral capsid antigen p18, glycoprotein 350 (gp350), the potential cross-reacting protein anoctamin 2 (ANO2) and the level of sNfL, a marker of axonal injury. Results: EBNA1 (latency) seroreactivity increased in the pre-MS group, at 15-20 years before clinical MS onset, followed by gp350 (lytic) seroreactivity (p=0.001-0.009), ANO2 seropositivity appeared shortly after EBNA1-seropositivity in 16.7% of pre-MS cases and 10.0% of controls (p=0.001).With an average lag of almost a decade after EBV, sNfL gradually increased, mainly in the increasing subgroup of seropositive pre-MS cases (p=8.10-5 compared with non-MS controls). Seropositive pre-MS cases reached higher sNfL levels than seronegative pre-MS (p=0.038). In the EBNA1-seropositive pre-MS group, ANO2 seropositive cases had 26% higher sNfL level (p=0.0026). Conclusions: Seroreactivity against latent and lytic EBV antigens, and in a subset ANO2, was detectable on average a decade before the appearance of a gradually increasing axonal injury occurring in the last decade before the onset of clinical MS. These findings strengthen the hypothesis of latent EBV involvement in the pathogenesis of MS.
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| 58. |
- Karlsson, Jan-Olof, 1944, et al.
(författare)
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Inhibition of Glycogen Synthase Kinase (GSK-3) Protects Against Oxidative Stress and Attenuates Apoptosis in Human Lens Epithelial Cells and the Mouse Lens in Organ Culure
- 2005
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Ingår i: Invest. Ophthalmol. Vis. Sci.. ; 46:5
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Konferensbidrag (refereegranskat)abstract
- Purpose: GSK-3 may regulate Wnt signaling, gene expression, the cell cycle, cell differentiation and apoptosis. Inhibition of GSK-3 can be obtained via the structurally unrelated substances lithum or Kenpaullone. The lens and the lens epithelial cells are excellent models to study the role of this enzyme. Methods: Primary cultures of human lens epithelial cells (HLEC) or the mouse lens in organ culture were exposed to the GSK-3 inhibitors lithium (2 mM) or Kenpaullone (2 {micro}M) for times upp to 24h.The cells were, before or after treatment, placed in medium containing fluorogenic indicators of oxidative damage. DCFH-DA was used to assay peroxides, mitochondrial function was evaluated with Rhodamine 123 and JC-1, monochlorobimane was used to assay intracellular glutathione (GSH) levels, Proteolytic activities were assayed, on line, with cell-permeable fluorogenic substrates.Proteasome and calpain activities were assayed with LLVY-AMC, Cathepsin B with RR-AMC or FR-AMC. Metalloproteases were assayed with AAF-AMC. Caspase-3, 8 and 9 were assayed in cell extracts with DEVD-, IETD- or LEHD-AMC, respectively. Results: The mitochondrial membrane potential and the level of GSH increased by 10% after treatment of HLEC with Li or Kenpaullone for 24h. No change was observed for peroxide production. The basal (low) level of caspase-3 activity was decreased by at least 20%. No significant effects were found concerning caspase-8 or 9 activities. No effect was observed on the activity of calpain, the proteasome, metalloproteases and cathepsin D/E activity.The whole mouse lens in organ culture showed essentially the same elevated mitochondrial potential. The GSH increase was even more evident in the whole lens preparation. Conclusions: Inhibition of GSK-3 may protect against oxidative stress (and cataract) via prevention of MPT induction and attenuate apoptosis in HLEC.
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| 59. |
- Kondziella, Daniel, 1976, et al.
(författare)
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Hypertension in spontaneously hypertensive rats occurs despite low plasma levels of homocysteine
- 2008
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Ingår i: Physiological Research. - 0862-8408. ; 57:3, s. 487-490
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Tidskriftsartikel (refereegranskat)abstract
- Hyperhomocysteinemia has been suggested to induce hypertension due to its role in endothelial dysfunction. However, it remains controversial whether homocysteine and hypertension are truly causally related or merely loosely associated. To test the hypothesis that hyperhomocysteinemia occurs in Spontaneously Hypertensive Rats (SHR) we measured plasma levels of homocysteine in 10 male adult SHR and in 10 normotensive controls using Ion Exchange Chromatography. In addition, plasma concentrations of the 22 most common amino acids were measured to explore the relation of homocysteine with amino acid metabolism. Plasma levels of homocysteine were significantly lower in SHR (4.1 micromol/L +/-0.1) than in controls (7.2 micromol/L +/- 0.3; p<0.00001). The amounts of aminobutyric acid (ABU), alanine, citrulline and valine were decreased as well, whereas we found increased levels of aspartate, glutamate, glutamine, histidine and ornithine. Thus, contrary to our hypothesis, hypertension in SHR occurs despite low plasma levels of homocysteine. We provide a new hypothesis whereby reduced conversion of arginine to citrulline is related to increased ornithine levels, but decreased bioavailability of nitric oxide, resulting in impaired blood vessel relaxation and hypertension. In conclusion, our findings do not necessarily exclude that homocysteine and hypertension might be pathophysiologically connected, but corroborate the notion that hypertension can arise due to mechanisms independent of high homocysteine levels.
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| 60. |
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