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1.  Comparable Autoantibody Serum Levels against Amyloid- and Inflammation-Associated Proteins in Parkinson’s Disease Patients and Controls 
PLoS ONE  2014;9(2):e88604.
Naturally occurring autoantibodies (NAbs) against a number of potentially disease-associated cellular proteins, including Amyloid-beta1–42 (Abeta1–42), Alpha-synuclein (Asyn), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and S100 calcium binding protein B (S100B) have been suggested to be associated with neurodegenerative disorders, in particular Alzheimer’s (AD) and Parkinson’s disease (PD). Whereas the (reduced) occurrence of specific NAbs in AD is widely accepted, previous literature examining the relation of these NAb titres between PD patients and controls, as well as comparing these levels with demographic and clinical parameters in PD patients have produced inconsistent findings. We therefore aimed, in a cross-sectional approach, to determine serum titres of the above NAbs in a cohort of 93 PD patients (31 of them demented) and 194 controls. Levels were correlated with demographic and clinical variables, cerebrospinal fluid Abeta1–42, total tau and phospho-tau levels, as well as with single nucleotide polymorphisms (SNPs) of genes which either have been reported to influence the immune system, the amyloid cascade or the occurrence of PD (ApoE, GSK3B, HLA-DRA, HSPA5, SNCA, and STK39). The investigated NAb titres were neither significantly associated with the occurrence of PD, nor with demographic and clinical parameters, neurodegenerative markers or genetic variables. These results argue against a major potential of blood-borne parameters of the adaptive immune system to serve as trait or state markers in PD.
PMCID: PMC3931625  PMID: 24586351
2.  Serum and Cerebrospinal Fluid Levels of Transthyretin in Lewy Body Disorders with and without Dementia 
PLoS ONE  2012;7(10):e48042.
Parkinson’s disease (PD) without (non-demented, PDND) and with dementia (PDD), and dementia with Lewy bodies (DLB) are subsumed under the umbrella term Lewy body disorders (LBD). The main component of the underlying pathologic substrate, i.e. Lewy bodies and Lewy neurites, is misfolded alpha-synuclein (Asyn), and - in particular in demented LBD patients - co-occurring misfolded amyloid-beta (Abeta). Lowered blood and cerebrospinal fluid (CSF) levels of transthyretin (TTR) - a clearance protein mainly produced in the liver and, autonomously, in the choroid plexus - are associated with Abeta accumulation in Alzheimer’s disease. In addition, a recent study suggests that TTR is involved in Asyn clearance. We measured TTR protein levels in serum and cerebrospinal fluid of 131 LBD patients (77 PDND, 26 PDD, and 28 DLB) and 72 controls, and compared TTR levels with demographic and clinical data as well as neurodegenerative markers in the CSF. Five single nucleotide polymorphisms of the TTR gene which are considered to influence the ability of the protein to carry its ligands were also analyzed. CSF TTR levels were significantly higher in LBD patients compared to controls. Post-hoc analysis demonstrated that this effect was driven by PDND patients. In addition, CSF TTR levels correlated negatively with CSF Abeta1–42, total tau and phospho-tau levels. Serum TTR levels did not significantly differ among the studied groups. There were no relevant associations between TTR levels and genetic, demographic and clinical data, respectively. These results suggest an involvement of the clearance protein TTR in LBD pathophysiology, and should motivate to elucidate TTR-related mechanisms in LBD in more detail.
PMCID: PMC3485000  PMID: 23133543
3.  Evaluation of non-linear blending in dual-energy computed tomography 
European journal of radiology  2008;68(3):409-413.
Dual-energy CT scanning has significant potential for disease identification and classification. However, it dramatically increases the amount of data collected and therefore impacts the clinical workflow. One way to simplify image review is to fuse CT datasets of different tube energies into a unique blended dataset with desirable properties.
A non-linear blending method based on a modified sigmoid function was compared to a standard 0.3 linear blending method. The methods were evaluated in both a liver phantom and patient study. The liver phantom contained six syringes of known CT contrast which were placed in a bovine liver. After scanning at multiple tube currents (45, 55, 65, 75, 85, 95, 105, and 115 mAs for the 140-kV tube), the datasets were blended using both methods. A contrast-to-noise (CNR) measure was calculated for each syringe. In addition, all eight scans were normalized using the effective dose and statistically compared. In the patient study, 45 dual-energy CT scans were retrospectively mixed using the 0.3 linear blending and modified sigmoid blending functions. The scans were compared visually by two radiologists.
For the 15, 45, and 64 HU syringes, the non-linear blended images exhibited similar CNR to the linear blended images; however, for the 79, 116, and 145 HU syringes, the non-linear blended images consistently had a higher CNR across dose settings. The radiologists qualitatively preferred the non-linear blended images of the phantom. In the patient study, the radiologists preferred non-linear blending in 31 of 45 cases with a strong preference in bowel and liver cases.
Non-linear blending of dual energy data can provide an improvement in CNR over linear blending and is accompanied by a visual preference for non-linear blended images. Further study on selection of blending parameters and lesion conspicuity in non-linear blended images is being pursued.
PMCID: PMC2743374  PMID: 18990521
Dual-energy computed tomography; Image processing; Data fusion
4.  Targeting of cancer stem cell marker EpCAM by bispecific antibody EpCAMxCD3 inhibits pancreatic carcinoma 
Patients with pancreatic cancer have a poor survival rate, and new therapeutic strategies are needed. Epithelial cell adhesion molecule (EpCAM), suggested as a marker for cancer stem cells, is over-expressed on most pancreatic tumour cells but not on normal cells and may be an ideal therapeutic target. We evaluated the anti-tumour efficiency of bispecific EpCAMxCD3 antibody linking tumour cells and T lymphocytes. In NOD SCID mice, EpCAMxCD3 had a long serum half-life (t1/2∼ 7 days). EpCAMxCD3 significantly retarded growth of BxPC-3 pancreatic carcinoma xenografts. For mimicking a pancreatic cancer microenvironment in vitro, we used a three-dimensional tumour reconstruct system, in which lymphocytes were co-cultured with tumour cells and fibroblasts in a collagen matrix. In this in vivo–like system, EpCAMxCD3 potently stimulated production of the effector cytokines IFN-γ and TNF-α by extracorporally pre-activated lymphocytes. Moreover, compared with a bivalent anti-CD3 antibody, EpCAMxCD3 more efficiently activated the production of TNF-α and IFN-γ by non-stimulated peripheral blood mononuclear cells. Most excitingly, we demonstrate for the first time that EpCAMxCD3 induces prolonged contacts between lymphocytes and tumour cells, which may be the main reason for the observed anti-tumour effects. As an important prerequisite for future use in patients, EpCAMxCD3 did not alter lymphocyte migration as measured by time-lapse video microscopy. Our data may open a way to improve the immune response and treatment outcome in patients with pancreatic cancer.
PMCID: PMC4516549  PMID: 20196789
bispecific antibody; cancer stem cells; cancer immunotherapy; EpCAM; pancreatic carcinoma; lymphocytes; tumour microenvironment

Results 1-4 (4)