6 research outputs found
Modulation of macrophage antitumor cytostasis by endogenous leukotrienes
Using resident peritoneal macrophages, this
study was focussed on the activating role of endogenous
leukotrienes in the regulation of macrophage antitumor
cytostatic activity in response to inflammatory stimuli.
Inhibitors and inducers of leukotrienes synthesis were used to
modulate the macrophage antitumor cytostatic function and to
identify the essential leukotriene(s) and enzymes involved in
inhibition of tumor cell growth by activated macrophages.
Induction of high macrophage antitumor activity by modulation
of leukotriene biosynthesis might represent an efficient
immunotherapeutic tool.
- The main aim of the present work was to study the
possible interrelationship between induction of antitumor
cytostasis and of production of prostanoids and leukotrienes by
murine peritoneal macrophages stimulated with the calcium
ionophore A23187. A method of cell separation by velocity
sed~mentation was adapted for obtaining macrophage-enriched
preparations from the resident peritoneal macrophage
populatio
A Large-Scale Full GBA1 Gene Screening in Parkinson's Disease in the Netherlands
Background: The most common
genetic risk factor for Parkinsonâs disease known is a
damaging variant in the GBA1 gene. The entire GBA1
gene has rarely been studied in a large cohort from a
single population. The objective of this study was to
assess the entire GBA1 gene in Parkinsonâs disease
from a single large population.
Methods: The GBA1 gene was assessed in 3402
Dutch Parkinsonâs disease patients using nextgeneration sequencing. Frequencies were compared
with Dutch controls (n = 655). Family history of
Parkinsonâs disease was compared in carriers and
noncarriers.
Results: Fifteen percent of patients had a GBA1 nonsynonymous variant (including missense, frameshift, and
recombinant alleles), compared with 6.4% of c
Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.
BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies
Technology in Motion Tremor Dataset: TIM-Tremor
Data was collected within the Technology in Motion project (protocol registered as NL54281.058.15), aimed at developing patient friendly and unobtrusive techniques to characterize motor function in patients with neurological disorders. In this context we used video cameras combined with depth sensors (RGB-D sensors, Microsoft KinectTM v2) and 2 accelerometer sensors (ACL300, Biometrics Ltd, Newport, UK) to objectively quantify the frequency and amplitude of tremor of the upper extremity.
This dataset contains 55 patient recorded at performing a set of tasks. For each patient and each task, we record a short seqeuence and provide: (i) Kinect RGB video recording, (ii) Kinect depth map recording encoded as a video, (iii) Kinect depth map aligned with the RGB video, (iv) accelerometer recordings of the 2 sensors. We aditionally, provide an overall labeling file containing for each patient: tremor ratings per arm, and tremor diagnosis
More detailed description can be found in documentation
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Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's
Objective: We hypothesized that specific mutations in the ÎČâglucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas nonâneuropathic GD mutations confer intermediate progression rates. Methods: A total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of genetic variation in GBA on longitudinal cognitive decline were evaluated using mixed random and fixed effects and Cox proportional hazards models. Results: Overall, 10.3% of patients with PD and GBA sequencing carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence interval [CI], 1.60â6.25) and a hastened decline in MiniâMental State Exam scores compared to noncarriers (p = 0.0009). Carriers of complex GBA alleles (0.7%) had an HR of 3.22 (95% CI, 1.18â8.73; p = 0.022). By contrast, the common, nonâneuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92â4.18) or nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89â2.05) did not reach significance. Interpretation Mutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into âhigh gear.â These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674â68
Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's
Objective: We hypothesized that specific mutations in the ÎČ-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non-neuropathic GD mutations confer intermediate progression rates. Methods: A total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of genetic variation in GBA on longitudinal cognitive decline were evaluated using mixed random and fixed effects and Cox proportional hazards models. Results: Overall, 10.3% of patients with PD and GBA sequencing carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence interval [CI], 1.60â6.25) and a hastened decline in MiniâMental State Exam scores compared to noncarriers (p = 0.0009). Carriers of complex GBA alleles (0.7%) had an HR of 3.22 (95% CI, 1.18â8.73; p = 0.022). By contrast, the common, non-neuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92â4.18) or nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89â2.05) did not reach significance. Interpretation: Mutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into âhigh gear.â These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674â685