4,295 research outputs found
Diagnosing Sporadic Creutzfeldt-Jakob Disease by the Detection of Abnormal Prion Protein in Patient Urine
IMPORTANCE: Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder associated with the accumulation of infectious abnormal prion protein through a mechanism of templated misfolding. A recent report has described the detection of abnormal prion protein in the urine of patients with variant CJD (vCJD) using protein misfolding by cyclic amplification, which was apparently absent in the more common sporadic form of CJD (sCJD). A noninvasive diagnostic test could improve early diagnosis of sCJD and, by screening donations, mitigate the potential risks of prion transmission through human urine–derived pharmaceuticals. Here, we describe the adaptation of the direct detection assay, developed originally as a blood test for vCJD, for the detection of disease-associated prion protein in urine samples from patients with sCJD.
OBJECTIVE: To determine the feasibility of sCJD diagnosis by adaptation of an established vCJD diagnostic blood test to urine.
DESIGN, SETTINGS AND PARTICIPANTS: This retrospective, cross-sectional study included anonymized urine samples from healthy nonneurological control individuals (n = 91), patients with non-prion neurodegenerative diseases (n = 34), and patients with prion disease (n = 37) of which 20 had sCJD. Urine samples obtained during the Medical Research Council PRION-1 Trial, the National Prion Monitoring Cohort Study, and/or referred to the National Prion Clinic or Dementia Research Centre at the National Hospital for Neurology and Neurosurgery in the United Kingdom.
MAIN OUTCOMES AND MEASURES: Presence of sCJD infection determined by an assay that captures, enriches, and detects disease-associated prion protein isoforms.
RESULTS: A total of 162 samples were analyzed, composed of 91 normal control individuals (51 male, 33 female, and 7 not recorded), 34 neurological disease control individuals (19 male and 15 female), and 37 with prion disease (22 male and 15 female). The assay’s specificity for prion disease was 100% (95% CI, 97%-100%), with no false-positive reactions from 125 control individuals, including 34 from a range of neurodegenerative diseases. In contrast to a previous study, which used a different method, sensitivity to vCJD infection was low (7.7%; 95% CI, 0.2%-36%), with only 1 of 13 patients with positive test results, while sensitivity to sCJD was unexpectedly high at 40% (95% CI, 19%-64%).
CONCLUSIONS AND RELEVANCE: We determined 40% of sCJD urine sample results as positive. To our knowledge, this is the first demonstration of an assay that can detect sCJD infection in urine or any target analyte outside of the central nervous system. Urine detection could allow the development of rapid, molecular diagnostics for sCJD and has implications for other neurodegenerative diseases where disease-related assemblies of misfolded proteins might also be present in urine
The GEEC2 spectroscopic survey of Galaxy Groups at
We present the data release of the Gemini-South GMOS spectroscopy in the
fields of 11 galaxy groups at , within the COSMOS field. This forms
the basis of the Galaxy Environment Evolution Collaboration 2 (GEEC2) project
to study galaxy evolution in haloes with across cosmic
time. The final sample includes spectroscopically--confirmed members with
per cent complete for galaxies within the virial
radius, and with stellar mass . Including
galaxies with photometric redshifts we have an effective sample size of galaxies within the virial radii of these groups. We present group
velocity dispersions, dynamical and stellar masses. Combining with the GCLASS
sample of more massive clusters at the same redshift we find the total stellar
mass is strongly correlated with the dynamical mass, with
. This stellar
fraction of per cent is lower than predicted by some halo occupation
distribution models, though the weak dependence on halo mass is in good
agreement. Most groups have an easily identifiable most massive galaxy (MMG)
near the centre of the galaxy distribution, and we present the spectroscopic
properties and surface brightness fits to these galaxies. The total stellar
mass distribution in the groups, excluding the MMG, compares well with an NFW
profile with concentration , for galaxies beyond . This is
more concentrated than the number density distribution, demonstrating that
there is some mass segregation.Comment: Accepted for publication in MNRAS. The appendix is omitted due to
large figures. The full version will be available from the MNRAS website and
from http://quixote.uwaterloo.ca/~mbalogh/papers/GEEC2_data.pdf. Long data
tables are available from MNRAS or by contacting the first autho
How do professional development programs on comparing solution methods and classroom discourse affect students' achievement in mathematics? The mediating role of students’ subject matter justifications
Comparing solution methods fosters strategy flexibility in equation solving. Productive classroom discourse such as Accountable Talk (AT) orchestrated by teachers can improve students' justifications during classroom discussions and achievement. Do students' subject matter justifications during classroom discourse mediate the effect of teachers' professional development (PD) programs focused on comparing and AT on students’ mathematics achievement? We investigated whether two PD programs (comparing or comparing+AT) compared to a control group increased the number of students justifications, and whether this affected mathematics achievement (strategy flexibility, procedural knowledge, and conceptual knowledge). The study (739 9th and 10th grade students in 39 classes) had an experimental pre-post control group design. Both PD programs significantly increased students justifications compared to the control group. The results of our multilevel path models showed significant small mediation effects in the comparing+AT group on procedural and conceptual knowledge. No mediation effects were found in the comparing group
Decreased expression of the Id3 gene at 1p36.1 in ovarian adenocarcinomas
The molecular events that drive the initiation and progression of ovarian adenocarcinoma are not well defined. We have investigated changes in gene expression in ovarian cancer cell lines compared to an immortalized human ovarian surface epithelial cell line (HOSE) using a cDNA array. We identified 17 genes that were under-expressed and 10 genes that were over-expressed in the cell lines compared to the HOSE cells. One of the genes under-expressed in the ovarian cancer cell lines, Id3, a transcriptional inactivator, was selected for further investigation. Id3 mRNA was expressed at reduced levels in 6 out of 9 ovarian cancer cell lines compared to the HOSE cells while at the protein level, all 7 ovarian cancer cell lines examined expressed the Id3 protein at greatly reduced levels. Expression of Id3 mRNA was also examined in primary ovarian tumours and was found in only 12/38 (32%) cases. A search was conducted for mutations of Id3 in primary ovarian cancers using single stranded conformation polymorphism (SSCP) analysis. Only one nucleotide substitution, present also in the corresponding constitutional DNA, was found in 94 ovarian tumours. Furthermore no association was found between LOH at 1p36 and lack of expression of Id3. These data suggest that Id3 is not the target of LOH at 1p36. © 2001 Cancer Research Campaign http://www.bjcancer.co
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