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- Amarzguioui, Mohammed, et al.
(författare)
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Extensive Intimal Apolipoprotein A1-Derived Amyloid Deposits in a Patient with an Apolipoprotein A1 Mutation
- 1998
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 242:3, s. 534-539
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Tidskriftsartikel (refereegranskat)abstract
- In the aortic intima amyloid deposits are often associated with atherosclerotic plaques. In a recent study of one patient with aortic intimal amyloid the major fibril protein was an N-terminal fragment of apolipoprotein A1 (apoA1) consisting of 69 amino acid residues. In the present study, we have screened the apoA1 gene for mutations in autopsy cases with aortic intimal amyloid immunohistochemically positive for apoA1, using single stranded conformational polymorphism (SSCP) analysis and DNA sequencing. All cases except one had a normal apoA1 gene sequence. One case of exceptionally severe atherosclerosis combined with extensive intimal amyloid deposits showed an apoA1 deletion corresponding to Lys 107. Thus, wild type apoA1 is amyloidogenic but our findings suggest that the expression of a mutant apoA1-form may be associated with enhanced amyloidogenicity.
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| 3. |
- Peng, S., et al.
(författare)
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A computer-based training system for breast fine needle aspiration cytology
- 2002
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 196:1, s. 113-121
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Tidskriftsartikel (refereegranskat)abstract
- Fine-needle aspiration (FNA) cytology is a rapid and inexpensive technique used extensively in the diagnosis of breast disease. To remove diagnostic subjectivity, a diagnostic decision support system (DDSS) called CytoInform© has been developed, based on a Bayesian belief network (BBN) for the diagnosis of breast FNAs. In addition to acting as a DDSS, the system implements a computer-based training (CBT) system, providing a novel approach to breast cytology training. The system guides the trainee cytopathologist through the diagnostic process, allowing the user to grade each diagnostic feature using a set of on-screen reference images as visual clues. The trainee positions a slider on a spectrum relative to these images, reflecting the similarity between the reference image and the microscope image. From this, an evidence vector is generated, allowing the current diagnostic probability to be updated by the BBN. As the trainee assesses each clue, the evidence entered is compared with that of the expert through the use of a defined teaching file. This file records the relative severity of each clue and a tolerance band within which the trainee must position the slider. When all clues in the teaching case have been completed, the system informs the user of inaccuracies and offers the ability to reassess problematic features. In trials with two pathologists of different experience and a series of ten cases, the system provided an effective tool in conveying diagnostic evidence and protocols to trainees. This is evident from the fact that each pathologist only misinterpreted one case and a total of 86%/88% (experienced/inexperienced) of all clues assessed were interpreted correctly. Significantly, in all cases that produced the correct final diagnostic probability, the route taken to that solution was consistent with the expert's solution. Copyright © 2001 John Wiley & Sons, Ltd.
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| 5. |
- Segerman, Anna, et al.
(författare)
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Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition
- 2016
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 17:11, s. 2994-3009
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Tidskriftsartikel (refereegranskat)abstract
- Intratumoral heterogeneity is a hallmark of glioblastoma multiforme and thought to negatively affect treatment efficacy. Here, we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability among clones, including a range of responses to radiation and drugs. This widespread variability was observed as a continuumof multitherapy resistance phenotypes linked to a proneural-mesenchymal shift in the transcriptome. Multitherapy resistance was associated with a semi-stable cell state that was characterized by an altered DNA methylation pattern at promoter regions of mesenchymal master regulators and enhancers. The gradient of cell states within the GIC compartment constitutes a distinct form of heterogeneity. Our findings may open an avenue toward the development of new therapeutic rationales designed to reverse resistant cell states.
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| 6. |
- Carlsson, Jenny, 1977-, et al.
(författare)
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An indirect competitive immunoassay for insulin autoantibodies based on surface plasmon resonance
- 2008
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Ingår i: Biosensors and Bioelectronics. - : Elsevier BV. - 0956-5663. ; 24:4, s. 876-881
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a sensitive and specific method based on surface plasmon resonance (SPR) for detection of insulin autoantibodies (IAA) in serum samples from individuals at high risk of developing type 1 diabetes (T1D). When measuring trace molecules in undiluted sera with label-free techniques like SPR, non-specific adsorption of matrix proteins to the sensor surface is often a problem, since it causes a signal that masks the analyte response. The developed method is an indirect competitive immunoassay designed to overcome these problems. Today, IAA is mainly measured in radio immunoassays (RIAs), which are time consuming and require radioactively labeled antigen. With our SPR-based immunoassay the overall assay time is reduced by a factor of >100 (4 days to 50 min), while sensitivity is maintained at a level comparable to that offered by RIA.
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| 8. |
- Carlsson, Jenny, 1977-, et al.
(författare)
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Determination of insulin autoantibodies using surface plasmon resonance: A screening study of newly diagnosed type 1 diabetes patients
- 2008
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We have investigated the screening potential of a surface plasmon resonance (SPR)-based indirectcompetitive immunoassay for quantification of insulin autoantibodies (IAA) in sera from childrennewly diagnosed with type 1 diabetes (T1D), using a radioimmunoassay (RIA) as reference technique.The two methods agreed well with respect to sample classification of 54 sera from newly diagnosedT1D children and 32 reference sera from non-diabetic children. Interestingly, five samples from newlydiagnosed T1D patients classified as IAA-negative according to RIA were IAA-positive with the SPRbasedassay, suggesting that the SPR-based assay might provide a higher sensitivity than the referenceRIA. However, 14 percent of the analyzed samples (five samples from non-diabetics and seven fromnewly diagnosed T1D patients) gave rise to anomalously high and easily distinguishable responses withthe SPR-based method, precluding IAA-quantification. A considerable part of the paper is devoted to adiscussion of possible causes of these anomalous responses. They were not due to temporary changesin the status of the patients, such as infections at the time of sampling, and also not related tocomplement activation. It is speculated whether a plausible explanation should instead be sought in theexistence of anti-idiotypic antibodies to IAA.
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