BioVision: An application for the automated image analysis of histological sections

Chubb, Charles; Inagaki, Yoshi; Sheu, Phillip C.‐Y.; Cummings, Brian J.; Wasserman, A.; Head, Elizabeth; Cotman, Carl W.

doi:10.1016/j.neurobiolaging.2005.08.023

Cited by 29 publications

(25 citation statements)

References 16 publications

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“…Immunostained coronal tissue sections, serially cut within the hippocampus beginning from interaural (1.68 mm)/bregma (Ϫ2.12 mm) to interaural (2.16 mm)/ bregma (Ϫ1.64 mm), were analyzed. A␤-positive plaques were quantified from high resolution images of the same brain areas within the anti-Trx(A␤15) 4 -treated hemisphere and the contralateral mock-treated hemisphere using BioVision (50) and Neurolucida software programs (MicroBrightField, Williston, VT). BioVision differentiates and counts plaques from the background neuropil, whereas Neurolucida extracts the data from the BioVision images, exporting it to Excel (Microsoft, Redmond, WA) for statistical analysis.…”

Section: Methodsmentioning

confidence: 99%

Conformation-sensitive Antibodies against Alzheimer Amyloid-β by Immunization with a Thioredoxin-constrained B-cell Epitope Peptide

Moretto

Bolchi

Rivetti

et al. 2007

Journal of Biological Chemistry

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Immunotherapy against the amyloid-␤ (A␤) peptide is a valuable potential treatment for Alzheimer disease (AD). An ideal antigen should be soluble and nontoxic, avoid the C-terminally located T-cell epitope of A␤, and yet be capable of eliciting antibodies that recognize A␤ fibrils and neurotoxic A␤ oligomers but not the physiological monomeric species of A␤. We have described here the construction and immunological characterization of a recombinant antigen with these features obtained by tandem multimerization of the immunodominant B-cell epitope peptide A␤1-15 (A␤15) within the active site loop of bacterial thioredoxin (Trx). Chimeric Trx(A␤15) n polypeptides bearing one, four, or eight copies of A␤15 were constructed and injected into mice in combination with alum, an adjuvant approved for human use. All three polypeptides were found to be immunogenic, yet eliciting antibodies with distinct recognition specificities. The anti-Trx(A␤15) 4 antibody, in particular, recognized A␤42 fibrils and oligomers but not monomers and exhibited the same kind of conformational selectivity against transthyretin, an amyloidogenic protein unrelated in sequence to A␤. We have also demonstrated that anti-Trx(A␤15) 4 , which binds to human AD plaques, markedly reduces A␤ pathology in transgenic AD mice. The data indicate that a conformational epitope shared by oligomers and fibrils can be mimicked by a thioredoxin-constrained A␤ fragment repeat and identify Trx(A␤15) 4 as a promising new tool for AD immunotherapy.Antipeptide antibodies are valuable tools for probing structure-function relationships in proteins as well as for therapeutic and diagnostic applications. When immunotherapy is the ultimate goal, the sequence span of the peptide, and thus the nature of the epitope(s) associated with it, as well as the conformational selectivity of the resulting antibodies may also be dictated by safety reasons. This is the case of the amyloid-␤ (A␤) 2 peptide, a major neuropathological hallmark (1-3) and a promising immunotherapeutic target of Alzheimer disease (AD) (4 -7). Following the encouraging results obtained with A␤42 vaccination in transgenic mouse models of AD (8 -10), a Phase II clinical trial utilizing preaggregated A␤42 as an antigen and the QS-21 saponin as an immunoadjuvant (AN-1792 vaccine) was halted due to the occurrence of meningoencephalitis in ϳ6% of treated patients (11-13). T-cell-mediated autoimmunity produced by the C-terminal portion of A␤ (14) along with a predominantly pro-inflammatory (T helper 1) immunoresponse and cross-reactivity with the presumably physiological monomeric forms of A␤ (A␤38 -43 peptides plus the amyloid-␤ precursor protein have been hypothesized as the main causes of these adverse effects (15-17). Of further concern is the fact that not only plaques but also soluble A␤ oligomers should be bound by a therapeutically effective antibody (18 -20). The latter represent an intermediate conformation prior to fibril formation and are presently considered as the most proximate causative agents of . S...

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Section: Methodsmentioning

confidence: 99%

Conformation-sensitive Antibodies against Alzheimer Amyloid-β by Immunization with a Thioredoxin-constrained B-cell Epitope Peptide

Moretto

Bolchi

Rivetti

et al. 2007

Journal of Biological Chemistry

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“…The automated detection of amyloid plaques on large dataset of histological sections remains mainly manual or semiautomatic and based on basic image processing methods using histogram or color image analysis [2]. More recently, an approach using statistical model based on prior operator expertise has been proposed [3]. Nevertheless, most of these approaches remain tedious and time consuming.…”

Section: Introductionmentioning

confidence: 99%

A standardized Method to Automatically Segment Amyloid Plaques in Congo Red Stained Sections from Alzheimer Transgenic Mice

Teboul

Feki

Dubois

et al. 2007

2007 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society

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Automated detection of amyloid plaques (AP) in post mortem brain sections of patients with Alzheimer disease (AD) or in mouse models of the disease is a major issue to improve quantitative, standardized and accurate assessment of neuropathological lesions as well as of their modulation by treatment. We propose a new segmentation method to automatically detect amyloid plaques in Congo Red stained sections based on adaptive thresholds and a dedicated amyloid plaque/tissue modelling. A set of histological sections focusing on anatomical structures was used to validate the method in comparison to expert segmentation.

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“…We have utilised normalisation by tissue area using pixel counting algorithms as this can be utilised for both sampling approaches. The tissue area calculation by pixel counting algorithm is widely used in a variety of scientific fields [42,43]. The process of data normalisation utilised within this study has been described elsewhere [44].…”

Section: Methodsmentioning

confidence: 99%

Chromatographic analysis of age-related changes in mucosal serotonin transmission in the murine distal ileum

Parmar

Fidalgo

Yeoman

et al. 2012

Chemistry Central Journal

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BackgroundIn the upper bowel, alterations in motility and absorption of key nutrients have been observed as part of the normal ageing process. Serotonin (5-HT) is a key signalling molecule in the gastrointestinal tract and is known to influence motility, however little is known of how the ageing process alters 5-HT signalling processes in the bowel.ResultsAn isocratic chromatographic method was able to detect all 5-HT precursors and metabolites. Using extracellular and intracellular sampling approaches, we were able to monitor all key parameters associated with the transmission process. There was no alteration in the levels of tryptophan and 5-HTP between 3 and 18 month old animals. There was a significant increase in the ratio of 5-HT:5-HTP and an increase in intracellular 5-HT between 3 and 18 month old animals suggesting an increase in 5-HT synthesis. There was also a significant increase in extracellular 5-HT with age, suggesting increased 5-HT release. There was an age-related decrease in the ratio of intracellular 5-HIAA:extracellular 5-HT, whilst the amount of 5-HIAA did not change with age. In the presence of an increase in extracellular 5-HT, the lack of an age-related change in 5-HIAA is suggestive of a decrease in re-uptake via the serotonin transporter (SERT).ConclusionsWe have used intracellular and extracellular sampling to provide more insight into alterations in the neurotransmission process of 5-HT during normal ageing. We observed elevated 5-HT synthesis and release and a possible decrease in the activity of SERT. Taken together these changes lead to increased 5-HT availability and may alter motility function and could lead to the changes in adsorption observed in the elderly.

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BioVision: An application for the automated image analysis of histological sections

Cited by 29 publications

References 16 publications

Conformation-sensitive Antibodies against Alzheimer Amyloid-β by Immunization with a Thioredoxin-constrained B-cell Epitope Peptide

Conformation-sensitive Antibodies against Alzheimer Amyloid-β by Immunization with a Thioredoxin-constrained B-cell Epitope Peptide

A standardized Method to Automatically Segment Amyloid Plaques in Congo Red Stained Sections from Alzheimer Transgenic Mice

Chromatographic analysis of age-related changes in mucosal serotonin transmission in the murine distal ileum

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