508 research outputs found
Concordance of c-kit mutational status in matched primary and metastatic cutaneous canine mast cell tumors at baseline
BackgroundMutation analysis of proto-oncogene c-kit (c-kit) is advisable before starting treatment with tyrosine kinase inhibitors in dogs with mast cell tumor (MCT), including those with metastatic disease. Testing is usually performed on primary tumors, assuming that c-kit mutation status does not change in metastasis.Hypothesis/ObjectivesTo give an insight into the mutational processes and to make a recommendation on the use of c-kit mutational analysis in the clinical setting.AnimalsTwenty-one client-owned dogs with metastatic MCT.MethodsDogs undergoing resection or biopsy for both primary and matched metastatic MCT were prospectively enrolled. Total RNA or DNA was extracted from primary MCT and corresponding metastases. Exons 8, 9, and 11 were amplified by PCR and sequenced. Genetic features between primary MCT and metastases were compared. Their correlation with clinicopathologic features was investigated.ResultsConcordance (mutated or wild-type) of mutational status, evaluable in 21 primary and matched metastatic (20 nodal and 1 splenic) MCTs, was 100%. Three new c-kit mutations were identified. No significant correlation was detected between c-kit mutation and clinicopathologic features.Conclusions and Clinical ImportanceProto-oncogene c-kit mutational status is conserved between any primary and its matched secondary tumor, suggesting that both can be used for c-kit mutational testing. Targeted therapies might be also used to treat metastatic disease
Encapsulation of human articular chondrocytes into 3D hydrogel : phenotype and genotype characterization
This chapter is intended to provide a summary of the current materials used in cell encapsulation technology
as well as methods for evaluating the performance of cells encapsulated in a polymeric matrix. In
particular, it describes the experimental procedure to prepare a hydrogel matrix based on natural polymers
for encapsulating and culturing human articular chondrocytes with the interest in cartilage regeneration.
Protocols to evaluate the viability, proliferation, differentiation, and matrix production of
embedded cells are also described and include standard protocols such as the MTT and [3H] Thymidine
assays, reverse transcription polymerase chain reaction (RT-PCR) technique, histology, and immunohistochemistry
analysis. The assessment of cell distribution within the 3D hydrogel construct is also described
using APoTome analysis.(undefined
Novel injectable gel encapsulating human articular chondrocytes for cartilage tissue repair and regeneration
[Excerpt] Cartilage tissue loss, as a result of trauma, congenital disorders and diseases of joints, involving structural damage of articular cartilage surface, is a substantial clinical problem representing a major
challenge for cartilage tissue engineering. The aim of our study was to evaluate the in vitro and in vivo behavior of human articular chondrocytes encapsulated within a novel carrageenan in situ injectable
hydrogel for cartilage tissue engineering and regeneration. Human articular chondrocytes (Hac) were expanded using a well defined serum free medium able to support cell proliferation and
differentiation with high cell chondrogenicity. [...]info:eu-repo/semantics/publishedVersio
Measurement with Persons: A European Network
The European âMeasuring the Impossibleâ Network MINET promotes new research activities in measurement dependent on human perception and/or interpretation. This includes the perceived attributes of products and services, such as quality or desirability, and societal parameters such as security and well-being. Work has aimed at consensus about four âgenericâ metrological issues: (1) Measurement Concepts & Terminology; (2) Measurement Techniques: (3) Measurement Uncertainty; and (4) Decision-making & Impact Assessment, and how these can be applied specificallyto the âMeasurement of Personsâ in terms of âMan as a Measurement Instrumentâ and âMeasuring Man.â Some of the main achievements of MINET include a research repository with glossary; training course; book; series of workshops;think tanks and study visits, which have brought together a unique constellation of researchers from physics, metrology,physiology, psychophysics, psychology and sociology. Metrology (quality-assured measurement) in this area is relativelyunderdeveloped, despite great potential for innovation, and extends beyond traditional physiological metrology in thatit also deals with measurement with all human senses as well as mental and behavioral processes. This is particularlyrelevant in applications where humans are an important component of critical systems, where for instance health andsafety are at stake
Membrane biogenesis. In vitro cleavage, core glycosylation, and integration into microsomal membranes of sindbis virus glycoproteins.
A lymphofollicular microenvironment is required for pathological prion protein deposition in chronically inflamed tissues from scrapie-affected sheep
In sheep scrapie, pathological prion protein (PrPSc) deposition occurs in the lymphoreticular and central nervous systems. We investigated PrPSc distribution in scrapie- affected sheep showing simultaneous evidence of chronic lymphofollicular, lymphoproliferative/non-lymphofollicular,and/or granulomatous inflammations in their mammary gland, lung, and ileum. To do this, PrPSc detection was carried out via immunohistochemistry and Western Blotting techniques, as well as through inflammatory cell immunophenotyping. Expression studies of gene coding for biological factors modulating the hostâs inflammatory response were also carried out. We demonstrated that ectopic PrPSc deposition occurs exclusively in the context of lymphofollicular inflammatory sites, inside newly formed and well-organized lymphoid follicles harboring follicular dendritic cells. On the contrary, no PrPSc deposition was detected in granulomas, even when they were closely located to newly formed lymphoid follicles. A significantly more consistent expression of lymphotoxin α and ÎČ mRNA was detected in lymphofollicular inflammation compared to the other two types, with lymphotoxin α and ÎČ signaling new lymphoid folliclesâ formation and, likely, the occurrence of ectopic PrPSc deposition inside them. Our findings suggest that, in sheep co-affected by scrapie and chronic inflammatory conditions, only newly formed lymphoid follicles provide a suitable micro-environment that supports the scrapie agentâs replication in inflammatory sites, with an increased risk of prion shedding through body secretions/excretions.[...
Indagini istologiche, immunoistochimiche e immunobiochimiche in capre clinicamente sane provenienti da un focolaio di scrapie
Nel corso del 2003, nellâambito del piano di
sorveglianza passiva sulle Encefalopatie
Spongiformi Trasmissibili (TSEs), per la prima
volta in Sardegna, Ăš stata diagnosticata
istologicamente ed immunoistochimicamente la
scrapie in una capra. Il soggetto proveniva da un
gregge nel quale da 2 anni si manifestava una
patologia polimorfa caratterizzata talvolta da
sintomi neurologici e da una mortalitĂ intorno al
20%. Sulla base della legge attualmente in vigore
in Italia si Ăš proceduto allâabbattimento di tutte le
capre presenti in allevamento (n = 93). Durante
lâabbattimento venivano prelevati da ciascun
capo obex, linfonodi retrofaringei e tonsille.
Lâesame istologico dellâobex non evidenziava
quadri lesivi di tipo spongiforme mentre lâesame
immunoistochimico del tessuto nervoso e linfatico
evidenziava la presenza di cinque soggetti nello
stato pre-clinico della malattia
Novel injectable gel (system) as a vehicle for human articular chondrocytes in cartilage tissue regeneration
We developed a novel injectable carrageenan/fibrin/hyaluronic acid-based hydrogel with in situ
gelling properties to be seeded with chondrogenic cells and used for cartilage tissue engineering
applications. We first analysed the distribution within the hydrogel construct and the phenotype of
human articular chondrocytes (HACs) cultured for 3 weeks in vitro. We observed a statistically
significant increase in the cell number during the first 2 weeks and maintenance of cell
viability throughout the cell culture, together with the deposition/formation of a cartilage-specific
extracellular matrix (ECM). Taking advantage of a new in vivo model that allows the integration
between newly formed and preexisting cartilage in immunodeficient mice to be investigated, we
showed that injectable hydrogel seeded with human articular chondrocytes was able to regenerate
and repair an experimentally made lesion in bovine articular cartilage, thus demonstrating the
potential of this novel cell delivery system for cartilage tissue engineering.The authors are grateful to Recco orthopaedic staff members for the collaboration and patients for bioptic material donation as well as to Mrs Daniela Marubbi for histological assistance. This work was supported by funds from the Italian MUR (FIRB-Tissuenet project), the European Union-funded STREP project, HIPPOCRATES (Grant No. NMP3-CT-2003-505758) and the European NoE EXPERTISSUES project (Grant No. NMP3-CT-2004-500283)
Multilingual Autoregressive Entity Linking
We present mGENRE, a sequence-to- sequence system for the Multilingual Entity Linking (MEL) problemâthe task of resolving language-specific mentions to a multilingual Knowledge Base (KB). For a mention in a given language, mGENRE predicts the name of the target entity left-to-right, token-by-token in an autoregressive fashion. The autoregressive formulation allows us to effectively cross-encode mention string and entity names to capture more interactions than the standard dot product between mention and entity vectors. It also enables fast search within a large KB even for mentions that do not appear in mention tables and with no need for large-scale vector indices. While prior MEL works use a single representation for each entity, we match against entity names of as many languages as possible, which allows exploiting language connections between source input and target name. Moreover, in a zero-shot setting on languages with no training data at all, mGENRE treats the target language as a latent variable that is marginalized at prediction time. This leads to over 50% improvements in average accuracy. We show the efficacy of our approach through extensive evaluation including experiments on three popular MEL benchmarks where we establish new state-of-the-art results. Source code available at https://github.com/facebookresearch/GENRE
Stem cell plasticity: time for a reappraisal?
n recent years an increasing number of publications have claimed that adult mammalian stem cells (SC) may be capable of differentiating across tissue lineage boundaries and that this plasticity may represent a novel therapeutic strategy for tissue regeneration. However, after a first phase of excitement, the issue of somatic SC plasticity remains controversial and the therapeutic perspectives are still elusive. In this review, we examine the general mechanisms which govern the function of SC, the identification and functional characterization of adult SC of different tissues and their putative capacity to transdifferentiate into mature cells of different origin. The potential clinical applications of adult SC for regenerative medicine are also discussed in each chapter. The method employed for preparing this review was the informal consensus development. Members of the Working Group on SC met four times and discussed the single points, previously assigned by the Chairman (S.T.), in order to achieve an agreement on different opinions and approve the final manuscript. All the authors of the present review have been working in the field of SC and have contributed original papers to peer-reviewed journals. In addition to the authors' own work, the present review examines articles published in journals covered by the Science Citation Index and Medline
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