scholarly journals Challenges of an Emerging Disease: The Evolving Approach to Diagnosing Devil Facial Tumour Disease

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 27
Author(s):  
Camila Espejo ◽  
Amanda L. Patchett ◽  
Richard Wilson ◽  
A. Bruce Lyons ◽  
Gregory M. Woods
Keyword(s):  
Schwann Cell ◽  
Diagnostic Techniques ◽  
Specific Protein ◽  
Serum Samples ◽  
Phenotypic Differences ◽  
Latent Stage ◽  
Devil Facial Tumour Disease ◽  
Transmissible Cancer ◽  
Fundamental Research ◽  
Cell Phenotypes

Devil Facial Tumour Disease (DFTD) is an emerging infectious disease that provides an excellent example of how diagnostic techniques improve as disease-specific knowledge is generated. DFTD manifests as tumour masses on the faces of Tasmanian devils, first noticed in 1996. As DFTD became more prevalent among devils, karyotyping of the lesions and their devil hosts demonstrated that DFTD was a transmissible cancer. The subsequent routine diagnosis relied on microscopy and histology to characterise the facial lesions as cancer cells. Combined with immunohistochemistry, these techniques characterised the devil facial tumours as sarcomas of neuroectodermal origin. More sophisticated molecular methods identified the origin of DFTD as a Schwann cell, leading to the Schwann cell-specific protein periaxin to discriminate DFTD from other facial lesions. After the discovery of a second facial cancer (DFT2), cytogenetics and the absence of periaxin expression confirmed the independence of the new cancer from DFT1 (the original DFTD). Molecular studies of the two DFTDs led to the development of a PCR assay to differentially diagnose the cancers. Proteomics and transcriptomic studies identified different cell phenotypes among the two DFTD cell lines. Phenotypic differences were also reflected in proteomics studies of extracellular vesicles (EVs), which yielded an early diagnostic marker that could detect DFTD in its latent stage from serum samples. A mesenchymal marker was also identified that could serve as a serum-based differential diagnostic. The emergence of two transmissible cancers in one species has provided an ideal opportunity to better understand transmissible cancers, demonstrating how fundamental research can be translated into applicable and routine diagnostic techniques.

scholarly journals Cathelicidin-3 associated with serum extracellular vesicles enables early diagnosis of a transmissible cancer

2021 ◽  
Author(s):  
Camila Espejo ◽  
Richard Wilson ◽  
Ruth J. Pye ◽  
Julian C. Ratcliffe ◽  
Manuel Ruiz-Aravena ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Biomarker Discovery ◽  
Extracellular Vesicle ◽  
Conservation Strategies ◽  
Tasmanian Devil ◽  
Serum Samples ◽  
Visual Identification ◽  
Devil Facial Tumour Disease ◽  
Transmissible Cancer ◽  
One Year

AbstractThe identification of practical early diagnosis biomarkers is a cornerstone of improved prevention and treatment of cancers. Such a case is devil facial tumour disease (DFTD), a highly lethal transmissible cancer afflicting virtually an entire species, the Tasmanian devil (Sarcophilus harrisii). Despite a latent period that can exceed one year, to date DFTD diagnosis requires visual identification of tumour lesions. To enable earlier diagnosis, which is essential for the implementation of effective conservation strategies, we analysed the extracellular vesicle (EV) proteome of 87 Tasmanian devil serum samples. The antimicrobial peptide cathelicidin-3 (CATH3) was enriched in serum EVs of both devils with clinical DFTD (87.9% sensitivity and 94.1% specificity) and devils with latent infection (i.e., collected while overtly healthy, but 3-6 months before subsequent DFTD diagnosis; 93.8% sensitivity and 94.1% specificity). As antimicrobial peptides can play a variety of roles in the cancer process, our results suggest that the specific elevation of serum EV-associated CATH3 may be mechanistically involved in DFTD pathogenesis. This EV-based approach to biomarker discovery is directly applicable to improving understanding and diagnosis of a broad range of diseases in other species, and these findings directly enhance the capacity of conservation strategies to ensure the viability of the imperilled Tasmanian devil population.

scholarly journals A ten-year follow-up of human leptospirosis in Uruguay: an unresolved health problem

2012 ◽  
Vol 54 (2) ◽  
pp. 69-76 ◽  
Author(s):  
Felipe Schelotto ◽  
Elba Hernández ◽  
Sabina González ◽  
Alicia Del Monte ◽  
Silvana Ifran ◽  
...  
Keyword(s):  
Young Male ◽  
Standard Technique ◽  
Signs And Symptoms ◽  
Complete Recovery ◽  
Laboratory Diagnosis ◽  
Diagnostic Techniques ◽  
Clinical Feature ◽  
Serum Samples ◽  
Microbiological Methods ◽  
Major Factors

Leptospira spp. are delicate bacteria that cannot be studied by usual microbiological methods. They cause leptospirosis, a zoonotic disease transmitted to humans through infected urine of wild or domestic animals. We studied the incidence of this disease in the Uruguayan population, its epidemiologic and clinical features, and compared diagnostic techniques. After examining 6,778 suspect cases, we estimated that about 15 infections/100,000 inhabitants occurred yearly, affecting mainly young male rural workers. Awareness about leptospirosis has grown among health professionals, and its lethality has consequently decreased. Bovine infections were probably the principal source of human disease. Rainfall volumes and floods were major factors of varying incidence. Most patients had fever, asthenia, myalgias or cephalalgia, with at least one additional abnormal clinical feature. 30-40% of confirmed cases presented abdominal signs and symptoms, conjunctival suffusion and altered renal or urinary function. Jaundice was more frequent in patients aged > 40 years. Clinical infections followed an acute pattern and their usual outcome was complete recovery. Laboratory diagnosis was based on indirect micro-agglutination standard technique (MAT). Second serum samples were difficult to obtain, often impairing completion of diagnosis. Immunofluorescence was useful as a screening test and for early detection of probable infections.

scholarly journals EVALUATION OF ELEVEN IMMUNOCHROMATOGRAPHIC ASSAYS FOR SARS-CoV-2 DETECTION: INVESTIGATING DENGUE CROSS-REACTION

2020 ◽  
Author(s):  
Beatriz Araujo Oliveira ◽  
Lea Campos de Oliveira ◽  
Franciane Mendes de Oliveira ◽  
Geovana Maria Pereira ◽  
Regina Maia de Souza ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
High Sensitivity ◽  
Diagnostic Techniques ◽  
Cross Reactivity ◽  
Cross Reaction ◽  
List Type ◽  
Rt Pcr ◽  
Serum Samples ◽  
Igm Antibodies ◽  
Good Agreement

AbstractBackgroundCOVID-19 disease (Coronavirus disease 2019) caused by SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) is widespread worldwide, affecting more than 11 million people globally (July 6th, 2020). Diagnostic techniques have been studied in order to contain the pandemic. Immunochromatographic (IC) assays are feasible and low cost alternative for monitoring the spread of COVID-19 in the population.MethodsHere we evaluate the sensitivity and specificity of eleven different immunochromatographic tests in 98 serum samples from confirmed cases of COVID-19 through RT-PCR and 100 negative serum samples from blood donors collected in February 2019. Considering the endemic situation of Dengue in Brazil, we also evaluated the cross-reactivity with Dengue using 20 serum samples from patients with confirmed diagnosis for Dengue collected in early 2019 through four different tests.ResultsOur results demonstrated agreement between immunochromatographic assays and RT-PCR, especially after 10 days since the onset of symptoms. The evaluation of IgG and IgM antibodies combined demonstrated a strong level of agreement (0.85) of IC assays and RT-PCR. It was observed cross-reactivity between Dengue and COVID-19 using four different IC assays for COVID-19 diagnosis. The specificity of IC assays to detected COVID-19 IgM antibodies using Dengue serum samples varied from 80% to 85%; the specificity of IgG detection was 100% and total antibody was 95%.ConclusionsWe found high sensitivity, specificity and good agreement of IC assays, especially after 10 days onset of symptoms. However, we detected cross-reactivity between Dengue and COVID-19 mainly with IgM antibodies demonstrating the need for better studies about diagnostic techniques for these diseases.HighlightsImmunochromatographic assays demonstrated high sensitivity and specificity and good agreement with the gold-standard RT-PCR;Increase in sensitivity and specificity of assays using samples collected after the 10th day of symptoms;Cross-reaction with Dengue serology in evaluation of IgM.

scholarly journals Antibody titers measured by commercial assays are correlated with neutralizing antibody titers calibrated by international standards

2021 ◽  
Author(s):  
Yu-An Kung ◽  
Chung-Guei Huang ◽  
Sheng-Yu Huang ◽  
Kuan-Ting Liu ◽  
Peng-Nien Huang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Diagnostic Techniques ◽  
International Standards ◽  
World Health ◽  
Serum Samples ◽  
Antibody Titers ◽  
Health Organization

The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.

scholarly journals Infectious disease and sickness behaviour: tumour progression affects interaction patterns and social network structure in wild Tasmanian devils

2020 ◽  
Vol 287 (1940) ◽  
pp. 20202454
Author(s):  
David G. Hamilton ◽  
Menna E. Jones ◽  
Elissa Z. Cameron ◽  
Douglas H. Kerlin ◽  
Hamish McCallum ◽  
...  
Keyword(s):  
Social Network ◽  
Cancer Progression ◽  
Population Change ◽  
Tumour Progression ◽  
Interaction Patterns ◽  
Social Network Structure ◽  
Devil Facial Tumour Disease ◽  
The Social ◽  
Transmissible Cancer ◽  
Host Behaviour

Infectious diseases, including transmissible cancers, can have a broad range of impacts on host behaviour, particularly in the latter stages of disease progression. However, the difficulty of early diagnoses makes the study of behavioural influences of disease in wild animals a challenging task. Tasmanian devils ( Sarcophilus harrisii ) are affected by a transmissible cancer, devil facial tumour disease (DFTD), in which tumours are externally visible as they progress. Using telemetry and mark–recapture datasets, we quantify the impacts of cancer progression on the behaviour of wild devils by assessing how interaction patterns within the social network of a population change with increasing tumour load. The progression of DFTD negatively influences devils' likelihood of interaction within their network. Infected devils were more active within their network late in the mating season, a pattern with repercussions for DFTD transmission. Our study provides a rare opportunity to quantify and understand the behavioural feedbacks of disease in wildlife and how they may affect transmission and population dynamics in general.

scholarly journals Genistein attenuated gastric inflammation and apoptosis in Helicobacter pylori-induced gastropathy in rats

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Prasong Siriviriyakul ◽  
Duangporn Werawatganon ◽  
Nisarat Phetnoo ◽  
Kanjana Somanawat ◽  
Tanittha Chatsuwan ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Inflammatory Mediators ◽  
Kinase Inhibitor ◽  
Specific Protein ◽  
Control Group ◽  
Sprague Dawley ◽  
Serum Samples ◽  
Necrosis Factor Alpha ◽  
Tunel Reaction ◽  
H Pylori

Abstract Background Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis, peptic ulcer diseases and cancer. Genistein (4′,5,7-trihydroxyisoflavone), a tyrosine-specific-protein kinase inhibitor, has been shown to exert an anti-inflammatory property. The aim of this study was to examine the treatment effects of genistein and its mechanisms in rats with H. pylori infection. Methods Eighteen male Sprague-Dawley rats were divided into three groups (6 rats per group): (1) control group (Con); (2) H. pylori infected group (HP): the rats were inoculated with H. pylori (108− 1010 CFU/mL; 1 mL/rat.) for 3 consecutive days; and (3) HP + genistein group (HP + Gen): the rats were inoculated with H. pylori as above. Then, they were gavaged with genistein (16 mg/kg BW) for 14 days. Gastric tissue was used for the determination of nuclear factor (NF)-κB expression by immunohistochemistry (IHC), degree of apoptosis by the terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) reaction, and histopathology. Serum samples were used to measure the levels of tumor necrosis factor-alpha (TNF-α) and cytokine-induced neutrophil chemoattractant-1 (CINC-1). Results Rats in the HP group had significantly higher levels of pro-inflammatory mediators, NF-κB expression and apoptotic cells when compared with the Con group, and these markers significantly decreased in HP + Gen group when compared with the HP group. The histopathology of HP group showed moderate gastric inflammation and many HP colonization. Gastric pathology in HP + Gen group demonstrated the attenuation of inflammatory cell infiltration and H. pylori colonization. Conclusion Genistein exerted its gastroprotective effects through the reduction of pro-inflammatory mediators, nuclear receptor NF-κB expression and gastric mucosal apoptosis in rats with H. pylori-induced gastropathy.

scholarly journals Detection of pregnancy in sheep using an ELISA for pregnancy-specific protein B

2018 ◽  
Vol 66 (2) ◽  
pp. 329-336
Author(s):  
Tímea Milisits-Németh ◽  
Orsolya Gabriella Balogh ◽  
István Egerszegi ◽  
László Kern ◽  
R. Garth Sasser ◽  
...  
Keyword(s):  
Accurate Method ◽  
Specific Protein ◽  
Economic Benefits ◽  
Seasonal Breeding ◽  
Serum Samples ◽  
Mating Period ◽  
Blood Samples ◽  
Sheep Production ◽  
Protein B

The early detection of pregnancy and the determination of fetal numbers have economic benefits in sheep production because of the seasonal breeding patterns where missing a breeding opportunity means the loss of one productive year. The purpose of this study was to evaluate the efficacy of the B6-HRP ELISA for ovine pregnancy-specific protein B (oPSPB) measurement in the detection of pregnancy and estimation of fetal numbers in different sheep breeds. BioPRYN® ELISA assay kit was used for the detection of pregnancy in the experimental animals. Ninety-three ewes of three breeds (British Milksheep – BM, Lacaune – L and Transylvanian Racka – TR), each from three farms in Hungary, were included in the study. BM and L ewes were artificially inseminated (AI). Thirty-five days after AI, all ewes were examined by transabdominal ultrasound. The TR flock was mated naturally over a six-week period. At the end of the mating period, the ewes were similarly examined by ultrasound. Blood samples were taken from all pregnant ewes twice (35 and 65 days after AI), and serum samples were assayed by the BioPRYN test. It can be concluded that the detection of serum PSPB by ELISA is a much easier, safer, less expensive and highly accurate method for the detection of ovine pregnancy. Although some breed-related differences were detectable at 35 and 65 days post breeding, no differences in oPSPB levels were found in pregnant ewes carrying different numbers of fetuses.

scholarly journals Insulin-Like Growth Factor I (IGF-I) Receptor Overexpression Abolishes the IGF Requirement for Differentiation and Induces a Ligand-Dependent Transformed Phenotype in C2 Inducible Myoblasts*

Endocrinology ◽  
1997 ◽  
Vol 138 (12) ◽  
pp. 5210-5219 ◽  
Author(s):  
Magali Navarro ◽  
Bruno Barenton ◽  
Veronique Garandel ◽  
Juergen Schnekenburger ◽  
Henri Bernardi
Keyword(s):  
Growth Factors ◽  
Troponin T ◽  
Soft Agar ◽  
Specific Protein ◽  
Eukaryotic Expression ◽  
Type I ◽  
Phenotypic Differences ◽  
Human Type ◽  
Type I Igf Receptor ◽  
Igf I

Abstract Insulin-like growth factors (IGFs) stimulate both proliferation and differentiation of myogenic cell lines, and these actions are mostly mediated through the type I IGF receptor (type I IGF-R). To further investigate the role of this receptor in phenotypic characteristics of C2 murine myoblasts, we overexpressed the human type I IGF-R in the inducible clone of C2 cells, which requires IGFs in the differentiation medium to undergo terminal differentiation. Inducible myoblasts were transfected with either the eukaryotic expression vector pNTK or pNTK containing the human type I IGF-R complementary DNA, and we isolated two clones named Ind-Neo and Ind-R, respectively. Binding and autophosphorylation experiments indicate that Ind-R cells express about 10 times as much type I IGF-R compared with Ind-Neo control cells and that the transfected type I IGF-R is functional in Ind-R cells. We show that overexpression of the human type I IGF-R makes inducible myoblasts able to differentiate spontaneously, as assessed by expression of the myogenic transcription factors MyoD and myogenin, detection of the muscle-specific protein troponin T, and myotube formation. Moreover, when exposed to IGF-I, Ind-R cells lose contact inhibition, grow in the presence of a low level of growth factors and form colonies in soft agar, which is characteristic of a ligand-dependent transformed phenotype. It emerges from this study that 1) the type I IGF-R is strongly involved in the phenotypic differences between inducible and permissive cells with respect to the differentiation program; and 2) overexpression causes this receptor to act as a ligand-dependent transforming protein in muscle cells. We suggest that type I IGF-R abundance and level of activation may determine the efficiency of the autocrine mode of action of IGFs and discriminate their biological functions.

A Modified Approach to Inducing Bone Marrow Stromal Cells to Differentiate into Cells with Mature Schwann Cell Phenotypes

2016 ◽  
Vol 25 (4) ◽  
pp. 347-359 ◽  
Author(s):  
Yutian Liu ◽  
Jianghai Chen ◽  
Wei Liu ◽  
Xiaocheng Lu ◽  
Zhenyu Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Schwann Cell ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Cell Phenotypes

scholarly journals Contemporary and historical selection in Tasmanian devils ( Sarcophilus harrisii ) support novel, polygenic response to transmissible cancer

2021 ◽  
Vol 288 (1951) ◽  
pp. 20210577
Author(s):  
Amanda R. Stahlke ◽  
Brendan Epstein ◽  
Soraia Barbosa ◽  
Mark J. Margres ◽  
Austin H. Patton ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Rapid Evolution ◽  
Gene Sets ◽  
Devil Facial Tumour Disease ◽  
Evolutionary Response ◽  
Recent Emergence ◽  
Transmissible Cancer ◽  
Or Gene ◽  
Genomic Regions ◽  
Sarcophilus Harrisii

Tasmanian devils ( Sarcophilus harrisii ) are evolving in response to a unique transmissible cancer, devil facial tumour disease (DFTD), first described in 1996. Persistence of wild populations and the recent emergence of a second independently evolved transmissible cancer suggest that transmissible cancers may be a recurrent feature in devils. Here, we compared signatures of selection across temporal scales to determine whether genes or gene pathways under contemporary selection (six to eight generations) have also been subject to historical selection (65–85 Myr). First, we used targeted sequencing, RAD-capture, in approximately 2500 devils in six populations to identify genomic regions subject to rapid evolution. We documented genome-wide contemporary evolution, including 186 candidate genes related to cell cycling and immune response. Then we used a molecular evolution approach to identify historical positive selection in devils compared to other marsupials and found evidence of selection in 1773 genes. However, we found limited overlap across time scales, with only 16 shared candidate genes, and no overlap in enriched functional gene sets. Our results are consistent with a novel, multi-locus evolutionary response of devils to DFTD. Our results can inform conservation by identifying high priority targets for genetic monitoring and guiding maintenance of adaptive potential in managed populations.

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