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Frontiers in Veterinary Science 2021Chronic wasting disease (CWD) is a transmissible prion disorder, primarily affecting free-ranging and captive cervids in North America (United States and Canada), South...
Chronic wasting disease (CWD) is a transmissible prion disorder, primarily affecting free-ranging and captive cervids in North America (United States and Canada), South Korea, and Europe (Finland, Norway, and Sweden). Current diagnostic methods used in the United States for detection of CWD in hunter harvested deer involve demonstration of the causal misfolded prion protein (PrP) in the obex or retropharyngeal lymph nodes (RLNs) using an antigen detection ELISA as a screening tool, followed by a confirmation by the gold standard method, immunohistochemistry (IHC). Real-time quaking-induced conversion (RT-QuIC) assay is a newer approach that amplifies misfolded CWD prions and has facilitated CWD prion detection in a variety of tissues, body fluids, and excreta. The current study was undertaken to compare ELISA, IHC, and RT-QuIC on RLNs ( = 1,300 animals) from white-tailed deer (WTD) in Michigan. In addition, prescapular, prefemoral and popliteal lymph nodes collected from a small subset ( = 7) of animals were tested. Lastly, the location of the positive samples within Michigan was documented and the percentage of CWD positive RLNs was calculated by sex and age. ELISA and RT-QuIC detected PrP in 184 and 178 out of 1,300 RLNs, respectively. Of the 184 ELISA positive samples, 176 were also IHC positive for CWD. There were seven discordant results when comparing IHC and ELISA. RT-QuIC revealed that six of the seven samples matched the IHC outcomes. One RLN was negative by IHC, but positive by ELISA and RT-QuIC. RT-QuIC, IHC, and ELISA also detected PrP in prescapular, prefemoral and popliteal lymph nodes. CWD infection heterogeneities were observed in different age and sex groups, with young males having higher CWD prevalence. All, except one, CWD positive RLNs analyzed were from ten Counties geographically located in the West Michigan region of the Lower Peninsula. Taken together, we show evidence that the RT-QuIC assay is comparable to ELISA and IHC and could be helpful for routine CWD detection in surveillance programs. RT-QuIC also demonstrated that CWD prions are distributed across lymph nodes in a variety of anatomic locations. A multi-laboratory validation on blinded sample panels is underway and is likely to help to provide insight into the variability (lab-to-lab), analytical sensitivity, and specificity of gold standard diagnostics vs. RT-QuIC assay.
PubMed: 35118153
DOI: 10.3389/fvets.2021.824815 -
G3 (Bethesda, Md.) Jul 2022Despite implementation of enhanced management practices, chronic wasting disease in US white-tailed deer (Odocoileus virginianus) continues to expand geographically....
Despite implementation of enhanced management practices, chronic wasting disease in US white-tailed deer (Odocoileus virginianus) continues to expand geographically. Herein, we perform the largest genome-wide association analysis to date for chronic wasting disease (n = 412 chronic wasting disease-positive; n = 758 chronic wasting disease-nondetect) using a custom Affymetrix Axiom single-nucleotide polymorphism array (n = 121,010 single-nucleotide polymorphisms), and confirm that differential susceptibility to chronic wasting disease is a highly heritable (h2= 0.611 ± 0.056) polygenic trait in farmed US white-tailed deer, but with greater trait complexity than previously appreciated. We also confirm PRNP codon 96 (G96S) as having the largest-effects on risk (P ≤ 3.19E-08; phenotypic variance explained ≥ 0.025) across 3 US regions (Northeast, Midwest, South). However, 20 chronic wasting disease-positive white-tailed deer possessing codon 96SS genotypes were also observed, including one that was lymph node and obex positive. Beyond PRNP, we also detected 23 significant single-nucleotide polymorphisms (P-value ≤ 5E-05) implicating ≥24 positional candidate genes; many of which have been directly implicated in Parkinson's, Alzheimer's and prion diseases. Genotype-by-environment interaction genome-wide association analysis revealed a single-nucleotide polymorphism in the lysosomal enzyme gene ARSB as having the most significant regional heterogeneity of effects on chronic wasting disease (P ≤ 3.20E-06); with increasing copy number of the minor allele increasing susceptibility to chronic wasting disease in the Northeast and Midwest; but with opposite effects in the South. In addition to ARSB, 38 significant genotype-by-environment single-nucleotide polymorphisms (P-value ≤ 5E-05) were also detected, thereby implicating ≥ 36 positional candidate genes; the majority of which have also been associated with aspects of Parkinson's, Alzheimer's, and prion diseases.
Topics: Animals; Alzheimer Disease; Codon; Deer; Gene-Environment Interaction; Genome-Wide Association Study; Genotype; Parkinson Disease; Prion Diseases; Wasting Disease, Chronic; Polymorphism, Single Nucleotide
PubMed: 35536181
DOI: 10.1093/g3journal/jkac109 -
Respiratory Physiology & Neurobiology Dec 2017The modulation of cough by microinjections of codeine in 3 medullary regions, the solitary tract nucleus rostral to the obex (rNTS), caudal to the obex (cNTS) and the...
The modulation of cough by microinjections of codeine in 3 medullary regions, the solitary tract nucleus rostral to the obex (rNTS), caudal to the obex (cNTS) and the lateral tegmental field (FTL) was studied. Experiments were performed on 27 anesthetized spontaneously breathing cats. Electromyograms (EMG) were recorded from the sternal diaphragm and expiratory muscles (transversus abdominis and/or obliquus externus; ABD). Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. Bilateral microinjections of codeine (3.3 or 33mM, 54±16nl per injection) in the cNTS had no effect on cough, while those in the rNTS and in the FTL reduced coughing. Bilateral microinjections into the rNTS (3.3mM codeine, 34±1 nl per injection) reduced the number of cough responses by 24% (P<0.05), amplitudes of diaphragm EMG by 19% (P<0.01), of ABD EMG by 49% (P<0.001) and of expiratory esophageal pressure by 56% (P<0.001). Bilateral microinjections into the FTL (33mM codeine, 33±3 nl per injection) induced reductions in cough expiratory as well as inspiratory EMG amplitudes (ABD by 60% and diaphragm by 34%; P<0.01) and esophageal pressure amplitudes (expiratory by 55% and inspiratory by 26%; P<0.001 and 0.01, respectively). Microinjections of vehicle did not significantly alter coughing. Breathing was not affected by microinjections of codeine. These results suggest that: 1) codeine acts within the rNTS and the FTL to reduce cough in the cat, 2) the neuronal circuits in these target areas have unequal sensitivity to codeine and/or they have differential effects on spatiotemporal control of cough, 3) the cNTS has a limited role in the cough suppression induced by codeine in cats.
Topics: Abdominal Muscles; Animals; Antitussive Agents; Blood Pressure; Cats; Codeine; Cough; Diaphragm; Disease Models, Animal; Dose-Response Relationship, Drug; Electromyography; Female; Male; Medulla Oblongata; Microinjections; Respiratory Muscles
PubMed: 28778649
DOI: 10.1016/j.resp.2017.07.011 -
Veterinary Microbiology Oct 2014Sheep scrapie is a transmissible spongiform encephalopathy (TSE), progressive and fatal neurodegenerative diseases of the central nervous system (CNS) linked to the...
Sheep scrapie is a transmissible spongiform encephalopathy (TSE), progressive and fatal neurodegenerative diseases of the central nervous system (CNS) linked to the accumulation of misfolded prion protein, PrP(Sc). New Zealand Cheviot sheep, homozygous for the VRQ genotype of the PRNP gene are most susceptible with an incubation period of 193 days with SSBP/1 scrapie. However, the earliest time point that PrP(Sc) can be detected in the CNS is 125 days (D125). The aim of this study was to quantify changes to the transcriptome of the thalamus and obex (medulla) at times immediately before (D75) and after (D125) PrP(Sc) was detected. Affymetrix gene arrays were used to quantify gene expression in the thalamus and Illumina DGE-tag profiling for obex. Ingenuity Pathway Analysis was used to help describe the biological processes of scrapie pathology. Neurological disease and Cancer were common Bio Functions in each tissue at D75; inflammation and cell death were major processes at D125. Several neurological receptors were significantly increased at D75 (e.g. CHRNA6, GRM1, HCN2), which might be clues to the molecular basis of psychiatric changes associated with TSEs. No genes were significantly differentially expressed at both D75 and D125 and there was no progression of events from earlier to later time points. This implies that there is no simple linear progression of pathological or molecular events. There seems to be a step-change between D75 and D125, correlating with the detection of PrP(Sc), resulting in the involvement of different pathological processes in later TSE disease.
Topics: Animals; Brain; Disease Progression; Gene Expression Profiling; Genotype; Microarray Analysis; New Zealand; PrPSc Proteins; Scrapie; Sheep, Domestic; Time Factors; Transcriptome
PubMed: 25183238
DOI: 10.1016/j.vetmic.2014.07.026 -
Journal of Wildlife Diseases Jan 2022Throughout North America, chronic wasting disease (CWD) has emerged as perhaps the greatest threat to wild cervid populations, including white-tailed deer (WTD;...
COMPARISON OF CHRONIC WASTING DISEASE DETECTION METHODS AND PROCEDURES: IMPLICATIONS FOR FREE-RANGING WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) SURVEILLANCE AND MANAGEMENT.
Throughout North America, chronic wasting disease (CWD) has emerged as perhaps the greatest threat to wild cervid populations, including white-tailed deer (WTD; Odocoileus virginianus). White-tailed deer are the most sought-after big game species across North America with populations of various subspecies in nearly all Canadian provinces, the contiguous US, and Mexico. Documented CWD cases have dramatically increased across the WTD range since the mid-1990s, including in Minnesota, US. CWD surveillance in free-ranging WTD and other cervid populations mainly depends upon immunodetection methods such as immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) on medial retropharyngeal lymph nodes and obex. More recent technologies centered on prion protein amplification methods of detection have shown promise as more sensitive and rapid CWD diagnostic tools. Here, we used blinded samples to test the efficacy of real-time quaking-induced conversion (RT-QuIC) in comparison to ELISA for screening tissues collected in 2019 from WTD in southeastern Minnesota, where CWD has been routinely detected since 2016. Our results support previous findings that RT-QuIC is a more sensitive tool for CWD detection than current antibody-based methods. Additionally, a CWD testing protocol that includes multiple lymphoid tissues (e.g., medial retropharyngeal lymph node, parotid lymph node, and palatine tonsil) per animal can effectively identify a greater number of CWD detections in a WTD population than a single sample type (e.g., medial retropharyngeal lymph nodes). These results show that the variability of CWD pathogenesis, sampling protocol, and testing platform must be considered for the effective detection and management of CWD throughout North America.
Topics: Animals; Canada; Deer; Electron Spin Resonance Spectroscopy; Wasting Disease, Chronic
PubMed: 34695201
DOI: 10.7589/JWD-D-21-00033 -
Multiple Sclerosis and Related Disorders May 2019Neuromyelitis Optica (NMO) is an autoimmune astrocytopathic disorder due to AQP4 antibodies.
BACKGROUND
Neuromyelitis Optica (NMO) is an autoimmune astrocytopathic disorder due to AQP4 antibodies.
OBJECTIVES
To analyse clinical, neuroimaging features in NMO patients and assess the efficacy of various therapeutics.
METHODS
AQP4+ve NMO patients were diagnosed based on consensus diagnostic criteria.
RESULTS
101 AQP4+ve NMO patients were seen with female (90) predominance. Adult population (71.3%) formed the larger group followed by pediatric (19.8%) and late-onset (8.9%). Myelopathy (36.2%) was most commonly seen followed by optic neuritis (19.1%), brainstem (17.1%), opticomyelopathy (16.1%), area postrema involvement (10.5%) and encephalopathy (1%). Encephalopathy and brainstem/cerebellar involvement were most common in pediatric population while opticomyelopathy was more common in late-onset patients. Hyperintensities of lower medulla was seen in 67.3% subjects and 49.5% had involvement of obex. Differential T2 hyperintensity of the long segment myelitis was found in 30.7%. Plasmapheresis was given in 71 subjects followed by maintenance therapy. Most of them showed significant improvement with EDSS score of 1 in 30.7%.
CONCLUSIONS
Clinical manifestations in AQP4+ve NMO patients may vary depending on the age at onset of illness. MRI features affecting cervicomedullary junction, obex, differential T2 hyperintensities of the spinal cord may form a useful diagnostic clue. Plasmapheresis is helpful in achieving remission along with immunomodulation.
Topics: Adolescent; Adult; Aged; Aquaporin 4; Autoantibodies; Child; Female; Humans; Immunosuppressive Agents; India; Magnetic Resonance Imaging; Male; Middle Aged; Neuromyelitis Optica; Plasmapheresis; Severity of Illness Index; Young Adult
PubMed: 30743086
DOI: 10.1016/j.msard.2019.01.032 -
The Journal of Veterinary Medical... Nov 2021There has been no report on Chronic wasting disease (CWD) cases in Japan to date; however, there is concern about the geographic spread of CWD. To clarify the CWD status...
There has been no report on Chronic wasting disease (CWD) cases in Japan to date; however, there is concern about the geographic spread of CWD. To clarify the CWD status in Japan, we conducted CWD monitoring using real-time quaking-induced conversion (RT-QuIC) assay which can detect the low level of CWD prions. A total of 690 obex samples collected from sika deer and Reeves's muntjac in Hokkaido and Honshu was tested for CWD prions. No CWD-positive cases were found, suggesting that CWD is nonexistent in Japan. Our results also indicate that RT-QuIC assay is useful for continuous monitoring of CWD. Furthermore, nucleotide sequence analysis of the PrP gene revealed sika deer in Japan harbor CWD susceptible allele.
Topics: Animals; Biological Assay; Deer; Japan; Prions; Wasting Disease, Chronic
PubMed: 34556606
DOI: 10.1292/jvms.21-0368 -
Journal of Veterinary Diagnostic... Nov 2014Vascular hamartomas are non-neoplastic developmental anomalies of vessels. Cases of cerebral vascular hamartomas have been previously reported in dogs and cats. A...
Vascular hamartomas are non-neoplastic developmental anomalies of vessels. Cases of cerebral vascular hamartomas have been previously reported in dogs and cats. A 4-week-old Freiberger foal had shown persistent problems with breathing and swallowing since birth, and bilateral laryngeal paralysis was diagnosed. The foal subsequently developed left sided facial nerve paralysis and a secondary corneal ulcer in the left eye. Necropsy revealed a pinkish mass in the obex region of the brain. The mass was further investigated by histology and immunohistochemistry. Histologically, the mass consisted of many thin-walled, blood-filled vascular structures of variable diameter involving the white matter of the obex. The lining cells were immunohistochemically positive for factor VIII (von Willebrand factor) interpreted as endothelial cells. The endothelial lining showed also variable immunoreactivity for smooth muscle actin and vimentin. Normal neural parenchyma labeled with antibodies directed against glial fibrillary acidic protein and neuron-specific enolase was present between the vascular proliferations. A diagnosis of focal vascular hamartoma in the obex was made. The development of clinical signs is attributed to the compression of the surrounding neural parenchyma.
Topics: Animals; Animals, Newborn; Brain Diseases; Fatal Outcome; Fourth Ventricle; Hamartoma; Horse Diseases; Horses; Immunohistochemistry
PubMed: 25261460
DOI: 10.1177/1040638714548681 -
Veterinary Research Oct 2016Scrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform encephalopathies (TSE's) affecting sheep and goats. Susceptibility of goats to scrapie is...
Scrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform encephalopathies (TSE's) affecting sheep and goats. Susceptibility of goats to scrapie is influenced by polymorphisms of the prion protein gene (PRNP) of the host. Five polymorphisms are associated with reduced susceptibility to TSE's. In the study presented here caprine samples from a scrapie eradication program on Cyprus were genotyped and further characterized using BioRad TeSeE rapid test, histological, immunohistochemical and biochemical methods. In total 42 goats from 20 flocks were necropsied from which 25 goats showed a positive result in the rapid test, a spongiform encephalopathy and an accumulation of pathological prion protein (PrP) in the obex. PrP deposits were demonstrated in the placenta, peripheral nervous and lymphoreticular system. Two animals showed PrP-accumulations in peripheral tissues only. By discriminatory immunoblots a scrapie infection could be confirmed for all cases. Nevertheless, slight deviations in the glycosylation pattern might indicate the presence of different scrapie strains. Furthermore scrapie samples from goats in the current study demonstrated less long term resistance to proteinase K than ovine or caprine BSE control samples. Reduced scrapie susceptibility according to the PRNP genotype was demonstrated (Fishers Exact test, p < 0.05) for the goats with at least one polymorphism (p = 0.023) at the six codons examined and in particular for those with polymorphisms at codon 146 (p = 0.016). This work characterizes scrapie in goats having implications for breeding and surveillance strategies.
Topics: Animals; Cyprus; Female; Goat Diseases; Goats; Prion Diseases; Prion Proteins
PubMed: 27716411
DOI: 10.1186/s13567-016-0379-0 -
Veterinary Research Jun 2020In a study originally designed to find potential risk factors for bovine spongiform encephalopathy (BSE) we examined tissues from 403 Holstein Frisian cattle in total....
In a study originally designed to find potential risk factors for bovine spongiform encephalopathy (BSE) we examined tissues from 403 Holstein Frisian cattle in total. These included 20 BSE cattle and their 236 birth- and feeding cohort animals plus 32 offspring, 103 age, breed and district-matched control cattle and further twelve cattle with neurological signs. In addition to the obex, we examined the celiac ganglion, cervical cranial ganglion, trigeminal ganglion and proximal ganglion of the vagus nerve using histological techniques. Unexpectedly, we found a high number of neurofibroma, a benign peripheral nerve sheath tumor consisting of Schwann cells, fibroblasts and perineural cells. The neurofibroma were present only in the celiac ganglion and found during histologic examination. With a frequency of 9.91% in BSE cattle and their cohorts (case animals) and 9.09% in the age, breed and district matched control animals there seems to be no correlation between the occurrence of BSE and neurofibroma. Benign peripheral nerve sheath tumors have been described more often in cattle than in other domestic animals. Usually, they are incidental macroscopic findings in the thoracic ganglia during meat inspection. To our knowledge, there are no previous systematic histologic studies including bovine celiac ganglia at all. The high incidence of celiac ganglia neurofibroma may play a role in the frequently occurring abomasal displacements in Holstein Frisian cattle as the tumors might cause a gastrointestinal motility disorder. At present a genetic predisposition for these neoplasms cannot be ruled out.
Topics: Animals; Cattle; Cattle Diseases; Cohort Studies; Female; Ganglia, Sympathetic; Germany; Incidence; Male; Neurofibroma; Risk Factors
PubMed: 32552868
DOI: 10.1186/s13567-020-00800-1