Massey Research Online - Browsing by Author "Munday JS"

Browsing by Author "Munday JS"

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A domestic cat whole exome sequencing resource for trait discovery
(Springer Nature Limited, 2021-03-30) Rodney AR; Buckley RM; Fulton RS; Fronick C; Richmond T; Helps CR; Pantke P; Trent DJ; Vernau KM; Munday JS; Lewin AC; Middleton R; Lyons LA; Warren WC
Over 94 million domestic cats are susceptible to cancers and other common and rare diseases. Whole exome sequencing (WES) is a proven strategy to study these disease-causing variants. Presented is a 35.7 Mb exome capture design based on the annotated Felis_catus_9.0 genome assembly, covering 201,683 regions of the cat genome. Whole exome sequencing was conducted on 41 cats with known and unknown genetic diseases and traits, of which ten cats had matching whole genome sequence (WGS) data available, used to validate WES performance. At 80 × mean exome depth of coverage, 96.4% of on-target base coverage had a sequencing depth > 20-fold, while over 98% of single nucleotide variants (SNVs) identified by WGS were also identified by WES. Platform-specific SNVs were restricted to sex chromosomes and a small number of olfactory receptor genes. Within the 41 cats, we identified 31 previously known causal variants and discovered new gene candidate variants, including novel missense variance for polycystic kidney disease and atrichia in the Peterbald cat. These results show the utility of WES to identify novel gene candidate alleles for diseases and traits for the first time in a feline model.
A Sub-Acute Dosing Study of Saxitoxin and Tetrodotoxin Mixtures in Mice Suggests That the Current Paralytic Shellfish Toxin Regulatory Limit Is Fit for Purpose.
(MDPI (Basel, Switzerland), 2023-07-03) Finch SC; Webb NG; Boundy MJ; Harwood DT; Munday JS; Sprosen JM; Somchit C; Broadhurst RB
Paralytic shellfish poisoning is a worldwide problem induced by shellfish contaminated with paralytic shellfish toxins. To protect human health, a regulatory limit for these toxins in shellfish flesh has been adopted by many countries. In a recent study, mice were dosed with saxitoxin and tetrodotoxin mixtures daily for 28 days showing toxicity at low concentrations, which appeared to be at odds with other work. To further investigate this reported toxicity, we dosed groups of mice with saxitoxin and tetrodotoxin mixtures daily for 21 days. In contrast to the previous study, no effects on mouse bodyweight, food consumption, heart rate, blood pressure, grip strength, blood chemistry or hematology were observed. Furthermore, no histological findings were associated with dosing in this trial. The dose rates in this study were 2.6, 3.8 and 4.9 times greater, respectively, than the highest dose of the previous study. As rapid mortality in three out of five mice was observed in the previous study, the deaths are likely to be due to the methodology used rather than the shellfish toxins. To convert animal data to that used in a human risk assessment, a 100-fold safety factor is required. After applying this safety factor, the dose rates used in the current study were 3.5, 5.0 and 6.5 times greater, respectively, than the acute reference dose for each toxin type set by the European Union. Furthermore, it has previously been proposed that tetrodotoxin be included in the paralytic shellfish poisoning suite of toxins. If this were done, the highest dose rate used in this study would be 13 times the acute reference dose. This study suggests that the previous 28-day trial was flawed and that the current paralytic shellfish toxin regulatory limit is fit for purpose. An additional study, feeding mice a diet laced with the test compounds at higher concentrations than those of the current experiment, would be required to comment on whether the current paralytic shellfish toxin regulatory limit should be modified.
Altered Hypoxia-Induced and Heat Shock Protein Immunostaining in Secondary Hair Follicles Associated with Changes in Altitude and Temperature in Tibetan Cashmere Goats
(MDPI (Basel, Switzerland), 2021-09-25) He Y; Liu X; De J; Kang S; Munday JS; Bleach E
This experiment compared secondary hair follicles (SFs) in Tibetan cashmere goats from two different steppes that were at different altitudes and had different temperatures. Twenty-four 2-year-old goats were studied. Twelve goats were from Rikaze in Tibet which is at an altitude of above 5000 m with an average temperature of 0 °C. The other 12 studied goats were from Huan County of Gansu Province which is around 2000 m above sea level with an average temperature of 9.2 °C. The structural features of SFs were assessed using light microscopy and transmission electron microscopy. The presence of HIF-1a, HIF-2a, HIF-3a, HSP27, and HOXC13 proteins was studied using immunohistochemistry and immunofluorescence. Light and electron microscopy revealed that the SFs of the Tibetan cashmere goats that lived in the Rikaze Steppe were in the proanagen stage in May. However, the SFs of the goats from the lower warmer Huan County were in the anagen stage at the same time. Immunohistochemistry revealed intense immunostaining for HIF-1a protein in the inner root sheath (IRS) and hair shaft (HS); immunostaining against HIF-2a in the outer root sheath (ORS) and IRS; HIF-3a protein immunostaining in the ORS; HSP27 immunostaining in the ORS, IRS, and HS; and HOXC13 immunostaining in the ORS and HS. HIF-1a protein expression in the IRS and HS was higher than the expression in the ORS (p < 0.05) while the expression of HIF-2a protein was higher in the ORS and IRS than the HS (p < 0.05). The expression of HIF-3a protein was higher in the ORS than in the IRS (p < 0.05). Expression of HOXC13 protein was higher in the ORS than in the IRS and HS (p < 0.05). Immunostaining of HIF-1a, HIF-2a, and HSP27 protein was significantly higher in SFs from cashmere goats from Rikaze than in goats from Huan (p < 0.05). In contrast, HOX13 protein immunostaining was significantly higher in cashmere goats from Huan than from Rikaze (p < 0.05). Significant differences were observed in the SFs of cashmere goats from two locations that differ in altitude and temperature. This suggests the differences in the secondary hair follicles could be due to the hypoxia and lower temperatures experienced by the goats in Rikaze. These results are useful in understanding how altitude and temperature influence SF development. Hair produced by the SFs are used for down fiber. Therefore, understanding of the factors that influence SF development will allow the production and harvest of these valuable fibers to be maximized.
Amplification of Ovis aries papillomavirus type 2 DNA from an ovine cutaneous fibropapilloma.
(John Wiley and Sons, Inc., 2024-04-01) Munday JS; Klobukowska HJ; Nicholson K
Seven of 60 Perendale sheep within a flock developed single or multiple exophytic masses on their distal hind limbs. A mass was excised from one sheep and histological evaluation revealed epidermal and mesenchymal proliferation, papillomavirus-induced keratinocyte changes and marked keratohyalin clumping. Ovis aries papillomavirus type 2 DNA sequences were amplified using PCR.
Anal fibropapillomas containing bovine papillomavirus type 2 DNA in two groups of heifers
(Taylor and Francis Group on behalf of the New Zealand Veterinary Association, 11/06/2018) Munday JS; Cullum AA; Thomson NA; Bestbier M; McCormack T; Julian AF
CASE HISTORY Anal warts were observed in heifers in two unrelated groups of animals. Heifers in one group developed visible warts 4 months after manual rectal examination and heifers in the other group developed warts 5 months after examination using a hand-held rectal ultrasound probe. CLINICAL FINDINGS Large exophytic proliferative anal masses were observed in 5/15 (33%) heifers in one group and 13/149 (9%) heifers in the second group. Heifers in the second group were also noted to have similar masses on the underside of the tail at sites previously used for venepuncture and some of the heifers had skin warts. Despite the large size of the anal masses, none of the heifers showed clinical signs of systemic illness. HISTOPATHOLOGICAL FINDINGS An anal mass was removed from one heifer in each of the two groups. Sections from both masses showed hyperplastic epithelium covering a proliferation of well-differentiated fibroblasts consistent with fibropapillomas. Small numbers of cells within the epidermis had clear cytoplasm with clumped keratohyalin granules. MOLECULAR BIOLOGY Bovine papillomavirus (BPV) type 2 DNA was amplified from both fibropapillomas by PCR. DIAGNOSIS Multiple anal fibropapillomas associated with BPV-2. CLINICAL RELEVANCE Bovine anal fibropapillomas have only been reported in heifers that have undergone rectal examination, and infection of anal microabrasions in an immunologically naïve animal appears to be associated with disease development. The source and method of spread of BPV-2 within these groups could not be determined. However spread of BPV-2 within the groups by the veterinarian performing rectal examinations may have been most likely. While these fibropapillomas had a dramatic appearance, like fibropapillomas elsewhere on the body, they did not have any significant effect on the health of the affected heifers. As these lesions can be diagnosed by clinical examination and self-resolve without treatment, it is important that veterinarians are aware of this rare manifestation of papillomavirus infection of cattle.
Canis Familiaris Papillomavirus Type 26: A Novel Papillomavirus of Dogs and the First Canine Papillomavirus within the Omegapapillomavirus Genus.
(MDPI (Basel, Switzerland), 2024-04-12) Munday JS; Bond SD; Piripi S; Soulsby SJ; Knox MA; Christensen N
Domestic dogs are currently recognized as being infected by 25 different canine papillomavirus (CPV) types classified into three genera. A short sequence from a novel CPV type was amplified, along with CPV1, from a papilloma (wart) from the mouth of a dog. The entire 7499 bp genome was amplified, and CPV26 contained putative coding regions that were predicted to produce four early proteins and two late ones. The ORF L1 showed less than 62% similarity for all previously sequenced CPV types but over 69% similarity to multiple Omegapapillomavirus types from a variety of Caniform species including the giant panda, Weddel seal, and polar bear. Phylogenetic analysis confirmed CPV26 clusters within the Omegapapillomavirus genus. Specific primers were used to investigate the presence of CPV26 DNA within a series of 37 canine proliferative lesions. CPV26 DNA was amplified from one lesion, a cutaneous papilloma that also contained CPV6. This is the first time a PV type within the Omegapapillomavirus genus has been detected in a non-domestic species and this provides evidence that the omegapapillomaviruses infected a common ancestor of, and then co-evolved with, the Caniform species. Whether CPV26 causes disease is uncertain, but the absence of an E7 protein may suggest low pathogenicity.
Detection of a novel papillomaviral sequence in viral plaques confined to the pinna of a dog.
(John Wiley and Sons, Inc., 2023-08-01) Munday JS; Orbell G; Robinson L
A raised plaque that contained histological evidence of papillomavirus infection and sequences from a novel papillomavirus type developed close to the ear canal of a 14-year-old West Highland white terrier. The plaque was excised, and further plaques developed within the same area of pinna.
Detection of a Novel Papillomavirus Type within a Feline Cutaneous Basal Cell Carcinoma
(MDPI (Basel, Switzerland), 2022-12-01) Munday JS; Hunt H; Orbell G; Pfeffer H; Bennett P
A 4 cm diameter exophytic mass was excised from the left flank of a 10-year-old domestic short-haired cat. Histology of the superficial aspects of the mass revealed epidermal cells arranged in nests and trabeculae while the deeper parts of the mass consisted of small round cells arranged in sheets or bundles of elongate spindle-shaped cells. A diagnosis of basal cell carcinoma (BCC) was made. Approximately 40% of the cells throughout the neoplasm contained prominent papillomaviral (PV)-induced cell changes. The BCC recurred three months after excision and grew rapidly. At this time a smaller mass was observed on the thorax. Due to the rapid recurrence of the BCC, the cat was euthanatized. As in the initial mass, histology of the recurrent mass revealed pleomorphic cells that often contained PV-induced cell changes. In contrast, the thoracic mass appeared as a more typical BCC and contained no histological evidence of PV infection. A novel PV DNA sequence was amplified from the flank BCC. While the sequence was most (75.1%) similar to Felis catus papillomavirus (FcaPV) 6, the level of similarity between the sequences is consistent with a novel PV type. No PV DNA was amplifiable from the thoracic mass. The case is unique due to the histological features of the BCC and the presence of a putative novel PV type. Observations from the present case add to the number of PV types associated with disease in cats as well as increasing the spectrum of PV-induced lesions in this species.
Development of a Nomogram to Predict the Outcome for Patients with Soft Tissue Sarcoma.
(MDPI (Basel, Switzerland), 2023-03-29) Bray JP; Munday JS; Dobson J; Hayes A; Hughes K
Soft tissue sarcomas (STSs) are common cutaneous or subcutaneous neoplasms in dogs. Most STSs are initially treated by surgical excision, and local recurrence may develop in almost 20% of patients. Currently, it is difficult to predict which STS will recur after excision, but this ability would greatly assist patient management. In recent years, the nomogram has emerged as a tool to allow oncologists to predict an outcome from a combination of risk factors. The aim of this study was to develop a nomogram for canine STSs and determine if the nomogram could predict patient outcomes better than individual tumour characteristics. The current study provides the first evidence in veterinary oncology to support a role for the nomogram to assist with predicting the outcome for patients after surgery for STSs. The nomogram developed in this study accurately predicted tumour-free survival in 25 patients but failed to predict recurrence in 1 patient. Overall, the sensitivity, specificity, positive predictive, and negative predictive values for the nomogram were 96%, 45%, 45%, and 96%, respectively (area under the curve: AUC = 0.84). This study suggests a nomogram could play an important role in helping to identify patients who could benefit from revision surgery or adjuvant therapy for an STS.
Equus caballus papillomavirus Type 7 is a rare cause of equine penile squamous cell carcinomas.
(Elsevier B.V., 2024-08-01) Munday JS; Knight CG; Bodaan CJ; Codaccioni C; Hardcastle MR
Penile squamous cell carcinomas (SCCs) are common, potentially life-threatening neoplasms of horses. They are well-recognized to be caused by Equus caballus papillomavirus (EcPV) type 2, although EcPV2 cannot be detected in all cases. A 23-year-old standardbred gelding developed multiple penile in situ and invasive SCCs that contained histological evidence of PV infection. By using both consensus and specific PCR primers, these lesions were found to contain EcPV7 DNA, but not DNA from EcPV2 or any other PV type. To determine how frequently EcPV7 is present in equine penile SCCs, specific primers were used to detect EcPV2 and EcPV7 in a series of 20 archived samples. EcPV7 was the only PV detected in one, both EcPV2 and 7 were detected in five, and only EcPV2 was detected in 14 SCCs. EcPV7 DNA was also detected in three of 10 archived oropharyngeal SCCs, although only as a co- infection with EcPV2. This is the first report of EcPV7 causing disease in horses. These results suggest EcPV7 could cause a subset of equine penile SCCs, and this is the first evidence that PV types other than EcPV2 can cause these neoplasms. The detection of EcPV7 in the oropharyngeal SCCs suggests a potential role of this PV type in the development of these SCCs. There were no clinical or histological features that differentiated lesions containing EcPV7 DNA from those containing EcPV2 DNA. If EcPV7 causes a proportion of equine penile SCCs, vaccines to prevent EcPV2 infection may not prevent all equine penile SCCs.
Evidence from a Series of 104 Equine Sarcoids Suggests That Most Sarcoids in New Zealand Are Caused by Bovine Papillomavirus Type 2, although Both BPV1 and BPV2 DNA Are Detectable in around 10% of Sarcoids
(MDPI (Basel, Switzerand), 2021-10-29) Munday JS; Orbell G; Fairley RA; Hardcastle M; Vaatstra B; Bailey S
Equine sarcoids are common mesenchymal neoplasms of horses that are caused by cross-species infection by deltapapillomaviruses. While bovine papillomavirus (BPV) 1 and 2 are the most common causes, there are differences between countries regarding which of these BPV types cause the majority of sarcoids. Additionally, no causative PV can be detected in a subset of sarcoids, suggesting that other PV types could be rarer causes of these neoplasms. In the present study, consensus PCR primers and PCR primers specific for the five deltapapillomavirus types currently known to cause mesenchymal neoplasia (BPV1, BPV2, BPV13, BPV14, and Ovis aries PV2 DNA) were used to investigate the presence of PV DNA in 104 sarcoids from three defined regions in New Zealand and from two distinct time periods separated by 15 years. PV DNA was detected in 94 (90.4%) sarcoids. Of the sarcoids containing PV DNA, 83 (88.3%) contained only BPV2 DNA, 9 (9.6%) BPV1 and BPV2 DNA, and 2 (2.1%) only BPV1 DNA. No other PV types were detected. The predominance of BPV2 is consistent with studies of sarcoids from North America but dissimilar to studies of sarcoids from Europe and Australia. Detection rates of BPV1 and BPV2 were similar in sarcoids from different regions of New Zealand and in sarcoids from different time periods. These results suggest that most equine sarcoids in New Zealand are caused by BPV2 and thus if vaccines are developed to prevent sarcoids, vaccines that provide good protection against BPV2 will be required in this country.
Felis catus papillomavirus type 2 virus-like particle vaccine is safe and immunogenic but does not reduce FcaPV-2 viral loads in adult cats
(Elsevier BV, 2019-07) Thomson NA; Howe L; Weidgraaf K; Thomas DG; Young V; Ward VK; Munday JS
Felis catus papillomavirus type 2 (FcaPV-2) commonly infects the skin of domestic cats and has been associated with the development of skin cancer. In the present study, a FcaPV-2 virus-like particle (VLP) vaccine was produced and assessed for vaccine safety, immunogenicity, and impact on FcaPV-2 viral load. This is the first report of the use of a papillomavirus VLP vaccine in domestic cats. The FcaPV-2 VLP vaccine was given to ten adult cats that were naturally infected with FcaPV-2, and a further ten naturally infected cats were sham vaccinated as a control group. The rationale for vaccinating cats already infected with the virus was to induce neutralizing antibody titers that could prevent reinfection of new areas of skin and reduce the overall viral load, as has been demonstrated in other species. Reducing the overall FcaPV-2 viral load could reduce the risk for subsequent PV-associated cancer. The vaccine in this study was well-tolerated, as none of the cats developed any signs of local reaction or systemic illness. In the treatment group, the geometric mean anti-papillomavirus endpoint antibody titers increased significantly following vaccination from 606 (95% CI 192-1913) to 4223 (2023-8814), a 7.0-fold increase, although the individual antibody response varied depending on the level of pre-existing antibodies. Despite the immunogenicity of the vaccine, there was no significant change in FcaPV-2 viral load in the treatment group compared to the control group, over the 24 week follow-up period. A possible reason is that FcaPV-2 was already widespread in the basal skin layer of these adult cats and so preventing further cells from becoming infected had no impact on the overall viral load. Therefore, these results do not support the use of a FcaPV-2 VLP vaccine to reduce the risk for PV-associated cancer in cats in which FcaPV-2 infection is already well established. However, these results justify future studies in which the vaccine is administered to younger cats prior to FcaPV-2 infection becoming fully established.
Genomic Characterisation of Canis Familiaris Papillomavirus Type 24, a Novel Papillomavirus Associated with Extensive Pigmented Plaque Formation in a Pug Dog
(MDPI (Basel, Switzerland), 2022-10-26) Munday JS; Gedye K; Knox MA; Ravens P; Lin X; Dalianis T
Numerous large dark plaques developed over the ventrum, legs and head of a 9-year-old pug dog over a 4-year-period. Histology confirmed a diagnosis of viral pigmented plaque and a short section of a novel papillomavirus (PV) type was amplified using consensus PCR primers. Taking advantage of the circular nature of PV DNA, 'outward facing' PCR primers allowed amplification of the full sequence. As this is the 24th PV known to infect dogs, the novel PV was designated canine papillomavirus (CPV) type 24. The CPV24 genome contained putative coding regions for 5 early proteins and 2 late ones. The CPV24 open reading frame L1 showed the highest (78.2%) similarity to CPV4 and phylogenetic analysis showed that CPV24 clustered with CPV4 and CPV16 suggesting CPV24 is the third species 2 Chipapillomavirus type identified in dogs. This is the third report of extensive pigmented plaques covering a high proportion of the skin. Both previous cases were caused CPV4 and, considering the high genetic similarity between CPV4 and CP24, infection by these CPV types may predispose to more severe clinical disease. In addition, as plaques caused by CPV16 appear more likely to progress to neoplasia, the detection of a species 2 Chipapillomavirus within a pigmented plaque may indicate the potential for more severe disease.
Genomic Characterization of Canis Familiaris Papillomavirus Type 25, a Novel Papillomavirus Associated with a Viral Plaque from the Pinna of a Dog
(MDPI (Basel, Switzerland), 2023-06-02) Munday JS; Gedye K; Knox MA; Robinson L; Lin X
A 14-year-old West Highland White terrier dog developed multiple raised plaques that were confined to the concave surface of the right pinna. Histology allowed a diagnosis of viral plaque, although the lesions contained some unusual microscopic features. A papillomaviral (PV) DNA sequence was amplified from the plaque using consensus PCR primers. The amplified sequence was used as a template to design 'outward facing' PCR primers, which allowed amplification of the complete PV DNA sequence. The sequence was 7778 bp and was predicted to code for five early genes and two late genes. The ORF L1 showed the highest (83.9%) similarity to CPV15, and phylogenetic analysis revealed the novel PV clustered with the species 3 ChiPVs. The novel PV was designated as canine papillomavirus (CPV) type 25. As CPV25 was not previously detected in a canine viral plaque, this PV type may be a rare cause of skin disease in dogs. However, as plaques that remain confined to the pinna were not previously reported in dogs, it is possible that CPV25 could be more common in plaques from this area of skin. The findings from this case expand the number of PV types that cause disease in dogs. Evidence from this case suggests that, compared to the other canine ChiPV types, infection by CPV25 results in viral plaques in atypical locations with unusual histological features.
Identification of Felis catus papillomavirus 3 in skin neoplasms from four cats.
(2018-03) Munday JS; Thomson NA; Henderson G; Fairley R; Orbell GM
Bowenoid in situ carcinomas (BISCs) are papillomavirus (PV)-induced skin neoplasms that are thought to be caused by Felis catus papillomavirus (FcaPV) 2. As BISCs are typically multiple and can become extensive, they can be difficult to treat. Herein we describe 4 cats that developed skin neoplasms that contained FcaPV-3 DNA. One cat developed multiple basal cell carcinomas (BCCs), 1 a BISC with unusual extension into hair follicles, and 2 developed a single typical-appearing BISC. All neoplasms contained prominent PV-induced cell changes and intense p16CDKN2a protein immunostaining. Results from these 4 cats provide evidence that FcaPV-3 could cause a proportion of feline skin cancers, albeit less frequently than FcaPV-2. Excision of the typical BISCs and the BCCs appeared curative. Although the cat with the unusual BISC was euthanized because of the large size of the lesion, evidence from these 4 cats suggests that skin neoplasms that contain FcaPV-3 DNA may have a less aggressive clinical behavior than those associated with FcaPV-2. A consistent feature of the neoplasms in all 4 cats was the presence of prominent basophilic intracytoplasmic inclusion bodies; these inclusions have not been reported in lesions caused by FcaPV-2, to our knowledge, and their detection may allow differentiation between the different PV types and could therefore be a useful prognostic feature.
Immunostaining for VEGF and Decorin Predicts Poor Survival and Recurrence in Canine Soft Tissue Sarcoma.
(MDPI (Basel, Switzerland), 2023-03-28) Bray JP; Perrott MR; Munday JS; van der Weyden L
The aim of this study was to investigate whether using immunohistochemistry to detect the angiogenic proteins vascular endothelial growth factor (VEGF) and decorin can help predict the risk of local recurrence of, or death from, canine soft tissue sarcoma (STS). VEGF and decorin were detected using validated immunohistochemical methods on 100 formalin-fixed paraffin-embedded samples of canine STS. The tumours had been resected previously, with clinical outcome determined by questionnaire. Each slide was assessed by light microscopy and the pattern of immunostaining with VEGF and decorin determined. Patterns of immunostaining were then analysed to detect associations with outcome measures of local recurrence and tumour-related death. High VEGF immunostaining was significantly (p < 0.001) associated with both increased local recurrence and reduced survival time. The distribution of decorin immunostaining within the tumour was significantly associated with survival time (p = 0.04) and local tumour recurrence (p = 0.02). When VEGF and decorin scores were combined, STS with both high VEGF and low decorin immunostaining were more likely to recur or cause patient death (p < 0.001). The results of this study suggest that immunostaining of VEGF and decorin may help predict the risk of local recurrence of canine STS.
Longitudinal study of the effect of sporidesmin toxicity on lamb production and serum biochemistry in a flock of 46 Romney ewes using a standardised measure of liver damage.
(2022-07) Lawrence KE; Flay KJ; Munday JS; Aberdein D; Thomson NA; Vignes M; Ridler AL
AIMS: To evaluate the effect of sporidesmin toxicity on production outcomes and serum biochemistry analytes in mixed age Romney ewes, using a standardised measure of liver damage. METHODS: This was a prospective longitudinal study following 46 mixed age Romney ewes from sporidesmin intoxication in April 2019, to slaughter 8 months later. The ewes were blood-sampled up to eight times, with a panel of serum biochemistry tests performed on the final six samples. However, only gamma-glutamyl transferase (GGT) activity was measured in the first two samples collected at the end of sporidesmin intoxication and 2 weeks later. Body condition score, ewe weight and production data were also recorded. Using a standardised liver score, based on histology of liver samples collected at slaughter, ewes were assigned to one of three liver disease categories (LDC); low, middle, and high. These were then used as the outcome or predictor variables for statistical analyses. Finally, two separate decision tree models, using recursive partitioning (RP), were fitted to the biochemistry data and to the GGT data collected at FE outbreak, to predict ewes in the low LDC. RESULTS: There was no evidence of a difference for the effect of LDC on ewe weight (p = 0.86) with ewes, on average, gaining weight to weaning. Weaning percent, lamb rearing percent and ewe flock efficiency were lower in ewes with high LDC, and scanning-to-weaning lamb loss was significantly higher in sheep with high LDC (p = 0.02). Serum activities of GGT and glutamate dehydrogenase and concentration of globulin were significantly lower in sheep with low LDC than in sheep with middle or high LDC (p < 0.05). However, there was no evidence of a difference for the effect of LDC on other biochemistry variables (p > 0.05). The final RP model for the biochemistry data categorised ewes as low LDC if their GGT was <122 IU/L, 3 months after sporidesmin intoxication, or if their GGT was <514 IU/L, <18 days after sporidesmin intoxication. CONCLUSIONS AND CLINICAL RELEVANCE: Sheep with gross and histological evidence of severe sporidesmin-induced liver damage were able to maintain or gain body weight, suggesting that sporidesmin intoxication alone is not causative of poor body condition. Similarly, many of the serum biochemistry tests were not associated with evidence of liver damage. Lamb production was reduced in ewes with evidence of severe liver damage and the decision tree model showed promise as a basis to select ewes for culling.
Lower-Than-Expected Vitamin A Concentrations in a Commercial Diet Associated with Uroliths and Pyelonephritis in Rats
(MDPI (Basel, Switzerland), 2022-05-18) Munday JS; Castillo-Alcala F; Jaros P; Satou T
Five of 95 rats in an oral safety study developed uroliths, with two of these rats also developing pyelonephritis. Histology of the urinary tract revealed squamous metaplasia suggestive of vitamin A deficiency. Analysis of the diet showed around half the expected concentration of vitamin A, although the concentrations were close to the published nutritional requirements for rats. Due to the presence of squamous metaplasia of the transitional epithelium and the low vitamin A concentration in the diet, a presumptive diagnosis of vitamin A deficiency was made, although an interaction between the low vitamin A concentrations and other dietary components appears possible. Although the uroliths did not cause clinical signs of disease, the lesions observed during this study could have been misinterpreted as being due to the test substance. Observations from this study highlight the need for high-quality food to ensure background lesions do not develop when performing safety studies in rats.
Magnetic resonance imaging shows spinal curvature in Chinook salmon (Oncorhynchus tshawytscha) is associated with chronic inflammation of peri-vertebral soft tissues.
(John Wiley and Sons, Inc., 2024-03-01) Lovett BA; Firth EC; Perrott MR; Munday JS; Pontre BP; Lydon A-MP; Symonds JE; Preece MA; Herbert NA
Chinook salmon (Oncorhynchus tshawytscha) farmed in New Zealand are known to develop abnormal spinal curvature late in seawater production. Its cause is presently unknown, but there is evidence to suggest a neuromuscular pathology. Using magnetic resonance imaging (MRI), we evaluated the relationship between soft tissue pathology and spinal curvature in farmed Chinook salmon. Regions of interest (ROIs) presenting as pathologic MRI signal hyper-intensity were identified from scans of 24 harvest-sized individuals: 13 with radiographically-detectable spinal curvature and 11 without. ROIs were excised from individuals using anatomical landmarks as reference points and histologically analysed. Pathologic MRI signal was observed more frequently in individuals with radiographic curvature (92%, n = 12) than those without (18%, n = 2), was localized to the peri-vertebral connective tissues and musculature, and presented as three forms: inflammation, fibrosis, or both. These pathologies are consistent with a chronic inflammatory process, such as that observed during recovery from a soft tissue injury, and suggest spinal curvature in farmed Chinook salmon may be associated with damage to and/or compromised integrity of the peri-vertebral soft tissues. Future research to ascertain the contributing factors is required.
Multimodal Blockade of the Renin-Angiotensin System in the Treatment of Cancer in Dogs Has Mild Adverse Effects in Some Dogs.
(MDPI (Basel, Switzerland), 2024-06-17) Dittmer KE; Wetzel S; Odom T; Munday JS; Flatt EA; Wilson IJ; Hughes C; Tan ST; Ferreira F; Sparger EE
The renin-angiotensin system (RAS) is increasingly being recognized to play a role in the tumor microenvironment, promoting tumor growth. Studies blocking a single part of the RAS have shown mixed results, possibly due to the existence of different bypass pathways and redundancy within the RAS. As such, multimodal blockade of the RAS has been developed to exert more complete inhibition of the RAS. The aim of the present study was to assess the safety of multimodal RAS blockade in dogs. Five dogs (four with appendicular osteosarcoma, one with oral malignant melanoma) were treated with atenolol, benazepril, curcumin, meloxicam, and metformin. The dogs underwent clinical examination, blood pressure measurement, and hematology and serum biochemistry tests performed at 0, 1, 3, 6, 9, and 12 weeks, then every 3 months thereafter. End-of-life decisions were made by the owners. None of the dogs developed hypotension. One dog had intermittent vomiting during the 64 weeks it was on the trial. One dog had a one-off increase in serum SDMA(symmetrical dimethylarginine) concentration. Dogs were euthanized at weeks 3 (osteosarcoma), 10 (osteosarcoma), 17 (osteosarcoma), and 26 (oral malignant melanoma), and one dog was still alive at the end of the trial at 64 weeks (osteosarcoma). This is the first assessment of multimodal blockade of the RAS in dogs, and the results suggest it causes only mild adverse effects in some animals. The efficacy of the treatment was not assessed due to the small number of dogs. This pilot study allows for future larger studies assessing multimodal RAS blockade for the treatment of canine cancer.

Browsing by Author "Munday JS"

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