Publications by authors named "Sean McDonough"

128 Publications

Bacterial culture and immunohistochemical detection of bacteria and endotoxin in cats with suppurative cholangitis-cholangiohepatitis syndrome.

J Am Vet Med Assoc 2021 Dec 21:1-18. Epub 2021 Dec 21.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY.

Objective: To characterize the frequency and type of bacterial infection by culture- and immunohistochemical (IHC)-based methods and determine the impact of infection on clinical features and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome (S-CCHS).

Animals: 168 client-owned cats with S-CCHS (cases).

Procedures: Clinical features, bacterial culture results, culture-inoculate sources, and survival details were recorded. Cases were subcategorized by comorbidity (extrahepatic bile duct obstruction, cholelithiasis, cholecystitis, ductal plate malformation, biopsy-confirmed inflammatory bowel disease, and biopsy-confirmed pancreatitis) or treatment by cholecystectomy or cholecystoenterostomy. Culture results, bacterial isolates, Gram-stain characteristics, and IHC staining were compared among comorbidities. Lipoteichoic acid IHC staining detected gram-positive bacterial cell wall components, and toll-like receptor expression IHC reflected pathologic endotoxin (gram-negative bacteria) exposure.

Results: Clinical features were similar among cases except for more frequent abdominal pain and lethargy in cats with positive culture results and pyrexia, abdominal pain, and hepatomegaly for cats with polymicrobial infections. Bacteria were cultured in 93 of 135 (69%) cats, with common isolates including Enterococcus spp and Escherichia coli. IHC staining was positive in 142 of 151 (94%) cats (lipoteichoic acid, 107/142 [75%]; toll-like receptor 4, 99/142 [70%]). With in-parallel interpretation of culture and IHC-based bacterial detection, 154 of 166 (93%) cats had bacterial infections (gram-positive, 118/154 [77%]; gram-negative, 111/154 [72%]; polymicrobial, 79/154 [51%]). Greater frequency of bacterial isolation occurred with combined tissue, bile, and crushed cholelith inoculates. Infection and gram-positive bacterial isolates were associated with significantly shorter long-term survival times.

Clinical Relevance: S-CCHS was associated with bacterial infection, pathologic endotoxin exposure, and frequent polymicrobial infection in cats. Combined tissue inoculates improved culture detection of associated bacteria.
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http://dx.doi.org/10.2460/javma.20.10.0552DOI Listing
December 2021

Determination of correlation of proximal sesamoid bone osteoarthritis with high-speed furlong exercise and catastrophic sesamoid bone fracture in Thoroughbred racehorses.

Am J Vet Res 2021 Jun;82(6):467-477

Objective: To examine whether proximal sesamoid bone (PSB) articular cartilage and bone osteoarthritic changes or palmar osteochondral disease (POD) scores were associated with exercise history and catastrophic PSB fracture in Thoroughbred racehorses.

Samples: PSBs from 16 Thoroughbred racehorses (8 with and 8 without PSB fracture).

Procedures: Exercise history was collected, and total career high-speed furlongs was used as the measure of total exercise per horse. At necropsy, medial and lateral condyles of the third metacarpus from each forelimb were assigned a POD score, followed by imaging with micro-CT for evaluation of osteophyte size. Three investigators that were blinded to the type of PSB (fracture or no fracture) used the Osteoarthritis Research Society International (OARSI) scoring system to evaluate acellularity, chondrocyte necrosis, cartilage fibrillation, chondrone formation, safranin O stain uptake, and tidemark advancement of 1 central sagittal tissue section/PSB (4 PSBs/horse). Cartilage thickness and bone necrosis were scored on the basis of histologic examination.

Results: POD score, osteophyte size score, percentage of bone necrosis, tidemark advancement, chondrone formation, and total OARSI score were greater in horses with more accrued total career high-speed furlongs. Scores for POD, osteophyte size, fibrillation, acellularity, chondrone formation, and total OARSI were greater for horses with PSB fracture.

Conclusions And Clinical Revelance: OARSI scoring revealed that more advanced osteoarthritic changes strongly correlated with total career high-speed furlongs and PSB fracture. However, the effect of exercise was dominant, suggesting that exercise history will be important to include in future models that aim to assess risk factors for catastrophic PSB fracture.
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http://dx.doi.org/10.2460/ajvr.82.6.467DOI Listing
June 2021

Pathology in Practice.

J Am Vet Med Assoc 2021 May;258(10):1087-1090

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http://dx.doi.org/10.2460/javma.258.10.1087DOI Listing
May 2021

Pathogenesis, MicroRNA-122 Gene-Regulation, and Protective Immune Responses After Acute Equine Hepacivirus Infection.

Hepatology 2021 09 11;74(3):1148-1163. Epub 2021 Jun 11.

Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

Background And Aims: Equine hepacivirus (EqHV) is phylogenetically the closest relative of HCV and shares genome organization, hepatotropism, transient or persistent infection outcome, and the ability to cause hepatitis. Thus, EqHV studies are important to understand equine liver disease and further as an outbred surrogate animal model for HCV pathogenesis and protective immune responses. Here, we aimed to characterize the course of EqHV infection and associated protective immune responses.

Approach And Results: Seven horses were experimentally inoculated with EqHV, monitored for 6 months, and rechallenged with the same and, subsequently, a heterologous EqHV. Clearance was the primary outcome (6 of 7) and was associated with subclinical hepatitis characterized by lymphocytic infiltrate and individual hepatocyte necrosis. Seroconversion was delayed and antibody titers waned slowly. Clearance of primary infection conferred nonsterilizing immunity, resulting in shortened duration of viremia after rechallenge. Peripheral blood mononuclear cell responses in horses were minimal, although EqHV-specific T cells were identified. Additionally, an interferon-stimulated gene signature was detected in the liver during EqHV infection, similar to acute HCV in humans. EqHV, as HCV, is stimulated by direct binding of the liver-specific microRNA (miR), miR-122. Interestingly, we found that EqHV infection sequesters enough miR-122 to functionally affect gene regulation in the liver. This RNA-based mechanism thus could have consequences for pathology.

Conclusions: EqHV infection in horses typically has an acute resolving course, and the protective immune response lasts for at least a year and broadly attenuates subsequent infections. This could have important implications to achieve the primary goal of an HCV vaccine; to prevent chronicity while accepting acute resolving infection after virus exposure.
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http://dx.doi.org/10.1002/hep.31802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435542PMC
September 2021

What is your diagnosis? Impression smear from a liver mass in a dog.

Vet Clin Pathol 2021 06 8;50(2):290-292. Epub 2021 Mar 8.

Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.

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http://dx.doi.org/10.1111/vcp.12952DOI Listing
June 2021

Equine leptospirosis: Experimental challenge of Leptospira interrogans serovar Bratislava fails to establish infection in naïve horses.

Equine Vet J 2021 Jul 25;53(4):845-854. Epub 2021 Mar 25.

Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.

Background: Little information is available about experimental inoculation of leptospirosis in horses and the pathogenicity of Leptospira interrogans serovar Bratislava in this host.

Objectives: To determine the serological, clinical, pathological and haematological responses of horses to L. interrogans serovar Bratislava strain PigK151.

Study Design: Randomised controlled in vivo experiment.

Methods: Ten seronegative female foals were divided into 2 groups, control (n = 4) and challenged (n = 6). The challenged group received 1 × 10 leptospires divided equally between topical ocular and intraperitoneal injections. Blood and urine samples were analysed. The temperature was recorded daily for the first 9 days, then weekly. Sera were tested by microscopic agglutination test (MAT). Automated complete blood count, differential and chemistry panel were performed. Histopathological analysis was performed on sections of liver, kidney, urinary bladder, uterine body and pineal gland. Sample culturing was performed from blood, urine, liver, kidney, reproductive tract and vitreous humour.

Results: No pyrexia was noted. PCR and culture were negative from all samples. Differences between groups were found in CBC, differential counts and serum biochemistry panel (or profile), suggesting that leptospiral challenge triggered an inflammatory response. No evidence of leptospirosis was found from histopathological analysis. All challenged foals developed a humoral response. The MAT allowed the confirmation of the infecting serovar at a later stage, but it also revealed cross-reactive results that were further explained by genomic analysis.

Main Limitations: This experimental challenge had two main limitations: (a) the results might have varied if another strain from the same serovar had been used and (b) the use of another route of infection and a higher bacterial dose might have achieved colonisation.

Conclusions: Based on these findings, it may suggest that L. interrogans serovar Bratislava is neither pathogenic nor host-adapted serovar for horses, although these results might have varied if another strain from the same serovar had been used instead.
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http://dx.doi.org/10.1111/evj.13442DOI Listing
July 2021

Veterinary forensic pathology standards.

J Forensic Sci 2021 05 12;66(3):1176. Epub 2021 Feb 12.

Department of Pathology and Population Medicine, College of Veterinary Medicine, Midwestern University, Glendale, AZ, USA.

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http://dx.doi.org/10.1111/1556-4029.14683DOI Listing
May 2021

sclerokeratitis in a cat.

J Am Vet Med Assoc 2020 Dec;257(12):1280-1287

Case Description: A 12-year-old neutered male domestic shorthair cat with chronic anterior uveitis and secondary glaucoma of the right eye was examined for persistent blepharospasm 2 weeks after corneal debridement and grid keratotomy for nonhealing superficial ulcerative keratitis.

Clinical Findings: Examination of the right eye revealed a central superficial corneal ulcer associated with corneal epithelial and subepithelial infiltrates and mild aqueous flare. Structures consistent with amoeboid cysts and trophozoites were detected in the cornea by in vivo confocal microscopy. Suppurative keratitis was identified cytologically. An spp was isolated through culture and identified by a PCR assay of corneal specimens.

Treatment And Outcome: Symptomatic and antiamoebic (polyhexamethylene biguanide 0.02% ophthalmic solution) treatments were instituted. Over the following 6 weeks, the cat lost vision in the affected eye and lesions progressed to nonulcerative stromal keratitis associated with a dense paracentral corneal stroma ring infiltrate and anterior lens luxation. The globe was enucleated, and lymphoplasmacytic sclerokeratitis, anterior uveitis, and retinal detachment were noted. organisms were detected within the corneal stroma and anterior sclera with histologic and immunohistochemical stains. The amoebae were classified to the T4 genotype by DNA sequencing. The cat had no medical problems attributed to infection over 36 months after enucleation, until the cat was lost to follow-up.

Clinical Relevance: Naturally acquired sclerokeratitis is described in a cat for the first time. infection should be considered for cats with superficial corneal disease refractory to appropriate treatments and especially occurring after ocular trauma, including keratotomy.
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http://dx.doi.org/10.2460/javma.257.12.1280DOI Listing
December 2020

Evaluation of new leptospiral antigens for the diagnosis of equine leptospirosis: An approach using pan-genomic analysis, reverse vaccinology and antigenic selection.

Equine Vet J 2021 Sep 3;53(5):1025-1035. Epub 2020 Dec 3.

Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

Background: The current gold standard diagnostic test for leptospirosis is the microscopic agglutination test (MAT), which has many drawbacks; therefore, the development of a better and easier serological test for leptospirosis is needed.

Objectives: To apply reverse vaccinology (RV) and antigenic selection on the assortment of leptospiral targets and evaluate their potential for use as reagents for the diagnosis of equine leptospirosis.

Study Design: Cross-sectional study.

Methods: The antigenic selection parameters were: proteins with antigenicity score ≥0.5 (VaxiJen), at least one B cell epitope and size between 10 and 275 KDa. New leptospiral proteins were cloned, expressed and serologically screened against equine sera (n = 128) on a single analysis and comparative combinations. Sensitivity (Se) and specificity (Sp), accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated. A BLAST with nucleotide and protein sequences was used to identify the serovar or species specificity.

Main Limitations: This cross-sectional analysis had three main limitations: (a) The equine sera used in these tests were limited to sera submitted to the Animal Health Diagnosis Center and were only tested against seven serovars; (b) MAT results were considered being 'perfect', and the highest titre presented was considered being the infecting serovar, which may not hold true; (c) The strains used to represent the serovars and the limited number of different serovars and species included in the genetic analysis, which leads to the possibility that these proteins might be present in different species or serovars that perhaps would be seroprevalent in another geographic region.

Conclusions: The new leptospiral antigens described in this research could increase the sensitivity and specificity of ELISA for detection of Leptospira exposure and the detection of leptospirosis in horses along with support from other clinical signs. Some of these new antigens might be used to improve the detection of infecting serovar.
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http://dx.doi.org/10.1111/evj.13380DOI Listing
September 2021

Clinical, clinicopathologic, and hepatic histopathologic features associated with probable ketoconazole-induced liver injury in dogs: 15 cases (2015-2018).

J Am Vet Med Assoc 2020 Jun;256(11):1245-1256

Objective: To characterize clinical, clinicopathologic, and hepatic histopathologic features and outcome for dogs with probable ketoconazole-induced liver injury.

Animals: 15 dogs with suspected ketoconazole-induced liver injury that underwent liver biopsy.

Procedures: Medical record data were summarized regarding signalment, clinical signs, clinicopathologic and hepatic histopathologic findings, concurrent medications, ketoconazole dose, treatment duration, and outcome.

Results: Median age and body weight were 8.2 years (range, 5 to 15 years) and 13.0 kg (28.6 lb; range, 8.2 to 38.0 kg [18.0 to 83.6 lb]), respectively. The most common breed was Cocker Spaniel (n = 5). All dogs received ketoconazole to treat cutaneous infections. Median daily ketoconazole dose was 7.8 mg/kg (3.5 mg/lb; range, 4.4 to 26.0 mg/kg [2.0 to 11.8 mg/lb]), PO. Treatment duration ranged from 0.3 to 100 cumulative weeks (intermittent cyclic administration in some dogs); 6 dogs were treated for ≤ 10 days. Common clinical signs included lethargy, anorexia, and vomiting. All dogs developed high serum liver enzyme activities. Hepatic histopathologic findings included variable lobular injury, mixed inflammatory infiltrates, and conspicuous aggregates of ceroid-lipofuscin-engorged macrophages that marked regions of parenchymal damage. Five dogs developed chronic hepatitis, including 3 with pyogranulomatous inflammation. Of the 10 dogs reported to have died at last follow-up, survival time after illness onset ranged from 0.5 to 165 weeks, with 7 dogs dying of liver-related causes.

Conclusions And Clinical Relevance: Findings for dogs with hepatotoxicosis circumstantially associated with ketoconazole treatment suggested proactive monitoring of serum liver enzyme activities is advisable before and sequentially after initiation of such treatment.
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http://dx.doi.org/10.2460/javma.256.11.1245DOI Listing
June 2020

Developing mechanically robust, triazole-zwitterionic hydrogels to mitigate foreign body response (FBR) for islet encapsulation.

Biomaterials 2020 02 21;230:119640. Epub 2019 Nov 21.

Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, 14853, USA. Electronic address:

Zwitterionic hydrogels such as those based on polycarboxybetaine (PCB) or polysulfobetaine (PSB) have potential for various biomedical applications, due to their biocompatibility and low biofouling properties. However, the poor mechanical properties of zwitterionic hydrogels developed to date remain a challenge, severely limiting their practical uses. To improve the mechanical properties without compromising their zwitterionic feature or biocompatibility, we designed a new class of zwitterionic hydrogels by introducing triazole moieties into the hydrogel monomers that could form energy-dissipating π-π stacking. Compared to conventional zwitterionic hydrogels, the triazole-zwitterionic (TR-ZW) ones exhibited similarly excellent antifouling properties, but were much more mechanically robust with higher stretchability (250% tensile strain), better compression-resistance (89% compressive strain and 65% compression for at least 10 cycles without any crack) and better folding-resistance. In addition, upon subcutaneous implantation in mice, the TR-ZW hydrogels induced significantly lower foreign body responses (FBR) (i.e. less fibrosis and more blood vessel formation relative to a poly(2-hydroxyethyl methacrylate) hydrogel control). As an example of their potential applications, we showed the use of the TR-ZW hydrogels for islet encapsulation and transplantation and demonstrated diabetes correction up to ~1 month in mice in the convenient subcutaneous site.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119640DOI Listing
February 2020

Leptospirosis trends in China, 2007-2018: A retrospective observational study.

Transbound Emerg Dis 2020 May 16;67(3):1119-1128. Epub 2019 Dec 16.

Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY, USA.

Leptospirosis is one of the most common and neglected tropical waterborne diseases in China, causing serious economic losses, and constituting a significant public health threat. Leptospirosis has recently received increased attention and is considered a re-emerging infectious disease in many countries. The incidence of leptospirosis among people suggests that occupation, age, season, sex and water recreational activities are significant risk factors. The aim of this study was to describe the epidemiological profiles of leptospirosis in China during the 2007-2018 period. The morbidity data of leptospirosis by age, season (month), gender, occupation and geographic location (different provinces) were obtained from the public health science data centre of China for subsequent epidemiological analysis. The results indicate that the incidence of leptospirosis has shown a slow downward trend from 2007 to 2018, but morbidity rates were still relatively high (0.0660-0.0113). The incidence of leptospirosis varied in different provinces of China; cases localized mainly to the Southern and Central provinces, areas with warm weather and ample rainfall. Older people (aged 60-75), males, farmers, students and field workers were high-risk populations. During the 2007-2018 observation period, morbidity rates increased beginning in May, remained at high levels in August and September and decreased after November. The present investigation highlights the re-emergence of leptospirosis in some provinces of China (especially in Yunnan and Fujian) and shows that leptospirosis remains a serious public health threat. The results of this study should enhance measures taken for the prevention, control, and surveillance of leptospirosis in China.
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http://dx.doi.org/10.1111/tbed.13437DOI Listing
May 2020

Immunohistochemical Labeling of Low-Density Lipoprotein Receptor and Scavenger Receptor Class B Type 1 Are Increased in Canine Lymphoma.

Front Vet Sci 2018 11;5:340. Epub 2019 Jan 11.

Department of Population Medicine and Diagnostic Services, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.

Altered lipid metabolism is a well-documented hallmark of neoplastic transformation and impacts disease progression. Two major lipoprotein receptors, the low-density lipoprotein receptor (LDL-R) and scavenger receptor class B, type 1 (SR-BI) are overexpressed in a number of cancer types in people. These receptors serve to deliver cholesterol to the tumor cells and have been used to target drug therapies. In this study, we performed a retrospective analysis of LDL-R and SR-B1 expression in canine lymphoma using archived formalin-fixed tissue samples. Cases were immunophenotyped and classified according to World Health Organization (WHO) standards prior to immunostaining for the LDL_R and SR-B1. A total of 45 cases were evaluated; 21 high grade B (HGB), 11 low grade B (LGB), 7 high grade T (HGT), and 6 low grade T (LGT) lymphomas. One sided Wilcoxon rank sum tests were used to compare staining intensity between neoplastic and hyperplastic lymphoid tissue. The relationships between histological score and tumor grade and score and stage at presentation were assessed using non-parametric Kruskal-Wallis tests. Neoplastic lymphoid tissue expressed higher levels of both receptors compared to reactive lymph nodes. Median LDL-R score was 85.0 (interquartile range = 101.7), Median SR-B1 score was 209.0 (interquartile range 105.2). No relationship between LDL-R or SR-B1 staining score and tumor grade or phenotype was found. Serum cholesterol concentration was compared between dogs with high and low grade tumors using a two sample -test, and correlations between cholesterol concentration and histological score, and between the score for the two receptors were determined using a Spearman correlation. The high expression level of these lipoprotein receptors on most of the tumors could underlie the lack of relationship between score and tumor grade. The overexpression of LDL-R and SR-B1 in canine lymphoma holds therapeutic potential particularly in dogs that overexpress one or both of these receptors, and this warrants further investigation.
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http://dx.doi.org/10.3389/fvets.2018.00340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336922PMC
January 2019

Reference limits for hepatic bile duct-to-arteriole and bile duct-to-portal tract ratios in healthy cats.

Am J Vet Res 2019 Jan;80(1):15-23

OBJECTIVE To establish reference limits for hepatic bile duct-to-arteriole ratio (BD:A) and bile duct-to-portal tract ratio (BD:PT) in healthy cats and assess whether these parameters could be used to support a diagnosis of biliary ductopenia in cats. SAMPLE Hepatic biopsy samples from healthy cats (n = 20) and cats with ductopenia (2). PROCEDURES Hepatic biopsy samples from healthy cats were used to count the number of bile ducts and hepatic arterioles in 20 portal tracts for each cat. Mean BD:A and mean BD:PT for each cat were calculated, and these values were used to determine reference limits for mean BD:A and mean BD:PT. Results of histologic evaluation, including immunohistochemical staining in some instances, were compared for healthy cats versus cats with ductopenia. RESULTS Of the 400 portal tracts from healthy cats, 382 (95.5%) and 396 (99.0%) had BD:A and BD:PT, respectively, ≥ 1.0, with less variability in BD:A. Mean BD:A and BD:PT were markedly lower in both cats with ductopenia, compared with values for healthy cats. However, only mean BD:A for cats with ductopenia was below the reference limit of 0.59. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that systematic evaluation of BD:A, with a lower reference limit of 0.59 to define biliary ductopenia in cats, may be a discrete and easily applied morphometric tool to enhance detection of ductopenia in cats. However, application of this ratio required evaluation of ≥ 20 portal tracts with cross-sectioned portal elements to determine a mean BD:A value.
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http://dx.doi.org/10.2460/ajvr.80.1.15DOI Listing
January 2019

Biodegradable amino acid-based poly(ester amine) with tunable immunomodulating properties and their in vitro and in vivo wound healing studies in diabetic rats' wounds.

Acta Biomater 2019 01 30;84:114-132. Epub 2018 Nov 30.

Department of Fiber Science and Apparel Design, Cornell University, Ithaca, NY 14853-4401, USA. Electronic address:

The objective of this study is to design a new family of biodegradable synthetic polymeric biomaterials for providing a tunable inhibition of macrophage's nitric oxide synthase (NOS) pathway. l-Arginine (Arg) is the common substrate for NOS and arginase. Both two metabolic pathways participate in the wound healing process. An impaired wound healing, such as diabetic or other chronic wounds is usually associated with an overproduction of NO by macrophages via the NOS pathway. In this study, a new family of l-nitroarginine (NOArg) based polyester amide (NOArg-PEA) and NOArg-Arg PEA copolymers (co-PEA) were designed and synthesized with different composition ratios. The NOArg-PEA and NOArg-Arg co-PEAs are biodegradable (more than 50% degradation in vitro in 4 days at 37 °C), biocompatible and did not activate the resting macrophage immune response per se. When classically activated or alternatively activated macrophages (CAM/AAM) were incubated with NOArg-PEA and NOArg-Arg co-PEAs, the treatments decreased the NO production of CAM, increased the arginase activity in both CAM and AAM, increased TGF-β1 production of CAM to various degrees and had no significant effect on TNF-α production. Diabetic rat models were used to evaluate the efficacy of NOArg-PEA and NOArg-Arg co-PEAs on wound healing. Diabetic rats treated with 2-NOArg-4 PEA, 2-NOArg-4-Arg-4 20/80, and 2-NOArg-4-Arg-4 50/50 biomaterials achieved 40%-80% faster-wound healing when compared with the control on day 7. The data from the histological and immunohistochemical analysis showed that the 2-NOArg-4-Arg-4 20/80 and 2-NOArg-4-Arg-4 50/50 treatments led to more AAM phenotypes (CD206) and arginase I production in wound tissue than the control during the first 7 days, i.e., suggesting pro-healing wound microenvironment with improved re-epithelialization of wound healing. A similar trend was retained until day 14. The 2-NOArg-4-Arg-4 20/80 and 2-NOArg-4-Arg-4 50/50 treatments also increased the collagen deposition and angiogenesis in the healing wound between day 7 and day 14. Both in vitro and in vivo data of this study showed that this new family of NOArg-Arg co-PEA biomaterials have the potential as viable alternatives for treating impaired wound healing, such as diabetic or other types of chronic wounds. STATEMENT OF SIGNIFICANCE: Diabetic or other chronic wounds is usually associated with an overproduction of NO and pro-inflammatory signals by macrophages. Arginine supplement or NOS inhibitors administration failed to achieve an expected improved wound healing because of the dynamic complexity of arginine catabolism, the difficulty in transition from pro-inflammatory to pro-healing, and the short-term efficacy. We designed and synthesized a new family of water-soluble and degradable nitroarginine-arginine polyester amides to rebalance NOS/arginase metabolism pathways of macrophages. They showed tunable immunomodulating properties in vitro. The in vivo studies were performed to evaluate their efficacy in accelerating the healing. These new biomaterials have the potential as viable alternatives for treating impaired wound healing. The general audience of Acta Biomaterialia should be interested in these findings.
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http://dx.doi.org/10.1016/j.actbio.2018.11.053DOI Listing
January 2019

Nonarticular osseous cyst-like lesions of the intermedioradial carpal bone may be incidental magnetic resonance imaging findings in dogs.

Vet Radiol Ultrasound 2018 Nov 25;59(6):715-720. Epub 2018 Jun 25.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853.

As magnetic resonance imaging (MRI) becomes more readily available and more frequently utilized in the assessment of canine carpal lameness, both normal variations and early pathologic conditions must be recognized to optimize patient care and provide accurate diagnosis. On cross sectional studies of the canine carpus, cyst-like lesions have been detected at the dorsolateral aspect of the intermedioradial carpal bone. The cross-sectional imaging and histologic properties of these lesions have not been described. The purpose of this observational study is to evaluate the MRI and histologic features of these cyst-like lesions in a cohort of clinically sound dogs. It was hypothesized that the lesions would show features similar to intraosseous ganglion cysts of the human wrist. Twenty-five cadaveric canine carpi were obtained and a total of 13 lesions were detected on MRI. Based on MRI, six carpi with lesions of varying size and one normal carpus were submitted for histological evaluation. Five of the abnormal carpi had nonarticular cyst-like lesions; one specimen with a positive magnetic resonance image for a cyst-like lesion had no cyst-like lesion on histology. Conspicuity of a medium-size lesion as evaluated on radiographs was poor. Given the presence of these nonarticular cyst-like lesions in a population of clinically sound patients, their clinical importance is uncertain. The development of these lesions may relate to altered mechanics or genetic predispositions, requiring additional study.
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http://dx.doi.org/10.1111/vru.12658DOI Listing
November 2018

New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of Common Biological Product.

Emerg Infect Dis 2018 02;24(2):303-310

Equine serum hepatitis (i.e., Theiler's disease) is a serious and often life-threatening disease of unknown etiology that affects horses. A horse in Nebraska, USA, with serum hepatitis died 65 days after treatment with equine-origin tetanus antitoxin. We identified an unknown parvovirus in serum and liver of the dead horse and in the administered antitoxin. The equine parvovirus-hepatitis (EqPV-H) shares <50% protein identity with its phylogenetic relatives of the genus Copiparvovirus. Next, we experimentally infected 2 horses using a tetanus antitoxin contaminated with EqPV-H. Viremia developed, the horses seroconverted, and acute hepatitis developed that was confirmed by clinical, biochemical, and histopathologic testing. We also determined that EqPV-H is an endemic infection because, in a cohort of 100 clinically normal adult horses, 13 were viremic and 15 were seropositive. We identified a new virus associated with equine serum hepatitis and confirmed its pathogenicity and transmissibility through contaminated biological products.
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http://dx.doi.org/10.3201/eid2402.171031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5782890PMC
February 2018

Extended low-resolution structure of a antigen offers high bactericidal antibody accessibility amenable to vaccine design.

Elife 2017 12 6;6. Epub 2017 Dec 6.

Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, United States.

Pathogens rely on proteins embedded on their surface to perform tasks essential for host infection. These obligatory structures exposed to the host immune system provide important targets for rational vaccine design. Here, we use a systematically designed series of multi-domain constructs in combination with small angle X-ray scattering (SAXS) to determine the structure of the main immunoreactive region from a major antigen from , LigB. An anti-LigB monoclonal antibody library exhibits cell binding and bactericidal activity with extensive domain coverage complementing the elongated architecture observed in the SAXS structure. Combining antigenic motifs in a single-domain chimeric immunoglobulin-like fold generated a vaccine that greatly enhances leptospiral protection over vaccination with single parent domains. Our study demonstrates how understanding an antigen's structure and antibody accessible surfaces can guide the design and engineering of improved recombinant antigen-based vaccines.
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http://dx.doi.org/10.7554/eLife.30051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749957PMC
December 2017

Matrix-Induced Autologous Chondrocyte Implantation (MACI) Using a Cell-Seeded Collagen Membrane Improves Cartilage Healing in the Equine Model.

J Bone Joint Surg Am 2017 Dec;99(23):1987-1998

Histogenics Corporation, Waltham, Massachusetts.

Background: Autologous chondrocyte implantation (ACI) using a collagen scaffold (matrix-induced ACI; MACI) is a next-generation approach to traditional ACI that provides the benefit of autologous cells and guided tissue regeneration using a biocompatible collagen scaffold. The MACI implant also has inherent advantages including surgical implantation via arthroscopy or miniarthrotomy, the elimination of periosteal harvest, and the use of tissue adhesive in lieu of sutures. This study evaluated the efficacy of the MACI implant in an equine full-thickness cartilage defect model at 1 year.

Methods: Autologous chondrocytes were seeded onto a collagen type-I/III membrane and implanted into one of two 15-mm defects in the femoral trochlear ridge of 24 horses. Control defects either were implanted with cell-free collagen type-I/III membrane (12 horses) or were left ungrafted as empty defects (12 horses). An additional 3 horses had both 15-mm defects remain empty as nonimplanted joints. The repair was scored by second-look arthroscopy (12 weeks), and necropsy examination (53 weeks). Healing was assessed by arthroscopic scoring, gross assessment, histology and immunohistology, cartilage matrix component assay, and gene expression determination. Toxicity was examined by prostaglandin E2 formation in joint fluid, and lymph node morphology combined with histologic screening of organs.

Results: MACI-implanted defects had improved gross healing and composite histologic scores, as well as increases in chondrocyte predominance, toluidine blue-stained matrix, and collagen type-II content compared with scaffold-only implanted or empty defects. There was minimal evidence of reaction to the implant in the synovial membrane (minor perivascular cuffing), subchondral bone, or cartilage. There were no adverse clinical effects, signs of organ toxicity, or evidence of chondrocytes or collagen type-I/III membrane in draining lymph nodes.

Conclusions: The MACI implant appeared to improve cartilage healing in a critical-sized defect in the equine model compared with collagen matrix alone.

Clinical Relevance: These results indicate that the MACI implant is quick to insert, provides chondrocyte security in the defect, and improves cartilage healing compared with ACI.
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http://dx.doi.org/10.2106/JBJS.16.00603DOI Listing
December 2017

The pathogenesis of paraesophageal empyema in dogs and constancy of radiographic and computed tomography signs are linked to involvement of the mediastinal serous cavity.

Vet Radiol Ultrasound 2018 Mar 30;59(2):169-179. Epub 2017 Nov 30.

Department of Clinical Sciences, Cornell University, Ithaca, NY, 14853.

The mediastinal serous cavity is a normal anatomic space in the caudal mediastinum. Aims of this anatomic and case series study were to describe the signs of pathologic expansion of the mediastinal serous cavity observed during computed tomography (CT), review the underlying anatomy, perform a literature review, and evaluate the medical records of several dogs with mediastinal serous cavity empyema (paraesophageal empyema). The mesothelial lined mediastinal serous cavity is a cranial extension of the omental bursa, separated from the peritoneal cavity by the diaphragm, in the dorsal part of the caudal mediastinum, to the right of the esophagus, between the heart base and diaphragm. In five adult, large-breed dogs with surgically and histologically confirmed paraesophageal empyema, macroscopic plant material was found at surgery in two dogs, adherence to adjacent lung was present in three different dogs, accessory lobectomy was performed in two dogs with subacute-chronic pyogranulomatous pneumonia, and one dog had concurrent pyothorax and mediastinitis, but none had esophageal abnormalities. This study expands our understanding of the pathogenesis and basis for the imaging appearance of paraesophageal empyema in dogs by clarifying the underlying anatomic structures that direct development of this condition. The term empyema accurately describes this condition because the purulent material accumulates within an existing body cavity. The study also provides initial evidence that the development of paraesophageal empyema might be due to local extension of lung disease, such as foreign body migration or pneumonia. Computed tomography was helpful for diagnosis, assessing size, and determining the spread of disease.
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http://dx.doi.org/10.1111/vru.12582DOI Listing
March 2018

Canine Hepatitis Associated with Intrahepatic Bacteria in Three Dogs.

J Am Anim Hosp Assoc 2018 Jan/Feb;54(1):65-70. Epub 2017 Nov 13.

From the Blue Pearl Veterinary Partners, New York, New York (J.I., A.E.); Veterinary Specialists of North Texas, Dallas, Texas (D.P.B.); College of Veterinary Medicine, Cornell University, Ithaca, New York (S.P.M., K.W.S.); and SAGE Centers for Veterinary Specialty and Emergency Care, Campbell, California (B.N.).

This case report describes the detection of intrahepatic bacteria in formalin-fixed paraffin-embedded histopathological sections from three dogs with neutrophilic, pyogranulomatous, or lymphoplasmacytic hepatitis and cholangiohepatitis. In each of these cases, eubacterial fluorescence in situ hybridization enabled colocalization of intrahepatic bacteria with neutrophilic and granulomatous inflammation in samples that were negative for bacteria when evaluated by routine hematoxylin and eosin histopathology augmented with histochemical stains. Positive responses to antimicrobial therapy were observed in of 2 out of 2 patients that were treated with antimicrobials. These findings suggest that eubacterial fluorescence in situ hybridization analysis of formalin-fixed paraffin-embedded histopathological sections is more sensitive than conventional histochemical stains for the diagnosis of bacteria-associated canine hepatitis.
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http://dx.doi.org/10.5326/JAAHA-MS-6492DOI Listing
January 2019

Reduction of Thoroughbred racing fatalities at New York Racing Association racetracks using a multi-disciplinary mortality review process.

J Vet Diagn Invest 2017 Jul 14;29(4):465-475. Epub 2017 Jun 14.

Departments of Population Medicine and Diagnostic Sciences (Palmer, Mohammed), College of Veterinary Medicine, Cornell University, Ithaca, NY.

Between January 1, 2013 and December 31, 2015, findings of a New York State Gaming Commission-Cornell University postmortem examination program were utilized in a multi-disciplinary mortality review process to review 129 racing fatalities at Thoroughbred racetracks operated by the New York Racing Association (NYRA). Musculoskeletal fractures comprised 79% of the fatalities; cardiopulmonary conditions accounted for 12% of the fatalities. Other causes of death included gastrointestinal (3%), respiratory (5%), and central nervous system (2%) conditions. Fetlock failure represented 50% of the musculoskeletal fatalities. The general distribution of these findings was very similar to that reported by the California Animal Health and Food Safety Laboratory System during the same period. These findings, used in conjunction with a comprehensive mortality review process and regulatory reform, have contributed to a significant reduction of the incidence of Thoroughbred racing fatalities at NYRA racetracks during the period of this review.
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http://dx.doi.org/10.1177/1040638717713051DOI Listing
July 2017

Characterization of aminoaciduria and hypoaminoacidemia in dogs with hepatocutaneous syndrome.

Am J Vet Res 2017 Jun;78(6):735-744

OBJECTIVE To characterize aminoaciduria and plasma amino acid concentrations in dogs with hepatocutaneous syndrome (HCS). ANIMALS 20 client-owned dogs of various breeds and ages. PROCEDURES HCS was definitively diagnosed on the basis of liver biopsy specimens (n = 12), gross and histologic appearance of skin lesions (4), and examination of skin and liver biopsy specimens (2) and presumptively diagnosed on the basis of cutaneous lesions with compatible clinicopathologic and hepatic ultrasonographic (honeycomb or Swiss cheese pattern) findings (2). Amino acid concentrations in heparinized plasma and urine (samples obtained within 8 hours of each other) were measured by use of ion exchange chromatography. Urine creatinine concentration was used to normalize urine amino acid concentrations. Plasma amino acid values were compared relative to mean reference values; urine-corrected amino acid values were compared relative to maximal reference values. RESULTS All dogs had generalized hypoaminoacidemia, with numerous amino acid concentrations < 50% of mean reference values. The most consistent and severe abnormalities involved glutamine, proline, cysteine, and hydroxyproline, and all dogs had marked lysinuria. Urine amino acids exceeding maximum reference values (value > 1.0) included lysine, 1-methylhistidine, and proline. CONCLUSIONS AND CLINICAL RELEVANCE Hypoaminoacidemia in dogs with HCS prominently involved amino acids associated with the urea cycle and synthesis of glutathione and collagen. Marked lysinuria and prolinuria implicated dysfunction of specific amino acid transporters and wasting of amino acids essential for collagen synthesis. These findings may provide a means for tailoring nutritional support and for facilitating HCS diagnosis.
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http://dx.doi.org/10.2460/ajvr.78.6.735DOI Listing
June 2017

Tumor collision of uterine adenocarcinoma and leiomyosarcoma in a goat.

J Vet Diagn Invest 2017 Sep 19;29(5):696-699. Epub 2017 Apr 19.

Department of Clinical Sciences (Dockweiler, Fubini, Le, Donnelly, Gilbert, and Cheong), College of Veterinary Medicine, Cornell University, Ithaca, NY.

An aged mixed-breed goat doe was presented with a 9-mo history of serosanguineous vaginal discharge. Vaginal speculum examination revealed serosanguineous discharge but otherwise no abnormalities. Transrectal ultrasonography showed normal ovaries and multifocal cystic lesions within the uterus. Ovariohysterectomy was recommended because of a strong suspicion of neoplasia. Multiple, non-resectable masses were noted in and around the uterus intraoperatively, and euthanasia was elected. Autopsy revealed multiple masses within the uterus, cervix, and lung parenchyma. Histologically, the masses within the uterus represented a likely collision tumor of primary adenocarcinoma and leiomyosarcoma. Our report highlights the importance of obtaining biopsy samples of all masses because the lesions described showed significantly different biological behavior. This information is vital to guide treatment and prognosis.
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http://dx.doi.org/10.1177/1040638717705411DOI Listing
September 2017

High-water-content and resilient PEG-containing hydrogels with low fibrotic response.

Acta Biomater 2017 04 20;53:100-108. Epub 2017 Feb 20.

Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, United States. Electronic address:

Hydrogels such as those based on polyethylene glycol (PEG) are broadly used in biomedicine where high water contents, robust mechanical properties such as resilience and favorable interactions with the body are often simultaneously desirable. However, the mechanical properties of conventional hydrogels often degrade rapidly after swelling or with increasing water content, limiting their potential in many applications. Here we describe a new class of PEG-containing hydrogels that remain highly resilient after maximum swelling. We achieved the hydrogels by incorporating reversible "dual" hydrogen bonding into highly coiled, elastic PEG networks. These hydrogels, due to their high water content and high mechanical resilience, can form highly permeable, yet durable and easy-to-handle cell delivery devices without any additional structural support. In addition, optimization of chemical composition resulted in hydrogels with superior bio-inertness, inducing much less fibrosis upon subcutaneous implantation in mice than a polyhydroxyethylmethacrylate (PHEMA) hydrogel control.

Statement Of Significance: Hydrogels such as polyethylene glycol (PEG)-based ones are broadly used in the biomedical world. Examples include wound dressings, tissue scaffolds, medical implants, biosensors and drug or cell delivery devices. In many of these applications, robust mechanical property, high water content (or facile mass transfer) and favorable interactions with the body are often simultaneously desirable. However, the mechanical property of hydrogels often degrades rapidly after swelling or with increasing water content. Here we report a new class of PEG-based hydrogels that simultaneously possess high water content, high mechanical resilience and low fibrotic response upon subcutaneous implantation in mice. These hydrogels may therefore find broad applications in biomedicine.
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http://dx.doi.org/10.1016/j.actbio.2017.02.028DOI Listing
April 2017

Phosphorylated Radix Cyathulae officinalis Polysaccharides Act as Adjuvant via Promoting Dendritic Cell Maturation.

Molecules 2017 Jan 10;22(1). Epub 2017 Jan 10.

College of Veterinary Medicine, Cornell University, Ithaca, NY 14850, USA.

The aim of this study was to investigate whether phosphorylated polysaccharides (pRCPS) used as adjuvant with foot-and-mouth disease vaccine (FMDV) can stimulate specific humoral and cellular immune responses in ICR mice. The results demonstrated that pRCPS significantly up-regulated FMDV-specific IgG, IgG1, IgG2b and IgG2a antibody levels and splenocyte proliferation. pRCPS also promoted the killing activities of cytotoxic T lymphocytes (CTL) and natural killer cells (NK). In addition, pRCPS enhanced the expression levels of IL-2, IL-4, and IFN-γ in CD4⁺ T cells and the level of IFN-γ in CD8⁺ T cells. Importantly, pRCPS enhanced the expression of MHCII, CD40⁺, CD86⁺, and CD80⁺ in dendritic cells (DCs). This study indicated that phosphorylation modification could increase immune-enhancing activities of RCPS, and pRCPS could promote humoral and cellular immune responses through facilitating DC maturation.
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http://dx.doi.org/10.3390/molecules22010106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155757PMC
January 2017

Angiogenic Factors Correlate with T Cell Immune Reconstitution and Clinical Outcomes after Double-Unit Umbilical Cord Blood Transplantation in Adults.

Biol Blood Marrow Transplant 2017 01 21;23(1):103-112. Epub 2016 Oct 21.

Hematology-Oncology and Cancer Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Electronic address:

Umbilical cord blood (UCB) is a valuable graft source for allogeneic hematopoietic stem cell transplantation (HSCT) in patients who lack adult donors. UCB transplantation (UCBT) in adults results in delayed immune reconstitution, leading to high infection-related morbidity and mortality. Angiogenic factors and markers of endothelial dysfunction have biologic and prognostic significance in conventional HSCT, but their role in UCBT has not been investigated. Furthermore, the interplay between angiogenesis and immune reconstitution has not been studied. Here we examined whether angiogenic cytokines, angiopoietin-1 (ANG-1) and vascular endothelial growth factor (VEGF), or markers of endothelial injury, thrombomodulin (TM) and angiopoietin-2 (ANG-2), associate with thymic regeneration as determined by T cell receptor excision circle (TREC) values and recovery of T cell subsets, as well as clinical outcomes in adult recipients of UCBT. We found that plasma levels of ANG-1 significantly correlated with the reconstitution of naive CD4CD45RA and CD8CD45RA T cell subsets, whereas plasma levels of VEGF displayed a positive correlation with CD4CD45RO T cells and regulatory T cells and a weak correlation with TRECs. Assessment of TM and ANG-2 revealed a strong inverse correlation of both factors with naive T cells and TRECs. The angiogenic capacity of each patient's plasma, as determined by an in vitro angiogenesis assay, positively correlated with VEGF levels and with reconstitution of CD4 T cell subsets. Higher VEGF levels were associated with worse progression-free survival and higher risk of relapse, whereas higher levels of TM were associated with chronic graft-versus-host disease and nonrelapse mortality. Thus, angiogenic factors may serve as valuable markers associated with T cell reconstitution and clinical outcomes after UCBT.
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http://dx.doi.org/10.1016/j.bbmt.2016.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489056PMC
January 2017

Neoplasia in 125 donkeys (Equus asinus): literature review and a survey of five veterinary schools in the United States and Canada.

J Vet Diagn Invest 2016 Nov 3;28(6):662-670. Epub 2016 Oct 3.

Private pathology practice, Maupin, OR (Davis)College of Veterinary Medicine, Oregon State University, Corvallis, OR (Valentine, Gordon)College of Veterinary Medicine, Cornell University, Ithaca, NY (McDonough)Veterinary Diagnostic Laboratory, College of Veterinary Medicine and Biological Sciences, Colorado State University, Fort Collins, CO (Schaffer)Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada (Allen)Department of Pathology, Microbiology & Immunology, University of California-Davis, Davis, CA (Pesavento).

A diagnosis of neoplasia was noted in 125 of 357 donkeys (35%) in our review of medical records from 5 veterinary schools in the United States and Canada. Equine sarcoid was the most common tumor in our study, accounting for 72% of all tumors and 82% of cutaneous tumors. Soft-tissue sarcomas were the second most common skin tumors. All other types of neoplasia were rare. Important differences in the occurrence of neoplasia in donkeys compared to horses included the rarity or absence of squamous cell carcinoma in any organ system and gray horse melanoma. Lymphosarcoma, the most common malignant tumor in horses, appears to be very rare in donkeys. We report several tumors in donkeys including melanocytoma, peripheral nerve sheath tumor, and gastrointestinal stromal tumor. Our data demonstrate commonalities as well as differences in neoplastic diseases of donkeys and horses. Understanding differences in carcinogenesis among these 2 closely related species can inform researchers pursuing pathogenic mechanisms of equine disease and inform veterinary diagnosticians regarding tumor prevalence.
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http://dx.doi.org/10.1177/1040638716665659DOI Listing
November 2016

Leptospira Immunoglobulin-Like Protein B (LigB) Binds to Both the C-Terminal 23 Amino Acids of Fibrinogen αC Domain and Factor XIII: Insight into the Mechanism of LigB-Mediated Blockage of Fibrinogen α Chain Cross-Linking.

PLoS Negl Trop Dis 2016 09 13;10(9):e0004974. Epub 2016 Sep 13.

Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.

The coagulation system provides a primitive but effective defense against hemorrhage. Soluble fibrinogen (Fg) monomers, composed of α, β and γ chains, are recruited to provide structural support for the formation of a hemostatic plug. Fg binds to platelets and is processed into a cross-linked fibrin polymer by the enzymatic clotting factors, thrombin and Factor XIII (FXIII). The newly formed fibrin-platelet clot can act as barrier to protect against pathogens from entering the bloodstream. Further, injuries caused by bacterial infections can be confined to the initial wound site. Many pathogenic bacteria have Fg-binding adhesins that can circumvent the coagulation pathway and allow the bacteria to sidestep containment. Fg expression is upregulated during lung infection providing an attachment surface for bacteria with the ability to produce Fg-binding adhesins. Fg binding by leptospira might play a crucial factor in Leptospira-associated pulmonary hemorrhage, the main factor contributing to lethality in severe cases of leptospirosis. The 12th domain of Leptospira immunoglobulin-like protein B (LigB12), a leptospiral adhesin, interacts with the C-terminus of FgαC (FgαCC). In this study, the binding site for LigB12 was mapped to the final 23 amino acids at the C-terminal end of FgαCC (FgαCC8). The association of FgαCC8 with LigB12 (ELISA, KD = 0.76 μM; SPR, KD = 0.96 μM) was reduced by mutations of both charged residues (R608, R611 and H614 from FgαCC8; D1061 from LigB12) and hydrophobic residues (I613 from FgαCC8; F1054 and A1065 from LigB12). Additionally, LigB12 bound strongly to FXIII and also inhibited fibrin formation, suggesting that LigB can disrupt coagulation by suppressing FXIII activity. Here, the detailed binding mechanism of a leptospiral adhesin to a host hemostatic factor is characterized for the first time and should provide better insight into the pathogenesis of leptospirosis.
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http://dx.doi.org/10.1371/journal.pntd.0004974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021285PMC
September 2016

Domestic dogs (Canis lupus familiaris) and forensic practice.

Forensic Sci Med Pathol 2016 Dec 12;12(4):530-531. Epub 2016 Sep 12.

T8 008A Veterinary Research Tower, Cornell University, Ithaca, NY, USA.

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http://dx.doi.org/10.1007/s12024-016-9808-7DOI Listing
December 2016
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