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Topic:Immunology

The equine immune system is a complex network of cells, tissues, and organs that work collaboratively to defend against pathogens and maintain homeostasis. It consists of innate and adaptive components, each with distinct functions and mechanisms. The innate immune system provides the first line of defense through physical barriers, phagocytic cells, and the complement system. The adaptive immune system involves lymphocytes, such as B cells and T cells, which generate specific responses to antigens and provide immunological memory. Research in equine immunology explores the interactions between these components, the impact of genetic and environmental factors on immune function, and the development of vaccines and therapeutics. This page gathers peer-reviewed studies and scholarly articles focusing on the mechanisms, regulation, and clinical applications of the equine immune system in health and disease.
Antibody and cellular immune responses of naïve mares to repeated vaccination with an inactivated equine herpesvirus vaccine.
Vaccine    September 16, 2015   Volume 33, Issue 42 5588-5597 doi: 10.1016/j.vaccine.2015.09.009
Wagner B, Goodman LB, Babasyan S, Freer H, Torsteinsdóttir S, Svansson V, Björnsdóttir S, Perkins GA.Equine herpesvirus type 1 (EHV-1) continues to cause severe outbreaks of abortions or myeloencephalopathy in horses despite widely used vaccination. The aim of this work was to determine the effects of frequent vaccination with an inactivated EHV vaccine on immune development in horses. Fifteen EHV-1 naïve mares were vaccinated a total of 5 times over a period of 8 months with intervals of 20, 60, 90 and 60 days between vaccine administrations. Total antibody and antibody isotype responses were evaluated with a new sensitive EHV-1 Multiplex assay to glycoprotein C (gC) and gD for up to 14 mon...
Allergens in veterinary medicine.
Allergy    September 11, 2015   Volume 71, Issue 1 27-35 doi: 10.1111/all.12726
Mueller RS, Janda J, Jensen-Jarolim E, Rhyner C, Marti E.Allergic diseases in animals are increasingly gaining importance in veterinary practice and as research models. For intradermal testing and allergen immunotherapy, a good knowledge of relevant allergens for the individual species is of great importance. Currently, the knowledge about relevant veterinary allergens is based on sensitization rates identified by intradermal testing or serum testing for allergen-specific IgE; crude extracts are the basis for most evaluations. Only a few studies provide evidence about the molecular structure of (particularly) dust mite, insect and mould allergens in...
Equine recurrent uveitis: Lessons from and for autoimmune anterior uveitis in humans.
Veterinary journal (London, England : 1997)    September 9, 2015   Volume 206, Issue 3 245-246 doi: 10.1016/j.tvjl.2015.09.003
Hughes KJ.No abstract available
Enhanced heme accessibility in horse heart mini-myoglobin: Insights from molecular modelling and reactivity studies.
Archives of biochemistry and biophysics    September 9, 2015   Volume 585 1-9 doi: 10.1016/j.abb.2015.09.005
Mini-myoglobin (mini-HHMb) is a fragment of horse-heart myoglobin (HHMb) considered to be the prototype of the product encoded by the central exon of the HHMb gene. For this reason, mini-HHMb has been studied extensively showing that carbonylation and oxygenation properties of the ferrous form are similar to those of the full-length protein, while kinetics and thermodynamics of azide binding to the ferric form are significantly different from those of HHMb. To analyze the structure-function relationships in mini-HHMb and the role of conformational fluctuations in ligand accessibility, the mole...
Recombinant Culicoides obsoletus complex allergens stimulate antigen-specific T cells of insect bite hypersensitive Shetland ponies in vitro.
Veterinary dermatology    September 8, 2015   Volume 26, Issue 6 467-e109 doi: 10.1111/vde.12251
Meulenbroeks C, van der Meide NM, Willemse T, Rutten VP, Tijhaar E.Ponies may suffer from Insect bite hypersensitivity (IBH), an allergic IgE-mediated pruritic skin disorder, induced by allergens from biting midges of the Culicoides spp. Objective: To determine whether recombinant Culicoides obsoletus allergens are able to activate T cells of ponies exposed to C. obsoletus and whether these allergen-specific responses differ between IBH-affected and healthy ponies. Methods: Ten IBH-affected Shetland ponies and 10 age-matched healthy controls taken from the same stables, to ensure similar exposure to midges. Methods: Peripheral blood mononuclear cells (PBMC) w...
Genetic Susceptibility to Rhodococcus equi.
Journal of veterinary internal medicine    September 4, 2015   Volume 29, Issue 6 1648-1659 doi: 10.1111/jvim.13616
McQueen CM, Dindot SV, Foster MJ, Cohen ND.Rhodococcus equi pneumonia is a major cause of morbidity and mortality in neonatal foals. Much effort has been made to identify preventative measures and new treatments for R. equi with limited success. With a growing focus in the medical community on understanding the genetic basis of disease susceptibility, investigators have begun to evaluate the interaction of the genetics of the foal with R. equi. This review describes past efforts to understand the genetic basis underlying R. equi susceptibility and tolerance. It also highlights the genetic technology available to study horses and des...
Mitogen-activated kinase pathway activation in epidermal lamellae in the acute stages of carbohydrate overload laminitis models and the effect of regional deep hypothermia on signalling pathways.
Equine veterinary journal    August 29, 2015   Volume 48, Issue 5 633-640 doi: 10.1111/evj.12488
Gardner AK, Kelly CS, van Eps AW, Burns TA, Watts MR, Belknap JK.In sepsis models, mitogen-activated protein kinases (MAPKs) are reported to incite inflammatory injury to tissues and are purported to be a therapeutic target. Objective: To assess MAPK signalling in lamellae in sepsis-related laminitis (SRL) at different time points after induction of laminitis via carbohydrate overload, and to determine the effect of regional deep hypothermia (RDH) on MAPK signalling. Methods: In vitro study using archived tissue samples. Methods: Lamellar concentrations of MAPKs were assessed in archived lamellar samples from 2 studies: 1) the starch gruel model of SRL with...
Cell Surface Glycan Changes in the Spontaneous Epithelial-Mesenchymal Transition of Equine Amniotic Multipotent Progenitor Cells.
Cells, tissues, organs    August 26, 2015   Volume 200, Issue 3-4 212-226 doi: 10.1159/000433420
Lange-Consiglio A, Accogli G, Cremonesi F, Desantis S.Amniotic epithelial cells (AECs) spontaneously transform into amniotic mesenchymal cells (AMCs) in vitro during cell culture. Glycocalyx was analyzed to identify the glycan pattern in AECs, AMCs and epithelial-mesenchymal transdifferentiated cells (EMTCs). Pure cell cultures were derived using cloned AEC and AMC cell lines obtained by the dilution technique from amniotic membranes. Mesenchymal cells generated by differentiation of clonal epithelial cells were considered transdifferentiated. Immunocytoscreen, in vitro multipotent differentiation and molecular characterization of EMTCs were perf...
Applied Protein and Molecular Techniques for Characterization of B Cell Neoplasms in Horses.
Clinical and vaccine immunology : CVI    August 26, 2015   Volume 22, Issue 11 1133-1145 doi: 10.1128/CVI.00374-15
Badial PR, Tallmadge RL, Miller S, Stokol T, Richards K, Borges AS, Felippe MJ.Mature B cell neoplasms cover a spectrum of diseases involving lymphoid tissues (lymphoma) or blood (leukemia), with an overlap between these two presentations. Previous studies describing equine lymphoid neoplasias have not included analyses of clonality using molecular techniques. The objective of this study was to use molecular techniques to advance the classification of B cell lymphoproliferative diseases in five adult equine patients with a rare condition of monoclonal gammopathy, B cell leukemia, and concurrent lymphadenopathy (lymphoma/leukemia). The B cell neoplasms were phenotypically...
Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a+ Monocytic Cells upon Adhesion to Endothelial Cells.
Journal of virology    August 19, 2015   Volume 89, Issue 21 10912-10923 doi: 10.1128/JVI.01589-15
Laval K, Favoreel HW, Poelaert KC, Van Cleemput J, Nauwynck HJ.Equine herpesvirus type 1 (EHV-1) is a main cause of respiratory disease, abortion, and encephalomyelopathy in horses. Monocytic cells (CD172a(+)) are the main carrier cells of EHV-1 during primary infection and are proposed to serve as a "Trojan horse" to facilitate the dissemination of EHV-1 to target organs. However, the mechanism by which EHV-1 is transferred from CD172a(+) cells to endothelial cells (EC) remains unclear. The aim of this study was to investigate EHV-1 transmission between these two cell types. We hypothesized that EHV-1 employs specific strategies to promote the adhesion o...
Increased risk of horse sensitization in southwestern Iranian horse riders.
International journal of occupational medicine and environmental health    August 1, 2015   Volume 28, Issue 5 909-913 doi: 10.13075/ijomeh.1896.00471
Moghtaderi M, Farjadian S, Hosseini Z, Raayat A.The aim of this study has been to investigate the frequency of sensitization to horse allergens and clinical symptoms in horse riders. Methods: A total of 42 horse riders and 50 healthy individuals were examined by means of skin prick tests for a panel of horse and common animal allergens, and pulmonary function tests were done by spirometry. Results: The rate of sensitization to horse allergens was 31% as proven by the skin prick test in horse riders whereas horse sensitization was not seen in the control group. Occupational allergy symptoms were reported by 19 horse riders. Two horse riders ...
Equine immunoglobulins and organization of immunoglobulin genes.
Developmental and comparative immunology    July 26, 2015   Volume 53, Issue 2 303-319 doi: 10.1016/j.dci.2015.07.017
Walther S, Rusitzka TV, Diesterbeck US, Czerny CP.Our understanding of how equine immunoglobulin genes are organized has increased significantly in recent years. For equine heavy chains, 52 IGHV, 40 IGHD, 8 IGHJ and 11 IGHC are present. Seven of these IGHCs are gamma chain genes. Sequence diversity is increasing between fetal, neonatal, foal and adult age. The kappa light chain contains 60 IGKV, 5 IGKJ and 1 IGKC, whereas there are 144 IGLV, 7 IGLJ, and 7 IGLC for the lambda light chain, which is expressed predominantly in horses. Significant transcriptional differences for IGLV and IGLC are identified in different breeds. Allotypic and allel...
Comparative morphological evaluation of domestic animal cornea.
Veterinary ophthalmology    July 20, 2015   Volume 19, Issue 4 297-304 doi: 10.1111/vop.12298
Nautscher N, Bauer A, Steffl M, Amselgruber WM.This study described corneal morphology in different domestic animals using histological and immunohistochemical methods. Specifically, we evaluated the species-specific distribution pattern of cytokeratins (CKs) and aquaporins (AQPs) to assess their contribution to the strength and transparency of the cornea, respectively. Methods: Corneal sections (2 μm thick) were obtained from 28 pigs, 11 cows, two goats, six horses, four dogs, and five cats and stained with hematoxylin-eosin and periodic acid-Schiff (PAS) reaction. Immunohistochemistry was also performed using CK1 to 3 and AQP1 and 5 an...
Serum concentrations of allergen-specific IgE in horses with equine recurrent airway obstruction and healthy controls assessed by ELISA.
Veterinary clinical pathology    July 14, 2015   Volume 44, Issue 3 391-396 doi: 10.1111/vcp.12274
Niedzwiedz A, Jaworski Z, Kubiak K.Equine recurrent airway obstruction (RAO), also known as heaves, is one of the most common respiratory problems in older horses. When RAO-affected horses stay pastured or in a dust-free environment for a prolonged time, clinical signs as well as airway inflammation wane. A number of environmental, immunologic, infectious, and genetic factors play an important role in the pathogenesis of RAO, and the immunologic basis of this disease is still poorly understood. Objective: The aim of this study was to investigate the concentrations of allergen-specific IgE in the serum of horses suffering from R...
Immunohistochemical Expression of Collagens in the Skin of Horses Treated with Leukocyte-Poor Platelet-Rich Plasma.
BioMed research international    July 7, 2015   Volume 2015 893485 doi: 10.1155/2015/893485
de Souza MV, Silva MB, Pinto Jde O, Lima MB, Crepaldi J, Lopes GF, dos Santos HB, Ribeiro RI, Thomé RG.This study evaluated the immunohistochemical expression of type I (COL I) and III (COL III) collagens during the healing process of skin treated with leukocyte-poor platelet-rich plasma (LP-PRP). Seven healthy gelding crossbred horses aged 16 to 17 years were used. Two rectangle-shaped wounds were created surgically in the right and left gluteal regions. Twelve hours after wound induction, 0.5 mL of the LP-PRP was administered in each edge of the wounds of one of the gluteal regions. The contralateral region was used as control (CG). Three samples were obtained: after wound induction (T0), 1...
Expression of T helper type 17 (Th17)-associated cytokines and toll-like receptor 4 and their correlation with Foxp3 positive cells in rectal biopsies of horses with clinical signs of inflammatory bowel disease.
Veterinary journal (London, England : 1997)    July 7, 2015   Volume 206, Issue 1 97-104 doi: 10.1016/j.tvjl.2015.07.003
Olofsson KM, Hjertner B, Fossum C, Press CM, Lindberg R.Inflammatory bowel disease (IBD) in horses is an idiopathic disorder, encompassing different types of chronic intestinal inflammation. The pathogenesis of the disease remains to be established, but it has been suggested that an imbalance between regulatory T cells (Tregs) and T helper 17 (Th17)-associated cytokines and altered toll-like receptor 4 (TLR4) expression is associated with intestinal inflammation in other species. The aim of the present study was to quantify Tregs in rectal biopsies from horses affected with IBD by immunohistochemistry and to evaluate expression of genes encoding in...
Equine recurrent uveitis: Human and equine perspectives.
Veterinary journal (London, England : 1997)    July 3, 2015   Volume 206, Issue 1 22-29 doi: 10.1016/j.tvjl.2015.06.017
Malalana F, Stylianides A, McGowan C.Equine recurrent uveitis (ERU) is a spontaneous disease characterised by repeated episodes of intraocular inflammation. The epidemiology of ERU has not been fully elucidated, but the condition appears to be much more common in horses than is recurrent uveitis in humans, especially in certain breeds and geographical regions. Both humans and horses show a similarly altered immune response and a marked autoimmune response as the primary disease pathophysiology. However, an inciting cause is not always clear. Potential inciting factors in horses include microbial agents such as Leptospira spp. Mic...
Changes in Serum Strongylus Vulgaris-Specific Antibody Concentrations in Response to Anthelmintic Treatment of Experimentally Infected Foals.
Frontiers in veterinary science    July 1, 2015   Volume 2 17 doi: 10.3389/fvets.2015.00017
Nielsen MK, Scare J, Gravatte HS, Bellaw JL, Prado JC, Reinemeyer CR.Strongylus vulgaris is the most pathogenic nematode parasite of horses. Its extensive migration in the mesenteric blood vessels can lead to life-threatening intestinal infarctions. Recent work has shown that this parasite is still identified among managed horse populations. A serum enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of migrating larvae of S. vulgaris. Previous work has documented an increase in ELISA values following larvicidal treatment with ivermectin and suggested that the target parasite antigen is primarily produced by the later larval stages. T...
Novel in vitro diagnosis of equine allergies using a protein array and mathematical modelling approach: a proof of concept using insect bite hypersensitivity.
Veterinary immunology and immunopathology    June 27, 2015   Volume 167, Issue 3-4 171-177 doi: 10.1016/j.vetimm.2015.06.013
Marti E, Wang X, Jambari NN, Rhyner C, Olzhausen J, Pérez-Barea JJ, Figueredo GP, Alcocer MJ.Insect bite hypersensitivity (IBH) is a seasonal recurrent skin allergy of horses caused by IgE-mediated reactions to allergens present in the saliva of biting insects of the genus Culicoides, and possibly also Simulium and Stomoxys species. In this work we show that protein microarrays containing complex extracts and pure proteins, including recombinant Culicoides allergens, can be used as a powerful technique for the diagnosis of IBH. Besides the obvious advantages such as general profiling and use of few microliters of samples, this microarray technique permits automation and allows the gen...
Polysynovitis in a horse due to Borrelia burgdorferi sensu lato infection–Case study.
Annals of agricultural and environmental medicine : AAEM    June 23, 2015   Volume 22, Issue 2 247-250 doi: 10.5604/12321966.1152074
Passamonti F, Veronesi F, Cappelli K, Capomaccio S, Reginato A, Miglio A, Vardi DM, Stefanetti V, Coletti M, Bazzica C, Pepe M.Lyme borreliosis (LB) is a multi-systemic tick-borne disease affecting both humans and animals, including horses, and is caused by a group of interrelated spirochetes classified within the Borrelia burgdorferi sensu lato (s.l.) complex. Despite the high reported seroprevalence in the European equine population for B. burgdorferi s.l., to-date no documented clinical cases have been described. A 6-year-old Paint gelding was referred with a history of three weeks of fever, intermittent lameness and digital flexor tendon sheath effusion of the right hind limb. Based on a strict diagnostic protocol...
Local and systemic effect of transfection-reagent formulated DNA vectors on equine melanoma.
BMC veterinary research    June 11, 2015   Volume 11 132 doi: 10.1186/s12917-015-0422-9
Mählmann K, Feige K, Juhls C, Endmann A, Schuberth HJ, Oswald D, Hellige M, Doherr M, Cavalleri JM.Equine melanoma has a high incidence in grey horses. Xenogenic DNA vaccination may represent a promising therapeutic approach against equine melanoma as it successfully induced an immunological response in other species suffering from melanoma and in healthy horses. In a clinical study, twenty-seven, grey, melanoma-bearing, horses were assigned to three groups (n = 9) and vaccinated on days 1, 22, and 78 with DNA vectors encoding for equine (eq) IL-12 and IL-18 alone or in combination with either human glycoprotein (hgp) 100 or human tyrosinase (htyr). Horses were vaccinated intramuscularl...
Antibody and Viral Nucleic Acid Testing of Serum and Cerebrospinal Fluid for Diagnosis of Eastern Equine Encephalitis.
Journal of clinical microbiology    June 10, 2015   Volume 53, Issue 8 2768-2772 doi: 10.1128/JCM.00647-15
Sherwood JA, Brittain DC, Howard JJ, Oliver J.Eastern equine encephalitis diagnostic serum antibody can appear 6 days after the onset of symptoms, and its numbers can increase 4-fold in 4 days, arguing for early and frequent serum testing. In populations where cerebrospinal fluid viral nucleic acid testing sensitivity and specificity remain undetermined, cerebrospinal antibody testing should also be performed.
VP2 Exchange and NS3/NS3a Deletion in African Horse Sickness Virus (AHSV) in Development of Disabled Infectious Single Animal Vaccine Candidates for AHSV.
Journal of virology    June 10, 2015   Volume 89, Issue 17 8764-8772 doi: 10.1128/JVI.01052-15
van de Water SG, van Gennip RG, Potgieter CA, Wright IM, van Rijn PA.African horse sickness virus (AHSV) is a virus species in the genus Orbivirus of the family Reoviridae. There are nine serotypes of AHSV showing different levels of cross neutralization. AHSV is transmitted by species of Culicoides biting midges and causes African horse sickness (AHS) in equids, with a mortality rate of up to 95% in naive horses. AHS has become a serious threat for countries outside Africa, since endemic Culicoides species in moderate climates appear to be competent vectors for the related bluetongue virus (BTV). To control AHS, live-attenuated vaccines (LAVs) are used in Afri...
Immunomodulatory Role of Adipose-Derived Stem Cells on Equine Endometriosis.
BioMed research international    June 9, 2015   Volume 2015 141485 doi: 10.1155/2015/141485
Falomo ME, Ferroni L, Tocco I, Gardin C, Zavan B.Endometriosis is a degenerative process due to a chronic inflammatory damage leading to extracellular matrix components deposition and glandular fibrosis. It is known that mesenchymal stem cells secrete a wide range of bioactive molecules, some of them modulating the immune inflammatory response, and others providing regeneration and remodeling of injured tissue. We have performed in vitro experiments in order to analyze the capability of allogenic equine adipose-derived stem cells (ADSCs) to infiltrate mares' endometrial tissues and to stimulate the expression of cytokines and metallopeptidas...
Antibody responses after vaccination against equine influenza in the Republic of Korea in 2013.
The Journal of veterinary medical science    June 9, 2015   Volume 77, Issue 11 1517-1521 doi: 10.1292/jvms.15-0192
Kim EJ, Kim BH, Yang S, Choi EJ, Shin YJ, Song JY, Shin YK.In this study, antibody responses after equine influenza vaccination were investigated among 1,098 horses in Korea using the hemagglutination inhibition (HI) assay. The equine influenza viruses, A/equine/South Africa/4/03 (H3N8) and A/equine/Wildeshausen/1/08 (H3N8), were used as antigens in the HI assay. The mean seropositive rates were 91.7% (geometric mean antibody levels (GMT), 56.8) and 93.6% (GMT, 105.2) for A/equine/South Africa/4/03 and A/equine/Wildeshausen/1/08, respectively. Yearlings and two-year-olds in training exhibited lower positive rates (68.1% (GMT, 14) and 61.7% (GMT, 11.9)...
Systemic leukopenia, evaluation of laminar leukocyte infiltration and laminar lesions in horses with naturally occurring colic syndrome.
Research in veterinary science    June 5, 2015   Volume 101 15-21 doi: 10.1016/j.rvsc.2015.05.014
Laskoski LM, Locatelli-Dittrich R, Valadão CA, Deconto I, Gonçalves KA, Montiani-Ferreira F, Brum JS, de Brito HF, de Sousa RS.The present study was aimed at identifying laminar lesions and leukocyte infiltration in hoof laminar tissue of horses with colic syndrome and its correlation with the total leukocyte count before death. Six healthy horses were used as control group (CG), and eighteen horses with lethal gastrointestinal disease were divided into two groups: leukopenic group (LG) with seven leukopenic horses, and non-leukopenic group (NLG) with 11 horses with total leukocyte count within reference range for the species. Leukocyte infiltration was examined by immunohistochemistry. Laminar lesions were observed i...
Equine health questionnaire.
The Veterinary record    May 31, 2015   Volume 176, Issue 22 580 doi: 10.1136/vr.h2790
Scantlebury C.No abstract available
Platelet-Rich Gel Supernatants Stimulate the Release of Anti-Inflammatory Proteins on Culture Media of Normal Equine Synovial Membrane Explants.
Veterinary medicine international    May 18, 2015   Volume 2015 547052 doi: 10.1155/2015/547052
Ríos DL, López C, Carmona JU.The aims were as follows: (1) to evaluate the effects at 48 and 96 h of two concentrations (25 and 50%) of leukocyte and platelet-rich gel (L-PRG) and pure PRG (P-PRG) supernatants on the production/degradation in normal equine synovial membrane explants (SME) of platelet derived growth factor isoform BB, transforming growth factor beta-1, tumor necrosis factor alpha, interleukin (IL-) 4 (IL-4), IL-1 receptor antagonist (IL-1ra), and hyaluronan (HA) synthesis and (2) to correlate these molecules with their respective PRG supernatant treatments. SME from 6 horses were cultured for 96 h with...
Local and systemic effect of transfection-reagent formulated DNA vectors on equine melanoma.
BMC veterinary research    May 14, 2015   Volume 11 107 doi: 10.1186/s12917-015-0414-9
Mählmann K, Feige K, Juhls C, Endmann A, Schuberth HJ, Oswald D, Hellige M, Doherr M, Cavalleri JM.Equine melanoma has a high incidence in grey horses. Xenogenic DNA vaccination may represent a promising therapeutic approach against equine melanoma as it successfully induced an immunological response in other species suffering from melanoma and in healthy horses. In a clinical study, twenty-seven, grey, melanoma-bearing, horses were assigned to three groups (n = 9) and vaccinated on days 1, 22, and 78 with DNA vectors encoding for equine (eq) IL-12 and IL-18 alone or in combination with either human glycoprotein (hgp) 100 or human tyrosinase (htyr). Horses were vaccinated intramuscularly, a...
Sarcocystis fayeri-Induced Granulomatous and Eosinophilic Myositis in 2 Related Horses.
Veterinary pathology    May 8, 2015   Volume 52, Issue 6 1191-1194 doi: 10.1177/0300985815584073
Herd HR, Sula MM, Starkey LA, Panciera RJ, Johnson EM, Snider TA, Holbrook TC.This report describes 2 genetically related paint mares, case Nos. 1 and 2, presented to the Oklahoma State University Boren Veterinary Medical Teaching Hospital for chronic weight loss and abnormal gait, respectively. Notable findings in both cases included marked persistent eosinophilia and multiple intramuscular lateral thoracic masses. Histologic examination of masses revealed eosinophilic, centrally necrotic granulomas and marked eosinophilic myositis. Granulomas in case No. 1 also contained intralesional Sarcocystis sp material, and adjacent muscle fibers contained intact protozoal cysts...
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