Topic:Amyloidosis
Amyloidosis in horses is a condition characterized by the abnormal deposition of amyloid proteins in various tissues and organs, leading to impaired function and potential organ failure. In equines, amyloidosis is relatively rare but can have significant clinical implications when present. The condition arises when misfolded proteins aggregate into insoluble fibrils, which are then deposited extracellularly in tissues such as the liver, kidneys, and spleen. This deposition disrupts normal tissue architecture and function, potentially leading to clinical signs such as weight loss, edema, and organ dysfunction. Diagnosis is typically confirmed through biopsy and histopathological examination, revealing the characteristic amyloid deposits. This page compiles peer-reviewed research studies and scholarly articles that explore the pathophysiology, clinical presentation, diagnostic challenges, and management strategies for amyloidosis in horses.
Bullous amyloidosis in a horse: first description in veterinary medicine. Bullous amyloidosis is a rare disease in humans that has not been described in a veterinary species in the peer-reviewed literature. The human disease is characterised by haemorrhagic vesicles and bullae on the skin and mucosae, which form due to amyloid deposition. Objective: To describe the clinical features, laboratory analysis and histopathological features of an unique presentation of bullous disease in a horse. Methods: A 17-year-old thoroughbred mare presented for weight loss and severe oral cavity ulcers. Methods: Investigations involved haematological evaluation, chemistry profiles, g...
Horse Placental Extract Enhances Neurogenesis in the Presence of Amyloid β. Human placental extract and animal-derived placental extracts from pigs and horses host a wide range of biological activities. Several placental products are used as medicines, cosmetics, and healthcare substances worldwide. However, the use of placental extracts for neuronal functioning is currently not established because the number of relevant studies is limited. A few previous reports suggested the neuroprotective effect and dendrite genesis effect of placental extract. However, no studies have reported on neurogenesis in placental extracts. Therefore, we aimed to investigate the effects o...
Concurrent thoracic mesothelioma and thyroid C-cell adenoma with amyloid deposition in an aged horse. A 21-year-old American Saddlebred mare died with a history of weight loss and breathing difficulties of 1 month duration. Post-mortem examination revealed a copious pleural effusion with multifocal to coalescing numerous white to grey nodular masses on the serosal surface of the pericardium, lungs and thoracic cavity. In addition, the left thyroid gland was markedly enlarged. A thoracic mesothelioma and C-cell adenoma with amyloid deposits of the left thyroid gland were diagnosed by histopathology and confirmed by immunohistochemistry employing antibodies against cytokeratin (CK), vimentin an...
Histological assessment of β-amyloid precursor protein immunolabelled rectal biopsies aids diagnosis of equine grass sickness. An accurate, minimally invasive, ante-mortem diagnostic test for equine grass sickness (EGS) is currently lacking. Although histological examination of haematoxylin and eosin-stained rectal biopsies for chromatolytic neurons is insensitive as a diagnostic test for EGS, we hypothesised that its diagnostic accuracy could be improved by immunolabelling for β-amyloid precursor protein (β-APP), which has increased expression in cranial cervical ganglia (CCG) neuronal perikarya in EGS. Objective: To develop a grading scheme for assessing the distribution and intensity of β-APP immunoreactivity wi...
Nasal and ocular amyloidosis in a 15-year-old horse. Localized nasal, conjunctival and corneal amyloidosis was diagnosed in a 15-year-old pony with nasal and conjunctival masses and severe dyspnoea. Multiple swellings had been evident in the nostrils for at least two years and had gradually increased in size before presentation due to dyspnoea and exercise intolerance. Surgical debulking of the masses was performed and histological examination revealed large amounts of extracellular, hyaline, eosinophilic, Congo red positive material in the lamina propria of the nasal mucosa. A tentative diagnosis of localized nasal amyloidosis was made. The tre...
Characterization of amyloid in equine recurrent uveitis as AA amyloid. Two horses with chronic uveitis and histological lesions consistent with equine recurrent uveitis (ERU) were examined. Microscopical findings in the ciliary body included deposits of amyloid lining the non-pigmented epithelium, intracytoplasmic, rod-shaped, eosinophilic inclusions and intraepithelial infiltration of T lymphocytes. Ultrastructural examination of the ciliary body of one horse confirmed the presence of abundant extracellular deposits of non-branching fibrils (9-11 nm in diameter) consistent with amyloid. Immunohistochemistry revealed strong positive labelling for AA amyloid and m...
EcPV2 DNA in equine papillomas and in situ and invasive squamous cell carcinomas supports papillomavirus etiology. Equine penile papillomas, in situ carcinomas, and invasive carcinomas are hypothesized to belong to a continuum of papillomavirus-induced diseases. The former ones clinically present as small grey papules, while the latter 2 lesions are more hyperplasic or alternatively ulcerated. To test the hypothesis that these lesions are papillomavirus-induced, samples of 24 horses with characteristic clinical and histologic findings of penile papillomas or in situ or invasive squamous cell carcinomas were collected. As controls, 11 horses with various lesions--namely, Balanoposthitis (6 cases), melanoma ...
Mutations in or near the transmembrane domain alter PMEL amyloid formation from functional to pathogenic. PMEL is a pigment cell-specific protein that forms physiological amyloid fibrils upon which melanins ultimately deposit in the lumen of the pigment organelle, the melanosome. Whereas hypomorphic PMEL mutations in several species result in a mild pigment dilution that is inherited in a recessive manner, PMEL alleles found in the Dominant white (DW) chicken and Silver horse (HoSi)--which bear mutations that alter the PMEL transmembrane domain (TMD) and that are thus outside the amyloid core--are associated with a striking loss of pigmentation that is inherited in a dominant fashion. Here we show...
Expression and purification of active recombinant equine lysozyme in Escherichia coli. Equine lysozyme (EL) is a calcium (Ca)-binding lysozyme and is an intermediary link between non-Ca-binding C-type lysozyme and alpha-lactalbumin. The feature of lysozymes to assemble into the fibrils has recently gained considerable attention for the investigation of the functional properties of these proteins. To study the structural and functional properties of EL, a synthetic gene was cloned and EL was overexpressed in Escherichia coli as a fused protein. The His-tagged recombinant EL was accumulated as inclusion bodies. Up to 50 mg/l of the recombinant EL could be achieved after purificati...
Protein oligomerization induced by oleic acid at the solid-liquid interface–equine lysozyme cytotoxic complexes. Protein oligomeric complexes have emerged as a major target of current research because of their key role in aggregation processes in living systems and in vitro. Hydrophobic and charged surfaces may favour the self-assembly process by recruiting proteins and modifying their interactions. We found that equine lysozyme assembles into multimeric complexes with oleic acid (ELOA) at the solid-liquid interface within an ion-exchange chromatography column preconditioned with oleic acid. The properties of ELOA were characterized using NMR, spectroscopic methods and atomic force microscopy, and showed...
Equine lysozyme: the molecular basis of folding, self-assembly and innate amyloid toxicity. Calcium-binding equine lysozyme (EL) combines the structural and folding properties of c-type lysozymes and alpha-lactalbumins, connecting these two most studied subfamilies. The structural insight into its native and partially folded states is particularly illuminating in revealing the general principles of protein folding, amyloid formation and its inhibition. Among lysozymes EL forms one of the most stable molten globules and shows the most uncooperative refolding kinetics. Its partially-folded states serve as precursors for calcium-dependent self-assembly into ring-shaped and linear amyloi...
Intermediate amyloid oligomers of lysozyme: Is their cytotoxicity a particular case or general rule for amyloid? In the current study we investigated the molecular mechanisms of cytotoxicity of amyloid oligomers of horse milk lysozyme. We have shown that lysozyme forms soluble amyloid oligomers and protofibrils during incubation at pH 2.0 and 4.5 and 57 degrees C. These structures bind the amyloid-specific dyes thioflavin T and Congo Red, and their morphology and size were analyzed by atomic force microscopy. Monomeric lysozyme and its fibrils did not affect the viability of three cell types used in our experiments including primary murine neurons and fibroblasts, as well as neuroblastoma cell line IMR-3...
Kinetics of amyloid aggregation of mammal apomyoglobins and correlation with their amino acid sequences. In protein deposition disorders, a normally soluble protein is deposited as insoluble aggregates, referred to as amyloid. The intrinsic effects of specific mutations on the rates of protein aggregation and amyloid formation of unfolded polypeptide chains can be correlated with changes in hydrophobicity, propensity to convert alpha-helical to beta sheet conformation and charge. In this paper, we report the aggregation rates of buffalo, horse and bovine apomyoglobins. The experimental values were compared with the theoretical ones evaluated considering the amino acid differences among the sequen...
Acute hemoperitoneum in horses: a review of 19 cases (1992-2003). The medical records of 19 horses with acute hemoperitoneum were reviewed. The causes for the hemoperitoneum were idiopathic (8 horses), splenic hematoma with capsular tear (7), bleeding from the reproductive tract (3), multicentric hemangiosarcoma (1), and systemic amyloidosis (1). The affected horses were between 4 and 32 years of age (median 11.5 years). The most consistent findings on initial examination were depression, tachycardia, tachypnea, pale mucous membranes, prolonged capillary refill time, colic, and abdominal discomfort. Less common clinical signs included abdominal distention, p...
Systemic AL amyloidosis associated with multiple myeloma in a horse. AL amyloidosis is the most common type of systemic amyloidosis in humans, and it is frequently associated with multiple myeloma. But, AL amyloidosis is very rare in domestic animals. A 16-year-old Quarter horse gelding was diagnosed with systemic AL amyloidosis associated with multiple myeloma. Clinical problems were rapid weight loss, muscle atrophy, soft unformed stool, and ventral edema. Grossly, diffuse gastrointestinal hemorrhage, markedly thickened jejunal mucosa, and splenomegaly were present. Microscopically, diffuse severe amyloid deposits were present in the lamina propria of glandul...
Does the cytotoxic effect of transient amyloid oligomers from common equine lysozyme in vitro imply innate amyloid toxicity? In amyloid diseases, it is not evident which protein aggregates induce cell death via specific molecular mechanisms and which cause damage because of their mass accumulation and mechanical properties. We showed that equine lysozyme assembles into soluble amyloid oligomers and protofilaments at pH 2.0 and 4.5, 57 degrees C. They bind thioflavin-T and Congo red similar to common amyloid structures, and their morphology was monitored by atomic force microscopy. Molecular volume evaluation from microscopic measurements allowed us to identify distinct types of oligomers, ranging from tetramer to oc...
Amyloid protofilaments from the calcium-binding protein equine lysozyme: formation of ring and linear structures depends on pH and metal ion concentration. The calcium-binding equine lysozyme has been found to undergo conversion into amyloid fibrils during incubation in solution at acidic pH. At pH 4.5 and 57 degrees C, where equine lysozyme forms a partially unfolded molten globule state, the protein forms protofilaments with a width of ca. 2 nm. In the absence of Ca(2+) the protofilaments are present as annular structures with a diameter of 40-50 nm. In the presence of 10 mM CaCl(2) the protofilaments of equine lysozyme are straight or curved; they can assemble into thicker threads, but they do not appear to undergo circularisation. At pH 2.0, ...
Amylopectinosis in fetal and neonatal Quarter Horses. Three Quarter Horses, a stillborn filly (horse No. 1), a female fetus aborted at approximately 6 months of gestation (horse No. 2), and a 1-month-old colt that had been weak at birth (horse No. 3), had myopathy characterized histologically by large spherical or ovoid inclusions in skeletal and cardiac myofibers. Smaller inclusions were also found in brain and spinal cord and in some cells of all other tissues examined. These inclusions were basophilic, red-purple after staining with periodic acid-Schiff (both before and after digestion with diastase), and moderately dark blue after staining wi...
The acute phase serum amyloid A protein (SAA) in the horse: isolation and characterization of three isoforms. Serum amyloid A (SAA) from acute phase horse serum was isolated using hydrophobic interaction chromatography, gel filtration and ion exchange chromatography. Three SAA isoforms with different isoelectric points, i.e. SAA pI 8.0, SAA pI 9.0 and SAA pI 9.7, were identified by two-dimensional electrophoresis and further characterized with amino acid sequence analysis. These isoforms were found in similar concentrations in all animals investigated, with SAA pI 9.7 constituting about half of the total SAA content. Partial amino acid sequence analysis verified the previously published heterogeneous ...
Cutaneous amyloidosis in a horse with lymphoma. A horse with malignant lymphoma (histiolymphocytic) and cutaneous amyloidosis is described. The lymphoma involved the dura mater of the spinal cord and some of the peripheral lymph nodes. Multifocal amyloid deposits were present in the skin and subcutis of the ventral abdomen but not within the lymphoma cell infiltrates or in the viscera.
Eosinophilic nodular dermatoses. This article describes the etiology, clinical signs, diagnosis, and treatment of various equine nodular diseases. Although of different etiologies, this group of diseases shares a common histologic reaction pattern characterized by infiltration of eosinophils and collagen degeneration. Collagenolytic granuloma, axillary nodular necrosis, unilateral papular dermatosis/eosinophilic folliculitis, amyloidosis, habronemiasis, and mast cell tumors are discussed.
Studies on the presence of magnesium in visceral amyloid. The Magneson and Titan yellow tests were used to detect Mg in amyloid deposits in primary and secondary amyloidosis, in a pituitary tumour and in a case of equine cutaneous amyloidosis. Especially vascular amyloid deposits turned out to contain high levels of Mg. The significance of these findings remains unclear at present. Competition between Mg and Ca, the relationship between Mg in elastic fibres and amyloid P-component, and the high water content of amyloid along with the interaction of Mg with water are discussed.
Equine cutaneous amyloidosis derived from an immunoglobulin lambda-light chain. Immunohistochemical, immunochemical and chemical results. Amyloid deposits from equine cutaneous nodular amyloidosis associated with extramedullary plasmacytoma were classified immunohistochemically as equine immunoglobulin lambda-light chain-derived and designated eA lambda (HIP). For chemical identification, the amyloid fibril proteins were separated on Sephadex G-100 in 6M guanidine.HCl. Polypeptides of predominantly 24 kDa and 50 kDa were found by polyacrylamide gel electrophoresis. They have preponderance of immunoglobulin lambda-antigenic determinants as detected by immunodiffusion and immunoblotting. Since the N-terminus of the major proteins ...
Clinical chemical constituents in relation to liver amyloidosis in serum-producing horses. Serum activities of gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), aspartate aminotransferase (AST), and concentrations of total bilirubin and total bile acids were screened during a 5 year period in 27 horses used for production of hyperimmune serum. The horses investigated were regularly immunized with live cultures of the endotoxin-releasing bacteria Escherichia coli or Pasteurella multocida, the individual animals having undergone such treatment for periods varying from 2 weeks to 10 years. In a majority of the horses, GGT-activity had increased within 6 to 7 years of first h...
Conjunctival and nasal amyloidosis in a horse. AMYLOID is the extra-cellular deposition of hyaline proteinaceous material of various types, with the characteristic of green birefringence of Congo Red stained sections under polarised light. It is of wide veterinary importance (Jako 1971; Woo and Gorman 1989). In the horse, it occurs as a complication of chronic inflammation or antigenic stimulation (Jakob 1971; Husebekk et al 1986; van Andel, Gruys, Kroneman and Veerkamp 1988; Vanhooser, Reinemeyer and Held 1988) and as an unusual cause of tumour-like masses in the rostral nasal cavity (Shaw, Gunson and Evans 1987; van Andel et al 1988). Ra...
Systemic amyloidosis in a mare. A mare with chronic cachexia had multiple skin nodules, abdominal masses (attached and free floating), and large lymph nodes. Fine-needle aspiration cytologic evaluation of a skin mass revealed multinucleated giant cells surrounding eosinophilic material. Histologic evaluation revealed extensive amyloid deposits within the masses, lymph nodes, and the interstitium of many organs. The presence of systemic (visceral) and organ-limited (cutaneous) forms of amyloid is rare in horses. Amyloid congophilia was retained after potassium permanganate oxidation. The fibrils were thus distinct from the AA...
Immunoglobulin lambda-light-chain-derived amyloidosis (A lambda) in two horses. Tumorous amyloid deposits in the nasal mucosa of two horses differed from generalized AA-amyloidosis with respect to clinical features, organ distribution, and resistance to KMnO4 treatment. Using a panel of antibodies directed against different human amyloid fibril proteins and employing the peroxidase-anti-peroxidase (PAP) technique, we showed the described equine amyloid to be A lambda-type, as demonstrated by immunohistochemical cross-reactivity. Consequently, we identified a second amyloid class in horses and showed that immunoglobulin light-chain-derived amyloid may also be present in an...