Localized amyloidosis in canine mammary tumors

Histopathologic and immunohistochemical examinations were performed on localized amyloidosis associated with mammary tumors in two dogs. These tumors were identified as adenoma and adenocarcinoma. An acellular, amorphous pale eosinophilic material (amyloid) was observed in the lumina of acini lined by neoplastic cells and in the stroma of the tumors. Concentrically laminated pale eosinophilic bodies (corpora amylacea) were also found in the lumina of the acini. Amyloid and corpora amylacea stained positively with Congo red with and without 5% potassium permanganate pretreatment and revealed a green birefringence under polarized light. Corpora amylacea showed an occasional Maltese-cross pattern. Immunohistochemically, amyloid and corpora amylacea usually stained positively with anti-bovine alpha-casein antibody but negatively with anti-human amyloid AA, anti-bovine kappa-light and lambda-light chains, anti-human lactoferrin, anti-human transferrin, anti-human secretory component, and anti-human polyglucosan antibodies. These findings suggested that the amyloid deposition in these canine mammary tumors was related to lactating casein.     

Pathology of AA amyloidosis in domestic sheep and goats

We describe the main pathologic changes in small ruminants affected by AA amyloidosis, together with the partial sequence of the protein involved. Twenty-one sheep and one goat were selected for presenting macroscopic kidney lesions compatible with systemic amyloidosis. Available tissue samples were studied by histologic, immunopathologic, and ultrastructural means. Renal lesions were characterized grossly by pale cortical surfaces with scattered, miliary, whitish-yellow foci and on cut cortical surfaces by straight, whitish-yellow striations. Gangrenous pneumonia was observed in 16 out of 21 affected sheep (76.2%), although other chronic inflammations were also observed. Amyloid was detected in all grossly affected kidneys using Congo red staining, lesions being most remarkable in glomeruli, affecting 95.5% of animals studied. Congophilic deposits were also observed in intertubular interstitium (68.2%) and medulla (57.1%). All amyloid-affected animals presented proximal convoluted tubule lesions, mostly characterized by an increase in diameter and by hyaline granular degeneration that were responsible for the macroscopic appearance of the kidney. Histologically, amyloid was also seen in blood vessels, spleen, liver, lymph nodes, gastrointestinal tract, and adrenal glands. All amyloid deposits demonstrated greenish-yellow birefringence with polarized light, and the antisera prepared against goat amyloid extracts specifically reacted with birefringent congophilic deposits of both sheep and goats. Ultrastructurally, these deposits were formed by masses of straight, nonbranching fibrils located predominantly in the basement membranes of glomerular capillaries and in the mesangium. Partial sequence of the protein in sheep and goats indicated a high degree of homology with the previously reported sequence of sheep Serum Amyloid A.     

Senile cardiac amyloidosis in the dog

Thirty-two cases of senile cardiac amyloidosis from a routine necropsy material of 594 dogs were studied. The age of the affected dogs ranged from 10 to 16 years. Amyloid was observed in the intramural arteries and arterioles, predominantly in the ventricular myocardium. The vessels were often obturated with amyloid, and myocardial necroses and fibroses were common consequences of the vascular lesions. In three cases amyloid deposits were also observed in the main subepicardial coronary arteries. In contrast to man, only slight interstitial amyloid degeneration was found in four of the dogs observed. Amyloid in the mitral valves, tricuspid valves and aortic cusps was observed in six, two and three cases respectively. It was concluded that the distribution of senile cardiac amyloidosis in the heart of the dog differs considerably from that in man.     

Amyloidosis in black-footed cats (Felis nigripes)

A high prevalence of systemic amyloidosis was documented in the black-footed cat (Felis nigripes) based on a retrospective review of necropsy tissues (n = 38) submitted as part of ongoing disease surveillance. Some degree of amyloid deposition was present in 33 of 38 (87%) of the examined cats, and amyloidosis was the most common cause of death (26/38, 68%). Amyloid deposition was most severe in the renal medullary interstitium (30/33, 91%) and glomeruli (21/33, 63%). Other common sites included the splenic follicular germinal centers (26/31, 84%), gastric lamina propria (9/23, 39%), and intestinal lamina propria (3/23, 13%). Amyloid in all sites stained with Congo red, and in 13 of 15 (87%) cats, deposits had strong immunoreactivity for canine AA protein by immunohistochemistry. There was no association with concurrent chronic inflammatory conditions (P = .51), suggesting that amyloidosis was not secondary to inflammation. Adrenal cortical hyperplasia, a morphologic indicator of stress that can predispose to amyloid deposition, was similarly not associated (P = .09) with amyloidosis. However, adrenals were not available from the majority of cats without amyloidosis; therefore, further analysis of this risk factor is warranted. Heritability estimation suggested that amyloidosis might be familial in this species. Additionally, tissues from a single free-ranging black-footed cat had small amounts of amyloid deposition, suggesting that there could be a predilection for amyloidosis in this species. Research to identify the protein sequence of serum amyloid A (SAA) in the black-footed cat is needed to further investigate the possibility of an amyloidogenic SAA in this species.     

Immunohistochemical studies on canine cerebral amyloid angiopathy and senile plaques.

Amyloid protein was isolated from the cerebral meninges of 4 aged dogs with cerebral amyloid angiopathy. By immunoblot analysis, antiserum against synthetic oligo-peptide consisting of 1-28 amino acid of amyloid beta protein recognized prominent wide band ranging from 14 to 18 kilodalton (kd). When amyloid samples were solubilized by formic acid, the antiserum recognized lower molecular weight band ranging from 3 to 4 kd. Immunohistochemical studies on cerebral amyloid angiopathy and senile plaques were performed in 17 aged dogs. Anti-amyloid beta protein serum labeled amyloid deposits in cerebral vessel walls and senile plaques. Compact deposits of beta protein were detected in primitive or classical plaques. After using formic acid pretreatment, diffuse deposits of beta protein in the neuropil representing diffuse plaques were detectable. Classical and primitive plaques reacted with antiserum against glial fibrillary acidic protein, while not with antisera against alpha 1-antichymotrypsin, IgG and IgM. Amyloid deposits in the intestines of aged dogs examined, did not react with anti-amyloid beta protein serum.     

Oxazolone-induced gastrointestinal disorders enhance the oral transmission of AA amyloidosis in mice

Amyloid A (AA) amyloidosis is a lethal disease characterized by systemic AA amyloid deposition, and is reported in many animal species. Despite experiments have shown that AA amyloidosis can be transmitted orally, horizontal transmission and cross-species transmission are concerns, the transmission mechanism has been unknown. In this study, we examined the oral transmission efficiency of AA amyloidosis using oxazolone-induced gastrointestinal disorder mice. As a result, the upper or lower gastrointestinal disorder groups developed more severe amyloid deposition in systemic tissues than the group without gastrointestinal disorders. The results of this study suggest that gastrointestinal damage promotes the oral transmission of AA amyloidosis.     

Amyloidosis in two Stejneger's beaked whales (Mesoplodon stejnegeri) stranded at the Sea of Japan.

Amyloidosis is a disease characterized by the tissue deposition of autologous extracellular fibrillar proteins that can result in compression of adjacent tissues. Amyloidosis is well-recognized in a wide variety of animals, including mammals, birds, and reptiles. However, to date, there is only one report of amyloidosis in cetaceans. During 1999 and 2000, among 12 Stejneger's beaked whales (Mesoplodon stejnegeri) that were stranded along the Sea of Japan's coast, amyloidosis was found in two whales (case 1, 498 cm, male; case 2, 520 cm, female). For this study population, the prevalence rate of amyloidosis was approximately 17%. These two animals were considered physically and sexually mature based on body length, external features, gonad characteristics, and skeletal features. Livers were notably swollen, fragile, and pale (brownish yellow) on gross examination. A large deposit of amyloid was found in Disse's spaces along with marked atrophy of the hepatocytes. Numerous granulomas, including many nematodes (Crassicauda sp.), were found along with amyloid deposition in the kidneys. Amyloid was also detected in the heart, spleen, adrenal gland, and pancreas. Amyloid in both cases was identified by typical morphology on H&E and Congo red staining. Electron microscopy displayed a typical network of fine fibrils measuring about 11 nm in diameter. This is the first report of amyloidosis in two Stejneger's beaked whales stranded on the coast of the Sea of Japan.     

Diagnosis of secondary amyloid in bovine renal amyloidosis

In paraffin sections, using histochemical methods and the indirect immunofluorescence technique for protein AA, the amyloid of different types of bovine renal amyloidosis was characterized and compared with amyloid of other species, including man. The bovine amyloid was found to be of the secondary type in all cases.Resume Sur des coupes incluses dans de la paraffine, en utilisant des méthodes histochimiques et l'immunofluorescence indirecte pour la protéine AA, la substance amyloïde de différents types d'amyloïdose rénale bovine a été caractérisée et comparée avec celle d'autres espèces y compris l'homme Dans tous les cas la substance amyloïde a été classée comme une sustance amyloïde secondaire.

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Kurzfassung Bei Anwendung histochemischer Methoden und der indirekten Immunofluoreszenztechnik zum Nachweis des Proteins AA wurde in Paraffinschnitten das Amyloid bei verschiedenen Formen der bovinen Nierenamyloidose charakterisiert und mit Amyloid anderer Spezies einschliesslich des Menschen verglichen. Das bovine Amyloid gehörte in allen Fällen zum sekundären Typ.

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Riassunto Usando metodi istochimici e la tecnica dell'immunofluorescenza indiretta per la proteina AA, la sostanza amiloide nei diversi tipi di amiloidosi renale del bovino, in sezioni di paraffina, è stata caratterizzata e confrontata con la sostanza amiloide di altre specie, uomo compreso. La sostanza amiloide del bovino è risultata essere di tipo secondario in tutti i casi.

     

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 (secondary) fibrils that are found in most cases of equine amyloidosis, suggesting that this mare may have had primary amyloidosis. Regardless of fibril type, the presence of multinucleated giant cells in association with eosinophilic material in cytologic preparations of skin nodules may suggest a differential diagnosis of amyloidosis in horses.     

Amyloidosis in the black-footed ferret (Mustela nigripes).

This study describes clinical, histologic, immunohistochemical and electron microscopic features of amyloid A amyloidosis occurring in black-footed ferrets (Mustela nigripes) from eight U.S. zoological institutions. Ferrets had nonregenerative anemia, serum chemistries consistent with chronic renal disease, and proteinuria. Amyloid was present in a variety of tissues, but it was most severe in renal glomeruli and associated with tubular protein loss and emaciation. Congo red/potassium permanganate (KMnO4) and immunohistochemical stains revealed that the amyloid was of the AA type. Concurrent diseases and genetic predisposition were considered the most important contributing factors to development of amyloidosis. Analysis of the genetic tree did not reveal convincing evidence of a common ancestor in the affected ferrets, but a genetic predisposition is likely because all the captive black-footed ferrets are related.     

Amyloidosis in rhesus monkeys with rheumatoid arthritis and enterocolitis.

Generalized amyloidosis was diagnosed by light and electron microscopy in 4 of 5 monkeys (Macaca mulatta) that had a history of chronic arthritis or chronic intermittent diarrhea, or both. Clinical signs and lesions of arthritis in the monkeys were compatible with diagnostic criteria for rheumatoid arthritis. Shigella sp was cultured from 1 monkey, and 2 other monkeys had colonic lesions characteristic of shigellosis. At necropsy, gross changes attributed to amyloid were seen only in the liver. Amyloid deposits in the liver, spleen, mesenteric lymph nodes, kidney, heart, adrenal glands, and other organs were determined by staining reactions and fine structural characteristics.     

Immunohistochemical identification of generalized AA-amyloidosis in a mountain gazelle (Gazella gazella)

Generalized amyloidosis was diagnosed post-mortem in a mountain gazelle (Gazella gazella). To test whether the amyloid deposits consisted of amyloid-A fibril protein a series of monoclonal and polyclonal antibodies directed against amyloid-A fibril protein of different species was applied to formalin-fixed paraffin sections using the indirect immunoperoxidase technique. The immunohistochemical results showed a moderate cross-reaction of gazelle amyloid with human, murine, hamster, and canine amyloid-A fibril protein. A strong cross-reaction, however, was found with one of two monoclonal anti-human amyloid-A antibodies and with an antiserum against bovine amyloid-A fibril protein, the amyloid fibril protein of another ungulate. These results demonstrate the presence of amyloid-A fibril protein in the gazelle amyloid and illustrate the diagnostic value of cross-reacting anti-amyloid-A antibodies for the identification of amyloid-A-amyloidosis in species and in individuals in which amyloid has not yet been examined.     

Plasma cell myeloma producing IgG, IgM, and IgA immunoglobulins in a cow.

A diagnosis of plasma cell myeloma was made in a 6-year-old Holstein cow that showed continuous nosebleed, progressing emaciation, and hyperglobulinemia. Necropsy revealed enlargement of the caudal mesenteric lymph nodes. Lymph nodes and spleen were infiltrated by neoplastic plasma cells. Renal lymph nodes, bone marrow, and kidneys also were affected. Amyloid-like material that was negative for Congo red was present in most of the affected lymph nodes. Congo red-positive amyloid material was noted in spleen, kidneys, liver, and adrenal glands. Neoplastic plasma cells exhibited immunohistochemical reactions for lambda-light chain and 3 classes of heavy chain but not for kappa-light chain. Nonamyloid deposits were labeled with antisera against lambda-light chain and heavy chains. Plasmacytoid cells, which stained positively for IgG, IgM, or IgA, were intermingled in all lesions. Production of 3 types of immunoglobulins may be caused by heavy-chain class switching, constantly occurring in certain proportions.     

Expression of Recombinant bovine L-selectin in Escherichia coli and insect cells.

Bovine L-selectin was expressed in bacteria using pGEX vector and in insect cells infected with recombinant baculovirus in order to obtain recombinant protein for preparation of specific antiserum and its functional studies. In bacterial expression, L-selectin fusion protein with glutathione S-transferase was detected in the insoluble fraction with the expected molecular weight of 60 kDa by SDS-PAGE and reacted with anti-bovine CD62L monoclonal antibody in immunoblot analysis. In insect cells infected with recombinant baculovirus, a band corresponding to L-selectin was not observed in SDS-PAGE with protein staining, but they apparently reacted with anti-bovine CD62L monoclonal antibody in immunoblot analysis. Furthermore, the indirect immunofluorescence test revealed that bovine L-selectin was efficiently expressed on the surface of Sf9 cells infected with recombinant baculovirus, and flow cytometric analysis showed that the percentage of CD62L positive cells in bovine PBMC was about 66% and that most Sf9 cells infected with recombinant baculovirus had specific immunofluorescence.     

Immunohistochemical identification of amyloid, using an anti-human serum amyloid P component (SAP) antibody, is possible in ruminants but not in dogs and cats

Amyloidosis represents a heterogenous group of diseases that have in common the deposition of fibrils composed of proteins of beta-pleated sheet structure, a structure which can be specifically identified by histochemistry using the Congo red or similar stains. Amyloid consists primarily of the amyloid fibrils but also of the amyloid P component (AP). This component, which is identical with the serum counterpart (SAP), is found in all types of human amyloid, and immunohistochemical identification of AP has been proposed as an adjunct to the universal, type-independent diagnosis of human amyloidosis. In the present study of animal amyloidosis, we compared the amyloid-specific Congo red stain with an immunohistochemical protocol using an anti-human SAP antibody for the identification of amyloid in formalin fixed tissue samples. The species and types of amyloidoses investigated were: (i) seven cows, one yak (Bos grunniens), and one sheep affected with amyloidosis of presumed AA type, (ii) one dog with a pancreatic endocrine tumour producing amyloid of presumed AIAPP type, (iii) two cats with presumed AIAPP-amyloidosis of the islets of Langerhans, one cat with presumed AA-amyloidosis, and one cat with an amyloid-producing odontogenic tumour. Intense immunostaining co-localized with amyloid, identified by its congophilia and green birefringence, using a protocol without any antigen retrieval in each of the seven cows, the yak and the sheep. The method seemed more sensitive in the ruminants than the Congo red stain, but was unable to detect amyloid in the dog and the cats regardless of the application of various antigen retrieval protocols. However, specific identification of amyloid still rests on the Congo red method or similar histochemical techniques.     

Generalized amyloidosis in an Eastern Bongo (Tragelaphus eurycerus isaaci)

Amyloidosis has been described in a wide range of domestic and wild species and man. A 10-yr-old male Eastern (Mountain) Bongo (Tragelaphus eurycerus isaaci) was submitted for postmortem examination after a period of 24-hr malaise. Gross examination found evidence of biventricular cardiac hypertrophy, congestive heart failure, and focal pulmonary abscessation. Histologic changes in the heart were consistent with hypertrophic change. Amyloid deposits were found within the liver, kidney medulla, heart, adrenal cortex, and pituitary gland and were confirmed as reactive systemic amyloid (AA) by immunohistochemistry. The pulmonary abscessation was thought to be the stimulus for excessive serum amyloid associated protein production leading to the reactive systemic amyloidosis. Colloidal goiter was also identified as an incidental finding.     

Preparation of anti-bovine and porcine mu chain sera

Absorption of anti-L chain antibodies contained in anti-IgM sera immunized with purified bovine and porcine IgM was undertaken by affinity chromatography on a column of Sepharose 4B, coupled with the normal follicular fluids of the respective species as an immunosorbent. Anti-L chain antibodies in both anti-IgM sera were completely absorbed without incurring reduction of the antibody titer, and anti-bovine and anti-porcine mu chain sera were prepared.     

Amyloidosis in the bovine kidney

After a survey of the most important literature on amyloidosis the results of the authors own studies on amyloidosis in the bovine kidney are reported. The macroscopical and microscopical features of the various types of bovine renal amyloidosis are described. In most cases predominantly medullary depositions occurred (types A, B, C and D). In a series of over 1000 cases only six kidneys with glomerular amyloid were found (type E). All these, however, contained some medullary amyloid as well. It is questionable whether the different types of kidney lesions contain different forms of amyloid or represent variants of the same disorder. Clinico-pathological studies may solve this problem.Medullary amyloid may be a subclinical disease. In clinically normal slaughter cattle it occurred in 2.7% of 1326 animals. In clinically normal dairy cattle (including young animals) it occurred in 2.6% of 378 animals and the incidence appeared to increase with age. In the medullary amyloid deposits different amyloid-containing cell types were found. The intracellular amyloid was arranged in parallel fibrils and was localized in lysosomes. Induced phagocytosis of bovine amyloid by rat macrophages appeared to result in similar vacuoles, indicating that phagocytosis may occur in the bovine cells. In the literature parallel intralysosomal amyloid has been interpreted as formation of amyloid in these vacuoles.An attempt is made to elucidate the pathogenesis of amyloidosis.

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Kurzfassung Nach der Beschreibung der wichtigsten Literaturangaben von Amyloidose werden die eigene Befunde von Amyloidose der Niere des Rindes besprochen. Die makroskopischen und mikroskopischen Eigenschaften der Nierenamyloidose des Rindes werden beschrieben. In den meisten Fällen gab es vor allem medulläre Ablagerungen (Typ A, B, C, und D). Bei über 1000 untersuchten Rindernieren wurden nur 6 Nieren mit hauptsächlich glomerulärem Amyloid gefunden (Typ E). Dieser Typ enthielt ausserdem ein wenig medulläres Amyloid in allen Fällen. Es ist die Frage, ob die verschiedenen Typen von Nierenlaesionen verschiedene Amyloidformen enthalten oder Varianten der selben Krankheit sind. Klinisch-pathologische Untersuchungen müssen diese Frage zu lösen versuchen.Medulläres Amyloid könnte eine subklinische Krankheit darstellen: Bei klinisch gesunden Schlachtrindern kam es in 2.7% von 1326 Tieren vor. Bei klinisch gesundem Milchvieh (einschliesslich Jungvieh) kam es in 2.6% von 378 Tieren vor, wobei mit steigendem Alter eine Zunahme gefunden wurde.Bei den medullären Amyloidablagerungen wurden mehrere amyloid-enthaltende Zelltypen gefunden. Das intrazelluläre Amyloid zeigte eine paralle Anordnung der Fibrillen und war lokalisiert in Lysosomen. Bei durch Injektion von Rinderamyloid bei Ratten induzierte Phagocytose zeigten sich die gleichen Vakuolen. Dieser Befund weist darauf hin dass Phagozytose auch bei Rindern eine Möglichkeit sein kann. In der Literatur wird paralleles intralysosomales Amyloid als örtlich entstanden erklärt. Schliesslich werden einige Untersuchungsrichtungen gezeigt, die möglicherweise zur pathogenese der Amyloidose führen könnten.

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Resume Après avoir résumé les points les plus importants de l'amyloidose relevés dans la littérature, l'auteur présente le résultat de ses observations. Il décrit l'aspect macroscopique et microscopique de l'amyloidose rénale des bovins. Dans la plupart des cas prédominent les dépôts médullaires (types A, B, C, D). Sur 1000 cas, il a trouvé 6 reins avec dépôts glomérulaires (type E), et partiellement médullaires.Une question se pose: les différents types de lésions rénales contiennent-ils diverses substances amyloides ou bien répresententils des variants d'un même affection. Des recherches clinico-histopathologiques devraient pouvoir apporter une réponse.L'amyloidose medullaire peut être une maladie sub-clinique. 2,7% de cas ont été décelés sur 1326 bovins de boucherie cliniquement sains et 2,6% sur 378 vaches laitières (y compris les jeunes) cliniquement saines.Les différents types de cellules contenant la substance amyloide existent dans les dépôts médullaires. La substance amyloide intracellulaire se présente en arrangements parallèles et est localisée dans les lysosomes. La phagocytose induits de la substance amyloide par les macrophages de Rat apparait sous la forme de vacuoles semblables, indiquant que la phagocytose peut se manifester dans les cellules bovines. Dans la littérature, la substance amyloid intra-lysosomale parailèle a été interpretée comme étant une formation de la substance amyloide de ces vacuoles.L'auteur suggere finalement quelques recherches pour élucider la pathogénie de l'amyloidose.

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Riassunto L'autore presenta il risultato delle sue osservazioni dopo aver riassunto i punti piu importanti dell'amiloidosi riportati in litteratura. Descrive sia l'aspetto macroscopico che microscopico dell'amiloidosi. Nella maggior parte dei casi precominano i depositi midollari (tipi A, B, C, D). Su 1.000 casi, ha trovato sei reni con depositi glomerulari (tipo E) e parzialmente midollari. Si pone la domanda se i diversi tipi di lesioni renali contangano sostanze amiloidi diverse, oppure se rappresentano dell varianti di una stessa affezione. Ricerche clinico-isopatologiche dovrebbero poter dare una risposta.L'amiloidosi midollare puo essere una malattia sub-clinica: il 2,7% dei casi e stato rilevato su 1.326 bovini da macello clinicamente sani, e su 378 vacche da latte clinicamente sane (ivi comprese le giovani), il tasso rilevato e del 2,6%. Nei depositi amilodali midollari si sono trovato vari tipi cellulari contenenti l'amiloide.L'amiloide intracellulare, che si localizza nei lisosomi, si presenta in strutture parallele. La fagocitosi della sostanza amiloide indotta dae microfaghi di ratto compare sotto forma di vacuoli simili, indicando che la fagocitosi puo manifestarsi nelle cellule bovine. In litterature, la sostanza amiloidale intralysomale parallela e stata interpretata come una formazione di sostanza amiloidale in questi vacuoli. Infine, l'autore suggerisce di fare alcune ricerche per chiarire la patogenesi dell'amiloidosi.

     

Enhancement of interleukin-2 production by bovine peripheral blood mononuclear cells treated with the combination of anti-programmed death-ligand 1 and cytotoxic T lymphocyte antigen 4 chimeric monoclonal antibodies

Our previous studies demonstrate the therapeutic efficacy against bovine diseases of an anti-bovine programmed death-ligand 1 (PD-L1) chimeric antibody. In humans, PD-1 and PD-L1 antibodies are more effective when combined with an antibody targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and these combination therapies are therefore clinically used. Here we generated an anti-bovine CTLA-4 chimeric antibody (chAb) to enhance the therapeutic efficacy of the PD-L1 antibody. We further analyzed the effects of dual blockade of CTLA-4 and PD-1 pathways on T-cell responses. The established anti-bovine CTLA-4 chAb showed comparable blocking activity on the binding of bovine CTLA-4 to CD80 and CD86 as the anti-bovine CTLA-4 mouse monoclonal antibody. Anti-bovine CTLA-4 chAb also significantly increased IL-2 production from bovine peripheral blood mononuclear cells (PBMCs). Further, the combination of anti-CTLA-4 chAb with anti-PD-L1 chAb significantly upregulated IL-2 production by PBMCs. These results suggest that the combination of antibodies have higher potential to enhance immune responses against pathogens compared with single administration.     

Familial renal amyloidosis in Chinese Shar Pei dogs

Renal amyloidosis was diagnosed in 14 young Chinese Shar Pei dogs, all of which were related. Clinical signs were those of renal failure and included vomiting, anorexia, lethargy, polydipsia, polyuria, weight loss, and dehydration. Some dogs had a history of intermittent fever and joint swelling. Laboratory findings also were compatible with renal failure and included azotemia, hyperphosphatemia, low total CO2 content in serum, isosthenuria, proteinuria, and hypercholesterolemia. All dogs had medullary deposition of amyloid, and 9 of 14 (64%) had glomerular involvement. The remaining renal lesions were typical of end-stage renal disease. In some dogs, amyloid deposits were found in other tissues (eg, liver, spleen, stomach, small intestine, myocardium, lymph node, prostate gland, thyroid gland, and pancreas). Amyloid deposits were sensitive to potassium permanganate oxidation, suggesting the presence of amyloid protein AA.