[Autoimmune diseases in dogs and their impact for breeding programs with special reference of the Nova Scotia Duck Tolling Retriever]. / Autoimmunkrankheiten und deren Bedeutung in der Hundezucht am Beispiel des Nova Scotia Duck Tolling Retriever.

INTRODUCTION: Autoimmune diseases are of considerable importance in dog breeding. An increased risk of diseases with genetic predisposition is present especially in breeds with a limited genetic diversity. Strict breeding regulations and a high degree of self responsibility of the breeders are essential to prevent these diseases. There are only a few DNA tests available for detecting carriers of genes predisposing for autoimmune diseases. In this review, we describe the special situation in the Nova Scotia Duck Tolling Retriever, who has a special predisposition for Systemic Lupus Erythematosus (SLE) and for Immune-mediated Rheumatoid Disease (IMRD), as well as for Steroid-Responsive Meningitis Arteritis (SRMA) and Juvenile Addison's Disease (JADD). In addition a short overview on the pathogenesis of autoimmune disease is presented.

INTRODUCTION: Les maladies auto-immunes ont une signification de plus en plus importante et croissante dans l'élevage de chiens. Les races spéciales avec une base d'élevage étroite et une diversité génétique associée limitée sont prédisposées. Un élevage responsable, visant à exclure des animaux particulièrement prédisposés, permet de contrôler la recrudescence des maladies auto-immunes chez les chiens de race. Actuellement, des tests ADN individuels sont proposés, permettant d'identifier les porteurs de gènes. Cette revue systématique décrit la prédisposition particulière du Retriever de la Nouvelle-Écosse pour le lupus érythémateux disséminé et le rhumatisme à médiation immunitaire, la méningite-artérite sensible aux stéroïdes et le syndrome juvénile d'Addison. Mais avant cela, la pathogenèse des maaladies auto-immunes est présentée resp. récapitulée.

[Tularemia in a jogger woman after the attack by a common buzzard (Buteo buteo): A "One Health" case report]. / Tularämie nach Angriff eines Mäusebussards auf eine Joggerin: Ein "One Health"-Fallbericht.

INTRODUCTION: A female jogger was attacked by a common buzzard (Buteo buteo) and was scratched lightly at the back of the head. One week later she was taken ill with high fever and headache which was later diagnosed as ulcero-glandular tularemia in regional lymph nodes, caused by Francisella tularensis. Recovery was only achieved after several weeks of systemic antibiotic treatment (Gentamicin/ Ciprofloxacine). Tularemia is a well known zoonotic disease, called "rabbit fever", mainly affecting rabbits and hares, but also small rodents. Human infection occurs often following tick bites or bloodsucking insects, or in hunters or slaughterers handling infected animals. Bites by mice have also been reported as a cause of tularemia. For the first time we report this case of tularemia as a result of an attack by a bird of prey. We assume that the bird acted as a vector just carrying the F. tularensis on its claws or beak, but we cannot exclude an infection of the bird itself. Several other joggers had also been attacked by a common buzzard in the same area shortly after the above described event and one of these also became infected with F. tularensis.

Apoptosis in Bovine viral diarrhea virus (BVDV)-induced mucosal disease lesions: a histological, immunohistological, and virological investigation.

Cattle persistently infected with a noncytopathic Bovine viral diarrhea virus (BVDV) are at risk of developing fatal "mucosal disease" (MD). The authors investigated the role of various apoptosis pathways in the pathogenesis of lesions in animals suffering from MD. Therefore, they compared the expression of caspase-3, caspase-8, caspase-9, and Bcl-2L1 (Bcl-x) in tissues of 6 BVDV-free control animals, 7 persistently infected (PI) animals that showed no signs of MD (non-MD PI animals), and 11 animals with MD and correlated the staining with the localization of mucosal lesions. Caspase-3 and -9 staining were markedly stronger in MD cases and were associated with mucosal lesions, even though non-MD PI animals and negative controls also expressed caspase-9. Conversely, caspase-8 was not elevated in any of the animals analyzed. Interestingly, Bcl-x also colocalized with mucosal lesions in the MD cases. However, Bcl-x was similarly expressed in tissues from all 3 groups, and thus, its role in apoptosis needs to be clarified. This study clearly illustrates ex vivo that the activation of the intrinsic, but not the extrinsic, apoptosis pathway is a key element in the pathogenesis of MD lesions observed in cattle persistently infected with BVDV. However, whether direct induction of apoptosis in infected cells or indirect effects induced by the virus are responsible for the lesions observed remains to be established.

Distribution of Borna disease virus antigen and RNA in tissues of naturally infected bicolored white-toothed shrews, Crocidura leucodon, supporting their role as reservoir host species.

Borna disease is a severe viral-induced disorder of the central nervous system of horses, sheep, and a few other animal species, occurring in certain areas of central Europe. Pathogenesis and epidemiology of natural Borna disease virus (BDV) infections are still not fully understood; several unique epidemiologic features, however, point toward the existence of BDV reservoir populations other than the final hosts. In this study, 69 mice and 12 shrews were trapped and examined. The virus distribution was investigated in detail in 2 BDV-positive bicolored white-toothed shrews, Crocidura leucodon, by immunohistochemistry and TaqMan real-time reverse transcription polymerase chain reaction (RT-PCR). RT-PCR amplification products were sequenced, and the sequences were compared. These shrews had been collected in a BDV-endemic geographical region using live traps and did not show obvious clinical or pathological disease signs. BDV antigen and nucleic acid were identified in several organs, including the brain, mainly in nerve tissue and neurons, respectively, but also in parenchymal cells (eg, hepatocytes, Leydig cells) and epithelial cells, particularly of the respiratory and urogenital tract.

Mucosal lesions in a sheep infected with the Border Disease Virus (BDV).

A 28-week-old sheep was presented at the animal hospital because of chronic emaciation, anemia and slight diarrhea. Due to poor general condition and bad prognosis the animal was euthanized and submitted for postmortem investigation. Multiple erosions and ulcerations were found in the dorsal region of the tongue, the pharynx, the hard palate, in the esophagus and the ruminal pillars. Histologically, these lesions consisted of necrosuppurative inflammation. The animal was tested positive for pestivirus antigen both by immunohistochemical and by virological examination (cell culture, antigen capture ELISA and RT-PCR). A non-cytopathic Border Disease Virus was identified, and sequencing revealed a virus belonging to the BDV-3 cluster. Based on the macroscopical, histological, immunohistological and virological results this case was diagnosed as Border Disease with mucosal lesions. This is the first report of such a case in Switzerland.

Clinical findings in 28 cattle with traumatic pericarditis.

Traumatic pericarditis was confirmed postmortem in 28 cattle that had shown signs of a heart rate of more than 100 bpm, distended jugular veins and muffled heart sounds or abnormal pericardial sounds. The heart rate was higher than normal in 24 of them, and in 18 of these it ranged from 100 to 130 bpm. Twenty of the cattle had muffled heart sounds and 10 had pericardial sounds, such as splashing, rubbing or squeaking sounds. Both jugular veins were distended in 24 of the cattle, and 15 had oedema of the throat region, brisket and ventral abdomen. The most important laboratory findings were a reduced clotting time in the glutaraldehyde test in 26 animals, leucocytosis in 22 and a higher than normal concentration of fibrinogen in 19. There was an increase in the activity of gamma-glutamyl transferase in 20, and of aspartate aminotransferase in 15, and in the concentration of bilirubin in 11 of the cattle, indicative of hepatic congestion. A definitive diagnosis of traumatic pericarditis was made on the basis of the clinical findings in 15 of the 28 animals, all of which had typical signs of the disease. In another eight animals, traumatic pericarditis was suspected, although one of the characteristic signs was absent. A tentative but incorrect diagnosis of valvular endocarditis was made in three animals, and a similarly incorrect diagnosis of traumatic reticuloperitonitis was made in the other two.

Lesion profiles and gliosis in the brainstem of 135 Swiss cows with bovine spongiform encephalopathy (BSE).

Lesion profiles are considered to be an important tool for the comparison of the various animal and human spongiform encephalopathies and to obtain information upon prion strain variations. Histological and immunohistochemical reactions (PrPsc, GFAP) in 13 brain areas at 4 levels in the brainstem from 135 BSE-positive and 45 BSE-negative cases were retrospectively evaluated. In this retrospective study a lesion profile based on histological features was worked out on the basis of BSE cases originating from Switzerland over a period of ten years. They were confirmed post mortem by histology and immunohistology. Our findings were reviewed in comparison with lesion profiles published in England. No striking differences comparing type and quality of lesions in the relevant areas between the Swiss and the English cases were evident. Moreover, the lesion profiles and the character of the lesions did not differ between animals born before or after the offal feeding ban, which supports the hypothesis that the Swiss epidemic is sustained by the same single, stable strain of the BSE agent, which is probably the same as in the English epidemic. There was a good correlation between PrPsc accumulation and spongiform changes, in particular in those areas which were morphologically most affected. Astrocytosis in BSE was quantified. A significant rise in GFAP-positive cells could be shown comparing the brain stem nuclei of BSE affected with BSE-unaffected cattle, despite considerable variation between the cases and between the nuclei. The observed astrocytosis did correlate with vacuolation of the neuropil and of perikarya as well as with PrPsc accumulation.

Immunohistochemical diagnosis of persistent infection with Bovine Viral Diarrhea Virus (BVDV) on skin biopsies.

Detection of persistent infection with BovineViral Diarrhea Virus (BVDV) is essential for both epidemiological and clinical reasons. In addition to the classical virological methods such as virus isolation in tissue culture, ELISA and RT-PCR, immunohistochemistry of skin biopsies has become a useful and reliable tool. Assuming that the presence of BVDV antigen in skin structures is restricted to persistent infection, this method could differentiate from transient infection. In order to answer this question, 6 calves were experimentally infected orally with a non-cytopathic genotype 1 BVDV strain belonging to the subtype k.The calves developed fever, mucopurulent nasal discharge, coughing and leucopenia with relative lymphopenia. Immunohistochemistry of skin biopsies taken daily up to day 13-post infection did not reveal any evidence of BVDV infection. BVDV was, however, isolated from blood samples on cell cultures. Anti-NS3-antibody-ELISA and serum neutralization tests showed that all six calves seroconverted. We conclude that in acute BVDV infections, with genotype 1 and the subtypes found in Switzerland (b, e, h and k) viral antigen is not found in epidermal structures of the skin. In contrast, persistently infected animals test positive for BVD viral antigen by immunohistochemistry of the skin.

Clinical findings and treatment of 94 cattle presumptively diagnosed with listeriosis.

The clinical findings and treatment of 94 cattle with listeriosis are described. The general behaviour and condition of the animals were mostly moderately to severely disturbed. A common abnormality in posture was an exaggerated forward or sideward stance, and 11 of the animals were recumbent. More than half of the animals were ataxic and 22 circled. The most frequent cranial neurological signs observed were facial nerve paralysis, salivation, strabismus, reduced or absent pupillary light reflex, reduced or absent tongue movement and head tilt. The haematological and biochemical findings did not contribute to the diagnosis of listeriosis, but they were useful indicators of dehydration and the acid-base status of the animal. Forty-four of 57 of the animals had high leucocyte counts in the cerebrospinal fluid (CSF), mostly mononuclear cells. Eighty-seven of the animals were treated with various antibiotics (penicillin G, oxytetracycline, amoxicillin, and amoxicillin and gentamicin combined), but there was no significant difference in the success rate of the different treatments. Only two of the nine recumbent animals that were treated survived. Univariable analysis suggested that animals that were recumbent, excited, with an absent or weak menace reflex, nystagmus, high numbers of leucocytes in the CSF, high serum concentrations of urea and calcium and high serum activities of aspartate aminotransferase and creatine kinase, and an acid-base deficit, had a smaller chance of surviving. When a logistic regression model was constructed, only recumbency, excitement and a weak or absent menace reflex remained significant factors affecting the likelihood of survival.

Histomorphological and immunohistochemical findings in testes, bulbourethral glands and brain of immunologically castrated male piglets.

The aim of this study was the histological and immunohistochemical evaluation and comparison of testicular, bulbourethral and brain tissue in immunized and intact control boars. Fourteen male piglets, aged between 10 and 16 weeks, were vaccinated twice subcutaneously 4 to 5 weeks apart with Improvac, an anti-GnRH vaccine. The pigs were sacrificed 1 to 16 weeks following the second injection. Testicular weight was recorded and various tissue samples were collected and fixed in formalin and Bouin's fixative for histological examination. In addition, 2 boars were immunized five times and slaughtered 60 weeks after the last injection. Histological and immunohistological studies performed on testes and epididymes showed clear signs of atrophy in the immunized animals and a significant reduction in paired testes weight was seen in treated boars. Microscopically, the mean diameter of the seminiferous tubules was markedly reduced. Spermatogonia as well as few spermatocytes were visible between the Sertoli cells and Leydig cells were atrophic. None or only few spermatozoa were detected in the epididymis. The bulbourethral glands of immunocastrated pigs were smaller than in control pigs and showed histological evidence of atrophy. Immunohistological detection of LH and FSH in the pituitary gland of treated and control boars showed no quantifiable difference in the amount of these two gonadotropins and no lesions were visible in the hypothalamus and the pituitary gland. From our findings it can be concluded that the anti-GnRH vaccine Improvac induces severe atrophy of testes and bulbourethral glands in immunized pigs. This effect appears to be reversible, depending on the immune response of each animal and the time elapsed after the last booster injection.

Synaptophysin: an immunohistochemical marker for animal dysautonomias.

Equine and feline dysautonomias are characterized histopathologically by degenerating neurons with chromatolysis, pyknotic and sometimes eccentric nuclei, and loss of Nissl substance in the peripheral autonomic ganglia. Because it may be difficult to distinguish pathological from post-mortem changes in affected ganglia by histopathological examination, synaptophysin was evaluated as an immunohistochemical marker. Degenerating neurons showed strong intracytoplasmic labelling indicating abnormal accumulation of synaptophysin. It was concluded that synaptophysin immunohistochemistry is a helpful tool for detecting degenerating neurons in equine (grass sickness) and feline (Key-Gaskell syndrome) dysautonomias.

Clinical and pathological findings in a goat with cerebral gliomatosis.

This report describes a buck with cerebral gliomatosis. The animal was severely apathetic to somnolent. Neurological examination revealed generalised ataxia and hyper-metria of the fore limbs. There was bilateral mydriasis and severely decreased menace and pupillary light reflexes. Sensitivity to pricking with a needle was markedly reduced over the entire body. There was a delayed response to adduction, abduction and crossing of the limbs and rocking of the animal. Examination of cerebrospinal fluid indicated mild mixed-cell inflammation. Based on all of the findings, an abscess or tumour of the central nervous system with localisation in the cerebrum was suspected. Because of the grave prognosis, the goat was euthanased and a post mortem examination performed. No macroscopic abnormalities were seen in any of the organs including the brain. Histologically, there was extensive diffuse glial cell hyperplasia in the white matter of the cerebral hemispheres and in the brain stem.

[Swiss scrapie surveillance. I. Clinical aspects of neurological diseases in sheep and goats]. / Scrapie-Uberwachung in der Schweiz. I. Klinische Aspekte von neurologischen Erkrankungen bei Schaf und Ziege.

Small ruminants infected with scrapie show a large range of often unspecific clinical symptoms. The most-often described signs, locomotion, sensibility and behavioural disorders and emaciation, rarely occur together, and cases have been described in which only one of those signs was detectable.Thus, formulating a well-circumscribed definition of a clinical suspect case is difficult. Most animals with CNS-effecting diseases such as listeriosis, polioencephalomacia, cerebrospinal nematidiasis and enterotoxemia will, in a thorough neurological examination, show at least some scrapie-like symptoms. Among the 22 neurological field cases examined in this study, a goat with cerebral gliomatosis and hair lice showed the closest similarity to clinical scrapie. The unilateral deficiency of the cerebral nerves has potential as an clinical exclusion criterion for scrapie. However, the laboratory confirmation--or exclusion--of scrapie remains important. It thus needs to be realized that a consistent and thorough examination of neurologically diseased small ruminants (including fallen stock) is the backbone of a good surveillance system for these diseases. This should be a motivation for submitting adult sheep and goats for neuropathological examination.

Animal model for dermolytic mechanobullous disease: sheep with recessive dystrophic epidermolysis bullosa lack collagen VII.

A severe congenital mechanobullous disease with dermolytic blistering and recessive inheritance is described in sheep. The affected animals of wild and inbred flocks of the breed Weisses Alpenschaf (WAS) have blisters of skin, oral mucosa, tongue, and esophagus at birth or within the first week of life. Exungulation occurs early, and severe erosions in the mouth lead to difficulty in feeding. Electron microscopic examination revealed sub-lamina densa splitting in natural or fresh friction blisters and absence of identifiable anchoring fibrils in clinically uninvolved skin. Antigen mapping localized laminin and collagen IV to the blister roof. Indirect immunofluorescence staining with antibodies to collagen VII, the major structural component of the anchoring fibrils, demonstrated a complete absence of reaction in clinically uninvolved tissues of the affected sheep, whereas in normal sheep a strong linear fluorescence was seen at the epithelial-mesenchymal basement membrane zone. Dermal extracts of normal sheep contained intact collagen VII, but epidermal and dermal extracts from the affected sheep lacked this collagen or its fragments in immunoblotting experiments. Based on genetic, clinical, ultrastructural, and immunochemical findings, the sheep disorder corresponds to the severe mutilating subtype of recessive dystrophic epidermolysis bullosa in humans and can be used as an animal model to investigate the human disorder.

Lesion of the area postrema/nucleus of the solitary tract (AP/NTS) attenuates the anorectic effects of amylin and calcitonin gene-related peptide (CGRP) in rats.

The area postrema/nucleus of the solitary tract (AP/NTS) region plays an important role in the control of food intake since it receives peripheral satiety signals via splanchnic and vagal afferents. Due to the lack of the blood brain barrier in this region, blood borne signals can directly be monitored in the AP/NTS. Furthermore, receptors for anorectic peptides such as amylin or calcitonin gene-related peptide (CGRP) have been found in the AP/NTS. It was therefore the aim of the present study to investigate the role of the AP/NTS region in mediating the anorectic effects of these peptides. Thermal ablation of the AP/NTS resulted in a significant reduction of the anorectic effects of IP injected amylin (5 microg/kg) and CGRP (5 microg/kg) in food deprived rats. The anorectic actions of CCK and BBS were also reduced by the AP/NTS lesion which agrees with previous studies. We conclude that the AP/NTS region is an important brain site for mediating the anorectic effects of amylin and CGRP. It remains to be clarified whether this effect is due to amylin and CGRP action on receptors within the AP/NTS region or peripheral receptors on afferent nerves projecting to the AP/NTS.

Spontaneous Borna disease in sheep and horses: immunophenotyping of inflammatory cells and detection of MHC-I and MHC-II antigen expression in Borna encephalitis lesions.

Borna disease (BD) has been recognized as a virally induced T-cell dependent immunopathological disorder of the central nervous system (CNS), as shown by experimental infection of rats with Borna disease virus (BDV). In contrast to the rat model, little is known about the pathogenesis of spontaneous BD in sheep and horses. The present study describes the brain lesions of 12 ovine and 11 equine cases of naturally occurring BD. A set of monoclonal and polyclonal antibodies was used in order to determine the cells operative in encephalitic lesions and to detect expression of MHC-I and MHC-II products in the brains of affected animals. In all cases investigated, a reaction pattern similar to that reported for the acute phase of BD in experimentally infected rats was noted. In brief, the majority of inflammatory cells in perivascular infiltrates (PVI) as well as parenchymal and meningeal infiltrates were CD3 +. CD4 + cells outnumbered CD8 + cells in PVI as well as in the parenchyma. Macrophages (defined by lysozyme immunoreactivity) were seen less often and B-cells or plasma cells (cells positive for lambda or kappa light chains) were demonstrated at lower numbers. TCR-1 + cells were found on very rare occasions in PVI of some sheep. MHC-I and MHC-II products were constantly expressed on inflammatory cells but inconsistently on astrocytes and neurons. Neuronal degeneration was not a major feature.

Panleukopenia-like syndrome of FeLV caused by co-infection with FeLV and feline panleukopenia virus.

To study the effect of interferon on feline leukemia virus (FeLV) infection, 30 specific pathogen free (SPF) cats were infected with the apathogenic FeLV A Glasgow. Unexpectedly, between 5 and 8 weeks after FeLV infection, all 19 cats with persistent FeLV infection but not the FeLV-negative cats died from a panleukopenia-like syndrome. No feline panleukopenia virus (FPLV) antigen was found in feces by latex agglutination, enzyme-linked immunosorbent assay (ELISA) or immunoelectron microscopy. No enteropathogenic bacteria were found. Histopathology revealed changes resembling those of FPLV infection such as destruction of crypts and pancytopenia of bone marrow. Neither clinical signs nor seroconversion to FPLV could be induced by transmitting intestinal extracts to two SPF cats. However, FPLV antigen was demonstrated by immunofluorescence assay in intestinal cryostat sections of diseased animals. FPLV could also be demonstrated in intestinal extracts by immunoelectron microscopy, by latex agglutination and ELISA after anti-FPLV antibodies were removed from immune-complexed FPLV by ultracentrifugation over a CsCl gradient at pH 2.0. From these experiments it was concluded that the panleukopenia-like syndrome of FeLV may not be caused by FeLV alone but at least in some cases by co-infection with FeLV and FPLV. In addition, some form of 'cooperation' between FeLV and FPLV must be postulated because neither virus alone induced symptoms.

Borna disease in naturally infected cattle.

Based on the immunohistochemical demonstration of viral antigen and on the histological brain lesions, Borna disease was diagnosed in a cow and a bull which had suffered from a severe, subacute progressive disorder of the central nervous system. Virus-specific antigen was characteristically localized in neurons, predominantly in the perikaryon and dendrites. In a serum sample available from one of the animals a Borna disease virus antibody titre of 1 in 80 was demonstrated. This is the first report of the natural disease in cattle.

An immunohistochemical study of the distribution of border disease virus in persistently infected sheep.

Three seronegative sheep persistently infected with Border disease virus and six seropositive, non-viraemic sheep were examined for the cellular distribution of the agent. These animals originated from a closed flock which had been kept in an isolation facility for 5 years. They were killed and immediately necropsied. There were no gross abnormalities other than reduced body weight of the persistently infected sheep. Two samples of each major organ were collected. The first sample was fixed by immersion in formalin and processed for histological examination, which showed no lesions unequivocally attributable to the viral infection. The second sample was snap-frozen for immunohistochemical examination. This revealed viral antigen in all organs of the persistently infected, but in none of the seropositive animals. The infected cells included smooth muscle cells of hollow organs and blood vessels, epithelial cells of the alimentary tract and urogenital organs, lymphocytes in lymphoid organs, endocrine cells, neurons and glial cell.