[Enzootic spinal ataxia in fallow and wild red deer in Upper Bavaria]. / Enzootische spinale Ataxie bei Dam- und Rotwild in Gehegen in Oberbayern.

Since 1993 several cases of spinal ataxia occurred in adult red and/or fallow deer in four farms in Southern Bavaria. The disease based on a secondary copper deficiency due to a high level of molybden and a low level of copper content in the feed. Some of the animals suffer from a severe disturbance of motion. In most cases the animals are shot at the beginning of illness. Histologically the most important lesions are in the spinal cord consisting mainly in a bilateral symmetric degeneration of dorsolateral and ventral areas of the white matter. Degeneration is caused by lamellar disintegration of the myelin connected with deposition of fine-granulated substances detectable by electronmicroscopical investigation. In the liver and other organs we always found a hemosiderosis which is also believed to be caused by copper deficiency.

Congenital myopathy in Braunvieh x Brown Swiss calves.

A hitherto unknown skeletal muscle disorder is described in six Braunvieh x Brown Swiss calves. The animals showed rapidly progressing muscular weakness and became recumbent within 2 weeks of birth. Histological examination of skeletal muscle revealed a marked variation in muscle fibre size, internally placed nuclei, segmental loss of cross-striation with disorganization of myofibrils, and accumulation of nemaline rods. The most distinctive histological finding was intracytoplasmic, homogeneous, mostly crescent-shaped areas at the periphery of numerous muscle fibres. Electron microscopically, accumulations of tightly packed, parallel filamentous structures, about 20 nm in diameter, were detected in these areas. Enzyme histochemistry showed that all muscle fibre types were affected. Vimentin and dystrophin immunohistochemistry revealed normal antigen distribution within connective tissue components and at the periphery of each muscle fibre, respectively. The lesions could be readily distinguished from other neurological and neuromuscular disorders previously described in Braunvieh x Brown Swiss or American Brown Swiss Cattle. The disease appears to be a novel congenital myopathy in this breed, and a hereditary aetiology is suspected.

Depression of the somatotropic cells in the bovine pituitary gland due to application of recombinant bovine somatotropin--an immunohistochemical and morphometric study.

The morphological alterations in the bovine pituitary gland resulting from the administration of recombinant bovine somatotropin (rBST) are described. Three groups of German Simmental heifers (12 animals for each group) were treated. Group 1 received a placebo (vehicle), group 2320 mg and group 3640 mg of a prolonged-release formulation of rBST at 2 week intervals. Treatments were started with an average body weight of 286 +/- 2.5 kg and continued until one week before the animals were slaughtered with an average body weight of 520 +/- 3.2 kg. Double immunohistochemical labelling using rabbit anti-prolactin (PRL) and chicken anti-BST antibodies was performed on paraffin serial sections of the pituitary glands. Morphometric analyses revealed a dose-dependent decrease of the volume fraction of the somatotropic cells due to a reduction in number and a diminution of the mean cellular volume. No significant differences in the volume fraction of the mammotropic cells were seen. The recorded reduction of the somatotropic cells is thought to be the result of a negative feedback upon the secretory activity as a result of long-term rBST treatment.

Alexander's disease in a Bernese mountain dog.

We present a case of Alexander's disease (AD) in a Bernese mountain dog. The male dog had a clinical history of tremors of the hind legs and posterior weakness, which deteriorated rapidly to posterior paresis and tetraparesis. After a disease duration of 4 weeks the dog was euthanatized at 13 weeks of age. Macroscopically the brain showed moderate enlargement of the lateral ventricles. Histologically there was marked proliferation of astrocytes with abnormally large cell bodies in the white matter of the brain and the white and gray matter of the spinal cord. In these regions numerous round, club-shaped, or elongated deposits consistent with Rosenthal fibers (RFs) were found. They were most prominent in perivascular, subependymal, and subpial areas where they were perpendicularly arranged. Additionally there was considerable loss of myelin. Immunohistologically the RFs were positive for glial fibrillary acidic protein and alpha B-crystallin. Under the electron microscope the RFs were found to be located in the cell bodies and processes of astrocytes and appeared as osmiophilic irregularly formed bodies of uneven size with distinct borders that were tightly associated with glial filaments. The histological, immunohistochemical, and ultrastructural findings of this canine case of AD are identical with those in human cases.

Spongiform central nervous system myelinopathy in African dwarf goats.

A novel spongiform myelinopathy of the central nervous system (CNS) of eleven African dwarf goats was examined by light and electron microscopy. Histological lesions consisted of extensive vacuolation predominantly of the white matter of the diencephalon, midbrain and cerebellar peduncles, as well as of spinal white matter. Ultrastructurally, vacuoles were shown to be intramyelinic, resulting from the splitting of the outer myelin lamellae at the intraperiod line. A few oligodendrocytes showed vacuolar degeneration of cell bodies and processes. Inflammatory reactions were absent. The observed lesions point to an unknown primary damage of oligodendroglia and central myelin. A hereditary background of the disorder is suspected as all investigated dwarf goats were half-brothers or -sisters and partly descended from the mating of adult females with their own sire.

Rhinencephalic glial cell nests and their possible role in glioma formation: morphometric studies do not reveal significant differences between brachycephalic and dolichocephalic dogs.

Gliomas frequently occur in boxer dogs and are often located in the rhinencephalic allocortex. This brain region contains unusual glial cell nests (GCN). The presence of structural abnormalities in the GCN in the boxer dog might indicate that they are involved in the development of gliomas, which would explain the predisposition of this canine breed for glioma formation. Therefore, the brains of six brachycephalic (boxer dogs) and five dolichocephalic dogs were investigated morphometrically. The volumes of the whole brain, the allocortex, and the GCN were estimated following Cavalieri's principle. Unbiased estimates of the numerical density and total number of the two prevailing cell populations within the GCN were obtained using the optical disector method. There was no significant difference for the estimated parameters between brachycephalic and dolichocephalic dogs. The results of the present study did not show any evidence of boxer dog-specific features of the GCN, thus, failing to explain the striking glioma predisposition of boxer dogs.

[Neuroscience and veterinary medicine]. / Neurowissenschaften und Tiermedizin.

Clinical neurology in veterinary medicine did receive its initial secure basis by Hermann DEXLER in Vienna during late fall of 19th century. He could demonstrate that knowledges in neuroanatomy and -pathology are basis requirements for a reliable interpretation of morbid entities of central and peripheral nervous system. During the following decades a varied development of neurosciences was to be observed in veterinary medicine, comparing different countries. In general, the most important influences--based upon comparative neuromorphology--came from pathologists. Thus, infectious morbid entities, hereditary diseases, malformations, neurodegenerative diseases, neurooncology, and traumatology had become central challenges for neuroscientists. In this context it is no surprise that BSE has brought a tremendous impact on research work in the whole field of human and animal spongiform encephalopathies. Regrettably, the integration of clinical neurology and neuropathology within the teaching programmes of the European veterinary colleges, especially in Germany, has still not reached a satisfactory level. Specific training procedures realized by several schools in USA and UK might serve as sound examples in view of the permanent growing importance of neurological diseases in large and small animal practice.

In-situ hybridization for demonstration of equine herpesvirus type 1 DNA in paraffin wax-embedded tissues and its use in horses with disseminated necrotizing myeloencephalitis.

The detection of equine herpesvirus type 1 (EHV-1) in infected cell cultures, and in tissues taken at necropsy, by the in-situ hybridization technique is described. A 4.9 kb Bam HI fragment of EHV-1 vaccine strain RacH was used as a probe after labelling with [alpha-32P] thymidine 5'-triphosphate ([32P]TTP) or digoxigenin-deoxyuridine 5'-triphosphate (dUTP). Both probes specifically detected EHV-1 DNA in either cytospin or paraffin wax-embedded preparations of infected cells. The digoxigenin-labelled probe was further used to examine tissue sections of equine fetuses which had been aborted due to EHV-1 infection. In all cases positive hybridization signals were mainly associated with the nuclei. Positive results were confirmed by immunostaining of EHV-1 antigen in adjacent sections. However, both methods failed to detect EHV-1 in spinal cord sections of six horses suffering from disseminated necrotizing myeloencephalitis (DNM). These results support the hypothesis that DNM is not caused by a productive viral infection of parenchyma of the nervous system but is immunologically mediated.

Spinal dysmyelination in cross-bred brown Swiss calves.

The occurrence of a congenital neurological disorder "spinal dysmyelination" in cross-bred calves in Denmark is reported. A total of 36 affected calves of the Red Danish Dairy breed X American Brown Swiss were detected. The calves occurred in a clear familiar pattern consistent with an autosomal recessively inherited trait, and the parents could be traced to a common ancestor. Clinically the disease was characterized by congenital lateral recumbency, opisthotonos, extension of the limbs, normal to increased reflexes, and normal alertness. At histological examination dysmyelination occurred constantly in specific spinal tracts.

Age-dependent changes in the glial cell nests of the canine rhinencephalic allocortex. A morphometric study.

In the present study, the morphological features as well as the age-dependent changes of the glial cell nests (GCN) within the rhinencephalic allocortex of the dog are described. A combination of two stereological methods, i.e., Cavalieri's principle and the optical disector, was used to obtain unbiased estimates of the volumes of the whole brain, the allocortex, and the GCN. Furthermore, the numerical densities and total number of the two prevailing populations of undifferentiated cells within these nests were determined. Cells with medium-sized dark nuclei (CMD) and cells with large pale nuclei (CLP) were distinguished. The volume of the GCN in relation to the volume of the allocortex decreased with increasing age. The numerical density and the total number of all cells of the GCN and of the CMD were reduced with age, whereas the numerical density and number of the CLP increased with advancing age. Similar morphological features as well as age-dependent changes have already been described of the cell populations in the subependymal layer. Therefore, in analogy, we presume that the glial cells of the GCN have emigrated from the subependymal layer. The significance of these age-dependent changes remains as obscure as does the function of the GCN.

Spinal dysmyelination in new-born brown Swiss x Braunvieh calves.

In four new-born Braunvieh calves suffering from connate recumbency and body tremor, a hitherto not described myelination disorder of the spinal cord was examined. Bilateral symmetric hypo- as well as demyelination in several spinal tracts were the most conspicuous findings, affecting the ascending gracile funiculus, the ascending dorsolateral spinocerebellar tract, and the mainly descending sulcomarginal tract. Deficient myelin production, loss of myelin, consecutive axonal degenerations, and prominent astrogliosis within these tracts were the histological hallmarks of the disease. This possibly inherited primary myelination disorder of the spinal cord differs markedly from known hereditary neurological diseases in Brown Swiss and Braunvieh cattle, respectively, i.e. the weaver-syndrome and the spinal muscular atrophy.

Rabies virus neuritic paralysis: immunopathogenesis of nonfatal paralytic rabies.

Two pathogenetically distinct disease manifestations are distinguished in a murine model of primary rabies virus infection with the Evelyn-Rokitnicky-Abelseth strain, rabies virus neuritic paralysis (RVNP) and fatal encephalopathogenic rabies. RVNP develops with high incidence in immunocompetent mice after intraplantar infection as a flaccid paralysis restricted to the infected limb. The histopathologic correlate of this monoplegia is a degeneration of the myelinated motor neurons of the peripheral nerve involved. While, in this model, fatal encephalopathogenic rabies develops only after depletion of the CD4 subset of T lymphocytes and without contribution of the CD8 subset, RVNP is identified as an immunopathological process in which both the CD4 and CD8 subsets of T lymphocytes are critically implicated.

[Spinal muscle atrophy in Brown Swiss x Braunvieh cross calves]. / Spinale Muskelatrophie (SMA) bei Kälbern aus Brown Swiss x Braunvieh-Kreuzungen.

The report describes seven SMA-cases in descendents of crossbreeds of American Brown Swiss x Deutsches Braunvieh. Symptoms and course: After initially normal development of the calves for one to six weeks the disease set in suddenly followed by a rapid lethal course of one to one and a half weeks duration due to asphyxia and/or secondary diseases. Only one case was reported having been sick since birth (?). Characteristic signs were rapidly progressing muscular atrophy, paresis and paralysis of the limbs, the trunk and the diaphragm, usually accompanied by progressive dyspnoea. Signs of congenital neuromyodysplasia (arthrogryposis) of different degree were present in four of the seven calves. Six calves had contracted a secondary pneumonia. Blood gas analysis (6/7) revealed a compensated (1x) or decompensated (4x) respiratory acidosis. Neurohistological findings: Degeneration and loss of motor neurons in the ventral horns of the spinal cord and neurogenic muscular atrophy. Immunohistochemistry revealed a pronounced accumulation of type 200 kD-neurofilaments in perikarya and dendrites of ventral horn motoneurons indicating disturbed mechanisms of the axonal transport. The disease seems to be inherited as a recessive trait.

[Unexpected transgene expression of a mammary-specific growth hormone gene construct in Bergmann glial cells of the mouse]. / Unerwartete transgene Expression eines gesäugespezifischen Wachstumshormon-Genkonstruktes in den Bergmann-Gliazellen der Maus.

Pronuclear microinjection was used to produce transgenic mice harboring gene constructs, in which 110 base pairs (WAP1) or 2.4 kilobases (WAP2) of the 5' flanking sequences of the whey acidic protein (WAP) gene were fused to human growth hormone (hGH)-coding sequences. Female WAP-hGH transgenic mice expressed the transgenes in the mammary gland, the expression of the WAP2-hGH transgene mirroring that of the endogenous WAP gene. When other organs were examined, high level expression of hGH was observed in the brains of WAP2-hGH transgenic mice. Using in situ hybridization and immunohistochemistry, hGH expression from the transgene was seen to occur specifically in Bergmann glia cells. While normally neither WAP nor hGH is expressed in this type of cell, it appears that a combination of the regulatory region of the WAP gene and the hGH structural gene results in a novel tissue specificity in Bergmann glia cells.

Morphological, immunocytochemical and growth characteristics of three human glioblastomas established in vitro.

The human glioblastoma-derived cell lines 86HG-39, 87HG-28 and 87HG-31, used for the production of monoclonal antibodies (mAbs) against glioma-associated antigens (GAA), were characterized in terms of morphology, growth behaviour, chromosomes and antigen expression. In the primary tumours, differential expression of glial fibrillary acidic protein, S100 protein, Leu-7 and GAA as defined by mAbs MUC 2-39, MUC 2-63 and MUC 8-22 was demonstrated. Receptors for epidermal growth factor (EGFr) and nerve growth factor (NGFr) were found in many cells in short-term cultures, but the transferrin receptor (Tr) was found in only a few cells of 87HG-28. In permanent cell lines, differentiation antigens and EGFr decreased and Tr increased markedly. NGFr and GAA remained stable. Transplantation tumours of 86HG-39 were partly positive for Tr and GAA. Chromosomal analysis revealed that the 86HG-39 and 87HG-28 cell lines had a hypodiploid or diploid stem line with lines in the hypotetraploid to tetraploid region for 50 in vitro passages. The 87HG-31 cell line had chromosomal patterns in the hypotriploid to triploid region. A gain of chromosomes was seen in the groups C7, C8, C10, D14, F19, F20, G21, G22. The variability of antigens in these tumours and especially during long-term cultivation probably reveals an ability to influence the growth of malignant glioma cells via the respective effector molecules.

[The differential diagnosis of spinal cord malformations in cattle]. / Zur Differentialdiagnose von Rückenmarksmissbildungen beim Rind.

Hereditary developmental disorders of the CNS, especially spinal cord, are of increasing importance in the bovine species. Therefore, congenital spinal malformations of non-hereditary origin have to be ruled out by carefully directed neuromorphological procedures. The two cases of malformation of the spinal cord reported were not accompanied by vertebral defects: The first one represents a complete diplomyelia of the caudal lumbo-sacral medulla in an 18 months old Brown Swiss heifer, the second one a circumscribed hydromyelia of the fifth lumbal segment, based on an incomplete dysraphic defect, in a 4 months old male German Simmental calf. Problems of diagnostic measures and of terminology, concerning differentiation between diplomyelia and diastematomyelia, were discussed in detail.

Production of antibodies to canine distemper virus in chicken eggs for immunohistochemistry.

The present study describes the application of egg yolk antibodies in immunohistochemistry. In order to obtain specific antibodies against canine distemper virus (CDV), chickens were immunized with attenuated virus. Distinct antibody titres in serum and yolk could be detected by means of a modified plaque/focus immunoassay (ELISA) two weeks after a second immunization. The lower concentrations in corresponding yolk globulin preparations are attributed to the loss of antibodies caused by the isolation procedure (dextran and ammonium sulfate precipitation). After verification of the antibody specificity by indirect immunofluorescence technique high titred globulin fractions were employed in immunohistochemistry using the Avidin-Biotin-Complex method. A specific and distinct immunostaining in formalin fixed and paraffin embedded brain sections of CDV-infected dogs was obtained. The advantages of egg yolk antibodies for immunological purposes are discussed in detail.

[Diabetic neuropathy in dogs and cats--a bioptic electron microscopic study]. / Diabetische Neuropathie bei Hund und Katze--eine bioptisch-elektronenmikroskopische Studie.

Electron microscopic examination of peripheral nerves within dermal corium based upon skin biopsies (punch diameter = 6 mm) of chronic diabetic dogs and cats in comparison with normal controls revealed that more than 90% of the diabetic animals (31/34 dogs, 9/10 cats) had developed characteristic neuropathies. The main features were of axonal atrophy of myelinated and unmyelinated fibers, demyelination and - to a lesser degree - intraaxonal accumulation of glycogen (about 25%). In contrast with human diabetic polyneuropathy vascular basement membranes were throughout of normal appearance. Thickening of the perineural basement membranes were observed in a few canine cases only. Diagnostic procedures as well as questions on pathogenesis are discussed in detail.