Immunological aspects of experimental brain tumors (review).

Evidence that experimental neural tumors contain glia specific and glioma-associated antigens is reviewed. The fact that glioma cells share antigens with normal glia cells is of crucial importance for the histogenetic immunodiagnosis of intracranial neoplasms. Moreover, the increasing use of in vitro techniques in neuro-oncology has accentuated the necessity for employment of cell-type characteristic antigens. This allows for objective identification of the various types of brain tumor cells, and also for ascertaining the neurological nature of long-term cultured cells. Humoral and cell-mediated immune reactions to gliomas could be demonstrated in autochthonous and syngeneic hosts. Since glioma-associated antigens are rather weak and glioma cells are low immunogens, various approaches for enhancing glioma-cell immunogenicity have been described, such as treatment with membrane-modifying enzymes, or haptenization with various chemicals. Recently, nitrophenylation of glioma cells has become available for artificially increasing the immunogenicity of these cells. Furthermore, methods have recently been worked out by which monoclonal antibodies of predefined specificity can be produced in order to analyze the nature of glioma-associated antigens. Such methods may have a significant impact on clinical immunodiagnostics, and perhaps on the development of new immunotherapeutic approaches.

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.

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.

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.

[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.

[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.

[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.

[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.

[The diagnosis of primary olfactory mucosa neoplasms demonstrated by an esthesioneuroepthelioma in the dog]. / Zur Diagnose primärer Riechschleimhauttumoren, dargestellt an einem Asthesioneuroepitheliom beim Hund.

In context with the first light and electron microscopic description of a spontaneous esthesioneuroepithelioma in a dog (10 year old female Labrador) general morpho- and etiopathogenetic problems concerning olfactory neoplasias were discussed. Because of its specific location and growth pattern, especially the development of true rosettes and pseudo-rosettes, the tumor was evaluated light microscopically as an esthesioneurogeneic one. The final classification was based upon ultrastructural peculiarities, as occurrence of ciliar structures, characteristic intercellular junctions, and the - although rare - appearance of dense cored vesicles.

Ultrastructure of retinal pigment epithelial and neural cells in the neuronal ceroid-lipofuscinosis affected Dalmatian dog.

Ubiquitous accumulation of lipopigments, entailing lamellar, fingerprint, and curvilinear bodies in varying cell types of the retina, and, in addition, peculiar circular inclusions within retinal pigment epithelial cells in the retina of two Dalmatian dogs afflicted with neuronal ceroid-lipofuscinosis, emphasize the identity of its retinal ultrastructural pathology to that observed in NCL-affected English setters, while the retinal layers appear largely preserved. The circular inclusions in RPE cells are unique to canine NCL; they are not encountered in human NCL, nor in primary non-NCL retinal dystrophies of other canine species. Their origin and pathogenesis, so far, remain subject to speculation, rather than to convincing explanation.

Retinal ultrastructure of neuronal ceroid-lipofuscinosis in the dalmatian dog.

Ultrastructural studies of the retinae in two NCL-affected Dalmatian dogs revealed ubiquitous accumulation of lipopigments in numerous cell types of the retina, the fine structure of which closely resembled that seen in NCL-affected English setters. Photoreceptors and other retinal cell types were largely intact. These findings show that the retinal involvement in NCL of our Dalmatian dogs is identical to that of NCL-affected English setters. It also shows that in canine NCL a severe retinopathy, regularly encountered in human childhood NCL, does not develop. Thus, the NCL of Dalmatian dogs--and English setters--represents a reliable model to study human NCL, but for human retinopathia pigmentosa perhaps only at its earliest stage.

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.

[Transplacental induction of neurogenic tumors in rabbits (author's transl)]. / Transplacentare neuroonkogene Wirkung von Athylnitrosoharnstoff beim Kaninchen während der frühen Graviditätsphase.

The oncogenic effect of ethylnitrosourea (ENU) on rabbits during the organogenesis was studied. ENU, dissolved in sodium phosphate (pH 6.0), was injected in a 50 mg/kg dosis intravenously in pregnant dams between the 8th and 10th day of gestation. From 12 offspring 8 grew up normally and appeared unremarkably until 30--36 months of age when neurologic signs first developed. Six rabbits showed one or more tumors along the peripheral nerves. Two rabbits were bearing brain gliomas in the vicinity of the 3rd ventricle. The tumors of the peripheral nervous system (PNS) were of variable size and soft consistency; they had a cut surface of spongy and even cystic appearance. Histologically, the PNS tumors resemble Schwannomas of the Antoni B type. An ultrastructural study of these neoplasms disclosed cells featuring a basal lamina type of lining characteristics of Schwann cells. These findings demonstrate that the exposure of rabbits to ENU during organogenesis results in the induction of neurogenic tumors which become clinically manifest late in life. It seems, therefore, that the selective oncogenic effect of ENU on the nervous tissues of the exposed animals depends exclusively on the stage of organogenesis at which the drug is brought to bear upon the target organ anlage.