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R Fatzer

Publications and source records attributed to R Fatzer.

At least 19 recordsLinked to original sources
PubMed2002

[Intracranial astrocytomas in eight cats: clinical and pathological findings].

Intracranial astrocytomas are rarely diagnosed in cats. Clinical and pathological aspects of these tumors are more often described in humans and dogs. The classification scheme used in human medicine is of important prognostic value. We have analyzed clinical neurological and pathological findings from 8 cats with intracranial astrocytomas. The animals were 10.1 years old in average and presented with a history of tetraparesis (n = 3), epilepsy (n = 2), loss of balance (n = 3) and dyspnoe (n = 1). The latter cat died immediately after the first presentation while the other animals were euthanized because of a progressive course of the symptoms despite therapy. Even though feline astrocytomas, that we could classify into 4 different types in this study, are clinically and pathologically well correlated with those of other species, a prognostically useful classification has never been established before.

Animals↗
PubMed2002

A novel nonsuppurative meningoencephalitis in young greyhounds in Ireland.

Fourteen 4- to 18-month-old vaccinated Greyhounds (10 males, 4 females) from three kennels in southern Ireland presented over a 2-year period with acute or insidious onset neurological signs. Head tilting, ataxia, recumbency, circling, and blindness were commonly observed, and animals were dull, dehydrated, and had lost weight. Hematologic and biochemical parameters reflected dehydration but were otherwise unremarkable. Microscopic examination revealed severe diffuse and focal gliosis and gemistocytosis accompanied by mononuclear cell perivascular cuffing in caudate nucleus and cortical gray matter of the cerebrum and in the periventricular gray matter of the anterior brainstem. Milder lesions were noted in the caudal brainstem, cranial spinal cord, and in the molecular layer of the cerebellum. This was accompanied by a lymphocyte and plasma cell infiltration of the cerebral and cerebellar meninges. Demyelination, neuropil necrosis, neuronophagia, and vasculitis were not observed. No inclusion bodies, fungi, or protozoal cysts were seen. Additional serologic and molecular pathology tests also failed to determine a cause, suggesting that these cases may represent a previously undiagnosed condition in the dog.

Animals↗
PubMed2002

Inducible nitric oxide synthase and nitrotyrosine in listeric encephalitis: a cross-species study in ruminants.

Listeria monocytogenes (LM) is a Gram-positive facultative intracellular bacterium that causes fatal meningoencephalitis in humans and ruminants. A current paradigm predicts that intracellular bacteria are controlled by nitric oxide (NO) whose synthesis is catalyzed by inducible nitric oxide synthase (iNOS). The ability of macrophages (Mphi) to express iNOS shows extreme interspecies variability. Here the expression of iNOS and synthesis of NO was studied in listeric encephalitis of cattle, sheep, and goats. iNOS was expressed by a subset of Mphi in cerebral microabscesses in all three species. The level of iNOS expression and the density of cells per lesion expressing iNOS was highest in cattle, intermediate in sheep, and lowest in goats. The accumulation of nitrotyrosine (NT), an indicator of local NO synthesis, was observed in lesions of cattle but not in those of small ruminants. The density of iNOS-expressing cells in lesions was inversely correlated with the number of bacteria. No species differences were observed in regard to reactive oxygen intermediate (ROI) production by stimulated granulocytes, using the flow cytometric dihydrorhodamine-123 (DHR) method indicating ROI generation. Thus, the marked species differences in iNOS expression, NT accumulation, and LM content in lesions of ruminants with listeric encephalitis are explained by different amounts of ROI produced. It suggests that variations in the ability of Mphi to synthesize NO are of pathophysiological significance in listeriosis.

Animals↗
PubMed2001

Targeted screening of high-risk cattle populations for BSE to augment mandatory reporting of clinical suspects.

In Switzerland, the first case of bovine spongiform encephalopathy (BSE) was diagnosed in November 1990. Case numbers peaked in 1995, with a total of 352 BSE cases identified by 30 April 2000. Reporting of clinically suspect cattle is currently the most commonly used method world-wide to detect BSE cases. The effectiveness of mandatory reporting depends on a variety of factors; for other diseases passive surveillance underestimates the incidence of clinical cases. The efficiency of passive surveillance systems for BSE will remain unknown until screening tests able to identify clinically affected cattle have been applied in several countries. This paper provides the first detailed description of a targeted screening programme for BSE. Two populations of cows >24 months of age were included in the targeted screening: (i) cows found dead or culled on site where the carcass was submitted to rendering (fallen stock) and (ii) cows with health-related problems unfit for routine slaughter that were slaughtered under emergency procedures (emergency slaughter). Between 1992 and 1999, on average 81 clinical BSE suspects per year were reported to the veterinary authorities (passive surveillance), of which 43% were confirmed with BSE. A total of 30 clinical cases were captured by passive surveillance and an additional 20 BSE cases detected by targeted screening between May 1999 and April 2000. The odds of finding a BSE case was 49 times higher in the fallen stock and 58 times higher in emergency-slaughtered cattle when compared to passive surveillance. The targeted screening of fallen stock and emergency-slaughtered cattle considerably increased the number of detected cases in this 12-month period. Targeted-screening cases were on average 4 months younger than the clinical suspect cases. In conclusion, post-mortem testing of fallen stock and emergency-slaughtered cows >24 months for BSE is an important active surveillance element within a total surveillance system that principally is based on mandatory reporting of clinical suspect cases. Without ante-mortem screening tests to detect BSE-infected cattle during the incubation period, a combination of effectively functioning passive and active BSE surveillance strategies might be the only approach to assess the BSE situation reliably in a given country or region - and it is necessary to substantiate claims of freedom from the disease.

Animals↗
PubMed2001

Nitric oxide is protective in listeric meningoencephalitis of rats.

The bacterium Listeria monocytogenes causes meningoencephalitis in humans. In rodents, listeriosis is associated with granulomatous lesions in the liver and the spleen, but not with meningoencephalitis. Here, infant rats were infected intracisternally to generate experimental listeric meningoencephalitis. Dose-dependent effects of intracisternal inoculation with L. monocytogenes on survival and activity were noted; 10(4) L. monocytogenes organisms induced a self-limiting brain infection. Bacteria invaded the basal meninges, chorioid plexus and ependyme, spread to subependymal tissue and hippocampus, and disappeared by day 7. This was paralleled by recruitment and subsequent disappearance of macrophages expressing inducible nitric oxide synthase (iNOS) and nitrotyrosine accumulation, an indication of nitric oxide (NO.) production. Treatment with the spin-trapping agent alpha-phenyl-tert-butyl nitrone (PBN) dramatically increased mortality and led to bacterial numbers in the brain 2 orders of magnitude higher than in control animals. Treatment with the selective iNOS inhibitor L-N(6)-(1-iminoethyl)-lysine (L-NIL) increased mortality to a similar extent and led to 1 order of magnitude higher bacterial counts in the brain, compared with controls. The numbers of bacteria that spread to the spleen and liver did not significantly differ among L-NIL-treated, PBN-treated, and control animals. Thus, the infant rat brain is able to mobilize powerful antilisterial mechanisms, and both reactive oxygen and NO. contribute to Listeria growth control.

Animals↗
PubMed2001

Necrotizing meningoencephalitis associated with cortical hippocampal hamartia in a Pekingese dog.

A 4-year-old male Pekingese dog was referred to the clinic with a history of recurrent seizures and progressive abnormal gait and behavior, which did not respond to treatment. At necropsy, a large cortical defect in the right temporo-parietal cortex, malacia of subcortical white matter, right basal nuclei, and capsula interna, as well as abnormalities of the right hippocampus were observed. Histological examination of the brain revealed moderate to severe nonsuppurative meningoencephalitis in the left cerebral hemisphere and extensive infarction-like lesions with milder inflammation in the right hemisphere. In the right hippocampus, the pyramidal cells were arranged in a gyrus-like pattern and intermingled with gemistocytic and fibrillary astrocytes. The histopathological features of the inflammatory lesions were consistent with necrotizing meningoencephalitis and resembled those described in so-called Pug dog encephalitis. The hippocampal changes were interpreted as dysplasia (monolateral hippocampal cortical hamartia), unrelated to clinical signs and necrotizing inflammatory lesions.

Amoxicillin↗
PubMed2001

Paradoxical vestibular disease with trigeminal nerve-sheath tumor in a dog.

A thirteen-year old spayed female poodle was referred because of atrophy of temporal and masseter muscles on the left and head tilt and episodical circling to the right side. Additionally, decreased facial sensation, absent menace reaction, palpebral and corneal reflexes on the left side, as well as ipsilateral hemiparesis and tongue palsy were noticed. Generalised vestibular ataxia and hypermetria in the front limbs were present. Based on the clinical signs, the presumptive anatomical localization of the lesion was the cerebellopontine angle including parts of the caudal brainstem with involvement of the trigeminal, facial and hypoglossal nerves. Involvement of either flocculonodular lobe or the caudal cerebellar peduncle on the left side causing paradoxical vestibular disease was suspected. On magnetic resonance imaging a large enhancing lesion in the area of the left cerebellopontine angle involving the trigeminal nerve and compressing cerebellum and brainstem was seen. Because of the poor prognosis the dog was euthanized on the owner's request. This space occupying lesion could be identified as a trigeminal neurofibrosarcoma/schwannoma on post mortem histopathological examination.

Animals↗
PubMed2000

A monomer-dimer equilibrium of a cellular prion protein (PrPC) not observed with recombinant PrP.

Both the purified normal (protease-sensitive) isoform of the prion protein (PrP(C)) (Pergami, P., Jaffe, H., and Safar, J. (1996) Anal. Biochem. 236, 63-73) and recombinant prion protein (PrP) have been found to be in monomeric form (Mehlhorn, I., Groth, D., Stockel, J., Moffat, B., Reilly, D., Yansura, D., Willet, W. S., Baldwin, M., Fletterick, R., Cohen, F. E., Vandlen, R., Henner, D., and Prusiner, S. B. (1996) Biochemistry 35, 5528-5537; and this paper), and therefore PrP(C)-PrP(C) interactions were previously unknown. In this report we confirm recombinant PrP to be a monomer by analytical ultracentrifugation. However, by three lines of evidence (enzyme-linked immunosorbent assay (ELISA), cross-linking experiments, and size exclusion chromatography) we could also demonstrate that, under native conditions, at least part of the native bovine PrP(C) exists as a monomer-dimer equilibrium. A bovine PrP(C)-specific immuno-sandwich ELISA was developed and calibrated with recombinant PrP (Meyer, R. K., Oesch, B., Fatzer, R., Zurbriggen, A., and Vandevelde, M. (1999) J. Virol. 73, 9386-9392). By this ELISA we identified a distinct PrP(C) fraction and partially purified this protein. When serial dilutions of brain homogenate or partially purified PrP(C) were measured, using the peptide antibody C15S, a nonlinear dose-response curve was obtained. This nonlinearity was shown not to be due to an artifact of the procedure but to a monomer-dimer equilibrium of PrP(C) with preferential binding of the antibody to the dimer. From the curvature we could deduce the association constant (3.9 x 10(8) M(-1) at 37 degrees C). Accordingly, DeltaG degrees of the reaction was calculated (-48.6 kJ M(-1)), and DeltaH degrees (9.5 kJ M(-1)) as well as DeltaS degrees (0.2 kJ K(-1) M(-1)) were extrapolated from the van't Hoff plot. When serial dilutions of monomeric recombinant PrP were tested, only a straight line was obtained, supporting our hypothesis. Additional evidence of dimer formation was revealed by Western blotting of partially purified PrP(C) cross-linked by the homobifunctional cross-linker BS(3). Finally, size exclusion chromatography of partially purified PrP(C) fractions revealed an additional shoulder not observed with recombinant PrP. The difference in respect of dimer formation between native PrP(C) and recombinant PrP could be explained by the lack of glycosylation of the latter.

Animals↗
PubMed2000

Presumed immune-mediated cerebellar granuloprival degeneration in the Coton de Tuléar breed.

An unusual form of cerebellar granuloprival degeneration was observed in three male Coton de Tuléar puppies between 12 and 14 weeks of age from different litters showing progressive cerebellar signs beginning at 8 weeks after birth. Pathological examinations revealed a shrunken cerebellum. Histopathologically the granular cells were diminished or almost completely absent, some 'torpedos' of Purkinje cells were present. There was a marked gliosis, and occasionally small inflammatory foci were present. A marked diffuse T cell infiltration (CD3(+) cells) occurred in the lesions, B cells did not appear. CD18 staining showed an upregulation of microglial cells at the lesion site. Histopathologically the lesions resembled paraneoplastic cerebellar degeneration which is caused by an autoimmune mediated T cell reaction. This congenital condition in the Coton de Tuléar dog breed could be based on a genetically defined immune defect leading to autoimmune destruction of the granular cells.

Animals↗
PubMed2000

DNA vaccine encoding nucleocapsid and surface proteins of wild type canine distemper virus protects its natural host against distemper.

Canine distemper virus (CDV), a member of the genus Morbillivirus induces a highly infectious, frequently lethal disease in dogs and other carnivores. Current vaccines against canine distemper consisting of attenuated viruses have been in use for many years and have greatly reduced the incidence of distemper in the dog population. However, certain strains may not guarantee adequate protection and others can induce post vaccinal encephalitis. We tested a DNA vaccine for its ability to protect dogs, the natural host of CDV, against distemper. We constructed plasmids containing the nucleocapsid, the fusion, and the attachment protein genes of a virulent canine distemper virus strain. Mice inoculated with these plasmids developed humoral and cellular immune responses against CDV antigens. Dogs immunized with the expression plasmids developed virus-neutralizing antibodies. Significantly, vaccinated dogs were protected against challenge with virulent CDV, whereas unvaccinated animals succumbed to distemper.

Animals↗
PubMed2000

Detection of PrP(Sc) in subclinical BSE with the paraffin-embedded tissue (PET) blot.

The appearance of a new variant of CJD (vCJD) in young patients has caused considerable public concern and there is evidence that this novel disease is caused by the same agent as BSE. BSE is a prion disease that became epidemic in the UK, with a peak incidence in January 1993. New test systems should aim to identify BSE-infected cattle early in the incubation period. We compared the established histological and immunohistochemical methods and the Western blot method used by Prionics with the PET blot method that detects prion PrP(Sc) deposits in formalin-fixed and paraffin-embedded tissue. Investigating the obex region with the PET blot, all BSE cases were detectable and no false positive cases occurred. From the Swiss culling program, five clinically healthy cattle out of 1761 were identified as incubating BSE. With the PET blot method four of them showed the same PrP(Sc) deposition pattern that was seen in clinical BSE, though less conspicuous. In one of the five cases, PrP(Sc) was restricted to two brain stem nuclei, a pattern that was reported to be the first manifestation of PrP(Sc) deposits in the brain after peripheral infection and one that occurs after half of the incubation time. In this case, histology and Western blot were negative.

Animals↗
PubMed1999

Modelling the expected numbers of preclinical and clinical cases of bovine spongiform encephalopathy in Switzerland.

The objective of this study was to model the expected numbers of cattle incubating bovine spongiform encephalopathy (BSE) and the numbers of clinical cases of BSE in the Swiss cattle population between 1984 and 2005. The results were compared with the observed number of clinical BSE cases and with the results of a culling and testing scheme on herdmates of cattle with BSE. The age distribution of the Swiss cattle population, the age-at-death distribution of the first 235 BSE cases and exposure information were used to calculate the expected number of infected cattle in each birth cohort and the resulting numbers of clinical cases and survivors incubating the disease for each year. The model which did not assume any under-reporting of cases fitted the observed epidemic curve of clinical cases reasonably well, and predicted that the Swiss BSE epidemic would come to an end between 2003 and 2005. The age of survivors incubating BSE is increasing. The higher than expected incidence of subclinical cases observed in animals from the culling scheme is most probably the result of the heterogeneous distribution of infected animals and affected herds in the population. The results of the model need to be taken into account when designing surveillance and testing schemes for BSE.

Age Distribution↗
PubMed1999

Validation of a western immunoblotting procedure for bovine PrP(Sc) detection and its use as a rapid surveillance method for the diagnosis of bovine spongiform encephalopathy (BSE).

In this report we document the results of several independent studies testing the sensitivity, specificity and reliability of the Prionics Western blotting (PWB) procedure to detect bovine and ovine disease-specific, protease-resistant prion protein (PrP(Sc)). Validation of the technique was obtained by blind analysis of samples from cattle affected with bovine spongiform encephalopathy (BSE), clinically normal animals or cattle with neurological diseases unrelated to BSE. Overall, very high sensitivity, specificity and reliability was observed. It became clear that sampling of the correct brain region and the method used for protein extraction are important factors for correct diagnosis. Furthermore, we tested the usefulness of the PWB technique as an instrument for surveillance purposes. We analyzed animals from a culling scheme as well as older animals from abattoirs to determine the number of subclinical BSE cases detectable by histopathological examination, immunohistochemistry for PrP(Sc) and PWB. In both studies, BSE-affected animals with no overt clinical symptoms were detected. These results demonstrate the usefulness of the PWB procedure in surveillance systems serving as a rapid diagnostic tool to identify animals subclinically infected with BSE.

Animals↗
PubMed1999

Nuclear DNA fragmentation and immune reactivity in bovine spongiform encephalopathy.

To investigate whether apoptosis contributes to neuronal degeneration in bovine spongiform encephalopathy (BSE), morphological changes consistent with apoptosis were sought and in-situ end labelling (ISEL) was applied, in a series of 20 BSE cases and 10 age-matched normal control cattle. Apoptotic changes were not found in neurons but were occasionally seen in glial cells. Relatively few ISEL-positive neurons were found, but many labelled nuclei were seen in glial cells in certain areas. None of the labelled cells showed morphological features of apoptosis. ISEL(+)cells occurred in areas of spongiform change and other areas of grey matter lacking spongiform change. Some association was found between degree of cellular DNA fragmentation and accumulation of abnormal prion protein (PrP(Sc)). Interestingly, small or moderate numbers of T lymphocytes, not present in the normal central nervous system (CNS), were detected in the CNS parenchyma in most BSE cases. There was a pronounced astrogliosis, but markers of macrophage or microglial activation were only slightly increased. The results indicate that nuclear DNA vulnerability is enhanced in certain neuroanatomical areas in BSE, but evidence that apoptosis plays a role in neuronal loss in BSE was very limited. 1999 Harcourt Publishers Ltd.

Animals↗