L Haas

University of Veterinary Medicine Hannover, Hannover, Lower Saxony, Germany

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Publications (44)86.53 Total impact

  • Article: Viral infectivity and intracellular distribution of matrix (M) protein of canine distemper virus are affected by actin filaments.
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    ABSTRACT: To investigate the role of cytoskeletal components in canine distemper virus (CDV) replication, various agents were used that interfere with turnover of actin filaments and microtubules. Only inhibition of actin filaments significantly reduced viral infectivity. Analysis of the intracellular localization of the viral matrix (M) protein revealed that it aligned along actin filaments. Treatment with actin filament-disrupting drugs led to a marked intracellular redistribution of M protein during infection as well as transfection. In contrast, the localization of the CDV fusion (F) protein was not significantly changed during transfection. Thus, a M protein-actin filament interaction appears to be important for generation of infectious CDV.
    Archives of Virology 09/2010; 155(9):1503-8. · 2.11 Impact Factor
  • Article: Border disease virus (BDV) infections of small ruminants in Turkey: a new BDV subgroup?
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    ABSTRACT: Blood samples from sheep and/or goats from eight small ruminant flocks in the Turkish provinces of Aydin and Burdur were tested for the presence of Pestiviruses using an antigen-capture ELISA. From clinically affected animals, pathological and immunohistochemical findings were recorded. Post mortem examination of a virus-positive lamb showing abnormal fleece and paralysis of the hind legs revealed nonsuppurative meningoencephalomyelitis with hypomyelinogenesis. By immunohistochemistry Pestivirus antigen was detected in all parts of the brain including cerebellum, cerebral hemispheres and midbrain. Two Pestivirus isolates from a sheep and a goat kid, respectively, were isolated from samples that were positive in the antigen-capture ELISA. Genetic typing using the 5'-NTR (288bp) and N(pro) (738bp) showed that both were Border disease virus (BDV) isolates. By phylogenetic analysis, they formed a cluster clearly separated from the known clusters BDV-1 to BDV-6 and might therefore represent a new subgroup (BDV-7?). This is the first report confirming the occurrence and partial characterisation of BDV infection in small ruminants in Turkey.
    Veterinary Microbiology 11/2008; 135(3-4):374-9. · 3.33 Impact Factor
  • Article: Phocine distemper virus: characterization of the morbillivirus causing the seal epizootic in northwestern Europe in 2002.
    Archives of Virology 02/2008; 153(5):951-6. · 2.11 Impact Factor
  • Article: [Familial occurrence of a congenital defect of the keratinisation of the skin in German Angus calves].
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    ABSTRACT: Congenital dysfunction of the keratinisation of the epithelium was diagnosed in two female German Angus calves born on the same farm. The relationship coefficient between the two affected Angus calves was 34.38%. The clinical findings were similar to ichthyosis congenita as the alterations of the skin were present at birth and the levels of zinc in the blood were not decreased. However, parakeratosis could not be completely excluded as skin alterations were partly parakeratotic. On account of the close relationship between the two affected calves a genetic cause is likely for the present cases.
    DTW. Deutsche tierärztliche Wochenschrift 02/2007; 114(1):25-9. · 0.41 Impact Factor
  • Article: Antigenic characterization of phocine distemper virus causing mass mortality in 2002 and its relationship to other morbilliviruses.
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    ABSTRACT: The antigenic relationship between the phocine distemper virus (PDV) strain causing the epidemic in 2002 and the PDV strain of 1988, canine distemper virus from two dogs and one marten, and one measles virus strain was investigated in vivo and in vitro using monospecific polyclonal and monoclonal antibodies directed against five different proteins of canine or phocine distemper virus (N, P, M, F, H). Epitopic mapping revealed no difference between the PDV strains causing the epidemics in 1988 or 2002. However, the use of these antibodies allowed discrimination between different morbilliviruses including a vaccine strain of canine distemper virus. The major differences among the investigated morbilliviruses were found in the H protein.
    Archives of Virology 02/2007; 152(8):1559-64. · 2.11 Impact Factor
  • Article: [Aphakia in a German Holstein calf].
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    ABSTRACT: Aphakia and further malformations of both eyes were diagnosed in a female German Holstein calf. Besides aphakia of the left eye, the calf exhibited microphthalmia, glaucoma and a hypoplastic uveoscleral tissue. Additional findings in the right eye were buphthalmus and glaucoma. Instead of aphakia, pathohistological and investigations revealed a very small (microphakia) and luxated lens. Neither the clinical nor the pathological examination revealed further malformations of other organs. A BVD infection could be excluded as cause for the ocular malformations observed. A deficiency or excess of vitamine A was unlikely because this would have also applied to all other calves born at the same time on the farm. An inbreeding coefficient of 3.168% for the malformed calf and the exclusion of environmental causes for these malformations of the eyes let us suppose a hereditary problem.
    DTW. Deutsche tierärztliche Wochenschrift 10/2006; 113(9):355-7. · 0.41 Impact Factor
  • Article: [Case report: Ectopia cordis in a German Holstein calf].
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    ABSTRACT: A case of ectopia cordis pectoralis was diagnosed in a black and white coloured German Holstein calf. The heart and pericard were displaced through a fissure in the breastbone. The heart was connected with the thoracic cavity by its large vessels. Besides of the ectopia cordis no other defects of the heart were noticed. The liver was deformed and many organs showed passive hyperaemia. The calf was well developed and died under birth. The lungs were not ventilated. The malformed calf was inbred on a bull used for artificial insemination with an inbreeding coefficient of 3.125%. The ectopia cordis probably resulted from the fissure of the breastbone.
    DTW. Deutsche tierärztliche Wochenschrift 08/2006; 113(7):281-4. · 0.41 Impact Factor
  • Article: [Genetic typing of classical swine fever viruses--a review].
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    ABSTRACT: Classical swine fever (CSF) is a notifiable disease of domestic pigs and wild boar. It is caused by the highly contagious CSF virus and in its acute form the disease generally results in high morbidity and mortality. Due to the great economical impact an outbreak can cause to the pig industry it is one of the most important swine diseases worldwide. To limit the damage in the case of a new outbreak it is necessary to identify the virus as fast as possible. This information helps epidemiologists to trace the origin of the virus and to follow the virus spread. Genetic typing revealed that CSF virus genotypes, subgroups and types show a regional distribution making it an important tool for epidemiologists. Meanwhile, besides epidemiological data and nucleotide sequences from European isolates, information from isolates from South- and Central America, the Caribbean, Asia and recently from South Africa have become available. The data are stored in a database in the EU Reference Laboratory for CSF, accessible by the WWW (http://viro08.tiho-hanno ver.de). A new module was implemented that allows efficient automated genotyping.
    DTW. Deutsche tierärztliche Wochenschrift 05/2006; 113(4):134-8. · 0.41 Impact Factor
  • Article: Implementation of two-step vaccination in the control of bovine viral diarrhoea (BVD).
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    ABSTRACT: Bovine viral diarrhoea (BVD) control/eradication programmes based on the test and removal of persistently infected cattle without use of vaccination were first introduced by the Scandinavian countries in the early 1990s. Within the last 10 years the programmes have proven to be very successful and have served as a blueprint for several other European regions. However, in areas with high cattle densities, intense animal trade and high BVD prevalence this control approach is risky, because there is a high probability that herds, which have been cleared of persistently infected (PI) animals and have become partly or fully susceptible to reintroduction of the virus, will come in contact with a BVD virus (BVDV) infected animal. A combination of the test and removal strategy with subsequent systematic vaccination of cattle could overcome this problem. The goals of vaccination in such a programme is protection against reintroduction of BVDV into herds free from PI cattle and foetal protection of pregnant animals accidentally exposed to the virus. Two-step vaccination is based on the use of inactivated BVDV-1 vaccine for priming followed by a live attenuated vaccine booster 4 weeks later. The immune response elicited by such a vaccination scheme has proven to be long lasting and foetal infection after challenge with BVDV-1 and BVDV-2 was prevented in pregnant animals 5 months after vaccination. These findings suggest that the implementation of a two-step vaccination in the initial phase of control programmes in addition to test and removal of PI animals in areas with high cattle densities and endemic BVD is practical and efficacious.
    Preventive Veterinary Medicine 12/2005; 72(1-2):109-14; discussion 215-9. · 2.05 Impact Factor
  • Article: [Analysis of bulk milk samples using polymerase chain reaction: an additional tool for bovine viral diarrhea monitoring].
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    ABSTRACT: Programmes for the eradication and control of infections with bovine viral diarrhea virus (BVDV) concentrate on the identification and elimination of persistently infected (PI) animals. The identification of these animals is mainly based on the detection of viral antigen using ELISA techniques. Protocols detecting viral nucleic acid using RT-PCR have been described recently. Due to high costs the German model recommends screening of animals of 9 up to 36 months of age. Screening of bulk milk samples using RT-PCR technology would allow a system independent of age. The aim of the present study was to test whether bulk milk samples (1433 including max. 50 animals each) collected in four counties of Lower Saxony are suitable for a complementary identification of PI animals via RT-PCR. Thirty-one bulk milk samples derived from 27 dairy herds were BVDV positive, corresponding to 2.3 % of the herds analysed in this study. Two samples first scored doubtful. Follow up tests revealed lactating PI animals in most cases (18). In other cases the epidemiological status of the herd, i.e. high sero-prevalence and/or presence of PI animals among non-lactating cattle, suggested a transient infection detected in the first bulk milk sample. These results demonstrate that monitoring of lactating cattle of any age using RT-PCR is a very sensitive, economically effective additional method for the identification of PI animals.
    DTW. Deutsche tierärztliche Wochenschrift 05/2005; 112(4):130-5. · 0.41 Impact Factor
  • Article: Spontaneous human herpes virus type 1 infection in a chinchilla (Chinchilla lanigera f. dom.).
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    ABSTRACT: A 1-year-old male chinchilla with a 2-week history of conjunctivitis suffered subsequently from neurological signs comprising seizures, disorientation, recumbency and apathy. After 3 weeks of progressive central nervous disease the animal was killed in view of the poor prognosis. A non-suppurative meningitis and polioencephalitis with neuronal necrosis and intranuclear inclusion bodies were observed at necropsy and by light microscopy. The brain stem and cerebral cortices were most severely affected. Both eyes displayed ulcerative keratitis, uveitis, retinitis and retinal degeneration, and optical neuritis. Additionally, a purulent rhinitis with focal erosions, epithelial degeneration and intranuclear inclusion bodies was present. Ultrastructurally, herpes virus particles were detected in neurons of the brain. Immunohistochemistry with antisera specific for human herpes virus types 1 and 2 resulted in viral antigen labeling in neurons, glial cells and in neuronal processes. Viral antigen was found in the rhinencephalon, cerebral cortices, hippocampus, numerous nuclei of the brain stem, single foci in the cerebellum, and in a solitary erosive lesion of the right nasal vestibulum. Viral antigen was not detected in the eyes. The virus was isolated from the CNS, and nucleic acid sequence analysis of the glycoprotein B and the DNA polymerase revealed a sequence homology with human herpes virus type 1 of 99% and 100%, respectively. The clinical signs, the distribution of the lesions and the viral antigen suggest a primary ocular infection with subsequent spread to the CNS. Chinchillas are susceptible to human herpes virus 1 and may play a role as a temporary reservoir for human infections.
    Acta Neuropathologica 01/2003; 104(6):674-8. · 9.32 Impact Factor
  • Article: Induction of apoptotic cellular death in lymphatic tissues of cattle experimentally infected with different strains of rinderpest virus.
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    ABSTRACT: The presence, type, and extent of cellular death in lymphatic tissues of cattle experimentally infected with rinderpest virus strains of different virulence was investigated morphologically. Cells with DNA strand breaks were identified in histological sections of palatine tonsil, spleen, and mesenteric and mandibular lymph nodes by the TUNEL (terminal desoxynucleotidyl transferase-mediated dUTP nick end labelling) assay. In addition, representative samples of lymphatic tissues were examined by transmission electron microscopy. The results indicated that cellular disassembly in lymphatic tissues was caused by both apoptosis and oncosis. Cells with DNA strand breaks were observed in follicular and parafollicular areas of lymphatic tissues and their numbers were determined. A significant correlation was found between the number of TUNEL-positive cells and viral virulence. These results suggest that, in addition to oncosis, apoptotic cellular death in lymphatic tissues contributes substantially to the pathogenesis of rinderpest.
    Journal of Comparative Pathology 08/2002; 127(1):14-21. · 1.65 Impact Factor
  • Article: The hemagglutinin of canine distemper virus determines tropism and cytopathogenicity.
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    ABSTRACT: Canine distemper virus (CDV) and measles virus (MV) cause severe illnesses in their respective hosts. The viruses display a characteristic cytopathic effect by forming syncytia in susceptible cells. For CDV, the proficiency of syncytium formation varies among different strains and correlates with the degree of viral attenuation. In this study, we examined the determinants for the differential fusogenicity of the wild-type CDV isolate 5804Han89 (CDV(5804)), the small- and large-plaque-forming variants of the CDV vaccine strain Onderstepoort (CDV(OS) and CDV(OL), respectively), and the MV vaccine strain Edmonston B (MV(Edm)). The cotransfection of different combinations of fusion (F) and hemagglutinin (H) genes in Vero cells indicated that the H protein is the main determinant of fusion efficiency. To verify the significance of this observation in the viral context, a reverse genetic system to generate recombinant CDVs was established. This system is based on a plasmid containing the full-length antigenomic sequence of CDV(OS). The coding regions of the H proteins of all CDV strains and MV(Edm) were introduced into the CDV and MV genetic backgrounds, and recombinant viruses rCDV-H(5804), rCDV-H(OL), rCDV-H(Edm), rMV-H(5804), rMV-H(OL), and rMV-H(OS) were recovered. Thus, the H proteins of the two morbilliviruses are interchangeable and fully functional in a heterologous complex. This is in contrast with the glycoproteins of other members of the family Paramyxoviridae, which do not function efficiently with heterologous partners. The fusogenicity, growth characteristics, and tropism of the recombinant viruses were examined and compared with those of the parental strains. All these characteristics were found to be predominantly mediated by the H protein regardless of the viral backbone used.
    Journal of Virology 08/2001; 75(14):6418-27. · 5.40 Impact Factor
  • Article: Analysis of the H gene, the central untranslated region and the proximal coding part of the F gene of wild-type and vaccine canine distemper viruses.
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    ABSTRACT: This paper summarizes the results of the genetic analysis of several parts of the genome of canine distemper virus (CDV) field isolates and vaccine viruses. The haemagglutinin (H) gene analysis showed that recent viruses did not differ significantly from vaccine strains. The analysis of the long untranslated region between the matrix (M) and fusion (F) gene revealed distinct genetic heterogeneity. The putative F protein start codon AUG461 of vaccine strain Onderstepoort was found to be mutated in all wild-type isolates and in another vaccine strain. The proximal coding part of the F gene was well conserved. Phylogenetic analysis of this segment showed the presence of several cocirculating CDV genotypes.
    Veterinary Microbiology 10/1999; 69(1-2):15-8. · 3.33 Impact Factor
  • Article: [Emergence of "new" viral zoonoses].
    I Greiser-Wilke, L Haas
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    ABSTRACT: In the last two to three decades a significant increase of viral zoonotic infections was observed. These zoonoses are not only newly (or previously unrecognized) emerging diseases, but also due to the reappearance of diseases thought to have been defeated (re-emerging diseases). "New" viral diseases can arise when viruses broaden their host-range (monkey poxvirus; equine morbillivirus), or can be a consequence of intrinsic properties of the virus itself, such as high mutation rates (influenza A virus). Most new or reemerging viral zoonoses are due to infections with hemorrhagic viruses. Many of them are transmitted by insects (arboviruses, e.g. yellow fever virus) or by rodents (e.g. Hanta viruses), others by contact with patients and nosocomial infections (e.g. Ebola virus). The emergence and increase of these diseases are a consequence of anthropogenic environmental changes, such as distortions of the ecological balance and changes in agriculture. In addition, the uncontrolled growth of the cities in tropical and subtropical regions without improvement of the public health measures and the increasing international animal trade and travel also favour the spread and recurrence of these diseases.
    DTW. Deutsche tierärztliche Wochenschrift 09/1999; 106(8):332-8. · 0.41 Impact Factor
  • Article: Rapid and sensitive detection of immunoglobulin M (IgM) and IgG antibodies against canine distemper virus by a new recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay.
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    ABSTRACT: Canine distemper morbillivirus (CDV) infection causes a frequently fatal systemic disease in a broad range of carnivore species, including domestic dogs. In CDV infection, classical serology provides data of diagnostic and prognostic values (kinetics of seroconversion) and is also used to predict the optimal vaccination age of pups. Routine CDV serology is still based on time- and cost-intensive virus neutralization assays (V-NA). Here, we describe a new capture-sandwich enzyme-linked immunosorbent assay (ELISA) that uses recombinant baculovirus-expressed nucleocapsid (N) protein of a recent CDV wild-type isolate (2544/Han95) for the detection of CDV-specific antibodies in canine sera. Recombinant antigen was produced with high efficacy in Heliothis virescens larvae. The capture-sandwich ELISA enabled a clear-cut qualitative evaluation of the CDV-specific immunoglobulin G (IgG) and IgM serostatuses of 196 and 35 dog sera, respectively. Inter-rater agreement analysis (kappa = 0.988) indicated that the ELISA can be used unrestrictedly as a substitute for the V-NA for the qualitative determination of CDV-specific IgG serostatus. In an attempt to semiquantify N-specific antibodies, a one-step-dilution (alpha method) IgG-specific ELISA was implemented. Alpha values of >/=50% showed very good inter-rater agreement (kappa = 0.968) with V-NA titers of >/=1/100 50% neutralizing dose (ND50) as measured against the central European CDV wild-type isolate 2544/Han95 in canine sera originating from northern Germany. An ND50 titer of 1/100 is considered a threshold, and titers of >/=1/100 indicate a resilient, protective immunity. CDV N-specific antibodies of the IgM class were detected by the newly developed ELISA in 9 of 15 sera obtained from dogs with symptoms of acute distemper. In leucocytes of 5 of the 15 dogs (all of which were also IgM positive) CDV RNA was detected by reverse transcription (RT)-PCR. The recombinant capture-sandwich ELISA detecting N-specific antibodies of the IgG class provided superior sensitivity and specificity and thus represents a rapid and cost-effective alternative to classical CDV V-NA. By detection of specific IgM antibodies, the ELISA will be complementary to RT-PCR and V-NA in the diagnosis of acute distemper infections.
    Journal of Clinical Microbiology 05/1999; 37(4):1049-56. · 4.15 Impact Factor
  • Article: Application of a computer program for genetic typing of classical swine fever virus isolates from Germany.
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    ABSTRACT: The commercial software program HLA SequiTyper (Amersham Pharmacia Biotech), designed originally for human leukocyte antigen typing, was adapted for rapid typing of classical swine fever (CSF) virus isolates. The program compares new sequence data with those stored in a database file and calculates the most probable assignment. For generating the CSF virus sequence database, 150 bp of the 5' nontranslated genomic region (5'-NTR) from 88 German classical swine fever virus isolates from outbreaks between 1984 and 1997 were solid-phase sequenced directly after RT-PCR amplification. Sequence alignments showed that they all belonged to the previously defined genetic group 2. Within this group, six different subgroups could be distinguished, and were designated according to the geographic location where they are either still endemic or where they appeared most commonly. The advantage of using the HLA SequiTyper program is that it reads directly the sequence files as generated by the ALF sequencer (Amersham Pharmacia Biotech), making any manipulations unnecessary. In addition, a constant quality control of the raw sequence data can be achieved, as more than one sequence from the same isolate can be evaluated at once. Using this approach, new CSF isolates can be typed within 2 days.
    Journal of Virological Methods 12/1998; 75(2):141-50. · 2.01 Impact Factor
  • Article: Genetic analysis of the central untranslated genome region and the proximal coding part of the F gene of wild-type and vaccine canine distemper morbilliviruses.
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    ABSTRACT: Located between the open reading frames encoding the matrix (M) and the fusion (F) protein the morbillivirus genome contains an unusually large non-coding intercistronic region (M-F UTR) of up to 5.6% of the full length genome. Any function(s) of this region have largely remained obscure. Here, we analyze the M-F UTR and the proximal coding part of the downstream F gene of several recent canine distemper morbillivirus (CDV) wild-type (wt) isolates and vaccine strains. While the F gene coding part appeared to be highly conserved (about 93% homology), a considerable degree of strain-specific variation of up to 21.4% was evident when comparing the M-F UTR. Phylogenetic analysis revealed a co-circulation of several contemporary CDV genotypes within a close geographic range (central Europe). A remarkably distinct CDV wt lineage, so far detected only in mustelids, is displayed. A rather non-scattered pattern of mutations within the M-F UTR suggested superimposition of RNA sequence and/or secondary structure constraints. Extensive folding in the long (460 nt) and moderately GC-rich 5'-UTR of the F mRNA was evident, particularly around the putative F protein translation initiation codon (AUG461 of the Onderstepoort vaccine strain). The region immediately preceding the putative F initiation site also harbored the only mutation unique to both vaccine strains within the F-5'UTR (position 455: Awt vs. Cvac). The putative F protein start codon, AUG461, was found to be mutated to AUA or GUA in all wt isolates analyzed and in another vaccine strain (Rockborn). Possible consequences for F protein translation initiation in wt CDV are discussed.
    Virus Genes 02/1998; 17(3):259-70. · 1.85 Impact Factor
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    Article: Characterization of the genome of feline foamy virus and its proteins shows distinct features different from those of primate spumaviruses.
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    ABSTRACT: The genome of the feline foamy virus (FeFV) isolate FUV was characterized by molecular cloning and nucleotide sequence analysis of subgenomic proviral DNA. The overall genetic organization of FeFV and protein sequence comparisons of different FeFV genes with their counterparts from other known foamy viruses confirm that FeFV is a complex foamy virus. However, significant differences exist when FeFV is compared with primate foamy viruses. The FeFV Gag protein is smaller than that of the primate spumaviruses, mainly due to additional MA/CA sequences characteristic of the primate viruses only. Gag protein sequence motifs of the NC domain of primate foamy viruses assumed to be involved in genome encapsidation are not conserved in FeFV. FeFV Gag and Pol proteins were detected with monospecific antisera directed against Gag and Pol domains of the human foamy virus and with antisera from naturally infected cats. Proteolytic processing of the FeFV Gag precursor was incomplete, whereas more efficient proteolytic cleavage of the pre125Pro-Pol protein was observed. The active center of the FeFV protease contains a Gln that replaces an invariant Gly residue at this position in other retroviral proteases. Functional studies on FeFV gene expression directed by the promoter of the long terminal repeat showed that FeFV gene expression was strongly activated by the Bell/Tas transactivator protein. The FeFV Bell/Tas transactivator is about one-third smaller than its counterpart of primate spumaviruses. This difference is also reflected by a limited sequence similarity and only a moderate conservation of structural motifs of the different foamy virus transactivators analyzed.
    Journal of Virology 10/1997; 71(9):6727-41. · 5.40 Impact Factor
  • Article: Analysis of the haemagglutinin gene of current wild-type canine distemper virus isolates from Germany.
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    ABSTRACT: The haemagglutinin (H) gene sequences from three wild-type canine distemper viruses (CDV) isolated during 1994-1995 were sequenced to determine whether contemporary strains had undergone significant genetic changes relative to the currently used vaccine strains. The new isolates were closely related to each other (> 99%) and displayed about 90-91% sequence homology to the Onderstepoort and Convac vaccine strains. There were one to four additional potential glycosylation sites compared to the vaccine strains which were also present in a German dog CDV isolate dating from 1990. However, only a very slight reduction in neutralizing titre against the new isolates was found when compared with the Onderstepoort and Rockborn vaccine strains. Cysteine and proline residues were well conserved indicating a conserved three dimensional structure for the protein. By phylogenetic analysis the recent isolates showed a narrow clustering close to the previous canine isolates indicating a linear pattern of evolutionary changes. A comparison with published CDV H gene sequences suggested the presence of different lineages of CDV on a global scale and possible cocirculation of more than one genotype of CDV.
    Virus Research 05/1997; 48(2):165-71. · 2.94 Impact Factor

Institutions

  • 1998–2010
    • University of Veterinary Medicine Hannover
      • • Institute of Virology
      • • Institute of Animal Breeding and Genetics
      Hannover, Lower Saxony, Germany
  • 2008
    • Ankara University
      • Department of Internal Medicine (Faculty of Veterinary Medicine)
      Ankara, Ankara, Turkey
  • 1990–1993
    • Medizinische Hochschule Hannover
      • Institute for Pathology
      Hannover, Lower Saxony, Germany