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F J Kaup

Publications and source records attributed to F J Kaup.

At least 19 recordsLinked to original sources
PubMed2005

[Species-specific primate husbandry].

With about 300 species primates represent one of the largest animal groups within mammals. They are kept in zoological gardens, as laboratory animals or in private ownership. Against this background it is difficult to define all species-specific aspects of a primate husbandry. The paper describes the basic requirements for primates like nutrition, possibilities for social interactions and species specific behaviour, stimuli for activities, health care and environmental conditions. Although no definitive regulations exist by law, the Appendix A (Species-specific Provisions for Non-human Primates) of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS 123) will be of great importance in the future.

Animal Husbandry↗
PubMed2003

[Electron microscopic investigation of CD4+ lymphocyte cell line C8166 after infection with simian immunodeficiency virus (SIV)].

The SIV infection of rhesus macaques (Macaca mulatta) is the most appropriate animal model in HIV research. The permanent human T-cell line C8166 is used for in vitro SIV propagation. This paper describes ultrastructural features of the cells after infection with SIVmac. The C8166 cells are ultrastructurally characterized by a heterogenous morphology which is independent of the infection. SIV induced cell syncytia are observed 18 hours after infection. Viral particles and budding occur 48 hours p.i with a peak at the day 8. Viral particles present the typical lentiviral morphology. Using the monoclonal antibody anti SIVp28 and ultra small (0.8 nm) immunogold-silver enhancement technique, we are able to demonstrate SIV antigen immunoelectron microscopically. Therefore, this ultrastructural method is suitable to detect SIV antigen in in vivo experiments with C8166 cells from day 8 p.i. serving as positive control.

Animals↗
PubMed2002

SIV-associated lymphomas in rhesus monkeys (Macaca mulatta) in comparison with HIV-associated lymphomas.

A retrospective study was performed to characterize malignant lymphomas of 16 Simian immunodeficiency virus (SIV)-infected rhesus monkeys (Macaca mulatta), 2-9 years of age, on the basis of clinical data, histologic and immunophenotypic results, and cell death indices compiled with the TdT-mediated X-duTP nick end labeling method. We particularly focused on providing immunohistochemical evidence of expression products of EBNA2, Bc12, c-Myc, P21, P53, and Bc16. Results were compared with data from the literature on human HIV-associated lymphomas. According to the updated Kiel classification, the lymphomas were classified as 11 centroblastic lymphomas, three immunoblastic lymphomas, one Burkitt-like lymphoma, and one immunocytoma. Using antibodies to CD20, the B-cell origin of tumor cells was demonstrated. SIV antigen was not demonstrated in the tumor cells. Infection with rhesus lymphocryptovirus was present in 94% of the monkeys. Lymphomas revealed expression of Bc12 in 15/16 (94%), c-Myc in 14/16 (88%), P21 in 10/ 16 (63%), P53 in 12/16 (75%), and Bc16 in 1/16 (6%) monkeys. This study provided evidence that the expression of these gene products, which are thought to play an important role in cell proliferation and apoptosis in HIV- and non-HIV-associated lymphomas, are also involved in the pathogenesis of lymphomas in SIV-infected rhesus monkeys. A tentative relationship between the described gene products and the cell death indices was established for the expression of Bc12. The present primate model represents a suitable animal model for studying the pathogenesis of AIDS-associated lymphomas.

Animals↗
PubMed2002

Reactivation of a Trypanosoma cruzi infection in a rhesus monkey (Macaca mulatta) experimentally infected with SIV.

Trypanosoma cruzi-like flagellates were incidentally noted in blood smears of a routinely monitored rhesus monkey experimentally infected with the simian immunodeficiency virus (SIV). Immunodeficiency in the course of the SIV infection reactivated a chronic infection of Chagas' disease that had been unnoticed when the macaque was imported to Europe. The animal developed no specific clinical symptoms of American trypanosomiasis, but histologically a chagasic myocarditis was detected. Analysis of the small subunit rRNA gene of the trypanosome identified the protozoan as T. cruzi.

Animals↗
PubMed2002

[Primates as experimental animals].

The term "primates" comprises a varied group of animals, consisting of more than 250 different species. The close evolutionary relationship to man resulted in the use of nonhuman primates as subjects of study for scientists from different research fields. In biomedical research the use of primates is restricted to questions which cannot be answered by animals with less developed physiological senses. Primates play an important role in infectious disease research, as many pathogens relevant to humans can be transferred to selected primate species. In the last few decades this applied especially for HIV-infections of man, viral hepatitides, herpesvirus infections and for quite a long time for agents of transmissible spongiform encephalopathies, too. In neurobiology, primates play an outstanding role due to the morphological-structural and functional resemblance of their CNS to that of man. Due to new developments in biomedicine, in particular in the field of gene therapeutics, it has to be expected that primates will have to be used also in future as animal models for the welfare of human health.

Animals↗
PubMed2002

[Basic research on BSE transmission to people].

Prion diseases of animal and man belong to neurological diseases with amyloidal deposition of the respective proteins. As to prion disease, the cellular prionprotein is in its abnormal isoform(s) an essential component of prionprotein aggregates found in affected tissue. In contrast to all neurodegenerative diseases like Morbus Alzheimer or Huntington's disease, prion diseases are transmissible. Therefore, prion diseases were designated Transmissible Spongiform Encephalopathies (TSE). The diseases are well known since decades. Scrapie was first described around 1750, a BSE case was reported in the 1850, most likely a misdiagnosis, and in 1920/1930 the human Creutzfeldt-Jakob disease (CJD) had been described. Transmission of CJD i.e. Kuru had been suspected in the early 1950s and erronously classified as slow virus disease. The CJD transmission posed a problem to humans when transplants from CJD cases were used for treatment. Fortunately, these iatrogenic transmissions remained limited. But with the advent of BSE and appearance of variant CJD cases in the UK and some places in Europe scientists suspected that transmission from cattle to man could have happened. From animal models we know of successful transmission via several routes. Species barriers do not completely prevent transmission. Rather transmission barriers might exist controlling individual susceptibility against prions. Modes of transmission, susceptibility for transmission, identification of receptor molecules as well as molecular mechanisms of the transmission process are intensely investigated. Current knowledge let us to assume that inapparent stages of prion infection pretend a (not existing) species barrier. This inapparent infection preceeds overt disease and, thus, most re-search focuses on the development of highly sensitive assay systems for detection of minute amounts of pathological prionprotein in suspected cases. Inapparence also should warn us to underestimate BSE or human vCJD cases; at present, 124 in Europe and one probable case in Hongkong (7 March 2002). Whether BSE had spread to other parts of the world by animal nutrition components or meat can neither be excluded nor confirmed at this time. New data on transmission and consequences of BSE for the human population are summarized in this review.

Animals↗
PubMed2001

First outbreak of callitrichid hepatitis in Germany: genetic characterization of the causative lymphocytic choriomeningitis virus strains.

Callitrichid hepatitis (CH) is a highly fatal, rodent-borne zoonosis of New World primates (family Callitrichidae) caused by lymphocytic choriomeningitis virus (LCMV). It is unclear whether virulence in Callitrichidae is associated with specific genetic or phylogenetic markers of the virus as only a partial S RNA sequence of a single CH-associated isolate is known. In a period of 10 months, three pygmy marmosets (Cebuella pygmaea) and one Goeldi's monkey (Callimico goeldii) died from CH in a German zoo. LCMV was most likely transmitted by wild mice. Infection was associated with characteristic histopathological lesions in liver, brain, and lymphoid tissue. Virus sequences from all callitrichids and a captured mouse were > or =99.2% identical. LCMV strains from a pygmy marmoset and the Goeldi's monkey were isolated in cell culture and the 3.4-kb S RNA was completely sequenced. Both strains differed considerably in their genetic and phylogenetic characteristics from known LCMV strains, including the previously described CH-associated strain. These data show that CH is widespread and can be caused by distantly related LCMV strains.

Amino Acid Sequence↗
PubMed2001

Three spontaneous lymphomas in a colony of cotton-top tamarins (Saguinus oedipus).

Cotton-top tamarins are well known for their prevalence to idiopathic colitis and adenocarcinomas. At the same time, information on the incidence of spontaneous lymphomas in this highly endangered species is rare. Records, 212 in total, of cotton-top tamarins (Saguinus oedipus) necropsied at the German Primate Centre between 1979 and 1998 were viewed to establish the prevalence of lymphoid neoplasms. Neoplastic lymphoid cell growth was mentioned in three necropsy records. Immunohistology was performed in all three cases on the remaining formalin-fixed, paraffin-embedded tissue using antibodies against CD20, CD3, lysozyme, Ki-67, IgM, IgG, kappa, lambda and EBNA-2. Combining histological and immunohistological results, the lymphomas could be differentiated into two low-grade T-cell lymphomas and one high-grade multicentric polymorphic B-cell lymphoma. This corresponds to a 1.4% incidence of lymphomas in our cotton-top tamarin population over a period of 19 years. Although frozen material was not available and virological testing could not be carried out, clinical or histological evidence did not support an aetiological role of Herpes (H.) saimiri, H. ateles, simian T-cell leukaemia virus type 1 (STLV-1) or Epstein-Barr-related herpesvirus in any of these cases. The lymphomas were considered to be spontaneous.

Animals↗
PubMed2001

Immunohistochemical detection of simian immunodeficiency virus (SIV) in rectal mucosa of experimentally infected rhesus macaques (Macaca mulatta).

Experimental simian immunodeficiency virus (SIV) infection is the most appropriate animal model for human HIV infection. Eight male rhesus monkeys (Macaca mulatta) were intravenously or intrarectally infected with SIVmac251/MPBMC to comparatively investigate the distribution and spread of the virus within the rectum during the course of the disease. SIV-positive cells were immunohistochemically detected in rectal biopsies obtained at days 3 and 7 and week 2, 4 and 12 postinfection. SIV-expressing cells were detected for the first time at one week after experimental infection and were present in the lamina propria and lymph follicles. Numbers of positive cells per individual animal varied strongly in time, with a more rapid rise in animals with rapid progression of the disease. Differences were not observed between intravenous and intrarectal infection. Our observations support the significance of the intestinal tract as target organ in initial pathogenesis of SIV infection.

Animals↗
PubMed2001

Experimental Helicobacter pylori infection of rhesus macaques (Macaca mulatta).

The aim of the present study was to establish an animal model for Helicobacter pylori (H. pylori) infection at the German Primate Centre in rhesus monkeys (Macaca mulatta). During the experiments the susceptibility of three animals to different H. pylori strains of human origin was tested. In a follow-up study gastric biopsies from three different sites were investigated in regular intervals using microbiological, histological, electron microscopical and molecular biological methods to evaluate the presence of bacterial colonization and the occurrence of gastritis. It was possible to establish a persistent experimental infection. The rather long follow-up period of 18 months offered the possibility to demonstrate a permanent H. pylori infection in the gastric mucosa of the test animals. The three animals have now been successfully colonized with H. pylori for 18 months and presented a chronic active gastritis confirmed by microbiological and histological methods. By molecular typing, the identity of the isolates recovered from the animals was shown. It was possible to demonstrate that one infection strain outcompeted the second one. Taken together, prerequisites exist for making use of an attractive and useful animal model in rhesus monkeys especially for long term observations.

Animals↗
PubMed2001

Analysis of potential porcine endogenous retrovirus (PERV) transmission in a whole-organ xenotransplantation model without interfering microchimerism.

The question whether porcine xenografts can lead to porcine endogenous retrovirus (PERV) infection of recipients is critical for the evaluation of the safety of pig-to-man xenotransplantation. Unfortunately, polymerase chain reaction (PCR)-based analysis of potential PERV infections in nonhuman-primate whole-organ xenotransplantation models is hampered by false positive results due to chimeric porcine cells. To avoid the inherent analytical problem of xenomicrochimerism, we developed a non-life-supporting pig-to-primate kidney xenotransplantation model: porcine kidneys were transplanted, whereas the functioning recipient kidneys remained in situ. Subsequent to rejection (after 2 hours to 15 days), xenografts were removed, and recipients remained alive for up to 287 days. Immunosuppressive therapy based on cyclophosphamide, cyclosporine, and steroids was maintained for 28 days after transplantation. Using appropriate PCR assays, xenochimerism was found in tissue samples and partly even in peripheral blood leukocytes (PBLs) while the porcine kidneys were in situ. After graft removal, xenochimerism was no longer detectable, thus allowing analysis for possible PERV transmission.

Animals↗
PubMed2001

Callitrichid nutrition and food sensitivity.

Captive callitrichids are prone to developing intestinal problems. Their captive and natural diets differ enormously, and diet has been suggested to play a major role in wasting marmoset syndrome. Proteins in wheat, soy and milk are included in callitrichid diets of most colonies and have been linked to an immune reaction in Saguinus oedipus and Callithrix jacchus. In the present study of 23 males and females of the two species, wheat protein was tested but soy and milk products were excluded. One group had wheat and the other had rice in their diet. Blood samples and biopsies from the colon were taken. Results showed changes in the colon and an immune reaction to gliadin, a wheat protein related to coeliac disease in humans. A further immune reaction was also observed. Suggestions for further study and exclusion of cereal in the diet of these small, New World primates are discussed.

Animals↗
PubMed2001

Cellular and humoral immune response in progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a fatal, demyelinating disease caused by JC virus (JCV) in patients with severe immunosuppression. We studied the JCV-specific cellular and humoral immune response in 7 healthy donors (HD), 6 human immunodeficiency virus-1 (HIV-1)-infected patients without PML (HIV), 4 HIV-1-negative patients with PML (PML), and 8 HIV-1-positive patients with PML (HIV/PML). As antigens, recombinant virus-like particles of the major structural protein VP1 (VP1-VLP) of JCV, tetanus toxoid (TT), or the mitogen phytohemagglutinin (PHA) were used. Proliferation of peripheral blood mononuclear cells (PBMC) after stimulation with the VP1-VLP was significantly suppressed in PML and HIV/PML patients compared to HD. After antigen stimulation the production of interferon-gamma (IFN-gamma) was reduced in PML, in HIV/PML, and in HIV patients. The production of interleukin-10 (IL-10), however, was elevated in HIV/PML patients. Neither proliferation nor cytokine production correlated with the presence of JCV DNA in PBMC. The immunoglobulin G serum antibody titer to the VP1-VLP was slightly elevated in HIV, elevated in PML, and highly elevated in HIV/PML patients compared to HD. The development of PML appears to coincide with a general impairment of the Th1-type T-helper cell function of cell-mediated immunity.

Cytokines↗
PubMed2001

Expression of the simian Epstein-Barr virus-encoded latent membrane protein-1 in malignant lymphomas of SIV-infected rhesus macaques.

During the course of simian immunodeficiency virus (SIV) infection, nearly 15% of rhesus macaques (Macaca mulatta) and up to 40% of cynomolgus macaques (Macaca fascicularis) developed SIV-associated non-Hodgkin's lymphomas. Most of these malignant lymphomas harbored lymphocryptoviruses, which are closely related to the human Epstein-Barr virus (EBV; Herpesvirus M. mulatta and Herpesvirus M. fascicularis). To characterize the oncogenic role of simian EBV infection for lymphomagenesis during SIV infection, expression of the EBV-encoded latent membrane protein-1 (LMP-1) was analyzed in malignant lymphomas of SIV-infected rhesus macaques. Nine seropositive rhesus macaques suffering from B-cell lymphomas during the late phase of SIV infection were euthanized. Latency stages of EBV infection within malignant lymphomas and simian EBV-infected lymphoblastoid cell lines (LCL8664, H50) were characterized by analyzing expression of the EBV-encoded nuclear antigens EBNA-1, EBNA-2, and small RNAs EBER1/2. In parallel, the presence of viral LMP-1 transcripts was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Results were compared with findings in AIDS-associated malignant lymphomas in two patients infected with human immunodeficiency virus (HIV)-1. Rhesus macaques developed high-grade B-cell lymphomas of the centroblastic (five of nine), immunoblastic (two of nine), centroblastic-centrocytic (one of nine), and Burkitt-like (one of nine) subtypes within 18-29 months postinfection with SIV(mac)251/32H. The presence of Herpesvirus M. mulatta was detected in eight of nine cases. Transcription of the viral oncogene LMP-1 could be demonstrated within the simian EBV-infected cell lines as well as in four of nine SIV-associated malignant lymphomas. These four cases and both of the HIV-1-related non-Hodgkin's lymphomas expressed the full spectrum of latent EBV gene products (LMP-1, EBER1/2, EBNA-1, EBNA-2) and were thus classified as latency type III stages of EBV infection. Simian EBV infection was demonstrated in 90% of lymphomas in SIV-infected rhesus macaques. Analysis of LMP-1 expression suggests an important role for this viral oncogene in the pathogenesis of both SIV and HIV-1-associated malignant lymphomas.

Animals↗
PubMed2000

Homozygosity for a conserved Mhc class II DQ-DRB haplotype is associated with rapid disease progression in simian immunodeficiency virus-infected macaques: results from a prospective study.

In human immunodeficiency virus type 1 (HIV-1)-infected individuals, disease progression varies considerably. This is also observed after experimental infection of macaques with simian immunodeficiency virus (SIV). Major histocompatibility complex (MHC) genes may influence disease progression in both species. Homozygosity for Mhc-Mamu (Macaca mulatta)-DQB1*0601 was previously identified to be associated with rapid disease progression in SIV-infected macaques. To validate the association of this genotype with disease progression, a prospective study was carried out. Six unrelated monkeys homozygous for Mamu-DQB1*0601 and DRB1*0309-DRB*W201 and 6 heterozygous monkeys were infected with SIVmac. Five of the homozygous and only 1 of the heterozygous monkeys died rapidly after infection, with manifestations of AIDS. These results were validated by a retrospective survival analysis of 71 SIV-infected monkeys. The identified DQ-DRB genotype is frequent among monkeys of different breeding colonies and allows a fairly reliable selection before infection of monkeys predisposed for rapid disease progression.

Animals↗
PubMed2000

Phenotype, intestinal morphology, and survival of homozygous and heterozygous endothelin B receptor--deficient (spotting lethal) rats.

BACKGROUND/PURPOSE: Spotting lethal (sl) rats, a model for Hirschsprung's disease, recently have been found to carry a deletion in the endothelin B (ET(B)) gene, causing functional lack of ET(B) receptors. The ET(B) receptor mediates, together with and in counterbalance to the ET(A) receptor, endothelin actions on vessels, cell proliferation, and migration. The authors investigated the effect of homozygosity (sI/sI) or heterozygosity (+/sl) on phenotype, intestinal morphology, and survival. METHODS: Weight, circumference, and serum albumin were measured. Histological tests of major organs and immunoperoxidase reaction for Peripherin, glial fibrillary acid protein (GFAP), and S-100 in small and large intestine were performed. Peripherin-immunostained sections of colon and jejunum were analyzed morphometrically. Screening for sepsis included search for enterocolitis, bacterial infection, endotoxin, and iNOS mRNA. RESULTS: Sl/sl rats died within 4 weeks of life, showing an early and a later death group. Serum albumin levels were decreased in sl/sl rats, whereas signs of sepsis were rare. Immunostaining uncovered alterations in nerve and glial cells in the whole gut of sl/sl rats, and to a subtle degree also in +/sl rats, which appear clinically normal. Morphometric quantification yielded statistically significant alterations in sl/sl rats only. No obvious abnormalities were found in other organs. CONCLUSIONS: Sl/sl rats die from malnutrition rather than sepsis, too early for ischemic complications to occur. Rats of the later death group are a suitable model for studying the ET8 receptor in vivo. Subtle abnormalities in the enteric nervous system of heterozygous rats underline the critical role of the "gene dose" for functional compensation.

Animals↗