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Biomedical subjects

K Weijer

Publications and source records attributed to K Weijer.

At least 37 records · Page 2Linked to original sources
PubMed1991

Allotransplantation of K248 feline mammary carcinoma cell line in cats. A model for monoclonal antibody guided detection and therapy of human breast cancer.

In response to the need for appropriate models for monoclonal antibody guided detection and therapy of human breast cancer, we developed an allogeneic host-tumor model by injecting K248C and K248P cells into cats. A comparison between the K248C- and K248P-induced tumors with respect to biological behavior and histological appearance was made throughout the study. Allotransplantation of tumor cells was performed both in newborn cats and fetal cats between days 42 and 51 of gestation, but only tumor cells injected by the latter approach resulted in tumor growth in all animals injected. Both tumor cell lines gave rise to progressively growing tumors at the site of injection, metastatic spread of tumor cells to various organs, and death from progression 2-4 months after birth. The predominant histological appearance of the K248C and K248P allografts resembled the cribriform and tubulo-papillary growth patterns, respectively, of the original tumor from which the two cell lines were derived. Autopsy of 1-day kittens showed that metastasis started already in the fetus in the short period between injection of tumor cells and birth. Three predominant patterns of metastases were identified: the pulmonary/pleural type, the abdominal type, and the soft tissue type. A lower incidence of metastases was found in bones and brain. The K248C allografts formed significantly more metastases of the abdominal type than K248P tumors (p less than 0.05). No difference in survival was observed between animals with K248C or K248P allografts. The difference in take rate and latency period between K248C and K248P in athymic mice does not seem to be present in the feline host. The similarity of the present model to spontaneous feline and human mammary carcinoma is discussed.

Animals↗
PubMed1990

Feline immunodeficiency virus (FIV) infection in the cat as a model for HIV infection in man: FIV-induced impairment of immune function.

To assess the value of feline immunodeficiency virus (FIV) infection as a model for human immunodeficiency virus (HIV) infection in man, we studied the impairment of certain immunological functions following natural or experimental FIV infection. Proliferative responses of peripheral blood mononuclear cells (PBMC) from symptomatic and asymptomatic cats after naturally or experimentally acquired FIV infection, induced by activation with the mitogens concanavalin A, pokeweed mitogen, or lipopolysaccharide or by stimulation with human interleukin-2 (IL-2), were significantly lower than the proliferative responses found with PBMC from noninfected control cats. Also IL-2 production levels of mitogen-activated PBMC from naturally infected symptomatic cats were significantly reduced. These data confirm that the pathogenesis of FIV infection in the cat, like HIV infection in man, is characterized by a serious malfunction of the immune system.

Animals↗
PubMed1990

An enzyme linked immunosorbent assay (ELISA) for the detection of feline immunodeficiency virus (FIV) antigen in cell culture and FIV specific antibodies in feline serum.

Recently, a newly discovered lentivirus--Feline Immunodeficiency Virus (FIV)--was identified as the cause of an AIDS-like syndrome in the cat. For the detection of FIV antigen in cell culture, an antigen capture ELISA was developed. In this assay FIV specific IgG was used as a capture antibody and the same preparation coupled to biotine as a conjugate. With this test viral antigen could be demonstrated in FIV infected cell cultures within four days after infection and the assay proved to be at least as sensitive as a reverse transcriptase test in demonstrating virus infected cultures. A modification of this assay in which a titrated amount of FIV antigen was incubated with dilutions of serum samples of naturally or experimentally infected cats, allowed the detection of FIV specific antibodies. In a serological survey, conducted among cats with different clinical histories in The Netherlands and The Federal Republic of Germany, the antibody inhibition ELISA was compared with a commercially (IDEXX) available indirect ELISA system. It was shown that both assays identified nine seropositive cats among 200 animals with a history of undefined chronic disease, whereas no positive reactions were obtained with 65 serum samples from apparently healthy animals. Both assays also gave positive results with serum samples from experimentally infected cats, within five weeks after infection. Of an additional panel of eight serum samples which had been found positive in the IDEXX indirect ELISA system, only five were found positive in the antibody inhibition ELISA and western blotting assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Control of feline leukaemia virus.

Feline leukaemia virus (FeLV) usually occurs in its natural species, the domestic cat. FeLV is also important to human individuals as a comparative model, as it may cause a variety of diseases, some malignant and some benign, such as immunosuppression, which bears a resemblance to AIDS (acquired immune deficiency syndrome) in man. FeLV is transmitted among cats by contagion. The main sources of infection are persistently infected carrier cats which continuously excrete virus. Dissemination of FeLV among cats may be prevented by identifying infected carrier cats and removing them from contact with non-infected cats. Removal programmes using indirect immunofluorescence antibody tests were applied successfully in The Netherlands. The proportion of FeLV-positive cats decreased from 9% in 1974 to approximately 3% in 1985 during such a programme. The results of a removal programme carried out in a catbreeders' society were even better: the incidence of cats positive for FeLV decreased from 11% in 1974 to less than 2% within 4 years. None of the cats tested in this society has been found to be positive for FeLV since 1984. Besides removal programmes, other methods of control, such as pre-exposure treatment, were developed to prevent the spread of FeLV. We attempted to protect kittens against oronasal infection with FeLV by treatment with virus-neutralizing (VN) monoclonal antibodies (MoAbs) directed against an epitope on the viral glycoprotein gp70. However, no protection was achieved. It is unlikely that the amount of VN antibodies, the mode and route of their application or the infectious dose of FeLV used can account for this failure. Other possible explanations for the lack of protective effect are that (i) the restricted epitope specificity of the MoAb preparation used may have led to selection of neutralization-resistant virus mutants, or (ii) other mechanisms than virus neutralization (complement-mediated lysis, antibody-dependent cell cytotoxicity), that may be involved in protection, function less efficiently with MoAb. However, in the light of our finding that an early anti-idiotypic response is observed in all cats following administration of the MoAb preparation, the rapid clearance of anti-FeLV MoAb from the circulation is a more likely explanation. Efforts were further made to develop a vaccine for controlling FeLV infection. The immunostimulating complex vaccine (FeLV-ISCOM vaccine), a subunit vaccine in which FeLV gp70 is presented in a particular manner, looks promising. The protective effect of FeLV-ISCOM vaccine was studied by vaccinating six 8-week-old SPF cats with ISCOM, followed by oronasal challenge with FeLV.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Serological responses in cats vaccinated with FeLV ISCOM and an inactivated FeLV vaccine.

Various approaches have been considered for generation of effective and safe vaccines against retroviruses, including HIV, with limited success. In the present vaccination study, encompassing 137 household cats, we have composed an experimental ISCOM subunit vaccine containing gp70 of feline leukaemia virus (FeLV)--the external glycosylated envelope protein, and the transmembrane protein p15E, with a commercial available inactivated FeLV vaccine (Leukocell). The two vaccines were estimated to contain approximately the same amount of gp70 antigen and the cats were immunized three times according to the recommendations of the commercial vaccine. A control preparation not containing gp70 or p15E was also included. During the observation period of 200 days all cats remained healthy and no virus was isolated during the isolation attempts. The serological responses were measured in ELISA, membrane immunofluorescence (MIF) and virus neutralization (VN) tests. In contrast to the cats in the other groups almost all ISCOM-vaccinated cats responded by seroconversion or increased titres in the three tests. The development of specific antibodies to gp70 and p15E were confirmed in Western blot. These results clearly illustrate the potential of the ISCOM structure for the development of safe and effective vaccines against retroviruses.

Animals↗
PubMed1989

Induction of anti-viral immune response by immunization with monoclonal anti-idiotype antibodies directed to private idiotopes.

Syngeneic monoclonal anti-idiotypic antibodies were raised against idiotopes on neutralizing monoclonal antibodies with specificity for feline leukemia virus and canine parvovirus. The anti-idiotypic antibodies were shown to recognize paratope-related private idiotopes. Mice were injected with the monoclonal anti-idiotypic antibodies and the sera of these mice were screened for antiviral reactivities. Antibodies to both feline leukemia and canine parvovirus could be induced as determined by ELISA. These results suggest that anti-idiotypic antibodies which detect private idiotopes and thus do not represent internal images of viral antigens may be considered as candidates for the induction of antiviral immunity.

Animals↗
PubMed1988

[Prevalence of FTLV (feline T-lymphotropic lentivirus) infections in cats in The Netherlands and in West Germany].

The prevalence in the Netherlands and the Free Republic of Germany (FRG) of the newly discovered retrovirus of cats, which causes an immunodeficiency syndrome in this species and is termed feline T-lymphotropic lentivirus (FTLV), was estimated by conducting a serological survey among cats with different histories of disease. In an enzyme-linked immunosorbent assay (Petcheck, Agritech Trademark, Portland, USA) 265 samples of cats with chronic disease symptoms, and 78 samples of clinically healthy cats in the Netherlands, and 138 samples of cats with chronic disease symptoms in the FRG, were tested for the presence of FTLV-specific antibodies. All these samples had been taken from cats which were negative for FeLV antigen in the immunofluorescence test. In the groups of chronically ill animals 18 (7%) and 6 (4.5%) seropositive animals were found respectively, whereas in the group of clinically healthy cats no seropositive animals could be demonstrated.

Animals↗
PubMed1987

[Feline leukemia virus (FeLV) and FeLV-associated diseases in cats: a review].

Feline leukaemia virus (FeLV) usually occurs in its natural species, the domestic cat. FeLV is also important to human individuals as a comparative model, as FeLV may cause a variety of diseases which are partly malignant and partly benign, such as immunosuppression which bears a resemblance to AIDS (acquired immune deficiency syndrome) in man. Although FeLV is a common infective agent, the incidence of disease due to FeLV is much higher in cats kept in closed households in which several of them are present than it is in free-range cats. Consequently, diseases caused by FeLV are frequently diagnosed in pedigree cats which are often maintained in relatively large numbers. FeLV is transmitted among cats by contagion. The main sources of infection are persistantly infected FeLV carrier cats which continuously excrete virus from the mouth and in other secretions. The majority of cats infected with FeLV will produce neutralising antibodies. Cats which are unable to do so, will become permanently infected. The prognosis is bad in these cats: 90 per cent will die within five years. Various techniques are used to detect FeLV. The most common method, the indirect immunofluorescence (IFA) test, is performed on air-dried blood smears. The results of the IFA agree with that are almost completely identical to those of the virus isolation test. Another test is ELISA (enzyme-linked immunosorbent assay), which produces approximately 10 per cent more positive results which are probably due to circulating FeLV antigens. Dissemination of FeLV among cats may be prevented by identifying infected carrier cats and removing them from contact with non-infected cats. Removal programmes using indirect immunofluorescent antibody (IFA) tests were used successfully in the Netherlands. The proportion of FeLV-positive cats decreased from 9 per cent in 1974 to approximately 3 per cent in 1985 during such a removal programme. During the above period, the removal programme was carried out in the society of Dutch cat breeders 'Felikat', the programme being made compulsory on all members of the society. The incidence of cats positive for FeLV decreased from over 11 per cent in 1974 to less than 2 per cent within four years. None of the cats tested in this society was found to be positive for FeLV in 1984 and 1985. Besides removal programmes, other methods of control, such as vaccination, were developed to prevent the spread of FeLV. The FeLV-immunostimulating complex vaccine (FeLV-ISCOM vaccine) a subunit vaccine in which FeLV-gp70 is presented in a particular manner, seems to be promising.

Animals↗
PubMed1986

Post-exposure treatment with monoclonal antibodies in a retrovirus system: failure to protect cats against feline leukemia virus infection with virus neutralizing monoclonal antibodies.

We have attempted to protect kittens against oronasal infection with FeLV (strain A/Glasgow-1) by treatment with a mixture of two virus-neutralizing (VN) MAbs (IgGl, K) directed against the same epitope on the viral glycoprotein gp70. Ten SPF 9-week-old kittens were infected on day 0 with 10(6) ffu FeLV and subsequently inoculated i.m. with MAbs every 2 days over a 20-day period at different times after infection. The results clearly show that no protection was achieved. It is unlikely that the amount of VN antibodies, the mode and route of their application or the infectious dose of FeLV used can account for the failure to protect cats against infection. Other possibilities which may explain the lack of protective effect are that the restricted epitope specificity of the MAb preparation used may have led to selection of neutralization-resistant virus mutants, or that other mechanisms than virus neutralization (complement-mediated lysis, antibody-dependent cell cytotoxicity), that may be involved in protection, function less efficiently with MAb. However, in the light of our finding that an early anti-idiotypic response is observed in all cats following administration of the MAb preparation, the rapid clearance of anti-FeLV MAb from the circulation is a more likely explanation. The data presented support our hypothesis that by administration of MAb-as compared to polyclonal antibody-a more vigorous anti-idiotypic response is elicited due to the presentation of only a limited set of idiotopes. This potential drawback of rapid clearance of MAbs as a consequence of an anti-idiotypic response might be overcome by the use of mixtures of MAbs resulting in a more heterogeneous set of idiotypic determinants.

Animals↗
PubMed1985

Induction of protective immune response in cats by vaccination with feline leukemia virus iscom.

An effective candidate subunit vaccine consisting of the gp 70/85 of feline leukemia virus (FeLV) was prepared by using the immunostimulating complex (iscom) method for the presentation of membrane proteins of enveloped viruses. Two 32-wk-old specific pathogen-free (SPF) cats were immunized with a FeLV iscom vaccine prepared from the supernatant fluid of the FL74 tumor cell line without adjuvant. Both cats developed FeLV serum antibodies, as measured in an enzyme-linked immunosorbent assay (ELISA) and in a virus neutralization test. A proportion of the antibodies were directed to an epitope located on gp70/85, which was shown in competition ELISA with a peroxidase-labeled virus-neutralizing monoclonal antibody to be shared by all three subtypes of FeLV. The protective effect of FeLV iscom was studied by vaccinating six 8-wk-old SPF cats with iscom prepared from cell culture supernatant of another tumor cell line F422, followed by oronasal challenge with 10(6) ffu FeLV-A (strain Glasgow-1). Six unvaccinated cats were also challenged with the same dose of FeLV. The vaccinated cats developed FeLV serum antibodies, some of which were directed to the shared epitope on gp70/85. At 10 wk after challenge, none was viremic, whereas three of the control cats had developed FeLV viremia. The potential of FeLV iscom as a vaccine against FeLV-associated disease in cats, and of iscom vaccines for protection against mammalian retrovirus infections, is discussed.

Adjuvants, Immunologic↗
PubMed1983

Prognostic factors in feline mammary carcinoma.

Feline mammary carcinoma and canine mammary cancer were evaluated as models for future experimental therapy. Those tumor characteristics known to be of special prognostic significance in human mammary cancers were tested for their prognostic significance in the cat and were compared with those in the dog. The statistical analysis presented is based on a prospective follow-up study of 202 cats treated surgically by mastectomy and by block dissection. Thirty-five factors (general, anamnestic, clinical and histologic data, and data on therapy) were analyzed for relationships with survival, with local recurrence, and with each other. Of the 17 significant relationships found between survival and the direct factors, only 7 remained significant after correction. The factors that related to survival independently of each other were age, diameter of the primary tumor, presence of tumor-positive lymph nodes as judged by microscopic examination, number of mitotic figures, necrosis of the primary tumor, and histologic verification of completeness of surgical treatment. The value of statistical analysis for use in prospective studies of human mammary cancer is discussed.

Animals↗
PubMed1982

A comparison of three methods of feline leukaemia virus diagnosis.

Samples of blood from pet cats were examined for evidence of feline leukaemia virus (FeLV) by three techniques: virus isolation, immunofluorescence and an enzyme-linked immunosorbent assay (ELISA) Leukassay F. There was good agreement between the results from virus isolation and immunofluorescence. However, about 30 per cent of cats which were positive for FeLV antigen by ELISA were negative by either of the other tests. The status of most of these cats was unchanged four or 12 weeks later.

Animals↗
PubMed1980

Feline mammary tumours and dysplasias. Conclusions based on personal studies and some suggestions for future research.

Feline mammary tumours and dysplasias were studied by various methods: morphological, electron-microscopical, immunotlogical and virological. The most important conclusion was that cats with mammary tumours (benign and malignant tumours and lesions, the significance of which is not known so far) may be suitable animal models for the study of certain features of human mammary tumours; for instance, the study of the relationship between particular histological and biological characteristics of mammary carcinoma and the prognosis; the study of the question whether a virus (or viruses) does (do) or does (do) not play a role in the pathogenesis or growth of mammary tumours; the study of the possible presence of specific cellular and/or humoral immunity to mammary tumours and the study of the possible effects of progestogens on the mammary gland. As the study can not be regarded as a self-contained entity, it should be continued; this applies particularly to those parts of the study, that offer the best prospects for comparative investigations.

Animals↗