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Biomedical subjects

J G Vos

Publications and source records attributed to J G Vos.

At least 109 records · Page 6Linked to original sources
PubMed1984

Antitumor effect, cardiotoxicity, and nephrotoxicity of doxorubicin in the IgM solid immunocytoma-bearing LOU/M/WSL rat.

Antitumor activity, cardiotoxicity, and nephrotoxicity induced by doxorubicin were studied in LOU/M/WSL inbred rats each bearing a transplantable solid IgM immunocytoma. Animals with a tumor (diameter, 15.8 +/- 3.3 mm) were treated with iv injections of doxorubicin on 5 consecutive days, followed by 1 weekly injection for 7 weeks (dose range, 0.015-4.0 mg/kg body wt). Tumor regression was observed with 0.5 mg doxorubicin/kg. Complete disappearance of the tumor was induced with 1.0 mg doxorubicin/kg. Histologic evidence of cardiotoxicity scored as grade III was only observed at a dose of 1.0 mg doxorubicin/kg. Light microscopic evidence of renal damage was seen above a dose of 0.5 mg doxorubicin/kg, which resulted in albuminuria and very low serum albumin levels. In the group that received 1.0 mg doxorubicin/kg, the serum albumin level decreased from 33.6 +/- 4.1 to 1.5 +/- 0.5 g/liter. Ascites and hydrothorax were observed simultaneously. The same experiments were performed with non-tumor-bearing rats, in which no major differences were observed. In conclusion, antitumor activity, cardiotoxicity, and nephrotoxicity were studied simultaneously in the same LOU/M/WSL rat. Albuminuria due to renal damage led to extremely low serum albumin levels, so ascites and hydrothorax were not necessarily a consequence of the observed cardiomyopathy.

Albuminuria↗
PubMed1983

The athymic nude rat. IV. Immunocytochemical study to detect T-cells, and immunological and histopathological reactions against Trichinella spiralis.

The anti-parasite response was investigated after oral infection of athymic nude (rnu/rnu) rats and heterozygous (+/rnu) littermates with 1000 muscle larvae of Trichinella spiralis. No IgM, IgG and IgE antibodies were detected in serum of rnu/rnu rats. Expulsion of adult worms from the small intestine was prolonged (worms were nearly all expelled at days 14 and 91 in +/rnu and rnu/rnu rats respectively). The yield of muscle larvae in the carcasses of nude rats at day 91 was 33 times higher than in +/rnu rats. In contrast to the strong inflammatory reaction in the parasitized tongue of +/rnu rats, no infiltration was observed in rnu/rnu rats. Using an immunoperoxide method with monoclonal anti-rat T-cell antibody, no T cells were identified in spleen, mesenteric lymph node and Peyer's patches. These data support earlier studies that the nude rat lacks functional T cells. As the counts of connective tissue mast cells (CTMC), intestinal mast cells (IMC) and globule leucocytes (GL) in small intestine of uninfected rnu/rnu rats were equal or higher than in +/rnu rats, it is concluded that the origin of these cells is thymus-independent. In contrast to +/rnu rats, infection of rnu/rnu rats induced no increase of CTMC, IMC or GL. Thus, these cells depend on T cells to undergo proliferation. Finally, results of this study were inconclusive whether IMC are precursors for GL, or that they represent independent cell populations.

Animals↗
PubMed1983

Antitumor activity, induction of cross-resistance, and nephrotoxicity of a new platinum analogue, cis-1,1-diaminomethylcyclohexaneplatinum(II) sulfate, and of cis-diamminedichloroplatinum(II) in an immunocytoma model in the LOU/M rat.

A newly synthesized platinum analogue, cis-1,1-diaminomethylcyclohexaneplatinum(II) sulfate (TNO-6), was compared with cis-diamminedichloroplatinum(II) (cis-DDP) for antitumor activity and nephrotoxicity. Antitumor activity was determined in an IgM immunocytoma model in the LOU/M rat. Tumor cells were inoculated on the left flank, and therapy was started when a tumor diameter of 10 to 30 mm was reached. At the start of the therapy, the primary tumor had already metastasized to the draining lymph node and liver. Both platinum compounds, dissolved in 5% glucose water, induced an almost complete tumor regression within 10 to 14 days (average, 84% tumor load reduction) and prolonged survival, compared to that of nontreated animals. The antitumor activity induced by repeated i.p. administration of cis-DDP and TNO-6 reached its maximum at a dose of 1.0 mg/kg body weight (twice a week for 7 weeks). This treatment regimen resulted in a highest tolerable dose for cis-DDP of 1.0 mg/kg and for TNO-6 of 2.0 mg/kg. However, when rats were treated with a 2.0-mg/kg dose of TNO-6, no increase in antitumor activity was obtained. For both platinum compounds, tumor recurrence occurred in almost all animals within 2 to 7 days after the maximum tumor load reduction. Tumors that recurred were found to be cross-resistant to both platinum compounds tested but were sensitive to treatment with doxorubicin (Adriamycin). With regard to toxicity, repeated administration of TNO-6 (1.0 mg/kg twice a week for 7 weeks) induced less decrease of body weight than did cis-DDP. For TNO-6, even in the highest dose investigated (2.0 mg/kg twice a week for 7 weeks), no nephrotoxicity was observed on histological examination of kidney and blood urea and creatinine values, whereas for cis-DDP nephrotoxicity was still present in the lowest dose investigated (0.5 mg/kg). From the comparison of the antitumor activity and nephrotoxicity of TNO-6 and cis-DDP, administered i.p. in 5% glucose solution, it is concluded that both drugs have comparable antitumor activity and potency. In contrast to the effects of cis-DDP, no nephrotoxicity was observed with TNO-6; thus, TNO-6 might be a good alternative to cis-DDP in avoiding nephrotoxicity during platinum therapy.

Animals↗
PubMed1982

Acnegenic activity of 3-methylcholanthrene and benzo[a]pyrene, and a comparative study with 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rabbit and hairless mouse.

The non-halogenated hydrocarbons 3-methylcholanthrene (MC) and benzo[a]pyrene (BP) were tested for acnegenic activity using the rabbit ear test. Both compounds induced characteristics follicular hyperkeratosis, although their acnegenic potency was approximately 4 orders of magnitude lower when compared to the potent acnegen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These results are discussed in view of the hypothesis that the acnegenic activity of TCDD and its congeners is mediated through stereospecific binding to a cytosolic receptor protein. In an experiment with hairless (hrhr) mice, which mutant has been described as an animal model for testing acnegenic potency, reduction in sebaceous gland tissue but no follicular hyperkeratosis was observed after application of a total dose of 0.4 microgram TCDD on the back skin. At a 10 times lower dose, no effects were seen. The hairless mouse strain used was responsive to TCDD as judged from the dose-related increase in the activity of aryl hydrocarbon hydroxylase (AHH) in liver microsomes, the increased liver weight and the histopathological changes in the liver. In comparison, a total dose of 0.12 microgram TCDD produced a strong follicular hyperkeratosis in the rabbit ear. From these results and from literature data, the adequacy of the hairless mouse for the testing of compounds for acnegenic potency is questioned.

Acne Vulgaris↗
PubMed1982

Weight increase of the thyroid gland as a tentative screening parameter to detect the illegal use of thyreostatic compounds in slaughter cattle.

A total of 45 normal or enlarged thyroid glands of adult slaughter cattle were weighed and analyzed by thin-layer chromatography for the presence of residues of the following thyreostatic compounds: thiouracil, methylthiouracil, propylthiouracil, phenylthiouracil, and methimazole. In 21 glands, mostly from imported animals, residues of methylthiouracil or methimazole were detected. These thyroids ranged in weight from 68-245 g (mean value 118 g). Glands in which no residues were found, varied in weight between 20 and 124 g (mean value 42 g). Taking an upper limit of 60 g as normal, 4 out of 22 were false-positive' with respect to the 5 thyreostatic compounds screened for, while no false-negative cases were scored. On the basis of these results the weight increase of the thyroid gland is proposed as a simple indirect parameter in the screening for the illegal use of thyreostatic compounds in slaughter cattle.

Animals↗
PubMed1982

Use of the enzyme-linked immunosorbent assay (ELISA) in immunotoxicity testing.

Based on an earlier described macromethod for the routine measurement of IgM and IgG in rat sera, a mechanized micro enzyme-linked immunosorbent assay (ELISA) was developed. The assay was performed in the wells of microtiter plate thus minimizing the quantities of reagents and antisera needed. Data on reproducibility of the assay and calculation of IgM and IgG levels are provided. For the functional assessment of the humoral immunity of the rat, ELISA is a powerful tool. In an earlier report, assays for the titration of thymus-independent IgM antibodies to E. coli LPS and the IgM and IgG response to the thymus-dependent antigen tetanus toxoid were described. More recently it was shown that the antigen ovalbumin elicits a thymus-dependent IgM, IgG and IgE response which could be readily measured with the enzyme immunoassay, as well as a delayed-type hypersensitivity reaction. As the optimum ovalbumin concentration for both types of reactions was the same, it is concluded that the ovalbumin model offers the advantage that both humoral and cellular immunity can be studies simultaneously in the same animal.

Animals↗
PubMed1981

The use of tannic acid fixation for the electron microscope visualization of fluorochrome-labelled antibodies attached to cell surface antigens.

Tannic acid as a prefixative for EM purposes was introduced by Futaesaku et al. (1972). The fixative creates conditions for enhancing electron density of different protein materials. By using a mixture of tannic acid and glutaraldehyde as prefixative, followed by a routine procedure of postfixation (OsO4) and poststaining (uranylacetate and lead citrate), membrane bound antibodies not conjugated with electron dense markers are made visible under the electron microscope.

Animals↗
PubMed1981

Screening and function studies in immunotoxicity testing.

After a short introduction of various chemical of environmental concern that have been shown to alter cell-mediated or humoral immune responses, a screening procedure is given to detect possible immunotoxic properties of chemicals. The different parameters in this screening programme include growth, weight and histology of lymphoid and endocrine organs, haematology, as well as serum immunoglobulin concentrations. Next, different functional tests are discussed to assess the cell-mediated immunity, the humoral immunity, and the phagocytosis by macrophages in the rat. These tests should be performed when in a screening study an indication of immunotoxicity is found at a relevant dose level. The aim of functional assessment is to determine the functional significance of an effect on the immune response. As the data available at present clearly show that the developing organism is more at risk to the immunomodulating effects of different chemicals than the corresponding adult, functional assessment of immune effects should preferably be carried out after combined pre- and postnatal exposure.

Animals↗
PubMed1980

Immunotoxicity assessment: screening and function studies.

As a screening procedure to detect immunotoxic effects, different parameters are discussed. These criteria include growth, weight and histology of lymphoid and endocrine organs, haematology, as well s serum immunoglobulin concentrations which can be quantified using the enzyme-linked immunosorbent assay (ELISA). Secondly, different function tests are discussed to assess in the rat the cell-mediated immunity, the humoral immunity and the phagocytosis by macrophages. These tests should be performed when in a screening study an indication of immunotoxicity is found at a relevant dose level. The aim of functional assessment is to determine the functional significance of an effect on the immune response and to gain more insight into the mode of action of the chemical. Finally, examples are given of compounds that suppress or stimulate immune responses; and advantages are discussed of performing function tests during the development phase of the immune system.

Animals↗
PubMed1980

Ultrastructural studies of peripheral blood lymphocytes in T cell-depleted rabbits. A scanning and transmission electron microscopic analysis.

Density separation of purified peripheral blood leucocytes from T-cell depleted rabbits on a linear Ficoll-metrizoate gradient has been applied to obtain different leucocyte fractions. Two lymphocyte fractions separated on density seem to have different characteristics, both morphologically and immunologically. In this study these two fractions have been characterized ultrastructurally by using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and a relationship has been established between the surface architecture (SEM), the cell size (SEM/TEM) and surface-Ig/C3-receptors (LM, light microscopy). Finally three types of lymphocytes have been described in the two lymphocyte fractions separated on density. Morphometric information such as cell size, cell shape, eu-/heterochromatin ratio in the nucleus and the nucleus-/cell ratio have been correlated to the stage of activation of the B lymphocyte in a representative density separation.

Animals↗