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C F Kuper

Publications and source records attributed to C F Kuper.

49 records · Page 3Linked to original sources
PubMed1986

Spontaneous pathology of the thymus in aging Wistar (Cpb:WU) rats.

Spontaneous thymic lesions were investigated in Wistar (Cpb:WU) rats. Thymic tumors were not uncommon and most showed medullary differentiation. Thymic involution was investigated in a limited group of animals in which the survival rate for males and females was similar. The histological pattern of thymic involution differed between sexes. Severe thymic involution occurred more frequently in males than in females and at an earlier age.

Aging↗
PubMed1985

Effects of feeding stannous chloride on different parts of the gastrointestinal tract of the rat.

The effects of feeding inorganic tin on the gastrointestinal tract were examined in rats. Three groups of male weanling Wistar rats were fed a diet to which 0, 250, or 500 ppm Sn2+ had been added as SnCl2. A fourth group was subjected to feed restriction by pair feeding with the 500-ppm group. Comparison of the data from the tin-fed groups with both the control and the reduced diet groups allowed discrimination between effects of reduced feed intake and Sn2+ effects. Independent of the reduced feed intake, Sn2+ affected hemoglobin concentration in the blood and several small intestine parameters. Total length of the small intestine, as well as absolute and relative weights, was increased. An increase was also observed in the migration of epithelial cells along the villus, as revealed by [3H]thymidine incorporation and autoradiography in rats fed 900 ppm Sn2+ for 4 weeks. Stereo-light microscopy and scanning electron microscopy revealed the formation of ridge-like villi due to Sn2+ feeding and a decreased number of villi per unit surface. These data suggest that an increase in cell turnover in the small intestine, due to Sn2+, was responsible for these changes.

Animals↗
PubMed1985

Effects of endotoxin-treatment on inflammatory cell infiltrates in murine Meth A sarcoma.

The effect of intravenously injected endotoxin on inflammatory cells within solid Meth A tumours was studied and central hyperaemia, necrosis and early collapse were observed macroscopically at 4, 24 and 48 h, respectively. The effects were studied in semithin sections and cytocentrifuge preparations of the tumours. The inflammatory cell reaction evoked by the tumours in untreated animals was relatively slight. It was located predominantly around the lateral margins of the tumours and only a few inflammatory cells were found inside the tumour. Prominent effects of endotoxin included a transient increase of mononuclear inflammatory cells in the centre of the tumour by 4 h and a reduction of the influx of lymphocytes, observed in and around the margin of control tumours, by 48 h. Mast cells formed an important part of the inflammatory cell infiltrate, but no distinct changes in number and appearance were observed with time or following treatment. Total host cell numbers within tumours did not increase significantly upon endotoxin-treatment. Results suggest that a direct cytotoxic action of host cells cannot account for the extensive tumour damage observed. Rather, endotoxin-induced regression seems to be related to decreased lymphocyte numbers.

Animals↗
PubMed1985

Glass fibers and vapor phase components of cigarette smoke as cofactors in experimental respiratory tract carcinogenesis.

Syrian golden hamsters were given intratracheal instillations of glass fibers with or without BP suspended in saline, once a fortnight for 52 weeks; the experiment was terminated at week 85. No tumors of the respiratory tract were observed in hamsters treated with glass fibers alone. There was no indication that glass fibers enhanced the development of respiratory tract tumors induced by BP. In another study Syrian golden hamsters were exposed to fresh air or to a mixture of 4 major vapor phase components of cigarette smoke, viz. isoprene (800----700 ppm), methyl chloride (1000----900 ppm), methyl nitrite (200----190 ppm) and acetaldehyde (1400----1200 ppm) for a period of at most 23 months. Some of the animals were also given repeated intratracheal instillations of BP or norharman in saline. Laryngeal tumors were found in 7/31 male and 6/32 female hamsters exposed only to the vapor mixture, whereas no laryngeal tumors occurred in controls. The tumor response of the larynx most probably has to be ascribed entirely to the action of acetaldehyde. Simultaneous treatment with norharman or BP did not affect the tumor response of the larynx. Acetaldehyde may occur in the vapor phase of cigarette smoke at levels up to 2000 ppm. Chronic inhalation exposure of rats to acetaldehyde at levels of 0 (controls), 750, 1500 or 3000----1000 ppm resulted in a high incidence of nasal carcinomas, both squamous cell carcinomas of the respiratory epithelium and adenocarcinomas of the olfactory epithelium. It was discussed that acetaldehyde may significantly contribute to the induction of bronchogenic cancer by cigarette smoke in man. No evidence was obtained for a role of isoprene, methyl chloride or methyl nitrite in the induction of lung cancer by cigarette smoke.

Acetaldehyde↗
PubMed1984

Role of vasoactive amines in the antitumor activity of endotoxin.

To estimate a possible role of vasoamines in the antitumor action of endotoxin, effects of isoproterenol, serotonin and adrenaline on subcutaneously transplanted murine Meth A sarcoma and the capacity of these agents to elicit antitumor factors were studied. Macroscopically all agents induced tumor necrosis and a temporal tumor growth stop, but only endotoxin was capable of induction of complete tumor regression. Histology showed that all agents induced hyperemia by 4 h and hemorrhagic necrosis by 24 h. The latter was located superficially at the outside of tumors. Only serotonin and especially endotoxin induced substantial non-hemorrhagic necrosis in the remaining part of the tumors. Endotoxin induced a profound inhibition of the mitotic activity within the tumor, the effect of other agents was considerably less. Only endotoxin induced high levels of tumor necrosis factor, heat stable cytostatic factors and interferon in the circulation of mice treated with Corynebacterium parvum 14 days earlier. It is concluded that these and other data provide indirect but circumstantial evidence for a role of vasoamines in the induction of hyperemia and hemorrhagic necrosis by endotoxin. The latter two effects are probably causally related. It is suggested that non-toxic vasoamines may be useful adjuvants to other treatments of cancer.

Animals↗
PubMed1984

Evaluation of histological changes in the kidneys of the alloxan diabetic rat by means of factor analysis.

Renal histopathology data, obtained in a 3-month feeding study of the effects of different carbohydrates and polyols in the alloxan diabetic rat, have been subjected to factor analysis. The results indicate a primary and a secondary effect of the diabetic state on the kidney of the rat. The primary effect, the 'diabetes factor', was associated with hyperglycaemia and was responsible for dilatation of proximal and distal tubules in the cortex and the formation of dilated distal tubules with coarsely vacuolated, glycogen-containing epithelial cells. The secondary effect, named the 'individual response factor', was associated with inflammatory processes. In both males and females it included a 'degeneration factor' which manifested itself in an increased number of basophilic tubules and a thickening of basal laminae in the Bowman's capsules. In males it also involved a 'protein factor', which caused expansion of the mesangial matrix and the appearance of proximal tubules filled with eosinophilic material and lined with vacuolated epithelial cells. The analysis indicates that the kidneys of alloxan diabetic rats fed diets containing polyols were affected less than those of rats fed diets containing carbohydrates.

Animals↗
PubMed1983

Antitumour activity of endotoxin, concanavalin A and poly I: C and their ability to elicit tumour necrosis factor, cytostatic factors, and interferon in vivo.

Concanavalin A, endotoxin, poly I: C, and tumour necrosis serum (TNS) were compared for antitumour activity against Meth A sarcoma transplanted in syngeneic BALB/c mice and their capacity to induce tumour necrosis factor (TNF), heat-stable cytostatic factors, and heat-labile interferon in the blood of normal and Corynebacterium parvum-pretreated mice. All the agents induced hyperemia and inhibition of mitosis at 4 h, and by 24 h many tumours had a dark necrotic centre. Subsequent tumour growth was inhibited and in some of the treated mice tumours regressed completely. Poly A: U and normal mouse serum did not induce regression and their effects were less marked in all other respects, suggesting that these events may be linked. The necrotizing effects of concanavalin A and poly I: C are unlikely to be mediated by TNF, because neither agent could mimic endotoxin in eliciting RNase-resistant necrotizing and regressing activity in the serum of mice pretreated with C. parvum. Poly I: C did not induce strong cytostatic activity in the sera of C. parvum-treated mice, and for this and other reasons these factors are unlikely to be responsible for the observed effects. Concanavalin A, endotoxin, and poly I: C induced high levels of serum interferon but purified interferon had only weak antitumour activity in the Meth A system, suggesting that interferon may not be the mediator. From these and other data it is concluded that there is no clear relationship between the capacity of the agents to induce tumour necrosis and their capacity to elicit TNF, cytostatic factors, and interferon.

Animals↗
PubMed1982

Influence of adrenoceptor blockade on endotoxin-induced histopathological changes in murine Meth A sarcoma.

Histological examination of subcutaneous murine Meth A sarcomata 4 h after administration of endotoxin revealed an overt but superficial vasodilation, which had largely disappeared after 24 h. At this time hemorrhagic necrosis could be observed in that region mainly featured by degenerating tumour cells, diffuse hemorrhage and blood vessels filled with a yellow substance probably derived from disintegrated erythrocytes. Administration of the alpha-adrenoceptor antagonist phenoxybenzamine or the beta-adrenoceptor antagonist propranolol caused decrease of vasodilation at 4 h but an increase at 24 h especially after phenoxybenzamine. Only the latter agent prevented the induction of hemorrhagic necrosis by endotoxin. Endotoxin reduced tumour size within 24 h, which was prevented by both adrenoceptor blocking agents. Administration of these agents alone even enhanced tumour size. Mitotic activity of Meth A sarcoma was greatly reduced already 4 h after endotoxin injection. This was not significantly changed by both adrenoceptor antagonists, while these agents alone probably stimulate tumour cell division between 4 and 24 h after administration. The histological data are discussed in relation to earlier data on the influence of adrenoceptor blockade on endotoxin-induced hemorrhagic necrosis and tumour regression.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Nitrite-induced adrenal effects in rats and the consequences for the no-observed-effect level.

In a previous subchronic oral toxicity study with potassium nitrite, hypertrophy of the adrenal zona glomerulosa was observed for all nitrite levels examined including the lowest level of 100 mg/litre. This present study was carried out, therefore, to establish a no-observed-effect level (NOEL) for nitrite. Groups of 10 male and 10 female 6-wk-old Wistar rats received KNO2 at levels of 12.5, 25, 50, 100 or 3000 mg/litre or NaNO2 at levels of 81 or 2432 mg/litre in the drinking water for 13 wk. The nitrite content of the drinking water in the latter two groups was equal to that of the 100 and 3000 mg KNO2/litre groups, respectively. Potassium and sodium concentrations were equalized in the corresponding test groups with KCl and NaCl, respectively. General health, behaviour and survival were not affected by the ingestion of nitrite. Body weight and food and liquid intake were slightly decreased in the 3000 mg KNO2/litre and 2432 mg NaNo2/litre groups for both sexes. Methaemoglobin concentration was significantly elevated in rats of both high-dose nitrite groups in wk 4 and 12, while slight increases in a number of red blood cell variables occurred with 3000 mg KNO2/litre in females in wk 12. Relative kidney weights were increased in both high-dose nitrite groups. In wk 4, plasma aldosterone and corticosterone levels were slightly decreased in males with 2432 mg NaNO2/litre and plasma corticosterone in females with 3000 mg KNO2/litre but not in wk 13. Systolic blood pressure was not affected by nitrite. Microscopic examination revealed slight hypertrophy of the adrenal zona glomerulosa in animals of the 100 and 3000 mg KNO2/litre and of the 81 and 2432 mg NaNO2/litre groups, the incidence and degree being dose related. The results obtained with 100 and 3000 mg KNO2/litre in the drinking water were comparable with those found at the same levels in the previous 90-day study. The effects with sodium nitrite were similar to those observed with potassium nitrite. The biological significance of the adrenal zona glomerulosa hypertrophy is discussed. It is concluded that the NOEL of KNO2 is 50 mg/litre in the drinking water, equivalent to about 5 mg/kg body weight/day.

Administration, Oral↗
PubMedDate not supplied

Pathology of the thymus: changes induced by xenobiotics and gene targeting.

Studies on the thymus in pathologic conditions have been of great help in the elucidation of the function of the organ in T-cell development. The first examples come from congenital immunodeficiency states in man and laboratory animals. A number of toxic substances affect different components of the thymus already at exposure levels where there is no effect on the peripheral immune system. In some cases, this thymotoxic effect has been causally related to defects in the peripheral immune system (immunodeficiency and autoimmunity). In recent years immunodeficient states have been created in mouse by disruption of genes coding immunologically relevant molecules. Studies on such gene 'knock-out' mice have shown that a number of molecules are indispensable for appropriate T-cell development at different stages in the thymus, whereas others are dispensable. It is concluded that the experimental approach combining gene targeting and exposure to thymotoxic xenobiotics will present interesting tools for further studies in thymus research.

Animals↗
PubMedDate not supplied

Histopathologic approaches to detect changes indicative of immunotoxicity.

Toxicologic pathology is crucial in the identification and characterization of health effects following exposure to xenobiotics, mainly in toxicity experiments in rodents. Regarding regulatory toxicology, histopathology of lymphoid organs and tissues is a cornerstone in the identification of immunotoxic compounds. A 2-tier testing system is usually employed in which the first tier is a general screen for (immuno)toxicity and the second tier consists of specific immune function studies, including host resistance tests or mechanistic studies. The role attributed to histopathology of lymphoid organs in the updated Organisation for Economic Cooperation and Development and Food and Drug Administration guidelines requires improvement and standardization of the histopathology procedures. Optimalization and standardization was started in an international collaborative immunotoxicity study (ICICIS). However, several problems were left unaddressed, mostly because of the few compounds tested in this study. Based on the results of the ICICIS study and the morphologic changes induced by immunotoxic/immunomodulatory compounds observed in other investigations, suggestions are given to further improve the identification and (semi)quantification of histopathologic changes in lymphoid organs and tissues.

Animals↗
PubMedDate not supplied

Intestinal T lymphocytes of different rat strains in immunotoxicity.

In order to study the intestinal mucosal immune cells, with emphasis on single T lymphocytes, an inventory was made of single and organized lymphocytes in the epithelium and lamina propria of the small intestines of untreated Wistar, Fischer 344, and Lewis rats. The single and organized lymphocytes were examined microscopically. In addition, the single lymphocytes in the epithelium (IEL) and lamina propria (LPL) were analyzed by flow cytometry. Next, the use of flow cytometry analysis was explored to detect changes in the IEL T-lymphocyte population in subacute oral studies with the immunomodulating agents azathioprine and hexachlorobenzene. Untreated random-bred Wistar rats exhibited a large interindividual variability in IEL composition, while the variability was small in inbred Fischer 344 and Lewis rats. The explorative study with the 2 model immunomodulating compounds demonstrated that hexachlorobenzene increased the number of intraepithelial T lymphocytes with CD8+ phenotype at the cost of T cells with CD4+ phenotype in Lewis rats. Azathioprine did not induce distinct effects on the percentages of IEL. The data indicate that the intraepithelial lymphocytes in the intestines are a potential target for orally administered immunomodulating compounds and should therefore receive more attention in toxicologic pathology studies.

Animals↗