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Biomedical subjects

E J Ruitenberg

Publications and source records attributed to E J Ruitenberg.

At least 73 records · Page 4Linked to original sources

Effect of a Trichinella spiralis infection on the distribution of mast cell precursors in tissues of thymus-bearing and non-thymus-bearing (nude) mice determined by an in vitro assay.

The frequency of precursor cells capable of giving rise to cells with characteristics of mucosal mast cells in tissues from thymus-bearing and non-thymus-bearing (nude) mice orally infected with Trichinella spiralis was determined with an in vitro assay. Analysis of the frequency of mast cell precursors in bone marrow, blood, spleen and small intestinal tissue revealed similar frequencies of mast cell precursors in bone marrow from both thymus-bearing and athymic mice. These frequencies in bone marrow were not affected by infection. However, in blood and spleen from thymus-bearing mice at Day 7 post-infection (p.i.), and in the gut at Day 14 p.i., significant increases of mast cell precursor frequencies were detected. In contrast, no significant increase was observed in the tissues of infected nude mice. These data are in accordance with in vivo findings, indicating that a mucosal mast cell response in the gut is both thymus and antigen dependent. It was concluded that a mucosal mast cell response to infection with T. spiralis is probably due to local proliferation and maturation of residing mast cell precursors, that this response might be amplified by an influx of precursor cells from the blood into the gut, and that both phenomena are T-cell dependent.

Animals↗

[Trichinella spiralis as a teacher or the parasite-host relationship between a threadworm and an institute].

The present paper provides a review of activities of the National Institute of Public Health in the field of studies on Trichinella spiralis in man and animals. The development of a system of (immune) surveillance of infections due to Trichinella in pigs has been central since the early sixties. Both the fluorescent antibody technique introduced in 1967 and the enzyme-linked immunosorbent assay (ELISA) published in 1974 are examples of these efforts. The method was standardised and, specifically, the ELISA method was mechanized. Comparative studies were done as part of the activities of the EEC working party concerned with trichinosis. The two methods were officially accepted by the EEC. Studies in the slaughter-house as well as in the piggeries (so-called 'in process control') are possible on the basis of the ELISA technique, in which method interest is also being taken in the United States today. Conceivably, industry in Europe will also become interested in the principles of good manufacturing practice, in which certification of slaughtered animals, based on negative results of ELISA studies (without any further inspection in the slaughter-house) will be possible in theory. In addition to the object directly aimed at, i.e. improvement of the method of detection in pigs, designed to prevent human trichinosis, studies on the parasite Trichinella spiralis centered, among other things, on closer examination of the immune response and effector mechanisms in regard to this nematode infection, in which particularly studies on the role of so-called intestinal mast cells produced interesting new views on the subject of (immunological) regulation.

Academies and Institutes↗

Immune reactivity in cattle with ocular squamous cell carcinoma after intralesional BCG immunotherapy.

Lymphocyte stimulation with Con A and specific immune reactivity to BCG (antibody formation to BCG and DTH reaction to PPD) were determined in BCG-treated, surgically treated and untreated cows with ocular squamous cell carcinoma. In tumor-bearing cows the Con A-induced proliferation of lymphocytes was reduced when compared to healthy controls. This suppression consisted of a reduced blastogenic response to Con A of lymphocytes from tumor-bearing cows, and the presence of a factor in the sera of these animals, as these sera suppressed the blastogenic response of lymphocytes from healthy cows. BCG had only a minor influence on the suppressive activity. Antibodies to BCG were demonstrated in 50% of the BCG-treated animals. The formation of antibodies was not influenced by intradermal injection of PPD of Mycobacterium bovis. Absorption of a BCG antibody containing serum with BOSCC tumor extracts did not reveal the existence of cross reacting antigens between BCG and BOSCC. Pretherapeutic and posttherapeutic Con A reactivity could not be correlated with clinical response. Of the 30 BCG treated cows 29 developed a positive DTH reaction to PPD. Correlation between clinical response and immune reactivity was seen only with regard to the DTH reaction to PPD: this reaction remained positive for a longer period after treatment in animals with a favorable clinical outcome than in nonresponding animals.

Animals↗

Equine sarcoid: BCG immunotherapy compared to cryosurgery in a prospective randomised clinical trial.

A total of 30 horses with single or multiple sarcoid tumors of the skin were randomly divided into three treatment groups: (i) cryosurgical treatment, (ii) intralesional immunotherapy with a live BCG vaccine, (iii) intralesional immunotherapy with a BCG cell wall preparation. Complete tumour regression was obtained in all 10 cryosurgically treated horses, in 6 of 10 live BCG treated horses, and in 7 of 10 BCG cell wall treated horses. One live BCG and 2 BCG cell wall treated horses showed partial tumour regression of more than 50% of the tumour area. Eleven horses with sarcoid tumours were not eligible for random allocation in the trial because unfavourable site or size of the tumour precluded cryosurgical treatment. These animals were treated with BCG cell wall vaccine except for 1 animal, which was treated with live BCG. In 4 cases this treatment was combined with cytoreductive surgery of the tumour. In this prognostically unfavourable group 8 animals showed complete tumour regression and 3 animals did not respond. Regression after BCG immunotherapy appeared to correlate with size (larger tumours worse response) and localization of the sarcoid (less favourable results in the limb), and increase in peripheral blood leucocytes after the first injection. Horses with a positive delayed type hypersensitivity reaction to PPD before the start of treatment showed a tendency to more favourable prognosis than PPD negative horses. No correlation was present between regression and single or multiple presence of sarcoids, increase in body temperature after injection of BCG and the formation of specific antibodies to BCG. None of the cured animals have shown tumour recurrence 3 to 40 months following treatment.

Animals↗

The effects of intravesical and intradermal application of a new B.C.G. on the dog bladder.

Intravesical and intradermal application of B.C.G. (Bacillus Calmette Guérin) has proven to be effective in the prophylaxis of recurrence of superficial bladder carcinoma after transurethral resection and in the treatment of carcinoma in situ (C.I.S.) in man. Different strains of B.C.G. have been used for this purpose. In this article a new strain of B.C.G. (B.C.G.-R.I.V.M.) has been tested to assess its toxicity. The effects of intravesical and intradermal application of B.C.G.-R.I.V.M. were studied on normal and on coagulated canine urothelium. In this study no general side effects of B.C.G.-R.I.V.M. were seen. Only minor local changes occurred in the bladder wall. Small granulomas were found in the suburothelial tissue. No granulomas or signs of active inflammation were observed in the pelvic lymphnodes, spleen and liver. Because B.C.G.-R.I.V.M. seemed to be a safe agent in the dog we have started to use it for prophylaxis in superficial bladder cancer in man.

Administration, Intravesical↗

Histological evaluation of immunologically mediated tumor regression of the line 10 guinea pig hepatocarcinoma.

The histology of immunologically mediated tumor regression was studied in the syngenic strain 2 guinea pig/line 10 hepatocellular carcinoma tumor system. Tumor regression was induced non-specifically by the intralesional injection of living Bacillus Calmette-Guérin (BCG) in 7-day-old established tumors (diameter 8-10 mm). In untreated line 10 tumors at day 7 a mild to moderate inflammatory reaction was present, which consisted mainly of small mononuclear cells; in addition large mononuclear cells and basophils were present. Intratumoral BCG-treatment induced a prominent increase in the inflammatory reaction due to an influx of small and large mononuclear cells and neutrophils. Small mononuclear cells were identified mainly as lymphocytes whereas large mononuclear cells belonged mainly to the macrophage line. Intratumoral administration of BCG resulted in a granulomatous reaction. A time-related decrease in the number of tumor cells and an increase in inflammation, associated with purulent lysis of the granulomatous tissue, was observed. Specific immune-mediated tumor rejection occurred in animals both after active immunization and after adoptive transfer of immune spleen cells. In actively immunized animals the tumor cells were rapidly rejected and from day 4 onwards no tumor cells could be detected at the injection site. Lymphocytes were the major component of the inflammatory reaction; large mononuclear cells were present to a lesser extent and basophilic granulocytes were regularly observed. After adoptive transfer of immunity with immune spleen cells given simultaneously with an intradermal innoculation of tumor cells, an essentially similar rejection reaction was found, although tumor cell rejection was delayed. Lymphocytes and large mononuclear cells were found in equal proportions, whereas basophilic granulocytes were always present in smaller numbers. After BCG-induced regression and in adoptively transferred immune rejection, a fibroblast component was more prominent than in untreated control tumors. This reaction tended to isolate smaller tumor cell areas into islets of decreasing sizes. In contrast with the fibroblast component of growing tumors, the proliferative pre-existing fibrous tissue in tumors undergoing regression or rejection showed a loosely arranged architecture and contained a marked cellular infiltrate. From the results of the present study it was concluded that the morphological expression of line 10 tumor rejection varies. Without immune cells, BCG is needed for the induction of a local inflammatory reaction, which was granulomatous in type and eventually led to complete tumor cell eradication.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Seropositivity in Dutch Crohn's disease patients against primed nude mouse lymph nodes, and the difference with lymphocytotoxic antibodies.

Sera from patients with Crohn's disease have been reported to show positive immunofluorescence with lymph nodes of nude mice primed with a filtrate of intestinal tissue affected with Crohn's disease. An indirect immunofluorescence assay was used to test sera of 63 unrelated patients with Crohn's disease, 21 with ulcerative colitis and 36 control subjects against lymph nodes of athymic nude (nu/nu) mice which had been injected with Crohn's disease and ulcerative colitis intestinal tissue filtrates. Forty nine per cent of Crohn's disease patients, 10% of ulcerative colitis patients and 3% of control sera reacted against lymph nodes of mice injected injected with ulcerative colitis intestinal tissue filtrates, 18% of Crohn's disease sera were with intestinal tissue homogenate from Dutch Crohn's patients. With the lymph nodes of mice injected with ulcerative colitis intestinal tissue filtrates, 18% of Crohn's disease sera were positive, whereas all ulcerative colitis and control sera were negative. Lymph nodes from 18 of the 19 mice injected with Crohn's disease tissue filtrates reacted with Crohn's disease sera, whereas only three of these 19 mice reacted with ulcerative colitis sera. A comparative study, carried out in parallel with Crohn's disease filtrate induced hyperplastic lymph nodes from the Bilthoven colony (W2) and from the New York colony (E671) using sera from 54 Crohn's disease patients from Leiden, showed immunoreactivity with 44 and 57% of the Crohn's disease sera against the two hyperplastic lymph nodes. Thirty six of the 54 Crohn's disease sera (67%) reacted with either or both lymph nodes. Only 11% of the Crohn's disease sera which were examined for immunofluorescence and lymphocytotoxic antibodies had lymphocytotoxic antibodies, whereas 40% and 46% of the same sera showed positive immunofluorescence against E671 and W2, respectively. Absorption studies indicated that lymphocytotoxic antibodies activity and the immunofluorescence against the primed nude mouse lymph node are mediated by different serum antibodies in Crohn's disease. The reproducibility of the nude mouse immunofluorescence test system for a preferential immunoreactivity of Crohn's disease sera against Crohn's disease tissue primed murine lymph nodes has been confirmed by the present study. Further studies are necessary to find out whether crossreactive antigen(s) as recognised by some of the Crohn's disease sera in mice injected with ulcerative colitis tissue filtrate is similar to the antigen(s) detected by Crohn's disease sera in mice injected with Crohn's disease tissue filtrates.

Absorption↗

Thymus independence of eosinophilia induced by a non-parasite antigen.

Eosinophilia is primarily a T-cell-dependent phenomenon, related to helminthic infections. Using a rat model (+/rnu), it has been shown that keyhole limpet hemocyanin (KLH) in complete Freund's adjuvant (CFA) induced blood eosinophilia, but only after pretreatment with cyclophosphamide (CY). CY alone caused an eosinophilopenia which was reversed by CFA or KLH-CFA treatment. Eosinophilia was also induced in congenitally athymic rnu/rnu rats after CY pretreatment and KLH-CFA stimulation, the response being of a similar order as that in +/rnu animals. It is concluded that a non-parasite antigen can induce blood eosinophilia after pretreatment with CY, the response being thymus-independent. This model may be appropriate to study the biological significance of the eosinophil response.

Animals↗

[The histological study: an important parameter in checking the use of anabolics. Past, present, future?].

The histological methods used in checking the administration of oestrogens to fattening calves, introduced in the Netherlands in 1967, are discussed. Because of the increased use of combined treatment with oestrogens and androgens (both synthetic and natural), the suitability of the above histological techniques has become doubtful. Moreover, exogenous natural steroid hormones were not found to constitute any hazard to public health and could be safely used in husbandry. If administration of such anabolics is permitted the reasons for histological examination would cease to exist.

Anabolic Agents↗

Clinico-pathological aspects of immunotherapy by intralesional injection of BCG cell walls or live BCG in bovine ocular squamous cell carcinoma.

Bovine ocular squamous cell carcinoma (BOSCC) of clinical stage I, mostly situated in the third eyelid, was chosen as a therapy model for squamous cell carcinoma of the head and neck in humans. Block resection was found to be the best method of treatment. Regression was noticed in 19 out of 30 cows treated intratumourously with a single injection of live BCG or BCG cell wall vaccine, followed by recurrence in 8 cases. In 2 untreated cows, complete lasting regression occurred. Regression was significantly more frequently encountered in intratumourously treated cows than in controls. Regression was associated with a high mitotic index, severe infiltrating growth and small amounts of cellular (lymphoid) infiltration. Metastasis was found in 14 out of 50 cows: 5 in 10 untreated controls, 8 in 30 BCG treated cows and 1 in 10 surgically treated cows. The growth rate of progressively growing untreated and of some treated tumours was not associated with the mitotic index nor with other morphological characteristics tested. The mitotic index was found to be higher in the deep infiltrating layer than in the superficial layer of the primary tumour, suggesting that a single biopsy is not sufficiently representative for cell kinetic studies.

Animals↗

Effects of macrophage activity on the antibody-dependent cytotoxicity against Trichinella spiralis newborn larvae: an in vitro cytotoxicity and ultrastructural study.

The effect of the activity of macrophages on the antibody-dependent cytotoxicity against Trichinella spiralis newborn larvae was studied in vitro. Macrophages present in peritoneal exudates from mice genetically selected for high and low antibody production (HL and LL, respectively) showed an inverse cytotoxic effect. Cells from HL mice were ineffective, whereas cells from LL mice had a very high killing capacity. Ultrastructural studies of cells after incubations of up to 36 h supported these observations. Furthermore, peritoneal macrophages from congenitally athymic (nu/nu) mice showed a higher killing potential than cells from thymus-bearing littermates (+/nu) mice. The activity of the latter cells could be increased by in vitro pretreatment of the mice with Calmette-Guérin bacillus, a well-known macrophage stimulating agent. The results indicate that macrophages, although not the only effector cells, may play an important role in the defence against T. spiralis newborn larvae.

Animals↗

Selective localization of tumor-immune spleen cells at the tumor challenge site after adoptive transfer of line 10 tumor immunity in strain 2 guinea pigs.

In this study, the distribution of immune spleen cells was investigated after adoptive transfer of immunity in inbred strain 2 guinea pigs. Spleen cells obtained from line 10 immune donor animals became specifically restimulated in vitro with 3 M KCl-extracted line 10 soluble proteins, but not with 3 M KCl-extracted line 1 or liver proteins. After 4 days culture in vitro, these specifically restimulated immune spleen cells retained their antitumor activity in vivo after adoptive transfer. The specifically restimulated immune spleen cells were radiolabeled with [3H]thymidine, 1 X 10(8) viable cells were adoptively transferred in tumor-bearing guinea pigs, and their distribution was investigated. As controls for the specific localization of the immune cells at the line 10 tumor, the presence of labeled cells was studied in the contralateral transplanted line 1 hepatoma as well as in cellular inflammatory reactions elicited by injection with incomplete Freund's adjuvant (IFA) and complete Freund's adjuvant (CFA). A significantly higher localization of the labeled immune spleen cells in the line 10 tumor and the first and second draining lymph nodes of the line 10 challenge site were found when compared to the influx of these cells in the line 1 tumor and the nontumor antigen-related inflammatory reactions. Because our immune donor animals were immunized with a mixture of line 10 cells and BCG, these animals are immune to both. Line 10 immune spleen cells were restimulated in vitro with PPD and were radiolabeled. These PPD-restimulated immune spleen cells showed no preferential localization at the line 10 tumor challenge site but, as expected, a tendency for localization at the CFA (H37Ra) injection site. Furthermore, PPD-reactive spleen cells from BCG-immunized guinea pigs showed a significantly higher accumulation at the CFA injection site compared to the IFA injection site and the line 10 and line 1 tumor challenge site. From the results, it is concluded that line 10 tumor-immune and BCG-immune spleen cells are two distinct cell populations, and that the existence of cross-reacting antigens between BCG and the line 10 hepatocarcinoma are of no importance for the rejection of the line 10 tumor by immune spleen cells.

Animals↗