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L Binderup

Publications and source records attributed to L Binderup.

105 records · Page 6Linked to original sources
PubMed1980

Immunological effects of D-penicillamine during experimental induced inflammation in rats.

Administration of D-penicillamine (50 mg/kg/day orally) to rats with adjuvant arthritis for up to 42 days significantly modified the incorporation of 3H-thymidine (3H-TdR) in concanavalin A (Con A)-stimulated lymph node cells. Treatment with D-penicillamine abolished the ability of macrophages from arthritic rats to inhibit lymphocyte responsiveness to Con A and lipopolysaccharide (LPS) 14 days after the induction of the disease. Increased T-cell responsiveness to Con A was found from day 14 to 35 in cultures of unseparated and adherent-cell-depleted lymph node cells from D-penicillamine-treated arthritic rats. B-cell responsiveness to LPS was not affected. Experiments with bovine serum albumin gradient-separated lymph node cells confirmed these findings and indicated that treatment with D-penicillamine may specifically enhance T-helper cell responsiveness to Con A. It is suggested that administration of D-penicillamine may interfere with macrophage function during the course of an immunologically induced chronic inflammation, leading to an increased response of T-helper cells. The theoretical implications of these findings are discussed.

Animals↗
PubMed1980

D-penicillamine in vivo enhances lymphocyte DNA synthesis: role of macrophages.

Administration of D-penicillamine (50 mg/kg/day orally) for 4 days increased the uptake of 3H-thymidine (3H-TdR) in unstimulated and concanavalin-A-stimulated unseparated lymph node and spleen cells from Lewis rats. Increased 3H-TdR incorporation was also found in cultures depleted of adherent cells. D-Penicillamine treatment did not increase the incorporation of 3H-TdR in lymph node and spleen cells from rats concomitantly treated with the selective macrophage toxin silica. In contrast, treatment with D-penicillamine during the last 4 days of silica treatment sometimes resulted in a marked decrease in 3H-TdR incorporation. It is suggested that D-penicillamine treatment in vivo is able to enhance the responsiveness of the lymphocytes, dependent on the presence of functionally intact macrophages. The increased response vanished after 2-3 weeks, even with continuous administration of D-penicillamine.

Animals↗
PubMed1980

Splenic suppressor cells in adjuvant arthritic rats: effect of D-penicillamine.

Adherent spleen cells from rats with adjuvant arthritis inhibit the incorporation of 3H-thymidine into DNA and 3H-leucine into protein in nonadherent spleen lymphocytes, stimulated by the mitogens Concanavalin A and E. coli Lipopolysaccharide. This suppressive activity was abolished by pretreatment of the adherent cells with the selective macrophage toxin silica. It is suggested that suppressor macrophages directly, or through interaction with suppressor T cells, inhibit the response of lymphocytes to mitogens by inhibition of cellular protein synthesis, followed by inhibition of DNA-synthesis and death of about 30% of the lymphocytes. Treatment of adjuvant arthritis rats with D-penicillamine resulted in significantly increased incorporation of 3H-thymidine in spleen lymphocytes, compared to cultures from untreated, arthritic rats. This approach may prove useful in the investigation of cellular interactions in a model of immunologically induced inflammation and provide a tool for the evaluation of the effects of immunoregulatory drugs.

Animals↗
PubMed1979

Peritoneal macrophages from adjuvant arthritic rats enhance tumour cell growth in vitro.

Peritoneal macrophages from rats with adjuvant arthritis enhance the incorporation of 3H-thymidine in 2 tumour cell lines in vitro. Maximal enhancement is found during the development of the secondary lesions, and it is suggested that the immunologic commitment of the macrophages could interfere with their regulation of tumour cell proliferation in vivo.

Animals↗
PubMed1979

Delayed hypersensitivity to tuberculin in rats: effects of antirheumatic drugs.

The effects of different antirheumatic drugs administered according to various dosing regimes on tuberculin hypersensitivity in rats have been assessed quantitating the changes of exudate volume and mononuclear cells immigration at the site of challenge. Dosing at the time of sensitization with aurothiomalate and D-penicillamine enhanced the cell immigration which was decreased by similar treatment with levamisole. Cyclophosphamide increased the exudate formation. Indomethacin had no effect. Dosing at the time of challenge caused a marked reduction of both the parameters by aurothiomalate and cyclophosphamide and enhancement by levamisole. D-penicillamine increased only the cellular immigration and indomethacin the exudate formation. Long treatment with aurothiomalate and cyclophosphamide suppressed the responses. Similar treatment with D-penicillamine and levamisole produced a significant enhancement. Indomethacin had no effect. The relevance of these findings to the testing and mode of action of antirheumatic drugs is discussed.

Animals↗
PubMed1978

D-penicillamine and macrophages: modulation of lymphocyte transformation by concanavalin A.

Pretreatment with D-Penicillamine of rat peritoneal macrophages markedly influences their ability to modulate Concanavalin A stimulated [3H]thymidine incorporation in non-adherent rat lymph node cells. Untreated macrophages added in high numbers to the lymphocytes (ratio lymphocytes/macrophage 7.5 : 1) depress their [3H]thymidine incorporation. Pretreatment with D-Penicillamine further reduces this response. Lower proportions of untreated macrophages (ratio 15 : 1) exert a stimulatory effect on the lymphocytes. This response is reversed by pretreatment of macrophages with D-Penicillamine. Addition of untreated macrophages in very low proportions (40 : 1 and 75 : 1) is without effect on the [3H]thymidine incorporation by the lymphocytes. This response is markedly stimulated by pretreatment of the macrophages with D-Penicillamine. The culture of macrophages in the presence of D-Penicillamine increases their incorporation of [3H]D-glucosamine, but it is without effect on their incorporation of [3H]L-leucine. It is suggested that D-Penicillamine enhances the functional activity of the macrophage in the regulation of the lymphocyte response to mitogens.

Animals↗
PubMed1978

Characterization of inhibitor(s) of lymphocyte activation in serum from rats with adjuvant arthritis.

Serum from adjuvant arthritic rats inhibits the concanavalin A- (Con A) and lipopolysaccharide-induced stimulation of lymph node cells, leaving the basal and phytohemagglutinin-stimulated 3H-thymidine incorporation unaffected. Con A-stimulated 3H-thymidine uptake is also inhibited in rat spleen and peripheral blood lymphocytes and in dog peripheral blood lymphocytes. The intensity of the inhibitory activity in serum is positively correlated with the intensity of the secondary lesions of adjuvant arthritis. Inhibitory activity was not found in serum from rats bearing nystatin-induced inflammation. Serum fractionation studies indicated that the inhibitory activity cannot be attributed to low molecular weight alpha2-glycoproteins or to gamma-globulins and alpha2-macroglobulins, but it is present in a fraction migrating with beta-globulins. The inhibitory activity in arthritic rat serum is reduced by treatment with non-steroidal anti-inflammatory drugs, but is unaltered by D-penicillamine. It is suggested that this inhibitory activity is part of the systemic response to an immunologically mediated inflammation.

Animals↗
PubMed1976

Actinomycin D peritonitis in rats: a tool for the study of early events in inflammation.

The injection of 50 microgram i.p. of actinomycin D produces, in rats, a biphasic inflammatory reaction. The first short lasting phase (approximately 24 h) is characterized by the decrease of the peritoneal cells number, by the increase of the levels of both cAMP and cGMP in the peritoneal cells and by the increased synthesis and release of lysosomal enzymes from these cells. The second long lasting phase (greater than 120 h) is characterized by the exudate formation, intense cellular immigration, continuous release of lysosomal enzymes, return to or below the normal values of the intracellular levels of cyclic nucleotides. The treatment of rats with a steroidal drug reduces the beta-glucuronidase release and, concomitantly, the intracellular cyclic nucleotides levels. Indomethacin is ineffective.

Animals↗
PubMedDate not supplied

Comparison of calcipotriol with selected metabolites and analogues of vitamin D3: effects on cell growth regulation in vitro and calcium metabolism in vivo.

Calcipotriol is a novel vitamin D3 analogue developed for topical treatment of psoriasis. Calcipotriol is believed to act via regulation of cell proliferation and differentiation. In this respect calcipotriol is as potent as 1 alpha, 25(OH)2D3, the physiologically active form of vitamin D3, but its calcaemic activity in vivo is 100 to 200 times lower. In the present investigation, the effects of calcipotriol on cell growth regulation in vitro and on calcium metabolism in vivo were compared to those exerted by a number of metabolites and analogues of vitamin D3. Besides 1 alpha, 25(OH)2D3, these included the two physiologically occurring metabolites 25(OH)D3 and 24,25(OH)2D3, and the two synthetic analogues 1 alpha (OH)D3 and 1 alpha, 24(OH)2D3. 25(OH)D3 and 24,25(OH)2D3 were shown to be inactive both in vitro and in vivo. 1 alpha (OH)D3 was found to have a low biological activity in vitro, but was highly calcaemic in vivo after biotransformation to 1 alpha, 25(OH)2D3. Calcipotriol, 1 alpha, 24(OH)2D3 and 1 alpha, 25(OH)2D3 were all three potent regulators of cell proliferation and differentiation in vitro. In vivo, only calcipotriol showed a greatly reduced calcaemic activity after both oral and intravenous administration. It is concluded that calcipotriol, with a reduced risk of inducing calcaemic side-effects upon absorption from the skin, possesses a favourable therapeutic profile for topical treatment of hyperproliferative diseases.

Animals↗
PubMedDate not supplied

Combination therapy of a vitamin D3 analog and all-trans-retinoic acid: effect on human breast cancer in nude mice.

BACKGROUND: Vitamin D3 analogs and all-trans-retinoic acid (ATRA) are able to inhibit the growth of a variety of malignant cells. MATERIAL AND METHODS: We examined the ability of three vitamin D3 analogs to inhibit the growth of a human mammary cancer cell line (MCF-7) in Beige Nude xid (BNX) mice either alone or with ATRA. Vitamin D3 analogs 1,25 dihydroxyvitamin D3 (code name, compound C), 1,25 (OH)2-16-ene-23-yne-19-nor-26,27-F6-D3 (compound LH) and 24a,26a,27a,-trihomo-22,24-diene-1,25(OH)2D3 (EB1089) were used. RESULTS: The antitumor effect of ATRA alone was greater than that of either of the vitamin D3 analogs alone, and an additive effect was observed when a vitamin D3 analog and ATRA were administered together. EB1089 was the most potent vitamin D3 analog; and EB1089 plus ATRA was the most potent combination decreasing the tumor mass nearly 3-fold compared to tumors of diluent control mice. None of the animals became hypercalcemic. Their complete blood counts, serum electrolyte analysis as well as their liver and renal functions were all fairly similar and within the normal range. CONCLUSION: This combination of a vitamin D3 analog and ATRA has the potential to be an adjuvant therapy for breast cancer.

Animals↗
PubMedDate not supplied

Cyanoguanidine CHS 828 induces programmed cell death with apoptotic features in human breast cancer cells in vitro.

The cyanoguanidine CHS 828 was recently shown to possess potent anti-tumour effects both in vitro and in vivo. The exact mechanism of action of CHS 828 is not known, but recent results have indicated that induction of programmed cell death may be one mechanism by which CHS 828 exerts its anti-tumour effects. To investigate this aspect in more detail, we studied the effect of CHS 828 and the reference compound Taxol beta on programmed cell death in human breast cancer cells in vitro. Both compounds were found to induce DNA fragmentation in the cells. However, microscopic examination of the cells demonstrated that CHS 828 and Taxol triggered different types of cell death. In the CHS 828-treated cultures most cells were found to be Annexin-V positive, indicating that these cells were early apoptotic cells, while no morphological characteristics of classical apoptosis were seen. In contrast, the cells in the Taxol-treated cultures displayed morphological features characteristic of classical apoptotic cells, but no Annexin-V positive cells could be observed. These findings together with the previously reported potent effects of CHS 828 on tumour cells, makes CHS 828 a promising new agent for the treatment of cancer patients.

Annexin A5↗
PubMedDate not supplied

D-penicillamine, lymphocytes, and macrophages: an account of experimental investigations in vivo.

A short oral treatment with D-penicillamine of normal rats increased responsiveness of spleen and lymph node lymphocytes to concanavalin A, depending on the presence of functionally intact macrophages. This effect vanished after 2 to 3 wk despite continued treatment. In adjuvant arthritic rats, a suppressed response of lymph node lymphocytes occurs concomitantly with the development of the secondary lesion. This inhibition caused by suppressive macrophage activity was abolished by D-penicillamine treatment, which enhanced T helper cell function. This effect disappeared when permanent crippling developed with residual minimal inflammatory reaction. These findings may give further insight into the drug's effects and side effects.

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