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Biomedical subjects

C J Dunn

Publications and source records attributed to C J Dunn.

At least 91 records · Page 5Linked to original sources
PubMed1983

Pharmacological control of osteoclastic motility.

We separated osteoclasts from bone and observed the effect of several known and potential mediators of the control of bone resorption on their cytoplasmic motility. We already found that calcitonin (CT), a hormone that inhibits bone resorption, regularly causes complete inhibition of cytoplasmic motility, specific for osteoclasts, through a trypsin-sensitive membrane receptor [1]. We report here that prostaglandin I2 (PGI2) and dibutyryl cyclic AMP induce an identical change in osteoclastic behavior. We found that theophylline, which inhibits intracellular cyclic AMP degradation, and which itself had no effect on osteoclastic motility, potentiated the cytoplasmic inhibition caused by CT, PGI2, and cyclic AMP. This suggests that PGI2 and CT cause cytoplasmic quiescence by increasing the intracellular level of cyclic AMP, a view compatible with the known ability of CT to increase cyclic AMP in bone [2]. Parathyroid hormone (PTH), PGE2, and 1,25 dihydroxycholecalciferol (1,25 (OH)2D3), hormones known to stimulate osteoclasts, did not stimulate the activity of either active or quiescent isolated osteoclasts. The undoubted ability of these hormones to stimulate osteoclastic activity in vivo may therefore be mediated through a primary hormonal interaction with another cell type.

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PubMed1979

Potassium permanganate induced calcergy: a model to study the effects of drugs on hydroxyapatite crystal deposition.

Hydroxyapatite crystal deposition is thought to play a role in the inflammatory episodes of osteoarthritis. A plaque of hydroxyapatite crystals was produced by local subcutaneous injection of a potassium permanganate solution. Transmission electron microscopy with X-ray energy spectroscopy was used to identify the crystal deposits as hydroxyapatite. The effects of dexamethasone, indomethacin, ethane 1-hydroxy-1, 1-diphosphonate (EHDP) and dichloromethylene diposphonate (Cl2MDP) on the development of the apatite plaque was studied. EHDP strongly inhibited the apatite deposition. Cl2MDP slowed the natural resorption of the apatite plaque. Dexamethasone and indomethacin failed to affect the crystal deposition process. The results suggest that EHDP could inhibit crystal deposition in the osteoarthritic joint and that Cl2MDP might have a role in slowing apatite crystal shedding from osteoarthritic cartilage and so reduce the synovitis seen in Osteoarthritis.

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PubMed1979

The role of kallikrein in leukocyte migration inhibition.

Previous studies from this department have established the presence of leukocyte migration inhibition activity in acute nonimmune inflammatory rat pleural exudates, induced by different irritants, which involved coagulation phenomenon. In the present investigation we present evidence for a role of kallikrein in the leukocyte migration inhibition phenomenon exhibited by acute pleural exudate in rates depleted of kininogens by intravenous injection of cellulose sulfate.

Animals↗
PubMed1979

Leukocyte migration inhibition activity of nonimmune acute inflammatory pleural exudate.

Material with leuckocyte migration inhibition (LMI) activity has been demonstrated in various types of nonimmunologically induced acute pleural inflammatory exudates. This activity is present in inflammatory cell-free exudate and appears to involved the deposition of fibrin around the migrating leukocyte, resulting in "cell-trapping." This is supported by the fact that removal or inhibition of fibrin formation leads to loss of exudate LMI activity. Both fibrinogen and complement as well as vitamin K-dependent clotting factors appear to be required for LMI activity. The mechanism involved in the LMI reaction and its significance in nonimmune and cell-mediated immune inflammation are discussed.

Animals↗
PubMed1979

Cyclic adenosine 3', 5'-monophosphate and the mechanism of action of three common anti-inflammatory drugs.

1 The effects of indomethacin, dexamethasone and colchicine on cyclic adenosine 3', 5'-monophosphate (cyclic AMP) concentration in leucocytes during a crystal-induced pleurisy in rats were studied. 2 Each of the drugs significantly increased leucocyte cyclic AMP content within 3 h of the injection of crystals. 3 By 6 h, leucocyte cyclic AMP levels returning toward control levels and could not be sustained at the higher level by an additional administration of the respective anti-inflammatory drug.

Animals↗
PubMed1978

Induction of macrophage DNA synthesis in vitro by non-immunological inflammatory exudates: effect of irradiation and thymus or bone marrow cell reconstitution.

An acute inflammatory exudate possesses mitogenic activity in that it is able to induce both DNA synthesis and proliferation of macrophages in vitro. This activity is reduced however if the inflammatory exudate is obtained from irradiated rats (900 r). Transfer of bone marrow syngeneic cells into irradiated rats does not reverse this reduction. On the contrary the decrease of mitogenic activity is more pronounced. On the other hand transfer of thymic syngeneic cells not only restores the mitogenic activity of inflammatory exudate from irradiated rats but increases it. Transfer of both types of cell together fully restores the mitogenic activity of inflammatory exudate. It is postulated that the mitogenic activity of inflammatory exudate could be related to thymic cells and that T lymphocytes may be involved in non-specific inflammatory reactions.

Animals↗
PubMed1978

The leucocoyte disappearance reaction in non-immune acute inflammation.

Injection of a variety of irritants (saline, ovalbumin, compound 48/80 and powdered glass) into the rat pleural cavity induced the disappearance of pleural leucocytes during the first two hours of the reaction. This phenomenon, termed the leucocyte disappearance reaction (LDR), was suppressed by treatment with the anticoagulants heparin and warfarin. The in-vitro incubation of normal, or inflammatory pleural leucocytes resulted in the deposition of dense interconnecting meshwork of fibrin only upon addition of fibrinogen to the culture medium. It is suggested from these results that the LDR is related to the clotting system, involving leucocyte-derived enzyme(s) analogous to those of the clotting system (e.g., tissue thromboplastin), which convert fibrogen to fibrin, resulting in cell-trapping and subsequent "disappearance" of pleural leuococytes. Similarities were observed betweeen the LDR in non-immune inflammation and the macrophage disappearance reaction of cell-mediated immunity. The significance of these phenomena in the inflammatory process, both immune and non-immune, is discussed.

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PubMed1977

Stimulation of macrophage DNA synthesis in culture by different types of acute non immunological inflammatory exudates.

Acute non immunological inflammatory pleural exudates provoked by four different irritants and collected 4 hours later have been shown to be capable of stimulating DNA synthesis, in rat peritoneal macrophages in culture. It is postulated that a mitogenic factor, "Inflammatory Mitogenic Factor for Macrophages" IMF (M), could be responsible for this phenomenon. There may be a correlation between the protein concentration of the exudates and its mitogenic activity.

Animals↗
PubMed1977

The value of multifactorial screening for anti-inflammatory activity as shown by coumarin.

Different types of acute inflammatory pleural reactions have been used as a means of detecting the anti-inflammatory potential of a particular drug coumarin. The latter had some type of activity in all the reactions. However, whereas coumarin inhibited leucocyte accumulation induced by dextran it had no effect on the volume of fluid exudate. Conversely, coumarin reduced the volume of exudate in the Arthus reaction whereas the cellular infiltrate remained unaltered. Leucocytes from dextran-induced exudate (predominantly polymorphs) removed from animals pretreated with coumarin showed marked inhibition of migration in vitro. This correlated well with the suppression by coumarin of the dextran-induced leucocyte response in vivo. Coumarin administered in vivo was also shown to stimulate phagocytosis of latex by mouse peritoneal macrophages in vitro. These findings are discussed with respect to the evaluation of anti-inflammatory drug activity and to the mode of action of coumarin.

Animals↗
PubMed1976

Inflammatory mechanisms in the newborn.

Both the vascular and cellular aspects of inflammation were studied in rats aged from 6 hours to 2 months. The onset of a vascular permeability reaction was found to vary according to the age of rat and type of permeability agent injected. Induction of acute inflammations (turpentine pleurisy, 48/80 and dextran-induced foot oedema) in new born rats revealed a marked reduction of exudate/oedema formation compared with adult rats. These observations were related to a lack of histamine and 5-HT-mediated increased vascular permeability during the inflammatory reactions of newborn rats. Qualitative differences were observed between the acute inflammatory pleural cell exudates of newborn and adult rats after intra-pleural injection of dextran. In contrast to adults, polymorphs were observed to dominate the newborn reaction, and the peak accumulation of these cells was delayed. The mononuclear cells of 4-day lesions induced by sub-cutaneous implantation of glass coverslips showed a higher rate of mitosis in newborn animals, compared with adults. Ultrastructural studies of the mononuclear cells of peritoneal exudates induced by carrageenan indicated that those of newborn rats contained fewer lysosomes than adults. The Golgi apparatus of newborn mononuclear cells was observed to be poorly-developed compared with adult mononuclear cells.

Animals↗
PubMed1976

Studies on delayed hypersensitivity pleural exudates in guinea pigs. I. Demonstration of substances in the cell-free exudate which cause inhibition of mononuclear cell migration in vitro.

Leucocyte migration inhibitory (MI) activity was investigated in vitro in the delayed hypersensitivity reaction induced by intrapleural injection of PPD into FCA-sensitized guinea-pigs. During the initial reaction (6 h) two types of antigen-dependent MI activity were detected in serum and cell-free exudate. One was of high molecular weight and associated with immunoglobulin and the other was of low molecular weight and appeared to be related to so-called "antigen-dependent MIF". As the reaction progressed (i.e. 12-24 h), two types of antigen-dependent MI activity were revealed in exudate, but not in serum. One was high molecular weight and the other was low molecular weight and thought to be related to so-called "antigen-independent MIF". Similar experiments were performed on the reverse passive Arthus reaction in the pleural cavity of guinea-pigs. A high molecular weight MI activity was detected in 6-h cell-free exudate and was found to be antigen-independent. "So-called MIF" was not found in this reaction.

Animals↗
PubMed1976

Studies on delayed hypersensitivity pleural exudates in guinea-pigs. II. The interrelationship of monocytic and lymphocytic cells with respect to migration activity.

The in vitro migration activity of monocytic cells and the effect of lymphocytes in the delayed hypersensitivity (DH) reaction induced by intrapleural injection of PPD into FCA-sensitized guinea-pigs was investigated. The in vitro migration of exudate mononuclear cells was lower than that of comparable blood cells, and continued to decrease as the reaction progressed. An inverse relaationship was observed between the migration area and cell volume of mononuclear cells from both blood and exudate. Similar experiments were performed on the reversed passive Arthus (RPA) reaction in the pleural cavity of guinea-pigs. For 6-h exudate, the mononuclear cell migration exceeded that for blood mononuclear cells. However, the migration of mononuclear cells from 18-h exudates was markedly reduced. As with DH, an inverse relationship between the migration area and cell volume was observed with the mononuclear cells of RPA exudates. Following the addition of antigen, the migration of DH exudate mononuclear cells was inhibited whereas the exudate mononuclear cells of the RPA reaction remained unaffected. For DH, the inhibition of migration induced by antigen appeared to be related to the non-adherent cells of 6-h exudates, and both the adherent and non-adherent cells of 18-h exudates.

Animals↗
PubMed1976

An appraisal of the interrelationships between prostaglandins and cyclic nucleotides in inflammation.

The evidence supporting the role of prostaglandins and cyclic nucleotides "in vitro" has been reviewed. The pro-inflammatory role of prostaglandins of the E series (PGE) is typified by its ability to induce increased vascular permeability. Prostaglandins of the F series (PGF) may be anti-inflammatory via their inhibitory effect on increased vascular permeability. However, a paradox exists which suggests that PGE may also be anti-inflammatory via its stimulatory effect on cyclic AMP synthesis as shown "in vitro" (e.g. decreased leucocyte lysosomal enzyme secretion; decreased lymphocyte cytotoxicity and mitosis; decreased release of mediators from sensitized tissues during anaphylaxis). Conversely PGF is capable of stimulating cyclic GMP which augments the processes listed above, and may therefore be termed pro-inflammatory. An attempt has been made to correlate these findings with "in vivo" studies which support the anti-inflammatory role of cyclic GMP. However, the significance of PGE and PGF in the inflammatory response "in vivo" appears to be more complex. It is suggested that greater emphasis should be placed on the "in vivo" study of beta-adrenergic and cholinergic mediators, substances which induce the anti- and pro-inflammatory effects of cyclic AMP and cyclic GMP "in vitro", respectively.

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