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Biomedical subjects

J Bird

Publications and source records attributed to J Bird.

At least 73 records · Page 4Linked to original sources

The modulation of peritoneal macrophage chemiluminescence by acute pleural inflammation, prostanoids and cyclo/lipoxygenase inhibitors.

The chemiluminescent (CL) response of peritoneal macrophages was suppressed by induction 4 h earlier of an inflammatory reaction in the pleural cavity which was negated by prior administration of indomethacin, ketoprofen and BW 755C. These changes were accompanied by a concomitant rise in peritoneal PGI2 levels which was abolished by drug pretreatment. In vitro treatment of normal peritoneal macrophages with PGI2 inhibited their subsequent CL response. Indomethacin and ketoprofen produced elevated CL of macrophages obtained from untreated controls in vitro which was blocked by the lipoxygenase inhibitor NDGA. BW 755C and NDGA in vitro strongly inhibited macrophage CL and partially inhibited CL in a cell-free system. Use of these drugs in vivo demonstrated that indomethacin and ketoprofen augmented the CL response of peritoneal macrophages while BW 755C had no effect. These results suggest the inflammatory process per se can modulate the functions of macrophages in parts of the body remote from the inflammatory site. Moreover this modulation may be under the control of the prostanoid system.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

An appraisal of the technique of polymorphonuclear leukocyte chemiluminescence as a means to detect compounds with antiinflammatory activity.

The measurement of luminol-dependent chemiluminescence of inflammatory rat polymorphonuclear leukocytes (PMNs), when exposed to opsonized zymosan particles, has been used as a possible screening system for nonsteroidal antiinflammatory drugs (NSAID). An in vitro system may be used to detect NSAIDs, however the sensitivity is not of a high order. On the other hand an inhibitor of the lipoxygenase system (NDGA) and a dual lipo-cyclooxygenase inhibitor (BW755c) are easily detectable at low concentrations (10(-6)M). In parallel, an in vivo system has been developed, using rat PMNs from the same source, but pretreating the animals with drugs before induction of the inflammatory reaction and subsequent PMN collection. In this case NSAIDs, steroids, and dual lipo-cyclooxygenase inhibitors were readily detectable. It is suggested that this in vitro-in vivo system may prove useful in the detection of compounds that inhibit the lipoxygenase system or which have steroidal-like characteristics.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Modifications of host defence mechanisms by an acute non-immunological inflammatory reaction.

Mice developing an acute non-immunological inflammatory reaction were examined for modification of specific and non-specific defence mechanisms on the basis of previous observations that these animals displayed an increased resistance to bacterial and parasitic infections but an impaired resistance to neoplasia. Local acute inflammation was induced by injection into the pleural cavity of a non-antigenic, endotoxin-free irritant--calcium pyrophosphate microcrystals or low-molecular-weight dextran. Effector functions of macrophages at remote sites from the inflammatory focus were markedly stimulated. This was shown by: (a) an accelerated elimination of Listeria monocytogenes in the liver and spleen of mice with inflammation; (b) the acquisition of cytostatic activity for tumour cells by peritoneal macrophages; and (c) an enhancement of chemiluminescence emission and superoxide production in response to phagocytosis. Natural killer activity of spleen and peritoneal cells was stimulated in a biphasic manner. In contrast, cytolytic T cell differentiation upon in vitro immunization of spleen cells against allogeneic tumour cells was impaired. All these effects were observed very early (2 h) after the onset of inflammation and were still detectable at least 3 days after the inflammatory process had disappeared.

Animals↗

Release of interleukin I and low-molecular-weight lymphocyte-activating factors by rat peritoneal macrophages and its enhancement by acute non-specific inflammatory processes.

Peritoneal macrophages harvested from rats undergoing an acute non-specific inflammatory reaction induced by an injection of calcium pyrophosphate (CaPP) into the pleural cavity released increased amounts of interleukin I (IL-I)-like material. Lymphocyte-activating factors were also found in ultrafiltrates of the macrophage supernatants below 10 kd and 5 kd. A similar pattern of activity was observed when lysates of the macrophages were tested. In addition pre-exposure of normal peritoneal macrophages to an acute pleural inflammatory exudate before supernatant production enhanced the release of lymphocyte-activating factors found both in the unfractionated supernatant and a sub-5-kd ultrafiltrate. Thus these results demonstrate that an acute inflammatory reaction, initiated by a non-antigenic stimulus is able to stimulate macrophages remote from the inflammatory site to produce a factor which behaves like IL-I in a standard IL-I assay. The presence of low-molecular-weight factors (less than 5 kd) with similar activity may suggest that degradation of IL-I has taken place to yield active fragments. Acute inflammatory exudate also augments release of these factors which may be important in the pathogenesis of inflammation.

Animals↗

The reactivity of neutrophils at the site of an acute inflammatory reaction as measured by chemiluminescence.

In this study the technique of luminol-enhanced chemiluminescence (LECL), which was shown to be dependent on the generation of superoxide anion, has been employed to investigate the reactivity of polymorphonuclear leukocytes found at the site of inflammation. Cells derived from the pleural cavity of rats undergoing an acute inflammatory reaction initiated by an intrapleural injection of calcium pyrophosphate or normal serum demonstrated a significantly higher chemiluminescent response compared to cells derived from animals injected with plasma, saline or phosphate-buffered saline. In addition in vitro studies showed that calcium pyrophosphate crystals could stimulate the cells per se and could increase their reactivity.

Animals↗

Modification of the chemiluminescent response of rat thymocytes to concanavalin A by the acute non-specific inflammatory process.

Using the technique of concanavalin A-induced chemiluminescence (CL) as a measure of lymphocyte reactivity it has been demonstrated that the acute non-specific inflammatory process initiated by a non-diffusible, non-antigenic, endotoxin free irritant, was able to enhance the CL response of rat thymocytes. Maximum enhancement was observed 48 h after initiation of the inflammatory reaction. Serum derived from animals undergoing an acute inflammatory reaction as used above was fractionated using the technique of ultrafiltration to yield a fraction of molecular weight range 500-2000 daltons. When this fraction was cultured in vitro for 22 h with normal thymocytes, the CL response to concanavalin A was greatly enhanced when compared to thymocytes cultured in the presence of an equivalent fraction of normal serum. These findings demonstrate that during an acute non-immunological inflammatory reaction the function of the hosts thymocytes is enhanced. Furthermore, a low molecular weight factor (500-2000), with thymocyte stimulating activity, may be recovered from the serum of such animals very quickly (within 2 h) after initiation of the acute inflammation.

Animals↗

An in vitro effect of an acute non-specific inflammatory serum on rat lymphocytes proliferative response to PHA.

This study has demonstrated that serum obtained from animals undergoing an acute inflammatory reaction induced by an intrapleural injection of dextran is able to modulate the proliferative response to PHA of lymph node and spleen cells in vitro. This response is dependent on the concentration of the inflammatory serum and on the time of collection of the serum during the acute inflammatory process. At low concentrations of serum (0.5%) stimulatory activity was observed at all time points. At higher concentrations (1%) inhibitory activity was present in 24 and 72 h sera. These results support the previous observation that the acute non-specific inflammatory reaction is able to modify the function of different cell types. It has been suggested that both stimulatory and inhibitory factors are present and the balance between these changes during the course of the inflammatory reaction.

Animals↗

Teaching psychiatry to nonpsychiatrists: II. A model curriculum.

It is becoming increasingly clear that psychiatric and psychosocial needs of medical patients are not being adequately met. This need has led to an increasing emphasis on the psychiatric education of nonpsychiatrists at varying levels of experience. Given the many problems involved in these educational efforts, as well as the paucity of evaluation studies and the uncertainty of results, the authors argue that the systematic application of empirically-validated educational principles may lead to greatly improved effectiveness. In the first section of a two-part series, the authors reviewed educational methodology as it relates to the development of objectives, the selection of teaching procedures, and the use of evaluation techniques. The present paper, part-two, describes in detail a "model" curriculum for primary care residents that was developed according to these principles of educational methodology.

Curriculum↗

Direct and indirect in vivo stimulation of LAF-like production induced by acute nonspecific inflammatory processes.

Peritoneal macrophages harvested from animals undergoing an acute non-immunological inflammatory reaction induced by an injection of calcium pyrophosphate ( CaPP ) or dextran into the pleural cavity showed an enhanced level of production of a lymphocyte activating factor (LAF) like material. On the other hand, macrophages harvested from the site of inflammation did not show enhanced production of this activity when compared to macrophages derived from normal controls. This enhanced activity was observed for up to two/three days after initiation of the inflammatory reaction and was obtained in both the presence and absence of lipopolysaccharide (LPS) during in vitro cultivation. Thus these results demonstrate that the acute inflammatory reaction, initiated by a non-antigenic stimulus ( CaPP ), is able to stimulate macrophages remote from the inflammatory site to produce a factor which behaves like LAF in a standard LAF assay.

Animals↗

Effects of supernatants and lysates of polymorphonuclear leukocytes--lymphocyte mitogenic factors.

Rat polymorphonuclear leukocytes (PMNs), harvested from the site of a non-specific acute inflammatory reaction, liberated into culture fluids factors which not only enhanced the phytohaemagglutinin-induced proliferative response of thymocytes and lymph node cells, but were also mitogenic for these cells. This activity was associated with low molecular weight molecules (less than 10,000 daltons) and both these activities were also found in lysates of these PMNs. Our results suggest that inflammatory PMNs both contain and are able to release low molecular weight factors which can modulate lymphocyte function.

Animals↗

In vivo effects of an acute nonimmunological inflammation in rats on the lymphoproliferative response to mitogens.

Lymphoid cells (spleen, lymph node and thymus) derived from rats after induction of an acute nonimmunological inflammatory reaction responded to various mitogens (Phytohemagglutinin, PHA; Concanavalin A, Con A; Lipopolysaccharide, LPS) with increased proliferation when compared with cells derived from normal animals. In the absence of mitogens, lymphoid cells from animals undergoing an acute nonimmunological inflammation demonstrated enhanced proliferation compared with cells from normal animals. These results clearly demonstrated that during acute nonimmunological inflammation the reactivity of lymphoid cells was increased.

Acute Disease↗

Anti-inflammatory activity of the epimers of N-propyl 20 xi-dihydroprednisolonamide.

The epimers of a steroid carboxamide, N-propyl 20 alpha- and 20 beta -dihydroprednisolonamide, were evaluated for their local and systemic effects on granuloma formation, pituitary-adrenal function and liver glycogen content in rats. When the carboxamides were administered locally, the 20 beta-epimer exhibited greater activity than the 20 alpha-epimer in suppressing cotton pellet granuloma formation. Neither epimer had suppressive effects on thymus weight and plasma corticosterone levels at the dose level used. When the carboxamides were administered systemically, they were pharmacologically inactive. Furthermore, in acute pharmacological studies, the carboxamides neither increased tyrosine aminotransferase activity and glycogen deposition in the liver nor decreased plasma corticosterone levels and relative thymus weight.

Adrenal Glands↗

Nucleic acid metabolism in the nucleus and cytoplasm of angiosperm meiocytes.

Over the course of flowering plant evolution many important stages in the life cycle have become compressed into the period between the premeiotic mitosis and gamete maturation. For this reason the changes in structure or chemistry that take place at this time are not easily ascribed to particular 'developmental stages'. During the meiotic process itself striking changes occur in levels of cytoplasmic and nuclear RNA, while DNA is synthesized in both the chromosomes and organelles. Evidence is presented indicating that a large proportion of the m- and rRNA is purged from the meiocyte cytoplasm by a combination of normal degradation and the activity of specific hydrolases. DNA synthesis in both the plastids and mitochondria precedes the re-differentiation of these organelles, while that in the chromosomes occurs in two major peaks, as has previously been reported (Hotta & Stern, 1971). High-resolution autoradiography did not indicate either peak of DNA synthesis to be localized within the synaptonemal complex, although final confirmation of this conclusion must await further investigation. Examination of these events in organisms where meiosis is removed from other stages of the life cycle suggests that the degradation of RNA and the chromosomal DNA synthesis are features which regularly accompany the meiotic process. The significance of these findings is discussed in terms of the hypothesis that there is at least one stage in the life cycle of all plants at which a purge of information-carrying molecules takes place.

Cell Differentiation↗

Rat and human polymorphonuclear leukocyte derived lymphocyte stimulatory factors.

The kinetic release of lymphocyte activating factors by inflammatory rat polymorphonuclear leukocytes (PMNs) into culture fluid was studied. PMNs, collected from the pleural cavity of rats 4 hours after injection of either calcium pyrophosphate (CaPP) or normal plasma, released into the supernatant culture fluid, factors which enhanced the phytohaemagglutinin-induced proliferative response of normal lymph node cells or thymocytes, the optimal culture time being 24 hours. A major portion of these lymphocyte activating factors was found in the ultrafiltrates (less than 10,000 daltons) of PMN supernatants. The activities in both unfractionated supernatant and the ultrafiltrate were significantly enhanced if PMNs were exposed to Concanavalin A (Con A) or inflammatory exudate prior to supernatant production. Also, these were not species specific as rat PMN supernatant can stimulate the phytohaemagglutinin-induced response of human lymphocytes and, conversely, human PMN factors can stimulate rat thymocytes.

Animals↗

Effects of supernatants and lysates of polymorphonuclear leucocytes: macrophage stimulatory factors.

Polymorphonuclear leucocytes (PMN) were harvested from the site of a non-specific acute inflammatory reaction. When cultured in vitro for 24 h the cells liberated into the supernatant factors which could enhance the proliferation of normal macrophages in the absence and presence of the mitogen phytohaemagglutinin (PHA). Similar activity was found in lysates of these cells. Using the technique of ultrafiltration it was shown that the mitogenic factors present in both PMN supernatants and lysates were under 10 000 daltons molecular weight. In addition, the chemiluminescent responses of normal macrophages were also enhanced by PMN supernatant, lysate and their respective ultrafiltrates. Our results suggest that the PMNs, which are the most abundant cell type during acute inflammation, both contain and are able to liberate low-molecular-weight macrophage-stimulatory factors which may be important in our understanding of the pathogenesis of inflammation.

Animals↗

Putrescine--a potent endogenous anti-inflammatory substance in inflammatory exudates.

Sponge-induced exudate from the rat and saline extracts of normal rat liver and rat liver damaged in situ by dimethylnitrosamine have been assayed for putrescine, spermidine and spermine levels. The three physiological oligoamines have been examined for anti-inflammatory activity by the carrageenan-induced oedema rat model and spermidine and putrescine were found to be anti-inflammatory with putrescine being about ten times as active as spermidine. Putrescine was also anti-inflammatory in the adjuvant arthritic rat model. Thioacetamide and theophylline were also anti-inflammatory and theophylline doubled the level of putrescine in rat liver. It was concluded that putrescine was a potent anti-inflammatory factor in the inflammatory exudates and extracts examined.

Animals↗

Anti-inflammatory factors in sponge-induced exudate in the rat.

Sterile polyester sponge-induced exudates in the rat have been investigated for high molecular weight substances with anti-inflammatory activity against carrageenan-induced oedema in the rat. The only substances found with this activity were dialysable molecules. Crude but sterile protein fractions isolated from exudate stabilized guinea-pig macrophages at low concentrations. The proteins present in exudates appeared to be identical to normal rat plasma proteins. It is concluded that anti-inflammatory activity associated with high molecular substances in exudate may have been due to bacterial contamination.

Acid Phosphatase↗