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Biomedical subjects

C Winder

Publications and source records attributed to C Winder.

At least 37 records · Page 2Linked to original sources

Expression of procoagulant activity by equine lung macrophages: stimulation by blood lymphocytes.

Increases in procoagulant activities (PCA) in equine lung macrophages were induced by non-adherent blood lymphocytes which were prestimulated with phytohaemagglutinin for 48 to 72 hours or by supernatants harvested from prestimulated blood lymphocyte cultures. However, prestimulated lymphocyte suspensions themselves expressed PCA which was most probably derived from contaminating monocytes. Because non-adherent cells from lymphocyte suspensions may have attached to adherent macrophages, cells within lymphocyte suspensions might have contributed to the PCAs expressed by lymphocyte-stimulated lung macrophages. Stimulation of lung macrophages for 24 hours by supernatants of phytohaemagglutinin-prestimulated blood lymphocytes induced a significantly greater PCA increase than stimulation by phytohaemagglutin alone. Thus, cytokines from lymphocyte cultures might have triggered or enhanced PCA induction. Direct stimulation of lung cell preparations with phytohaemagglutinin for 48 hours resulted in a progressive increase of PCA in only two of five specimens tested. The failure to induce PCA in three specimens could be due to the absence of sufficient numbers of T cells within the adherent lung cell preparations. In conclusion, PCA response of equine lung macrophages might be lymphocyte-stimulated in which case PCA might be a useful tool for monitoring the processes of cell-mediated immunity in horses.

Animals↗

Spontaneous and lipopolysaccharide-induced expression of procoagulant activity by equine lung macrophages in comparison with blood monocytes and blood neutrophils.

The procoagulant activity (PCA) associated with equine bronchoalveolar lavage cells was determined and compared with that expressed by peripheral blood mononuclear cells and neutrophils. Lung cell preparations from horses affected with chronic pulmonary disease were included in all experiments and there was no difference in the qualitative type of response compared with lung cells which were obtained from healthy horses. Significant amounts of PCA were expressed by cells freshly procured from bronchoalveolar lavages of healthy and diseased horses. When adherent lung cells were kept in culture for some time, cell-associated PCA slightly decreased within 4 h, reached its lowest point after approximately 24 h and rose again during the second week of culture. In contrast, freshly isolated blood mononuclear cells or neutrophils expressed little PCA. Following culture for 24 h, mononuclear cells began to express increased PCA levels. Both cultivated lung cells (comprised mainly on alveolar macrophages) and blood mononuclear cells responded to LPS by dramatically increased PCA expression, whereas neutrophils showed a small augmentation of PCA on LPS stimulation. Fresh mononuclear cells and cultivated lung cells differed in their PCA response to LPS in several respects. Blood mononuclear cells were more sensitive to LPS than lung macrophages and responded to a 100-fold lower LPS concentration than the latter. Mononuclear cell-associated PCA peaked 4 h after stimulation whereas that of cultured macrophages continued to increase up to 24 h after stimulation. Lung macrophages cultured in adherence responded to LPS stimulation with a much higher PCA increase than macrophages cultured in suspension, in teflon containers. However, the culture vessel did not influence the PCA expressed by unstimulated cells. PCA expression depended to a large extent on transcription and translation, as evidenced by a 60-85% reduction of PCA in cycloheximide- or actinomycin D-treated, LPS-stimulated lung macrophages. PCA was largely cell-associated; only a small proportion of cell-associated PCA was shed into the medium. The PCA associated with mononuclear cells and with lung macrophages was tissue factor because of its dependence on clotting factor VII and its independence from clotting factor VIII. The expression of PCA by freshly isolated cells, the lower sensitivity to LPS, and the loss of PCA in the first 24 h of cultivation are indicative of in vivo activation of lung macrophages.

Animals↗

Neutrophil migration induced by equine respiratory secretions, bronchoalveolar lavage fluids and culture supernatants of pulmonary lavage cells.

Supernatants of equine respiratory secretions enhanced the migration of equine neutrophils into the lower compartments of Boyden chambers. Checkerboard analysis revealed that the neutrophil migration promoting activity (NMPA) of secretion specimens was in great part caused by chemokinesis, irrespective of the neutrophil score of the specimen. The NMPA of respiratory secretions was correlated neither with the neutrophil score of the secretion specimen nor with the severity of the chronic pulmonary disease. Respiratory secretions collected while horses were kept under low dust or under dusty housing conditions induced migration of neutrophils in the same order of magnitude. The number of migrated neutrophils and the procoagulant activity (PCA) within respiratory secretion specimens was positively correlated; however, the meaning of this finding is not yet clear. None of the nine cell-free supernatants of bronchoalveolar lavage fluid, which were assayed undiluted, induced significant neutrophil migration, although some samples contained up to 4.0 x 10(5) neutrophils/ml. In vitro culture of lung lavage cells, which mainly comprised macrophages and lymphocytes, without stimulation or with the addition of low doses of phytohemagglutinin (PHA) resulted in the secretion of NMPA which was in great part chemotactic. However, culture supernatants of lung cell preparations which were stimulated by lipopolysaccharide (LPS) or by PHA-prestimulated lymphocytes reduced the migration of neutrophils compared with the supernatants of control cells. NMPA within culture supernatants had a highly significant negative correlation with the PCA of macrophages within the lung cell preparations. Our results imply that a complicated and sophisticated regulation underlies neutrophil accumulation within the airways of horses affected with chronic pulmonary disease. Future experiments are required to assess the biological significance of the factors modulating neutrophil migration which are present in the respiratory secretions and in the culture supernatants of equine lung lavage cells.

Animals↗

Separation of equine bronchopulmonary lavage cells by density gradient centrifugation and expression of procoagulant activity in unpurified cells and cell subpopulations.

Bronchopulmonary lavage was performed in 10 healthy horses and in 39 horses with chronic pulmonary disease. The predominant cell types were macrophages in healthy horses and neutrophils in severely diseased horses. Procoagulant activity (PCA) was detected in all 32 cell-free supernatants examined and in all 49 unpurified cell suspensions. Cells were separated by centrifugation on discontinuous gradients prepared either with Percoll or with Metrizamide. Macrophages were enriched in subpopulations of low density. Neutrophils could not be purified by density gradient centrifugation using either gradient medium. PCAs of cell subpopulations were plotted against their respective macrophage, neutrophil, and lymphocyte content. PCA was positively correlated with macrophage content (P less than 0.001) and negatively correlated with neutrophil (P less than 0.02) and lymphocyte (P less than 0.001) content. Therefore, PCA of equine lung cells most likely originates from macrophages as shown in other species. The density shift of lung neutrophils requires further investigation.

Animals↗

A fresh start. Report of a one-day workshop on occupational asthma in the aluminium industry.

The workshop was successful from a number of viewpoints. It achieved the general goal of a greater understanding of respiratory problems in the aluminium industry. A free exchange of information and attitudes occurred. While the prevalence of asthma was not high compared with other occupational asthmas, it was noteworthy. The industry had embarked on a programme for the development of standard criteria of diagnosis and of the collection of statistics that related to the condition. Some concerns remain. It is to be hoped that further developments will be derived from the workshop, including opportunities for research and for a better understanding of the occupational-health issues and practices in the primary aluminium industry in Australasia.

Aluminum↗

Putative serotonergic bipolar and amacrine cells in the chicken retina.

Four populations of putative serotonergic cells could be detected in the chicken retina by histofluorescence and immunohistochemistry. Numerous (10,000/mm2) small (6 micron diameter) bipolar cells were located towards the middle of the inner nuclear layer, as were sparser (1000/mm2) larger (12 micron diameter) amacrine cells. Very sparse large (greater than 30 micron diameter) and more numerous small (12 micron diameter) ganglion cells were also detected. Prominent fibre plexuses were detected in the inner plexiform layer, close to the inner nuclear and ganglion cell layers, and appeared to be formed by the processes of the bipolar cells, amacrine cells and at least the large ganglion cells. Exogenous serotonin (5-HT) was detected in the chicken retina. From the effects of neurotoxins on 5-HT levels and 5-HT-like immunoreactivity (5-HTLI), most of this appeared to be associated with the amacrine cells. 5-HTLI bipolar cells were selectively destroyed by intravitreal injections of 5-10 nmol of kainic acid, while 5-HTLI amacrine cells were destroyed by N-methyl-D,L-aspartic acid and 5,7-dihydroxytryptamine. The sensitivity of the bipolar cells to kainic acid indicates that they are OFF-cells.

5,7-Dihydroxytryptamine↗

Procoagulant activity in respiratory tract secretions from horses with chronic pulmonary disease.

Cell-free supernatants (sol phases), obtained after centrifugation (50,000 x g for 45 minutes) of respiratory tract secretions from horses with chronic pulmonary disease, were assayed for procoagulant activity (PCA) in a one-stage clotting assay. Of the 103 specimens tested, 59% (61) contained PCA. Procoagulant activity was detected most often in respiratory tract secretions of severely affected horses and was correlated with the quantity of neutrophils in the respiratory tract secretions. In 12 of the 17 secretions tested, the clotting time was decreased in a dose-dependent manner. However, in the coagulation assay, some reversal of PCA or inhibition of coagulation was observed in 4 secretion specimens when greater volumes of sol phase were added. Procoagulant activity was characterized tentatively as tissue factor, because it was temperature stable and was inhibited by phospholipase C and by concanavalin A. Clotting was induced in factor VIII-deficient human plasma; however, with the exception of 1 respiratory secretion specimen, clotting was not enhanced in factor VII-deficient human plasma. Procoagulant activity is a useful indicator of airway inflammation.

Animals↗

Review of 125 children 6 years of age and under who were sexually abused.

The authors present a chart review of 125 children, 6 years of age and under, who presented between early 1981 and mid 1983 to an acute care hospital because of sexual abuse. They represented one-third of the cases of alleged sexual abuse between infancy and 18 years of age referred to the hospital's multidisciplinary sexual abuse team. The ratio of females to males was 3.3:1. Sixty percent of the children were victims of intrafamilial abuse. Of the preschoolers, 72.5% were victims of intrafamilial abuse. At school age there was a reversal with 73% of 6 year olds being abused by extrafamilial offenders. The duration of the abusive relationship was greater in intrafamilial abuse. Purposeful disclosures were more frequent overall but were significantly less frequent when the perpetrator was intrafamilial or when the child was a preschooler. Two-thirds of the children had physical and/or behavioral symptoms. Parents of children who had been the victims of intrafamilial abuse were more likely to be separated or divorced. The difficulties in assessing young victims of alleged sexual abuse and the implications of the findings in this review are discussed.

Child Abuse↗

Influences of endogenous dopamine on carotid body discharge and ventilation.

Ventilatory and carotid body responses to hypoxia have been related to the endogenous release of dopamine by use of the antagonist drug haloperidol. The published studies have produced conflicting data for ventilation. However, antagonist drugs can act at multiple anatomical sites, on multiple pharmacological receptors, often at different dosages, and have nonspecific actions at high dosage. For these reasons, we have undertaken a systematic study of haloperidol dose-response curves with particular emphasis on the lowest possible concentrations of drug. In five cats anesthetized with pentobarbital sodium (30-35 mg/kg), single- or few-fiber afferent recordings of the carotid body showed that haloperidol increased the discharge during both basal and asphyxic conditions, the increments being proportional to haloperidol dosage (0.1-1,000 micrograms/kg). Increments of ventilation were also produced, these increments increasing only over the lower range of dosage; at the highest haloperidol dosage, the dose response showed a tendency to plateau or inflect downward, suggesting the appearance of an opposing inhibitory mechanism.

Animals↗

The experimental administration of lead to rats in neuropathological and behavioural studies.

The experimental investigation of the effects of lead have been studied for nearly 20 years. In that time, a variety of neurobiological processes have been reported to be altered following ingestion of lead. Most routes of administration and a bewildering number of doses have been employed to administer lead to experimental animals. However, inadequate characterization of dose regimes has impaired understanding of any effects, and their correlation to conditions of human exposure. As an index of lead burden, blood lead remains the most reliable means of assessing recent lead absorption. It is clear that a large number of model systems and dosing regimes do not address the problems of human clinical or subclinical lead intoxication. It is also clear from brain lead measurements in experimental animals that lead is selectively sequestered into specific areas of the control nervous system.

Aging↗

The effect of perinatal lead administration on the ontogeny of striatal enkephalin levels in the rat.

The effect of administration of lead in the maternal drinking water from conception to weaning on enkephalin levels in the developing rat striatum was studied between 10 and 100 days after birth. Concentrations of 300 and 1000 ppm Pb produced no overt toxicity in terms of effects on body and brain weight. However, marked differences in striatal enkephalins were observed. In lead-dosed animals enkephalin content was up to 50% lower at 10 and 21 days postpartum, and in addition lead appeared to delay the attainment of adult levels of this opioid neurotransmitter. Measures at later time points indicated that the effects of lead on enkephalin are reversible. The results suggest that lead depresses and delays the ontogeny of the enkephalinergic system within the striatum.

Animals↗