Biomedical subjects

M M Little

Publications and source records attributed to M M Little.

8 recordsLinked to original sources

PubMed1993

Platelet-activating factor-induced human eosinophil transendothelial migration: evidence for a dynamic role of the endothelium.

Stimulated migration of eosinophils out of the bloodstream and into the lung is key in the development of tissue eosinophilia and inflammation in asthma. Platelet-activating factor (PAF) has been implicated as an important inflammatory mediator in asthma pathogenesis in part because of its chemotactic capacity. We therefore studied the ability of PAF to induce human peripheral blood eosinophil migration through naked filters and human umbilical vein endothelial cells (HUVECs) cultured on these filters. PAF induced eosinophil migration through both barriers in a time-dependent fashion, with maximal eosinophil migration occurring at 180 min. Significant eosinophil migration was observed at PAF concentration > or = 0.1 microM and was dose dependent up to 10.0 microM. No significant differences in eosinophil chemotactic responses were noted between naked filter and HUVEC barriers. The PAF receptor antagonist, WEB 2086, inhibited (> 85%) eosinophil transendothelial migration when co-incubated with PAF or when used as a pretreatment of either the eosinophils or HUVECs. However, WEB 2086 pretreatment of HUVECs did not inhibit PAF-induced neutrophil transendothelial migration, nor did it affect leukotriene B4-induced neutrophil or eosinophil transendothelial migration. Thus, the data indicate that the endothelial cell plays an important role in PAF-induced eosinophil inflammatory processes. Moreover, these data suggest that PAF's pathogenic role in asthma may in part be due to its ability to stimulate eosinophil migration across endothelial barriers and into the airways.

Azepines↗

PubMed1991

Comparison of platelet-activating factor-induced chemotaxis of normodense and hypodense eosinophils.

Platelet-activating factor (PAF)-induced eosinophil (EOS) migration is an important event in the development of tissue eosinophilia and allergic inflammation. EOSs are heterogeneous cells in that different states of activation have been ascribed to EOSs of varying densities. We therefore studied the ability of PAF to induce hypodense and normodense EOS chemotaxis. Both hypodense and normodense EOSs were isolated in pure form from seven subjects and studied concurrently. Dose-response and time-course experiments indicated no significant differences in PAF-induced hypodense versus normodense EOS chemotactic responses. Hypodense and normodense cells achieved maximal chemotaxis in response to 1 mumol/L of PAF, and maximal chemotaxis was achieved at 2 hours. However, marked differences in PAF-induced EOS chemotactic responses existed between patients. We conclude that PAF is a potent EOS chemoattractant, and despite reported differences in metabolic activity, normodense and hypodense EOSs exhibit similar chemotactic responsiveness to PAF.

Adult↗

PubMed1989

Azelastine inhibits stimulated histamine release from human lung tissue in vitro but does not alter cyclic nucleotide content.

To investigate the mechanism by which azelastine may be effective therapeutically in asthma, we studied its ability to inhibit anti-IgE- and calcium ionophore A23187-stimulated histamine release from human lung and to alter lung cyclic nucleotide levels. Significant inhibition of histamine release from both anti-IgE- and A23187-stimulated human tissue was apparent after 30 minutes preincubation of the lung tissue in azelastine. Significant inhibition of anti-IgE-stimulated histamine release was consistently seen in azelastine concentrations greater than or equal to 5 microM, and was dose dependent (r = 0.71, p less than 0.05) with maximal mean inhibition of 53 +/- 11%. For A23187-stimulated lung tissue, consistent inhibition of histamine release was not found until we used 30 microM azelastine, mean 35 +/- 11%. Inhibition in azelastine concentrations below 30 microM was variable and not significant. Lung cyclic AMP and cyclic GMP content was not significantly altered by incubation of lung tissue in 100 microM azelastine. We conclude that azelastine inhibits stimulated histamine release from human lung tissue in vitro but does not alter cyclic nucleotide content.

Antibodies, Anti-Idiotypic↗

PubMed1989

Azelastine inhibits IgE-mediated human basophil histamine release.

To examine the mechanism potentially contributing to therapeutic efficacy of azelastine in allergic rhinitis and asthma, we studied the effect of azelastine on stimulated histamine release from basophils prepared as a mixed leukocyte suspension from human blood. Azelastine was found to significantly inhibit anti-IgE-stimulated basophil histamine release. Time-course experiments indicated that the inhibitory effect of azelastine was immediate and that preincubation of basophils in azelastine was not necessary. In dose-response experiments with azelastine, 1 to 100 mumol/L, significant inhibition of histamine release was consistently observed in azelastine concentrations greater than or equal to 10 mumol/L. This inhibition was dose dependent (r = 0.96; p less than 0.001) with maximal mean inhibition of 91 +/- 8% at 100 mumol/L of azelastine.

Basophils↗

PubMed1989

Elevated BAL fluid histamine levels and parenchymal pulmonary disease in rheumatoid arthritis.

To determine the amount of histamine in BAL fluid in subjects with RA and to ascertain if elevated histamine levels were associated with parameters of active pulmonary disease, we measured BAL fluid histamine levels in 31 subjects with RA and 36 normal subjects. The subjects with RA had a significantly greater mean BAL histamine level than the normal subjects, (313 +/- 154 pg/ml vs 18 +/- 8 pg/ml; p less than 0.05). When the subjects with RA were divided into three groups based on chest radiograms (1 = normal; 2 = pleural disease only; 3 = interstitial or nodular disease), we found that subjects in group 3 had significantly lower values for TLC and D. Subjects in group 3 also had higher percentages of BAL neutrophils and eosinophils and higher BAL histamine levels (group 1, 115 +/- 52 pg/ml; group 2, 30 +/- 30 pg/ml; and group 3, 1,182 +/- 709 pg of histamine per milliliter). Moreover, BAL histamine levels were negatively correlated with TLC (r = -0.46; p = 0.01) and FVC (r = -0.45; p = 0.01) and positively correlated with BAL neutrophils (r = 0.6; p = 0.0003) and BAL eosinophils (r = 0.89; p = 0.0001). These data suggest that the BAL histamine level may be a useful marker to determine the activity of pulmonary disease in RA.

Arthritis, Rheumatoid↗

PubMed1986

Depression and hemispheric site of cerebral vascular accident.

In order to investigate the possible role of left and right hemisphere neural structures in the manifestation of depression, 50 left brain damaged and 50 right brain damaged stroke inpatients were administered the Zung Depression Scale (ZD S) during the course of the rehabilitation phase of their treatment. These subjects were randomly chosen from all stroke patients receiving rehabilitation services who could be administered the ZDS. Approximately 30% of these subjects, regardless of the site of lesion, were clinically depressed. The severity of depression was independent of demographic factors and time since injury. Right brain damaged patients reported significantly more sleep disturbance, psychomotor agitation and pervasive sense of sadness. These results were discussed in light of previous findings that damaged to the left hemisphere results in greater depression. A model of reactive depression that results from neurological disability was proposed to partially account for these findings.

Journal Article↗

PubMed1986

Clinical memory tests and everyday memory.

This study examined the relationship between clinical memory tests and everyday memory abilities. Fifty older adults were given clinical memory tests, a battery of everyday tasks and a self-report questionnaire of memory problems. The interrelationships among these groups of memory assessment measures were studied using Pearson correlations and multivariate canonical analysis. The resulting intercorrelations and canonical variate loadings were low to moderate in overall magnitude. The self-assessment of memory problems had a much lower relationship to everyday and clinical memory tasks. The self-assessment of memory for reading material had the strongest relationship to clinical memory tests. In general, these results moderately support the use of clinical memory tests to predict everyday memory ability.

Journal Article↗

PubMed1984

Combined intracoronary streptokinase and percutaneous coronary angioplasty for reperfusion of chronic total coronary occlusion.

In a 40 year old man with a 1 month total occlusion of a dominant right coronary artery, persistent angina despite medical management indicated inadequate coronary collateral supply to the posterolateral myocardium originally supplied by the totally occluded vessel. Initial attempts at reperfusion of the chronically occluded vessel with an angioplasty guide wire and balloon were unsuccessful. However, administration of intracoronary streptokinase resulted in partial reperfusion, after which successful wire-guided balloon angioplasty was accomplished. This case illustrates the potential utility of combining a thrombolytic agent with angioplasty in attempting reperfusion for management of selected cases of chronic total coronary artery occlusion.

Adult↗