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Biomedical subjects

W Boyle

Publications and source records attributed to W Boyle.

At least 37 records · Page 2Linked to original sources

Acute effects of cocaine on catecholamines and cardiac electrophysiology in the conscious dog.

To evaluate the electrophysiologic and neurohumoral effects of cocaine on the sinus node, atrium, atrioventricular node, and His-Purkinje system, 14 conscious dogs were studied before and after an infusion titrated to maximum tolerance or to increase the systolic blood pressure by at least 15%. Plasma cocaine and catecholamine levels, blood pressure, surface and intracardiac electrograms were recorded. Programmed electrical stimulation was performed from the right atrium. The sinoatrial conduction time, paced PR interval, atrioventricular nodal conduction time, atrioventricular nodal effective refractory period and blood pressure increased. Plasma noradrenaline, adrenaline and dopamine increased and remained at two to three times control levels throughout the study although plasma cocaine levels declined. Adrenaline levels were strongly correlated with the hemodynamic response while plasma cocaine levels were not. No sustained spontaneous atrial or ventricular arrhythmias were recorded after cocaine infusion. Atrial fibrillation with a slow ventricular response was induced by pacing after cocaine in only three dogs. There were no significant changes in pacing threshold, right intra-atrial conduction time, infranodal conduction time, heart rate, QRS or QT. No pacing induced infranodal block occurred. The cocaine dose rate infused was 2.8 +/- 1.2 mg/kg; cocaine plasma levels were 1402 +/- 885 ng/mL immediately after the initial infusion and 525 +/- 321 ng/mL at the end of the study. It is concluded that in normal canine heart cocaine increases blood pressure, sinoatrial conduction time, atrioventricular nodal effective refractory period, paced PR interval, atrioventricular nodal conduction time, plasma catecholamines and susceptibility to atrial fibrillation. These findings cannot be explained solely by increased sympathetic nervous system activity and suggest participation of the parasympathetic nervous system.

Animals

Cystic hamartomata of lung and kidney: a spectrum of developmental abnormalities.

We report on a developmental malformation of the lung and kidney which has not been previously described and which we have chosen to call "cystic hamartomata of the lung and kidney" to emphasize the non-malignant nature of these lesions. We also confirm a previous case report by Weinberg and Zumwalt [1977] as a different distinct disorder that results in a multifocal cystic hamartomata of the lung with associated marked parenchymal overgrowth of the kidney (the Weinberg-Zumwalt syndrome). These cases represent a spectrum of abnormal morphogenesis affecting both kidney and lung. Patients 1 and 2 presented during infancy with abdominal masses and hypertension due to bilateral multilocular cysts of the kidney with associated hamartomatous pulmonary cysts; patient 2 also had one area of cellular mesoblastic nephroma. Patient 3 demonstrated markedly hyperplastic renomegaly with medullary dysplasia in association with bilateral cystic hamartomata of the lungs. During the fifth week of gestation, the ureteric bud invades the unsegmented mesoderm that becomes the metanephric system, and the lung bud invades the splanchic mesoderm, which provides the stimulus for its growth. We suggest that the predominant pattern of a congenital kidney or lung hamartoma might reflect the timing of a prenatal neoplastic event affecting these developmental processes.

Hamartoma Syndrome, Multiple

Depletion by monolayer binding of specific precursors of antibody-forming cells directed against cellular antigens.

Conditions have been established to permit poly-L-lysine (PLL)-attached cell monolayers to adsorb specific antibody-forming cell precursors (AFCP) from immune spleen cell populations as a negative selection technique. In a model system, sheep red blood cell (SRBC) immune spleen cells were adsorbed onto SRBC monolayers and the cells remaining non-adherent transferred to irradiated recipients. Subsequent to SRBC immunization, these recipients showed up to 95% reduction in splenic anti-SRBC plaque-forming cells (PFC) compared with recipients of control cell populations which had not been exposed to a SRBC monolayer. The depletion observed was shown to be antigen-specific and the extent of depletion comparable with that attained by removal of anti-SRBC AFCP as rosettes. The depletion of AFCP directed against mouse (EL4) and human (QIMR-WIL) leucocyte antigens was then examined. Mixtures of spleen cells immune to EL4 and WIL cells were adsorbed onto PLL-attached monolayers of EL4 or WIL cells, and spleen cells remaining non-adherent transferred to irradiated recipients which were then immunized with either of these cell types. Analysis of recipient serum samples by determination of antibody titre and by immunoblotting indicated that the response to the cell type used in the adsorbing monolayer had been specifically depleted while the response to the other cell type remained unchanged or only slightly impaired. The maximum level of depletion occurred on Day 7 after transfer and declined thereafter. The application of this procedure to improve the frequency of production of spleen cell hybridomas directed against leucocyte differentiation antigens is discussed.

Animals

Isolation of macrophages from human placenta.

Human placentae have been extracted with combinations of enzymes to optimize the release of mononuclear phagocytes. A mixture of trypsin-DNAase used in sequential extraction was found to provide the best yield of adherent cells which were stable in culture. The majority of adherent cells exhibited phagocytic function and expression of receptor for IgG-Fc (FcR). Subsequent studies established that these functions were co-expressed by the same cells. The FcR+ cells were also shown by immunofluorescence with monoclonal antibodies to display monocyte-macrophage distinctive antigens and class I and class II MHC antigens. The placenta has thus been shown to provide a rich source of class II-positive macrophages suitable for immunological studies.

Antigens, Surface

In vivo and in vitro analyses of the immunogenicity of B16 melanoma cells.

In vitro grown B16, an H-2b melanoma cell line, was found to kill B10 (H-2b), B10.BR (H-2k), CBA (H-2k), and BALB/c (H-2d) but not B10.D2 (H-2d) mice. BALB/c mice could be protected against a lethal dose of B16 by co-administration of H-2b spleen or peritoneal exudate cells, suggesting B16 was susceptible to an immune response but unable to induce it. However, evidence for the immunogenicity of B16 tumour in vivo was shown in two ways--(i) by immunization with irradiated B16 before lethal tumour challenge, and (ii) by demonstration of specific immunity in BALB/c mice which survived a low dose of viable B16 tumour. The resistance of most B10.D2 mice to doses of B16 tumour which were lethal to four other strains of mice was also compatible with the immunogenicity of B16 in vivo. By contrast, B16 was unable to induce a primary Tc-cell response in vitro but was able to induce a secondary response. The significance of these results for theories of T cell immunity to foreign tissue and for improving immunogenicity of tumours is discussed.

Animals

Enrichment and expansion of specific antibody-forming cells by adoptive transfer and clustering, and their use in hybridoma production.

Adoptive transfer regimens have been examined as a method of enriching and expanding antibody-forming cells (AFC). When spleens from mice which had reverted to memory or from those at the peak of an AFC response were transferred to syngeneic irradiated recipients, a comparable enrichment in AFC of about 10-fold was found. However, recently re-stimulated spleen cells gave much better expansion of total AFC in the recipient mice. The degree of expansion was examined using different routes and timing of antigen stimulus and AFC recovery. With the optimum protocol found the AFC pool obtained from adoptively-transferred recipients was on average 80-fold greater than from conventionally re-immunised mice in a number of experiments. Further enrichment of the AFC was shown by an in vitro clustering technique which gave suspensions with AFC enriched to better than 1 cell in 10. Cluster-enriched and adoptive-transfer enriched populations were both shown to give a much higher incidence of successful specific hybridoma production than spleen cells from conventionally re-immunised mice.

Animals

Separate clones of cytotoxic T lymphocytes are generated against private and public H-2 antigens.

By cytolysis and monolayer absorption tests, the kinetics of the generation of CBA/H cytotoxic lymphocytes (Tc) in response to stimulation by H-2b antigens have been analyzed in vitro. The Tc population which reacts with public antigens of H-2b and H-2d strains shows peak activity in culture at 4 to 5 days, then rapidly decreases. The population with cytotoxic activity against the private antigens of H-2b cells peaks later and persists longer. The antipublic cytolytic activity was shown to be specific and not attributable to antibody-dependent cell-mediated cytotoxicity (ADCMC), but was attributable to Ly1-, 2+ effector cells. By suitable conditions of absorption on C57BL/10 monolayers, the precursors of the antiprivate clone could be selectively removed without impairing the antipublic H-2d response. These and previous results present an argument that the cross-reactivity which Tc display on different H-2 haplotypes is attributable to clones directed against shared determinants and is not attributable to low affinity binding of Tc activated by private H-2 antigens.

Absorption

Depression of peripheral lymphocyte proliferation and hemolytic antibody production in passively enhanced rat renal allograft recipients.

Specific suppression of renal allograft rejection in two strain combinations of rats by passive enhancement was associated with depression of both peripheral lymphocyte proliferation and hemolytic antibody production. Variations in these responses were related to allograft survival in individual rats. In general, these studies confirm the value of monitoring both the lymphocyte proliferation and hemolytic antibody responses for the prediction of subsequent rejection, and for evaluating the efficacy of the enhancement therapy.

Animals