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Biomedical subjects

H H Newball

Publications and source records attributed to H H Newball.

At least 37 records · Page 2Linked to original sources
PubMed1981

Anaphylactic release of thromboxane A2, prostaglandin D2, and prostacyclin from human lung parenchyma.

Antigen challenge of passively sensitized chopped human lung resulted in the generation of several arachidonic acid cyclooxygenase metabolites (AACM): thromboxane A2 (TxA2) as measured by its stable metabolite TxB2, prostaglandin D2 (PgD2), prostacyclin (PgI2) as measured by its stable metabolite 6-keto-PgF1 alpha, prostaglandin F2 alpha (PgF2 alpha), and prostaglandin E (PgE). The kinetics of AACM release after antigen challenge paralleled histamine release. All AACM were released in an antigen dose-dependent manner and reached maximal release at antigen concentrations lower than those required for maximal histamine release. Quantitatively, of the AACM measured, PgD2 and PgI2 were found to predominate in anaphylactic reactions of human lung parenchyma. Generation of PgD2 and PgI2 were 3- to 7-fold greater than that of other AACM measured. Thromboxane B2 was generated in quantities comparable to PgE and PgF2 alpha. Studies were designed to test the hypothesis that lung smooth muscle contraction per se can account for the generated AACM that are released during anaphylaxis of the lung. The studies compared antigen-induced AACM generation with methacholine-induced (10(-4) M) AACM generation. The failure to confirm this hypothesis was especially evident for PgD2 where release was dependent on mast cell activation. Thromboxane A2, PgD2, and PgI2 have been reported to have potent effects on smooth muscle. Our data suggested that these AACM are generated in such sufficient quantities that they may function in important aspects of the modulation of hypersensitivity responses in human lungs.

Anaphylaxis↗
PubMed1980

Prostaglandin F-2 alpha functions as a local hormone on human airways.

Vasoactive hormones may be classified either as 'local' or as 'circulating', depending on whether they are or are not removed by the pulmonary circulation. Prostaglandin F-2 alpha is partially removed by the human pulmonary circulation. We examined the hypothesis that, with respect to the human lung, PGF-2 alpha functions as a local mediator. Prostaglandin F-2 alpha was given to normal and asthmatic subjects via both intravenous and aerosolized routes, and we measured specific airway conductance, spirometry, functional residual capacity, and closing volume. Aerosolized PGF-2 alpha induced significant changes of all measured parameters in both normals and asthmatics, while intravenous PGF-2 alpha-induced changes were limited to the FVC in both normals and asthmatics. The data suggest that intravenous PGF-2 alpha induced constriction of peripheral lung units. The greater sensitivity of the peripheral lung units of asthmatics versus normals to PGF-2 alpha, suggest that the increased sensitivity of airway smooth muscle of asthmatics versus normals to PGF-2 alpha is not restricted to the conducting airways, but extends to the smooth muscle of the peripheral lung units. The data is consistent with the hypothesis that, with respect to the lung, PGF-2 alpha functions as a local hormone, but, furthermore, suggest that, possibly of greater importance than the definition of a hormone as 'local' or 'circulating', is the definition of the intrinsic properties of the muscles on which the hormone is exerting its effects.

Adolescent↗
PubMed1980

Basophil mediators and their release, with emphasis on BK-A.

During IgE-mediated events, basophils secrete small molecular weight mediators (histamine, slow reacting substance, Eosinophil chemotactic factor) which are thought to participate in inflammatory processes. We here describe the IgE-mediated secretion of large molecular weight mediators which have the potential for the activation of the Hageman factor dependent pathways, and the generation of biologically active peptides. These large molecular weight basophil derived mediators may, through the activation of the Hageman factor dependent pathways, influence mechanisms which participate in both acute and chronic cell-mediated inflammatory processes. We suggest that these proteases may participate not only as mediators of the immediate hypersensitivity reaction, but may also function in important aspects of the entire inflammatory response.

Autacoids↗
PubMed1980

Antigen-induced IgE-mediated degranulation of human basophils.

The events associated with antigen-induced, IgE-mediated degranulation of human basophils from allergic donors were studied ultrastructurally. Partially purified cells were examined prior to addition of antigen and after incubation with antigen or control buffer for 15 seconds to 60 minutes. Reactions were stopped instantaneously by adding fixative directly to the cell suspension. After fixation the cells were exposed to cationized ferritin as a sensitive probe for demonstrating possible continuities between the cytoplasmic granules and the cell surface. Ficoll-Hypaque-isolated basophils were of three types: Type I, cells containing basophil granules with a full complement of particles; type II, cells containing some full granules but also variable numbers of cytoplasmic vacuolar structures having the size and shape of basophilic granules but having reduced or no particle content (partially fixed or empty granules); and type III, basophils containing only empty granules. Following exposure to specific antigen, basophils of all three types underwent degranulation characterized by the fusion of the membranes bounding single basophilic granules with the plasma membrane and leading to extrusion of content. Cells in the process of degranulation (type IV and V basophils) were characterized by communications between individual granules and the cell exterior. Identification of such communications was facilitated by cationized ferritin which entered granules having open communications with the cell surface. Without this marker, the number of such communications would have been seriously underestimated, either because they were extremely narrow, tortuous, or outside the plane of section. The majority of individual basophilic granules fused singly and separately with the plasma membrane, in contrast to guinea pig basophil and rat mast cell degranulation where intercommunicating clusters of granules fused with the plasma membrane at a single point. The particle and membrane contents of extruded granules frequently remained adherent to the surface of type IV and V basophils and were not immediately solubilized. Morphologic evidence of degranulation progressed with time of exposure to antigen, exhibiting kinetics that paralleled histamine release. Cells in control incubations, and rare basophils that had been exposed to antigen E, failed to degranulate. Fully degranulated (type VI) basophils were viable cells that had a markedly irregular surface and were devoid of basophilic granules but retained the minor population of small perinuclear granules.

Basophils↗
PubMed1979

Anaphylactic release of a basophil kallikrein-like activity. I. Purification and characterization.

These studies describe the IgE-mediated relase of a basophil kallikrein-like enzyme that is an arginine esterase and is inhibited by plasma, diisopropylphosphofluoridate, and Trasylol. The substrate specificity for the synthetic amino acid ester substrates p-toluenesulfonyl-L-arginien methyl ester, benzoyl-arginine methyl ester, and acetyl-tyrosine methyl ester is similar for the basophil enzyme and plasma kallikrein. The interaction of arginine esterase-active fractions from ion-exchange (DEAE-Sephacel) and gel filtration (Sepharose 6B) chromatography, with human plasma kininogen, generates immunoreactive kinin. The basophil arginine esterase and kinin-generating activities co-chromatograph on Sepharose 6B and the quantity of kinin generated is, in general, proportional to the arginine esterase activity of the column fractions, suggesting that these two activities are subserved by the same protease. The ability of this protease to generate kinin equally well from heat- and acid-treated plasma, as from fresh human plasma, suggests that this protease has kallikrein-like activity. These data suggest that kallikrein-like activity can be generated from human basophils as a direct result of a primary IgE-mediated immune reaction, thus providing a potential link between reactions of immediate hypersensitivity and the plasma and(or) tissue kinin-generating systems.

Anaphylaxis↗
PubMed1979

Anaphylactic relase of a basophil kallikrein-like activity. II. A mediator of immediate hypersensitivity reactions.

This report describes the immune release of a new mediator from human peripheral leukocytes, a basophil kallikrein-like activity (BK-A). The release process is initiated by the interaction of antigen on anti-IgE with cell-bound IgE, and appears to be similar in mechanism to the relase of histamine and other mediators of the immediate hypersensitivity reaction. The dose-response relationships and kinetics of histamine and BK-A release from antigen-challenged peripheral leukocytes are similar. The relase of the BK-A is calcium and temperature dependent, requires metabolic energy, and is controlled by hormone-receptor interactions that influence the cellular level of cyclic AMP, as has been described for other mediators of immediate hypersensitivity reactions. The data indicate that the interaction of BK-A with human plasma kininogen, generates immunoreactive kinin. We conclude that the antigen-IgE interation leads to the release from human basophils of a new mediator, a basophil kallikrein-like activity which may well be a link between reactions of immediate hypersenstivitity and the plasma and/or tissue kinin-generating systems.

Anaphylaxis↗
PubMed1979

Activation of human Hageman factor by a leukocytic protease.

We earlier reported the IgE-mediated release of a basophil kallikrein of anaphylaxis (BK-A) which, like plasma kallikrein, is an arginine esterase and cleaves human plasma kininogen generating immunoreactive kinin. We herein report that, like plasma kallikrein, preparations rich in this basophil protease also activate human Hageman Factor by proteolytic cleavage of the zymogen molecule into light and heavy chains. These fragments of 28,000 and 52,000 daltons are similar in size to those produced during activation of Hageman Factor by plasma kallikrein. Exposure of Hageman Factor (bound to a negatively charged surface) to BK-A led to the proteolytic cleavage of Hageman Factor producing a 28,000 molecular weight fragment (HFa) which is functionally active and capable of activating prekallikrein to kallikrein. We conclude that, during anaphylaxis, basophils may release a protease that is capable of cleaving and activating Hageman Factor, thus providing a mechanism for initiating the in vivo activation of the Hageman Factor dependent systems.

Anaphylaxis↗
PubMed1979

Basophil kallikrein of anaphylaxis (BK-A)--purification and characterization.

These studies describe the IgE-mediated release of a basophil kallikrein of anaphylaxis (BK-A) that has arginine esterase activity and is inhibited by plasma, DFP, and Trasylol. The interaction of BK-A active fractions from ion exchange (DEAE-Sephacel) and gel filtration (Sepharose 6B) chromatography, with human plasma kininogen generates immunoreactive kinin. The BK-A and kinin-generating activities co-chromatograph on DEAE-Sephacel and Sepharose 6B columns, and the quantity of kinin generated is, in general, proportional to the BK-A activity of the column fractions, suggesting that these two activities are subserved by the same protease. These data suggest that kallikrein-like activity can be generated from human basophils as a direct result of a primary IgE-mediated immune reaction, thus providing a potential link between reactions of immediate hypersensitivity and the plasma and/or tissue kinin-generating systems.

Anaphylaxis↗
PubMed1978

Collateral ventilation in man.

To determine whether collateral ventilation (defined as the ventilation of alveolar structures through passages or channels that bypass the normal airways) changes with age or emphysema, we compared the mechanics of collateral ventilation in seven young normal subjects, three old normal subjects and five patients with emphysema. In supine normal subjects at the end of a quiet expiration, resistance to airflow was greater through collateral channels than through bronchi and bronchioles. In emphysema, airways resistance could exceed collateral resistance, causing air to flow preferentially through collateral pathways. We conclude that high collateral resistance minimizes collateral airflow in supine normal subjects. When peripheral airways become obstructed or obliterated in emphysema, collateral channels may provide for more even distribution of ventilation.

Adult↗
PubMed1977

The influence of atropine and cromolyn on human bronchial hyperreactivity to aerosolized prostaglandin F2 alpha.

The mechanism of prostaglandin F2 alpha(PGF2alpha)-induced airway constriction was explored by determining the influence of atropine and cromolyn on the bronchoconstrictive properties of PGF2alpha. Increasing doses of aerosolized PGF2alpha were given (150, 300, 600, 1200 microgram) and the response of subjects was determined by measurements of spirometry, specific airway conductance (SGaw), and closing volumes. In normal subjects, PGF2alpha induced small but significant decreases of SGaw and spirometric parameters (FVC, FEV1), whereas there was no effect on the closing volumes. In contrast, in asthmatics, PGF2 alpha induced large decreases of SGaw and spirometric parameters. Asthmatics experienced severe and prolonged shortness of breath and wheezing, whereas normal controls experienced neither. Neither atropine nor atropine plus cromolyn was capable of preventing or substantially reversing the PGF2alpha-induced symptoms and airway constriction. The data suggest that reflex bronchoconstriction via irritant receptors is not a major mechanism of PGF2alpha-induced airway constriction. Although a minor vagally mediated reflex component may participate in the PGF2alpha-induced bronchoconstriction, it is masked by an overwhelming non-reflex mechanism that is probably a direct constricting effect of airways smooth muscle that is exquisitely sensitive to PGF2alpha.

Adolescent↗
PubMed1977

Chronic obstructive airway disease in patients with Sjögren's syndrome.

To determine the incidence of airway disease in Sjögren's syndrome, respiratory function was evaluated in 13 patients with this disorder. Six patients had clear evidence of airway disease without overt evidence of loss of elastic recoil, and 7 patients had normal pulmonary function studies. Five of the 6 patients with abnormal pulmonary function studies had never smoked cigarettes. Of the patients with severe airway disease, all had exertional dyspnea but none had chronic cough with sputum production or recurrent bronchospasm. The 3 patients with the most severely impaired pulmonary function studies showed abnormal single-breath nitrogen curves, increased residual volumes, and hypoxemia, whereas static pressure-volume curves and maximal static elastic recoil at total lung capacity were within predicted norms. Lung biopsy of 2 patients showed mononuclear cell infiltration aroung narrowed small airways. We concluded that certain patients with Sjögren's syndrome develop an unusual type of chronic obstructive airway disease, which is probably a result of a chronic mononuclear cell inflammatory process similar to that seen in their salivary and lacrimal glands. The data suggest that human airways should be considered another target organ of Sjögren's syndrome. Earlier reports have stressed the association of a restrictive pulmonary defect with Sjögren's syndrome. Our data suggest that the restrictive pulmonary defect seen in patients with the complete variation of Sjögren's syndrome is probably the result of the associated connective tissue disorder, rather than the result in the sicca complex.

Adult↗
PubMed1976

Effects of alternate-day prednisone therapy on respiratory function in myasthenia gravis.

To determine the effects of alternate-day prednisone therapy on respiratory function in myasthenia gravis, eight patients were evaluated during "days on" and "days off" prednisone. The patients were treated with long-term (up to three years), high-single-dose, alternate-day oral prednisone. After patients had been controlled with alternate-day prednisone they had no episodes of acute respiratory insufficiency or myasthenic crises. Although a small reduction in respiratory function during the day off prednisone was seen in some patients, the change was not statistically significant for the group and was probably physiologically unimportant in most patients. The data indicate that in myasthenic patients who have no underlying lung disease respiratory function is not significantly compromised by administering the prednisone on alternate days.

Adolescent↗