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J Widdicombe

Publications and source records attributed to J Widdicombe.

30 records · Page 2Linked to original sources
PubMed1995

Relationships among the composition of mucus, epithelial lining liquid, and adhesion of microorganisms.

Airway surface liquid (ASL) is complex and comes from many sources, in particular glands and epithelium. The mucoglycoproteins present bind to bacteria. Bacterial membranes contain adhesins that bind to receptors on the mucus. The bound bacteria multiply and release toxins that diffuse to the epithelium and damage or destroy it, inhibiting mucociliary transport. The damaged epithelium releases products such as phospholipids into the ASL. These change the physical properties of the mucus and also promote mucus secretion, which may block smaller airways. Airway surface liquid contains constituents such as immunoglobulins, lysozyme, and lactoferrin and neutrophil products such as proteases that act on bacteria. Few bacteria adhere to healthy epithelium. To adhere, most require damaged tissue with membrane receptors that encourage bacterial invasion. If the epithelium is destroyed, bacteria adhere to the basement membrane or extracellular matrix. A damaged epithelium can also cause hyperresponsiveness of airway secretory mechanisms, with increased gland secretion that in turn interacts with the bacteria.

Bacterial Adhesion↗
PubMed1992

Physiologic control. Anatomy and physiology of the airway circulation.

Both for the nose and the lower airways there is an extensive subepithelial capillary network. That for the nose is fenestrated, and this is true for the tracheobronchial tree of rats, guinea pigs, and hamsters, and for that of human asthmatics. However, healthy humans, dogs, and sheep have capillaries without fenestrations except for those close to neuroepithelial bodies and submucosal glands. Deeper in the mucosa there is a capacitance system of vessels, conspicuous in the nose but present also in the lower airways of rabbits and sheep and, to a lesser extent, in those of dogs and humans. Both for the nose and the lower airways, parasympathetic nerves are vasodilator, sympathetic nerves are vasoconstrictor, and sensory nerves are able to release dilator neuropeptides. Most inflammatory and immunologic mediators are vasodilator. A conspicuous difference between the nasal and lower airway vasculatures is the presence of arteriovenous anastomoses only in the former. Countercurrent mechanisms also exist in the nose to increase its efficiency in air conditioning, but they have not been established for the trachea. The pulmonary vasculature could be part of such a system for the bronchi. Distension of the airway vasculature thickens the mucosa, probably both by vascular distension and by edema formation. The latter can lead to exudation into the airway lumen. These processes have not been well quantitated, and the balance sheet of capillary and capacitance vessel volumes, interstitial liquid volume, and exudate volume needs to be worked out in physiologic and pathologic conditions.

Air↗
PubMed1988

Afferent neural pathways in cough and reflex bronchoconstriction.

Cough and bronchoconstriction are airway reflexes that protect the lung from inspired noxious agents. These two reflexes can be evoked both from the larynx and tracheobronchial tree and also from some extrarespiratory sites. Within the airways, certain sites are particularly sensitive to stimulation of cough (larynx and points of proximal airway branching), whereas bronchoconstriction can be triggered from the whole of the tracheobronchial tree. In the larynx, "irritant" receptors with myelinated afferents mediate cough and bronchoconstriction. Little seems to be known about laryngeal nonmyelinated afferents and their reflexes. In the tracheobronchial tree and lung, slowly adapting stretch receptors (SARs) and rapidly adapting stretch receptors (RARs) have opposing effects on airway tone, the former mediating bronchodilation and the latter bronchoconstriction. In cough, on the other hand, they operate concurrently, a mediatory role for RARs and a facilitatory role for SARs. C-fiber endings (bronchial and pulmonary) mediate bronchoconstriction. Inhalation of so-called "selective" C-fiber stimulants induces cough, but excitation of RARs has not been eliminated, and the possibility also exists that the cough is secondary to other lung actions mediated by these nerve endings. Although cough and bronchoconstriction may be mediated by the same type of receptor, they seem to have separate afferent neural pathways.

Afferent Pathways↗
PubMed1987

Effects of inflammatory and other mediators on airway vascular beds.

The bronchial arteries extend to all lung structures in man with the exception only of the alveolar wall. In addition to providing nutrition to the lungs, the bronchial vessels can also function as a hemodynamic and gas-exchange system due to anastomoses with the pulmonary arteries; they also play a significant role in controlling the clearance of chemical mediators, regulating the development of airway wall edema, and controlling heat exchange in the tracheobronchial tree. We have measured the effects of inflammatory and other mediators on tracheal mucosal thickness and the changes in tracheal vascular resistance in dogs. Bradykinin, histamine, and methacholine had large "vasodilator" effects, decreasing vascular resistance, and they also clearly increased the thickness of the mucosa. Substance P, VIP, PGF2 alpha, and PGE1 had as large a response on vascular resistance as the drugs mentioned above, but only had small effects in increasing tracheal mucosal thickness. Salbutamol fell between these 2 groups with regard to the pattern of response. Phenylephrine had an opposite action, causing an increase in vascular resistance and a decrease in mucosal thickness. Despite the vasodilatation and the increase in vascular permeability due to vasoactive drugs, the changes in mucosal thickness were rather small and could not be correlated with the decreases in vascular resistance due to the different drugs. Such changes are unlikely to have an appreciable effect on tracheal airway resistance. The change in mucosal thickness may be more significant in those parts of the airways where the ratio of change in mucosal thickness to the radius of adjacent lumen is large, such as the nose and small conducting airways.

Animals↗
PubMed1987

Cyclic adenosine monophosphate-dependent kinase in cystic fibrosis tracheal epithelium.

Cl-impermeability in cystic fibrosis (CF) tracheal epithelium derives from a deficiency in the beta-adrenergic regulation of apical membrane Cl- channels. To test the possibility that cAMP-dependent kinase is the cause of this deficiency, we assayed this kinase in soluble fractions from cultured airway epithelial cells, including CF human tracheal epithelial cells. Varying levels of cAMP were used in these assays to derive both a Vmax and apparent dissociation constant (Kd) for the enzymes in soluble extracts. The cAMP-dependent protein kinase from CF human tracheal epithelial cells has essentially the same Vmax and apparent Kd as non-CF human, bovine, and dog tracheal epithelial cells. Thus, the total activity of the cAMP-dependent kinases and their overall responsiveness to cAMP are unchanged in CF.

Cystic Fibrosis↗
PubMed1985

Control of airway caliber.

Tracheobronchial smooth muscle tone may be affected by 4 nervous mechanisms: (1) Vagal cholinergic parasympathetic nerves, which are the main agents for resting tone and most reflex bronchoconstrictions. Their activity is blocked by atropinic drugs. (2) Sympathetic adrenergic dilator nerves, which may act mainly on beta-adrenoceptors in the pulmonary bronchi; alternatively, they may inhibit ganglionic transmission in the vagal constrictor pathway. (3) Vagal nonadrenergic dilator nerves (NAIS). The neurotransmitter at these nerves is probably vasoactive intestinal polypeptide (VIP), although purines could be involved. The role of this system in physiologic and pathologic conditions has not been established. (4) Local axon constrictor reflexes in afferent nerves. These respond to mucosal irritation and cause local smooth muscle contraction by release of substance P. Their importance has not yet been assessed. The motor innervation of the airways is activated reflexly by many stimuli, some of which cause constriction and others dilation. Most of the reflexes are blocked by atropine, which suggests that the cholinergic constrictor pathway is dominant. Other responses include changes in laryngeal caliber and secretion of mucus. Aspirations into the airways will lead to bronchoconstriction, laryngospasm, and secretion of mucus, as well as to respiratory and cardiovascular reflexes. The balance, effectiveness, and development of these responses requires much further study.

Adrenergic Fibers↗
PubMedDate not supplied

Sensory mechanisms.

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Animals↗