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Biomedical subjects

J M Butler

Publications and source records attributed to J M Butler.

At least 37 records · Page 2Linked to original sources

Computed tomography of aqueous humour outflow pathways.

The anterior chamber of adult Rhesus monkeys (Macaca mulatta) was perfused with a radio-opaque contrast medium (Amipaque; mol. wt 789 daltons) at controlled intraocular pressure (IOP), and its subsequent distribution examined by computed tomography. In the living monkey no contrast medium was detectable outside the anterior chamber, even after prolonged (8 hr) perfusion. However, if the animal was then killed, and the IOP maintained artificially at its previous level, opacity appeared immediately throughout the anterior segment. Subsequent scans showed the contrast medium to diffuse into the anterior orbital tissues, and to move posteriorward through the globe wall and extraocular muscles. None entered the vitreous body and very little progressed behind the point at which the extraocular muscles exited from Tenon's capsule. Elevation of IOP did not appear to accelerate this posterior diffusion. It is inferred that in vivo contrast medium passing into the posterior, non-conventional aqueous drainage pathway is cleared immediately by the circulating blood in the uvea and possibly also the extraocular muscle. Tenon's capsule may provide a barrier to further intra-orbital diffusion.

Animals

Sensory neural mechanisms in contraction of the rabbit isolated sphincter pupillae: analysis of the responses to capsaicin and electrical field stimulation.

Electrical field stimulation produced contractions of the rabbit isolated iris sphincter muscle which were completely blocked by tetrodotoxin (10(-6) M). Low frequency (0.16-5 Hz) responses were atropine-resistant, but were prevented by sensory (trigeminal) denervation, and were considered to be owing to antidromic stimulation of sensory nerves. Higher frequency (10-40 Hz) responses were apparently unaffected by atropine alone (3 X 10(-7) M) and unaltered by sensory denervation, but were completely blocked by a combination of both. Thus at higher frequencies both cholinergic and sensory nerves would seem to be activated. Capsaicin-induced contraction of the isolated iris sphincter muscle, previously shown to be dependent upon an intact and functional sensory nerve supply, was not suppressed by atropine (3 X 10(-7) M) or by tetrodotoxin (10-6 M). Capsaicin therefore, although acting via sensory nerves, does not seem to require axonal conduction or Na+ flux to produce a response. This pain-producing substance may therefore act directly on sensory elements to release a mediator without requiring excitation of adjacent fibres by axon reflex. Contractile responses to capsaicin and also to low-frequency electrical stimulation were partially inhibited by morphine (5 X 10(-5) M), which in contrast had no effect on responses to carbachol or to substance P. Thus, at the peripheral as at the central endings of these bipolar primary afferent fibres, morphine may inhibit the release of the putative mediator.

Animals

Unidirectional transport mechanism of horseradish peroxidase in the vessels of the iris.

When horseradish peroxidase (HRP) is introduced into the blood stream it is retained in the lumen of the iridial vessels. In this paper, we report that when the same tracer is perfused into the anterior chamber of macaque monkeys, it permeates the stroma of the iris and penetrates the lumen of iridial vessels by transcellular vesicular transport. This unidirectional movement of HRP out of the eye is not inhibited by ouabain or fluoroacetate.

Animals

Increase in SP-like immunoreactivity in nerve fibres of rabbit iris and ciliary body one to four months following sympathetic denervation.

Substance P (SP) levels in rabbit iris-ciliary body preparations were found to be significantly elevated 30 days after removal of the superior cervical ganglion when compared with the contralateral unoperated side. These elevated levels were still apparent after two and three months. Immunohistochemical studies, using a monoclonal antibody to SP, revealed an increase in the density of SP-immunoreactive nerve fibres in the region of the iris dilator muscle and in the ciliary processes one to four months after sympathectomy, although the density of these fibres in other regions of the iris was not altered.

Animals

Increased leukocyte histamine release with elevated cyclic AMP-phosphodiesterase activity in atopic dermatitis.

Maximal leukocyte histamine release in response to concanavalin A was significantly higher in a group of 16 adult patients with moderate to severe atopic dermatitis when compared to 13 adult nonatopic, normal subjects. In a further four atopic dermatitis patients, histamine release was similar to that in the normal group suggesting the existence of "high-releaser" and "low-releaser" subsets within the atopic dermatitis group. Leukocyte cAMP phosphodiesterase activity was significantly higher in the high-releaser group than in the low-releaser and normal groups. High and low histamine release responses showed strong correlations with high and low phosphodiesterase activities. Pretreatment with the experimental cAMP phosphodiesterase inhibitor Ro-20-1724 in high releasers reduced the histamine release to normal levels. These findings suggest that increased histamine "releasability" in atopic dermatitis is related to abnormalities in cyclic nucleotide regulation. Basophil percentages within the leukocyte preparation and the histamine content per basophil were not significantly different between the atopics and normals. Histamine release did not correlate significantly with serum IgE levels.

3',5'-Cyclic-AMP Phosphodiesterases

Pruritic dermatitis in asthmatic basenji-greyhound dogs: a model for human atopic dermatitis.

A recurrent, nonseasonal pruritic dermatitis manifested as lichenified plaques and as inflammatory nodules and papules in each of fourteen basenji-greyhound (B-G) crossbreed dogs, all of which demonstrated both nonspecific and Ascaris-specific airway hyperreactivity, with changes in pulmonary mechanics of the same order as those seen in symptomatic human asthma. Other features analogous to human atopic disease included blunted cyclic adenosine monophosphate (cAMP) responsiveness to beta adrenergic agents and in vivo release of histamine and slow-reacting substance of anaphylaxis in response to antigen aerosol challenge. The dermatitis appears to be a manifestation of the atopic state in these dogs and may provide an animal model for the study of human atopic dermatitis.

Animals

Unidirectional vesicular transport mechanism in retinal vessels.

When horseradish peroxidase (HRP) is introduced into the bloodstream, it is retained in the lumen of the retinal vessels (blood-retina barrier). In this paper, we report that when the same tracer is injected into the vitreous body, it penetrates the lumen of retinal vessels by transcellular vesicular transport. This unidirectional movement of macromolecules out of the eye is not inhibited by ouabain, fluoroacetate, or low temperatures.

Animals

Mapping, quantitative distribution and origin of substance p- and VIP-containing nerves in the uvea of guinea pig eye.

VIP- and substance P-like immunoreactivities were found in considerable concentrations (VIP: 17.3 +/- 4.8 pmol/g, mean +/- SEM; substance P:11.1 +/- 1.8 pmol/g) in the uveal portion of the guinea pig eye. Immunocytochemistry localised these two regulatory peptides to nerve fibres found principally in a plexus in the iris (substance P) and in an extensive network surrounding the blood vessels of the choroid (VIP). A remarkable anatomical demarcation of the two types of peptide-containing nerves was established by the staining of substance P-containing nerves, which stops at the level of the ciliary body. This uveal area is known to be involved in the ocular responses to nociceptive stimuli. At the ultrastructural level, immunoreactivity for both peptides was localised to distinct subpopulations of p-type nerves, distinguishable by the size of their large dense-cored vesicles. Those immunoreactive for VIP were significantly larger (p less than 0.0005) than those immunoreactive for substance P (95 +/- 7 nm and 82 +/- 9 nm respectively; mean +/- SD). Interruption of the trigeminal pathway produced a remarkable decrease of substance P immunoreactivity in the anterior portion of the uvea (9.1 +/- 1.5 pmol/g, mean +/- SEM, control; 5.3 +/- 1.3 pmol/g, denervated), but not of VIP immunoreactivity in the choroid. Following colchicine treatment, VIP-immunoreactive neuronal cell bodies were localised in the choroid. The separate anatomical localisations and distributions of the two uveal peptides appear to be related to their different origins and functional roles in the response of the eye to noxious stimuli.

Acetylcholinesterase

Shigella endotoxin-induced ocular inflammation in the normal and sensory denervated rabbit eye.

Injection of Shigella endotoxin (2 mug) into the vitreous chamber of a normal rabbit eye induces on infiltration of polymorphonuclear leucocytes, miosis, a moderately intense dilation of iris, conjunctival and limbal vessels, and a breakdown in the blood-aqueous and blood-vitreal barriers. Significant amounts of soluble blood protein and prostaglandin-like (PG) material are found in the aqueous and vitreous humours withdrawn at 24 h. Endotoxin injected into the sensory denervated eye elicits similar vascular changes which appear to occur less rapidly than in normal eyes. conversely, the levels of aqueous and vireal PG-like material, as well as the capacity of excised irides to form PG from exogenous precursors, seems greater in the denervated eyes. If PG is an important mediator of ocular changes in the early phases, the results suggest that the action of this inflammatory autacoid in facilitating the ocular changes is less effective in eyes deprived of functional sensory nerves.

Animals

The effects of sensory denervation on the responses of the rabbit eye to prostaglandin E1, bradykinin and substance P.

1 Six to eight days after diathermic destruction of the fifth cranial nerve in the rabbit, the ocular hypertensive and miotic responses to intracameral administration of capsaicin, bradykinin, and prostaglandin E1 were greatly reduced or completely abolished. The response to substance P was not abolished. 2 A response could still be obtained to chemical irritants 36 h after coagulation of the nerve and it is deduced that manifestation of the response is dependent upon functional sensory nerve terminals, and is independent of central connections. 3 It is suggested that prostaglandin E1 and bradykinin act directly upon the sensory nerve endings and that propagation of the response is augmented by axon reflex. 4 In view of the ability of substance P to induce miosis in the denervated eyes, it is presumed that its actions are not mediated via sensory nerves. 5 It is considered possible that the mediator(s) released from sensory nerve endings after chemical irritation or antidromic stimulation may act in the same way as substance P with regard to the miotic effect. 6 Synthetic substance P will only produce ocular hypertension in doses which induce a maximal miotic response. This may either be a question of access or a partial resemblance to the endogenous mediator.

Animals

Axon reflex in ocular injury: sensory mediation of the response of the rabbit eye to laser irradiation of the iris.

Laser irradiation of the rabbit iris produces an injury response consisting of prolonged miosis, uveal vasodilation and a transient rise of intraocular pressure (IOP) accompanied by a breakdown of the blood-aqueous barrier. This response has hitherto been attributed partly to prostaglandin (PG) mediation and partly to mediation by a non-cholinergic nervous pathway thought to be sensory in fuction. Responses of the rabbit eye to laser irritation were examined at specified intervals after diathermic coagulation of the epigasserian nerve tract. Both the intensity of the pupillary constriction and the increase in IOP were almost unaltered at 90 minutes but progressively decreased until at 4 days there was essentially no response to high energy laser irradiation in the denervated eye. It was evident that manifestation of the response is largely dependent upon the presence of intact and functional sensory nerves, and it is proposed that endogenous PGs exert some, if not all of their effects via sensory nerve endings. It is suggested that those terminals which are directly stimulated, whether by laser irradiation or by PGs formed during the injury, release some mediator to cause pupillary constriction. From thes terminals impulses pass orthodromically and antidromically by axon reflex to release further mediator from terminals in the region of the ciliary vessels or the major arterial circle. In this way the response is propagated and augmented.

Animals