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Biomedical subjects

A Kidd

Publications and source records attributed to A Kidd.

14 recordsLinked to original sources

Increase of microliths in inactive salivary glands of cat.

Secretory inactivity could be a factor in the formation of microliths, and so their occurrence in feline salivary glands after the secretory inactivity produced by parasympathectomy was investigated. Parasympathectomy was followed by a greatly increased occurrence of microliths in the submandibular salivary gland, but not in the parotid and sublingual, which may relate to residual secretory activity in these glands. This discovery suggests that secretory inactivity may indeed be a factor in the production of microliths in human salivary glands, and consequently of chronic sialadenitis and sialothiasis.

Animals

Suspected adverse reactions to medicines during 1989.

There was an increase in reports of suspected adverse reactions to veterinary medicines in 1989 with 329 reports (compared with 206 in 1988), from veterinary surgeons, farmers and the public, comments the Veterinary Medicines Directorate (VMD). Suspected adverse reactions to clostridial/pasteurella vaccines in sheep were a dominant feature and important experience was gained both in terms of liaison with the farming press, and in handling large scale incidents involving PML products. The general trend towards increased reporting of adverse drug effects continues. The UK is the only EC member state to have a PML system and the VMD is looking with some urgency at ways of ensuring the more representative reporting of all categories of drug. Substantial liaison with the veterinary pharmaceutical industry occurred during the year and 204 product reports were requested from companies.

Analgesics

Factors affecting the secretion of submandibular salivary kallikrein in cats.

Glandular kallikrein has been assessed in submandibular saliva, homogenates and plasma by the fluorimetric substrate D-Val-Leu-Arg-7-amino-4-trifluoromethylcoumarin (AFC) and histochemically in tissue sections by the 4-methoxy-2-naphthylamide (MNA) analogue. Nerve stimulation was used to produce salivary secretion. Parasympathetic saliva contained low concentrations of kallikrein, independently of any circulating catecholamines from the adrenals. Sympathetic saliva contained very high concentrations of kallikrein; the amounts in individual drops rapidly reached a peak then declined gradually. Adrenergic blocking drugs during mixed parasympathetic and sympathetic stimulation showed that beta-adrenergic effects normally increase the secretion of kallikrein in response to the alpha-adrenergic influence from sympathetic nerve impulses. Small amounts of a glandular kallikrein-like activity are present in the plasma. Effluent blood from the submandibular gland before, during and after stimulation of either nerve gave no indication that submandibular kallikrein passes from the glandular compartment to the blood under conditions of unobstructed salivary flow. Excision of the chorda tympani indicated that parasympathetic nerve impulses are required for the normal resynthesis of submandibular kallikrein. The secretion of salivary kallikrein is essentially an exocrine function but its role in the saliva remains obscure. The results suggest that sudden mobilization of kallikrein may occur at times into the saliva and that a separate population of adrenergic axons, under separate central control, may pass to the striated ducts specially for this purpose.

Animals

Use of different derivatives of D-Val-Leu-Arg for studying kallikrein activities in cat submandibular glands and saliva.

Glandular kallikrein shows a special selectivity for D-Val-Leu-Arg-4-methoxy-2-naphthylamide in comparison with other potential oligopeptide substrates and it provides a useful histochemical substrate, although the reaction may not always be specific. However, in cat submandibular saliva, a biochemical assay using the closely related D-Val-Leu-Arg-7-amino-4-trifluoromethylcoumarin (AFC) as substrate, which affords more sensitive detection, showed that soya bean trypsin inhibitor causes no inhibition. This indicates that there are unlikely to be contaminating enzymes competing for the substrate in this body fluid. Support for this observation has been gained by the useful new enzyme overlay membrane technique for fluorescent assessment of reactive bands of enzymes after isoelectric focusing, using membranes of cellulose acetate impregnated with D-Val-Leu-Arg-AFC. Comparison of results after isoelectric focusing of purified cat submandibular kallikrein with samples of cat submandibular saliva confirmed that the substrate is monospecific for kallikrein in saliva of the cat. This knowledge has enabled us to start assessing the dynamics of the secretion of kallikrein by the gland. Testing individual drops of saliva has shown that an amazingly rapid mobilization of kallikrein occurs in high concentrations on sympathetic nerve stimulation. The corresponding oligopeptide-based inhibitor D-Val-Leu-Arg-chloromethyl ketone was found to be strongly inhibitory of the amidase reaction by kallikrein but showed a low specificity for kallikrein. Nevertheless, its effects have been tested in vivo by the intravascular route and it caused an increase in the resting salivary vascular resistance whether administered close-arterially or intravenously. Thus, it would seem that a kallikrein-like protease does influence the background tone in the vessels and the source of this enzyme is thought to be mast cells.

Amino Acid Chloromethyl Ketones

New observations on the innervation of striated ducts in submandibular glands of cats, including possible peptidergic nerves.

The presence of hypolemmal axons between striated duct cells in submandibular glands of cats has been established electron microscopically. Axons were found between "light" cells, between "light" and "dark" cells and between "light" and basal cells. Hypolemmal axons were observed most frequently in the junctional region between striated and intercalary ducts. They were often more common in younger animals. "Dark" cells with numerous processes sometimes appeared to have a special relationship with hypolemmal axons. Most of the hypolemmal axons in striated ducts contained characteristic agranular vesicles of the cholinergic type, about 40 nm in diameter; many of these axons also contained large dense cored vesicles of the peptidergic type, about 100 nm in diameter and possessing a more clear outer halo. No adrenergic axons have been observed beneath the basal lamina of striated ducts, even after use of 5-OHDA. The possibility that some of the hypolemmal axons in striated ducts are peptidergic and their possible functions are discussed. Apart from other activities these axons may have a role in supplying special trophic factors to the cells, helping them in their developmental specialisation and maintaining them in normal condition. An absence of such factors after parasympathetic decentralisation may be responsible for the dramatic atrophic changes in striated duct cells, especially since the atrophy in the gland is not solely due to an absence of acetylcholine activation.

Animals

Correlation between thyrotropin-displacing activity and human thyroid-stimulating activity by immunoglobulins from patients with Graves' disease and other thyroid disorders.

Several reports have been published on the anti-TSH receptor antibody in putative autoimmune thyroid disorders using a radioreceptor assay. We have carried out correlative studies between the ability of serum immunoglobulins to displace radiolabeled TSH from the thyroid plasma membrane receptor [TSH-displacing activity (TDA)] and that of actual stimulation of the human thyroid gland [human thyroid-stimulating activity (hTSA)] in Graves' and other thyroid diseases and in control subjects. TDA was assayed by the use of a radioligand technique, while the activation of adenylate cyclase in human thyroid slices was measured as an index of hTSA. The same immunoglobulins were employed for both assays. In this series, positive TDA and hTSA values were found in 70.4% and 81.5% of the samples in active untreated Graves' disease, respectively. Samples from normal persons and from several patients with toxic nodular goiter gave generally negative results in both assays; in a small proportion of patients with either subacute thyroiditis or Hashimoto's thyroiditis, the TDA was positive but hTSA proved to be negative. In Graves' disease (including those patients on propylthiouracil) in remission and treated with 131I, the correlation between TDA and hTSA was not significant (r = 0.309; P greater than 0.1); even when the procedures were compared in the untreated group alone, there was no significant correlation between the two activities (r = 0.309, P greater than 0.1). These studies indicate that 1) significant TDA and hTSA are observed in Graves' disease; nevertheless, the correlation between them is not significant; 2) the hTSA assay appears to be more sensitive and specific than the TDA assay; and 3) TDA may not be synonymous with thyroid stimulation.

Cell Membrane

Effects of secretory nerve stimulation on acid phosphatase and peroxidase in submandibular saliva and acini in cats.

The effects of parasympathetic or sympathetic nerve stimulation either alone, or in combination, on the acid phosphatase-containing central acinar cells and the peroxidase-containing demilunar cells of the cat submandibular salivary gland have been investigated by histochemical and cytochemical techniques. The results obtained with these techniques were correlated with biochemical assays for both enzymes in the saliva secreted. The results indicate that, although both sets of nerves probably affect both sets of cells, the predominant secretory effect of parasympathetic stimulation is on the central cells and, conversely, the predominant secretory effect of sympathetic stimulation is on the demilunes. Sympathetic stimulation appeared also to have initiated synthesis of peroxidase in the demilunar cells, especially when it was superimposed upon parasympathetic stimulation.

Acid Phosphatase

Acid phosphatase and peroxidase in "resting" acinar cells of the major salivary glands of cats and their possible movement into secretory granules.

After fixation of perarterial perfusion using an aldehyde mixture, salivary tissues were prepared for ultrastructural cytochemistry of acid phosphatase or peroxidase. Great variations in the distributions of the reaction product occurred, often within the same cell. Acid phosphatase staining occurred not only in lysosomes and sometimes in a GERL system, but a diffuse cytoplasmic component was also found in submandibular central acinar cells and to a lesser extent in parotid acini and variable staining occurred in the secretory granules of these cells. Peroxidase was variably associated with rough endoplasmic reticulum in submandibular demilunar cells, parotid acini, and more strongly in some sublingual cells. The secretory granules of the latter were darkly stained, but in parotid granules there was variable staining and least staining occurred in the granules of submandibular demilunes. These results are thought to indicate that not all enzymes present in secretory granules have reached there by an elective secretory process. Sometimes they appear to have entered the granules haphazardly, possibly having been enzymes associated with intracellular cisternal channels for transport or metabolism of other secretory substances and ultimately to have passed into the cisternal channels by chance or as part of a natural removal of redundant material.

Acid Phosphatase

Effects of nerve stimulation and denervation on secretory material in submandibular striated duct cells of cats, and the possible role of these cells in the secretion of salivary kallikrein.

Striated ducts in cats after 24 hours starvation normally contained glycogen, especially in the basal regions. They also contained neutral mucin and tryptophan in apical parts of "light" cells and small irregular "secretory" granules were found in a similar distribution by electron microscopy.--Parasympathetic nerve stimulation caused a loss of glycogen but no apparent change in the apical secretory material, despite a copious secretion.--Sympathetic stimulation caused a loss of glycogen and an extensive depletion of apical secretory material, although the salivary flow was small.--Parasympathetic denervation caused progressive atrophy of striated ducts and oedematous degeneration of some cells occurred. Persisting "light" cells tended to contain few basal infoldings, few mitochondria and little apical secretory material.--Sympathetic denervation caused a loss of apical secretory material between 2-4 days, which may have been due to "degeneration activation". Thereafter little change was evident but some ductal atrophy had occurred by 32 days.--These changes in ductal secretory material correspond more closely than acinar changes to the alterations in glandular and salivary kallikrein resulting from similar experiments by other workers. It therefore seems likely that submandibular salivary kallikrein in the cat is present in the secretory material of striated ducts.

Animals