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Biomedical subjects

J R Garrett

Publications and source records attributed to J R Garrett.

At least 127 records · Page 7Linked to original sources
PubMed1982

Permeability of canine submandibular glands to blood-borne horseradish peroxidase during parasympathetic secretion.

Potential permeability pathways exist between central acinar cells in submandibular glands of dogs and they are large enough to allow the passage of molecules of horseradish peroxidase (HRP) under certain conditions. During gentle submandibular secretion caused by parasympathetic nerve stimulation detectable amounts of HRP passed into the saliva as long as the concentration of HRP in the blood reaching the gland was high enough. Morphological results indicated that the passage was mainly via leaky junctions between acinar cells. It is likely that this movement was by passive permeation because it required a high concentration gradient, was slow to occur and gradually reached a peak; the actual amounts to reach the saliva under physiological conditions were small and depended on the effective concentration of HRP reaching the gland. A satisfactory reproducible secretory regime has been developed, using short periods of stimulation alternating with rest pauses. Using these conditions gradually increasing amounts of HRP reached the saliva and first samples of saliva during each stimulation period contained more HRP than subsequent samples from the same stimulation period. It is possible that contraction of myoepithelial cells, at the outset of each stimulation period, contributed to this increased movement by acting on HRP-containing fluid in spaces between themselves and the acinar cells, thereby causing an increased filtration pressure to be exerted on underlying tight junctions.

Animals↗
PubMed1982

Permeability of canine submandibular glands to blood-borne horseradish peroxidase: effects of transient ductal obstruction during secretion.

Outflow obstruction of the submandibular duct, for a short period during parasympathetic secretion, caused an increase in glandular permeability to horseradish peroxidase. Higher frequencies of parasympathetic nerve stimulation during the obstructive period induced greater increases in the permeability. It is likely that the intraluminal distensions had disrupted some tight junctions and so permitted a greater paracellular leakiness. The damage tended to induce ballooning between striated ductal cells, similar to the appearances observed by Emmelin, Garrett & Gjörstrup (1977 a) when sympathetic secretion was accompanied by myoepithelial contraction against a raised outflow pressure. The present results have been compared with experimental data from other workers and give support to the idea that tight junctions can behave in a sieve-like manner towards the back-diffusion of molecules across them. This work indicates that there is a great need for care in permeability studies. It is possible that some permeability changes observed by other workers may have been the consequences of physical damage between cells. Our findings reinforce the need for morphological assessment of the glands after permeability experiments. In man it is likely that naturally occurring or artificially induced obstructive events may at times create similar permeability changes and these may enable protective substances to pass from the blood to the saliva. This affords possible explanation for such phenomena as the therapeutic value that often accrues from sialography and the efficacy of many different antibiotics in obstructive sialadenitis, despite the fact that most antibiotics do not normally permeate to the saliva.

Animals↗
PubMed1982

Simultaneous myocardial revascularization and carotid endarterectomy.

Two methods for performing simultaneous carotid endarterectomy and coronary artery bypass grafting (CABG) were compared in 73 patients. A technique for performing carotid endarterectomy during cardiopulmonary bypass providing hypothermic cerebral protection was used in 37 patients (group 1). The 36 other patients (group 2) underwent carotid endarterectomy immediately before cardiopulmonary bypass was instituted. The mean age, New York Heart Association functional class, ventricular function and extent of carotid disease were similar in the two groups. The proportion of patients with previous myocardial infarction or stroke was higher in group 1 (p less than 0.05). One permanent neurologic deficit (technical error) and one transient neurologic deficit occurred in group 1 and none in group 2 (NS). Twenty-seven patients (37%) had left main disease, compared with an institutional incidence of 14.2% for all coronary operations. Five of seven patients who died early (three in group 1 and four in group 2) had left main disease. No advantage of one method over the other could be demonstrated. Patients with left main coronary artery disease and carotid disease have an increased operative risk.

Aged↗
PubMed1981

Myenteric plexus of the hind-gut: developmental abnormalities in humans and experimental studies.

Intraluminal pressure studies on patients with congenital aganglionosis showed that the aganglionic rectum contracted in an uncoordinated manner and failed to relax. Histochemical assessment of the innervation helped to explain the variable severity of the symptoms in this condition. It is concluded that (1) absence of ganglia prevents normal coordinated peristalsis and creates an obstructive element; (2) absence of reflex relaxation adds to the obstruction; (3) the degree of uncoordinated motor activity in distal aganglionic bowel probably relates to the number of cholinesterase-positive nerves in the circular muscle and adds another variable obstructive element; and (4) deficient innervation of distal ganglionic bowel probably creates a poor propulsive force and so accentuates more distal obstructive factors. Neurohistochemical and functional studies in the anorectum of cats reveal a somewhat different innervation pattern from that in humans but show that sphincteric tone is mainly due to alpha-adrenergic neural activity. Reflex relaxation of the internal anal sphincter is a complex function in which inhibitory responses override motor responses, and it involves an important non-adrenergic non-cholinergic component. The role of cholinergic nerves in the sphincter remains uncertain. Neurohistochemical assessment of full thickness biopsy specimens of rectal muscle from patients with disabling constipation shows that developmental neuronal dysplasias of the hind-gut may be divided into three main categories: (1) aganglionosis (Hirschsprung's disease), (2) hypoganglionosis and (3) hyperganglionosis, and that the different neuronal elements may be affected to differing degrees in individuals within each group. Resection of the aganglionic bowel is required in congenital aganglionosis but the combined diagnostic-therapeutic procedure of anorectal myotomy has been found beneficial in patients with hypoganglionosis.

Animals↗
PubMed1981

Permeability of submandibular salivary glands in dogs to blood-borne horseradish peroxidase (HRP). I. Perarterial bolus injection in "resting" glands.

Horseradish peroxidase (HRP) was administered to the submandibular glands of dogs by close-arterial bolus-type injections, and its localisation was examined histochemically by light and electron microscopy. The HRP became widespread in the interstices of the glands and reached many central acinar lumina via scattered localised parts of their "tight" junctional complexes. Reaction product was less often found in the lumina of demilunes, which suggested that the intercellular junctions there were less "leaky". HRP was often found in sizeable spaces between myoepithelial cells and the underlying parenchymal cells; such large spaces have not been observed in this situation in other species. The possibility that permeability pathways may arise intermittently at different sites in the adhering mechanisms between the acinar cells is discussed. It is concluded that potential paracellular permeability pathways for macromolecules exist in these glands and, if the concentration gradient is sufficiently high, molecules even as large as those of HRP can to some extent permeate passively from the interstices to the saliva. In "resting" glands the principal permeability site is between the central acinar cells.

Animals↗
PubMed1981

Functional and structural studies concerning the control of activity in zygomatic glands of cats.

The zygomatic gland of the cat consists of at least two parts, separated by a septum, and each drains by a separate duct opening on a mucosal ridge postero-medial to the parotid orifice. It is composed on thin-walled ducts and tubulo-acini, containing mainly mucous cells, but scattered cap cells are also present. In cats under chloralose anaesthesia there is a spontaneous flow of extremely viscous saliva and often, in addition, there is a reflexly elicited component to the secretion. In fact, in contrast to the other major salivary glands, the zygomatic gland is easily made to secrete reflexly even in deep] anaesthesia, e.g. by pinching ipsilateral parts of the tongue, by stimulation of the oesophagus mimicking swallowing, or by afferent excitation of ipsilateral lingual, glossopharyngeal or vagal nerves. The efferent link of the reflex arc is contained in the buccal branch of the mandibular nerve. Section of this nerve abolishes these reflexes, and two weeks later a great loss of acetylcholinesterase positive nerves can be demonstrated in the gland. Efferent stimulation of the buccal nerve evokes a lively secretion that is not affected by hexamethonium but is abolished by atropine. Histochemically, adrenergic nerves are also found surrounding the acini and these nerves disappear after excision of the superior cervical ganglion. Electrical stimulation of the cervical sympathetic trunk causes some secretion, mainly by way of beta 1-adrenoreceptors. Myoepithelial cells are present around the tubulo-acini, and indications of the effect caused by their contraction on the flow from the glands have been observed. Such activity can be induced reflexly and it is then abolished by cutting the buccal nerve or by injecting atropine.

Acetylcholinesterase↗
PubMed1980

Localisation of esteroproteases in 'resting' salivary glands from different species and the effects of the organophosphorus inhibitor E600.

The distribution of reaction sites for esteroproteases has been assessed in 'resting' salivary glands from rats, guinea-pigs, cats, dogs and rabbits using the new substrate N-acetyl-L-methionine alpha-naphthyl ester (Lexow et al. 1979). Two main types of activity were observed in the parenchyma. 1) Condensed staining was present on the luminal sides of certain ducts in some, but not all, glands, and this type of staining was always most conspicuous in the submandibular glands of each species. It is likely that this periluminal esteroprotease activity arises from secretory enzymes that will pass into the saliva. Their greater presence in submandibular glands may have association with specialised licking activities. 2) Variable diffuse cytoplasmic staining was present in certain acinar cells from some, but not all, glands. This was most pronounced in the mucous cells of zygomatic glands from dogs. It is considered that the enzymes demonstrated in acinar cells are involved in processing secretory products rather than in being secretory themselves. The possibility that this includes 'signal peptidase' is discussed. Ductal activity in rats, cats and guinea-pigs had some relationship with sites of tryptophan staining but not in rabbits or dogs. Any relationship with acinar staining was less evident. Mast cells, showing strong esteroprotease staining, were present in variable numbers in the different glands. Preliminary attempts to qualify the enzymes being demonstrated were made by using the inhibitor E600. This substance inhibited all activity in acinar cells from each species, and in rabbits and dogs it also inhibited the ductal activity as well. However, in rats and guinea-pigs it had little or no effect on the ductal activity and in cats it had only a small inhibitory effect on the ductal activity. E600 had no obvious inhibitory effects on mast cell activity.

Animals↗
PubMed1979

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↗
PubMed1979

Activities of salivary myoepithelial cells: a review.

Historical developments concerning salivary myoepithelial cells have been outlined and structural features of the cells have been described. Evidence from structural and functional studies supports the belief that myoepithelial cells usually have a dual innervation by parasympathetic as well as sympathetic nerves, and impulses from both types of nerve cause the cells to contract. Functional assessment using salivary flow phenomena and intraluminal pressure changes have been used to determine, so far as is possible, the effects of myoepithelial contractions. In some instances tissues have been examined structurally after such experimental procedures. These investigations indicate that salivary myoepithelial activity 1. Speeds up the outflow of saliva 2. Reduces luminal volume 3. Contributes to the secretory pressure 4. Supports the underlying parenchyma 5. Helps salivary flow to overcome increases in peripheral resistance. However, beyond a certain point, this may lead to sialectatic damage of striated ducts with increase in glandular permeability. Myoepithelial activity may also help to expel parenchymal cell contents in certain instances.

Adrenergic Fibers↗
PubMed1979

Changes in the main submandibular salivary duct of rabbits resulting from ductal ligation.

Normal submandibular ducts from rabbits have been examined by mucosubstance histochemistry, transmission and scanning electron microscopy. The results were compared with the appearances of ducts removed 4...6 weeks after ligation. The normal ducts were composed mainly of columnar "light" cells and basal cells but, in addition, some "dark" cells and scattered goblet containing sulphated mucins were always present. The luminal surface of the ductal cells possessed numerous microvilli protruding into the lumen, and a rim of negatively charged mucin was present on this surface of these cells. After ligation the ducts became greatly distended by their fluid contents which remained under pressure until the duct was incised. The epithelial cells were flattened and appeared to contain less cytoplasm per cell; "light" cells, basal cells and "dark" cells were still recognisable. Goblet cells were much more plentiful than in the control ducts and often protruded into the lumen despite the increased intraluminal pressure. The development of a number of ciliated cells had also occurred and they were often situated close to goblet cells. Lymphatic vessels were more prominent around the ligated ducts. Luminal microvilli were less numerous than in the control ducts but the rim of negatively charged mucin on the luminal surface of ductal cells was more conspicuous. Mixed inflammatory cells were present within the lumina of ligated ducts especially in those parts adjacent to the ductal cells. No inflammatory cell has been observed passing through the wall of a main duct and the possibility exists that these cells had entered lumina within the gland and migrated from there to the main duct. The above findings may serve to help our understanding or physiological events in the ducts.

Animals↗