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Biomedical subjects

A Kidd

Publications and source records attributed to A Kidd.

At least 19 recordsLinked to original sources
PubMed1997

Non-photic signalling in the suprachiasmatic nucleus.

Scheduled arousal by handling and sub-cutaneous saline injection entrains the free-running clock of the adult Syrian hamster and outbred (ID(ICR)) but not inbred (C57B16) mice. Syrian hamsters bearing lesions of the intergeniculate leaflet of the thalamus remain able to entrain and phase-shift to light, but the lesions block completely entrainment by serial arousal, even though lesioned animals continue to respond acutely to the arousing cue. This suggests that the innervation from the IGL to the SCN is a necessary component of the pathways which signal an aroused state to the clock. Siberian hamsters do not entrain to serial arousal but they do entrain to serial injections of melatonin, whereas in adult Syrian hamster, systemic treatment with melatonin has no effect above that of arousal. In contrast to the adult, the foetal and neonatal Syrian hamster can be entrained by melatonin. These variations in sensitivity correlate with inter-specific and developmental differences in the pattern and level of expression of melatonin receptors in the SCN. The perinatal hamster can also be entrained by dopaminergic agonists. SCN tissue from neonatal Syrian hamsters was used to characterise the biochemical actions of dopamine and melatonin. In primary culture and tissue explants, forskolin, dopamine and glutamatergic agonists all stimulated the phosphorylation of the transcription factor CREB. This probably occurred via convergent actions through Ca2+ (glutamate) and cyclic AMP-dependent (forskolin, dopamine) signalling pathways. Dopamine induced phospho-CREB-ir exclusively in GABA-ir neurons and melatonin reversed this effect of dopamine, indicative of an inhibitory Gi protein linking via the Mel1a receptor to adenylyl cyclase. The regulation of phospho-CREB by multiple entraining cues in the SCN highlights its position as a point of convergence for regulators of the clock, and indicates a possible role in entrainment.

Afferent Pathways↗
PubMed1996

A Scottish family with Bazex-Dupré-Christol syndrome: follicular atrophoderma, congenital hypotrichosis, and basal cell carcinoma.

Bazex-Dupre-Christol syndrome (BDCS) is an X linked dominant disorder of the hair follicle characterised by follicular atrophoderma, multiple basal cell carcinomas, hypotrichosis, milia, and localised hypohidrosis. Follicular atrophoderma (FA) are follicular funnel shaped depressions, "ice pick marks", seen most commonly on the dorsum of the hands. We describe the first known Scottish family with this syndrome, five affected members spanning three generations. They have hypohidrosis confined to the face, coarse hair, dry skin, milia, and follicular atrophoderma. All the adults have a history of multiple basal cell carcinomas. None of them has any skeletal feature suggestive of Gorlin's syndrome. The clinical features, skin histology, and scanning electron microscopic (SEM) examination of the hair are described and illustrated. The features are compared with 15 previous reports of BDCS and four reports in which this is a possible diagnosis are also reviewed. BDCS should be considered as a differential diagnosis in patients with early onset or familial basal cell carcinomas.

Adult↗
PubMed1995

Ascertainment of myotonic dystrophy through cataract by selective screening.

Myotonic dystrophy (DM) almost always results from the expansion of an unstable (CTG)n repeat. The mutation can be detected directly. Affected patients with cataracts may have minimal additional signs of the disorder, but all are at risk of life threatening complications. We have studied the efficacy of detecting new families with myotonic dystrophy by selectively screening cataract patients. Selection criteria were: age under 60 with no obvious precipitating factor (except non-insulin dependent diabetes mellitus (NIDDM)); patients of any age with other signs suggestive of myotonic dystrophy detected by the ophthalmologist. Ninety-six patients were tested prospectively; 17 others under 55 were screened retrospectively. All patients were counselled by a clinical geneticist before testing. The patients' DNA was analysed using the DNA probe/restriction enzyme combinations GB2.6/EcoRI, KB1.4/BglI and polymerase chain reaction (PCR). Six patients have been found to have a mutation, three (3.1%) in the prospective group and three (17.6%) in the retrospective group. Three of these patients had minimal myotonic dystrophy and three had classical DM.

Adolescent↗
PubMed1994

Adenovirus infection enhances in vitro adherence of Streptococcus pneumoniae.

Viruses are thought to facilitate bacterial infections of the respiratory tract, but the mechanisms are poorly understood. The present study analyzed the effect of adenovirus on bacterial adherence to human respiratory tract epithelial cells. The human lung carcinoma cell line A549 was infected with adenovirus of types 1, 2, 3, 4, 5, and 9. At a multiplicity of infection of 75 particles per cell, cytopathic effects occurred in 75 to 100% of the cells within 48 h. The virus-infected cells were harvested at various times after infection and analyzed for the ability to bind strains of Haemophilus influenzae and Streptococcus pneumoniae. Adenovirus (types 1, 2, 3, and 5) commonly causing respiratory tract infections increased the binding of adherent S. pneumoniae strains to the cells. This effect was not seen for other adenovirus types. Adenovirus infection did not change the adherence of cells of poorly adhering strains of S. pneumoniae or H. influenzae. The increase in adherence of S. pneumoniae could be inhibited by the DNA synthesis inhibitor cytosine arabinofuranoside, which is known to block the late phase of the adenovirus infection. When electron microscopy was used, there was no evidence that virus particles bound directly to bacteria. Adherence was not affected by pretreatment of the cells with virus particles or viral proteins. This suggested that adenovirus infection upregulated receptors for S. pneumoniae. The increased attachment may be one mechanism by which viruses precondition the respiratory mucosa for bacterial infection.

Adenoviridae↗
PubMed1993

The innervation of salivary glands as revealed by morphological methods.

Salivary secretion is nerve mediated. The salivary glands are supplied by parasympathetic and sympathetic efferent nerves which travel to the glands by separate routes. Once in the glands the axons from each type of nerve intermingle and travel together in association with Schwann cells, forming Schwann-axon bundles. Two types of neuro-effector relationships exist with salivary parenchymal and myoepithelial cells: epilemmal (outside the parenchymal basement membrane) and hypolemmal (within the parenchymal basement membrane). Their relative frequencies with either type of nerve differ greatly between glands and species. Salivary blood vessels receive epilemmal innervations by both sympathetic and parasympathetic axons. The classical transmitters--acetylcholine in parasympathetic and noradrenaline in sympathetic axons--are stored in small vesicles. A variety of non-conventional neuropeptide transmitters have also been found in salivary nerves by immunohistochemistry, and they occur in large dense-cored vesicles. Prolonged high frequency stimulation has been found to cause depletion of large dense-cored vesicles from glandular nerves. In recent years afferent nerves have started to be identified and are found in greatest numbers around the main salivary ducts, where they may form a hypolemmal association with the epithelial cells. Functional studies demonstrate complex interactions between parasympathetic and sympathetic nerves. Morphological assessments of changes in the parenchymal cells after nerve stimulations or denervations add greatly to our understanding of the nerve functions. At least four types of influence can be exerted on salivary parenchymal cells by the nerves: hydrokinetic (water mobilizing), proteokinetic (protein secreting), synthetic (inducing synthesis), and trophic (maintaining normal functional size and state). In respect to each role, wide glandular and species differences exist between the relative contributions made by each type of nerve.

Animals↗
PubMed1993

Correlation of HBeAg/anti-HBe, ALT levels, and HBV DNA PCR results in HBsAg-positive patients.

A highly sensitive polymerase chain reaction (PCR) was used to analyse serum samples from HBsAg-positive patients in Sweden. Forty-two chronic carriers were tested, five of whom were of Swedish origin. Of the total, there were 13 HBeAg-positive and 27 anti-HBe-positive patients, while 1 patient was negative for both HBeAg and anti-HBe and one was positive for both markers. Nine of the 13 HBeAg-positive carriers and only 7 of the 27 anti-HBe-positive carriers had elevated alanine transaminase (ALT) levels (P = 0.01). Two PCR tests of marginally different sensitivity were used on all patient samples. All 13 HBeAg-positive patients and the patients with and lacking both HBeAg and anti-HBe markers, respectively, were positive in both PCR tests. One HBeAg-positive patient was shown to shed hepatitis B virus (HBV) DNA in both saliva and urine. Twelve of the 27 anti-HBe-positive carriers, 6 of whom had elevated ALT levels, were PCR positive. The remaining 15 had no evidence of HBV DNA and all but 1 had normal ALT levels. A positive PCR result was more common in those anti-HBe-positive patients with elevated ALT levels (P < 0.02). The precore gene from 18 samples was sequenced and, with a few exceptions, showed a high degree of conservation. We suggest that in the absence of optimal tests for infectivity of serum from HBsAg-positive patients, and until PCR becomes more widely available, all anti-HBe-positive patients with elevated ALT levels be considered highly infectious.

Acute Disease↗
PubMed1992

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↗
PubMed1990

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↗
PubMed1987

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↗
PubMed1985

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↗
PubMed1984

Constipation and congenital disorders of the myenteric plexus.

Full-thickness muscle biopsies have been taken from patients with severe disabling chronic constipation that has not responded to conservative measures. Assessment by neurohistochemical techniques has revealed that a range of neuronal dysplasias of the myenteric plexus are responsible in many cases; these include aganglionosis (Hirschsprung's disease), hypoganglionosis and hyperganglionosis. In cases considered unlikely to be Hirschsprung's disease on clinical grounds, the procedure used has often been anorectal myectomy; this has not only provided tissue for diagnosis but has also been of therapeutic value in most cases of hypoganglionosis and some cases reported as 'normal'.

Adult↗
PubMed1982

Kallikrein-like activity in salivary glands using a new tripeptide substrate, including preliminary secretory studies and observations on mast cells.

The tripeptide substrate D-val-leu-arg-4-methoxy-2-naphthylamine gave a precise localization of reaction product in cryostat sections of aldehyde-fixed salivary glands from a number of species, with Fast Blue B as the capture reagent. In submandibular glands, there was strong staining of the granules in granular tubules of rats and hamsters and somewhat less in mice. Submandibular striated ducts showed variable periluminal staining in a finer granular form; it was abundant in guinea-pigs, strong in cats but somewhat less pronounced in dogs. Parotid glands contained less reactivity with none detectable in hamsters and guinea-pigs. In the rabbit, neither gland showed any reaction. Mast cells were densely stained in glands from cats and dogs; they were less reactive in rats and unstained in the other species. The closely related 7-amino-4-trifluoromethylcoumarin derivative of the tripeptide has been found highly satisfactory for assessing activity in submandibular saliva from cats. Preliminary functional studies indicate that an extensive rapid secretion of enzyme occurs into saliva on sympathetic stimulation, with a corresponding depletion of reactive material from the striated ducts in tissue sections. Far less mobilization of enzyme occurs into saliva on parasympathetic stimulation with no obvious change in the histochemical reaction of striated ducts. The possible significance of these findings in cats is discussed. Extensive qualitative and quantitative studies are required to evaluate enzyme and substrate specificities in each species. Nevertheless, derivatives of D-val-leu-arg offer great promise for the functional testing of kallikrein-like reactivity both by histochemical means on cells and biochemically in their secretions.

Animals↗