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Biomedical subjects

R Lloyd

Publications and source records attributed to R Lloyd.

At least 19 recordsLinked to original sources

Nitric oxide synthase and cGMP activity in the salivary glands of the American dog tick Dermacentor variabilis.

We colocalized nitric oxide synthase (NOS) activity in epithelial cells that surround the salivary gland duct in female Dermacentor variabilis with NADPH diaphorase histochemistry and immunohistochemistry using a polyclonal anti-endothelial NOS. Using size-exclusion chromatography, a fraction with a molecular mass of about 185 kDa that had diaphorase activity was eluted from tick salivary gland homogenate. This fraction converted arginine to citrulline with the production of nitric oxide (NO), which was detected by using electron spin resonance spectroscopy. The complete activity of the diaphorase fraction was dependent on NADPH, FAD, tetrahydrobiopterin, calmodulin, (CaM), and Ca(2+), but was not dependent on dithiothreitol. The arginine analog N(G)-monomethyl-L-arginine inhibited the activity of this fraction. NO and arginine activated soluble guanylate cyclase to produce cGMP in dopamine-stimulated isolated salivary glands. Dopamine-stimulated isolated salivary glands treated with tick saline containing either EDTA, the NOS inhibitor N(G)-nitro-L-arginine methyl ester, or the calcium/CaM binding inhibitor W-7 showed no increase in cGMP. The NO donor sodium nitroprusside significantly increased cGMP levels in unstimulated isolated salivary glands. A possible function for NO in salivation by this ixodid tick is discussed.

Animals↗

The oxygen consumption associated with unloaded walking and load carriage using two different backpack designs.

The purpose of this study was to assess the energy expenditure associated with load carriage using both a traditional rucksack and a new rucksack design, the AARN rucksack, which incorporates front balance pockets. Nine volunteers walked at 3 km h(-1) at various uphill and downhill gradients on a treadmill without a load and carrying a load of 25.6 kg in each of the rucksacks. The oxygen consumption associated with both of the loading conditions was significantly (P < 0.001) higher than that associated with unloaded walking at all downhill gradients tested, although there was no significant difference between the two loading conditions. During the uphill gradients the oxygen consumption associated with the AARN pack was significantly (P < 0.05) lower than that associated with the traditional pack at the 0%, 5%, 10% and 20% gradients. The mean (%) differences at these gradients, expressed in ml x kg(-1) x min(-1) were 1.18 (9%), 1.45 (8%), 1.76 (8%) and 1.88 (6%), respectively. On average for the whole protocol, the oxygen consumption associated with the AARN rucksack was 5% lower than that associated with the traditional rucksack [mean (SD) 17.28 (7.46) ml x kg(-1) x min(-1) for the AARN pack and 18.20 (7.84) ml x kg(-1) x min(-1) for the traditional pack]. The findings of the present study suggest that a load carriage system that allows the load to be distributed between the back and font of the trunk is more appropriate for carrying relatively heavy loads than a system that loads the back only.

Adult↗

Immunolocalization of vascular endothelial growth factor in the GH3 cell line.

The question of whether vascular endothelial growth factor (VEGF) is expressed in the GH3 cell line was investigated using immunocytochemistry, immunoelectron microscopy, and Western blotting. Using immunocytochemistry, VEGF was demonstrated in approximately 90% of the cells. Immunopositivity was localized mainly in the paranuclear Golgi region. In a small minority of cells, diffuse cytoplasmic immunostaining was also noted. By immunoelectron microscopy VEGF was evident in the secretory granules, cytoplasmic vesicles, rough endoplasmic reticulum, and the Golgi apparatus. Western blotting confirmed the results of the morphologic studies. It can be concluded that VEGF, which is know to induce angiogenesis and to increase vascular permeability, is produced in the prolactin- and growth hormone (GH)-secreting GH3 cell line. The functional role of VEGF in the GH3 cells is unknown. It is possible that this growth factor affects endocrine activity of GH3 cells by a paracrine mechanism.

Animals↗

Kinetic changes associated with load carriage using two rucksack designs.

This study assessed changes in kinetics from unloaded walking associated with load carriage using both a traditional and a new rucksack design that incorporates front balance pockets (AARN). Nine subjects walked at 3(+/-0.05) km x h(-1) over a force plate unloaded and carrying 25.6 kg in each of the rucksacks. The order of trials was randomized and speed-controlled by use of photoelectric cells and a millisecond timer. Anteroposterior and vertical ground reaction forces were analyzed using repeated measures ANCOVA (speed covariate). There was a trend for the AARN pack to elicit a shorter support time than the traditional pack, 1.025+/-0.049 versus 1.037+/-0.06 s (p = 0.056), while the unloaded condition produced the shortest support time, 1.016+/-0.04 s. Both braking and propulsive forces for the rucksacks were significantly greater than for unloaded walking. While there was no significant difference between the packs for the braking force, the AARN pack produced a significantly lower (p<0.05) propulsive force than the traditional rucksack, 0.79+/-0.2 versus 0.94+/-0.16 N x kg bodyweight(-1). Both rucksacks produced significantly greater (p<0.001) vertical force peaks than unloaded walking, the increases being proportional to the increase in system weight. These findings indicate that there may be some advantage in terms of propulsive force production for the front/back system.

Analysis of Variance↗

Nursing rotas. Shift up.

Trusts may wish to consider more flexible, staggered daytime shifts, which accommodate married nurses--for instance, 9.30 am-3.30 pm on weekdays with longer hours at weekends/on nights to ensure that contractual requirements are met. For larger trusts, creche/nursery facilities may solve the problem. After-school clubs on site on a voluntary basis may also mean that more married women and unmarried women with children could more easily accommodate standard shifts. The tribunal decision seems to condone the provision of somewhat ad hoc training and supervision, whereas in professional practice continuous supervision and participation in professional developments are essential elements in the provision of safe, high-quality clinical practice.

Contract Services↗

Sliding dermoid cyst. A case report.

Dermoid cysts of the oral cavity usually present as a solitary, painless mass in the midline or, on occasion, more laterally in the submandibular region. A patient is described who presented with a mass in the submandibular region, which could be made to appear or disappear at will. This unusual manifestation occurred as the cyst plunged around the posterior border of the mylohyoid on tensing the floor of the mouth.

Adolescent↗

Massetolides A-H, antimycobacterial cyclic depsipeptides produced by two pseudomonads isolated from marine habitats.

Massetolides A-H (1-8), novel cyclic depsipeptides, and the known compound viscosin (9) have been isolated from cultures of two Pseudomonas sp. isolated from a marine alga and a marine tube worm, respectively. Massetolide A (1) and viscosin (9) exhibit in vitro antimicrobial activity against Mycobacterium tuberculosis and Mycobacterium avium-intracellulare. Precursor-directed biosynthesis has been used to generate unnatural massetolides 11-13 incorporating nonprotein amino acids.

Anti-Bacterial Agents↗

Mutator tRNAs are encoded by the Escherichia coli mutator genes mutA and mutC: a novel pathway for mutagenesis.

We have previously described the mutator alleles mutA and mutC, which map at 95 minutes and 42 minutes, respectively, on the Escherichia coli genetic map and which stimulate transversions; the A.T-->T.A and G.C-->T.A substitutions are the most prominent. In this study we show that both mutA and mutC result from changes in the anticodon in one of four copies of the same glycine tRNA, at either the glyV or the glyW locus. This change results in a tRNA that inserts glycine at aspartic acid codons. In view of previous studies of missense suppressor tRNAs, the mistranslation of aspartic acid codons is assumed to occur at approximately 1-2%. We postulate that the mutator tRNA effect is exerted by generating a mutator polymerase and suggest that the epsilon subunit of DNA polymerase, which provides a proofreading function, is the most likely target. The implications of these findings for the contribution of mistranslation to observed spontaneous mutation rates in wild-type strains, as well as other cellular phenomena such as aging, are discussed.

Alleles↗

Pathogenesis of gastric metaplasia of the human duodenum: role of Helicobacter pylori, gastric acid, and ulceration.

BACKGROUND & AIMS: The pathogenesis of gastric metaplasia (GM) in the duodenum is unclear. The aim of this investigation was to study the effect on the extent of GM of ulcer healing, Helicobacter pylori eradication, and acid suppression singly and in combination. The relationship between GM and gastroduodenal inflammation and H. pylori infection density was also studied. METHODS: Duodenal and gastric antral biopsy specimens were obtained from H. pylori-positive patients with duodenal ulcer and from H. pylori-positive nonulcer subjects. Biopsy procedures from patients with duodenal ulcer were repeated after 6 months of treatment. Nonulcer subjects were treated symptomatically and did not undergo re-endoscopy. RESULTS: Ulcer healing alone produced no change in GM or in gastroduodenal inflammation. H. pylori eradication produced a 42% reduction in GM and improvement in inflammation. Acid suppression produced a 43% reduction in GM but without a significant change in inflammation. A combination of H. pylori eradication and acid suppression produced an additive effect with a 66% reduction in GM. A positive relationship was detected between the extent of GM and antral H. pylori density, duodenitis score, and antral gastritis score. CONCLUSIONS: This study shows that the extent of duodenal GM is unrelated to the presence or absence of ulceration but is partly due to H. pylori and partly due to acid.

Adult↗

Prospective screening of dyspeptic patients by Helicobacter pylori serology.

Helicobacter pylori infection is associated with 95% of duodenal ulcers and more than 80% of gastric ulcers. Several reports have indicated that screening for H pylori may avoid subsequent endoscopic examination. We screened 183 dyspeptic patients, aged under 45, by taking a history of sinister symptoms and regular use of non-steroidal anti-inflammatory drugs (NSAIDs), together with serological testing for H pylori. Endoscopy was performed on 113 patients, of whom 90 (49%) were seropositive, 14 (8%) had sinister symptoms, and 9 (5%) had used NSAIDs regularly. In 34 (19%) patients we detected peptic ulceration. The remaining 70 (38%) patients who were H pylori seronegative, had no sinister symptoms, and had not taken NSAIDs (screen-negative), did not undergo endoscopy but were returned to their primary care physician for treatment of symptoms. At subsequent reassessment (of the non-endoscoped group), symptom severity (p = 0.002), interference with life events (p = 0.01), and medication (p = 0.0002) were all significantly lower in the 6 months after screening than in the 6 month period before screening. Only three screen-negative patients were re-referred after screening but their endoscopic findings were normal. Thus, 67 (36%) endoscopies were avoided. When the non-endoscoped screen-negative patients were compared with a cohort of endoscoped screen-negative patients, the groups did not differ in terms of symptom severity (odds ratio 1.12, 95% CI 0.53-2.35, p = 0.77) or interference with life events (0.82, 0.38-1.76, p-0.61). However, medication use was significantly less (0.37, 0.17-0.80, p = 0.01) in those who did not have an endoscopy. Our study indicates that colonisation screening based on H pylori serology, a history of sinister symptoms, or a history of NSAID use was worthwhile in dyspeptic patients. We avoided 37% of endoscopies and reduced drug usage without disadvantaging those not endoscoped.

Adult↗

Neurochemical correlates of the Klüver-Bucy syndrome by in vivo microdialysis in monkey.

The Klüver-Bucy syndrome is a well known consequence of lesions of the temporal lobe, but the neural mechanisms remain obscure. To elucidate the neurochemical changes in this syndrome, we utilized in vivo microdialysis of amygdala and hypothalamus in two Cebus monkeys (C. apella) before and after bilateral lesions of the temporal pole (TP). Both subjects were housed and observed in a social group when not being dialyzed. Behavioral changes consequent to the TP lesion included early postoperative anorexia, adipsia, hunched posture, tameness, and lethargy. Subsequently loss of fear, hyperorality, loss of social rank, and social withdrawal were observed. Neurochemical changes in amygdala included fall in DA metabolites, increase in NE, and fall in 5-HIAA. The amino acids glutamate and aspartate were both lower postoperatively but more so in the subject with the greatest behavioral changes. Similar changes were noted in hypothalamus except for DA metabolites which remained unchanged. The Klüver-Bucy syndrome consequent to ablation of the temporal pole appears related to a partial deafferentation of excitatory projections to amygdala, along with a lowering of DA and 5-HIAA and an increase in NE.

Animals↗

Sites of synthesis of chromogranins A and B in the human brain.

The sites of synthesis of the chromogranins A and B, and their potential processed peptides, were examined by quantitating the levels of chromogranin A and B mRNA in various regions of the human brain by Northern blot analysis. Chromogranin A and B mRNA expression in the brain is region-specific and confined to grey matter. In situ hybridization histochemistry detected chromogranin A and B mRNA in pyramidal neurons of human cerebral cortex. Cell-specific expression in subpopulations of cerebrocortical neurons suggest that chromogranin A and B gene products may play a role in central neuronal function.

Brain↗

Relationship between increased cyclic AMP-phosphodiesterase activity and abnormal adenylyl cyclase regulation in leukocytes from patients with atopic dermatitis.

Atopic dermatitis (AD) is characterized by a variety of abnormal physiologic and pharmacologic responses in the skin. Leukocyte abnormalities of the cyclic nucleotide system include increased cAMP phosphodiesterase (PDE) and adenylyl cyclase activities. We have evaluated the possibility that a defect of the inhibitory GTP-binding protein (Gi) might cause inadequate modulation of adenylyl cyclase activity in AD leukocytes. We carried out a series of studies assessing adenylyl cyclase and Gi subunits in monocyte membranes. Using both pertussis toxin ribosylation and direct monoclonal antibody labeling of Gi proteins, we have shown evidence for a decrease or possible absence of one of the Gi proteins in atopic monocyte membranes. A genetic defect or toxin-mediated abnormality in leukocyte membrane Gi could account for these findings. Increased cAMP degradation by PDE may be a compensatory mechanism for increased cAMP synthesis that is regulated by GTP-binding proteins. But this increased PDE activity also rendered AD leukocytes hypo-responsive to immunofunction regulatory signals mediated by cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗