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Biomedical subjects

N Turner

Publications and source records attributed to N Turner.

At least 55 records · Page 3Linked to original sources

The treatment of epiphora with balloon dacryocystoplasty.

We examine a new treatment for epiphora: balloon dilatation of the nasolacrimal duct, or dacryocystoplasty. The procedure, which was performed as an out-patient procedure under local anaesthetic, was carried out on 20 patients with epiphora, 17 due to anatomical and 3 due to functional obstruction. There was an overall success rate of 60%, with complete relief of symptoms in 4 patients and a symptomatic improvement in another 8 (follow-up 2-9 months, mean 4.2 months). All patients tolerated the procedure well with minimal per-operative and post-operative discomfort. A higher success rate was seen in those patients with either a low anatomical or a functional obstruction. The procedure can be easily repeated and, if unsuccessful, still allows a dacryocystorhinostomy to be performed at a later date.

Adolescent↗

Proton transport and Na+/H+ exchange in vesicles isolated from sockeye salmon (Oncorhynchus nerka) kidneys during migration from salt to fresh water.

Renal epithelial function, proton flux and sodium stimulated proton flux, was observed in vesicles isolated from the brush border of the proximal tubule of Sockeye Salmon (Oncorhynchus nerka) during migration. Brush border membrane vesicles (BBMV) were isolated from the body kidney of Sockeye Salmon using aggregation/differential centrifugation techniques. Vesicle purity was tested using a series of epithelial and basal lateral markers including alkaline phosphatase, maltase, gamma-glutamyl transferase (GGTP), Mg(2+)-activated ATP-ase, Na(+)+K(+)-activated ATPase, and 5'-nucleotidase and the lysosomal marker acid phosphatase. An enrichment/depletion factor for each marker was determined by comparison of purified BBMV with kidney homogenate. Vesicles exhibit an enrichment factor for alkaline phosphatase, GGTP, maltase, Mg(2+)-activated ATP-ase, Na(+)+K(+)-activated ATPase, and 5'-nucleotidase. A depletion factor was observed for acid phosphatase. Vesicle integrity was tested by measuring the time course of proton flux in the presence of a pH gradient. Amiloride sensitive sodium stimulated proton flux was observed in these vesicles. The presence of sodium caused a saturable increase in the rate of proton flux, indicating the activity of a sodium/proton antiport protein in BBMV.

Acclimatization↗

Characterization of a simian virus 40-transformed human podocyte cell line producing type IV collagen and exhibiting polarized response to atrial natriuretic peptide.

Biology of glomerular visceral epithelial cells ("podocytes") and their role in inflammatory process remain obscure, partly because of the lack of well-differentiated podocyte cultures. We have established a human cell line by transfecting with a replication-defective SV40 plasmid (pSVHB1), a primary culture of podocytes derived from an enriched preparation of unencapsulated glomeruli free of tubule and Bowman's capsule contaminants. Podocyte specificity of the primary culture was assessed by a dual immunomorphological and functional approach. The resulting cell line (HGVEC.SV1) was cloned and the clonal cells were adapted to hormonally defined medium supplemented with only 2% newborn bovine serum. Clone A4 has been exhibiting over 35 passages, a combination of markers unique to podocytes, including expression of vimentin, podocalyxin, ectoenzymes (CALLA antigen and mRNA), heparan-sulfate proteoglycans (molecular mass of core protein = 75 kDa), and production of type IV collagen (alpha 1 and alpha 5 chains) established by immunoprecipitation and Northern blot analysis. Cytokeratin was detected in rare cellular foci and the search of Von Willebrand factor was negative. This clonal cell line has been used to demonstrate: (1) that human podocytes are highly sensitive to atrial natriuretic peptide (ANP) which induced a dose-dependent increase in cGMP production (x20 at 0.5 microM ANP), and (2) that secretion of ANP-stimulated cGMP is dramatically polarized as 93% of extracellular cGMP were released in the apical medium when filter-grown HGVEC. SV1A4 cells were stimulated at their basal pole.

Antigens, Differentiation↗

The effect of dry and humid hot air inhalation on expired relative humidity during exercise.

It has been previously demonstrated that under certain environmental conditions, expired air is not fully water saturated because of the low relative humidity of the first part of the expirate. This finding is of interest to those involved in respirator research, particularly those who design and test robotic metabolic simulators. These simulators must accurately mimic the physiological responses of human airways to breathing air of various temperatures and relative humidities (RHs). Because these responses are not fully quantified, this study examined the mean relative humidity of expired air during four inspired air conditions: cool dry (26 degrees C, 60% RH), cool humid (26 degrees C, 95% RH), hot dry (45 degrees C, 11% RH), and hot humid (45 degrees C, 95% RH). These conditions were administered during three exercise intensities: rest, low (35% VO2max), and moderate (70% VO2max). As compared to the cool dry (CD) condition, frequency of breathing (f) was 9.3% lower and tidal volume (VT) was 9.4% greater across all exercise intensities for the hot humid (HH) condition (p less than 0.05). Mean expired relative humidity (ERH) was substantially lower for the hot dry (HD) condition as compared to the other three conditions during each sampling period. These findings support the conclusion that the mean ERH of expired air depends upon several respiratory and environmental factors in addition to inspired air temperature.

Adolescent↗

Molecular cloning of the human Goodpasture antigen demonstrates it to be the alpha 3 chain of type IV collagen.

To characterize the autoantigen of Goodpasture's (anti-glomerular basement membrane) disease, a molecule of 26-kD reactive with autoantibodies from patients' sera was purified from collagenase digests of sheep glomerular basement membrane. Short internal amino acid sequences were obtained after tryptic or cyanogen bromide cleavage, and used to deduce redundant oligonucleotides for use in the polymerase chain reaction on cDNA derived from sheep renal cortex. Molecules of 175 bp were amplified and found to come from two cDNA sequences. One was identical to that of a type IV collagen chain (alpha 5) cloned from human placenta and shown to be expressed in human kidney. The other was from a type IV collagen chain with close similarities to alpha 1 and alpha 5 chains, and was used to obtain human cDNA sequences by cDNA library screening and by further polymerase chain reaction amplifications. The correspondence of the derived amino acid sequence of the new chain with published protein and cDNA sequences shows it to be the alpha 3 chain of type IV collagen. Its gene, COL4A3, maps to 2q36-2q37. The primary sequence and other characteristics of this chain confirm that it carries the Goodpasture antigen.

Amino Acid Sequence↗

Isolation from commercial aurintricarboxylic acid of the most effective polymeric inhibitors of von Willebrand factor interaction with platelet glycoprotein Ib. Comparison with other polyanionic and polyaromatic polymers.

Solutions of commercial aurintricarboxylic acid (ATA) inhibit ristocetin- or shear stress-induced, von Willebrand factor (vWF)-mediated platelet aggregation by interacting with vWF and blocking its attachment to platelet membrane glycoprotein Ib. ATA has also been shown to prevent cyclic platelet clumping in a dog model of coronary artery thrombosis. Because these ATA solutions are actually a heterogeneous mixture of polyanionic, polycarboxylic polyaromatic polymers of molecular weight (Mr) 200 to greater than 6,000, we separated the most effective inhibitory components of commercial ATA using exclusion chromatography. ATA polymers larger than Mr 700 inhibited ristocetin-induced, vWF-mediated platelet aggregation more effectively than smaller ATA polymers, whereas shear-induced, vWF-mediated platelet aggregation was optimally inhibited by ATA polymers of Mr greater than or equal to 2,500. Platelet aggregation mediated by vWF was not inhibited by a nonphenolic, polyanionic polymer (polyglutamic acid) or by a polyphenolic ATA-like polymer (aurin) devoid of carboxyl groups. Polyanionic, polysulfonated aromatic polymers (polystyrene sulfonate) of Mr 35, 17.4, 8, and 4.6 x 10(3) inhibited ristocetin- and shear-induced, vWF-mediated aggregation with less potency on a mass/volume basis than large polymers of ATA. We conclude that a polyanionic, polycarboxylated, polyphenolic ATA polymer of Mr 2,500 is optimally potent as an inhibitor of shear- and ristocetin-induced, vWF-mediated platelet aggregation and is likely to be more effective than solutions of commercial ATA as an anti-arterial thrombotic agent.

Adenosine Diphosphate↗

British community norms for the Brief Symptom Inventory.

British community norms (N = 376) for the Brief Symptom Inventory (Derogatis & Spencer, 1982) are presented. Means are significantly higher than previously published US norms for all symptom dimensions, and show variability according to age, sex and work status. The proportion of 'cases' in the sample is similar to other British estimates. It is recommended that culturally relevant norms should be established and used in future work with this instrument.

Adolescent↗

Urinary N tau-methylimidazole acetic acid excretion in respiratory disease.

N tau-methylimidazole acetic acid (N tau-MIAA) is the principal urinary metabolite of histamine. The basal urinary excretion rate of N tau-MIAA was determined as 0.117 +/- 0.008 (SE) mg/h, with a renal clearance for N tau-MIAA of 273 +/- 27 ml/min implying active secretion. After subpharmacological infusion of histamine (50 ng.kg-1.min-1 over 2 h) in five volunteers that increased plasma histamine from 0.28 +/- 0.04 to 0.71 +/- 0.15 ng/ml, urinary excretion of N tau-MIAA over 8 h was increased by less than 17% compared with a control saline infusion. Urinary N tau-MIAA excretion in normal controls (273 +/- 14 micrograms/mmol creatinine) was similar to that observed in patients with severe acute asthma (253 +/- 22 micrograms/mmol), antigen-induced bronchoconstriction (269 +/- 21 micrograms/mmol), seasonal allergic rhinitis (304 +/- 31 micrograms/mmol), and clinically stable bronchiectasis (270 +/- 22 micrograms/mmol). In contrast, large increases in metabolite excretion (greater than 7,000 micrograms/mmol creatinine) were observed in a patient with systemic mastocytosis where very high plasma histamine levels were recorded (greater than 500 ng/ml) and marked systemic hemodynamic effects occurred. We conclude that urinary N tau-MIAA will only be increased in pathologies where sustained hyperhistaminemia occurs and that increased local histamine production in the lung or the upper airway does not cause a measurable change in the basal urinary excretion of this metabolite.

Adult↗

Aortic dissection masquerading as systemic disease--the post-dissection syndrome.

Three patients presented with a prolonged illness accompanied by fever, weight loss, high ESR, neutrophilia, abnormal liver function tests, urinary abnormalities and, in one case, splinter haemorrhages and impairment of renal function. Aortic dissection was diagnosed 3-12 weeks after the onset of the illness, and probably accounted for the entire syndrome. All abnormalities resolved spontaneously over the following months. There are few similar cases in the literature, and the syndrome could easily pass unrecognized. Aortic dissection should be considered as a possible cause of any systemic illness of sudden onset, but especially if there is an initial history of chest or abdominal pain, or evidence of previous hypertension or other risk factors.

Aortic Dissection↗

Urinary leukotriene E4 after antigen challenge and in acute asthma and allergic rhinitis.

The leukotrienes LTC4, D4, and E4 are potent bronchoconstrictor agents and are thought to have an important role in asthma. Urinary LTE4, a stable urinary end-product of LTC4 and LTD4, was measured, by means of high-performance liquid chromatography and radioimmunoassay. LTE4 excretion followed a log-normal distribution in twenty-nine healthy controls, with a geometric mean of 23.8 (95% confidence interval 19.9-28.2) ng/mmol creatinine. Urine was collected from eight atopic subjects for 3 h after antigen inhalation and a control urine collection was made a week later at the same time of day. Urinary LTE4 was significantly higher after antigen challenge than in the control sample (153.7 [87.1-271.3] vs 23.5 [13.7-69.5] ng/mmol creatinine; p less than 0.01). Urinary LTE4 was also measured in twenty patients with severe acute asthma and nine patients with seasonal allergic rhinitis. Mean urinary LTE4 was higher in the asthmatic patients (78.3 [46.5-131.8] ng/mmol creatinine) than in normal subjects (p less than 0.01), although there was substantial overlap into the normal range. The urinary LTE4 values of the rhinitis patients were within the normal range whether or not they had symptoms. LTC4 and LTD4 were also found in bronchoalveolar lavage fluid from one of the three atopic subjects challenged with antigen before lavage, and in a single patient who underwent lavage after admission with severe acute asthma. These studies provide evidence that leukotrienes are released in vivo in man after antigen challenge and in acute asthma.

Acute Disease↗

Physical performance during combinations of hypercapnic, resistive, and hot air breathing.

Performance time for a 3.2-km (2-mi) run at maximal voluntary speed was determined for 12 subjects under seven experimental conditions: resistance breathing (R), hypercapnia (C), hot air breathing (H), and combinations R + C, R + H, H + C, and R + H + C. The tests were performed on a treadmill at 5% grade. Performance time was increased significantly when the subjects were exposed to resistance breathing alone (9%) or to any combination condition containing resistance (16%-31%). The effect of breathing resistance was not specific to the presence or absence of C, H, or their combination. Nevertheless, the physiological effects were not additive and could not be predicted by knowing the effects of the individual stresses. Performance time also was increased in Condition H + C (9%). Pulmonary ventilation was the most affected physiological variable, significantly reduced in Conditions R, H, C + R, H + R, and H + C + R. In conclusion, a multistress approach should be used when determining physiological responses or performance limitations brought about by real or simulated industrial respirator-wear conditions.

Adult↗

Investigation by electron paramagnetic resonance spectroscopy of the molybdenum centre of respiratory nitrate reductase from Paracoccus denitrificans.

The molybdenum centre of respiratory nitrate reductase from Paracoccus denitrificans has been investigated by e.p.r. spectroscopy of Mo(V). In common with the centres of the analogous enzymes from Escherichia coli and Pseudomonas aeruginosa, it undergoes a pH- and anion-dependent transition between two different e.p.r. signal-giving species. Comparison of the relevant e.p.r. parameters extracted with the help of computer simulations reveals ligation of the metal in the active centres of the three enzymes to be identical.

Electron Spin Resonance Spectroscopy↗

Procarbazine is a potent mutagen at the heterozygous thymidine kinase (tk +/-) locus of mouse lymphoma assay.

Procarbazine (Natulan) is a potent inducer of gene mutations at the heterozygous tk +/- locus in L5178Y mouse lymphoma cells in the presence of Aroclor-induced rat liver S9 metabolic activation (approximately 10(-3) mutant frequency at 10 micrograms/ml) while exerting a far weaker effect in the absence of S9. This mutagenicity is fairly robust with respect to the quantitative composition of the S9 mix and to variations in mouse lymphoma assay protocols (soft agar cloning versus 'microwell' assays). The high proportion of small colony tk -/- mutants induced by procarbazine together with the far weaker mutagenic response at the hemizygous hgprt locus in these same cells is interpreted in terms of a chromosomal or multi-gene mutational mechanism. Although procarbazine is clastogenic in vivo, it does not appear to be so under standard protocols using cultured human lymphocytes (+/- S9). It is not yet clear why this should be so, especially in light of its apparent clastogenicity in mouse lymphoma cells.

Animals↗

Aurin tricarboxylic acid: a novel inhibitor of the association of von Willebrand factor and platelets.

Shear stress activated platelets undergo aggregation in the presence of large or unusually large von Willebrand factor (vWF) multimers without the addition of ristocetin or any other exogenous chemical. This phenomenon may be analogous to the platelet aggregation that leads to thrombosis in the narrowed arteries and arterioles of patients with atherosclerosis or vasospasm. A triphenyl-methyl compound, aurin tricarboxylic acid (ATA), inhibits shear-induced, vWF-mediated platelet aggregation in platelet-rich plasma (PRP) in concentrations above 200 mumol/L and in buffer suspensions of washed platelets at a concentration of 0.1 mumol/L. In a concentration-dependent manner, ATA also inhibits ristocetin-induced, vWF-mediated platelet clumping in both fresh and formaldehyde-fixed platelet suspensions. This inhibition can be overcome by increasing the concentration of vWF, following the kinetics of first order competitive inhibition. ATA prevents the attachment to platelets of the largest vWF multimeric forms found in normal plasma and of the unusually large vWF multimers derived from endothelial cells. The rate of aggregation and degree of inhibition by ATA is not accounted for by the binding of ristocetin or calcium. Arachidonic acid- and adenosine diphosphate (ADP)-induced aggregation are not inhibited by ATA. Platelets incubated with ATA can be easily separated from the compound. However, ATA binds to large vWF multimeric forms and inhibits their ristocetin-induced interaction with platelet glycoprotein Ib. Because ATA also inhibits shear-induced, vWF-mediated platelet aggregation in vitro in the absence of ristocetin, it may be a useful prototype compound to impede the development of arterial thrombosis in vivo.

Aurintricarboxylic Acid↗

The molybdenum iron-sulphur protein from Desulfovibrio gigas as a form of aldehyde oxidase.

The molybdenum iron-sulphur protein originally isolated from Desulfovibrio gigas by Moura, Xavier, Bruschi, Le Gall, Hall & Cammack [(1976) Biochem. Biophys. Res. Commun. 72, 782-789] has been further investigated by e.p.r. spectroscopy of molybdenum(V). The signal obtained on extended reduction of the protein with sodium dithionite has been shown, by studies at 9 and 35 HGz in 1H2O and 2H2O and computer simulations, to have parameters corresponding to those of the Slow signal from the inactive desulpho form of various molybdenum-containing hydroxylases. Another signal obtained on brief reduction of the protein with small amounts of dithionite was shown by e.p.r. difference techniques to be a Rapid type 2 signal, like that from the active form of such enzymes. In confirmation that the protein is a molybdenum-containing hydroxylase, activity measurements revealed that it had aldehyde:2,6-dichlorophenol-indophenol oxidoreductase activity. No such activity towards xanthine or purine was observed. Salicylaldehyde was a particularly good substrate, and treatment of the protein with it also gave rise to the Rapid signal. Molybdenum cofactor liberated from the protein was active in the nit-1 Neurospora crassa nitrate reductase assay. It is concluded that the protein is a form of an aldehyde oxidase or dehydrogenase. From the intensity of the e.p.r. signals and from enzyme activity measurements, 10-30% of the protein in the sample examined appeared to be in the functional form. The evolutionary significance of the protein, which may represent a primitive form of the enzyme rather than a degradation product, is discussed briefly.

Aldehyde Oxidase↗