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R Burgoyne

Publications and source records attributed to R Burgoyne.

13 recordsLinked to original sources

A sticker-based model for DNA computation.

We introduce a new model of molecular computation that we call the sticker model. Like many previous proposals it makes use of DNA strands as the physical substrate in which information is represented and of separation by hybridization as a central mechanism. However, unlike previous models, the stickers model has a random access memory that requires no strand extension and uses no enzymes; also (at least in theory), its materials are reusable. The paper describes computation under the stickers model and discusses possible means for physically implementing each operation. Finally, we go on to propose a specific machine architecture for implementing the stickers model as a microprocessor-controlled parallel robotic workstation. In the course of this development a number of previous general concerns about molecular computation (Smith, 1996; Hartmanis, 1995; Linial et al., 1995) are addressed. First, it is clear that general-purpose algorithms can be implemented by DNA-based computers, potentially solving a wide class of search problems. Second, we find that there are challenging problems, for which only modest volumes of DNA should suffice. Third, we demonstrate that the formation and breaking of covalent bonds is not intrinsic to DNA-based computation. Fourth, we show that a single essential biotechnology, sequence-specific separation, suffices for constructing a general-purpose molecular computer. Concerns about errors in this separation operation and means to reduce them are addressed elsewhere (Karp et al., 1995; Roweis and Winfree, 1999). Despite these encouraging theoretical advances, we emphasize that substantial engineering challenges remain at almost all stages and that the ultimate success or failure of DNA computing will certainly depend on whether these challenges can be met in laboratory investigations.

Computer Simulation↗

2',3'-Cyclic nucleotide 3'-phosphodiesterase is associated with mitochondria in diverse adrenal cell types.

In this study, we have examined the expression and intracellular localisation of the myelin protein 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in bovine adrenal medullary chromaffin cell cultures. By immunoblotting, using two distinct anti-CNP monoclonal antibodies, CNP was detected in medullary cell cultures and expression of CNP was confirmed by reverse transcription and PCR amplification. CNP did not leak from digitonin-permeabilised chromaffin cells, suggesting that there is no cytosolic pool of this protein. Immunofluorescence studies with both antibodies showed that all cells in the medullary chromaffin cell culture were stained with a punctate appearance consistent with an intracellular localisation for CNP. More specifically it was demonstrated that CNP is co-localised with mitochondria. Various cell types in chromaffin cell cultures were stained with a mitochondrial pattern and CNP staining was co-localised with mitochondrial staining. These results show that CNP is a widely expressed protein that is associated with mitochondria and provides new clues as to its cellular function outside of myelin structures.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Pulmonary surfactant films affected by solvent vapors.

Pulmonary surfactant obtained from rabbit lung lavage was evaluated with the pulsating bubble surfactometer. Because surfactant forms a monomolecular film at the air-liquid interface consisting mainly of phospholipids, solvent vapors, which might be inhaled, could have a destructive influence on the surfactant monolayer. To assess the risk of such an inhalation, vapors from five solvents--halothane, chloroform, enflurane, acetone, and diethyl ether--were made to flow into the bubble of the surfactometer as it pulsated for 30 sec, i.e., during 10 pulsations. The vapors from halothane and chloroform, excellent solvents of dipalmitoyl-phosphatidylcholine (DPPC), had a destabilizing effect evidenced by the fact that surface tension at minimal bubble size increased from 0 to as high as 20 mN/m. When the vapors were replaced with a flow of room air, the pressure tracing promptly returned to normal. The concentration of halothane vapor, however, had to be at least 20%, a concentration much higher than that used for anesthesia, to have a destabilizing effect on pulmonary surfactant. Twenty-five percent enflurane vapor had a less pronounced yet conspicuous impact. With 25% acetone and diethyl ether vapors, poor solvents of DPPC, surface tension at minimal bubble size remained unaffected. We conclude that vapors of halothane and chloroform, if inhaled in high concentration, might instantaneously obliterate the stabilizing effect of pulmonary surfactant but that anesthetic concentrations of halothane have no effect.

Acetone↗

Pulmonary surfactant release in fetal rabbits: immediate and delayed response to terbutaline.

The fetal lung responds to beta-receptor agonists with a release of surfactant from type II alveolar cells, if such stimulation were intense or long-lasting, the supply might become depleted and, while the supply is being restored, there could be a surfactant deficiency. With experiments on pregnant rabbits, this hypothesis was put to the test and found to be true. At a gestational age of 27.75 days, fetuses received the beta 2-receptor agonist terbutaline, 0.1 or 0.01 mg intramuscularly, or saline only. At the same stage of pregnancy, other does were infused with 7.2 to 9.6 mg of terbutaline or given Ringer's solution. The fetuses were put to death at intervals of 1 to 48 hours, and the lungs were examined. At 1 hour and also at 2 and 3 hours after injection of 0.1 mg of terbutaline, pressure-volume loops demonstrated improved compliance and stability compared to those of controls, but at 24 hours the situation was reversed. At 48 hours there was no difference. At 12 hours from the start of the infusion, pressure-volume loops clearly showed that fetuses of does receiving terbutaline were at a disadvantage. We conclude that terbutaline depleted surfactant stores and, while these stores are being replenished, there is a surfactant deficiency in the alveolar space. Phospholipid analysis supported our conclusion.

Animals↗

Lung expansion and survival in rabbit neonates treated with surfactant extract.

Preterm rabbit fetuses, delivered on the 27th day of gestation, were studied following upper airway instillation with either natural surfactant (NSA) obtained from the lavage of adult rabbit lungs or with a protein-free suspension of lipids extracted from lung wash (ESA). First, lung compliance was studied postmortem. The administration of 25 microliters of either preparation resulted in greater hysteresis (P less than 0.05) than was observed in control fetuses receiving no surfactant material. Increasing the phospholipid concentration stepwise from 10 to 50 mg/ml improved airway expansion and stability. No further improvement was encountered with concentrations greater than 50 mg/ml. There was no significant difference in compliance response between NSA and ESA. Morphometry of the lungs also indicated that the two preparations had an equal effect on compliance. Second, it was determined how neonatal survival was affected by a pharyngeal deposition, prior to the first breath, of 50 microliters NSA or ESA. Both treatment groups demonstrated improved survival (P less than 0.001) when compared with controls receiving no pharyngeal deposition. These findings offer further support to the concept that protein is not required for the efficacy of a surfactant supplementation. The equivalence of the two preparations suggests that a sterile suspension of a protein-free surfactant extract could be used to prevent or treat respiratory distress in preterm neonates.

Animals↗

Surfactant supplementation in the preterm rabbit: effects of applied volume on compliance and survival.

Preterm rabbit neonates, delivered on the 27th day of gestation, were treated before the first breath with a tracheal instillation of ESA, a suspension of lipids extracted from pulmonary surfactant. Lung compliance development and neonatal survival were studied after treatment to determine the effect of suspension volume and concentration. Compliance development was not dependent on either delivery volume or suspension concentration, but rather on the quantity of phospholipids instilled. Indices of improved expansion and stability demonstrated a dose response relationship up to 1.1 mg phospholipid per g lung. Larger doses neither improved nor detracted from the response. The ability of the neonates to survive and adapt to an air breathing environment was influenced by the instillation volume. Viability was reduced when the treatment volume exceeded 16% of the functional residual capacity. Prophylactic surfactant supplementation therapy may be useful in preventing the development of neonatal respiratory distress syndrome. Surfactant extract may prove acceptable for both prophylaxis and treatment of established respiratory distress syndrome.

Animals↗

Pulmonary surfactant release in fetal rabbits as affected by terbutaline and aminophyllin.

Terbutaline; a beta2-adrenergic agonist, and aminophyllin, a phosphodiesterase inhibitor, were given separately, or in combination, to rabbit fetuses on the 28th day of gestation. The possibility of these drugs causing a release of pulmonary surfactant was evaluated 3 h after i.m. injection directly to the fetus. Lung compliance was studied and lung lavage fluid assessed as regards content to total phospholipid phosphorus, lecithin/sphingomyelin (L/S) ratio, and surface activity. It was found that terbutaline, in a dose of 0.1 mg, had a significant (p less then 0.05) effect on each of the four parameters studied and, when given in a dose of 0.05 mg, significantly affected all except L/S ratio. Aminophyllin, in a dose of 10 mg, resulted in a 40% mortality, but in the surviving fetuses the drug had no significant (p greater than 0.05) effect on any of the four parameters. When 5 mg aminophyllin was given together with 0.05 mg terbutaline, the effect could be attributed to terbutaline.

Aminophylline↗

Incidental intoxication with phencyclidine.

Utilizing a sensitive and specific gas chromatography nitrogen detector (GC2-N) method we have demonstrated phencyclidine (PCP) in the blood of a 65-year-old widowed Mexican-American woman who lived in a second floor apartment directly over an illegal laboratory utilizing open-vat methods of PCP synthesis. This is the first proof of such incidental PCP intoxication, although police officers regularly complain of developing symptoms of intoxication after raiding such clandestine laboratories and handling the confiscated products. The presumed mechanism of incidental intoxication with PCP and the psychiatric manifestations of this patient are described and discussed.

Chromatography, Gas↗

Isoxsuprine infusion to the pregnant rabbit and its effect on fetal lung surfactant.

Rabbit does, pregnant on the 28th day, were infused with isoxsuprine 2.5 mg/kg body weight/h in 50 ml 5% glucose, or with glucose only. The isoxsuprine caused maternal heart rate to increase and blood pressure, mean and diastolic, to decrease. The volume of fetal pulmonary fluid (FPF) and the wet lung weight/body weight ratio were significantly lowered by isoxsuprine. Lecithin/sphingomyelin ratio of FPF in isoxsuprine-infused animals was higher, compared with controls, not infused. Minimal surface tension of FPF, evaluated with pulsating bubble, was significantly lower in treated fetuses. Histologic examination of the fetal lungs after fixation with potassium dichromate and mercuric chloride showed that in isoxsuprine-treated litters FPF contained more granular and sudanophilic material. The results offer further evidence that isoxsuprine causes dehydration of fetal lungs and a release of pulmonary surfactant.

Animals↗

Isoxsuprine-induced release of pulmonary surfactant in the rabbit fetus.

Rabbit fetuses were injected intramuscularly with 0.5 mg. of isoxsuprine on the twenty-eighth day of gestation. They were killed in utero four hours after the injection, and fetal pulmonary fluid (FPF) was collected through a tracheal catheter. The quantity of FPF and the lung weight/body weight ratio were both significantly less in the isoxsuprine-treated fetuses than in control fetuses. Surface activity, evaluated with pulsating bubble, and the lecithin/sphingomyelin (L/S) ratio were greater in FPF from isoxsuprine-treated animals than in control samples. We concluded that isoxsuprine is able to dehydrate the fetal lung and cause a release of surfactant stored in type II pneumocytes. This latter conclusion was supported by a significant decrease in the number of lamellar inclusions observed in these cells.

Amniotic Fluid↗

Oxygen consumption of the newborn rabbit treated with pulmonary surfactant.

A method is described for measuring oxygen consumption of small animals. It was used for 151 newborn rabbits delivered on the 27th, 28th, 29th, and 30th day of gestation. Half of the neonates were given a pharyngeal deposition of a concentrated surfactant (SA) suspension prior to their first breath. The remaining neonates served as controls. The survival rate among the immature rabbits treated with SA was significantly higher. The treatment did not affect oxygen consumption in any age-group. With increasing maturity, the neonates consumed more oxygen, and the controls delivered on the 30th day of gestation consumed 29.6 +/- SEM 4.2 ml oxygen per kilogram and minute.

Age Factors↗