Experimental challenge of cattle with German atypical bovine spongiform encephalopathy (BSE) isolates.

For almost two decades after the discovery of the first bovine spongiform encephalopathy (BSE) case, it was generally accepted that only one BSE strain existed globally. However, in 2004, two novel BSE forms (L-type and H-type) were separately identified in two different European Member States, forms that differed from the classical (C-type) form by their biochemical properties and by the pattern of PrP(Sc) deposition as determined by immunohistochemistry (IHC). 60 atypical BSE cases have been identified worldwide as of November 2010, including one H- and one L-type BSE case each in Germany. However, it was not known whether the biological properties (pathogenesis and agent distribution, as well as transmissibility to other species) of these novel forms were the same as in classical BSE cases. Eleven calves were thus challenged intracranially, five with the German H-type and six with German L-type BSE cases. The experimental design and the clinical studies, followed by laboratory testing, are described in this manuscript.

Population Data BC: Supporting population data science in British Columbia.

BACKGROUND: Population Data BC (PopData) was established as a multi-university data and education resource to support training and education, data linkage, and access to individual level, de-identified data for research in a wide variety of areas including human and community development and well-being. APPROACH: A combination of deterministic and probabilistic linkage is conducted based on the quality and availability of identifiers for data linkage. PopData utilizes a harmonized data request and approval process for data stewards and researchers to increase efficiency and ease of access to linked data. Researchers access linked data through a secure research environment (SRE) that is equipped with a wide variety of tools for analysis. The SRE also allows for ongoing management and control of data. PopData continues to expand its data holdings and to evolve its services as well as governance and data access process. DISCUSSION: PopData has provided efficient and cost-effective access to linked data sets for research. After two decades of learning, future planned developments for the organization include, but are not limited to, policies to facilitate programs of research, access to reusable datasets, evaluation and use of new data linkage techniques such as privacy preserving record linkage (PPRL). CONCLUSION: PopData continues to maintain and grow the number and type of data holdings available for research. Its existing models support a number of large-scale research projects and demonstrate the benefits of having a third-party data linkage and provisioning center for research purposes. Building further connections with existing data holders and governing bodies will be important to ensure ongoing access to data and changes in policy exist to facilitate access for researchers.

Distribution of circulation rates within a single tissue type.

An analysis is undertaken to determine the continuous distribution of circulation rates which would be necessary for a single tissue type to display a simple exponential response for the exchange of a solute with blood. It is shown that there can be no more than one real solution. This indicates that heterogeneous circulation cannot be invoked to explain anomalies to the popular assumption that blood perfusion is the process limiting the rate of blood-tissue exchange.

Chemical facilitation of thermal conduction in physiological systems.

Experimental evidence supports the concept that solutes capable of reversible chemical reaction can passively facilitate thermnal conduction within their solutions. Myoglobin and bicarbonate are suggested as energy carriers in muscle, having the combined capacity for conveying all waste metabolic heat produced under normal physiological conditions. The concept is extended to convective heat transfer in vivo; this implicates hemoglobin.

Role of surface-active phospholipids in gastric cytoprotection.

Intragastric administration of a liposomal surfactant suspension markedly reduced acid-induced gastric ulcerogenesis and bleeding in rats. The concentration of surface-active molecules intrinsically present in the gastric mucosa was increased two to six times by administration of 16,16-dimethyl prostaglandin E2. Thus, local accumulation of surface-active phospholipids may be an integral component of the cytoprotective mechanism activated by prostaglandin treatment.

Methods for peak assignment in low-resolution multidimensional NMR cross-correlation relaxometry.

Several NMR protocols are presented for assigning peaks in complex T1-T2 spectra, including the effects of varying the spectrometer frequency and the CPMG pulsing rate. Extensions into a third dimension based on chemical-shift; diffusion- and field-cycled weighted T1-T2 cross-correlation methods are also explored as a means of peak assignment. We illustrate the power of these novel techniques with reference to simple aqueous sucrose solutions, but the methodology should be generally applicable.

Motional relativity and industrial NMR sensors.

We explore the implications of motional relativity in NMR and show that sample translation can be used to acquire NMR signals without the need for pulsed RF excitation or pulsed magnetic field gradients. Novel single-shot, on-line NMR acquisition protocols for samples being conveyed at high speed are discussed and preliminary results using a low-cost, on-line prototype NMR sensor are presented.

'Free' surfactant in gastric aspirates and bronchoalveolar lavage in children with and without reflux oesophagitis.

AIM: Dipalmitoylphosphatidycholine (DPPC) is the characteristic and main constituent of surfactant. Adsorption of surfactant to epithelial surfaces may be important in the masking of receptors. The aims of the study were to (i) compare the quantity of free DPPC in the airways and gastric aspirates of children with gastroesophageal reflux disease (GORD) to those without and (ii) describe the association between free DPPC levels with airway cellular profile and capsaicin cough sensitivity. METHODS: Children aged <14 years were defined as 'coughers' if a history of cough in association with their GORD symptoms was elicited before gastric aspirates and nonbronchoscopic bronchoalveolar lavage (BAL) were obtained during elective flexible upper gastrointestinal endoscopy. GORD was defined as histological presence of reflux oesophagitis. Spirometry and capsaicin cough-sensitivity test was carried out in children aged >6 years before the endoscopy. RESULTS: Median age of the 68 children was 9 years (interquartile range (IQR) 7.2). Median DPPC level in BAL of children with cough (72.7 microg/mL) was similar to noncoughers (88.5). There was also no significant difference in DPPC levels in both BAL and gastric aspirates of children classified according to presence of GORD. There was no correlation between DPPC levels and cellular counts or capsaicin cough-sensitivity outcome measures. CONCLUSION: We conclude that free DPPC levels in the airways and gastric aspirate is not influenced by presence of cough or GORD defined by histological presence of reflux oesophagitis. Whether quantification of adsorbed surfactant differs in these groups remain unknown. Free DPPC is unlikely to have a role in masking of airway receptors.

A low-field, low-cost Halbach magnet array for open-access NMR.

A working prototype of a novel low-cost Halbach-array-based NMR system is described. The new design provides open access to the sample relative to conventional NMR magnet designs and this facilitates the simultaneous use of multi-sensor techniques on the same sample, in which NMR/MRI can potentially be combined with other spectroscopies such as impedance spectroscopy, laser scattering and rheological experiments.

A common physical basis for the gastric mucosal barrier and the action of sucralfate.

A novel explanation for the action of sucralfate in gastric ulcers has been proposed based on a new theory for gastric mucosal protection derived, in effect, from the very common industrial practice of adsorbing surfactants to surfaces needing protection against acid. Standard physical tests have been employed to show that sucralfate is highly surface-active at both liquid and solid interfaces, with the capability to be adsorbed--but not as active as the indigenous surface-active phospholipid (SAPL). This finding can explain the ability of sucralfate to "bind" to an ulcer site. Unlike SAPL or surfactants in general, adsorbed sucralfate does not render hydrophilic surfaces hydrophobic, suggesting a dual role in substituting for both SAPL and the mucus needed to stabilize it. Electron microscopy, using a novel fixation procedure specifically designed to allow for the known properties of any gastric mucosal barrier, revealed essentially the same oligolamellar lining of SAPL as previously reported in rats. Prolonged (16-day) exposure to sucralfate did not appear to change the situation, whereas there were as many, if not more, lamellar bodies (freshly secreted SAPL) adjacent to the stomach wall. Mucus-free oxyntic ducts showed the same oligolamellar lining as controls. An interesting new finding was the presence of oligolamellar SAPL as the intergranular matrix of gastric mucus--as though preparing to protect the next layer in anticipation of the surface mucin granules being eroded.

Rapidly alternating curvature ("oil canning") as a mechanism preventing alveolar edema.

This study has been designed to investigate the concept that the passage of red blood cells (clearly seen "bulging" into the air space in all scanning electron micrographs of the alveolar surface) can produce a net force tending to return any excess fluid to the interstitium. Measurements of surface tension over the time frame and probable surface area excursion incurred by a passing red blood cell show an appreciably higher value corresponding to the expanding surface, which is convex with respect to air, than when it is compressing and concave. The mean difference in surface tension of about 16 dyn/cm (mN/m) translates into a net driving force of approximately 6 mmHg induced by this rapidly alternating microcurvature reflecting the highly dynamic state of the living alveolar wall. The significance of the microcurvature of the alveolar surface is emphasized in relation to surfactant function.

Graphite-like lubrication of mesothelium by oligolamellar pleural surfactant.

Six studies have been completed to reevaluate pleural surfactant as a possible boundary lubricant in mesothelial sliding. It is capable of remarkable antiwear action, giving a mean scar diameter on a standard "four-ball test" comparable to the best commercially available lubricants and reducing friction to values anticipated from lamellated solid lubricants such as graphite. Pleural surfaces displayed appreciable hydrophobicity, which was almost eliminated by rinsing with a lipid solvent from which phospholipid was recovered and quantified. These quantities indicated that equivalent of 7.3 adsorbed monolayers of surface-active phospholipid, which was in general agreement with the number of layers of a graphite-like surface coating visualized by electron microscopy by use of a novel fixation procedure that avoids conventional aldehydes known to destroy hydrophobic surfaces. Graphite-like (dry) lubrication by adsorbed surface-active phospholipid is discussed as an excellent lubrication system available wherever the distribution of fluid allows the pleura to make contact.

An alternative view of the role(s) of surfactant and the alveolar model.

Currently, the study of surfactant proteins is much in vogue, but, in the early days, the physics underlying surfactant function was treated somewhat superficially, leaving assumptions that have become culturally embedded, such as the "bubble" model of the alveolus. This review selectively reexamines these assumptions, comparing each combination of alveolar model and role of surfactant for compatibility with the major features of pulmonary mechanics and alveolar stability, morphology, and fluid balance.

Transpulmonary passage of venous air emboli.

Twenty-seven paralyzed anesthetized dogs were embolized with venous air to determine the effectiveness of the pulmonary vasculature for bubble filtration or trapping. Air doses ranged from 0.05 to 0.40 ml X kg-1 X min-1 in 0.05-ml increments with ultrasonic Doppler monitors placed over arterial vessels to detect any microbubbles that crossed the lungs. Pulmonary vascular filtration of the venous air infusions was complete for the lower air doses ranging from 0.05 to 0.30 ml X kg-1 X min-1. When the air doses were increased to 0.35 ml X kg-1 X min-1, the filtration threshold was exceeded with arterial spillover of bubbles occurring in 50% of the animals and reaching 71% for 0.40 ml X kg-1 X min-1. Significant elevations were observed in pulmonary arterial pressure and pulmonary vascular resistance. Systemic blood pressure and cardiac output decreased, whereas left ventricular end-diastolic pressure remained unchanged. The results indicate that the filtration of venous bubbles by the pulmonary vasculature was complete when the air infusion rates were kept below a threshold value of 0.30 ml X kg-1 X min-1.

Release and lubricating properties of amniotic surfactants and the very hydrophobic surfaces of the amnion, chorion, and their interface.

Surface hydrophobicity of 17 fresh human chorioamniotic membranes was measured as the contact angle (theta) subtended when a drop of saline is placed upon any non-wettable surface. The contact angle averaged 75.5 +/- 4.2 degrees and 76.8 +/- 5.6 degrees on the epithelial surfaces of the amnion and chorion, respectively. The interface proved to be particularly hydrophobic, averaging 108.2 +/- 8.7 degrees on the amnionic side and 121.7 +/- 4.2 degrees on the chorionic side, especially when compared with 108 degrees for Teflon. High surface hydrophobicity implies good boundary (solid-to-solid) lubrication, good release from neighboring tissues, and water repellency, which is a possible factor enabling the chorioamniotic membrane to retain amniotic fluid. Good release (68 to 71%) and boundary lubrication (coefficient of kinetic friction = 0.24 +/- 0.072) were obtained from oriented monolayers of the phospholipid extracted from samples of human amniotic fluid obtained from term patients by amniocentesis. These results support the concept that the amnionic and chorionic membrane surfaces exhibit good release and boundary lubrication probably imparted by adsorbed surfactant.

Surfactants identified in lung lymph and their ability to act as abhesives.

Phospholipid has been extracted from pulmonary lymph collected from 10 dogs. Thin-layer chromatography was used to identify phosphatidylcholine (PC) 55.6 +/- 2.9%, sphingomyelin 21.3 +/- 1.7%, phosphatidylethanolamine 11.2 +/- 4.9%, and lysophosphatidylcholine 5.9 +/- 0.8%. All extracts proved highly surface active, reducing the surface tension of saline to 27.7 +/- 0.7 dyn/cm upon 80% film compression and increasing the maximum contact angle on glass (theta) from 7 +/- 1 to 47.4 +/- 1.4 degrees. The hydrophobic properties induced on glass were further demonstrated by the ability to cause saline to withdraw and expose a dry surface. A standard adhesion test was used to measure the "tack" produced by the major proteins in lymph. However, when the surface energy of the hydrophilic glass surfaces was reduced by a monolayer of lymph phospholipid extract or an equivalent mixture of synthetic surfactants, the adhesive force was reduced by 79 +/- 4% for albumin and 55 +/- 4% for globulin. As a 0.1% liposomal suspension, PC gave 55% release with albumin. Reversible bonding of the lumen of lymph vessels by the "tacky" proteins present is discussed as a possible factor contributing to the large changes in flow resistance known to occur in the pulmonary lymphatic system.

An NMR relaxation study of the state of water in gelatin gels.

A combination of 1H and 23Na NMR is used to probe the dynamic state of water in gelatine gels as the water content is lowered from 70% to dryness. A sharp increase in the proton and sodium transverse relaxation rates is observed as the water content falls from 20 to 15% while the proton longitudinal and dipolar cross relaxation rates show a maximum at ca. 15%. We show that these observations can be understood if monolayer coverage occurs at 15% and multilayers of less strongly interacting hydration water are formed between 15 and 20%. Above 20% the water appears to behave as an unperturbed bulk phase.

Echo-planar imaging relaxometry to measure the viscosity of a model meal.

A method for measuring noninvasively the viscosity of a polysaccharide model meal using the known relationship between relaxation times and polysaccharide concentration in solution in vitro is presented. The aim is to develop a method for monitoring digesta viscosity in vivo, using EPI to capture the motion of the gastrointestinal lumen. The transverse relaxation rate T-12 of locust bean gum solutions was calibrated against the zero-shear viscosity at 37 degreesC. Differences in viscosity were distinguished significantly using T-12 measurements. T-12 and viscosity were insensitive to exposure to gastric juice and changes in pH, and the model meal was well received by volunteers and provided good contrast in vivo in EPI images. Therefore it would be possible to use this method to monitor the changes in meal viscosity within the gastric lumen in vivo.

Arrest of metastatic cells: agents promoting and inhibiting instant non-specific adhesion by fibronectin.

A standard mechanical test was used to quantify instant non-specific adhesion provided in vitro by fibronectin and to demonstrate how this adhesive found on circulating tumour cells can be decreased in potency by 65% when the adherents are coated with dipalmitoyl phosphatidylcholine (DPPC). By comparison, the binding force is increased 97% by addition of sialic acid found on the more potent metastatic cells. The very tacky adhesive resulting from this mixture now fails to be inhibited by DPPC but not by phosphatidylethanolamine found in blood (1). These factors could determine whether a metastatic cell will arrest upon initial contact with a potential host tissue.