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Biomedical subjects

B A Hills

Publications and source records attributed to B A Hills.

At least 19 recordsLinked to original sources

Abnormalities of surfactant in children with recurrent cyanotic episodes.

The mechanism of recurrent cyanotic episodes in infants and children is not known, but a deficiency of surfactant is a possible cause. We have measured the amount of surfactant collected by bronchoalveolar lavage from two children with recurrent cyanotic episodes and from two controls with anatomical airway obstructions. We also assessed the physical properties of the surfactant by changing the surface area (A) of a monolayer and measuring its surface tension (gamma). The cases had lower amounts of surfactant extracted, which could explain some of the abnormalities of the gamma/A loops. However, the finding that the cases had reversed loops (ie, the surface tension is higher during monolayer compression than during expansion) shows that there is also a qualitative abnormality. These features suggest a possible diagnostic test if not a mechanism for this disorder.

Airway Obstruction

A mucosal barrier of gastric surfactant identified in the human stomach.

Using a special fixation procedure avoiding glutaraldehyde, an oligolamellar lining has been demonstrated by electronmicroscopy on the luminal surface of the human stomach and, with more lamellations, on the epithelial surfaces of oxyntic ducts and parietal cells. These results indicate that, in the human stomach, there is indeed a gastric mucosal barrier consisting of a multi-laminated structure of surface-active phospholipid (SAPL). This gastric surfactant is probably produced in parietal cells and surface mucus cells in which lamellar bodies and some prominent multi-focal lamellated agglomerates of SAPL were prevalent. These findings of a gastric mucosal barrier similar in structure and function to a very thin polyethylene liner are compatible with previous information about the hydrophobicity of the gastric mucosa, the clinical correlation of hydrophobicity with peptic ulceration and the action of barrier breakers (including Helicobacter pylori). It is speculated that the administration of exogenous gastric surfactant in various forms may be effective for inexpensive long-term maintenance of the ulcer patient treated acutely by more conventional means.

Gastric Mucosa

Gastric mucosal barrier: barrier to hydrogen ions imparted by gastric surfactant in vitro.

A simple experiment is described which shows how the highly surface active ingredient of gastric surfactant (DPPC) can be deposited on a filter paper to reduce the rate of transmission of hydrogen ions by one to two orders of magnitude. This finding is compatible with previous studies implying that the hydrophobic layer of surface active phospholipid provides the gastric mucosal barrier as a distinct physical entity.

1,2-Dipalmitoylphosphatidylcholine

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.

Capillaries

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.

Animals

A hydrophobic oligolamellar lining to the vascular lumen in some organs.

Various endothelial surfaces from sheep and humans have been studied for their hydrophobicity using a standard method based on the angle of contact (theta) of the surface with a droplet of saline placed on it. Most surfaces were relatively hydrophilic (theta less than 25 degrees) but some were distinctly hydrophobic with theta exceeding 65 degrees for sheep pulmonary vein, left ventricle, and aorta, and human umbilical vein. These results are discussed as compatible with the theory that surface-active phospholipid (surfactant) migrates from lung tissue into the pulmonary circulation or reaches intravascular sites from other sources. Transmission electron microscopy of cerebral vessels demonstrated an oligolamellar lining of surfactant on many endothelial surfaces, bridging the "tight" junctions between endothelial cells in many cases. Lamellar bodies were found adjacent to the endothelium. The oligolamellar surfactant lining and lamellar bodies are discussed as potentially very important factors in influencing bubble formation on vessel walls. It is believed to impart hydrophobicity while it could also determine the microgeometry of any crevices vital for bubble formation or retention.

Animals

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.

Adsorption

Microbubble damage to the blood-brain barrier: relevance to decompression sickness.

Decompression sickness affecting the nervous system is still a serious problem in diving, but the mechanisms involved are in dispute. Although microbubbles can be detected in the pulmonary artery on decompression using ultrasound, mammalian lungs are competent filters for microbubbles larger than 20 microns in diameter. It has been assumed that smaller bubbles released by the lungs are harmless, because there is evidence that they do not arrest in the cerebral circulation. We injected 15 +/- 5 microns diameter microbubbles in 5 ml of plasma slowly into the right carotid artery of anesthetized guinea pigs. At intervals of 1, 2, or 3 h postinjection, 2% trypan blue in 2 ml of plasma was injected into the same artery or the contralateral carotid artery. A control animal for each experiment was injected with 5 ml of plasma only, followed by the injection of dye at the same interval. After the animals were killed, the brains were examined for evidence of blood-brain barrier dysfunction. All animals at 1 h, and 9 out of 10 animals at 2 h after the injection of microbubbles, showed extravasation of the albumin-binding dye in the ipsilateral hemisphere, indicating gross blood-brain barrier dysfunction. In each of the matched controls, the barrier in the neocortex remained intact. At Hour 3 the barrier was impermeable to the trypan blue in both experimental and control animals. These experiments demonstrate that microbubbles impair the blood-brain barrier integrity to protein, causing focal edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

A physical identity for the gastric mucosal barrier.

An oligolamellar lining which is probably phospholipid has been demonstrated on the gastric mucosal surface of the rat by transmission electron microscopy using fixation procedures specially developed to avoid the destruction of hydrophobic surfaces. This structure is unlikely to be an artefact since the use of two hydrophobic probes in epifluorescence microscopy gave emissions characteristic of oligolamellar phospholipid prepared in vitro. Moreover, lipid solvents almost eliminated both the fluorescence and the hydrophobicity. An oligolamellar lining was seen also on deeper structures, including oxyntic ducts and canaliculi in parietal cells, and it might offer a physical basis for the hitherto elusive gastric mucosal barrier. Parietal cells were also found to contain multilamellar bodies which, in the lung at least, represent phospholipid (surfactant) in a particularly surface-active form and one conducive to its deposition on tissue surfaces. This suggests that the parietal cell could gear the protection (surfactant) to the potential insult (acid) by secreting both together. The demonstration of a simple physical barrier preventing the stomach from digesting itself is discussed in regard to suggesting the use of certain surface-active foods which could be beneficial in preventing gastric ulcers and their recurrence after the acute phase has been treated using conventional therapies.

Animals

A physical approach to coeliac disease.

The morphological changes used to confirm a diagnosis of coeliac disease (CD) are precisely those predicted if the surface energy of the interface between duodenal epithelium and the luminal contents were raised to levels comparable to those demonstrated by the hydrophobic nature of the stomach wall. This hypothesis pursues the concept that, in coeliac patients, the gastric mucosal barrier (GMB) is effectively extended from the stomach to coat the duodenum, thus closing the window of absorption in the Gl tract. If studies are correct which indicate that the GMB is a physical reality provided by an adsorbed monolayer of surface-active phospholipid (surfactant) which renders surfaces hydrophobic, then it could also act as a barrier to the absorption of nutrients in the duodenum. Gluten, or its more active polypeptide fragment gliadin, exacerbates the situation in CD by acting as very effective carriers for the insoluble phospholipid which is deposited at the duodenal surface where they are digested by brush-border and pancreatic enzymes.

Biological Transport, Active

Multiple roles for surface-active phospholipid in hypertension.

The elusiveness of the agent responsible for primary hypertension and the diversity of its impact upon the body, as reflected by the widely differing and almost independent avenues of research in this field, indicate that the answer could lie with a particularly common substance in the body acting at various levels of fundamental physiological function. This hypothesis pursues some basic physics of phospholipid whereby a change in quantity or quality can affect the capability to generate extreme surface activity manifest as the numerous properties which this agent can impart to blood and to adjacent surfaces by adsorption. Nine possible roles are traced by which surface-active phospholipid could impinge upon neurogenic control of blood pressure, the effects of circulating relaxing factors, blood rheology, atherosclerosis, and the major renal aspects of control by diuresis and association with the antihypertensive neutral renomedullary lipid. This multi-faceted approach offers mechanisms by which diet can affect blood pressure in addition to the traditional emphasis upon the deposition of atheroma.

Blood Pressure

Oligolamellar nature of the articular surface.

The osmiophilic lining of the articular surface has been studied by electron microscopy and shown to be oligolamellar phospholipid by employing special nondestructive fixation procedures. This finding was confirmed using hydrophobic probes in epifluorescence microscopy and by other simple tests of hydrophobicity. Oligolamellar phospholipid was also observed within the subchondral matrix while lamellar bodies, phospholipid in its most surface-active state, were found in the type of canals which can result from superficial fibrillation. The results are discussed as consistent with a previously proposed hypothesis whereby joints are lubricated by shearing between surface lamellae of phospholipid just as occurs in graphite when writing with a pencil.

Animals

Surface-active phospholipid in muscle lymph and its lubricating and adhesive properties.

In order to investigate the role of phospholipid in facilitating lymph flow, "deep-thigh" lymph was collected from ten anesthetized dogs and analyzed for phospholipids using thin-layer chromatography. The lymph was found to be surface active at liquid and at solid surfaces at which it deposited a hydrophobic monolayer in vitro. Extracted phospholipid was found to be an effective release agent as a monolayer, reducing the force of adhesion of 5% protein solutions by 76% according to a standard test for tacky glues. The same monolayers were effective lubricants, reducing friction by 96%; while mixtures of the same phospholipids from synthetic sources gave similar results for release and lubrication. Surfaces in contact with extracellular fluid or lymph in vivo were found to be hydrophobic with a drop of saline on semitendinosus muscle fibers displaying a contact angle of 40.2 degrees +/- 7.2 degrees. The results are considered compatible with the hypothesis that surface-active phospholipid facilitates the flow of lymph; while it could also provide boundary lubrication for sliding of connective tissue in locomotion and for any relative movement of motor units in muscle contraction and fatigue.

Animals

Surfactant approach to the gastric mucosal barrier: protection of rats by banana even when acidified.

Physical studies of their suspensions have shown bananas to be highly surface active at both liquid-air and solid-liquid interfaces which they render hydrophobic by adsorption of phospholipid detected by thin-layer chromatography and by staining. Electron microscopy of the fruit has demonstrated lamellar bodies--the same form in which phospholipid is so surface-active in the lung. When administered to intact rats and scored by two methods (ulcer length and area), banana imparted appreciable (75%) protection against acid insult (1 ml of 0.8 N HCl) in a dose-dependent manner not attributable to "bulking" or buffering as it was equally effective at a pH of 2. The best protection (89% by ulcer length) was obtained with banana vortexed with milk (1:1), this mixture offering the possibility of a simple foodstuff on which to maintain patients treated acutely by suppressing acid secretion pharmacologically. These studies support Davenport's original concept of a gastric mucosal barrier--but one whose physical reality is provided by an adsorbed layer of surface-active phospholipid (surfactant).

Animals

Possible role of adsorbed surfactant in controlling membrane permeability and function.

It is well established in the physical sciences that the adsorption of a monolayer of certain surfactants onto the surface of a synthetic membrane used for ultrafiltration can greatly modify its permeability to water and its ability to transmit small solute molecules and ions of physiological interest. In this hypothesis, it is proposed that, when indigenous surfactant is adsorbed to certain membranes in the body, it can similarly modify their permeability. Since adsorption can be a rapidly reversible process, this would provide a simple physical means of controlling the overall level of physiological activity of the membrane and, possibly, an additional means of differentiating membranes according to function. The hypothesis raises many questions concerning its applicability to the general structure of biological membranes, the nature of the surfactant, its ability to adsorb to solid surfaces and the reasons why such a coating may have been missed. There are then the questions of which membranes might benefit most and what happens if the coating is too sparse or is removed unintentionally.

Animals

Oligolamellar lubrication of joints by surface active phospholipid.

Six studies have been undertaken to test the hypothesis that oligolamellar phospholipid adsorbed to the articular surface contributes to joint lubrication. Synovial fluid (SF) proved highly surface active, rapidly depositing phosphatidylcholine (DPPC) on glass surfaces, rendering them hydrophobic--a property of well rinsed articular surface removable by the same fat solvents known to increase joint friction by 150%. Electron microscope studies demonstrated lamellar bodies (surface active DPPC) on the articular surface and in SF and lamellated phospholipid in light scrapings of joint surfaces. These were consistent with the quantity of phospholipid recovered by solvent rinsing. Friction measurements in vitro demonstrated excellent boundary lubrication imparted by multimolecular layers of DPPC under high load with coefficients of kinetic friction reaching physiological ranges (0.002-0.005).

1,2-Dipalmitoylphosphatidylcholine

Surface hydrophobicity and water transport of the toad urinary bladder: effects of vasopressin.

The present study investigated whether the hydrophobic properties (wettability) of the luminal surface of the toad urinary bladder might play a role in modulating water transport across this epithelium. In the absence of vasopressin (ADH), water transport across the tissue was low, while luminal surface hydrophobicity (water contact angle) was relatively high. Following stimulation by ADH, water transport increased and surface hydrophobicity decreased. The addition of indomethacin to inhibit ADH-induced prostaglandin synthesis did not reduce these actions of ADH. In an attempt to alter water transport in this tissue, a liposomal suspension of surface-active phospholipids was administered to the luminal surface. This addition had no detectable influence on the low basal rates of water transport, but blocked the ADH-induced stimulation of water transport. We suggest that surface-active phospholipids on the toad bladder luminal membrane may contribute to the hydrophobic characteristics of this tissue. ADH may act to decrease surface hydrophobicity, facilitating the movement of water molecules across an otherwise impermeable epithelium. This surface alteration may be associated with the appearance of water channels in the apical membrane.

Animals