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D J Faulkner

Publications and source records attributed to D J Faulkner.

At least 55 records · Page 3Linked to original sources
PubMed1990

Identification of okadaic acid from a Caribbean dinoflagellate, Prorocentrum concavum.

Lipid-soluble toxins were isolated from a Caribbean strain of the epiphytic dinoflagellate Prorocentrum concavum Fukuyo. The major lipid-soluble toxin (LD50 = 210 +/- 15 micrograms/kg i.p. in mice) was purified by normal and reversed-phase column chromatography and characterized by 1H NMR and mass spectrometry. The toxin was identified as okadaic acid by interpretation of the spectral data. Okadaic acid was previously identified as a toxic component of the related species P. lima (Ehrenberg) Dodge. The finding of okadaic acid production in P. concavum and P. lima, abundant primary producers in the ciguatera-endemic Caribbean, suggests that the role of this toxin in the etiology of ciguatera may be more significant than previously thought.

Animals↗
PubMed1989

Luffolide, a novel anti-inflammatory terpene from the sponge Luffariella sp..

Luffolide (4) is a minor metabolite of the sponge Luffariella sp. from Palau. The structure of luffolide was determined by single crystal X-ray analysis. Luffolide is relatively unstable and undergoes a complex cyclization reaction to give the hexacyclic products 5 and 6. Luffolide (4) has some of the anti-inflammatory properties of manoalide (1): this may help to define the chemical reaction between manoalide (1) and phospholipase A2.

Animals↗
PubMed1989

Liver resection without blood transfusion.

A personal series of 58 liver resections was reviewed to identify technical factors minimizing blood transfusions. We identified a concept of vascular isolation prior to parenchymal division (VIP) which used singularly or in combination the following methods of vascular control: parenchymal compression, Pringle maneuver, hepatic venous tourniquet, hilar division, hepatic vein division, and Heaney maneuver. VIP significantly decreased the need for transfusion; of 34 patients with VIP only 2 (6 percent) required transfusion, whereas of 24 patients without VIP, 18 (75 percent) required transfusion (p less than 0.001).

Adult↗
PubMed1989

Gallstones: fragmentation with a tunable dye laser and dissolution with methyl tert-butyl ether in vitro.

The authors tested whether gallstone fragmentation with a tunable dye laser would speed dissolution with methyl tert-butyl ether (MTBE) and allow successful in vitro dissolution of calcified stones. Twelve sets of three stones matched for size and weight were obtained from 11 surgically resected human gallbladders and one common bile duct operation. Computed tomography was used to determine presence and distribution of calcium. One stone from each set was either chemically analyzed, mechanically fragmented with the laser, or left intact. Fragmented and intact stones were subjected to MTBE dissolution for 12 hours or until fragments were 2 mm or less in diameter. All five laser-treated, noncalcified gallstones dissolved completely, compared with four of five intact stones. All six laser-treated, calcified gallstones dissolved completely, compared with only one of six intact stones. The solitary calcified common bile duct stone, whether fragmented or intact, did not completely dissolve. Speed of dissolution was significantly faster for laser-treated stones (P = .04). The authors conclude that laser fragmentation of gallstones increases the speed of subsequent MTBE dissolution and allows successful dissolution of calcified gallstones.

Cholelithiasis↗
PubMed1989

Manoalide: structure-activity studies and definition of the pharmacophore for phospholipase A2 inactivation.

Manoalide is a potent antiinflammatory marine natural product and a direct inactivator of venom phospholipase A2 (PLA2; EC 3.1.1.4). Manoalide has been shown to irreversibly inhibit PLA2, with the corresponding modification of a selective number of lysine residues. The mechanism of inactivation has not yet been elucidated and structure-activity relationship studies were, therefore, performed in order to determine the contributions of the various functional groups incorporated in the gamma-hydroxybutenolide, alpha-hydroxydihydropyran, and trimethylcyclohexenyl ring systems to the efficacy (irreversibility) and potency of this series of inhibitors. These studies indicate that 1) the presence of the hemiacetal in the alpha-hydroxydihydropyran ring is required for irreversible binding of manoalide, 2) the gamma-hydroxybutenolide ring is involved in the initial interaction of manoalide with PLA2, and 3) the hydrophobic nature of the trimethylcyclohexenyl ring system allows nonbonded interactions between manoalide and PLA2 that enhance the potency of these analogs. These structure-activity relationship studies suggest that the closed ring form of manoalide is the predominant molecular species that accounts for the selective and potent inhibition of PLA2 by manoalide. Elucidation of the mechanism awaits further detailed physicochemical studies on the structure of the manoalide (analog)-protein adducts in model systems and using PLA2.

Aldehydes↗
PubMed1989

Onchidal: a naturally occurring irreversible inhibitor of acetylcholinesterase with a novel mechanism of action.

Onchidal has been identified as the major lipid-soluble component of the defensive secretion of the mollusc Onchidella binneyi, and it has been proposed as the compound responsible for the chemical protection of Onchidella [Bioorg. Chem. 7:125-131 (1978)]. In support of this hypothesis, we now report that onchidal can be found in several different species of Onchidella and that it is toxic to fish. Because onchidal is an acetate ester similar to acetylcholine, its ability to interact with nicotinic acetylcholine receptors and acetylcholinesterase was investigated. Although onchidal did not prevent the binding of 125I-alpha-bungarotoxin to nicotinic acetylcholine receptors, it inhibited acetylcholinesterase in a progressive, apparently irreversible, manner. The apparent affinity of onchidal for the initial reversible binding to acetylcholinesterase (Kd) was approximately 300 microM, and the apparent rate constant for the subsequent irreversible inhibition of enzyme activity (kintact) was approximately 0.1 min-1. Onchidal was a substrate for acetylcholinesterase, and approximately 3250 mol of onchidal were hydrolyzed/mol of enzyme irreversibly inhibited. The calculated kcat for onchidal was 325 min-1. Irreversible inhibition resulted from either onchidal itself or a reactive intermediate in the enzyme-catalyzed hydrolysis of onchidal, rather than from the hydrolysis products of onchidal. Irreversible inhibition of enzyme activity was prevented by coincubation with reversible agents that either sterically block (edrophonium and decamethonium) or allosterically modify (propidium) the acetylcholine binding site. Enzyme activity was not regenerated by incubation with oxime reactivators; therefore, the mechanism of irreversible inhibition does not appear to involve acylation of the active site serine. Because onchidal contains a potentially reactive alpha,beta-unsaturated aldehyde, irreversible inhibition of acetylcholinesterase may result from formation of a novel covalent bond between the toxin and the enzyme. Thus, this novel toxin could potentially be exploited in the design of a new class of anticholinesterase insecticides and in the identification of amino acids that contribute to the binding and hydrolysis of acetylcholine.

Acetylcholinesterase↗
PubMed1988

Visual function and rhodopsin levels in humans with vitamin A deficiency.

Details of rod and cone dysfunction in vitamin A deficiency have been studied in two subjects with primary biliary cirrhosis and one with Crohn's disease, all of whom presented with symptoms of night blindness. Visual function in the mid-peripheral retina was monitored with two-color adaptometry and rhodopsin levels were measured by fundus reflectometry. Initially all three subjects had no measurable rod function and delayed cone adaptation. In one case the dark-adapted cone threshold was also elevated. Oral supplementation with vitamin A restored visual function to normal within 8 days in all subjects. During supplementation, cone function was restored more rapidly than that of rods, though the pattern of recovery was similar for each receptor type. Final thresholds improved first, though the rates at which they were reached were abnormally slow. As recovery continued, adaptation kinetics returned to normal. When rod adaptation was delayed, the regeneration of rhodopsin was also abnormally slow. When rod final threshold was 2 log units higher than normal, rhodopsin regeneration was incomplete, reaching about 70% of the normal level. The initial stages of visual dysfunction during onset of vitamin A deficiency were studied in one subject, and were found to mirror the pattern seen during recovery: rod adaptation was initially slower than normal, but reached completion. Cone adaptation remained normal until rod function was almost absent.

Adult↗
PubMed1988

Recurrent abdominal abscess caused by retained colorectum after proctocolectomy.

In two patients recurrent pelvic abscesses resulted from retention of colorectal mucosa after proctocolectomy. In both patients sepsis occurred more than 10 years after colectomy and was corrected by identification and removal of retained colonic mucosa. Retained colorectum should be considered in the differential diagnosis in a patient who has an abscess years after undergoing colon resection.

Abdomen↗
PubMed1988

The distribution and kinetics of visual pigments in the cat retina.

An imaging fundus reflectometer has been used to study the distribution and regeneration of visual pigments in the retina of the adult living cat. Measurements were made over an area of tapetal retina extending 25 degrees nasal and 40 degrees temporal to the area centralis on the horizontal meridian and 5 degrees inferior to 40 degrees superior on the vertical meridian. The measured density differences show large variations with retinal location, with values in the central retina up to 60% higher than those in the superior region. The area of high density differences forms a horizontal streak. There are two peaks of density difference values, one centered on the area centralis and the second in the nasal section of the streak. Spectral measurements indicate that the contribution of cone pigments is negligible everywhere except at the area centralis, where it is about 5%. The distribution of density differences is shown to correlate well with anatomical data if the effects of fundal stray light are taken into account and if it is assumed that the cross section of light capture by the rods is determined by the dimensions of the inner segments. The time required for essentially complete regeneration of rhodopsin depends on retinal location, varying from about 80 min in the superior retina to more than 90 min in the regions of peak densities.

Animals↗
PubMed1988

Two types of visual dysfunction in autosomal dominant retinitis pigmentosa.

Visual thresholds and rhodopsin levels were determined in nine subjects with autosomal dominant retinitis pigmentosa. The subjects fell into two groups, corresponding to two subtypes of the disease revealed by two-color, dark-adapted static perimetry. In the first of these subtypes, rod-mediated function was variably reduced and was accompanied by a corresponding reduction in cone function in the same retinal region. Dark-adapted threshold elevations varied in a way consistent with decreased quantal absorption by the rods as a result of reduced rhodopsin levels. In the second subtype, rod function was greatly reduced or absent throughout the retina, while cone function was much less severely affected. Although the levels of rhodopsin were only about half of normal, they were much too great to account for the visual threshold elevations on the basis of decreased probabilities of absorption by the visual pigment. Rhodopsin regeneration appeared to follow normal kinetics in patients from both groups. The results indicate that the examples of the two psychophysical subtypes of AD RP investigated here have very different disease manifestations.

Adult↗
PubMed1987

Rhodopsin topography and rod-mediated function in cats with the retinal degeneration of taurine deficiency.

Cats on a taurine-deficient diet were studied with imaging fundus reflectometry and full-field electroretinography. The pattern of rhodopsin loss and the natural history of the disease were determined from maps of the rhodopsin distribution in the central and nasal retina of cats with different degrees of severity of the retinopathy. Rhodopsin loss is first detectable in a focal region of the central retina. Subsequently, there are decreases in rhodopsin in the paracentral and nasal midperipheral retina. The horizontal streak of high rhodopsin levels is preferentially reduced in this retinopathy. The b-wave amplitude of the rod-dominated ERG is markedly reduced in cats with only mildly decreased levels of rhodopsin in the peripheral retina. In an affected cat with moderate rhodopsin loss in the central retina but minimal loss nasally, a light-microscopic study of the retina showed that there was disorganization and shortening of rod outer segments and loss of rod photoreceptor cells in the areas of reduced rhodopsin levels.

Animals↗
PubMed1986

Stimulus contaminants in checkerboard patterns.

Variations in the mean luminance of a reversing checkerboard produced on a monitor were assessed by two methods and found to be less than 0.3 cd m-2 This quantity is much less than the amount found by other investigators.

Electricity↗
PubMed1984

Human rhodopsin measurement using a T.V.-based imaging fundus reflectometer.

An imaging fundus reflectometer for in vivo mapping of rhodopsin levels is described. The instrument is based on a high-sensitivity television camera attached to a Zeiss fundus camera, which enables areas of retina of angular subtense 25 degrees to be examined at a resolution of about 1 degree. Digital processing techniques are used to average the video signal spatially and temporally and to analyse the spatial information. Measurements with an artificial eye indicate that performance is comparable to that of photomultiplier-based systems. Rhodopsin levels and regeneration data for a normal human subject are presented; these are consistent with published values. The map of visual pigment levels derived from these normal data is contrasted with that for a subject with a patchy retinal dysfunction (autosomal dominant retinitis pigmentosa).

Adult↗
PubMed1983

An automated statis perimeter/adaptometer using light emitting diodes.

An automated static perimeter/adaptometer is described which measures thresholds with lights of 2 wavelengths. The instrument uses light-emitting diodes to produce the stimuli and is controlled by a small computer, making it very suitable for clinical testing of large numbers of patients. The use of 2 LEDs with different peak emission wavelengths (530 and 660 nm) permits an assessment of the relative state of rod and cone mechanisms in a particular region of the retina either during dark adaptation or when the eye is fully dark adapted.

Dark Adaptation↗