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J L Wright

Publications and source records attributed to J L Wright.

At least 127 records · Page 7Linked to original sources
PubMed1992

Detection of new 7-O-acyl derivatives of diarrhetic shellfish poisoning toxins by liquid chromatography-mass spectrometry.

A novel method for the detection of acylated diarrhetic shellfish poisoning toxins is reported. Direct determination of these compounds is possible using high performance liquid chromatography coupled with ion-spray mass spectrometry. An extract, purified from the digestive glands of toxic mussels (Mytilus edulis) contaminated with okadaic acid, dinophysistoxin-1, and a recently reported analog, dinophysistoxin-2, was also shown to contain small amounts of dinophysistoxin-3, a mixture of 7-O-acyl ester derivatives of dinophysistoxin-1. In addition, acyl ester derivatives of okadaic acid and dinophysistoxin-2 were also detected by direct LC-MS analysis and confirmed by analysis of their hydrolysis products. This is the first report of the detection of other naturally occurring 7-O-acyl esters similar to dinophysistoxin-3.

Acylation↗
PubMed1992

Effects of cigarette smoke on the clearance of short asbestos fibres from the lung and a comparison with the clearance of long asbestos fibres.

Long asbestos fibres are generally considered to have greater disease-producing potential than short asbestos fibres. However, recent reports have suggested that short fibre asbestos appears to be as effective an inducer of macrophage growth factors and toxic oxygen species as long fibre asbestos, but that short fibres are readily removed from lung and do not gain access to tissues. Because smoke is believed to impair the clearance of asbestos fibres from lung, we examined the clearance of a short (geometric mean length 1.3 microns) amosite preparation administered by intratracheal instillation to guinea-pigs. Half the animals in each group were exposed to the smoke of 10 cigarettes daily. Animals were sacrificed 1 day, 1 week, or 1 month later, the macrophages recovered by lavage, and fibre concentrations and sizes determined by analytical electron microscopy in macrophages and lung tissue. A 30-fold increase was seen in total numbers of fibres retained in macrophages in smokers compared to non-smokers by 1 month, and there was an eightfold increase in retention of short fibres in the lung tissue by 1 month. By contrast, a long fibre amosite preparation (geometric mean length 8.9 microns) showed approximately the same increase in fibre retention in macrophages, but only a twofold increase in tissue retention. We conclude that (1) cigarette smoke markedly impairs the clearance of short amosite fibres from the lung with enhanced retention of fibres in both macrophages and tissue; (2) the effects of smoke on short fibre tissue retention appear to be greater than those on long fibre retention; (3) with the long fibre preparation, smoke causes increased tissue retention of relatively shorter fibres; (4) for both fibre size experiments, the increase in total fibres in macrophages in smoke-exposed animals reflects an increase in the total number of fibre-containing macrophages, rather than an increase in the number of fibres phagocytized per macrophage; (5) enhanced short fibre retention markedly increases total fibre surface area, a parameter which has been suggested as a measure of fibre toxicity, to the point where short fibres might under some circumstances have roughly the same potential toxicity as long fibres. These observations suggest that short asbestos fibres could play an important role in the pathogenesis of some types of asbestos-related disease in cigarette smokers.

Animals↗
PubMed1992

Otitis media.

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Acute Disease↗
PubMed1991

Acute effects of human recombinant tumor necrosis factor-alpha on the cerebral vasculature of the rat in both normal brain and in an experimental glioma model.

The effects of intravenous (IV) infusion of human recombinant tumor necrosis factor-alpha (rTNF-alpha, Cetus) on normal brain and malignant glioma in rats were examined. Twelve Fischer 344 rats were given either a single injection of 10(6) U rTNF-alpha or injections of 5 x 10(5) U rTNF-alpha for three days. One day post-rTNF-alpha injection(s), rats were injected IV with horseradish peroxidase (HRP) to determine blood-brain barrier (BBB) breakdown and, one hour later, were perfused with an aldehyde fixative and processed for histologic examination. Treatment of normal rats with rTNF-alpha by either dosage or schedule caused no remarkable histopathologic changes in the brain and no alteration in BBB integrity. Human glioma models were produced by intracerebal inoculation of 10(4) syngeneic RT-2 glioma cells into the right parietal lobe of 30 rats. Animals received single IV injections of 10(6) U human rTNF-alpha or its excipient (TNF-E) as above on day 3, 7, or 10 post-tumor inoculation or multiple injections of 5 x 10(5) U rTNF-alpha beginning on day 7, 10, or 12 post-tumor inoculation. With a single IV injection of either rTNF-alpha or its excipient, 3-day models showed a similar pattern of HRP extravasation limited to the extracellular space of the tumor inoculation site. In 7-day models treated with a single IV injection of rTNF-alpha or TNF-E, HRP extravasated throughout the tumor, but did not exceed peritumoral margins. In 10-day models treated with a single injection of TNF-E, HRP was found only in the tumor and immediate peritumoral regions while rTNF-alpha-treated rats showed more extensive areas of BBB breakdown with HRP evident throughout the entire right hemisphere and extending via the corpus callosum into the contralateral hemisphere. Pericapillary halos were also evident around the small blood vessels within the edematous areas of the corpus callosum. Within tumors, hemorrhagic necrosis and adherence of neutrophils to vessels was observed only in animals treated with rTNF-alpha at 10 days post-tumor inoculation. Multiple IV injections of rTNF-alpha in 7 and 10-day models triggered widespread hemorrhagic necrosis, neutrophil adherence and infiltration in the tumor. There was also extravasation and diffusion of HRP from the site of glioma into the contralateral hemisphere. Twelve-day models treated with multiple rTNF-alpha injections, in addition, showed irregular luminal surfaces and gaps between adjacent endothelial cells of tumor vasculature.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Long-term pulmonary hypertension produced by cigarette smoking is associated with subendocardial fibrosis and inflammation of the right ventricle: a morphometric analysis in the guinea pig model.

We have developed a guinea pig model of cigarette smoking induced lung disease, whereby animals exposed for several months to cigarette smoke develop emphysematous lung destruction as well as mild pulmonary hypertension with increased muscularization of the arterioles. To ascertain whether the animals with pulmonary hypertension had structural alterations of the right ventricle, we morphologically determined the volume proportion of inflammatory cells, fibrosis, and muscle cytoplasm and nuclei, and compared these values to those of age matched animals not exposed to smoke. We found that there was a significantly increased volume proportion of both fibrous tissue and inflammatory cells in the subendocardial myocardium after 12 months of cigarette smoke exposure, but not after 3 or 6 months. Since the degree of pulmonary hypertension, and the weight of the right ventricle were similar at the 3 time periods, we conclude that the inflammatory cell infiltrate and fibrosis in the subendocardial myocardium are manifestations of long term pulmonary hypertension, rather than any indication of co-existant damage to the myocardium as a result of the smoke exposure. These features would be compatible with the "right ventricular hypothesis" of Morrison (8) for the development of cor pulmonale, with the pathological changes seen as a result of a dysequilibrium between oxygen supply and demand in the right ventricle.

Animals↗
PubMed1990

Diffusion in porous materials above the percolation threshold.

The diffusion of water-soluble solutes in water-soaked porous media was studied by following the release of benzoic acid from poly(vinyl stearate) matrices. The results were analyzed using a pseudo-steady-state diffusion model coupled with the fundamental concepts of percolation theory. The results of the study indicated that the relationship between the bulk diffusion coefficient of benzoic acid in the polymer matrix and the porosity was well described by percolation scaling laws. A very low percolation threshold (0.07) was experimentally observed for this system.

Benzoates↗
PubMed1990

Active oxygen species mediate asbestos fiber uptake by tracheal epithelial cells.

To examine the mechanism whereby asbestos fibers penetrate tracheal epithelial cells, we exposed rat tracheal explants to amosite asbestos alone, or with varying concentrations of substances that scavenge active oxygen species (catalase and superoxide dismutase) or prevent formation of active oxygen species (deferoxamine). All three agents decreased asbestos fiber uptake in a dose-response fashion, but no agent provided complete protection against fiber penetration. We conclude that uptake of amosite asbestos fibers is mediated in part by active oxygen species (most likely OH.), but that other mechanisms of fiber uptake must also exist.

Animals↗
PubMed1990

Surgical treatment of obliterative otitis externa.

Seven patients with fibrous obliteration of the ear canal due to long-standing otitis externa were seen at St Mary's Hospital during the past 10 years. Two patients underwent bilateral surgery making a total of 9 ear cases. Two patients developed early restenosis within 6 months of permeatal excision of the fibrous core and skin grafting, and one patient had late stenosis 4 years following postaural excision, meatoplasty and skin grafting. Two of these patients opted for revision surgery and a total of 6 patients (8 ear cases) underwent postaural excision with Körner flap canalplasty, enlargement of the bony ear canal and skin grafting. The average hearing gain was 25 dB in the speech frequencies and only one restenosis was seen at 3 years. This was successfully revised. Radical excisional surgery with a wide bony canalplasty is recommended in this condition.

Adult↗
PubMed1990

Cigarette smoke causes physiologic and morphologic changes of emphysema in the guinea pig.

To investigate the long-term effect of cigarette smoke on pulmonary structure and function, we exposed groups of guinea pigs to the smoke of 10 cigarettes each day, 5 days per week, for 1, 3, 6, and 12 months. We found that the guinea pigs developed progressive lung destruction (emphysema) and alterations in their pulmonary function tests similar to that seen in humans with cigarette smoke-induced chronic obstructive lung disease. This method of smoke-induced lung destruction should provide a good model for the study of the early changes of emphysema.

Animals↗
PubMed1990

Chemistry, biology, and toxicology of domoic acid and its isomers.

The causative agent of toxicity in cultured mussels from a localized area of eastern Prince Edward Island has been identified as domoic acid, a neuroexcitatory amino acid. The toxin was isolated by a number of different bioassay-directed separation techniques including high-performance liquid chromatography (HPLC), high-voltage paper electrophoresis (HVPE), and ion-exchange chromatography, and characterized by a number of spectroscopic techniques including ultraviolet, infrared, mass spectrometry, and nuclear magnetic resonance. The isolation and purification methods are described in detail and some new analytical data for domoic acid are reported. A plankton bloom at the time of the outbreak gave positive mouse bioassays and consisted almost entirely of the pennate diatom, Nitzschia pungens f. multiseries. A positive correlation was found between the number of N. pungens cells and the concentration of domoic acid in the plankton. N. pungens f. multiseries isolated from Cardigan Bay produced domoic acid de novo during stationary phase culture at levels (1 to 10 pg/cell) comparable to values estimated for N. pungens in the plankton samples. We conclude that N. pungens was the major source of the domoic acid in toxic mussels in eastern Prince Edward Island. The recurrence, in November 1988, of a monospecific bloom of N. pungens and the presence of domoic acid in plankton and mussels reinforces this conclusion.

Animals↗
PubMed1990

An autopsy study of the structure of the small vessels in biopsies from the lingula and upper and lower lobes: implications for vascular assessment.

We examined the structure of the muscular pulmonary arteries in the three lung sites most often used for lung biopsy. In a subset of cases, we also examined tissue from the central portion of the lower lobe. In each vessel we measured the area of intima and muscle media and expressed these data as a percentage of the total tissue area; vessel size was standardized by using the length of the internal elastic lamina. We found that no one biopsy site best represented the arterial structure of the central aspect of the lower lobe. The lingula had greater numbers of arteries which met the criteria for assessment from than did the other biopsy sites. The vessel structure was similar between the lingula and peripheral aspect of the upper lobe, but the lingula had a slightly increased area of muscle media and decreased intima when compared with the superior segment of the lower lobe. This was not a function of vessel size, since the overall cumulative distribution curve of percent muscle divided by length of internal elastic lamina was also shifted between lingula and lower lobe. We conclude that, in the assessment of arterial vascular structure, any of the standardly used biopsy sites can be representative of the lung. Although there may be differences in structure between the sites in individual patients depending on concurrent disease in any of the sites, there is no consistent site effect on vessel structure. If a formal morphometric evaluation of arterial structure is required, the lingula appears to have more vessels which fit the criteria for assessment.

Autopsy↗
PubMed1989

Histopathological and blood-brain barrier changes in rats induced by an intracerebral injection of human recombinant interleukin 2.

Adoptive immunotherapy utilizing human recombinant interleukin 2 (rIL-2) in conjunction with lymphokine-activated killer cells has shown some efficacy in the treatment of various types of cancers, particularly renal carcinoma and melanoma. Intravenous administration of rIL-2, with or without lymphokine-activated killer cells, produces a variety of serious side effects and approximately one-third of the patients experience a decrease in neurological status. Our previous investigations in animals have indicated that a single intravenous injection of rIL-2 can compromise the integrity of the blood-brain barrier (BBB). The present study examined the histopathological effect and BBB changes in rats which occur after a single intracerebral injection of rIL-2, its excipient, or saline into the parietal lobe. Animals were killed at various intervals up to 8 days (1 hour after intravenous injection of horseradish peroxidase), and the brain tissue was sectioned and processed for light microscopy. All animals showed increased cerebrovascular permeability for horseradish peroxidase due to traumatic BBB disruption at 4, 12, and 24 hours after injection. Extravasation of horseradish peroxidase persisted at 3 and 8 days only in animals injected with rIL-2. Injections of rIL-2 led to an increased leukocytic infiltration into the injection site, perivascular cuffing, and localized edema by 24 hours, which continued to increase over the 8-day study period. These results suggest that a single injection of human rIL-2 into the brain of rats induces an influx of leukocytes into the brain and may contribute to the cellular events that perpetuate a trauma-induced compromise in the integrity of the BBB.

Animals↗
PubMed1989

Rapid short-term clearance of chrysotile compared with amosite asbestos in the guinea pig.

Compared with amphibole forms of asbestos, chrysotile asbestos fails to accumulate in lung tissue; the mechanism of this effect is disputed. To investigate this problem, we administered a mixture of the amphibole, amosite, and chrysotile to guinea pigs by intratracheal instillation. At 1 day, 1 week, and 1 month after instillation, animals were killed, and the numbers, types, sizes, and compositions of fibers in the lungs were determined by analytical electron microscopy. Both chrysotile and amosite fiber concentrations decreased with time, but relative chrysotile clearance was significantly greater than amosite clearance. There was no evidence of magnesium leaching from chrysotile fibers of any size at any time. Analysis of fiber lengths and widths showed a time trend toward shorter and narrower fibers (particularly toward fibers of less than 2 microns long and less than 0.025 microns wide) for chrysotile. This effect was not seen for amosite. We conclude that (1) failure of chrysotile accumulation in lung results from preferential chrysotile clearance during the first few days to weeks after exposure; (2) there is no evidence that fiber dissolution plays a role in chrysotile clearance; (3) preferential clearance may be a result of fragmentation and rapid removal of chrysotile fibers.

Animals↗