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Biomedical subjects

C F Simpson

Publications and source records attributed to C F Simpson.

At least 19 recordsLinked to original sources
PubMed1993

A reappraisal of the carcinogenicity of surface modified asbestos fibres.

A previous study using intrapleural administration of surface-modified amosite asbestos showed a difference in the number of pleural mesotheliomas induced with C18-hydrocarbon derivatised fibres compared to native amosite asbestos. The study has been repeated with larger groups of animals (30) under specific pathogen free conditions, resulting in an increase in the mean animal survival time for both fibre-treated groups. Under these conditions there was no significant difference between the numbers of pleural mesotheliomas induced by C18 hydrocarbon-modified amosite asbestos and native amosite asbestos. The major difference between the two studies was the mean time to death from tumour of rats exposed to fibres. The C18 amosite treated rats in the first study may not have had a mean survival time long enough to allow mesotheliomas to develop.

Animals↗
PubMed1990

Surface modification can affect the carcinogenicity of asbestos.

A sample of amosite asbestos was modified by effectively adding C8 and C18 hydrocarbon chains to the fibre surfaces. The altered fibres interacted less readily with cells in vitro and were less cytotoxic. In whole animals the number of mesotheliomas produced by the C8 material was the same as that with the parent material but the tumours occurred earlier. The C18 derivatized fibre was markedly less active in the production of tumours. This is the first report demonstrating that similar size fibres with differing surfaces have different pathogenic properties.

Animals↗
PubMed1990

Interaction of amosite and surface-modified amosite with a V79-4 (Chinese hamster lung) cell line.

We have been examining a number of chemically modified mineral fibers, derived from amosite asbestos, by in vitro methods to clarify the role of the fiber surface in determining biological activity. The various fibers have identical size distributions but differ in their affinities for components of the cell membrane. They were treated with boiling toluene or chemically modified by treatment with alkyldimethylchlorosilanes (R = C8, C18) that react with free-surface hydroxyl groups to form the corresponding siloxanes. Fibers in MEM supplemented with 15% fetal calf serum were added to a suspension of V79-4 cells labeled with tritiated thymidine and the mixture was incubated. Aliquots of this mixture were spun down on a density gradient to determine the degree of cell-fiber interaction. At 37 degrees C native amosite (UICC standard) stuck to cells within 15 min of incubation, and the amount of sticking was maximum within 70 min. Decreasing the temperature decreased the amount of sticking, and at 20 degrees C no sticking was observable. The chemically modified amosite and the amosite treated with boiling toluene did not stick to the cells even after 70 min. Soaking the toluene-treated amosite with aqueous solutions at room temperature for 48 hr produced a material that had the same sticking properties as the original untreated fiber. These results indicate that the silanol content, and possibly the degree of hydration of the fiber surface, is important for a fiber to stick to a cell surface.

Animals↗
PubMed1985

Lesions in the liver and kidney of Dirofilaria immitis-infected dogs following treatment with ivermectin.

Six dogs with spontaneous heartworm disease were injected with a single dose of ivermectin. After 48 h of treatment, microfilariae counts were reduced by 92%-98% of pretreatment counts. In pretreatment biopsies examined by light and electron microscopy, microfilariae were unaltered in the sinusoids of the liver and also in the glomerular capillaries and interstitial blood vessels of the kidney. However, there was irregular thickening and dense deposits in the basement membranes of glomerular capillaries, along with a modest increase in mesangial cells and matrix. In post-treatment liver biopsies examined by light microscopy, there were numerous granulomas in the sinusoids which contained degenerated microfilariae. In post-treatment kidney biopsies there was moderate thickening of glomerular basement membranes along with pronounced proliferation of mesangial cells and matrix. Glomerular capillaries were partially or completely occluded by degenerated microfilariae. In addition, there were interstitial granulomas in the kidney. It was observed with the aid of electron microscopy that highly vacuolated and degenerated microfilariae were incorporated into granulomas in the liver sinusoids of post-treatment biopsies. In post-treatment kidney biopsies glomerular capillaries were usually occluded by degenerated microfilariae. Basement membranes were thickened and contained dense deposits. Mesangial cells and matrix were extensively increased. Interstitial granulomas in the kidney contained dead microfilariae.

Animals↗
PubMed1985

Ultrastructure of the intraerythrocytic stage of Cytauxzoon felis.

The erythrocytes of 2 cats experimentally infected with Cytauxzoon felis were examined by light and electron microscopy. In stained blood smears, parasitized erythrocytes usually contained a single, roundish organism, but occasionally up to 4 were present in a cell. Chains of these roundish organisms also were seen. Elongated parasites, sometimes with ear-like projections, were present in a few erythrocytes. By electron microscopy, the parasite contained a poorly defined nucleus, rough endoplasmic reticulum, ribosomes, nonplicated mitochondria, food vacuoles, and a cytostome on its limiting membrane. Usually, the parasite was oval, but budding forms also were evident. Crystalloid inclusions were present in parasitized and nonparasitized erythrocytes.

Animals↗
PubMed1985

Ultrastructure of schizonts in the liver of cats with experimentally induced cytauxzoonosis.

Schizonts in the liver of 2 cats with cytauxzoonosis were studied by both light and electron microscopies. By light microscopy, the cytoplasm of macrophages in the sinusoids and small vascular channels contained schizonts with cytomeres or both cytomeres and mature merozoites. By electron microscopy, it was determined that schizogony occurred in 4 stages. The earliest stage was the presence of a multilobed structure containing finely granular protoplasm in the cytoplasm of the macrophage. The 2nd stage was an increase in height and number of the lobulations on the surface of the schizont. The 3rd stage involved the development of cytomeres and the appearance of a polar ring and rhoptries in everted sacculations on the cytomere membrane. Nuclei and mitochondria were incorporated into the sacculations before the release of mature merozoites into the host cell cytoplasm. In the last stage of schizogony, following massive merozoite formation and reduction in size of the schizont, residual nuclei divided by multiple fission. Each nuclear division became incorporated into a developing merozoite having preformed rhoptries, mitochondria, and a polar ring.

Animals↗
PubMed1985

Neurotoxic and antihypertensive effects of phenytoin in turkeys.

Broad-Breasted White male turkeys were fed a control diet until 4 weeks of age, at which time they were randomized into a control group and two treatment groups which received 0.06% (38.7 mg/kg) and 0.09% (58.2 mg/kg) phenytoin, respectively, until termination of the experiment at 12 weeks of age. Plasma concentrations of phenytoin on the two dosages were 8.0 +/- 0.8 and 15.7 +/- 1.7 micrograms/ml. Systemic arterial blood pressure in the control turkeys was 214 +/- 5/171 +/- mm Hg and was reduced in a dose-related fashion to 185 +/- 8/143 +/- 11 and 156 +/- 5/125 +/- 4 mm Hg in the two treatment groups; likewise, the rate of systolic ejection (dp/dt maximum) was less in the phenytoin-treated turkeys. Heart rate also dropped significantly with drug administration but the difference between the two treatment groups was not significant. Evidence of neurotoxicity developed in 25% of the turkeys on the lower drug schedule; these birds had mean plasma phenytoin levels of 12.8 micrograms/ml as contrasted to the concentration of 8.0 micrograms/ml for the entire group. On 0.09% phenytoin 50% of the birds had abnormal signs and a mean phenytoin concentration of 20.5 micrograms/ml, whereas the mean drug level for the entire group on this drug level was 15.7 micrograms/ml. Early signs of neurotoxicity developed within 2 to 3 days of initiation of phenytoin and consisted of extensor rigidity of the neck and hyperactivity; at the higher drug concentrations, back pedaling and somersaulting appeared. General health and weight gain were not affected. No qualitative or quantitative changes were found in the Purkinje cells in the cerebellum of the affected turkeys.

Animals↗
PubMed1984

A unique connective tissue structure in the aortic media of the chicken.

The interstitium between smooth muscle cells in the media of the abdominal aorta of the chicken contains basement membranes, glycosaminoglycan, stout elastic fibers, extensive bundles of collagenous fibers, and a unique striated structure. In cross section, this striated, hexagonal structure resembles a honeycomb, each hexagon consisting of 6 isosceles triangles. Microtubule-like structures are present at each corner and center of a hexagon, and 3 delicate filaments are located equidistantly between putative microtubules. The periodicity evident in longitudinal section is the result of a constant repetition of microtubule-like elements. From staining with phosphotungstic acid it appears that the striated connective tissue structures are proteinacous and might serve as a reinforcing structure where smooth muscle cells are separated by dilated extracellular spaces.

Animals↗
PubMed1984

Cartilaginous metaplasia of the thoracic aorta of control turkeys and exacerbation by beta-aminopropionitrile.

Seventeen of sixty distal extremities of the thoracic aortas of 12-week-old control male turkeys and 37 of 40 distal extremities of the aortas of turkeys fed 0.07% beta-aminopropionitrile (BAPN) from 4 to 12 weeks of age contained areas of cartilaginous metaplasia when examined by light microscopy. The cartilaginous areas were generally elongated and located in the subendothelium of control turkeys, but a roundish area of cartilage was occasionally evident in the deep media. The magnitude of chondroplasia was enhanced by feeding BAPN; the extensive lesion usually extended from the subendothelium to deep in the media. Regardless of treatment, chondrocytes were pleomorphic, contained vacuoles, and had cytoplasmic processes. The cells were separated by pools of proteoglycans and connective tissue. The ultrastructure of chondrocytes in the aortas of both treatment groups was typical of this cell type. They had undulations or projections of the cell membranes. The cisternae of endoplasmic reticulum were dilated and contained electron-translucent material which was similar to extracellular proteoglycans. Golgi apparatus, free ribosomes, mitochondria, glycogen granules, filaments, and a centriole also were present in the cytoplasm. The extracellular matrix, which included collagenous and elastic fibers and also delicate fibrils and interconnecting matrix granules, separated adjacent chondrocytes by spaces of varying size.

Aminopropionitrile↗
PubMed1984

Tetrameres columbicola (Nematoda: Spiruridae) infection of pigeons: ultrastructure of the gravid female in glands of the proventriculus.

The light and electron microscopies of Tetrameres columbicola gravid females in sections of the parasitized proventriculus of pigeons were studied. By light microscopy, the most conspicuous structures in the sectioned parasite were the intestine, ovary, and especially the uterus that contained numerous eggs. By electron microscopy, there was a thick mat of pigment-coated microvilli on the surfaces of the intestinal epithelial cells. The germinal zone of the ovary contained nonmembrane-bound oocytes, but oocytes were confined by a membrane in the growth zone of the ovary. The core of the spermatheca contained oocytes and the periphery harbored sperm. In this location, the unfertilized oocyte had pseudopods; sperm had invaginations of the plasma membrane. After fertilization, there was proliferation of ribosomes within the oocyte. Embryonating eggs in the uterus had thick shells and were partially enveloped by elongations of the uterine epithelial cells. Surfaces of the epithelial cells were pleated and they had electron opaque areas at the points of the pleats. Larvae in eggs had a well developed annulated cuticle and muscular layer. Somatic muscle cells had tailed appendages that protruded into the pseudocoelom. The single layer of cells beneath the hypodermis had lateral processes at the base of the cells that interdigitated with similarly elongated processes of adjacent muscle cells. Striated fibers were present in the central portion of the cells.

Animals↗
PubMed1983

Modulation by propranolol of the lysyl cross-links in aortic elastin and collagen of the aneurysm-prone turkey.

dl-Propranolol (propranolol) fed to immature and mature aneurysm-prone turkeys (Broad-Breasted White, BBW) for 6 weeks significantly raised the tensile strength of tissue rings from the abdominal aorta. The drug-mediated increase in tensile strength values was dose-related and independent of its heart rate- and arterial pressure-lowering effects. Propranolol acts, in part, by (a) stimulating lysyl oxidase to produce greater amounts of reactive aldehydes for intermolecular cross-links, (b) enhancing the progression of chemically unstable to stable forms of intermolecular elastin cross-links (lysinonorleucine and the desmosines), and (c) reducing the density of the age-related intermolecular cross-linking of collagen (pyridinoline). These propranolol effects on the lysyl cross-links were demonstrated in both the immature and mature animals and suggest a heretofore unrecognized potential for this widely used cardiovascular drug.

Aneurysm↗
PubMed1983

The B-aminopropionitrile-fed turkey: a model for detecting potential drug action on arterial tissue.

Broad-breasted white male turkeys develop hypertension, tachycardia and aortic arteriosclerosis spontaneously by approximately 5 weeks of age. When fed B-aminopropionitrile (BAPN), aortic tensile strengths are lowered, and a high percentage of the turkeys die from aortic dissecting aneurysms. There are essentially no deaths from aneurysms when either dl-propranolol or reserpine is fed in concert with BAPN; practolol and soltalol partially protect the BAPN-fed turkey from lethal aneurysms while hydralazine and phenelzine sulphate potentiate mortality from aneurysms. Dl-propranolol decreases and reserpine increases dP/dtmax and both drugs lower arterial pressure and heart rate when fed with BAPN. Such diets also decrease the ultrastructural disarray of collagenous and elastic fibres in the media of the abdominal aorta that occurs from the feeding of BAPN and thereby raise aortic tensile strength. Sotalol and practolol when fed to BAPN-fed turkeys lower blood pressure and dP/dtmax, but neither drug affects aortic tensile strength and both counteract the deleterious effect of BAPN on the ultrastructure of collagenous and elastic fibres to a minor degree. Phenelzine sulphate does not affect arterial pressure while hydralazine reduces arterial pressure; both drugs decrease aortic tensile strength and increase the ultrastructural disruption of aortic elastin and collagen in the BAPN turkey. The results suggest that dl-propranolol, reserpine, phenelzine sulphate, and hydralazine have an action on aortic tissue and indicate the usefulness of the BAPN-fed turkey as a model for identifying potential drug effects on aortic elastin and collagen.

Aminopropionitrile↗
PubMed1983

Mortality, hemodynamics, and aortic properties among male and female turkeys fed beta-aminopropionitrile.

Broad-Breasted White turkeys were randomized into four treatment groups at 4 weeks of age in each of three trials. Group 1, males, and Group 2, females, were fed an unsupplemented (control) diet from 4 to 10 weeks of age. Group 3, males, and Group 4, females, were fed the control diet supplemented with 0.07% beta-aminopropionitrile (BAPN). The experiments were terminated at 10 weeks of age. There was no mortality among male and female turkeys fed the control diet or significant differences in blood pressure, heart rate, aortic tensile strength, or aortic hydroxyproline between these males and females. Sixty-five percent of the males and 21% of the females fed BAPN died of dissecting aneurysms; blood pressure, heart rate, and dp/dt max were not altered as a result of feeding BAPN. Aortic tensile strength was higher in control turkeys than those fed BAPN, but males fed BAPN had the lowest value. Males fed BAPN also had the lowest aortic hydroxyproline content. Ultrastructural alterations of aortic elastic and collagen fibers were more severe in males than females fed BAPN. Aortic changes did not occur in control turkeys.

Aminopropionitrile↗
PubMed1983

Effect of high levels of Larvadex on reproduction in Leghorn breeders.

The insect growth inhibitor, Larvadex, was fed to egg type breeder hens for 8 weeks at levels of 0, 50, 100, 500, 1000, and 2000 ppm and to the same strain of males at 0 and 2000 ppm. All birds were kept in individual cages. Fertility was determined following artificial insemination. Egg production was significantly increased in Experiment 1 but numerically decreased in Experiment 2 by feeding 1000 ppm Larvadex. Feeding 2000 ppm significantly decreased egg production in both experiments. Egg weight was highest at 100 ppm and decreased with higher treatment levels. Specific gravity of eggs was improved with all Larvadex treatments. Fertility was not affected by treatment of females or males. Hatchability was reduced by the 1000 and 2000 ppm levels in the hen's diet. Semen quality was not significantly affected by feeding Larvadex at 2000 ppm.

Animals↗