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C J Kennedy

Publications and source records attributed to C J Kennedy.

At least 19 recordsLinked to original sources
PubMed2005

Evidence of a distinct lipid fraction in historical parchments: a potential role in degradation?

Parchment, a biologically based material obtained from the processed hides of animals such as cattle and sheep, has been used for millennia as a writing medium. Although numerous studies have concentrated on the structure and degradation of collagen within parchment, little attention has been paid to noncollagenous components, such as lipids. In this study, we present the results of biochemical and structural analyses of historical and newly manufactured parchment to examine the potential role that lipid plays in parchment stability. The lipid fraction extracted from the parchments displayed different fatty acid compositions between historical and reference materials. Gas chromatography, small-angle X-ray scattering, and solid-state NMR were used to identify and investigate the lipid fraction from parchment samples and to study its contribution to collagen structure and degradation. We hypothesize that the origin of this lipid fraction is either intrinsic, attributable to incomplete fat removal in the manufacturing process, or extrinsic, attributable to microbiological attack on the proteinaceous component of parchments. Furthermore, we consider that the possible formation of protein-lipid complexes in parchment over the course of oxidative degradation may be mediated by reactive oxygen species formed by lipid peroxidation.

Animals↗
PubMed2004

Impacts of carbamate pesticides on olfactory neurophysiology and cholinesterase activity in coho salmon (Oncorhynchus kisutch).

Many freshwater aquatic environments in the Pacific Northwest of North America contain neurotoxic pesticides, an issue of concern given the use of many of these habitats by Pacific salmon (Oncorhynchus sp.). Pesticides such as carbamates are known to affect fundamental physiological systems (such as the enzyme acetylcholinesterase (AChE)), and have been shown to affect salmonid olfactory-mediated behaviors. A neurophysiological measure of olfactory function, the electro-olfactogram (EOG), was used in this study to examine the impacts of acute localized exposure to three carbamates (the insecticide carbofuran, the antisapstain IPBC, and the fungicide mancozeb) on olfactory function in the coho salmon (Oncorhynchus kisutch). We also examine the potential for these pesticides to alter AChE levels in the primary olfactory system and brain with brief exposures (30 min to only the olfactory rosette (OR)). In results, we find that the EOG in coho salmon is highly sensitive to brief localized exposures of two of these three carbamate pesticides. The effective nominal concentration required to cause a 50% reduction in EOG amplitude (EC50) for carbofuran was 10.4 microg/l and for IPBC was 1.28 microg/l. For mancozeb, the EC50 was higher at 2.05 mg/l. All three carbamates also affected AChE activity levels in the OR and brain (BR): carbofuran exposure at 200 microg/l significantly inhibited AChE activity in the OR, and both IPBC and mancozeb significantly increased AChE activity in BR at multiple concentrations with acute localized exposure. These carbamate effects highlight the sensitivity of salmon olfactory neurophysiology to pesticides acting not only potentially via AChE-inhibition, but also by other currently unknown modes of action.

Analysis of Variance↗
PubMed2004

Influence of diet and ration level on benzo[a]pyrene metabolism and excretion in rainbow trout (Oncorhynchus mykiss).

Juvenile rainbow trout (Oncorhynchus mykiss) were fasted or fed one of three isoenergetic diets varying in protein and lipid content at full satiation levels or half rations for up to 9 weeks. At 3, 6, and 9 weeks, fish in each treatment group were dosed intraperitoneally with 10 mg tritiated benzo[a]pyrene [3H]-B[a]P/kg (B[a]P) to examine the effects of diet composition and energy intake on xenobiotic biotransformation and excretion. The percent dose eliminated during the experiment did not differ among fish receiving the different diet compositions or rations (range 73% to 84%). However, it was significantly decreased (to 53%) in the group that was fasted for 9 weeks. Examination of fish fasted for 6 and 9 weeks showed a significant increase in the proportion of phase I metabolites and a concomitant decrease in the proportion of phase II metabolites found in bile compared with all other groups. Also, fish that were fasted for 9 weeks produced proportionately less 9,10-dihydroxy-benzo[a]pyrene-trans-9,10-diol, more 3-hydroxybenzo[a]pyrene and 9-hydroxybenzo[a]pyrene, and more glucuronic acid conjugates compared with all other groups. Thus, dietary protein and lipid concentration did not appear to affect either the rate of B[a]P metabolism or its excretion; however, prolonged fasting resulted in a shift in metabolite profiles and decreased excretion.

Animal Feed↗
PubMed2004

Molecular interactions in collagen and chitosan blends.

Molecular interactions between collagen and chitosan (CC) have the potential to produce biocomposites with novel properties. We have characterised the molecular interactions in CC complexes by viscometry, wide angle X-ray scattering and Fourier transform infrared spectroscopy. It was found that CC are miscible at the molecular level and exhibit interactions between the components; X-ray diffraction of CC blends indicate that the collagen helix structure is lost in CC films with increasing chitosan content. Non-linear viscometic behaviour with decreasing chitosan content is interpreted as evidence of a third structural phase formed as a complex of CC. The blending of collagen with chitosan gives the possibility of producing new bespoke materials for potential biomedical applications.

Biocompatible Materials↗
PubMed2003

The effects of stress on the association between hsp70 and the glucocorticoid receptor in rainbow trout.

The purpose of this study was to characterize the association between hepatic heat shock protein 70 (hsp70) and the glucocorticoid receptor in rainbow trout that were exposed to heat stress, cortisol, and beta-naphthoflavone. This study is the first to document that the glucocorticoid receptor complex in rainbow trout hepatic tissues contains hsp70. Heat stress significantly increased levels of total cellular hsp70, and by discerning the association of hsp70 with the glucocorticoid receptor, we demonstrated that heat stress significantly increased the amount of hsp70 not bound to the glucocorticoid receptor, while significantly decreasing the amount of hsp70 bound to the glucocorticoid receptor. By calculating the ratio of hsp70 bound to the glucocorticoid receptor, to the total number of glucocorticoid receptors, stress (heat stress and cortisol-treatment) promoted the association of hsp70 with the glucocorticoid receptor. These findings demonstrate a functional and structural link between hsp70 and the glucocorticoid receptor in rainbow trout, and raise questions regarding the existence of a complex, interrelated stress response that spans all levels of biological organization within the whole animal.

Animals↗
PubMed2000

The effect of bioaccumulated selenium on mortalities and deformities in the eggs, larvae, and fry of a wild population of cutthroat trout (Oncorhynchus clarki lewisi).

To determine if elevated concentrations of waterborne selenium (Se), caused by coal mining, in the Elk River in southeastern British Columbia, may be causing reproductive or teratogenic effects in wild cutthroat trout (Oncorhynchus clarki lewisi), fertilized eggs from exposed and reference fish were raised in the laboratory. Eggs from each female were reared separately and the percent mortalities and deformities were related to the selenium content of the eggs. Selenium concentrations in females from the exposed site were highest in the liver (36.6 +/- 22.5 microg/g dry weight, range: 18.3 to 114), followed by the eggs (21.0 +/- 18.3 microg/g, range: 8.7 to 81.3) and the muscle (12.5 +/- 7.7 microg/g, range: 6.7 to 41). Despite these elevated egg Se concentrations, there was no significant effect on fertilization; time to hatch; percent hatch; or egg, larvae, and fry deformities or mortalities. Reproductive failure and embryonic terata have been reported at much lower egg Se concentrations in other fish species. The lack of any toxic response in this study may be due to an evolved tolerance to higher tissue Se concentrations in a population of fish living in a seleniferous river system.

Abnormalities, Drug-Induced↗
PubMed2000

Benzo[a]pyrene toxicokinetics in rainbow trout (Oncorhynchus mykiss) acclimated to different salinities.

The effects of environmental salinity on the distribution, metabolism, and elimination of benzo[a]pyrene (B[a]P) were examined in mature rainbow trout. Trout acclimated to either fresh water (0 ppt, FW) or sea water (20 ppt, SW) for 3 weeks received a single 10 mg/kg intra-arterial injection of [(3)H]-benzo[a]pyrene (B[a]P) at their acclimation salinity or when subjected to an acute salinity change. Statistically significant differences in the percent body burden of B[a]P-derived radioactivity in various tissues were seen between fish in FW versus SW. Significant differences in the distribution of B[a]P and its metabolites were also noted when fish were subjected to an acute salinity change after chemical injection. Modulation of B[a]P metabolism by environmental salinity included: (1) significant differences in the proportions of Phase I metabolites in the bile of FW- (2.3%) versus SW-acclimated (14.1%) fish, and (2) alterations in the accumulations of specific metabolites (predominantly t-9, 10-dihydrodiol-B[a]P in FW fish, and 3-hydroxy-B[a]P in SW fish). The percentages of the [(3)H]-B[a]P dose eliminated by 48 h was similar in FW and SW fish, but decreased in fish subjected to an acute salinity change (FW 98.8% eliminated, FW:SW 90.4%, SW 98.1%, and SW:FW 93.1%). Pharmacokinetic modeling confirmed that acute salinity changes can result in longer terminal half-lives and slower total body clearances of B[a]P.

Adaptation, Physiological↗
PubMed1999

Thermal modulation of the toxicokinetics of benzo[a]pyrene in isolated hepatocytes of sablefish (Anoplopoma fimbria), black rockfish (Sebastes melanops), and chub mackerel (Scomber japonicus).

Hepatocytes from sablefish (Anoplopoma fimbria), black rockfish (Sebastes melanops) and chub mackerel (Scomber japonicus) were isolated from 11 degrees C acclimated animals. The uptake, metabolism, and excretion of benzo[a]pyrene (B[a]P) in hepatocytes was measured at 6, 11 and 19 degrees C. Chub mackerel hepatocyte uptake rates were significantly lower (0.012 +/- 0.003 microg/s per g cell) at 11 degrees C than black rockfish (0.028 +/- 0.009 microg/s per g cell) or sablefish (0.032 +/- 0.012 microg/s per g cell) hepatocytes at all temperatures. Hepatocytes metabolized B[a]P to phase I (1-8%) and phase II (92-99%) metabolites. Accumulation of phase II metabolites was lower in chub mackerel hepatocytes (0.016 +/- 0.004 microg/h per g cell), than black rockfish (0.052 +/- 0.012 microg/h per g cell), or sablefish hepatocytes (0.060 +/- 0.015 microg/h per g cell). Phase II metabolite accumulation increased greatest with temperature in chub mackerel hepatocytes (Q10 = 1.94 +/- 0.30), followed by sablefish (Q10 = 1.65 +/- 0.30), and rockfish (Q10 = 1.38 +/- 0.30). Sablefish hepatocytes had higher excretion rates of phase II metabolites (0.010 +/- 0.0023 microg/h per g cell), than mackerel (0.0046 +/- 0.0009 microg/h per g cell) or rockfish hepatocytes (0.0029 +/- 0.0008 microg/h per g cell). Phase II metabolite excretion rates increased with temperature only in sablefish hepatocytes (Q1O = 1.67 +/- 0.76). These differences in toxicokinetics may indicate distinct consequences for various species exposed to xenobiotics.

Animals↗
PubMed1999

Development and characterization of a cell line from Pacific herring, Clupea harengus pallasi, sensitive to both naphthalene cytotoxicity and infection by viral hemorrhagic septicemia virus.

A cell line, PHL, has been successfully established from newly hatched herring larvae. The cells are maintained in growth medium consisting of Leibovitz's L-15 supplemented with 15% fetal bovine serum (FBS), and have been cryopreserved and maintain viability after thawing. These cells retain a diploid karotype after 65 population doublings. PHL are susceptible to infection by the North American strain of viral hemorrhagic septicemia (VHS) virus, and are sensitive to the cytotoxic effects of naphthalene, a common environmental contaminant. Naphthalene is a component of crude and refined oil, and may be found in the marine environment following acute events such as oil spills. In addition, chronic sources of naphthalene contamination include offshore drilling and petroleum contamination from areas such as docks and marinas that have creosote-treated docks and pilings and also receive constant small inputs of petroleum products. This cell line should be useful for investigations of the toxicity of naphthalene and other petroleum components to juvenile herring. In addition, studies of the VHS virus will be facilitated by the availability of a susceptible cell line from an alternative species.

Animals↗
PubMed1998

A study of the lethal and sublethal toxicity of polyphase P-100, an antisapstain fungicide containing 3-iodo-2-propynyl butyl carbamate (IPBC), on fish and aquatic invertebrates.

The acute toxicity of Polyphase P-100, an antisapstain wood preservative that contains 97% 3-iodo-2-propynyl butyl carbamate (IPBC), was determined for three species of fish (coho salmon, rainbow trout, and starry flounder) and three species of aquatic invertebrates (Daphnia magna, Hyalella azteca, and Neomysis mercedis). The 96-h LC50 values for the various fish species exposed to Polyphase P-100 ranged from 95 ppb for coho smolts (Oncorhynchus kisutch) to 370 ppm for juvenile starry flounder (Platichthys stellatus). The sensitivity of coho to Polyphase P-100 was altered by their developmental stage. Coho embryos were six to nine times more tolerant of Polyphase P-100 than coho alevins, which were twice as tolerant as coho smolts. The 48-h LC50 values for the invertebrates D. magna, H. azteca, and N. mercedis were 40 ppb, 500 ppb, and 2,920 ppb, respectively. In addition to a wider range of sensitivity to Polyphase P-100 compared with the fish species, the invertebrate species were characterized by a shallower concentration-response. In acute, 24-h sublethal tests with juvenile starry flounder and rainbow trout, there was no primary or secondary stress response (changes in hematocrit, leucocrit, hemoglobin concentration, plasma lactate concentration, and plasma cortisol concentration) at concentrations up to 50% of the 96-h LC50 value. The acute toxicity of a 1:8 mixture of Polyphase P-100 and Bardac 2280 (another antisapstain compound that contains didecyldimethylammonium chloride [DDAC] as the active ingredient) was close to additive for fish, but not for invertebrate species. The acute toxicity of the mixture was seven to eight times more than additive for H. azteca, but two to three times less than additive for D. magna. Some sublethal stress responses were revealed with the mixture that were not observed with the test chemicals alone.

Animals↗
PubMed1998

beta-Naphthoflavone abolishes interrenal sensitivity to ACTH stimulation in rainbow trout.

We report for the first time that beta-naphthoflavone (BNF) abolishes ACTH stimulation of cortisol production in rainbow trout (Oncorhynchus mykiss). There was significantly higher hepatic cytochrome P450 content and ethoxyresorufin O-de-ethylase and uridine-5'-diphosphoglucuronic acid transferase activities in BNF-treated fish than in sham-treated controls. BNF did not significantly affect either plasma turnover or tissue distribution of [3H]cortisol-derived radioactivity. Hepatic membrane fluidity and hepatocyte capacity for cortisol uptake were not altered by BNF as compared with the sham-treated fish. These results taken together suggest that BNF does not affect cortisol-clearance mechanisms in trout. A 3 min handling disturbance period elicited a plasma cortisol response in the sham-treated fish; however, the response in the BNF-treated fish was muted and significantly lower than in the sham fish. This in vivo response corroborates the lack of interrenal sensitivity to ACTH in vitro in the BNF-treated fish, suggesting that BNF affects the ACTH pathway in trout. Our results suggest the possibility that cytochrome P450-inducing compounds may affect cortisol dynamics by decreasing interrenal responsiveness to ACTH stimulation in fish, thereby impairing the physiological responses that are necessary for the animal to cope with the stressor.

Adrenocorticotropic Hormone↗
PubMed1997

Handling stress does not affect the expression of hepatic heat shock protein 70 and conjugation enzymes in rainbow trout treated with beta-naphthoflavone.

A response in heat shock protein 70 (hsp 70) expression in the beta-naphthoflavone (BNF) treated rainbow trout (Oncorhynchus mykiss) corresponded to altered metabolic status of the liver as evidenced by the lower phosphoenolpyruvate carboxykinase (PEPCK), lactate dehydrogenase and 3-hydroxyacylcoA dehydrogenase activities. The BNF-induced increase in hsp70 levels and conjugation enzyme activities (phase I and phase II) were not modified by handling stress. Indeed handling stress did not affect either hsp 70 levels or conjugation enzyme activities in trout liver. The decrease in hepatic PEPCK activity in the BNF group may be responsible for the attenuation of the increase in liver glucose concentration after a 3 min handling stress in this species, suggesting that BNF affects liver gluconeogenic capacity in this species. Handling stress elicited a plasma cortisol and glucose response in both the sham and BNF group, however, the cortisol response with BNF was erratic compared with the sham, implying alterations in the cortisol dynamics post-stress. These results show for the first time that BNF affects cellular metabolic responses to stress and suggests the possibility of using hsp 70 as a biomarker for toxic effects in trout.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1997

Retinal detachment caused by retinal dialysis.

PURPOSE: To determine the characteristics of patients developing retinal detachment secondary to retinal dialysis in Western Australia and to confirm the clinical impression that these patients had a low rate of proliferative vitreoretinopathy (PVR). METHODS: A retrospective analysis of the records of 1601 consecutive patients with rhegmatogenous retinal detachment identified 71 patients in whom the retinal detachment was caused by a retinal dialysis. RESULTS: The majority of these patients were young adults (mean age of 30 years) and the male to female ratio was 1.3:1. Seventy per cent of patients provided a history of significant trauma to the affected eye. Sporting injuries, assault, and motor vehicle injuries together accounted for 72% of identifiable trauma. Examination revealed a dialysis of the inferotemporal quadrant in 75% of cases and despite obvious signs of chronicity of the associated retinal detachment (such as intraretinal macrocysts and demarcation lines) in approximately one-third of the eyes, only 5.6% developed grade CI PVR either pre- or postoperatively. CONCLUSION: The present study supports the view that it is the low rate of PVR that explains the good prognosis and high surgical success rate for retinal detachments caused by retinal dialysis. It is postulated that a major reason for the low rate of PVR is that the vitreous base attachment to the posterior margin of a retinal dialysis acts as a significant barrier to the migration of potentially proliferative retinal pigment epithelial cells. This may lead to containment of the responsible proliferative cells within the loculated subretinal space.

Adolescent↗
PubMed1996

Oxygen consumption and energy metabolism of the early mouse embryo.

Oxygen consumption of preimplantation and early postimplantation mouse embryos has been measured using a novel noninvasive ultramicrofluorescence technique, based on an oil-soluble, nontoxic quaternary benzoid compound pyrene, whose fluorescence is quenched in the presence of oxygen. Pyruvate and glucose consumption, lactate production, and glycogen formation from glucose were also measured. Preimplantation mouse embryos of the strain CBA/Ca x C57BL/6 were cultured in groups of 10-30 in 2 microliters of modified M2 medium containing 1 mmol l-1 glucose, 0 mmol l-1 lactate, and 0.33 mmol l-1 pyruvate, for between 4-6 hr. Day 6.5 and 7.5 embryos were cultured singly in 40 microliters M2 medium for between 2-3 hr. Oxygen consumption was detected at all stages of development, including, for the first time, in the early postimplantation embryo. Consumption remained relatively constant from zygote to morula stages before increasing in the blastocyst and day 6.5-7.5 stages. When expressed as QO2 (microliters/mg dry weight/hr), oxygen consumption was relatively constant from the one-cell to morula stages before increasing sharply at the blastocyst stage and declining to preblastocyst levels on days 6.5 and 7.5. Pyruvate was consumed during preimplantation stages, with glucose uptake undetectable until the blastocyst stage. Glucose was the main substrate consumed by the 6.5 and 7.5 day embryo. The proportions of glucose accounted for by lactate appearance were 81%, 86%, and 119% at blastocyst, day 6.5, and day 7.5 stages, respectively. The equivalent figures for glucose incorporated into glycogen were 10.36%, 0.21%, and 0.19%, respectively. The data are consistent with a switch from a metabolism dependent on aerobic respiration during early preimplantation stages to one dependent on both oxidative phosphorylation and aerobic glycolysis at the blastocyst stage, a pattern which is maintained on days 6.5 and 7.5. Our technique for measuring oxygen consumption may have diagnostic potential for selecting viable embryos for transfer following assisted conception techniques in man and domestic animals.

Animals↗
PubMed1996

Correlation between autofluorescent debris accumulation and the presence of partially processed forms of cathepsin D in cultured retinal pigment epithelial cells challenged with rod outer segments.

The purpose of the present study was to investigate the accumulation of rod outer segment (ROS)-derived debris in cultured human retinal pigment epithelial cells (RPE). The RPE cell layer is responsible for the phagocytosis and digestion of photoreceptor outer segments. Due to the immense volume of photoreceptor-derived material processed by the RPE cells, even minor changes in the efficiency of ROS processing may cause the accumulation of lipofuscin and photoreceptor derived debris. In this work, 17 RPE cultures were established from the globes of eye bank donors whose ages ranged from 18 to 79 years. Third passage cultures were challenged with bovine ROS and the accumulation of an autofluorescent debris was quantified using a flow cytometer. It was demonstrated that ROS challenge greatly increased the rate of autofluorescent debris accumulation. The accumulation of autofluorescent debris varied significantly from culture to culture. This variation was independent of the phagocytosing capacity of individual cultures and was not age dependent. To further investigate the factors which may be responsible for these differences, the presence of cathepsin D, an aspartic protease responsible for 80% of proteolysis of rhodopsin, was analysed by Western blot. Although the 34 kDa active form of cathepsin D was found in all cultures, in 41% of the cultures higher-molecular-weight forms of cathepsin D were additionally present, thus providing a multimer form of cathepsin D in these cultures. The rate of autofluorescent debris accumulation in cultures possessing a multimer form of cathepsin D was significantly greater (mean 42.3, S.D. +/- 19.8) than those in cultures having a singlet active form (mean 18.8, S.D. +/- 5.5) at 34 kDa (Student's t-test, DF = 15, t = 6.834, P < 0.001). The former cultures included one from a donor with age related macular degeneration, the latter cultures included one from a donor with diabetic retinopathy. This study demonstrates that the rate of autofluorescent debris accumulation in cultured RPE cells is not age dependent, but is an intrinsic property of the donor RPE cells that is possibly related to the presence of a multimer form of the lysosomal enzyme cathepsin D.

Animals↗
PubMed1996

The pathogenesis of polychromatic cholesterol crystals in the anterior chamber.

PURPOSE: Polychromatic cholesterol crystal of the anterior chamber are an interesting and unusual finding. This paper examines the different pathogenetic mechanisms leading to the formation of these clinically detectable anterior chamber crystals. METHODS: Three aetiologically different cases which exhibited polychromatic crystals in the anterior chamber were reviewed. Aqueous samples were examined by wet field microscopy in all cases and additionally by electron microscopy in one of these. One enucleated globe was available for histopathology. RESULTS: Typical highly refringent cholesterol crystals were identified in the aqueous of all cases. In the first case, the cholesterol crystals developed following the breakdown of vitreous and anterior chamber haemorrhage. In the second case, the cholesterol appeared to derive from the subretinal fluid of a chronic total retinal detachment in the absence of any intraocular haemorrhage. The cholesterol crystals of the final case resulted from phacolysis and were associated with a marked neutrophil response and the presence of proteinaceous crystals consistent with the crystallins. CONCLUSIONS: Anterior chamber cholesterolosis is a secondary phenomenon that always occurs as a result of an ocular disease process. Although the prognosis is dismal for chronically diseased eyes displaying cholesterol crystals in the anterior chamber, the prognosis for eyes with phacolysis may be excellent.

Adult↗
PubMed1996

Suprachoroidal effusion following argon laser trabeculoplasty.

PURPOSE: This is first report of suprachoroidal effusion occurring subsequent to argon laser trabeculoplasty (ALT). METHODS: Review of the records of the patients in question. RESULTS: A 77-year-old woman with bilateral pseudophakia and primary open-angle glaucoma was treated with ALT when her visual fields deteriorated despite topical timolol therapy. Although ALT was initially performed without complication in one eye, treatment of the other eye led to a choroidal detachment. This was associated with temporary reduction in visual acuity, shallowing of the anterior chamber and hypotony. CONCLUSION: Suprachoroidal effusion appears to be another complication of ALT. In the reported case, this application and its effects were temporary and resolved with conservative management.

Aged↗