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Biomedical subjects

J D Kelly

Publications and source records attributed to J D Kelly.

At least 55 records · Page 3Linked to original sources

Various treatment techniques on signs and symptoms of delayed onset muscle soreness.

Eccentric activities are an important component of physical conditioning and everyday activities. Delayed onset muscle soreness (DOMS) can result from strenuous eccentric tasks and can be a limiting factor in motor performance for several days after exercise. An efficacious method of treatment for DOMS would enhance athletic performance and hasten the return to activities of daily living. The purpose of this study was to identify a treatment method which could assist in the recovery of DOMS. In the selection of treatment methods, emphasis was directed toward treatments that could be rendered independently by an individual, therefore making the treatment valuable to an athletic trainer in team setting. DOMS was induced in 70 untrained volunteers via 15 sets of 15 eccentric contractions of the forearm extensor muscles on a Lido isokinetic dynamometer. All subjects performed a pilot exercise bout for a minimum of 9 weeks before data collection to assure that DOMS would be produced. Data were collected on 15 dependent variables: active and passive wrist flexion and extension, forearm girth, limb volume, visual analogue pain scale, muscle soreness index, isometric strength, concentric and eccentric wrist total work, concentric and eccentric angle of peak torque. Data were collected on six occasions: pre- and post-induced DOMS, 20 minutes after treatment, and 24, 48, and 72 hours after treatment. Subjects were randomly assigned to 1 of 7 groups (6 treatment and 1 control). Treatments included a nonsteroidal anti-inflammatory drug, high velocity concentric muscle contractions on an upper extremity ergometer, ice massage, 10-minute static stretching, topical Amica montana ointment, and sublingual A. montana pellets. A 7 x 6 ANOVA with repeated measures on time was performed on the delta values of each of the 15 dependent variables. Significant main effects (p < .05) were found for all of the dependent variables on time only. There were no significant differences between treatments. Therefore, we conclude that none of the treatments were effective in abating the signs and symptoms of DOMS. In fact, the NSAID and A. montana treatments appeared to impede recovery of muscle function.

Journal Article↗

The importation of the black rhinoceros (Diceros bicornis) from Zimbabwe into Australia.

The paper describes a program to import and breed black rhinoceros ex situ at Western Plains Zoo in Australia. Nine rhinoceros (7 females and 2 males) captured in 1992 in Chete National Park, Zimbabwe, were transported to Australia via Cocos Island. The veterinary treatment of the animals before and during quarantine in Zimbabwe and on Cocos (Keeling) Islands is described. Three animals died; an adult male on Cocos Islands and a juvenile male and an adult female at Western Plains Zoo, Dubbo, New South Wales. The juvenile male died as a result of trauma sustained shortly after arrival and the two adults after developing a severe hepatopathy. The group of 6 females and an additional 4 males imported from the USA in 1994 have adapted well to captivity and to the climate and environment of central west New South Wales.

Adaptation, Physiological↗

Laser lithotripsy for ureteric calculi: results in 250 patients.

Two hundred and fifty patients with 290 stones presenting to the Department of Urology were treated with the Candela MDL 2000 Laser Lithotripter. Overall stone clearance rate was 95%. The more proximal the calculus the lower the success rate. Ninety eight percent of stones in the lower ureter, 95% of mid ureteric and 91% of upper ureteric stones were cleared. The major complication was perforation which occurred in 6% of cases. This procedure is a safe and effective treatment for ureteric calculi and is associated with a low complication rate and a high clearance rate. Laser lithotripsy is the optimum ureteroscopic method of treating ureteric calculi and is complimentary to extra corporeal shock wave lithotripsy.

Adolescent↗

Covalent binding of (+) 7S-trans-7,8-dihydrobenzo [a]pyrene-7,8-diol to trout DNA: P-450- and peroxidation-dependent pathways.

Bioactivation in vivo of pure (+) 7S-trans-7,8-dihydrobenzo[a]pyrene- 7,8-diol ((+) BP-7,8-DHD) was investigated in rainbow trout. Embryos, microinjected with 0.01-1.0 microgram of [3H]-(-)-7S-trans-7,8-dihydrobenzo[a]-pyrene-7,8-diol-anti-9,10-epoxide ((-) anti-BPDE), exhibited a dose-dependent increase in DNA adduction. Subsequently, microinjection of trout embryos with [14C] (+) BP-7,8-DHD also demonstrated a dose-dependent increase in DNA adduction. To determine the relative contribution of P-450-dependent versus peroxidation-dependent epoxygenation of (+)-BP-7,8-DHD, trout embryos were co-injected with [14C]-(+)-BP-7,8-DHD and either beta-naphthoflavone (BNF) (CYP1A1 inducer) or carbon tetrachloride (CCl4) (lipid peroxidation enhancer). Co-injection with BNF tended to enhance covalent binding to DNA, which was consistent with rapid induction of CYP1A1. Co-injection with CCl4, significantly increased covalent binding of [14C]-(+)-BP-7,8-DHD to DNA, suggesting a contribution from non-enzymic cooxidation. 32P-Postlabeling analysis of liver DNA adducts following i.p. injections of (+) BP-7,8-DHD did not detect appreciable amounts of (-) anti-BPDE-dG from juvenile trout fed control diets or diets containing hydrogen peroxide or BNF. On the contrary, BNF pre-feeding markedly enhanced the levels of an adduct which co-chromatographed with authentic (+) syn-BPDE-dG. These results confirm that trout are capable of metabolically activating BP-DHD to the ultimate carcinogen BPDE and that BNF stimulates CYP1A1-dependent epoxygenation, but peroxidation-dependent activation may not contribute significantly to the bioactivation of BP-7,8-DHD in vivo.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Hepatocarcinogenic potency of mixed and pure enantiomers of trans-7,8-dihydrobenzo[a]pyrene-7,8-diol in trout.

The hepatocarcinogenic potency of pure and racemic trans-7,8-dihydrobenzo[a]pyrene-7,8-diol was investigated in embryos and sac-fry rainbow trout. Embryos microinjected with (+/-)-trans-7,8-dihydrobenzo[a]pyrene-7,8-diol ((+/-) BP-7,8-DHD) developed liver tumors 9 months after hatching. However, this exposure protocol resulted in high mortalities. Microinjection of newly hatched sac-fry with 0.01-1.0 microgram of (+/-) BP-7,8-DHD resulted in a dose-dependent production of liver tumors (0-13%) similar to the results with embryos but without the problem of high mortalities. Co-injection of sac-fry with (+/-) BP-7,8-DHD and either beta-naphthoflavone or carbon tetrachloride significantly enhanced the tumor response (approx. 3-fold). The relative carcinogenic potencies of the pure (+) and (-) enantiomers of BP-7,8-DHD were evaluated by microinjection into sac-fry at doses of 0.5-5.0 micrograms. The results demonstrated that the (-) enantiomer was 4-18 times more potent than the (+). Mixed carcinomas were the most prevalent liver tumors observed. These results demonstrate that trout embryos and sac-fry are both responsive to hepatocarcinogenesis initiation by injection with BP-7,8-DHD. The marked enhancement seen with co-injection of sac-fry with beta-naphthoflavone or carbon tetrachloride suggests that both cytochrome P-450-dependent and lipid peroxidation-dependent pathways could be involved in bioactivation of this compound, presumably through epoxidation at the 9,10-position. As is the case with mammals, the (-) enantiomer of BP-7,8-DHD is a more potent carcinogen than the (+) enantiomer.

Animals↗

Experimental autoimmune pinealitis in the rat: ultrastructure and quantitative immunocytochemical characterization of mononuclear infiltrate and MHC class II expression.

Lewis rats immunized with Peptide M (an oligopeptide epitope of the S-antigen protein) developed experimental autoimmune uveoretinitis (EAU) and experimental autoimmune pinealitis (EAP). Temporal changes in mononuclear infiltrate to the pineal gland were quantitated by computer image analysis of sections immunostained with monoclonal antibodies to specific mononuclear populations. T helper/inducer cells (W3/25+) and monocyte/macrophages (OX-42+) were elevated during the early phases of inflammation (day 15) while cytotoxic/suppressor T cells (OX-8+) were elevated at days 15 and 21. Expression of MHC class II (OX-6) was markedly enhanced on pineal glia, but was not present on vascular endothelia during EAP. Ultrastructurally, many capillaries exhibited thickenings of the endothelia and basal lamina. EAP had little effect on the fine structure of pinealocytes and glia and there was little evidence of cellular destruction by day 21, in contrast to the extensive retinal destruction resulting from EAU. These findings suggest fundamental differences between EAU and EAP related to mechanisms of antigen processing/recognition in autoimmune diseases. Our study further indicates the importance of EAP as a model to investigate neuroendocrine-immune interactions.

Animals↗

Technetium-99m-tetrofosmin as a new radiopharmaceutical for myocardial perfusion imaging.

A new cationic complex, [99mTc(tetrofosmin)2O2]+, where tetrofosmin is the ether functionalized diphosphine ligand 1,2-bis[bis(2-ethoxyethyl)phosphino]ethane, has been synthesized and evaluated for potential use in myocardial perfusion imaging. The structure of the complex has been determined by x-ray crystallography of the 99Tc analog. In comparison with previously reported 99mTc complexes of alkyl-phosphines, the tetrofosmin species shows substantially increased clearance from nontarget tissue, especially blood and liver. A freeze-dried kit formulation has been developed. The kit provides a product of high radiochemical purity up to 8 hr after reconstitution at room temperature.

Animals↗

Alterations in lipid peroxidation, antioxidant enzymes, and carcinogen metabolism in liver microsomes of vitamin E-deficient trout and rat.

Feeding rainbow trout for 16 weeks a diet in which the levels of vitamin E were reduced 70-fold resulted in marked depletion (18-fold) of vitamin E levels in liver microsomes from these fish. The susceptibility of hepatic microsomes to lipid peroxidation in vitro and the levels of plasma and liver microsomal lipid hydroperoxides generated in vivo were markedly elevated in vitamin E-depleted trout. No appreciable alterations were observed in the liver microsomal cytochrome P450-dependent mixed-function oxidase system or in the fatty acid composition of trout liver microsomal membranes. Livers from rats fed a vitamin E-deficient diet for 10 weeks also had significantly lower levels of microsomal vitamin E. In addition, total cytochrome P450 levels were depressed (15%) and cytosolic glutathione was enhanced (40%) in livers from rats fed the vitamin E-depleted diet. Covalent binding of [3H]-(+)-benzo[a]pyrene-7,8-dihydrodiol to exogenous DNA in vitro was enhanced with liver microsomes from vitamin E-deficient trout and these fish were much more sensitive to the acute toxicity of this carcinogenic polycyclic aromatic hydrocarbon. These results indicate that trout may be a useful model for studying the significance of peroxidative pathways in carcinogenesis and their manipulation by dietary antioxidants.

Animals↗

Dietary hydrogen peroxide enhances hepatocarcinogenesis in trout: correlation with 8-hydroxy-2'-deoxyguanosine levels in liver DNA.

The tumor-enhancing effect of hydrogen peroxide (H2O2) in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-initiated rainbow trout hepatocarcinogenesis was investigated and correlated with the levels of the mutagenic DNA adduct 8-hydroxy-2'-deoxyguanosine (oh8dG). In addition, the protective role of vitamin E was examined in relation to tumor enhancement and oh8dG levels in liver DNA. Trout were fed diets containing two levels of vitamin E (1000 or 20 mg/kg wet wt), each of which were made up to contain three levels of H2O2 (0, 600 or 3000 p.p.m.). Dietary vitamin E levels had no significant effect on tumor incidence or levels of oh8dG in liver DNA. On the other hand, dietary H2O2 enhanced liver tumors in a dose-dependent manner. Liver tumor incidence correlated significantly with the mean level of liver DNA oh8dG content (r = 0.87). We conclude that the H2O2 tumor-enhancing effect coincides with higher levels of oh8dG in the trout liver genome. Thus, rainbow trout may be a useful model for the study of the relationship of oh8dG levels in vivo to enhancement or promotion of carcinogenesis and its modulation by dietary enhancers and inhibitors of oxidative stress.

8-Hydroxy-2'-Deoxyguanosine↗

Platelet-derived growth factor (PDGF) stimulates PDGF receptor subunit dimerization and intersubunit trans-phosphorylation.

High affinity binding of platelet-derived growth factor (PDGF) has been proposed to involve the interaction of the dimeric PDGF ligand with two receptor subunits, designated alpha and beta. We have cloned and expressed a human PDGF receptor cDNA which differs in sequence from the beta-subunit and which has the PDGF binding properties and monoclonal antibody recognition, predicted for the alpha-subunit. Scatchard analysis indicated that PDGF-AA and PDGF-AB bound to transfected alpha-subunits with affinities of Kd = 0.06 and 0.05 nM, respectively. PDGF-BB bound with a significantly lower affinity (Kd = 0.4 nM). Nevertheless, this affinity is still great enough to mediate substantial PDGF-BB binding at physiological concentrations and would be considered to be "high affinity." We have used wild-type and kinase-inactive human beta-subunits to show that PDGF binding promotes receptor subunit dimerization in intact cells. In addition, we found that PDGF stimulates tyrosine phosphorylation of the kinase-inactive beta-subunit when it is expressed with alpha-subunits. The kinase-inactive beta-subunits were phosphorylated at tyrosine 857 and 751, the major phosphorylation sites of the wild-type beta-subunit, indicating either that intra- and intermolecular phosphorylation occurs on the same sites, or that a significant fraction of receptor tyrosine phosphorylation is intermolecular.

Animals↗

Morphological and histochemical comparison of the cells elicited by ectopic bone implants and tibial osteoclasts.

Pellets of mineralized and demineralized bone and a composite mixture of mineralized and demineralized, devitalized bone particles were implanted subcutaneously on the dorsal body wall of young adult rats. Two weeks post-implantation, the pellets were removed and processed for histochemical and morphological analyses. Rat proximal tibia was also processed for evaluation. The levels of tartrate-resistant acid phosphatase (TRAP) activity in the multinucleated giant cells (MNGCs) from each of the three implants and from osteoclasts were assessed using an image analyzer. The osteoclasts from the proximal tibia and the majority of MNGCs from the demineralized implants demonstrated high levels of TRAP activity. MNGCs from the mineralized implants showed either a low level or absence of TRAP activity. Most MNGCs from the composite implants exhibited a low level of TRAP activity; however, there was a population of cells that demonstrated a high level of reaction product, similar to that seen in the tibia and demineralized implant. Morphologically, osteoclasts from the proximal tibia and from the osteogenic demineralized implant exhibited ruffled borders. A small population of MNGCs from the composite implant also revealed osteoclastic features. In summary, MNGCs from the mineralized implant did not exhibit a level of TRAP reaction product or morphology similar to osteoclasts, while the majority of cells from the demineralized implant and a subpopulation of the MNGCs elicited by the composite implant did demonstrate TRAP expression and morphology similar to osteoclasts. The expression of osteoclastic characteristics in cells at an ectopic site may be dependent on accessory signals from the skeletal microenvironment; such signals appear to be absent from or incomplete in the mineralized implants but appear to be present when demineralized bone particles are implanted.

Acid Phosphatase↗

Use of paramagnetic chelated metal derivatives of polysaccharides and spin-labeled polysaccharides as contrast agents in magnetic resonance imaging.

Soluble and insoluble polysaccharides were derivatized with diethylenetriaminepentaacetic acid (DTPA) and/or spin-labeled with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). Polysaccharides derivatized with DTPA were prepared via cyanogen bromide activation, coupling to a diamine linker, and to DTPA anhydride. Spin-labeled polysaccharides were also prepared via cyanogen bromide activation. The extent of derivatization for dextran (18 kDa) was about 120 glucose units per DTPA, and for cellulose and starch about 15-30 units per DTPA. For spin-labeled polysaccharides, the average loading ranged from 1 nitroxide per 16 glucose units for starch to 181 for dextran (82 kDa). These derivatized paramagnetic polysaccharides were shown to be more effective relaxants than the small paramagnetic molecules alone. Both soluble and insoluble polysaccharide-linker-DTPA-Gd(III) complexes were effectively cleared from the body (rats) after oral administration. After intravenous administration, the biodistribution of dextran-linker-DTPA-Gd(III) complexes differed significantly from that of GdDTPA. Reduction of the nitroxide by ascorbic acid was retarded in the polysaccharide derivatives, particularly in starch derivatized with both nitroxide and linker-DTPA-Cu(II). These agents showed contrast enhancement in the gastrointestinal tract of rabbits.

Animals↗

Lipophilic 99mTc-nitride radiopharmaceuticals as potential myocardial imaging agents.

Monocationic 99mTc-nitrido complexes of a variety of diphosphine ligands have been prepared and the in vivo distribution of such cations has been examined in Sprague-Dawley rats. These complexes show initially high myocardial uptake with subsequent wash-out in this animal model. The lack of myocardial retention can be attributed to the facile in vivo reduction of these cations.

Animals↗

Quantification of tartrate resistant acid phosphatase activity using a computerized image analysis system.

Tartrate resistant acid phosphatase (TRAP) has been accepted as a marker for identification of osteoclasts. A method is reported here for quantitating TRAP using an image analysis system. The amount of the enzyme specific to osteoclasts can be used to differentiate osteoclasts from other cells capable of TRAP expression. TRAP expression characteristic of the osteoclast was compared with that of multi-nucleated giant cells (MNGC)s recruited to the site of subcutaneously implanted mineralized bone matrix. Two weeks post-implantation, the pellets were removed and processed for the demonstration of TRAP along with rat proximal tibiae. A large amount of TRAP was consistently expressed by the in situ osteoclasts. The MNGCs associated with the mineralized bone implants expressed little if any TRAP reaction product. Using this system, the amount of TRAP reaction product or any other enzyme reaction product expressed can be objectively and reproducibly quantitated.

Acid Phosphatase↗

Prostaglandin production by the largest preovulatory follicles in the domestic hen (Gallus domesticus).

An injection of 5 micrograms of gonadotropin-releasing hormone (GnRH) into hens 8 h prior to oviposition advanced the expected time of oviposition by approximately 1 h. The plasma concentration of progesterone increased approximately 1 h earlier in GnRH-injected hens in comparison to saline-injected hens. The plasma concentration of 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) increased significantly (p less than 0.05) at the time of oviposition in both the GnRH- and saline-injected hens. Significantly (p less than 0.05) greater concentrations of prostaglandin F2 alpha (PGF2 alpha) were assayed in media containing the largest preovulatory follicles collected at oviposition than in media containing the second and fifth largest preovulatory follicles collected at the same time. No prostaglandin was detected in media containing small, nonhierarchial follicles. The concentration of PGF2 alpha in media containing granulosa cells from the largest preovulatory follicle was significantly greater (p less than 0.05) than in media containing 4 times as many theca cells. Ovine luteinizing hormone (oLH) alone or in combination with arachidonic acid had no effect on PGF2 alpha output from granulosa cells collected 6 h before oviposition, whereas A23187 caused a small stimulation of PGF2 alpha output. However, treating cells first with oLH and then with A23187 stimulated a 15- to 20-fold increase in PGF2 alpha. None of these stimuli enhanced the already high output of PGF2 alpha when added to incubations of granulosa cells collected within 5 min after oviposition. These data suggest that the granulosa cells of the largest preovulatory follicle are the major intraovarian source of prostaglandin and that production of PGF2 alpha is associated with the preovulatory surges of gonadotropins and steroid hormones preceding oviposition.

Animals↗