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Biomedical subjects

J A Cameron

Publications and source records attributed to J A Cameron.

At least 37 records · Page 2Linked to original sources

Increase in brain nitric oxide synthase activity in daunorubicin-treated rats.

Anthracyclines such as daunorubicin are very effective anticancer agents. These drugs are known to cause side effects including cardiotoxicity. Anthracyclines are neurotoxic to laboratory animals. Nitric oxide is a novel and very important chemical messenger in the brain. However, at higher levels, nitric oxide causes well defined neurotoxicity. Therefore, we determined nitric oxide synthase activity in rat brain after daunorubicin treatment in an effort to explain the neurotoxicity produced by anthracyclines. Male Sprague-Dawley rats were treated with different subcutaneous doses of daunorubicin (0.1-4.0 mg/kg/week for five weeks) while control animals were injected with phosphate buffered saline. There was a significant increase (80%) of nitric oxide synthase activity in daunorubicin-treated animals as compared to controls. This activity was inhibited by N-monomethyl-L-arginine (NMMA), nitroarginine, N-6-aminohexyl-5-chloro-1-napthalene sulfonamide (W-7), a calmodulin antagonist, suggesting that the nitric oxide synthase activity is calmodulin dependent. Further, our in vitro studies demonstrated that daunorubicin interacted with calmodulin as measured by N-phenyl-1-napthylamine (NPN) fluorescence. These results indicate that daunorubicin increases nitric oxide synthase activity in rat brain which may increase the levels of nitric oxide. The increased levels of nitric oxide may cause neurotoxicity. Our results further indicate that daunorubicin interacts with calmodulin and enhances nitric oxide synthase activity which is dependent on calmodulin.

Animals↗

Fusarium polycaprolactone depolymerase is cutinase.

Polycaprolactone (PCL), a synthetic polyester, is degraded by a variety of microorganisms, including some phytopathogens. Many phytopathogens secrete cutinase, a serine hydrolase that degrades cutin, the structural polymer of the plant cuticle. We compared wild-type strains and a cutinase-negative gene replacement mutant strain of Fusarium solani f. sp. pisi (D. J. Stahl and W. Schäfer, Plant Cell 4:621-629, 1992) and a wild-type strain of Fusarium moniliforme to show that Fusarium cutinase is a PCL depolymerase. The wild-type strains, but not the mutant strain, (i) degraded PCL and used it as a source of carbon and energy, (ii) showed induction of secreted PCL depolymerase and an esterase activity of cutinase when grown in the presence of cutin, and (iii) showed induction of PCL depolymerase and an esterase activity of cutinase when grown in the presence of a hydrolysate of PCL, which contains PCL oligomers that are structurally similar to the natural inducers of cutinase. These results together with other details of regulation and conditions for optimal enzyme activity indicate that the Fusarium PCL depolymerase, required for degradation and utilization of PCL, is cutinase.

Biodegradation, Environmental↗

Pyogenic granulomas of the cornea.

BACKGROUND: Pyogenic granulomas are vascular inflammatory lesions that represent an aberrant wound healing response. They typically arise from mucous membranes or skin. Pyogenic granulomas primarily involving the cornea have been rarely reported. METHODS: Between January 1983 and July 1994, 14 patients with histologically proven pyogenic granulomas of the cornea were treated. RESULTS: The precipitating event was a persistent epithelial defect in nine patients. Ocular surface disease was present in all patients. Predisposing conditions included indolent corneal ulceration, cry eye syndrome, trachoma, trichiasis, alkali burn, multiple topical drug use, previous orbital irradiation, and ocular cicatricial pemphigoid. CONCLUSIONS: Ophthalmologists should be aware that pyogenic granulomas may involve the cornea and include this entry in the differential diagnosis of tumors involving the limbus or cornea. The typical clinical appearance, rapid growth, minimal staining with rose bengal dye, response to topical steroids, and associated ocular surface disease help to distinguish this lesion from a neoplastic epithelial tumor of the conjunctiva or cornea.

Adolescent↗

Shield ulcers and plaques of the cornea in vernal keratoconjunctivitis.

BACKGROUND: Shield-shaped corneal ulcers and plaques are serious sight-threatening corneal manifestations of vernal keratoconjunctivitis. There are few reports describing the management of these patients and their outcomes. METHODS: The clinical presentation, treatment, and outcome of 66 shield ulcers and/or plaques in 55 eyes of 41 patients with vernal keratoconjunctivitis were studied in this retrospective study of patients treated at King Khaled Eye Specialist Hospital during an 11-year period. RESULTS: Patients with shield ulcers where the base of the ulcer was transparent usually had rapid re-epithelialization and an excellent visual outcome with medical treatment alone. Patients with shield ulcers and visible plaque formation had delayed re-epithelialization when receiving only medical treatment. Complications of delayed re-epithelialization consisted of bacterial keratitis in five eyes, amblyopia in one eye, and strabismus in one patient. CONCLUSIONS: Patients with shield ulcers and/or plaques that do not re-epithelialize once active vernal keratoconjunctivitis has been controlled should have surgical intervention. In this series, a simple scraping of the base and margins of the ulcer with removal of the inflammatory material (i.e., the plaque) resulted in rapid re-epithelialization in 20 of 23 ulcers and plaques. An algorithm for treating shield ulcers and/or plaques is presented based on the experience at this institution.

Administration, Topical↗

Factors affecting the clinical efficiency of ultrasonic endodontics: a scanning electron microscopy study.

The purpose of this pilot study was to investigate some of the clinical variables in ultrasonic endodontics. forty extracted human teeth with a single, straight root 21-25 mm in length were prepared using combinations of the following variables: hand or ultrasonic instrumentation; apical seat prepared to file sizes 35, 40, 45 or 50; 1 ml of water, 4% sodium hypochlorite or EDTAC as irrigant between each instrument size; three brands of ultrasound generator and inserts; a 'low', 'medium' or 'high' effective power output; a tuned or untuned circuit; post-instrumentation ultrasonic irrigation with either 4% sodium hypochlorite, EDTAC, or the two used in sequence. The specimens were viewed in a scanning electron microscope and scored for the presence or absence of a smear layer at levels < 1 mm, 5 mm and 10 mm from the apical seat. The most effective combination, as tested, was hand instrumentation to file size 40 with 1 ml EDTAC irrigation between each instrument size, supplemented by intermittent flush irrigation with EDTAC with ultrasound then 4% sodium hypochlorite with ultrasound. This technique left a minimum smear layer restricted to the apical seat. Other combinations of instrumentation and irrigation were not consistent in their effectiveness.

Dentin↗

The choice of irrigant during hand instrumentation and ultrasonic irrigation of the root canal: a scanning electron microscope study.

The purpose of this study was to investigate the use of 4 per cent sodium hypochlorite and 15 per cent EDTAC, either alone or in conjunction, as irrigants during hand instrumentation and ultrasonic irrigation of the root canal. Thirty-six extracted human teeth, each with a single, straight root 21-25 mm long were hand-instrumented through a clinical access cavity to file size 40. One millilitre of the test irrigant was used after each instrument size. Canal debridement was completed with an intermittent flush irrigation technique with one or both of the test irrigants activated by ultrasound at a medium effective power output. The specimens were sectioned longitudinally, viewed in a scanning electron microscope and scored for the presence or absence of debris and smear layer at levels less than 1 mm, 5 mm, and 10 mm from the apical seat. Under the conditions of this experiment the most effective regime was irrigation with 1 mL EDTAC after each instrument size, followed by two 30 second exposures to ultrasound+EDTAC then four 30 second exposures to ultrasound + 4 per cent sodium hypochlorite. The specimens in this group were free from retained pulp tissue and superficial smear layer, had the lowest debris scores at the < 1 mm and 5 mm levels, and the lowest total debris score. All of the techniques tested produced smear-free canals at the 10 mm level.

Dental Pulp↗

Effects of high cholesterol and n-3 polyunsaturated fish oil diets on tissue and serum lipid composition in male rats.

The correlation between dietary cholesterol, high plasma lipids and cardiovascular disease is well recognized in many species. The purpose of the present study was to examine the effects of high cholesterol and moderately high fat intake of n-3 polyunsaturated fish oil diets on serum lipids in male rats. Male rats were fed either 21% menhaden oil (Control) or 21% menhaden oil with high (2%) cholesterol (MOC) for eight weeks. Whole blood was collected, and analyzed spectrophotometrically for serum cholesterol, triglycerides and lipoproteins. The selected tissues were carefully removed, weighed and analyzed for lipid profiles. The aortas were removed and lipogenesis determined. The results showed that except for spleen the total percent lipid content of heart, lung, liver, adrenal, kidney and brain was not affected in the MOC group. The percent fat content of spleen but not the weight was elevated by 4 fold compared to control. The hematocrit values in the MOC group were unaltered. Serum cholesterol was elevated by 62%, whereas the serum triglycerides and HDL cholesterol were unaltered in MOC group when compared to the MO control. High cholesterol feeding did not affect aortic lipogenesis in the MOC group compared to the control. These results suggest that cholesterol feeding along with n-3 polyunsaturated fish oil diet did not attenuate the anti-atherosclerotic effects of fish oil with the exception of serum cholesterol.

Animals↗

Corneoscleral abscess resulting from a broken suture after cataract surgery.

An 82-year-old man had pain and decreased vision in his right eye 15 months after uncomplicated cataract surgery. Examination revealed a large corneoscleral abscess with a 2 mm x 1 mm area of fluorescein staining at the base of a broken protruding 10-0 nylon suture. Streptococcus pneumoniae was isolated from both the suture and base of the ulcer. Despite intensive topical, subconjunctival, and systemic antibiotics, a large corneal perforation developed, necessitating a 10 mm tectonic penetrating keratoplasty. Long-term follow-up of patients after cataract surgery is important and should include an inspection of the limbal wound and removal of loose or broken exposed sutures. Suture-related complications will be eliminated if clinical studies prove the safety and efficacy of sutureless cataract surgery.

Abscess↗

Synthetic copolymer kit for radionuclide blood-pool imaging.

UNLABELLED: A synthetic blood pool imaging agent labeled with 99mTc is reported. METHODS: The agent, methoxypolyethylene glycol-poly-L-lysyl-diethylenetriaminepentaacetate monoamide was synthesized from a covalent graft copolymer of methoxypolyethylene glycol succinate (molecular weight 5.1 kD) and poly-L-lysine (molecular weight average 35.6 kD) with subsequent modification of the product with diethylenetriamineacetyl residues. The polymer was formulated into a kit that contained Sn(II) and sodium acetate for radiolabeling with 99mTc. Biodistribution studies were performed in rats. Blood-pool imaging and blood clearance determination was carried out in rabbits and in a rhesus monkey. RESULTS: The 99mTc-labeled agent [specific activity greater than 3.7 GBq/mg; radiochemical purity more than 98% by thin-layer and high-performance liquid chromatography (HPLC)] demonstrated remarkable stability in solution (pH 5.5-6.5) with no radioactive products of degradation detectable by HPLC even at 24 hr postlabeling. The agent exhibited prolonged circulation in the blood with a half-life of 31.5 hr in rabbits. Biodistribution in rats showed a lack of substantial accumulation of the agent in the reticuloendothelial system. Sequential acquisitions were performed in a rhesus monkey. The 99mTc-labeled polymer kit was compared with the 99mTc-red blood cells (RBCs) labeled in vitro. Both methods produced similar heart-to-lung ratios. The ratios remained essentially unchanged for up to 15 hr postinjection. CONCLUSION: The 99mTc-labeled methoxypolyethylene glycol-poly-L-lysyl-diethylenetriamine pentaacetate monoamide is an attractive alternative to radiolabeled RBCs for blood pool imaging applications.

Animals↗

Test of a model for the effects of retinoic acid on urodele limb regeneration.

Previous studies have shown that in axolotls (Ambystoma mexicanum), retinoic acid (RA) treatment evokes pattern completion in limb regenerates derived from anterior and dorsal half zeugopodia (lower arms and legs), but causes regenerative failure in posterior and ventral half zeugopodia. Pattern completion in anterior and dorsal half limbs may be explained by postulating that intercalary regeneration occurs in the antero-posterior (AP) and dorsoventral (DV) axes between blastema cells that are posteriorized (anterior half limb) or ventralized (dorsal half limb) by RA, and circumferential anterodorsal cells that remain unaffected by RA and thus maintain their original positional identities. The contrasting regenerative failure of RA-treated posterior and ventral half zeugopodia may likewise be explained by postulating that all the blastema cells in the posterior half are posteriorized, and all the cells in the ventral half are ventralized by RA, thus eliminating differentials in transverse positional identity essential for blastema formation and outgrowth. To test these postulates we grafted blastemas derived from limbs halved in the AP and DV axes of control and RA-treated animals to untreated whole limb stumps and analyzed the patterns of supernumerary (SN) regeneration. The site or location of SN formation will demonstrate (1) whether RA has posteriorized and ventralized the positional identity of the blastema cells and (2) if blastema cells in the periphery of the anterodorsal quadrant of the limb are resistant to these RA-induced changes in positional identity.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambystoma↗

Corneal abnormalities in Ehlers-Danlos syndrome type VI.

Eleven patients with blue sclera, limbus-to-limbus corneal thinning, hypermobile joints, and consanguineous parents were examined between January 1983 and September 1991. The clinical diagnosis was consistent with the Ehlers-Danlos syndrome type VI phenotype in all patients. A "halo" sign at the limbus was present in all patients. Corneal rupture occurred in seven patients (nine eyes) either spontaneously or following minimal trauma. Acute hydrops occurred in three patients. Bilateral microcornea was present in one patient and two patients had a unilateral increased corneal diameter as a result of secondary glaucoma after trauma. Peripheral sclerocornea was present bilaterally in five patients. Curvature abnormalities included cornea plana, keratoconus, and keratoglobus.

Adolescent↗

Keratoglobus.

Twelve adult patients with keratoglobus are described. Associated ocular conditions included orbital pseudotumor, vernal keratoconjunctivitis in three patients, chronic marginal blepharitis with chronic eye rubbing, and glaucoma after penetrating keratoplasty surgery. Hydrops occurred in 19 of the 21 eyes with keratoglobus. Surgical procedures to treat keratoglobus included large-diameter lamellar and penetrating keratoplasty, and limbus-to-limbus epikeratoplasty.

Adolescent↗

Results of lamellar crescentic resection for pellucid marginal corneal degeneration.

Five eyes in four patients with pellucid marginal corneal degeneration were treated by lamellar crescentic resection of the thinned area inferiorly. Normal-thickness stroma was then reapposed to normal-thickness stroma with multiple interrupted 10-0 polypropylene sutures. If excessive central corneal steepening along a vertical meridian was present three months after surgery, selected sutures were cut and removed depending on the slit-lamp appearance, keratometry reading, and photokeratograph pattern. Improvement of visual acuity to 20/40 or better was obtained in four of the five eyes with a follow-up of 27 to 40 months (mean, 31.8 months). Early loosening of sutures resulted in a recurrence of corneal thinning and astigmatism in one eye. Pannus developed inferiorly in all five eyes.

Adolescent↗

Retinoic acid-induced change in anteroposterior positional identity in regenerating axolotl limbs is dose-dependent.

Retinoic acid (RA) induces pattern duplication in the proximodistal (PD) axis of axolotl limb regenerates. The effect is dose-dependent, with the maximum extent of duplication being evoked at a dose of 150 micrograms RA/g body weight. The same dose of RA induces maximum pattern completion in the anteroposterior (AP) axis of regenerating anterior half or double anterior half limbs. RA inhibits the regeneration of posterior half or double posterior half limbs (Kim, W.S., and Stocum, D.L. [1986] Dev Biol 114:170-179). The effects of lower doses of RA on the AP axis of limb regenerates have not been tested and thus it is not known whether the effects of RA on positional identity in this axis are dose-dependent or are all-or-none. To answer this question, we examined the effects of a range of doses of RA on AP positional identity in regenerating double anterior and double posterior axolotl forelimbs and hindlimbs constructed by exchanging the anterior and posterior halves of right and left zeugopodia as either autografts or homografts. Ten days after the exchange, the double half zeugopodia were amputated through their distal ends. At 4 days postamputation, the animals were injected intraperitoneally with 20, 50, 75, or 100 micrograms RA/g body weight and the constructs allowed to regenerate for at least 6 weeks. Control double anterior forelimbs and hindlimbs formed symmetrical regenerates with an average of two and 1.8 anterior digits, respectively. RA treatment induced the blastema of double anterior zeugopodia to regenerate missing posterior structures in mirror-image patterns and to duplicate zeugopodial and stylopodial elements in the PD axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambystoma↗

Deep corneal scarring in pellucid marginal corneal degeneration.

Crescent-shaped, deep corneal scars were observed in seven (39%) of 18 patients with pellucid marginal corneal degeneration. The scars most likely represent a degenerative change related to the precipitous alteration in curvature of the cornea in that area.

Adolescent↗