Biomedical subjects

S M Roberts

Publications and source records attributed to S M Roberts.

At least 19 recordsLinked to original sources

PubMed1992

Clinical and histologic evaluation of the prolapsed third eyelid gland in dogs.

Eighteen prolapses of the gland of the third eyelid in 17 Beagles were randomly allocated to 3 groups, which included nontreated (group 1, n = 6), excised (group 2, n = 4), and surgically repositioned (group 3, n = 8) glands. A schirmer tear test (STT) was performed on affected and normal (control) eyes for 5 consecutive days on weeks 0 (baseline), 2, 4, 6, 8, 10, 12, 16, 18, 20, and 24. All prolapsed third eyelid glands were excised and examined histologically. Ten female and 7 male Beagles were used in the prospective study. Mean age at prolapse was 35.1 weeks (range, 6 to 89 weeks). Control STT data revealed a population mean of 22.2 +/- 2.1 mm/min. Complications developed in 4 of 6 eyes when the gland was allowed to remain in a prolapsed position. Complications for group-1 eyes were significantly (P < 0.005) greater than those for eyes in groups 2 and 3 (0 of 12). Comparison of affected and control eye baseline data revealed decreased STT values for eyes with prolapsed glands (P < 0.01). Mean differences between affected and control eyes were 2.2, 2.0, and 3.4 mm/min for groups 1, 2, and 3, respectively. A significant (P < 0.001) decrease in lacrimation (0.2 to 3.1 mm/min) in group-2 eyes was detected after removal of the gland. Tear production for affected eyes of nontreated dogs fluctuated above and below that of control eyes prior to excision of the prolapsed gland of the third eyelid; however, with time, affected and control eye STT values were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The effect of nedocromil sodium on the isolated rabbit vagus nerve.

Nedocromil sodium depolarized the isolated rabbit vagus nerve. The depolarization was blocked by DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid) and did not occur when the nerve was bathed in solutions low in chloride. After depolarization the nerve was refractory to nedocromil sodium for an hour. It is suggested that nedocromil sodium can affect a chloride channel.

Animals↗

PubMed1992

Enzyme-linked immunosorbent assays for the detection of Toxoplasma gondii-specific antibodies and antigens in the aqueous humor of cats.

Serum and aqueous humor samples, collected from 14 clinically normal cats and 96 cats with clinical evidence of intraocular inflammation, were assayed with ELISA for Toxoplasma gondii-specific immunoglobulin M (IgM), T gondii-specific IgG, T gondii-specific antigens, total IgG, and total IgM. Additionally, serum was assayed with ELISA for feline leukemia virus p27 antigen and antibodies against the feline immunodeficiency virus as well as with an immunofluorescent antibody assay for antibodies against feline coronaviruses. Calculation of the Goldmann-Witmer coefficient (C-value) for the T gondii-specific antibodies detected in aqueous humor established the likelihood of local antibody production. Serologic evidence of present or prior infection by an infectious agent was found in 81.9% of the clinically affected cats from which serologic results were available (77/94 cats). Seropositive results for toxoplasmosis were found in 74.0% of the clinically affected cats. Anterior segment inflammation was found in 93.1% (81/87 cats from which information was available) of the clinically affected cats, most of which were older males. Toxoplasma gondii-specific antibodies were not detected in the aqueous humor of 6 seropositive, clinically normal cats. The C-values for aqueous T gondii antibodies were greater than 1 in 44.8% of the cats and greater than 8 in 24.0% of the cats. Response to treatment with clindamycin HCl was positive in 15/20 (75%) of the T gondii-seropositive, clinically affected cats treated with this drug. In 13/15 (86.7%) T gondii-seropositive, clinically affected cats having a C-value greater than 1, response to treatment with clindamycin HCl was positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Crystal structure of a chimeric Fab' fragment of an antibody binding tumour cells.

The crystal structure of a chimeric Fab' fragment of a monoclonal antibody is presented. The Fab' comprises the murine light chain and heavy chain variable domains of the carcinoma-binding antibody B72.3 fused to the constant domain of human kappa, and the first constant domain and hinge domain of human gamma 4, respectively. A model for the Fab' has been determined by molecular replacement and refined to a resolution of 3.1 A with an R-factor of 17.6%. The additional residues that distinguish a Fab' from a Fab fragment are seen to be disordered in the crystals. The H3 hypervariable loop is short and adopts a sharp hairpin turn in a conformation that results from an interaction between the lysine side-chain of H93 and the main-chain carbonyl group of H96. The remaining hypervariable loops display conformations similar to those predicted from the canonical structures approach, although loop H2 is apparently displaced by a salt-bridge formed between H55 Asp and the neighbouring H73 Lys. These and other features of the structure likely to be important in grafting the hypervariable loops to an otherwise human framework are discussed.

Amino Acid Sequence↗

PubMed1992

Cocaethylene hepatotoxicity in mice.

Cocaethylene is a novel metabolite of cocaine formed in the presence of ethanol. When administered to ICR male mice in dosages ranging from 10 to 50 mg/kg, i.p., cocaethylene was found to produce dose-dependent hepatic necrosis in the midlobular zone (zone 2). Severity of the lesion was maximal 12-24 hr after administration. A transient but significant decrease in hepatic glutathione content was observed 1 hr after cocaethylene administration. Pretreatment with the cytochrome P450 inhibitors cimetidine (200 mg/kg, i.p., in divided doses) or SKF 525A (50 mg/kg, i.p.) diminished toxicity. Pretreatment of mice with the esterase inhibitor diazinon (10 mg/kg, i.p.) increased cocaethylene hepatotoxicity, as did pretreatment with the cytochrome P450 inducing agents phenobarbital (80 mg/kg/day, i.p., for 3 days) or beta-naphthoflavone (40 mg/kg/day, i.p., for 3 days). Phenobarbital pretreatment also caused a shift in the morphologic site of necrosis from midzonal to peripheral lobular (zone 1) regions. The type of hepatic lesion produced by cocaethylene, its morphologic distribution (including the shift with phenobarbital treatment), the potency of cocaethylene in producing this effect, and the apparent requirement of oxidative metabolism for hepatoxicity were all remarkably similar to observations with its parent compound, cocaine, in this and earlier studies. This suggests that these compounds produce liver toxicity through the same or similar mechanisms.

Alanine Transaminase↗

PubMed1992

An assay for cocaethylene and other cocaine metabolites in liver using high-performance liquid chromatography.

Cocaethylene (benzoylecgonine ethyl ester or ethyl cocaine) is a transesterification product of cocaine and ethanol that has been observed in the urine of individuals using these drugs in combination. There is evidence that cocaethylene is pharmacologically active, and its formation in vivo may contribute to the toxicity of cocaine. A new method is presented here which enables the quantification of cocaethylene and cocaine, as well as the cocaine metabolites benzoylecgonine and norcocaine in liver tissue. This method utilizes high-performance liquid chromatography with uv detection (235 nm), and the propyl ester of cocaine is used as an internal standard. Liver homogenates are first buffered with 0.1 N dibasic potassium phosphate (pH 9.1) and then extracted with methylene chloride:isopropanol (9:1). Extraction efficiencies were approximately 75-85% for the compounds of interest. The coefficient of variation for replicate determinations (N = 10) of cocaethylene concentration was 5.75%, with comparable values obtained for cocaine, norcocaine, and benzoylecgonine. The detection limit for cocaethylene, based on a peak height threefold greater than background noise, was approximately 1.7 ng of injected compound. Using this method, it was demonstrated that cocaethylene is present in mouse liver following cocaine and ethanol administration, with an apparent rapid rate of formation and elimination.

Animals↗

PubMed1992

Cocaine hepatotoxicity: influence of hepatic enzyme inducing and inhibiting agents on the site of necrosis.

Cocaine-induced hepatotoxicity has been reported in human beings and is well documented in mice. One interesting feature of this toxicity that appears to be common to both species is an apparent shift in the intraacinar site of necrosis under circumstances known to alter cocaine metabolism. However, the evidence in human subjects is limited, and studies elucidating the mechanism of this phenomenon cannot be performed in human beings. Although future studies in mice may define the basis of this mechanism, the current evidence is a somewhat fragmented composite of studies using different mouse strains and enzyme-inducing agents. Therefore a comprehensive pathologic investigation was initiated for the purpose of identifying and establishing an animal model suitable for studying this phenomenon. In naive ICR mice a single 60 mg/kg dose of cocaine was found to produce midzonal (zone 2) coagulative necrosis. In mice whose oxidative metabolism had been increased with beta-ionone or in which esterase metabolism had been inhibited by diazinon, the severity of the toxicity was increased but the intraacinar origin of the lesion did not change. However, when the oxidative microsomal metabolism of ICR mice was induced by phenobarbital or beta-naphthoflavone, the acinar zone affected was dramatically different. Phenobarbital induction produced zone 1 necrosis, whereas beta-napthoflavone induction caused necrosis in zone 3. The site of necrosis corresponded with the distribution of cocaine, and its metabolites were identified with colloidal gold-conjugated antibody probes. The results of this study suggest that the agents shifting the location of cocaine-induced hepatic necrosis alter the intraacinar site of protein binding of cocaine and its metabolites.

Alanine Transaminase↗

PubMed1992

Some recent developments in the use of enzyme catalysed reactions in organic synthesis.

The following processes are discussed in this article: enzyme-catalysed hydrolyses of carboxylic acid esters and amides, phosphate esters, nitriles and epoxides; esterification and inter-esterification reactions catalysed by enzymes; reduction of ketones to secondary alcohols using whole-cell systems or isolated dehydrogenases; oxidation of alicyclic and aromatic substrates using mono-oxygenases and dioxygenases in bacteria and fungi including enzyme-catalysed Baeyer-Villiger oxidations; aldol reactions, formation of optically active cyanohydrins and enzyme-catalysed acyloin type reactions. The use of these biocatalytic methods for the stereo-controlled preparation of important target structures is reviewed and some of the future directions for the biotransformation area are discussed.

Biotransformation↗

PubMed1992

Equine vision and optics.

Vision is a marvelous sense, critical to the well-being and functional use of horses. Anatomic, optical, and visual acuity generalities are presented. The constituents of unsoundness due to equine ocular disease are discussed, and recommendations are made.

Animals↗

PubMed1992

Congenital ocular anomalies.

This discussion provides an idea of the diversity and relative prevalence of certain congenital ocular conditions of horses. Many are not difficult to diagnose, yet curative treatment may be impossible. When dealing with owners of horses affected with unusual anomalies, responsible client service requires veterinarians to provide accurate information and to know where answers to unusual questions can be found. Again, most veterinarians never encounter all of the diverse congenital defects. As a result, the horse owner frequently receives misinformation. Hopefully, this brief coverage of congenital ocular anomalies will provide useful information and assist in appropriate communication to concerned parties.

Animals↗

PubMed1992

Ocular cosmetic and prosthetic devices.

Specific details on surgical procedures, although not covered here, are available in other references. Factors enhancing the overall cosmetic appearance obtained with procedures are emphasized, providing information that should allow veterinarians to offer clients a good cosmetic appearance and effective treatment for disfiguring ocular problems in their horses. Questions regarding procedures should be addressed to your referral ophthalmologist or, in the case of a corneoscleral prosthesis, the ocularist assisting.

Animals↗

PubMed1991

Crystallization and preliminary X-ray diffraction study of a chimaeric Fab' fragment of antibody binding tumour cells.

Crystals have been obtained of a chimaeric Fab' fragment that binds to a tumour-associated mucin-like glycoprotein TAG72. The Fab' fragment comprises the variable heavy and light-chain domains of a murine monoclonal antibody, B72.3, coupled to human gamma 4 and kappa constant regions. The crystals are orthorhombic and belong to the space group P2(1)2(1)2(1), with unit cell dimensions a = 67.9 A, b = 94.2 A and c = 208.8 A. Diffraction to 2.6 A resolution was observed using synchrotron radiation. Despite the acute radiation sensitivity of the crystals a full native data set has been collected using the Weissenberg camera at the Photon Factory synchrotron. These data will be used for molecular replacement calculations in an attempt to elucidate the structure of this chimaeric Fab' fragment.

Animals↗

PubMed1991

Examination of the role of catecholamines in hepatic glutathione suppression by cold-restraint in mice.

Cold-restraint stress was found to produce a depression in hepatic glutathione content and to elevate circulating catecholamine levels in four mouse strains--ICR, NIH, B6C3F1, and ND/4. Serum norepinephrine concentrations were significantly elevated after cold-restraint (2--3 h) in all strains, and serum epinephrine levels were increased in the B6C3F1 and ND/4 strains. In time-course studies conducted using ND/4 mice, the decline in hepatic glutathione concentrations was found to slightly precede increases in serum epinephrine and norepinephrine concentrations. Also, pretreatment with phentolamine, an alpha-adrenoreceptor antagonist compound shown in previous studies to block epinephrine-induced hepatic glutathione suppression, had no effect on glutathione losses from cold-restraint. These observations are inconsistent with catecholamines as sole mediators of cold-restraint induced hepatic glutathione depression. Two other endogenous substances elevated during stress, corticosteroids and glucagon, were found to diminish glutathione concentrations in the liver in ND/4 mice when administered exogenously. The effects of catecholamines (epinephrine), corticosteroids (hydrocortisone) and glucagon were not additive, i.e. the depression in glutathione when these agents were administered in combination was generally no greater than that induced when the most effective agent was administered alone. It is postulated that during cold-restraint stress multiple endogenous agents are released which are independently capable of causing a depression in hepatic glutathione content.

Animals↗

PubMed1991

Epidemiologic study of ocular/adnexal squamous cell carcinoma in horses.

Proportional hospital accession ratios for equine ocular/adnexal squamous cell carcinoma (SCC) were determined for 14 colleges of veterinary medicine participating in the Veterinary Medical Data Program between January 1978 and December 1986. Comparison of the ratios with their respective geographical, physical data has shown an increased prevalence of SCC with an increase in longitude, altitude, or mean annual solar radiation. In contrast, prevalence of SCC increased with a decrease in latitude. Between January 1978 and December 1988, 147 horses with ocular/adnexal SCC were admitted to the Colorado State University Veterinary Teaching Hospital. Diagnosis was confirmed by histologic examination of appropriate tissue specimens. Medical records provided information regarding month and year of admission and diagnosis, age at diagnosis, breed, gender, and hair color. Comparison with a randomly selected hospital control population revealed an increased prevalence of ocular/adnexal SCC with an increase in age (P less than 0.001). Compared with Quarter Horses, draft breeds (Belgian, Clydesdale, and Shire) and Appaloosas had a significantly (P less than 0.001) greater prevalence of ocular/adnexal SCC. Sexually intact males and females were significantly (P less than 0.001) less likely (5 and 2 times, respectively) to have ocular/adnexal SCC when compared with castrated males. The prevalence of ocular/adnexal SCC was significantly greater for all hair colors when compared with bay, brown, or black (P less than 0.01).

Age Factors↗

PubMed1991

Prognostic factors and survival of horses with ocular/adnexal squamous cell carcinoma: 147 cases (1978-1988).

Between January 1978 and December 1988, 147 horses with ocular/adnexal squamous cell carcinoma (SCC) were admitted to the Colorado State University Veterinary Teaching Hospital (CSU-VTH). Diagnosis was confirmed by histologic examination of appropriate tissue specimens. Medical records and communication with owners, referring veterinarians, or both provided information regarding initial examination, treatment at the CSU-VTH, and final outcome. At initial examination, 123 (83.7%) horses had unilateral involvement and 24 (16.3%) horses had bilateral involvement. The nictitating membrane, nasal canthus, or both (28.1%); limbus (27.5%); and eyelid (22.8%) were most commonly affected. In addition to the ocular/adnexal location, SCC was found elsewhere in 14 (9.5%) horses at initial examination. Adequate follow-up (greater than or equal to 4 months) for examination of tumor recurrence and survival analysis was obtained for 125 (85.0%) cases. After treatment at the CSU-VTH, tumor recurred in 30.4% of the cases. Tumor location, multiple vs single tumors at initial diagnosis, and CSU-VTH treatment modality influenced the recurrence of tumors. Survival analysis revealed a good prognosis for horses with ocular/adnexal SCC. Although undefined, a conservative estimate of the median survival time was 47 months. Six factors (treatment prior to referral, tumor location, tumor size, single or multiple tumors, treatment modality at the CSU-VTH, and recurrence or nonrecurrence) were analyzed to determine their relation with survival. Treatment prior to referral, multiple vs single tumors at initial examination, and treatment modality used at the CSU-VTH did not influence survival. Tumor location influenced survival; SCC involving the eyelid or orbit was associated with the poorest prognosis. Tumor stage (maximal dimension) was inversely related with survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Potentiation of carbon tetrachloride hepatotoxicity by phenylpropanolamine.

Hepatic necrosis produced by carbon tetrachloride (0.02, 0.06, or 0.20 ml/kg, ip) in mice was found to be potentiated by simultaneous cotreatment with phenylpropanolamine (200 mg/kg, ip), a drug with catecholamine-like pharmacologic effects. The ability to potentiate carbon tetrachloride-induced hepatic necrosis was shared by a compound with agonist effects relatively selective for alpha 2-adrenoreceptors (clonidine, 5 mg/kg, ip), but not by specific alpha 1-adrenoreceptor agonists (phenylephrine, up to 100 mg/kg, ip and methoxamine, up to 50 mg/kg, ip) or by the beta-adrenoreceptor agonist isoproterenol (up to 100 mg/kg, ip). Yohimbine (5 mg/kg, ip), a selective alpha 2-adrenoreceptor antagonist, completely blocked the potentiating effect of phenylpropanolamine on carbon tetrachloride hepatotoxicity, providing further evidence that the increased hepatotoxic response with phenylpropanolamine cotreatment was mediated through alpha 2-adrenoreceptor stimulation. Four potential mechanisms for phenylpropanolamine potentiation of liver injury from carbon tetrachloride were examined: (1) increased concentrations of carbon tetrachloride in the liver from greater absorption or altered distribution; (2) diminished food consumption leading to a starvation-like increase in responsiveness to carbon tetrachloride; (3) impaired detoxification through a depletion of hepatic glutathione content; and (4) enhanced toxicity produced by elevated core body temperature. None of these potential mechanisms was supported by the experimental results. It is concluded that phenylpropanolamine and related compounds potentiate carbon tetrachloride hepatotoxicity through a mechanism involving alpha 2-adrenoreceptor stimulation that has yet to be identified.

Animals↗

PubMed1991

Hepatic glutathione suppression by the alpha-adrenoreceptor stimulating agents phenylephrine and clonidine.

The effects of alpha-adrenoreceptor stimulation on hepatic glutathione content were examined in ICR male mice using a selective alpha 1-adrenoreceptor stimulating agent, phenylephrine, and a selective alpha 2-adrenoreceptor stimulating drug, clonidine. Phenylephrine produced a dose-dependent depression in hepatic glutathione levels when administered by the intraperitoneal (i.p.) route, with a maximum extent of depression of approximately 30% occurring in both male and female mice. Phenylephrine was ineffective by the intracerebroventricular route, indicating a peripheral site of action which would be consistent with the mechanism(s) suggested by earlier in vitro studies using rat liver. Clonidine, an alpha 2-adrenoreceptor stimulating agent, also depressed hepatic glutathione concentrations in a dose-dependent manner. The maximum extent of depression (approx. 45%) from clonidine administered by the i.p. route was somewhat greater than that from phenylephrine, and the apparent potency was about 10-fold greater. Unlike phenylephrine, clonidine was effective when administered by the intracerebroventricular route. Pretreatment of mice with phenylephrine (100 mg/kg, i.p.) resulted in a potentiation of hepatic necrosis from a mildly hepatotoxic dose of acetaminophen (400 mg/kg, i.p.). The results of these experiments suggest that the changes in glutathione homeostasis produced by alpha-adrenoreceptor stimulation may be sufficient to impair detoxification mechanisms.

Acetaminophen↗

PubMed1991

Fluorocarbocyclic nucleosides: synthesis and antiviral activity of 2'- and 6'-fluorocarbocyclic 2'-deoxy guanosines.

A series of four isomeric 2'- and 6'-fluorocarbocyclic guanosine analogues have been prepared and evaluated as potential anti-herpes agents. The racemic 2' beta-fluoro isomer 2-amino-1,9-dihydro- 9-[(1 alpha, 2 alpha, 3 beta, 4 alpha)-2-fluoro-3-hydroxy-4- (hydroxymethyl)cyclopentyl]-6H-purin-6-one (11a, C-AFG) and its 2' alpha-fluoro epimer 11b plus the chiral 6' beta-fluoro isomer 2-amino-1,9-dihydro-9-[[1S-(1 alpha, 2 alpha, 3 alpha, 4 beta)]- 2-fluoro-4-hydroxy-3-(hydroxymethyl)cyclopentyl]-6H-purine-6-one (11c) and its 6' alpha-fluoro epimer 11d were prepared from their respective fluoro amino diol hydrochlorides (6a,d). For comparison, the furanosyl compound 9-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)guanine (17, AFG) was prepared by coupling 2-amino-6-chloropurine with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-alpha- D-arabinofuranosyl bromide followed by base hydrolysis. The 6' alpha-fluoro derivative 11d exhibited comparable activity to that of acyclovir (ACV) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro but was greater than 30-fold more active than ACV against HSV-1 and HSV-2 in vivo in the mouse systemic model. The 2' beta-fluoro derivative (11a, C-AFG) was extremely potent in vitro against HSV-1 and HSV-2 (ID50 0.006 and 0.05 micrograms/mL) and in vivo it was greater than 2 orders of magnitude more potent than ACV against HSV-1 and 70-fold more potent against HSV-2. The 2' alpha-fluoro 11b and 6' beta-fluoro 11c isomers were much less active.

Antiviral Agents↗