Biomedical subjects

S M Roberts

Publications and source records attributed to S M Roberts.

At least 73 records · Page 4Linked to original sources

PubMed1993

Use of orbital implants after enucleation in dogs, horses, and cats: 161 cases (1980-1990).

Eye enucleations performed on 109 dogs, 29 horses, and 23 cats involved placement of 136 silicone orbital implants and 7 mesh implants. Mean follow-up times were 2.4 years (range, 3 weeks to 9 years) in dogs, 3.4 years (range, 10 days to 10.5 years) in horses, and 1.5 years (range, 3 weeks to 7.5 years) in cats. Implants failed in 1 of 96 dogs (1.04%), 3 of 29 horses (10.3%), and 3 of 18 cats (16.7%). Implant failure was attributable to various causes in all species; however, cats appeared to be more prone to late extrusion that were dogs and horses. Implantation of an orbital prosthesis was a safe and inexpensive method for improving cosmetic appearance after enucleation in dogs, horses, and cats.

Animals↗

PubMed1993

Phenylpropanolamine potentiation of acetaminophen-induced hepatotoxicity: evidence for a glutathione-dependent mechanism.

Pretreatment of male ICR mice with the adrenergic agonist phenylpropanolamine (200 mg/kg, ip) resulted in a marked potentiation of hepatotoxicity produced by acetaminophen (400 mg/kg, ip). Enhanced liver necrosis with phenylpropanolamine pretreatment was evident both by measurement of serum aminotransferase activity and by histopathologic examination. Several lines of experimental evidence suggest this interaction is a result of the hepatic glutathione depression produced by alpha-adrenergic compounds, which adds to the glutathione depression caused by toxic, or nearly toxic, doses of acetaminophen. First, the potentiation of acetaminophen hepatotoxicity was time-dependent, being observed only when phenylpropanolamine was administered as a 3-hr pretreatment and not when given 1 hr before, with, or 3 hr after acetaminophen. The 3-hr interval between phenylpropanolamine and acetaminophen doses corresponds to the characteristic lag period required for alpha-adrenergic agents (including phenylpropanolamine) to produce significant and maximal effects on hepatic glutathione content. Second, dose-response relationships for phenylpropanolamine and acetaminophen were such that increased toxicity was observed only when the interaction was sufficient to lower hepatic glutathione concentrations below a level regarded as critical in preventing acetaminophen-induced hepatotoxicity. Third, when animals were pretreated with two nonadrenergic depletors of hepatic glutathione, diethylmaleate (125 mg/kg, ip) or the glutathione synthesis inhibitor buthionine sulfoximine (222 mg/kg, ip), at doses producing glutathione depletion approximating that observed with the adrenergic agents, acetaminophen hepatotoxicity was potentiated to the same extent. From these observations it is postulated that a variety of adrenergic compounds known to deplete hepatic glutathione by a moderate 30-50% may potentiate the hepatotoxicity of acetaminophen and possibly other hepatotoxic compounds for which glutathione conjugation is an important detoxification pathway.

Acetaminophen↗

PubMed1993

Study of procainamide hapten-specific antibodies in rabbits and humans.

Procainamide (PA) is the drug most commonly associated with the induction of autoantibodies and drug-related lupus (DRL). While the majority of these patients express autoantibodies, antibodies to the parent drug and metabolites, PA-hydroxylamine (PAHA) or nitroso-PA (NOPA), have not been reported in humans. Hapten-carrier conjugates were prepared using human hemoglobin (HgB) or autologous rabbit erythrocytes with PAHA or NOPA. PA was conjugated to rabbit serum albumin (RSA) or egg albumin (OVA) via diazotization and condensation methods. Rabbits were immunized with hapten conjugates in Freund's adjuvant. These hapten-carrier compounds (5-10 micrograms/ml) were used as test antigens for antibodies in sera from the rabbits and 40 patients on chronic PA treatment. 10 SLE patients, 33 elderly and 20 young normal controls by ELISA. Type I and II collagens were also used as test antigens for human sera. Sera from rabbits immunized with the PA compounds had elevated IgG antibody values to PA, PAHA and NOPA, but no autoantibodies. Absorption of the rabbit sera with the PA compounds reduced the antibody levels; ssDNA and histones failed to inhibit the total binding values. Mean binding to PA-OVA was 0.95 +/- 0.41 for PA patients and 1.37 +/- 0.26 standard error of means (S.E.M.) in the SLE patients compared to 0.37 +/- 0.14 S.E.M. in the normal sera (P < or = 0.05); similar binding values to PAHA-HgB and NOPA-HgB were also observed. Sixty-eight percent of the PA patients had antibodies to type II collagen. Elevated binding values to PA compounds were inhibited by absorption of human sera with ssDNA or total histones; absorption with PA or PAHA had no significant effect. These findings suggest that sera from PA patients containing high titers of autoantibodies cross-react in vitro with unrelated antigens.

Adult↗

PubMed1993

Polychlorinated biphenyl exposure and human disease.

Polychlorinated biphenyls (PCBs) continue to be of great environmental and occupational health interest. This review summarizes the major clinical findings reported in individuals incurring the greatest PCB exposure--those persons working in the manufacture or repair of electrical capacitors or transformers. The potential target organs addressed in the studies reviewed include the liver, lungs, skin, cardiovascular system, nervous system, certain endocrine systems, the blood/immune system, and the gastrointestinal and urinary tracts. After careful analysis, the weight of evidence suggests the only adverse health effects attributable to high, occupational PCB exposures are dermal. This review confirms and extends the observations of others, ie, that the collective occupational experience with PCB fluids provides no evidence for adverse PCB effects on any other organ systems.

Cohort Studies↗

PubMed1993

Genetic, immunologic and biotransformation studies of patients on procainamide.

This report represents follow-up observations of a unique long-term study of patients on procainamide (PA) for various cardiac arrhythmias. Serologic and clinical evaluations associated with drug-related autoimmunity were assessed and patients were characterized for factors postulated to influence susceptibility to autoimmunity, including acetylator phenotype, oxidative metabolism of PA, HLA class profile, and production of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Fifty-two percent had IgM and 70% IgG antibodies to total histones; 67% had IgG antibodies to histone H2A/H2B. Patients were equally divided between fast and slow acetylators. N-oxidative metabolism of PA was indicated by the presence of urinary nitroprocainamide, which correlated with elevated titers of antihistone antibodies. There was a significant incidence of the DQw7 split of DQw3 in PA patients when compared to controls, and the frequency of antibodies to total histones and H2A/H2B was significantly increased in the DQw7 patients. C4A*QO and C4B*QO alleles were more frequent in the PA patients than in controls. IL-1 and TNF production was not different in patients compared to controls. These data suggest that certain genetic factors may serve as markers for PA-related autoimmunity.

Aged↗

PubMed1993

Detection of Toxoplasma gondii antigen-containing immune complexes in the serum of cats.

Enzyme-linked immunosorbent assays for the detection of Toxoplasma gondii antigen-containing IgM immune complexes (T gondii-specific IgM-IC) and IgG immune complexes (T gondii-specific IgG-IC) in the serum of cats were developed. Serum from clinically ill, naturally infected cats; healthy, naturally infected cats; and healthy cats experimentally inoculated with T gondii was assayed. All combinations of T gondii-specific IgM, IgG, antigens, IgM-IC, and IgG-IC were detected in naturally infected and experimentally infected cats. Clinically ill cats and cats with ocular signs of toxoplasmosis were more likely than healthy cats to have T gondii-specific IC in serum. It was concluded that T gondii-specific IC form in the serum of cats, may play a role in clinical disease development, and affect the results of T gondii-specific IgM, IgG, and antigen serologic assays.

Animals↗

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↗