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Biomedical subjects

D W Roberts

Publications and source records attributed to D W Roberts.

At least 127 records · Page 7Linked to original sources
PubMed1989

Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Review of employment and chemical production records at a Missouri chemical plant and of questionnaires with self-reported occupational exposure to 2,3,7,8-tetrachloro-dibenzo-p-dioxin (2,3,7,8-TCDD) for 16 Missouri workers has explained the wide diversity of 2,3,7,8-TCDD levels previously reported in the workers' adipose tissue (3.5-750 ppt on whole-weight basis). We show that the highest exposures reported to date in the United States occurred in a group of nine production workers who made products contaminated with 2,3,7,8-TCDD. The nine workers had adipose tissue levels with a mean of 246 ppt and a range of 42 to 750 ppt. Seven persons who worked at the same chemical company, but not in the 2,3,7,8-TCDD-contaminated process, had a mean of 8.7 ppt and a range of 3.5 to 25.8 ppt. We also report serum levels of 2,3,7,8-TCDD in these individuals. The adipose tissue from a subset of four production workers with elevated levels of 2,3,7,8-TCDD and seven Missouri residents with normal 2,3,7,8-TCDD levels was also analyzed for other isomers of the PCDDs and PCDFs. The mean adipose tissue level of 2,3,7,8-TCDD in the subset of production workers was 45 times higher than the mean level in the unexposed Missouri residents, but similar levels of the other PCDDs and PCDFs were found in both groups.

Adipose Tissue↗
PubMed1989

The stereotactic operating microscope: accuracy refinement and clinical experience.

Accuracy of a stereotactic operating microscope, by which imaging data may be superimposed on the operative field without a stereotactic frame, has been most limited by the resolution of imaging information. Using newer algorithms and pilot pole calibration of the digitizer, an error in registration of 2 mm and in contour display of 3 mm has been demonstrated. Greatest utility of the system clinically has been in providing navigational guidance to small lesions undergoing resection.

Brain Neoplasms↗
PubMed1989

Reduced formation of lesions in the DNA of a multidrug-resistant L1210 subline selected for teniposide resistance.

Earlier studies have suggested that higher cellular levels of teniposide (VM-26) are required for the inhibition of growth in L1210/VM-26 sublines than in parental L1210 cells. On the basis of this observation, we hypothesized that resistance to VM-26, which is partly attributed to multidrug resistance, also resulted in reduced formation of DNA lesions by the drug. In confirmation of this hypothesis, equitoxic concentrations of VM-26 produced fewer breaks in the DNA of LIa5 microM cells, the prototype L1210/VM-26 subline, than in that of L1210 cells. Previously, potassium cyanide (KCN) and verapamil were shown to increase the levels of VM-26 in LIa5 microM but not L1210 cells. These agents also selectively increased the formation of breaks in the DNA of LIa5 microM but not L1210 cells. The DNA unknotting assay with phage P4 DNA indicated equivalent DNA type II topoisomerase activity in nuclear extracts of LIa5 microM and L1210 cells. The factor that reduced the formation of breaks in cellular LIa5 microM DNA by VM-26 provided less protection against equitoxic levels of doxorubicin, to which LIa5 microM cells are cross-resistant.

Animals↗
PubMed1989

The use of graphitized carbon black in solid phase extraction: comparison with C18 bonded silica gel.

Preliminary studies on the properties of a commercially available graphitized carbon black for the solid-phase (or liquid-solid) extraction of drugs and metabolites from biological fluids such as urine and plasma are described. A variety of basic drugs, all of the beta-blocker type, were efficiently extracted from dog plasma and subsequently recovered from the adsorbent using chloroform-methanol mixtures. Similarly metabolites of the non-steroidal anti-flammatory drug ibuprofen also were efficiently extracted from human urine. The proportions of methanol and chloroform used for elution were found to be critical to ensure complete recoveries of adsorbed material. Proton NMR studies of the column eluates from both carbon and C18 bonded silica gel extraction cartridges revealed differences in capacity and selectivity following the application of ibuprofen containing metabolite samples.

Adrenergic beta-Antagonists↗
PubMed1989

Alkyl and aryl carcinogen adducts detected in human peripheral lung.

Human peripheral lung tissue samples were obtained at autopsy from 17 individuals of known occupational and smoking histories. A spectrum of different carcinogen-DNA adducts was detected using a variety of sensitive techniques. High-pressure liquid chromatography-linked synchronous fluorescent spectrophotometry and an ultrasensitive enzyme radioimmunoassay detected adducts derived from benzo[a]pyrene diol epoxide and other apparent polycyclic aromatic hydrocarbons. An amplified enzyme-linked immunosorbent assay demonstrated the presence of 4-aminobiphenyl-DNA adducts in many of these samples. A number of these specimens also contained O6-alkyldeoxyguanosine as measured by 32P-postlabeling techniques. Thus this pilot study indicates not only that human lung contains a spectrum of carcinogen-DNA adducts, but also that a full scale molecular dosimetry study of human exposure to both aryl and alkyl chemical carcinogens is warranted.

Adolescent↗
PubMed1989

A frameless stereotaxic operating microscope for neurosurgery.

A new system, which we call the frameless stereotaxic operating microscope, is discussed. Its purpose is to display CT or other image data in the operating microscope in the correct scale, orientation, and position without the use of a stereotaxic frame. A nonimaging ultrasonic rangefinder allows the position of the operating microscope and the position of the patient to be determined. Discrete fiducial points on the patient's external anatomy are located in both image space and operating room space, linking the image data and the operating room. Physician-selected image information, e.g., tumor contours or guidance to predetermined targets, is projected through the optics of the operating microscope using a miniature cathode ray tube and a beam splitter. Projected images superpose the surgical field, reconstructed from image data to match the focal plane of the operating microscope. The algorithms on which the system is based are described, and the sources and effects of errors are discussed. The system's performance is simulated, providing an estimate of accuracy. Two phantoms are used to measure accuracy experimentally. Clinical results and observations are given.

Algorithms↗
PubMed1989

Epitope characterization of acetaminophen bound to protein and nonprotein sulfhydryl groups by an enzyme-linked immunosorbent assay.

The oxidation of acetaminophen to N-acetyl-p-benzoquinone imine and its subsequent binding to protein sulfhydryl groups may be important in the observed toxicity of acetaminophen. An avidin biotin-amplified competitive enzyme-linked immunosorbent assay has been developed which utilizes solid phase acetaminophen bound to metallothionein and antiserum obtained from rabbits that were immunized with 3-(N-acetyl-L-cystein-S-yl)acetaminophen covalently bound to keyhole-limpet hemocyanin. Over 25 synthetic analogs of acetaminophen conjugates and structurally similar compounds have been ranked relative to their ability to compete in the avidin biotin-amplified enzyme-linked immunosorbent assay. The most effective inhibitor was 3-(N-acetyl-L-cystein-S-yl)acetaminophen, which had an observed 50% inhibitory concentration of 120 fmol/well. Approximately 6200-fold higher concentrations of unbound acetaminophen and 5.2 x 10(6)-fold higher concentrations of N-acetyl-L-cysteine were required for comparable inhibition. It was demonstrated with acetaminophen analogs that the hydroxyl group and the N-acetyl moiety of acetaminophen were important in epitope recognition. A 5000-fold decrease in detection was observed when the analog did not contain the hydroxyl group or when the N-acetyl moiety was replaced with a hydroxyl substituent. Recognition by antibody was also dependent upon the stereochemistry of the analogs. The 50% inhibitory concentration for 3-(L-cystein-S-yl)acetaminophen was 2300 fmol/well, whereas a 25-fold higher concentration of 3-(D-cystein-S-yl)acetaminophen was required for 50% inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1989

Immunochemical quantitation of 3-(cystein-S-yl)acetaminophen adducts in serum and liver proteins of acetaminophen-treated mice.

Using a recently developed enzyme-linked immunosorbent assay specific for 3-(cystein-S-yl)acetaminophen adducts we have quantitated the formation of these specific adducts in liver and serum protein of B6C3F1 male mice dosed with acetaminophen. Administration of acetaminophen at doses of 50, 100, 200, 300, 400 and 500 mg/kg to mice resulted in evidence of hepatotoxicity (increase in serum levels of alanine aminotransferase and aspartate aminotransferase) at 4 hr in the 300, 400 and 500 mg/kg treatment groups only. The formation of 3-(cystein-S-yl)acetaminophen adducts in liver protein was not observed in the groups receiving 50, 100 and 200 mg/kg doses, but was observed in the groups receiving doses above 300 mg/kg of acetaminophen. Greater levels of adduct formation were observed at the higher doses. 3-(Cystein-S-yl)acetaminophen protein adducts were also observed in serum of mice receiving hepatotoxic doses of acetaminophen. After a 400 mg/kg dose of acetaminophen, 3-(cystein-S-yl)acetaminophen adducts in the liver protein reached peak levels 2 hr after dosing. By 12 hr the levels decreased to approximately 10% of the peak level. In contrast, 3-(cystein-S-yl)acetaminophen adducts in serum protein were delayed, reaching a sustained peak 6 to 12 hr after dosing. The dose-response correlation between the appearance of serum aminotransferases and 3-(cystein-S-yl)acetaminophen adducts in serum protein and the temporal correlation between the decrease in 3-(cystein-S-yl)acetaminophen adducts in liver protein and the appearance of adducts in serum protein are consistent with a hepatic origin of the adducts detected in serum protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1988

Immunochemical quantitation of DNA adducts derived from the human bladder carcinogen 4-aminobiphenyl.

To assess target-tissue exposure to the human urinary bladder carcinogen 4-aminobiphenyl (ABP), we have developed a sensitive immunochemical method for measuring the major arylamine-DNA adduct formed, N-(guan-8-yl)-ABP (Gua-C8-ABP). High-affinity polyclonal antisera from rabbits immunized with N-(guanosin-8-yl)-ABP coupled to keyhole limpet hemocyanin were characterized and shown to have high specificity for antigenic determinants on the purine and biphenyl rings of Gua-C8-ABP and minimal cross-reactivity with ABP, deoxyguanosine, or hydrolyzed DNA. Assay standards containing ABP-modified DNA were prepared by reacting [3H]N-hydroxy-ABP with calf thymus DNA. DNA samples were hydrolyzed with trifluoroacetic acid and dried under vacuum, and the residues were dissolved in dimethyl sulfoxide under argon. Using a streptavidin-biotin amplified enzyme-linked immunosorbent assay, DNA hydrolysates competed at 25 micrograms DNA/microtiter well for a limiting amount of anti-keyhole limpet hemocyanin-(Gua-C8-ABP) in the presence of excess solid-phase bovine serum albumin-(Gua-C8-ABP) coating antigen. The limit of sensitivity for this assay using 25 micrograms DNA was 2 adducts/10(8) nucleotides. Gua-C8-ABP adducts in liver and bladder epithelial DNAs were readily quantified after p.o. administration of 5 mg/kg ABP to dogs. This methodology is capable of detecting adducts at levels of biological significance and should be applicable to human target-tissue dosimetry.

Aminobiphenyl Compounds↗
PubMed1988

Behaviorally conditioned suppression of murine T-cell dependent but not T-cell independent antibody responses.

The aversive and immunosuppressive effects of cyclophosphamide (CY, 250 mg/kg IP), an unconditioned stimulus (UCS), were paired with the presentation of a novel saccharine flavored drinking solution (SAC), a conditioned stimulus (CS), in female Balb/c mice. The objective was to determine the temporal relationship between presentation of the CS (SAC) and immunization with sheep red blood cell (SRBCs), a T-cell dependent antigen, and type III pneumococcal polysaccharide (S3), a T-cell independent antigen, on subsequent antibody responses. Reexposure to the CS or UCS occurred on days -4, -2, 0, +2, or +4 relative to immunization. Primary antibody responses in each group were measured six days following immunization. A strong association between the CS and the UCS developed, producing flavor aversions as evidenced by decreased SAC consumption. CY administration by itself consistently suppressed both types of antibody responses. CS presentation (i.e., SAC) had no significant effect on anti-S3 antibody response. However, the anti-SRBC response was significantly depressed following CS exposure. Exposure to the CS only on days -4 or +2 relative to immunization resulted in statistically significant suppression of antibody response to SRBC's while exposure on days -2, 0, and +4 resulted in anti-SRBC antibody suppression that did not reach significance. These results support the hypothesis that conditioning of antibody responses is relatively specific for T-cell dependent antigens, and that the timing of CS presentation relative to immunization is important in conditioning a suppression of antibody responses.

Animals↗
PubMed1988

Methyl groups as antigenic determinants in skin sensitisation.

The methylating agents, methyl dodecane sulphonate, methyl hexadecane sulphonate and methyl hexadec-3-ene sulphonate are strong skin sensitisers, cross-reactive with one another, in guinea pig adjuvant tests. Differences in potency are observed among these 3 compounds, and the possible reasons for this are discussed. Isoeugenol fails to elicit a sensitisation response when challenged onto guinea pigs sensitised to methyl dodecane sulphonate, indicating that the mechanism of isoeugenol sensitisation is not based on methyl transfer. It is proposed that, in skin sensitisation involving small haptenic groups, antigenic specificity is directed not against the haptenic groups but against portions of the carrier protein whose configuration has been modified as a result of the carrier-hapten reaction. This concept is supported by published data on cross-reactivity patterns with enantiomeric pairs of alpha-methylene-gamma-butyrolactone derivatives.

Alkanesulfonates↗
PubMed1988

Magnetic resonance imaging in the diagnosis and treatment of Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum).

Lhermitte-Duclos disease is a rare disorder characterized by a slowly enlarging mass lesion in the cerebellum. The pathophysiology of the disease is poorly understood, but recent reports have suggested that a clinically significant mass may recur many years after total gross removal of the tumor. Computed tomography and angiography have been relatively insensitive in imaging the tumor either at presentation or during the postoperative period. The authors present three patients with histologically proven Lhermitte-Duclos disease who have undergone magnetic resonance imaging (MRI). In the first case, preoperative T1- and T2-weighted images clearly demonstrated the location and extent of the lesion, which was verified at operation. In the other two cases, only postoperative images were obtained. These demonstrated the extent of residual tumor and indicate a high probability of lesion expansion during periods of 4 and 10 years, respectively. We conclude that MRI is an important tool in both the diagnosis and the treatment of patients with Lhermitte-Duclos disease.

Adult↗
PubMed1988

Assessment of exposure and susceptibility to aromatic amine carcinogens.

As a consequence of human exposure to carcinogenic aromatic amines, biochemical approaches to risk assessment have emphasized metabolic determinants of individual susceptibility and quantification of arylamine-macromolecular adducts. A known genetic polymorphism in humans, hepatic arylamine acetyltransferase activity, has been associated with differences in individual susceptibility to urinary bladder (slow acetylators) and colorectal (rapid acetylators) cancers. Similarly, the high specificity of an inducible human cytochrome P450 towards the N-oxidation of 4-aminobiphenyl and other aromatic amines is consistent with metabolic differences that can be used to predict relative human risk. Exposure to aromatic amines has also been documented, primarily by quantification of adducts with protein or DNA. Using 32P-postlabelling methods and a competitive avidin/biotin-amplified enzyme-linked immunoassay, we have estimated 4-aminobiphenyl-DNA adduct levels in surgical samples of human peripheral lung and urinary bladder epithelium and report values ranging from 2 to 97 adducts per 10(8) nucleotides.

Acetylation↗
PubMed1988

The effects of modern cementing techniques on the longevity of total hip arthroplasty.

Modern prosthetic design and cementing techniques have dramatically improved femoral component fixation. Compared to studies reported in the 1970s, the incidence of radiographic loosening for periods up to 5 years postoperatively has been reduced by at least a factor of 10. These results are the benchmark by which alternative forms of femoral component fixation must be measured. With the likelihood of increased longevity of total hip arthroplasty resulting from improved fixation, the problems of wear debris from the bearing surfaces and loss of bone stock with time will become preeminent.

Bone Cements↗