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Biomedical subjects

D W Roberts

Publications and source records attributed to D W Roberts.

At least 145 records · Page 8Linked to original sources
PubMed1987

Tumorigenic responses to lindane in mice: potentiation by a dominant mutation.

Obese mottled yellow Avy/a, lean pseudoagouti Avy/a and lean black a/a (YS X VY) F-1 hybrid female mice were fed diet containing 160 p.p.m. lindane (gamma-hexachlorocyclohexane) for 6, 12, 18 or 24 months. Clara cell hyperplasia was present in a majority of the mice after six months of lindane ingestion; however, more yellow mice (77%) than pseudoagouti (50%) or black (56%) mice had developed this lesion. Continued ingestion of lindane increased the incidence of Clara cell hyperplasia and resulted in similar prevalences in the three phenotypes. Lung tumors associated with lindane ingestion for 24 months were found only in yellow (19%) and pseudoagouti (14%) mice but not in the black mice. Prevalences of hepatocellular adenomas and carcinomas were very low (less than 10%) in untreated pseudoagouti and black mice. Lindane ingestion for 24 months resulted in an hepatocellular adenoma prevalence of 12% in pseudoagouti mice and 3% in black mice; comparable hepatocellular carcinoma prevalences were 5% and 1%. Among yellow mice fed lindane diet for 24 months, adenoma prevalence was 35% (9% among untreated controls) but carcinoma prevalence was only 17% (13% among controls). The tumorigenic responses evoked by lindane feeding in the lean pseudoagouti Avy/a mice but not in the black a/a mice indicate, for the first time, that the Avy gene itself, in the absence of obesity, sensitizes cells to transformation. The greater prevalence of hepatocellular adenomas in obese yellow Avy/a than in lean pseudoagouti Avy/a mice implicates obesity-associated factors in tumor promotion. Similarly, the increased prevalence of hepatocellular carcinomas in untreated obese yellow Avy/a mice, as compared to lean pseudoagouti mice, implicates obesity-associated factor as favoring histiotypic progression of liver tumors. Thus, the Avy gene not only sensitizes cells to respond to tumorigenic stimuli but also, by the induction of obesity, enhances promotion and progression of transformed cells.

Adenoma↗
PubMed1987

Structure-activity relationships for skin sensitisation potential of diacrylates and dimethacrylates.

Apparently conflicting guinea pig sensitisation data on diacrylates and dimethacrylates, published by 3 groups of authors, are analysed in terms of the RAI model. This model, correlating sensitisation score with a combination of induction dose, chemical reactivity and lipophilicity, enables the major discrepancies to be rationalised. The data provide a striking example of the overload effect, in that some of the diacrylates have failed to show sensitisation when tested at high induction doses, but are revealed as strong sensitisers when tested by other authors at lower induction doses.

Acrylates↗
PubMed1987

Iridium-192 brachytherapy in combination with interstitial microwave-induced hyperthermia for malignant glioma.

A phase I clinical trial assessing the feasibility and safety of hyperthermia in combination with 192Ir brachytherapy (60 Gy) for the treatment of malignant glioma now includes 14 patients. Hyperthermia (42-43 degrees C at tumor margin for 60 min) has been induced using stereotactically implanted afterloading catheters and a microwave (915 or 2,450 MHz) antenna array. Thermometry recorded along each catheter confirms the general ability of the technique to heat such volumes, but thermal heterogeneities are documented. Transient or permanent worsening of previous neurologic deficit, seen in 7 patients, has been the most common morbidity.

Adult↗
PubMed1987

Effect of commissurotomy on complex partial epilepsy in patients without a resectable seizure focus.

Twenty-five patients in a series of 51 undergoing partial or complete section of the corpus callosum for the treatment of intractable epilepsy experienced complex partial seizures among their seizure types preoperatively. Ten of these 25 patients have experienced no further complex partial seizures. Reduction in severity of seizures has been found in 11 of the 15 patients still experiencing this seizure type, and 3 have had greater than 80% frequency reduction. These findings are consistent with the electrophysiologic observations of Lieb on the relative unimportance of the hippocampal commissure in man and the behavioral observations of Quesney on unilateral versus bilateral temporal lobe seizure activity.

Corpus Callosum↗
PubMed1987

A sensitive immunochemical assay for acetaminophen-protein adducts.

The hepatotoxicity of acetaminophen may be mediated by the reactive metabolite N-acetyl-p-benzoquinone imine which binds covalently to protein primarily as 3-(cystein-S-yl)acetaminophen. We have developed an avidin biotin-amplified competitive enzyme-linked immunosorbent assay to detect protein-bound acetaminophen. This assay utilizes antisera from rabbits immunized with 3-(N-acetyl-L-cystein-S-yl)acetaminophen coupled via the carboxyl group to primary amino groups on the protein keyhole-limpet hemocyanin. The competitive enzyme-linked immunosorbent assay utilizes metallothionein derivatized with N-acetyl-p-benzoquinone imine (acetaminophen-bound metallothionein) and quantitation was obtained by competition of acetaminophen-derivatives for a limited amount of antibody in the presence of excess solid phase acetaminophen-bound metallothionein. Synthetic 3-(N-acetyl-L-cystein-S-yl)acetaminophen, acetaminophen bound to mouse 9,000 X g supernatant, 100,000 X g supernatant, microsomes, as well as acetaminophen-bound metallothionein were inhibitory. The 50% inhibition for 3-(N-acetyl-L-cystein-S-yl)acetaminophen was 110 fmol/well. In contrast, free acetaminophen was 6200 times less efficient as an inhibitor. The mean 50% inhibition for protein-bound acetaminophen was 2.89 pmol/well. The utility of the method to detect acetaminophen-protein adducts in biological samples was confirmed by detection of NADPH-dependent binding of acetaminophen to microsomal proteins.

Acetaminophen↗
PubMed1986

2,3,7,8-Tetrachlorodibenzo-p-dioxin levels in adipose tissue of exposed and control persons in Missouri. An interim report.

The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly known as dioxin, was measured in the adipose tissue of 39 persons with a history of residential, recreational, or occupational exposure in Missouri and in 57 persons in a control group. All participants had detectable levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in their adipose tissue, but the exposed group had significantly higher levels. Levels of six of the exposed persons were more than five times greater than the level of the highest control. Measuring 2,3,7,8-tetrachlorodibenzo-p-dioxin in adipose tissue provides a much improved index of exposure, an important advance for research studies evaluating the possible health effects of this compound.

Adipose Tissue↗
PubMed1986

Development of an avidin-biotin amplified enzyme-linked immunoassay for detection of DNA adducts of the human bladder carcinogen 4-aminobiphenyl.

4-Aminobiphenyl (ABP) is a known human urinary bladder carcinogen which is present in tobacco smoke and may be ubiquitous in the environment. As a biological monitor of carcinogen exposure, we have developed an immunological method for measuring the predominant carcinogen-DNA adduct of ABP, N-(deoxyguanosin-8-yl)-ABP (dG-C8-ABP). Rabbits were immunized with keyhole limpet hemocyanin (KLH) conjugate prepared by a periodate oxidation and coupling of N-(guanosin-8-yl)-ABP (rG-C8-ABP) to the protein. The resulting polyclonal antisera was systematically characterized using dual inhibitor methodology augmented by specialized computer and software support; and a competitive avidin-biotin enzyme-linked immunoassay (A-B ELISA) assay employing polyclonal rabbit anti-KLH-(rG-C8-ABP) was developed. Under the assay conditions described, the detection limit for dG-C8-ABP was 18 fmol/well. The relative lack of reactivity toward ABP, N-acetyl-4-aminobiphenyl, N-(deoxyadenosin-8-yl)-ABP, N-(deoxyguanosin-8-yl)-2-aminofluorene and deoxyguanosine as inhibitors indicated that primary specificity involves epitopes found on the purine and biphenyl rings. Results emphasize the need to define polyclonal anti-adduct sera operationally in the context of the antigen/assay system used to evaluate it. Assay sensitivity was achieved by decreasing the amount of antibody and solid-phase antigen in the competitive portion of the assay and the use of avidin-biotin as well as enzymatic amplification. This methodology is a useful alternative to other ultrasensitive techniques and should be directly applicable to the detection of ABP-DNA adducts in exposed human populations.

Aminobiphenyl Compounds↗
PubMed1986

QSAR for upper-respiratory tract irritation.

A recent paper by Muller and Greff (Fd. Chem. Toxicol., 22 (1984) 661) presents QSAR equations for upper respiratory tract irritation by compounds falling into various chemical families. In the present paper the relationships are analysed further. It is found that a general QSAR equation, covering a diverse range of structures, correlates the biological activity reported by Muller and Greff with a single physicochemical parameter, TB'. The parameter TB' is the boiling point at atmospheric pressure (TB), adjusted for compounds with Trouton constants different from 22 cal deg-1 mol-1: TB' = (Tr X TB/22) + 40(1 - Tr/22) where Tr is the Trouton constant. Some of the compounds studied were found to be more irritant than predicted by the general equation: their enhanced activity can be rationalised in terms of their chemical reactivity as electrophiles, their metabolism to electrophiles, or their hydrolysis to more irritant products.

Acetates↗
PubMed1986

Radiographic comparison of cementing techniques in total hip arthroplasty.

Using a single prosthetic design, the authors conducted a radiographic comparison of the results of changes in cementing techniques in 58 total hip arthroplasties with respect to the initial postoperative and equivalent follow-up radiographs. The study period, 1975-1982, spanned the advent of cement restrictors, canal preparation, and pressurization techniques. In matched patients, the use of modern cementing techniques and canal preparation led to a significant improvement in the initial postoperative radiographic appearance and subsequent loosening rate of the femoral component, suggesting that these techniques may change the expected rate of late femoral component loosening, based on previous studies done with prepressurization cementing techniques.

Aged↗
PubMed1986

Interstitial hyperthermia and iridium brachytherapy in treatment of malignant glioma. A phase I clinical trial.

An oncolytic effect of hyperthermia in the 42 degrees to 43 degrees C range has been previously demonstrated in cell culture and animal models. To apply this modality clinically, an interstitial microwave antenna array system has been developed for the delivery of controlled hyperthermia to an intracranial tumor volume, and a Phase I clinical trial involving six patients with malignant gliomas was undertaken. The protocol to study technical feasibility and patient tolerance combined interstitial iridium-192 irradiation and interstitial hyperthermia with 60-minute hyperthermia sessions immediately before and after brachytherapy. After-loading catheters suitable for both treatment modalities were implanted using a computerized tomography-assisted technique. Thermometry data confirmed the ability of a microwave antenna system to achieve reliable temperature distributions, and reasonable patient tolerance was documented.

Adult↗
PubMed1986

A frameless stereotaxic integration of computerized tomographic imaging and the operating microscope.

A computer-based system has been developed for the integration and display of computerized tomography (CT) image data in the operating microscope in the correct perspective without requiring a stereotaxic frame. Spatial registration of the CT image data is accomplished by determination of the position of the operating microscope as its focal point is brought to each of three CT-imaged fiducial markers on the scalp. Monitoring of subsequent microscope positions allows appropriate reformatting of CT data into a common coordinate system. The position of the freely moveable microscope is determined by a non-imaging ultrasonic range-finder consisting of three spark gaps attached to the microscope and three microphones on a rigid support in the operating room. Measurement of the acoustic impulse transit times from the spark gaps to the microphones enables calculation of those distances and unique determination of the microscope position. The CT data are reformatted into a plane and orientation corresponding to the microscope's focal plane or to a deeper parallel plane if required. This reformatted information is then projected into the optics of the operating microscope using a miniature cathode ray tube and a beam splitter. The operating surgeon sees the CT information (such as a tumor boundary) superimposed upon the operating field in proper position, orientation, and scale.

Evaluation Studies as Topic↗
PubMed1985

Interhemispheric commissurotomy for congenital hemiplegics with intractable epilepsy.

Five patients with congenital hemiplegia and intractable epilepsy had interhemispheric commissurotomy (the split-brain operation). After intervals of 2 to 12 years, the response has been excellent in four cases. One patient had moderate benefit. There were no late complications. Commissurotomy seems to be substantially better than hemispherectomy for this syndrome.

Adolescent↗
PubMed1984

Humoral immune dysfunction as a result of prenatal exposure to diphenylhydantoin: correlation with the occurrence of physical defects.

The effect of prenatal exposure to diphenylhydantoin (DPH) on postnatal immune function of offspring was studied using a longitudinal experimental design and in vivo immunoassays. Maternal Balb/c mice were dosed by gavage on gestation days 9 through 18 with 0, 20, 40, or 60 mg/kg DPH. Humoral immune function was assessed by measuring the serum antibody levels to type III pneumococcal polysaccharide 5 days after immunization by radioimmunoassay. Cell-mediated immune function was assessed by measuring the delayed-type hypersensitivity response to the contact allergen oxazolone using a micrometer method. A dose-related suppression of humoral immune function was observed in male and female offspring at 25 days but not at 15 weeks of age. Cell-mediated immunity was not affected by prenatal DPH exposure at 25 days or 15 weeks of age. Offspring developed purulent eye exudates at 12 days of age; the incidence and persistence was related to DPH dose. The immunosuppressive effect of DPH on humoral immune function was significantly greater in offspring born with open eye defect than in similarly treated but physically normal offspring. The results suggest that prenatal exposure to DPH may adversely affect the normal development and expression of humoral immune function, particularly in those offspring with other manifestations of DPH's developmental toxicology.

Abnormalities, Drug-Induced↗
PubMed1984

Effect of nutritional copper deficiency on adjuvant arthritis and immunocompetence in the rat.

Both severe and marginal copper deficiency were produced in male Sprague Dawley rats prior to induction of adjuvant arthritis. Degree of copper deficiency was confirmed by analysis of plasma, liver, and brain samples prior to adjuvant injection. Incidence of adjuvant arthritis was the same in both copper deficient and control animals although the severity was slightly but not statistically less in the former. However, recovery from foot edema was impaired in copper-deficient animals, while marginally copper-deficient animals recovered at the same rate as did controls. Plasma copper concentration increased in response to the injection of adjuvant and the increase was directly related to dietary copper content. Plasma zinc concentration was decreased in arthritic animals and the decrease was inversely correlated to paw edema. Liver copper, zinc, and iron concentrations in arthritic animals remained unchanged or increased slightly in comparison to the corresponding non-injected controls. Copper-deficient rats were immunosuppressed as demonstrated by impaired responsiveness to the T-cell dependent contact sensitizing agent oxazolone and diminished capacity to respond to the T-cell independent antigen Type III pneumococcal polysaccharide. Although a statistical difference in paw volumes was not found for group of animals fed diets differing in copper content, it is postulated that copper deficiency may alter the severity and kinetics of adjuvant arthritis by impairing aspects of the immune response and the tissue repair processes subsequent to injury.

Animals↗
PubMed1984

Differential effects of the mottled yellow and pseudoagouti phenotypes on immunocompetence in Avy/a mice.

Whereas genetic factors are known to influence both susceptibility to carcinogens and the capacity to respond to specific antigenic stimuli, little is known regarding the influence of phenotype per se. With this in mind, we utilized (YS x VY)F1 hybrid mice consisting of genetically identical (Avy/a) but phenotypically distinct (mottled yellow and pseudoagouti) mice as well as congeneic (a/a) black mice to evaluate immunocompetence as a function of genotype and phenotype. Mottled yellow Avy/a mice, which are fat and have increased susceptibility to neoplasia, presented an immunologic profile characterized by decreased antibody response to the T-cell-dependent immunogen tetanus toxoid, enhanced antibody response to the T-cell-independent immunogen type III pneumococcal polysaccharide, decreased (unadjusted) rates of carbon clearance, and increased levels of serum IgA. In contrast, pseudoagouti Avy/a mice were immunologically comparable to black a/a mice. The data demonstrate that differences in phenotypic expression between genetically identical mice may significantly alter immune function.

Alleles↗
PubMed1984

Preliminary report: intracranial cholinergic drug infusion in patients with Alzheimer's disease.

After toxicity studies in dogs, a preliminary feasibility trial of the continuous intracranial infusion of a muscarinic agonist was begun in four patients with biopsy-documented Alzheimer's disease. During the last 8 months, a totally implantable infusion system has been used to deliver bethanechol chloride into the cerebrospinal fluid of these patients at doses of 0.05 to 0.7 mg/day. Complications have been few and resolved spontaneously or were easily reversible. The subjective response to this treatment has been encouraging, with reports of improved cognitive and social function during drug infusion and a return to base line function with single-blind saline placebo infusions. Obviously, further evaluation will be necessary to demonstrate the efficacy of this treatment, and a double-blind placebo-controlled crossover trial is now being done. However, we think the preliminary results are encouraging and warrant the consideration of this approach as a potential treatment in patients with Alzheimer's disease.

Aged↗