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Biomedical subjects

B D Wilson

Publications and source records attributed to B D Wilson.

At least 55 records · Page 3Linked to original sources
PubMed1989

Amiodarone-induced pulmonary toxicity in the rat.

A rat model of amiodarone-induced pulmonary toxicity is described. The rats were fed, by gavage, 175 mg/kg/day of amiodarone hydrochloride suspended in methyl cellulose. Controls received methyl cellulose alone. Groups of rats were examined after 1, 3, 6, 9, and 12 weeks of feeding. We found that drug-fed rats had significantly more macrophages, neutrophils, and lymphocytes in the bronchoalveolar lavage (BAL). The early increase in cellularity was due to an increase in macrophages, and the macrophage count peaked after 6 weeks of drug treatment. The number of neutrophils in the experimental animals remained high throughout the course of the experiment. An increasing number of lymphocytes was seen in the BAL between 6 and 12 weeks of drug treatment. Protein in the lavage fluid was significantly elevated after 12 weeks of amiodarone exposure. Histologic sections were abnormal after 3 weeks of drug treatment, characterized by interstitial thickening with accumulation of mononuclear cells and alveoli packed with large foamy macrophages. There was only minimal evidence of fibrosis. This model appears to be very similar to human amiodarone-induced pulmonary toxicity and should be useful for the study of the pathogenesis of amiodarone-induced toxicity.

Administration, Oral↗
PubMed1989

Does amiodarone inhibit T3 binding to solubilized nuclear receptors in vitro?

One of the proposed mechanisms of action of amiodarone is by interfering with T3-receptor interactions. However, reports in the literature on this matter are contradictory and, in an attempt to resolve these contradictions, the effects of amiodarone on T3 binding to solubilized nuclear receptors from rat liver were investigated. A drug concentration-related competitive inhibition of T3 binding occurred in the presence of considerable amiodarone precipitation. Measurement of the proportion of soluble amiodarone over the range where significant inhibition of T3 binding was observed, revealed that the soluble amiodarone decreased over this range. Since the amiodarone preparation was free of any contaminant, these findings suggested that a product generated from amiodarone during incubation was responsible for the inhibition. HPLC analysis of the soluble amiodarone fraction indicated that, during incubation, two substances were generated from the parent compound. However, only the concentration of one of the substances continually increased whereas the other decreased with increasing concentrations of amiodarone added to the samples. These findings suggest that the inhibition of T3 binding to solubilized nuclear receptors in the presence of amiodarone results from the generation of a specific product from the amiodarone under certain conditions during incubation.

Amiodarone↗
PubMed1988

Neutrophil accumulation and cutaneous responses in experimental cutaneous candidiasis of genetically complement-deficient mice.

Mice deficient in the fifth component of complement were studied for their ability to respond to and clear experimental cutaneous Candida albicans infections. The complement-deficient animals took longer to clear the infections and developed a significantly greater delayed hypersensitivity response to Candida than did normal animals. However, although the serum of the complement-deficient animals was incapable of generating in vitro chemotactic activity for neutrophils after appropriate stimulation, the epidermal neutrophilic infiltrate in the Candida-infected skin of these animals was equivalent to that in the normal animals. The progression of the infection, including the early relocation of the invading Candida pseudohyphae to a more superficial site in the stratum corneum and the thickening of the epidermis itself, was also similar in the complement-deficient and normal animals. Therefore, although mice lacking the fifth complement component cannot generate complement-derived serum chemotactic factors and are somewhat less efficient in clearing experimental cutaneous candidiasis, the accumulation of neutrophils in the Candida-infected skin of these animals and their initial cutaneous responses to the infections are normal.

Abscess↗
PubMed1988

The gait of pacers. 1: kinematics of the racing stride.

Standardbred pacers have been studied under race conditions to describe the gait of the pacer, and to determine relationships between stage of the race, finish order and selected gait kinematics. Overlap increased with the stage of the race while pacing speed decreased marginally for low order pacers and increased for high order finishers. High order finishing pacers appear to have greater stance and stride lengths than do low order finishers. Pacers could be separated into low order and high order groups on the basis of their movement patterns. High order pacers exhibited greater ranges of limb motion than did low order finishers.

Animals↗
PubMed1988

The gait of pacers. 2: factors influencing pacing speed.

Standardbred pacers were studied at four different nominated speeds and selected gait kinematics were analysed to determine factors which contribute to pacing speed. A deterministic model is proposed in which pacing speed is a function of stride length and stride timing variables. Stance length and suspension time remained relatively constant over the different pacing speeds. Variables which discriminated best between pacing speeds were suspension length and overlap time. At near maximal speed, the pacers increased speeds with increased stride length. This was attributed to an increased suspension length with little difference in suspension times. A 22 per cent increase in pacing speed resulted in a 13 per cent increase in stride length, 26 per cent increase in suspension distance, 8 per cent increase in stride frequency, 35 per cent and 16 per cent increases in advanced placement and completion times and a 23 per cent decrease in the period of overlap.

Animals↗
PubMed1987

Inhibition of prostaglandin biosynthesis by etodolac. I. Selective activities in arthritis.

Etodolac is the first anti-inflammatory drug belonging to the tetrahydropyranoindole class. In contrast to several other common anti-inflammatory drugs, etodolac exhibited an unusually high potency as an inhibitor of established adjuvant arthritis relative to its activity against carrageenan paw edema in the rat. This phenomenon led us to investigate whether the ability of NSAIDs to inhibit prostaglandin biosynthesis differed between cultures of macrophages, which are present in inflammatory exudates, and cultures of synoviocytes and chondrocytes, which contribute to inflammation of the articulating joint. Although other anti-inflammatory drugs were found to be equally active in all three cell types, etodolac was found to be much more effective on the cells of the joint than on the macrophage. This differential activity may be responsible for the striking efficacy of etodolac as an anti-arthritic drug.

Acetates↗
PubMed1986

Participation of neutrophils and delayed hypersensitivity in the clearance of experimental cutaneous candidiasis in mice.

Involvement of neutrophils and delayed hypersensitivity in the clearance of Candida albicans infections was investigated with the use of a model of the disease in inbred mice. Experimental infections were produced by rubbing C albicans onto the shaved skin of the flank without the use of occlusive dressings. After a single infection, delayed hypersensitivity to Candida developed in C57BL/6 mice, and the infection cleared more rapidly than in C3H/He mice, in which delayed hypersensitivity did not develop. In both strains, the organisms were associated with neutrophilic microabscesses in the upper epidermis within 1 day of inoculation; by 3 days, the organisms and microabscesses had become relocated to a site just above the skin surface. At this time, the epidermis was intact under the microabscesses and significantly thickened, which indicated that epidermal proliferation had occurred. Delayed hypersensitivity reactions accelerated clearance of the infection, apparently by increasing the rate of removal of the microabscesses and associated organisms from the skin surface. However, delayed hypersensitivity was not an absolute requirement for clearance, because in animals of the C3H/He strain, in which delayed hypersensitivity did not develop during the first infection, the infection was eventually cleared. It is postulated that in these infections an important defense mechanism may be the enhancement, perhaps by the neutrophilic infiltrate, of epidermal proliferation early in the infection such that the infecting organisms are moved to a location above the skin surface from which they can be more easily removed by other processes, including delayed hypersensitivity reactions.

Animals↗
PubMed1985

Effects of pH and ionic strength on the binding of L-tri-iodothyronine to the solubilized nuclear receptor.

K'A (apparent association constant) and Bmax. (total receptor concentration) describing the interaction of tri-iodothyronine (T3) and its solubilized rat liver nuclear receptor (R) are found to be moderately consistent in successive preparations, but both quantities diminished after a few days. To achieve comparability in the effects of ionic strength (I) and of pH on K'A and Bmax, appropriate measurements have been made simultaneously on single preparations. K'A and Bmax. were found to be effectively unchanged over the range I0.05-0.60. Both parameters have been measured over the range pH 6.4-9.0 and the values of K'A analysed in terms of the 4'-OH ionization of T3 and that of a cationic acidic group, shown to require pK' = 7.6. This group could be identified either with the terminal alpha-NH3+ of T3 or with a group (RH+) in the receptor site. On the balance of evidence the first possibility is the more likely, in which case the variation of Bmax. with pH is ascribed to conformational changes in the receptor protein.

Animals↗
PubMed1985

Scaling segmental moments of inertia for individual subjects.

The purpose of this investigation was to validate methods of scaling human segmental moments of inertia for the transverse principal axis. Firstly, two methods of scaling Chandler et al.'s (Pamphlets DOT HS-801 430 and AMRL TR-74-137, Wright Patterson Air Force Base, OH, 1975) mean subject data to estimate the segmental moments of inertia were used. Chandler et al.'s data were scaled using body mass and segment length (formula 1) or body mass and standing height (formula 2). These data were then compared with a procedure of using the cadaver whose anthropometric measurements most closely match those of the subject. The difference between the criterion data (Chandler's subject data) and scaled values were plotted on scatter diagrams with confidence limits of p less than 0.05 at d.f. = 17. For procedure 1, 43% of the scaled values were plotted within the confidence limits using formula (2) (mass and standing height), compared with 26% for formula (1) (mass and segment length). Formula (1) markedly underestimated the tallest and heaviest subjects. In procedure 2, only 16% and 21% of the scaled values, using formula (1) and (2), respectively, fell within the confidence limits. Results suggested that scaling formulae approximate the moment of inertia of body segments with only limited accuracy. However, if scaling was to be adopted then mean moment of inertia data from an appropriate data set, using the formula that incorporates subject mass and standing height, gave results closest to the criterion value.

Anthropometry↗
PubMed1985

Linear IgA bullous dermatosis. An immunologically defined disease.

Linear IgA bullous dermatosis (LABD) can mimic bullous pemphigoid (BP) and/or dermatitis herpetiformis (DH) both clinically and histologically. LABD, however, can be distinguished from BP and DH by direct immunofluorescent (IF) demonstration of linear IgA deposits along the basement membrane zone. A retrospective study of 234 cases of BP, 27 cases of LABD, 60 cases of DH, and 20 cases of cicatricial pemphigoid (CP) revealed that BP patients are significantly older than LABD or DH patients and LABD patients are significantly older than DH patients. BP and CP occur more frequently in women (65-70%) than LABD or DH (44-48%). The frequencies of C3 deposits in the basement membrane zone (BMZ) are significantly higher in BP (85%) compared with LABD (18.5%) and DH (28.3%). LABD patients varied in their response to various therapeutic agents. Some responded to corticosteroids and some to sulfones alone, whereas others required a combination of corticosteroids and sulfones.

Adolescent↗
PubMed1984

Deterioration of axonal membranes induced by phenolic pro-oxidants. Roles of superoxide radicals and hydrogen peroxide.

The susceptibility of axons to oxidative free radicals generated by pro-oxidant neurotoxins and related compounds was tested by applying the reagents to the disheathed ventral nerve trunk of the crayfish. Electrophysiological characteristics of the axons, including spike amplitude and rise time, were recorded, using intracellular glass microelectrodes. L-Dopa, or L-dopa in the presence of copper-(bis)-histidine (Cu-his), did not change significantly the electrophysiological characteristics of the axon. A 20 mM concentration of 6-hydroxydopamine (6-OHDA), 20 mM 6-OHDA in an anaerobic environment, and 20 mM 6-OHDA with inactivated catalase-SOD accelerated the rate of decline of the spike amplitude with time to 5-8 times the control rate. Simultaneously, parallel increases in rise time and spike duration were observed, consistent with partial depolarization of the resting membrane presumably resulting from increased permeability. Catalase, superoxide dismutase (SOD), or a mixture of catalase and SOD all afforded partial protection, catalase having the least protective effect, and catalase + SOD the greatest. In contrast, 20 mM H2O2, 2 mM H2O2, or Cu-his alone did not significantly accelerate deterioration of the axon. Most of the damage results from the interaction of H2O2 with O-2, rather than from the direct action of either species. p-Hydroxyphenylpyruvate (pHPP) in the presence of Cu-his induced a similar accelerated deterioration of the axon to 4.2 times the control rate. Catalase plus SOD partially protected against this effect, but either enzyme alone was not significantly protective.

Animals↗
PubMed1984

The binding of thyroid hormone receptors to DNA.

The behaviour of tri-iodothyronine (T3)- and thyroxine (T4)-receptor complexes when bound to native DNA-cellulose is reported. Equal and large proportions of both T3- and T4-receptor complexes bind to DNA but although T3-receptor complexes are 99% recoverable by 0.5 M NaCl buffer elution, only 60-70% of the T4-receptor complexes are regained. The balance appears as free T4, apparently released as the T4-receptor complexes bind to the DNA whilst the corresponding receptor remains bound. This effect is independent of T4-receptor complex/DNA ratio up to ca. 4 fmol/micrograms DNA, of the presence of an equal amount of unoccupied receptor and of an eight-fold concentration range of both T4-receptor complex and DNA at a fixed ratio, in the cellulose matrix. Pre-formed receptor-DNA material, likewise, only accepts some 60% of the expected quantity of T4 whereas the capacity for T3 appears to be similar to that of free receptors.

Animals↗
PubMed1984

Hypersensitivity pneumonitis in rabbits. Modulation of pulmonary inflammation by long-term aerosol challenge with antigen.

Immunized rabbits that were aerosol challenged for 2 to 3 wk with pigeon dropping extract, an etiologic agent of hypersensitivity pneumonitis, developed chronic pulmonary inflammation associated with cell-mediated immunity in bronchoalveolar cells. However, prolonged aerosol challenge for 12 wk resulted in the diminution of pulmonary inflammation (modulation) and the loss of demonstrable cell-mediated immunity. This was probably not due to loss of sensitized lymphocytes that mediated pulmonary inflammation. Furthermore, rabbits undergoing modulation when they were challenged with an unrelated antigen were refractory to the development of pulmonary inflammation for at least 9 wk. After this refractory period, animals reimmunized and aerosol challenged with pigeon dropping extract displayed an anamnestic response and produced pulmonary lesions that were strikingly similar to the histopathology of human hypersensitivity pneumonitis.

Aerosols↗
PubMed1982

The specific binding of the thyroid hormones to matrix isolated from rat liver nuclei.

Specific binding sites for the thyroid hormones have been demonstrated in the liver nuclear matrix, a structural framework of the nucleus. When labelled 3,5,3'-tri-iodo-L-thyronine ([125I]T3) is injected into rats, 5% of the total nucleus bound T3 is bound to the matrix after 1 hour. However, when either isolated nuclei or isolated nuclear matrices were incubated with [125I]T3 in vitro, a 3- to 7-fold greater number of specific T3 binding sites were revealed in the nuclear matrix. The properties of the matrix-associated thyroid hormone binding sites were investigated in vitro. These binding sites showed limited capacity and high affinity for T3; the equilibrium association constant (Ka) was 1,3 x 10(9) M-1 and the binding capacity was 20,2 fmol T3 per 100 microgram matrix protein.

Animals↗