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Biomedical subjects

S D Carter

Publications and source records attributed to S D Carter.

At least 163 records · Page 9Linked to original sources

Differences between plasma and synovial fluid fibronectin.

Fibronectin is a high molecular weight glycoprotein of plasma and tissue fluids, and one of its functions is to opsonise particulate material. Chromatographic and electrophoretic analyses showed that the main components of fibronectin are biochemically similar in rheumatoid patients' plasma and synovial fluid. But synovial fluid fibronectin also contains a slow-moving component seen on two-dimensional immunoelectrophoresis, suggesting the presence of fibronectin complexes. Affinity chromatography provided evidence that these involved IgG, and in vitro studies showed that fibronectin influenced the reaction between IgG and anti-IgG. Synovial fluid fibronectin is functionally active in binding to gelatin in an haemagglutination assay, and it gave a relatively higher degree of haemagglutination than did plasma fibronectin, supporting the concept of multivalent fibronectin complexes in synovial fluid. These results suggest synovial fluid fibronectin may be involved in the opsonic removal of IgG-containing complexes from synovial fluid.

Arthritis, Rheumatoid↗

A new assay for IgG rheumatoid factor activity and its use to analyse rheumatoid factor reactivity with human IgG isotypes.

A new assay for IgGRF activity is described which employs human IgGFc as the antigen and a radiolabelled monoclonal antibody directed against human IgG (CHI domain) as the developing antibody. Using this assay IgGRF activity against human IgG isotypes was measured and most sera from RA patients were shown to react predominantly with IgG1 and IgG2 but few reacted with IgG3 and IgG4. The same sera were tested for IgMRF to the IgG isotypes. IgG2 was the best antigen, IgG1 and IgG4 were less so and reactivity with IgG3 was the lowest. IgGRF without associated IgMRF was obtained, its specificity compared to that of IgMRF, and found to be broadly similar. With the new assay high levels of serum IgGRF were found in those RA patients with extraarticular disease but not in RA patients with synovitis alone.

Antibodies, Monoclonal↗

Age-dependent changes in gastrointestinal transport and retention of particulate manganese oxide in the rat.

Translocation of inhaled particulates from the nasopharynx and upper tracheobronchial area to the gastrointestinal tract is a major route of exposure for particles with a mass median diameter of greater than 1 micron. Previous studies in this laboratory with particulate Mn3O4 have shown that preweanling rats have substantially higher tissue Mn concentrations than similarly treated adults, indicating possible differences in uptake or elimination or both. This study was conducted to evaluate changes in gastrointestinal movement and retention of particulate Mn3O4 in the preweanling and weaned rat. 85Sr-labeled microspheres were used to evaluate gastrointestinal transit rate (TR), while particulate Mn3O4 was used to evaluate particulate retention at selected ages. The results show that stomach retention time in the preweanling is at least twice that of the postweanling (90 min versus 42 min). In general, intestinal TR was not different in any of the ages evaluated, while transit time increased as intestinal length increased. Analysis of the Mn data demonstrated that the preweanling rat had a two-component retention curve with half-times of between 2 and 6 h for the short component and of between 24 and 26 h for the long component. In the postweanling rat, only one component was identified, with a half-time of between 2 and 5 h.

Age Factors↗

Complement activating properties of complexes containing rheumatoid factor in synovial fluids and sera from patients with rheumatoid arthritis.

The relationship between complexes containing rheumatoid factor and complexes activating complement was examined in synovial fluids and sera from patients with rheumatoid arthritis (RA). In each case this was performed by quantifying the amount of rheumatoid factor bound by solid phase Fab'2 anti-C3 and/or solid phase conglutinin. Both anti-C3 coated and conglutinin coated microtitre plates bound high levels of complexes containing rheumatoid factor from sera of RA patients with vasculitis. Unexpectedly, these complexes were detected in synovial fluids from only a minority of RA patients with synovitis. However, RA synovial fluids did contain other complexes as shown by the presence of complement consuming activity, C1q binding material and immunoglobulin attaching to conglutinin. It is considered that in RA synovial fluids the complexes containing RF and those activating complement are not necessarily the same whilst in vasculitic sera the complexes containing rheumatoid factor also activate complement.

Adult↗

Effect of benomyl on the reproductive development of male rats.

Benomyl, a systemic fungicide, was administered to male Sprague-Dawley rats during the prepuberal, pubertal, or postpubertal stage of reproductive development. Animals received 5 or 10 daily treatments of 0, 125, 200, 250, 500, or 1000 mg benomyl/kg . d by gavage. Observations were made at selected intervals after exposure and included hematological parameters, body weight, tissue weights, total epididymal sperm counts, vas deferens sperm concentration, serum follicle-stimulating hormone ( sFSH ) levels, and testicular histology. Data presented here suggest that there is an age-related difference in sensitivity to benomyl. Animals that received benomyl treatments during prepuberty showed no significant treatment effects in tissue weights, total epididymal sperm counts, vas deferens sperm concentration, or sFSH . Animals that received at least 250 mg/kg . d during puberty or postpuberty showed one or more of the following effects: decreased testicular or epididymal weights, decreased epididymal sperm count, decreased vas deferens sperm concentrations, and/or testicular lesions. Histological examination of testicular tissue indicated a higher incidence of diffuse hypospermatocytogenesis in pubertal (20% of the treated animals) and postpubertal (40% of the treated animals) animals that were exposed to benomyl. These values were compared with those of the treated prepubertal animals, which had a 10% incidence of diffuse hypospermatocytogenesis , and with all of the control animals, which had no occurrences of this testicular lesion.

Animals↗

Mononuclear phagocytes in rheumatoid arthritis: Fc-receptor expression by peripheral blood monocytes.

Fc receptor expression by enriched monocytes from rheumatoid arthritis (RA) patients and age and sex matched controls (healthy subjects) was compared by measuring the uptake of IgG on monocytes in a competitive radioassay. The association constant (Ka) between IgG and the monocytes and the number of Fc binding sites per cell was calculated from Scatchard plots of 4 degrees C binding data. RA monocytes had increased expression of Fc receptors as compared with those of controls. This increase was particularly pronounced in those RA patients affected by extra-articular disease. There were significant correlations between the numbers of Fc receptors on monocytes and both C1q binding and anticomplementary activity but none between monocyte Fc receptor numbers and serum rheumatoid factors (IgG and IgM). It is considered that monocyte handling of circulating immune complexes is unimpaired in RA and that monocytes make an adaptive response to increased levels of immune complexes.

Aged↗

Clearance and organ localization of particles and soluble complexes in mice with circulating complexes.

The clearance and organ localization of a number of substances cleared by either Fc-dependent or -independent mechanisms was studied in normal mice and in mice with endogenously produced persistent circulating complexes. Clearance of covalent dimers of mouse IgG, chicken IgG and ovalbumin were no different between the two groups of mice. By contrast, hepatic and splenic uptake of dimeric mouse IgG (but not of chicken IgG or ovalbumin dimer) was impaired in the mice with persisting complexes. Surprisingly the rate of clearance of sheep red blood cells (SRBC) was increased in mice with persisting complexes as was hepatic uptake of polyvinyl pyrrolidone. It is suggested that the mononuclear phagocytes of mice with persistent circulating complexes are non-specifically stimulated while their ability to take up soluble complexes by Fc-dependent attachment is selectively impaired.

Animals↗

Effect of benomyl on reproduction in the male rat.

Adult Sprague-Dawley male rats (65 days of age) received 10 daily treatments of 0, 200 or 400 mg benomyl/kg/day by gavage. Body weight, tissue weights, total epididymal sperm counts and sperm concentration from the vas deferens were measured 14 days after the last treatment. Testicular histology was evaluated in the 0 and 400 mg/kg/day groups. Significant findings included 35-48% depressions in the total epididymal sperm counts and in the vas deferens sperm concentrations in adult animals treated with 200 or 400 mg/kg/day. Histological evaluations of testicular sections from 6 adult animals in the 400 mg/kg/day group indicated a slight to moderately severe hypospermatocytogenesis in 2 animals and a slight to severe generalized hypospermatogenesis in 2 animals. Caudal epididymis weight were significantly (P less than 0.05) depressed with benomyl treatment. No treatment effects were found in body weight, liver, kidney, tests, or seminal vesicle weights.

Animals↗

Chronic ingestion of Mn3O4 by rats: tissue accumulation and distribution of manganese in two generations.

Sprague-Dawley rats were chronically exposed to particulate Mn3O4 through two generations. At specific ages, observations were made of growth, tissue content, and distribution of Mn and Fe as affected by chronic exposure to Mn through an Fe-sufficient diet and an Fe-deficient diet. Chronic dietary Mn3O4 resulted in dose-related increases in Mn accumulation, and a concomitant Fe deficiency promoted Mn accumulation. In general, the addition of substantial amounts of Mn to either diet depressed tissue Fe levels.

Aging↗

Effects of chronic manganese (Mn3O4) exposure on selected reproductive parameters in rats.

Long-Evans rats were chronically exposed to dietary Mn3O4 beginning on d 1 of gestation and continuing through 224 d of age. Dietary concentrations of Mn, as Mn3O4, were 350, 1050, and 3500 ppm and were applied in either a normal Fe 240 ppm) or a low-Fe (20 ppm) basal diet. General toxic effects were apparent in young animals at a dietary dose of 3500 ppm Mn and were enhanced by concomitant Fe deficiency. Fertility was reduced in the group exposed to 3500 ppm Mn with a diet containing sufficient Fe. Male reproductive development was delayed by Mn treatment, as measured by testes weight, sperm count, and serum follicle-stimulating hormone and testosterone concentrations.

Animals↗

Human monocyte binding of homologous monomer and complexed IgG.

Human peripheral blood monocyte binding of homologous IgG has been studied using monomer and covalently cross-linked dimer and trimer. A competitive radioassay using enriched monocytes was employed to determine the association constant (Ka) and the number of receptor sites per cell. Monomer and dimer bound with very similar Ka values (7.15 X 10(7) and 7.14 X 10(7)LM-1) whereas a slightly higher figure was obtained with trimer (8.9 X 10(7)LM-1). The number of receptor sites for dimer and trimer (90.5 and 107.5 X 10(3)/cell, respectively) were much greater than for monomer (14.5 X 10(3)/cell). Inhibition of dimer and trimer binding by monomer gave heterogenous Scatchard plots, each with two components. These findings suggest that human peripheral blood monocytes possess two types of Fc receptor, one of high affinity binding monomer and complexes and one of low affinity which predominantly binds complexes.

Biopolymers↗

Chronic ingestion of Mn3O4 by young rats: tissue accumulation, distribution, and depletion.

Mn accumulation, distribution, and disappearance were evaluated in selected tissues of preweanling rats dosed daily with particulate Mn3O4 for 12 or 27 d postpartum. Significant findings include a high rate of Mn absorption and localization in tissues, especially the cerebrum, hypothalamus, and pituitary. In these tissues, the return of Mn concentrations to control levels was much slower when Mn dosing was continued beyond 18-20 d postpartum.

Animals↗

Characterisation of activated lymphocytes in the peripheral blood of patients with rheumatoid arthritis.

The extent and nature of lymphocyte activation in the circulation in rheumatoid arthritis (RA) was investigated. Peripheral blood lymphocytes (PBL) from RA patients and healthy controls were separated into a number of discrete fractions by density in discontinuous Ficoll density gradients. Low density (activated) lymphocytes were found at significantly higher levels in RA, particularly in patients with clinically active disease. Conversely, patients with clinically inactive RA had normal levels of activated lymphocytes. Lymphocyte populations within the ficoll gradient fractions were detected by E rosettes, staining for surface Ig, and by different avidities of EA binding. The activated population in RA was shown to be relatively depleted of T cells, enriched in surface Ig-bearing lymphocytes, and depleted of lymphocytes with high avidity EA binding. The evidence suggests that many of the activated PBL in RA are B blasts.

Arthritis, Rheumatoid↗

Chronic manganese oxide ingestion in rats: hematological effects.

Hematological values were studied in Long Evans rats after chronic exposure to manganese oxide (Mn3O4). Data were obtained at selected ages from the P0 through the F2 generation. Effects of exposure to Mn3O4 during Fe deficiency were determined by placing half of the animals on a low-Fe diet (20 mg/kg) while the other half were maintained on a normal-Fe diet (240 mg/kg). Animals treated with Mn3O4 and maintained on a normal-Fe diet showed little variation from controls through 100 d of age. However, animals (24-100 d of age) maintained on a low-Fe diet and receiving Mn treatment during the prenatal and postnatal periods developed microcytic anemia. Irrespective of the dietary Fe level, serum creatinine levels decreased in the groups receiving 400 and 1100 ppm Mn while serum Ca and P levels increased in the group receiving 1100 ppm Mn at 100 d of age. Serum values for lactate dehydrogenase, alkaline phosphatase (100 d of age), and serum glutamic-oxaloacetic transaminase (224 d of age) were elevated for all animals on low-Fe diets. Globulin, albumin (100 d of age), and glucose (224 d of age) levels were depressed in all low-Fe groups.

Animals↗

Chronic manganese oxide administration to preweanling rats: manganese accumulation and distribution.

Mn accumulation was evaluated in selected tissues of preweanling rats dosed daily with particulate Mn3O4. Significant findings include a high rate of Mn accumulation in the preweanling rat; a Mn dose-related acceleration of postpartum liver iron depletion; a Mn dose-related depression in red blood cells, hematocrit, hemoglobin, body weight, and survival by 21 d postpartum; and a Mn distribution in tissues with liver greater than brain greater than or equal to kidney greater than testes at 18-21 d of age.

Aging↗