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Biomedical subjects

J J Castles

Publications and source records attributed to J J Castles.

At least 37 records · Page 2Linked to original sources

Multicenter comparison of naproxen and indomethacin in rheumatoid arthritis.

In a double-blind, crossover study, naproxen, 250 mg twice a day, naproxen, 500 mg taken at bedtime, and indomethacin, 25 mg four times a day, were compared in 132 patients with rheumatoid arthritis; six centers participated in the study. Objective indices of arthritis activity, such as number of clinically active joints, walking time, and duration of morning stiffness, were nearly identical for the three treatment regimens. Of particular interest was the observation that efficacy of a single daily dose of naproxen was comparable to that of the twice-daily dosage. Naproxen was better tolerated than indomethacin, as shown by a statistically significant difference in the incidence of CNS complaints.

Adult↗

Activities of purine pathway enzymes in gouty human fibroblasts aged in vitro.

The finite life-span of fibroblasts in culture may reflect aging at the cellular level and gout is clinical condition whose incidence also increases with age. In order to better understand the age-related changes in purine metabolism, activities of purine degrading (adenosine deaminase and 5'-nucleotidase) and reutilizing (adenine phosphoribosyltransferase, hypoxanthine phosphoribosyl-transferase and adenosine kinase) enzymes were measured in serially cultured skin fibroblasts from normal subjects and from gouty patients who overproduce uric acid. Serially cultured fibroblasts from gouty overproducers of uric acid displayed increased purine enzyme levels with increasing cell passage while fibroblasts from normal donors showed little change in activity. There was no alteration in relative degrading and reutilizing enzyme levels. The data suggest an increase in the rate of purine turnover in aging gouty fibroblasts compared with normal fibroblasts.

Adult↗

The activity of purine salvage pathway enzymes in murine and horse models of congenital and acquired dysimmunity.

Previous studies of human congenital immunodeficiency states and in vitro observations of lymphocyte response to mitogens have implicated two purine salvage pathway enzymes, andenosine deaminase (ADA) and nucleoside phosphorylase (NP), as critical in the normal maturation and/or function of the immune system. Based on this information, ADA and NP activities were examined in a variety of congenital and acquired animal models of dysimmunity. The animals studied herein included: congenitally athymic (nude) mice; congenitally asplenic mice; congenitally athymic-asplenic mice; motheaten mice; New Zealand mice; and Arabian foals with severe combined immunodeficiency. No significant differences in the activities of ADA and NP were observed in any of these animals when compared with either normal littermates or animals with intact immune function. Major species differences were apparent when erythrocyte ADA acitivty was compared between mice and horses. In contrast, only minor strain alterations in ADA or NP activity were noted between several inbred groups of mice.

Adenosine Deaminase↗

Immunopathogenesis of Libman-Sacks endocarditis. Assessment by light and immunofluorescent microscopy in two patients.

The possible contribution of immunological mechanisms in the development of Libman-Sacks endocarditis was studied in 2 patients with systemic lupus erythematosus who underwent aortic valve replacement. Sections of verrucous lesions, stained with haematoxylin and eosin, showed three apparently distinct zones: an outer exudative zone of fibrin, nuclear debris, and haematoxylin-stained bodies; a middle organizing zone of proliferating capillaries and fibroblasts; and an inner zone of neovascularization which showed distinct, thin-walled junctional vessels. The striking finding was the apparently selective deposition of immunoglobulins and complement identified by direct immunofluorescence, within the walls of the small junctional vessels of the zone of neovascularization. We suggest that the observed immune deposits are immune complexes and that circulating immune complexes may play a critical role in the growth and proliferation of the verrucous lesion.

Aortic Valve↗

The biology of the rheumatoid synovial cell.

Over the past 15 years, many of the elaborate research techniques of cell biology and biochemistry have been applied toward discovering the cause of rheumatoid arthritis. Consequently, it is valuable to review the morphological, physiological and biochemical alterations that have been observed in rheumatoid synovial cells. All of the changes observed suggest that a viral agent may form the basis for these alterations. However, studies to date have failed to isolate or identify the putative causative virus and the search continues.

Arthritis, Rheumatoid↗

Noninfectious canine arthritis: the inflammatory, nonerosive arthritides.

Noninfectious, nonerosive arthritis was seen as an important manifestation of a number of chronic systemic diseases of the dog. Sixty-three dogs with this type of arthritis were seen at the Veterinary Medical Teaching Hospital during an 18-month period between 1973 and 1975. Of these dogs, 29 had systemic lupus erythematosus, 15 had arthritis in association with some chronic infectious disease process, and 19 had a similar type of arthritis, but without serologic evidence of systemic lupus erythematosus or any chronic infectious disease process.

Animals↗

Noninfectious canine arthritis: rheumatoid arthritis.

Chronic unremitting, generally symmetric, erosive polyarthritis was studied in 8 dogs. The disease had clinical, serologic, radiographic, and pathologic changes similar to those of rheumatoid arthritis of man. The condition occurred mainly in smaller breeds of dogs, with time of onset from 8 months to 8 years of age, Characteristic radiographic changes were seen in the joints several weeks to several months after the appearance of the initial lameness. Synovial fluid contained an increased number of neutrophils, and synovial fluid and synovial tissues were sterile for anaerobic and aerobic bacteria, mycoplasma, chlamydia, and viruses. Corticosteroids were therapeutically ineffective in all of the cases; however, corticosteroids, cyclophosphamide, and azathioprine were effective when used in combination in several dogs.

Animals↗

HLA-B27 and modified bone formation.

Of the many associations between histocompatibility antigens and human diseases a prominent one is that between HLA-B27 and inflammatory arthropathies. Hypotheses to explain this association include the B27 gene being linked to a specific immune-response gene required for disease expression and the B27 antigen acting via molecular mimicry with a microorganism or as a microorganism receptor. Alternatively, the HLA-B27 gene might be closely related to a gene which influences bone formation. The finding of a significant association between B27 and Forestier's disease, a disease characterised by abundant new bone formation, supports such a hypothesis.

Aged↗

Fistulization of rheumatoid joints. Spectrum of identifiable syndromes.

Eight patients with rheumatoid arthritis developed cutaneous fistulae adjacent to affected joints. Rheumatoid factor was positive in eight patients; subcutaneous nodules were noted in seven. Two patients had features of rheumatoid vasculitis. A spectrum of syndrome characterized by cutaneous fistulae was observed. Three patients showed classical fistulous rheumatism. Four patients developed septic arthritis which subsequently fistulized; in two, infection was associated with total joint replacement. One patient showed a cutaneous sinus accompanying a large calf cyst. A variety of diagnoses must be considered when cutaneous fistulae appear near joints in patients with rheumatoid arthritis.

Aged↗

Aminoacyltransferase I-catalysed binding of phenylalanyl-transfer ribonucleic acid to muscle ribosomes from normal and diabetic rats.

The aminoacyltransferase I-catalysed binding of phenylalanyl-tRNA (unfractionated Escherichia coli B tRNA acylated with radioactive phenylalanine and 19 non-radioactive amino acids) to skeletal-muscle ribosomes from diabetic rats was less than that to ribosomes from normal rats when the Mg(2+) concentration was low (7.5mm); whereas just the reverse was true when the concentration of the cation was higher (15mm). Thus the Mg(2+) dependency of aminoacyltransferase I-catalysed binding of phenylalanyl-tRNA to ribosomes from normal and diabetic rats paralleled the effect of Mg(2+) concentration on synthesis of polyphenylalanine reported before. During incubation at 7.5mm-Mg(2+) phenylalanyl-tRNA was bound only to ribosomes bearing nascent peptidyl-tRNA. There are fewer such ribosomes in a preparation from the muscle of diabetic animals because diabetic animals synthesize less protein in vivo. Thus the difference in polyphenylalanine synthesis in vitro is adequately explained by the difference in enzyme-catalysed binding of phenylalanyl-tRNA to ribosomes, however, the basis of the difference in protein synthesis in vivo is still unknown.

Acyltransferases↗