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Biomedical subjects

J J Castles

Publications and source records attributed to J J Castles.

At least 19 recordsLinked to original sources
PubMed1988

Localization, molecular weight and immunoglobulin subclass response to Aspergillus fumigatus allergens in acute bronchopulmonary aspergillosis.

A specimen of Aspergillus fumigatus was isolated from a patient with acute bronchopulmonary aspergillosis (ABPA). Cultures were allowed to propagate and were separated into spores and mycelium to greater than 95% homogeneity. Extracts of both the spores and mycelium were prepared and used for study by both dot blot analysis and immunoblotting to study the major allergens. By dot blot analysis, 22 of 22 patients with ABPA and none of 10 healthy controls reacted with mycelium when probed for both IgG and IgE anti-Aspergillus reactivity. Similar results were obtained when these extracts were separated on polyacrylamide gel electrophoresis and then probed; this included both IgG and IgE reactivity. Further, the reactivity to preparations of whole extract was absorbed with mycelium but not spores. Several distinct protein bands were detected with IgG, ranging from 30 to 110 kilodaltons (kD). In contrast, the majority of patients with ABPA, when studied for IgE reactivity, reacted only with a 70-kD protein, although 1 out of 22 patients reacted with a 30-kD protein. Subclass analysis of IgG reactivity demonstrated that 90% of reactive sera contained IgG2 and 73% IgG4 reactivity. IgG1 and IgG3 reactivity were present but less frequently detected. The use of immunoblotting will enable the identification of relevant allergens. Further, the demonstration that the allergenicity is located primarily in mycelium will allow more definitive studies of allergen isolation for studies of reactivity and, ultimately, cloning of the 70-kD protein and, finally, epitope mapping.

Acute Disease↗
PubMed1979

Studies of congenitally immunologic mutant New Zealand mice. II. Absence of T cell progenitor populations and B cell defects of congenitally athymic (nude) New Zealand Black (NZB) mice.

Congenitally athymic (nude) mice on an NZB, NZW, and BALB/c background were produced by repetitive selective backcrossing. F'12 generation nude mice of these three strains were compared to their littermate nu/+ controls with respect to survival, histology, blood counts, splenic surface markers, response to mitogens, spontaneous plaque-forming cells, and appearance of naturally occurring thymocytotoxic antibodies (NTA). Under specific pathogen-free conditions, NZB nude mice survive less than 3 weeks, dying of a runting-like disease with infection by local normally noninvasive organisms. A contributing factor to his premature death is the relative absence of T cell progenitor populations in the NZB nude vs NZW nude or BALB/c nude groups. Furthermore, NZB nude mice have a significantly earlier appearance of NTA than nu/+ littermates and likewise appear to have heightened spontaneous polyclonal B cell responses against the haptens dansyl, nitroiodophenyl, trinitrophenyl,2,4 dinitrophenyl, and sulfonate. It is suggested that NZB mice have several critical immunologic defects, including abnormalities of thymic epithelial cells, T cell differentiation pathways, and chronically polyclonal activated B cell populations. These defects interact to produce the clinical expression of autoimmunity.

Animals↗
PubMed1979

Altered responsiveness to mitogens in subgroups of patients with juvenile rheumatoid arthritis.

Thirty patients with juvenile rheumatoid arthritis (JRA) were compared to an age-matched control population with respect to lymphocyte transformation by the mitogens Concanavalin A, Phytohemagglutinin-P, Pokeweed and Lipopolysaccharide, as well as for the relative frequency of E-rosette and Ig-bearing cells in peripheral blood. The data were analysed according to sex, age of onset, mode of onset and disease activity. Lymphocytes from patients with a pauciarticular pattern of onset of JRA responded to mitogens in a similar fashion as normal volunteers, whereas lymphocytes from patients with both a polyarticular and Still's mode of onset had a diminished response to the mitogens. However, this reduction was noteworthy only during periods of disease activity; during periods of remission, lymphocytes from the patients responded similarly to lymphocytes from normals. In contrast to this reduction in mitogen stimulation in these subgroups of patients with JRA, all patients with JRA--irrespective of disease activity or mode of onset--were similar to controls with respect to the percentage of E-rosette and Ig-bearing cells. These alterations in mitogen responsiveness could not be attributed to therapy. Finally, the abnormalities of lymphocyte transformation in patients with polyarticular and Still's mode of onset represent secondary features of disease and are not due to a generalized predisposition or abnormality of cell mediated immunity.

Adolescent↗
PubMed1978

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↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1976

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↗
PubMed1976

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↗