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Biomedical subjects

S E Walker

Publications and source records attributed to S E Walker.

At least 163 records · Page 9Linked to original sources
PubMed1981

Slow-reacting substance from alveolar macrophages--a mechanism of asthma?

The effects of alveolar macrophages on bronchial reactivity were studied in vitro to determine whether these cells could provide a pathogenetic link between cellular components of the inflammatory response, chemical medication of smooth muscle contraction and possible local mechanism of asthma. Alveolar macrophages harvested from rabbit lungs produced consistent and prolonged contractile responses in guinea-pig tracheal rings. The contractile material had the pharmacological and physical properties of slow-reacting substance (SRS) and, in particular, it was completely antagonized by minute concentrations (5 ng/ml) of a specific SRS antagonist, FPL 55712. The average contractile response per 10(6) macrophages was quantitatively equivalent to that produced by 76 ng methacholine. These findings not only support the view that local mechanisms may be of relevance in the pathogenesis of asthma, but could also have possible implications for therapy.

Animals↗
PubMed1981

Stability and sterility of cimetidine admixtures frozen in minibags.

The stability and sterility of cimetidine hydrochloride admixtures after freezing for extended periods were investigated. Cimetidine hydrochloride, 300 mg, was added to each of six 50-ml minibags containing 5% dextrose injection. The cimetidine concentration was determined and the bags were frozen for up to 30 days. After freezing for the appropriate length of time, the bags were thawed. Cimetidine concentrations were determined by high-pressure liquid chromatography immediately and then daily for eight days while the admixtures were refrigerated. Sterility tests were carried out throughout the study. Data were analyzed by least-squares linear regression to test for trends. The cimetidine hydrochloride admixtures were stable while frozen for up to 30 days and for at least eight days following thawing when kept under refrigeration. Sterility of the admixture was maintained throughout the study period.

Cimetidine↗
PubMed1980

Resistance to therapy in mature Palmerston North mice treated with cyclophosphamide or hydrocortisone sodium succinate.

Inbred Palmerston North (PN) mice are a newly recognized model of systemic lupus erythematosus. In this study PN mice with established autoimmune disease were treated until death with cyclophosphamide (8 mg/kg/day) or hydrocortisone (10 mg/kg/day). These doses had previously been found to prevent or suppress disease in another lupus model, the NZB/NZW mouse. In the PN strain, autoantibodies, severity of glomerulonephritis, and longevity were not influenced by treatment. Furthermore, the incidence of neoplasms was not increased in PN mice receiving prolonged therapy with immunosuppressive drugs. Unlike NZB/NZW mice, PN mice were resistant to the effects of Cyclophosphamide and hydrocortisone.

Animals↗
PubMed1980

Frentizole therapy of active systemic lupus erythematosus.

Frentizole is a benzimidazoleurea that has immunosuppressive properties in mice. Eleven steroid-treated patients with active systemic lupus erythematosus received frentizole (150-350 mg/day) in combination with stable or decreasing doses of prednisone in an open label trial. Nine patients completed at least one 21- to 75-day course of therapy with this drug. Clinical parameters of disease improved in 8 of these 9 patients. Mean DNA binding decreased by 28%, mean CH50 increased by 20%, and mean absolute lymphocyte and T cell counts decreased by 25-26%. Granulocytopenia was not observed. Three patients developed reversible hepatic toxicity. Clinical and serologic improvement was noted in 3 patients who accepted a second 90-day course of frentizole therapy.

Adolescent↗
PubMed1980

The filling of molten and thixotropic formulations into hard gelatin capsules.

Problems in the formulation and manufacture of conventional solid dose form products include the variation of fill weight and drug content, dissolution control of poorly water soluble drugs and dust generated during manufacture giving rise to cross contamination. We have examined the application of a liquid filling technique for the manufacture of hard gelatin capsules as a means of overcoming some of these. Filling materials are based on water-soluble hot melt polymers such as polyethylene glycol or water-dispersible thixotropic systems of pharmaceutical oils with thixotropic additives. A Zanasi LZ64 capsule filling machine was adapted to fill liquids using filling pump. No dust is generated during filling and 20 microgram doses of drug can be accurately filled without extensive processing. The formulations are simple and do not require specialist ingredients such as lubricants, binders, disintegrants and flow aids. The method of manufacture is reduced to a simple mixing and direct filling operation. The system may be applied to promote the dissolution of poorly water soluble drugs using solid solutions or solid dispersions. Slow release formulations are also available using suitable retard excipients.

Capsules↗
PubMed1979

Accelerated appearance of neoplasms in female NZB/NZW mice treated with high-dose cyclophosphamide.

Prolonged immunosuppressive therapy with cyclophosphamide increases the prevalence of neoplasms in NZB/NZW mice, an animal model of systemic lupus erythematosus. The current study was designed to compare the oncogenic properties of high dose cyclophosphamide with a low dose therapeutic regimen. Female NZB/NZW mice received life-long therapy with "high dose" cyclophosphamide, 16 mg/kg/day, or "low-dose" cyclophosphamide, 5.7 mg/kg/day; control mice received saline. High dose therapy clearly accelerated appearance of neoplasms. Seventeen of 19 mice treated with high-dose cyclophosphamide developed neoplasms at the mean age of 61 weeks. Fifty-seven percent of these tumors were mammary carcinomas. Neoplasms appeared in all mice treated with low dose; mean longevity in this treatment group was 80 weeks (compared to high dose treated mice, P less than 0.001). Carcinomas, pulmonary adenomas, and lymphomas were the most common tumors in mice receiving low dose therapy. Positive tests for ANA were suppressed in high dose treated mice. AntiDNA antibody levels and glomerulonephritis were decreased significantly in both groups of cyclophosphamide-treated mice compared to controls. It was concluded that the high daily dose of immunosuppressive drug was related to early oncogenesis in autoimmune NZB/NZW mice.

Adenoma↗
PubMed1978

Diagnostic significance of antibody to native deoxyribonucleic acid in children with juvenile rheumatoid arthritis and other connective tissue diseases.

Sera of children with juvenile rheumatoid arthritis and other connective tissue diseases were tested for antibodies to native DNA by a radiolabeled-binding assay. Normal values were obtained in 130 children with JRA, including 28 with uveitis and 14 with selective IgA deficiency. Normal values were also found in sera from children with dermatomyositis, scleroderma, polyarteritis, ankylosing spondylitis, and a variety of other nonconnective tissue diseases. The only sera with elevated DNA-binding assays were from children with systemic lupus erythematosus. On the basis of these data, increased levels of antibodies to native DNA distinguished patients with active SLE from children with JRA.

Adolescent↗
PubMed1978

Prolonged lifespan and high incidence of neoplasms in NZB/NZW mice treated with hydrocortisone sodium succinate.

This study investigated the effects of prolonged corticosteroid therapy on the course of spontaneous autoimmune disease and oncogenesis in NZB/NZW mice, an animal model of systemic lupus erythematosus. Twenty young female NZB/NZW mice were treated until death with low-dose hydrocortisone sodium succinate (3.3 mg/kg/day), and 21 mice received high-dose hydrocortisone (10 mg/kg/day). Fifteen control mice were injected with saline. Long-term therapy with either dose of hydrocortisone effectively prevented renal disease and prolonged lifespans in NZB/NZW mice. Fifty-six percent of low-dose treated animals developed neoplasms, and 38% of mice in this treatment group died with renal disease. Neoplasms caused death in 76% of mice receiving high-dose treatment. Long-term hydrocortisone therapy was associated with a predominance of sarcomas, which appeared in aged mice after a long period of treatment. In earlier studies conducted in this laboratory, cyclophosphamide treatment prolonged life in NZB/NZW mice. Ninety-seven percent of cyclophosphamide-treated mice developed neoplasms; most tumors were lymphomas or carcinomas. It was concluded that neoplasms occur commonly in old NZB/NZW mice with lives prolonged by immunosuppressive or antiinflammatory drugs. Nevertheless, the specific therapeutic agent used in each study influenced the types of neoplasms appearing in treated mice.

Animals↗
PubMed1978

Palmerston North mice, a new animal model of systemic lupus erythematosus.

This report describes a previously unrecognized animal model of SLE, the PN mouse. Although outbred PN mice were studied originally as models of polyarteritis nodosa, their inbred descendants have autoimmune disease which closely resembles SLE. In the current study, positive indirect immunofluorescence tests for ANA appeared when the mice were 5 months old, and 80% of mice were ANA-positive at 10 months of age. Anti-DNA were detected in sera from newborn mice and from 53% of mice under 2 months of age. Seventy-six percent of PN mice developed anti-DNA at the age of 10 months. Glomerular deposits of IgG, IgM, IgA, and complement appeared at 2 to 4 weeks of age, and examination of renal tissue by electron microscopy showed basement membrane thickening and dense intramembranous deposits. Neoplasms arose in 14% of PN mice. Female mice died earlier than male mice, and the most common causes of death were glomerulonephritis and arteritis. It was concluded that the serologic and histologic characteristics of disease in PN mice resembled SLE.

Animals↗
PubMed1978

Stimulated autoantibody response and increased longevity in NZB/NZW mice treated with cyclophosphamide and tilorone.

The experiment described in this report was designed to study the effects of immunostimulatory therapy in cyclophosphamide-treated hybrid New Zealand mice. Autoantibodies, renal histology and neoplasms were studied in seventeen female NZB/NZW mice treated with daily injections of the potent immunosuppressive drug, cyclophosphamide. Results were compared with fifteen female NZB/NZW mice who received both cyclophosphamide and tilorone, an interferon inducer which stimulates the immune system. Fifteen control mice received saline. The controls died with spontaneous arteritis and immune complex glomerulonephritis; their mean age at death was 46 weeks. In the cyclophosphamide group anti-DNA antibodies and renal disease were suppressed. Mean longevity was prolonged significantly to 80 weeks. Two mice died of iatrogenic causes, and the remaining fifteen mice died with neoplasms. Eleven mice had multiple neoplasms; a total of twenty-seven neoplasms appeared. In mice receiving combination therapy, autoantibody responses were not suppressed. Nevertheless, glomerulonephritis was controlled partially and the mean lifespan was prolonged to 82 weeks. Eighteen neoplasms appeared in ten mice in the combination treatment group, and five mice had more than one neoplasm. The appearance of lymphomas was delayed in mice receiving two drugs. It was concluded that concurrent therapy with tilorone stimulated autoantibody production and altered the expected pattern of neoplasia in cyclophosphamide-treated NZB/NZW mice.

Animals↗
PubMed1977

Relation of titred peripheral pattern ANA to anti-DNA and disease activity in systemic lupus erythematosus.

This study compared the clinical usefulness of the peripheral pattern detected in immunofluorescent antinuclear antibody (ANA) testing with anti-DNA measured by the modified Farr technique. 48 patients with active or inactive systemic lupus erythematosus (SLE) were studied at one point in the course of their disease. There was no association between titres of serum giving a peripheral ANA pattern (tp-ANA) and anti-DNA values. Tp-ANA did not correlate with activity of SLE. In contrast with this finding, anti-DNA correlated with severity of renal disease, decreased serum complement, and number of SLE criteria. In a separate group of 9 patients with flare-ups of SLE, tp-ANA and anti-DNA fell as disease activity was controlled. Nevertheless, these two parameters were independent of one another. It was concluded that tp-ANA did not accurately reflect anti-DNA or activity of SLE.

Adolescent↗
PubMed1976

Suppressed hetergeneous antinuclear antibody response in lymphomabearing NZB/NZW mice.

A long-term study of cyclophophamide-induced suppression of auto-immune disease in NZB/NZW mice demonstrated the oncogenic potential of this alkylating agent. In seven of ten mice dying with lymphomas, retrospective examination of serial tests for heterogeneous ANA showed terminal decreases of titres or reversion of tests to negative. Suppressed titres were found in one of seven mice dying with other tumours and in four of twenty-nine mice succumbing to renal disease-vasculitis. Transplantation studies confirmed the association between growing lymphoma tissue and decreasing ANA titres. In the immunosuppressed host with connective tissue disease, the loss of certain auto-antibodies may signal development of a lymphoreticular neoplasm. Tumour-induced impairment of auto-immune responsiveness may reflect the loss of specific ANA that fulfil a protective role and inhibit neoplastic growth.

Animals↗