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Biomedical subjects

A G Alexander

Publications and source records attributed to A G Alexander.

At least 19 recordsLinked to original sources
PubMed1996

Can clinical response to cyclosporin in chronic severe asthma be predicted by an in vitro T-lymphocyte proliferation assay?

This study tests the hypothesis that the clinical response to cyclosporin therapy of patients with chronic severe asthma is related to the sensitivity of their T-lymphocytes to the antiproliferative effects of cyclosporin in vitro. In a previous study, we observed such a relationship with glucocorticoids and the same lectin-driven proliferation assay was used in the present study. Peripheral blood mononuclear cells were obtained from 33 patients participating in a cross-over trial of oral cyclosporin therapy during both cyclosporin and placebo treatment periods, and cultured in the presence of phytohaemagglutinin and serial dilutions of cyclosporin and dexamethasone. Proliferation was measured by tritiated thymidine uptake. Both cyclosporin and dexamethasone inhibited T-lymphocyte proliferation in a concentration-dependent manner in vitro at concentrations encompassing those achieved in peripheral blood during therapy in vivo. T-lymphocytes from the asthmatic patients showed a range of sensitivity to the antiproliferative effects of cyclosporin, but this could not be correlated with improvements in peak expiratory flow rate (PEFR) or forced expiratory volume in one second (FEV1) during cyclosporin therapy as compared with placebo. In contrast to previous observations with glucocorticoids, this in vitro T-lymphocyte proliferation assay is not predictive of clinical response to cyclosporin therapy in chronic severe asthmatics.

Asthma↗
PubMed1995

Clinical response to cyclosporin in chronic severe asthma is associated with reduction in serum soluble interleukin-2 receptor concentrations.

Activated T-lymphocytes play an important role in asthma pathogenesis and release soluble interleukin-2 receptor (sIL-2R), which can be detected in the serum. In a recent randomized, cross-over trial we showed that cyclosporin, an inhibitor of T-lymphocyte activation, improved lung function in patients with chronic severe asthma. To investigate whether changes in serum sIL-2R concentration could be related to clinical response we prospectively compared serum sIL-2R concentrations in patients during cyclosporin and placebo treatment. Peripheral venous blood was obtained from 22 patients during the last 4 weeks of both the cyclosporin and placebo treatment periods and serum stored at -80 degrees C pending measurement of sIL-2R concentration by enzyme immunoassay. Soluble IL-2R was detected in all samples at a concentration range of 191-2,297 U.ml-1. Mean serum concentrations of sIL-2R were significantly lower on cyclosporin therapy (560 U.ml-1) as compared with placebo (676 U.ml-1). The decreases in serum sIL-2R concentrations associated with cyclosporin therapy in these patients correlated with the percentage increases in their morning peak expiratory flow rate (PEFR) measurements on cyclosporin as compared with placebo. These data demonstrate that in patients with chronic severe asthma, cyclosporin therapy which results in clinical improvement is associated with a decrease in serum concentrations of sIL-2R. This is compatible with the hypothesis that cyclosporin ameliorates asthma, at least partly, by inhibition of T-lymphocyte activation.

Asthma↗
PubMed1994

Serum interleukin 5 concentrations in atopic and non-atopic patients with glucocorticoid-dependent chronic severe asthma.

BACKGROUND: Interleukin (IL)-5 is thought to play a part in asthmatic bronchial mucosal inflammation and is a potential therapeutic target. Detectable serum IL-5 concentrations have been found previously in a proportion of patients with acute severe asthma, but not in the same patients following oral glucocorticoid therapy or in normal controls. A study was undertaken to investigate whether or not IL-5 is detectable in the serum of patients with glucocorticoid-dependent chronic severe asthma. METHODS: Serum concentrations of IL-5 were measured in 29 patients with stable oral glucocorticoid-dependent chronic severe asthma (mean PEFR 59.7% predicted) and seven normal controls using a specific enzyme-linked immunoassay calibrated with recombinant human IL-5 standards (lower limit of sensitivity 40 pg/ml). RESULTS: Interleukin 5 was detectable in the serum of 15 of the 29 patients at a median concentration of 150 pg/ml (range 40-690), but was undetectable in the serum of all the control subjects. The patients with detectable serum IL-5 concentrations did not differ from those with undetectable concentrations in terms of atopic status, disease severity (percentage predicted PEFR or FEV1), prednisolone dosage, serum IgE concentrations, or peripheral eosinophil count. CONCLUSIONS: Interleukin 5 is detectable in the serum of a proportion of both atopic and non-atopic patients with chronic severe asthma, and concentrations in these patients were higher than in normal controls. These observations are compatible with the hypothesis that IL-5 release occurs in these patients during a period of stable asthma despite systemic glucocorticoid therapy.

Adult↗
PubMed1992

Trial of cyclosporin in corticosteroid-dependent chronic severe asthma.

The treatment of chronic severe asthma is unsatisfactory for many patients. In a randomised, double-blind, placebo-controlled, crossover trial we have tested whether cyclosporin, which is thought to act primarily by inhibition of T lymphocyte activation, improves lung function in corticosteroid-dependent asthmatics. After a 4-week run-in period, 33 patients with longstanding asthma (mean duration 27 years), and who had required continuous oral corticosteroids for a mean of 9.3 years, were randomised to receive either cyclosporin (initial dose 5 mg/kg per day) or placebo for 12 weeks, crossing over after a 2-week washout period. Mean baseline forced expiratory volume in 1 s (FEV1) was 60.1% of the predicted value. 2 patients failed to complete the protocol and 1 withdrew because of hypertrichosis. Cyclosporin therapy resulted in a mean increase above placebo of 12.0% in morning peak expiratory flow rate (PEFR; p less than 0.004) and 17.6% in FEV1 (p less than 0.001). The frequency of disease exacerbations requiring an increased prednisolone dose was reduced by 48% in patients on cyclosporin compared with placebo (p less than 0.02). Diurnal variation in PEFR decreased by a mean of 27.6% (p = 0.04). Cyclosporin for 12 weeks was well tolerated by this group of chronic asthmatics, in whom the mean whole-blood trough concentration was 152 micrograms/l. These findings provide further evidence of a role for activated T lymphocytes in the pathogenesis of asthma. Specific pharmacological targeting of this cell could form the basis of a novel approach to the treatment of asthma.

Adult↗
PubMed1991

Identification of a mycoplasmal protein which binds immunoglobulins nonimmunologically.

Immunoblotted protein samples from several strains of Mycoplasma hominis and from one strain of Mycoplasma arginini each contain a polypeptide of a molecular mass of 95,000 to 105,000 Da which binds immunoglobulin nonimmunologically. Immunoblots from these organisms were probed with alkaline phosphatase-conjugated goat anti-rabbit immunoglobulin, conjugated goat immunoglobulin G (IgG) Fab fragments, and conjugated goat IgG Fc fragments. The polypeptide bound the goat anti-rabbit molecules and the Fab fragments but not the Fc fragments. These reactions could be blocked with nonimmune unconjugated goat IgG and unconjugated human IgM. Controls probed with alkaline phosphatase alone did not stain. Binding of the conjugated preparations to whole mycoplasmal cells was dependent on concentrations of both conjugate and cells for the goat anti-rabbit preparation and for Fab. The mycoplasmal polypeptide may be a light-chain-specific reactant.

Animals↗
PubMed1987

Analysis of protein antigens of Mycoplasma hominis: detection of polypeptides involved in the human immune response.

Immunoblotting of polypeptide antigens after polyacrylamide gel electrophoresis was used to analyze clinical strains of Mycoplasma hominis. There was increased antibody titer for polypeptides comprising a wide range of molecular sizes between paired sera obtained from patients with indication of invasive infection. Eight of these antigens were shown to be candidate surface antigens. Absorption of hyperimmune rabbit serum with intact cells resulted in elimination or reduction in intensity of bands for these molecules. The antigens p115 and p98 appeared to be present in each of six clinical strains that were compared by reaction with the reference rabbit antiserum. There was considerable diversity of migration position for the remaining antigens in the profiles of these six strains.

Antigens, Bacterial↗
PubMed1985

The problems of collecting the Körner minimum data set at a District Psychiatric Hospital.

The Körner report recommends that there should be an annual census of all in-patients in psychiatric units who have been there in excess of one year. A study involving the collection of the 'Körner Minimum Data Set' at a district psychiatric unit found that the current patient information system does not always provide adequate or accurate information. It is also found that seeking these data is time-consuming if the census enumerator is not involved with patient care. It is therefore suggested that the most accurate information on long stay psychiatric patients might be obtained if such a census were conducted and coded by DHSS collectors using a special census form to be completed by the ward doctor. The accuracy of medical records might also be improved if the completion of the front sheet of the case notes were made the responsibility of the ward doctor.

Concurrent Review↗
PubMed1980

Evaluation of the use of colour transparencies for scoring gingivitis.

The effects of altering exposure, angle at which the exposure was made, magnification, type of flash, and the method of viewing, on scoring gingivitis from colour transparencies were evaluated. The results of this study suggest that, by using a standardised photographic technique, the scoring of gingivitis from colour transparencies is a valid procedure. However, many practical drawbacks arose, indicating that this method is not entirely satisfactory.

Color↗
PubMed1980

Characterization of the strain-specific and common surface antigens of Mycoplasma arginini.

A combination of quantitative immunoelectrophoresis and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis was used to determine location and molecular weights of surface membrane antigens of four strains of Mycoplasma arginini. Two major surface antigens were identified for M. arginini by absorption of antiserum with whole cells: one surface antigen was strain specific, electrophoretically fast, and prominently located on the surface, whereas the other surface antigen was common to the four strains and of intermediate electrophoretic mobility. Three of the four strains of M. arginini (G-230, 23243, and 27389) possessed immunologically strain-specific antigens which did not cross-react, whereas the leonis strain lacked an immunologically detectable unique surface antigen. A monospecific antiserum prepared against immune precipitates of the strain-specific antigen of strain G-230 detected three polypeptides of 74,000, 44,000, and 17,000 daltons in SDS-polyacrylamide gels of membrane preparations. All four strains shared the common surface antigen which appeared considerably more hydrophobic than the strain-specific surface antigen because it could only be demonstrated by charge-shift immunoelectrophoretic conditions (addition of deoxycholate to the nonionic detergent). Monospecific antiserum to the common antigen of strain G-230 reacted with all four M. arginini strains, but did not react with two other arginine-utilizing species, and recognized three polypeptides of 40,000, 29,000, and 20,000 daltons in membranes of strain G-230. Whereas the common surface antigen is a likely target for conventional serological reactions used for identification of the species M. arginini, strain-specific antigen cannot fulfill this role but must participate in other surface reactions.

Antigens, Bacterial↗
PubMed1980

The removal of carbon particles from the buccal surface of upper incisors and canines (by saliva and mechanical movement).

Clearance time of carbon particles from the buccal surfaces of upper incisor and canine teeth was measured, and its possible relationship with plaque accumulation and gingival inflammation was assessed. The average clearance time observed was 20.75 minutes. Factors influencing particle removal were found to be significantly related to the severity of gingival inflammation but not to differences in plaque accumulation. Thus the factors involved in particle clearance may modify the gingival response to plaque. Alternatively, small changes in gingival contour as a result of the inflammatory process may alter significantly the ability of these factors to remove particulate matter.

Carbon↗
PubMed1978

Application of charge shift electrophoresis to antigenic analysis of mycoplasmic membranes by two-dimensional (crossed) immunoelectrophoresis.

Both the anodic migration and resolution of membrane antigens of Mycoplasma arginini were greatly improved in two-dimensional immunoelectrophoresis by incorporating both a neutral detergent, Triton X-100, and an anionic detergent, sodium deoxycholate, in the agarose support for first phase electrophoresis. The mobility of cytoplasmic antigens was unaffected at concentrations of 0.1% or less of sodium deoxycholate.

Antigens, Bacterial↗
PubMed1977

Characterization of membrane and cytoplasmic antigens of Mycoplasma arginini by two-dimensional (crossed) immunoelectrophoresis.

Two-dimensional immunoelectrophoresis was employed to electrophoretically identify membrane and cytoplasmic antigens of Mycoplasma arginini G-230. Five distinct cytoplasmic antigens were observed in soluble fractions prepared by digitonin lysis with electrophoretic mobilities (relative to bovine albumin) ranging from 0.36 to 0.86; four of these were common to other M. arginini strains: leonis and 23243. Five membrane antigens were identified, two of which (0.4 and 0.2) were common to the other M. arginini strains. The most prominent antigenic component of the membrane fraction (the complex membrane antigen) was electrophoretically heterogeneous, showing four antigenically related components with electrophoretic mobilities of 1.2, 0.95 to 0.76 and 0.05. The complex membrane antigen was exposed on the outside of the mycoplasmic cell because absorption of antiserum with live organisms removed antibody to this component. Antibodies to two other membrane components (0.6 and 0.2) were removed by absorption with Triton-solubilized membranes, but not by untreated membranes, indicating that these components were, at best, little exposed on either membrane surface. Antiserum was prepared against the complex membrane antigen using precipitin lines from two dimensional electropherograms as the immunogen. This antiserum reacted only with the complex membrane antigen and did not react with the other M. arginini strains, indicating that the complex membrane antigen was unique to strain G-230.

Antigens, Bacterial↗
PubMed1977

Gingival retraction.

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Dental Impression Technique↗