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Biomedical subjects

R J Booth

Publications and source records attributed to R J Booth.

At least 55 records · Page 3Linked to original sources

Constitutive production by the WEHI-3 cell line of B cell growth and differentiation factor that co-purifies with interleukin 1.

The myelomonocytic cell line WEHI-3 produces constitutively a factor that affects the growth and differentiation of murine B cells in culture. This cell line also secretes colony-stimulating factors (CSF), interleukin 1 (IL 1) but not interleukin 2. Sequential purification through AcA54 gel filtration, DEAE-Sephacel ion exchange chromatography, and buffer electrofocussing clearly resolved the B cell growth and differentiation factor (BGDF) from the CSF activities but failed to separate BGDF from IL 1. The WEHI-3-derived material responsible for BGDF/IL 1 activity, however, exhibited different behavior on DEAE chromatography (elution at 175 mM NaCl) to that reported for IL 1 from the P388D1 cell line (elution at 50 mM NaCl). B cell growth and differentiation could be induced by WEHI-3 BGDF/IL 1 in cultures of normal spleen cells depleted of T cells and adherent cells but not in cultures of spleen cells from B cell-deficient CBA/N mice, even though thymocytes from such mice displayed a normal response to IL 1. Significant B cell proliferation induced by BGDF/IL 1 was apparent only in the presence of submitogenic concentrations of anti-mouse IgM antibodies, but under these conditions few antibody-forming cells (AFC) were generated. In contrast, B cell differentiation to AFC occurred in the presence of the factor alone, and this response was inhibited by anti-IgM. Thus there appeared to be a reciprocal relationship between B cell proliferation and differentiation induced by BGDF/IL 1. The significance of these results is discussed in the light of other recent studies of BGDF.

Animals↗

Beta-adrenergic-receptor blockers and antinuclear antibodies in hypertension.

It has recently been reported that the Beta-adrenergic receptor-blocker acebutolol accelerates the development of antinuclear antibodies (ANAs) in hypertensive patients. We examined data from over 1500 hypertensive patients to determine whether this effect is associated with other beta blockers. Groups of patients treated with acebutolol, atenolol, labetalol, and pindolol all displayed increased development of ANAs relative to patients on other medication. When patients taking methyldopa (a drug associated with a high ANA incidence) were excluded from the analysis, only acebutolol retained an association (P less than 0.001) with ANA production. Sequential studies to assess the development of ANAs in patients during the course of beta-blocker treatment revealed a similar pattern. With methyldopa patients excluded, the fraction of patients developing ANAs was less then 10% for all but atenolol (10.9%), labetalol (13.8%), and acebutolol (33%). Thus, although some of the beta blockers may be associated with an increase in ANA incidence, the dramatic effects of acebutolol do not appear to be a group property.

Adrenergic beta-Antagonists↗

Double-stranded DNA antibodies: a comparison of four methods of detection.

Thirty-four antinuclear antibody (ANA) positive systemic lupus erythematosus (SLE) sera were tested for antibodies to double-stranded DNA (dsDNA) simultaneously using Farr, haemagglutination, Crithidia luciliae (CL) kinetoplast fluorescence and human metaphase chromosome fluorescence assays. Significant correlation (p less than 0 x 05) was found between the Farr and CL assays, with the two fluorescence tests (CL and metaphase) displaying the greatest degree of association (p = 0 x 00001). No correlation could be demonstrated between the haemagglutination test and any of the other three assays. Six hundred and ninety-one sera from patients with a range of provisional rheumatological diagnoses were prospectively analysed for dsDNA antibodies using Farr and metaphase assays. A correlation coefficient of 0 x 84 was obtained between the two assays. The metaphase assay provides comparable results to other more established assays, and because it is simple, reliable and sensitive, it should be seriously considered for routine use in testing for dsDNA antibodies.

Antibodies, Antinuclear↗

A comparative trial of intra-nasal beclomethasone dipropionate and sodium cromoglycate in patients with chronic perennial rhinitis.

A double-blind crossover study has compared intra-nasal sodium cromoglycate (SCG) with beclomethasone dipropionate (BDP), and both drugs with placebo, in fifty-two chronic perennial rhinitis patients. BDP was significantly more effective in relieving symptoms than SCG (76.9% and 50% of the patients improved respectively, P < 0.01). Both drugs were more active than placebos but while BDP was very clearly more effective (P < 0.0005) SCG was only marginally better than its placebo (P < 0.05, Fisher; P = 0.068, chi 2). BDP was selected by 56% of the patients as the best agent for continuing therapy at the end of the trial. By contrast SCG was preferred by the same number of patients as chose the two placebos (11.5%).

Administration, Intranasal↗

Tissue antibodies in a healthy New Zealand population.

The occurrence of antinuclear, smooth muscle, parietal cell, reticulum, thyroid microsomal and mitochondrial autoantibodies in the sera of 1641 healthy males and 959 healthy females was investigated. Females were also treated for antibodies to adrenal cortex and salivary gland. A rising frequency of autoantibodies with increasing age was observed in both sexes with the average frequency being 19.3 percent for females and 15.9 percent for males. The most commonly detected autoantibodies were those directed against reticulin and thyroid microsomes. Mitochondrial, adrenal and salivary gland autoantibodies, and antinuclear antibody titres greater than 1:32 occurred so rarely in the healthy population that their appearance in patients should be regarded as a possible indication of clinical disease.

Adolescent↗

Influence of prazosin on the development of antinuclear antibodies in hypertensive patients.

A recent publication suggested that antinuclear antibodies (ANA) occur in up to one third of patients treated with the hypotensive drug prazosin (Minipress). We have examined a large group of hypertensive patients and found ANA in 9.7% of 145 patients taking prazosin and in 12.2% of hypertensive patients on any treatment regimen. Excluding patients taking methyldopa (a drug associated with a high ANA incidence), the ANA incidence fell to 6.9% in the prazosin-treated group and to 7.2% of all treated hypertensives. Of over 350 untreated hypertensive patients, 6.0% had ANA. Prazosin did not increase the ANA incidence in patients on or off various drug combinations including beta blockers and diuretics. Analysis of the data by age and sex confirmed our conclusion that prazosin therapy is not accompanied by an increase in ANA.

Adrenergic beta-Antagonists↗

The proliferative capacity of human T lymphocyte subpopulations in a continuous culture system.

The continuous growth of subpopulations of human T lymphocytes was investigated using a culture system containing conditioning factors from mitogen-stimulated lymphocytes. Cultures of purified peripheral blood lymphocytes rapidly became enriched for T lymphocytes, detected as sheep erythrocyte rosette-forming cells, and could be maintained for up to a month in an actively growing state. Subpopulations of T lymphocytes bearing Fc receptors for IgM(T.M) or IgG(T.G) could not be detected in these cultures unless the cells were first washed and cultured for 3 days in medium devoid of conditioning factors. During this second culture step, many of the cells reverted from a large, blast-like state to a small lymphocyte morphology and proportion of the T lymphocytes re-expressed Fc receptors. The proportions of T.M and T.G lymphocytes so detected remained constant throughout the continuous culture period indicating that the system permitted the proliferation of all T lymphocytes. Fractionation studies supported this conclusion by demonstrating that purified T, T.M and T.G but not B lymphocyte populations proliferated when cultured in the presence of conditioned medium. The majority of cells in cultures of purified T.M lymphocytes re-expressed IgM Fc receptors following reculture in unconditioned medium. However, the re-expression of IgG Fc receptors by cultured T.G lymphocytes could not be achieved.

Cell Division↗

A microculture system for generating haemolytic antibody responses from human tonsillar lymphocytes.

Small numbers of Ficoll-Hypaque purified human tonsillar lymphocytes were stimulated with PWM to produce SRBC-specific PFC in a microculture system. The magnitude of the response varied among different tonsils but was typically between 200 and 1000 PFC/10(6) cells cultured. Little or no response was observed in the absence of PWM. SRBC failed to stimulate a SRBC-specific response and the presence of this antigen in PWM-stimulated cultures depressed the response. The time of the maximum response was inversely related to the number of cells cultured. In addition, the duration of the response was limited by rapid depletion of critical medium requirements and/or build up of inhibitory factors especially when the cell concentration exceeded 5 x 10(5) cells/culture. This effect could be partially overcome by daily feeding of cultures with fresh medium. Fractionation studies indicated a requirement for both T and B cell populations. Constant efficiency of PFC production with respect to cell number could be achieved by the addition of inactivated autologous 'filler' cells. The significance of these results and applicability of the microculture system to a detailed analysis of human antibody responses will be discussed.

Antibody Formation↗

Antibody responses of human lymphocytes in vitro. Specificity and physical properties of plaque-forming cell precursors.

When human tonsillar lymphocytes are cultured with pokeweed mitogen they generate a larger number of antibody-secreting cells. A substantial number of the plaque-forming cells generated have specificity for sheep erythrocytes but very few are specific for either bovine or horse erythrocytes. We have investigated the physical properties of sheep erythrocyte-specific precursors and have found that they have the characteristics of larger lymphocytes and are heterogeneous with respect to density. Our results support the concept that the percursors which can be induced by pokeweed mitogen to develop into plaque-forming cells belong to a pre-activated sub-population of lymphocytes.

Animals↗

Antibody responses of human lymphocytes in vitro. Enhancing effects of hydrocortisone.

Cultures of human tonsillar lymphocytes stimulated by pokeweed mitogen in the presence of hydrocortisone succinate generate more sheep red blood cell-specific plaque-forming cells than when the hydrocortisone is absent. Such enhancement is even more marked when sheep red blood cells and pokeweed mitogen are present in cultures. This contrasts with the inability of sheep red blood cells to enhance pokeweed mitogen-stimulated response in cultures lacking hydrocortisone. Hydrocortisone causes greater enhancement when the concentration of cells in culture is high than when it is low. These data are consistent with hydrocortisone inhibiting the activity of suppressor cells which would otherwise mask helper effects.

Animals↗