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Biomedical subjects

J Gordon

Publications and source records attributed to J Gordon.

At least 181 records · Page 10Linked to original sources
PubMed1993

Functional interaction between beta 2-adrenoceptor agonists and interleukin-4 in the regulation of CD23 expression and release and IgE production in human.

Normal human peripheral blood mononuclear cells (PBMC) produced IgE when stimulated with IL-4. In the present report it was shown that beta 2-adrenoceptor agonists, salbutamol and fenoterol, potentiated the IL-4-induced IgE production without significantly affecting the expression of the low affinity receptor for IgE at the cell surface of monocytes and B lymphocytes. However, beta 2-adrenoceptor agonists were shown to enhance at day 7 the IL-4-induced release of the soluble form of CD23 (sCD23) by PBMC. This effect was specific since a beta-adrenoceptor antagonist, D,L-propranolol, inhibited the IL-4-induced IgE production by these cells. Alternatively, the beta 2-adrenoceptor agonists inhibited the production by these cells of interferon-gamma (IFN-gamma) but did not affect the production of IL-4 when stimulated with phytohemagglutinin A + a phorbol ester. These data suggest that beta 2-adrenoceptor agonists influence the IL-4-induced IgE production in humans by enhancing the release of sCD23 and inhibiting the production of endogenous IFN-gamma. In addition to the effect on the IL-4-induced IgE production it was shown that beta 2-adrenoceptor agonists potentiated the effect of IL-4 on a human promonocytic cell line, U 937, by enhancing CD23 expression and release and by inducing the differentiation of these cells into monocyte-like cells. Taken together, these data indicate that beta 2-adrenoceptor agonists potentiated the effect of IL-4 and that this functional interaction is different considering the cell-lineage and the stage of differentiation of these cells.

Adrenergic beta-Agonists↗
PubMed1993

IL-2 expands and maintains IgM plasmablasts from a CD5+ subset contained within the germinal centre cell-enriched (surface IgD-/CD39- buoyant) fraction of human tonsil.

IL-2 was found to promote the rapid growth of a minority population contained within the germinal centre (GC) cell-enriched (CD39- and/or IgD- buoyant) fraction of human tonsillar B lymphocytes. The cells emerging in response to IL-2 had a high mitotic index and morphologically resembled plasmablasts. Cultures could be maintained in the absence of feeder cells for up to 3 weeks in IL-2 and were characterized by large amounts of IgM in their supernatants: approximately 40% of the cells contained readily detectable cytoplasmic IgM by day 10 of culture. Negligible quantities of IgG and IgA were found. The target population for IL-2-driven expansion and IgM secretion was smIg+/CD38+ and was subject to suppression by anti-IgM antibody. While only 8% of cells within the GC cell-enriched fraction were CD5+ (compared with 15% of high density resting B cells), their removal led to an 83% reduction in the amount of IgM produced in response to IL-2, IL2 selectively expanded this minor CD5+ subset such that by day 6 of culture they comprised 57% of all viable cells. Cultures established with IL-2 showed increasing expression of cytoplasmic Bcl-2 and withdrawal of growth factor resulted in cell death via apoptosis. We discuss these results in relation to CD5+ B cells and their potential role in antibody responses to TD antigens.

Adenosine Triphosphatases↗
PubMed1993

Distribution of cAMP in secondary follicles and its expression in B cell apoptosis and CD40-mediated survival.

Apoptosis occurs at a high rate among B cells in germinal centres (GCs). Isolated GC B cells undergo apoptosis spontaneously when cultured in vitro: such self-destruction can be arrested by protein kinase C-activating phorbol esters and by ligating surface CD40. This study sought to explore whether the cAMP-dependent second messenger system played a role in the regulation of GC cell apoptosis and in ligand-promoted survival. First, the distribution of cAMP in GCs was analysed by immunofluorescence staining and confocal laser scanning microscopy in situ: cytoplasmic cAMP was expressed by all cells but was most abundant in the constitutive cells of the light zones, where GC B cell apoptosis and rescue occur. Isolated GC B cells were found to express higher levels of cAMP than quiescent B lymphocytes as assessed both by a competitive binding assay and a newly developed flow cytometric method. Culturing GC B cells alone increased cAMP level, while those cells rescued with the phorbol ester phorbol myristate acetate (PMA) and anti-CD40 exhibited decreased cAMP levels. Resting B lymphocytes showed no change in cAMP level following culture alone, but a significant increase in cAMP levels when co-cultured with PMA and anti-CD40. These data suggest that given identical signals, resting B cells and GC B cells exhibit differential regulation of the cAMP-dependent second messenger system; moreover, this second messenger system appears to be involved in the regulation of apoptosis in GC B cells.

Antigens, CD↗
PubMed1993

Beta 2-adrenoceptor stimulation augments the IL-4-induced CD23 expression and release and the expression of differentiation markers (CD14, CD18) by the human monocytic cell line, U 937.

The effect of beta 2-adrenoceptor agonists and interleukin-4 (IL-4) on the CD23 expression on, and release from, the human promonocytic cell line, U 937, was investigated. As assessed by flow cytometry, incubation of U 937 cells in the presence of salbutamol, fenoterol or IL-4 induced a concentration- and time-dependent increase in CD23 expression, that was maximal after 48 hr and followed by a decrease thereafter. In addition, salbutamol potentiated the effect of IL-4, the optimal concentration of the drug being a function of the concentration of this cytokine. This synergy between IL-4 and beta 2-adrenoceptor agonists was also observed for the release of the soluble form of CD23. The effect on CD23 expression of salbutamol and fenoterol, but not of IL-4, was blocked in the presence of D,L-propranolol (1 microM) or butoxamine (1 microM). The alpha-adrenoceptor agonist, norepinephrine (1 microM), was ineffective in inducing CD23 expression or potentiating the one evoked by IL-4. Salbutamol down-regulated the expression of Fc gamma RI (CD64) and Fc gamma RII (CD32) whereas IL-4 was ineffective. Only when added together at the onset of the culture did salbutamol and IL-4 induce, after 48 hr, the expression of the monocyte marker, CD14. The expression of CD18 was up-regulated in response to salbutamol either alone or in combination with IL-4, this cytokine alone being inefficient. These data suggest that IL-4 and beta 2-adrenoceptor agonists induce differentiation of U 937 cells into monocyte-like cells.

Adrenergic beta-Agonists↗
PubMed1993

Inhibition by glucocorticoid and staurosporine of IL-4-dependent CD23 production in B lymphocytes is reversed on engaging CD40.

IL-4 synergizes with signals delivered through CD40 both for the induction of CD23/Fc epsilon RII expression and for IgE synthesis. Moreover, engagement of CD40 on the B cell surface by MoAb overcomes the ability of interferons, transforming growth factor-beta, or anti-CD19 to inhibit IL-4-dependent change. We now report that occupancy of CD40 relieves potent suppression of IL-4-induced CD23 production by glucocorticoid or the relatively broad-acting kinase inhibitor staurosporine. Interruption of the IL-4 signal was observed with concentrations of staurosporine considered to be selective for protein kinase C (PKC) inhibition (IC50 = 10 nM) but not with genistein or tyrphostins, effective inhibitors of tyrosine kinase activity. On ligation of CD40, staurosporine no longer inhibited the IL-4 signal: at concentrations of between 1 and 20 nM, staurosporine actually increased by as much as 100% the rate of CD23 production stimulated on simultaneous activation through CD40 and IL-4R. Such augmentation was not observed when the more specific PKC inhibitor RO-31-8220 was used; indeed, CD40 engagement was unable to overcome the ability of this inhibitor to block IL-4-promoted CD23 induction (IC50 = 10 microM). Occupancy of CD40 did, however, thwart completely the usual ability of prednisolone to inhibit the IL-4 signal leading to CD23 induction. Activation through CD40 left inhibition of phorbol ester-induced CD23 expression by staurosporine, RO-31-8220, or glucocorticoid unchecked. These findings further highlight the intimate level of cross-talk existing between CD40 and IL-4R on resting B lymphocytes to promote CD23 expression, a phenotypic change which preludes IgE synthesis.

Alkaloids↗
PubMed1993

A developmentally regulated DNA-binding protein from mouse brain stimulates myelin basic protein gene expression.

Transcription of the myelin basic protein (MBP) gene is regulated in a cell-type-specific and developmental stage-specific manner during myelin formation in the murine central nervous system. The 5'-flanking region of the MBP gene contains several regulatory elements that differentially contribute to the cell-type-specific transcription of MBP in cells derived from the central nervous system. The proximal element, termed MB1, which is located between nucleotides -14 and -50 with respect to the RNA start site, has previously been shown to have characteristics of a cell-type-specific enhancer element. In this study, we used band shift and UV cross-linking assays to identify DNA-binding proteins in mouse brain nuclear extract which interact with the MB1 element. Fractionation of these extracts has allowed the identification of a 38- to 41-kDa nuclear protein, derived from mouse brain tissue at the peak of myelination, which specifically binds the MB1 DNA sequence. Fractions enriched in the MB1-binding protein have been shown to stimulate transcription of the MBP promoter in extract derived from HeLa cells. MB1 binding protein activity is expressed in a tissue-specific and development stage-specific pattern which coincides with the pattern of MBP transcription, suggesting that this protein may be a biologically relevant transcription factor for the MBP gene in vivo.

Aging↗
PubMed1993

Which motoric condition is most effective for teaching spelling to students with and without learning disabilities?

The purpose of this study was to determine the efficacy of three motoric conditions (writing, tracing, and computer keyboarding) on the spelling performance of 24 third- and fourth-grade students without learning disabilities (NLD) (15 males, 9 females) and 24 third- and fourth-grade students with learning disabilities (LD) (16 males, 8 females). This study applied empirically based procedures for teaching spelling, examined student performance over time, and incorporated student interviews concerning their preference for motoric condition. For number of words spelled and proportion of bi-grams (correct letter sequences) used correctly, significant differences were found between the LD and NLD groups, both at posttest and follow-up, with the NLD students learning to spell more words and apply more correct bi-grams than the students with LD. There was no significant effect for condition for either words spelled or bi-grams, indicating that students did not learn significantly more words in the writing, tracing, or computer condition. There was also a significant time effect indicating that the accuracy of both groups decreased over time from posttest to follow-up for both words and bi-grams. Interviews revealed that students in both groups preferred the computer condition; however, they believed that they learned best in the writing and tracing conditions.

Child↗
PubMed1993

Blood donor motivation: a survey of minority college students.

Ninety-five percent of all blood donors are Caucasian. To investigate why minorities are under-represented as blood donors, a random sample of 120 minority college students were surveyed about attitudes and behavior regarding blood donations. This sample of minority students had donated blood at the same rate (33%) and for the same positive motivation (altruism) and negative motivations (for those who did not donate--fear, medical excuses, didn't think of it, no time) as Caucasian donors. The low rate of blood donations by minorities is not due to their membership in ethnic groups per se, but to other variables such as education and socioeconomic level. A recruitment strategy based on the results of this study is presented.

Adult↗
PubMed1993

Regulation of survival in normal and neoplastic B lymphocytes.

The regulation of survival is clearly a vital component in deciding the fate of normal and malignant cells. In cell populations subject to selection through apoptosis, dysregulation of this mechanism could disrupt homeostasis with the potential overproduction of affected clones. Germinal centres are the sites of such selection for B cells proliferating in response to T-dependent antigen: two tumours arising at these sites--Burkitt lymphoma (BL) and follicular centre cell (FCC) lymphoma--show aberrations in their capacity to undergo programmed cell death (PCD). Here, we summarize present knowledge on the factors, both extra- and intracellular, which regulate survival in normal and malignant B cells arising in germinal centres.

Antigens, CD↗
PubMed1993

Clinical significance of methicillin-sensitive and methicillin-resistant Staphylococcus aureus in UK hospitals and the relevance of povidone-iodine in their control.

This review summarizes the natural history, clinical relevance and basis of control of Staphylococcus aureus infection in UK hospitals, stressing the central role of asymptomatic carriage by patients and staff in persistence of this prolific and versatile nosocomial pathogen. The clinical relevance of methicillin-resistant and methicillin-sensitive S. aureus (MRSA and MSSA) is considered in terms of prevalence and spectrum of invasive and toxigenic infections produced, correlated with host and parasite risk factors. An assessment is made of arguments why the acquisition of methicillin-resistance or multiple antibiotic resistance might justify more than conventional methods of containment and how the control policy is influenced by the expression of enhanced virulence and epidemicity. Guidelines for control of epidemic MRSA (EMRSA) are discussed with reference to justification, feasibility and efficacy. As elimination of carriage is crucial to the success of any rational control policy the relative merits of topical antibiotics and antiseptic agents are compared. The bacterial efficacy of povidone-iodine, chlorhexidine and mupirocin are evaluated as a basis for eradication of MRSA.

Carrier State↗
PubMed1993

Obsessive compulsive disorder.

Taking over the management of a patient who has a complex diagnostic label should not prevent us from being alert to the development of new symptoms and the need to offer appropriate management strategies. This article also demonstrates the cost-effectiveness of 'long term' GP attendance versus hospitalisation or institutional care.

Activities of Daily Living↗
PubMed1993

One-step competitive immunochromatographic assay for semiquantitative determination of lipoprotein(a) in plasma.

Numerous studies have associated high concentrations of lipoprotein(a) [Lp(a)] with atherosclerosis. We developed a rapid, one-step competitive immunochromatographic assay to measure Lp(a) in plasma. The assay is performed on a nitrocellulose membrane strip and the result is determined by a visual readout of rust-colored colloidal selenium. The assay is based on the principle that Lp(a) in the sample will compete with Lp(a)-coated colloidal selenium for binding to the anti-Lp(a) monoclonal antibody immobilized on the assay strip in the format of four ladder bars. The number of capture bars that appear as a result of the formation of colloidal selenium color is proportional to the concentration of the Lp(a) protein in the samples. The strip assay semiquantitatively measures Lp(a) concentrations ranging from 0 to 180 mg/L of Lp(a) protein in serum, plasma, or fingerstick whole-blood samples. This assay appears very useful for quick identification of individuals with above-normal concentrations of plasma Lp(a) protein (> 70 mg/L), and has potential for monitoring a patient's response to treatment with Lp(a)-lowering drugs.

Animals↗
PubMed1992

Second-messenger pathways involved in the regulation of survival in germinal-centre B cells and in Burkitt lymphoma lines.

Spontaneous apoptosis in germinal-centre (GC) B cells can be prevented by treatment with anti-immunoglobulin (Ig). By contrast, susceptible group-I Burkitt lymphoma (BL) cells can be driven to apoptosis by anti-Ig. The second-messenger pathways involved in the regulation of apoptosis in GC B lymphocytes and in BL cell lines were studied using pharmacological agonists or inhibitors of intracellular calcium ([Ca2+]i) and protein kinase C (PKC). Anti-Ig was found to mobilize Ca2+ in group-I cells. Pre-incubation with the Ca2+ chelator EGTA partially reduced apoptosis induced by anti-Ig or by Ca2+ ionophore in group-I BL cells. Activation of PKC with phorbol ester reduced such Ca(2+)-driven programmed cell death (PCD) to control levels of apoptosis. Apoptosis in group-I BL cell lines could also be triggered by the kinase inhibitors staurosporine and Ro-31-8220 at concentrations selective for PKC activity. Expression of the bcl-2 protein in BL group-I cells following gene transfer affords protection from apoptosis induced by ionomycin or anti-Ig. In the present study, bcl-2 was additionally found to protect from apoptosis driven by staurosporine. The high levels of spontaneous apoptosis exhibited by normal GC B cells were reduced, but not abrogated, by co-culture with phorbol ester. These results indicate that, in group-I BL cells, imbalance in the phosphoinositide pathway of signalling, in favour of [Ca2+]i and away from PKC, results in apoptosis: constitutive phosphorylation of key proteins by PKC may therefore suppress apoptosis in BL as well as in GC B cells.

Apoptosis↗