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Biomedical subjects

J Gordon

Publications and source records attributed to J Gordon.

At least 19 recordsLinked to original sources
PubMed1992

Ligation of CD23 triggers cAMP generation and release of inflammatory mediators in human monocytes.

Transduction through the CD23 molecule (Fc epsilon RII) was analyzed in normal human monocytes using monoclonal antibodies to CD23 (MHM6 and 135) and IgE/anti-IgE immune complexes. Monocytes expressing an increased amount of CD23 molecules were obtained by stimulation with IL-4 (30 U/ml). Anti-CD23 mAb as well as IgE/anti-IgE immune complexes were unable to induce any significant calcium mobilization [Ca2+]i in CD23-bearing monocytes whereas they elicited [Ca2+]i increase in B lymphocytes of the same donors. Despite their failure to induce calcium mobilization, the same CD23 ligands triggered a dose-dependent increase of intracellular cAMP, with a maximum 20 to 30 min after the onset of stimulation. This effect is mediated via CD23 inasmuch as: 1) F(ab)'2 fragments are as active as intact anti-CD23 mAb and 2) it is not observed in CD23- monocytes. The increase in cAMP was only partially altered in the presence of 1 microM indomethacin suggesting that it was not due to the release of PG. The possible role of CD23 in the activation of human monocytes was next documented by showing that anti-CD23 mAb and IgE/anti-IgE immune complexes induced the generation of IL-6 and of thromboxane B2 by CD23+ but not by CD23- monocytes. In addition, the IgE/anti-IgE-induced IL-6 production was potentiated in the presence of cAMP inducer such as the beta 2-adrenoceptor agonist salbutamol. These results indicate that ligation of CD23 induces cAMP generation in CD23+ human monocytes and that CD23 may regulate the IgE-dependent functions in normal human monocytes.

Acute-Phase Reaction↗
PubMed1992

Inositol lipids and phosphates in the proliferation and differentiation of lymphocytes and myeloid cells.

It is established that receptor-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate is an essential signalling reaction in the responses of many haemopoietic cells to stimuli: examples include platelet activation, antigen-driven initiation of cell proliferation in mature B and T lymphocytes and histamine release by mast cells, and chemotaxis and oxygen radical generation by neutrophils. However, the roles of inositol lipids and phosphates in the development of haemopoietic and immune cells are less well understood. This paper discusses three such situations: the sequential employment of phosphatidylinositol 4,5-bisphosphate hydrolysis and cyclic AMP accumulation as two signals essential to the action of the B lymphocyte-stimulatory cytokine interleukin 4; the involvement of antigen receptor-triggered inositol lipid hydrolysis in apoptotic elimination of immature anti-self T lymphocytes in the fetal mouse thymus; and the possible role of changes in the levels of abundant inositol polyphosphates in the differentiation of HL-60 promyelocytic cells and of normal human myeloid blast cells.

Bone Marrow Cells↗
PubMed1992

Factors modifying survival pathways of germinal center B cells. Glucocorticoids and transforming growth factor-beta, but not cyclosporin A or anti-CD19, block surface immunoglobulin-mediated rescue from apoptosis.

The tendency for germinal center (GC) B cells to enter apoptosis is suppressed on engaging antigen receptor with immobilized anti-immunoglobulin; cross-linking of surface CD40 by monoclonal antibodies provides an additional signal for rescuing GC cells from programmed death. These observations are believed to reflect events that, in vivo, would allow for the selection of centrocytes which have undergone somatic mutation on Ig V-region genes to generate antigen receptor of high affinity. The purpose of the present study was to identify factors capable of modifying the survival pathways of GC cells. Transforming growth factor-beta, at an optimal concentration of 1 ng/ml, was found to inhibit surface immunoglobulin (sIg)-mediated rescue of GC cells but had no influence on survival promoted through CD40. Both routes of rescue were blocked by the glucocorticoid prednisolone at pharmacological concentrations (ID50 = 10(-7) M). Cyclosporin A, an antagonist of sIg-mediated signaling in resting B cells, failed to block rescue of GC cells through either of the receptor-activated pathways. Antibody to CD19--which also suppresses the activation of resting B cells--not only left GC cell rescue undiminished, but rather provided a modest survival signal of its own; interferon-alpha behaved similarly while interferon-gamma failed to influence GC cell survival in either direction.

Antibodies↗
PubMed1992

In-vitro evaluation of povidone-iodine and chlorhexidine against methicillin-resistant Staphylococcus aureus.

The in-vitro activity of povidone-iodine (PVP-I) and chlorhexidine (CHX) against 33 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) was evaluated by a quantitative suspension test method. Bactericidal potency was measured by the logarithmic reduction factors (LRFs) achieved with each strain, tested at dilutions 25-800 over exposure times 30-300 s using a challenge of approximately 10(7) colony forming units (cfu) ml-1. The mean LRFs achieved over all dilutions, times and strains were significantly higher for PVP-I than CHX. PVP-I exhibited a superior killing effect whether measured by rate of kill or final LRF achieved. This difference was highly significant as judged by analysis of variance (P less than 0.001). Full efficacy of an antiseptic has been defined as a safe LRF greater than five. Over the dilution range 25-200 this was achieved by CHX with only three of 33 strains. In contrast, PVP-I achieved full efficacy with all 33 strains.

Chlorhexidine↗
PubMed1992

Lack of [3H]quinuclidinyl benzylate binding to biologically relevant binding sites on mononuclear cells.

We analyzed the binding characteristics of [3H]quinuclidinyl benzylate ([3H]QNB), a muscarinic cholinergic ligand, to rat and human mononuclear cells (MNC). Under various assay conditions, atropine-sensitive, saturable binding occurred with an apparent Kd of 10 nM. Conditions which disrupted the MNC membrane reduced total binding and eliminated specific binding. Muscarinic agonists were unable to inhibit [3H]QNB binding to MNC at concentrations up to 10(-2) M. Stereoisomers dexetimide and levetimide were equipotent inhibitors of binding (IC50 2 x 10(-5) M). We conclude that, although atropine-sensitive binding of [3H]QNB to MNC occurs, the binding is not consistent with the presence of a biologically relevant muscarinic cholinergic receptor.

Adult↗
PubMed1992

Occupancy of CD72 (the CD5 counterstructure) enhances interleukin-4-dependent CD23 expression in resting B lymphocytes.

CD72, the human homologue of murine Lyb-2, was recently identified as a counterstructure to CD5. An antibody to CD72 (BU40) has been found to mimic interleukin-4 (IL-4) both in its ability to activate resting B cells into the early G1 phase of cell cycle and to augment the expression of major histocompatibility complex (MHC) class II antigen; unlike IL-4, the CD72-clustered antibody fails to induce the expression of CD23. We now report that engagement of CD72 by the IgG monoclonal antibody BU40 potentiates the capacity of IL-4--when used at optimal concentrations--to promote CD23 production in human B cells. The degree of enhancement arising from occupancy of CD72 ranged from two- to fivefold. Importantly, antibody to CD72 was also found to diminish the concentration required for IL-4 to promote CD23 expression to a level equivalent to that maximally achieved when using IL-4 alone. Engagement of CD72 by BU40 not only increased the amount of cell-associated CD23 induced by IL-4 but also led to augmented release of soluble material into the culture medium. Monovalent Fab fragments of BU40 antibody were as efficient as intact antibodies at synergizing with IL-4 for enhanced expression and release of CD23: thus simple tethering without the need for receptor cross-linking was sufficient to invoke change through CD72. Enhancement of CD23 expression via CD72 appeared to be selective for IL-4-dependent induction: the turn on of CD23 by tumour-promoting phorbol ester was left unaltered on the addition of BU40 antibody. Engagement of CD72 had no effect on the IL-4-promoted hyperexpression of surface IgM. The findings are discussed within the context of the molecular and functional interactions occurring during T-B collaboration.

Antibodies, Monoclonal↗
PubMed1979

Effect of intracerebral vasculitis on regional cerebral blood flow.

Regional cerebral blood flow was measured by the xenon 133-inhalation method in a 40-year-old man during an acute exacerbation of intracranial vasculitis. Neurologic function was quantitated by the Halstead-Reitan Neuropsychological test battery. The patient was also studied during remission that was induced by steroid therapy. Vasculitis produced a diffuse encephalopathy with generalized reduction in cerebral blood flow. During remission, only local symptoms secondary to a small cerebral infarction remained and regional cerebral blood flow returned to the normal range. There seems to be a close correlation between the severity of symptoms in cerebral vasculitis and reduction of flow through diseased vessels.

Adult↗
PubMed1979

Chronic myelomonocytic leukemia with paraproteinemia but no detectable plasmacytosis: a detailed cytological and immunological study.

A patient with chronic myelomonocytic leukemia with IgG K paraproteinemia, but no detectable plasmacytosis, is described. The patient was entering a blastic phase at the time of the most detailed studies. Cytological, cytochemical, and ultrastructural studies revealed a mixed myeloid proliferation with granulocytic forms predominating over monocytic elements. A variety of ultrastructural abnormalities, including defective granulation, was observed but no cells with highly developed rough endoplasmic reticulum were observed. Immunological marker studies showed that the mature myeloid cells possessed receptors for the Fc of IgG and weakly expressed the Ia-like P29/34 antigen. The mature myeloid cells also expressed both surface and intracytoplasmic Ig restricted to IgG K, and this IgG K persisted after 4 weeks in culture. A reverse plaque assay showed that the myeloid cells were capable of releasing IgG K in vitro, but studies involving the incorporation of radio-labeled amino acids showed no detectable Ig production by the myeloid cells. The possible interpretations of these data are discussed in some detail in relation to previous reports of paraproteinemia in myeloid proliferative disorders.

Aged↗
PubMed1979

Cell separation with staphylococcal protein A immunoadsorbent surfaces.

An 'indirect" cell separation technique was developed using protein A, in which each specific antiserum was first reacted with the cells to be processed. Separation was then achieved on antibody/protein A immunoadsorbent surfaces, where the final antibody coupled to the protein A was one which was directed against the specific antisera previously reacted with the cells. Only small volumes of specific antisera were required to effect separation either on a small or large scale with excellent specificity, cell viability and total cell recoveries. Theoretically, the technique would function with any Ig class of specific antisera from any species and would not be restricted to mammalian protein A binding IgG specific antisera, allowing considerable expansion in the number of antisera able to be utilized.

Antibodies↗
PubMed1979

The B lymphocyte-deprived mouse as a tool in immunobiology.

The purpose of this article is to demonstrate that mice subjected to continuous injections with anti-IgM antibodies, initiated within one day of birth, or in adulthood, lose all their B lymphocyte functions, but retain T lymphocyte reactivity. The B lymphocyte status of these mice was analyzed by histology, radioautography, serum immunoglobulin levels, the antibody response and reactivity to LPS in vitro. T lymphocyte functions were evaluated in vivo by tumor allograft rejection, contact sensitization, and in vitro by reactivity to mitogens and allogeneic cells. On the basis of the results described, it is suggested that the anti-IgM-treated mouse may be considered as a balid and useful experimental model of the "T mouse".

Aging↗
PubMed1979

Multiple phosphorylation of ribosomal protein S6 during transition of quiescent 3T3 cells into early G1, and cellular compartmentalization of the phosphate donor.

At 5 min after quiescent cells are induced to enter G1 there is a large increase in the amount of 32P incorporated into 40S ribosomal protein S6. Here we show that changes in the specific activities of 32Pi and [gamma-32P]ATP in stimulated as compared to quiescent cultures do not account for this large increase. Instead, we demonstrate by decreased electrophoretic mobility on two-dimensional polyacrylamide gels that this increase is due to a quantitative increase in the total amount of phosphate incorporated into S6. Furthermore, pulse-chase experiments show that the phosphate that is incorporated into S6 is metabolically stable during at least the first 60 min of induction and that the incorporation of 32P into S6 responds immediately to the replacement of 32Pi by Pi in the medium, in contrast to [gamma-32P]ATP which changes very slowly. Thus, the S6 phosphate donor must be a compartment separate from that of the total cellular ATP.

Adenosine Triphosphate↗
PubMed1979

Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.

A method has been devised for the electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets. The method results in quantitative transfer of ribosomal proteins from gels containing urea. For sodium dodecyl sulfate gels, the original band pattern was obtained with no loss of resolution, but the transfer was not quantitative. The method allows detection of proteins by autoradiography and is simpler than conventional procedures. The immobilized proteins were detectable by immunological procedures. All additional binding capacity on the nitrocellulose was blocked with excess protein; then a specific antibody was bound and, finally, a second antibody directed against the first antibody. The second antibody was either radioactively labeled or conjugated to fluorescein or to peroxidase. The specific protein was then detected by either autoradiography, under UV light, or by the peroxidase reaction product, respectively. In the latter case, as little as 100 pg of protein was clearly detectable. It is anticipated that the procedure will be applicable to analysis of a wide variety of proteins with specific reactions or ligands.

Animals↗