Search PubMed⌕ Search

Biomedical subjects

J Gordon

Publications and source records attributed to J Gordon.

At least 325 records · Page 18Linked to original sources
PubMed1986

Autocrine growth of human B lymphocytes: maintained response to autostimulatory factors is the special feature of immortalization by Epstein-Barr virus--a hypothesis.

The autocrine growth profile of human B lymphocytes transformed with Epstein-Barr virus (EBV) was found to comprise three distinct components: a B-cell growth factor (BCGF); an interleukin-1 (IL-1)-like activity; an activity requiring cell-to-cell contact for its action. Observations on the inhibition of the EBV-carrying Daudi lymphoma line by alpha-interferon indicated that loss of response to these autostimulatory factors was underlying growth cessation. Furthermore, a putative receptor for BCGF was found to be down-regulated on B cells stimulated with non-transforming mitogens but constitutively expressed following EBV-transformation. Taken together with recent evidence that normal B cells produce autostimulatory factors, these findings suggest that the special feature of autocrine growth by EBV-immortalized cells is a maintenance of what should normally be a transient phenotype, possibly through deregulation of receptor expression. This hypothesis is discussed.

B-Lymphocytes↗
PubMed1986

The repertoire of anti-TNP antibodies in mice neonatally suppressed with anti-IgM.

Previous studies have shown that mice immunized with TNP-Ficoll when young, adult, or aged expressed different repertoires of anti-TNP antibodies. The aim of the present study was to find out whether this age-related nonrandom progression was driven by antigen, and whether it was regulated by the immune network through surface-Ig receptors on B lymphocytes. The approach utilized was to block receptor expression on B lymphocytes of mice by the chronic administration of anti-IgM from birth for approximately 1 year, and then compare their subsequent antibody response to that of age-matched control animals. The results obtained have shown that the age-dependent shift in the anti-TNP repertoire expressed could take place in animals whose B lymphocytes were blind to antigen and anti-id for the greater part of their lives and thus suggest that the regulatory events responsible for this shift may be (surface Ig) receptor independent.

Animals↗
PubMed1986

Concentration of doxycycline in human gingival fluid.

Doxycycline is a synthetic tetracycline compound whose main advantages over tetracycline hydrochloride are increased oral absorption, prolonged serum half-life and decreased gastrointestinal side-effects. The purpose of this study was to measure the concentration of doxycycline in gingival fluid and blood after oral administration. 4 volunteers were given doses of 100 mg doxycycline every 12 h on the first day of antibiotic administration followed by a maintenance dose of 100 mg per day for an additional 4 days. 3 of these volunteers were also given tetracycline hydrochloride every 6 h for 5 days either 1 month before or after doxycycline administration to compare gingival fluid levels of these 2 tetracycline compounds. Gingival fluid was sampled from 4 gingival sites in each volunteer at hourly intervals from hours 0 to 6, 9, 24, 27, 48 to 54, 57, 72, 75, 96 to 102 and 105. Blood was sampled by finger puncture at hours 0, 3, 6, 24, 48, 54, 72, 96 and 102. Antibiotic levels in gingival fluid and blood were measured using an agar diffusion assay method. The results demonstrated that doxycycline achieved much higher levels in the gingival fluid than in blood and yielded comparable gingival fluid levels to those achieved by tetracycline hydrochloride. Doxycycline levels in gingival fluid ranged between 1.2 micrograms/ml and 8.1 micrograms/ml in the first 24 h and generally achieved 3-10 micrograms/ml after 48 h. Blood levels after 48 h ranged between 2.1 micrograms/ml and 2.9 micrograms/ml. Tetracycline hydrochloride in gingival fluid after 48 h was generally in the range of 4 micrograms/ml-10 micrograms/ml with blood levels between 2.2 micrograms/ml and 3.4 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1986

Operation and performance of an automatic metaphase finder based on the MRC fast interval processor.

The Medical Research Council's fast interval processor (FIP) has been adapted for metaphase finding and selection. This article summarizes recent improvements to the hardware, and describes the selection of image features. The system uses a highly simplified but effective clustering procedure to reduce computation time, and incorporates a ranking algorithm based on computed cluster features so that high-quality metaphases can be preferentially selected. Experimental results indicate that the system can detect high-quality metaphases rapidly in "rich" material and a high proportion of the available metaphases in "sparse" material. It can handle a wide range of material with good repeatability of performance.

Automation↗
PubMed1986

Inosiplex treatment of acquired immunodeficiencies: a clinical model for effective immunomodulation.

Patients with various conditions associated with immunologic deficiency (cancer, radiotherapy, surgery, burns, aging, prodromal Acquired Immunodeficiency Syndrome, were treated with inosiplex (INPX) at a dose of 3-4 g/day for periods of time ranging from 1 week to several months. Patients were evaluated clinically, and immunologically with the following assays; natural killer (NK) cytotoxicity, T-lymphocyte count, mitogen-induced proliferation, E rosettes, and skin test reactivity. The data resulting from this large and varied population were quite consistent and reproducible, and indicated that INPX treatment was effective in simultaneously reducing the incidence of complications, infections and mortality while enhancing the immune status of the patient. It has therefore been concluded that an immunopharmacologically active agent such as INPX can elicit important clinical benefits in patients with disorders of diverse etiology, perhaps through modulation of an immunologic defect that is common to a variety of seemingly unrelated conditions.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Control of human B-lymphocyte replication. I. Characterization of novel activation states that precede the entry of G0 B cells into cycle.

Tonsillar B lymphocytes of a particularly high buoyant density were prepared essentially free of contaminating monocytes and T cells. When exposed to anti-immunoglobulin, such cells initiated the hydrolysis of inositol phospholipids. This provides a postulated 'dual signal' for growth through the liberation of intracellular calcium stores and the activation of protein kinase C. Nevertheless, neither anti-immunoglobulin nor direct agonists of this bifurcating pathway (respectively, calcium ionophore and the phorbol ester TPA) were capable, when used alone, of driving cells out of G0 and into RNA synthesis. All three agents did, however, induce two activation antigens at the surface of G0 B cells, which included CD23, p45 and a lineage-unrestricted antigen identified by the monoclonal antibody BK.19.9. Cells that had been exposed to calcium ionophore, but not those activated with either TPA or anti-immunoglobulin, revealed further change indicated by an increased accessibility of their native DNA for the intercalating dye acridine orange. Cells receiving full mitogenic signals in the form of Staphylococcus aureus Cowan Strain I (SAC) or a combination of TPA and calcium ionophore showed the same initial sequelae but continued to enter the cell cycle and progress through to DNA synthesis. The observations identify two phases in the early activation of human B cells, both in terms of various temporal events, and the signals required to promote each activation state. before entering the proliferative cycle. Thus, the exit of human B cells from G0 appears subject to multiple controls that precede those associated with G1 and later phases of the cell cycle.

Antigens, Surface↗
PubMed1986

Control of human B-lymphocyte replication. II. Transforming Epstein-Barr virus exploits three distinct viral signals to undermine three separate control points in B-cell growth.

Highly purified resting (Go) B lymphocytes were monitored for their response to transforming Epstein-Barr virus (B95-8 strain), to a non-transforming mutant (P3HR-1) containing a deletion in the EBNA-2 coding region, and to inactivated virus of either type. All preparations induced an early appearance of two activation antigens, which included the CD23,p45 ("Blast-2') antigen. Thus, virus binding was sufficient for an initial activation step. Further change required an active viral genome. Infection with the P3HR-1 strain prompted the exit of cells out of Go but led to an arrest in the early G1 phase of the cycle. While initially showing sequels to activation indistinguishable from those observed with P3HR-1 virus, cells infected with B95-8 virus continued through G1 to express late activation antigens, enter S-phase and complete the replicative cycle. The addition of the phorbol ester TPA was found to compensate for the abortive cell cycle entry achieved with the P3HR-1 mutant, but could not supplement the minimal activation observed with inactivated virus. These findings demonstrate that the Epstein-Barr virus undermines three separate control points in the growth cycle of human B lymphocytes, and exploits three distinct viral signals to achieve this end.

Antigens, Viral↗
PubMed1986

Autocrine models of B-lymphocyte growth. II. Interleukin-1 supports the proliferation of transformed lymphoblasts but not the stimulation of resting B cells triggered through their receptors for antigen.

Purified, monocyte-derived interleukin-1 (IL-1) was found to provide growth support for Epstein-Barr virus (EBV) transformed B-lymphocytes seeded at densities below which their own autostimulatory factors were limiting. By contrast, highly purified resting B cells triggered via their receptors for antigen failed to respond to identical preparations of IL-1 by DNA synthesis. That successful priming of the B cells had occurred was evidenced by a transient rise in RNA synthesis and the ability of the cells to respond to T-cell supernatants by DNA synthesis. The findings indicate that while IL-1 might perform an autostimulatory function in B lymphocyte proliferation it is not by itself sufficient to provide growth support for resting B cells activated through their receptors for antigen. The implications of these observations for autocrine models of B-cell growth are discussed.

Antibodies, Anti-Idiotypic↗
PubMed1985

Synergism between diacylglycerols and calcium ionophore in the induction of human B cell proliferation mimics the inositol lipid polyphosphate breakdown signals induced by crosslinking surface immunoglobulin.

Resting human tonsillar B cells were stimulated to divide by heat killed Staphylococcus aureus Cowan strain 1 which was shown to induce hydrolysis of phosphatidylinositol 4, 5-bisphosphate known to give rise to diacylglycerol and an increase in cytosolic free calcium. Addition of the diacylglycerols, 1-oleoyl-2 acetyl glycerol or sn-1, 2-dioctanoylglycerol, together with the calcium ionophore ionomycin to B cell cultures induced marked cell proliferation whereas these agents were ineffective when used alone. Both diacylglycerols were shown to compete with [3H] phorbol 12,13 dibutyrate in binding to protein kinase C. These data support the hypothesis that synergism between cytosolic calcium and endogenous diacylglycerol, which activates protein kinase C, is involved in signal transduction in the proliferation of human B cells.

B-Lymphocytes↗
PubMed1985

Size and map locations of early transcription products on the Autographa californica nuclear polyhedrosis virus genome.

The size classes and map locations of early transcripts of Autographa californica nuclear polyhedrosis virus were identified by probing Northern blots with cloned viral DNA fragments. Twelve abundant and 30 minor transcripts were detected by 4 hr postinfection. There was an increase in the abundancy and number of virus-specific transcripts between 6 and 8 hr postinfection, coincident with the onset of DNA replication. The change in transcription pattern did not occur in cells infected at the nonpermissive temperature with a DNA-negative mutant indicating that these early transcripts were synthesized prior to the initiation of viral DNA replication. Two early transcripts, 4.6 and 1.1 kb, mapped to the genomic region of the temperature-sensitive lesion, between 60.1 and 62.0%.

Animals↗
PubMed1985

Antigenic structure of histone H2B.

Antigenic determinants of histone H2B were localized using a series of 23 overlapping fragments of H2B obtained either by chemical and enzymatic cleavage of the histone or by solid-phase peptide synthesis. The ability of peptides to bind H2B antibodies was measured in an enzyme-linked immunosorbent assay, using antisera directed against calf thymus and chicken erythrocyte H2B as well as four anti H2B monoclonal antibodies obtained from autoimmune mice. Seven antigenic determinants were localized in the H2B molecule in the vicinity of residues 1-11, 6-18, 15-25, 26-35, 50-65, 94-113 and 114-125. Two of these determinants (residues 6-18 and 26-35) were revealed only through the binding properties of antibodies isolated from autoimmune mice. The usual correlation between hydrophilicity and antigenicity was found to hold for four of the epitopes, and the N- and C-termini of H2B were both antigenically active.

Amino Acids↗
PubMed1985

Capacity of B-lymphocytic lines of diverse tumor origin to produce and respond to B-cell growth factors: a progression model for B-cell lymphomagenesis.

Human cell lines established from cases of acute lymphoblastic leukemia, lymphosarcoma, Burkitt's lymphoma and multiple myeloma and representing stages of B-lymphocyte development ranging from pre-B through to plasma cells, were assessed for their ability to produce and respond to B-cell growth factors (BCGF). All B-cell lines studied were found to be constitutive producers of a growth activity which assisted the S-phase entry of normal activated B-cells and provided growth support for lymphoblastoid cells transformed by Epstein-Barr virus. Furthermore, all lines responded by enhanced proliferation to supernatants from a BCGF-producing T-cell hybridoma. Not all lines, however, displayed autostimulation to their own supernatants and no tumor B-cell line appeared totally dependent on soluble factors for its growth. Non-tumorigenic B-cell lines, by contrast, revealed a strict dependency on homologous growth factor for their continued proliferation in suspension culture. The findings support a progression model of lymphomagenesis based upon the utilization, production and, ultimately, emancipation from growth-promoting soluble factors.

B-Lymphocytes↗
PubMed1985

Senescence of a human lymphoblastoid clone producing anti-Rhesus(D).

The exploitation of Epstein-Barr virus transformation to generate human lymphoblastoid clones (LCL) producing antibody of predefined specificity has proved highly inefficient. Observations reported here on a cloned LCL producing anti-Rhesus(D) may provide an explanation for the low success rate. Over a few months this clone manifested a progressive loss of capacity to maintain growth in culture. Evidence consistent with terminal differentiation to a cell with the properties of a nonproliferating plasma cell was obtained. These late cells differed from those in the earlier actively cycling phase in that they were no longer able to respond to autostimulatory growth factors although they continued to produce them. This irreversible senescence leading to the death of the clone may be a common feature of virally transformed B cells and this would explain many of the difficulties encountered on this route to the production of human monoclonal antibodies.

Cell Survival↗
PubMed1985

Characterization of chronic lymphocytic leukemia (CLL) cells with low density of surface membrane bound immunoglobulins (smIg).

The study consists of 6 CLL patients with leukemic blood lymphocytes lacking T-cell characteristics and with smIg on only a very small fraction of the cells detected by microscopy or FACS analysis after direct immunofluorescence (IFL) staining. Using B-cell specific monoclonal antibodies all leukemias were found to be of the B-cell type. SmIg, mainly of IgD-class and the monotypic light chain, was detected on a large number of cells in all cases when using direct IFL. No lymphocyte clone was judged to be of the pre-B-cell type or represented fully differentiated terminal B-cells. CLL cells from the individual cases probably represent intermediate B-cell maturation steps. The results lend no support to the suggestion that this subtype of CLL necessarily belongs to an early stage of differentiation just beyond the pre-B-cell level.

Antibodies, Monoclonal↗
PubMed1985

T-cell function in B-lymphocyte-deprived mice.

Previous work has identified selective defect(s) in T cells in mice deprived of B lymphocytes by the chronic administration of anti-IgM antibody. Experiments described in the present communication revealed that anti-IgM-treated mice do not possess T cells with surface Ia and FcR, and, unlike T cells from normal animals, they also fail to bind these molecules in vitro. Functional assays disclosed that an anti-suppressor pathway which relies on Ia+ donor and acceptor T cells is interrupted in these mice at both levels. These observations may provide an insight to explain the selective failure of some T cells when B lymphocytes have been deleted.

Animals↗
PubMed1985

Lymphocyte activation by purified HLA-DR molecules fused into autochthonous "stimulating cells".

Affinity-purified Ia molecules derived from the Daudi cell line were reconstituted into vesicles with Sendai virus envelope glycoproteins. These vesicles inserted into human peripheral leukocytes could induce stimulation of autologous lymphocytes, as measured by thymidine uptake, 6 days later. It is suggested that this method could provide a means to study allostimulation at the molecular level.

Cell Membrane↗
PubMed1985

Behavioral effects of xylamine-induced depletions of brain norepinephrine: interaction with LSD.

Male rats were treated with a combination of systemic fluoxetine and intraventricular xylamine (under ether anesthesia) to deplete brain norepinephrine (NE) in the projection areas of the locus coeruleus. Four days later, control and lesioned rats were tested following injections of either saline or 80 micrograms/kg LSD in a Behavioral Pattern Monitor which recorded the sequential patterns of their locomotor and investigatory (holepokes) responses. Liquid chromatographic measures of brain monoamines confirmed that xylamine reduced hippocampal NE by 80.8% and hypothalamic NE by 26% without affecting levels of serotonin or dopamine. Relative to controls, NE-depleted rats exhibited repetitive spatial patterns of locomotion with no alteration in the amount or rate of habituation of locomotor activity. Lesioned animals made fewer rearings and holepokes, particularly early in the hour test session. When given 80 micrograms/kg LSD, sham-lesioned rats exhibited the expected decreases in entries into and time spent in the center of the chamber, an increase in time spent in the corners, and fewer holepokes and rearings early in the session. With the exception of the effect on rearings and holepokes, the effects of LSD were diminished in rats depleted of brain NE. These results indicate that this profile of behavioral effects of LSD, which has been interpreted as a potentiation of neophobia, may be dependent upon the noradrenergic projections of the locus coeruleus.

Animals↗