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Biomedical subjects

J Gordon

Publications and source records attributed to J Gordon.

At least 289 records · Page 16Linked to original sources
PubMed1988

Soluble CD23 is released by B lymphocytes cycling in response to interleukin 4 and anti-Bp50 (CDw40).

An enzyme-linked immunoassay was developed to quantitate the production of soluble CD23 from cycling B lymphocytes. This molecule has identity both with B cell-derived B cell growth factor and with an IgE-binding factor. B lymphocytes, which had been stimulated for 3 days with phorbol dibutyrate and calcium ionophore, washed and recultured, failed to produce detectable levels of CD23 over the following 3 days. Soluble CD23 was found, however, in the supernatant of cultures where recombinant interleukin 4 had been included. The level of CD23 rose dramatically when anti-Bp50 had also been added. By contrast, anti-Bp50, alone or together with low molecular weight T cell-derived B cell growth factor, failed to promote the release of CD23 in detectable amounts. There was a strong correlation between the appearance of soluble CD23 in culture supernatants and the expression of CD23 on the surface of restimulated cells. The level of CD23 release appeared to relate more to the continued cycling of cells than to their differentiation to immunoglobulin secretion. These findings are discussed with particular emphasis on the role of CD23 as an important multi-functional lymphokine in B lymphocyte physiology.

B-Lymphocytes↗
PubMed1988

Interleukin 4 and soluble CD23 as progression factors for human B lymphocytes: analysis of their interactions with agonists of the phosphoinositide "dual pathway" of signalling.

Human B lymphocytes pre-activated for 24 h with a combination of phorbol dibutyrate [P(Bu)2] and ionomycin were found to provide excellent targets for assessing the detailed action of B cell progression factors. Both recombinant interleukin 4 (IL 4) and affinity-purified 25-kDa fragment of the CD23 molecule (sol-CD23) were shown to be active in this assay. While the progression activity of IL 4 was enhanced by continued co-culture with P(Bu)2, that of sol-CD23 was found to be more strictly dependent upon such a joint application with the phorbol ester. Similar requirements were observed for triggering cell-cycle progression in the pre-activated B cells when using a stimulating CD23 antibody. Ionomycin, in contrast to P(Bu)2, did not augment either IL 4 or sol-CD23 in these assays but did enhance significantly the progression activity of an anti-CDw40 antibody. When added to B cells concomitantly with, or prior to, a high dose of phorbol ester, IL 4 unexpectedly down-regulated the subsequent mitogenic response to this agent whereas, when added 24 h later, IL 4 up-regulated such stimulations. The latter sequence of additions resulted in a particularly dramatic induction of CD23 at the B cell surface, much more so than seen when B cells were incubated with either IL 4 alone or with IL 4 and P(Bu)2 together. This up-regulation of surface CD23 was, in turn, mirrored by the appearance of large amounts of the soluble form of the molecule in such cultures. The findings are discussed with reference to possible mechanisms through which IL 4 and CD23 interact to exert their multiple actions on B cell regulatory pathways.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1988

Asymmetries in ON and OFF visual pathways of humans revealed using contrast-evoked cortical potentials.

Positive- and negative-contrast stimuli yield the perceptions of brightness and darkness, respectively, and are processed separately by ON and OFF neural pathways. The properties of these morphologically and pharmacologically distinct subsystems were measured in humans by recording visual evoked potentials (VEPs). These electrical responses from the visual cortex were elicited by novel positive- and negative-contrast stimuli, designed to emphasize, selectively, contributions from ON and OFF pathways. Results revealed differential processing of the two types of contrast information, suggesting asymmetries in ON and OFF subsystems; OFF subsystems have finer spatial tuning and greater contrast gain than ON subsystems. These VEPs may be useful in diagnosing neurological disorders that involve primarily one subsystem.

Adult↗
PubMed1988

A comparison of alternative theoretical approaches to smoking cessation and relapse.

Two theoretical approaches to smoking cessation were compared. Participants were randomly assigned either to (a) a traditional treatment program that used contingency contracting and that emphasized the necessity for absolute abstinence (AA) or to (b) a relapse-prevention (RP) treatment that focused on gradual acquisition of nonsmoking skills. It was hypothesized that participants in the RP treatment would be less successful initially but would have better maintenance skills and thus would relapse less during a 1-year follow-up period. Each program was evaluated in two formats: group-based treatment and self-help materials. Results indicated comparable 1-year abstinence rates for all treatments, although more participants dropped out of the self-help formats. Participants in the RP intervention were more likely to lapse sooner after quitting and were more likely to quit again during the 1-year maintenance period. Exploratory analyses of successful participants suggested that women were more successful in the RP program and that men had greater success with the AA approach.

Adult↗
PubMed1988

Acute airway obstruction in a seven-month-old infant with epiglottitis.

A seven-month-old male infant with epiglottitis developed acute airway obstruction in the operating room during halothane induction. This case suggests that epiglottitis should be suspected in any child, regardless of age, who presents with stridor, respiratory distress, dysphagia, or "tripoding," and it reiterates the need for prompt airway management.

Acute Disease↗
PubMed1988

Identification of simulated patients by interns in a casualty setting.

Fifty-four interns agreed to a study in which their clinical performance in an out-patient unit with standardized patients was recorded on videotape. In order to examine whether they could distinguish standardized from real patients, the interns were asked to note any patients who they thought might be simulating their complaints and report these to the researchers at the end of each 2-day period of study. Thirty-two of the interns were assessed again at the end of their internship, using the same clinical problems presented by different simulators. The consultations took place in the casualty department of a large urban hospital. At the beginning of the year there were 152 consultations with standardized patients and 328 consultations with appropriate genuine patients. Standardized patients were identified definitely as 'not genuine' in only 12 of the 152 consultations (sensitivity 7.8%) whereas 320 of the 328 genuine consultations were accepted by the interns as genuine (specificity 97.8%). When the level of confidence required to distinguish the two groups was reduced from 'definite' to 'probable', the number of correctly identified simulator consultations increased to 36/152 (27%) but the rate of misclassification of genuine patients also increased from 8 to 37 out of 328 consultations (11%). At the end of the year there were 81 consultations with standardized patients and 149 consultations with genuine patients. Identification rates were only slightly changed. We conclude that simulator identification is not a problem in applying standardized patients to evaluate the quality of care provided in a hospital casualty.

Clinical Competence↗
PubMed1988

Buoyant density characterization of neoplastic cell populations in patients with chronic B-lymphocytic leukemia.

Leukemic cells from a series of patients with chronic B-lymphocytic leukemia (CLL) were analyzed for their buoyant density on discontinuous Percoll gradients. The density profile varied markedly between different patients and also between samples from different body compartments within the same patient. A good correlation was observed between buoyant density and maturation stage of the leukemic clones as judged by Ig-expression and their reactivity with a panel of monoclonal antibodies. Phorbol-ester-induced changes in the leukemic cells were found to be accompanied by a general decrease in their buoyant density. No correlation between density and clinical parameters such as cell counts, clinical stage and survival could be noted. Buoyant density characterization of leukemic B-cell populations is seen as a useful, rapid and simple marker of compartmentalization within the B-lymphocyte maturation spectrum but its clinical relevance remains to be established.

Antigens, Surface↗
PubMed1988

Molecular characterization of a prominent antigen of the vaccinia virus envelope.

During vaccinia virus (VV) assembly a major polypeptide migrating with an apparent MW of 35K, designated Ag35, is expressed as an early function and becomes an integral component of the lipoprotein envelope surrounding the mature virion. In a previous study evaluating humoral immunity to VV, a prominent response against Ag35 was invariably detected in immunized mice. In the context of our continuing investigations of the structure and function of the vaccinia envelope, with a view to alteration in antigenicity of this agent when used as a vaccine vector for foreign antigens, we carried out detailed mapping of the Ag35 gene, as well as determination of the nucleotide sequence. Use of hybridization-arrested translation, coupled with immunoprecipitation, located this gene within a 2.7-kbp EcoRI fragment of the larger 8.7-kbp HindIII H fragment. By means of S1 endonuclease resistance analysis a viral transcript was identified at the site of the Ag35 gene, where the occurrence of an open reading frame (ORF), corresponding to the transcript, was deduced from DNA sequence determination. However, the ORF encodes a polypeptide of only 22,300 Da predicted MW, which is much lower than the apparent MW estimated from SDS-polyacrylamide gel electrophoresis. The size discrepancy is not due to glycosylation or phosphorylation of Ag35 but may result from a proline-rich sequence which occurs in this polypeptide. To confirm that the ORF recognized in this study does, indeed, encode Ag35, the gene was expressed as a beta-galactosidase fusion protein in pUC19; Escherichia coli transformed with the relevant clones expressed a polypeptide of the appropriate molecular weight and antigenicity, when tested by Western blots. Regarding secondary structure and hydropathicity it can be predicted from the DNA sequence that Ag35 is highly hydrophilic but contains a hydrophobic region at the carboxy terminus, perhaps providing the stretch involved in membrane insertion. Computer search of a bank of protein sequences revealed an unusually strong similarity of 68% between the Ag35 at amino acid positions 44-121 and the G glycoprotein of respiratory syncytial virus at positions 189-264.

Antigens, Viral↗
PubMed1988

Role of cytokines in the restoration of the delayed-type hypersensitivity reaction of anergic patients.

Soluble mediators from peripheral blood lymphocytes activated either by skin test antigens or by alloantigens restored the delayed type hypersensitivity (DTH) reaction in the majority of anergic surgical patients who are at increased risk for sepsis and mortality. Antigen had to be injected together with the mediators and the individual had to be reactive to the antigen for restoration. These results suggest that restoration of the DTH response depends on the ability of cytokines produced and acting in a non-specific manner to promote the response of the anergic patients' specific antigen-sensitive cells to antigen.

Aged↗
PubMed1988

Stimulation of B-chronic lymphocytic leukemia populations by recombinant interleukin-4 and other defined growth-promoting agents.

Monoclonal populations from 10 cases of phenotypically well-characterized B-chronic lymphocytic leukemia (B-CLL) and from a single case of hairy cell leukemia were assessed for their ability to respond by mitogenic stimulation to a number of agents described as growth-promoting for normal B cells. These included the recombinant factors interleukin-1 (IL1), IL2, IL4, IL5, and gamma-interferon, partially purified B cell growth factor (BCGF), B cell stimulatory factor 2 (BSF2), and a CDw40 antibody to the Bp50 antigen. With only few exceptions, no factor or combination of factors stimulated B-CLL populations directly to DNA synthesis. By marked contrast, the hairy cells were responsive to IL4, BCGF, and the CDw40 antibody. B-CLL cells could become responsive with the inclusion of the phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) as co-stimulant such that half of the populations were now activated by IL4, particularly when BCGF was also present. Populations refractory to IL4 were, nonetheless, still responsive to BCGF. In only three cases was a significant effect seen with IL2. gamma-interferon could be either inhibitory or stimulatory and, in a few cases, modulated specifically the effects of IL4. In contrast to normal B cell activations, neither the CDw40 antibody nor a calcium ionophore synergized with TPA for stimulating the majority of B-CLL populations. BSF2 was stimulatory in the two cases examined while both IL1 and IL5 were ineffective where studied. No simple correlation was observed between the patterns of responsiveness and the expression of a panel of CD markers assayed on cells both freshly isolated and after TPA stimulation. The data demonstrate a functional heterogeneity not disclosed by simple phenotypic analysis and also indicate the range of activities which can impinge on the growth regulation of monoclonal B cell populations.

Antibodies, Monoclonal↗
PubMed1988

The marmoset B-lymphoblastoid cell line (B95-8) produces and responds to B-cell growth and differentiation factors: role of shed CD23 (sCD23).

The EBV-producing marmoset B-cell line (B95-8), commonly used as a source of EBV for stimulation and transformation of human B cells, was shown to proliferate in response to supernatants containing human B-cell growth factors (BCGF) derived from PHA-activated T cells or the KG-la cell line, and to a commercial low molecular weight BCGF (BCGFlow), but not to recombinant human IL-4 (rhIL-4). In this respect, B95-8 responded in much the same way as human EBV-transformed lymphoblastoid cell lines (LCL). In contrast, B95-8 did not secrete immunoglobulin in response to B-cell differentiation factor (BCDF) containing supernatants from the KG-la cell line, nor to BCGFlow, or IL-6 obtained from the T24 bladder carcinoma cell line, whereas significant responses were obtained with human EBV-transformed LCL. Both B95-8 and control EBV-transformed human LCL secreted BCGF and BCDF detected with the indicator B-cell lines CESS, L4, and HFB1, but only the human LCL secreted BCGF detectable in co-stimulation assays with TPA-activated tonsillar B cells. Unlike EBV-transformed LCL, B95-8 did not express detectable surface CD23, and did not release into the culture medium soluble CD23 (sCD23) recognized by an EIA for the human molecule. Although not releasing detectable sCD23, B95-8 cells did proliferate in response to purified human sCD23, and were found to be 1000 times more sensitive in this assay than EBV-transformed LCL. This may provide a basis for a sensitive bioassay for sCD23. Unlike EBV-transformed LCL, it seems that in vitro proliferation of B95-8 may involve an autocrine loop which does not depend on CD23.

Animals↗
PubMed1988

Mitogenic stimulation of human B lymphocytes via the inositol phospholipid 'dual pathway' of signalling requires persistent activation of both second messenger arms.

Highly purified resting tonsillar B lymphocytes mount an efficient mitogenic response on exposure to appropriate combinations of tumour-promoting phorbol esters and calcium ionophores, agents that mimic the biochemical second messengers generated through the cross-linking of surface immunoglobulins. By using agents that bind reversibly we show here that both signals need to be applied continuously in order for cells to proceed optimally to DNA synthesis. The data are consistent with the notion that, in the absence of 'help' from T lymphocytes or antigen-presenting cells, a chronic, persistent stimulation through antigen receptors is necessary to elicit a significant B-cell response.

B-Lymphocytes↗
PubMed1987

Molecular cloning and in vivo expression of a precursor to rat mitochondrial aspartate aminotransferase.

A 2.4 kilobase cDNA for rat mitochondrial aspartate aminotransferase (E.C. 2.6.1.1.) was isolated and sequenced. The predicted presequence is 93% homologous to the presequences of the enzyme from pig and mouse. The predicted amino acid sequence of the mature enzyme differs from that determined directly by amino acid sequencing (Huynh, Q.K., Sakakibara, R., Watanabe, T., and Wada, H. (1981) J. Biochem. (Tokyo) 90, 863-875) at 13 amino acids residues. The most important difference is at position 140 where the cDNA encodes a tryptophanyl residue rather than the previously reported glycine. This critical residue is now seen to be conserved in all aspartate aminotransferases. The coding region of this cDNA was inserted into the plasmid cloning vector pKK233-2 and used to stably express an unfused precursor in Escherichia coli JM105.

Amino Acid Sequence↗
PubMed1987

Skin window chambers, a novel method for recovering the cells involved in delayed-type hypersensitivity.

A method is described for the recovery of cells involved in the delayed-type hypersensitivity (DTH) reaction in man. A small plastic chamber was placed over DTH sites from which the stratum corneum had been removed by tape stripping. The chambers were then filled with serum. Analysis of cells harvested at 24 and 48 h has shown an antigen-dependent increment in mononuclear and polymorphonuclear cells in donors with a DTH response. T cell clones were established from the recovered cells; these will provide a useful adjunct to a functional analysis of cells participating in the DTH reaction.

Adult↗
PubMed1987

Anti-proliferative effects of interferons on Daudi Burkitt lymphoma cells: induction of cell differentiation and loss of response to autocrine growth factors.

Treatment of Daudi B-lymphoblastoid cells with low concentrations of either natural or recombinant human alpha-interferons inhibits cell proliferation and modulates the expression of a number of cell-surface antigens. Using a panel of monoclonal antibodies (MAbs) identifying determinants expressed at the surface of normal plasma cells, and polyclonal antibodies against surface and cytoplasmic immunoglobulin, we have found that growth inhibition is accompanied by plasmacytoid differentiation. Assays of growth stimulation of heterologous cells indicate that the culture medium from interferon-treated Daudi cells contains substantially more B-cell growth factor activity than that from control cells. However, the interferon-treated cells exhibit an impaired ability to respond to both these autocrine factors and exogenous factors produced by another Burkitt lymphoma line. These findings show that, in the case of Daudi cells, growth inhibition by interferons is closely associated with both terminal differentiation and a refractoriness to growth factors. In this system IFN-alpha may therefore be considered to be a B-cell differentiation factor, suggesting a possible basis for the anti-proliferative effects observed with certain human B-cell malignancies.

Antibodies, Monoclonal↗