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J Gordon

Publications and source records attributed to J Gordon.

At least 37 records · Page 2Linked to original sources
PubMed1996

Transforming growth factor-beta 1 cooperates with anti-immunoglobulin for the induction of apoptosis in group I (biopsy-like) Burkitt lymphoma cell lines.

Group I Burkitt lymphoma (BL) cell lines, which retain the original biopsy phenotype, have been shown to enter apoptosis in response to a number of external stimuli including serum deprivation, thermal shock, addition of calcium ionophore, and ligation of surface immunoglobulin (Ig) by antibody. Transforming growth factor-beta 1 (TGF beta 1) is known to cause growth arrest in BL lines. Here we show that while it is by itself capable of promoting some degree of apoptosis in group IBL cells, TGF beta 1 cooperates with anti-immunoglobulin to this end. Trimeric soluble recombinant human CD40 ligand (sCD40L) was able to inhibit apoptosis induced by the combination of agonists to some degree, but such rescue proved to be short-lived. Both TGF beta 1 and anti-Ig individually caused BL cells to undergo growth arrest at the G1 phase of cell cycle before their entry into apoptosis: the consequence of sCD40L addition was to maintain the cells in cycle for longer. No induction of the apoptosis-protecting gene, bcl-2, occurred in the presence of sCD40L. These findings are discussed, particularly highlighting the relationship existing between survival and the cell cycle. The strong cooperative effects observed between anti-Ig and TGF beta 1 in promoting apoptosis and the inability of CD40 to signal for long-term rescue raise the potential for a novel therapeutic attack on B-cell lymphoma.

Animals↗
PubMed1996

Cerebral demyelination syndrome in a patient treated with 5-fluorouracil and levamisole. The use of thallium SPECT imaging to assist in noninvasive diagnosis--a case report.

BACKGROUND: The use of 5-fluorouracil (5-FU) and levamisole in patients with Stage III adenocarcinoma of the colon has now become standard. There have been several reports of a multifocal cerebral demyelination syndrome following 5-FU and levamisole administration. METHODS: We describe a patient who developed focal neurologic symptoms while being treated with levamisole and 5-FU in whom the diagnosis of central nervous system (CNS) metastases was considered. RESULTS: A magnetic resonance imaging (MRI) scan showed a diffuse, multifocal white matter process. Diagnostic evaluation did not support a diagnosis of CNS metastasis. 201Thallium chloride single photon emission computed tomography (SPECT) study was cold. A stereotactic brain biopsy disclosed demyelination but not tumor. The patient had complete functional resolution of symptoms with 1 month of dexamethasone therapy, although follow-up MRI scans have shown persistent abnormality on T2-weighted images. CONCLUSIONS: In patients receiving 5-FU and levamisole who develop focal neurologic symptoms with an abnormal MRI scan, the diagnosis of CNS metastasis should not be made without a thorough diagnostic evaluation. We suggest the use of 201thallium chloride SPECT imaging to support the diagnosis of multifocal leukoencephalopathy related to 5-FU and levamisole. In atypical cases, a stereotactic brain biopsy may be required for confirmation.

Adenocarcinoma↗
PubMed1996

Signals for survival and apoptosis in normal and neoplastic B lymphocytes.

B lymphocytes are subject to selection within germinal centers following somatic hyper-mutation on immunoglobulin variable region genes based on their ability to bind antigen with high affinity. Non-selected cells die by apoptosis. Tumors with features of germinal center B cells include follicular center cell lymphoma and Burkitt's lymphoma. We have used the latter extensively as a neoplastic model of germinal center cells and have compared directly the behaviour of cell lines derived from biopsy material with that of the normal counterparts. Here we describe some of our findings in the two systems with regard to signals regulating survival and apoptosis.

Animals↗
PubMed1996

The utility of optical waveguide DNA array hybridization and melting for rapid resolution of mismatches, and for detection of minor mutant components in the presence of a majority of wild type sequence: Statistical model and supporting data.

We have derived a statistical model to determine binding and dissociation kinetics of oligonucleotide-antibody-microparticle complexes to oligonucleotides on a surface illuminated by the evanescent wave. The model supports the extremely rapid binding kinetics previously observed and predicts very rapid thermal dissociation kinetics. Experimental results confirmed the model and showed that the most rapid heating available achieved meltoff in 8 s with discrimination of single base differences. Similarly, a model of particulate labels with multiple points of interaction predicted that the system would be very sensitive to a minority of matched interactions in the presence of a majority of mismatched interactions. Conversely, the system would be relatively insensitive to the presence of a higher proportion of matched species. These predictions are born out by experiment. A 1:10 mixture of matched:mismatched gave a melting curve which was approximately the sum of melting curves of the two species alone, and a 50:50 mixture gave a melting curve almost indistinguishable from the highest melting component. Thus, the system will be amenable to detection of infrequent mutations in the presence of an excess of the wild type allele provided the mutant sequence is present on the chip. Further, it lends itself to high throughput automation due to the rapidity with which the thermal melt can be achieved.

DNA↗
PubMed1996

Laser-Doppler flowmetry measurements of subcortical blood flow changes after fluid percussion brain injury in rats.

Laser-Doppler flowmetry (LDF) was used to record subcortical cerebral blood flow in hippocampus and striatum immediately following parasaggital fluid percussion brain injuries of mild to moderate severity (2.58 +/- 0.09 atm, 10-11 msec duration) in spontaneously breathing anesthetized rats. At 5 min postinjury, mean blood flow decreased bilaterally by 20-30% in both brain structures, and remained significantly reduced during the remainder of the 60 min postinjury recording interval. Blood flow did not change in the sham-injured rats. Subsequent beam-walk, beam-balance, and rope-hang assessments revealed significant neurological impairments in the injured rats but not in the sham controls. The magnitude of the blood flow changes and the severity of the ensuing neurological impairment were significantly correlated. Histopathological assessments revealed hemorrhagic contusions within ipsilateral cortical regions, occasional neuronal necrosis within underlying thalamus and CA3 and CA4 sectors of the hippocampus, and neuronal cell loss in the hilus of the dentate gyrus. In a second series of experiments, radiolabeled microspheres were used to validate the LDF blood flow measurements. The microsphere measurements revealed that the preinjury baseline and postinjury right hippocampal blood flow changes were not significantly altered by the intrahippocampal presence of an LDF probe, verifying that the LDF probe was not by itself an unacceptably disruptive influence on local cerebrovascular reactivity. Moreover, when right hippocampal blood flow was simultaneously evaluated in injured rats by both techniques, the relative blood flow changes were significantly correlated. These results indicate that laser-Doppler flowmetry provides a potentially useful means to appreciate acute regional cerebrovascular changes relative to other measures of outcome after brain trauma.

Animals↗
PubMed1996

Co-ligation of surface IgM and CD40 on naive B lymphocytes generates a blast population with an ambiguous extrafollicular/germinal centre cell phenotype.

We have previously shown that dual occupancy of sigM and CD40 - essential receptors in T-dependent B cell responses - by antibodies held on CD32-L cells results in the rapid proliferation of resting human B lymphocytes in a cytokine-independent manner. Here we report the detailed phenotype of the blast population emerging in such cultures. By 3 days the levels of CD19 and CD20 have increased 4- and 2-fold respectively: such high level expression of these two pan-B markers is characteristic of cells of germinal centre (GC) origin. B cells co-stimulated via sIgM and CD40 express low level CD23 and almost half become CD5(+); they also acquire CD38 and - importantly - CD77, both of these being selective markers of GC B cells. Expression of sigM and IgD is down-regulated on these cells and a minor, but significant, population of IgG+ cells appears. In marked contrast to GC B cells, the population proliferating in response to dual occupancy of sigM and CD40 has up-regulated and strongly expresses CD44. Morphologically, the cells are heterogeneous but there is a dominant blastic cell type with relatively scanty cytoplasm and having multiple nucleoli, both of which are characteristic of centroblasts; nevertheless, these cells remain morphologically distinct from freshly isolated GC B cells and do not show hallmark features of centrocytes. Although there is substantial cell death occurring by days 6-7 in these cultures, there is no morphological evidence for apoptosis. Thus, the proliferating population that emerges from the dual engagement of antigen receptor and CD40 on resting B cells appears to be bestowed with some features of GC B cells but has others which are incompatible with that particular stage of differentiation. The possibility that it might represent (i) a blast stage that is transitional between activation in T zones and entry into the follicle or (ii) a precursor population that colonizes the primary follicle prior to GC formation is discussed.

ADP-ribosyl Cyclase↗
PubMed1996

An economic evaluation of laparoscopic versus open inguinal hernia repair.

BACKGROUND: The rapid and widespread introduction of minimal access surgery has major implications for the National Health Service. It cannot be assumed that replacing an open procedure with a minimal access alternative will be cost-effective. Laparoscopic inguinal hernia repair is a procedure for which the potential economic benefits are particularly unclear. It is currently being adopted in many centres, although limited evidence on its clinical and cost-effectiveness exists. METHODS: This economic comparison of laparoscopic versus open hernia repair was undertaken on data collected on 104 patients undergoing surgery on a day case basis, in the context of a randomized controlled trial. RESULTS: The mean total health service cost of laparoscopic repair was 1074 pounds versus 489 pounds for open repair [mean difference in total health service costs 583 pounds; 95 percent confidence interval (CI) 265 pounds-904 pounds]. This difference was largely accounted for by the difference in theatre costs. Laparoscopic repair remained significantly more expensive for most but not all of the scenarios explored in the sensitivity analysis. The direction of the cost-effectiveness ratio was not sensitive to assumptions about long-term recurrence. Neither was it sensitive to halving the operating time in the laparoscopic arm of the trial. When both operating time and the costs of consumables were reduced, laparoscopic repair remained more expensive, but results for this scenario did not achieve statistical significance on this sample size. CONCLUSIONS: Laparoscopic hernia repair appears an expensive option in most plausible situations. Furthermore, many uncertainties still exist about long-term outcome after the procedure and about the conditions necessary to maximize cost-effectiveness. Large-scale randomized studies to evaluate laparoscopic hernia repair are currently under way to address these issues. We suggest that further evidence is awaited before this technology is further diffused.

Adolescent↗
PubMed1996

Adsorption of bacteriocins by ingestible silica compounds.

Bacteriocins including nisin, pediocin PO2, brevicin 286 and piscicolin 126 were adsorbed from culture supernates by various food-grade porous silica anti-caking agents and the food colourant, titanium dioxide. All the porous silica (calcium silicate or silicon dioxide) materials showed substantial capacity in adsorbing bacteriocin activities from the culture supernate and biological activity was recovered in the adsorbents. In contrast, the food colourant titanium dioxide adsorbed most of the bacteriocin activity from the supernate, with minimal biological activity retained in the adsorbent. Experiments with piscicolin 126 showed that optimum adsorption could be achieved with Micro-Cel E within 30 min, independent of the supernate pH (2.0-10.0). Piscicolin activity of up to 5 x 10(7) AU g(-1) of Micro-Cel E was obtained after adsorption from culture supernates and the adsorbed piscicolin demonstrated substantial biological activity against Listeria monocytogenes in both broth and a milk growth medium.

Adsorption↗
PubMed1996

Characterization of the chemical and antimicrobial properties of piscicolin 126, a bacteriocin produced by Carnobacterium piscicola JG126.

A novel peptide bacteriocin produced by the lactic acid bacterium Carnobacterium piscicola JG126 isolated from spoiled ham was purified and characterized. This bacteriocin, designated piscicolin 126, inhibited the growth of several gram-positive bacteria, especially the food-borne pathogen Listeria monocytogenes, but had no effect on the growth of a number of yeasts and gram-negative bacteria. Bactericidal activity was not destroyed by exposure to elevated temperatures at low pH values; however, bactericidal activity was lost at high pH values, especially when high pH values were combined with an elevated temperature. Piscicolin 126 activity was not affected by catalase, lipase, or lysozyme but was destroyed by exposure to a range of proteolytic enzymes. Piscicolin 126 was purified to homogeneity and was found to be a peptide having a molecular weight of 4,416.6 +/- 1.9. A sequence analysis revealed that this compound is a cystibiotic (class IIa) bacteriocin containing 44 amino acid residues and one intrapeptide disulfide ring. Piscicolin 126 has regions of homology with some other bacteriocins obtained from lactic acid bacteria and is most closely related to sakacin P and pediocin PA-1 (levels of identity, 75 and 55%, respectively). Addition of piscicolin 126 to a devilled ham paste test food system inhibited the growth of L. monocytogenes for at least 14 days. Piscicolin 126 was more effective than two commercially available bacteriocin preparations tested in the same system.

Amino Acid Sequence↗
PubMed1995

The normal cell cycle activation program is exploited during the infection of quiescent B lymphocytes by Epstein-Barr virus.

B lymphocytes in the peripheral circulation are maintained in a non-proliferative state. Antigen recognition stimulates limited proliferation, whereas infection with Epstein-Barr virus (EBV) results in continual proliferation and the outgrowth of immortal cell lines. Because it is not clear at which point in cell cycle the peripheral B lymphocytes are arrested, we characterized the expression of several cell cycle-associated genes in quiescent and stimulated cells. We show that the expression of four cell genes, cdc-2, cyclin E, CD23, and cyclin D2, are up-regulated approximately 100-fold as a result of EBV-mediated immortalization. Because these genes play a positive role in cell proliferation, we suggest that this regulatory switch contributes to controlling entry into the cell cycle. Transient stimulation of quiescent B lymphocytes with either a cocktail of anti-CD40, anti-IgM, and IL4, or EBV results in the rapid expression of the same four genes, suggesting that, after infection, EBV exploits the normal program of B-lymphocyte cell cycle activation.

Adult↗
PubMed1995

Real-time detection of DNA hybridization and melting on oligonucleotide arrays by using optical wave guides.

The challenge of the Human Genome Project is to increase the rate of DNA sequence acquisition by two orders of magnitude to complete sequencing of the human genome by the year 2000. The present work describes a rapid detection method using a two-dimensional optical wave guide that allows measurement of real-time binding or melting of a light-scattering label on a DNA array. A particulate label on the target DNA acts as a light-scattering source when illuminated by the evanescent wave of the wave guide and only the label bound to the surface generates a signal. Imaging/visual examination of the scattered light permits interrogation of the entire array simultaneously. Hybridization specificity is equivalent to that obtained with a conventional system using autoradiography. Wave guide melting curves are consistent with those obtained in the liquid phase and single-base discrimination is facile. Dilution experiments showed an apparent lower limit of detection at 0.4 nM oligonucleotide. This performance is comparable to the best currently known fluorescence-based systems. In addition, wave guide detection allows manipulation of hybridization stringency during detection and thereby reduces DNA chip complexity. It is anticipated that this methodology will provide a powerful tool for diagnostic applications that require rapid cost-effective detection of variations from known sequences.

Base Sequence↗
PubMed1995

Engagement of CD20 suppresses apoptosis in germinal center B cells.

In a screen of 67 monoclonal antibodies (mAb) included in the Blind Panel of B cell antibodies for the 5th International Workshop on Human Leukocyte Differentiation Antigens, only the CD20 mAb--included as a positive control for immunophenotyping studies--was found to suppress the spontaneous apoptosis which occurs in human germinal center (GC) B cells when placed in tissue culture at 37 degrees C. Further detailed study using the 1F5 mAb confirmed this observation, showing that rescue from apoptosis via CD20, while not as efficient as that obtained on ligating CD40, was of similar magnitude to that achieved on engagement of surface immunoglobulin (sIg) by immobilized antibody. Also similar to anti-Ig, the CD20 mAb rescued from apoptosis without priming for the proliferation of GC B cells: this was quite different to its action on resting, non-GC B cells, where it provides a potent priming signal for cell cycle progression in response to IL-4 or anti-CD40. Unlike the survival signal engendered via sIg, CD20 engagement neither mobilized Ca2+ from intracellular stores or opening of a Ca2+ channel with 1F5, nor did it affect the ability of anti-Ig to open a Ca2+ gate in GC B cells. An unexpected feature of CD20-mediated rescue of GC B cells from apoptosis was a failure to turn on Bcl-2 expression.

Antibodies, Monoclonal↗
PubMed1995

Simultaneous analysis of mutant and normal alleles for multiple cystic fibrosis mutations by the ligase chain reaction.

The ligase chain reaction (LCR) involves repetitive cycles of ligation of two adjacent pairs of oligonucleotides to form longer ligated products in a template-dependent manner. This study demonstrates the application of LCR for analysis of multiple small mutations. We adapted the technology for the simultaneous determination of the normal and mutant alleles in a competition format, as well as multiple mutations in a multiplex format. For these purposes, we used mutations causing cystic fibrosis, namely the delta F508, W1282X, and G551D mutations. Blunt ligation was compared to a strategy with a single base gap on one or both strands to be filled by thermostable polymerase prior to ligation. Blunt or gap strategies worked well for detection of the delta F508 mutation. Detection of the W1282X mutation worked well with a blunt strategy when high K+ concentration (180-220 mM) was used to reduce template-independent ligation. For reliable detection of the G551D mutation, we used mismatches in the oligonucleotides 2-5 bp away from the ligation site and hot start of the reaction to achieve allele specificity. Excellent discrimination of mutations was achieved using competitive LCR with six oligonucleotides (two common on one side of the mutation plus two wild type and two mutant on the opposite side with the mutation site at the end adjacent to the common oligonucleotides) and with multiplex-competitive LCR using 12 oligonucleotides to detect both alleles for two mutations in a single tube.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1995

Sensitivity to change of health status measures in a randomized controlled trial: comparison of the COOP charts and the SF-36.

This study compared the sensitivity to change of comparable dimensions of a multi-item multi-dimensional health status measure (the SF-36) with the equivalent single item domains on the Dartmouth COOP charts. One hundred and twenty nine patients were randomized to either day case laparoscopic surgery (n = 60) or open inguinal hernia repair (n = 69). Respondents completed the SF-36 and COOP charts at baseline (prior to surgery) and at follow up at 10 days and 6 weeks. Equivalent dimensions of physical functioning, mental health/emotional condition, social activities, pain and overall condition/general health on the two questionnaires were compared. Despite slightly different pictures of change provided by the physical functioning and 'overall condition/general health' dimensions the general picture of change provided by the two instruments was similar. At 10 days, patients who underwent open surgery reported far greater levels of dysfunction than those who underwent laparoscopic surgery on both questionnaires. At 6 weeks the pain dimension of both questionnaires indicated a large improvement from baseline, whilst no other domain on either questionnaire for either group indicated such improvement. The general picture of change provided by the two measures was similar. The results suggest that both the SF-36 and the COOP charts may prove suitable for the assessment of health perception outcomes in surgical clinical trials. Differences on certain domains were caused in large measure by the nature of the questions posed. The study once again highlights the importance of checking item content to determine the suitability of any particular measure for a given study.

Adult↗
PubMed1995

CD40 and its ligand: central players in B lymphocyte survival, growth, and differentiation.

This article brings together information garnered over the last 10 years on the B cell-associated CD40 surface glycoprotein. The discovery in 1992 of a natural counterstructure, the CD40 ligand (CD40L), which can be rapidly induced on T-cells has hastened research and increased interest in this area dramatically. It has become clear that CD40 and its ligand are central players in B cell responses to T-dependent antigens. The capacity of CD40 to deliver signals for B cell growth, differentiation and survival is covered together with discussion of the signal transduction pathways which operate to bring about these changes. Future issues surrounding this important receptor-ligand pair are discussed.

Animals↗
PubMed1995

The delayed hypersensitivity response and host resistance in surgical patients. 20 years later.

OBJECTIVE: A 20-year follow-up was conducted on research into the implications of a lack of a delayed-type hypersensitivity (DTH) skin test response among surgical patients. SUMMARY BACKGROUND DATA: The authors' original report showed that a failed DTH response was associated with increased hospital mortality, but the role of specific and nonspecific host defense elements, comorbid factors, nutritional supplementation, and the mechanism for anergy in this adverse outcome was unknown. METHODS: A data base of 4292 patients was analyzed and reported on individual studies designed to answer some of the above questions. RESULTS: Prospective studies showed a strong association between the DTH response and mortality: reactive patients, 2.9% (75/2576); anergic patients, 20.9% (239/1142, chi square = 265, p < 0.0000001). Antibody response to protein antigens was reduced in anergic patients. Antibody response to polysaccharide antigens was normal in all patients. The hallmark of anergy is a lack of T cells in the skin, as measured by mRNA signal (CD3) for T cells. The nonspecific component of host defense, as measured by circulating and exudate polymorphonuclear cell function, showed no statistically significant difference between elective reactive and elective anergic patients. Notwithstanding some mild malnutrition in anergic patients, parental nutrition failed to correct the DTH response or many of the cellular immune functions measured. CONCLUSIONS: Over the last 5 years, because of a reduction in overall patient mortality, the contribution of a reduced DTH response to septic related mortality has lost statistical significance in elective surgical patients. A reduced DTH response maintains its strong association to sepsis-related mortality in intensive care/trauma patients, and this is the group on which future research efforts should be concentrated.

Aged↗
PubMed1995

An enzyme-linked immunosorbent assay specific for transient (29-37-kDa) fragments of soluble CD23/IgE-binding factors.

The low-affinity IgE receptor (Fc epsilon RII) of B cells and monocytes--also known as CD23--is released from the cell surface by proteolytic cleavage to yield a series of soluble fragments which can accumulate in cell culture supernatants and body fluids. Of these, the most stable is a 25-kDa molecule which is generated from transient intermediates ranging in size from 29 to 37 kDa. It has been claimed that these latter species act as IgE-promoting factors while the 25-kDa molecule is endowed with various cytokine-like activities which are independent of IgE binding. We describe here a novel enzyme-linked immunosorbent assay (ELISA) which allows for the distinction between these two classes of soluble CD23. It is based on the observation that the CD23 antibody EBVCS1 can capture recombinant 29-kDa and 37-kDa fragments of CD23 but does not bind to the 25-kDa species: when EBVCS5 is used as the capture antibody, all three fragments are bound. The availability of these differential ELISA should facilitate investigations on the biological properties of CD23 fragments in health and disease.

Enzyme-Linked Immunosorbent Assay↗