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Biomedical subjects

J Gordon

Publications and source records attributed to J Gordon.

At least 163 records · Page 9Linked to original sources
PubMed1994

Maternal serum screening in the Sioux Lookout Zone. Complicated test for an unspecified need.

We investigated whether the incidence of fetal abnormalities among patients in Sioux Lookout Zone differs from incidence elsewhere in Canada, whether First Nations people would agree to screening, how information could be disseminated, and what practical considerations would affect implementation. Incidence appears to be similar to elsewhere, but First Nations people's cultural and spiritual beliefs and the difficulty of taking action once results are confirmed make current screening programs inappropriate.

Chorionic Gonadotropin↗
PubMed1994

Central role of CD40 and its ligand in B lymphocyte responses to T-dependent antigens.

In order to mount an effective antibody response to soluble and certain other types of antigens, B cells need help from T cells. Recently, an important receptor-ligand pair has been identified as essential for successful cognate interaction between these two classes of lymphocytes. CD40 was first identified as a receptor-like molecule on B cells which when ligated by antibody could deliver signals to prime for growth, differentiation, or survival. Later its counterstructure--termed CD40 ligand (CD40L)--was discovered to be an inducible type II glycoprotein of helper T cells. In this review, the central role of the CD40-CD40L interaction in the various phases of the B cell response to T-dependent antigens is discussed drawing from both in vitro and in vivo studies.

Animals↗
PubMed1994

Temporal tuning and the development of lateral interactions in the human visual system.

PURPOSE: The authors examined the development of lateral interactions between neurons in the human visual system through the use of visual evoked potentials (VEPs) elicited by windmill-dartboard stimuli. Previously, these VEPs have revealed two distinct types of lateral interactions (short-range and long-range) in adults. This study aims to track the development of these interactions in the first 6 months of life. METHOD: Windmill-dartboard stimuli were generated by a computer-controlled visual stimulator and presented on an oscilloscope display. VEPs to these stimuli were obtained from a group of human infants between 14 days and 6 months of age and from a group of adults who served as a basis for comparison. Fourier analysis was used to retrieve amplitude and phase measures of the relevant frequency components of the response. RESULTS: Amplitude measures of the VEP components elicited by the windmill-dartboard stimulus showed that the attenuation of the second harmonic frequency component (reflecting long-range lateral interactions) was essentially adultlike at all temporal frequencies for the majority of infants. In contrast, the amplitude of the fundamental frequency component (thought to reflect short-range lateral interactions) exhibited a low-pass temporal tuning function in infants that differed dramatically from adults. Additional immaturities were observable in the phase of the fundamental component of the infant VEPs. CONCLUSIONS: Evidence for the presence of some degree of lateral interaction was seen in even the youngest infant. Long-range lateral interactions appear to mature rapidly in infancy, whereas short-range lateral interactions show a much longer developmental time-course, and their properties are dependent on temporal frequency.

Contrast Sensitivity↗
PubMed1994

Three clinical trials comparing xylitol- and sorbitol-containing chewing gums for their effect on supragingival plaque accumulation.

Studies have evaluated the effects of xylitol when administered in chewing gum, as a dietary substitute for sugar, in dentifrice and in mouthrinse. Three clinical trials were conducted to further investigate chewing gums containing xylitol or xylitol/sorbitol mixtures for their ability to reduce plaque accumulation when compared to a sorbitol containing gum. These studies all had two phases; supragingival prophylaxis with an assessment of plaque accumulation to be used for balanced assignment for the second phase, which assessed plaque regrowth following a second supragingival prophylaxis and various chewing gum regimens. In the first trial of xylitol/sorbitol versus sorbitol gum only, the combination gum had a significantly greater reduction in plaque growth. In the second trial, different regimens of chewing gums with xylitol/sorbitol and sorbitol alone were compared. The combined average of the plaque regrowth scores for the subjects chewing the xylitol/sorbitol gum was significantly better than that for the sorbitol gum alone. The final trial evaluated two regimens in two forms (stick and pellet) of a xylitol gum versus a sorbitol gum. Both xylitol-containing gum forms were statistically superior to the sorbitol gum in retarding plaque regrowth.

Adolescent↗
PubMed1993

Cells recovered from human DTH reactions: phenotypic and functional analysis.

Using the skin window chamber (SC) technique T cells were recovered from DTH reactions elicited by either PPD or Candida (CAN) in three healthy individuals. Analysis of representative panels of clones established in limiting dilution cultures from SC and blood disclosed a 2.6-, 10-, and 314-fold higher incidence of antigen-specific T cells in SC than in blood. Thirty CD4+ and 13 CD8+ antigen-specific clones were recovered from SC. Eight of 14 CD4+ clones displayed lectin-mediated cytotoxicity (as compared to 2/10 from blood) and 4/5 CD8+ clones were also cytotoxic. The CD4+ clones from SC, but not from blood could be divided into two groups, one producing IFN-gamma and IL-2, and the other providing help for Ig synthesis. Among the CD8+ SC clones analyzed the noncytotoxic clone could provide help for Ig synthesis but produced no IFN-gamma, whereas the other four showed the opposite pattern. Analysis of the fluid phase of SCs from positive DTH reactions disclosed high levels of TNF and IFN-gamma; neither was detected from SC's covering sites injected with nonspecific antigens.

Antigens↗
PubMed1993

Electrophysiological tests of neural models: evidence for nonlinear binocular interactions in humans.

Evoked cortical potentials were used to test neural models of binocular interactions in humans. The critical feature that distinguished between basic models was whether the two monocular signals combined linearly or nonlinearly. Stimuli were presented separately and simultaneously to two eyes with the relative temporal phase parametrically varied. Fourier analysis was applied to the recorded electroencephalogram to measure the frequency response of the visual cortex to this stimulation. Comparisons of the models' predictions with the experimental results indicate that the greatest contribution to the cortical response originates in a neural pathway that contains nonlinear binocular combination, and a smaller contribution originates in a pathway with linear binocular combination. Current models, based on psychophysical studies of humans and on single-cell neurophysiological investigations of cats, are inadequate to explain these results. A model of binocular interaction is proposed that does account for the present findings and is also supported by neurophysiological studies on monkeys. This model, which contains both nonlinear and linear binocular interactions, has profound implications for perceptual processing.

Cerebral Cortex↗
PubMed1993

Stimulation of tyrosine phosphorylation without inositol lipid hydrolysis in human B lymphocytes on engaging CD72.

Occupancy of CD72 on resting tonsillar B cells by monoclonal antibodies (mAb) promotes entry into the G1 phase of the cell cycle with an accompanying increase in MHC Class II expression and provides a co-stimulus to immobilized anti-mu for driving DNA synthesis. We now report that engagement of CD72 by mAb stimulates tyrosine phosphorylation in B cells with a peak of activity seen at 5-10 min. Two major substrates of 29 and 57 kDa showed a basal level of phosphorylation which increased with time, while a 40 kDa protein and several other minor components were phosphorylated de novo on the addition of mAb to CD72. Inositol lipid hydrolysis was found to be unperturbed, although a shallow rise in the basal level of intracellular free Ca2+ was provoked on engaging CD72. Receptor cross-linking was not a requirement for signaling human B cells through CD72: simple occupancy by univalent antibody was sufficient both to trigger the rise in basal [Ca2+]i and to promote DNA synthesis.

Antigens, CD↗
PubMed1993

Polymorphonuclear cell-mediated vascular injury in anergic surgical patients.

We examined the responses of primed polymorphonuclear neutrophils (PMNs) adhered to vascular endothelium, which can lead to endothelial cell damage as a mechanism of the capillary leak syndrome, the main cause of death in anergic patients. We tested PMNs from (1) preoperative reactive patients, (2) preoperative anergic patients, (3) anergic patients in the surgical intensive care unit, and (4) healthy controls for in vitro adherence and cytotoxicity on cultured human vein endothelial cells. Adherence of PMNs was 12.9% +/- 3.9% in preoperative anergic patients and 13.1% +/- 3.2% in anergic patients in the surgical intensive care unit compared with 9.0% +/- 2.1% in preoperative reactive patients (P < .05). Cytotoxicity was 6.0% +/- 2.8% in preoperative reactive patients, 13.7% +/- 4.1% in preoperative anergic patients, and 14.3% +/- 4.6% in anergic patients in the surgical intensive care unit. The PMNs from preoperative anergic patients were more cytotoxic against human vein endothelial cells when stimulated by Staphylococcus epidermidis or formyl-methionyleucylphenylalanine. We conclude that PMNs from anergic surgical patients adhere more to endothelial cells and can produce increased cytotoxicity that may lead to detrimental results.

Adult↗
PubMed1993

A subset of anti-CD21 antibodies promote the rescue of germinal center B cells from apoptosis.

Germinal center cells (GCC) are programmed to die by apoptosis unless they receive a positive signal for rescue. The primary signal in vivo is believed to be dependent on interaction with antigen held as immune complexes on follicular dendritic cells (FDC), a subset of which express large amounts of CD23, a low-affinity receptor for IgE. Recombinant soluble CD23 (sCD23) and interleukin-1 have been found to potentiate the survival of GCC in vitro. Recently, CD23 was shown to interact specifically with a ligand other than IgE, namely CD21 (CR2/Epstein-Barr virus receptor). In the present study, we show that a subset of anti-CD21 monoclonal antibodies behave similarly to soluble CD23 in their effect on GCC inasmuch as they: (i) diminish the occurrence of apoptosis; (ii) promote a plasmacytoid appearance in rescued cells; (iii) up-regulate expression of the Bcl-2 proto-oncogene. These findings indicate that FDC-derived CD23 exerts its effects on GCC via CD21.

Antibodies, Monoclonal↗
PubMed1993

Engagement of CD40 lowers the threshold for activation of resting B cells via antigen receptor.

Cross-linking of surface Ig (sIg) on resting B cells can generate intracellular signals; however, for T-dependent antigens to promote growth and differentiation additional surface receptors must be engaged. Ligation of CD40 can stimulate B cell proliferation in the presence of interleukin-4. A recently identified counterstructure for CD40 is found on T helper cells and is believed to represent the cognate ligand for B cell activation. This study investigates the role of CD40 as an accessory molecule in sIg-dependent B cell activation. Simultaneous ligation of sIg and CD40 by monoclonal antibodies (mAb) in the presence of mouse L cells which express human Fc gamma receptor type II (Fc gamma RII-L cells) results in potent stimulation of small resting B cells. When CD40 is co-ligated, picomolar concentrations of mouse IgG1 anti-mu, and anti-delta mAb can stimulate B cell proliferation. This requires interaction of the anti-Ig mAb with the Fc gamma RII-L cells: a mouse IgG2a anti-mu mAb which is not recognized by Fc gamma RII, was > or = 1000-fold less effective. These findings suggest a mechanism for B cell activation whereby engagement of T cells via CD40 and its cognate ligand provides potent enhancement of signals delivered through sIg. Based on these observations, models for the activation of B cells by T-dependent antigens are presented.

Antibodies, Monoclonal↗
PubMed1993

Suppression of apoptosis in normal and neoplastic human B lymphocytes by CD40 ligand is independent of Bc1-2 induction.

The tendency of isolated germinal center (GC) B cells to undergo apoptosis was suppressed by recombinant cell-bound CD40 ligand (CD40L): after 2 days at 37 degrees C, > 80% of cells remained viable in the presence of CD40L as compared to < 1% in control cultures. CD40L sustained a high rate of DNA synthesis in GC cells and was more effective than monoclonal antibody to CD40 in this regard. Group I Burkitt lymphoma (BL) cell lines induced to undergo apoptosis with anti-immunoglobulin or calcium ionophore were also protected by CD40L. In BL cells, this route of rescue was not accompanied by induction of Bc1-2 protein, the expression of which has been linked to hemopoietic cell survival. Bc1-2 was induced in GC cells responding to CD40L, but its appearance was a relatively late event not reaching significant levels over controls until day 2 of culture. Thus induction of Bc1-2 appears to be secondary to the survival signal imparted by CD40L. These findings are discussed in relation to a potential role for CD40L in supporting B cell tumors in vivo and the discovery that the molecular defect in the X-linked Hyper-IgM syndrome is targeted to the CD40L gene.

Animals↗
PubMed1993

Protein tyrosine phosphorylation is mandatory for CD40-mediated rescue of germinal center B cells from apoptosis.

Spontaneous apoptosis in germinal center (GC) B cells can be arrested either by engaging cell surface immunoglobulin (Ig) with immobilized ligand or, more effectively, by treatment with soluble monoclonal antibody (mAb) directed against CD40. The present study examines the intracellular signal transduction pathways through which rescue from spontaneous apoptosis is engendered in GC B cells following ligation of surface CD40. Cross-linking the surface CD40 of GC B cells with mAb consistently resulted in enhanced tyrosine phosphorylation on a number of distinct substrates: this process could be blocked, in a dose-dependent fashion, by pre-treating GC B cells with the selective protein tyrosine kinase(s) (PTK) inhibitor, herbimycin A. Moreover, the pattern of phosphorylation on tyrosine observed following treatment with anti-CD40 was remarkably similar to that triggered by polyvalent anti-Ig. By contrast, anti-CD40 failed to stimulate the increase in inositol 1,4,5-trisphosphate and cytosolic free calcium observed in both GC B cells and resting B lymphocytes following ligation of surface Ig. The involvement of the signaling pathways generated in the rescue of GC B cells from apoptosis was studied by using selective inhibitors of PTK and of extracellular and intracellular Ca2+. Pre-incubation with the PTK inhibitor herbimycin A (5 microM) abrogated anti-CD40-mediated rescue of GC B cells from apoptosis, while genistein (40 microM) and the tyrphostins AG490 (10 microM) and AG814 (25 microM) significantly inhibited this process. Consistent with these results, herbimycin A (5 microM) abolished the expression of the 26 kDa bcl-2 protooncogene product, which confers resistance to apoptosis, normally observed following culture with anti-CD40. The Ca2+ chelators BAPTA and EGTA did not significantly affect CD40-promoted rescue. Taken together, these results indicate that CD40 of GC B cells is coupled to functional PTK but not to the phosphatidylinositol signaling pathway and that tyrosine phosphorylation is mandatory for CD40-mediated rescue of GC B cells from apoptosis.

Antibodies, Monoclonal↗
PubMed1993

Immunoelectron microscope localization of snRNP, hnRNP, and ribosomal proteins in mouse spermatogenesis.

We have studied the ultrastructural distribution of heterogeneous nuclear ribonucleoproteins (hnRNPs), small nuclear ribonucleoproteins (snRNPs), and ribosomal proteins during mouse spermatogenesis and spermiogenesis by means of specific antibodies and immunocytochemistry. All the above components were detectable from primary spermatocytes until the spermatid elongation phase, when the RNA synthetic activity is known to cease. Ribosomal protein (P1/P2 and L7) labeling disappeared as early as during the acrosome phase, and nucleoli were no longer labeled even during the cap phase. The nucleoplasmic structures labeled with the different anti-nucleoplasmic RNP immunoprobes corresponded, until the acrosome phase, to those previously observed as targets of the same antibodies in the nucleoplasm of somatic cell nuclei. Clusters of interchromatin granules of spermatocyte and early spermatid nuclei exhibit some labeling for hnRNP when compared with nuclei of Sertoli cells or previously analyzed liver or tissue culture cells, where these structural constituents usually remain weakly labeled or unlabeled. In spermatids in step 10, another type of nuclear granule, resembling perichromatin granules, but occurring in aggregates, can be observed. These structural constituents were labeled with antibodies recognizing nucleoplasmic snRNP antigens and therefore suggesting a non-nucleolar origin of these granules. Finally, we have observed nucleoplasmic areas of fibrogranular material, occurring only in primary spermatocytes. These components were labeled with anti-ribosomal protein antibodies but did not contain either hnRNPs or snRNPs.

Acrosome↗
PubMed1993

Clones of T cells discriminate between native and deglycosylated forms of MHC class II antigen in allostimulation.

The aim of this study was to clarify the role of the oligosaccharide side chains of MHC Class II antigens in allostimulation. The approach was to cleave the oligosaccharides from protein by subjecting plasma membranes (PM) of the Daudi cell line to chemical deglycosylation yielding deglycosylated (dgl) proteins and a supernatant fraction containing plasma membrane oligosaccharides (dgl sup). MHC Class II antigens affinity purified from the native and the dgl PM were inserted into the plasma membrane of peripheral blood leukocytes (PBL) used as stimulators in a mixed leukocyte reaction (MLR). Cells used as stimulators and as responders were from the same donor. Both native and to a lesser extent the dgl antigen could elicit a proliferative as well as a cytolytic (CML) response. A comparable reduction in the CML reaction was also obtained when native antigen was used to elicit effector cells, but the target was stripped of N-linked oligosaccharides by pretreatment with tunicamycin (TM). Five clones of responding cells raised against the native antigen were studied. Two gave proliferative reactions of equal magnitude to native and to dgl antigen alike, while three responded only to the native form. These three clones did not lyse TM-treated target cells. Inhibition experiments of CML were performed with either the dgl sup containing Daudi PM oligosaccharides or with an anti MHC-Class II MoAb. CML reactivity of the three clones which responded to native antigen was blocked by the dgl sup but not by the anti-MHC antibody. Conversely, the reaction of the two clones reactive to both forms of antigen was only inhibited by the anti-MHC antibody using intact or TM-treated targets. Accordingly, in terms of the latter set of clones oligosaccharide side chains of MHC may not be required for allostimulation. Data obtained with the set of three clones suggest that oligosaccharides could act as target of cytotoxic T cells.

Cell Line↗
PubMed1993

Antibodies to murine CD40 stimulate normal B lymphocytes but inhibit proliferation of B lymphoma cells.

A rat anti-mouse CD40 antiserum has been prepared by hyperimmunisation of Lewis rats with a highly purified preparation of the recombinant extracellular domain of murine CD40. This antiserum specifically binds CD40-expressing L cell transfectants, but not untransfected L cells, and induces vigorous proliferation of highly purified small dense B cells obtained from the spleens of unstimulated mice. Anti-CD40-induced B cell proliferation can be augmented by the addition of IL-4 and is inhibited by purified recombinant soluble mouse CD40. Interestingly the same anti-CD40 antiserum specifically inhibits the in vitro growth of A.20 murine B lymphoma cells. The specificity of this inhibition can be demonstrated by reversing the effect with purified recombinant soluble mouse CD40. These data implicate CD40 as a possible target for therapeutic intervention in the treatment of B lymphomas.

Animals↗
PubMed1993

A study of protein kinase C isozyme distribution in relation to Bcl-2 expression during apoptosis of epithelial cells in vivo.

The steady-state population of stratified squamous epithelium is maintained by balanced cell proliferation and apoptosis. Protein kinase C (PKC) is intimately involved in the regulation of cell proliferation and cell survival. In order to gain insight into the mechanisms regulating apoptosis, the immunocytochemical localization of six PKC isozymes (PKC-alpha, -beta, -delta, -epsilon, -gamma, and -zeta) were studied in the surface epithelium of the human tonsil by immunofluorescence staining and confocal laser scanning microscopy. All cells expressed cytoplasmic PKC-alpha, -beta, -delta, -epsilon, and -zeta; PKC-delta and -epsilon were most abundant in viable epithelial cells while PKC-alpha and -beta expression was most intense in cells undergoing apoptosis. PKC-beta and -delta were also present in the nucleus of viable epithelial cells coexpressing cytoplasmic Bcl-2, an oncogene product which protects from apoptosis. Nuclear expression of these isozymes did not correlate with epithelial cell mitosis, as defined by proliferating cell nuclear antigen. Thus, differential subcellular localization of PKC isoforms is associated with the regulation of epithelial cell apoptosis in situ.

Apoptosis↗
PubMed1993

Inhibition of human neurotropic virus (JCV) DNA replication in glial cells by camptothecin.

Progressive multifocal leukoencephalopathy is a subacute demyelinating disease of the central nervous system (CNS) resulting from opportunistic infections in immunocompromised patients infected with a common polyomavirus, JC virus (JCV). Unlike other polyomaviruses, JCV exhibits an unusually narrow tissue tropism by primarily infecting glial cells of the CNS. JCV DNA replication is similar to that of the well-characterized papovavirus, SV40, which requires the viral early protein T-antigen and host-replication factors including DNA polymerases and DNA topoisomerase I. In this study we have been able to effectively block replication of viral DNA in glial cells using camptothecin, a drug which inhibits DNA topoisomerase activity. Pulse-treatment of cells with non-toxic levels of camptothecin specifically blocks viral DNA replication with no inhibitory effect on host transcription and translation processes as examined by viral gene expression in the transfected cells. Furthermore, drug treatment of the cells exhibits no significant effect on DNA topoisomerase I gene transcription. We further demonstrate that repeated pulse-treatment of cells with the drug is required for complete blockage of viral DNA replication. The importance of these findings in the treatment of AIDS encephalopathy is discussed.

Antineoplastic Agents↗