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J Daley

Publications and source records attributed to J Daley.

At least 145 records · Page 8Linked to original sources
PubMed1989

Isolated human follicular dendritic cells display a unique antigenic phenotype.

In the present study, follicular dendritic cells (FDCs) were purified to homogeneity in order to define the lineage and function of these cells. FDCs were identified by their characteristic morphology and by their expression of receptors for the third complement component, the myeloid-restricted antigen CD14, and the FDC antigen DRC-1. Unclustered FDCs displayed a unique antigenic phenotype since they expressed several B- and myeloid lineage-restricted antigens, but lacked T and NK cell antigens as well as the leukocyte common antigen. FDCs expressed adhesion molecules, including most of the VLA proteins, intercellular adhesion molecule 1 (ICAM-1), and CD11b. FDCs could be isolated to homogeneity by their intense staining with anti-CD14 using flow cytometric cell sorting. These highly purified FDCs expressed CD14 and CD21 but lacked CD20. This antigen pattern and characteristic morphology confirmed that these cells were, in fact, homogeneous FDC preparations. Analysis of polymerase chain reaction-amplified cDNA from highly purified FDCs showed no transcripts for IL-6. The isolation of homogeneous FDC populations will be important for the analysis of the functional role of FDCs within the lymphoid follicle.

Antigens, Differentiation↗
PubMed1989

Expression and regulation of CD5 on in vitro activated human B cells.

The T cell-associated antigen CD5 has been shown to play an important role in the regulation of T cell activation. Monoclonal antibodies directed against CD5 upregulate helper function, and induce interleukin 2 (IL2) production by mature T cells as well as thymocytes. CD5 is also expressed on subsets of B cells associated with autoantibody production, and CD5+ B cells are present in increased numbers in patients with rheumatoid arthritis and systemic lupus erythematosis. More recently CD5 has been found to be present on human B lymphocytes following in vitro activation with phorbol myristate acetate. To date a similar functional role for CD5 has not to date been demonstrated for B cells. In this study we have shown that structurally similar CD5 molecules are present on activated B cells and T cells. In addition, CD5 on both stimulated B cells and T cells is phosphorylated, which may be important in the function of CD5 following activation. CD5 protein or mRNA was not detected on unstimulated splenic B cells depleted of any CD5+ cells. To investigate the control of CD5 expression, we examined a series of cytokines either alone or in combination for their effect on the induction of CD5. CD5 expression was specifically inhibited by IL4 but not by the other cytokines tested. This inhibition was very specific as IL4 did not inhibit the expression of other B cell activation antigens including CD25, B5, T9 and CD23 as well as the pan-B cell antigen CD20. The addition of other cytokines did not increase or reverse the inhibition of CD5 expression by IL4. This inhibition was demonstrated by immunofluorescence and flow cytometric analysis. Immunoprecipitation studies of 125I-labeled activated B cells demonstrated that there was a decrease in cell surface CD5 protein, and not simply inhibition of expression of a particular epitope. Northern blot analysis demonstrated that the expression of CD5 mRNA was markedly inhibited in the presence of IL4, whereas the induction of the protooncogene c-myb was unaffected. This suggests that IL4 inhibits CD5 protein expression on activated B cells by reducing the amount of CD5 mRNA transcription or increasing the degradation of CD5 mRNA. The role of the T cell-derived lymphokine IL4 in regulating CD5 expression may be important in the disease states characterized by increased numbers of CD5+ B cells.

Antigens, Differentiation↗
PubMed1989

Arterial dilation and reduced wave reflection. Benefit of dilevalol in hypertension.

We compared dilevalol (an isomer of labetalol), 200-400 mg daily, against atenolol, 50-100 mg daily, in a double-blind, crossover, placebo-controlled trial with respect to effects on arterial distensibility (measured as pulse wave velocity [PWV]) and wave reflection (assessed from carotid pressure wave contour). Twelve patients of mean age 58 years (range 44-73 years) with essential hypertension (supine diastolic blood pressure 95-114 mm Hg) took active therapy for 12 weeks, separated by a 2-4 week placebo period. Carotid pressure waveforms were recorded noninvasively by applanation tonometry with a Millar micromanometer-tipped probe. PWV was measured between carotid and femoral arteries (aortic PWV), carotid and radial arteries (arm PWV), and femoral and pedal arteries (leg PWV). Early wave reflection was calculated from the ratio of the height of the peak of the carotid wave above its shoulder to the pulse pressure and was expressed as an augmentation index. Both drugs were equally effective in reducing brachial sphygmomanometric pressure and PWV in all three regions (active vs. placebo, p less than 0.001), but there was no significant difference between the two active therapies. However, the augmentation index (averaged during the treatment period) was significantly lower with dilevalol (19%) than with atenolol (28%, p less than 0.01), corresponding to a greater decrease of 5-8 mm Hg in carotid systolic pressure compared with the brachial artery. Although both drugs were equally effective in reducing arterial distensibility, the vasodilating action of dilevalol gave added benefit in reducing wave reflection, presumably through its vasodilatory effect on peripheral conduit arteries.

Adult↗
PubMed1989

Hyponatraemia and Moduretic-grand mal seizures: a review.

Three cases are presented which emphasize the importance of hyponatraemia as a cause of grand mal seizures. The combination of hydrochlorothiazide and amiloride appears to increase the risk of hyponatraemia. We discuss the aetiology and treatment of hyponatraemia and review the necessity for such combination therapy. We recommend caution in prescribing diuretics and preparations such as Moduretic should be used only in those few patients shown to need potassium supplementation.

Aged↗
PubMed1989

Abnormal T-lymphocyte subsets in type I diabetes.

Type I (insulin-dependent) diabetes mellitus is a slow autoimmune disease associated with the selective destruction of beta-cells in the islets of Langerhans. Recent studies in humans indicate that autoantibodies to insulin and islets of Langerhans appear years before overt diabetes and identify a normoglycemic prediabetic state. To determine whether type I diabetes mellitus represents a generalized immunologic disorder, we studied the phenotypic characteristics of peripheral blood lymphocytes from all stages, i.e., prediabetic, new-onset diabetic, and long-term diabetic patients, with the anti-2H4 monoclonal antibody CD45R, which defines a human suppressor-inducer subset, and the anti-4B4 monoclonal antibody CDw29, which defines a human helper-inducer subset of peripheral blood lymphocytes. All 22 prediabetic patients had elevated T4+2H4+ (suppressor-inducer) cells and reciprocal depressed T4+4B4+ (helper-inducer) cells compared with healthy age-matched control subjects. In addition, the T4/T8 ratio in prediabetic patients was decreased compared with the age-matched control subjects. The abnormal T4+2H4+ and T4+4B4+ subsets were resolved in 20 new-onset and 15 long-term diabetic patients. Family studies showed that the changes in the 2H4 and 4B4 antigens were not part of an inherited polymorphic determinant, because these markers were normal in unaffected siblings and parents. Ten prediabetic patients were restudied greater than 1 yr after the original analysis and showed the persistence of the observed changes. This abnormal increase in suppressor-inducer cells and decrease in helper-inducer cells among islet and insulin antibody-positive prediabetic patients may be of help in understanding diabetes pathogenesis and may also be an early noninvasive screening tool for the detection of the prediabetic state.

Adolescent↗
PubMed1989

Studies of in vitro activated CD5+ B cells.

Human B lymphocytes undergo distinct phenotypic changes following activation with antigen and polyclonal mitogens. Increasing interest has focused on the unique subpopulation of B cells that expresses the CD5 antigen. In this study, we examined the signals that induce the expression of CD5 on normal splenic B cells. Only 12-O-tetradecanoylphorbol-13-acetate (TPA) induced CD5 expression on highly purified splenic B cells, whereas anti-immunoglobulin (anti-Ig), Epstein-Barr virus, anti-CD20, recombinant interleukin-1 (rIL-1), rIL-2, rIL-4, recombinant interferon-gamma (rINF-gamma), and B-cell growth factor all failed to induce CD5 expression. The expression of CD5 was detected on the cell surface by 48 hours and decreased by 96 hours. Dual-fluorochrome analysis demonstrated that the CD5+ B cells coexpressed the B-cell activation antigens B5, IL-2 receptor, and CD23, thereby providing phenotypic evidence that this B-cell subpopulation is activated. In vitro studies of dual-fluorochrome-sorted, TPA-stimulated splenic B cells demonstrated significantly greater tritiated thymidine incorporation and Ig secretion by the CD20+ CD5- cells than by the CD20+ CD5+ subset. These phenotypic and functional studies are consistent with the notion that TPA-induced CD5+ B cells are a subset of in vitro activated B lymphocytes.

Antigens, CD20↗
PubMed1988

Pre-exposure of human B cells to recombinant IL-1 enhances subsequent proliferation.

The reported effects of the monocyte-derived cytokine IL-1 on human B lymphocytes are both varied and controversial. IL-1 has been reported to augment both proliferation and Ig secretion of previously activated human B cells. In the present study highly purified splenic B cells were cultured with rIL-1 before, simultaneously with, and after the addition of the polyclonal B cell mitogen, anti-Ig. rIL-1 had no significant effect on B cell proliferation when added simultaneously with or after B cell activation with anti-Ig. However, incubation of splenic B cells with rIL-1 for 24 h before stimulation with anti-Ig appeared to enhance mitogenesis. With the observation that rIL-1 exerted effects on resting B cells, the effect of rIL-1 on several events which accompany B cell activation was examined. rIL-1 failed to stimulate RNA synthesis, effect increases in cell size or intracellular Ca2+ levels, or lead to the hyperexpression of MHC class II or B cell activation Ag. These studies suggest that rIL-1 does not activate B cells but primes them to respond to subsequent activation.

Antibodies, Anti-Idiotypic↗
PubMed1988

Optical assessment of dental pulp vitality.

The assessment of dental pulp vitality is an important part of oral diagnosis. Conventional tests stimulate the nerves in the pulp and rely on a subjective response from the patient. The use of an optical method for assessment of pulp vitality has been investigated. Fibre optic light guides were used to transmit light to and from the tooth and signal processing was employed to enhance the resulting signal. Valid pulse signals were differentiated from artefactual signals by analysis of signal parameters. Artefactual signals were found to have coefficients of variability that are greater than 40% for amplitude and greater than 25% for phase. With this technique it has been possible to recognize a pulse signal from over 70% of healthy teeth. Further work is in progress to develop the technique to a state where it can be used as a routine clinical tool.

Algorithms↗
PubMed1988

Defective expression of the 2H4 molecule after autologous mixed lymphocyte reaction activation in systemic lupus erythematosus patients.

Previous studies demonstrated that patients with active systemic lupus erythematosus (SLE), especially those with active renal disease, had a marked reduction in T4+2H4+ suppressor inducer cells in their peripheral blood. However, it was puzzling to find that active SLE patients without renal diseases often had normal percentages of T4+2H4+ cells. In the present study, we attempted to determine whether active SLE patients bearing normal percentages of T4+2H4+ cells had a defect in their expression of the 2H4 molecule on T4+ cells after autologous mixed lymphocyte reaction (AMLR) activation. The peripheral blood lymphocytes (PBL) from 50 SLE patients with normal percentages of T4+2H4+ cells (greater than or equal to 7% in PBL) were studied and the results were compared with those of 40 normal individuals. The density of the 2H4 molecule on T4 cells from normal controls increased during the 7-d AMLR; in contrast T4 cells from patients with SLE, especially those with active SLE, had defective expression of the 2H4 antigen after AMLR activation. Patients with inactive SLE, like normals, showed an increase in the 2H4 molecule after AMLR activation. Moreover, a strong correlation was observed between percent suppression of pokeweed mitogen (PWM)-driven IgG synthesis and the density of the 2H4 antigen on AMLR-activated T4 cells. Serial analysis of patients with SLE showed that the density of the 2H4 antigen expression and the suppressor inducer activity of AMLR-activated T4 cells were inversely correlated with disease activity. Thus, defective expression of the 2H4 antigen may be an important mechanism for the failure of active SLE patients with normal percentages of T4+2H4+ cells to generate suppression.

Adolescent↗
PubMed1987

B7, a B-cell-restricted antigen that identifies preactivated B cells.

After activation with antigen or mitogen, a number of cell surface proteins appear that are not expressed on resting B cells. To date, a number of B lineage restricted and associated activation antigens have been reported that appear at distinct intervals after in vitro activation. In this report, we describe a new B lineage restricted activation antigen (B7) that appears within 24 hr of in vitro stimulation. The expression of B7 antigen, which is detected on a minor subpopulation of B cells isolated from peripheral blood and lymphoid tissues, is strongly induced following stimulation with either anti-immunoglobulin or Epstein-Barr virus. In contrast, B7 was not detected on resting or activated T cells or monocytes. The B7 antigen was expressed on a subset of B cell lines and B cell neoplasms, but was not detected on leukemias and lymphomas of T cell or myeloid origin. B7 was distinguished from other B cell restricted and associated activation antigens by its unique pattern of expression on a variety of hemopoietic cell lines. The biochemical characterization of B7, that it is a single chain protein of 60 kDa, further distinguishes it from other B cell activation antigens. The functional importance of the B7 antigen was demonstrated when splenic B cells were fractionated into the B7+ and B7- populations. The peak of proliferation in response to anti-Ig, appeared earlier within the B7+ population. These studies suggest that B7 antigen identifies a subpopulation of B cells that are preactivated or primed in vivo, and have an accelerated response to subsequent activation via cross-linking of surface Ig.

Animals↗
PubMed1987

Identification and cloning of a prethymic precursor T lymphocyte from a population of common acute lymphoblastic leukemia antigen (CALLA)-positive fetal bone marrow cells.

We have cloned common acute lymphoblastic leukemia (CALLA)-positive cells from human fetal bone marrow containing less than 1 in 10,000 E-RFC in round-bottomed microtiter wells (one cell per well) using the autocloning unit of an EPICS-V cell sorter. Expansion of such cells (with IL-2 and heavily irradiated autologous thymocytes as feeder cells) resulted in growth in 6-14% of the wells (mean, 11%) with cells with mature T lymphocyte phenotype. Two-color fluorescence analysis of outgrowing cultures furthermore ascertained that these cells had differentiated through a phase of simultaneous expression of T4 and T8 antigens and at the same time expression of the thymocyte-associated T6 antigens. Thus, given the fact that 10-20% of T cell acute lymphoblastic leukemia (T-ALLs) are CALLA+, we have been able to identify a human prethymic T lymphocyte population that might be the normal counterpart of precursor cell to the CALLA+ T-ALL cell.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Selective loss of the suppressor-inducer T-cell subset in progressive multiple sclerosis. Analysis with anti-2H4 monoclonal antibody.

The T4+ lymphocyte population includes a subset that induces suppressor T lymphocytes (T8+ cells) and can be distinguished by dual-color fluorescence analysis with anti-2H4 and anti-T4 monoclonal antibodies. To investigate the possible role of these cells in multiple sclerosis, we used anti-2H4 antibody to characterize peripheral-blood lymphocyte subsets in 63 patients with multiple sclerosis that was progressive, stable, or acute (relapsing-remitting). Twenty-three of 37 patients with progressive multiple sclerosis had a selective decrease in the number and percentage of peripheral-blood T cells that induce suppressor cells (T4+2H4+ cells), whereas only 3 of 16 patients with stable disease and 2 of 10 patients in the midst of an acute attack had a significant decrease. These selective decreases of circulating T4+2H4+ cells occurred in only 1 of 34 patient controls with other neurologic diseases and in 2 of 50 healthy controls (P less than 0.0001 by Fisher's exact test). The absolute number of T4+2H4+ cells and the percentage of reactivity in the populations studied were 187 +/- 28 per cubic millimeter and 8.3 +/- 1 percent in patients with progressive multiple sclerosis; 353 +/- 60 per cubic millimeter and 14.5 +/- 2 percent in patients with stable disease; 368 +/- 72 and 14.6 +/- 2.1 percent in patients with acute disease; 402 +/- 64 and 15.6 +/- 2 percent in controls with other neurologic diseases; and 519 +/- 44 and 19.7 +/- 1 percent in healthy controls. Functional studies using a pokeweed mitogen-driven IgG assay demonstrated a correlation between decreased numbers of T4+2H4+ cells and increased production of IgG in vitro. Family studies showed that the 2H4 antigen was not part of an inherited polymorphic antigenic determinant. Our results suggest that in progressive multiple sclerosis decreases in inducers of suppressor T cells may permit the activation of cells reactive with elements of the central nervous system.

Adult↗
PubMed1987

Stimulation of T cells via the TAP molecule, a member in a family of activating proteins encoded in the Ly-6 locus.

T-cell activating protein, TAP, is a Ly-6 encoded 12,000 dalton glycoprotein involved in the activation of murine T cells. TAP is distinct from other known surface activating structures, such as the T cell receptor/T3 complex and Thy-1. This study investigates the mechanism of activation via the TAP molecule. Soluble alpha TAP monoclonal antibody (MAb) is sufficient for T cell activation. This, however, requires cross-linking because F(ab) monovalent antibody is not stimulatory unless cross-linked by a second antibody. Immediately after cross-linking, there is a rapid influx of calcium, which is comparable with concanavalin A or T cell receptor triggered responses. Subsequently, interleukin 2 (IL 2) is produced, and IL 2 receptors (IL 2R) are expressed. TAP-stimulated T cell proliferation is driven by this autocrine pathway because it is inhibited by alpha IL 2R MAb. Thus TAP-mediated activation appears to share a common final pathway with other mitogenic stimuli. A nonactivating alpha TAP MAb was observed to stimulate T cells upon additional cross-linking. Given this observation, we asked whether other Ly-6 linked proteins might share similar activating potential. We show that at least three distinct Ly-6 linked molecules are capable of stimulating T hybrid clones and/or heterogeneous T lymphocytes. Thus it appears that the Ly-6 locus encodes a family of activating cell surface molecules.

Animals↗
PubMed1987

Preexposure of resting B cells to interferon-gamma enhances their proliferative response to subsequent activation signals.

In this report we demonstrate that pretreatment of resting splenic B cells with IFN-gamma increases their mitogenic response to subsequent activating stimuli. This effect is completely blocked by neutralizing anti-IFN-gamma antibodies. By contrast, a similar effect induced by partially purified BCGF is not completely inhibited by anti-IFN-gamma antibody, inferring that as in the mouse, a B-cell-specific factor may also induce increased responsiveness to mitogens in resting B cells. The mechanism of this response was analyzed. Phenotypic and cell cycle analyses of the IFN-gamma-treated cells following activation were not significantly different from control cells with respect to kinetics, although as expected from thymidine uptake, more cells were actively cycling. Even when a very early manifestation of cell activation, Ca2+ flux was examined, no response to IFN-gamma alone was evoked, and the response to subsequent activation was identical to that of control cells. These data show that IFN-gamma did not directly activate B cells, but primed B cells in a manner which amplified subsequent mitogenesis.

Antibodies, Anti-Idiotypic↗
PubMed1987

A defect of immunoregulatory T cell subsets in systemic lupus erythematosus patients demonstrated with anti-2H4 antibody.

The cell surface phenotype of peripheral blood lymphocytes (PBL) of systemic lupus erythematosus (SLE) patients was characterized with the anti-2H4 monoclonal antibody that defines the human suppressor inducer subset. The T4+2H4+ population of cells has been shown to be critical for the activation of T8+ suppressor cells. Patients with SLE has a markedly decreased percentage of T4+2H4+ cells (13 +/- 2%) in their PBL compared with normal controls (21 +/- 1%) (P less than 0.001). This reduction was greatest in patients with active SLE, especially those with renal disease. Serial analysis of patients with SLE and renal disease showed a correlation between percent positive circulating T4+2H4+ cells and disease activity. Moreover, there was a significant correlation between a low percentage of T4+2H4+ cells and decreased suppressor-inducer function in autologous mixed lymphocyte reaction-activated T4+ cells from SLE patients. Thus, a deficiency exists in SLE patients with active renal disease in the T4+2H4+ suppressor-inducer T cell subset.

Adolescent↗