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J Daley

Publications and source records attributed to J Daley.

36 records · Page 2Linked to original sources
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↗
PubMed1987

Expression of B cell activation antigens on normal and malignant B cells.

In an attempt to relate the functional events of B cell activation with changes in cell surface molecules, we have used a panel of monoclonal antibodies directed against cell surface antigens expressed on activated but not resting B cells, to determine a sequence of activation antigen expression following anti-immunoglobulin stimulation. Within the first 24 hr of culture with anti-Ig, resting splenic B cells were induced to express B5 and interleukin-2 receptor (IL-2R) and subsequently express T9 and BB1 by 48 hr. Maximum antigen expression was seen by day 3 with the majority of cells expressing B5, IL-2R, T9, and BB1, and fewer numbers of cells expressing Blast-1 and Blast-2. By day 6, the expression of these antigens significantly decreased. Dual fluorochrome staining of anti-Ig activated B cells demonstrated heterogeneity of activation antigen expression, suggesting the existence of subpopulations of activated B cells. In an attempt to relate the non-Hodgkin's lymphomas (NHLs) to this sequence of activation, 69 tumor samples from patients with B cell NHLs were then examined for expression of these activation antigens. Histologically defined subgroups of B cell NHLs demonstrated differential expression of activation antigens with B5, BB1, and T9 exhibiting the widest distribution, whereas IL-2R, Blast-1, and Blast-2 demonstrated more limited expression. The finding that no B cell malignancy phenotypically resembles the small resting B lymphocyte coupled with the observation that virtually all B cell NHLs examined expressed activation antigens suggests that these tumors may be the neoplastic counterparts of subpopulations of activated B lymphocytes.

Antibodies, Monoclonal↗
PubMed1987

Normal cellular counterparts of B cell chronic lymphocytic leukemia.

In an attempt to compare B cell chronic lymphocytic leukemia (B-CLL) with its normal cellular counterpart, the cell surface phenotype of 100 cases of B-CLL was determined by using a panel of monoclonal antibodies (MoAbs) directed against B cell-restricted and -associated antigens. The majority of B-CLL cells expressed Ia, B4 (CD19), B1 (CD20), B2 (CD21), surface immunoglobulin (sIg), and T1 (CD5) but lacked C3b (CD35) receptors. In contrast, the overwhelming majority of small unstimulated B cells expressed Ia, B4, B1, B2, sIg, and C3b receptors but lacked detectable T1. Small numbers of weakly sIg+ cells could be identified in peripheral blood and tonsil that coexpressed the B1 and T1 antigens. Approximately 16% of fetal splenocytes coexpressed B1, T1, weak sIg, B2, and Ia but lacked C3b receptors and therefore closely resembled most B-CLL cells. With the phenotypic differences between the majority of small unstimulated B cells and B-CLL cells, we examined normal in vitro activated B cells and B-CLL cells for the expression of B cell-restricted and -associated activation antigens. Of 20 cases examined, virtually all expressed B5, and approximately 50% of the cases expressed interleukin-2 receptors (IL-2R) and Blast-1. Normal B cells were activated with either anti-Ig or 12-0-tetradecanoylphorbol-beta-acetate (TPA) and then were examined for coexpression of B1, T1, and the B cell activation antigens B5 and IL-2R. Only cells activated with TPA coexpressed B1 and T1 as well as B5 and IL-2R. B cells activated with either anti-Ig or TPA proliferated in the presence of IL-2, whereas B-CLL cells did not, although they all expressed the identical 60-kilodalton proteins by immunoprecipitation. These studies are consistent with the notion that B-CLL resembles several minor subpopulations of normal B cells including a population of B cells that are activated in vitro directly through the protein kinase C pathway.

Antibodies, Anti-Idiotypic↗
PubMed1985

The proprietary hospital industry: a financial analysis 1972-1982.

This paper evaluates the performance of both specific firms within the American for-profit hospital industry and the industry as a whole. First, traditional financial analysis is used to evaluate individual publicly traded for-profit chains. Then, industry performance from 1973 to 1982 is evaluated using a set of measures based on Modern Portfolio Theory. The traditional financial analysis indicates that the industry seems increasingly profitable as well as increasingly healthy from the perspective of utilizing its assets and reducing its collection period. However, the industry's rapid growth rate has strained its ability to use additional debt funding and has created a potentially dangerous liquidity position. Measures based on Modern Portfolio Theory indicate that the average return of the industry has improved over the past 5 years. However, its risk has also increased. Nevertheless, the increase in risk is more than offset by the increased average return. In addition, recent legislation designed 'to reward the efficient' has introduced a significant degree of uncertainty into the industry's performance for the coming years. Thus, hospitals' ability to maintain the substantial profitability and rate of growth they have experienced over the past decade will depend on how well they will adapt to the changing environment.

Cost Control↗
PubMed1985

The characteristics of training in ambulatory medicine in U.S. residencies.

To determine the characteristics of training in ambulatory internal medicine, all internal medicine residency programs in the United States were surveyed in 1981-82. Thirty-eight percent of 477 hospitals responded. Quantitative information was sought regarding the specific features of the ambulatory residency programs, formal teaching conferences, supervision of residents, and evaluation of residents in ambulatory care. According to the responses, the training of the small cadre of primary care residents does emphasize ambulatory medical experience, supervised by an increasing number of faculty members in general medicine. Formal post-clinic conferences, analogous to inpatient attending rounds, are held substantially more often in hospitals with primary care programs than in hospitals without primary care programs. Formal ambulatory teaching conferences stress both traditional topics important in internal medicine and psychosocial issues. However, the authors could detect little effect of these activities in primary care programs on the training of traditional internal medicine residents even within the same hospital.

Ambulatory Care↗
PubMedDate not supplied

Predicting hospital-associated mortality for Medicare patients. A method for patients with stroke, pneumonia, acute myocardial infarction, and congestive heart failure.

We created a microcomputer-based system that uses characteristics of the patient at admission to predict death within 30 days of hospital admission for Medicare patients with stroke, pneumonia, myocardial infarction, and congestive heart failure. These conditions account for 13% of discharges and 31% of 30-day mortality for Medicare patients over 64 years of age. The system was calibrated on a stratified, random sample of 5888 discharges (about 1470 for each condition) from seven states, with stratification by hospital type to make the sample nationally representative. The predictors must be specially abstracted from the medical record. The cross-validated R2 for predictions is 0.14 to 0.25, which is better than the values for other systems for which we have data. Risk-adjusted predicted group mortality rates may be useful in interpreting information on unadjusted mortality rates, and patient-specific predictions may be useful in identifying unexpected deaths for clinical review.

Aged↗
PubMedDate not supplied

Comorbidities, complications, and coding bias. Does the number of diagnosis codes matter in predicting in-hospital mortality?

OBJECTIVE: Incomplete coding of secondary diagnoses may bias assessments of patient risks of poor outcomes using administrative health care databases, most of which allow only five diagnoses. The Medicare program is expanding the number of possible diagnoses from five to nine, aiming to improve coding completeness. We examined the impact of having more diagnosis codes available on assessments of risk of death. DESIGN: We used 1988 computerized hospital discharge abstract data from California, which allow up to 25 diagnoses per discharge, to select a sample of hospitalized patients and assessed the relationship between the presence of 29 specific secondary diagnoses and the risk of in-hospital death. SETTING: Nonfederal acute-care hospitals in California. STUDY POPULATION: All patients at least 65 years of age who were hospitalized for stroke, pneumonia, acute myocardial infarction, or congestive heart failure in California in 1988 (N = 162,790). MAIN OUTCOME MEASURES: Relative risk of death for each specific secondary diagnosis. RESULTS: Many conditions that on a clinical basis would be expected to increase the risk of death, such as adult-onset diabetes mellitus, previous myocardial infarction, angina, and ventricular premature beats, were associated with a lower risk of in-hospital death. CONCLUSIONS: Bias against coding of chronic or comorbid conditions on the computerized discharge abstracts of patients who die best explains these results. Efforts to improve diagnosis coding completeness solely by increasing the number of available coding spaces may not succeed.

Aged↗
PubMedDate not supplied

Interpreting hospital mortality data. The role of clinical risk adjustment.

This study uses national Medicare data as well as data that were abstracted to calibrate the Medicare Mortality Predictor System to assess the usefulness of a risk adjustment system in interpreting hospital mortality rates. The majority of variation in annual hospital death rates for the four conditions studied (stroke, pneumonia, myocardial infarction, and congestive heart failure) is chance variability that results from the relatively small numbers of patients treated in most hospitals in a year. For hospitals in the highest and lowest quartiles of observed death rates, the difference between observed rates and those predicted by the Medicare Mortality Predictor System is not quite on third smaller than the difference between observed rates and unadjusted national rates. Risk adjustment methods do not show whether the unexplained difference in mortality rates results from differences in effectiveness of care or unmeasured differences in patient risk at the time of admission. Risk-adjusted mortality rates, therefore, should be supplemented by review of the actual care rendered before conclusions are drawn regarding effectiveness of care.

Aged↗