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J Daley

Publications and source records attributed to J Daley.

At least 19 recordsLinked to original sources
PubMed1992

Follicular dendritic cells inhibit human B-lymphocyte proliferation.

In germinal centers, B lymphocytes are intimately associated with follicular dendritic cells (FDCs). It has been hypothesized that FDCs are involved in the regulation of B-cell growth and differentiation through cell-cell interactions. In this study, highly enriched preparations of FDCs were isolated by cell sorting using the FDC restricted monoclonal antibody DRC-1. When irradiated FDCs were cultured with mitogen stimulated B cells, B cell 3H-TdR uptake was inhibited by up to 80%. This inhibitory effect was not seen when paraformaldehyde fixed FDCs were added to B-cell cultures, suggesting that the FDCs needed to be metabolically active. Moreover, supernatants from cultured FDCs were similarly able to inhibit B-cell proliferation. These results demonstrate that FDCs may downregulate the clonal expansion of B cells that occurs within lymphoid follicles as part of the normal physiologic immune response. Potentially, the loss of the inhibitory role of FDCs in vivo may be of importance in certain infectious and neoplastic processes in which germinal centers are affected.

B-Lymphocytes↗
PubMed1992

Observations on production of hemolysin, heat-labile enterotoxin and antimicrobial drug resistance among enterotoxigenic Escherichia coli from pigs.

A total of 52 isolates of Escherichia coli belonging to enterotoxigenic serotypes from piglets with diarrhea were examined for hemolysis, production of cholera-like enterotoxin (LT) and susceptibility to 10 antimicrobial drugs. A strong association between production of LT and hemolysis was seen. Ninety percent of 29 hemolylic isolates were LT+ whereas 100% of 23 nonhemolytic isolates were LT- in a commercial latex agglutination assay. Antimicrobial susceptibility tests employing disc diffusion showed that resistance to trimethoprim-sulfamethoxazole (TMS), neomycin and tetracycline was significantly less among LT+ isolates compared to LT- ones. Enrofloxacin was the only antimicrobial drug to which all the 52 isolates were susceptible.

Animals↗
PubMed1992

Pharmacotherapy of depression in the medically ill: directions for future research.

A common problem facing the psychiatric consultant and the medical practitioner is evaluating depression in patients with concurrent medical illnesses. Depression is difficult to recognize in the medically ill, often presenting with "masked" symptoms and organized into unique syndromes. A primary concern of the clinician is identifying those patients who are likely to benefit from an antidepressant trial. Although antidepressants have been shown to sometimes be of benefit in medical populations, the symptoms predicting antidepressant response remain poorly defined. Important directions for future research include 1) evaluating the safety and efficacy of newer antidepressants in the medically ill and 2) identifying those depressive syndromes that may be responsive to pharmacotherapy.

Adult↗
PubMed1992

A description and clinical assessment of the Computerized Severity Index.

Recent initiatives expanding health care data networks have increasingly emphasized severity of illness information, both to improve fairness of hospital payment and to assist in widespread assessment of hospital and physician quality. The Computerized Severity Index (CSI), one of the newest severity tools to generate interest, is disease specific and produces scores from 1 to 4 at both the disease and overall patient levels. Severity is defined as "the treatment difficulty presented to physicians due to the extent and interactions of patient's diseases." The clinical logic of the severity rating system is readily available through the "severity matrices" associated with over 820 disease groups. Questions exist about the CSI's dependence on diagnostic coding and the qualitative nature of some of the clinical criteria. More study is required to assess the utility of the CSI for various health policy purposes.

Baltimore↗
PubMed1992

A method for screening the quality of hospital care using administrative data: preliminary validation results.

Applying a computerized algorithm to administrative data to help assess the quality of hospital care is intriguing. As Iezzoni and colleagues point out, there are major differences of opinion as to the worth of such efforts. This article significantly advances the state of the art in using administrative data to screen for potential quality-of-care problems. In addition, this work on identifying complications of care goes well beyond the emphasis of many government organizations on hospital mortality rates. One question, however, not raised in the paper is: What is a practical upper limit to the sensitivity and specificity in comparing computerized screen results with the consensus judgments of a group of independent physicians? Advanced statistical techniques (such as bootstrapping) might be used to estimate the stability of consensus judgments by physician groups. When the judgments of two groups of physicians are compared with each other, the resulting sensitivity and specificity will not be .99! In addition, more training of members of the physician panels would probably have increased interrater reliability. While acknowledging this problem, the researchers' detailed analysis of the panel results is intriguing and represents a model for such studies. It is hoped that the authors will follow up on the avenues opened here. Furthermore, what degree of accuracy is necessary to identify facilities with higher-than-expected rates of complications? The authors discuss problems involved in using administrative data to target hospitals and departments for more costly in-depth reviews of quality. It is hoped that the promising findings that are reported here will be validated in other studies. Certainly their algorithms should find a ready audience in insurers and hospitals willing to try them out. Finally, should we expect additional research to lead to improvement in the authors' algorithms? I believe the algorithms will prove difficult to improve upon; but perhaps we should not worry about this. At some point, however, the cost of trying to identify and correct quality problems in "minimally outlier" hospitals will exceed the benefits, particularly given alternative uses for the funds. Might we now be close the the "flat of the curve" in the development of such systems for identification of quality problems? This issue should be discussed much further in future studies.

Abstracting and Indexing↗
PubMed1992

Signaling function of reconstituted CD16: zeta: gamma receptor complex isoforms.

Natural killer cells express an Fc receptor for IgG (CD16) in association with disulfide-linked dimers composed of two homologous subunits: the zeta chain of the T cell antigen receptor complex and the gamma chain of the mast cell/basophil Fc receptor for IgE. The ability of zeta and gamma to transduce CD16-mediated activation signals was compared by reconstituting distinct CD16 receptor isoforms composed of various combinations of zeta- and gamma-containing dimers. Stably transformed non-hematopoietic and hematopoietic cell lines were established that expressed chimeric molecules comprising the extracellular domain of CD16 joined to the transmembrane and intracellular domains of zeta or gamma. Reconstituted CD16 receptor complexes triggered Ca2+ influx, tyrosine phosphorylation, and IL-2 production in stable transformants of the Jurkat T cell line. However, cross-linking of the CD16/gamma chimera induced a specific pattern of tyrosine phosphorylation and was more efficient at signal transduction than a CD16, zeta-zeta complex, suggesting that zeta and gamma cytoplasmic domains may be coupled to distinct tyrosine kinase pathways that differentially regulate CD16-mediated activation signals. By contrast, both CD16/zeta and CD16/gamma chimeric molecules were not functional in stable transformants of the fibroblast Chinese Hamster Ovary cell line, indicating a requirement for downstream signaling components present in hematopoietic cells. Finally, the zeta transmembrane domain appears to preferentially associate with CD16 rather than the CD3:TCR complex, suggesting that a hierarchy of molecular interactions governs NK and T cell differentiation.

Animals↗
PubMed1992

Ethical issues.

The HIV virus and the associated worldwide pandemic pose enormous biomedical, clinical, and social dilemmas for health care providers, biomedical researchers, policy analysts, and the public at large 10 years after its discovery. Many of these dilemmas and challenges are captured in the difficult ethical issues the HIV epidemic has highlighted for primary care physicians. Given the vanishingly small risk to primary care providers of acquiring HIV infection in office practice and the rapidly increasing prevalence of the virus, a clear ethical obligation to care for HIV-infected patients exists for primary care physicians. Primary care providers should be sensitive to the potentially sensitive nature of patient risk status and HIV testing results and balance confidentiality in the medical record with the "need to know" the patient's clinical status by other health care professionals. Every attempt should be made by the primary care provider to encourage HIV-infected patients to act responsibly toward their intimate sexual partners and inform them of their HIV status to take appropriate precautions against acquiring the virus. Primary care providers should also model responsible shared decision making and goal setting with HIV-infected patients early in the course of the disease, laying the foundation for subsequent decision making later in the course of the illness. Finally, considerable controversy exists about the responsibilities of HIV-infected providers to inform patients of their status; professional and public policy in this area is in rapid flux. Undoubtedly, the HIV epidemic will continue to challenge us and force careful examination of many of the critical dilemmas in modern biomedical ethics.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Clonal analysis of T-cell deficiencies in autotransplant recipients.

We have used limiting dilution culture methods to determine the frequency of mitogen-responsive T cells in peripheral blood of patients after bone marrow autotransplantation, and have compared their responsiveness to that of allotransplant recipients and normal controls. Autotransplant patients were found to have low responder cell frequencies in tests for lymphokine-secreting helper function, and for IL-2 dependent proliferator and cytotoxic function. Multiple regression analysis showed that function was lower in autotransplant patients than in allorecipients, and lower in male patients for all three functional assays. Patients with clinically significant infection tended to have lower proliferative function in both transplant groups and lower cytotoxic function in the allotransplant population. Graft-versus-host disease was associated with lower T-cell function, but was present only in the allotransplant group; therefore, it cannot account for the even lower levels of function observed in the autotransplant population. Because we observe deficits in T-cell regeneration in autotransplant recipients that are even more severe than in allorecipients, we postulate that cellular immunodeficiency after bone marrow transplantation may reflect limitations in thymic-dependent repopulation rather than an effect of genetic disparity between host and donor (eg, clinical or subclinical graft-versus-host).

Adult↗
PubMed1991

Expression and tyrosine phosphorylation of the T cell receptor zeta-subunit in human thymocytes.

Recent evidence suggests that the zeta-subunit of the TCR complex plays a critical role in transducing signals initiated by the Ag receptor heterodimer. Because thymic maturation involves specific interactions between the TCR complex and thymic stromal cells, the zeta-subunit has been postulated to also play a role in this process. To assess the potential for zeta to contribute to thymocyte maturation, we have used an anti-zeta mAb (TIA-2) to quantitate its expression in mature (CD3bright) and immature (CD3dim and CD3-) populations of human thymocytes. Using both flow cytometric and immunoblotting analysis, we found that the relative expression of TCR-zeta varied directly with the surface expression of CD3. Importantly, TCR-zeta was detected in the majority of CD3- thymocytes, indicating that its expression precedes the surface appearance of CD3:TCR. In thymocytes, TCR-zeta was found to be constitutively phosphorylated on tyrosine residues. The relative expression of phospho-zeta varied directly with the maturational stage of the thymocyte, with the mature (CD3bright), single positive cells accounting for most of the phospho-zeta found in the human thymus. The expression of phospho-zeta could be significantly increased by activating thymocytes with mAb reactive with either CD3 or CD2. These results suggest that TCR-zeta is functionally linked to the major thymocyte activation receptors.

Cell Differentiation↗
PubMed1991

Practice patterns in the treatment of acutely ill hospitalized asthmatic patients at three teaching hospitals. Variability in resource utilization.

STUDY OBJECTIVE: Our objective was to determine the extent to which patterns of diagnostic and therapeutic practice differ among hospitals caring for acutely ill hospitalized asthmatic patients in a single city. DESIGN: Our study comprised a retrospective review of the records of patients admitted to the hospital for the treatment of acute asthma. SETTING: Three large teaching hospitals in Boston were the setting. PATIENTS: One hundred twenty-seven patients between 18 and 50 years of age who were admitted to the medical services specifically for the treatment of asthma were studied. INTERVENTIONS: There were no interventions. MEASUREMENTS AND MAIN RESULTS: For this group of patients with similar histories of asthma, clinical presentation, and severity of asthma, the diagnostic tests used within 12 hours of admission and the frequency and volume of diagnostic laboratory testing throughout the admission differed significantly among the three hospitals. Spirometry, the test bearing most directly on the severity of the asthmatic attack, was not used routinely as a criterion for admission or discharge at any of the hospitals. Other tests of uncertain efficacy, such as chest x-ray films, were used frequently at some of the hospitals. Patients at all three hospitals were treated similarly with intensive combined regimens of methylxanthines, sympathomimetics, and corticosteroids and had similar mean lengths of stay. The use of chest physical therapy, which has not yet been demonstrated to be effective in acute asthma, differed significantly among the three hospitals. CONCLUSIONS: We conclude that considerable variability exists in the diagnostic evaluation of acutely ill hospitalized asthmatic patients in the three hospitals; little variability exists in the pharmacologic treatment of these patients. In the absence of data on outcome regarding functional improvement and reductions in morbidity, we are unable to recommend a preferred pattern of practice from this study.

Acute Disease↗
PubMed1991

Intensity of in-hospital care for persons with AIDS.

We evaluated the intensity of medical care for 30 consecutive AIDS patients at one hospital, using methodology based on the Delay Tool of Selker et al. Of 25 AIDS patients who survived hospitalization, 15 had at least one delay day in the hospital. Major factors associated with care that could have been provided at an alternative site included difficulty with skilled nursing facility placement in 20% of the patients, difficulty coordinating out-of-hospital care in 28%, and scheduling of outpatient surgical procedures in 12%. For the 15 patients who could have received some of their care at a lower intensity setting, a median of 7 hospital days could have been potentially saved with better coordination of outpatient care and increased availability of skilled nursing facilities. The five patients who died in hospital also used large amounts of resources and had long lengths of stay. Prior studies of non-AIDS patients revealed similar results, suggesting that, for reasons of quality of care, quality of life, and economics, policy-makers must develop managed care programs, skilled nursing facilities that accept AIDS patients, inpatient psychiatry facilities, and increased hospice availability.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Reconstitution of T-cell function after CD6-depleted allogeneic bone marrow transplantation.

Patients who undergo allogeneic bone marrow transplantation (BMT) are clinically immunodeficient for a prolonged period after engraftment. In the present study, we examined immune function after BMT in a series of patients who had received HLA compatible sibling marrow grafts purged of T cells with anti-CD6 monoclonal antibody and complement. None of the patients in this analysis received immunomodulating agents and none had developed graft-versus-host disease (GVHD). Initially after BMT, natural killer (NK) cells are the predominant cell type, giving way to CD3+, CD5+ T cells after 4 to 8 weeks. Despite the return of normal numbers of T lymphocytes post-BMT phenotypic analysis reveals several long-term abnormalities, including an inverted T4:T8 ratio and a significant fraction of CD3+ T cells that do not co-express CD6. In mitogenic assays, stimulation by either nonspecific lectin (phytohemagglutinin; PHA) or antibodies to the CD2 surface structure (anti-T11(2) + anti-T11(3)) results in decreased levels of T-cell proliferation compared with controls for over 18 months post-BMT. In contrast, the ability of unstimulated peripheral blood mononuclear cells (PBMC) to respond to recombinant interleukin-2 (rIL-2) is relatively intact, most likely reflecting early functional reconstitution of the NK cell population. To further characterize the prolonged abnormalities in T-cell proliferation after PHA or CD2 stimulation, we examined more proximal events in T-cell activation such as induction of IL-2 receptor expression and stimulus-induced intracellular calcium flux. We found that the induction of IL-2 receptor (p55) after in vitro activation, although initially abnormal, recovers completely by 6 months post-BMT. We also found that, after CD2 stimulation, calcium flux in T cells was normal immediately after engraftment. In contrast, after stimulation with anti-CD3 antibodies, a large population of T cells do not develop intracellular calcium flux compared with controls. We conclude that despite the recovery of normal numbers of T lymphocytes early after engraftment of CD6-depleted marrow, these T cells exhibit several physiologic and functional abnormalities that persist for varying intervals post-BMT. At present, it is unclear which of these specific defects is most closely associated with increased susceptibility to infectious agents after BMT.

Adolescent↗
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↗