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D C Adelman

Publications and source records attributed to D C Adelman.

At least 19 recordsLinked to original sources
PubMed1997

Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody.

Treatment of allergic disease by decreasing circulating IgE with anti-IgE Abs is currently under clinical study. Based on previous unrelated studies, it appeared likely that Fc(epsilon)RI expression on basophils and mast cells might also be regulated by levels of circulating IgE Ab. Therefore, the expression of IgE and Fc(epsilon)RI on human basophils was examined in 15 subjects receiving humanized anti-IgE mAb intravenously. Treatment with the anti-IgE mAb decreased free IgE levels to 1% of pretreatment levels and also resulted in a marked down-regulation of Fc(epsilon)RI on basophils. Median pretreatment densities of Fc(epsilon)RI were approximately 220,000 receptors per basophil and after 3 mo of treatment, the densities had decreased to a median of 8,300 receptors per basophil. Flow cytometric studies, conducted in parallel, showed similar results and also showed in a subset of 3 donors that receptors decreased with a t1/2 of approximately 3 days. The responsiveness of the cells to IgE-mediated stimulation using anti-IgE Ab was marginally decreased (approximately 40%) while the response of the same cells to stimulation with dust mite Ag, Dermatophagoides farinae, was reduced by approximately 90%. One possible explanation for these results is that Fc(epsilon)RI density is directly or indirectly regulated by plasma-free IgE levels.

Adult↗
PubMed1996

CD45 isoforms on human CD4+ T-cell subsets.

We have examined the level of surface expression and functional properties of leukocyte function associated antigen-1, very late antigen-4, and CD45 isoforms on a panel of human CD4+ T-cell clones representative of TH0, TH1, and TH2 cells. There were no qualitative differences in the expression of these antigens among the three types of CD4+ T-cell clones. However, CD45RB was the only CD45 isoform that provided a costimulatory signal in a solid-phase antibody-induced cellular proliferation assay. Additionally, the antigen-induced proliferative response of T-cell clones was inhibited by soluble anti-CD45RO and anti-CD45RB antibodies. Our results suggest that CD45 isoforms differentially provide costimulatory signals to T cells. However, the ability of each CD45 isoform to provide a costimulatory signal does not differ among the TH0, TH1, or TH2 T-cell populations.

CD4-Positive T-Lymphocytes↗
PubMed1994

The cross-reactivity and immunology of beta-lactam antibiotics.

Allergic reactions to beta-lactam antibiotics are well described; however, only the immunochemistry of penicillin has been characterised. Although the major determinant of benzylpenicillin (penicillin G) is commercially licensed for diagnostic applications, minor determinants are only available at some centres to be used for identification of hypersensitive individuals. Cephalosporins share a common bicyclic nuclear structure with penicillin and most cross-reactivity is generated to the beta-lactam ring. It is not possible to determine the actual incidence of cross-reactivity between penicillins and cephalosporins, but evidence suggests the true rate is lower than usually appreciated. In vitro testing demonstrates extensive cross-reactivity between penicillin and the carbapenems. Although the rate of clinical cross-reactivity is not known, imipenem should not be given to patients with proven penicillin hypersensitivity. In contrast, aztreonam and the monobactams can be safely given to penicillin-allergic patients.

Anti-Bacterial Agents↗
PubMed1993

Isotype-specific regulation of human lymphocyte production of immunoglobulins by sustained exposure to vasoactive intestinal peptide.

Exposure of lymphocytes to nanomolar to micromolar concentrations of vasoactive intestinal peptide (VIP) for 1 to 3 days only modestly suppressed or enhanced the production of IgA and IgM, but not IgG. The effects of twice daily additions of 10(-12) to 10(-7) mol/L VIP for up to 18 days on pokeweed mitogen-stimulated peripheral blood mononuclear cells (PBMCs) from normal human subjects was examined by quantifying the production of IgG, IgM, and IgA. The maximum suppression of IgG by 10(-9) mol/L VIP was 79% +/- 33% (mean +/- SD) (range, 41% to 97%; p < 0.015) on day 9 and 84% +/- 1% (range, 74% to 96%; p < 0.0001) on day 14 and was significant at 6 x 10(-10) to 4 x 10(-9) mol/L VIP. Suppression of IgM production by 10(-9) mol/L VIP was significant and was observed first on day 5 and persisted through day 14. VIP did not alter IgA production or affect the proliferation or viability of PBMCs. The production of IgE by interleukin-4 stimulated PBMCs was enhanced consistently in two subjects but not in two other subjects. The duration of exposure to nanomolar concentrations of VIP is thus a critical determinant of its immunoregulatory effect, as manifested by late suppression of production of IgG and IgM and concurrent enhancement of production of IgE in some subjects.

B-Lymphocyte Subsets↗
PubMed1991

Biologic response modifiers in primary immunodeficiency disorders.

OBJECTIVE: To propose a new classification for the primary immunodeficiency disorders and to review potential therapeutic applications of biologic response modifiers in these disorders. DATA SOURCE: Relevant articles were identified through a search of MEDLINE using the following indexing terms: primary immunodeficiencies (and subclassifications), and human immunomodulators (and subclassifications). STUDY SELECTION: Articles were critically reviewed and included if relevant. DATA SYNTHESIS: The primary immunodeficiency disorders are classified according to functional abnormalities, specifically, abnormalities in early cellular maturation, differentiation, regulatory cell function, enzymatic function, and cytokine responses. Such a classification clarifies the potential role of biologic response modifiers in primary immunodeficiency disorders. Intravenous gammaglobulin and histamine-2 (H2)-receptor blockers modify regulatory cell function; retinoids modify abnormal cellular differentiation, gene transfer and enzyme replacement can be applied in disorders characterized by specific functional gene abnormalities; and interferons modify abnormal cytokine responses. Interleukin-2, thymic hormones, transfer factor, and levamisole appear to affect multiple functional defects. CONCLUSIONS: Biologic response modifiers are currently important ancillary tools in the treatment of immunodeficiency disorders, and their therapeutic role will become even more important in the future. Multi-center cooperative trials of new and existing agents are needed to fully define their roles and efficacy in the treatment of these disorders.

Cytokines↗
PubMed1991

13-cis retinoic acid enhances in vivo B-lymphocyte differentiation in patients with common variable immunodeficiency.

Retinoic acid (RA) has been demonstrated to drive both phenotypic and functional in vitro differentiation of B cell hybridomas from patients with common variable immunodeficiency (CVI) who manifest an "intrinsic" defect in terminal B cell differentiation (J Exp Med 1988;168: 55-71). Therefore, we conducted an open trial to determine the effects of oral 13-cis RA (0.5 mg/kg/day; 12 weeks receiving and 12 weeks without drug) on in vivo B cell differentiation in subjects with CVI. At various times before, during, and after drug administration, patients' B cells were tested for changes in cell-surface phenotype and in vitro immunoglobulin production in response to recombinant cytokines. Before 13-cis RA, all patients had decreased Leu-8 coexpression on CD20+ cells. Seven of eight subjects demonstrated "normalization" of this phenotype after 8 to 16 weeks of 13-cis RA administration. Patients whose B cells demonstrated more than normal CD20 display also had a fall toward normal in this parameter. These effects persisted for 6 to 12 weeks after drug was stopped. It appears that 13-cis RA drives B cells of patients with CVI to express a more differentiated cell-surface phenotype and may promote functional differentiation in some patients.

Administration, Oral↗
PubMed1990

Neuroimmunology.

Explore the source record for details and available documents.

Animals↗
PubMed1990

Elevated serum interleukin-6 associated with a failure in B cell differentiation in common variable immunodeficiency.

Interleukin-6 (IL-6/B cell stimulatory factor 2) has been found to drive activated human B-lymphocytes through the final stages of differentiation to become immunoglobulin-producing cells. Most patients with common variable immunodeficiency (CVI) have B-lymphocytes that fail to differentiate into high-rate immunoglobulin-secreting cells in vivo and in vitro. In view of (1) the known effects of IL-6 to promote B-lymphocyte terminal differentiation and (2) the defect in differentiation in B-lymphocytes of patients with CVI, we believed that it was important to analyze the role of this cytokine in patients with CVI. Using an IL-6-dependent murine hybridoma cell line in a bioassay, serum IL-6 levels were determined in 17 patients with CVI and in eight normal control subjects. Thirteen of the 17 patients with CVI exhibited serum IL-6 levels that were twofold to 18-fold higher than the range (mean, +2 SD) of normal control subjects. Spontaneous IL-6 production by peripheral blood mononuclear cells (PBMC) of patients with CVI was significantly higher than that from normal control subjects, whereas lipopolysaccharide maximally stimulated IL-6 production by PBMCs of patients with CVI or PBMCs of normal control subjects was equivalent. A substance inhibitory of IL-6 bioactivity was found in equivalent amounts in sera of both patients and normal control subjects. Sera from patients with CVI with high IL-6 bioactivity were found to have saturated this IL-6 inhibitory substance, thus resulting in large amounts of free IL-6 in the sera. These studies suggest that the failure of B cells from patients with CVI to terminally differentiate into high-rate immunoglobulin-secreting cells cannot be attributed to a decrease in the serum levels of IL-6 and that the increased circulating IL-6 levels in patients with CVI result from hyperproduction rather than decreased use of IL-6. The persistently elevated levels of IL-6 observed in some patients with CVI may secondarily result in the induction of the neoplastic and autoimmune phenomena associated with this disease.

Agammaglobulinemia↗
PubMed1990

Neuropeptides, mast cells and allergy: novel mechanisms and therapeutic possibilities.

Diverse neuropeptides are released by neuroendocrine and immune cells at the sites of allergic and inflammatory reactions. The neuropeptides and other neuromediators affect functions of smooth muscle, microvasculature and secretory cells, and are potent stimuli of mast cell, lymphocyte and other leucocyte contributions to such reactions. The distinctive immune sources, structures and cellular receptors for neuromediators suggest the possibility of novel pathogenetic mechanisms and levels of pharmacological intervention specific for neuroregulation of immunity and hypersensitivity.

Humans↗
PubMed1990

Role of lymphotoxin in expression of interleukin 6 in human fibroblasts. Stimulation and regulation.

IL-6 is a cytokine with a number of biological functions, including stimulation of immunoglobulin synthesis and proliferation of early hematopoietic stem cells. We showed that lymphotoxin stimulated accumulation of IL-6 mRNA in human fibroblasts (W138) in a dose-responsive fashion; tumor necrosis factor-alpha (TNF-alpha) was about threefold more potent than lymphotoxin. Further experiments suggested that stimulation by lymphotoxin was independent of protein kinase C activity, did not require new protein synthesis, and was at least in part a result of increased stabilization of IL-6 mRNA. t1/2 of the IL-6 transcripts increased from 0.3 h in unstimulated cells to 0.85 h in cells stimulated with lymphotoxin. In addition, stimulators of protein kinase C, including phorbol esters and teleocidin, enhanced accumulation of IL-6 mRNA. Cycloheximide (CHX), inhibitor of protein synthesis, also markedly increased levels of IL-6 mRNA. Both CHX and activators of protein kinase C increased by greater than 16-fold the stability of IL-6 mRNA. Further, dose-response studies showed that sodium fluoride (NaF), activator of G-binding proteins, and ouabain, inhibitor of Na+/H+ pump, increased levels of IL-6 mRNA. NaF stimulated IL-6 mRNA levels independent of protein kinase C activity. These results suggest that stimulators of several pathways of signal transduction increase levels of IL-6 mRNA and posttranscriptional stabilization is, in part, the mechanism that many of these signals, including lymphotoxin, use to increase levels of IL-6 RNA.

Cell Line↗
PubMed1989

Acute respiratory emergencies in emergency treatment of the injured athlete.

Exercise and physical fitness are becoming increasingly popular in our society. As a result there are more individuals who are at risk for the development of acute respiratory emergencies associated with sports and athletics. EIB is a common feature of asthma and is characterized by a postexercise fall in FEV1 of more than 10 per cent. Although a variety of medications have been used for the prevention of EIB, cromolyn sodium and inhaled adrenergic agonists have been shown to be the most effective. EIA and cholinergic urticaria are two physical allergies in which hypotension can be brought on by exercise. In some individuals, EIA develops only in association with the ingestion of a particular food. Associated with sports and recreational activities in alpine areas is the risk of developing acute high-altitude medical problems. One of the most dramatic and potentially life threatening is high-altitude pulmonary edema. The management of this condition can be problematic, particularly if rapid descent to lower elevations is not possible. Although rare, spontaneous pneumothorax and pulmonary emboli do develop in the otherwise well-conditioned athlete. These entities must be considered when the physician evaluates any athlete in whom acute cough and dyspnea develop.

Acute Disease↗
PubMed1988

Retinoic acid induces the differentiation of B cell hybridomas from patients with common variable immunodeficiency.

Human-human B cell hybridomas constructed from B lymphocytes of common variable immunodeficiency (CVI) patients and the nonsecreting cell line WIL2/729 HF consistently secrete low levels of Ig and appear to retain a defect characteristic of the CVI patient's B cells. We assessed the differentiative capacity of retinoic acid (RA) on these hybridomas, as well as on hybridomas constructed from normal B cells and from patients with selective IgA deficiency. RA at concentrations varying between 10(-5) and 10(-9) M augmented IgM secretion 4-20-fold from four of four CVI hybridomas tested, but did not affect Ig secretion from normal or IgA-deficiency hybridomas. In support of this elevated Ig secretion, RA enhanced the de novo synthesis of biosynthetically labeled light (kappa) and heavy (mu) Ig (up to 4- and 15-fold, respectively) in the CVI hybridoma line JK32.1. The increase in IgM synthesis/secretion could not be accounted for by RA-induced alteration in the cell cycle. In inducing this increase in IgM production, RA was found to affect two aspects of Ig gene expression: (a) the steady-state levels of heavy and light chain mRNAs were enhanced, and (b) the processing of mu heavy chain transcripts to the secreted mRNA form became favored over the membrane mRNA form. We also show that expression of Leu-17 (CD38), a surface marker that is re-expressed in the late pre-plasma stage of B cell development, was increased by RA from less than 20% to greater than 90% of the total cell population, with a concomitant 4-10-fold augmentation in the mean fluorescence intensity. Changes in both Leu-17 expression and de novo Ig synthesis were prominent by 24 h, but could be observed as early as 8 h after induction. Taken together, our study demonstrates that RA affects a marked alteration in the differentiated state of the CVI hybridoma clones. This finding suggests that retinoids can enhance the functional capabilities of B cells with defects in maturation and support further studies to evaluate their clinical potential in CVI.

B-Lymphocytes↗
PubMed1988

Imipenem cross-reactivity with penicillin in humans.

We examined the potential for IgE-mediated cross-reactivity between the carbepenems, a new class of beta-lactam antibiotics, represented by imipenem, and penicillins. In vivo skin testing with the relevant imipenem and penicillin determinants was undertaken. Having determined the concentrations of imipenem materials that did not induce false positive skin tests in nonpenicillin-allergic control subjects, we tested 40 subjects with a history of penicillin-allergic reactions. Twenty of these subjects were found to be nonallergic to penicillin on skin testing, and none of these subjects reacted to the imipendem determinants. In contrast, half the 20 subjects who were positive to one or more penicillin determinants also reacted to imipenem reagents. There was a good correlation between the penicillin and imipenem reagents to which the patients reacted. Imipenem should only be administered to penicillin-allergic subjects with similar precautions of penicillin administration to such patients.

Cross Reactions↗