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Biomedical subjects

E A Lerner

Publications and source records attributed to E A Lerner.

At least 37 records · Page 2Linked to original sources
PubMed1995

Specific induction of cAMP in Langerhans cells by calcitonin gene-related peptide: relevance to functional effects.

Epidermal Langerhans cells (LC) are associated anatomically with epidermal nerves, and a product of these nerves, calcitonin gene-related peptide (CGRP), inhibits the antigen-presenting capacity of LC and macrophages. As the CGRP receptor appears to be coupled to Gs alpha protein, which in turn activates adenylate cyclase, the ability of CGRP to induce cAMP in LC was examined and correlated with functional effects. LC were isolated from murine epidermal cells using antibodies on magnetic microspheres. Exposure to CGRP induced a significant increase in cAMP content, which could be inhibited by coculture with a truncated form of CGRP [CGRP-(8-37)] that is a specific competitive inhibitor of CGRP. Substance P and calcitonin failed to induce cAMP in LC. Although culture in CGRP reduced the ability of murine epidermal cells enriched for LC content to present pigeon cytochrome c to a responsive clone or to present antigen for elicitation of delayed-type hypersensitivity in immune mice, culture in forskolin had little or no effect on antigen presentation despite increased cAMP content of LC as much or more than that induced by CGRP. The effect of CGRP on antigen presentation in these systems could be blocked with CGRP-(8-37). CGRP inhibited the induction of B7-2 by lipopolysaccharide on peritoneal macrophages and a LC line, whereas calcitonin did not. CGRP induces specific accumulation of cAMP in LC and inhibits LC antigen-presenting function by a receptor-mediated event. However, the induction of cAMP by itself does not account for inhibition of antigen presentation. Suppression of the expression of B7-2 may be one mechanism by which CGRP inhibits antigen presentation.

Animals↗
PubMed1995

Vasorelaxant and second messenger effects of maxadilan.

Maxadilan is a potent vasodilator isolated from salivary gland extracts of the sand fly. Although cutaneous vasodilatation is probably the most important physiologic effect of maxadilan (i.e., assisting the sand fly in obtaining a blood meal), it also has effects on other vascular beds. In rabbit isolated aorta, recombinant maxadilan exhibited endothelium-independent relaxations with an IC50 of 24 nM for norepinephrine-induced (1 microM) contractions. Synthetic maxadilan had one-third the potency, with a corresponding IC50 of 74 nM for norepinephrine-induced (1 microM) contractions. Pretreatment with a number of receptor and channel blockers, including tetraethylammonium (1 mM), glyburide (1 microM), barium (0.5 mM), indomethacin (10 microM), propranolol (10 microM), cimetidine (10 microM) and nifedipine (10 microM) did not affect maxadilan-induced relaxations. After treatment with maxadilan, contractions recurred very slowly over approximately 40 min. At a concentration of 1 microM, maxadilan induced a 2- to 3-fold increase in cellular cyclic AMP levels. Maxadilan's activity was selective according to vessel type, with maximal activity in rabbit aorta and mesenteric artery and no activity in porcine and bovine coronary arteries. These studies suggest that maxadilan acts by raising the intracellular levels of cyclic AMP in the smooth muscle of selected blood vessels.

Animals↗
PubMed1994

American cutaneous leishmaniasis: in situ characterization of the cellular immune response with time.

The cellular nature of the infiltrate in the skin of patients with American cutaneous leishmaniasis was characterized by immunohistochemistry. The study population consisted of patients in Ceara, Brazil, an area where Leishmania braziliensis is endemic. Biopsies were taken from lesions present for 0.5-4 months duration and sections were stained with antibodies to T cells, T cell subsets, B cells, and macrophage markers to quantitate these cell types. The T cells accounted for 37.0 +/- 7.6% (mean +/- SD) of the infiltrate. The average percentages of CD4- and CD8-positive T cells were similar to each other, 20.4 +/- 9.0% and 19.9 +/- 6.7%, respectively. Interleukin-2 receptor-positive cells and B cells were infrequent, 3.7 +/- 3.0% and 2.3 +/- 3.1%, respectively. When the relationship between the age of the lesion at biopsy and the cellular phenotype was examined, it was noted that the percentage of positive cells remained fixed for all cell types except for that of gamma delta cells, which decreased with time. It is likely that gamma delta T cells are important in the early phase of the immune response to L. braziliensis and may, in general, be important in the early immune response of granulomatous diseases.

Adolescent↗
PubMed1993

Salivary gland extracts from the deerfly contain a potent inhibitor of platelet aggregation.

Salivary gland extracts of the deerfly contain a potent inhibitor of platelet aggregation, which assists the insect in obtaining a blood meal. The extract prevents platelet aggregation induced by ADP, thrombin, and collagen and inhibits fibrinogen binding to the glycoprotein IIb/IIIa receptor on platelets. The active component in deerfly salivary gland extract appears to be a protein that is comparatively more potent than the disintegrins present in viper venoms. Isolation and characterization of this protein may provide different directions in therapeutics and studies of normal platelet physiology.

Adenosine Diphosphate↗
PubMed1993

Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide.

Several observations suggest interactions between the immune and nervous systems. Psoriasis and atopic dermatitis may worsen with anxiety and have been associated with anomalous neuropeptide regulation. Neurotransmitters affect lymphocyte function and lymphoid organs are innervated. Calcitonin gene-related peptide (CGRP) is a neuropeptide and vasodilator that modulates some macrophage functions, including antigen presentation in vitro. CGRP is associated with Langerhans cells (LC) in oesophageal mucosa, particularly during inflammation, is present in epidermal nerves and is associated with Merkel cells. We examined the ability of CGRP to modulate LC antigen-presenting function and asked if CGRP-containing nerves impinge on LC. We report here that CGRP-containing nerve fibres are intimately associated with LC in human epidermis and CGRP is found at the surface of some LC. In three functional assays CGRP inhibited LC antigen presentation. These findings indicate that CGRP may have immunomodulatory effects in vivo and suggest a locus of interaction between the nervous system and immunological function.

Adult↗
PubMed1993

T-cell receptor V beta expression in normal human skin.

The skin-associated immune system is the first line of defense against pathogenic attack from the environment and is simultaneously tolerant to localized autoantigens and to antigens of the normal microbial flora. The T-cell receptor (TCR) repertoire of skin lymphocytes may therefore be influenced by the skin microenvironment. We studied the expression of TCR beta-chain variable region (V beta) genes in normal skin by a polymerase chain reaction-based comparative method. When comparing the amplification of V beta genes in peripheral blood and normal skin, we found that TCR V beta 1, -7, -14, and -16 were often highly expressed in skin relative to peripheral blood, whereas V beta 5.1 was often highly expressed in peripheral blood mononuclear cells but not in skin. These results demonstrate that the TCR repertoire of skin lymphocytes is not determined by random sampling of peripheral blood mononuclear cells but may be molded by the interaction with self antigens and/or the normal microbial flora in the microenvironment of the skin.

Base Sequence↗
PubMed1992

Maxadilan. Cloning and functional expression of the gene encoding this potent vasodilator peptide.

Maxadilan is a potent vasodilator peptide released into the skin when the sand fly Lutzomyia longipalpis, an important vector of leishmania, probes for a blood meal. As several lines of evidence suggest that this peptide may play a critical role in the enhancement of leishmania infectivity attributed to sand fly saliva, the peptide has been proposed as a candidate antigen for a leishmanial vaccine. Although maxadilan is the most potent vasodilator peptide known and shares several properties with calcitonin gene-related peptide (CGRP), studies of its structure, physiological effects, and biological roles have been limited by the miniscule quantities available. Here we report the isolation of cDNA and genomic DNA clones that encode maxadilan. The predicted translation product shows no significant homology with any previously isolated proteins. The coding DNA has been expressed in Escherichia coli and the purified recombinant peptide is biologically active with a specific activity comparable to the natural peptide. Recombinant maxadilan will be useful in studies of vascular biology and could lead to novel therapeutic and prophylactic agents.

Amino Acid Sequence↗
PubMed1991

Isolation of maxadilan, a potent vasodilatory peptide from the salivary glands of the sand fly Lutzomyia longipalpis.

Blood feeding by the sand fly Lutzomyia longipalpis is aided by the presence of a vasodilator in its salivary glands. This novel vasodilator has been isolated by reversed-phase high-performance liquid chromatography. Ten nanograms of the vasodilator are present in the extract of a pair of sand fly salivary glands. It has 500 times the vasodilatory activity of calcitonin gene-related peptide, previously the most potent vasodilator peptide known. This novel peptide is thus called maxadilan.

Amino Acids↗
PubMed1991

Healthy individuals and patients with systemic lupus erythematosus have unique, person-specific spectra of antibodies detectable on immunoblots.

Through the technique of immunoblotting, the spectrum and organ specificity of antibodies in healthy individuals and patients with systemic lupus erythematosus were examined. It was demonstrated that healthy individuals and patients with autoimmune disease have antibodies, some tissue specific and some not tissue specific, which are present in a pattern that is unique to each individual.

Adrenal Glands↗
PubMed1988

Chemical and pharmacologic agents that cause hyperpigmentation or hypopigmentation of the skin.

The list of chemicals and drugs that can result in alteration of skin color is slowly growing. Inflammatory processes can lead to either post-inflammatory hyperpigmentation or hypopigmentation. In non-inflammatory situations, chemical deposition can result in hyperpigmentation, whereas chemically induced destruction of melanocytes or their products may result in hypopigmentation.

Humans↗
PubMed1987

Whither the ANA?

Explore the source record for details and available documents.

Antibodies, Antinuclear↗
PubMed1984

Monoclonal antibodies specific for Ia glycoproteins raised by immunization with activated T cells: possible role of T cellbound Ia antigens as targets of immunoregulatory T cells.

Two monoclonal antibodies, Y-3P and Y-8P, specific for conventional mouse Ia glycoprotein antigens are described. Both were raised by repeated immunization of primed mice with activated T cells over a period of 1 yr, and both detect a new and broad public Ia specificity. Both of the antibodies react with I-A subregion-controlled A alpha:A beta complexes of all mouse strains apart from the responder strain (H-2d), as well as the equivalent of A alpha:A beta complexes in rats carrying seven independent haplotypes. These antibodies have great utility as almost universal Ia reagents. On the basis of these results, we propose that Ia antigens presented to the immune system bound to activated T cells are immunogenic, and may induce the production of Ia antibodies of novel and broad specificity. In addition, we propose that such bound Ia glycoproteins could be a target for immunoregulatory T cells, and could account for the specificity of suppression of graft-vs-host reactions and Ia-restricted helper T cells observed by others in F1 animals injected with parental T cells.

Animals↗
PubMed1983

Monoclonal antibody reveals H-2-linked quantitative and qualitative variation in the expression of a Qa-2 region determinant.

We have produced a monoclonal antibody, Y-7, that reacts with a Qa-2 region-controlled determinant. Cellular and strain distribution analyses, coupled with quantitative variation in the amount of Y-7 antigen expressed among strains, provide overwhelming evidence that Y-7 reacts with the Qa-2a determinant. The determinant detected by Y-7 is differentially expressed in T and B lymphocytes in a strain specific manner. Y-7 reacts with the majority of T lymphocytes (greater than 95%) and approximately one-half of B lymphocytes in certain strains (+ + strains), and with the majority of T lymphocytes (greater than 95%) and no B lymphocytes in other strains (+ strains). T lymphocytes in + strains express approximately three fold less of the Y-7 determinant than T lymphocytes from + + strains. In addition, we show that the Y-7 determinant is expressed in approximately one-third to one-half of Lyb-3-, 5- B lymphocytes. Possible mechanisms determining quantitative and qualitative variation in the expression of the Y-7 determinant in T and B lymphocytes are discussed.

Animals↗
PubMed1983

Idiotypic cross-reaction between MRL autoantibodies and a BALB/c myeloma.

Y2, a monoclonal anti-Sm antibody of MRL origin, demonstrates an idiotype commonly expressed in autoimmune MRL mice, although not necessarily associated with anti-Sm activity. To identify non-anti-Sm antibodies with this common idiotype, a rabbit anti-Y2 anti-idiotypic antiserum was tested for activity with other MRL hybridoma products (HP) as well as BALB/c myelomas. Idiotypic cross-reactivity was thus demonstrated for Y2 and the product of the BALB/c fusing cell line 45.6TG1.7 (M45), an antibody without known antigen binding activity. This determinant was denoted the Y2-M45 idiotype and its presence in serum and other antibodies tested by an inhibition ELISA. The idiotype was demonstrated on some, but not all, MRL HP's tested and was not confined to antibodies of a unique specificity. The idiotype was also present in sera of some normal as well as autoimmune strains of mice with highest levels in two strains bearing the lpr gene. These results indicate that idiotypes of anti-Sm antibodies are not exclusive to the pathologic setting but may be found commonly expressed in mice with antibodies of a variety of binding activity.

Animals↗