Search PubMed⌕ Search

Biomedical subjects

M Kaliner

Publications and source records attributed to M Kaliner.

137 records · Page 8Linked to original sources
PubMed1973

A sequence of biochemical events in the antigen-induced release of chemical mediators from sensitized human lung tissue.

Five sequential steps interspaced between the antigen activation of human lung fragments sensitized with IgE and the release of the chemical mediators, histamine and slow-reacting substance of anaphylaxis (SRS-A), have been delineated. The experimental design that permits this analysis is based upon the capacity to maintain the serine esterase essential to mediator release in its diisopropylphosphofluoridate (DFP)-resistant precursor state despite antigen challenge and upon the ability to arrest reversibly the reaction sequence by various manipulations. When sensitized lung fragments are challenged with antigen in the presence of DFP, a serine esterase is converted to its active DFP-inhibitable state; this conversion is prevented if antigen challenge in the presence of DFP occurs in calcium-free buffer indicating that immunologic activation of the esterase requires extracellular calcium. The fact that calcium depletion alone does not impair antigen-induced histamine release implies that prevention of esterase activation depends upon both the absence of extracellular calcium and the inactivation of any active esterase by DFP to prevent an autocatalytic feedback activation. Arresting the antigen-induced activation of the serine esterase by the combination of DFP in calcium-free buffer precludes the sequence from reaching the labile, 2-deoxyglucose (2-DG)-inhibitable, energy-requiring step, indicating that proesterase activation precedes this energy-requiring stage. The 2-DG-inhibitable step precedes a second calcium-requiring, EDTA-inhibitable stage, as EDTA prevents glucose reversal of 2-DG inhibition of antigen-challenged tissue, while the presence of 2-DG does not prevent calcium reversal of EDTA inhibition. The finding that isoproterenol prevents calcium reversal of EDTA inhibition of mediator release suggests that the inhibitory site of action of increased concentrations of cyclic AMP is coincident with or subsequent to the second calcium-requiring, EDTA-inhibitable step. Therefore, the sequence of biochemical events initiated by the interaction of antigen with tissue-fixed IgE antibodies appears to proceed from the calcium-requiring activation of a DFP-sensitive serine esterase; the further autocatalytic activation of the esterase; a 2-DG-inhibitable energy requirement; a second calcium-requiring, EDTA-inhibitable stage; and a cyclic AMP-inhibitable step to the release of histamine and SRS-A.

Antigen-Antibody Reactions↗
PubMed1973

The modulating influence of cyclic nucleotides upon lymphocyte-mediated cytotoxicity.

The capacity of allosensitized thymus-derived lymphocytes to destroy target cells bearing donor alloantigens is modulated by the cellular levels of cyclic AMP and cyclic GMP. Increases in the cyclic AMP levels of attacking lymphocytes by stimulation with prostaglandin E(1), isoproterenol, and cholera toxin inhibit lymphocyte-mediated cytotoxicity; whereas, depletion of cyclic AMP with imidazole enhances cytotoxicity. The augmentation of cytotoxicity produced by cholinergic stimulation with carbamylcholine is not associated with alterations in cyclic AMP levels and is duplicated by 8-bromo-cyclic GMP. The effects of activators of adenylate cyclase, cholinomimetic agents, and 8-bromocyclic GMP are upon the attacking and not the target cells and occur at the time of initial interaction of attacking and target cells. Indeed, the level of cyclic nucleotide (cyclic AMP and cyclic GMP) at the time of initial cell-to-cell interaction determines the extent of cytotoxicity.

Animals↗
PubMed1972

Immunological release of histamine and slow reacting substance of anaphylaxis from human lung.

The immunologic release of histamine and slow reacting substance of anaphylaxis (SRS-A) from human lung tissue can be enhanced by stimulation with either alpha adrenergic agents (phenylephrine or norepinephrine in the presence of propranolol) or cholinergic agents (acetylcholine or Carbachol). The finding that atropine prevents cholinergic but not comparable alpha adrenergic enhancement is consistent with the view that cholinergic and alpha adrenergic agonists interact with separate receptor sites on the target cells involved in the immunologic release of chemical mediators. The consistent qualitative relationship between the antigen-induced release of mediators and the level of cyclic adenosine monophosphate (cyclic AMP) as measured by the isolation of (14)C-labeled cyclic AMP after incorporation of adenine-(14)C into the tissues or by the cyclic AMP binding protein assay suggests that changes in the level of this cyclic nucleotide mediate adrenergic modulation of the release of histamine and SRS-A. The addition of 8-bromo-cyclic guanosine monophosphate (cyclic GMP) produces an enhancement of the immunologic release of mediators while dibutyryl cyclic AMP is inhibitory. As cholinergic-induced enhancement was not associated with a measurable change in the levels of cyclic AMP, the possibility is suggested that cyclic GMP may be the intracellular mediator of cholinergic-induced enhancement of the immunologic release of histamine and SRS-A.

Acetylcholine↗
PubMedDate not supplied

Analysis of human nasal mucous glycoproteins.

Human nasal turbinates were cultured in the presence of 3H-glucosamine, which is incorporated into nasal mucous glycoproteins. Nasal mucous glycoprotein was then characterized biochemically, and the effects of various neurohormones and immunologic stimulation on mucous glycoprotein release were analyzed. Fractionation of nasal mucous glycoprotein by gel filtration chromatography revealed a molecular size range of 2 to 200 X 10(5) (as judged by protein markers) but displayed a single, acidic charge, as reflected both in a narrow elution pattern from DEAE-cellulose and a sharp isoelectric focusing point of 2.6. Highly enriched nasal mucous glycoprotein preparations consisted of 80 per cent carbohydrate and 20 per cent protein (by weight) and included enzymatically cleavable carbohydrate side chains with molecular weights of 1,600 to 1,800. Thus, nasal mucous glycoproteins are a family of molecules that express uniform acidic charge characteristics and a wide range of molecular sizes. Cholinergic stimulation of atropine-inhibitable muscarinic receptors increased nasal mucous glycoprotein release in a dose-related manner, as did alpha-adrenergic stimulation. However, beta-adrenergic stimulation did not affect mucous glycoprotein release. Immunologic stimulation of nasal mast cells by either reversed anaphylaxis or antigen challenge after passive sensitization caused both histamine release and increased mucous glycoprotein release. Thus, nasal turbinates provide an accessible source of tissue for the analysis of nasal mucus secretion and mast cell degranulation and may provide a model for the study of pharmacologic approaches to the universally experienced discomfort of rhinorrhea.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

Increased urine histamine and contrast media reactions.

Urine samples were collected from 200 subjects undergoing intravenous pyelography. The urine histamine levels were compared with those of 132 normal control subjects, 11 subjects with systemic mastocytosis, six subjects with idiopathic anaphylaxis, and ten subjects experiencing mild anaphylactic reactions during allergy immunotherapy. Compared with normal controls, as a group, all subjects receiving intravenous contrast media had increased urine histamine (P less than 0.05 by Student's t-test) while those subjects experiencing adverse reactions had considerably larger increases. The urine histamine levels in the subjects experiencing systemic reactions were in the same range as those observed in patients having mild anaphylactic reactions to immunotherapy and somewhat lower than those found in idiopathic anaphylaxis or systemic mastocytosis. These data suggest that some histamine release accompanies infusions of contrast media in all subjects and that larger amounts of histamine release are associated with adverse reactions.

Adolescent↗
PubMedDate not supplied

Enhancement of histamine--induced vascular permeability in guinea pigs infected with Bordetella bronchiseptica.

In the nasal mucosa, histamine induces vascular permeability, stimulates nociceptive nerves, and recruits parasympathetic reflexes that regulate glandular exocytosis. Unilateral histamine nasal provocations were performed in a group of guinea pigs in the prodromal stage of undiagnosed Bordetella bronchiseptica infection. Vascular permeability in the histamine challenged nostrils was increased approximately 2- to 4-fold compared to healthy animals (p < 0.001). The duration of significant vascular leak was prolonged from 10 to 30 minutes. In the contralateral, nonchallenged nostrils, secretion of total protein and albumin, but not exudation of intravenously infected 125I-bovine serum albumin, was increased, suggesting an augmentation of parasympathetic reflexes without changes in contralateral vascular leak. These observations suggest that Bordetella bronchiseptica infection leads to hyperresponsiveness to histamine in the nasal mucosa with increased vascular permeability and recruitment of nociceptive nerve-parasympathetic reflexes.

Animals↗
PubMedDate not supplied

Treatment of sinusitis in the next millennium.

Sinusitis is an increasingly more important disease due to its increasing prevalence, costs, and recognition. Most acute sinusitis episodes follow colds or acute allergic rhinitis. Chronic sinusitis is most commonly due to allergic and nonallergic rhinitis or anatomical defects in the nose. Several common immunologic abnormalities usually present as sinusitis and may be recognized first by the allergist-immunologist. Treatment involves a carefully selected antibiotic prescribed for an adequate period of time, nasal hygiene using nasal saline washes, topical nasal corticosteroids, and decongestants. Medical management of sinusitis tends to be effective, even in patients with long-standing sinus disease.

Acute Disease↗