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Biomedical subjects

M Kaliner

Publications and source records attributed to M Kaliner.

At least 109 records · Page 6Linked to original sources
PubMed1981

Prostaglandin-generating factor of anaphylaxis. Identification and isolation.

Anaphylaxis of human lung in vitro is accompanied by prostaglandin (PG) formation. To search for factors capable of generating PG, supernatants prepared by reversed anaphylaxis of human lung tissue were added to guinea pig lung and PG formation examined. The PG-generating activity fractionated between Mr = 500 and 5000 by ultramembrane filtration and was designated prostaglandin-generating factor of anaphylaxis or PGF-A. Partially purified PGF-A was soluble in 80% ethanol and insoluble in chloroform or ethyl acetate. Paper chromatography of anti-IgE-treated human lung preparations revealed a ninhydrin-positive spot at RF 0.27 to 0.41 with PG-generating activity. When subjected to gel filtration on Sephadex G-50 or G-25, PGF-A demonstrated peak PG-generating capacity at Mr = 1200 to 1800. Peak fractions were pooled and chromatographed on CM52 cellulose with PGF-A activity eluting at 0.16 to 0.3 M NH4COOH. The pooled peak of PGF-A activity from Sephadex G-25 filtration and CM52 chromatography eluted as a single peak at 0.024 M NH4HCO3 on DE52. Application of the peak off DE52 to a paper chromatogram revealed a single ninhydrin-positive spot with an RF 0.27 to 0.41 with the capacity to generate PGs. Amino acid analysis of three purifications revealed the following: Glu/Asp/Gly/Ser/Thr (6:3:2:1:1). Based on these analyses, a Mr = 1450 was calculated for the PGF-A. Therefore, PGF-A represents a novel mediator of lung anaphylaxis which may be partly responsible for PG generation accompanying allergic reactions.

Amino Acids↗
PubMed1981

Autonomic abnormalities and autoantibodies to beta-adrenergic receptors.

We identified autoantibodies to beta 2-adrenergic receptors in the plasma of three apparently normal subjects, four patients with allergic asthma, one subject who was "preallergic" (at risk of allergy), and one patient with cystic fibrosis. Although these antibodies appeared to be heterogeneous, they shared the ability to affect binding of [125]protein A to calf-lung membranes, to inhibit beta-adrenergic ligand binding to calf-lung bet-adrenergic receptors, and to precipitate solubilized calf-lung beta-adrenergic receptors in an indirect immunoprecipitation assay. The presence of autoantibodies to beta-adrenergic receptors in these subjects correlates with abnormal autonomic responsiveness characterized by alpha-adrenergic and cholinergic hypersensitivity and beta-adrenergic hyposensitivity. These findings suggest that autoantibodies to beta-adrenergic receptors may play a part in the development of ment of autonomic abnormalities.

Adult↗
PubMed1981

Measurement of urinary histamine: development of methodology and normal values.

A small portion of the histamine that circulates through the kidney is excreted intact. Thus, the measurement of histamine in urine may be employed to monitor fluctuations in plasma histamine and has several advantages: stability, accessibility, and the opportunity for retrospective analysis. A method for measuring urine histamine was developed based on cation-exchange chromatography, organic solvent extraction, o-phthalaldehyde condensation, and measurement of fluorescence. However, because the histamine measured by this procedure was higher than that measured by other techniques, a portion of each sample was digested wtih diamine oxidase and the difference between the two portions of each sample, after isolation and fluorescent assay, was taken to reflect histamine. Normal urinary histamine levels of 13 +/- 8 ng/ml, 14 +/- 9 micrograms/24 hr, or 14 +/- 12 ng/mg creatinine/ml were found. Male and female subjects excreted equivalent concentrations; spot, short-timed, or 24-hr collections provided equivalent results; and histamine in frozen urine was stable greater than or equal to 6 mo. Two patients with systemic mastocytosis and two with idiopathic anaphylaxis had elevated urine histamine levels. Monitoring urine histamine may be useful in assessment of conditions in which histamine plays a role.

Adult↗
PubMed1981

Effects of infused histamine on asthmatic and normal subjects: comparison of skin test responses.

The effect of histamine infused intravenously at sequentially increasing concentrations (0.05, 0.1, 0.25, 0.5, and 1 microgram/kg/min) on the wheal responses to intradermal histamine and compound 48/80 in eight normal and five asthmatic subjects and to allergen skin tests in five asthmatic subjects was measured. These measurements were repeated following pretreatment with the H-1 antagonist hydroxyzine or the H-2 antagonist cimetidine, either alone or in combination. Histamine infused in progressively increasing concentrations had no effect on histamine, compound 48/80, or allergen skin tests either before or after H-1 or H-2 antihistamine treatment. No significant difference was found in the concentration of histamine or compound 48/80 required to elicit a 10-mm wheal in normal or asthmatic patients. Pretreatment with the H-2 antagonist alone had no effect on histamine or compound 48/80 skin tests in either group. However, the H-1 antagonist significantly reduced the wheal response to histamine (p less than 0.05 normal; p less than 0.025 asthmatics) and compound 48/80 (p less than 0.05 normal; p less than 0.025 asthmatics) in both groups. The combination of H-1 and H-2 histamine antagonists was not significantly different from the H-1 antagonist alone. Antigen skin testing was suppressed 82% by the hydroxyzine alone; no significant suppression was induced by cimetidine alone, and the combination of hydroxyzine plus cimetidine was only slightly more effective than hydroxyzine alone. The results indicate that blockade of histamine H-2 receptors with cimetidine has little or no additive effect on H-1 antagonist-suppressed skin test responses to histamine, compound 48/80, or antigen. Furthermore, the capacity of histamine to suppress histamine release in vitro from basophils was not demonstrated in vivo assessing skin mast cell responses. This observation combined with earlier studies on the human lung mast cell, which also failed to demonstrate that histamine had an inhibitory action, suggests that the human mast cell may not respond to histamine like the basophil and that this discrepancy may represent a fundamental difference in the cell types.

Adolescent↗
PubMed1981

The effects of histamine and prostaglandin D2 on rat mast-cell cyclic AMP and mediator release.

The possibility that histamine may play a functional role in modulating mast-cell secretion, as has been suggested for basophil degranulation, has both physiologic and pharmacologic implications. Therefore the capacity of histamine to influence rat peritoneal mast-cell (RPMC) cyclic AMP levels and reversed anaphylatic degranulation as reflected in the release of 3H-serotonin (5-HT) was examined. To ascertain that RPMC were functionally responsive to exogenous hormonal stimulation, assessment of prostaglandin (PG) D2 effects on cyclic AMP and 5-HT release were determined in parallel. Although PGD2 (100 microM) increased cyclic AMP and inhibited 5-HT release in the presence of 50 microM aminophylline, histamine (up to 1000 microM) was ineffective was ineffective in both. However, 1000 microM histamine in the presence of 500 microM aminophylline was capable of transiently increasing RPMC cyclic AMP (for 15 to 30 sec) and under these conditions of suppressing 5-HT release. The receptor subtype involved in the suppressive actions of histamine appeared to be of the H-1 type as reflected in the capacity of specific H-1 agonists to reproduce the inhibition of 5-HT release, whereas neither H-2 agonists nor H-2 antagonists had any influence. Thus, under conditions in which phosphodiesterase enzymatic action is impaired, histamine in extremely high concentrations is able to modulate mast-cell secretion. However, it seems very unlikely that this action of histamine has any physiologic significance.

Aminophylline↗
PubMed1981

Effects of arachidonic acid, monohydroxyeicosatetraenoic acid and prostaglandins on the release of mucous glycoproteins from human airways in vitro.

Human lung explants maintained in culture for 7 d incorporate [(3)H]glucosamine into mucous glycoproteins. Ethanol-precipitable, glucosamine-labeled mucous secretion was measured, and the effects of different pharmacologic agents upon this secretion were investigated. Anaphylaxed human lung generates prostaglandin (PG) synthesis and increased mucous release. Arachidonic acid (AA), PGA(2), PGD(2), and PGF(2alpha) significantly increased mucous glycoprotein release, whereas PGE(2) significantly reduced release. Evidence which suggests that lipoxygenase products of AA augment mucous release includes the following: (a) Nonsteroidal anti-inflammatory drugs (NSAID: acetylsalicylic acid and indomethacin) increase mucous release while preventing prostaglandin formation. (b) The increase in mucous release induced by AA or NSAID is additive once the agents are combined. (c) Several nonspecific lipoxygenase inhibitors (eicosa-5,8,11,14-tetraynoic acid; vitamin E; nordihydroguaiaretic acid; and alpha-naphthol) inhibit mucous release. Three additional lines of evidence directly indicate that monohydroxyeicosatetraenoic acid (HETE) causes increased mucous release: (a) the addition of a mixture of synthetic HETE (24-600 nM) increases mucous release; (b) pure 12-HETE (1-100 nM) also increases mucous release; (c) mucous release is increased synergistically by the combination of HETE and NSIAD. These data taken together demonstrate that HETE are capable of increasing mucous release and that conditions which may influence HETE production alter mucous release. Thus, although not directly demonstrating HETE production by human airways, the data strongly suggest that lipoxygenase products of AA in airways may profoundly influence mucous release; and it seems possible that lipoxygenase inhibitors may have a role in treating bronchorrhea.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1981

The mast cell.

The mast cell is the cellular basis for immediate hypersensitivity reactions. The specificity of the immediate hypersensitivity reaction is attributable to IgE molecules fixed to specific membrane receptors which, when stimulated by specific antigen, initiates the process of degranulation of the mast cell. The granules provide three separate sources of biologic activity: performed or primary mediators, newly generated or secondary mediators, and activities associated with the granular matrix. A number of biologic consequences are generated in response to these mediators and these include: increased vascular permeability, vasodilation, smooth muscle spasm, polymorphonuclear leukocyte chemotaxis, stimulation of adenylate and guanylate cyclase, superoxide radical generation, prostaglandin formation, mucous and gastric acid secretion, hypotension, tissue destruction, and mononuclear leukocyte infiltration. This pharmacopia of activities accounts for the clinical aspects of allergic diseases, suggests that the mast cell granule may be involved in the host's defense against parasitic infections, and is compatible with a suggested role of the mast cell as a widely distributed, monocellular endocrine system.

Animals↗
PubMed1980

Cholinergic nervous system and immediate hypersensitivity. II. An analysis of pupillary responses.

We studied the pupillary responses of various subjects to carbamylcholine chloride (CCC) in order to assess cholinergic responsiveness. Using the concentration of topical CCC required to induce greater than or equal to 1 mm miosis in the dark as the end point, we compared the responses of five groups of subjects: normal controls; patients with allergic asthma, allergic rhinitis, or intrinsic asthma; and a group who had reproducibly positive skin tests in the absence of symptoms. Subjects with allergic rhinitis or allergic asthma were significantly more sensitive than were normal controls. The patients with positive skin test and negative history were as sensitive as their symptomatic cohorts, suggesting that pupillary cholinergic hyperresponsiveness exists in atopic individuals regardless of symptoms. A small group with intrinsic asthma was examined and found to be even more sensitive than any of the atopic subjects. Thus abnormal hyperresponsiveness of the pupillary constrictor muscles to a topically instilled cholinomimetic has been found in all groups of atopic subjects plus nonallergic asthmatics. Analysis of pupillary responses may prove useful in assessment of autonomic responsiveness.

Adolescent↗
PubMed1980

Immunologic and neuropharmacologic stimulation of mucous glycoprotein release from human airways in vitro.

Human bronchial airways obtained after surgical resection were maintained in tissue culture for 24-48 h. Incorporation of [(3)H]- or [(14)C]-glucosamine, [(14)C]threonine, or Na(2)[(35)S]O(4) to the culture media resulted in biosynthesis of two radiolabeled glycoproteins-one filtering in the exclusion volume of Sepharose 2B, and the other filtering with an approximate molecular weight of 400,000. Both fractions had similar elution patterns from DEAE-cellulose anion exchange chromatography. [(3)H]Glucosamine was incorporated equally into the two fractions. The effects of anaphylaxis, histamine, and several neurohormones upon the release of [(3)H]glucosamine-labeled glycoproteins were analyzed, making no attempt to separate the two glycoprotein fractions. Three lines of evidence were found suggesting that mast-cell degranulation increases mucous release from cultured airways. (a) Supernatant fluids from anaphylaxed peripheral human lung that contained 200-400 ng/ml histamine and 400-1,000 U/ml slow-reacting substance of anaphylaxis (SRS-A) increased release by 40+/-18%. (b) The addition of antigen to IgE-sensitized airways led to the release of 26+/-7% of the total histamine and a 36+/-14% increase in mucous release. (c) Reversed anaphylaxis with anti-IgE antibodies induced a 36+/-6% release of histamine from the airways and an increase in the release of mucous glycoproteins of 25+/-9%. Exogenous histamine added to airways increased mucous glycoprotein release, an effect prevented by cimetidine, an H-2 antagonist. Selective histamine H-2, but not H-1 agonists increased mucous glycoprotein release, suggesting the possibility that anaphylaxis of airways results in increased mucous glycoprotein release partly through histamine H-2 stimulation.A cholinomimetic agonist, methacholine, increased mucous release; this response was prevented by atropine which alone had no effect. No response to beta-adrenergic stimulation with either isoproterenol or epinephrine was noted. However, alpha-adrenergic stimulation with either norepinephrine combined with propranolol or phenylephrine alone resulted in dose-related increases in glycoprotein release. Both alpha-adrenergic and cholinergic stimulation of human tissues induce the formation of guanosine 3',5'-phosphoric acid (cyclic GMP), and 8-bromo cyclic GMP added to the airways led to increased mucous secretion. Thus, it seems likely that neurohormones capable of stimulating cyclic GMP formation in human airways may lead to increased mucous glycoprotein release.

Anaphylaxis↗
PubMed1979

Alpha-adrenergic hyper-responsiveness in asthma.

Because alpha-adrenergic stimulation causes bronchoconstriction, the alpha-adrenergic responsiveness of 21 subjects with allergic asthma was compared with that of 16 subjects with allergic rhinitis and 38 normal control subjects. None of the patients had taken medications for at least 30 days before study. Alpha-adrenergic responsiveness was measured by the capacity of phenylephrine to constrict the cutaneous vascular bed and to dilate the pupillary sphincter muscle. Asthmatic subjects required 4.0 +/- 0.6 ng to reduce their cutaneous blood flow by 50 per cent, whereas normal controls required 32.0 +/- 7.5 ng (P less than 0.005) and subjects with allergic rhinitis required 23.7 +/- 9.4 ng (P less than 0.02). The pupils of asthmatic subjects dilated by greater than 0.5 mm in response to 1.8 +/- 0.14 per cent phenylephrine, patients with allergic rhinitis required 2.4 +/- 0.16 (P less than 0.01), and normal controls needed 2.7 +/- 0.07 (P less than 0.00001). Therefore, the patients with allergic asthma had significantly enhanced alpha-adrenergic responses when compared both to normal subjects and patients with allergic rhinitis; the possibility that increased alpha-adrenergic activity contributes to the asthmatic diathesis warrants further exploration.

Adolescent↗
PubMed1979

Prostaglandin generation by human and guinea pig lung tissue: comparison of parenchymal and airway responses.

Anaphylaxis of human lung is accompanied by the synthesis of prostaglandins (PG), including PGF2 alpha and PGE. In an analysis of the tissue source of these prostaglandins, parenchymal preparations of both human and guinea pig (GP) lungs were compared. Peripheral, relatively airway-free preparations of human lung generate PGF2 alpha and PGE in response to histamine and 2-methylhistamine, on H1 agonist, but not to dimaprit, an H2 agonist. GP parenchymal preparations respond in a similar fashion. Stimulation of these same preparations with KCl or carbachol caused no increase in the synthesis of either PG. In human airway preparations all three agonists (histamine, KCl, and carbachol) caused the selective generation of PGE. However, stimulation of GP airway preparations with the agonists caused the production of both PGE and PGF2 alpha. These data indicate that (1) human and GP peripheral lung tissues respond to H1, but not H2, stimulation with the generation of PGF2 alpha and PGE; (2) these parenchymal responses are specific and may not be attributed to muscle contraction; and (3) stimulation of muscle contraction in human airway preparations results in the selective generation of PGE while GP airways produce both PGE and PGF2 alpha.

Anaphylaxis↗