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Book: Neutral proteases of mast cells

Schwartz, Lawrence B.

15 tables

(Monographs in allergy ; 27)

1990

Author's details	vol. ed. L. B. Schwartz
Series title	Monographs in allergy ; 27
Collection
Keywords	Mast Cells / enzymology ; Peptide Hydrolases / metabolism ; Mastzelle ; Proteasen
Subject	EC 3.4 ; Proteinasen ; Peptidasen ; Proteolytisches Enzym ; Peptid-Hydrolasen
Size	VIII, 165 S. : Ill., graph. Darst.
Publisher	Karger
Publishing place	Basel u.a.
Publishing country	Switzerland
Document type	Book
HBZ-ID	HT003748891
ISBN	3-8055-5162-2 ; 978-3-8055-5162-5
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Heparin comes clean.

Schwartz, Lawrence B

The New England journal of medicine

2008 Volume 358, Issue 23, Page(s) 2505–2509

MeSH term(s)	Animals ; China ; Chondroitin Sulfates/pharmacology ; Complement Activation/drug effects ; Complement C3a/biosynthesis ; Complement C3a/drug effects ; Complement C5a/biosynthesis ; Complement C5a/drug effects ; Drug Contamination ; Heparin/pharmacology ; Humans ; Hypotension/chemically induced ; Kallikreins/drug effects ; Kallikreins/metabolism ; Kininogens/drug effects ; Kininogens/metabolism
Chemical Substances	Kininogens ; Complement C3a (80295-42-7) ; Complement C5a (80295-54-1) ; Heparin (9005-49-6) ; Chondroitin Sulfates (9007-28-7) ; Kallikreins (EC 3.4.21.-)
Language	English
Publishing date	2008-06-05
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMe0803599
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Article ; Online: Anaphylactic reaction to white-faced hornet sting and elevated baseline (asymptomatic) serum tryptase.

Lieberman, Phillip / Schwartz, Lawrence B

The journal of allergy and clinical immunology. In practice

2013 Volume 1, Issue 3, Page(s) 315

MeSH term(s)	Anaphylaxis/enzymology ; Anaphylaxis/immunology ; Anaphylaxis/pathology ; Animals ; Bites and Stings ; Humans ; Immunoglobulin E/biosynthesis ; Immunoglobulin E/blood ; Male ; Mast Cells/enzymology ; Mast Cells/immunology ; Mast Cells/pathology ; Mastocytosis/enzymology ; Mastocytosis/immunology ; Mastocytosis/pathology ; Middle Aged ; Risk Factors ; Severity of Illness Index ; Tryptases/biosynthesis ; Tryptases/blood ; Up-Regulation/immunology ; Wasp Venoms/adverse effects ; Wasp Venoms/immunology ; Wasps
Chemical Substances	Wasp Venoms ; Immunoglobulin E (37341-29-0) ; Tryptases (EC 3.4.21.59)
Language	English
Publishing date	2013-05
Publishing country	United States
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2012.10.003
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Article: Analysis of MC(T) and MC(TC) mast cells in tissue.

Schwartz, Lawrence B

Methods in molecular biology (Clifton, N.J.)

2006 Volume 315, Page(s) 53–62

Abstract: The MC(TC) and MCT types of human mast cells initially were recognized on the basis of the protease compositions of their secretory granules, with tryptase, chymase, carboxypeptidase A3, and cathepsin G in the former and only tryptase in the latter. ... ...

Abstract	The MC(TC) and MCT types of human mast cells initially were recognized on the basis of the protease compositions of their secretory granules, with tryptase, chymase, carboxypeptidase A3, and cathepsin G in the former and only tryptase in the latter. Antibodies against chymase and tryptase traditionally have been used to distinguish these mast cell types from one another. Antitryptase antibodies label all mast cells; antichymase labels only the MC(TC) type. To identify both types in a tissue section, a sequential double-labeling scheme was developed to first stain chymase-positive cells, thereby blocking their recognition by the antitryptase antibody, which will label only the chymase-negative mast cells. In general, these immunocytochemical techniques are more sensitive and specific than classical histochemical techniques for detecting mast cells.
MeSH term(s)	Biomarkers/analysis ; Cell Separation/methods ; Chymases ; Humans ; Immunohistochemistry/methods ; Mast Cells/chemistry ; Mast Cells/enzymology ; Mast Cells/immunology ; Mast Cells/ultrastructure ; Serine Endopeptidases/chemistry ; Serine Endopeptidases/metabolism ; Tryptases
Chemical Substances	Biomarkers ; Serine Endopeptidases (EC 3.4.21.-) ; Chymases (EC 3.4.21.39) ; Tryptases (EC 3.4.21.59)
Language	English
Publishing date	2006
Publishing country	United States
Document type	Journal Article
ISSN	1064-3745
ISSN	1064-3745
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Article: Diagnostic value of tryptase in anaphylaxis and mastocytosis.

Schwartz, Lawrence B

Immunology and allergy clinics of North America

2006 Volume 26, Issue 3, Page(s) 451–463

Abstract: Serum (or plasma) levels of total and mature tryptase measurements are recommended in the diagnostic evaluation of systemic anaphylaxis and systemic mastocytosis, but their interpretation must be considered in the context of a complete workup of each ... ...

Abstract	Serum (or plasma) levels of total and mature tryptase measurements are recommended in the diagnostic evaluation of systemic anaphylaxis and systemic mastocytosis, but their interpretation must be considered in the context of a complete workup of each patient. Total tryptase levels generally reflect the increased burden of mast cells in patients with all forms of systemic mastocytosis (indolent systemic mastocytosis, smoldering systemic mastocytosis, systemic mastocytosis associated with a hematologic clonal non-mast cell disorder, aggressive systemic mastocytosis, and mast cell leukemia) and the decreased burden of mast cells associated with cytoreductive therapies in these disorders. Causes of an elevated total tryptase level other than systemic mastocytosis must be considered, however, and include systemic anaphylaxis, acute myelocytic leukemia, various myelodysplastic syndromes, hypereosinophilic syndrome associated with the FLP1L1-PDGFRA mutation, end-stage renal failure, and treatment of onchocerciasis. Mature (beta) tryptase levels generally reflect the magnitude of mast cell activation and are elevated during most cases of systemic anaphylaxis, particularly with parenteral exposure to the inciting agent.
MeSH term(s)	Anaphylaxis/blood ; Anaphylaxis/diagnosis ; Anaphylaxis/enzymology ; Animals ; Humans ; Mastocytosis/blood ; Mastocytosis/diagnosis ; Mastocytosis/enzymology ; Time Factors ; Tryptases/blood
Chemical Substances	Tryptases (EC 3.4.21.59)
Language	English
Publishing date	2006-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	92606-1
ISSN	1557-8607 ; 0889-8561
ISSN (online)	1557-8607
ISSN	0889-8561
DOI	10.1016/j.iac.2006.05.010
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Article ; Online: Clinical communication: systemic capillary leak syndrome due to mast cell activation?

Van Winkle, Robert C / Malatack, J Jeffrey / Schwartz, Lawrence B / McGeady, Stephen J

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology

2019 Volume 122, Issue 4, Page(s) 428–429

MeSH term(s)	Anaphylaxis/blood ; Anaphylaxis/diagnosis ; Anaphylaxis/immunology ; Capillary Leak Syndrome/blood ; Capillary Leak Syndrome/diagnosis ; Capillary Leak Syndrome/immunology ; Child ; Diagnosis, Differential ; Humans ; Male ; Mast Cells/immunology ; Tryptases/blood
Chemical Substances	Tryptases (EC 3.4.21.59)
Language	English
Publishing date	2019-01-09
Publishing country	United States
Document type	Case Reports ; Letter
ZDB-ID	1228189-x
ISSN	1534-4436 ; 0003-4738 ; 1081-1206
ISSN (online)	1534-4436
ISSN	0003-4738 ; 1081-1206
DOI	10.1016/j.anai.2019.01.002
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Article ; Online: Inhibiting Isoprenylation Suppresses FcεRI-Mediated Mast Cell Function and Allergic Inflammation.

Dailey, Jordan M / Kee, Sydney A / Tharakan, Anuj / Kazi, Aslamuzzaman / Burchett, Jason R / Kolawole, Elizabeth Motunrayo / Boyd Ballance, William / Kotha, Aditya / Le, Quang T / Schwartz, Lawrence B / Straus, David B / Martin, Rebecca K / Sebti, Said M / Ryan, John J

Journal of immunology (Baltimore, Md. : 1950)

2023 Volume 211, Issue 4, Page(s) 527–538

Abstract: IgE-mediated mast cell activation is a driving force in allergic disease in need of novel interventions. Statins, long used to lower serum cholesterol, have been shown in multiple large-cohort studies to reduce asthma severity. We previously found that ... ...

Abstract	IgE-mediated mast cell activation is a driving force in allergic disease in need of novel interventions. Statins, long used to lower serum cholesterol, have been shown in multiple large-cohort studies to reduce asthma severity. We previously found that statins inhibit IgE-induced mast cell function, but these effects varied widely among mouse strains and human donors, likely due to the upregulation of the statin target, 3-hydroxy-3-methylgutaryl-CoA reductase. Statin inhibition of mast cell function appeared to be mediated not by cholesterol reduction but by suppressing protein isoprenylation events that use cholesterol pathway intermediates. Therefore, we sought to circumvent statin resistance by targeting isoprenylation. Using genetic depletion of the isoprenylation enzymes farnesyltransferase and geranylgeranyl transferase 1 or their substrate K-Ras, we show a significant reduction in FcεRI-mediated degranulation and cytokine production. Furthermore, similar effects were observed with pharmacological inhibition with the dual farnesyltransferase and geranylgeranyl transferase 1 inhibitor FGTI-2734. Our data indicate that both transferases must be inhibited to reduce mast cell function and that K-Ras is a critical isoprenylation target. Importantly, FGTI-2734 was effective in vivo, suppressing mast cell-dependent anaphylaxis, allergic pulmonary inflammation, and airway hyperresponsiveness. Collectively, these findings suggest that K-Ras is among the isoprenylation substrates critical for FcεRI-induced mast cell function and reveal isoprenylation as a new means of targeting allergic disease.
MeSH term(s)	Mice ; Humans ; Animals ; Receptors, IgE/metabolism ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/metabolism ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Farnesyltranstransferase/metabolism ; Mast Cells/metabolism ; Anaphylaxis/metabolism ; Signal Transduction ; Cell Degranulation ; Immunoglobulin E/metabolism ; Inflammation/metabolism ; Cholesterol/metabolism ; Prenylation
Chemical Substances	Receptors, IgE ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Farnesyltranstransferase (EC 2.5.1.29) ; Immunoglobulin E (37341-29-0) ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2023-07-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2200862
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Article ; Online: Presence or absence of elevated acute total serum tryptase by itself is not a definitive marker for an allergic reaction.

Sprung, Juraj / Weingarten, Toby N / Schwartz, Lawrence B

Anesthesiology

2015 Volume 122, Issue 3, Page(s) 713–714

MeSH term(s)	Anaphylaxis/diagnosis ; Anesthesia/adverse effects ; Drug Hypersensitivity/diagnosis ; Female ; Heart Arrest/diagnosis ; Histamine/blood ; Humans ; Male ; Shock/diagnosis ; Tryptases/blood
Chemical Substances	Histamine (820484N8I3) ; Tryptases (EC 3.4.21.59)
Language	English
Publishing date	2015-03
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	269-0
ISSN	1528-1175 ; 0003-3022
ISSN (online)	1528-1175
ISSN	0003-3022
DOI	10.1097/ALN.0000000000000584
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Article: Effector cells of anaphylaxis: mast cells and basophils.

Schwartz, Lawrence B

Novartis Foundation symposium

2004 Volume 257, Page(s) 65–74; discussion 74–9, 98–100, 276–85

Abstract: Systemic anaphylaxis arises when mast cells, possibly along with other cell types, are provoked to secrete mediators that evoke a systemic response. Mast cells in perivascular, respiratory, gastrointestinal and cutaneous tissues are likely involved, ... ...

Abstract	Systemic anaphylaxis arises when mast cells, possibly along with other cell types, are provoked to secrete mediators that evoke a systemic response. Mast cells in perivascular, respiratory, gastrointestinal and cutaneous tissues are likely involved, regardless of whether IgE or non-IgE-dependent pathways are invoked. Alpha/beta tryptases are selectively and abundantly produced by mast cells. Tryptase levels in the circulation provide a precise indicator of mast cell involvement. Mature beta tryptase is stored in secretory granules and is released when the cells are activated to degranulate, as occurs in anaphylaxis. Alpha/beta pro/pro' tryptases are spontaneously secreted by mast cells. Consequently, mature tryptase levels in serum (normally 1 ng/ml) are elevated in systemic anaphylaxis. Total tryptase levels (mature plus precursor forms), normally 1-15 ng/ml in baseline serum samples, are elevated in patients with systemic mastocytosis (> 20 ng/ml), a disease that also predisposes one to anaphylactic reactions. The assessment of basophils in systemic anaphylactic reactions has been problematic, because an assay for a specific releasable marker from this cell type has not been developed. Nevertheless, in cases of anaphylaxis in which elevations of histamine, but not tryptase, have been detected, it is enticing to speculate that basophil-dependent anaphylaxis may have occurred.
MeSH term(s)	Allergens/immunology ; Anaphylaxis/blood ; Anaphylaxis/epidemiology ; Anaphylaxis/immunology ; Anaphylaxis/physiopathology ; Autoimmunity/physiology ; Basophils/immunology ; Biomarkers ; Diagnosis, Differential ; Humans ; Inflammation Mediators/blood ; Inflammation Mediators/immunology ; Isoenzymes/blood ; Isoenzymes/genetics ; Isoenzymes/immunology ; Mast Cells/enzymology ; Mast Cells/immunology ; Mastocytosis, Systemic/immunology ; Serine Endopeptidases/blood ; Serine Endopeptidases/genetics ; Serine Endopeptidases/immunology ; Tryptases
Chemical Substances	Allergens ; Biomarkers ; Inflammation Mediators ; Isoenzymes ; Serine Endopeptidases (EC 3.4.21.-) ; Tryptases (EC 3.4.21.59)
Language	English
Publishing date	2004
Publishing country	England
Document type	Journal Article ; Review
ISSN	1528-2511
ISSN	1528-2511
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Article ; Online: Chronic Idiopathic Urticaria: Systemic Complaints and Their Relationship with Disease and Immune Measures

Doong, Judy C. / Chichester, Kris / Oliver, Eric T. / Schwartz, Lawrence B. / Saini, Sarbjit S.

The Journal of Allergy and Clinical Immunology: In Practice. 2017,

2017

Abstract: Patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) sometimes report systemic complaints (SC).We sought to determine the frequency and characteristics of SC among CIU patients, as well as the association of SC with disease measures, basophil ...

Abstract	Patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) sometimes report systemic complaints (SC).We sought to determine the frequency and characteristics of SC among CIU patients, as well as the association of SC with disease measures, basophil histamine release, and serum tryptase.Adult CIU patients were recruited from a university allergy clinic. Patients completed a disease symptom survey and underwent blood sampling for subsequent basophil histamine release and serum tryptase measurement.A total of 155 CIU patients were surveyed, with 103 reporting SC with concomitant hives as follows: joint pain or swelling (55.3%), headache/fatigue (47.6%), flushing (42.7%), wheezing (30.1%), gastrointestinal complaints (26.2%), and palpitations (9.7%). Patients with SC (CIU-SC) were compared to those without (CIU-NSC). Both groups had similar demographics (average age in 40s, majority female and Caucasian) and basophil histamine release profiles. CIU-SC had significantly greater disease duration (51.5% CIU-SC vs 30.8% CIU-NSC had >4 years duration), emergency department (ED) visits (41.7% vs 23.1% had >1 visit in the last year), CIU-related work absences (65% vs 27.5% had >1 day), oral corticosteroids use (84.5% vs 59.6%), quality of life (QoL) impairment (76.1 vs 59.2 SkinDex Score), and serum tryptase (5.1ng/ml vs 3.9ng/ml).Despite similar demographics and basophil profiles as CIU-NSC patients, CIU-SC patients have features of greater disease burden (work absences, ED visits, and corticosteroid use), QoL impairment, and baseline serum tryptase levels.
Keywords	Chronic idiopathic urticaria ; chronic spontaneous urticaria ; systemic complaints ; tryptase ; histamine ; quality of life ; CIU ; CSU ; SC ; NSC ; ED ; QoL ; HR ; USS
Language	English
Publishing place	Elsevier Inc.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2016.11.037
Database	NAL-Catalogue (AGRICOLA)

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