42 results on '"Butterfield JH"'
Search Results
2. Extracellular deposition of eosinophil granule major basic protein in lymph nodes of patients with Hodgkin's disease
- Author
-
Butterfield, JH, Kephart, GM, Banks, PM, and Gleich, GJ
- Abstract
Lymph nodes from each of the four histologic types of Hodgkin's disease were examined for the presence of eosinophils and for eosinophil degranulation by immunofluorescent localization of eosinophil granule major basic protein (MBP). Eosinophil degranulation shown by MBP deposition outside of eosinophils was found in six of eight nodes from patients with nodular sclerosing disease and in two of eight nodes from patients with lymphocyte depletion-type disease. Three nodes of the mixed cellularity type, one node of the lymphocyte predominance type, and one lymph node of the lymphocyte depletion type showed one or two small foci of extracellular MBP deposition. Lymph nodes from patients without Hodgkin's disease showed no extracellular deposition of MBP. Large numbers of eosinophils were found in seven of eight nodes of the nodular sclerosing variant, but were less frequently seen among the other types of Hodgkin's disease. The presence of extracellular MBP in lymph nodes of patients with Hodgkin's disease indicates that eosinophil degranulation commonly occurs and suggests that the released eosinophil granule proteins may participate in the inflammatory reaction in this disorder more extensively than is presently appreciated.
- Published
- 1986
- Full Text
- View/download PDF
3. Asthma treatment in a population-based cohort: putting step-up and step-down treatment changes in context.
- Author
-
Yawn BP, Wollan PC, Bertram SL, Lowe D, Butterfield JH, Bonde D, and Li JT
- Abstract
OBJECTIVE: To assess the frequency and types of visits related to modifications in the intensity of asthma medications. PATIENTS AND METHODS: We retrospectively reviewed the medical records of adults (aged 18-40 years) and children (aged 6-17 years) living in Olmsted County, Minnesota, to evaluate changes in asthma medications by dose and drug class and site and type of visit (routine vs unscheduled) at the time of changes. All records from all visits were reviewed for each patient to identify asthma-related visits at all sites of care from January 1, 2002, through December 31, 2003. RESULTS: The study consisted of 397 adults and children. In 255 patients, 597 asthma medication changes occurred. Step-up changes usually occurred because of an exacerbation or loss of control of asthma and adhered to the medication hierarchy in the national asthma guidelines. Twenty step-up changes involved skipping inhaled corticosteroid (ICS) monotherapy and moving directly to combined ICSs plus a long-acting beta-agonist (LABA). Lack of documentation of asthma symptom frequency or interference with activities made it impossible to determine whether these 'skips' were appropriate. Only 78 physician-directed step-down changes were documented, usually to a lower dose of combined ICSs and LABAs or a move from combined ICSs and LABAs to anti-inflammatory monotherapy. Patients initiated additional step-down changes between encounters. Step-down changes occurred at routine or follow-up asthma visits, but the limited number of such visits provided few opportunities for step-down care. CONCLUSION: The continuing episodic-style treatment of asthma aimed at exacerbation management facilitates step-up changes in asthma therapy. The dearth of asthma evaluation visits limited opportunities to step down use of asthma medications and to provide long-term asthma management. [ABSTRACT FROM AUTHOR]
- Published
- 2007
4. Metformin: A potential adjunct for treatment of systemic mastocytosis.
- Author
-
Butterfield JH and Bartemes K
- Abstract
Background: Systemic mastocytosis (SM) is a clonal disorder of mast cells in which the KIT Asp816Val mutation can be detected not only in mature mast cells but also in the hematopoietic stem cell and in non-mast cell lineages. Current treatment with tyrosine kinase inhibitors provides improved clinical responses in patients with advanced mastocytosis but no cures. Targeting of cancer stem cells (CSCs) resistant to chemotherapy and radiation therapy potentially could improve clinical outcomes in mastocytosis. In recent years, nonchemotherapeutic medications such as metformin have been repurposed for this role because of their ability to destroy CSCs from both solid tumors and leukemias and also because of their ability to act as chemosensitizers., Objective: We sought to determine whether those patients with both type 2 diabetes mellitus (DM2) and SM who were receiving metformin, which has been reported to inhibit CSCs, experienced clinical or laboratory benefit to their SM from this agent., Methods: Mayo Clinic databases were searched for patients with diagnoses of DM plus SM. The clinical courses of mastocytosis for patients with DM2 were compared among patients treated with metformin or by other means. Effects of metformin on human mast cell (HMC) leukemia line (HMC-1.1 and HMC-1.2) cell proliferation were tested in vitro ., Results: No patient treated with metformin before SM was diagnosed developed advanced forms of disease. A lower percentage of these patients had splenomegaly compared with other groups not treated with metformin, and none of these patients developed Janus kinase 2, tet methylcytosine dioxygenase 2, or serine and arginine-rich splicing factor 2 mutations. In vitro results showed that metformin inhibited the proliferation of both cell lines; HMC-1.1 cells were more sensitive to metformin., Conclusions: These preliminary findings suggest that early use of metformin to target CSCs has the possibility to complement current treatments available for SM., (© 2023 The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
5. Cryoablation versus rib plating: Is the real problem pain control or chest wall instability?
- Author
-
Butterfield JH, Reparaz LB, and Watson CM
- Abstract
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
- Published
- 2023
- Full Text
- View/download PDF
6. Trans-scapular approach to intrathoracic rib plating of upper rib fractures: An innovative technique.
- Author
-
Butterfield JH, Hessey JA, and Reparaz L
- Abstract
Competing Interests: The authors have no conflicts of interest to disclose. During the preparation of this work, no AI or AI-associated technologies were used in the writing process. The authors have reviewed and edited the content as needed and take full responsibility for the content of the publication.
- Published
- 2023
- Full Text
- View/download PDF
7. Updated Diagnostic Criteria and Classification of Mast Cell Disorders: A Consensus Proposal.
- Author
-
Valent P, Akin C, Hartmann K, Alvarez-Twose I, Brockow K, Hermine O, Niedoszytko M, Schwaab J, Lyons JJ, Carter MC, Elberink HO, Butterfield JH, George TI, Greiner G, Ustun C, Bonadonna P, Sotlar K, Nilsson G, Jawhar M, Siebenhaar F, Broesby-Olsen S, Yavuz S, Zanotti R, Lange M, Nedoszytko B, Hoermann G, Castells M, Radia DH, Muñoz-Gonzalez JI, Sperr WR, Triggiani M, Kluin-Nelemans HC, Galli SJ, Schwartz LB, Reiter A, Orfao A, Gotlib J, Arock M, Horny HP, and Metcalfe DD
- Abstract
Mastocytosis is a hematologic neoplasm characterized by expansion and focal accumulation of neoplastic mast cells (MC) in diverse organs, including the skin, bone marrow (BM), spleen, liver, and gastrointestinal tract. The World Health Organization classification divides the disease into prognostically distinct variants of cutaneous mastocytosis (CM) and systemic mastocytosis (SM). Although this classification remains valid, recent developments in the field and the advent of new diagnostic and prognostic parameters created a need to update and refine definitions and diagnostic criteria in MC neoplasms. In addition, MC activation syndromes (MCAS) and genetic features predisposing to SM and MCAS have been identified. To discuss these developments and refinements in the classification, we organized a Working Conference comprised of experts from Europe and the United States in August 2020. This article reports on outcomes from this conference. Of particular note, we propose adjustments in the classification of CM and SM, refinements in diagnostic criteria of SM variants, including smoldering SM and BM mastocytosis (BMM), and updated criteria for MCAS and other conditions involving MC. CD30 expression in MC now qualifies as a minor SM criterion, and BMM is now defined by SM criteria, absence of skin lesions and absence of B- and C-findings. A basal serum tryptase level exceeding 20 ng/mL remains a minor SM criterion, with recognition that hereditary alpha-tryptasemia and various myeloid neoplasms may also cause elevations in tryptase. Our updated proposal will support diagnostic evaluations and prognostication in daily practice and the conduct of clinical trials in MC disorders., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)
- Published
- 2021
- Full Text
- View/download PDF
8. Successful Long-Term Control of the Syndrome of Episodic Angioedema With Eosinophilia (Gleich Syndrome) With Low-Dose Imatinib Mesylate and Prednisone.
- Author
-
Butterfield JH
- Subjects
- Humans, Imatinib Mesylate, Male, Prednisone therapeutic use, Syndrome, Angioedema chemically induced, Angioedema drug therapy, Eosinophilia drug therapy
- Abstract
The syndrome of episodic angioedema with eosinophilia, first reported over 40 years ago, is a hypereosinophilic disorder that, uniquely, is not associated with end-organ pathology. However, patients develop a constellation of symptoms that include angioedema, urticaria, fatigue, and fever. Episodes are accompanied by massive hypereosinophilia and weight gain. Type II serum cytokine levels (IL-5, IL-13, IL-9, and IL-10) show cyclic variations peaking at or just prior to the peak of eosinophilia and an abnormal Th2 cell phenotype has been reported. Attacks may occur with predictable regularity and have been described in both adults and children. Glucocorticoid therapy reliably reverses symptoms with accompanying diuresis, defervesce, and normalization of the eosinophil count. In this report, a patient who had the syndrome of episodic angioedema with eosinophilia exceeding 20 years is reported. He has had no end-organ damage to date. Testing for the CHIC
2 deletion, a surrogate for the FIP1L1-PDGFRA fusion, was negative. Use of imatinib mesylate, initially as a steroid-sparing agent, and subsequently as a maintenance medication, plus low-dose prednisone has provided long-term control of hypereosinophilia and all clinical manifestations.- Published
- 2021
- Full Text
- View/download PDF
9. Preclinical human models and emerging therapeutics for advanced systemic mastocytosis.
- Author
-
Arock M, Wedeh G, Hoermann G, Bibi S, Akin C, Peter B, Gleixner KV, Hartmann K, Butterfield JH, Metcalfe DD, and Valent P
- Subjects
- Animals, Humans, Cell Line, Tumor metabolism, Cell Line, Tumor pathology, Mast Cells metabolism, Mast Cells pathology, Mastocytosis, Systemic genetics, Mastocytosis, Systemic metabolism, Mastocytosis, Systemic pathology, Models, Biological
- Abstract
Mastocytosis is a term used to denote a group of rare diseases characterized by an abnormal accumulation of neoplastic mast cells in various tissues and organs. In most patients with systemic mastocytosis, the neoplastic cells carry activating mutations in KIT Progress in mastocytosis research has long been hindered by the lack of suitable in vitro models, such as permanent human mast cell lines. In fact, only a few human mast cell lines are available to date: HMC-1, LAD1/2, LUVA, ROSA and MCPV-1. The HMC-1 and LAD1/2 cell lines were derived from patients with mast cell leukemia. By contrast, the more recently established LUVA, ROSA and MCPV-1 cell lines were derived from CD34
+ cells of non-mastocytosis donors. While some of these cell lines (LAD1/2, LUVA, ROSAKIT WT and MCPV-1) do not harbor KIT mutations, HMC-1 and ROSAKIT D816V cells exhibit activating KIT mutations found in mastocytosis and have thus been used to study disease pathogenesis. In addition, these cell lines are increasingly employed to validate new therapeutic targets and to screen for effects of new targeted drugs. Recently, the ROSAKIT D816V subclone has been successfully used to generate a unique in vivo model of advanced mastocytosis by injection into immunocompromised mice. Such a model may allow in vivo validation of data obtained in vitro with targeted drugs directed against mastocytosis. In this review, we discuss the major characteristics of all available human mast cell lines, with particular emphasis on the use of HMC-1 and ROSAKIT D816V cells in preclinical therapeutic research in mastocytosis., (Copyright© 2018 Ferrata Storti Foundation.)- Published
- 2018
- Full Text
- View/download PDF
10. BPR1J373, an Oral Multiple Tyrosine Kinase Inhibitor, Targets c-KIT for the Treatment of c-KIT-Driven Myeloid Leukemia.
- Author
-
Chen LT, Chen CT, Jiaang WT, Chen TY, Butterfield JH, Shih NY, Hsu JT, Lin HY, Lin SF, and Tsai HJ
- Subjects
- Animals, Apoptosis drug effects, Apoptosis Regulatory Proteins genetics, Apoptosis Regulatory Proteins metabolism, Cell Cycle drug effects, Cell Cycle genetics, Cell Line, Tumor, Cell Proliferation drug effects, Disease Models, Animal, Humans, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute metabolism, Leukemia, Myeloid, Acute pathology, Male, Mice, Mitochondria drug effects, Mitochondria metabolism, Mutation, Phosphorylation, Protein Kinase Inhibitors administration & dosage, Proto-Oncogene Proteins c-kit metabolism, Signal Transduction drug effects, Transcriptional Activation, Translocation, Genetic, Tumor Burden drug effects, Xenograft Model Antitumor Assays, Leukemia, Myeloid, Acute genetics, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins c-kit antagonists & inhibitors, Proto-Oncogene Proteins c-kit genetics
- Abstract
Acute myelogenous leukemia (AML) carrying t(8;21)(q22;q22) or inv(16)/t(16;16)(p13;q22) is classified as core binding factor (CBF)-AML and accounts for approximately 15% of AML. c-KIT mutation can be detected in 17%∼46% of CBF-AML and is associated with poor prognosis. c-KIT mutation is a crucial hit and cooperates with AML1-ETO resulting from t(8;21)(q22;q22) to cause overt AML. Tyrosine kinase inhibitors (TKI) targeting c-KIT, such as imatinib, has been used successfully to treat c-KIT driven gastrointestinal stromal tumors. However, the effect of TKI on c-KIT-driven leukemia, including CBF-AML and systemic mastocytosis (SM), has not been satisfactory. BPR1J373 is a 5-phenylthiazol-2-ylamine-pyriminide derivative targeting multiple tyrosine kinases. It was shown to inhibit cell proliferation and induce apoptosis in AML cells with constitutively activated c-KIT via inhibiting c-KIT phosphorylation and its downstream signals. The compound induced apoptosis by the mitochondrial intrinsic pathway through upregulation of proapoptotic proteins Bax and Bak and caspase 8 and 9 activation in c-KIT mutant Kasumi-1 cells. Furthermore, it induced cell-cycle arrest via targeting aurora kinase B in c-KIT wild-type KG-1 cells. The antitumor response of BPR1J373 was also shown in subcutaneously grafted SCID mice. BPR1J373 was shown to effectively suppress c-KIT phosphorylation of D816V mutation by treating c-KIT-null COS-1 cells transfected with c-KIT D816V mutant plasmid. In conclusion, BPR1J373 inhibits cell proliferation of c-KIT-driven AML cells via induction of apoptosis and cell-cycle arrest. It is also effective for multiple drug-resistant c-KIT D816V mutation. BPR1J373 deserves further development for clinical use in c-KIT-driven myeloid leukemia. Mol Cancer Ther; 15(10); 2323-33. ©2016 AACR., (©2016 American Association for Cancer Research.)
- Published
- 2016
- Full Text
- View/download PDF
11. Refractory intraoperative hypotension with elevated serum tryptase.
- Author
-
Sprung J, Larson KJ, Divekar RD, Butterfield JH, Schwartz LB, and Weingarten TN
- Abstract
Severe intraoperative hypotension has been reported in patients on angiotensin-converting enzyme inhibitors and angiotensin II receptor subtype 1 antagonists. We describe a patient on lisinopril who developed refractory intraoperative hypotension associated with increased serum tryptase level suggesting mast cell activation (allergic reaction). However, allergology workup ruled out an allergic etiology as well as mastocytosis, and hypotension recalcitrant to treatment was attributed to uninterrupted lisinopril therapy. Elevated serum tryptase was attributed to our patient's chronic renal insufficiency.
- Published
- 2015
- Full Text
- View/download PDF
12. Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal.
- Author
-
Valent P, Sotlar K, Sperr WR, Escribano L, Yavuz S, Reiter A, George TI, Kluin-Nelemans HC, Hermine O, Butterfield JH, Hägglund H, Ustun C, Hornick JL, Triggiani M, Radia D, Akin C, Hartmann K, Gotlib J, Schwartz LB, Verstovsek S, Orfao A, Metcalfe DD, Arock M, and Horny HP
- Subjects
- Bone Marrow Examination, Diagnosis, Differential, Disease Progression, Humans, Leukemia, Mast-Cell diagnosis, Leukemia, Myelomonocytic, Acute diagnosis, Leukemia, Myelomonocytic, Chronic diagnosis, Mast Cells pathology, Mastocytosis pathology, Leukemia, Mast-Cell classification, Leukemia, Myelomonocytic, Acute classification, Leukemia, Myelomonocytic, Chronic classification
- Abstract
Mast cell leukemia (MCL), the leukemic manifestation of systemic mastocytosis (SM), is characterized by leukemic expansion of immature mast cells (MCs) in the bone marrow (BM) and other internal organs; and a poor prognosis. In a subset of patients, circulating MCs are detectable. A major differential diagnosis to MCL is myelomastocytic leukemia (MML). Although criteria for both MCL and MML have been published, several questions remain concerning terminologies and subvariants. To discuss open issues, the EU/US-consensus group and the European Competence Network on Mastocytosis (ECNM) launched a series of meetings and workshops in 2011-2013. Resulting discussions and outcomes are provided in this article. The group recommends that MML be recognized as a distinct condition defined by mastocytic differentiation in advanced myeloid neoplasms without evidence of SM. The group also proposes that MCL be divided into acute MCL and chronic MCL, based on the presence or absence of C-Findings. In addition, a primary (de novo) form of MCL should be separated from secondary MCL that typically develops in the presence of a known antecedent MC neoplasm, usually aggressive SM (ASM) or MC sarcoma. For MCL, an imminent prephase is also proposed. This prephase represents ASM with rapid progression and 5%-19% MCs in BM smears, which is generally accepted to be of prognostic significance. We recommend that this condition be termed ASM in transformation to MCL (ASM-t). The refined classification of MCL fits within and extends the current WHO classification; and should improve prognostication and patient selection in practice as well as in clinical trials., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2014
- Full Text
- View/download PDF
13. Clonal mast cell disease not meeting WHO criteria for diagnosis of mastocytosis: clinicopathologic features and comparison with indolent mastocytosis.
- Author
-
Pardanani A, Chen D, Abdelrahman RA, Reichard KK, Zblewski D, Wood AJ, McClure RF, Butterfield JH, Hanson CA, and Tefferi A
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Immunoenzyme Techniques, Immunophenotyping, Male, Mastocytosis immunology, Middle Aged, Prognosis, Retrospective Studies, World Health Organization, Young Adult, Biomarkers, Tumor metabolism, Mast Cells pathology, Mastocytosis classification, Mastocytosis diagnosis
- Published
- 2013
- Full Text
- View/download PDF
14. Systemic mastocytosis in the elderly.
- Author
-
Butterfield JH and Weiler CR
- Subjects
- Aged, Aged, 80 and over, Cancer Care Facilities, Chromosome Aberrations, Cohort Studies, Eosinophilia complications, Eosinophilia epidemiology, Follow-Up Studies, Hematologic Diseases complications, Hematologic Diseases epidemiology, Humans, Incidence, Leukemia complications, Leukemia epidemiology, Mastocytosis, Systemic complications, Mastocytosis, Systemic diagnosis, Mastocytosis, Systemic genetics, Minnesota epidemiology, Myelodysplastic Syndromes complications, Myelodysplastic Syndromes epidemiology, Prognosis, Risk, Survival Analysis, Thrombocytopenia complications, Thrombocytopenia epidemiology, Tryptases blood, Aging, Mastocytosis, Systemic physiopathology
- Abstract
"Later onset" of systemic mastocytosis (SM) has been associated with a poorer prognosis. We examined clinical and laboratory findings, associated disorders, and survival in an older mastocytosis population. After receiving Mayo Clinic Institutional Review Board approval, we identified 42 patients aged 70 years and older at the time of diagnosis of SM. Associated disorders, cytogenetic abnormalities, laboratory findings, and survival were recorded. Only 10 patients had no associated hematologic disorder. Single or multiple chromosomal abnormalities, exclusive of the KIT Asp816Val mutation, were detected in eight patients (19%). KIT Asp816Val mutation was present in 14 patients, negative in three, and not tested in 25. Slight to marked bone marrow hypercellularity was observed in 33 patients (79%). Concurrent hematologic abnormalities included chronic myelomonocytic leukemia (n = 7), acute myelocytic leukemia (n = 1), myelodysplastic syndrome (MDS; n = 7), eosinophilia (n = 7), myelofibrosis (n = 1), myeloproliferative disorder (n = 1), multiple myeloma (n = 1), B-cell lymphoma (n = 1), and thrombocytopenia (n = 4). Eight patients had a hematologic disorder that preceded the diagnosis of SM. Tryptase levels were elevated in 38 of 39 patients tested. Survival from the diagnosis of SM was poor for patients with associated thrombocytopenia, leukemias, and MDS. In conclusion, patients with SM diagnosed at age 70 or older have an increased risk of secondary hematologic disorders and abnormal laboratory findings. Cytogenetic abnormalities are common, and survival is short in many SM patients with associated leukemias, MDS, or eosinophilia., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2013
- Full Text
- View/download PDF
15. ICON: Eosinophil Disorders.
- Author
-
Valent P, Klion AD, Rosenwasser LJ, Arock M, Bochner BS, Butterfield JH, Gotlib J, Haferlach T, Hellmann A, Horny HP, Leiferman KM, Metzgeroth G, Matsumoto K, Reiter A, Roufosse F, Rothenberg ME, Simon HU, Sotlar K, Vandenberghe P, Weller PF, and Gleich GJ
- Published
- 2012
- Full Text
- View/download PDF
16. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine.
- Author
-
Lim KH, Pardanani A, Butterfield JH, Li CY, and Tefferi A
- Subjects
- Adult, Aged, Aged, 80 and over, Benzamides, Bone Marrow pathology, DNA Mutational Analysis, DNA-Binding Proteins genetics, Dioxygenases, Drug Therapy, Combination, Female, Humans, Imatinib Mesylate, Interferon-alpha administration & dosage, Janus Kinase 2 genetics, Male, Mast Cells drug effects, Mast Cells metabolism, Mastocytosis, Systemic classification, Mastocytosis, Systemic genetics, Middle Aged, Mutation, Missense, Point Mutation, Prednisone administration & dosage, Prednisone therapeutic use, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins c-kit genetics, Retrospective Studies, Treatment Outcome, Young Adult, Cladribine therapeutic use, Hydroxyurea therapeutic use, Interferon-alpha therapeutic use, Mastocytosis, Systemic drug therapy, Piperazines therapeutic use, Pyrimidines therapeutic use
- Abstract
Cytoreductive therapy in systemic mastocytosis (SM) includes several drugs whose individual merit has not been well characterized. We retrospectively studied 108 Mayo Clinic patients who met the 2008 WHO diagnostic criteria for SM and received at least one cytoreductive drug. The numbers of patients who were evaluable for response to treatment with interferon-alpha with or without prednisone (IFN-alpha), hydroxyurea (HU), imatinib mesylate (IM) or 2-chlorodeoxyadenosine (2-CdA) were 40, 26, 22, and 22, respectively. The corresponding overall (major) response rates, according to recently published consensus criteria, were 53% (18%), 19% (0%), 18% (9%), and 55% (37%). The respective overall response rates in indolent SM, aggressive SM and SM associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD) were 60%, 60%, 45% for IFN-alpha, 0, 0, 21% for HU, 14%, 50%, 9% for IM and 56%, 50%, 55% for 2-CdA. The absence of mast cell mediator release symptoms in IFN-alpha-treated patients and presence of circulating immature myeloid cells in 2-CdA-treated patients predicted inferior response. TET2 mutational status did not influence treatment response. Although the major response rates with these four cytoreductive agents were still suboptimal and HU was mainly used in patients with SM-AHNMD, the current study favors 2-CdA or IFN-alpha as first-line current therapy in SM and identifies patients who are likely to respond to such therapy., ((c) 2009 Wiley-Liss, Inc.)
- Published
- 2009
- Full Text
- View/download PDF
17. Frequency of allergic or hematologic adverse reactions to ticlopidine among patients with allergic or hematologic adverse reactions to clopidogrel.
- Author
-
Lokhandwala JO, Best PJ, Butterfield JH, Skelding KA, Scott T, Blankenship JC, Buckley JW, and Berger PB
- Subjects
- Aged, Clopidogrel, Female, Humans, Male, Retrospective Studies, Risk Assessment, Severity of Illness Index, United States, Angioedema chemically induced, Drug Hypersensitivity etiology, Exanthema chemically induced, Neutropenia chemically induced, Platelet Aggregation Inhibitors adverse effects, Thrombocytopenia chemically induced, Ticlopidine adverse effects, Ticlopidine analogs & derivatives
- Abstract
Background: Clopidogrel and ticlopidine are structurally very similar. In patients with an allergic or hematologic adverse reaction to either one of these drugs, the likelihood that an allergic or hematologic adverse effect will develop to the other is unknown. It is also unknown whether a reaction to the second thienopyridine is likely to be life threatening., Methods and Results: Medical records from 2 academic institutions were reviewed to identify patients who had an allergic or hematologic adverse reaction to either of the 2 currently commercially available thienopyridines and who were subsequently prescribed the other thienopyridine. Patient demographics, details of the adverse reactions, and subsequent clinical course were reviewed. A total of 76 patients were identified with an allergic or hematologic adverse reaction to clopidogrel or ticlopidine who had also received the other thienopyridine. Fourteen (27%; 95% CI, 16 to 41) patients who had an allergic or hematologic adverse reactions to clopidogrel had a similar reaction to ticlopidine; none developed a life-threatening reaction. The most common reaction was a rash (93%)., Conclusions: In patients with an allergic or hematologic adverse reaction to one thienopyridine, there seems to be an increased frequency of such reactions to the other thienopyridine. However, no patient had a life-threatening reaction after exposure to the alternative thienopyridine.
- Published
- 2009
- Full Text
- View/download PDF
18. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors.
- Author
-
Lim KH, Tefferi A, Lasho TL, Finke C, Patnaik M, Butterfield JH, McClure RF, Li CY, and Pardanani A
- Subjects
- Adult, Aged, Aged, 80 and over, Bone Marrow Diseases pathology, Cell Transformation, Neoplastic pathology, Female, Humans, Male, Mastocytosis, Systemic blood, Mastocytosis, Systemic classification, Middle Aged, Prognosis, Survival Rate, Mastocytosis, Systemic mortality, Mastocytosis, Systemic pathology
- Abstract
Clinical phenotype in systemic mastocytosis (SM) is markedly variable, which complicates prognostication and decision making regarding the choice and timing of therapy. In a retrospective study of 342 consecutive adult patients with SM seen at the Mayo Clinic between 1976 and 2007, disease subdesignation according to the World Health Organization (WHO) proposal was indolent (ISM) in 159 (46%), with associated clonal hematologic non-mast cell lineage disease (SM-AHNMD) in 138 (40%), aggressive (ASM) in 41 (12%), and mast cell leukemia in 4 (1%). KITD816V was detected in bone marrow-derived DNA by allele-specific polymerase chain reaction (PCR) in 68% of 165 patients evaluated (ISM, 78%; ASM, 82%; SM-AHNMD, 60%; P = .03); JAK2V617F was detected in 4%, all in SM-AHNMD. Compared with those with nonindolent SM, life expectancy in ISM was superior and not significantly different from that of the age- and sex-matched US population. In addition, multivariable analysis identified advanced age, weight loss, anemia, thrombocytopenia, hypoalbuminemia, and excess bone marrow blasts as independent adverse prognostic factors for survival. The current study validates the prognostic relevance of the WHO subclassification of SM and provides additional information of value in terms of both risk stratification and interpretation of clinical presentation and laboratory results.
- Published
- 2009
- Full Text
- View/download PDF
19. Clostridium difficile toxins A and B directly stimulate human mast cells.
- Author
-
Meyer GK, Neetz A, Brandes G, Tsikas D, Butterfield JH, Just I, and Gerhard R
- Subjects
- Cell Degranulation, Cell Line, Cytokines metabolism, Cytoskeleton metabolism, Glucose metabolism, Hexosaminidases metabolism, Humans, Interleukin-8 immunology, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Prostaglandins D biosynthesis, Prostaglandins E biosynthesis, Signal Transduction drug effects, p38 Mitogen-Activated Protein Kinases metabolism, rho GTP-Binding Proteins antagonists & inhibitors, rho GTP-Binding Proteins metabolism, Bacterial Proteins immunology, Bacterial Toxins immunology, Clostridioides difficile pathogenicity, Enterotoxins immunology, Mast Cells immunology, Mast Cells microbiology
- Abstract
Clostridium difficile toxins A and B (TcdA and TcdB) are the causative agents of antibiotic-associated pseudomembranous colitis. Mucosal mast cells play a crucial role in the inflammatory processes underlying this disease. We studied the direct effects of TcdA and TcdB on the human mast cell line HMC-1 with respect to degranulation, cytokine release, and the activation of proinflammatory signal pathways. TcdA and TcdB inactivate Rho GTPases, the master regulators of the actin cytoskeleton. The inactivation of Rho GTPases induced a reorganization of the actin cytoskeleton accompanied by morphological changes of cells. The TcdB-induced reorganization of the actin cytoskeleton in HMC-1 cells reduced the number of electron-dense mast cell-specific granules. Accordingly, TcdB induced the release of hexosaminidase, a marker for degranulation, in HMC-1 cells. The actin rearrangement was found to be responsible for degranulation since latrunculin B induced a comparable hexosaminidase release. In addition, TcdB as well as latrunculin B induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 and also resulted in a p38 MAPK-dependent increased formation of prostaglandins D(2) and E(2). The autocrine stimulation of HMC-1 cells by prostaglandins partially contributed to the degranulation. Interestingly, TcdB-treated HMC-1 cells, but not latrunculin B-treated HMC-1 cells, showed a strong p38 MAPK-dependent increase in interleukin-8 release. Differences in the mast cell responses to TcdB and latrunculin B are probably due to the presence of functionally inactive Rho GTPases in toxin-treated cells. Thus, the HMC-1 cell line is a promising model for studying the direct effects of C. difficile toxins on mast cells independently of the tissue context.
- Published
- 2007
- Full Text
- View/download PDF
20. Control of hypereosinophilic syndrome-associated recalcitrant coronary artery spasm by combined treatment with prednisone, imatinib mesylate and hydroxyurea.
- Author
-
Butterfield JH and Sharkey SW
- Abstract
Uncontrolled hypereosinophilic syndrome is frequently associated with cardiovascular consequences that cause significant morbidity and mortality. The present article reports on a patient with hypereosinophilic syndrome in whom recurrent, recalcitrant coronary artery spasm and associated cardiac arrest were the predominant cardiac manifestations. No valvular abnormalities, evidence of mural thrombi or other cardiac findings commonly associated with hypereosinophilic syndrome were detected, and cardiac function remained normal. The serum tryptase level was normal, cysteine-rich hydrophobic domain 2 (CHIC2) deletion analysis of bone marrow cells was negative and no evidence of mastocytosis or other hematological disorder was found in the bone marrow. To allow for the reduction of prednisone, interferon-alpha-2b was added to the patient's program, but caused aggravation of chest pain and was discontinued. However, a combination of reduced prednisone dosage, imatinib mesylate and hydroxyurea successfully controlled the eosinophilia, and thereafter, episodes of coronary artery spasm did not recur. The clinical features of the present case suggest that, in some patients, hypereosinophilia may manifest as resistant coronary artery spasm and that aggressive control of eosinophilia is necessary.
- Published
- 2006
21. Functional and phenotypic studies of two variants of a human mast cell line with a distinct set of mutations in the c-kit proto-oncogene.
- Author
-
Sundström M, Vliagoftis H, Karlberg P, Butterfield JH, Nilsson K, Metcalfe DD, and Nilsson G
- Subjects
- Cell Culture Techniques, Cell Cycle immunology, Cell Division immunology, Cell Line, Humans, Immunophenotyping, Karyotyping, Mast Cells cytology, Phosphorylation, Proto-Oncogene Mas, Signal Transduction immunology, Stem Cell Factor metabolism, Tyrosine metabolism, Mast Cells immunology, Mutation, Proto-Oncogene Proteins c-kit genetics
- Abstract
The human mast cell line (HMC)-1 cell line is growth-factor independent because of a constitutive activity of the receptor tyrosine kinase Kit. Such deregulated Kit activity has also been suggested causative in gastrointestinal stromal tumours (GISTs) and mastocytosis. HMC-1 is the only established continuously growing human mast cell line and has therefore been widely employed for in vitro studies of human mast cell biology. In this paper we describe two sublines of HMC-1, named HMC-1(560 ) and HMC-1(560,816 ), with different phenotypes and designated by the locations of specific mutations in the c-kit proto-oncogene. Activating mutations in the Kit receptor were characterized using the pyrosequencing trade mark method. Both sublines have a heterozygous T to G mutation at codon 560 in the juxtamembrane region of the c-kit gene causing an amino acid substitution of Gly-560 for Val. In contrast, only HMC-1(560,816) cells have the c-kitV816 mutation found in mast cell neoplasms causing an Asp-->Val substitution in the intracellular kinase domain. Kit was constitutively phosphorylated on tyrosine residues and associated with phosphatidylinositol 3'-kinase (PI 3-kinase) in both variants of HMC-1, but this did not lead to a constitutive phosphorylation of Akt or extracellular regulated protein kinase (ERK), which are signalling molecules normally activated by the interaction of stem cell factor (SCF) with Kit. The documentation and characterization of two sublines of HMC-1 cells provides both information on the biological consequences of mutations in Kit and recognition of the availability of what in reality are two distinct cultured human mast cell lines.
- Published
- 2003
- Full Text
- View/download PDF
22. Systemic mast cell disease without associated hematologic disorder: a combined retrospective and prospective study.
- Author
-
Pardanani A, Baek JY, Li CY, Butterfield JH, and Tefferi A
- Subjects
- Adult, Aged, Biopsy, Needle, Female, Hematologic Diseases complications, Humans, Immunohistochemistry, Male, Mast Cells pathology, Mastocytosis, Systemic complications, Middle Aged, Probability, Prognosis, Prospective Studies, Retrospective Studies, Risk Assessment, Statistics, Nonparametric, Survival Analysis, Bone Marrow pathology, Hematologic Diseases mortality, Hematologic Diseases pathology, Mastocytosis, Systemic mortality, Mastocytosis, Systemic pathology, Neovascularization, Pathologic pathology
- Abstract
Objective: To study clinicopathologic correlations and identify prognostically important variables in patients with systemic mast cell disease (SMCD) who have no associated hematologic disorders., Patients and Methods: We identified 40 adult patients with SMCD without associated hematologic disorders. Clinical, laboratory, and bone marrow (BM) histologic findings at the time of referral were evaluated (November 1980-February 2001) for possible correlations with a history of aggressive systemic mastocytosis (retrospectively analyzed) as well as survival (prospectively analyzed)., Results: The median follow-up time from diagnosis was 108 months and from BM examination was 24 months. A history of aggressive systemic mastocytosis correlated significantly with increased BM mast cell (MC) content, unfavorable MC infiltration pattern, BM eosinophilia, and elevated serum alkaline phosphatase (SAP) level, but not with BM angiogenesis, reticulin fibrosis, or levels of MC mediators. Of these factors, increased BM MC content and elevated SAP level were also associated with shortened survival from time of referral., Conclusions: This study suggests that the BM MC burden, BM eosinophilia, and SAP level are prognostically important in SMCD without associated hematologic disorders. In contrast, BM angiogenesis, reticulin fibrosis, and levels of MC mediators showed no prognostic relevance.
- Published
- 2002
- Full Text
- View/download PDF
23. Human eosinophils produce neurotrophins and secrete nerve growth factor on immunologic stimuli.
- Author
-
Kobayashi H, Gleich GJ, Butterfield JH, and Kita H
- Subjects
- Adolescent, Adult, Cell Communication, Dactinomycin pharmacology, Humans, Immunoglobulin A pharmacology, Immunoglobulin G pharmacology, Interleukin-5 pharmacology, Middle Aged, Nasal Lavage Fluid chemistry, Nerve Growth Factor drug effects, Nerve Growth Factor genetics, Nerve Growth Factors drug effects, Nerve Growth Factors genetics, Neurons cytology, Neurons drug effects, Neurotrophin 3 biosynthesis, Neurotrophin 3 drug effects, Neurotrophin 3 genetics, RNA, Messenger metabolism, Receptors, Fc physiology, Rhinitis, Allergic, Seasonal metabolism, Eosinophils immunology, Eosinophils metabolism, Immunoglobulins pharmacology, Nerve Growth Factor metabolism, Nerve Growth Factors biosynthesis
- Abstract
Neurotrophins, such as nerve growth factor (NGF) and neurotrophin-3 (NT-3), are essential for development, function, and survival of peripheral sympathetic and sensory neurons. Most eosinophilic leukocytes in the human body are localized in mucosal tissues; however, the roles of eosinophils in human diseases are not fully understood. We found that human eosinophils constitutively express messenger RNA for NGF and NT-3, synthesize and store these proteins intracellularly, and continuously replenish them. Incubation of eosinophils with a transcription inhibitor, actinomycin D, for 8 hours completely depletes intracellular NGF and NT-3. New synthesis of NGF is enhanced by Fc-receptor-mediated stimuli, such as immunoglobulin (Ig)A and IgG immune complexes; in contrast, production of NT-3 is not affected by these stimuli. Notably, supernatants of eosinophils stimulated with IgA immune complex and interleukin 5 promote neurite extension of the PC-12 pheochromocytoma cell line; this effect is abolished by pretreatment of the supernatants with anti-NGF-neutralizing antibody. By enzyme-linked immunosorbent assay, substantial amounts of NGF protein are also detected in the supernatants of stimulated eosinophils. Furthermore, in patients with seasonal allergic rhinitis, the concentrations of NGF in nasal secretions correlate with the magnitudes of eosinophilic inflammation in the airway, suggesting a potential clinical implication of eosinophil NGF. Our observations propose a new pathologic mechanism by which eosinophils may contribute to enhanced neurologic responses in patients with allergic diseases and other eosinophilic disorders. Alternatively, eosinophils may play important roles in maintenance and restoration of homeostatic functions of mucosal tissues through the pleitropic activities of NGF.
- Published
- 2002
- Full Text
- View/download PDF
24. The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations.
- Author
-
Ma Y, Zeng S, Metcalfe DD, Akin C, Dimitrijevic S, Butterfield JH, McMahon G, and Longley BJ
- Subjects
- Animals, Apoptosis drug effects, Benzamides, Catalytic Domain genetics, Cell Division drug effects, Drug Resistance genetics, Enzyme Inhibitors pharmacology, Humans, Imatinib Mesylate, Mast Cells drug effects, Mast Cells enzymology, Mast Cells pathology, Mastocytosis drug therapy, Mastocytosis pathology, Phosphotransferases antagonists & inhibitors, Phosphotransferases genetics, Piperazines pharmacology, Proto-Oncogene Proteins c-kit drug effects, Pyrimidines pharmacology, Tumor Cells, Cultured, Mastocytosis enzymology, Mutation, Missense, Proto-Oncogene Proteins c-kit genetics
- Abstract
Mutations of c-KIT causing spontaneous activation of the KIT receptor kinase are associated with sporadic adult human mastocytosis (SAHM) and with human gastrointestinal stromal tumors. We have classified KIT-activating mutations as either "enzymatic site" type (EST) mutations, affecting the structure of the catalytic portion of the kinase, or as "regulatory" type (RT) mutations, affecting regulation of an otherwise normal catalytic site. Using COS cells expressing wild-type or mutant KIT, 2 compounds, STI571 and SU9529, inhibited wild-type and RT mutant KIT at 0.1 to 1 microM but did not significantly inhibit the Asp816Val EST mutant associated with SAHM, even at 10 microM. Using 2 subclones of the HMC1 mast cell line, which both express KIT with an identical RT mutation but which differ in that one also expresses the Asp816Val EST mutation, both compounds inhibited the RT mutant KIT, thereby suppressing proliferation and producing apoptosis in the RT mutant-only cell line. Neither compound suppressed activation of Asp816Val EST mutant KIT, and neither produced apoptosis or significantly suppressed proliferation of the cell line expressing the Asp816Val mutation. These studies suggest that currently available KIT inhibitors may be useful in treating neoplastic cells expressing KIT activated by its natural ligand or by RT activating mutations such as gastrointestinal stromal tumors but that neither compound is likely to be effective against SAHM. Furthermore, these results help establish a general paradigm whereby classification of mutations affecting oncogenic enzymes as RT or EST may be useful in predicting tumor sensitivity or resistance to inhibitory drugs.
- Published
- 2002
- Full Text
- View/download PDF
25. Diverse clinical outcomes of eosinophilic patients with T-cell receptor gene rearrangements: the emerging diagnostic importance of molecular genetics testing.
- Author
-
Butterfield JH
- Subjects
- Adult, Aged, Aged, 80 and over, Clone Cells metabolism, Clone Cells pathology, Eosinophilia pathology, Eosinophilia therapy, Female, Gene Rearrangement, Humans, Male, Middle Aged, T-Lymphocytes metabolism, T-Lymphocytes pathology, Treatment Outcome, Eosinophilia genetics, Genes, T-Cell Receptor genetics
- Abstract
Abnormal clones of clusters of differentiation (CD)3(-)CD4(+) or CD3(+)CD4(-)CD8(-) phenotypically abnormal lymphocytes have been identified in some patients who have the idiopathic hypereosinophilic syndrome. This report illustrates the disparate clinical courses of six eosinophilic patients with evidence of abnormal T-cell clones based on the finding of a T-cell receptor gene rearrangement. The data suggest that molecular genetics testing for T-cell receptor gene rearrangements should be included in the routine work-up of patients with idiopathic eosinophilia., (Copyright 2001 Wiley-Liss, Inc.)
- Published
- 2001
- Full Text
- View/download PDF
26. ATP modulates anti-IgE-induced release of histamine from human lung mast cells.
- Author
-
Schulman ES, Glaum MC, Post T, Wang Y, Raible DG, Mohanty J, Butterfield JH, and Pelleg A
- Subjects
- Adenine Nucleotides pharmacology, Adenosine pharmacology, Adenosine Triphosphate analogs & derivatives, Antibodies, Anti-Idiotypic pharmacology, Calcimycin pharmacology, Dose-Response Relationship, Drug, Drug Interactions, Histamine Release immunology, Humans, Ionophores pharmacology, Mast Cells immunology, Purinergic P2 Receptor Agonists, Purinergic P2 Receptor Antagonists, Uridine Triphosphate pharmacology, Adenosine Triphosphate pharmacology, Histamine Release drug effects, Immunoglobulin E immunology, Lung cytology, Mast Cells drug effects
- Abstract
Adenosine 5'-triphosphate (ATP) is released from the cytoplasm under physiologic and pathophysiologic conditions and enters the extracellular space, where it acts on a group of recently cloned cell-surface receptors termed P2-purinoceptors (subtypes P2X and P2Y). We examined the effects of extracellular ATP, uridine triphosphate (UTP), the stable ATP analogues alpha,betamethylene-ATP (alpha,betamATP), beta,gammamethylene-ATP (beta,gammamATP), and 2-methylthio-ATP (2mSATP), and adenosine (10(-6)-10(-3) M) on histamine release from human lung mast cells (HLMC) induced by anti-IgE and the calcium ionophore A23187. None of the nucleotides or adenosine directly induced histamine release. Adenosine exhibited a bimodal effect, enhancing histamine release at 10(-6) to 10(-4) M (P > 0.05, NS) and inhibiting it at 10(-3) M (P < 0.05). ATP (10(-4) M) enhanced anti-IgE-induced histamine release (10.9 +/- 2.7% to 19. 2 +/- 2.9%, n = 20, P < 0.01), but not ionophore A23187-induced histamine release (n = 10). The adenine nucleotides consistently enhanced anti-IgE-induced histamine release; the rank order for this action was: ATP > 2mSATP > alpha,betamATP > beta,gammamATP, suggesting mediation by a P2Y-purinoceptor subtype. The selective P2X purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2', 4'-disulfonic acid failed to influence the effect of ATP, further supporting P2Y-purinoceptor mediation of anti-IgE-induced histamine release. UTP, an agonist at P2Y-purinoceptors, also significantly enhanced anti-IgE-induced histamine release. Application of the reverse transcription-polymerase chain reaction indicated that HLMC constitutively express the messenger RNAs encoding the P2Y1- and P2Y2-purinoceptor subtypes, and not that encoding the P2X7-purinoceptor (i.e., P2Z), a subtype implicated in ATP-induced histamine release in rodent peritoneal mast cells. The data produced in the study suggest that ATP plays an important modulatory role in histamine release from HLMC, and that it may therefore be mechanistically involved in human allergic/asthmatic reactions.
- Published
- 1999
- Full Text
- View/download PDF
27. Expression of functional TrkA receptor tyrosine kinase in the HMC-1 human mast cell line and in human mast cells.
- Author
-
Tam SY, Tsai M, Yamaguchi M, Yano K, Butterfield JH, and Galli SJ
- Subjects
- Cell Line, Enzyme Activation, Flow Cytometry, Humans, Kinetics, Proto-Oncogene Proteins genetics, RNA, Messenger biosynthesis, RNA, Messenger genetics, Receptor Protein-Tyrosine Kinases genetics, Receptor, trkA, Receptors, Nerve Growth Factor genetics, Mast Cells metabolism, Nerve Growth Factors pharmacology, Proto-Oncogene Proteins biosynthesis, Receptor Protein-Tyrosine Kinases biosynthesis, Receptors, Nerve Growth Factor biosynthesis
- Abstract
Nerve growth factor (NGF) can influence mast cell development and function in murine rodents by interacting with its receptors on mast cells. We now report the identification of mRNA transcripts of full-length tyrosine kinase-containing trkA, trkB, and trkC neurotrophin receptor genes in HMC-1 human mast cell leukemia cells. Although HMC-1 cells lacked p75 mRNA, they expressed transcripts for the exon-lacking splice variant of trkA (trkAI), truncated trkB (trkB.T1), and truncated trkC. By flow cytometry, HMC-1 cells exhibited expression of TrkA, TrkB, and TrkC receptor proteins containing full-length tyrosine kinase domains. NGF stimulation of HMC-1 cells induced tyrosine phosphorylation of TrkA protein, increased expression of the early response genes c-fos and NGF1-A, and activation of ERK-mitogen-activated protein (MAP) kinase, results which indicate that TrkA receptors in HMC-1 cells are fully functional. Highly purified populations of human lung mast cells expressed mRNAs for trkA, trkB and trkC, whereas preparations of human umbilical cord blood-derived mast cells expressed mRNAs for trkA and trkC, but not trkB. Moreover, preparations of human umbilical cord blood-derived immature mast cells not only expressed mRNA transcript and protein for TrkA, but exhibited significantly higher numbers of chymase-positive cells after the addition of NGF to their culture medium for 3 weeks. In addition, HMC-1 cells expressed mRNAs for NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), the cognate ligands for TrkA, TrkB, and TrkC, whereas NGF and BDNF transcripts were detectable in human umbilical cord blood mast cell preparations. Taken together, our findings show that human mast cells express a functional TrkA receptor tyrosine kinase and indicate that NGF may be able to promote certain aspects of mast cell development and/or maturation in humans. Our studies also raise the possibility that human mast cells may represent a potential source for neurotrophins.
- Published
- 1997
28. Comparative immunophenotypic analysis of human mast cells, blood basophils and monocytes.
- Author
-
Agis H, Füreder W, Bankl HC, Kundi M, Sperr WR, Willheim M, Boltz-Nitulescu G, Butterfield JH, Kishi K, Lechner K, and Valent P
- Subjects
- Basophils immunology, Cell Culture Techniques, Female, Fluorescent Antibody Technique, Humans, Immunophenotyping, Integrins analysis, Mast Cells immunology, Monocytes immunology, Receptors, Cytokine analysis, Receptors, Fc analysis, Receptors, Immunologic analysis, Antigens, CD analysis, Basophils classification, Mast Cells classification, Monocytes classification
- Abstract
Mast cells (MC), blood basophils (Ba) and monocytes (Mo) are of haemopoietic origin. Lineage-relationships and transdifferentiation between MC and Mo, or MC and Ba, have been considered, based on common expression of antigens. In this study, comparative phenotypic analyses on MC, Ba and Mo and on respective cell lines were performed using monoclonal antibodies (mAb) to previously defined and novel CD antigens (CD1-130). By cluster analysis, the overall (all 130 CD) phenotypic relationships (given as similarity indices, SI), between primary cells (MC, Ba and Mo) and corresponding cell lines (HMC-1, KU-812, U937) were 0.716, 0.779 and 0.757, respectively. When primary cells were compared, lower SI values were found (MC versus Ba, 0.509; MC versus Mo, 0.625; Mo versus Ba, 0.698). More distant relationships were found between MC versus Ba and MC versus Mo, compared with Ba versus Mo, for adhesion receptor (R)-, complement R- and cytokine R profiles. Analysis of cytokine R revealed most significant dissimilarities between MC versus Ba and MC versus Mo (SI < 0.2). Moreover, in contrast to other CD subgroups and other lineages, MC and HMC-1 differed from each other in cytokine R expression (SI = 0.286). Cytokine R detectable on HMC-1 but not MC were granulocyte-macrophage colony-stimulating factor (GM-CSFR)alpha(CD116), CD40, Apo-1/FAS(CD95) and gp130(CD130). Cytokine R detectable on Ba but not MC, were interleukin-3 (IL-3)R alpha(CD123), IL-1RII(CD121b), IL-2R alpha(CD25) and CD40. In summary, MC, Ba and Mo display a unique CD profile with MC being the most distantly related cell. The most significant mismatch within a given lineage is the loss of cytokine R on mature MC as compared with normal myeloid progenitors and HMC-1 cells.
- Published
- 1996
- Full Text
- View/download PDF
29. Mast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangioma.
- Author
-
Qu Z, Liebler JM, Powers MR, Galey T, Ahmadi P, Huang XN, Ansel JC, Butterfield JH, Planck SR, and Rosenbaum JT
- Subjects
- Arthritis, Rheumatoid pathology, Base Sequence, Cell Line, Hemangioma pathology, Humans, Immunohistochemistry methods, Molecular Probes genetics, Molecular Sequence Data, Pulmonary Fibrosis metabolism, Pulmonary Fibrosis pathology, RNA, Messenger metabolism, Skin Neoplasms pathology, Staining and Labeling, Arthritis, Rheumatoid metabolism, Fibroblast Growth Factor 2 metabolism, Hemangioma metabolism, Mast Cells metabolism, Skin Neoplasms metabolism
- Abstract
Mast cells play an essential role during development of inflammation after chemical and immunological insults and have been implicated in tissue fibrosis and angiogenesis. The exact contribution of mast cells to these conditions is largely unknown. In this study, we found that a potent angiogenic and mitogenic polypeptide, basic fibroblast growth factor (bFGF), is localized to the majority of mast cells from normal skin and lung and in tissue samples characterized by fibrosis, hyperplasia, and neovascularization. Using specific antibodies to mast cell tryptase, tissue macrophage, and bFGF, we demonstrate that cytoplasmic bFGF immunoreactivity is localized to 96.8 +/- 9.6% of tryptase-positive cells in human fibrotic lung tissue (n = 10), 82.3 +/- 6.9% of tryptase-positive cells in rheumatoid synovia (n = 6), and 93.1 +/- 4.8% of tryptase-positive cells in skin hemangioma (n = 5). Moreover, these tryptase-positive cells comprise a major portion (86 to 97%) of nonvascular cells exhibiting cytoplasmic bFGF staining in these tissues. In contrast, macrophage-like cells contribute less than 10% of the bFGF-positive cells in the same samples. The specificity of the immunostaining results was supported by the finding that cultured human mast cells (HMC-1) express both bFGF mRNA and protein. Our data indicate that mast cells, a primary source of heparin, also serve as a significant source of a heparin-binding growth factor, bFGF, in these disease processes. These observations suggest that mast cells may contribute to these pathological conditions by releasing this polypeptide.
- Published
- 1995
30. Aspirin idiosyncrasy in systemic mast cell disease: a new look at mediator release during aspirin desensitization.
- Author
-
Butterfield JH, Kao PC, Klee GC, and Yocum MW
- Subjects
- Adult, Aspirin administration & dosage, Calcitonin blood, Calcitonin Gene-Related Peptide blood, Chymases, Epinephrine therapeutic use, Humans, Hypotension blood, Hypotension chemically induced, Imidazoles blood, Inflammation Mediators blood, Male, Mastocytosis blood, Prostaglandin D2 blood, Serine Endopeptidases blood, Tryptases, Aspirin adverse effects, Desensitization, Immunologic methods, Mastocytosis drug therapy
- Abstract
Objective: To report the clinical responses and mediator-release profiles of an aspirin-sensitive man with systemic mast cell disease during aspirin desensitization., Material and Methods: We quantified the release of six mediators during aspirin desensitization., Results: Although aspirin was administered cautiously with an initial dose of 20 mg, successful aspirin desensitization necessitated complete monitoring and resuscitation capabilities of a medical intensive-care unit for 4.5 days because of frequent, severe anaphylactoid responses. To our knowledge, this is the first report of a pronounced increase in plasma levels of the vasodilator peptide calcitonin gene-related peptide during episodes of aspirin-induced hypotension. Increases in plasma levels of calcitonin and serum levels of tryptase paralleled those of calcitonin gene-related peptide, but plasma levels of calcitonin remained increased for up to 18 hours. Urinary excretion of histamine and 1-methyl-4-imidazoleacetic acid also showed precipitous, although delayed, increases. Excretion of the prostaglandin D2 metabolite 11 beta-prostaglandin F2 alpha followed a bimodal pattern during aspirin desensitization; after severe hypotensive responses, the maximal value was more than 490,000 pg/mL, but the level decreased to less than 100 pg/mL after therapeutic serum levels of salicylate were attained., Conclusion: These data suggest that the hypotensive responses to aspirin in some patients with systemic mast cell disease may result from the combined effects of several mediators.
- Published
- 1995
- Full Text
- View/download PDF
31. IL-4 enhances IL-3 and IL-8 gene expression in a human leukemic mast cell line.
- Author
-
Buckley MG, Williams CM, Thompson J, Pryor P, Ray K, Butterfield JH, and Coleman JW
- Subjects
- Base Sequence, Cell Division immunology, Gene Expression drug effects, Gene Expression immunology, Humans, Interleukin-3 genetics, Interleukin-4 biosynthesis, Interleukin-4 genetics, Interleukin-8 genetics, Ionomycin pharmacology, Leukemia, Experimental immunology, Molecular Sequence Data, Polymerase Chain Reaction methods, RNA, Messenger genetics, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha biosynthesis, Tumor Necrosis Factor-alpha genetics, Interleukin-3 biosynthesis, Interleukin-4 immunology, Interleukin-8 biosynthesis, Mast Cells immunology
- Abstract
We examined the capacity of interleukin (IL)-4 to induce or enhance the expression of certain cytokines in resting and activated cells of the HMC-1 human leukemic mast cell line. The HMC-1 mast cells were cultured with or without recombinant human IL-4 and then activated with the calcium ionophore ionomycin. Stimulation of non-IL-4-treated cells with ionomycin (10 microM) for periods of 30 min to 8 hr induced expression of mRNA encoding IL-3, IL-4 and IL-8 but was without effect on levels of mRNA for tumour necrosis factor (TNF)-alpha or beta-actin. Culture of the cells with IL-4 (100 ng/ml) for 24 hr led to a small increase in resting levels of mRNA for IL-3 and IL-8 but not for IL-4, TNF-alpha or beta-actin. More notably, the IL-4 treatment produced a pronounced elevation of mRNA for IL-3 and IL-8 when the cells were subsequently activated with ionomycin. The IL-4 treatment produced a negligible effect on IL-4 mRNA, and no effect on TNF-alpha or beta-actin mRNA levels in ionomycin-activated cells. Quantitation of cDNA by competitive polymerase chain reaction (PCR) revealed that the IL-4 treatment produced a sixfold increase in ionomycin-induced levels of cellular IL-3 mRNA, a fourfold increase in induced IL-8 mRNA and less than a twofold increase in induced IL-4 mRNA. The IL-4 treatment led to a 15- to 20-fold increase in ionomycin-induced secretion of IL-3 product and a doubling of induced IL-8 product. These effects of IL-4 were not associated with increased mast cell numbers. We conclude that IL-4 alone is a weak activator of IL-3 and IL-8 gene expression in mast cells, but is able to enhance activation signals in stimulated mast cells leading to transcription and secretion of these two cytokines.
- Published
- 1995
32. Increased plasma calcitonin levels in systemic mast cell disease.
- Author
-
Yocum MW, Butterfield JH, and Gharib H
- Subjects
- Adult, Aspirin administration & dosage, Creatinine urine, Desensitization, Immunologic, Histamine urine, Humans, Imidazoles urine, Male, Mastocytosis drug therapy, Mastocytosis urine, Pentagastrin, Anaphylaxis chemically induced, Aspirin adverse effects, Calcitonin blood, Mastocytosis blood
- Abstract
Aspirin therapy for patients with systemic mast cell disease (SMCD) decreases the production of prostaglandin D2, which is thought to be a major mediator of flushing. Paradoxically, in 5 to 10% of patients with SMCD, administration of aspirin causes massive mediator release and an anaphylactoid reaction. We attempted aspirin desensitization in a 34-year-old man with SMCD (confirmed by bone marrow biopsy) who was incapacitated by severe flushing episodes and hypotension. His baseline mediator levels of plasma calcitonin, urinary histamine, and urinary N-methyl-imidazoleacetic acid were abnormal. Pentagastrin stimulation increased the plasma level of calcitonin from 47 pg/mL to 130 pg/mL (normal, less than or equal to 110) at 5 minutes. Oral aspirin desensitization was begun; however, after a cumulative dose of 620 mg, an anaphylactoid reaction ensued in conjunction with hypotension, abdominal cramping, and flushing. Coincidentally, 1 hour after the episode, the plasma calcitonin level increased from 37 pg/mL to 540 pg/mL, and the serum tryptase level increased from 1 ng/mL to 3.9 ng/mL. Six hours after the episode, the urine level of histamine increased from 90 micrograms/g creatinine to 337 micrograms/g creatinine, and the urinary N-methylimidazoleacetic acid increased from 32 mg/24 h to 81 mg/24 h. Hence, the patient had increased basal levels of plasma calcitonin that increased substantially during aspirin desensitization and increased to above the upper limit of normal during pentagastrin stimulation. Human mast cells may be capable of producing calcitonin or causing secretion of calcitonin in response to skeletal changes.
- Published
- 1994
- Full Text
- View/download PDF
33. Expression of multiple chemokine genes by a human mast cell leukemia.
- Author
-
Selvan RS, Butterfield JH, and Krangel MS
- Subjects
- Gene Expression Regulation, Neoplastic, Glucocorticoids pharmacology, Humans, Lymphocyte Activation, Mast Cells metabolism, RNA, Messenger metabolism, T-Lymphocytes drug effects, T-Lymphocytes immunology, T-Lymphocytes metabolism, Tumor Cells, Cultured, Cytokines genetics, Leukemia, Mast-Cell genetics
- Abstract
The chemokines are a large group of cytokines that are recognized to be important mediators of inflammation. In this study we show that the human mast cell leukemia line HMC-1 is a source of multiple chemokines, including I-309, monocyte chemoattractant protein 1, macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, RANTES, and interleukin-8. I-309 and MCP-1 transcripts are expressed at low levels in unstimulated HMC-1. However, phorbol ester treatment up-regulates these and other chemokine transcript levels and also up-regulates chemokine protein synthesis and secretion. Induction of chemokine transcripts in HMC-1 requires de novo protein synthesis. We compared the effects of anti-inflammatory glucocorticoids on the expression of chemokine genes in HMC-1 to their effects in activated T-cells. We find that methyl-prednisolone reduces MCP-1 but not other chemokine transcripts in HMC-1, even though there are distinct and more general effects on chemokine transcripts in activated T-cells. These effects are attributed to inhibition of transcription rather than transcript stability. Our results suggest that human mast cells may be a source of multiple chemokines, that glucocorticoids may inhibit the expression of only a subset of these chemokines, and that mast cells and T-cell chemokine expression may occur via distinct regulatory pathways.
- Published
- 1994
34. Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product.
- Author
-
Furitsu T, Tsujimura T, Tono T, Ikeda H, Kitayama H, Koshimizu U, Sugahara H, Butterfield JH, Ashman LK, and Kanayama Y
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Cell Line, DNA Primers, Granulocyte-Macrophage Colony-Stimulating Factor pharmacology, Humans, Interleukin-3 pharmacology, Mice, Molecular Sequence Data, Phosphotyrosine, Polymerase Chain Reaction, Proto-Oncogene Mas, Proto-Oncogene Proteins biosynthesis, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-kit, Receptor Protein-Tyrosine Kinases biosynthesis, Receptor Protein-Tyrosine Kinases metabolism, Receptors, Colony-Stimulating Factor biosynthesis, Receptors, Colony-Stimulating Factor metabolism, Recombinant Proteins pharmacology, Transfection, Tumor Cells, Cultured, Tyrosine analogs & derivatives, Tyrosine analysis, Leukemia, Mast-Cell genetics, Point Mutation, Proto-Oncogene Proteins genetics, Proto-Oncogenes, Receptor Protein-Tyrosine Kinases genetics, Receptors, Colony-Stimulating Factor genetics
- Abstract
The c-kit proto-oncogene encodes a receptor tyrosine kinase. Binding of c-kit ligand, stem cell factor (SCF) to c-kit receptor (c-kitR) is known to activate c-kitR tyrosine kinase, thereby leading to autophosphorylation of c-kitR on tyrosine and to association of c-kitR with substrates such as phosphatidylinositol 3-kinase (PI3K). In a human mast cell leukemia cell line HMC-1, c-kitR was found to be constitutively phosphorylated on tyrosine, activated, and associated with PI3K without the addition of SCF. The expression of SCF mRNA transcript in HMC-1 cells was not detectable by means of PCR after reverse transcription (RT-PCR) analysis, suggesting that the constitutive activation of c-kitR was ligand independent. Sequencing of whole coding region of c-kit cDNA revealed that c-kit genes of HMC-1 cells were composed of a normal, wild-type allele and a mutant allele with two point mutations resulting in intracellular amino acid substitutions of Gly-560 for Val and Val-816 for Asp. Amino acid sequences in the regions of the two mutations are completely conserved in all of mouse, rat, and human c-kit. In order to determine the causal role of these mutations in the constitutive activation, murine c-kit mutants encoding Gly-559 and/or Val-814, corresponding to human Gly-560 and/or Val-816, were constructed by site-directed mutagenesis and expressed in a human embryonic kidney cell line, 293T cells. In the transfected cells, both c-kitR (Gly-559, Val-814) and c-kitR (Val-814) were abundantly phosphorylated on tyrosine and activated in immune complex kinase reaction in the absence of SCF, whereas tyrosine phosphorylation and activation of c-kitR (Gly-559) or wild-type c-kitR was modest or little, respectively. These results suggest that conversion of Asp-816 to Val in human c-kitR may be an activating mutation and responsible for the constitutive activation of c-kitR in HMC-1 cells.
- Published
- 1993
- Full Text
- View/download PDF
35. The human mast cell chymase gene (CMA1): mapping to the cathepsin G/granzyme gene cluster and lineage-restricted expression.
- Author
-
Caughey GH, Schaumberg TH, Zerweck EH, Butterfield JH, Hanson RD, Silverman GA, and Ley TJ
- Subjects
- Base Sequence, Cathepsin G, Cells, Cultured, Chymases, DNA, Gene Expression Regulation, Enzymologic, Genetic Linkage, Granzymes, Humans, Molecular Sequence Data, Restriction Mapping, Cathepsins genetics, Mast Cells enzymology, Multigene Family, Serine Endopeptidases genetics
- Abstract
Genes encoding T-cell-receptor alpha/delta chains, neutrophil cathepsin G, and lymphocyte CGL/granzymes are closely linked on chromosomal band 14q11.2. The current work identifies the human mast cell chymase gene (CMA1) as the fourth protease in this cluster and maps the gene to within 150 kb of the cathepsin G gene. The gene order is centromere-T cell receptor alpha/delta-CGL-1/granzyme B-CGL-2/granzyme H-cathepsin G-chymase. Chymase and cathepsin G genes are shown to be cotranscribed in the human mast cell line HMC-1 and in U-937 cells. Other cells transcribe cathepsin G or CGL/granzyme genes, but not chymase genes, suggesting a capacity for independent regulation. Comparison of the 5' flank of the chymase gene with those of cathepsin G and CGL/granzymes reveals little overall homology. Only short regions of the 5' flanks of the human and murine chymase gene sequenced to date are similar, suggesting that they are more distantly related than human and rodent CGL-1/granzyme B, the flanks of which are highly homologous. The expression patterns and clustering of genes provide possible clues to the presence of locus control regions that orchestrate lineage-restricted expression of leukocyte and mast cell proteases.
- Published
- 1993
- Full Text
- View/download PDF
36. Immunofluorescent staining for mast cells in idiopathic pulmonary fibrosis: quantification and evidence for extracellular release of mast cell tryptase.
- Author
-
Hunt LW, Colby TV, Weiler DA, Sur S, and Butterfield JH
- Subjects
- Biopsy, Case-Control Studies, Cell Count, Cell Line, Chymases, Fluorescent Antibody Technique, Humans, Lung cytology, Lung pathology, Mast Cells pathology, Pulmonary Fibrosis pathology, Tryptases, Lung immunology, Mast Cells enzymology, Pulmonary Fibrosis immunology, Serine Endopeptidases metabolism
- Abstract
In many diseases, retrospective analysis for determining the presence of mast cells has been difficult because of their loss of metachromatic staining properties once tissue has undergone formalin fixation. We quantified mast cells in peribronchiolar tissue of idiopathic pulmonary fibrosis (IPF) and in normal human lung by using rabbit antiserum to human mast cell tryptase. In lung biopsy specimens from 15 patients with IPF, the mean number of mast cells per high-power field in connective tissue directly adjacent to the lumen of small airways (0.5 to 2 mm in diameter) and other fibrotic foci was 29.9 +/- 10.8 in comparison with 13.7 +/- 3.5 in 16 normal controls (P < 0.001). In addition, mast cells in cases of IPF had an altered appearance--irregularity of the plasma membrane and release of extracellular tryptase. We conclude that the number of mast cells is increased in IPF and that the altered appearance of the mast cells suggests that they are activated and undergoing degranulation.
- Published
- 1992
- Full Text
- View/download PDF
37. Eosinophil differentiation of human umbilical cord mononuclear cells and prolonged survival of mature eosinophils by murine EL-4 thymoma cell conditioned medium.
- Author
-
Ten RM, Butterfield JH, Kita H, Weiler DA, Fischkoff S, Ishizaka T, Sanderson CJ, and Gleich GJ
- Subjects
- Animals, Blood Proteins metabolism, Cell Differentiation, Cell Survival, Culture Media, Eosinophil Granule Proteins, Eosinophils drug effects, Eosinophils metabolism, Humans, Interleukin-5 pharmacology, Leukocytes, Mononuclear cytology, Peroxidases metabolism, Transcription, Genetic, Tumor Cells, Cultured immunology, Eosinophils cytology, Fetal Blood cytology, Ribonucleases
- Abstract
Umbilical cord mononuclear cells, HL-60 cells, HL-60 clones selected for eosinophil differentiation, and the eosinophil leukemia cell line EoL were tested for their ability to produce eosinophil peroxidase. HL-60 clones selected for eosinophil differentiation produced eosinophil peroxidase, as judged by staining of cells for cyanide-resistant peroxidase activity; however, these cells lost their ability to produce eosinophil peroxidase in long-term culture. In contrast, eosinophil precursors from human umbilical cord blood mononuclear cells stimulated with murine EL-4 conditioned medium (EL-4 CM) were regularly induced to eosinophil protein synthesis, including eosinophil peroxidase, major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin, as assessed by cyanide-resistant peroxidase and immunofluorescence staining. This induction by EL-4 CM is either at the level of gene transcription or mRNA stabilization, as shown by the increase of total mRNA for eosinophil peroxidase, major basic protein, and eosinophil-derived neurotoxin by Northern blot analyses. Purified peripheral blood eosinophils incubated for 4 days with EL-4 CM had increased survival over control eosinophils. Moreover, this enhanced survival was specifically blocked by antiserum to interleukin 5. Our results suggest that the effects of EL-4 CM on human umbilical cord mononuclear cells and mature eosinophils are due to the presence of interleukin 5.
- Published
- 1991
- Full Text
- View/download PDF
38. Interleukin 4 promotes expression of mast cell ICAM-1 antigen.
- Author
-
Valent P, Bevec D, Maurer D, Besemer J, Di Padova F, Butterfield JH, Speiser W, Majdic O, Lechner K, and Bettelheim P
- Subjects
- Antigens, CD metabolism, Blotting, Northern, Cell Adhesion Molecules metabolism, Cell Division drug effects, Flow Cytometry, Gene Expression drug effects, Humans, In Vitro Techniques, Intercellular Adhesion Molecule-1, Leukemia, Mast-Cell, RNA, Messenger genetics, Receptors, Interleukin-4, Receptors, Mitogen metabolism, Tumor Cells, Cultured, Up-Regulation, Antigens, CD genetics, Cell Adhesion Molecules genetics, Interleukin-4 pharmacology, Mast Cells physiology
- Abstract
Cell recognition molecules play a crucial role in the regulation of immune cells. We recently found that mast cells (MCs) express leukocyte recognition molecules, including ICAM-1 antigen, a natural ligand of LFA-1. We here report that interleukin 4 (IL-4), a pleiotropic cytokine and mast cell differentiation factor, selectively promotes expression of surface ICAM-1 antigen and ICAM-1 mRNA in human MCs. IL-4 also up-regulates ICAM-1 antigen in cells of monocyte/macrophage lineage but has no effect on ICAM-1 antigen expressed on basophils, fibroblasts, or lymphocytes. The increase in expression of mast cell/macrophage ICAM-1 antigen induced by IL-4 may contribute to the accumulation of leukocytes and facilitate cell-contact-dependent regulation of immune cells in inflamed tissues.
- Published
- 1991
- Full Text
- View/download PDF
39. Purification of tryptase from a human mast cell line.
- Author
-
Butterfield JH, Weiler DA, Hunt LW, Wynn SR, and Roche PC
- Subjects
- Amino Acid Chloromethyl Ketones pharmacology, Amino Acid Sequence, Amino Acids analysis, Animals, Cell Line, Chromatography, High Pressure Liquid, Electrophoresis, Polyacrylamide Gel, Fluorescent Antibody Technique, Glycerol pharmacology, Humans, Hydrogen-Ion Concentration, Leukemia, Mast-Cell enzymology, Leukemia, Mast-Cell pathology, Leukemia, Mast-Cell physiopathology, Mast Cells drug effects, Mast Cells pathology, Mastocytosis enzymology, Mastocytosis pathology, Mastocytosis physiopathology, Mercuric Chloride pharmacology, Mice, Mice, Nude, Molecular Sequence Data, Peptide Hydrolases analysis, Skin cytology, Dansyl Compounds, Mast Cells enzymology, Peptide Hydrolases isolation & purification
- Abstract
The neutral protease tryptase has been isolated from a human mast cell line, HMC-1. The HMC-1 line was established from the peripheral blood of a patient with mast cell leukemia and maintained as continuously proliferating clones in vitro and as solid mast cell tumors in nude mice. HMC-1-derived tryptase was purified by sequential chromatography on Dowex 1, DEAE 5 PW, and heparin-agarose. Purified tryptase has an apparent molecular weight of 150,000, as determined by molecular sieve HPLC, but migrates as a doublet of bands of 32/35,000 on SDS-PAGE gels. Maximal enzymatic activity was observed at pH 8.5. Cleavage of tosyl-L-arginine methyl ester by purified tryptase was inhibited by dansyl-L-glutamyl-glycyl-L-arginine chloromethyl ketone 2 HCl, HgCl2, tosyl-L-lysine chloromethyl ketone, leupeptin, and PMSF but not by benzamidine, aprotinin, tosyl-L-phenyl-alanine chloromethyl ketone, soybean trypsin inhibitor, human plasma, ovomucoid inhibitor, or lima bean trypsin inhibitor. Microsequencing of purified tryptase yielded an amino terminal sequence that was identical to that previously reported for human pituitary-derived tryptase.
- Published
- 1990
- Full Text
- View/download PDF
40. Localization of a molecule immunochemically similar to eosinophil major basic protein in human placenta.
- Author
-
Maddox DE, Kephart GM, Coulam CB, Butterfield JH, Benirschke K, and Gleich GJ
- Subjects
- Animals, Blood Proteins immunology, Cysts immunology, Eosinophil Granule Proteins, Female, Fluorescent Antibody Technique, Gestational Age, Humans, Placenta cytology, Placenta Diseases immunology, Placental Extracts immunology, Pregnancy, Rabbits, Trophoblasts immunology, Blood Proteins analysis, Eosinophils immunology, Placenta immunology, Ribonucleases
- Abstract
We have recently reported that human pregnancy is characterized by a 10- to 20-fold elevation of eosinophil major basic protein (MBP) immunoreactivity in maternal blood. Here we show, by immunofluorescence, that placental tissue specifically binds antibody to MBP in and around the placental X cells and placental-site giant cells and, using thin plastic sections, that placenta has no infiltrating eosinophils. The X cells line the inner aspects of placental septal cysts, and the cyst fluid, obtained by aspiration, contains immunoreactive MBP at concentrations of 100 micrograms/ml, a sixfold greater concentration than the highest levels measured in maternal blood. The soluble MBP immunoreactivities in placental homogenates and in maternal serum chromatograph identically on Sephadex G-50, and both these gestational MBP molecules migrate as though substantially larger than the MBP found in serum from patients with hypereosinophilic syndrome or purified from the eosinophil granule. Our inability to demonstrate eosinophils in maternal blood or placental tissue, coupled with the large quantities of immunoreactive MBP highly localized in placental cysts and the chromatographic behavior of this molecule, suggest that the MBP detected in human gestation is produced by placenta.
- Published
- 1984
- Full Text
- View/download PDF
41. Elevated serum levels in human pregnancy of a molecule immunochemically similar to eosinophil granule major basic protein.
- Author
-
Maddox DE, Butterfield JH, Ackerman SJ, Coulam CB, and Gleich GJ
- Subjects
- Animals, Binding, Competitive, Blood Proteins immunology, Blood Proteins physiology, Dose-Response Relationship, Immunologic, Eosinophil Granule Proteins, Eosinophilia diagnosis, Eosinophilia immunology, Female, Fetal Blood chemistry, Guinea Pigs, Humans, Infant, Newborn, Postpartum Period, Pregnancy, Pregnancy Proteins immunology, Pregnancy Proteins physiology, Blood Proteins analysis, Pregnancy Proteins analysis, Ribonucleases
- Abstract
We have shown that serum levels of a molecule immunochemically similar to eosinophil granule major basic protein (MBP) are elevated in pregnant women throughout gestation. MBP levels increase during gestation and plateau at approximately 7,500 ng/ml by the 20th wk (greater than 10-fold above normal). Levels return to normal after delivery, with a T1/2 of 13.7 d. The MBP in pregnancy serum is remarkably similar to the eosinophil granule MBP in that: (a) pregnancy MBP fully inhibits the binding of radiolabeled MBP standard in a double antibody radioimmunoassay; (b) this inhibition reaction is specific for human MBP because pregnancy serum produces no inhibition of the binding of radiolabeled guinea pig MBP in the guinea pig MBP radioimmunoassay; (c) in a two-site immunoradiometric assay for MBP, slopes of dose-response curves for pregnancy serum, purified MBP, and serum from a patient with hypereosinophilic syndrome are identical, and maximal binding is comparable; (d) reduction and alkylation of pregnancy sera increases measured MBP 100-fold, as previously shown for eosinophil granule MBP in serum; and (e) the MBP in pregnancy serum demonstrates the same pattern of heat lability as has been previously reported for MBP. Four observations have raised the possibility that the eosinophil is not the source of the MBP in pregnancy serum: (a) no correlation between serum MBP level and peripheral blood eosinophil count exists in pregnant women, in contrast to previous studies of patients with eosinophilia; (b) levels of three other eosinophil-associated proteins are normal or low in pregnancy sera, whereas the serum levels of these proteins are elevated in patients with eosinophilia; (c) the slopes of dose-response curves for pregnancy sera and MBP standards differ in the double antibody radioimmunoassay; and (d) the molecule in pregnancy serum elutes from Sephadex G-50 columns at the void volume, while eosinophil granule MBP and the MBP in serum of patients with eosinophilia elute at a volume consistent with the previously established molecular weight of 9,300. These findings suggest that the MBP in pregnancy serum is derived from a source other than the eosinophil.
- Published
- 1983
- Full Text
- View/download PDF
42. Giant eosinophil colonies from cultures of bone marrow cells.
- Author
-
Butterfield JH and Weiler D
- Subjects
- Cell Line, Culture Media, Granulocytes cytology, Humans, Macrophages cytology, Microscopy, Electron, Bone Marrow Cells, Eosinophils cytology
- Abstract
To date, the small size and slow growth of eosinophil colonies in vitro has hampered study of cloned eosinophils. We found enhanced eosinophil colony size and numbers in methylcellulose cultures of bone marrow cells utilizing defined supplemented bovine calf serum (DSBCS) in combination with EL4 conditioned medium (EL4-CM). At days 9, 16 and 23 significantly more eosinophil colonies and more cells/colony were present in cultures incubated with DSBCS/EL4-CM than in cultures incubated with fetal calf serum/EL4-CM. The ability to generate large numbers of eosinophils in vitro should facilitate study of cloned eosinophils.
- Published
- 1986
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.