Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A clinical and hematopathologic review of 66 patients with systemic mast cell disease (SMCD) was undertaken to investigate the frequency and the clinical significance of associated hematologic disorders. Twenty-two patients were found to have a second hematologic disorder, 19 of which involved the myeloid cells (ten dysmyelopoietic syndromes, five myeloproliferative disorders, three acute nonlymphocytic leukemias, and one chronic neutropenia), and three of which involved the lymphoid cells (three malignant lymphomas). A chromosome analysis of the bone marrow revealed abnormalities characteristic of neoplastic myeloid disorders in four patients. Five-year survival for patients with hematologic disorders was 28% compared with 61% for other SMCD patients (P = 0.004). Patients with hematologic disorders differed significantly from other SMCD patients in that they were about 7 years older (P = 0.039), and they presented more commonly with anemia (P less than 0.001) and constitutional symptoms (P = 0.007). These patients also had less frequent skin symptoms (P = 0.003) and urticaria pigmentosa (P = 0.018). By definition, patients with hematologic disorders had a greater percent of hematopoiesis (P less than 0.001) and decreased fat cells (P = 0.011) on bone marrow biopsies. A multivariate model demonstrated that the following independent variables were associated with the presence of hematologic disorders: low hemoglobin (P = 0.001), the absence of hepatomegaly (P = 0.016), high leukocyte count (P = 0.021), and the presence of pathologic fractures (P = 0.051). The frequent coexistence of SMCD with dysplastic and neoplastic disorders of myeloid cells is consistent with the concept that SMCD itself is a disorder of myeloid cells and that the mast cell may be myeloid in origin.
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PMID:Significance of systemic mast cell disease with associated hematologic disorders. 340 77

Six patients exhibiting severe pancytopenia or overt leukemia associated with myelofibrosis after chemotherapy for malignant disease have been investigated by immunologic techniques and ultrastructural cytochemistry. Initially, five patients displayed severe thrombocytopenia contrasting with mild neutropenia and anemia. Bone marrow biopsies showed a clear megakaryocytic proliferation and an excess of immature mononuclear cells. The demonstration of peroxidase activities at the ultrastructural level and immunofluorescence labeling with a panel of monoclonal antibodies, including an antiplatelet glycoprotein Ib and an antiglycoprotein IIb-IIIa complex, on blood or marrow cells, permitted identification of otherwise unidentifiable promegakaryoblastic proliferation. In two patients, the use of an immunoperoxidase technique with an antifactor VIII-R-Ag antibody has allowed direct confirmation of this diagnosis on bone marrow sections. This megakaryoblastic proliferation was not pure and was variably associated with blasts of other cell lines (erythroblasts or myeloblasts). Changes in the population of blasts were observed during evolution in two patients. The sixth patient had a mild thrombocytopenia associated with severe neutropenia and anemia. Bone marrow biopsy displayed a myelofibrosis and immature cells, without megakaryocytic proliferation. Ultrastructural study revealed a pure basophil-mast cell proliferation. In conclusion, in five of six patients with secondary acute leukemia associated with myelofibrosis, a proliferation of promegakaryoblasts was demonstrated using both immunofluorescent and ultrastructural cytochemical techniques.
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PMID:Therapy-related leukemia associated with myelofibrosis. Blast cell characterization in six cases. 638 Jul 2

Type I immediate hypersensitivity reactions in human and rat skin may be followed by late phase reactions (LPR). A consistent feature of both human and rat LPR is the early histologic appearance of neutrophils, which, in rats, is followed by the later appearance (8 to 24 hr) of mononuclear cells. To determine the importance of the neutrophil in the development of LPR, rats were depleted of neutrophils using parenteral injections of vinblastine sulfate (VS). VS produced a dose-dependent neutropenia, with the maximal effect on day 4. LPR that were induced with anti-IgE, isolated mast cell granules (MCG), or purified high (greater than 10,000 daltons) and low (500 to 10,000 daltons) m.w. fractions obtained from MCG were significantly abrogated in VS-treated rats. In neutropenic rats previously immunized with complete Freund's adjuvant, the intensity of inflammatory reactions produced by skin testing with purified protein derivatives was also significantly reduced. Administration of exogenous neutrophils to neutropenic animals partially reconstituted the reduced LPR. These data confirm and extend previous observations on the contribution of neutrophils to delayed hypersensitivity reactions and provide evidence that the neutrophil is critical for the development of rat cutaneous LPR as well.
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PMID:The biologic activity of mast cell granules. VI. The effect of vinblastine-induced neutropenia on rat cutaneous late phase reactions. 685 18

To investigate the possible role of mast cell or basophil histamine release in mediating platelet-activating factor (PAF) airway obstruction, we studied the effect of inhaled PAF (30 micrograms, single dose) on plasma histamine, bronchial caliber, and leukocyte and platelet counts in six patients with mild or moderate allergic asthma (mean age, 27 +/- 1.3 years; mean FEV1, 95 +/- 5 percent of predicted; mean PC20 methacholine, 1.46 +/- 0.36 mg/ml). Specific conductance (SGaw) FEV1, FEF25-75 percent, differential leukocyte and platelet counts, and plasma histamine (radioimmunoassay) were measured before and 5, 10, 15, and 20 min after PAF inhalation. Mean basal plasma histamine level was 0.28 +/- 0.04 ng/ml. Inhalation of PAF caused a fall in SGaw peaking at 5 min (43 +/- 9 percent) and a fall in FEV1 and FEF25-75 peaking at 10 min (19 +/- 10 percent and 30 +/- 13 percent, respectively). There was also a rapid and transient fall in circulating neutrophils at 5 min (from 3,096 +/- 204/mm3 to 2,551 +/- 158/mm3, p < 0.05) followed by a rebound neutrophilia. In contrast, plasma histamine level did not change significantly at any time measured. Conversely in the same asthmatics, a rapid rise in plasma histamine level (from 0.29 +/- 0.03 ng/ml at baseline to 0.53 +/- 0.06 ng/ml at 5 min; p < 0.01) was observed after an allergenic challenge (Dermatophagoides pteronyssinus) causing a fall in FEV1 peaking at 10 min (22 +/- 4 percent). Thus, inhaled PAF may induce airway obstruction and neutropenia in asthmatics without any significant change of plasma histamine level. These results indicate that it is unlikely that lung mast cells or basophils degranulate during PAF-induced bronchoconstriction.
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PMID:No increase in plasma histamine during PAF-induced airway obstruction in allergic asthmatics. 836 93

The efficacy and toxicity of CCNU (1-[2-chloroethyl]3-cyclohexyl-1-nitrosourea) were evaluated in 23 dogs with measurable mast cell tumors (MCT). Twenty-two dogs had cutaneous MCT and 1 dog had an intranasal MCT Nineteen (83%) dogs had biopsy of their original mass performed and 4 (17%) had aspiration cytology of masses. Of the 19 tumors histologically graded, 1 (5%) neoplasm was classified as grade I, 10 (53%) were grade II, and the remaining 8 (42%) were grade III. Dogs were treated with CCNU at a dosage of 90 mg/m2 body surface area every 3 weeks. Response could be evaluated in 19 dogs. Eight of the 19 dogs (42%) had a measurable response to CCNU. One dog had a durable complete response for 440 days. Seven dogs (37%) had a partial response for a median and mean duration of 77 days and 109 days, respectively (range, 21-254 days). Treatment with CCNU resulted in stable disease in 6 dogs (32%) for a median and mean duration of 78 days and 122 days, respectively (range, 42-347 days). The acute dose-limiting toxicity was neutropenia 7 days after administration of CCNU. The median and mean neutrophil counts 7 days after CCNU were 1,452 cells/microL and 1,683 cells/microL, respectively (n = 17). Other toxicoses were uncommon. CCNU should be considered an active agent in the treatment of MCT in dogs.
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PMID:Treatment of canine mast cell tumors with CCNU (lomustine). 1058 63

1-(2-Chloroethyl)3-cyclohexyl-1-nitrosourea (CCNU) is an alkylating agent in the nitrosourea subclass. A prospective evaluation of CCNU was done to determine the maximally tolerated dosage of CCNU in tumor-bearing cats. Response data were obtained when available. Twenty-five cats were treated with CCNU at a dosage of 50-60 mg/m3 body surface area. Complete hematologic data were available for 13 cats. Neutropenia was the acute dose-limiting toxicity. The median neutrophil count at the nadir was 1,000 cells/microL (mean, 2,433 cells/microL; range, 0-9,694 cells/microL). The time of neutrophil nadir was variable, occurring 7-28 days after treatment, and counts sometimes did not return to normal for up to 14 days after the nadir. Based on these findings, a 6-week dosing interval and weekly hematologic monitoring after the 1st treatment with CCNU are recommended. The nadir of the platelet count may occur 14-21 days after treatment. The median platelet count at the nadir was 43,500 cells/microL. No gastrointestinal, renal, or hepatic toxicities were observed after a single CCNU treatment, and additional studies to evaluate the potential for cumulative toxicity should be performed. Five cats with lymphoma and 1 cat with mast cell tumor had measurable responses to CCNU. Phase II studies to evaluate antitumor activity should be completed with a dosing regimen of 50-60 mg/m3 every 6 weeks.
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PMID:Phase I evaluation of CCNU (lomustine) in tumor-bearing cats. 1138 27

Nineteen dogs were identified that had mastocytemia (mast cells in venous blood samples) not associated with mast cell neoplasia. The first 10 dogs were identified by examination of blood films from dogs with suspected parvovirus enteritis (8), fibrinous pericarditis and pleuritis secondary to thoracic lacerations (1), and renal insufficiency of unknown cause (1). Because of the apparent association with acute enteritis, blood films from 52 suspected canine parvovirus cases were examined retrospectively and 8 mastocytemic dogs were found. An additional 52 canine blood films were randomly selected from the same retrospective time period and 1 mastocytemic dog was found that had pneumothorax, pelvic fractures, and hemorrhagic septic abdominal effusion secondary to renal hemorrhage and traumatized intestines. All mastocytemic dogs had acute inflammatory leukograms the day that mast cells were first detected: neutropenia with toxic neutrophils (4), neutropenia with a left shift (8), total neutrophil count within reference interval but with a left shift (5), or neutrophilia with a left shift (2). All dogs except the renal insufficiency case had circulating toxic neutrophils. Five dogs were mastocytemic on more than 1 day. The pathogenesis of the mastocytemia associated with the acute inflammatory disease was not determined.
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PMID:Mastocytemia in dogs with acute inflammatory diseases. 1533 38

An eight-year-old, male boxer dog was referred for the treatment of a large (5.5 x 5 cm), unresectable visceral mast cell tumour. The dog had a surgical resection performed one month before referral, and it had widespread metastases to the abdominal lymph nodes. The patient was treated with lomustine and prednisone and showed a rapid improvement and increased level of activity, weight gain and consistent tumour reduction. The patient remained in partial remission (defined as a greater than 50 per cent reduction in tumour volume) for seven months. Toxicity was acceptable and was limited to moderate anaemia and two episodes of neutropenia. At the completion of the seven months of therapy, the dog experienced a chemotherapy-induced sepsis, and the owners elected for euthanasia due to financial concerns. At that time, the tumour was still in partial remission. This case report suggests that a combination of lomustine and prednisone is an effective protocol for the palliation of aggressive visceral mast cell tumours.
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PMID:Lomustine for the treatment of gastrointestinal mast cell tumour in a dog. 1691 Nov 16

Pain intensity in chronic venous disease varies with the stage in the clinical-etiologic-anatomic-pathophysiologic (CEAP) classification but also with patient perception, pain being by definition subjective. The venous hypertension responsible for the varicose veins and trophic changes in CVD has a variety of algogenic repercussions in which leukocytes play a particular role, notably through their ability to roll along the vessel wall. Shear stress, hypoxia and stasis activate the marginated leukocytes to shed L-selectin from their surface and express integrins, matrix metalloproteinase 9, elastase, lactoferrin and free radicals. Meanwhile the endothelium expresses adhesion molecules that permit slow rolling on E-selectin followed by adhesion and tissue transmigration. Vein wall and valve areas in particular attract mast cells, monocyte-macrophages and T lymphocytes, and undergo remodeling. Sympathetic sensory C and Adelta fibers, which wrap around cutaneous venules and are also present in the venous intima and media, are nociceptors sensitive to the pain mediators concentrated within leukocytes, such as mast cell bradykinin, responsible for visceral pain. Neuronal inflammation combined with wall remodeling intensifies symptoms. Yet no direct link has so far been shown between pain and mast cell mediator levels. Leukocyte adhesion is also associated with the increased capillary permeability that leads to edema. Antileukocyte therapies include postural rest and venotonics which alone or in combination with compression have been shown to unstick and inhibit leukocytes. The micronized purified flavonoid fraction (MPFF) protects vascular endothelium against hypoxia and reduces adhesion molecule expression. Unlike other antileukocyte therapies, venotonics do not cause neutropenia.
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PMID:Leukocyte involvement in the signs and symptoms of chronic venous disease. Perspectives for therapy. 1772 58

Mast cells participate in pathophysiological processes that range from antimicrobial defense to anaphylaxis and inflammatory arthritis. Much of the groundwork for the understanding of mast cells was established in mice that lacked mast cells through defects in either stem cell factor or its receptor, Kit. Among available strains, C57BL/6-Kit(W-sh) (W(sh)) mice are experimentally advantageous because of their background strain and fertility. However, the genetic inversion responsible for the W(sh) phenotype remains poorly defined, and its effects beyond the mast cell have been incompletely characterized. We report that W(sh) animals exhibit splenomegaly with expanded myeloid and megakaryocyte populations. Hematopoietic abnormalities extend to the bone marrow and are reflected by neutrophilia and thrombocytosis. In contrast, mast cell-deficient WBB6F1-Kit(W)/Kit(W-v) (W/W(v)) mice display mild neutropenia, but no changes in circulating platelet numbers. To help define the basis for the W(sh) phenotype, a "DNA walking" strategy was used to identify the precise location of the 3' breakpoint, which was found to reside 67.5 kb upstream of Kit. The 5' breakpoint disrupts corin, a cardiac protease responsible for the activation of atrial natriuretic peptide. Consistent with this result, transcription of full-length corin is ablated and W(sh) mice develop symptoms of cardiomegaly. Studies performed using mast cell-deficient strains must consider the capacity of associated abnormalities to either expose or compensate for the missing mast cell lineage.
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PMID:Genetic inversion in mast cell-deficient (Wsh) mice interrupts corin and manifests as hematopoietic and cardiac aberrancy. 1898 2


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