Background-We compared cardiac mast cell (HHMC) density and the immunological and nonimmunological release of mediators from mast cells isolated from heart tissue of patients with idiopathic dilated (DCM) (nϭ24) and ischemic cardiomyopathy (ICM) (nϭ10) undergoing heart transplantation and from control subjects (nϭ10) without cardiovascular disease. Methods and Results-HHMC density in DCM (18.4Ϯ1.6 cells/mm 2 ) and ICM (18.4Ϯ1.5 cells/mm 2 ) was higher than that in control hearts (5.3Ϯ0.7 cells/mm 2 ; PϽ.01). The histamine and tryptase contents of DCM and ICM hearts were higher than those of control hearts. The histamine content of the hearts was correlated with mast cell density (r s ϭ.91; PϽ.001). Protein A/gold staining of heart tissue revealed stem cell factor (SCF), the principal growth, differentiating, and activating factor of human mast cells, in HHMC secretory granules. Histamine release from cardiac mast cells caused by immunological (anti-IgE and rhSCF) and nonimmunological stimuli (Ca 2ϩ ionophore A23187) was higher in patients with DCM and ICM compared with control subjects. Immunological activation of HHMC induced a significantly greater release of tryptase and LTC 4 in patients with DCM and ICM compared with control subjects. Conclusions-Histamine and tryptase content and mast cell density are higher in failing hearts than in control hearts. SCF, present in secretory granules of HHMC, might represent an autocrine factor sustaining mast cell hyperplasia in heart tissue in these patients. The increased local release of fibrogenic factors (eg, histamine, tryptase, and leukotriene C 4 ) might contribute to collagen accumulation in the hearts of patients with cardiomyopathy. 1 Mast cells are present in human heart tissue 2,3 and in adventia and intima of coronary arteries of patients with coronary artery disease. [4][5][6] Moreover, the in vitro immunological activation of human heart tissue with anti-IgE induces the release of histamine and prostaglandin D 2 . 7,8 The concentration of histamine and the density of mast cells are increased in the arteries of cardiac patients, 4,5,9 and coronary arteries from cardiac patients are hyperresponsive in vitro to histamine. 4 Furthermore, in vivo administration of histamine and other mast cell-derived mediators (peptide LTC 4 ) in humans causes significant cardiovascular effects. 10 -12 Finally, serum IgE levels are increased in patients with coronary artery disease. 13,14 Taken together, these observations raise the possibility that local activation of cardiac mast cells might contribute, through the release of vasoactive mediators, to certain cardiovascular diseases. 15,16 Fibrosis is a hallmark of failing hearts in DCM and ICM. 17 The cells and the mediators responsible for fibroblast proliferation and collagen accumulation in failing hearts in DCM and ICM are largely unknown. Mast cells are involved in many types of inflammation and repair processes and are found in increased numbers in fibrotic tissues. For example, increased mast cell density has be...
The Battery for the Assessment of Auditory Sensorimotor and Timing Abilities (BAASTA) is a new tool for the systematic assessment of perceptual and sensorimotor timing skills. It spans a broad range of timing skills aimed at differentiating individual timing profiles. BAASTA consists of sensitive time perception and production tasks. Perceptual tasks include duration discrimination, anisochrony detection (with tones and music), and a version of the Beat Alignment Task. Perceptual thresholds for duration discrimination and anisochrony detection are estimated with a maximum likelihood procedure (MLP) algorithm. Production tasks use finger tapping and include unpaced and paced tapping (with tones and music), synchronization-continuation, and adaptive tapping to a sequence with a tempo change. BAASTA was tested in a proof-of-concept study with 20 non-musicians (Experiment 1). To validate the results of the MLP procedure, less widespread than standard staircase methods, three perceptual tasks of the battery (duration discrimination, anisochrony detection with tones, and with music) were further tested in a second group of non-musicians using 2 down / 1 up and 3 down / 1 up staircase paradigms (n = 24) (Experiment 2). The results show that the timing profiles provided by BAASTA allow to detect cases of timing/rhythm disorders. In addition, perceptual thresholds yielded by the MLP algorithm, although generally comparable to the results provided by standard staircase, tend to be slightly lower. In sum, BAASTA provides a comprehensive battery to test perceptual and sensorimotor timing skills, and to detect timing/rhythm deficits.
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