Mutations in the FLT3 gene are the most common genetic alteration found in AML patients. FLT3 internal tandem duplication (ITD) mutations result in constitutive activation of FLT3 tyrosine kinase activity. The consequences of this activation are an increase in total phosphotyrosine content, persistent downstream signaling, and ultimately transformation of hematopoietic cells to factor-independe...

BACKGROUND The respiratory pump can be optimized to enhance circulation in patients with hypotension by having patients spontaneously breathe through a low level of inspiratory resistance. This can be achieved with an impedance threshold device (ITD) designed to provide 7 cm H2O resistance during spontaneous inspiration with minimal resistance during expiration. Little is known about the effect...

Acute myeloid leukemia (AML) with normal karyotype represents a clinically and molecularly heterogeneous disease. Molecular markers with prognostic significance have been examined to improve risk profile characterization of this group. Activating mutations on FLT3 receptor are one of the most common genetic alterations reported. However, the prevalence and prognostic significance of FLT3 geneti...

Spatial receptive fields of neurons in the auditory pathway of the barn owl result from the sensitivity to combinations of interaural time (ITD) and level differences across stimulus frequency. Both the forebrain and tectum of the owl contain such neurons. The neural pathways, which lead to the forebrain and tectal representations of auditory space, separate before the midbrain map of auditory ...

BACKGROUND The impedance threshold device (ITD) is designed to enhance venous return and cardiac output during cardiopulmonary resuscitation (CPR) by increasing the degree of negative intrathoracic pressure. Previous studies have suggested that the use of an ITD during CPR may improve survival rates after cardiac arrest. METHODS We compared the use of an active ITD with that of a sham ITD in ...

BACKGROUND We evaluated the influence of breathing through an inspiratory Impedance Threshold Device (ITD) on autonomic neural and cerebrovascular function. METHODS Eight subjects breathed through a sham ITD (0 cmH2O) and an active ITD (-7 cmH2O) in the supine position. We recorded the ECG, finger photoplethysmographic arterial pressure, cerebral blood flow velocity, and muscle sympathetic ne...

BACKGROUND Internal tandem duplication of FMS-like tyrosine kinase (FLT3-ITD) is well known to be involved in acute myeloid leukemia (AML) progression, but FLT3-ITD-negative AML cases account for 70% to 80% of AML, and the mechanisms underlying their pathology remain unclear. This study identifies protein tyrosine phophatase PRL-3 as a key mediator of FLT3-ITD-negative AML. METHODS A total of...

Binaural hearing, the ability to detect small differences in the timing and level of sounds at the two ears, underpins the ability to localize sound sources along the horizontal plane, and is important for decoding complex spatial listening environments into separate objects - a critical factor in 'cocktail-party listening'. For human listeners, the most important spatial cue is the interaural ...

Activating mutations of Flt3 are found in approximately one third of patients with acute myeloid leukemia (AML) and are an attractive drug target. Two classes of Flt3 mutations occur: internal tandem duplications (ITDs) in the juxtamembrane and point mutations in the tyrosine kinase domain (TKD). We and others have shown that Flt3-ITD induced aberrant signaling including strong activation of si...

Current clinical practice in programming a cochlear implant (CI) for individuals with single-sided deafness (SSD) is to maximize the transmission of speech information via the implant, with the implicit assumption that this will also result in improved spatial-hearing abilities. However, binaural sensitivity is reduced by interaural place-of-stimulation mismatch, a likely occurrence with a stan...