ABSTRACT
This study is the first to demonstrate that macrophage migration inhibitory factor (MIF), an immune system 'inflammatory' cytokine that is released by the developing otocyst, plays a role in regulating early innervation of the mouse and chick inner ear. We demonstrate that MIF is a major bioactive component of the previously uncharacterized otocyst-derived factor, which directs initial neurite outgrowth from the statoacoustic ganglion (SAG) to the developing inner ear. Recombinant MIF acts as a neurotrophin in promoting both SAG directional neurite outgrowth and neuronal survival and is expressed in both the developing and mature inner ear of chick and mouse. A MIF receptor, CD74, is found on both embryonic SAG neurons and adult mouse spiral ganglion neurons. Mif knockout mice are hearing impaired and demonstrate altered innervation to the organ of Corti, as well as fewer sensory hair cells. Furthermore, mouse embryonic stem cells become neuron-like when exposed to picomolar levels of MIF, suggesting the general importance of this cytokine in neural development.
Subject(s)
Ear, Inner/embryology , Intramolecular Oxidoreductases/physiology , Macrophage Migration-Inhibitory Factors/physiology , Nerve Growth Factors/physiology , Animals , Animals, Newborn , Cell Survival/drug effects , Cells, Cultured , Chick Embryo , Ear, Inner/drug effects , Ear, Inner/growth & development , Ear, Inner/metabolism , Intramolecular Oxidoreductases/genetics , Intramolecular Oxidoreductases/metabolism , Intramolecular Oxidoreductases/pharmacology , Macrophage Migration-Inhibitory Factors/genetics , Macrophage Migration-Inhibitory Factors/metabolism , Macrophage Migration-Inhibitory Factors/pharmacology , Mice , Mice, Knockout , Nerve Growth Factors/genetics , Nerve Growth Factors/metabolism , Nerve Growth Factors/pharmacology , Neurites/drug effects , Neurites/physiology , Neurons/cytology , Neurons/drug effects , Neurons/physiology , Organ of Corti/embryology , Organ of Corti/growth & development , Organ of Corti/metabolism , Spiral Ganglion/embryology , Spiral Ganglion/growth & development , Spiral Ganglion/metabolismABSTRACT
BACKGROUND: Fecal occult blood testing (FOBT) is one method to screen for colorectal cancer and to assess for gastrointestinal bleeding in hospitalized patients. Differences in the analytical sensitivity among various methods may have significant clinical repercussions. METHODS: We evaluated the analytical performance of 5 different FOBT methods (standard guaiac-based method and four immunochemical methods) using patient samples and spiked stool specimens. RESULTS: The analytical sensitivity measured using spiked stool samples varied from <8 to 1500 ug hemoglobin/gram of stool. In some cases the results differed significantly from the manufacturers reported analytical sensitivity. Analysis of 71 stool samples measured by all 5 methods showed a discrepant result in 31 cases (43.7%). The rate of positive samples varied by method from 8.5% to 42.2%. CONCLUSIONS: These results demonstrate significant differences in the analytical performance among FOBT methods. Careful method validation and selection of a method with appropriate sensitivity is essential when choosing an FOBT method for colorectal cancer screening or for the assessment of gastrointestinal bleeding in the emergency department and hospital inpatients.