The transcription factor HIF-1 is one of the principal mediators of homeostasis in human tissues exposed to hypoxia. It is implicated in virtually every process of rapid gene expression in response to low oxygen levels. The most common causes of tissue hypoxia are inflammation and/or insufficient circulation or a combination of both. Inflamed tissues and the areas surrounding malignant tumors are characterized by hypoxia and low concentrations of glucose. Serious and generalized inflammation can lead to sepsis and circulatory collapse resulting in acute or chronic tissue hypoxia in various vital organs which induces a rapid homeostatic process in all nucleated cells of affected organs in the human body. Under hypoxic conditions the alpha and beta subunits of HIF-1 make an active heterodimer and drive the transcription of over 60 genes important for cell survival, adaptation, anaerobic metabolism, immune reaction, cytokine production, vascularization and general tissue homeostasis. In addition, HIF-1 plays a key role in the development of physiological systems in fetal and postnatal life. It is also a critical mediator of cancer, lung and cardiovascular diseases. The better understanding of the functions of HIF-1 and the pharmacological modulation of its activity could mean a successful therapeutic approach to these diseases.

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Platelets express a single low affinity receptor for immunoglobulin, Fc␥RII, that triggers multiple cellular responses upon interaction with multivalent immune complexes. In this study we show that immobilized IgG is also a potent stimulant of platelet activation triggering adhesion, aggregation, massive dense granule secretion, and thromboxane production. Platelet adhesion to IgG was blocked by the Fc␥RII receptor-specific monoclonal antibody, IV.3. Pretreatment of the platelets with cytochalasin D to inhibit actin polymerization similarly prevented cell binding to IgG having no effect on platelet binding to fibrinogen. Platelet adhesion to IgG also led to the induction of tyrosine phosphorylation of multiple proteins including pp125 FAK and p72 SYK . These proteins were also tyrosine-phosphorylated in ␣ IIb ␤ 3 -deficient IgG-adherent platelets from patients with Glanzmann's thrombasthenia. These data demonstrate that Fc␥RII mediates pp125 FAK phosphorylation and platelet adhesion to IgG independent of the integrin ␣ IIb ␤ 3 . Treatment of the platelets with bisindolylmaleimide to inhibit protein kinase C prevented phosphorylation of pp125 FAK as well as several other proteins, but not p72 SYK phosphorylation. This study establishes that the Fc␥RII receptor mediates pp125 FAK phosphorylation via protein kinase C.Platelets express a single-chain low affinity receptor for immunoglobulin, Fc␥RII (1, 2). Fc␥ receptors expression is restricted to cells of hematopoietic lineage (3). Fc␥ receptor activation has been linked to diverse functions that include activation of tyrosine kinases, elevation of intracellular calcium, and regulation of transcription of genes encoding cytokines (3). In platelets, soluble immune complexes or crosslinking of the Fc␥RII receptor with secondary antibodies trigger a robust activation response that includes changes in intracellular calcium concentration, phosphatidic acid metabolism, and thromboxane production (4, 5). Additional activation responses in suspended platelets, including granule secretion and aggregation, are dependent on thromboxane production (4, 5). Fc␥RII ligation also triggers the induction of tyrosine phosphorylation of multiple cellular proteins (6). These include the Fc␥RII receptor itself (2, 6), a 40-kDa sialoglycoprotein that does not have an intrinsic kinase activity, and the Fc␥RII-associated protein-tyrosine kinase, p72 SYK (2, 6). p72 SYK , a homologue of the T cell-associated protein-tyrosine kinase ZAP-70, is a non-receptor tyrosine kinase containing two SH2 domains but no SH3 domain (7). Clustering of chimeric transmembrane proteins bearing intracellular SYK or its homologue ZAP-70 sequences in T cells is sufficient to trigger calcium mobilization and cytolytic effector functions (8, 9). Similarly, clustering of p72 SYK chimera introduced into rat basophilic leukemia (RBL-2H3) cells is sufficient to trigger cellular responses that include protein tyrosine phosphorylation and synthesis and release of allergic mediators (10). p72 SYK activation may thus prov...

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Identifying spinal injuries in trauma patients with altered mental status can be difficult. CT scanning and clinical examination are the basis of our spinal clearance, but screening “trauma protocol” spinal MRI is used to exclude occult injuries. We sought to evaluate the sensitivity of CT scanning for spinal injuries compared with our MRI protocol. Ninety-seven patients underwent MRI cervical spine trauma protocol during 2004. Twenty-nine patients were obtunded, 29 had neurologic symptoms, and 39 had spine pain. MRI confirmed the initial CT findings without new injuries in 83 cases. MRI reclassified fractures as degenerative changes in 12 cases. In 2 cases, the MRI identified new injuries: one a stable partial ligament tear, the second a T7 Chance fracture with ligamental disruption requiring operative fixation. There was no morbidity or mortality documented in obtaining the MRI studies. Overall negative predictive value of CT scanning of the spine was 98 per cent, the positive predictive value was 78 per cent, and the sensitivity and specificity was 94 per cent and 91 per cent, respectively. CT scanning of the cervical and axial spine is sensitive for spinal trauma but not specific. MRI trauma protocol should be reserved for cases when initial CT scanning is suggestive of traumatic injury.