A Patient With Hemoglobin SC Disease and Acute Ischemic Stroke Presenting With Altered Mental Status.

A 57-year-old woman with a history of hypertension, diabetes mellitus, obesity, asthma, and hemoglobin SC disease presented to the emergency department by her home health aide after she was found having altered mental status. According to her home health aide, the patient was responding with "Ok" to her questions for more than a day. The hemoglobin on admission was 8.5 g/dL. A magnetic resonance imaging (MRI) without contrast of the brain showed acute cortical infarcts superimposed on the old infarct zone. The patient received 1 unit of packed red blood cells and a session of exchange transfusion, in addition to aspirin, clopidogrel, and atorvastatin during the hospital stay. When a patient known to have sickle cell disease presents with acute neurological deficits, the first consideration is usually acute ischemic stroke due to vaso-occlusion in the cerebral vessels. However, it is essential to not overlook other potential causes of acute neurological deficits.

Multiple splenic infarcts: unusual presentation of hereditary spherocytosis associated with acute Epstein-Barr virus infection.

A 19-year-old African American woman presented to the emergency department with a history of left upper quadrant pain for a week, associated with nausea, malaise, loss of appetite, subjective fevers and chills. Her family history is significant for thalassemia in her maternal aunt, and hereditary spherocytosis in her brother, sister and cousin. A contrast-enhanced CT scan of the abdomen and pelvis revealed massive splenomegaly and multiple splenic infarcts. On the second day of admission, she developed a fever of 103°F. Further evaluation revealed acute Epstein-Barr virus (EBV) infection and hereditary spherocytosis. Her condition improved after 4 days on piperacillin/tazobactam, intravenous fluids, analgesics and antipyretics. Our case report describes a thorough clinical evaluation of a patient with fever, anaemia, massive splenomegaly and multiple splenic infarcts. It highlights the need for careful interpretation of multiple positive IgM results on viral serological testing that often accompanies acute EBV infections.

In brain, Axl recruits Grb2 and the p85 regulatory subunit of PI3 kinase; in vitro mutagenesis defines the requisite binding sites for downstream Akt activation.

Axl is a receptor tyrosine kinase implicated in cell survival following growth factor withdrawal and other stressors. The binding of Axl's ligand, growth arrest-specific protein 6 (Gas6), results in Axl autophosphorylation, recruitment of signaling molecules, and activation of downstream survival pathways. Pull-down assays and immunoprecipitations using wildtype and mutant Axl transfected cells determined that Axl directly binds growth factor receptor-bound protein 2 (Grb2) at pYVN and the p85 subunit of phosphatidylinositol-3 kinase (PI3 kinase) at two pYXXM sites (pY779 and pY821). Also, p85 can indirectly bind to Axl via an interaction between p85's second proline-rich region and the N-terminal SH3 domain of Grb2. Further, Grb2 and p85 can compete for binding at the pY821VNM site. Gas6-stimulation of Axl-transfected COS7 cells recruited activated PI3 kinase and phosphorylated Akt. An interaction between Axl, p85 and Grb2 was confirmed in brain homogenates, enriched populations of O4+ oligodendrocytes, and O4- flow-through prepared from day 10 mouse brain, indicating that cells with active Gas6/Axl signal through Grb2 and the PI3 kinase/Akt pathways.