Cloning and developmental expression analysis of the murine c-mer tyrosine kinase.

We have cloned the putative mouse homologue of the human c-mer receptor tyrosine kinase proto-oncogene. Comparison of the mouse and human c-mer amino acid sequences reveals an overall identity of 88%. Similar to the human, the extracellular region of the murine c-mer protein possesses two amino terminal immunoglobulin-like domains and two membrane proximal fibronectin type III domains, which places it in the Axl family of tyrosine kinases. Our analysis of the Axl family identifies eight different regions of amino acid consensus that have residues characteristic of this and no other tyrosine kinase family; six of the eight are within tyrosine kinase subdomains. The homology within the Axl family is highest between c-mer and c-eyk, the chicken proto-oncogene of the tumor virus gene product v-eyk. Northern analysis of adult tissues suggests that the mouse c-mer, although expressed in many tissues, has an expression pattern unique among Axl family members. In normal adult hematopoietic cells c-mer seems to be expressed predominantly if not exclusively in the monocytic lineage. Mouse c-mer is expressed during most, if not all, stages of embryological development beginning in the morula and blastocyst and progressing through the yolk sac and fetal liver stages. This early and consistent expression of c-mer was confirmed during in vitro differentiation of embryonic stem cells. The embryonic expression profile of c-mer suggests that this tyrosine kinase may play an important function in the developing mouse.

Sickle cell disease and aneurysmal subarachnoid hemorrhage.

While neurological complications are common in sickle cell disease, aneurysmal subarachnoid hemorrhage has been rarely reported. A case is presented of a young man with sickle cell disease and subarachnoid hemorrhage found to have two mid-basilar aneurysms, the largest of which had bled. Available literature suggests that this patient may be quite representative as nearly one half of documented cases have been noted to harbor multiple aneurysms, and posterior circulation involvement appears to be common. These anatomic features may relate to the pathophysiology of arterial destruction common in sickle cell disease.

Intraarterial sodium amytal administration to guide preoperative embolization of cerebral arteriovenous malformations.

In preoperative embolization of cerebral arteriovenous malformation (AVM), one difficulty frequently encountered is assessment of the risk of ischemic deficit, posed by proceeding with embolization. One technique to assist prediction of tolerance of devascularization involves superselective injection of sodium amytal into cerebral arteries, prior to and during embolization. Since September, 1985, we have performed 119 embolization procedures in 77 patients with cerebral AVM. Of these, 89 procedures in 60 patients involved superselective intracerebral catheterization and embolization with either polyvinyl alcohol (PVA) alone or in combination with platinum microcoils, surgical silk, or a mixture of ethanol and microfibrillar collagen. In 50 of these procedures, we superselectively administered sodium amytal intraarterially immediately prior to embolization, for purposes of functional testing. Groups of patients undergoing testing were compared to groups not tested prior to embolization, for development of transient or permanent neurologic deficits or cerebral hemorrhage, subsequent to embolization. Significantly better results, both in absolute numbers and severity of complications, were found when testing was employed. No complications of amytal administration were seen. In four cases, embolization was altered or discontinued based on development of a deficit at the time of amytal administration. We conclude that the brief anesthetic effect of intraarterial testing with sodium amytal is a safe and important adjunct during preoperative embolization of cerebral AVMs.