Cytotoxic T lymphocyte antigen 4 immunogloblin promotes neuronal differentiation in the grafts of embryonic stem cell-derived neural precursor cells.

For safe and efficient transplantation of embryonic stem cells (ESCs), it is important to reduce inflammatory and immune response by the host brain. Full activation of T cells in response to donor antigen requires the delivery of two separate but complimentary signals not only via T cell receptor following recognition of antigen, but also via antigen-nonspecific ligation of the costimulatory receptor-ligand pairs such as CD28:CD80/86. Cytotoxic T lymphocyte antigen 4 (CTLA4), structurally related to CD28, delivers an inhibitory signal after ligation to CD80/86, resulting in the termination of T cell immune responses. To investigate the role of this pathway in the survival and differentiation of neural progenitor cells (NPCs) from mouse ESCs, we transplanted the NPCs into mouse brains with or without CTLA4 immunogloblin (CTLA4-Ig). Immunohistochemical studies revealed that accumulation of inflammatory/immune cells in and around the graft was reduced by CTLA4-Ig. In contrast, the percentage of neurons in the graft was increased. These results suggest that CTLA4-Ig may promote neuronal differentiation during the treatment of neurological diseases with cell replacement therapy.

Endovascular treatment of a vertebral artery aneurysm via puncture of the surgically exposed vertebral artery.

We describe a case of subarachnoid hemorrhage due to a ruptured right vertebral artery (VA) aneurysm where endovascular therapy via a trans-femoral route was not feasible. Therefore we surgically exposed the VA and directly punctured it at the C4 level, followed by successful coil embolization. Direct access to the vertebral artery using an anterior surgical approach is an alternative in cases where the proximal side of the artery is occluded.

Novel drug delivery system using autologous fibrin glue--release properties of anti-cancer drugs.

To clarify the release properties of anti-cancer drugs from fibrin glue, a study was performed using several anti-cancer drugs with remarkably different physical properties. Concentrated fibrinogen, fibronectin, and coagulation factor XIII were prepared from healthy human plasma according to the cryoprecipitate method. Fibrin glue containing anti-cancer drugs was prepared as follows; the cryoprecipitate was mixed with each anti-cancer drug and aprotinin, then thrombin was added. These glues were incubated in PBS containing plasminogen and urokinase at 37 degrees C for seven days, and the medium was then sampled several times after centrifugation. The drug concentration in each sample was measured using HPLC. Fibrin glue without aprotinin was quickly hemolyzed and disappeared after 2--4 h. That with aprotinin was only slightly hemolyzed and more than half remained after 7 days. Mitomycin C and fluorouracil were quickly released from the glue regardless of the presence or absence of aprotinin. However, enocitabine was gradually released from glue with aprotinin although quickly released from that without. The rate of release of each drug from the glue with aprotinin correlated well with its hydrophobicity. Thus, to establish a sustained release system using fibrin glue, one should use the more lipophilic anti-cancer drugs and a fibrinolytic enzyme inhibitor.