Fibroblast growth factor (FGF)-2 is a potent neurotrophic and angiogenic peptide. To examine possible protective effects of FGF-2 gene expression against transient focal cerebral ischemia in rats, a replication defective, recombinant adenovirus vector expressing FGF-2, was injected intraventricularly 2 hours after middle cerebral artery occlusion (MCAO). The treatment group showed significant recovery compared with the vehicle-treated groups in terms of serial neurologic severity scores over the 35 days after MCAO. Further, 2,3,5-triphenyltetrazolium chloride staining showed that FGF-2 gene transfer decreased infarct volume by 44% as compared with that in the vehicle-treated groups at 2 days after MCAO. The same tendency of gene transfer effects on infarct volume was confirmed at 35 days after MCAO with hematoxylin/eosin staining. Enzyme-linked immunosorbent assay revealed that FGF-2 concentration was increased significantly at 2 days after MCAO, not only in cerebrospinal fluid but also in cerebral substance in the lesioned and treated animals. These results suggested that FGF-2 gene transfer using these adenoviral vectors might be a useful modality for the treatment of occlusive cerebrovascular disease even after the onset of stroke.

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Two monoclonal antibodies (mAb), MA6 and G28-5, have the common property of detecting markers expressed on both B lymphocytes and carcinomas: BLCa (B lymphocyte carcinoma cross-reacting antigen) and CDw40 (Bp50). A comparison of the reactivity of these mAb revealed that MA6 and G28-5 detect distinct epitopes with different cell line and tissue distributions. L cell transfectants expressing CDw40 were not bound by MA6 anti-BLCa, but were bound by G28-5 anti-CDw40. G28-5 or a CDw40-specific heterantiserum could not block the migration of BLCa, while MA6 antibody could. These results indicate that CDw40 and BLCa are distinct surface molecules. Both G28-5 anti-CDw40 and MA6 anti-BLCa mAb could provide progression signals for B cells activated by appropriate B cell activators such as phorbol esters or anti-immunoglobulin; however, only G28-5 anti-CDw40 and not MA6 was co-stimulatory with the anti-CD20 competence signal, demonstrating a clear difference in the CDw40 and BLCa-mediated progression signals. Apparently, these molecules, although structurally distinct, have related functions in B cell activation.

Background and Purpose-The proliferation of vascular smooth muscle cells (VSMCs) is a common feature associated with vascular proliferative disorders such as atherosclerosis and restenosis after balloon angioplasty. We examined the antiproliferative effects of recombinant replication-competent herpes simplex virus (HSV), hrR3, to proliferative VSMCs both in vitro and in vivo. Methods-Early passages of Sprague-Dawley rat VSMCs were infected with hrR3 at a low multiplicity of infection (0.01 to 1.0) to examine the in vitro cytotoxic activity of this recombinant HSV to VSMCs in a proliferative state. Sprague-Dawley rats underwent balloon dilatation injury of the left carotid artery to induce neointimal formation. The injured carotid arteries were infected with hrR3 five days after balloon injury. Two weeks after injury, the left carotid arteries were fixed, and the areas of the neointimal and medial layers were analyzed microscopically. Because the reporter Escherichia coli lacZ gene in hrR3 is expressed only in infected cells in which the virus is actively replicating, virus replication was confirmed by X-gal staining. Results-A morphometric analysis revealed that there were significant differences in the intima/media ratio between the HSV-treated group and mock-infected group (0.354Ϯ0.068 and 1.08Ϯ0.055, respectively). In the histological study (X-gal staining), positive X-gal staining was observed chiefly in the VSMCs in the medial layer just beneath the internal elastic lamina, indicating active viral replication. Conclusions-Virus-mediated cytocidal therapy using recombinant HSV vector is a promising modality for the treatment of the restenosis after balloon angioplasty. (Stroke. 1999;30:2431-2439.)