A new agent, DA, has been isolated from a spontaneously paralyzed mouse. Its biological properties and the pathology of lesions in experimental infection indicate close relationship with the Theiler group of encephalomyelitis viruses. Serological studies were inconclusive. The intracerebral neutralization test failed to reveal measurable antibody and other routes of inoculation were unsuitable because of low invasiveness of the agent. Repeated vaccination of females did not render their offspring resistant to homologous intracerebral challenge. The occurrence of early viremia is reported following intracerebral inoculation of the DA strain and also the known Theiler strains, 4727, FA, and GD-VII. The pathology of mice experimentally infected with DA and with known members of the Theiler group is described. Attention is called to the demyelinating lesion of the cord in mice surviving for several months and to the persistence of virus in the CNS of such animals. Another characteristic feature of the pathology was the degeneration of ventral nerve roots and in some mice of the peripheral nerves. Similar changes were not seen with strains of Theiler virus other than DA. Spheroidal bodies of undetermined significance were found in the lesions. Finally the occurrence of myositis after intracerebral inoculation, not only mice infected with the DA virus, but also with the 4727 and FA strains, is described and discussed.

CTX0E03 is a human neural stem cell line previously reported to reduce sensory motor deficits in a middle cerebral artery occlusion (MCAo) model of stroke. The objective of this study was to investigate if CTX0E03 treatment promotes angiogenesis. As stroke leads to damage of the vasculature in the brain, angiogenesis may contribute to the functional recovery. To test this hypothesis, the angiogenic activity of CTX0E03 was assessed both in vitro and in vivo. In vitro, CTX0E03 expression of trophic and proangiogenic factors was determined by real-time RT-PCR, Western blot, and ELISA, and its angiogenic activity was investigated in well-established angiogenesis assays. In vivo, angiogenesis was investigated in naive mice and MCAo rat brain and was evaluated by immunohistochemistry (IHC) using Von Willebrand factor (VWF), a marker of blood vessel formation, and BrdU/CD31 double labeling in naive mice only. In vitro results showed that CTX0E03-conditioned medium and coculture significantly increased total tubule formation compared with controls (p=0.002 and p=0.0008, respectively). Furthermore, CTX0E03 cells were found to be in direct association with the tubules by ICC. In vivo CTX0E03-treated brains demonstrated a significant increase in areas occupied by VWF-positive microvessels compared with vehicle-treated naive mice (two-way ANOVA, Interaction p<0.05, Treatment p<0.0001, Time p<0.0) and MCAo rat (p=0.001 unpaired t test, Welch's correction). CTX0E03-treated naive mouse brains showed an increase in BrdU/CD31 colabeling. In conclusion, in vitro CTX0E03 cells express proangiogenic factors and may promote angiogenesis by both release of paracrine factors and direct physical interaction. Furthermore, in vivo CTX0E03-treated rodent brains exhibited a significant increase in microvessels at the site of implantation compared with vehicle-injected groups. Taken together these data suggest that CTX0E03 cell therapy may provide significant benefit to stroke patients through upregulation of angiogenesis in the ischemic brain.

Intravascular ultrasound may be useful for studying the natural history of atherosclerotic lesions of different morphologies and for guiding interventional strategies. This study was designed to test the hypothesis that tissue appearance by intravascular ultrasound is related to the biomechanical properties of atheroma components. Forty-three atheroma caps were obtained from the abdominal aortas of 22 patients at autopsy and studied with an ultrasensitive, servo-controlled spectrometer. By measuring the static strain caused by increasing levels of compressive stress from 30 to 90 mm Hg, the uniaxial unconfined compression stiffness (ratio of stress to strain) was determined. After mechanical testing, specimens were imaged with a 6F, 20-MHz intravascular ultrasound transducer, and images were interpreted by an investigator who was unaware of the mechanical measurements. Specimens were classified as nonfibrous (n = 14), fibrous (n=18), or calcified (n=ll) based on intravascular ultrasound appearance. The static stiffnesses of the nonfibrous, fibrous, and calcified ultrasound classes were 41.2±18.8 kPa, 81.7±33.2 kPa, and 354.5±245.4 kPa, respectively (/?=0.0002 by analysis of variance). The times to reach static equilibrium (creep time) for the nonfibrous, fibrous, and calcified classes were 79.6±26.5 minutes, 50.2±20.0 minutes, and 19.4±8.1 minutes, respectively (/?=0.0007). Intravascular ultrasound appearance was most significantly related to biomechanical behavior when calcium deposits were noted; the differences in biomechanical behavior between nonfibrous and fibrous tissue appearances were less apparent Important biomechanical behavior of human atherosclerotic tissue can be predicted by intravascular ultrasound imaging; this technology may allow a detailed in vivo assessment of the stress-strain relation in diseased human arteries. (Arteriosclerosis and Thrombosis 1992;12:l-5) A therosclerotic lesions are often structurally / \ complex, with varying amounts of lipid, fi-J. \ -brous tissue, and calcium deposits. These components have different biomechanical behaviors that may explain why some plaques are more likely than others to rupture and cause occlusive thrombosis.1 Coronary angiography does not provide information about plaque structure beneath the endothelial surface (with the exception of severe calcification), so that evaluating the clinical importance of plaque structure antemortem has been limited to characterizing lumen geometry. 2Ultrasonic tissue-characterization methods can differentiate various pathological patterns of atherosclerosis, 3 and these patterns dramatically influence the biomechanical behavior of human plaque compo-