Bone marrow stromal cells, which normally give rise to bone, cartilage, adipose tissue, and hematopoiesissupporting cells, have been shown to differentiate in vitro and in vivo into neural-like cells. In this study, we examined the expression of neuronal and glial markers in human marrow stromal cells under culture conditions appropriate for neural stem cells, and compared the unsorted cell population to bone marrow CD133 + stem-like cells using immunofluorescence, Western blot, and functional patch-clamp analysis. Overall, the expression of the early neuronal marker β3-tubulin was most pronounced in the presence of DMEM/ F12 and neurotrophin 3 (NT3) or brain-derived neurotrophic factor (BDNF), when marrow stromal cells were cultured onto fibronectin. Electrophysiological examination, however, could not show fast sodium currents or functional neurotransmitter receptors in differentiated marrow stromal cells. CD133+ mesenchymal stem-like cells, but not CD34− cells, generally showed a higher expression of neuronal markers than did unsorted marrow stromal cells, and differentiated CD133+ cells more resembled neuron-like cells.

Background and Purpose-Graft-versus-host disease (GvHD) is a major complication after allogeneic bone marrow transplantation (BMT). The theory that the central nervous system (in addition to the peripheral nervous system) participates in GvHD has been supported by detection of cerebral lymphomononuclear infiltrates in experimental GvHD and the observation of cerebral angiitis-like disease in patients with chronic GvHD. Methods-In a murine BMT model, we investigated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on cerebral endothelium after allogeneic and syngeneic transplantation. Through the use of ICAM-1-knockout mice, the effect of ICAM-1 deficiency on cellular infiltration was evaluated. As an indicator of enhanced apoptotic cell death, we examined the cerebral expression of Fas antigen (Fas), the occurrence of the poly-ADP ribose polymerase p85 fragment, and the distribution of TUNEL positive-stained cells. Results-In close correlation with earlier findings of cerebral infiltration in the same animals, we found cerebral endothelial upregulation of ICAM-1 and especially of VCAM-1 in allogeneic recipients compared with syngeneic animals without GvHD and unmanipulated controls. In ICAM-1-knockout mice, leukocytic infiltration did not differ from that in wild-type animals. Neither cerebral histopathologic changes nor an apoptotic effect of cellular infiltrates on brain parenchyma could be detected. Key Words: immunohistochemistry Ⅲ cerebrovascular disorders Ⅲ endothelium, vascular Ⅲ graft-versus-host disease Ⅲ cell adhesion molecules N eurologic complications can occur in up to 70% of allogeneic bone marrow recipients, 1 and involvement of the central nervous system (CNS) has been reported because of the neurotoxicity of the conditioning regimen, neurovascular complications, and side effects of immunosuppression. Chronic graft-versus-host disease (GvHD), a systemic complication after allogeneic bone marrow transplantation (BMT), is known to cause peripheral neuromuscular disorders, 2,3 and there is growing evidence that it can also affect the CNS. In animal models of chronic GvHD, cerebral perivascular and parenchymal lymphomononuclear infiltrations and upregulation of major histocompatibility (MHC) class I and II antigens have been reported. 4 Chronic GvHD has also been considered a possible cause of cerebral ischemic and hemorrhagic complications in patients after allogeneic transplantation. 5 Because cellular adhesion molecules (CAMs) play a major role in the recruitment of leukocytes into the brain, we investigated the endothelial expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the brains of mice with chronic GvHD. The same animals were described earlier to have cerebral cellular infiltrations 6 ; we therefore sought to correlate these earlier findings with our results on vascular CAM expression. Through the use of ICAM-1-knockout mice, the influence of ICAM-1 deficiency on leukocyte infl...

Animal models for morphological investigations of anorectal malformations are barely known to pediatric surgeons. In this study the morphological characteristics of a spontaneous mutation of the house mouse, the so-called SD-mouse, are described. The semidominant gene SD exerts its influence on the anorectum, the urogenital system and the axial skeleton. Many heterozygous (SD/+) and all homozygous (SD/SD) animals die shortly after birth due to their malformations. Surviving heterozygotes, identified by their short and deformed tails, may be used for breeding purposes. According to Mendel's laws, mating of such heterozygous yields 75% more or less malformed animals which may be used for morphological investigations. The morphological features of these animals were investigated in 61 neonatal SD-mice (33 SD/SD, 28 SD/+) and in 10 normal controls by microdissection and in 49 animals (25 SD/SD, 20 SD/+ and four normal controls) by serial sections. Of these, all homozygous and 10 heterozygous SD mice had anorectal malformations. The spectrum of these malformations is wide: very complex malformations in SD/SD mice and high anorectal malformations in SD/+ mice. These are comparable to morphological features found in humans and piglets. Hence the SD mouse represents an animal model for morphologic and embryonic investigations of complex anorectal malformations.

Neuromuscular syndromes following allogeneic bone marrow transplantation (BMT), although occasionally described,were not the focus of studies concerning neurologic complications following bone marrow transplantation. In this study,we summarize different polyneuropathy syndromes following BMT and report on patients with myasthenia gravis and inflammatory neuromuscular disorders such as myositis or fasciitis. Concerning the etiology of neuropathies, a neurotoxicity of immunosuppressants,a preexisting disorder due to the underlying disease as well as an association with graft-versus-host disease (GVHD) is discussed.GVHD-associated polyneuropathies as well as muscular complications have been found to occur during the early BMT phase, while myasthenia gravis is a late neurologic complication of GVHD.

The urethral pressure profiles in 21 continent and 39 stressincontinent women were recorded by the Millar-microtransducer. An analysis of the profiles of the anterior, lateral and posterior urethral wall was performed and the most significant parameters for the urodynamic diagnosis of stress-incontinence were evaluated. It could be demonstrated, that the total tonometric urethral length, the functional urethral length and the maximal urethral closure pressure at rest are of little practical value for the urodynamic diagnosis of stress-incontinence. On the other hand an excellent correlation between urethral pressure profile under stress and anamnestic and clinical stress-incontinence was found. The analysis of the pressure profiles under stress of the anterior, lateral and posterior urethral wall showed, that these have a great variability depending on the urethral sector where the measurements are performed.