How rudimentary movements evolve into sophisticated ones during development remains unclear. It is often assumed that the primitive patterns of neural control are suppressed during development, replaced by entirely new patterns. Here we identified the basic patterns of lumbosacral motoneuron activity from multimuscle recordings in stepping neonates, toddlers, preschoolers, and adults. Surprisingly, we found that the two basic patterns of stepping neonates are retained through development, augmented by two new patterns first revealed in toddlers. Markedly similar patterns were observed also in the rat, cat, macaque, and guineafowl, consistent with the hypothesis that, despite substantial phylogenetic distances and morphological differences, locomotion in several animal species is built starting from common primitives, perhaps related to a common ancestral neural network.

Following liver injury, hepatic stellate cells (HSC) undergo proliferation and migrate into damaged areas in response to chemotactic factors. HSC have been shown to regulate leukocyte trafficking by secreting monocyte chemotactic protein-1 (MCP-1), a chemokine that recruits monocytes and lymphocytes. In this study, we explored whether MCP-1 exerts biological actions on HSC. HSC were isolated from normal human livers, cultured on plastic, and studied in their myofibroblast-like phenotype, and three different cells lines were used. Chemotaxis was measured in modified Boyden chambers. The tissue response to injury involves the coordinated recruitment and activation of a number of cells in the attempt to repair the damage provoked by toxic, infectious, or immunological mechanisms. Inflammatory cells recruited at sites of damage are responsible for the scavenging of the necrotic cells, whereas myofibroblasts secrete extracellular matrix components and restore the integrity of the tissue. Within the liver, hepatic stellate cells (HSC) are responsible for this second part of the wound-healing response. 1,2 In normal liver, HSC fulfill the role of retinoid storage and metabolism, and their phenotype is referred to as quiescent. However, following injury, HSC undergo differentiation toward an activated phenotype characterized by proliferation and increased secretion of extracellular matrix components. This process is associated with enhanced or de novo expression of receptors for several soluble mediators, such as platelet-derived growth factor (PDGF), transforming growth factor-␤, or thrombin, which mediate the increase in cell proliferation and extracellular matrix production. [3][4][5] Therefore, HSC are the main cell type involved in the deposition of matrix that leads to fibrosis and cirrhosis. Another feature of cells involved in tissue repair is their ability to migrate into the damaged areas according to concentration gradients of chemotactic factors. 6 We have recently shown that HSC share this ability to respond to chemotactic factors such as PDGF. 7 Recent investigation has pointed out additional characteristics of the HSC that are relevant for the hepatic wound healing response. 2 HSC have been shown to express several molecules that are capable of regulating leukocyte trafficking, including chemokines. [8][9][10][11][12] These latter are a group of cytokines that exhibit chemoattractant properties for relatively specific groups of leukocytes. Four classes of chemokines have been recognized according to the position of conserved cysteine residues and differences in the spectrum of target cells. 13 The group of CXC chemokines includes a variety of factors, such as interleukin-8, which are mainly, but not exclusively, chemotactic for neutrophils. 13 Lymphotactin, a cytokine that specifically attracts lymphocytes, is the only known member of the C class of chemokines. 13 A novel cell-associated chemokine characterized by a CX3C motif and higher molecular weight has been recently identified. 14 Chemokines of the ...

Chronic infection by HBV is the leading cause of hepatocellular carcinoma in man. Several lines of evidence suggest that the viral transactivator HBx plays a critical role in the molecular pathogenesis of HBVrelated HCC. To study the actual impact of HBx and the mechanism of its action, we have recently cloned and characterized a set of X-sequences from HCC in patients with chronic infection by HBV. In the present study, we have compared the e ects of HBx and its naturally arising mutants on cell growth and viability. We report that HBx inhibits clonal outgrowth of cells and induces apoptosis by a p53-independent pathway. Furthermore, HBx expression induced a late G1 cell cycle block prior to their counterselection by apoptosis. Importantly, mutations in the HBx-gene evolving in hepatocellular carcinoma abolished both HBx-induced growth arrest and apoptosis. Using a panel of engineered mutants we have mapped the growth suppressive e ect of HBx to domains shown to be required for its transactivating function. Based on these results, we propose that abrogation of the anti-proliferative and apoptotic e ects of HBx by naturally occurring mutations might render the hepatocytes susceptible to uncontrolled growth and contribute to multistep hepatocarcinogenesis associated with HBV-infection.

Rearrangement of bcl-2 was found with increased frequency in patients with chronic HCV infection and mixed cryoglobulinemia. The frequency was greatest in patients with type II mixed cryoglobulinemia. The high ratio of Bcl-2 to Bax in patients with bcl-2 rearrangement and disappearance of the rearrangement with antiviral therapy suggest that the translocation is associated with the antiapoptotic function of Bcl-2 and that HCV infection is linked to inhibition of B-cell apoptosis.