In macrophages, basal polyamine (putrescine, spermidine, and spermine) levels are relatively low but are increased upon IL-4 stimulation. This Th2 cytokine induces Arg1 activity, which converts arginine into ornithine, and ornithine can be decarboxylated by ODC to produce putrescine, which is further converted into spermidine and spermine. Recently, we proposed polyamines as novel agents in IL-4-dependent E-cadherin regulation in AAMs. Here, we demonstrate for the first time that several, but not all, AAM markers depend on polyamines for their IL-4-induced gene and protein expression and that polyamine dependency of genes relies on the macrophage type. Remarkably, Arg1-deficient macrophages display rather enhanced IL-4-induced polyamine production, suggesting that an Arg1-independent polyamine synthesis pathway may operate in macrophages. On the other side of the macrophage activation spectrum, LPS-induced expression of several proinflammatory genes was increased significantly in polyamine-depleted CAMs. Overall, we propose Arg1 independently produced polyamines as novel regulators of the inflammatory status of the macrophage. Indeed, whereas polyamines are needed for IL-4-induced expression of several AAM mediators, they inhibit the LPS-mediated expression of proinflammatory genes in CAMs.

Hepatoblastoma (HB) is the most common pediatric liver malignancy, comprising approximately 1% of all pediatric cancers. The disparate clinical staging systems and histologic classifications that were developed during the last decades, nevertheless, reflect the remaining difficulties and uncertainties in characterizing HB. Furthermore, the combination of surgery and (neo)adjuvant chemotherapy has improved patient outcomes dramatically. A poor prognosis is associated with large tumor size, multifocality, extrahepatic disease, and metastatic spread. The exact etiology of HB remains unknown, but the cytogenetic alterations, phenotypic features, and biologic aspects that accompany this neoplasm yield more and more insight into its pathogenesis. New cell‐biologic and molecular‐biologic insights may lead to the development of new treatment modalities, especially for patients with a bad prognosis. This review summarizes the different aspects of this intriguing tumor and discusses the current status of research and treatment for patients with HB. Cancer 2003;98:668–78. © 2003 American Cancer Society.DOI 10.1002/cncr.11585

The extracellular matrix (ECM) is an intricate network composed of an array of macromolecules capable of regulating the functional responsiveness of cells. Its composition greatly varies among different types of tissue, and dysregulation of its metabolism may contribute to vascular remodeling during the pathogenesis of various diseases, including atherosclerosis. In view of their antiatherosclerotic effects, the role of Ca2+ channel blockers in the metabolism of ECM was examined. Nanomolar concentrations of the five Ca2+ channel blockers amlodipine, felodipine, manidipine, verapamil, or diltiazem significantly decreased both the constitutive and platelet-derived growth factor BB-dependent collagen deposition in the ECM formed by human vascular smooth muscle cells and fibroblasts. The drugs inhibited the expression of fibrillar collagens type I and III and of basement membrane type IV collagen. Furthermore, Ca2+ channel blockers specifically increased the proteolytic activity of the 72-kDa type IV collagenase as shown by gelatin zymography and inhibited the transcription of tissue inhibitor of metalloproteinases-2.

Background: It remains unclear to what extent midgut rotation determines human intestinal topography and pathology. We reinvestigated the midgut during its looping and herniation phases of development, using novel 3D visualization techniques. Results: We distinguished 3 generations of midgut loops. The topography of primary and secondary loops was constant, but that of tertiary loops not. The orientation of the primary loop changed from sagittal to transverse due to the descent of ventral structures in a body with a still helical body axis. The 1^st secondary loop (duodenum, proximal jejunum) developed intraabdominally towards a left-sided position. The 2^nd secondary loop (distal jejunum) assumed a left-sided position inside the hernia before returning, while the 3^rd and 4^th secondary loops retained near-midline positions. Intestinal return into the abdomen resembled a backward sliding movement. Only after return, the 4^th secondary loop (distal ileum, cecum) rapidly “slid” into the right lower abdomen. The seemingly random position of the tertiary small-intestinal loops may have a biomechanical origin. Conclusions: The interpretation of “intestinal rotation” as a mechanistic rather than a descriptive concept underlies much of the confusion accompanying the physiological herniation. We argue, instead, that the concept of “en-bloc rotation” of the developing midgut is a fallacy of schematic drawings. Primary, secondary and tertiary loops arise in a hierarchical fashion. The predictable position and growth of secondary loops is pre-patterned and determines adult intestinal topography. We hypothesize based on published accounts that malrotations result from stunted development of secondary loops.