Organ differentiation

Patients admitted to the intensive-care unit (ICU) have severe pneumonia, and the etiology includes S. pneumoniae and H. influenzae as in the other categories however, the incidence of Legionella pneumophila increases in this setting and should be included in the organism differential. In addition, enteric gramnegative bacilli and S. aureus are more frequently the cause of the pneumonia. The recommendations are to treat with an... 

Kavlock, R.J., N. Chernoff, E. Rogers, D. Whitehouse, B. Carver, J. Gray, and K. Robinson. 1982. An analysis of fetotoxicity using biochemical endpoints of organ differentiation. Teratology 26 183-194. 

While changes in cell phenotypes have proved useful in some settings to characterize the immunotoxicity of xenobiotics,1 phenotypic analysis alone is often not a sensitive indicator of low dose immunotoxicity for many agents that alter immune function. Xenobiotics that exert selective toxicity on lymphoid and myeloid cells may be discovered through immunophenotypic analysis. However, most agents produce immunotoxicity at doses much lower than those required to produce cytotoxicity or interfere with primary lymphoid organ differentiation. Some of the most potent immunosuppressive chemicals that have been tested, such as cyclosporine A, do not alter immunophenotype at doses that are immunosuppressive. On the other hand, when phenotyping is linked to assessment of functional parameters of the cells, immunotoxic effects are more likely to be identified. 

In multicellular organisms, differentiated cell types specialize in one or more of the functions essential to the organism s survival. 

Sen A. G., Reddy G. V. and Rodrigues V. (2003) Combinatorial expression of Prospero, Seven-up, and Elav identifies progenitor cell types during sense-organ differentiation in the Drosophila antenna. Dev Biol. 254, 79-92. 

Teratogenicity specifically refers to the subcategory of pathological effects after the implantation of the embryo and up to the first 3 months of pregnancy in humans, where major tissues and organs differentiate and develop, and major malformations may result. 

Thomma, B.P.H.J., Tierens, K.F.M., Penninckx, I.A.M.A., Mauch-Mani, B., Broekaert, W.F. and Cammue, B.P.A., 2001b, Different micro-organisms differentially induce Arabidopsis disease response pathways. Plant Physiol. Biochem. 39 673-680. 

Including this toxicity in the area of idiosyncratic toxicity is justified since the lung is not thought of a typical target for cytotoxic chemotherapy. Rather, the toxicity results from an unexpected organ differential that results in an unexpected but not rare toxicity. Further, there are few indicators that will provide insight into if and when this toxicity will be encountered. 

Laminas (LMN-ACO) serve as scaffolds for the anchoring of nuclear chromatin. Neuroblastoma cells with lamina genes deleted and lacking nuclear lamina, fail to differentiate in response to retinoic acid treatment. Lamina-defective neuroblastoma xenografts released cells with accelerated locomotion lamina-free tumor cells formed large tumors rapidly, and exhibited resistance to chemotherapy (doxorubicin, etoposide, paclitaxel). Laminary structures in place were necessary for organ differentiation [1627]. 

When applied in higher quantity, the highly purified factor induces explants to form complexes of large yolk-rich cells, which clearly differ from undifferentiated ectoderm and which may be determined to form endodermal structures. The lack of organ differentiation could be explained by an absence of secondary inductive interactions when all cells of the explant are induced in the same direction. When the factor was diluted, or its time of action limited to 1-24 hours, organotypic differentiation of the explants (which were surrounded by an epithelium) was improved (Fig. 4). 

FALK-PETERSEN IB (2005) Comparative organ differentiation during early life stages of marine fish. Fish Shellfish Immunology, 19,397-412. 

Figure 3.5 Comparison of (a) volumetric and (b) surface renderings of the thorax derived from contrast-enhanced computed tomography images. In the volumetric rendering, both the aorta, which is filled with iodine contrast, and bone are displayed with the same color and transparency values and appear to be the same organ. In the surface rendering model, fewer features are visible, but organ differentiation is clearer, with the aorta now in red and the bone in gray.

Carpenedo, R. L., Bratt-Leal, A. M., Marklein, R. A. et al. 2009. Homogeneous and organized differentiation within embryoid bodies induced by microsphere-mediated delivery of small molecules. Biomateriah 30(13) 2507-15. 

Since a definite reciprocal correlation is found between RNA synthesis and DNA replication in the chromosomes, it is evident that RNA synthesis in the chromosomes must also possess a definite specific organization, differentiated in time and along the length of the chromosome. 

---