Livers from newborn mice homozygous for either one of the lethal deletions c14cos or c3H in chromosome 7 have drastically reduced levels of cytosolic phosphoenolpyruvate carboxykinase (GTP) [GTP:oxaloacetate carboxy-lyase

The concentration of the peptide mitogen epidermal growth factor (EGF) is hormonally and developmentally regulated in the granular convoluted tubule cells of the mouse submandibular gland. Using a labeled EGF nucleic acid probe, we have demonstrated that submandibular gland EGF mRNA concentrations increase during postnatal development of the gland and after the administration of testosterone or thyroid hormone. Recently, it was reported that EGF mRNA is present in kidney as well as a number of other mouse tissues. A comparison of EGF gene regulation in submandibular gland and kidney revealed that kidney EGF mRNA levels also increase during the postnatal period. Opposite sex differences were observed, with submandibular gland levels being about 16-fold higher in the male than in the female and kidney levels being 2- to 4-fold higher in the female than in the male. Renal EGF mRNA concentrations are less responsive to hormones than those in the submandibular gland. Renal EGF was localized immunocytochemically to the cells of distal convoluted tubules.

Previous studies demonstrated that 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a tumor promoter, is a potent inhibitor of inducer-mediated differentiation of murine erythroleukemia cells. Inhibition of cell differentiation was associated with inhibition of cell growth. The present studies, employing a cell line adapted for growth in TPA, demonstrate that inhibition of differentiation is not dependent upon inhibition of cell growth or a change in the cellfdivision cycle; neither is inhibition of differentiation accompanied by detectable effect on cell uptake of [3H]hexamethylene bisacetamide, the inducer used in these studies. TPA causes an inhibition of expression of all hexamethylene bisacetamide-inducible erythroid characteristics measured, including commitment to terminal cell division, accumulation of globin mRNA, and synthesis of globins, spectrin, heme synthetic enzymes (5-aminolevulinic acid dehydratase and uroporphyrinogen-I synthase) and heme. A hypothetical model for the inhibitory action of tumor promoters on terminal cell differentiation is discussed. 12-0-Tetradecanoyl-phorbol-13-acetate (TPA) is one of a group of plant diterpenes that are tumor promoters in the two-stage mouse skin carcinogenesis system (1-4). TPA is a reversible inhibitor of cell differentiation in several in vitro systems, including murine erythroleukemia cells (MELC) (5, 6), murine neuroblastoma cells (7), chicken myoblasts and chondroblasts (8,9), and the fibroblast-adipocyte conversion (10). It has been postulated that tumor promotion itself may involve interference in the process of differentiation (1, 6, 11). Of the several systems examined to date, MELC is the best characterized with respect to the molecular events during expression of differentiation. Upon exposure to various agents such as dimethyl sulfoxide (12), hexamethylene bisacetamide (HMBA) (13), or butyric acid (14), these cells initiate erythroid differentiation, including characteristic morphological changes (12), synthesis and accumulation of globin mRNA (15-18), synthesis of a and ( globins (19,20), increase in spectrin content (21,22), increase in the activity of heme synthetic enzymes and heme content (23,24), and loss of the capacity for cell division (12,25,26).We have previously found that TPA-mediated inhibition of differentiation is accompanied by an early and pronounced inhibition of cell growth (6,27). In the present studies we demonstrate that an effect on cell growth is not required for the effect on differentiation. Furthermore, we show that, under conditions in which TPA has no detectable effect on cell growth or uptake of inducer, it inhibits the expression of many characteristics of erythroid differentiation, including commitment to terminal cell division and accumulation of globin mRNA, globin, spectrin, heme synthetic enzymes, and heme. MATERIALS AND METHODSMELC, subclone DS19-1OTS, a TPA-sensitive cell line isolated from strain 745A-DS19, was maintained in culture and characterized as described (27). DS19-1OTS(TPA) cells were obtain...

Providing a context for learning information and requiring learners to teach specific content has been demonstrated to enhance knowledge retention. To enhance students' appreciation of the role of science and specifically histology in clinical reasoning, disease diagnosis, and treatment, a new teaching format was created to provide clinical context, promote integration and application of science knowledge, and to foster peer teaching and learning: the Clinico-Histologic Conference (CHC) for the Mount Sinai School of Medicine Histology course. Teams of six students were each assigned specific disease processes and were charged with creating oral presentations and handouts that taught their classmates about the clinical manifestations, etiopathogeneses, diagnoses, and treatments of the assigned processes, along with comparisons of normal histology to the pathology of the disease. Each team also created four questions, some of which were used on Histology written examinations. The physician facilitator evaluated the presentation and handouts. About two-thirds of students agreed the CHC enhanced appreciation of the importance of histology, provided a context for integration and application of basic science to patient care and enhanced their ability to teach their peers. Student feedback demonstrated that the CHCs were successful in promoting teamwork, peer teaching, and the application of histology to diagnose diseases. The authors believe that teaching basic science content in this new format enhanced student learning and application of medical knowledge, and that this new teaching format can be adopted by other medical school courses.