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The availability of gene-targeted mice deficient in the urokinase-type plasminogen activator (uPA), urokinase receptor (uPAR), tissue-type plasminogen activator (tPA), and plasminogen permits a critical, genetic-based analysis of the physiological and pathological roles of the two mammalian plasminogen activators. We report a comparative study of animals with individual and combined deficits in uPAR and tPA and show that these proteins are complementary fibrinolytic factors in mice. Sinusoidal fibrin deposits are found within the livers of nearly all adult mice examined with a dual deficiency in uPAR and tPA, whereas fibrin deposits are never found in livers collected from animals lacking uPAR and rarely detected in animals lacking tPA alone. This is the first demonstration that uPAR has a physiological role in fibrinolysis. However, uPAR-/-/tPA-/- mice do not develop the pervasive, multi-organ fibrin deposits, severe tissue damage, reduced fertility, and high morbidity and mortality observed in mice with a combined deficiency in tPA and the uPAR ligand, uPA. Furthermore, uPAR-/-/tPA-/- mice do not exhibit the profound impairment in wound repair seen in uPA-/-/tPA-/- mice when they are challenged with a full-thickness skin incision. These results indicate that plasminogen activation focused at the cell surface by uPAR is important in fibrin surveillance in the liver, but that uPA supplies sufficient fibrinolytic potential to clear fibrin deposits from most tissues and support wound healing without the benefit of either uPAR or tPA.

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Disruption of retinoic acid receptor (RAR) gamma in F9 embryonal carcinoma cells leads to aberrent differentiation and reduced activation of expression of several all-trans-retinoic acid (RA)-induced genes. We have analyzed the expression of several additional RA-responsive genes in RAR alpha- and RAR gamma-null F9 cells. The RA-induced activation of Cdx1, Gap43, Stra4, and Stra6 was specifically impaired in RAR gamma-null cells, supporting the idea that each RAR may regulate distinct subsets of target genes. To further investigate the role of RAR gamma in F9 cell differentiation, "rescue" cell lines reexpressing RAR gamma 2 or overexpressing either RAR alpha 1 or RAR beta 2 were established in RAR gamma-null cells. Reexpression of RAR gamma or overexpression of RAR alpha restored both target-gene activation and the differentiation potential. In contrast, over-expression of RAR beta only poorly restored differentiation, although it could replace RAR gamma for the activation of target genes. Functional redundancy between the various RARs is discussed.

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Treatment of small resting B cells with soluble F(ab')2 fragments of anti-IgM, an analogue of T-independent type 2 antigens, induced activation characterized by proliferation and the expression of surface CD5. In contrast, B cells induced to proliferate in response to thymus-dependent inductive signals provided by either fixed activated T-helper 2 cells or soluble CD40 ligand-CD8 (CD40L) recombinant protein displayed elevated levels of CD23 (Fc epsilon II receptor) and no surface CD5. Treatment with anti-IgM and CD40L induced higher levels of proliferation and generated a single population of B cells coexpressing minimal amounts of CD5 and only a slight elevation of CD23. Anti-IgM- but not CD40L-mediated activation was highly sensitive to inhibition by cyclosporin A and FK520. Sp-cAMPS, an analogue of cAMP, augmented CD40L and suppressed surface IgM-mediated activation. Taken together these results are interpreted to mean that there is a single population of small resting B cells that can respond to either T-independent type 2 (surface IgM)- or T-dependent (CD40)-mediated activation. In response to different intracellular signals these cells are induced to enter alternative differentiation pathways.

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PURPOSE: To evaluate and compare the visual, refractive, contrast sensitivity, and aberrometric outcomes with a diffractive bifocal and trifocal intraocular lens (IOL) of the same material and haptic design. METHODS: Sixty eyes of 30 patients undergoing bilateral cataract surgery were enrolled and randomly assigned to one of two groups: the bifocal group, including 30 eyes implanted with the bifocal diffractive IOL AT LISA 801 (Carl Zeiss Meditec, Jena, Germany), and the trifocal group, including eyes implanted with the trifocal diffractive IOL AT LISA tri 839 MP (Carl Zeiss Meditec). Analysis of visual and refractive outcomes, contrast sensitivity, ocular aberrations (OPD-Scan III; Nidek, Inc., Gagamori, Japan), and defocus curve were performed during a 3-month follow-up period. RESULTS: No statistically significant differences between groups were found in 3-month postoperative uncorrected and corrected distance visual acuity (P > .21). However, uncorrected, corrected, and distance-corrected near and intermediate visual acuities were significantly better in the trifocal group (P < .01). No significant differences between groups were found in postoperative spherical equivalent (P = .22). In the binocular defocus curve, the visual acuity was significantly better for defocus of -0.50 to -1.50 diopters in the trifocal group (P < .04) and -3.50 to -4.00 diopters in the bifocal group (P < .03). No statistically significant differences were found between groups in most of the postoperative corneal, internal, and ocular aberrations (P > .31), and in contrast sensitivity for most frequencies analyzed (P > .15). CONCLUSIONS: Trifocal diffractive IOLs provide significantly better intermediate vision over bifocal IOLs, with equivalent postoperative levels of visual and ocular optical quality.

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Contains seven photographic prints elevations and floor plans of Harvard College used in an article on "Old College" by Samuel E. Morison. Includes first, second, and third floor plans; north, south, and east elevations; and one overhead perspective of the structure.

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3 pt.3

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By Thomas Walter, M.A. ; Recommended by several ministers. ; [One line from Psalms]