bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological approach to diabetic retinopathy
Authors: José Pedro De La Cruz M. D. , José Antonio González‐Correa M. D. , Ana Guerrero M. D. , Felipe Sánchez de la Cuesta M. D. 
Published: March 2004

AbstractDiabetic retinopathy is the most frequent cause of legal blindness in the population of 30‐to‐70‐year olds. Whether retinopathy appears or not depends mainly on the duration of the disease and the degree of metabolic control the patient maintains. High blood glucose values lead to important changes in cellular metabolism and the main effects of these alterations are endothelial dysfunction that sets in motion the morphological process of diabetic retinopathy.The biochemical lesions caused by prolonged hyperglycemia can be positively influenced, but usually not normalized, pharmacologically with some groups of drugs, which are now under development. This makes tight control of glycemia a key measure in preventing the onset or progression of diabetic retinopathy, together with an effective program of ophthalmologic detection and follow‐up in patients with diabetes. Regarding the role of endothelial dysfunction, antiplatelet drugs have been shown to slow some aspects of the evolution of diabetic retinopathy in its initial stages, mainly a lower degree of microaneurysms. However, a new approach to controlling endothelial dysfunction shows promise, mainly through the vascular endothelial growth factor (VEGF) inhibitors. These agents may prove to be especially useful in the treatment of proliferative diabetic retinopathy. Other encouraging results have been obtained in studies of antioxidant drugs and inhibitors of the formation of advanced glycation end products.Once retinal lesions appear, preventive measures need to be redoubled, with special attention to controlling glycemia; however, it is also necessary to resort to laser photocoagulation. This intervention aims to eliminate areas of ischemia and to diminish the formation of retinal exudates. If this measure fails or if vitreous hemorrhage appears, the only remaining therapeutic measure is vitrectomy. Copyright © 2004 John Wiley & Sons, Ltd.
Periostin is expressed within the developing teeth at the sites of epithelial–mesenchymal interaction
Authors: Kruzynska‐Frejtag Agnieszka , Wang Jian , Maeda Manabu , Rogers Rhonda , Krug Edward , Hoffman Stanley , Markwald Roger R. , Conway Simon J. 
Published: March 2004

AbstractPeriostin was originally isolated as an osteoblast‐specific factor that functions as a cell adhesion molecule for preosteoblasts and is thought to be involved in osteoblast recruitment, attachment, and spreading. The protein was renamed “periostin” because of its expression in the periosteum and periodontal ligament, indicating a potential role in bone and maintenance of tooth structure. Periostin has structural similarity to insect fasciclin‐I and can be induced by TGF‐β and Bmp2. Because tooth and periodontium development is a well‐described genetic model for organogenesis governed by a reciprocal set of epithelial–mesenchymal interactions, thought to be controlled by various TGF‐β superfamily members, we investigated whether periostin is present during tooth morphogenesis. Both periostin mRNA and protein expression were analyzed throughout normal tooth development (embryonic day [E] 9.5–newborn) and within both Bmp4‐ and Msx2‐null embryos. Periostin mRNA is initially present within the E9.5 first branchial arch epithelium and then shifts to underlying ectomesenchyme. Both mRNA and protein are asymmetrically localized to the lingual/palatal and buccal side during the early epithelial–mesenchymal interactions. Periostin is also present in dental papilla cells and within the trans‐differentiating odontoblasts during the bell and hard tissue formation stages of tooth development. We suggest that periostin plays multiple roles as a primary responder molecule during tooth development and may be linked to deposition and organization of other extracellular matrix adhesion molecules during maintenance of the adult tooth, particularly at the sites of hard‐soft tissue interface. Developmental Dynamics 229:857–868, 2004. © 2004 Wiley‐Liss, Inc.
PI3K inhibitors block skeletogenesis but not patterning in sea urchin embryos
Authors: Bradham C.A. , Miranda E.L. , McClay D.R. 
Published: March 2004

AbstractSkeletogenesis in the sea urchin embryo is a simple model of biomineralization, pattern formation, and cell–cell communication during embryonic development. The calcium carbonate skeletal spicules are secreted by primary mesenchyme cells (PMCs), but the skeletal pattern is dictated by the embryonic ectoderm. Although the process of skeletogenesis is well characterized, there is little molecular understanding of the basis of patterning within this system. In this study, we examined the contribution of phosphatidylinositide 3‐kinase (PI3K)‐mediated signaling to the skeletogenic process in sea urchin embryos by using the well‐established PI3K inhibitors LY294002 and wortmannin. Our results show that PI3K inhibitors specifically and reversibly block skeletogenesis, and that this blockade occurs within the PMCs rather than in the ectoderm, because the inhibitors block spiculogenesis in cultured micromeres. Our results are consistent with a model in which PI3K signaling is required, not for pattern sensing or interpretation but rather for the biomineralization process itself in the sea urchin embryo. Developmental Dynamics 229:713–721, 2004. © 2004 Wiley‐Liss, Inc.
Atlas of Hox gene expression in the developing kidney
Authors: Patterson Larry T. , Potter S. Steven 
Published: March 2004

AbstractHox genes often play important roles in segment identity determination and organogenesis. To better understand the roles of Hox genes during kidney development, we performed an extensive analysis of their expression patterns. Section in situ hybridizations were used to define the expression of 37 Hox genes at embryonic day (E) 12.5, E13.5, E15.5, and E17.5 of kidney development. Several interesting principles emerged. First, the concept of colinearity was preserved. Hox genes from the more 3′ positions in clusters were more often expressed in the ureteric bud, which is derived from the anterior of the intermediate mesoderm. Second, Hox genes were expressed throughout the ureteric bud without any segment specificity. Third, in the different segments of the forming nephron we did observe overlapping domains of Hox gene expression, which initiated distally at the junction between the nephron and ureteric bud, and extended proximally variable distances. Finally, we observed that paralogous Hox genes often showed surprisingly diverse expression patterns. Indeed, contiguous genes on a single cluster more often showed similar expression patterns than paralogs. In summary, the resulting atlas of Hox gene expression provides a foundation for further study of the overlapping functions Hox genes in the developing kidney. Developmental Dynamics 229:771–779, 2004 © 2004 Wiley‐Liss, Inc.
Notch signaling can regulate endoderm formation in zebrafish
Authors: Kikuchi Yutaka , Verkade Heather , Reiter Jeremy F. , Kim Cheol‐Hee , Chitnis Ajay B. , Kuroiwa Atsushi , Stainier Didier Y.R. 
Published: March 2004

AbstractEarly in vertebrate development, the processes of gastrulation lead to the formation of the three germ layers: ectoderm, mesoderm, and endoderm. The mechanisms leading to the segregation of the endoderm and mesoderm are not well understood. In mid‐blastula stage zebrafish embryos, single marginal cells can give rise to both endoderm and mesoderm (reviewed by Warga and Stainier [2002] The guts of endoderm formation. In: Solnica‐Krezel L, editor. Pattern formation in zebrafish. Berlin: Springer‐Verlag. p 28–47). By the late blastula stage, however, single marginal cells generally give rise to either endoderm or mesoderm. To investigate this segregation of the blastoderm into cells with either endodermal or mesodermal fates, we analyzed the role of Notch signaling in this process. We show that deltaC, deltaD, and notch1 are expressed in the marginal domain of blastula stage embryos and that this expression is dependent on Nodal signaling. Activation of Notch signaling from an early stage leads to a reduction of endodermal cells, as assessed by sox17 and foxA2 expression. We further find that this reduction in endoderm formation by the activation of Notch signaling is preceded by a reduction in the expression of bonnie and clyde (bon) and faust/gata5, two genes necessary for endoderm formation (Reiter et al. [1999] Genes Dev 13:2983–2995; Reiter et al. [2001] Development 128:125–135; Kikuchi et al. [2001] Genes Dev 14:1279–1289). However, activation of Notch signaling in bon mutant embryos leads to a further reduction in endodermal cells, also arguing for a bon‐independent role for Notch signaling in endoderm formation. Altogether, these results suggest that Notch signaling plays a role in the formation of the endoderm, possibly in its segregation from the mesoderm. Developmental Dynamics 229:756–762, 2004. © 2004 Wiley‐Liss, Inc.
T‐box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers
Authors: Christoffels Vincent M. , Hoogaars Willem M.H. , Tessari Alessandra , Clout Danielle E.W. , Moorman Antoon F.M. , Campione Marina 
Published: March 2004

AbstractSpecific regions of the embryonic heart tube differentiate into atrial and ventricular chamber myocardium, whereas the inflow tract, atrioventricular canal, inner curvatures, and outflow tract do not. These regions express Tbx2, a transcriptional repressor. Here, we tested its role in chamber formation. The temporal and spatial pattern of Tbx2 mRNA and protein expression in mouse hearts was found to be complementary to that of chamber myocardium‐specific genes Nppa, Cx40, Cx43, and Chisel, and was conserved in human. In vitro, Tbx2 repressed the activity of regulatory fragments of Cx40, Cx43, and Nppa. Hearts of transgenic embryos that expressed Tbx2 in the prechamber myocardium completely failed to form chambers and to express the chamber myocardium‐specific genes Nppa, Cx40, and Chisel, whereas other cardiac genes were normally expressed. These findings provide the first evidence that Tbx2 is a determinant in the local repression of chamber‐specific gene expression and chamber differentiation. Developmental Dynamics 229:763–770, 2004. © 2004 Wiley‐Liss, Inc.
Microarray analysis of retinoid‐dependent gene activity during rat embryogenesis: Increased collagen fibril production in a model of retinoid insufficiency
Authors: Flentke George R. , Baker Mei W. , Docterman Kimberly E. , Power Susan , Lough John , Smith Susan M. 
Published: March 2004

AbstractRetinoic acid (RA) is an essential mediator of embryogenesis. Some, but not all, of its targets have been identified. We previously developed a rat model of gestational retinoid deficiency (RAD; Power et al. [1999] Dev. Dyn. 216:469–480) and generated embryos with developmental impairments that closely resemble genetic and dietary models of retinoid insufficiency. Here, we used microarray analysis and expression profiling to identify 88 transcripts whose abundance was altered under conditions of retinoid insufficiency, as compared with normal embryos. Among these, the induction by RAD of genes involved in collagen I synthesis (COL1A1, IA2 and VA2, prolyl‐4‐hydroxylase‐α1) and protein galactosylation (galactokinase, ABO galactosyltransferase, UDP‐galactose transporter‐related protein) was especially noteworthy because extracellular matrix regulates many developmental events. We also identified several genes involved with stress responses (cathepsin H, UBC2E, IGFBP3, smoothelin). Real‐time polymerase chain reaction analysis of selected candidates revealed excellent agreement with the array findings. Further validation came from the demonstration that these genes were similarly dysregulated in two genetic models of retinoid insufficiency, the retinol binding protein null‐mutant embryo and the Raldh2 null‐mutant embryo. In situ hybridization of RAD embryos found increased collagen IA1 and IGFBP3 mRNA within the connective mesenchyme and vasculature, respectively, and a failure to repress the growth factor midkine within the RAD neural tube. Many of the identified genes were not known previously to respond to retinoid status and will provide new insights to retinoid roles and to the consequences of retinoid insufficiency. Developmental Dynamics 229:886–898, 2004. © 2004 Wiley‐Liss, Inc.
IL‐1 acts on antigen‐presenting cells to enhance the in vivo proliferation of antigen‐stimulated naive CD4 T cells via a CD28‐dependent mechanism that does not involve increased expression of CD28 ligands
Authors: Khoruts Alexander , Osness Richard E. , Jenkins Marc K. 
Published: March 2004

AbstractThe basis of the adjuvant effect of IL‐1 on the clonal expansion of Ag‐specific CD4 T cells was measured in vivo using the TCR transgenic T cell adoptive transfer method. Injection ofAg plus IL‐1 caused naive CD4 T cells to proliferate to a greater extent than did injection of Ag alone. The T cells had to express CD28 to experience the beneficial effect of IL‐1 whereas the hosthad to express the type I IL‐1R, raising the possibility that IL‐1's adjuvant properties were related to induction of CD28 ligands on APC. Surprisingly, however, expression of CD28 ligands on DC and B cells was not affected by IL‐1. Therefore, the adjuvant properties of IL‐1 depend on a basal level of CD28 signaling but cannot be explained by enhanced CD28 signaling due to CD28 ligand induction.
The role of Toll‐like receptor 4 versus interleukin‐12 in immunity to respiratory syncytial virus
Authors: Ehl Stephan , Bischoff Ruth , Ostler Tobias , Vallbracht Simone , Schulte‐Mönting Jürgen , Poltorak Alexander , Freudenberg Marina 
Published: March 2004

AbstractToll‐like receptors (TLR) and IL‐12 represent key elements of innate immunity. Using C57BL/10 ScCr mice it was shown that TLR4 is important for control of infection with respiratory syncytial virus (RSV). Since these mice have an additional defect in the IL‐12R, we reinvestigated immunity to RSV in several C57BL/10 and BALB/c mouse strains lacking a functional TLR4, a functional IL‐12–IL‐12R interaction or both. In the absence of a functional IL‐12 axis, early virus control was impaired in C57BL/10 mice, but not in BALB/c mice. By contrast, TLR4 had no impact on RSV elimination. Pulmonary NK cell recruitment was impaired in IL‐12 deficient BALB/c mice and NK cytotoxicity was reduced in IL‐12/IL‐12R‐deficient mice of both genetic backgrounds. Absence of TLR4 had no impact on NK cell recruitment or NK activity nor on recruitment of other pulmonary inflammatory cells. Activation of RSV‐specific T cell immunity, including T cell mediated immunopathology, was normal in all mutant strains. These findings clearly argue against a significant role for TLR4 and define a limited role for IL‐12 in primary murine RSV infection.
Phenotypic classification of human CD8+ T cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector function
Authors: Tomiyama Hiroko , Takata Hiroshi , Matsuda Tomoko , Takiguchi Masafumi 
Published: March 2004

AbstractPhenotypic classification of human CD8+ T cells using three cell surface markers, CD27, CD28 and CD45RA, was recently suggested to be useful for identification of naive, memory and effector CD8+ T cells. However, it still remains unclear whether such classification precisely reflects functional classification of CD8+ T cells. To clarify this, we characterized each CD27CD28CD45RA subset of total and human cytomegalovirus (HCMV)‐specific CD8+ T cells by analyzing the expression of perforin and two chemokine receptors, CCR5 and CCR7, as well as their function. An inverse correlation between perforin and CD27 expression was found in all four CD28CD45RA subsets. Therefore, to achieve a phenotypic classification of CD8+ T cells that moreprecisely reflects their function, the CD27+ subset was divided into CD27low and CD27high subsets based on the expression level of CD27. Functional and flow cytometric analyses of CD27CD28CD45RA subsets showed that this phenotypic classification reflects functional classification of CD8+ T cells. HCMV‐specific CD8+ T cells from healthy HCMV‐seropositive individuals were predominantly found in effector and memory/effector subsets, indicating that HCMV‐specific effector CD8+ T cells are actively induced by HCMV replication in healthy HCMV carriers. Phenotypic analyses of CD8+ T cells using this classification will enable the characterization of antigen‐specific CD8+ T cells.
The anti‐inflammatory effects of 1,25‐dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin‐mediated T lymphocyte homing
Authors: Topilski Ian , Flaishon Liat , Naveh Yaron , Harmelin Alon , Levo Yoram , Shachar Idit 
Published: March 2004

AbstractThe fat soluble vitamin D3 metabolite 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3], and its nuclear receptor play an important role in regulating immune responses. While 1,25(OH)2D3 is known to inhibit transcription of cytokine genes that are required for Th1 differentiation or are products of differentiated Th1 cells, its role in regulating differentiation of Th2 cells is less clear. In this study, we show that 1,25(OH)2D3 has anti‐inflammatory effects in an in vivo Th2‐dependent asthma model. In addition, we demonstrate that 1,25(OH)2D3 down‐regulates the cytoskeleton rearrangement required for promoting integrin‐mediated adhesion of naive and effector CD4+ T cells. Finally, 1,25(OH)2D3 inhibits chemokine‐induced migration of naive cells and their homing to the lymph nodes. Thus, in addition to its regulation of cytokine transcription, 1,25(OH)2D3 regulates migration of cells and thus controls the skewing of various Th subsets in the secondary lymphoid organs and inhibits Th function at sites of inflammation.
CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion
Authors: Mayne Michael , Moffatt Teri , Kong Hong , McLaren Paul J. , Fowke Keith R. , Becker Kevin G. , Namaka Mike , Schenck Annette , Bardoni Barbara , Bernstein Charles N. , Melanson Maria 
Published: March 2004

AbstractDNA microarray profiling of CD4+ and CD8+ cells from non‐treated relapsing and remitting multiple sclerosis (MS) patients determined that the cytoplasmic binding partner of fragile X protein (CYFIP2, also called PIR121) was increased significantly compared to healthy controls. Western analysis confirmed that CYFIP2 protein was increased approximately fourfold in CD4+ cells from MS compared to inflammatory bowel disorder (IBD) patients or healthy controls. Because CYFIP2 acts as part of a tetrameric complex that regulates WAVE1 activation we hypothesized that high levels of CYFIP2 facilitate T cell adhesion, which is elevated in MS patients. Several findings indicated that increased levels of CYFIP2 facilitated adhesion. First, adenoviral‐mediated overexpression of CYFIP2 in Jurkat cells increased fibronectin‐mediated adhesion. Secondly, CYFIP2 knock‐down experiments using antisense oligodeoxynucleotides reduced fibronectin‐mediated binding in Jurkat and CD4+ cells. Thirdly, inhibition of Rac‐1, a physical partner with CYFIP2 and regulator of WAVE1 activity, reduced fibronectin‐mediated adhesion in Jurkat and CD4+ cells. Finally, inhibition of Rac‐1 or reduction of CYFIP2 protein decreased fibronectin‐mediated adhesion in CD4+ cells from MS patients to levels similar to controls. These studies suggest that overabndance of CYFIP2 protein facilitates increased adhesion properties of T cells from MS patients.
Enforced Bcl‐2 expression in B lymphocytes induces rheumatoid factor and anti‐DNA production, but the Yaa mutation promotes only anti‐DNA production
Authors: Kuroki Aki , Moll Thomas , López‐Hoyos Marcos , Fossati‐Jimack Liliane , Ibnou‐Zekri Nabila , Kikuchi Shuichi , Merino Jesús , Merino Ramón , Izui Shozo 
Published: March 2004

AbstractThe presence of rheumatoid factors (RF) is a characteristic feature of patients with rheumatoid arthritis, but not systemic lupus erythematosus. In this study, we have explored the role of theanti‐apoptotic Bcl‐2 protein and the Y‐linked autoimmune acceleration (Yaa) mutation in the production of IgG RF in comparison with IgG anti‐DNA autoimmune responses. Analysis in C57BL/6 mice, in their F1 hybrids with lupus‐prone NZW mice, and in bone marrow chimeras containing mixtures of C57BL/6 bcl‐2‐transgenic and BXSB non‐transgenic cells demonstrated that an enforced Bcl‐2 expression in B cells promoted the induction of IgG anti‐DNA production in these mice, while significant IgG RF responses were observed only in mice developing high levels of gp70‐anti‐gp70 immune complexes and lethal glomerulonephritis. Moreover, in contrast to a synergistic interaction between the Yaa mutation and Bcl‐2 overexpression on IgG anti‐DNA production, the Yaa mutation failed to enhance the production of IgG RF induced in bcl‐2‐transgenic mice. Our results reveal that defects in the regulation of B cell apoptosis play a critical role in the production of IgG RF, and that the Yaa mutation differentially modulates RF and anti‐DNA autoimmune responses, likely related to the nature of autoantigens involved in each autoimmune response.
Mini‐review: A pivotal role for innate immunity in the clearance of apoptotic cells
Authors: Roos Anja , Xu Wei , Castellano Giuseppe , Nauta Alma J. , Garred Peter , Daha Mohamed R. , van Kooten Cees 
Published: March 2004

AbstractApoptotic cells can be recognized and taken up by both macrophages and dendritic cells. Phagocytosis of apoptotic cells generally leads to active suppression of cytokine production by professional phagocytes. This is different from the response towards cells that die by necrosis, which induce a pro‐inflammatory cytokine profile. Uptake of apoptotic cells involves a large number of receptors and opsonins, which bind to cellular ligands exposed during the various stages of apoptotic cell death. Among the opsonins of apoptotic cells, complement factors, including C1q, and complement‐activating members of the pentraxin family play an important role. This is indicated by in vitro phagocytosis studies and supported by the susceptibility to systemic autoimmunity of carriersof genetic deficiencies for early complement proteins. The present review summarizes the role of molecules of innate immunity in the handling of apoptotic cells by macrophages and dendritic cells. It is proposed that C1q and other opsonins prevent autoimmunity and maintain self‐tolerance by supporting the efficient clearance of apoptotic material, as well as by actively modulating phagocyte function.
One‐ and Three‐Dimensional Coordination Polymers Containing Organic Ligands Produced Through in situ Hydrothermal Reactions
Authors: Hu Xi‐Xue , Pan Cheng‐Ling , Xu Ji‐Qing , Cui Xiao‐Bing , Yang Guang‐Di , Wang Tie‐Gang 
Published: March 2004

AbstractTwo novel coordination polymers of cobalt(II), [Co(µ3‐H2bbh)(phen)]n(1) and [Co(µ4‐H2bbh) (H2O)2]n(2) (phen = 1,10‐phenanthroline; H4bbh = benzene‐1,2,4,5‐tetracarbo‐1,2:4,5‐dihydrazide), in which H2bbh ligands are in situ generated by an acylation reaction of H4bta (H4bta = benzene‐1,2,4,5‐tetracarboxylic acid) with hydrazine hydrate under hydrothermal conditions have been synthesized and structurally characterized. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)